AU2015258271B2 - Adeno-associated virus cy.5 (AAVcy.5) sequences and recombinant AAVs comprising same - Google Patents

Abstract

H:\fmt\lntenvoven\NRPortbl\DCC\FMT50181_ I II.DOC-25/03/2013 A method for detecting and isolating AAV sequences in a sample of DNA obtained from tissue or cells is provided. The invention further provides AAV sequences identified by this method, and vectors constructed using these sequences.

Description

The invention further provides AAV sequences identified by this method, and vectors constructed using these sequences.

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2015258271 20 Nov 2015

ADENO-ASSOCIATED VIRUS cy.5 (AAVcy.5) SEQUENCES AND RECOMBINANT AAVs COMPRISING SAME

This is a divisional of Australian Patent Application No. 2012238302, the entire contents of which are incorporated herein by reference.

BACKGROUND OF THE INVENTION

Adeno-associated virus (AAV), a member of the Parvovirus family, is a small nonenveloped, icosahedral virus with single-stranded linear DNA genomes of 4.7 kilobases (kb) to 6 kb. AAV is assigned to the genus, Dependovirus, because the virus was discovered as a contaminant in purified adenovirus stocks. AAV's life cycle includes a latent phase at which

AAV genomes, after infection, are site specifically integrated into host chromosomes and an infectious phase in which, following either adenovirus or herpes simplex virus infection, the integrated genomes are subsequently rescued, replicated, and packaged into infectious viruses. The properties of non-pathogenicity, broad host range of infectivity, including non-dividing cells, and potential site-specific chromosomal integration make AAV an attractive tool for gene transfer.

Recent studies suggest that AAV vectors may be the preferred vehicle for gene therapy. To date, there have been 6 different serotypes of AAVs isolated from human or nonhuman primates (NHP) and well characterized. Among them, human serotype 2 is the first AAV that was developed as a gene transfer vector; it has been widely used for efficient gene transfer experiments in different target tissues and animal models. Clinical trials of the experimental application of AAV2 based vectors to some human disease models are in progress, and include such diseases as cystic fibrosis and hemophilia B.

What are desirable are AAV-based constructs for gene delivery.

SUMMARY OF THE INVENTION

In one aspect, the invention provides a novel method of detecting and identifying AAV sequences from cellular DNAs of various human and non-human primate (NHP) tissues using bioinformatics analysis, PCR based gene amplification and cloning technology, based on the nature of latency and integration of AAVs in the absence of helper virus co-infection.

In another aspect, the invention provides method of isolating novel AAV sequences detected using the above described method of the invention. The invention further comprises methods of generating vectors based upon these novel AAV serotypes, for serology and gene

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2015258271 03 Aug 2017 transfer studies solely based on availability of capsid gene sequences and structure of rep-cap gene junctions.

In still another aspect, the invention provides a novel method for performing studies of serology, epidemiology, biodistribution and mode of transmission, using reagents according to the invention, which include generic sets of primers/probes and quantitative real time PCR.

In yet another aspect, the invention provides a method of isolating complete and infectious genomes of novel AAV serotypes from cellular DNA of different origins using RACE and other molecular techniques.

In a further aspect, the invention provides a method of rescuing novel serotypes of

AAV genomes from human and NHP cell lines using adenovirus helpers of different origins.

In still a further aspect, the invention provides novel AAV serotypes, vectors containing same, and methods of using same.

In a particular aspect, the invention provides a recombinant adeno-associated virus (AAV) comprising an AAV capsid comprising vpl proteins having the sequence of amino acids 1 to 738 of SEQ ID NO: 85 (rh.20) or a sequence at least 95% identical to the full length of amino acids 1 to 738 of SEQ ID NO: 85, AAV vp2 proteins, and AAV vp3 proteins, wherein the recombinant AAV further comprises, packaged within the capsid a nucleic acid molecule comprising at least one AAV inverted terminal repeat (ITR), and a non-AAV nucleic acid sequence encoding a gene product operably linked to sequences which direct expression of the product in a host cell.

In a further aspect, the invention provides a recombinant adeno-associated virus (AAV) having an AAV capsid comprising AAV vpl proteins, AAV vp2 proteins having a sequence of amino acids 138 to 738 of SEQ ID NO:85 (rh.20) or a sequence at least 95% identical to the full-length of amino acids 138 to 738 of SEQ ID NO: 85, and AAV vp3 proteins, wherein the recombinant AAV further comprises, packaged within the capsid, a nucleic acid molecule comprising at least one AAV inverted terminal repeat (ITR) and a non-AAV nucleic acid sequence encoding a gene product operably linked to sequences which direct expression of the product in a host cell.

In another aspect, the invention provides a recombinant adeno-associated virus (AAV) having an AAV capsid comprising AAV vpl proteins, AAV vp2 proteins, and AAV vp3 proteins having a sequence of amino acids 204 to 738 of SEQ ID NO:85 (rh.20) or a sequence at least 95% identical to the full-length of amino acids 204 to 738 of SEQ ID NO: 85, wherein the recombinant AAV further comprises, packaged within the capsid, a

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2015258271 18 Dec 2017 nucleic acid molecule comprising at least one AAV inverted terminal repeat (ITR) and a non-AAV nucleic acid sequence encoding a gene product operably linked to sequences which direct expression of the product in a host cell.

In a further aspect, the invention provides a method of generating a recombinant 5 adeno-associated virus (AAV) comprising an AAV capsid comprising culturing a host cell containing: (a) a molecule encoding the AAV vpl capsid protein having a sequence of amino acids 1 to 738 of SEQ ID NO: 85, or a sequence which is at least 95% identical to the full length of SEQ ID NO: 85; (b) a functional rep gene; (c) a minigene comprising a nucleic acid molecule comprising at least one AAV inverted terminal repeat (ITR) and a non-AAV nucleic acid sequence encoding a gene product operably linked to sequences which direct expression of the product in a host cell; and (d) sufficient helper functions to permit packaging of the minigene into the AAV capsid protein under conditions which permit packaging of the minigene into the AAV capsid.

In yet another aspect, the invention provides a method for delivering a transgene product to a subject, said method comprising administering an adeno-associated virus (AAV) comprising an AAV capsid comprising AAV vpl proteins, AAV vp2 proteins, and AAV vp3 proteins having a sequence of amino acids 204 to 738 of SEQ ID NO:85 (rh.20) or a sequence at least 95% identical to the full-length of amino acids 204 to 738 of SEQ ID NO: 85, said AAV having packaged in the capsid a nucleic acid molecule comprising at least one AAV inverted terminal repeat (ITR) and a non-AAV nucleic acid sequence which encodes a gene product operably linked to sequences which direct expression thereof in a host cell.

These and other aspects of the invention will be readily apparent from the following detailed description of the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

Figs. 1A through 1AAAR provide an alignment of the nucleic acid sequences encoding at least the cap proteins for the AAV serotypes. The full-length sequences including the ITRs, the rep region, and the capsid region are provided for novel AAV serotype 7 [SEQ ID NO:1], and for previously published AAV1 [SEQ ID NO:6], AAV2 [SEQ ID NO:7]; and AAV3 [SEQ ID NO:8], Novel AAV serotypes AAV8 [SEQ ID NO:4] and AAV9 [SEQ ID NO:5] are the subject of co-fded applications. The other novel clones of the invention provided in this alignment include: 42-2 [SEQ ID NO:9], 42-8 [SEQ ID NO:27], 42-15 [SEQ ID NO:28], 422a

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5b [SEQ ID NO: 29], 42-lb [SEQ ID NO:30]; 42-13 [SEQ ID NO: 31], 42-3a [SEQ ID NO: 32], 42-4 [SEQ ID NO:33], 42-5a [SEQ ID NO: 34], 42-10 [SEQ ID NO:35], 42-3b [SEQ ID NO: 36], 42-11 [SEQ ID NO: 37], 42-6b [SEQ ID NO:38], 43-1 [SEQ ID NO: 39], 43-5 [SEQ ID NO: 40], 43-12 [SEQ ID NO:41], 43-20 [SEQ ID NO:42], 43-21 [SEQ ID NO: 43], 43-23 [SEQ ID NO:44], 43-25 [SEQ ID NO: 45], 44.1 [SEQ ID NO:47], 44.5 [SEQ ID NO:47], 223.10 [SEQ ID NO:48], 223.2 [SEQ ID NO:49], 223.4 [SEQ ID NO:50], 223.5 [SEQ ID NO:51], 223.6 [SEQ ID NO: 52], 223.7 [SEQ ID NO: 53], A3.4 [SEQ ID NO: 54], A3.5 [SEQ ID NO:55], A3.7 [SEQ ID NO: 56], A3.3 [SEQ ID NO: 57], 42.12 [SEQ ID NO: 58], 44.2 [SEQ ID NO: 59], The nucleotide sequences of the signature regions of AAV10 [SEQ ID NO:

117], AAV 11 [SEQ ID NO:

2b

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118] and AAV12 [SEQ ID NO:119] are provided in this figure. Critical landmarks in the structures of AAV genomes are shown. Gaps are demonstrated by dots. The 3’ ITR of AAV1 [SEQ ID NO:6] is shown in the same configuration as in the published sequences. TRS represents terminal resolution site. Notice that AAV7 is the only AAV reported that uses

GTG as the initiation codon for VP3.

Figs, 2A through 2F are an alignment of the amino acid sequences of the proteins of the vpl capsid proteins of previously published AAV serotypes 1 [SEQ ID NO:64], AAV2 [SEQ ID NO:70], AAV3 [SEQ ID NO: 71], AAV4 [SEQ ID NO:63], AAV5 [SEQ ID NO:114], and AAV6 [SEQ ID NO:65] and novel AAV sequences of the invention, including: Cl. [SEQ ID NO:60], C2 [SEQ ID NO:61], C5 [SEQ ID NO:62], A3-3 [SEQ ID NO:66], A3-7 [SEQ ID NO:67], A3-4 [SEQ ID NO:68], A3-5 [SEQ ID NO: 69], 3.3b [SEQ ID NO: 62], 223.4 [SEQ ID NO: 73], 223-5 [SEQ ID NO:74], 223-10 [SEQ ID NO:75], 2232 [SEQ ID NO:76], 223-7 [SEQ ID NO: 77], 223-6 [SEQ ID NO: 78], 44-1 [SEQ ID NO: 79], 44-5 [SEQ ID NO:80], 44-2 [SEQ ID NO:81], 42-15 [SEQ ID NO: 84], 42-8 [SEQ ID

NO: 85], 42-13 [SEQ ID NO:86], 42-3A [SEQ ID NO:87], 42-4 [SEQ ID NO:88], 42-5A [SEQ ID NO:89], 42-1B [SEQ ID NO:90], 42-5B [SEQ ID NO:91], 43-1 [SEQ ID NO: 92], 43-12 [SEQ ID NO: 93], 43-5 [SEQ IDNO:94], 43-21 [SEQ 1DNO:96], 43-25 [SEQ ID NO: 97], 43-20 [SEQ ID NO:99], 24.1 [SEQ ID NO: 101], 42.2 [SEQ ID NO:102], 7.2 [SEQ ID NO: 103], 27.3 [SEQ ID NO: 104], 16.3 [SEQ ID NO: 105], 42.10 [SEQ ID NO: 106],

42-3B [SEQ ID NO: 107], 42-11 [SEQ ID NO: 108], FI [SEQ ID NO: 109], F5 [SEQ ID

NO: 110], F3 [SEQ ID NO:111], 42-6B [SEQ ID NO: 112], 42-12 [SEQ ID NO: 113],

Novel serotypes AAV8 [SEQ ID NO:95] and AAV9 [SEQ ID NO:100] are the subject of cofiled patent applications.

Figs. 3A through 3C provide the amino acid sequences of the AAV7 rep proteins [SEQ ID NO:3],

DETAILED DESCRIPTION OF THE INVENTION

In the present invention, the inventors have found a method which takes advantage of the ability of adeno-associated virus (AAV) to penetrate the nucleus, and, in the absence of a helper virus co-infection, to integrate into cellular DNA and establish a latent infection. This method utilizes a polymerase chain reaction (PCR)-based strategy for detection, identification and/or isolation of sequences of AAVs from DNAs from tissues of human and non-human primate origin as well as from other sources. Advantageously, this method is

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2015258271 20 Nov 2015 also suitable for detection, identification and/or isolation of other integrated viral and nonviral sequences, as described below.

The invention further provides nucleic acid sequences identified according to the methods of the invention. One such adeno-associated virus is of a novel serotype, termed herein serotype 7 (AAV7). Other novel adeno-associated virus serotypes provided herein include AAV10, AAV11, and AAV12. Still other novel AAV serotypes identified according to the methods of the invention are provided in the present specification. See, Figures and Sequence Listing, which is incorporated by reference.

Also provided are fragments of these AAV sequences. Among particularly desirable

AAV fragments are the cap proteins, including the vpl, vp2, vp3, the hypervariable regions, the rep proteins, including rep 78, rep 68, rep 52, and rep 40, and the sequences encoding these proteins. Each of these fragments may be readily utilized in a variety of vector systems and host cells. Such fragments may be used alone, in combination with other AAV sequences or fragments, or in combination with elements from other AAV or non-AAV viral sequences. In one particularly desirable embodiment, a vector contains the AAV cap and/or rep sequences of the invention.

As described herein, alignments are performed using any of a variety of publicly or commercially available Multiple Sequence Alignment Programs, such as Clustal W”, accessible through Web Servers on the internet. Alternatively, Vector NTI utilities are also used. There are also a number of algorithms known in the art which can be used to measure nucleotide sequence identity, including those contained in the programs described above. As another example, polynucleotide sequences can be compared using Pasta, a program in GCG Version 6.1, Fasta provides alignments and percent sequence identity of the regions of the best overlap between the query and search sequences. For instance, percent sequence identify between nucleic acid sequences can be determined using Fasta with its default parameters (a word size of 6 and the NOPAM factor for the scoring matrix) as provided in GCG Version 6.1, herein incorporated by reference. Similar programs are available for amino acid sequences, e.g., the “Clustal X” program. Generally, any of these programs are used at default settings, although one of skill in the art can alter these settings as needed,

Alternatively, one of skill in the art can utilize another algorithm or computer program which provides at least the level of identify or alignment as that provided by the referenced algorithms and programs.

The term “substantial homology” or “substantial similarity,” when referring to a nucleic acid, or fragment thereof, indicates that, when optimally aligned with appropriate

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2015258271 20 Nov 2015 nucleotide insertions or deletions with another nucleic acid (or its complementary strand), there is nucleotide sequence identity in at least about 95 to 99% of the aligned sequences. Preferably, the homology is over full-length sequence, or an open reading frame thereof, or another suitable fragment which is at least 15 nucleotides in length. Examples of suitable fragments are described herein.

The term “substantial homology” or “substantial similarity,” when referring to amino acids or fragments thereof, indicates that, when optimally aligned with appropriate amino acid insertions or deletions with another amino acid, there is amino acid sequence identity in at least about 95 to 99% of the aligned sequences. Preferably, the homology is over full10 length sequence, or a protein thereof, e.g., a cap protein, a rep protein, or a fragment thereof which is at least 8 amino acids, or more desirably, at least 15 amino acids in length.

Examples of suitable fragments are described herein.

By the term “highly conserved” is meant at least 80% identity, preferably at least 90% identity, and more preferably, over 97% identity. Identity is readily determined by one of skill in the art by resort to algorithms and computer programs known by those of skill in the art.

The term “percent sequence identity” or “identical” in the context of nucleic acid sequences refers to the residues in the two sequences which are the same when aligned for maximum correspondence. The length of sequence identity comparison may be over the foil-length of the genome, the foil-length of a gene coding sequence, or a fragment of at least about 500 to 5000 nucleotides, is desired. However, identity among smaller fragments, e.g. of at least about nine nucleotides, usually at least about 20 to 24 nucleotides, at least about 28 to 32 nucleotides, at least about 36 or more nucleotides, may also be desired. Similarly, “percent sequence identity” may be readily determined for amino acid sequences, over the full-length of a protein, or a fragment thereof.

Suitably, a fragment is at least about 8 amino acids in length, and may be up to about 700 amino acids. Examples of suitable fragments are described herein.

The AAV sequences and fragments thereof are useful in production of rAAV, and are also useful as antisense delivery vectors, gene therapy vectors, or vaccine vectors. The invention further provides nucleic acid molecules, gene delivery vectors, and host cells which contain the AAV sequences of the invention.

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As described herein, the vectors of the invention containing the AAV capsid proteins of the invention are particularly well suited for use in applications in which the neutralizing antibodies diminish the effectiveness of other AAV serotype based vectors, as well as other viral vectors. The rAAV vectors of the invention are particularly advantageous in rAAV readministration and repeat gene therapy.

These and other embodiments and advantages of the invention are described in more detail below. As used throughout this specification and the claims, the terms comprising” and “including” and their variants are inclusive of other components, elements, integers, steps and the like. Conversely, the term “consisting” and its variants is exclusive of other components, elements, integers, steps and the like.

I. Methods of the Invention

A. Detection of Sequences Via Molecular Cloning

In one aspect, the invention provides a method of detecting and/or identifying target nucleic acid sequences in a sample. This method is particularly weli suited for detection of viral sequences which are integrated into the chromosome of a cell, e.g,, adenoassociated viruses (AAV) and retroviruses, among others. The specification makes reference to AAV, which is exemplified herein. However, based on this information, one of skill in the art may readily perform the methods of the invention on retroviruses [e.g., feline leukemia virus (FeLV), HTLVI and HTLVII], and lentivirinae [e.g., human immunodeficiency virus (HIV), simian immunodeficiency virus (SIV), feline immunodeficiency virus (FIV), equine infectious anemia virus, and spumavirinal)], among others; Further, the method of the invention may also be used for detection of other viral and non-viral sequences, whether integrated or non-integrated into the genome of the host cell.

As used herein, a sample is any source containing nucleic acids, e.g., tissue, tissue culture, cells, cell culture, and biological fluids including, without limitation, urine and blood. These nucleic acid sequences may be DNA or RNA from plasmids, natural DNA or

RNA from any source, including bacteria, yeast, viruses, and higher organisms such as plants or animals. DNA or RNA is extracted from the sample by a variety of techniques known to those of skill in the art, such as those described by Sambrook, Molecular Cloning: A Laboratory Manual (New York: Cold Spring Harbor Laboratory). The origin of the sample and the method by which the nucleic acids are obtained for application of the method of the

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2015258271 20 Nov 2015 invention is not a limitation of the present invention. Optionally, the method of the invention can be performed directly on the source of DNA, or on nucleic acids obtained (e.g., extracted) from a source.

The method of the invention invol ves subjecting a sample containing DNA to 5 amplification via polymerase chain reaction (PCR) using a first set of primers specific for a first region of double-stranded nucleic acid sequences, thereby obtaining amplified sequences.

As used herein, each of the “regions” is predetermin ed based upon the alignment ofthe nucleic acid sequences of at least two serotypes (e.g., AAV) or strains (e.g., lentiviruses), and wherein each of said regions is composed of sequences having a 5' end which is highly conserved, a middle which is preferably, but necessarily, variable, and a 3' end which is highly conserved, each of these being conserved or variabie relative to the sequences of the at least two aligned AAV serotypes. Preferably, the 5' and/or 3' end is highly conserved over at least about 9, and more preferably, at least 18 base pairs (bp).

However, one or both of the sequences at the 5’ or 3’ end may be conserved over more than 18 bp, more than 25 bp, more than 30 bp, or more than 50 bp at the 5' end. With respect to the variable region, there is no requirement for conserved sequences, these sequences may be relatively conserved, or may have less than 90, 80, or 70% identity among the aligned serotypes or strains.

Each of the regions may span about 100 bp to about 10 kilobase pairs in length. However, it is particularly desirable that one ofthe regions is a “signature region”,

i.e., a region which is sufficiently unique to positively identify the amplified sequence as being from the target source. For example, in one embodiment, the first region is about 250 bp in length, and is sufficiently unique among known AAV sequences, that it positively identifies the amplified region as being of AAV origin. Further, the variabie sequences within this region are sufficiently unique that can be used to identify the serotype from which the amplified sequences originate. Once amplified (and thereby detected), the sequences can be identified by performing conventional restriction digestion and comparison to restriction digestion patterns for this region in any of AAV1, AAV2, AAV3, AAV4, AAV5, or AAV6, or that of AAV7, AAV10, AAV 11, AAV 12, or any of the other novel serotypes identified by the invention, which is predetermined and provided by the present invention.

Given the guidance provided herein, one of skill in the art can readily identify such regions among other integrated viruses to permit ready detection and identification of these sequences. Thereafter, an optimal set of generic primers located

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2015258271 20 Nov 2015 within the highly conserved ends can be designed and tested for efficient amplification of the selected region from samples. This aspect of the invention is readily adapted to a diagnostic, kit for detecting the presence of the target sequence (e.g., AAV) and for identifying the AAV serotype, using standards which include the restriction patterns for the AAV serotypes described herein or isolated using the techniques described herein. For example, quick identification or molecular serotyping of PCR products can be accomplished by digesting the PCR products and comparing restriction patterns.

Thus, in one embodiment, the “signature region” for AAV spans about bp 2800 to about 3200 of AAV 1 [SEQ ID NO:6], and corresponding base pairs in AAV 2,

AAV3, AAV4, AAV5, and AAV6. More desirably, the region is about 250 bp, located within bp 2886 to about 3143 bp of AAV 1 [SEQ ID NO:6], and corresponding base pairs in AAV 2 [SEQ ID NO:7], AAV3 [SEQ ID NO8], and other AAV serotypes. See, Fig. 1. To permit rapid detection of AAV in the sample, primers which specifically amplify this signature region are utilized. However, the present invention is not limited to the exact sequences identified herein for the AAV signature region, as one of skill in the art may readily alter this region to encompass a shorter fragment, or a larger fragment of this signature region.

The PCR primers are generated using techniques known to those of skill in the art. Each of the PCR primer sets is composed of a 5’ primer and a 3’ primer. See, e.g.,

Sambrook et al, cited herein. The term “primer” refers to an oligonucleotide which acts as a point of initiation of synthesis when placed under conditions in which synthesis of a primer extension product which is complementary to a nucleic acid strand is induced. The primer is preferably single stranded. However, if a double stranded primer is utilized, it is treated to separate its strands before being used to prepare extension products. The primers may be about 15 to 25 or more nucleotides, and preferably at least 18 nucleotides. However, for certain applications shorter nucleotides, e.g., 7 to 15 nucleotides are utilized.

The primers are selected to be sufficiently complementary to the different strands of each specific sequence to be amplified to hybridize with their respective strands. Therefore, the primer sequence need not reflect the exact sequence of the region being amplified. For example, a non-complementary nucleotide fragment may be attached to the 5’ end of the primer, with the remainder of the primer sequence being completely complementary to the strand. Alternatively, non-complementary bases or longer sequences can be interspersed into the primer, provided that the primer sequence has sufficient

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2015258271 20 Nov 2015 complementarity with the sequence of the strand to be amplified to hybridize therewith and form a template for synthesis of the extension product of the other primer.

The PCR primers for the signature region according to the invention are based upon the highly conserved sequences of two or more aligned sequences (e.g., two or more AAV serotypes). The primers can accommodate less than exact identity among the two or more aligned AAV serotypes at the 5’ end or in the middle. However, the sequences at the 3’ end of the primers correspond to a region of two or more aligned AAV serotypes in which there is exact identity over at least five, preferably, over at least nine base pairs, and more preferably, over at least 18 base pairs at the 3’ end of the primers. Thus, the 3’ end of the primers is composed of sequences with 100% identity to the aligned sequences over at least five nucleotides. However, one can optionally utilize one, two, or more degenerate nucleotides at the 3’ end of the primer.

For example, the primer set for the signature region of AAV was designed based upon a unique region within the AAV capsid, as follows. The 5’ primer was based upon nt 2867-2891 of AAV2 [SEQ ID NO:7], 5’GGTAATTCCTCCGGAAATTGGCATT3’. See, Fig. 1. The 3’ primer was designed based upon nt 3096-3122 of AAV2 [SEQ ID NO:7], 5’GACTCATCAACAACAACTGGGGATTC-3’. Flowever, one of skill in the art may have readily designed the primer set based upon the corresponding regions of AAV 1, AAV3,

AAV4, AAV5, AAV6, or based upon the information provided herein, AAV7, AAV10,

AAV11, AAV12, or another novel AAV of the invention. In addition, still other primer sets can be readily designed to amplify this signature region, using techniques known to those of skill in the art.

B, Isolation of Target Sequences

As described herein, the present invention provides a first primer set which specifically amplifies the signature region of the target sequence, e.g., an AAV serotype, in order to permit detection of the target. In a situation in which further sequences are desired, e.g., if a novel AAV serotype is identified, the signature region may be extended. Thus, the invention may further utilize one or more additional primer sets.

Suitably, these primer sets are designed to include either the 5’ or 3’ primer of the first primer set and a second primer unique to the primer set, such that the primer set amplifies a region 5’ or 3’ to the signature region which anneals to either the 5’ end or the 3’ end of the signature region. For example, a first primer set is composed of a 5’ primer, Pi

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2015258271 20 Nov 2015 and a 3’ primer P2 to amplify the signature region. In order to extend the signature region on its 3’ end, a second primer set is composed of primer Pl and a 3’ primer P4, which amplifies the signature region and contiguous sequences downstream of the signature region. In order to extend the signature region on its 5’ end, a third primer set is composed of a 5’ primer, P5, and primer P2, such that the signature region and contiguous sequences upstream of the signature region are amplified. These extension steps are repeated (or performed at the same time), as needed or desired. Thereafter, the products results from these amplification steps are fused using conventional steps to produce an isolated sequence of the desired length.

The second and third primer sets are designed, as with the primer set for the signature region, to amplify a region having highly conserved sequences among the aligned sequences. Reference herein to the term “second” or “third” primer set is for each of discussion only, and without regard to the order in which these primers are added to the reaction mixture, or used for amplification. The region amplified by the second primer set is selected so that upon amplification it anneals at its 5’ end to the 3’ end of the signature region. Similarly, the region amplified by the third primer set is selected so that upon amplification it anneals at its 3’ end anneais to the 5’ end of the signature region. Additional primer sets can be designed such that the regions which they amplify anneal to the either the 5’ end or the 3’ end of the extension products formed by the second or third primer sets, or by subsequent primer sets.

For example, where AAV is the target sequence, a first set of primers (Pl and

P2) are used to amplify the signature region from the sample, in one desirable embodiment, this signature region is located within the AAV capsid. A second set of primers (Pl and P4) is used to extend the 3’ end of the signature region to a location in the AAV sequence which is just before the AAV 3’ ITR, i.e.. providing an extension product containing the entire 3’ end of the AAV capsid when using the signature region as an anchor. In one embodiment, the P4 primer corresponds to nt 4435 to 4462 of AAV2 [SEQ ID NO:7], and corresponding sequences in the other AAV serotypes. This results in amplification of a region of about 1.6 kb, which contains the 0.25 kb signature region. A third set of primers (P3 and P2) is used to extend the 5’ end of signature region to a location in the AAV sequences which is in the 3’ end of the rep genes, i.e., providing an extension product containing the entire 5’ end of the AAV capsid when using the signature region as an anchor. In one embodiment, the P3 primer corresponds to nt 1384 to 1409 of AAV2 [SEQ ID NO:7], and corresponding sequences in the other AAV serotypes. This results in amplification of a region of about 1.7

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2015258271 20 Nov 2015 kb, which contains the 0.25 kb signature region. Optionally, a fourth set of primers are used to further extend the extension product containing the entire 5’ end of the AAV capsid to also include the rep sequences. In one embodiment, the primer designated P5 corresponds to nt 108 to 133 of AAV2 [SEQ ID NO:7], and corresponding sequences in the other AAV serotypes and is used in conjunction with the P2 primer.

Following completion of the desired number of extension steps, the various extension products are fused, making use of the signature region as an anchor or marker, to construct an intact sequence. In the example provided herein, AAV sequences containing, at a minimum, an intact AAV cap gene are obtained. Larger sequences may be obtained, depending upon the number of extension steps performed.

Suitably, the extension products are assembled into an intact AAV sequence using methods known to those of skill in the art. For example, the extension products may be digested with Drain, which cleaves at the Drain site located within the signature region, to provide restriction fragments which are re-ligated to provide products containing (at a minimum) an intact AAV cap gene. However, other suitable techniques for assembling the extension products into an intact sequence may be utilized. See, generally, Sambrook et al, cited herein.

As an alternative to the multiple extension steps described above, another embodiment of the invention provides for direct amplification of a 3.1 kb fragment which allows isolation of full-length cap sequences. To directly amplify a 3.1 kb full-length cap fragment from NHP tissue and blood DNAs. two other highly conserved regions were identified in AAV genomes for use in PCR amplification of large fragments. A primer within a conserved region located in the middle of the rep gene is utilized (AVlns: 5' GCTGCGTCAACTGGACCAATGAGAAC 3', nt of SEQ ID NO:6) in combination with the 3' primer located in another conserved region downstream of the Cap gene (AV2cas: 5' CGCAGAGACCAAAGTTCAACTGAAACGA 3', SEQ ID NO: 7) for amplification of AAV sequences including the full-length AAV cap. Typically, following amplification, the products are cloned and sequence analysis is performed with an accuracy of > 99.9%. Using this method, the inventors have isolated at least 50 capsid clones which have subsequently been characterized. Among them, 37 clones were derived from Rhesus macaque tissues (rh.l - rh.37), 6 clones from cynomologous macaques (cy.l --- cy.6), 2 clones from Baboons (bb.l and bb.2) and 5 clones from Chimps (ch.l - ch.5). These clones are identified

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2015258271 20 Nov 2015 elsewhere in the specification, together with the species of animal from which they were identified and the tissues in that animal these novel sequences have been located.

C. Alternative method for isolating novel AAV

In another aspect, the invention provides an alternative method for isolating novel AAV from a cell. This method involves infecting the cell with a vector which provides helper functions to the AAV; isolating infectious clones containing AAV; sequencing the isolated AAV; and comparing the sequences of the isolated AAV to known AAV serotypes, whereby differences in the sequences of the isolated AAV and known AAV serotypes indicates the presence of a novel AAV.

in one embodiment, the vector providing helper functions provides essential adenovirus functions, including, e.g., Ela, Elb, E2a, E4ORF6. In one embodiment, the helper functions are provided by an adenovirus. The adenovirus may be a wild-type adenovirus, and may be of human or non-human origin, preferably non-human primate (NHP) origin. The DNA sequences of a number of adenovirus types are available from

Genbank, including type Ad5 [Genbank Accession No. M73260]. The adenovirus sequences may be obtained from any known adenovirus serotype, such as serotypes 2, 3, 4, 7, 12 and 40, and further including any of the presently identified human types [see, e.g., Horwitz, cited above]. Similarly adenoviruses known to infect non-human animals (e.g., chimpanzees) may also be employed in the vector constructs of this invention. See, e.g., US

Patent No. 6,083,716. In addition to wild-type adenoviruses, recombinant viruses or nonviral vectors (e.g., plasmids, episomes, etc.) carrying the necessary helper functions may be utilized. Such recombinant viruses are known in the art and may be prepared according to published techniques. See, e.g., US Patent No. 5,871,982 and US Patent 6,251,677, which describe a hybrid Ad/AAV virus. The selection of the adenovirus type is not anticipated to limit the following invention. A variety of adenovirus strains are available from the American Type Culture Collection, Manassas, Virginia, or available by request from a variety of commercial and institutional sources. Further, the sequences of many such strains are available from a variety of databases including, e.g., PubMed and GenBank.

In another alternative, infectious AAV may be isolated using genome walking technology (Siebert etal., 1995, Nucleic Acid Research, 23:1087-1088, FrieznerDegen et al., 1986. J. Biol. Chem. 261:6972-6985, BD Biosciences Clontech, Palo Alto,

CA). Genome walking is particularly well suited for identifying and isolating the sequences adjacent to the novel sequences identified according to the method of the invention. For

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2015258271 20 Nov 2015 example, this technique may be useful for isolating inverted terminal repeat (ITRs) of the novel AAV serotype, based upon the novel AAV capsid and/or rep sequences identified using the methods of the invention. This technique is also useful for isolating sequences adjacent to other AAV and non-AAV sequences identified and isolated according to the present invention. See, Examples 3 and 4.

The methods of the invention may be readily used for a variety of epidemiology studies, studies of biodistribution, monitoring of gene therapy via AAV vectors and vector derived from other integrated viruses. Thus, the methods are well suited for use in pre-packaged kits for use by clinicians, researchers, and epidemiologists.

II. Diagnostic Kit

In another aspect, the invention provides a diagnostic kit for detecting the presence of a known or unknown adeno-associated virus (AAV) in a sample. Such a kit may contain a first set of 5' and 3' PCR primers specific for a signature region of the A AV nucleic acid sequence. Alternatively, or additionally, such a kit can contain a first set of 5’ and 3’ PCR primers specific, for the 3.1 kb fragment which includes the full-length AAV capsid nucleic acid sequence identified herein (e.g., the AVlns and AV2cas primers.) Optionally, a kit of the invention may further contain two or more additional sets of 5' and 3' primers, as described herein, and/or PCR probes. These primers and probes are used according to the present invention amplify signature regions of each AAV serotype, e.g., using quantitative PCR.

The invention further provides a kit useful for identifying an AAV serotype detected according to the method of the invention and/or for distinguishing novel AAV from known AAV. Such a kit may further include one or more restriction enzymes, standards for AAV serotypes providing their “signature restriction enzyme digestions analyses”, and/or other means for determining the serotype of the AAV detected.

In addition, kits of the invention may include, instructions, a negative and/or positive control, containers, diluents and buffers for the sample, indicator charts for signature comparisons, disposable gloves, decontamination instructions, applicator sticks or containers, and sample preparator cups, as well as any desired reagents, including media, wash reagents and concentration reagents. Such reagents may be readily selected from among the reagents described herein, and from among conventional concentration reagents. In one desirable embodiment, the wash reagent is an isotonic saline solution which has been

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2015258271 20 Nov 2015 buffered to physiologic pH, such as phosphate buffered saline (PBS); the elution reagent is PBS containing 0.4 M NaCl, and the concentration reagents and devices. For example, one of skill in the art will recognize that reagents such as polyethylene glycol (PEG), or NH4SO4 may be useful, or that devices such as filter devices. For example, a filter device with a 100

K membrane would concentrate rAAV.

The kits provided by the present invention are useful for performing the methods described herein, and for study of biodistribution, epidemiology, mode of transmission of novel AAV serotypes in human and NHPs.

Thus, the methods and kits of the invention permit detection, identification, and isolation of target viral sequences, particularly integrated viral sequences. The methods and kits are particularly well suited for use in detection, identification and isolation of AAV sequences, which may include novel AAV serotypes.

In one notable example, the method of the invention facilitated analysis of cloned AAV sequences by the inventors, which revealed heterogeneity of proviral sequences between cloned fragments from different animals, all of which were distinct from the known six AAV serotypes, with the majority of the variation localized to hypervariable regions of the capsid protein. Surprising divergence of AAV sequences was noted in clones isolated from single tissue sources, such as lymph node, from an individual rhesus monkey. This heterogeneity is best explained by apparent evolution of AAV sequence within individual animals due, in part, to extensive homologous recombination between a limited number of co-infecting parenteral viruses. These studies suggest sequence evolution of widely disseminated virus during the course of a natural AAV infection that presumably leads to the formation of swarms of quasispecies which differ from one another in the array of capsid hypervariable regions. This is the first example of rapid molecular evolution of a DNA virus in a way that formerly was thought to be restricted to RNA viruses.

Sequences of several novel AAV serotypes identified by the method of the invention and characterization of these serotypes is provided.

III. Novel AAV Serotypes

A. Nucleic Acid Sequences

Nucleic acid sequences of novel AAV serotypes identified by the methods of the invention are provided. See, SEQ ID NO:1, 9 - 59, and 117 - 120, which are incorporated by reference herein. See also, Fig. 1 and the sequence listing.

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For novel serotype AAV7, the full-length sequences, including the AAV 5’ ITRs, capsid, rep, and AAV 3’ ITRs are provided in SEQ ID NO:1.

For other novel AAV serotypes of the invention, the approximately 3.1 kb fragment isolated according to the method of the invention is provided. This fragment contains sequences encoding full-length capsid protein and all or part of the sequences encoding the rep protein. These sequences include the clones identified below.

For still other novel AAV serotypes, the signature region encoding the capsid protein is provided. For example, the AAV10 nucleic acid sequences of the invention include those illustrated in Fig. 1 [See, SEQ ID NO:117, which spans 255 bases]. The

AAV11 nucleic acid sequences of the invention include the DNA sequences illustrated in

Fig. 1 [See, SEQ ID NO:118 which spans 258 bases]. The AAV12 nucleic acid sequences of the invention include the DNA sequences Illustrated in Fig. 1 [See, SEQ ID NO:119, which consists of 255 bases ]. Using the methodology described above, further AAV10, AAV11 and AAV12 sequences can be readily identified and used for a variety of purposes, including those described for AAV7 and the other novel serotypes herein.

Figure 1 provides the non-human primate (NHP) AAV nucleic acid sequences of the invention in an alignment with the previously published AAV serotypes, AAV 1 [SEQ ID NO:6], AAV2 [SEQ ID NO:7], and AAV3 [SEQ ID NO:8], These novel NHP sequences include those provided in the following Table I, which are identified by clone number:

Table 1

AAV Cap Sequence	Clone Number	Source
		Species	Tissue	SEQ ID NO (DNA)
Rh.l	Clone 9 (AAV9)	Rhesus	Heart	5
Rh.2	Clone 43.1	Rhesus	MLN	39
Rh.3	Clone 43.5	Rhesus	MEN	40
Rh.4	Clone 43.12	Rhesus	MLN	41
Rh.5	Clone 43.20	Rhesus	MLN	42
Rh.6	Clone 43.21	Rhesus	MLN	43
Rh.7	Clone 43.23	Rhesus	MLN	44

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Table 1 (cont’d)

Rh.8	Clone 43.25	Rhesus	MLN	45
Rh.9	Clone 44.1	Rhesus	Liver	46
Rh.10	Clone 44.2	Rhesus	Liver	59
Rh.ll	Clone 44.5	Rhesus	Liver	47
Rh.12	Clone 42. IB	Rhesus	MLN	30
Rh.13	42.2	Rhesus	MLN	9
Rli.14	Clone 42.3A	Rhesus	MLN	32
Rli.15	Clone 42.3B	Rhesus	MLN	36
Rh.16	Clone 42.4	Rhesus	MLN	33
Rh.17	Clone 42.5A	Rhesus	MLN	34
Rh.18	Clone 42.5B	Rhesus	MLN	29
Rli.19	Clone 42.6B	Rhesus	MLN	38
Rh.20	Clone 42.8	Rhesus	MLN	27
Rh.21	Clone 42.10	Rhesus	MLN	35
Rh.22	Clone 42.11	Rhesus	MLN	37
Rh.23	Clone 42.12	Rhesus	MLN	58
Rh.24	Clone 42.13	Rhesus	MLN	31
Rh.25	Clone 42.15	Rhesus	MLN	28
Rh.26	Clone 223.2	Rhesus	Liver	49
Rh.27	Clone 223.4	Rhesus	Liver	50
Rh.28	Clone 223.5	Rhesus	Liver	51
Rh.29	Clone 223.6	Rhesus	Liver	52
Rh.3Q	Clone 223.7	Rhesus	Liver	53
Rli.31	Clone 223.10	Rhesus	Liver	48
Rh.32	Clone Cl	Rhesus	Spleen, Duo, Kid & Liver	19
Rh.33	Clone C3	Rhesus		20
Rh.34	Clone C5	Rhesus		21
Rh.35	Clone FI	Rhesus	Liver	22
Rh.36	Clone F3	Rhesus		23
Rh.37	Clone F5	Rhesus		24
Cy.l	Clone 1.3	Cyno	Blood	14
Cy.2	Clone 13.3B	Cyno	Biood	15
Cy.3	Clone 24.1	Cyno	Blood	16
Cy.4	Clone 27.3	Cyno	Biood	17
Cy.5	Clone 7.2	Cyno	Blood	18
Cy.6	Clone 16,3	Cyno	Blood	10

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Table 1 (cont’d)

bb.l	Clone 29.3	Baboon	Blood	11
bb.2	Clone 29.5	Baboon	Blood	13
Ch.l	Clone A3.3	Chimp	Blood	57
Ch,2	Clone A3.4	Chimp	Blood	54
Ch.3	Clone A3,5	Chimp	Blood	55
Ch.4	Clone A3.7	Chimp	Blood	56

A novel NHP clone was made by splicing capsids fragments of two chimp adenoviruses into an AAV2 rep construct. This new clone, A3.1, is aiso termed Ch.5 [SEQ ID NO:20]. Additionally, the present invention includes two human AAV sequences, termed

H6 [SEQ ID NO:25] and H2 [SEQ ID NO:26],

The AAV nucleic acid sequences of the invention further encompass the strand which is complementary to the strands provided in the sequences provided in Fig. I and the Sequence Listing [SEQ ID NO:1, 9 - 59, 117 —120], nucleic acid sequences, as well as the RNA and cDNA sequences corresponding to the sequences provided in Fig. 1 and the

Sequence Listing [SEQ ID NO:1, 9 - 59, 117-120], and their complementary strands. Also included in the nucleic acid sequences of the invention are natural variants and engineered modifications of the sequences of Figi and the Sequence Listing [SEQ ID NO:1, 9 - 59, i 17-120], and their complementary strands. Such modifications include, for example, labels which are known in the art, methylation, and substitution of one or more of the naturally occurring nucleotides with a degenerate nucleotide.

Further included in this invention are nucleic acid sequences which are greater than 85%, preferably at least about 90%, more preferably at least about 95%, and most preferably at least about 98 to 99% identicai or homologous to the sequences of the invention, including Fig. i and the Sequence Listing [SEQ ID NO:1, 9 - 59, i 17-120].

These terms are as defined herein.

Also included within the invention are fragments of the novel AAV sequences identified by the method described herein. Suitable fragments are at least 15 nucleotides in length, and encompass functional fragments, i.e., fragments which are of biological interest. In one embodiment, these fragments are fragments of the novel sequences of Fig. 1 and the Sequence Listing [SEQ ID NO:1, 9 - 59, 117-120], their complementary strands, cDNA and RNA complementary thereto.

Examples of suitable fragments are provided with respect to the location of these fragments on AAV1, AAV2, or AAV7, However, using the alignment provided herein (obtained using the Clustal W program at default settings), or similar techniques for

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2015258271 20 Nov 2015 generating an alignment with other novel serotypes of the invention, one of skill in the art can readily identify the precise nucleotide start and stop codons for desired fragments.

Examples of suitable fragments include the sequences encoding the three variable proteins (vp) of the AAV capsid which are alternative splice variants: vpl [e.g., nt

825 to 3049 of AAV7, SEQ ID NO: 1]; vp2 [e.g., nt 1234 - 3049 of AAV7, SEQ ID NO: 1];

and vp 3 [e.g., nt 1434 - 3049 of AAV7, SEQ ID NO:1]. It is notable that AAV7 has an unusual GTG start codon. With the exception of a few house-keeping genes, such a start codon has not previously been reported in DNA viruses. The start codons for vpl, vp2 and vp3 for other AAV serotypes have been believed to be such that they permit the cellular mechanism of the host cell in which they reside to produce vpl, vp2 and vp3 in a ratio of 10%:10%:80%, respectively, in order to permit efficient assembly of the virion. However, the AAV7 virion has been found to assemble efficiently even with this rare GTG start codon. Thus, the inventors anticipate this it is desirable to alter the start codon of the vp3 of other AAV serotypes to contain this rare GTG start codon, in order to improve packaging efficiency, to alter the virion structure and/or to alter location of epitopes (e.g., neutralizing antibody epitopes) of other AAV serotypes. The start codons may be altered using conventional techniques including, e.g., site directed mutagenesis. Thus, the present invention encompasses altered AAV virions of any selected serotype, composed of a vp 3, and/or optionally, vp 1 and/or vp2 having start codons altered to GTG.

Other suitable fragments of AAV, include a fragment containing the start codon for the AAV capsid protein [e.g., nt 468 to 3090 of AAV7, SEQ ID NO:1, nt 725 to 3090 of AAV7, SEQ ID NO: 1, and corresponding regions of the other AAV serotypes]. Still other fragments of AAV7 and the other novel AAV serotypes identified using the methods described herein include those encoding the rep proteins, including rep 78 [e.g., initiation codon 334 of Fig 1 for AAV7], rep 68 [initiation codon nt 334 of Fig. 1 for AAV7], rep 52 [initiation codon 1006 of Fig. 1 for AAV7], and rep 40 [initiation codon 1006 of Fig. 1 for AAV7] Other fragments of interest may include the AAV 5' inverted terminal repeats ITRs, [nt 1 to 107 of Fig. 1 for AAV7]; the AAV 3' ITRs [nt 4704 to 4721 of Fig. 1 for AAV7], Pl 9 sequences, AAV P40 sequences, the rep binding site, and the terminal resolute site (TRS). Still other suitable fragments will be readily apparent to those of skill in the art. The corresponding regions in the other novel serotypes of the invention can be readily determined by reference to Figure 1, or by utilizing conventional alignment techniques with the sequences provided herein.

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In addition to including the nucleic acid sequences provided in the figures and Sequence Listing, the present invention includes nucleic acid molecules and sequences which are designed to express the amino acid sequences, proteins and peptides of the AAV serotypes of the invention. Thus, the invention includes nucleic acid sequences which encode the following novel AAV amino acid sequences: Cl [SEQ ID NO:60], C2 [SEQ ID NO:61], C5 [SEQ ID NO:62], A3-3 [SEQ ID NO:66], A3-7 [SEQ ID NO:67], A3-4 [SEQ ID NO:68], A3-5 [SEQ ID NO: 69], 3.3b [SEQ ID NO: 62], 223.4 [SEQ ID NO: 73], 223-5 [SEQ ID NO:74], 223-10 [SEQ ID NO:75], 223-2 [SEQ ID NO:76], 223-7 [SEQ ID NO:

77], 223-6 [SEQ ID NO: 78], 44-1 [SEQ ID NO: 79], 44-5 [SEQ ID NO:80], 44-2 [SEQ ID

NO:81], 42-15 [SEQ ID NO: 84], 42-8 [SEQ ID NO: 85], 42-13 [SEQ ID NO:86], 42-3A [SEQ ID NO:87], 42-4 [SEQ ID NO:88], 42-5A [SEQ ID NO:89], 42-1B [SEQ ID NO:90], 42-5B [SEQ ID NO:91], 43-1 [SEQ ID NO: 92], 43-12 [SEQ ID NO: 93], 43-5 [SEQ ID NO:94], 43-21 [SEQ ID NO:96], 43-25 [SEQ ID NO: 97], 43-20 [SEQ ID NO:99], 24.1 [SEQ ID NO: 101], 42.2 [SEQ ID NO: 102], 7.2 [SEQ ID NO: 103], 27.3 [SEQ ID NO: 104],

16.3 [SEQ ID NO: 105], 42.10 [SEQ ID NO: 106], 42-3B [SEQ ID NO: 107], 42-11 [SEQ

ID NO: 108], FI [SEQ ID NO: 109], F5 [SEQ ID NO: 110], F3 [SEQ ID NO:111], 42-6B [SEQ ID NO: 112], and/or 42-12 [SEQ ID NO: 113], and artificial AAV serotypes generated using these sequences and/or unique fragments thereof.

As used herein, artificial AAV serotypes include, without limitation, AAV with a non-naturally occurring capsid protein. Such an artificial capsid may be generated by any suitable technique, using a novel AAV sequence of the invention (e.g., a fragment of a vpl capsid protein) in combination with heterologous sequences which may be obtained from another AAV serotype (known or novel), non-contiguous portions of the same AAV serotype, from a non-AAV viral source, or from a non-viral source. An artificial AAV serotype may be, without limitation, a chimeric AAV capsid, a recombinant AAV capsid, or a “humanized” AAV capsid.

B. AAV Amino Acid Sequences, Proteins and Peptides

The invention provides proteins and fragments thereof which are encoded by the nucleic acid sequences of the novel AAV serotypes identified herein, including, e.g.,

AAV7 [nt 825 to 3049 of AAV7, SEQ ID NO: 1] the other novel serotypes provided herein. Thus, the capsid proteins of the novel serotypes of the invention, including: H6 [SEQ ID NO: 25], H2 [SEQ ID NO: 26], 42-2 [SEQ ID NO:9], 42-8 [SEQ ID NO:27], 42-15 [SEQ ID NO:28], 42-5b [SEQ ID NO: 29], 42-lb [SEQ ID NO:30]; 42-13 [SEQ ID NO: 31], 42-3a

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2015258271 20 Nov 2015 [SEQ ID NO: 32], 42-4 [SEQ ID NO:33], 42-5a [SEQ ID NO: 34], 42-10 [SEQ ID NO:35], 42-3b [SEQ ID NO: 36], 42-11 [SEQ ID NO: 37], 42-6b [SEQ ID NO:38], 43-1 [SEQ ID NO: 39], 43-5 [SEQ ID NO: 40], 43-12 [SEQ ID NO:41], 43-20 [SEQ ID NO:42], 43-21 [SEQ ID NO: 43], 43-23 [SEQ ID NO:44], 43-25 [SEQ ID NO: 45], 44.1 [SEQ ID NO:47],

44.5 [SEQ ID NO:47], 223.10 [SEQ ID NO:48], 223.2 [SEQ ID NO:49j, 223.4 [SEQ ID

NO:50], 223.5 [SEQ ID NO: 51], 223.6 [SEQ ID NO: 52], 223.7 [SEQ ID NO: 53], A3.4 [SEQ ID NO: 54], A3.5 [SEQ ID NO:55], A3.7 [SEQ ID NO: 56], A3.3 [SEQ ID NO:57], 42.12 [SEQ ID NO: 58], and 44.2 [SEQ ID NO: 59], can be readily generated using conventional techniques from the open reading frames provided for the above-listed clones.

The invention further encompasses AAV serotypes generated using sequences of the novel AAV serotypes of the invention, which are generated using synthetic, recombinant or other techniques known to those of skill in the art. The invention is not limited to novel AAV amino acid sequences, peptides and proteins expressed from the novel AAV nucleic acid sequences of the invention and encompasses amino acid sequences, peptides and proteins generated by other methods known in the art, including, e.g., by chemical synthesis, by other synthetic techniques, or by other methods. For example, the sequences of any of Cl [SEQ ID NO:60], C2 [SEQ ID NO:61], C5 [SEQ ID NO:62], A3-3 [SEQ ID NO:66], A3-7 [SEQ ID NO:67], A3-4 [SEQ ID NO:68], A3-5 [SEQ ID NO: 69], 3.3b [SEQ ID NO: 62], 223.4 [SEQ ID NO: 73], 223-5 [SEQ ID NO:74], 223-10 [SEQ ID

NO:75], 223-2 [SEQ ID NO:76], 223-7 [SEQ ID NO: 77], 223-6 [SEQ ID NO: 78], 44-1 [SEQ ID NO: 79], 44-5 [SEQ ID NO:80], 44-2 [SEQ ID NO:81], 42-15 [SEQ ID NO: 84], 42-8 [SEQ ID NO: 85], 42-13 [SEQ ID NO:86], 42-3A [SEQ ID NO:87], 42-4 [SEQ ID NO:88], 42-5A [SEQ ID NO:89], 42-1B [SEQ ID NO:90], 42-5B [SEQ ID NO:91], 43-1 [SEQ ID NO: 92], 43-12 [SEQ ID NO: 93], 43-5 [SEQ ID NO:94], 43-21 [SEQ ID NO:96],

43-25 [SEQ ID NO: 97], 43-20 [SEQ ID NO:99], 24.1 [SEQ ID NO: 101], 42.2 [SEQ ID

NO: 102], 7.2 [SEQ ID NO: 103], 27.3 [SEQ ID NO: 104], 16.3 [SEQ ID NO: 105], 42.10 [SEQ ID NO: 106], 42-3B [SEQ ID NO: 107], 42-11 [SEQ ID NO: 108], FI [SEQ ID NO: 109], F5 [SEQ ID NO: 110], F3 [SEQ ID NO:111], 42-6B [SEQ ID NO: 112], and/or 42-12 [SEQ ID NO: 113] by be readily generated using a variety of techniques.

Suitable production techniques are well known to those of skill in the art.

See, e.g., Sambrook et al, Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Press (Cold Spring Harbor, NY). Alternatively, peptides can also be synthesized by the well known solid phase peptide synthesis methods (Merrifield, J. Am. Chem. Soc., 85:2149

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2015258271 20 Nov 2015 (1962); Stewart and Young, Solid Phase Peptide Synthesis (Freeman, San Francisco, 1969) pp. 27-62). These and other suitable production methods are within the knowledge of those of skill in the art and are not a limitation of the present invention.

Particularly desirable proteins include the AAV capsid proteins, which are encoded by the nucleotide sequences identified above. The sequences of many of the capsid proteins of the invention are provided in an alignment in Fig. 2 and/or in the Sequence Listing, SEQ ID NO: 2 and 60 to 115, which is incorporated by reference herein. The AAV capsid is composed of three proteins, vpl, vp2 and vp3, which are alternative splice variants. The full-length sequence provided in these figures is that of vpl. Based on the numbering of the AAV7 capsid [SEQ ID NO:2], the sequences of vp2 span amino acid 138 - 737 of AAV7 and the sequences of vp3 span amino acids 203 - 737 of AAV7. With this information, one of skill in the art can readily determine the location of the vp2 and vp3 proteins for the other novel serotypes of the invention.

Other desirable proteins and fragments of the capsid protein include the constant and variable regions, located between hypervariable regions (HPV) and the sequences of the HPV regions themselves. An algorithm developed to determine areas of sequence divergence in AAV2 has yielded 12 hypervariable regions (HVR) of which 5 overlap or are part of the four previously described variable regions. [Chiorini et al, J. Virol, 73:1309-19 (1999); Rutledge et al, J. Virol., 72:309-319] Using this algorithm and/or the alignment techniques described herein, the HVR of the novel AAV serotypes are determined. For example, with respect to the number of the AAV2 vpl [SEQ ID NO:70], the HVR are located as follows: HVR1, aa 146-152; HVR2, aa 182-186; HVR3, aa 262-264; HVR4, aa 381-383; HVR5, aa 450-474; HVR6, aa 490-495; HVR7, aa500-504; HVR8, aa 514-522; HVR9, aa 534-555; HVR10, aa 581-594; HVR11, aa 658-667; and HVR12, aa 705-719.

Utilizing an alignment prepared in accordance with conventional methods and the novel sequences provided herein [See, e.g., Figure 2], one can readily determine the location of the HVR in the novel AAV serotypes of the invention. For example, utilizing Figure 2, one can readily determine that for AAV7 [SEQ ID NO:2]. HVR1 is located at aa 146 - 152; HVR2 is located at 182-187; HVR3 is located at aa 263-266, HVR4 is located at aa 383-385, HVR5 is located at aa 451-475; HVR6 is located at aa 491-496 of AAV7; HVR7 is located at aa 501505; HVR8 is located at aa 513-521; HVR9 is located at 533-554; HVR10 is located at aa 583-596; HVR11 is located at aa 660-669; HVR12 is located at aa 707-721. Using the

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2015258271 20 Nov 2015 information provided herein, the HVRs for the other novel serotypes of the invention can be readily determined.

In addition, within the capsid, amino acid cassettes of identity have been identified. These cassettes are of particular interest, as they are useful in constructing artificial serotypes, e.g., by replacing a HVR1 cassette of a selected serotype with an HVR1 cassette of another serotype. Certain of these cassettes of identity are noted in Fig. 2. See, Fig. 2, providing the Clustal X alignment, which has a ruler is dispiayed below the sequences, starting at 1 for the first residue position. The iine above the ruler is used to mark strongly conserved positions. Three characters (*, :,.) are used. “*” indicates positions which have a single, fully conserved residue. indicates that a “strong” group is fully conserved Indicates that a “weaker” group is fully conserved. These are all the positively scoring groups that occur in the Gonnet Pam250 matrix. The strong groups are defined as a strong score >0.5 and the weak groups are defined as weak score <0.5.

Additionaiiy, examples of other suitable fragments of AAV capsids include, with respect to the numbering of AAV2 [SEQ ID NO:70], aa 24 - 42, aa 25 - 28; aa 81 - 85; aal33-165; aa 134 - 165; aa 137-143; aa 154-156; aa 194-208; aa 261-274; aa 262-274; aa 171-173; aa 413-417; aa 449-478; aa 494-525; aa 534-571; aa 581-601; aa 660-671; aa 709723. Still other desirable fragments include, for example, in AAV7, amino acids 1 to 184 of SEQ ID NO:2, amino acids 199 to 259; amino acids 274 to 446; amino acids 603 to 659;

amino acids 670 to 706; amino acids 724 to 736; aa 185 to 198; aa 260 to 273; aa447 to 477; aa495 to 602; aa660 to 669; and aa707 to 723. Stiii other desirable regions, based on the numbering of AAV7 [SEQ ID NO:2], are selected from among the group consisting of aa 185 to 198; aa. 260 to 273; aa447 to 477;aa495 to 602; aa660 to 669; and aa707 to 723.

Using the alignment provided herein performed using the Clustal X program at default settings, or using other commercially or publicly available alignment programs at default settings, one of skill in the art can readily determine corresponding fragments of the novel AAV capsids of the invention.

Other desirable proteins are the AAV rep proteins [aa 1 to 623 of SEQ ID NO:3 for AAV7] and functional fragments thereof, including, e.g., aa 1 to 171, aa 172 to

372, aa 373 to 444, aa 445 to 623 of SEQ ID NO:3, among others. Suitably, such fragments are at least 8 amino acids in length. See, Fig. 3. Comparable regions can be identified in the proteins of the other novel AAV of the invention, using the techniques described herein and those which are known in the art. In addition, fragments of other desired lengths may be

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2015258271 20 Nov 2015 readily utilized. Such fragments may be produced recombinantly or by other suitable means, e.g., chemical synthesis.

The sequences, proteins, and fragments of the invention may be produced by any suitable means, including recombinant production, chemical synthesis, or other synthetic means. Such production methods are within the knowledge of those of skill in the art and are not a limitation of the present invention.

IV. Production of rAAV with novel AAV capsids

The invention encompasses novel, wild-type AAV serotypes identified by the invention, the sequences of which wild-type AAV serotypes are free of DNA and/or cellular material with these viruses are associated in nature. In another aspect, the present invention provides molecules which utilize the novel AAV sequences of the invention, including fragments thereof, for production of molecules useful in delivery of a heterologous gene or other nucleic acid sequences to a target cell.

The molecules of the invention which contain sequences of a novel AAV serotype of the invention include any genetic element (vector) which may be delivered to a host cell, e.g., naked DNA, a plasmid, phage, transposon, cosmid, episome, a protein in a non-viral delivery vehicle (e.g., a lipid-based carrier), virus, etc. which transfer the sequences carried thereon. The selected vector may be delivered by any suitable method, including transfection, electroporation, liposome delivery, membrane fusion techniques, high velocity DNA-coated pellets, viral infection and protoplast fusion. The methods used to construct any embodiment of this invention are known to those with skill in nucleic acid manipulation and include genetic engineering, recombinant engineering, and synthetic techniques. See, e.g,, Sambrook et al, Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Press,

Cold Spring Harbor, NY.

In one embodiment, the vectors of the invention contain sequences encoding a novel AAV capsid of the invention (e.g., AAV7 capsid, AAV 44-2 (rh.10), an AAV10 capsid, an AAV11 capsid, an AAV12 capsid), or a fragment of one or more of these AAV capsids. Alternatively, the vectors may contain the capsid protein, or a fragment thereof, itself.

Optionally, vectors of the invention may contain sequences encoding AAV rep proteins. Such rep sequences may be from the same AAV serotype which is providing the cap sequences. Alternatively, the present invention provides vectors in which the rep sequences are from an AAV serotype which differs from that which is providing the cap

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2015258271 20 Nov 2015 sequences. In one embodiment, the rep and cap sequences are expressed from separate sources (e.g., separate vectors, or a host celi and a vector). In another embodiment, these rep sequences are expressed from the same source as the cap sequences. In this embodiment, the rep sequences may be fused in frame to cap sequences of a different AAV serotype to form a chimeric AAV vector. Optionally, the vectors of the invention further contain a minigene comprising a selected transgene which is flanked by AAV 5' ITR and AAV 3' ITR.

Thus, in one embodiment, the vectors described herein contain nucleic acid sequences encoding an intact AAV capsid which may be from a single AAV serotype (e.g., AAV7 or another novel AAV). Alternatively, these vectors contain sequences encoding artificial capsids which contain one or more fragments of the AAV7 (or another novel AAV) capsid fused to heterologous AAV or non-AAV capsid proteins (or fragments thereof).

These artificial capsid proteins are selected from non-contiguous portions of the AAV7 (or another novel AAV) capsid or from capsids of other AAV serotypes. For example, it may be desirable to modify the coding regions of one or more of the AAV vpl, e.g., in one or more of the hypervariable regions (i.e., HPV1-12), or vp2, and/or vp3. In another example, it may be desirable to alter the start codon of the vp3 protein to GTG. These modifications may be to increase expression, yield, and/or to improve purification in the selected expression systems, or for another desired purpose (e.g., to change tropism or alter neutralizing antibody epitopes).

The vectors described herein, e.g., a plasmid, are useful for a variety of purposes, but are particularly well suited for use in production of a rAAV containing a capsid comprising AAV sequences or a fragment thereof. These vectors, including rAAV, their elements, construction, and uses are described in detail herein, .

In one aspect, the invention provides a method of generating a recombinant adeno25 associated virus (AAV) having an AAV serotype 7 (or another novel AAV) capsid, or a portion thereof. Such a method involves culturing a host ceil which contains a nucleic acid sequence encoding an adeno-associated virus (AAV) serotype 7 (or another novel AAV) capsid protein, or fragment thereof, as defined herein; a functional rep gene; a minigene composed of, at a minimum, AAV inverted terminal repeats (ITRs) and a transgene; and sufficient helper functions to permit packaging of the minigene into the AAV7 (or another novel AAV) capsid protein.

The components required to be cultured in the host cell to package an AAV minigene in an AAV capsid may be provided to the host cell in trans. Alternatively, any one or more

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2015258271 20 Nov 2015 of the required components (e.g., minigene, rep sequences, cap sequences, and/or helper functions) may be provided by a stable host cell which has been engineered to contain one or more of the required components using methods known to those of skill in the art. Most suitably, such a stable host cell will contain the required component(s) under the control of an inducible promoter. However, the required component(s) may be under the control of a constitutive promoter. Examples of suitable inducible and constitutive promoters are provided herein, in the discussion of regulatory elements suitable for use with the transgene. In still another alternative, a selected stable host cell may contain selected component(s) under the control of a constitutive promoter and other selected component(s) under the control of one or more inducible promoters. For example, a stable host ceil may be generated which is derived from 293 cells (which contain El helper functions under the control of a constitutive promoter), but which contains the rep and/or cap proteins under the control of inducible promoters. Stiil other stable host cells may be generated by one of skill in the art.

The minigene, rep sequences, cap sequences, and helper functions required for producing the rAAV of the invention may be delivered to the packaging host cell in the form of any genetic element which transfer the sequences carried thereon. The selected genetic element may be delivered by any suitable method, including those described herein. The methods used to construct any embodiment of this invention are known to those with skill in nucleic acid manipulation and include genetic engineering, recombinant engineering, and synthetic techniques. See, e.g., Sambrook et al, Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Press, Cold Spring Harbor, NY. Similarly, methods of generating rAAV virions are well known and the selection of a suitable method is not a limitation on the present invention. See, e.g., K. Fisher et al, J. Virol., 70:520-532 (1993) and US Patent

5,478,745.

A. The Minigene

The minigene is composed of, at a minimum, a transgene and its regulatory sequences, and 5’ and 3’ AAV inverted terminal repeats (ITRs). It is this minigene which is packaged into a capsid protein and delivered to a selected host cell.

1. The transgene

The transgene is a nucleic acid sequence, heterologous to the vector sequences flanking the transgene, which encodes a polypeptide, protein, or other product, of interest. The nucleic acid coding sequence is operatively linked to regulatory

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2015258271 20 Nov 2015 components in a manner which permits transgene transcription, translation, and/or expression in a host cell.

The composition of the transgene sequence will depend upon the use to which the resulting vector will be put. For example, one type of transgene sequence includes a reporter sequence, which upon expression produces a detectable signal. Such reporter sequences include, without limitation, DNA sequences encoding β-lactamase, β-galactosidase (LacZ), alkaline phosphatase, thymidine kinase, green fluorescent protein (GFP), chloramphenicol acetyltransferase (CAT), luciferase, membrane bound proteins including, for example, CD2, CD4, CDS, the influenza hemagglutinin protein, and others well known in the art, to which high affinity antibodies directed thereto exist or can be produced by conventional means, and fusion proteins comprising a membrane bound protein appropriately fused to an antigen tag domain from, among others, hemagglutinin or Myc.

These coding sequences, when associated with regulatory elements which drive their expression, provide signals detectable by conventional means, including enzymatic, radiographic, colorimetric, fluorescence or other spectrographic assays, fluorescent activating ceil sorting assays and immunological assays, including enzyme linked immunosorbent assay (ELISA), radioimmunoassay (RIA) and immunohistochemistry. For example, where the marker sequence is the LacZ gene, the presence of the vector carrying the signal is detected by assays for beta-galactosidase activity'. Where the transgene is green fluorescent protein or luciferase, the vector carrying the signal may be measured visually by color or light production in a luminometer.

However, desirably, the transgene is a non-marker sequence encoding a product which is useful in biology and medicine, such as proteins, peptides,

RNA, enzymes, or catalytic RNAs. Desirable RNA molecules include tRNA, dsRNA, ribosomal RNA, catalytic RNAs, and antisense RNAs. One example of a useful RNA sequence is a sequence which extinguishes expression of a targeted nucleic acid sequence in the treated animal.

The transgene may be used to correct or ameliorate gene deficiencies, which may include deficiencies in which normal genes are expressed at less than normal levels or deficiencies in which the functional gene product is not expressed. A preferred type of transgene sequence encodes a therapeutic protein or polypeptide which is expressed in a host cell. The invention further includes using multiple transgenes, e.g., to correct or ameliorate a gene defect caused by a multi-subunit protein. In certain situations, a

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2015258271 20 Nov 2015 different transgene may be used to encode each subunit of a protein, or to encode different peptides or proteins. This is desirable when the size of the DNA encoding the protein subunit is large, e.g., for an immunoglobulin, the platelet-derived growth factor, or a dystrophin protein. In order for the cell to produce the multi-subunit protein, a cell is infected with the recombinant virus containing each of the different subunits. Alternatively, different subunits of a protein may be encoded by the same transgene, in this case, a single transgene includes the DNA encoding each of the subunits, with the DNA for each subunit separated by an internal ribozyme entry site (IRES). This is desirable when the size of the DNA encoding each of the subunits is small, e.g., the total size of the DNA encoding the subunits and the IRES is less than five kilobases. As an alternative to an IRES, the DNA may be separated by sequences encoding a 2A peptide, which self-cleaves in a post-translational event. See, e.g., M.L. Donnelly, et al, J. Gen. Virol., 78(Pt 1):13-21 (Jan 1997); Furier, S., et al, Gene Ther., 8(11):864-873 (June 2001); Klump H., et al., Gene Ther., 8(10):811-817 (May 2001). This 2A peptide is significantly smaller than an IRES, making it well suited for use when space is a limiting factor. However, the selected transgene may encode any biologically active product or other product, e.g., a product desirable for study.

Suitable transgenes may be readily selected by one of skill in the art. The selection of the transgene is not considered to be a limitation of this invention.

2. Regulatory Elements

In addition to the major elements identified above for the minigene, the vector also includes conventional control elements necessary which are operably linked to the transgene in a manner which permits its transcription, translation and/or expression in a cell transfected with the plasmid vector or infected with the virus produced by the invention. As used herein, “operably linked sequences include both expression control sequences that are contiguous with the gene of interest and expression control sequences that act in trans or at a distance to control the gene of interest.

Expression control sequences include appropriate transcription initiation, termination, promoter and enhancer sequences; efficient RNA processing signals such as splicing and polyadenylation (polyA) signals; sequences that stabilize cytoplasmic mRNA; sequences that enhance translation efficiency (i.e., Kozak consensus sequence); sequences that enhance protein stability; and when desired, sequences that enhance secretion of the encoded product. A great number of expression control

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2015258271 20 Nov 2015 sequences, including promoters which are native, constitutive, inducible and/or tissuespecific, are known in the art and may be utilized.

Examples of constitutive promoters include, without limitation, the retroviral Rous sarcoma virus (RSV) LTR promoter (optionally with the RSV enhancer), the cytomegalovirus (CMV) promoter (optionally with the CMV enhancer) [see, e.g., Boshart et al, Cell, 41:521-530 (1985)], the SV40 promoter, the dihydrofoiate reductase promoter, the β-actin promoter, the phosphogiycerol kinase (PGK) promoter, and the EFla promoter [Invitrogen].

Inducible promoters allow regulation of gene expression and can be regulated by exogenously supplied compounds, environmental factors such as temperature, or the presence of a specific physiological state, e.g., acute phase, a particular differentiation state of the cell, or in replicating cells only. Inducible promoters and inducible systems are available from a variety of commercial sources, including, without limitation, Invitrogen, Clontech and Ariad. Many other systems have been described and can be readily selected by one of skill in the art. Examples of inducible promoters regulated by exogenously supplied promoters include the zinc-inducible sheep metallothionine (MT) promoter, the dexamethasone (Dex)-inducible mouse mammary tumor virus (MMTV) promoter, the T7 polymerase promoter system [WO 98/10088]; the ecdysone insect promoter [No et al, Proc. Natl. Acad. Sci. USA, 93:3346-3351 (1996)], the tetracycline-repressible system [Gossen et al, Proc. Natl. Acad. Sci. USA, 89:5547-5551 (1992)], the tetracycline-inducible system [Gossen et al, Science, 268:1766-1769 (1995), see also Harvey et al, Curr. Opin. Chem. Biol., 2:512-518 (1998)], the RU486-inducible system [Wang et al, Nat. Biotech., 15:239-243 (1997) and Wang et al, Gene Ther., 4:432-441 (1997)] and the rapamycin-inducible system [Magari et al, J. Clin. Invest., 100:2865-2872 (1997)]. Still other types of inducible promoters which may be useful in this context are those which are regulated by a specific physiological state, e.g., temperature, acute phase, a particular differentiation state of the cell, or in replicating cells only.

In another embodiment, the native promoter for the transgene will be used. The native promoter may be preferred when it is desired that expression of the transgene should mimic the native expression. The native promoter may be used when expression of the transgene must be regulated temporally or developmental^, or in a tissuespecific manner, or in response to specific transcriptional stimuli. In a further embodiment,

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2015258271 20 Nov 2015 other native expression control elements, such as enhancer elements, polyadenylation sites or Kozak consensus sequences may also be used to mimic the native expression.

Another embodiment of the transgene includes a transgene operably linked to a tissue-specific promoter. For instance, if expression in skeletal muscle is desired, a promoter active in muscle should be used. These include the promoters from genes encoding skeletal β-actin, myosin light chain 2A, dystrophin, muscle creatine kinase, as well as synthetic muscle promoters with activities higher than naturally-occurring promoters (see Li et al., Nat. Biotech., 17:241-245 (1999)). Examples of promoters that are tissue-specific are known for liver (albumin, Miyatake et al., J. Virol., 71:5124-32 (1997);

hepatitis B virus core promoter, Sandig et al., Gene Ther., 3:1002-9 (1996);

alpha-fetoprotein (AFP), Arbuthnot et al., Hum. Gene Ther., 7:1503-14 (1996)), bone osteocalcin (Stein et al., Mol. Biol. Rep., 24:185-96 (1997)); bone sialoprotein (Chen et al.,

J. Bone Miner. Res., 11:654-64 (1996)), lymphocytes (CD2, Hansal et al., J. Immunol., 161:1063-8 (1998); immunoglobulin heavy chain; T cell receptor a chain), neuronal such as neuron-specific enolase (NSE) promoter (Andersen et al., Cell. Mol. Neurobiol., 13:503-15 (1993)), neurofilament light-chain gene (Piccioli et al., Proc. Natl. Acad Sci. USA,

88:5611-5 (1991)), and the neuron-specific vgf gene (Piccioli et al., Neuron, 15:373-84 (1995)), among others.

Optionally, plasmids carrying therapeutically useful transgenes may also include selectable markers or reporter genes may include sequences encoding geneticin, hygromicin or purimycin resistance, among others. Such selectable reporters or marker genes (preferably located outside the viral genome to be rescued by the method of the invention) can be used to signal the presence of the plasmids in bacterial cells, such as ampicillin resistance. Other components of the plasmid may include an origin of replication. Selection of these and other promoters and vector elements are conventional and many such sequences are available [see, e.g., Sambrook et al, and references cited therein].

The combination of the transgene, promoter/enhancer, and 5’ and 3’ ITRs is referred to as a minigene for ease of reference herein. Provided with the teachings of this invention, the design of such a minigene can be made by resort to conventional techniques.

3. Delivery of the Minigene to a Packaging Host Cel l

The minigene can be carried on any suitable vector, e.g., a plasmid, which is delivered to a host cell. The plasmids useful in this invention may be

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2015258271 20 Nov 2015 engineered such that they are suitable for replication and, optionally, integration in prokaryotic cells, mammalian cells, or both. These plasmids (or other vectors carrying the 5' AAV ITR-heterologous molecule-3'ITR) contain sequences permitting replication of the minigene in eukaryotes and/or prokaryotes and selection markers for these systems.

Selectable markers or reporter genes may include sequences encoding geneticin, hygromicin or purimycin resistance, among others. The plasmids may also contain certain selectable reporters or marker genes that can be used to signal the presence of the vector in bacterial cells, such as ampicillin resistance. Other components of the p lasmid may include an origin of replication and an amplicon, such as the amplicon system employing the Epstein Barr virus nuclear antigen. This amplicon system, or other similar amplicon components permit high copy episomal replication in the cells. Preferably, the molecule carrying the minigene is transfected into the cell, where it may exist transiently. Alternatively, the minigene (carrying the 5' AAV ITR-heteroiogous molecule-3' ITR) may be stably integrated into the genome of the host cell, either chromosomally or as an episome. In certain embodiments, the minigene may be present in multiple copies, optionally in head-to-head, head-to-tail, or tail-to-tail concatamers. Suitable transfection techniques are known and may readily be utilized to deliver the minigene to the host cell.

Generally, when delivering the vector comprising the minigene by transfection, the vector is delivered in an amount from about 5 pg to about 100 pg DNA, and preferably about 10 to about 50 pg DNA to about 1 x 10⁴ cells to about 1 x 10^1J cells, and preferably about 10³ cells. However, the relative amounts of vector DNA to host cells may be adjusted, taking into consideration such factors as the selected vector, the delivery method and the host cells selected.

B. Rep and Cap Sequences

In addition to the minigene, the host ceil contains the sequences which drive expression of the novel AAV capsid protein (e.g., AAV7 or other novel AAV capsid or an artificial capsid protein comprising a fragment of one or more of these capsids) in the host cell and rep sequences of the same serotype as the serotype of the AAV ITRs found in the minigene. The AAV cap and rep sequences may be independently obtained from an AAV source as described above and may be introduced into the host cell in any manner known to one in the art as described above. Additionally, when pseudotyping a novel AAV capsid of the invention, the sequences encoding each of the essential rep proteins may be supplied by the same AAV serotype, or the sequences encoding the rep proteins may

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2015258271 20 Nov 2015 be supplied by different AAV serotypes (e.g., AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, or one of the novel serotypes identified herein). For example, the rep78/68 sequences may be from AAV2, whereas the rep52/40 sequences may from AAV1.

In one embodiment, the host cell stably contains the capsid protein under the control of a suitable promoter, such as those described above. Most desirably, in this embodiment, the capsid protein is expressed under the control of an inducible promoter. In another embodiment, the capsid protein is supplied to the host cell in trans. When delivered to the host cell in trans, the capsid protein may be delivered via a plasmid which contains the sequences necessary to direct expression of the selected capsid protein in the host cell. Most desirably, when delivered to the host cell in trans, the plasmid carrying the capsid protein also carries other sequences required for packaging the rAAV, e.g., the rep sequences.

In another embodiment, the host cell stably contains the rep sequences under the control of a suitable promoter, such as those described above. Most desirably, in this embodiment, the essential rep proteins are expressed under the control of an inducible promoter. In another embodiment, the rep proteins are supplied to the host cell in trans. When delivered to the host cell in trans, the rep proteins may be delivered via a plasmid which contains the sequences necessary to direct expression of the selected rep proteins in the host cell. Most desirably, when delivered to the host cell in trans, the plasmid carrying the capsid protein also carries other sequences required for packaging the rAAV, e.g., the rep and cap sequences.

Thus, in one embodiment, the rep and cap sequences may be transfected into the host cell on a single nucleic acid molecule and exist stably in the cell as an episome. In another embodiment, the rep and cap sequences are stably integrated into the genome of the ceil. Another embodiment has the rep and cap sequences transiently expressed in the host ceil. For example, a useful nucleic acid molecule for such transfection comprises, from 5' to 3', a promoter, an optional spacer interposed between the promoter and the start site of the rep gene sequence, an AAV rep gene sequence, and an AAV cap gene sequence.

Optionally, the rep and/or cap sequences may be supplied on a vector that contains other DNA sequences that are to be introduced into the host cells. For instance, the vector may contain the rAAV construct comprising the minigene. The vector may

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2015258271 20 Nov 2015 comprise one or more of the genes encoding the helper functions, e.g,, the adenoviral proteins El , E2a, and E4ORF6, and the gene for VAI RNA.

Preferably, the promoter used in this construct may be any of the constitutive, inducible or native promoters known to one of skill in the art or as discussed above. In one embodiment, an AAV P5 promoter sequence is employed. The selection of the AAV to provide any of these sequences does not limit the invention.

In another preferred embodiment, the promoter for rep is an inducible promoter, as are discussed above in connection with the transgene regulatory elements. One preferred promoter for rep expression is the T7 promoter. The vector comprising the rep gene regulated by the T7 promoter and the cap gene, is transfected or transformed into a cell which either constitutively or inducibly expresses the T7 polymerase. See WO 98/10088, published March 12, 1998.

The spacer is an optional element in the design of the vector. The spacer is a DNA sequence interposed between the promoter and the rep gene ATG start site.

The spacer may have any desired design; that is, it may be a random sequence of nucleotides, or alternatively, it may encode a gene product, such as a marker gene. The spacer may contain genes which typically incorporate start/stop and poly A sites. The spacer may be a non-coding DNA sequence from a prokaryote or eukaryote, a repetitive non-coding sequence, a coding sequence without transcriptional controls or a coding sequence with transcriptional controls. Two exemplary sources of spacer sequences are the λ phage ladder sequences or yeast ladder sequences, which are available commercially, e.g., from Gibco or Invitrogen, among others. The spacer may be of any size sufficient to reduce expression of the rep78 and rep6& gene products, leaving the rep52, rep4Q and cap gene products expressed at normal levels. The length of the spacer may therefore range from about 10 bp to about 10.0 kbp, preferably in the range of about 100 bp to about 8.0 kbp. To reduce the possibility of recombination, the spacer is preferably less than 2 kbp in length; however, the invention is not so limited.

Although the molecule(s) providing rep and cap may exist in the host cell transiently (i.e., through transfection), it is preferred that one or both of the rep and cap proteins and the promoter(s) controlling their expression be stably expressed in the host cell, e.g., as an episome or by integration into the chromosome of the host cell. The methods employed for constructing embodiments of this invention are conventional genetic engineering or recombinant engineering techniques such as those described in the references

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2015258271 20 Nov 2015 above. While this specification provides illustrative examples of specific constructs, using the information provided herein, one of skill in the art may select and design other suitable constructs, using a choice of spacers, P5 promoters, and other elements, including at least one translational start and stop signal, and the optional addition of polyadenylation sites.

In another embodiment of this invention, the rep or cap protein may be provided stably by a host cell.

C. The Helper Functions

The packaging host cell also requires helper functions in order to package the rAAV of the invention. Optionally, these functions may be supplied by a herpesvirus. Most desirably, the necessary helper functions are each provided from a human or non-human primate adenovirus source, such as those described above and/or are available from a variety of sources, including the American Type Culture Collection (ATCC), Manassas, VA (US). In one currently preferred embodiment, the host cell is provided with and/or contains an El a gene product, an Elb gene product, an E2a gene product, and/or an

E4 ORF6 gene product. The host cell may contain other adenoviral genes such as VAI RNA, but these genes are not required. In a preferred embodiment, no other adenovirus genes or gene functions are present in the host cell.

By “adenoviral DNA which expresses the El a gene product”, it is meant any adenovirus sequence encoding Ela or any functional Ela portion. Adenoviral

DNA which expresses the E2a gene product and adenoviral DNA which expresses the E4 ORF6 gene products are defined similarly. Also included are any alleles or other modifications of the adenoviral gene or functional portion thereof. Such modifications may be deliberately introduced by resort to conventional genetic engineering or mutagenic techniques to enhance the adenoviral function in some manner, as well as naturally occurring allelic variants thereof. Such modifications and methods for manipulating DNA to achieve these adenovirus gene functions are known to those of skill in the art.

The adenovirus Ela, Elb, E2a, and/or E4ORF6 gene products, as well as any other desired helper functions, can be provided using any means that allows their expression in a cell. Each of the sequences encoding these products may be on a separate vector, or one or more genes may be on the same vector. The vector may be any vector known in the art or disclosed above, including plasmids, cosmids and viruses. Introduction into the host cell of the vector may be achieved by any means known in the art or as disclosed above, including transfection, infection, electroporation, liposome delivery,

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2015258271 20 Nov 2015 membrane fusion techniques, high velocity DNA-coated pellets, viral infection and protoplast fusion, among others. One or more of the adenoviral genes may be stably integrated into the genome of the host cell, stably expressed as episomes, or expressed transiently. The gene products may all be expressed transiently, on an episome or stably integrated, or some of the gene products may be expressed stably while others are expressed transiently. Furthermore, the promoters for each of the adenoviral genes may be selected independently from a constitutive promoter, an inducible promoter or a native adenoviral promoter. The promoters may be regulated by a specific physiological state of the organism or cell (i.e., by the differentiation state or in replicating or quiescent cells) or by exogenously-added factors, for example.

D. Host Cells And Packaging Cell Lines

The host cell itself may be selected from any biological organism, including prokaryotic (e.g., bacterial) ceils, and eukaryotic cells, including, insect cells, yeast cells and mammalian cells. Particularly desirable host cells are selected from among any mammalian species, including, without limitation, cells such as A549, WEHI, 3T3, 10T1/2, BHK, MDCK, COS 1, COS 7, BSC I, BSC 40, BMT 10, VERO, WI38, HeLa, 293 cells (which express functional adenoviral El), Saos, C2C12, L cells, HT1080, HepG2 and primary fibroblast, hepatocyte and myoblast cells derived from mammals including human, monkey, mouse, rat, rabbit, and hamster. The selection of the mammalian species providing the cells is not a limitation of this invention; nor is the type of mammalian cell, i.e., fibroblast, hepatocyte, tumor cell, etc. The most desirable cells do not carry any adenovirus gene other than El, E2a and/or E4 ORF6; nor do they contain any other virus gene which could result in homologous recombination of a contaminating virus during the production of rAAV; and it is capable of infection or transfection of DNA and expression of the transfected DNA. In a preferred embodiment, the host cell is one that has rep and cap stably transfected in the cell.

One host cell useful in the present invention is a host cell stably transformed with the sequences encoding rep and cap. and which is transfected with the adenovirus El, E2a, and E4ORF6 DNA and a construct carrying the minigene as described above. Stable rep and/or cap expressing cell lines, such as B-50 (PCT/US98/19463), or those described in U.S. Patent No. 5,658,785, may also be similarly employed. Another desirable host cell contains the minimum adenoviral DNA which is sufficient to express E4 ORF6.

Yet other cell lines can be constructed using the novel AAV rep and/or novel AAV cap sequences of the invention.

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The preparation of a host ceil according to this invention involves techniques such as assembly of selected DNA sequences. This assembly may be accomplished utilizing conventional techniques. Such techniques include cDNA and genomic cloning, which are well known and are described in Sambrook et al., cited above, use of overlapping oligonucleotide sequences of the adenovirus and AAV genomes, combined with polymerase chain reaction, synthetic methods, and any other suitable methods which provide the desired nucleotide sequence.

Introduction of the molecules (as plasmids or viruses) into the host cell may also be accomplished using techniques known to the skilled artisan and as discussed throughout the specification. In preferred embodiment, standard transfection techniques are used, e.g., CaPtTj transfection or electroporation, and/or infection by hybrid adenovirus/AAV vectors into ceil lines such as the human embryonic kidney ceil line HEK 293 (a human kidney cell line containing functional adenovirus El genes which provides /rans-acting El proteins).

These novel AAV-based vectors which are generated by one of skill in the art are beneficial for gene delivery to selected host cells and gene therapy patients since no neutralization antibodies to AAV7 have been found in the human population. Further, early studies show' no neutralizing antibodies in cyno monkey and chimpanzee populations, and less than 15% cross-reactivity of AAV 7 in rhesus monkeys, the species from which the serotype was isolated. One of skill in the art may readily prepare other rAAV viral vectors containing the AAV7 capsid proteins provided herein using a variety of techniques known to those of skill in the art. One may similarly prepare still other rAAV viral vectors containing AAV7 sequence and AAV capsids of another serotype. Similar advantages are conferred by the vectors based on the other novel AAV of the invention.

Thus, one of skill in the art will readily understand that the AAV7 sequences of the invention can be readily adapted for use in these and other viral vector systems for in vitro, ex vivo or in vivo gene delivery. Similarly, one of skill in the art can readily select other fragments of the novel AAV genome of the invention for use in a variety of rAAV and non-rAAV vector systems. Such vectors systems may include, e.g., lentiviruses, retroviruses, poxviruses, vaccinia viruses, and adenoviral systems, among others. Selection of these vector systems is not a limitation of the present invention.

Thus, the invention further provides vectors generated using the nucleic acid and amino acid sequences of the novel AAV of the invention. Such vectors are

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2015258271 20 Nov 2015 useful for a variety of purposes, including for delivery of therapeutic molecules and for use in vaccine regimens. Particularly desirable for delivery of therapeutic molecules are recombinant AAV containing capsids of the novel AAV of the invention. These, or other vector constructs containing novel AAV sequences of the invention may be used in vaccine regimens, e.g., for co-delivery of a cytokine, or for delivery of the immunogen itself

V. Recombinant Viruses And Uses Thereof

Using the techniques described herein, one of skill in the art may generate a rAAV having a capsid of a novel serotype of the invention, or a novel capsid containing one or 10 more novel fragments of an AAV serotype identified by the method of the invention. In one embodiment, a full-length capsid from a single serotype, e.g., AAV7 [SEQ ID NO: 2] can be utilized. In another embodiment, a full-length capsid may be generated which contains one or more fragments of a novel serotype of the invention fused in frame with sequences from another selected AAV serotype. For example, a rAAV may contain one or more of the novel hypervariable region sequences of an AAV serotype of the invention. Alternatively, the unique AAV serotypes of the invention may be used in constructs containing other viral or non-viral sequences.

it will be readily apparent to one of skill in the art one embodiment, that certain serotypes of the invention will be particularly well suited for certain uses. For example, vectors based on AAV7 capsids of the invention are particularly well suited for use in muscle; whereas vectors based on rh.10 (44-2) capsids of the invention are particularly well suited for use in lung. Uses of such vectors are not so limited and one of skill in the art may utilize these vectors for deliveiy to other celi types, tissues or organs. Further, vectors based upon other capsids of the invention may be used for delivery to these or other celis, tissues or organs.

A. Delivery of Transgene

In another aspect, the present invention provides a method for delivery of a transgene to a host which involves transfecting or infecting a selected host cell with a vector generated with the sequences of the AAV of the invention. Methods for delivery are well known to those of skill in the art and are not a limitation of the present invention.

In one desirable embodiment, the invention provides a method for AAVmediated delivery of a transgene to a host. This method involves transfecting or infecting a

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Optionally, a sample from the host may be first assayed for the presence of antibodies to a selected AAV serotype. A variety of assay formats for detecting neutralizing antibodies are well known to those of skill in the art. The selection of such an assay is not a limitation of the present invention. See, e.g., Fisher et al, Nature Med., 3(3):306-312 (March 1997) and W. C. Manning et al, Human Gene Therapy, 9:477-485 (March 1, 1998). The results of this assay may be used to determine which AAV vector containing capsid proteins of a particular serotype are preferred for delivery, e.g., by the absence of neutralizing antibodies specific for that capsid serotype.

In one aspect of this method, the delivery of vector with a selected AAV capsid proteins may precede or follow delivery of a gene via a vector with a different serotype AAV capsid protein. Similarly, the delivery of vector with other novel AAV capsid proteins of the invention may precede or follow delivery of a gene via a vector with a different serotype AAV capsid protein. Thus, gene delivery via rAAV vectors may be used for repeat gene delivery to a selected host cell. Desirably, subsequently administered rAAV vectors carry the same transgene as the first rAAV vector, but the subsequently administered vectors contain capsid proteins of serotypes which differ from the first vector. For example, if a first vector has AAV7 capsid proteins [SEQ ID NO:2], subsequently administered vectors may have capsid proteins selected from among the other serotypes, including AAVl, AAV2, AAV3A, AAV3B, AAV4, AAV6, AAV 10, AAVl 1, and AAV 12, or any of the other novel AAV capsids identified herein including, without limitation: A3.1, H2, H6, Cl, C2,

C5, A3-3, A3-7, A3-4, A3-5, 3.3b, 223.4, 223-5, 223-10, 223-2, 223-7, 223-6, 44-1, 44-5, 44-2, 42-15, 42-8, 42-13, 42-3A, 42-4, 42-5A, 42-1B, 42-5B, 43-1, 43-12, 43-5, 43-21, 4325 25, 43-20, 24.1, 42.2, 7.2, 27.3, 16.3, 42.10, 42-3B, 42-11, FI, F5, F3, 42-6B, and/or 42-12.

The above-described recombinant vectors may be delivered to host cells according to published methods. The rAAV, preferably suspended in a physiologically compatible carrier, may be administered to a human or non-human mammalian patient. Suitable carriers may be readily selected by one of skill in the art in view of the indication for which the transfer virus is directed. For example, one suitable carrier includes saline, which may be formulated with a variety of buffering solutions (e.g., phosphate buffered saline). Other exemplary carriers include sterile saline, lactose, sucrose, calcium phosphate.

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2015258271 20 Nov 2015 gelatin, dextran, agar, pectin, peanut oil, sesame oil, and water. The selection of the carrier is not a limitation of the present invention.

Optionally, the compositions of the invention may contain, in addition to the rAAV and carrier(s), other conventional pharmaceutical ingredients, such as preservatives, or chemical stabilizers. Suitable exemplary preservatives include chlorobutanol, potassium sorbate, sorbic acid, sulfur dioxide, propyl gallate, the parabens, ethyl vanillin, glycerin, phenol, and parachlorophenol. Suitable chemical stabilizers include gelatin and albumin.

The viral vectors are administered in sufficient amounts to transfect the cells and to provide sufficient levels of gene transfer and expression to provide a therapeutic benefit without undue adverse effects, or with medically acceptable physiological effects, which can be determined by those skilled in the medical arts. Conventional and pharmaceutically acceptable routes of administration include, but are not limited to, direct delivery to the selected organ (e.g., intraportal delivery to the liver), oral, inhalation (including intranasal and intratracheal delivery), intraocular, intravenous, intramuscular, subcutaneous, intradermal, and other parental routes of administration. Routes of administration may be combined, if desired.

Dosages of the viral vector will depend primarily on factors such as the condition being treated, the age, weight and health of the patient, and may thus vary among patients. For example, a therapeutically effective human dosage of the viral vector is generally in the range of from about 1 ml to about 100 ml of solution containing concentrations of from about 1 x 10⁹ to 1 x 10¹⁶ genomes virus vector. A preferred human dosage may be about 1 x 10¹³ to 1 x 10¹⁶ AAV genomes. The dosage will be adjusted to balance the therapeutic benefit against any side effects and such dosages may vary depending upon the therapeutic application for which the recombinant vector is employed.

The levels of expression of the transgene can be monitored to determine the frequency of dosage resulting in viral vectors, preferably AAV vectors containing the minigene. Optionally, dosage regimens similar to those described for therapeutic purposes may be utilized for immunization using the compositions of the invention.

Examples of therapeutic products and immunogenic products for delivery by the AAV-containing vectors of the invention are provided below. These vectors may be used for a variety of therapeutic or vaccinal regimens, as described herein. Additionally, these vectors may be delivered in combination with one or more other vectors or active ingredients in a desired therapeutic and/or vaccinal regimen.

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B. Therapeutic Transgenes

Useful therapeutic products encoded by the transgene include hormones and growth and differentiation factors including, without {imitation, insulin, glucagon, growth hormone (GH), parathyroid hormone (PTH), growth hormone releasing factor (GRF), follicle stimulating hormone (FSH), luteinizing hormone (LH), human chorionic gonadotropin (hCG), vascular endothelial growth factor (VEGF), angiopoietins, angiostatin, granulocyte colony stimulating factor (GCSF), erythropoietin (EPO), connective tissue growth factor (CTGF), basic fibroblast growth factor (bFGF), acidic fibroblast growth factor (aFGF), epidermal growth factor (EGF), transforming growth factor a (TGFa), platelet10 derived growth factor (PDGF), insulin growth factors I and II (IGF-I and IGF-II), any one of the transforming growth factor β superfamily, including TGF β, activins, inhibins, or any of the bone morphogenic proteins (BMP) BMPs 1-15, any one of the heregluin/neuregulin/ARIA/neu differentiation factor (NDF) family of growth factors, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophins NT-3 and

NT-4/5, ciliary neurotrophic factor (CNTF), glial cell line derived neurotrophic factor (GDNF), neurturin, agrin, any one of the family of semaphorins/collapsins, netrin-1 and netrin-2, hepatocyte growth factor (HGF), ephrins, noggin, sonic hedgehog and tyrosine hydroxylase.

Other useful transgene products include proteins that regulate the immune system including, without limitation, cytokines and lymphokines such as thrombopoietin (TPO), interleukins (IL) IL-1 through IL-25 (including, IL-2, IL-4, IL-12, and IL-18), monocyte chemoattractant protein, leukemia inhibitory factor, granulocyte-macrophage colony stimulating factor, Fas ligand, tumor necrosis factors a and β, interferons α, β, and γ, stem ceil factor, flk-2/flt3 ligand. Gene products produced by the immune system are also useful in the invention. These include, without limitations, immunoglobulins IgG, IgM, IgA, IgD and IgE, chimeric immunoglobulins, humanized antibodies, single chain antibodies, T cell receptors, chimeric T cell receptors, single chain T cell receptors, class I and class II MHC molecules, as well as engineered immunoglobulins and MHC. molecules. Useful gene products also include complement regulatory proteins such as complement regulatory proteins, membrane co factor protein (MCP), decay accelerating factor (DAF), CR1, CF2 and CD59.

Still other useful gene products include any one of the receptors for the hormones, growth factors, cytokines, lymphokines, regulatory proteins and immune system

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2015258271 20 Nov 2015 proteins. The invention encompasses receptors for cholesterol regulation, including the low density lipoprotein (LDL) receptor, high density lipoprotein (HDL) receptor, the very low density lipoprotein (VLDL) receptor, and the scavenger receptor. The invention also encompasses gene products such as members of the steroid hormone receptor superfamily including glucocorticoid receptors and estrogen receptors, Vitamin D receptors and other nuclear receptors. In addition, useful gene products include transcription factors such as jun, fas, max, mad, serum response factor (SRF), AP-1, AP2, myb, MyoD and myogenin, ETSbox containing proteins, TFE3, E2F, ATF1, ATF2, ATF3, ATF4, ZF5, NFAT, CREB, HNF4, C/EBP, SPI, CCAAT-box binding proteins, interferon regulation factor (IRF-1), Wilms tumor protein, ETS-binding protein, STAT, GATA-box binding proteins, e.g., GATA-3, and the forkhead family of winged helix proteins.

Other useful gene products include, carbamoyl synthetase I, ornithine transcarbamyiase, arginosuccinate synthetase, arginosuccinate lyase, arginase, fumarylacetacetate hydrolase, phenylalanine hydroxylase, alpha-1 antitrypsin, glucose-615 phosphatase, porphobilinogen deaminase, factor VIII, factor IX, cystathione beta-synthase, branched chain ketoacid decarboxylase, albumin, isovaleryl-coA dehydrogenase, propionyl CoA carboxylase, methyl malonyl CoA mutase, giutaryl CoA dehydrogenase, insulin, betaglucosidase, pyruvate carboxylate, hepatic phosphorylase, phosphorylase kinase, glycine decarboxylase, H-protein, T-protein, a cystic fibrosis transmembrane regulator (CFTR) sequence, and a dystrophin cDNA sequence. Still other useful gene products include enzymes such as may be useful in enzyme replacement therapy, which is useful in a variety of conditions resulting from deficient activity of enzyme. For example, enzymes that contain mannose-6-phosphate may be utilized in therapies for lysosomal storage diseases (e.g., a suitable gene includes that encoding β-glucuronidase (GUSB)).

Other useful gene products include non-naturally occurring polypeptides, such as chimeric or hybrid polypeptides having a non-naturally occurring amino acid sequence containing insertions, deletions or amino acid substitutions. For example, singlechain engineered immunoglobulins could be useful in certain immunocompromised patients. Other types of non-naturally occurring gene sequences include antisense molecules and catalytic nucleic acids, such as ribozymes, which could be used to reduce overexpression of a target.

Reduction and/or modulation of expression of a gene is particularly desirable for treatment of hyperproliferative conditions characterized by hyperproliferating cells, as

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2015258271 20 Nov 2015 are cancers and psoriasis. Target polypeptides include those polypeptides which are produced exclusively or at higher levels in hyperproliferative cells as compared to normal cells. Target antigens include polypeptides encoded by oncogenes such as myb, myc, fyn, and the translocation gene bcr/abl, ras, src, P53, neu, trk and EGRF. In addition to oncogene products as target antigens, target polypeptides for anti-cancer treatments and protective regimens include variable regions of antibodies made by B cell lymphomas and variable regions of T cell receptors of T cell lymphomas which, in some embodiments, are also used as target antigens for autoimmune disease. Other tumor-associated polypeptides can be used as target polypeptides such as polypeptides which are found at higher levels in tumor cells including the polypeptide recognized by monoclonal antibody 17-1A and folate binding polypeptides.

Other suitable therapeutic polypeptides and proteins include those which may be useful for treating individuals suffering from autoimmune diseases and disorders by conferring a broad based protective immune response against targets that are associated with autoimmunity including cell receptors and cells which produce “self’-directed antibodies. T cell mediated autoimmune diseases include Rheumatoid arthritis (RA), multiple sclerosis (MS), Sjogren's syndrome, sarcoidosis, insulin dependent diabetes mellitus (IDDM), autoimmune thyroiditis, reactive arthritis, ankylosing spondylitis, scleroderma, polymyositis, dermatomyositis, psoriasis, vasculitis, Wegener's granulomatosis, Crohn's disease and ulcerative colitis. Each of these diseases is characterized by T cell receptors (TCRs) that bind to endogenous antigens and initiate the inflammatory cascade associated with autoimmune diseases.

C. Immunogenic Transgenes

Alternatively, or in addition, the vectors of the invention may contain AAV sequences of the invention and a transgene encoding a peptide, polypeptide or protein which induces an immune response to a selected immunogen. For example, immunogens may be selected from a variety of viral families. Example of desirable viral families against which an immune response would be desirable include, the picornavirus family, which includes the genera rhinoviruses, which are responsible for about 50% of cases of the common cold ; the genera enteroviruses, which include polioviruses, coxsackieviruses, echoviruses, and human enteroviruses such as hepatitis A virus; and the genera apthoviruses, which are responsible for foot and mouth diseases, primarily in non-human animals. Within the picornavirus family of viruses, target antigens include the VP1, VP2, VPS, VP4, and VPG. Another viral

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2015258271 20 Nov 2015 family includes the calcivirus family, which encompasses the Norwalk group of viruses, which are an important causative agent of epidemic gastroenteritis. Still another viral family desirable for use in targeting antigens for inducing immune responses in humans and nonhuman animals is the togavirus family, which includes the genera alphavirus, which include

Sindbis viruses, RossRiver virus, and Venezuelan, Eastern & Western Equine encephalitis, and rubivirus, including Rubella virus. The flaviviridae family includes dengue, yellow fever, Japanese encephalitis, St. Louis encephalitis and tick borne encephalitis viruses. Other target antigens may be generated from the Hepatitis C or the coronavirus family, which includes a number of non-human viruses such as infectious bronchitis virus (poultry), porcine transmissible gastroenteric virus (pig), porcine hemagglutinating encephalomyelitis virus (pig), feline infectious peritonitis virus (cats), feline enteric coronavirus (cat), canine coronavirus (dog), and human respiratory coronaviruses, which may cause the common cold and/or non-A, B or C hepatitis. Within the coronavirus family, target antigens include the El (also called M or matrix protein), E2 (also called S or Spike protein), E3 (also called HE or hemagglutin-elterose) glycoprotein (not present in all coronaviruses), or N (nucleocapsid). Still other antigens may be targeted against the rhabdovirus family, which includes the genera vesiculovirus (e.g., Vesicular Stomatitis Virus), and the general lyssavirus (e.g., rabies). Within the rhabdovirus family, suitable antigens may be derived from the G protein or the N protein. The family filoviridae, which includes hemorrhagic fever viruses such as

Marburg and Ebola virus may be a suitable source of antigens. The paramyxovirus family includes parainfluenza Virus Type 1, parainfluenza Virus Type 3, bovine parainfluenza Virus Type 3, rubulavirus (mumps virus, parainfluenza Virus Type 2, parainfluenza virus Type 4, Newcastle disease virus (chickens), rinderpest, morbillivirus, which includes measles and canine distemper, and pneumovirus, which includes respiratory syncytial virus.

The influenza virus is classified within the family orthomyxovirus and is a suitable source of antigen (e.g., the HA protein, the NI protein). The bunyavirus family includes the genera bunyavirus (California encephalitis, La Crosse), phlebovirus (Rift Valley Fever), hantavirus (puremala is a hemahagin fever virus), nairovirus (Nairobi sheep disease) and various unassigned bungaviruses. The arenavirus family provides a source of antigens against LCM and Lassa fever virus. The reovirus family includes the genera reovirus, rotavirus (which causes acute gastroenteritis in children), orbiviruses, and cultivirus (Colorado Tick fever, Lebombo (humans), equine encephalosis, blue tongue).

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The retrovirus family includes the sub-family oncorivirinal which encompasses such human and veterinary diseases as feline leukemia virus, HTLVI and HTLVII, lentivirinal (which includes human immunodeficiency virus (HIV), simian immunodeficiency virus (SIV), feline immunodeficiency virus (FIV), equine infectious anemia virus, and spumavirinal). Between the HIV and SIV, many suitable antigens have been described and can readily be selected. Examples of suitable HIV and SIV antigens include, without limitation the gag, pol, Vif, Vpx, VPR, Env, Tat and Rev proteins, as well as various fragments thereof. In addition, a variety of modifications to these antigens have been described. Suitable antigens for this purpose are known to those of skill in the art. For example, one may select a sequence encoding the gag, pol, Vif, and Vpr, Env, Tat and Rev, amongst other proteins. See, e.g., the modified gag protein which is described in US Patent 5,972,596. See, also, the HIV and SIV proteins described in D.H. Barouch et al, J. Virol.,

75(5):2462-2467 (March 2001), and R.R. Amara, et al, Science, 292:69-74 (6 April 2001). These proteins or subunits thereof may be delivered alone, or in combination via separate vectors or from a single vector.

The papovavirus family includes the sub-family polyomaviruses (BKU and JCU viruses) and the sub-family papillomavirus (associated with cancers or malignant progression of papilloma). The adenovirus family includes viruses (EX, AD7, ARD, O.B.) which cause respiratory disease and/or enteritis. The parvovirus family feline parvovirus (feline enteritis), feline panleucopeniavtrus, canine parvovirus, and porcine parvovirus. The herpesvirus family includes the sub-family alphaherpesvirinae, which encompasses the genera simplexvirus (HSVI, HSVII), varicellovirus (pseudorabies, varicella zoster) and the sub-family betaherpesvirinae, which includes the genera cytomegalovirus (HCMV, muromegalovirus) and the sub-family gammaherpesvirinae, which includes the genera lymphocryptovirus, EBV (Burkitts lymphoma), infectious rhinotracheitis, Marek’s disease virus, and rhadinovirus. The poxvirus family includes the sub-famiiy chordopoxvirinae, which encompasses the genera orthopoxvirus (Variola (Smallpox) and Vaccinia (Cowpox)), parapoxvirus, avipoxvirus, capripoxvirus, leporipoxvirus, suipoxvirus, and the sub-famiiy entomopoxvirinae. The hepadnavirus family includes the Hepatitis B virus. One unclassified virus which may be suitable source of antigens is the Hepatitis delta virus. Still other viral sources may include avian infectious bursal disease virus and porcine respiratory and reproductive syndrome· virus. The alphavirus family includes equine arteritis virus and various Encephalitis viruses.

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The present invention may also encompass immunogens which are useful to immunize a human or non-human animal against other pathogens including bacteria, fungi, parasitic microorganisms or multicellular parasites which infect human and non-human vertebrates, or from a cancer ceil or tumor cell. Examples of bacterial pathogens include.

pathogenic gram-positive cocci include pneumococci; staphylococci; and streptococci. Pathogenic gram-negative cocci include meningococcus; gonococcus. Pathogenic enteric gram-negative bacilli include enterobacteriaceae; pseudomonas, acinetobacteria and eikenella; melioidosis; salmonella; shigeila; haemophilus; moraxeiia; H. ducreyi (which causes chancroid); brucella; Franiselia tularensis (which causes tularemia); yersinia (pasteurella); streptobacillus moniliformis and spirillum; Gram-positive bacilli include listeria monocytogenes; erysipelothrix rhusiopathiae; Corynebacterium diphtheria (diphtheria); cholera; B. anthracis (anthrax); donovanosis (granuloma inguinale); and bartonellosis. Diseases caused by pathogenic anaerobic bacteria include tetanus; botulism; other clostridia; tuberculosis; leprosy; and other mycobacteria. Pathogenic spirochetal diseases include syphilis; treponematoses: yaws, pinta and endemic syphilis; and leptospirosis. Other infections caused by higher pathogen bacteria and pathogenic fungi include actinomycosis; nocardiosis; cryptococcosis, blastomycosis, histoplasmosis and coccidioidomycosis; candidiasis, aspergillosis, and mucormycosis; sporotrichosis; paracoccidiodomycosis, petriellidiosis, torulopsosis, mycetoma and chromomycosis; and dermatophytosis. Rickettsial infections include Typhus fever, Rocky Mountain spotted fever, Q fever, and Rickettsialpox. Examples of mycoplasma and chlamydial infections include: mycoplasma pneumoniae; lymphogranuloma venereum; psittacosis; and perinatal chlamydial infections. Pathogenic eukaryotes encompass pathogenic protozoans and helminths and infections produced thereby include: amebiasis; malaria; leishmaniasis;

trypanosomiasis; toxoplasmosis; Pneumocystis carinii', Trichans·, Toxoplasma gondii', babesiosis; giardiasis; trichinosis; filariasis; schistosomiasis; nematodes; trematodes or flukes; and cestode (tapeworm) infections.

Many of these organisms and/or toxins produced thereby have been identified by the Centers for Disease Control [(CDC), Department of Heath and Human

Services, USA], as agents which have potential for use in biological attacks. For example, some of these biological agents, include, Bacillus anthracis (anthrax), Clostridium botulinum and its toxin (botulism), Yersiniapestis (plague), variola major (smallpox), Francisella tularensis (tularemia), and viral hemorrhagic fever, all of which are currently classified as

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Category A agents; Coxiella bumetti (Q fever); Brucella species (brucellosis), Burkholderia mallei (glanders), Ricinus communis and its toxin (ricin toxin), Clostridium perfringens and its toxin (epsilon toxin), Staphylococcus species and their toxins (enterotoxin B), ail of which are currently classified as Category B agents; and Nipan virus and hantaviruses, which are currently classified as Category C agents. In addition, other organisms, which are so classified or differently classified, may be identified and/or used for such a purpose in the future. It will be readily understood that the viral vectors and other constructs described herein are useful to deliver antigens from these organisms, viruses, their toxins or other byproducts, which will prevent and/or treat infection or other adverse reactions with these biological agents.

Administration of the vectors of the invention to deliver immunogens against the variable region of the T cells elicit an immune response including CTLs to eliminate those T cells. In rheumatoid arthritis (RA), several specific variable regions of T cell receptors (TCRs) which are involved in the disease have been characterized. These TCRs include V-3, V-14, V-17 and Va-17. Thus, delivery of a nucleic acid sequence that encodes at least one of these polypeptides will elicit an immune response that will target T cells involved in RA. In multiple sclerosis (MS), several specific variable regions of TCRs which are involved in the disease have been characterized. These TCRs include V-7 and Va-10. Thus, delivery of a nucleic acid sequence that encodes at least one of these polypeptides will elicit an immune response that will target T cells involved in MS. In scleroderma, several specific variable regions of TCRs which are involved in the disease have been characterized. These TCRs include V-6, V-8, V-14 and Va-16, Va-3C, Va-7, Va-14, Va-15, Va-16,

Va-28 and Va-12. Thus, delivery of a nucleic acid molecule that encodes at least one of these polypeptides will elicit an immune response that will target T cells involved in scleroderma.

Optionally, vectors containing AAV sequences of the invention may be delivered using a prime-boost regimen. A variety of such regimens have been described in the art and may be readily selected. See, e.g,, WO 00/11140, published March 2, 2000, incorporated by reference.

Such prime-boost regimens typically involve the administration of a DNA (e.g,, plasmid) based vector to prime the immune system to second, booster, administration with a traditional antigen, such as a protein or a recombinant virus carrying the sequences encoding such an antigen. In one embodiment, the invention provides a method of priming

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2015258271 20 Nov 2015 and boosting an immune response to a selected antigen by delivering a plasmid DNA vector carrying said antigen, followed by boosting, e.g., with a vector containing AAV sequences of the invention.

In one embodiment, the prime-boost regimen involves the expression of 5 multiproteins from the prime and/or the boost vehicle. See, e.g., R.R. Amara, Science,

292:69-74 (6 April 2001) which describes a multiprotein regimen for expression of protein subunits useful for generating an immune response against HIV and SIV. For example, a DNA prime may deliver the Gag, Pol, Vif, VPX and Vpr and Env, Tat, and Rev from a single transcript. Alternatively, the SIV Gag, Pol and FIIV-1 Env is delivered.

However, the prime-boost regimens are not limited to immunization for HIV or to delivery of these antigens. For example, prim ing may involve delivering with a first chimp vector of the invention followed by boosting with a second chimp vector, or with a composition containing the antigen itself in protein form. In one or example, the primeboost regimen can provide a protective immune response to the virus, bacteria or other organism from which the antigen is derived. In another desired embodiment, the primeboost regimen provides a therapeutic effect that can be measured using convention assays for detection of the presence of the condition for which therapy is being administered.

The priming vaccine may be administered at various sites in the body in a dose dependent manner, which depends on the antigen to which the desired immune response is being targeted. The invention is not limited to the amount or situs of injection(s) or to the pharmaceutical carrier. Rather, the priming step encompasses treatment regimens which include a single dose or dosage which is administered hourly, daily, weekly or monthly, or yearly. As an example, the mammals may receive one or two priming injection containing between about 10 pg to about 50 pg of plasmid in carrier. A desirable priming amount or dosage of the priming DNA vaccine composition ranges between about 1 pg to about 10,000 pg of the DNA vaccine. Dosages may vary from about 1 pg to 1000 pg DNA per kg of subject body weight. The amount or site of injection is desirably selected based upon the identity and condition of the mammal being vaccinated.

The dosage unit of the DNA vaccine suitable for delivery of the antigen to the mammal is described herein. The DNA vaccine is prepared for administration by being suspended or dissolved in a pharmaceutically or physiologically acceptable carrier such as isotonic saline, isotonic salts solution or other formulations which will be apparent to those skilled in such administration. The appropriate carrier will be evident to those skilled in the

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2015258271 20 Nov 2015 art and will depend in large part upon the route of administration. The compositions of the invention may be administered to a mammal according to the routes described above, in a sustained release formulation using a biodegradable biocompatible polymer, or by on-site delivery using micelles, gels and liposomes.

Optionally, the priming step of this invention also includes administering with the priming DNA vaccine composition, a suitable amount of an adjuvant, such as are defined herein.

Preferably, a boosting composition is administered about 2 to about 27 weeks after administering the priming DNA vaccine to the mammalian subject. The administration of the boosting composition is accomplished using an effective amount of a boosting vaccine composition containing or capable of delivering the same antigen as administered by the priming DNA vaccine. The boosting composition may be composed of a recombinant viral vector derived from the same viral source or from another source. Alternatively, the “boosting composition” can be a composition containing the same antigen as encoded in the priming DNA vaccine, but in the form of a protein or peptide, which composition induces an immune response in the host. In another embodiment, the boosting vaccine composition includes a composition containing a DNA sequence encoding the antigen under the control of a regulatory sequence directing its expression in a mammalian cell, e.g., vectors such as well-known bacterial or viral vectors. The primary requirements of the boosting vaccine composition are that the antigen of the vaccine composition is the same antigen, or a crossreactive antigen, as that encoded by the DNA vaccine.

Suitably, the vectors of the invention are also well suited for use in regimens which use non-AAV vectors as well as proteins, peptides, and/or other biologically useful therapeutic or immunogenic compounds. These regimens are particularly well suited to gene delivery for therapeutic poses and for immunization, including inducing protective immunity. Such uses will be readily apparent to one of skill in the art.

Further, a vector of the invention provides an efficient gene transfer vehicle which can deliver a selected transgene to a selected host cell in vivo or ex vivo even where the organism has neutralizing antibodies to one or more AAV serotypes. In one embodiment, the vector (e.g,, an rAAV) and the cells are mixed ex vivo; the infected ceils are cultured using conventional methodologies; and the transduced cells are re-infused into the patient. Further, the vectors of the invention may also be used for production of a desired gene product in vitro. For in vitro production, a desired product (e.g., a protein) may be

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2015258271 20 Nov 2015 obtained from a desired culture following transfection of host cells with a rAAV containing the molecule encoding the desired product and culturing the cell culture under conditions which permit expression. The expressed product may then be purified and isolated, as desired. Suitable techniques for transfection, cell culturing, purification, and isolation are known to those of skill in the art.

The following examples illustrate several aspects and embodiments of the invention.

EXAMPLES

Example 1: PCR amplification, cloning and characterization of novel AAV sequences.

Tissues from nonhuman primates were screened for AAV sequences using a

PCR method based on oligonucleotides to highly conserved regions of known AAVs. A stretch of AAV sequence spanning 2886 to 3143 bp of AAV1 [SEQ ID NO:6’J was selected as a PCR amplicon in which a hypervariable region of the capsid protein (Cap) that is unique to each known AAV serotype, which is termed herein a “signature region,” is flanked by conserved sequences. In later analysis, this signature region was shown to be located between conserved residues spanning hypervariable region 3.

An initial survey of peripheral blood of a number of nonhuman primate species revealed detectable AAV in a subset of animals from species such as rhesus macaques, cynomologous macaques, chimpanzees and baboons. However, there were no AAV sequences detected in some other species tested, including Japanese macaques, pigtailed macaques and squirrel monkeys. A more extensive analysis of vector distribution was conducted in tissues of rhesus monkeys of the University of Pennsylvania and Tulane colonies recovered at necropsy. This revealed AAV sequence throughout a wide array of tissues.

A. Amplification of an AA V signature region

DNA sequences of AAV1-6 and AAVs isolated from Goose and

Duck were aligned to each other using “Clustal W” at default settings. The alignment for

AAV1-6, and including the information for the novel AAV7, is provided in Fig. 1. Sequence similarities among AAVs were compared.

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In the line of study, a 257 bp region spanning 2886 bp to 3143 bp of AAV 1 [SEQ ID NO: 6], and the corresponding region in the genomes of AAV 2-6 genomes [See, Fig. 1], was identified by the inventors. This region is located with the AAV capsid gene and has highly conserved sequences among at both 5’ and 3’ ends and is relatively variable sequence in the middle. In addition, this region contains a Dralll restriction enzyme site (CACCACGTC, SEQ ID NO: 15). The inventors have found that this region serves as specific signature for each known type of AAV DNA. In other words, following PCR reactions, digestion with endonucleases that are specific to each known serotypes and gel electrophoresis analysis, this regions can be used to definitively identify amplified DNA as being from serotype I, 2, 3, 4, 5, 6, or another serotype.

The primers were designed, validated and PCR conditions optimized with AAV1, 2 and 5 DNA controls. The primers were based upon the sequences of AAV2: 5’ primer, IS: bp 2867-2891 of AAV2 (SEQ ID NO:7) and 3’ primer, 18as, bp 3095-3121 of AAV2 (SEQ ID NO:7).

Cellular DNAs from different tissues including blood, brain, liver, lung, testis, etc. of different rhesus monkeys were studied utilizing the strategy described above. The results revealed that DNAs from different tissues of these monkeys gave rise to strong PCR amplifications. Further restriction analyses of PCR products indicated that they were amplified from AAV sequences different from any published AAV sequences.

PCR products (about 255 bp in size) from DNAs of a variety of monkey tissues have been cloned and sequenced. Bioinformatics study of these novel AAV sequences indicated that they are novel AAV sequences of capsid gene and distinct from each other. Fig. 1 includes in the alignment the novel AAV signature regions for AAV10-12 [SEQ ID NO:117, 118 and 119, respectively]. Multiple sequence alignment analysis was performed using the Clustal W (1.81) program. The percentage of sequence identity between the signature regions of AAV 1-7 and AAV 10-12 genomes is provided below.

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Table 1. Sequences for Analysis

Sequence #	AAV Serotype	Size (bp)
1	AAV I	258
2	AAV2	255
3 '	AAV3	255
4	AAV4	246
5	AAV5	258
6	AAV6	258
7	AAV7	258
10	AAV 10	255
11	A AV 11	258
12	AAV 12	255

Table 3. Pairwise Alignment (Percentage of Identity)

	AAV2	AAV3	AAV4	AAV5	AAV6	AAV7	AAV10	AAV11	AAV12
AAV1	90	90	81	76	97	91	93	94	93
AAV2		93	79	78	90	90	93	93	92
AAV3			80	76	90	92	92	92	92
AAV4				76	81	84	82	81	79
AAV5					75	78	79	79	76
AAV6						91	92	94	94
AAV7							94	92	92
AAV10								95	93
AAV11									94

Over 300 clones containing novel AAV serotype sequences that span the selected 257 bp region were isolated and sequenced. Bioinformatics analysis of these 300+ clones suggests that this 257 bp region is critical in serving as a good land marker or signature sequence for quick isolation and identification of novel AAV serotype.

B. Use of the signature region for PCR amplification.

The 257 bp signature region was used as a PCR anchor to extend

PCR amplifications to 5’ of the genome to cover the junction region of rep and cap genes 15 (1398 bp - 3143 bp, SEQ ID NO:6) and 3’ of the genome to obtain the entire cap gene sequence (2866 bp - 4600 bp, SEQ ID NO:6). PCR amplifications were carried out using the standard conditions, including denaturing at 95°C for 0.5-1 min, annealing at 60-65°C for 0.5-1 min and extension at 72° C for 1 min per kb with a total number of amplification cycles ranging from 28 to 42.

Using the aligned sequences as described in “A”, two other relative conserved regions were identified in the sequence located in 3’ end of rep genes and 5’ to the

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257 bp region and in the sequence down stream of the 257 bp fragment but before the AAV’ 3 ITR. Two sets of new primers were designed and PCR conditions optimized for recovery of entire capsid and a part of rep sequences of novel AAV serotypes. More specifically, for the 5’ amplification, the 5' primer, AVI Ns, was GCTGCGTCAACTGGACCAATGAGAAC [nt 1398-1423 of AAV1, SEQ ID NO:6] and the 3' primer was 18as, identified above. For the 3' amplification, the 5' primer was Is, identified above, and the 3' primer was AV2Las, TCGTTTCAGTTGAACTTTGGTCTCTGCG [nt 4435-4462 of AAV2, SEQ ID NO:7].

In these PCR amplifications, the 257 bp region was used as a PCR anchor and land marker to generate overlapping fragments to construct a complete capsid gene by fusion at the Dralll site in the signature region following amplification of the 5' and 3' extension fragments obtained as described herein. More particularly, to generate the intact AAV7 cap gene, the three amplification products (a) the sequences of the signature region; (b) the sequences of the 5' extension; and (c) the sequences of the 3' extension were cloned into a pCR4-Topo [Invitrogen] plasmid backbone according to manufacturer’s instructions.

Thereafter, the plasmids were digested with Dralll and recombined to form an intact cap gene.

In this line of work, about 80 % of capsid sequences of AAV7 and AAV 8 were isolated and analyzed. Another novel serotype, AAV9, was also discovered from Monkey #2.

Using the PCR conditions described above, the remaining portion of the rep gene sequence for AAV7 is isolated and cloned using the primers that amplify 108 bp to 1461 bp of AAV genome (calculated based on the numbering of AAV2, SEQ ID NO:7). This clone is sequenced for construction of a complete AAV7 genome without ITRs.

C. Direct Amplification of 3.1 kb Cap fragment

To directly amplify a 3.1 kb full-length Cap fragment from NHP tissue and blood DNAs, two other highly conserved regions were identified in AAV genomes for use in PCR amplification of large fragments. A primer within a conserved region located in the middle of the rep gene was selected (AVlns: 5'

GCTGCGTCAACTGGACCAATGAGAAC 3’, nt 1398-1423 of SEQ IDNO:6) in combination with the 3' primer located in another conserved region downstream of the Cap gene (AV2cas: 5* CGCAGAGACCAAAGTTCAACTGAAACGA 3', SEQ ID NO:7) for amplification of full-length cap fragments. The PCR products were Topo-cloned according to manufacturer’s directions (Invitrogen) and sequence analysis was performed by

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Qiagengenomics (Qiagengenomics, Seattle, WA) with an accuracy of > 99.9%. A total of 50 capsid clones were isolated and characterized. Among them, 37 clones were derived from Rhesus macaque tissues (rh.l - rh.37), 6 clones from cynomologous macaques (cy.l - cy.6), 2 ciones from Baboons (bb.l and bb.2) and 5 clones from Chimps (ch.l - ch.5).

To rule out the possibility that sequence diversity within the novel AAV family was not an artifact of the PCR, such as PCR-mediated gene spiicing by overlap extension between different partial DNA templates with homologous sequences, or the result of recombination process in bacteria, a series of experiments were performed under identical conditions for VP1 amplification using total ceiluiar DNAs. First, intact AAV7 and AAV8 plasmids were mixed at an equal molar ratio followed by serial dilutions. The serially diluted mixtures were used as templates for PCR amplification of 3.1 kb VP1 fragments using universal primers and identical PCR conditions to that were used for DNA amplifications to see whether any hybrid PCR products were generated. The mixture was transformed into bacteria and isolated transformants to look for hybrid clones possibly derived from recombination process in bacterial celis. In a different experiment, we restricted AAV7 and AAV8 plasmids with Msp I, Ava I and Hael, ail of which cut both genomes multiple times at different positions, mixed the digestions in different combinations and used them for PCR amplification of VP1 fragments under the same conditions to test whether any PCR products could be generated through overlap sequence extension of partial AAV sequences. In another experiment, a mixture of gel purified 5' 1.5 kb AAV7 VP1 fragment and 3' 1.7 kb AAV8 VP1 fragment with overlap in the signature region was serially diluted and used for PCR amplification in the presence and absence of 200 ng cellular DNA extracted from a monkey cell line that was free of AAV sequences by TaqMan analysis. None of these experiments demonstrated efficient PCR-mediated overlap sequence production under the conditions of the genomic DNA Cap amplification (data not shown). As a further confirmation, 3 pairs of primers were designed, which were located at different HVRs, and were sequence specific to the variants of clone 42s from Rhesus macaque F953, in different combinations to amplify shorter fragments from mesenteric lymph node (MLN) DNA from F953 from which clone 42s were isolated. All sequence variations identified in full-length Cap clones were found in these short fragments (data not shown).

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Example 2: Adeno-Associated Viruses Undergo Substantial Evolution in Primates During Natural Infections

Sequence analysis of selected AAV isolates revealed divergence throughout the genome that is most concentrated in hypervariable regions of the capsid proteins.

Epidemiologic data indicate that all known serotypes are endemic to primates, although isolation of clinical isolates has been restricted to AAV2 and AAVS from anal and throat swabs of human infants and AAV5 from a human condylomatous wart. No known clinical sequalae have been associated with AAV infection.

in an attempt to better understand the biology of AAV, nonhuman primates were used as models to characterize the sequlae of natural infections. Tissues from nonhuman primates were screened for AAV sequences using the PCR method of the invention based on oligonucleotides to highly conserved regions of known AAVs (see Example 1). A stretch of AAV sequence spanning 2886 to 3143 bp of AAV1 [SEQ ID NO:6] was selected as a PCR amplicon in which conserved sequences are flanked by a hypervariable region that is unique to each known AAV serotype, termed herein a “signature region.”

An initial survey of peripheral blood of a number of nonhuman primate species including rhesus monkeys, cynomologous monkeys, chimpanzees, and baboons revealed detectable AAV in a subset of animals from all species. A more extensive analysis of vector distribution was conducted in tissues of rhesus monkeys of the University of Pennsylvania and Tulane colonies recovered at necropsy. This revealed AAV sequence throughout a wide array of tissues.

The amplified signature sequences were subcloned into plasmids and individual transformants were subjected to sequence analysis. This revealed substantial variation in nucleotide sequence of clones derived from different animals. Variation in the signature sequence was also noted in clones obtained within individual animals. Tissues harvested from two animals in which unique signature sequences were identified (i.e., colon from 98E044 and heart from 98E056) were further characterized by expanding the sequence amplified by PCR using oligonucleotides to highly conserved sequences. In this way, complete proviral structures were reconstructed for viral genomes from both tissues as described herein. These proviruses differ from the other known AAVs with the greatest sequence divergence noted in regions of the Cap gene.

Additional experiments were performed to confirm that AAV sequences resident to the nonhuman primate tissue represented proviral genomes of infectious virus that is capable

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2015258271 20 Nov 2015 of being rescued and form virions. Genomic DNA from liver tissue of animal 98E056, from which AAV8 signature sequence was detected, was digested with an endonuclease that does not have a site within the AAV sequence and transfected into 293 cells with a plasmid containing an El deleted genome of human adenovirus serotype 5 as a source of helper functions. The resulting lysate was passaged on 293 cells once and the lysate was recovered and analyzed for the presence of AAV Cap proteins using a broadly reacting polyclonal antibody to Cap proteins and for the presence and abundance of DNA sequences from the PCR amplified AAV provirus from which AAV8 was derived. Transfection of endonuclease restricted heart DNA and the adenovirus helper plasmid yielded high quantities of AAV8 virus as demonstrated by the detection of Cap proteins by Western blot analysis and the presence of 10⁴ AAV8 vector genomes per 293 cell. Lysates were generated from a largescale preparation and the AAV was purified by cesium sedimentation. The purified preparation demonstrated 26 nm icosohedral structures that look identical to those of AAV serotype 2. Transfection with the adenovirus helper alone did not yield AAV proteins or genomes, ruling out contamination as a source of the rescued AAV,

To further characterize the inter and intra animal variation of AAV signature sequence, selected tissues were subjected to extended PCR to amplify entire Cap open reading frames.

The resulting fragments were cloned into bacterial plasmids and individual transformants were isolated and fully sequenced. This analysis involved mesenteric lymph nodes from three rhesus monkeys (Tulane/V223 - 6 clones; Tulane/T612 - 7 clones; Tulane/F953 - 14 clones), liver from two rhesus monkeys (Tulane/V251 -- 3 clones; Penn/OOEO33 - 3 clones), spleen from one rhesus monkey (Penn/97E043 -- 3 clones), heart from one rhesus monkey (IHGT/98E046- 1 clone) and peripheral blood from one chimpanzee (New Iberia/X133 - 5 clones), six cynomologous macaques (Charles

River/A1378, A3099, A3388, A3442, A2821, A3242 -- 6 clones total) and one Baboon (SFRB/8644 - 2 clones). Of the 50 clones that were sequenced from 15 different animals, 30 were considered non-redundant based on the finding of at least 7 amino acid differences from one another. The non-redundant VP1 clones are numbered sequentially as they were isolated, with a prefix indicating the species of non-human primate from which they were derived. The structural relationships between these 30 non-redundant clones and the previously described 8 AAV serotypes were determined using the SplitsTree program [Huson, D. H. SplitsTree: analyzing and visualizing evolutionary data. Bioinformatics 14,

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68-73 (1998)] with implementation of the method of split decomposition. The analysis depicts homopiasy between a set of sequences in a tree-like network rather than a bifurcating tree. The advantage is to enable detection of groupings that are the result of convergence and to exhibit phylogenetic relationships even when they are distorted by parallel events.

Extensive phylogenetic research will be required in order to elucidate the AAV evolution, whereas the intention here only is to group the different clones as to their sequence similarity.

To confirm that the novel VP1 sequences were derived from infectious viral genomes, cellular DNA from tissues with high abundance of viral DNA was restricted with an endonuclease that should not cleave within AAV and transfected into 293 cells, followed by infection with adenovirus. This resulted in rescue and amplification of AAV genomes from DNA of tissues from two different animals (data not shown).

VP1 sequences of the novel AAVs were further characterized with respect to the nature and location of amino acid sequence variation. AU 30 VP1 clones that were shown to differ from one another by greater than 1% amino acid sequence were aligned and scored for variation at each residue. An algorithm developed to determine areas of sequence divergence yielded 12 hypervariable regions (HVR) of which 5 overlap or are part of the 4 previously described variable regions [Kotin, cited above; Rutledge, cited above]. The threefold-proximal peaks contain most of the variability (HVR5-10). Interestingly the loops located at the 2 and 5 fold axis show intense variation as well. The HVRs 1 and 2 occur in the N-terminal portion of the capsid protein that is not resolved in the X-ray structure suggesting that the N-terminus of the VP1 protein is exposed on the surface of the virion.

Real-time PCR was used to quantify AAV sequences from tissues of 21 rhesus monkeys using primers and probes to highly conserved regions of Rep (one set) and Cap (two sets) of known AAVs. Each data point represents analysis from tissue DNA from an individual animal. This confirmed the wide distribution of AAV sequences, although the quantitative distribution differed between individual animals. The source of animals and previous history or treatments did not appear to influence distribution of AAV sequences in rhesus macaques. The three different sets of primers and probes used to quantify AAV yielded consistent results. The highest levels of AAV were found consistently in mesenteric lymph nodes at an average of 0.01 copies per diploid genome for 13 animals that were positive. Liver and spleen also contained high abundance of virus DNA. There were examples of very high AAV, such as in heart of rhesus macaque 98E056, spleen of rhesus

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2015258271 20 Nov 2015 macaque 97E043 and liver of rhesus macaque RQ4407, which demonstrated 1.5, 3 and 20 copies of AAV sequence per diploid genome respectively. Relatively low levels of virus DNA were noted in peripheral blood mononuclear cells, suggesting the data in tissue are not due to resident blood components (data not shown). It should be noted that this method would not necessarily capture all AAVs resident to the nonhuman primates since detection requires high homology to both the oligonucleotides and the real time PCR probe. Tissues from animals with high abundance AAV DNA was further analyzed for the molecular state of the DNA, by DNA hybridization techniques, and its cellular distribution, by in situ hybridization.

The kind of sequence variation revealed in AAV proviral fragments isolated from different animals and within tissues of the same animals is reminiscent of the evolution that occurs for many RNA viruses during pandemics or even within the infection of an individual. In some situations the notion of a wild-type virus has been replaced by the existence of swarms of quasispecies that evolve as a result of rapid replication and mutations in the presence of selective pressure. One example is infection by HIV, which evolves in response to immunologic and pharmacologic pressure. Several mechanisms contribute to the high rate of mutations in RNA viruses, including low fidelity and lack of proof reading capacity of reverse transcriptase and non-homologous and homologous recombination.

Evidence for the formation of quasispecies of AAV was illustrated in this study by the systematic sequencing of multiple cloned proviral fragments. In fact, identical sequences could not be found within any extended clones isolated between or within animals. An important mechanism for this evolution of sequence appears to be a high rate of homologous recombination between a more limited number of parenteral viruses. The net result is extensive swapping of hypervariable regions of the Cap protein leading to an array of chimeras that could have different tropisms and serologic specificities (i.e., the ability to escape immunologic responses especially as it relates to neutralizing antibodies).

Mechanisms by which homologous recombination could occur are unclear. One possibility is that + and - strands of different single stranded AAV genomes anneal during replication as has been described during high multiplicity of infections with AAV recombinants. It is unclear if other mechanisms contribute to sequence evolution in AAV infections. The overall rate of mutation that occurs during AAV replication appears to be relatively low and the data do not suggest high frequencies of replication errors. However, substantial rearrangements of the AAV genome have been described during lytic infection leading to the

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2015258271 20 Nov 2015 formation of defective interfering particles. Irrespective of the mechanisms that lead to sequence divergence, with few exceptions , vpl structures of the quasispecies remained intact without frameshifts or nonsense mutations suggesting that competitive selection of viruses with the most favorable profile of fitness contribute to the population dynamics.

These studies have implications in several areas of biology and medicine. The concept of rapid virus evolution, formerly thought to be a property restricted to RNA viruses, should be considered in DNA viruses, which classically have been characterized by serologic assays. It will be important in terms of parvoviruses to develop a new method for describing virus isolates that captures the complexity of its structure and biology, such as with HIV, which are categorized as general families of similar structure and function called Glades. An alternative strategy is to continue to categorize isolates with respect to serologic specificity and develop criteria for describing variants within serologic groups.

Example 3: Vectorology of recombinant AAV genomes equipped with AAV2 ITRs using chimeric plasmids containing AAV2 rep and novel AAV cap genes for serological and gene transfer studies in different animal models.

Chimeric packaging constructs are generated by fusing AAV2 rep with cap sequences of novel AAV serotypes. These chimeric packaging constructs are used, initially, for pseudotyping recombinant AAV genomes carrying AAV2 ITRs by triple transfection in

293 cell using Ad5 helper plasmid. These pseudotyped vectors are used to evaluate performance in transduction-based serological studies and evaluate gene transfer efficiency of novel AAV serotypes in different animal models including NHP and rodents, before intact and infectious viruses of these novel serotypes are isolated.

A. pAAV2GFP

The AAV2 plasmid which contains the AAV2 ITRs and green fluorescent protein expressed under the control of a constitutitive promoter. This plasmid contains the following elements: the AAV2 ITRs, a CMV promoter, and the GFP coding sequences.

B. Cloning of trans plasmid

To construct the chimeric trans-plasmid for production of recombinant pseudotyped AAV7 vectors, p5E18 plasmid (Xiao et al., 1999, J. Virol 73:3994-4003) was partially digested with Xho Ϊ to linearize the plasmid at the Xho I site at the position of 3169 bp only. The Xho I cut ends were then filled in and ligated back. This modified p5E18 plasmid was restricted with Xba I and Xho I in a complete digestion to remove the AAV2

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2015258271 20 Nov 2015 cap gene sequence and replaced with a 2267 bp Spe I/Xho I fragment containing the AAV7 cap gene which was isolated from pCRAAV7 6-5+15-4 plasmid.

The resulting plasmid contains the AAV2 rep sequences for Rep78/68 under the control of the AAV2 P5 promoter, and the AAV2 rep sequences for Rep52/40 under the control of the AAV2 Pl 9 promoter. The AAV7 capsid sequences are under the control of the AAV2

P40 promoter, which is located within the Rep sequences. This plasmid further contains a spacer 5' of the rep ORF.

C. Production of Pseudotyped rAA V

The rAAV particles (AAV2 vector in AAV7 capsid) are generated using an adenovirus-free method. Briefly, the cis plasmid (pAAV2.1 lacZ plasmid containing AAV2 ITRs), and the trans plasmid pCRAAV? 6-5+15-4 (containing the AAV2 rep and AAV7 cap) and a helper plasmid, respectively, were simultaneously co-transfected into 293 cells in a ratio of 1:1:2 by calcium phosphate precipitation.

For the construction of the pAd helper plasmids, pBGlO plasmid was purchased from Microbix (Canada). A RsrII fragment containing L2 and L3 was deleted from pBHGlO, resulting in the first helper plasmid, pAdAF13. Plasmid AdA FI was constructed by cloning Asp700/SalI fragment with a Pmel/Sgfl deletion, isolating from pBHGlO, into Bluescript. MLP, L2, L2 and L3 were deleted in the pAdAFl. Further deletions of a 2.3 kb Nrul fragment and, subsequently, a 0.5 kb Rsrll/Nrul fragment generated helper plasmids pAdAFS and pAdAF6, respectively. The helper plasmid, termed pAF6, provides the essential helper functions of E2a and E4 ORF6 not provided by the Elexpressing helper ceil, but is deleted of adenoviral capsid proteins and functional El regions).

Typically, 50 pg of DNA (cis:trans:helper) was transfected onto a 150 mm tissue culture dish. The 293 ceils were harvested 72 hours post-transfection, sonicated and treated with 0.5% sodium deoxycholate (37°C for 10 min.) Celi lysates were then subjected to two rounds of a CsCl gradient. Peak fractions containing rAAV vector are collected, pooled and dialyzed against PBS.

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Example 4: Creation of infectious clones carrying intact novel AAV serotypes for study of basic virology in human and NHP derived cell lines and evaluation of pathogenesis of novel AAV serotypes in NHP and other animal models.

To achieve this goal, the genome walker system is employed to obtain 5’ and

3’ terminal sequences (ITRs) and complete construction of clones containing intact novel

AAV serotype genomes.

Briefly, utilizing a commercially available Universal Genome Walker Kit [Clontech], genomic DNAs from monkey tissues or cell lines that are identified as positive for the presence of AAV7 sequence are digested with Dra I, EcoR V, Pvu II and Stu I endonucleases and ligated to Genome Walker Adaptor to generate 4 individual Genome Walker Libraries (GWLs). Using DNAs from GWLs as templates, AAV7 and adjacent genomic sequences will be PCR-amplified by the adaptor primer 1 (API, provided in the kit) and an AAV7 specific primer 1, followed by a nested PCR using the adaptor primer 2 (AP2) and another AAV7 specific primer 2, both of which are internal to the first set of primers.

The major PCR products from the nested PCR are cloned and characterized by sequencing analysis.

, In this experiment, the primers covering the 257 bp or other signature fragment of a generic A AV genome are used for PCR amplification of cellular DNAs extracted from Human and NHP derived cell lines to identify and characterize latent AAV sequences. The identified latent AAV genomes are rescued from the positive cell lines using adenovirus helpers of different species and strains.

To isolate infectious AAV clones from NHP derived cell lines, a desired cell line is obtained from ATCC and screened by PCR to identify the 257 bp amplicon, i.e., signature region of the invention. The 257 bp PCR product is cloned and serotyped by sequencing analysis. For these ceil lines containing the AAV7 sequence, the cells are infected with SV-15, a simian adenovirus purchased from ATCC, human Ad5 or transfected with plasmid construct housing the human Ad genes that are responsible for AAV helper functions. At 48 hour post infection or transfection, the cells are harvested and Hirt DNA is prepared for cloning of AAV7 genome following Xiao et al., 1999, J. Virol, 73:3994-4003.

Example 5 - Production of AAV Vectors

A pseudotyping strategy similar to that of Example 3 for AAV1/7 was employed to produce AAV2 vectors packaged with AAV1, AAV5 and AAV8 capsid proteins. Briefly,

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2015258271 20 Nov 2015 recombinant AAV genomes equipped with AAV2 ITRs were packaged by triple transfection of 293 cells with cis-plasmid, adenovirus helper plasmid and a chimeric packaging construct where the AAV2 rep gene is fused with cap genes of novel AAV serotypes. To create the chimeric packaging constructs, the Xho I site of p5E18 plasmid at 3169 bp was ablated and the modified plasmid was restricted with Xba I and Xho I in a complete digestion to remove the AAV2 cap gene and replace it with a 2267 bp Spe Ι/Xho I fragment containing the . AAV8 cap gene [Xiao, W., et al,, (1999) J Virol 73, 3994-4003], A similar cloning strategy was used for creation of chimeric packaging plasmids of AAV2/1 and AAV2/5. All recombinant vectors were purified by the standard CsCb sedimentation method except for

AAV2/2, which was purified by single step heparin chromatography.

Genome copy (GC) titers of AAV vectors were determined by TaqMan analysis using probes and primers targeting SV40 poly A region as described previously [Gao, G., et al., (2000) Hum Gene Ther 11, 2079-91].

Vectors were constructed for each serotype for a number of in vitro and in vivo 15 studies. Eight different transgene cassettes were incorporated into the vectors and recombinant virions were produced for each serotype. The recovery of virus, based on genome copies, is summarized in Table 4 below. The yields of vector were high for each serotype with no consistent differences between serotypes. Data presented in the table are average genome copy yields with standard deviation x 1O^|J of multiple production lots of 50 plate (150 mm ) transfections.

Table 4. Production of Recombinant Vectors

	AAV2/1	AAV2/2	AAV2/5	AAV2/7	AAV2/8
CMV	7.30 + 4.33	4.49 + 2,89	.5.19 + 5.19	3.42	0.87
LacZ	(n=9)	(n=6)	(n=8)	(n=l)	(n=l)
CMV	6.43 + 2.42	3.39 + 2.42	5.55 + 6.49	2.98 + 2.66	3.74 + 3.88
EGFP	(n=2)	(n=2)	(n=4)	(n=2)	(n=2)
ΊΓϊ&ί·»· LacZ	4.18 (n=l)	0.23 (n=l)	0.704 + 0.43 (n=2)	2.16 (n=l)	0.532 (n=l)
Alb A1AT	4.67 + 0,75 (n=2)	4.77 (n=l)	4.09 (n=l)	5.04 (n=l)	2.02 (n=l)
CB A1AT	0.567 (n=l)	0.438 (n=l)	2.82 (n=l)	2.78 (n=l)	0.816 + 0.679 (n=2)

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Table 4 (cont’d).

	AAV2/1	AAV2/2	AAV2/5	AAV2/7	AAV2/8
TBG rhCG	8.51 ±6.65 (n=6)	3.47 + 2.09 (n~5)	5.26 + 3.85 (n=4)	6.52 + 3.08 (n=4)	1.83 + 0.98 (n~ 5)
TBG cFIX	1.24+1.29 (n=3)	0.63 + 0.394 (n=6)	3.74 + 2.48 (n=7)	4.05 (n=l)	15.8 ±15.0 (n=5)

Example 6 - Serologic Analysis of Pseudotyped Vectors

C57BL/6 mice were injected with vectors of different serotypes of AAVCBA1 AT vectors intramuscularly (5 x 10^!1 GC) and serum samples were colfected 34 days later. To test neutralizing and cross-neutralizing activity' of sera to each serotype of A AV, sera was analyzed in a transduction based neutralizing antibody assay [Gao, G. P., et a!., (1996) J

Virol 70, 8934-43], More specifically, the presence of neutralizing antibodies was determined by assessing the ability of serum to inhibit transduction of 84-31 ceils by reporter viruses (AAVCMVEGFP) of different serotypes. Specifically, the reporter virus AAVCMVEGFP of each serotype [at multiplicity of infection (MOI) that led to a transduction of 90% of indicator ceils] was pre-incubated with heat-inactivated serum from animals that received different serotypes of AAV or from naive mice. After 1-hour incubation at 37° C, viruses were added to 84-31 cells in 96 well plates for 48 or 72- hour, depending on the virus serotype. Expression of GFP was measured by Fluorolmagin (Molecular Dynamics) and quantified by Image Quant Software. Neutralizing antibody titers were reported as the highest serum dilution that inhibited transduction to less than 50%.

The availability of GFP expressing vectors simplified the development of an assay for neutralizing antibodies that was based on inhibition of transduction in a permissive ceil line (i.e., 293 ceils stably expressing E4 from Ad5). Sera to selected AAV serotypes were generated by intramuscular injection of the recombinant viruses. Neutralization of AAV transduction by 1:20 and 1:80 dilutions of the antisera was evaluated (See Table 5 below).

Antisera to AAV1, AAV2, AAVS and AAVS neutralized transduction of the serotype to which the antiserum was generated (AAVS and AAV8 to a lesser extent than AAV1 and AAV2) but not to the other serotype (i.e., there was no evidence of cross neutralization suggesting that AAV 8 is a truly unique serotype).

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Table 5. Serological Analysis of New AAV Serotypes.

	%	nfection on 84-31 cells with AAVCMVEGFP virus:
AAV2/1	AAV2/2	AAV2/5	AAV2/7	AAV2/8
Serum dilution:	Serum dilution:	Serum dilution:	Serum dilution:	Serum dilution:
Sera:	Immunization Vector	1/20	1/80	1/20	1/80	1/2.0	1/80	1/20	1/80	1/20	1/80
Group 1	AAV2/1	0	0	100	100	100	100	100	100	100	100
Group 2	AAV2/2	100	100	0	0	100	100	100	100	100	100
Group 3	AAV2/S	100	100	100	100	16.5	16.5	100	100	100	100
Group 4	AAV2/7	100	100	100	100	100	100	61.5	100	100	100
Group 5	AAV2/8	100	100	100	100	100	100	100	100	26.3	60

Human sera from 52 normal subjects were screened for neutralization against selected serotypes. No serum sample was found to neutralize AAV2/7 and AAV2/8 while AAV2/2 and AAV2/1 vectors were neutralized in 20% and 10% of sera, respectively. A fraction of human pooled IgG representing a collection of 60,000 individual samples did not neutralize AAV2/7 and AAV2/8, whereas AAV2/2 and AAV2/1 vectors were neutralized at titers of serum equal to 1/1280 and 1/640, respectively.

Example 7 - In vivo Evaluation of Different Sero types of AAV Vectors

In this study, 7 recombinant AAV genomes, AAV2CBhAlAT, AAV2AlbhAlAT,

AAV2CMVrhCG, AAV2TBGrhCG, AAV2TBGcFIX, AAV2CMVLacZ and

AAV2TBGLacZ were packaged with capsid proteins of different serotypes. In all 7 constructs, minigene cassettes were flanked with AAV2 ITRs. cDNAs of human aantitrypsin (A1AT) [Xiao, W., et al., (1999) J Virol 73, 3994-4003] β-subunit of rhesus monkey choriogonadotropic hormone (CG) [Zoltick, P. W. & Wilson, J. M. (2000) Mol Ther 2, 657-9] canine factor IX [Wang, L., et al., (1997) Proc Natl Acad Sci USA 94, 11563-6] and bacterial β-glactosidase (i.e., Lac Z) genes were used as reporter genes. For liverdirected gene transfer, either mouse albumin gene promoter (Alb) [Xiao, W. (1999), cited above] or human thyroid hormone binding globulin gene promoter (TBG) [Wang (1997), cited above] was used to drive liver specific expression of reporter genes. In muscle-directed gene transfer experiments, either cytomegalovirus early promoter (CMV) or chicken β-actin promoter with CMV enhancer (CB) was employed to direct expression of reporters.

For muscle-directed gene transfer, vectors were injected into the right tibialis anterior of 4-6 week old NCR nude or C57BL/6 mice (Taconic, Germantown, NY), In liver-directed gene transfer studies, vectors were infused intraportally into 7-9 week old NCR nude or C57BL/6 mice (Taconic, Germantown, NY). Serum samples were collected intraorbitally at

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2015258271 20 Nov 2015 different time points after vector administration. Muscle and liver tissues were harvested at different time points for cryosectioning and Xgal histochemical staining from animals that received the lacZ vectors. For the re-administration experiment, C56BL/6 mice initially received AAV2/1, 2/2, 2/5, 2/7 and 2/8CBA1AT vectors intramuscularly and followed for

A1AT gene expression for 7 weeks. Animals were then treated with AAV2/8TBGcFIX intraportally and studied for cFIX gene expression.

ELISA based assays were performed to quantify serum levels of hAlAT, rhCG and cFIX proteins as described previously [Gao, G. P., et al., (1996) J Virol 70, 8934-43; Zoltick, P. W. & Wilson, J. M. (2000) Mol Ther 2, 657-9; Wang, L., et al., Proc Natl Acad Sci USA.

94, 11563-6], The experiments were completed when animals were sacrificed for harvest of muscle and liver tissues for DNA extraction and quantitative analysis of genome copies of vectors present in target tissues by TaqMan using the same set of primers and probe as in titration of vector preparations [Zhang, Y., et ah, (2001) Mol Ther 3, 697-707].

The performance of vectors base on the new serotypes were evaluated in murine models of muscle and liver-directed gene transfer and compared to vectors based on the known serotypes AAV1, AAV2 and AAV5. Vectors expressing secreted proteins (alphaantitrypsin (A1AT) and chorionic gonadotropin (CG)) were used to quantitate relative transduction efficiencies between different serotypes through ELISA analysis of sera. The cellular distribution of transduction within the target organ was evaluated using lacZ expressing vectors and X-gal histochemistry .

The performance of AAV vectors in skeletal muscle was analyzed following direct injection into the tibialis anterior muscles. Vectors contained the same AAV2 based genome with the immediate early gene of CMV or a CMV enhanced β-actin promoter driving expression of the transgene. Previous studies indicated that immune competent C57BL/6 mice elicit limited humoral responses to the human A1AT protein when expressed from AAV vectors [Xiao, W., et al., (1999) J Virol 73, 3994-4003].

In each strain, AAV2/1 vector produced the highest levels of A1AT and NNN2TI vector the lowest, with AAV2/7 and AAV2/8 vectors showing intermediate levels of expression. Peak levels of CG at 28 days following injection of nu/nu NCR mice showed the highest levels from AAV2/7 and the lowest from AAV2/2 with AAV2/8 and AAV2/1 in between. Injection of AAV2/1 and AAV2/7 lacZ vectors yielded gene expression at the injection sites in all muscle fibers with substantially fewer lacZ positive fibers observed with AAV2/2 and AAV 2/8 vectors. These data indicate that the efficiency of transduction with

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AAV2/7 vectors in skeletal muscle is similar to that obtained with AAV2/1, which is the most efficient in skeletal muscle of the previously described serotypes [Xiao, W. (1999), cited above; Chao, H., et al., (2001) Mol Ther 4, 217-22; Chao, H., et al., (2000) Mol Ther 2, 619-23].

Similar murine models were used to evaluate liver-directed gene transfer. Identical doses of vector based on genome copies were infused into the portal veins of mice that were analyzed subsequently for expression of the transgene. Each vector contained an AAV2 based genome using previously described liver-specific promoters (i.e., albumin or thyroid hormone binding globulin) to drive expression of the transgene. More particularly, CMVCG and TBGCG minigene cassettes were used for muscle and liver-directed gene transfer, respectively. Levels of rhCG were defined as relative units (RUs x 10^J). The data were from assaying serum samples collected at day 28, post vector administration (4 animals per group). As shown in Table 3, the impact of capsid proteins on the efficiency of transduction of Al AT vectors in nu/nu and C57BL/6 mice and CG vectors in C57BL/6 mice was consistent (See Table 6).

Table 6. Expression of β-unit of Rhesus Monkey Chorionic Gonadotropin (rhCG)

Vector	Muscle	Liver
AAV2/1	4.5 ± 2.1	1.6 ± 1.0
AAV2	0.5 ± 0.1	0.7 ± 0.3
AAV2/5	ND*	4.8 ± 0.8
AAV2/7	14.2 ± 2.4	8.2 ± 4.3
AAV2/8	4.0 ± 0.7	76.0 ± 22.8

* Not determined in this experiment.

In all cases, AAV2/8 vectors yielded the highest levels of transgene expression that ranged from 16 to 110 greater than what was obtained with AAV2/2 vectors; expression from AAV2/5 and AAV2/7 vectors was intermediate with AAV2/7 higher than AAV2/5. Analysis of X-Gal stained liver sections of animals that received the corresponding lacZ vectors showed a correlation between the number of transduced ceils and overall levels of transgene expression. DNAs extracted from livers of C57BL/6 mice who received the A1AT vectors were analyzed for abundance of vector DNA using real time PCR technology.

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The amount of vector DNA found in liver 56 days after injection con-elated with the levels of transgene expression (See Table 7). For this experiment, a set of probe and primers targeting the SV40 poly A region of the vector genome was used for TaqMan PCR. Values shown are means of three individual animals with standard deviations. The animals were sacrificed at day 56 to harvest liver tissues for DNA extraction. These studies indicate that AAV8 is the most efficient vector for liver-directed gene transfer due to increased numbers of transduced hepatocytes.

Table 7 - Real Time PCR Analysis for Abundance of AAV Vectors in nu/nu Mouse

Liver Following Injection of lxl0ⁿ Genome Copies of Vector.

AAV vectors/Dose Genome Copies per Cell

AAV2/lAlbAlAT	0.6 ±	0.36
AAV2AlbAlAT	0.003 + 0.001
AAV2/5AlbAlAT	0.83 ±	0.64
AAV2/7AIbAlAT	2.2 +	1.7
AAV2/8AlbAlAT	18 +	II

The serologic data described above suggest that AAV2/8 vector should not be neutralized in vivo following immunization with the other serotypes. C57BL/6 mice received intraportal injections of AAV2/8 vector expressing canine factor IX (10ⁿ genome copies) 56 days after they received intramuscular injections of Al AT vectors of different serotypes. High levels of factor IX expression were obtained 14 days following infusion of

AAV2/8 into naive animals (17+2 pg/ml, n=4) which were not significantly different that what was observed in animals immunized with AAV2/1 (31+23 pg/ml, n=4), AAV2/2 (16 pg/ml, n=2), and AAV2/7 (12 pg/ml, n=2). This contrasts to what was observed in AAV2/8 immunized animals that were infused with the AAV2/8 factor IX vector in which no detectable factor IX was observed (< 0.1 pg/ml, n=4).

Oligonucleotides to conserved regions of the cap gene did amplify sequences from rhesus monkeys that represented unique AAVs. identical cap signature sequences were found in multiple tissues from rhesus monkeys derived from at least two different colonies. Full-length rep and cap open reading frames were isolated and sequenced from single

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2015258271 20 Nov 2015 sources. Only the cap open reading frames of the novel AAVs were necessary to evaluate their potential as vectors because vectors with the AAV7 or AAV8 capsids were generated using the ITRs and rep from AAV2. This also simplified the comparison of different vectors since the actual vector genome is identical between different vector serotypes. In fact, the yields of recombinant vectors generated using this approach did not differ between serotypes.

Vectors based on AAV7 and AAVS appear to be immunologically distinct (i.e., they are not neutralized by antibodies generated against other serotypes). Furthermore, sera from humans do not neutralize transduction by AAV7 and AAVS vectors, which is a substantial advantage over the human derived AAVs currently under development for which a significant proportion of the human population has pre-existing immunity that is neutralizing [Chirmule, N., etal., (1999) Gene Ther 6, 1574-83],

The tropism of each new vector is favorable for in vivo applications.

AAV2/7 vectors appear to transduce skeletal muscle as efficiently as AAV2/1, which is the serotype that confers the highest level of transduction in skeletal muscle of the primate AAVs tested to date [Xiao, W., cited above; Chou (2001), cited above, and Chou (2000), cited above]. Importantly, AAV2/8 provides a substantial advantage over the other serotypes in terms of efficiency of gene transfer to liver that until now has been relatively disappointing in terms of the numbers of hepatocytes stably transduced. AAV2/8 consistently achieved a 10 to 100-fold improvement in gene transfer efficiency as compared to the other vectors. The basis for the improved efficiency of AAV2/8 is unclear, although it presumably is due to uptake via a different receptor that is more active on the basolateral surface of hepatocytes. This improved efficiency will be quite useful in the development of liver-directed gene transfer where the number of transduced cells is critical, such as in urea cycle disorders and familial hypercholesterolemia.

Thus, the present invention provides a novel approach for isolating new AAVs based on PCR retrieval of genomic sequences. The amplified sequences were easily incorporated into vectors and tested in animals. The lack of pre-existing immunity to AAV7 and the favorable tropism of the vectors for muscle indicates that AAV7 is suitable for use as a vector in human gene therapy and other in vivo applications. Similarly, the lack of preexisting immunity to the AAV serotypes of the invention, and their tropisms, renders them useful in delivery of therapeutic molecules and other useful molecules.

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Example 9 - Tissue Tropism Studies

In the design of a high throughput functional screening scheme for novel AAV constructs, a non-tissue specific and highly active promoter, CB promoter (CMV enhanced chicken β actin promoter) was selected to drive an easily detectable and quantifiable reporter gene, human a anti-trypsin gene, Thus only one vector for each new AAV clone needs to be made for gene transfer studies targeting 3 different tissues, liver, lung and muscle to screen for tissue tropism of a particular AAV construct. The following table summarizes data generated from 4 novel AAV vectors in the tissue tropism studies (AAVCBA1 AT), from which a novel AAV capsid clone, 44.2, was found to be a very potent gene transfer vehicle in all 3 tissues with a big lead in the lung tissue particularly. Table 8 reports data obtained (in pg AlAT/mL serum) at day 14 of the study.

Table 8

Vector	Target Tissue
	Lung	Liver	Muscle
AAV2/1	ND	ND	45+11
AAV2/5	0.6+0.2	ND	ND
AAV2/8	ND	84+30	ND
AAV2/rh.2 (43.1)	14+7	25+7.4	35+14
AAV2/rh.l0 (44.2)	23+6	53+19	46+11
AAV2/rh.l3 (42.2)	3.5+2	2+0.8	3.5+1.7
AAV2/rh.21 (42.10)	3.1+2	2+1.4	4.3+2

A couple of other experiments were then performed to confirm the superior tropism of AAV 44.2 in lung tissue. First, AAV vector carried CClOhAlAT minigene for lung specific expression were pseudotyped with capsids of novel AAVs were given to Immune deficient animals (NCR nude) in equal volume (50 μΐ each of the original preps without dilution) via intratracheal injections as provided in the following table. In Table 9, 50 μΐ of each original prep per mouse, NCR Nude, detection limit >0.033 pg/ml, Day 28

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Table 9

Vector	Total GC in 50 μϊ vector	μ§ of AlAT/ml with 50μ1 vector	of AlAT/ml with IxlO11 vector	Relative Gene transfer as compared to rh.10 (done 44.2)
2/1	3xl012	2.6±0.5	0.09±0.02	2,2
2/2	5.5x2O!1	<0.03	<0.005	<0.1
2/5	3.6xl0‘2	0.65+0.16	0.02+0.004	0.5
2/7	4.2xlOi2	l±0.53	0.02+0.01	0.5
2/8	7.5xiOn	0.9±0.7	0.12+0.09	2.9
2/ch.5 (A.3.1)	9xl012	1+0.7	0.01+0.008	0.24
2/rh.S (43.25)	4.6x1012	26+21	0.56+0.46	13.7
2/rh.lO (44.2)	2.8xl012	115±38	4.3 ±1.4	100
2/rh.l3 (42.2)	6xl012	7.3+0.8	0.12+0.01	2.9
2/rh.21 (42.10)	2,4xl012	9+0.9	0.38±0.04	9.3
2/rh.22 (42.11)	2,6xlQ12	6±0.4	0.23+0.02	5.6
2/rh.24 (42.13)	l.ixlO11	0.4+0.3	0.4+0.3	1

The vectors were also administered to immune competent animals (C57BL/6) in equal 5 genome copies (lxl0ⁿ GC) as shown in the Table 10. (IxlO¹¹ GC per animal, C57BL/6, day

14, detection limit >0.033 pg/ml)

Table 10

AAV Vector	μ§ of AlAT/ml with IxlO11 vector	Relative Gene transfer as compared to rh.10 (done 44.2)
2/1	0.076+0.031	2.6
2/2	0,1+0.09	3.4
2/5	0.0840.033	2.9
2/7	0,33+0.01	li
2/8	1.92+1.3	2.9
2/ch.5 (A.3.1)	0.048+0.004	1.6
2/rh.8 (43.25)	1.7+0.7	58
2/rh.lO (44.2)	2.93+1.7	100
2/rh.l3 (42.2)	0.45+0.15	15
2/rh.21 (42.30)	0.86+0.32	29
2/rh.22 (42.11)	0.38+0.18	13
2/rh.24 (42.13)	0.3+0.19	10

The data from both experiments confirmed the superb trap ism of clone 44.2 in lungdirected gene transfer.

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Interestingly, performance of clone 44.2 in liver and muscle directed gene transfer was also outstanding, close to that of the best liver transducer, AAV8 and the best muscle transducer AAV1, suggesting that this novel AAV has some intriguing biological significance.

To study serological properties of those novel AAVs, pseudotyped AAVGFP vectors were created for immunization of rabbits and in vitro transduction of 84-31 cells in the presence and absence of antisera against different capsids. The data are summarized below:

Table Ila. Cross-NAB assay in 8431 cells and adenovirus (Adv) coinfection

Infection in 8431 cells (coinfected with Adv) with:

Serum from rabbit immunized with:	109 GC	109 GC	109 GC	10!° GC
rh.13	rh.21	rh.22	rh.24
AAV2/42.2	AAV2/42.10	AAV2/42.11	AAV2/42.13
AAV2/1	1/20	1/20	1/20	No NAB
AAV2/2	1/640	1/1280	1/5120	No NAB
AAV2/5	No NAB	1/40	1/160	No NAB
AAV2/7	1/81920	1/81920	1/40960	1/640
AAV2/8	1/640	1/640	1/320	1/5120
Ch.5 AAV2/A3	1/20	1/160	1/640	1/640
rh.8 AAV2/43.25	1/20	1/20	1/20	1/320
rh.10 AAV2/44.2	No NAB	No NAB	No NAB	1/5120
rh.13 AAV2/42.2	1/5120	1/5120	1/5120	No NAB
rh.21 AAV2/42.10	1/5120	1/10240	1/5120	1/20
rh.22 AAV2/42.11	1/20480	1/20480	1/40960	No NAB
rh.24 AAV2/42.13	No NAB	1/20	1/20	1/5120

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Table 11b. Cross-NAB assay in 8431 cells andAdv coinfection

Infection in 8431 cells (coinfected with Adv) with:

Serum from rabbit immunized with:	109 GC	101°GC	101°GC	109 GC	109 GC
rh.12	ch.5	rh.8	rh.10	rh.20
AAV2/42.1B	AAV2/A3	AAV2/43.25	AAV2/44.2	AAV2/42.8.2
AAV2/1 '	No NAB	1/20480	No NAB	1/80	ND
AAV2/2	1/20	No NAB	No NAB	No NAB	ND
AAV2/5	No NAB	1/320	No NAB	No NAB	ND
AAV2/7	1/2560	1/640	1/160	1/81920	ND
AAV2/8	1/10240	1/2560	1/2560	1/81920	ND
ch.5 AAV2/A3	1/1280	1/10240	ND	1/5120	1/320
rh.8 AAV2/43.25	1/1280	ND	1/20400	1/5120	1/2560
rh.10 AAV2/44.2	1/5120	ND	ND	1/5120	1/5120
rh.13 AAV2/42.2	1/20	ND	ND	No NAB	1/320
rh.21 AAV2/42.10	1/20	ND	ND	1/40	1/80
rh.22 AAV2/42.11	No NAB	ND	ND	ND	No NAB
rh.24 ΑΑΝ2/42Λ3	1/5120	ND	ND	ND	1/2560

Table 12

Titer of rabbit sera	Titer after Boosting
Vector	Titer d21
ch.5	AAV2/A3		1/10,240	1/40,960
rh.8	AAV2/43.25		1/20,400	1/163,840
rh.10	AAV2/44.2		1/10,240	1/527,680
rh.13	AAV2/42.2		1/5,120	1/20,960
rh.21	AAV2/42.10		1/20,400	1/81,920
rh.22	AAV2/42.11		1/40,960	ND
rh.24	AAV2/42.13		1/5,120	ND

Table 13 a. infection in 8431 cells (coinfected with Adv) with GFP

	109 GC/weli	10s GC/weli	109 GC/weii	109 GC/weii	109 GC/weii	109 GC/weli
					ch.5
AAV2/1	AAV2/2	AAV2/5	AAV2/7	AAV2/8	AAV2/A3
# GFU/field	128	>200	95	56	13	4 S
83	>200	65	54	11	1

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Table 13b. Infection in 8431 cells (coinfected with Adv) with GFP

	109 GC/well	10s GC/well	109 GC/weil	109 GC/well	109 GC/well	10s GC/well	10s GC/weil
rh.8	rh.10	rh.13	rh.21	rh.22	rh.24	rh.12
AAV2/43.25	AAV2/44.2	AAV2/42.2	AAV2/42.10	AAV2/42.11	AAV2/42.13	AAV2/42.1B
# GFU/field	3	13	54	62	10	3	18
2	12	71	60	14	2	20
		48	47	16	3	12

Example 10 — Mouse Model of Familial Hypercholesterolemia

The following experiment demonstrates that the AAV2/7 construct of the invention delivers the LDL receptor and express LDL receptor in an amount sufficient to reduce the levels of plasma cholesterol and triglycerides in animal models of familial hypercholesterolemia.

A. Vector Construction

AAV vectors packaged with AAV7 or AAV8 capsid proteins were constructed using a pseudotyping strategy [Hildinger M, et al., J. Virol 2001; 75:6199-6203]. Recombinant AAV genomes with AAV2 inverted terminal repeats (ITR) were packaged by triple transfection of 293 cells with the c/s-plasmid, the adenovirus helper plasmid and a chimeric packaging construct, a fusion of the capsids of the novel AAV serotypes with the rep gene of AAV2. The chimeric packaging plasmid was constructed as previously described [Hildinger et al, cited above]. The recombinant vectors were purified by the standard CsCl₂ sedimentation method. To determine the yield TaqMan (Applied Biosystems) analysis was performed using probes and primers targeting the SV40 poiy(A) region of the vectors [Gao

GP, et al., Hum Gene Ther. 2000 Oct 10;l 1( 15):2079-91]. The resulting vectors express the transgene under the control of the human thyroid hormone binding globulin gene promoter (TBG).

B. Animals

LDL receptor deficient mice on the C57B1/6 background were purchased from the Jackson Laboratory (Bar Harbor, ME, USA) and maintained as a breeding colony. Mice were given unrestricted access to water and obtained a high fat Western Diet (high % cholesterol) starting three weeks prior vector injection. At day -7 as well at day 0, blood was obtained via retroorbitai bleeds and the lipid profile evaluated. The mice were randomly divided into seven groups. The vector was injected via an intraportal injection as previously

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2015258271 20 Nov 2015 described ([Chen SJ et al., Mol Therapy 2000; 2(3), 256-261]. Briefly, the mice were anaesthetized with ketamine and xylazine. A laparotomy was performed and the portal vein exposed. Using a 30g needle the appropriate dose of vector diluted in lOOul PBS was directly injected into the portal vein. Pressure was applied to the injection site to ensure a stop of the bleeding. The skin wound was closed and draped and the mice carefully monitored for the following day. Weekly bleeds were performed starting at day 14 after liver directed gene transfer to measure blood lipids. Two animals of each group were sacrificed at the time points week 6 and week 12 after vector injection to examine atherosclerotic plaque size as well as receptor expression. The remaining mice were sacrificed at week 20 for plaque measurement and determination of transgene expression.

Table 14

	Vector	dose	n
Group 1	AAV2/7-TBG-hLDLr	lx 1012 gc	12
Group 2	AAV2/7-TBG-hLDLr	3x I01! gc	12
Group 3	AAV2/7-TBG-hLDLr	lx 10” gc	12
Group 4	AAV2/8-TBG-hLDLr	lx 10!2gc	12
Group 5	AAV2/8-TBG-hLDLr	3x 10n gc	12
Group 6	AAV2/8-TBG-hLDLr	lxl0gc	12
Group 7	AAV2/7-TBG- LacZ	lx 1011 gc	16

C. Serum lipoprotein and liver function analysis

Blood samples were obtained from the retroorbital plexus after a 6 hour fasting period. The serum was separated from the plasma by centrifugation. The amount of plasma lipoproteins and liver transaminases in the serum were detected using an automatized clinical chemistry analyzer (ACE, Schiapparelii Biosystems, Alpha Wassermann)

D. Detection of transgene expression

LDL receptor expression was evaluated by immuno-fluorescence staining and Western blotting. For Western Blot frozen liver tissue was homogenized with lysis buffer ( 20 mM Tris, pH7.4, 130mM NaCl, 1% Triton X 100, proteinase inhibitor (complete, EDTA-free, Roche, Mannheim, Germany). Protein concentration was determined using the Micro BCA Protein Assay Reagent Kit (Pierce, Rockford, IL). 40 pg of protein was resolved on 4- 15% Tris-HCl Ready Gels (Biorad, Hercules, CA) and transferred to a nitrocellulose

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2015258271 20 Nov 2015 membrane (Invitrogen,). To generate Anti-hLDL receptor antibodies a rabbit was injected intravenously with an AdhLDLr prep (lxlO¹³ GC). Four weeks later the rabbit serum was obtained and used for Western Blot. A 1:100 dilution of the serum was used as a primary antibody followed by a HKP-conjugated anti-rabbit IgG and ECL chemiluminescent detection (ECL Western Blot Detection Kit. Amersham, Arlington Heights, IL).

E. Immunocytochemistry

For determination of LDL receptor expression in frozen liver sections immunohistochemistry analyses were performed. lOum cryostat sections were either fixed in acetone for 5 minutes, or unfixed. Blocking was obtained via a 1 hour incubation period with

10% of goat serum. Sections were then incubated for one hour with the primary antibody at room temperature. A rabbit polyclonal antibody anti-human LDL (Biomedical Technologies Inc., Stoughton, MA) was used diluted accordingly to the instructions of the manufacturer. The sections were washed with PBS, and incubated with 1:100 diluted fluorescein goat antirabbit IgG (Sigma, St Louis, MO). Specimens were finally examined under fluorescence microscope Nikon Microphot-FXA. In all cases, each incubation was followed by extensive washing with PBS. Negative controls consisted of preincubation with PBS, omission of the primary antibody, and substitution of the primary antibody by an isotype-matched nonimmune control antibody. The three types of controls mentioned above were performed for each experiment on the same day.

F. Gene transfer efficiency

Liver tissue was obtained after sacrificing the mice at the designated time points. The tissue was shock frozen in liquid nitrogen and stored at -80°C until further processing. DNA was extracted from the liver tissue using a QIAamp DNA Mini Kit (QIAGEN GmbH, Germany) according to the manufacturers protocol. Genome copies of

AAV vectors in the liver tissue were evaluated using Taqman analysis using probes and primers against the SV40 poly(A) tail as described above.

G. Atherosclerotic plaque measurement

For the quantification of the atherosclerotic plaques in the mouse aorta the mice were anaesthetized (10% ketamine and xylazine, ip), the chest opened and the arterial system perfused with ice-cold phosphate buffered saline through the left ventricle. The aorta was then carefully harvested, slit down along the ventral midline from the aortic arch down to the femoral arteries and fixed in formalin. The lipid-rich atherosclerotic plaques were stained with Sudan IV (Sigma, Germany) and the aorta pinned out flat on a

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2015258271 20 Nov 2015 black wax surface. The image was captured with a Sony DXC-960 MD color video camera. The area of the plaque as well as of the complete aortic surface was determined using Phase 3 Imaging Systems (Media Cybernetics).

H. Clearance of 1¹²⁵ LDL

Two animals per experimental group were tested. A bolus of 1¹²⁵ ~ labeled LDL (generously provided by Dan Rader, U Penn) was infused slowly through the tail vein over a period of 30 sec (1,000,000 counts of [I^!2i ]-LDL diluted in 100μ1 sterile PBS/ animal). At time points 3min, 30 min, 1,5hr, 3hr, 6hr after injection a blood sample was obtained via the retro-orbital plexus. The plasma was separated off from the whole blood and 10μ1 plasma counted in the gamma counter. Finally the fractional catabolic rate was calculated from the lipoprotein clearance data.

I. Evaluation of Liver Lipid accumulation

Oil Red Staining of frozen liver sections was performed to determine lipid accumulation. The frozen liver sections were briefly rinsed in distilled water followed by a 2 minute incubation in absolute propylene glycol. The sections were then stained in oil red solution (0.5% in propylene glycol) for 16 hours followed by counterstaining with Mayer’s hematoxylin solution for 30 seconds and mounting in warmed glycerin jellysolution.

For quantification of the liver cholesterol and triglyceride content liver sections were homogenized and incubated in chloroform/methanol (2:1) overnight. After adding of 0.05% H2SO4 and centrifugation for 10 minutes, the lower layer of each sample was collected, divided in two aliquots and dried under nitrogen. For the cholesterol measurement the dried lipids of the first aliquot were dissolved in 1% Triton X-100 in chloroform. Once dissolved, the solution was dried under nitrogen. After dissolving the lipids in ddfUO and incubation for 30 minutes at 37°C the total cholesterol concentration was measured using a Total Cholesterol Kit (Wako Diagnostics). For the second aliquot the dried lipids were dissolved in alcoholic KOH and incubated at 60°C for 30 minutes. Then 1M MgC12 was added, followed by incubation on ice for 10 minutes and centrifugation at 14,000 rpm for 30 minutes. The supernatant was finally evaluated for triglycerides (Wako

Diagnostics).

All of the vectors pseudotyped in an AAV2/8 or AAV2/7 capsid lowered total cholesterol, LDL and triglycerides as compared to the control. These test vectors also corrected phenotype of hypercholesterolemia in a dose-dependent manner. A reduction in

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Example 10 - Functional Factor IX Expression and Correction of Hemophilia A. Knock-Out Mice

Functional canine factor IX (FIX) expression was assessed in hemophilia B mice. Vectors with capsids of AAVl, AAV2, AAV5, AAV7 or AAV8 were constructed to deliver AAV2 5’ ITR - liver-specific promoter [ESP] - canine FIX - woodchuck hepatitis post-regulatory element (WPRE) - AAV2 3’ ITR , The vectors were constructed as described in Wang et al, 2000, Molecular Therapy 2: 154-158), using the appropriate capsids.

Knock-out mice were generated as described in Wang et al, 1997. Proc. Natl. Acad. Sci. USA 94: 11563-11566. This model closely mimic the phenotypes of hemophilia

B in human.

Vectors of different serotypes (AAVl, AAV2, AAVS, AAV7 and AAVS) were delivered as a single intraportal injection into the liver of adult hemophiliac C57B1/6 mice in a dose of 1x10¹¹ GC/mouse for the five different serotypes and one group received an AAV8 vector at a lower dose, lxlO¹⁰ GC/mouse. Control group was injected with lxl0ⁿ

GC of AAV2/8 TBG LacZ3. Each group contains 5-10 male and female mice. Mice were bled bi-weekly after vector administration.

1. ELISA

The canine FIX concentration in the mouse plasma was determined by an ELISA assay specific for canine factor IX, performed essentially as described by

Axelrod et al, 1990, Proc.Natl.Acad.Sci.USA, 87:5173-5177 with modifications. Sheep anticanine factor IX (Enzyme Research Laboratories) was used as primary antibody and rabbit anti-canine factor IX ((Enzyme Research Laboratories) was used as secondary antibody. Beginning at two weeks following injection, increased plasma levels of cFIX were detected for all test vectors. The increased levels were sustained at therapeutic levels throughout the length of the experiment, i.e., to 12 weeks. Therapeutic levels are considered to be 5% of normal levels, i.e,, at about 250 ng/mL.

The highest levels of expression were observed for the AAV2/8 (at I0ⁿ) and AAV2/7 constructs, with sustained superphysiology levels cFIX levels (ten-fold higher than the normal level). Expression levels for AAV2/8 (10¹ ’) were approximately 10 fold higher

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2. In Vitro Activated Partial Thromboplastin time (aPTT) Assay

Functional factor IX activity in plasma of the FIX knock-out mice was determined by an in vitro activated partial thromboplastin time (aPTT) assay-Mouse blood samples were collected from the retro-orbital plexus into 1/10 volume of citrate buffer. The aPTT assay was performed as described by Wang et al, 1997, Proc. Natl: Acad. Sci.

USA 94:11563-11566.

Clotting times by aPTT on plasma samples of all vector injected mice were within the normal range (approximately 60 sec) when measured at two weeks postinjection, and sustained clotting times in the normal or shorter than normal range throughout the study period (12 weeks).

Lowest sustained clotting times were observed in the animals receiving AAV2/8 (10¹¹) and AAV2/7. By week 12, AAV2/2 also induced clotting times similar to those for AAV2/8 and AAV2/7. However, this lowered clotting time was not observed for AAV2/2 until week 12, whereas lowered clotting times (in the 25 - 40 sec range) were observed for AAV2/8 and AAV2/7 beginning at week two.

Immuno-histochemistry staining on the liver tissues harvested from some of the treated mice is currently being performed. About 70-80% of hepatocytes are stained positive for canine FIX in the mouse injected with AAV2/8.cFIX vector.

B. Hemophilia B Dogs

Dogs that have a point mutation in the catalytic domain of the F.IX gene, which, based on modeling studies, appears to render the protein unstable, suffer from hemophilia B [Evans et al, 1989, Proc. Natl. Acad. Sci. USA, 86:10095-10099). A colony of such dogs has been maintained for more than two decades at the University of North Carolina, Chapel Hill. The homeostatic parameters of these dogs are well described and include the absence of plasma F.IX antigen, whole blood clotting times in excess of 60 minutes, whereas normal dogs are 6-8 minutes, and prolonged activated partial thromboplastin time of 50-80 seconds, whereas normal dogs are 13-28 seconds. These dogs experience recurrent spontaneous hemorrhages. Typically, significant bleeding episodes are successfully managed by the single intravenous infusion of 10 ml/kg of normal canine plasma; occasionally, repeat infusions are required to control bleeding.

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Four dogs are injected intraportally with AAV.cFIX according to the schedule below. A first dog receives a single injection with AAV2/2.cFIX at a dose of 3.7x10^{s 1} genome copies (GC)/kg. A second dog receives a first injection of AAV2/2.cFIX (2.8x10^l ’ GC/kg), followed by a second injection with AAV2/7.cFlX (2.3x10¹³ GC/kg) at day 1180. A third dog receives a single injection with AAV2/2.cFIX at a dose of 4.6x10¹² GC/kg. The fourth dog receives an injection with AAV2/2.cFIX (2.8x10¹² GC/kg) and an injection at day 995 with AAV2/7.cFIX (5xl0¹² GC/kg).

The abdomen of hemophilia dogs are aseptically and surgically opened under generai anesthesia and a single infusion of vector is administered into the portal vein. The animals are protected from hemorrhage in the peri-operative period by intravenous administration of normal canine plasma. The dog is sedated, intubated to induce general anesthesia, and the abdomen shaved and prepped. After the abdomen is opened, the spleen is moved into the operative field. The splenic vein is located and a suture is loosely placed proximal to a small distal incision in the vein. A needle is rapidly inserted into the vein, then the suture loosened and a 5 F cannula is threaded to an intravenous location near the portal vein threaded to an intravenous location near the portal vein bifurcation. After hemostasis is secured and the catheter balloon inflated, approximately 5.0 ml of vector diluted in PBS is infused into the portal vein over a 5 minute interval. The vector infusion is followed by a 5.0 ml infusion of saline. The balloon is then deflated, the callula removed and venous hemostasis is secured. The spleen is then replaced, bleeding vessels are cauterized and the operative wound is closed. The animal is extubated having tolerated the surgical procedure well. Blood samples are analyzed as described. [Wang et al, 2000, Molecular Therapy 2: 154-158]

Results showing correction or partial correction are anticipated for AAV2/7.

All publications cited in this specification are incorporated herein by reference. While the invention has been described with reference to a particularly preferred embodiments, it will be appreciated that modifications can be made without departing from the spirit of the invention. Such modifications are intended to fall within the scope of the claims.

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The reference in this specification to any prior publication (or information derived from it), or to any matter which is known, is not, and should not be taken as an acknowledgment or admission or any form of suggestion that that prior publication (or information derived from it) or known matter forms part of the common general knowledge in the field of endeavour to which this specification relates.

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Claims (269)

1. THE CLAIMS DEFINING THE INVENTION ARE AS FOLLOWS:

   1. A recombinant adeno-associated virus (AAV) comprising an AAV capsid comprising vpl proteins having the sequence of amino acids 1 to 738 of SEQ ID NO: 85 (rh.20) or a sequence at least 95% identical to the full length of amino acids 1 to 738 of SEQ ID NO: 85, AAV vp2 proteins, and AAV vp3 proteins, wherein the recombinant AAV further comprises, packaged within the capsid a nucleic acid molecule comprising at least one AAV inverted terminal repeat (ITR), and a non-AAV nucleic acid sequence encoding a gene product operably linked to sequences which direct expression of the product in a host cell.
2. 2. The recombinant AAV according to claim 1, wherein the sequence of the vpl proteins is at least 97% identical to the full length of amino acids 1 to 738 of SEQ ID NO: 85.
3. 3. The recombinant AAV according to claim 1, wherein the sequence of the vp 1 proteins is at least 99% identical to the full-length of amino acids 1 to 738 of SEQ ID NO: 85.
4. 4. The recombinant AAV according to claim 1, wherein the sequence of the vp 1 proteins is the full-length of amino acids 1 to 738 of SEQ ID NO: 85.
5. 5. A recombinant adeno-associated virus (AAV) having an AAV capsid comprising AAV vpl proteins, AAV vp2 proteins having a sequence of amino acids 138 to 738 of SEQ ID NO:85 (rh.20) or a sequence at least 95% identical to the full-length of amino acids 138 to 738 of SEQ ID NO: 85, and AAV vp3 proteins, wherein the recombinant AAV further comprises, packaged within the capsid, a nucleic acid molecule comprising at least one AAV inverted terminal repeat (ITR) and a non-AAV nucleic acid sequence encoding a gene product operably linked to sequences which direct expression of the product in a host cell.
6. 6. The recombinant AAV according to claim 5, wherein the sequence of the vp2 proteins is at least 97% identical to the full length of amino acids 138 to 738 of SEQ ID NO: 85.

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   2015258271 18 Dec 2017
7. 7. The recombinant AAV according to claim 5, wherein the sequence of the vp2 proteins is at least 99% identical to the full-length of amino acids 138 to 738 of SEQ ID NO: 85.
8. 8. The recombinant AAV according to claim 5, wherein the sequence of the vp2 proteins is the frill-length of amino acids 138 to 738 of SEQ ID NO: 85.
9. 9. A recombinant adeno-associated virus (AAV) having an AAV capsid comprising AAV vpl proteins, AAV vp2 proteins, and AAV vp3 proteins having a sequence of amino acids 204 to 738 of SEQ ID NO:85 (rh.20) or a sequence at least 95% identical to the full-length of amino acids 204 to 738 of SEQ ID NO: 85, wherein the recombinant AAV further comprises, packaged within the capsid, a nucleic acid molecule comprising at least one AAV inverted terminal repeat (ITR) and a non-AAV nucleic acid sequence encoding a gene product operably linked to sequences which direct expression of the product in a host cell.
10. 10. The recombinant AAV according to claim 9, wherein the sequence of the vp3 proteins is at least 97% identical to the frill length of amino acids 204 to 738 of SEQ ID NO: 85.
11. 11. The recombinant AAV according to claim 9, wherein the sequence of the vp3 proteins is at least 99% identical to the full-length of amino acids 204 to 738 of SEQ ID NO: 85.
12. 12. The recombinant AAV according to claim 9, wherein the sequence of the vp3 proteins is the full-length of amino acids 204 to 738 of SEQ ID NO: 85.
13. 13. The recombinant AAV according to claim 9 wherein the AAV ITR is from AAV2.
14. 14. A composition comprising a pharmaceutically compatible carrier and at least the recombinant AAV according to claim 1.

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15. 15. A composition comprising a pharmaceutically compatible carrier and at least the recombinant AAV according to claim 5.
16. 16. A composition comprising a pharmaceutically compatible carrier and at least the recombinant AAV according to claim 9.
17. 17. A method of generating a recombinant adeno-associated virus (AAV) comprising an AAV capsid comprising culturing a host cell containing: (a) a molecule encoding the AAV vpl capsid protein having a sequence of amino acids 1 to 738 of SEQ ID NO: 85, or a sequence which is at least 95% identical to the full length of SEQ ID NO: 85; (b) a functional rep gene; (c) a minigene comprising a nucleic acid molecule comprising at least one AAV inverted terminal repeat (ITR) and a non-AAV nucleic acid sequence encoding a gene product operably linked to sequences which direct expression of the product in a host cell; and (d) sufficient helper functions to permit packaging of the minigene into the AAV capsid protein under conditions which permit packaging of the minigene into the AAV capsid.
18. 18. A method for delivering a trans gene product to a subject, said method comprising administering an adeno-associated virus (AAV) comprising an AAV capsid comprising AAV vpl proteins, AAV vp2 proteins, and AAV vp3 proteins having a sequence of amino acids 204 to 738 of SEQ ID NO:85 (rh.20) or a sequence at least 95% identical to the full-length of amino acids 204 to 738 of SEQ ID NO: 85, said AAV having packaged in the capsid a nucleic acid molecule comprising at least one AAV inverted terminal repeat (ITR) and a non-AAV nucleic acid sequence which encodes a gene product operably linked to sequences which direct expression thereof in a host cell.

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    FIG. 1A

    1 50

    4 2 2 ..................................................

    42 8 ..................................................

    4215 ..................................................

    42_5b ..................................................

    42_lb ..................................................

    4213 ..................................................

    42_3a .................... ..............................

    42 4 .../.............................................

    42_5a ..................................................

    42_10 ..................................................

    42_3b ..................................................

    4211 ..................................................

    42_6b ..................................................

    4 31 ..................................................

    4 3 5 ..................................................

    4312 ..................................................

    4320 ..................................................

    43 21 ........................................ ..........

    43_23 ................. .................................

    43 25 ..................................................

    441 ..................................................

    44_5 ..................................................

    223_10 .............................. ....................

    223 2 ..................................................

    223 4 .................... ..............................

    223 5 .............................. ....................

    223 6 ..................................................

    223 7 ..................................................

    A3_4 .......... ........................................

    A3_5 ..................................................

    A3_7 ..........................-.......................

    A 33 .................... ..............................

    42_12 ..................................................

    AAV1 TTGCCCACTC CCTCTCTGCG CGCTCGCTCG CTCGGTGGGG CCTGCGGACC AAV2 TTGGCCACTC CCTCTCTGCG CGCTCGCTCG CTCACTGAGG CCGGGCGACC AAV3 TTGGCCACTC CCTCTATGCG CACTCGCTCG CTCGGTGGGG CCTGGCGACC

    AAV8 .......... . ....................................-

    AAVS ..................................................

    AAV7 TTGGCCACTC CCTCTATGCG CGCTCGCTCG CTCGGTGGGG CCTGCGGACC 44 2 ....................................*.............

    1 /105

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    Fig. IB

    100

    42_2

    42_8

    42_15

    42_5b

    42_lb

    42_13

    42_3a

    42_4

    42_5a

    42J.0

    42_3b

    42_11

    42_6b

    43_1

    43_5

    43_12

    43_20

    43_21

    43_23

    43_25

    44_1

    44_5

    223_10

    223_2

    223_4

    223_5

    223_6

    223_7

    A3_4

    A3_5

    A3_7

    A3_3

    42_12

    AAV1

    AAV2

    AAV3

    AAV8

    AAV9

    AAV7

    44 2

    Rep binding^site

    AAAGGTCCGC AGACGGCAGA GCTCTGCTCT GCCGGCCCCA CCGAGCGAGC AAAGGTCGCC CGACGCCCGG GCTTTGCCCG GGCGGCCTCA GTGAGCGAGC AAAGGTCGCC AGACGGACGT GCTTTGCACG TCCGGCCCCA CCGAGCGAGC

    AAAGGTCCGC AGACGGCAGA

    GCTCTGCTCT GCCGGCCCCA CCGAGCGAGC

    Rep binding site

    2/105

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    101

    Fig. 1C

    150

    Rep binding site

    ◄- 492 . ... .............I........................... 42 8 ..........

    42_15

    42_5b

    42_lb

    42_13

    42_3a

    42_4

    42_5a

    42_10

    42_3b

    42_11

    42_5b

    43__1

    43_5

    43_12

    43_20

    43_21

    43_23

    43_25

    44_1

    44_5

    223_10

    223_2

    223_4

    223_5

    223_6

    223_7

    A3_4

    A3_5

    A3_7

    A3_3

    42_12

    AAV1

    AAV2

    AAV3

    GAGCGCGCAG AGAGGGAGTG GGCAACTCCA TCACTAGGGG TAATCGCGAA

    GAGCGCGCAG AGAGGGAGTG GCCAACTCCA TCACTAGGGG TTC.......

    GAGTGCGCAT AGAGGGAGTG GCCAACTCCA TCACTAGAGG T.........

    AAV8 .......CAG AGAGGGAGTG GCCAACTCCA TCACTAGGGG TAG.CGCGAA

    AAV9 .......CAG AGAGGGAGTG GCCAACTCCA TCACTAGGGG TAATCGCGAA

    GAGCGCGCAT AGAGGGAGTG GCdAACTCCA TCACTAGGGG TA.CCGCGAA

    AAV7

    44_2 .........

    Λίβρ Binding site’

    TRS

    3/105

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    Fig. ID

    151 200

    42_2 42_8 42_15 42_5b 42_lb 42_13 42_3a 42_4 42_5a 42_10 42_3b 42JL1 42_6b 43_1 43_5 43_12 43_20 43_21 43_23 43_25 44_1 44_5 223_10 223_2 223_4 2 23_5 223_6 223_7 A3_4 A3_5 A3J7 A3_3 42_12 AAV1 AAV2

    AAV3 .......ATG

    AAV8 GCGCCTCCCA AAV9 GCGCCTCCCA AAV7 GCGCCTCCCA 44 2 ..........

    GCGCCTCCCA .......CTG

    CGCTGCCGCG TCAGCGCTGA GAGGGGTGGA GTCGTGACGT GCAGTGACGT AACGCGAAGC CGCTGCCGCG TCAGCGCTGA CGCTGCCGCG TCAGCGCTGA CGCTGCCGCG TCAGCGCTGA

    CGTAAATTAC GTCATAGGGG GAATTACGTC ATAGGGTTAG GCGCGAAGCG AGACCACGCC CGTAAATTAC GTCATAGGGG CGTAGATTAC GTCATAGGGG CGTAAATCAC GTCATAGGGG

    4/105

    PCT/USO2/33629

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    Fig. IE

    201 250

    Ebox/USF YY1_

    42 2 ... -X. . - . X..........................X.......X · ·

    42^8 ........................................

    42_15 ...................................................

    42_5b ..................................................

    42_lb .............................. ....................

    4213 ..................................................

    42_3a ..................................................

    4 2 4 ..................................................

    42 5a ..................................................

    4210 ..................................................

    42_3b ..................................................

    4211 ..................................................

    42_6b ..................................................

    4 31 ..................................................

    4 3 5 ..................................................

    43_12 ..................................................

    4320 ..................................................

    43 21 ..................................................

    43_23 ...........................- - · -............

    43 25 ..................................................

    4 41 ..................................................

    4 4 5 ..................................................

    223 10 .........................-........................

    223_2 ..................................................

    22 3 4 ..................................................

    223 5 ..................................................

    223 6 .......... ........................................

    223 7 ..................................................

    A3_4 ..................................................

    A3_5 ........................................ ..........

    A3_7 ..................................................

    A3_3 ..................................................

    42_12 ..................................................

    AAVl AGTGGTCCTG TATTAGCTGT CACGTGAGTG CTTTTGCGAC ATTTTGCGAC

    AAV2 GGAGGTCCTG TATTAGAGGT CACGTGAGT. GTTTTGCGAC ATTTTGCGAC

    AAV3 T.ACCAGCTG CGTCAGCAGT CAGGTGACC. CTTTTGGGAC AGTTTGCGAC

    AAV8 AGTGGTCCTG TATTAGCTGT CACGTGAGTG CTTTTGCGGC ATTTTGCGAC

    AAV9 AGTGGTCCTG TATTAGCTGT CACGTGAGTG CTTTTGCGAC ATTTTGCGAC

    AAV7 AGTGGTCCTG TATTAGCTGT CACGTGAGTG CTTTTGCGAC ATTTTGCGAC

    44 2 .....f-·· · t.........................V....... Γ ' '

    Ebox/USF YY1

    5/105

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    251

    Fig. IF

    300

    42_2

    42_8

    42_15

    42_5b

    42JLb

    42JL3

    42_3a

    42_4

    42_5a

    42_10

    42_3b

    42_11

    42_6b

    43_1

    43_5

    43_12

    43_20

    43_21

    43_23

    43_25

    44_1

    44_5

    223_10

    223_2

    223_4

    223_5

    223_6

    223_7

    A3_4

    A3_5

    A3_7

    A3_3

    42_12

    AAV1

    AAV2

    AAV3

    AAV8

    AAV9

    AAV7

    44_2

    P5/TATA

    .....................4

    ACCACGTGGC

    ACCATGTGGT

    ACCACGTGGC

    ACCACGTGGC

    ACCACATGGC

    ACCACGTGGC

    CATTTAGGGT ATATATGGCC CACGCTGGGT ATTTAAGCCC CGCTGAGGGT ATATATTCTC CATTTGAGGT ATATATGGCC CATTTGAGGT ATATATGGCC CATTTGAGGT ATATATGGCC

    Nb/TAl^

    GAGTGAGC.G GAGTGAGC-A GAGTGAGCGA GAGTGAGC.G GAGTGAGC.G GAGTGAGC.G

    AGCAGGATCT

    CGCAGGGTCT

    ACCAGGAGCT

    AGCAGGATCT

    AGCAGGATCT

    AGCAGGATC|^

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    301

    Fig. 1G

    42_2

    42_a

    42_15

    42_5b

    42_lb

    42_13

    42_3a

    42_4

    42_5a

    42_10

    42_3b

    42_11

    42_6b

    43_1

    43_5

    43_12

    43_20

    43_21

    43_23

    43_25

    4 4 J.

    44_5 223_10 223_2 223_4 223_5 223_6 223J7

    A3_4

    A3_5

    A3_7

    A3_3

    42_12

    AAVl

    AAV2

    AAV3

    AAV8

    AAV9

    AAV7

    44_2

    YY1/P5 RNA

    350

    Rep78/68 start ¢+::::::::::

    CCATTTTGAC .CGCGAAATT TGAACGAGCA GCAGCCATGC CGGGCTTCTA CCATTTTGAA GCGGGAGGTT TGAACGCGCA GCCGCCATGC CGGGGTTTTA CCATTTTGAC .CGCGAAATT TGAACGAGCA GCAGCCATGC CGGGGTTCTA CCATTTTGAC .CGCGAAATT TGAACGAGCA GCAGCCATGC CGGGCTTCTA CCATTTTGAC .CGCGAAATT TGAACGAGCA GCAGCCATGC CGGGCTTCTA CCATTTTGAC .CGCGAAATT TGAACGAGCA GCAGCCATGC CGGGTTTCTA

    YY1/P5 RNA Rep78/68 start

    7/105

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    Fig. 1H

    351 400

    42_2

    42_8 42_15 42_5b 42_lb 42_13 42_3a

    42_4 42_5a 42_10 42_3b 42_11 42_6b

    43_1

    43_5 43_12 43__20 43_21 43_23 43_25

    44_1

    44_5 223_10 223_2 223_4 223_5 223_6 223_7

    A3_4

    A3_5

    A3_7

    A3_3 42_12

    AAV1 CGAGATCGTG ATCAAGGTGC

    AAV2 CGAGATTGTG ATTAAGGTCC

    AAV3 CGAGATTGTC CTGAAGGTCC

    AAVS CGAGATCGTG ATCAAGGTGC

    AAV9 CGAGATTGTG ATCAAGGTGC

    AAV7 CGAGATCGTG ATCAAGGTGC

    44 2

    CGAGCGACCT GGACGAGCAC CTGCCGGGCA CCAGCGACCT TGACGGGCAT CTGCCCGGCA CGAGTGACCT GGACGAGCGC CTGCCGGGCA CGAGCGACCT GGACGAGCAC CTGCCGGGCA CGAGCGACCT GGACGAGCAC CTGCCGGGCA CGAGCGACCT GGACGAGCAC CTGCCGGGCA

    8/105

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    Fig. II

    401 450

    42_2

    42_8 42_15 42_5b 42_lb 42_13 42_3a

    42_4 42_5a 42_10 42_3b 42_11 42_6b

    43_1

    43_5 43_12 43_20 43_21 43_23 43_25

    44_1

    44_5 223_10 223 _2 223_4 223_5 223_6 223_7

    A3_4

    A3_5

    A3_7

    A3_3 42_12

    AAV1 TTTCTGACTC GTTTGTGAGC

    AAV2 TTTCTGACAG CTTTGTGAAC

    AAV3 TTTCTAACTC GTTTGTTAAC

    AAV 8 TTTCTGACTC GTTTGTGAAC

    AAV9 TTTCTGACTC TTTTGTGAAC

    AAV7 TTTCTGACTC GTTTGTGAAC

    44 2

    TGGGTGGCCG AGAAGGAATG GGAGCTGCCC TGGGTGGCCG AGAAGGAATG GGAGTTGCCG TGGGTGGCCG AGAAGGAATG GGACGTGCCG TGGGTGGCCG AGAAGGAATG GGAGCTGCCC TGGGTGGCCG AGAAGGAATG GGAGCTGCCC TGGGTGGCCG AGAAGGAATG GGAGCTGCCC

    9/105

    PCT/US02/33629

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    451

    Fig. 1J

    500

    42/

    42/ 42/5 42/b 42_lb 42/3 42/a

    42/ 4 2/a 42/0 42_3b 42/1 42/b

    43/

    43/

    43_12

    43/0

    43/1

    43/3

    43/5

    44/

    44/ 223/0 2 2 3 2 223/ 223/ 223/ 223/

    A3/

    A3_5

    A3_7

    A3_3

    42/2

    AAV1

    AAV2

    AAV3

    AAV8

    AAV9

    AAV7

    44/

    CCGGATTCTG ACATGGATCT GAATCTGATT GAGCAGGCAC CCCTGACCGT CCAGATTCTG ACATGGATCT GAATCTGATT GAGCAGGCAC CCCTGACCGT CCGGATTCTG ACATGGATCC GAATCTGATT GAGCAGGCAC CCCTGACCGT CCGGATTCTG ACATGGATCG GAATCTGATC GAGCAGGCAC CCCTGACCGT CCGGATTCTG ACATGGATCG GAATCTGATC GAGCAGGCAC CCCTGACCGT CCGGATTCTG ACATGGATCT GAATCTGATC GAGCAGGCAC CCCTGACCGT

    10/105

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    Fig. IK

    501 550

    4 2 2 ..................................................

    42_8 ..................................................

    42_15 ..................................................

    42_5b ..................................................

    42_lb ..................................................

    4213 ..................................................

    42_3a ..................................................

    4 24 ..................................................

    42_5a ..................................................

    4210 ...............................-..................

    42_3b ..................................................

    42_11 ..................................................

    42_6b ..................................................

    4 31 ..................................................

    43_5 ..................................................

    4312 ..................................................

    43 20 ..................................................

    43_21 ..................................................

    43_23 ..................................................

    43 25 .............................. ....................

    441 ..................................................

    44_5 ...................................................

    223_10 ..................................................

    223 2 ..................................................

    223^4 ..................................................

    223 5 ..................................................

    223_6 ..................................................

    223 7 ..................................................

    A3_4 ..................................................

    A3_5 ..................................................

    A3_7 ..................................................

    A3_3 .............................. ....................

    4212 ..................................................

    AAVl GGCCGAGAAG CTGCAGCGCG ACTTCCTGGT CCAATGGCGC CGCGTGAGTA AAV2 GGCCGAGAAG CTGCAGCGCG ACTTTCTGAC GGAATGGCGC CGTGTGAGTA AAV3 GGCCGAAAAG CTTCAGCGCG AGTTCCTGGT GGAGTGGCGC CGCGTGAGTA AAV8 GGCCGAGAAG CTGCAGCGCG ACTTCCTGGT CCAATGGCGC CGCGTGAGTA AAV9 GGCCGAGAAG CTGTAGCGCG ACTTCCTGGT CCAATGGCGC CGCGTGAGTA AAV7 GGCCGAGAAG CTGCAGCGCG ACTTCCTGGT CCAATGGCGC CGCGTGAGTA 4 4 2 ..................................................

    11/105

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    Fig. II

    551 600

    42_2

    42_8 42_15 42_5b 42_lb 42JL3 42__3a

    42_4 42_5a 42_10 42__3b 42_11 42_6b

    43_1

    43__5 43_1 2 43_20 43_21 43_23 43_25

    44_1

    44_5 223_10 223_2 223_4 223_5 223_6 223__7

    A3_4

    A3_5

    A3_7

    A3_3 42_12

    AAV1 AGGCCCCGGA GGCCCTCTTC

    AAV2 AGGCCCCGGA GGCCCTTTTC

    AAV3 AGGCCCCGGA GGCCCTCTTT

    AAV8 AGGCCCCGGA GGCCCTCTTC

    AAV9 AGGCCCCGGA GGCCCTCTTC

    AAV7 AGGCCCCGGA GGCCCTGTTC

    44 2

    TTTGTTCAGT TCGAGAAGGG CGAGTCCTAC TTTGTGCAAT TTGAGAAGGG AGAGAGCTAC TTTGTCCAGT TCGAAAAGGG GGAGACCTAC TTTGTTCAGT TCGAGAAGGG CGAGAGCTAC TTTGTTCAGT TCGAGAAGGG CGAGAGCTAC TTTGTTCAGT TCGAGAAGGG CGAGAGCTAC

    12/105

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    Fig. 1M

    601 650

    42 2 ..................................................

    42 8 ..................................................

    4215 ..................................................

    42_5b ..................................................

    42_lb ................................................ -

    4213 ..................................................

    42_3a ..................................................

    42_4 ..................................................

    42_5a ..................................................

    4210 ..................................................

    42_3b ..................................................

    4211 ..................................................

    42_6b ..................................................

    4 31 ..................................................

    43_5 ..................................................

    43_12 .................... ..............................

    43 20 ..................................................

    4321 ..................................................

    43_23 ..................................................

    43 25 ......................... · · ......................

    4 41 ..................................................

    4 4 5 ..................................................

    22310 ..................................................

    223_2 ...................................................

    223_4 ..................................................

    223 5 ..................................................

    223 6 ..................................................

    223 7 ........................................ ..........

    A3_4 ........................................... ......

    A3_5 ..................................................

    A3_7 , . ................................................

    A3_3 ..................................................

    42 12 ..................................................

    AAV1 TTCCACCTCC ATATTCTGGT GGAGACCACG GGGGTCAAAT CCATGGTGCT AAV2 TTCCACATGC ACGTGCTCGT GGAAACCACC GGGGTGAAAT CCATGGTTTT AAV3 TTCCACCTGC ACGTGCTGAT TGAGACCATC GGGGTCAAAT CCATGGTGGT AAV8 TTTCACCTGC ACGTTCTGGT CGAGACCACG GGGGTCAAGT CCATGGTGCT AAV9 TTTCACCTGC ACGTTCTGGT CGAGACCACG GGGGTCAAGT CCATGGTGCT AAV7 TTCCACCTTC ACGTTCTGGT GGAGACCACG GGGGTCAAGT CCATGGTGCT 4 4 2 ..................................................

    13/105

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    Fig, IN

    651 700

    42_2

    42_8 42_15 42_5b 42_lb 42_13 42_3a

    42_4 42_5a 42_10 42_3b 42_11 42_6b

    43_1

    43_5 43_12 43_20 43_21 43_23 43_25

    44_1

    44_5 223_10 223_2 223_4 223_5 223_6 223_7

    A3_4

    A3_5

    A3_7

    A3_3 42_12

    AAVl GGGCCGCTTC CTGAGTCAGA

    AAV2 GGGACGTTTC CTGAGTCAGA

    AAV3 CGGCCGCTAC GTGAGCCAGA

    AAV8 AGGCCGCTTC CTGAGTCAGA

    AAV9 AGGCCGCTTC CTGAGTCAGA

    AAV7 AGGCCGCTTC CTGAGTCAGA

    44 2

    TTAGGGACAA GCT.GGTGCA GACCATCTAC TTCGCGAAAA ACT. .GATTC- AGAGAATTTA TTAAAGAGAA GCT..GGTGA CCCGCATCTA TTCGGGAAAA GCTTGGTCCA GACCATCTAC TTCGGGAGAA GCT.GGTCCA GACCATCTAC TTCGGGAGAA GCT.. .. G.. GTCCAGACCA

    14/105

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    Fig. 10

    701 · 750

    42_2

    42_8 42J.5 42_5b 42_lb 42_13 42_3a

    42_4 42_5a 42_10 42_3b 42_11 42_6b

    43_1

    43_5 43_12 43_20 43_21 43_23 43_25

    44_1

    44_5 223_10 223_2 223_4 223_5 223_6 223_7

    A3_4

    A3_5

    A3_7

    A3_3 42_12

    AAV1 C.GCGGGATC GAGCCG.ACC

    AAV2 CCGCGGGATC GAGCCG.ACT

    AAV3 CCGCGGGGTC GAGCCG.CAG

    AAV8 CCGCGGGGTC GAGCCCCACC

    AAV9 C.GCGGGATC GAGCCG.ACC

    AAV7 TCTACCGCGG GGTCGAGCCC

    44 2

    CTGCCCAACT GGTTCGCGGT GACCAA.GAC TTGCCAAACT GGTTCGCGGT CACAAA...G CTTCCGAACT GGTTCGCGGT GACCAA.. - A TTGCCCAACT GGTTCGCGGT GACCAAAGAC CTGCCCAACT GGTTCGCGGT GACCAA.GAC ACGCTGCCCA ACTQGTTCGC GGTGACCAAG

    I

    15/105

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    Fig. IP

    751 000

    42_2

    42_8 42_15 42_5b 42_lb 42_13 42_3a

    42_4 42_5a 42_10 42_3b 42_11 42_6b

    43_1

    43_5 43_12 43__20 43_21 43_23 43_25

    44_1

    44_5 223_10 223_2 223_4 223_5 223_6 223_7

    A3_4

    A3_5

    A3_7

    A3_3 42_12

    AAV1 GCG.TAATGG

    AAV2 ACCAGAAATG

    AAV3 ACGCGAAATG

    AAV9 GCGGTAATGG

    AAV9 GCG.TAATGG

    AAV7 ACGCGTAATG

    44 2 ..........

    CGCCGGAGGG GGG.AACAAG GCGCCGGAGG CGGGAACAAG GCGCCGGGGG CGGGAACAAG CGCCGGCGGG GGGGAACAAG CGCCGGCGGG GGG.AACAAG GCGCCGGCGG GGGGAACAAG

    GTGGTGGACG AGTGCTACAT GTGGTGGATG AGTGCTACAT GTGGTGGACG ACTGCTACAT GTGGTGGACG AGTGCTACAT GTGGTGGACG AGTGCTACAT GTGGTGGACG AGTGCTACAT

    16/105

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    Fig, IQ

    801 850

    42_2

    42_8 42_15 42_5b 42_lb 42_13 42_3a

    42_4 42_5a 42_10 42_3b 42_11 42_6b

    43_1

    43_5 43_12 43_20 43_21 43_23 43_25

    44_1

    44_5 223_10 223_2 223_4 223_5 223_6 223_7

    A3_4

    A3_5

    A3_7

    A3_3 42_12

    AAV1 CCCCAACTAC

    AAV2 CCCCAATTAC

    AAV3 CCCCAACTAC

    AAVS CCCCAACTAC

    AAVS CCCCAACTAC

    AAV7 CCCCAACTAC

    44 2 ..........

    CTCCTGCCCA AGACTCAGCC TTGCTCCCCA AAACCCAGCC CTGCTCCCCA AGACCCAGCC CTCCTGCCCA AGACTCAGCC CTCCTGCCCA AGACTCAGCC CTCCTGCCCA AGACCCAGCC

    CGAGCTGCAG TGGGCGTGGA TGAGCTCCAG TGGGCGTGGA CGAGCTCCAG TGGGCGTGGA CGAGCTGCAG TGGGCGTGGA CGAGCTGCAG TGGGCGTGGA CGAGCTGCAG TGGGCGTGGA

    17/105

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    851

    Fig. IR

    900

    42_2

    42_8

    42_15

    42_5b

    42_lb

    42_13

    42_3a

    42_4

    42_5a

    42_10

    42_3b

    42_11

    42_6b

    43_1

    43_5

    43_12

    43_20

    43_21

    43_23

    43_25

    44_1

    44_5

    223JL0

    223_2

    223_4

    223_5

    223_6

    223J7

    A3_4

    A3_5

    A3_7

    A3_3

    42_12

    AAV1

    AAV2

    AAV3

    AAV8

    AAV9

    AAV7

    44_2

    P19/TATA

    P19 RNA

    CTAACATGGA GGAGTATATA AGCGCCTGTT TGAACCTGGC CGAGCGCAAA

    CTAATATGGA ACAGTATTTA AGCGCCTGTT TGAATCTCAC GGAGCGTAAA

    CTAACATGGA CCAGTATTTA AGCGCCTGTT TGAATCTCGC GGAGCGTAAA

    CTAACATGGA GGAGTATATA AGCGCGTGCT TGAACCTGGC CGAGCGCAAA

    CTAACATGGA GGAGTATATA AGCGCGTGCT TGAACCTGGC CGAGCGCAAA

    CTAACATGGA GGAGTATATA AGCGCGTGTT TGAACCTGGC ipGAACGCAAA

    ...............................T..........

    P19/TATA P19 RNA

    18/105

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    Fig. IS

    901 950

    42_2

    42_8 42_15 42_5b 42_lb 42_13 42_3a

    42_4 42_5a 42_10 42_3b 42_11 42_6b

    43_1

    4 3_5 43_12 43_20 43_21 43_23 43_25

    44_1

    44_5 223_10 223_2 223_4 223_5 223_6 223_7

    A3_4

    A3_5

    A3_7

    A3_3 42_12

    AAV1 CGGCTCGTGG CGCAGCACCT

    AAV2 CGGTTGGTGG CGCAGCATCT

    AAV3 CGGCTGGTGG CGCAGCATCT

    AAV8 CGGCTCGTGG CGCAGCACCT

    AAV9 CGGCTCGTGG CGCAGCACCT

    AAV7 CGGCTCGTGG CGCAGCACCT

    44 2

    GACCCACGTC AGCCAGACCC AGGAGCAGAA GACGCACGTG TCGCAGACGC AGGAGCAGAA GACGCACGTG TCGCAGACGC AGGAGCAGAA GACCCACGTC AGCCAGACGC AGGAGCAGAA GACCCACGTC AGCCAGACGC AGGAGCAGAA GACCCACGTC AGCCAGACGC AGGAGCAGAA
19. 19/105

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    Fig. IT

    951 1000

    42/

    42/

    42/5 42_5b 42/b 42/3 4 2/a

    42_4 42/a 42_10 42/b 42/ i 42/b

    43/

    43/

    43/2 43/0 43/1 43/3 43/5

    44/

    44/

    223/0 223/

    223_4 223/

    223/

    223/

    A3_4

    A3_5

    A3_7

    A3_3 42/2

    AAV1 CAAGGAGAAT

    AAV2 CAAAGAGAAT

    AAV3 CAAAGAGAAT

    AAV8 CAAGGAGAAT

    AAV9 CAAGGAGAAT

    AAV7 CAAGGAGAAT

    44 2 ..........

    CTGAACCCCA ATTCTGACGC CAGAATCCCA ATTCTGATGC CAGAACCCCA ATTCTGACGC CTGAACCCCA ATTCTGACGC CTGAACCCCA ATTCTGACGC CTGAACCCCA ATTCTGACGC

    GCCTGTCATC CGGTCAAAAA GCCGGTGATC AGATCAAAAA GCCGGTCATC AGGTCAAAAA GCCCGTGATC AGGTCAAAAA GCCCGTGATC AGGTCAAAAA GCCCGTGATC AGGTCAAAAA
20. 20/105

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    Fig. 1U

    1001

    1050

    Rep52/40—start codon

    42_2 ..............ψ.ψ.................................

    42_8 ..................................................

    42_15 ..................................................

    42_5b ..................................................

    42_lb ..................................................

    42_13 ..................................................

    42_3a ..................................................

    4 2 4 ..................................................

    42_5a ..................................................

    4210 ..................................................

    42_3b ..................................................

    4211 ..................................................

    42_6b ..................................................

    43_1 ..................................................

    43_5 ..................................................

    43_12 ..................................................

    4320 ..................................................

    43 21 ..................................................

    43 23 ..................................................

    4325 ..................................................

    441 ..................................................

    44_5 ..................................................

    223 10 ........................................ ..........

    223_2 ..................................................

    223_4 ................................... ...............

    223_5 ..................................................

    223 6 ..................................................

    223 7 .............................- ....................

    A3_4 ..................................................

    A3_5 ..................................................

    A3_7 .....................-............................

    A3_3 ..................................................

    4212 ..................................................

    AAV1 CCTCCGCGCG CTACATGGAG CTGGTCGGGT GGCTGGTGGA CCGGGGCATC AAV2 CTTCAGCCAG GTACATGGAG CTGGTCGGGT GGCTCGTGGA CAAGGGGATT AAV3 CCTCAGCCAG GTACATGGAG CTGGTCGGGT GGCTGGTGGA CCGCGGGATC AAV8 CCTCCGCGCG CTATATGGAG CTGGTCGGGT GGCTGGTGGA CCGGGGCATC AAV9 CCTCCGCGCG CTACATGGAG CTGGTCGGGT GGCTGGTGGA CCGGGGCATC AAV7 CCTCCGCGCG CTACATGGAG CTGGTCGGGT GGCTGGTGGA CCGGGGCATC

    44_2 .............·Τ· T·................................

    Rep 52/40 start
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    Fig. IV

    1051 1100

    42_2 ...............................................·. · ·

    42 8 ..................................................

    4215 ..................................................

    42_5b ..................................................

    42_lb ..................................................

    4213 ..................................................

    42_3a .......... ........................................

    42_4 ..................................................

    42 5 a ..................................................

    4210 ..................................................

    42_3b ..................................................

    42_11 ..................................................

    42_6b ..................................................

    4 31 ..................................................

    43 5 ..................................................

    43_12 ..................................................

    43 20 ..................................................

    43_21 ..................................................

    43_23 ..................................................

    43 25 ........................................ ........

    441 ..................................................

    44_5 .................. ..............................

    22310 ..................................................

    223 2 .....................-........ · · ..............- ·

    223 4 ..................................................

    223_5 ..................................................

    223_6 .................... ..............................

    223_7 ..................................................

    A3_4 ..................................................

    A3_5 ..................................................

    A3_7 ..................................................

    A3_3 ..................................................

    42_12 ..................................................

    AAVl ACCTCCGAGA AGCAGTGGAT CCAGGAGGAC CAGGCCTCGT ACATCTCCTT AAV2 ACCTCGGAGA AGCAGTGGAT CCAGGAGGAC CAGGCCTCAT ACATCTCCTT AAV3 ACGTCAGAAA AGCAATGGAT TCAGGAGGAC CAGGCCTCGT ACATCTCCTT AAV 8 ACCTCCGAGA AGCAGTGGAT CCAGGAGGAC CAGGCCTCGT ACATCTCCTT

    AAV9 ACCTCCGAGA AGCAGTGGAT CCAGGAGGAC CAGGCCTCGT ACATCTCCTT

    AAV7 ACCTCCGAGA AGCAGTGGAT CCAGGAGGAC CAGGCCTCGT ACATCTCCTT

    44 2 ..................................................
22. 22/105

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    Fig. 1W

    1101 1150

    42_2

    42_8 42_15 42_5b 42_lb 42_13 42_3a

    42_4 42_5a 42_10 42_3b 42_11 42_6b

    43_1

    43_5 43_12 43_20 43_21 43_23 43_25

    44_1

    44_5 223_10 223_2 223_4 223_5 223_6 223_7

    A3_4

    A3_5

    A3_7

    A3_3 42_12

    AAV1 CAACGCCGCT

    AAV2 CAATGCGGCC

    AAV3 CAACGCCGCC

    AAVS CAACGCCGCC

    AAV9 CAACGCCGCC

    AAV7 CAACGCCGCC

    44 2 ..........

    TCCAACTCGC GGTCCCAGAT TCCAACTCGC GGTCCCAAAT TCCAACTCGC GGTCCCAGAT TCCAACTCGC GGTCCCAGAT TCCAACTCGC GGTCCCAGAT TCCAACTCGC GGTCCCAGAT

    CAAGGCCGCT CTGGACAATG CAAGGCTGCC TTGGACAATG CAAGGCCGCG CTGGACAATG CAAGGCCGCG CTGGACAATG CAAGGCCGCG CTGGACAATG CAAGGCCGCG CTGGACAATG
23. 23/105

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    Fig. IX

    1151 1200

    422 ..................................................

    42_8 ..................................................

    4215 ..................................................

    42_5b ..................................................

    42_lb ..................................................

    42_13 ..................................................

    42_3a ..................................................

    4 2 4 ..................................................

    42_5a ..................................................

    42_10 ..................................................

    42_3b ..................................................

    42_11 ..................................................

    42_6b ..................................................

    431 ..................................................

    4 3 5 ..................................................

    43_12 ..................................................

    43_20 ..................................................

    43_21 ..................................................

    43 23 ..................................................

    43 25 .......................... .......-.............. · ·

    441 ..................................................

    4 4 5 ..................................................

    22310 ..................................................

    223 2 ..................................................

    223_4 ..................................................

    223_5 ..................................................

    223 6 ..................................................

    223_7 ..................................................

    A3_4 ..................................................

    A3_5 ..................................................

    A3_7 ..................................................

    A3_3 ..................................................

    42_12 ..................................................

    AAVl CCGGCAAGAT CATGGCGCTG ACCAAATCCG CGCCCGACTA CCTGGTAGGC AAV2 CGGGAAAGAT TATGAGCCTG ACTAAAACCG CCCCCGACTA CCTGGTGGGC AAV3 CCTCCAAGAT CATGAGCCTG ACAAAGACGG CTCCGGACTA CCTGGTGGGC AAV8 CCGGCAAGAT CATGGCGCTG ACCAAATCCG CGCCCGACTA CCTGGTGGGG AAV9 CCGGCAAGAT CATGGCGCTG ACCAAATCCG CGCCCGACTA CCTGGTAGGC AAV7 CCGGCAAGAT CATGGCGCTG ACCAAATCCG CGCCCGACTA CCTGGTGGGG 44 2 ..................................................
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    1201

    42_2 42_8 42_15 42_5b 42_lb 42_13 42_3a 42_4 42_5a 42_10 42_3b 42_11 42_6b 43_1 43_5 43_12 43_20 43_21 43_23 43_25 44_1 ,44_5 223_10 223_2 223_4 223_5 223_6 223J7 A3_4 A3_5 A3_7 A3_3 42_12 AAVl CCCGCTCCGC AAV2 CAGCAGCCCG AAV3 AGCAACCCGC AAV8 CCCTCGCTGC AAV 9 CCTTCACTTC AAV7 CCCTCGCTGC 44 2 ..........

    Fig. 1Y

    1250

    ............................GA ATTCGCCCTT TCTACGGCTG

    CCGCGGACAT TAAAACCAAC TGGAGGACAT TTCCAGCAAT CGGAGGACAT TACCAAAAAT CCGCGGACAT TACCCAGAAC CGGTGGACAT TACGCAGAAC CCGCGGACAT TAAAACCAAC

    CGCATCTACC GCATCCTGGA CGGATTTATA AAATTTTGGA CGGATCTACC AAATCCTGGA CGCATCTACC GCATCCTCGC CGCATCTACC GCATCCTGCA CGCATCTACC GCATCCTGGA
25. 25/105

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    Fig. 1Z

    1251 1300

    42_2 42_8 42_15 42_5b 42_lb 42_13 42_3a 42_4 42_5a 42_10 42_3b 42_11 42_6b 43_1 43_5 43_12 43_20 43_21 43_23 43_25 44_1 44_5 223_10 223_2 223_4 223_5 223_6 223_7 A3_4 A3_5 A3_7 A3_3 42_12 AAV1 GCTGAACGGC AAV2 ACTAAACGGG AAV3 GCTGAACGGG AAV8 TCTCAACGGC AAV9 GCTCAACGGC AAV7 GCTGAACGGG 44 2 ..........

    CGTCAACTGG ACCAATGAGA ACTTTCCCTT CAACGATTGC GTCGACAAGA

    TACGAACCTG CCTACGCCGG TACGATCCCC AATATGCGGC TACGATCCGC AGTACGCGGC TACGACCCTG CCTACGCCGG TACGACCCTG CCTACGCCGG TACGATCCTG CCTACGCCGG

    CTCCGTCTTT CTCGGCTGGG TTCCGTCTTT CTGGGATGGG CTCCGTCTTC CTGGGCTGGG CTCCGTCTTT CTCGGCTGGG CTCCGTCTTT CTCGGCTGGG CTCCGTCTTT CTCGGCTGGG
26. 26/105

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    Fig. 1AA

    1301 ¹³⁵θ

    42_2 42_8 42_15 42_5b 42_lb 42_13 42_3a 42_4 42_5a 42_10 42_3b 42_11 42_6b 43_1 43_5 43_12 43_20 43_21 43_23 43_25 44J.

    44_5 223_10 223_2 223_4 223_5 223_6 223_7 A3_4 A3_5 A3_7 A3_3 42_12 AAV1 CCCAGAAAAG AAV2 CCACGAAAAA AAV3 CGCAAAAGAA AAV8 CTCAGAAAAA AAV9 CACAAAAGAA AAV7 CCCAGAAAAA 44 2 ..........

    TGGTGATCTG GTGGGAGGAG GGCAAGATGA CGGCCAAGGT CGTGGAGTCC

    GTTCGGGAAG CGCAACACCA GTTCGGCAAG AGGAACACCA GTTCGGGAAG AGGAACACCA GTTCGGGAAA CGCAACACCA GTTCGGGAAA CGCAACACCA GTTCGGGAAG CGCAACACCA

    TCTGGCTGTT TGGGCCGGCC TCTGGCTGTT TGGGCCTGCA TCTGGCTCTT TGGGCCGGCC TCTGGCTGTT TGGACCCGCC TCTGGCTGTT TGGGCCGGCC TCTGGCTGTT TGGGCCCGCC
27. 27/105

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    Fig. 1AB

    1351 1400

    42_2 GAA TTCGCCCTTT

    42_8 GAA TTCGCCCTTT

    42_15 GAA TTCGCCCTTT

    42_5b GAA TTCGCCCTTT

    42_lb ..................................................

    42_13 GAA TTCGCCCTTT

    42_3a GAA TTCGCCCTTT

    42_4 ..................................................

    42_5a GA ATTCGCCCTT

    4210 ..................................................

    42_3b ..................................................

    42_11 GAA TTCGCCCTTT

    42_6b GCCAAGGCCA TTCTCGGCGG CAGCAAGGTG CGCGTGGACC AAAAGTGCAA

    43_1 GAA TTCGCCCTTT

    4 3_5 GAA TTCGCCCTTT

    43_12 GAA TTCGCCCTT.

    43_20 GAA TTCGCCCTTT

    43_21 GAA TTCGCCCTT.

    43_23 GAA TTCGCCCTT.

    43_25 GAA TTCGCCCTTT

    44_1 GAA TTCGCCCTTT

    44_5 GAA TTCGCCCTTT

    223_10 ..................................................

    223 2 ..................................................

    223 4 ................................................. .

    22 3 5 ..................................................

    223 6 ..................................................

    223_7 ..................................................

    A3_4 ......................................GA ATTCGCCCTT

    A3_5 ......................................GA ATTCGCCCTT

    A3_7 .............................A GCGGCCGCGA ATTCGCCCTT

    A3_3 ......................................GA ATTCGCCCTT

    42_12 .....................................GAA TTCGCCCTTT

    AAV1 ACCACGGGCA AGACCAACAT CGCGGAAGCC ATCGCCCACG CCGTGCCCTT

    AAV2 ACTACCGGGA AGACCAACAT CGCGGAGGCC ATAGCCCACA CTGTGCCCTT

    AAV3 ACGACGGGTA AAACCAACAT CGCGGAAGCC ATCGCCCACG CCGTGCCCTT

    AAV8 ACCACCGGCA AGACCAACAT TGCGGAAGCC ATCGCCCACG CCGTGCCCTT

    AAV9 ACCACGGGAA AGACCAACAT CGCAGAAGCC ATTGCCCACG CCGTGCCCTT

    AAV7 ACCACCGGCA AGACCAACAT TGCGGAAGCC ATCGCCCACG CCGTGCCCTT

    44_2 ......................................GA ATTCGCCCTT
28. 28/105

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    Fig. 1AC

    42_2 42_8

    42_15 42_5b 42_lb 42_13 42_3a

    42_4

    42_5a

    42_10

    42— 3b 42_11 4 2_ 6b

    43- 1

    43_5

    43- 12 43_20 43_21 43_23 4 3-2 ⁵

    44- ¹

    44_5

    223-10 223-2 223_4 223-5 223_6 223_7 A3_4 A3—5 A3_7 A3_3 42_12 AAVl AAV2 AAV3 AAV8 AAV9 AAV7 44 2

    1401

    CTACGGCTG

    CTACGGCTG

    CTACGGCTG

    CTACGGCTG

    CGTCAACTGG

    CGTCAACTGG

    CGTCAACTGG

    CGTCAACTGG

    ACCAATGAGA

    ACCAATGAGA

    ACCAATGAGA

    ACCAATGAGA

    ACTTTCCCTT

    ACTTTCCCTT

    ACTTTCCCTT

    ACTTTCCCTT

    1450

    CAACGATTGC

    CAACGATTGC

    CAACGATTGC

    CAACGATTGC

    CTACGGCTG

    CTACGGCTG

    CGTCAACTGG

    CGTCAACTGG

    ACCAATGAGA

    ACCAATGAGA

    ACTTTCCCTT

    ACTTTCCCTT

    CAACGATTGC

    CAACGATTGC

    CTACGGCTG CGTCAACTGG ACCAATGAGA ACTTTCCCTT CAACGATTGC

    CTACGGCTG CGTCAACTGG ACCAATGAGA ACTTTCCCTT CAACGATTGC GTCTTCCGC CCAGATCGAT CCCACCCCCG TGATCGTCAC TTCCAACACC CTACGGCTG CATCAACTGG ACCAATGAGA ACTTTCCCTT CAACGATTGC CTACGGCTG CGTCAACTGG ACCAATGAGA ACTTTCCCTT CAACGATTGC .... GGCTG CGTCAACTGG ACCAATGAGA ACTTTCCCTT CAACGATTGC CTACGGCTG. CGTCAACTGG ACCAATGAGA ACTTTCCCTT CAACGATTGC .... GGCTG CGTCAACTGG ACCAATGAGA ACTTTCCCTT CAACGATTGC CTACGGCTG CGTCAACTGG ACCAATGAGA ACTTTCCCTT CAACGATTGC CTACGGCTG CGTCAACTGG ACCAATGAGA ACTTTCCCTT CAACGATTGC CTACGGCTG CGTCAACTGG ACCAATGAGA ACTTTCCCTT CAACGATTGC CTACGGCTG CGTCAACTGG ACCAATGAGA ACTTTCCCTT CAACGATTGC

    TCTACGGCTG CGTCAACTGG ACCAATGAAA ACTTTCCCTT CAACGATTGC TCTACGGCTG CGTCAACTGG ACCAATGAAA ACTTTCCCTT CAACGATTGC TCTACGGCTG CGTCAACTGG ACCAATGAAA ACTTTCCCTT CAACGATTGC TCTACGGCTG CGTCAACTGG ACCAATGAAA ACTTTCCCTT CAACGATTGC .CTACGGCTG CGTCAACTGG ACCAATGAGA ACTTTCCCTT CAACGATTGC .CTACGGCTG CGTCAACTGG ACCAATGAGA ACTTTCCCTT CAATGATTGC .CTACGGGTG CGTAAACTGG ACCAATGAGA ACTTTCCCTT CAACGACTGT .CTACGGCTG CGTAAACTGG ACCAATGAGA ACTTTCCCTT CAACGATTGC .CTACGGCTG CGTCAACTGG ACCAATGAGA ACTTTCCCTT CAATGATTGC .CTACGGCTG CGTCAACTGG ACCAATGAGA ACTTTCCCTT CAACGATTGC .CTACGGCTG CGTCAACTGG ACCAATGAGA ACTTTCCCTT CAACGATTGC TCTACGGCTG CGTCAACTGG ACCAATGAGA ACTTTCCCTT CAACGATTGC
29. 29/105

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    42_2

    42_8

    42_15

    42_5b

    42_lb

    42_13

    42_3a

    42_4

    42_5a

    42_10

    42_3b

    42_11

    42j5b

    43_1

    43_5

    43_12

    43_20

    43_21

    43_23

    43_25

    44_1

    44_5

    223JL0

    223_2

    223_4

    223_5

    223_6

    223J7

    A3_4

    A3.5

    A3_7

    A3_3 4 2 J. 2

    AAVl

    AAV2

    AAV3

    AAV8

    AAV9

    AAV7

    44 2

    Fig. 1AD

    1451 1500 GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGCAAGATGA CGGCCAAGGT GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGCAAGATGA CGGCCAAGGT GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGCAAGATGA CGGCCAAGGT GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGCAAGATGA CGGCCAAGGT

    GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGCAAGATGA CGGCCAAGGT GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGCAAGATGA CGGCCAAGGT

    GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGCAAGATGA CGGCCAAGGT

    GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGCAAGATGA CGGCCAAGGT AACATGTGCG CCGTGATTGA CGGGAACAGC ACCACCTTCG AGCACCAGCA GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGCAAGATGA CGGCCAAGGT GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGCAAGATGA CGGCCAAGGT GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGCAAGATGA CGGCCAAGGT GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGCAAGATGA CGGCCAAGGT GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGCAAGATGA CGGCCAAGGT GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGCAAGATGA CGGCCAAGGT GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGCAAGATGA CGGCCAAGGT GTCGACAAGA TGTTGATCTG GTGGGAGGAG GGCAAGATGA CGGCCAAGGT GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGCAAGATGA CGGCCAAGGT

    GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGAAAGATGA CCGCCAAGGT GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGAAAGATGA CCGCCAAGGT GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGAAAGATGA CCGCCAAGGT GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGAAAGATGA CCGCCAAGGT GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGCAAGATGA CGGCCAAGGT GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGCAAGATGA CGGCCAAGGT GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGGAAGATGA CCGCCAAGGT GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGCAAGATGA CGGCCAAGGT GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGCAAGATGA CGGCCAAGGT GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGCAAGATGA CGGCCAAGGT GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGCAAGATGA CGGCCAAGGT GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGCAAGATGA CGGCCAAGGT
30. 30/105

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    Fig. 1AE

    42/

    42/

    42/5 42/b 42/b 42/3 4 2/a

    42/

    42/a

    42/0

    42/b

    42/1

    42/b

    43/

    43/

    43/2

    43/0

    43/1

    43/3

    43/5

    44/

    44/

    223/0

    223/

    223/

    223/

    223_6

    223/

    A3_4

    A3/

    A3_7

    A3/

    42/2

    AAV1

    AAV2

    AAV3

    AAV8

    AAV9

    AAV7

    44/

    1501

    CGTGGAGTCC

    CGTGGAGTCC

    CGTGGAGTCC

    CGTGGAGTCC

    CGTGGAGTCC

    CGTGGAGTCC

    GCCAAGGCCA

    GCCAAGGCCA

    GCCAAGGCCA

    GCCAAGGCCA

    GCCAAGGCCA

    GCCAAGGCCA

    TTCTCGGCGG

    TTCTCGGCGG

    TTCTCGGCGG

    TTCTCGGCGG

    TTCTCGGCGG

    TTCTCGGCGG

    CAGCAAGGTG

    CAGCAAGGTG

    CAGCAAGGTG

    CAGCAAGGTG

    CAGCAAGGTG

    CAGCAAGGTG

    1550

    CGCGTGGACC

    CGCGTGGACC

    CGCGTGGACC

    CGCGTGGACC

    CGCGTGGACC

    CGCGTGGACC

    CGTGGAGTCC GCCAAGGCCA TTCTCGGCGG CAGCAAGGTG CGCGTGGACC

    CGTGGAGTCC GCCAAGGCCA TTCTCGGCGG CAGCAAGGTG CGCGTGGACC GCCGTTGCAG GACCGGATGT TCAAATTTGA ACTCACCCGC CGTCTGGAGC CGTGGAGTCC GCCAAGGCCA TTCTCGGCGG CAGCAAGGTG CGCGTGGACC CGTGGAGTCC GCCAAGGCCA TTCTCGGCGG CAGCAAGGTG CGCGTGGACC CGTGGAGTCC GCCAAGGCCA TTCTCGGCGG CAGCAAGGTG CGCGTGGACC CGTGGAGTCC GCCAAGGCCA TTCTCGGCGG CAGCAAGGTG CGTGTGGACC CGTGGAGTCC GCCAAGGCCA TTCTCGGCGG CAGCAAGGTG CGTGTGGACC CGTGGAGTCC GCCAAGGCCA TTCTCGGCGG CAGCAAGGTG CGTGTGGACC CGTGGAGTCC GCCAAGGCCA TTCTCGGCGG CAGCAAGGTG CGTGTGGACC CGTGGAGTCC GCCAAGGCCA TTCTCGGCGG CAGCAAAGTG CGCGTGGACC CGTGGAGTCC GCCAAGGCCA TTCTCGGCGG CAGCAAAGTG CGCGTGGACC

    CGTGGAATCT GCCAAAGCCA TTCTGGGTGG AAGCAAGGTT CGTGTGGACC CGTGGAATCT GCCAAAGCCA TTCTGGGTGG AAGCAAGGTT CGTGTGGACC CGTGGAATCT GCCAAAGCCA TTCTGGGTGG AAGCAAGGTT CGTGTGGACC CGTGGAATCT GCCAAAGCCA TTCTGGGTGG AGGCAAGGTT CGTGTGGACC CGTGGAGTCC GCCAAGGCCA TTCTCGGCGG CAGCAAGGTG CGCGTGGACC CGTGGAGTCC GCCAAGGCCA TTCTCGGCGG CAGCAAGGTG CGCGTGGACC CGTGGAGTCG GCCAAAGCCA TTCTCGGAGG AAGCAAGGTG CGCGTGGACC CGTGGAGAGC GCCAAGGCCA TTCTGGGCGG AAGCAAGGTG CGCGTGGACC CGTGGAGTCC GCCAAGGCCA TTCTCGGCGG CAGCAAGGTG CGCGTGGACC CGTGGAGTCC GCCAAGGCCA TTCTCGGCGG CAGCAAGGTG CGCGTGGACC CGTGGAGTCC GCCAAGGCCA TTCTCGGCGG CAGCAAGGTG CGCGTGGACC CGTGGAGTCC GCCAAGGCCA TTCTCGGCGG CAGCAAAGTG CGCGTGGACC
31. 31/105

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    42_2

    42_a

    42_15

    42_5b

    42_lb

    42_13

    42_3a

    42_4

    42_5a

    42_10

    42_3b

    42~U

    42_6b

    43_1

    43_5

    43_12

    43_20

    43_21

    43_23

    43_25

    44_1

    44_5

    223_10

    223_2

    223_4

    223_5

    223_6

    223_7

    A3_4

    A3_5

    A3_7

    A3_3

    42_12

    AAVl

    AAV2

    AAV3

    AAVS

    AAV9

    AAV7

    44 2

    Fig. 1AF

    1551 1600

    AAAAGTGCAA GTCTTCCGCC CAGATCGATC CCACCCCCGT GATCGTCACT AAAAGTGCAA GTCTTCCGCC CAGATCGATC CCACCCCCGT GATCGTCACT AAAAGTGCAA GTCGTCCGCC CAGATCGACC CCACCCCCGT GATCGTCACC AAAAGTGCAA GTCGTCCGCC CAGATCGACC CCACCCCCGT GATCGTCACC

    AAAAGTGCAA GTCGTCCGCC CAGATCGATC CCACCCCCGT GATCGTCACT AAAAGTGCAA GTCGTCCGCC CAGATCGATC CCACCCCCGT GATCGTCACT

    AAAAGTGCAA GTCGTCCGCC CAGATCGACC CCACCCCCGT GATCGTCACC

    AAAAGTGCAA GTCTTCCGCC CAGATCGATC CCACCCCCGT GATCGTCACT ATGACTTTGG CAAGGTGACA AAGCAGGAAG TCAAAGAGTT CTTCCGCTGG AAAAGTGCAA GTCGTCCGCC CAGATCGACC CCACCCCCGT GATCGTCACC AAAAGTGCAA GTCGTCCGCC CAGATCGACC CCACCCCCGT GATCGTCACC AAAAGTGCAA GTCGTCCGCC CAGATCGACC CCACCCCCGT GATCGTCACC AAAAGTGCAA GTCTTCCGCC CAGATCGATC CCACCCCCGT GATCGTCACC AAAAGTGCAA GTCTTCCGCC CAGATCGATC CCACCCCCGT GATCGTCACC AAAAGTGCAA GTCTTCCGCC CAGATCGATC CCACCCCCGT GATCGTCACC AAAAGTGCAA GTCTTCCGCC CAGATCGATC CCACCCCCGT GATCGTCACC AAAAGTGCAA GCCGTCCGCC CAGATCGACC CCACCCCCGT GATCGTCACC AAAAGTGCAA GTCGTCCGCC CAGATCGACC CCACCCCCGT GATCGTCACC

    AGAAATGCAA

    AGAAATGCAA

    AGAAATGCAG

    AGAAATGCAA

    AAAAGTGCAA

    AAAAGTGCAA

    AGAAATGCAA

    AAAAGTGCAA

    AAAAGTGCAA

    AAAAGTGCAA

    AAAAGTGCAA

    AAAAGTGCAA

    GTCTTCGGCC

    GTCTTCGGCC

    GTCTTCGGCC

    GTCTTCGGCC

    GTCGTCCGCC

    GTCGTCCGCC

    GTCCTCGGCC

    GTCATCGGCC

    GTCGTCCGCC

    GTCGTCCGCC

    GTCGTCCGCC

    GTCGTCCGCC

    CAGATCGACC

    CAGATCGACC

    CAGATCGACC

    CAGATCGACC

    CAGATCGACC

    CAGATCGACC

    CAGATAGACC

    CAGATCGAAC

    CAGATCGACC

    CAGATCGACC

    CAGATCGACC

    CAGATCGACC

    CGACTCCGGT

    CGACTCCGGT

    CGACTCCGGT

    CGACTCCGGT

    CCACCCCCGT

    CCACCCCCGT

    CGACTCCGGT

    CCACTCCCGT

    CCACCCCCGT

    CCACTCCCGT

    CCACCCCCGT

    CCACCCCCGT

    GATTGTCACC

    GATTGTCACC

    GATTGTCACC

    GATTGTCACC

    GATCGTCACC

    GATCGTCACC

    GATCGTCACC

    GATCGTCACC

    GATCGTCACC

    GATCGTCACC

    GATCGTCACC

    GATCGTCACC
32. 32/105

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    42_2

    42_8

    42_15

    42_5b

    42_lb

    42_13

    42_3a

    42_4

    42_5a

    42_10

    42_3b

    42JL1

    42_6b

    43JL

    43_5

    43_12

    43_20

    43_21

    43_23

    43_25

    44_1

    44_5

    223_10

    223_2

    223_4

    223_5

    223_6

    223J7

    A3_4

    A3_5

    A3_7

    A3_3

    42_12

    AAV1

    AAV2

    AAV3

    AAVS

    AAV9

    AAV7

    44_2

    Fig. 1AG

    1601 1650 TCCAACACCA ACATGTGCGC TGTGATTGAC GGGAACAGCA CCACCTTCGA TCCAACACCA ACATGTGCGC CGTGATTGAC GGGAACAGCA CCACCTTCGA TCCAACACCA ACATGTGCGC CGTGATTGAC GGGAACAGCA CCACCTTCGA TCCAACACCA ACATGTGCGC CGTGATTGAC GGGAACAGCA CCACCTTCGA

    TCCAACACCA ACATGTGCGC CGTGATTGAC GGGAACAGCA CCACCTTCGA TCCAACACCA ACATGTGCGC CGTGATTGAC GGGAACAGCA CCACCTTCGA

    TCCAACACCA ACATGTGCGC CGTGATTGAC GGGAACAGCA CCACCTTCGA

    TCCAACACCA

    GCGCAGGATC

    TCCAACACCA

    TCCAACACCA

    TCCAACACCA

    TCCAACACCA

    TCCAACACCA

    TCCAACACCA

    TCCAACACCA

    TCCAACACCA

    TCCAACACCA

    TCTAACACCA

    TCTAACACCA

    TCTAACACCA

    TCTAACACCA

    TCCAACACCA

    TCCAACACCA

    TCCAACACCA

    TCCAACACCA

    TCCAACACCA

    TCCAACACCA

    TCCAACACCA

    TCCAACACCA

    ACATGTGCGC

    ACGTGACCGA

    ACATGTGCGC

    ACATGTGCGC

    ACATGTGCGC

    ACATGTGCGC

    ACATGTGCGC

    ACATGTGCGC

    ACATGTGCGC

    ACATGTGCGC

    ACATGTGCGC

    ACATGTGCGC

    ACATGTGCGC

    ACATGTGCGC

    ACATGTGCGC

    ACATGTGCGC

    ACATGTGCGC

    ACATGTGCGC

    ACATGTGCGC

    ACATGTGCGC

    ACATGTGCGC

    ACATGTGCGC

    ACATGTGCGC

    CGTGATTGAC

    GGTGGCGCAT

    CGTGATTGAC

    CGTGATTGAC

    CGTGATTGAC

    CGTGATTGAC

    CGTGATTGAC

    CGTGATTGAC

    CGTGATTGAC

    CGTGATTGAC

    CGTGATTGAC

    CGTGATTGAC

    CGTGATTGAC

    CGTGATTGAC

    CGTGATTGAC

    CGTGATTGAC

    CGTGATTGAC

    CGTGATTGAC

    CGTGATTGAC

    CGTGATTGAC

    CGTGATTGAC

    CGTGATTGAC

    CGTGATTGAC

    GGGAACAGCA

    GAGTTCTACG

    GGGAACAGCA

    GGGAACAGCA

    GGGAACAGCA

    GGGAACAGCG

    GGGAACAGCA

    GGGAACAGCA

    GGGAACAGCA

    GGGAACAGCA

    GGGAACAGCA

    GGAAACTCGA

    GGAAACTCGA

    GGAAACTCGA

    GGAAACTCGA

    GGGAACAGCA

    GGGAACAGCA

    GGGAACTCAA

    GGGAACAGCA

    GGGAACAGCA

    GGGAACAGCA

    GGGAACAGCA

    GGGAACAGCA

    CCACCTTCGA

    TCAGAAAGGG

    CCACCTTCGA

    CCACCTTCGA

    CCACCTTCGA

    CCACCTTCGA

    CCACCTTCGA

    CCACCTTCGA

    CCACCTTCGA

    CCACCTTCGA

    CCACCTTCGA

    CCACCTTCGA

    CCACCTTCGA

    CCACCTTCGA

    CCACCTTCGA

    CCACCTTCGA

    CCACCTTCGA

    CGACCTTCGA

    CCACCTTCGA

    CCACCTTCGA

    CCACCTTCGA

    CCACCTTCGA

    CCACCTTCGA
33. 33/105

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    42_2 42_8 42_15 42_5b 42_lb 42_13 42_3a 42_4 42_5a 42_10

    42— 3b 42_11 42_6b

    43_1 43_5 43_12

    43- 20 43_21 43-23 43-25

    44-1 44_5 223_10 223_2 223-4 223_5 223_6 223_7 A3-4 GCACCAGCAG A3-5 GCACCAGCAG A3-7 GCACCAGCAG A3_3 GCACCAGCAG 42_12 GCACCAGCAG AAV1 GCACCAGCAG AAV2 ACACCAGCAG AAV3 GCATCAGCAG AAV8 GCACCAGCAG AAV9 GCACCAGCAG AAV7 GCACCAGCAG 44 2 GCACCAGCAG

    Fig. 1AH

    1651 1700

    GCACCAGCAG GCACCAGCAG GCACCAGCAG GCACCAGCAG CCGTTACAAG CCGTTACAAG CCGTTGCAGG CCGTTACAAG ACCGGATGTT ACCGGATGTT ACCGGATGTT ACCGGATGTT CAAATTTGAA CAAATTTGAA CAAATTTGAA CAAATTTGAA CTCACCCGCC CTCACCCGCC CTCACCCGCC CTCACCCGCC GCACCAGCAG GCACCAGCAG CCGTTACAAG CCGTTACAAG ACCGGATGTT ACCGGATGTT CAAATTTGAA CAAATTTGAA CTCACCCGCC CTCACCCGCC GCACCAGCAG CCGTTGCAGG ACCGGATGTT CAAATTTGAA CTCACCCGCC

    GCACCAGCAG CCGTTACAAG ACCGGATGTT CAAATTTGAA CTCACCCGCC TGGAGCCAAC AAGAGACCCG CCCCCGATGA CGCGGATAAA AGCGAGCCCA GCACCAGCAG CCGTTGCAGG ACCGGATGTT CAAGTTCGAA CTCACCCGCC GCACCAGCAG CCGTTGCAGG ACCGGATGTT CAAGTTCGAA CTCACCCGCC GCACCAGCAG CCGTTGCAGG ACCGGATGTT CAAGTTCGAA CTCACCCGCC GCACCAGCAG CCGTTGCAGG ACCGGATGTT CAAATTTGAA CTCACCCGCC GCACCAGCAG CCGTTGCAGG ACCGGATGTT CAAATTTGAA CTCACCCGCC GCACCAGCAG CCGTTGCAGG ACCGGATGTT CAAATTTGAA CTCACCCGCC GCACCAGCAG CCGTTGCAGG ACCGGATGTT CAAATTTGAA CTCACCCGCC GCACCAGCAG CCGTTGCGGG ACCGGATGTT CAAGTTTGAA CTCACCCGCC GCACCAGCAG CCGTTGCAGG ACCGGATGTT CAAGTTTGAA CTCACCCGCC

    CCGTTGCAAG ACCGGATGTT CCGTTGCAAG ACCGGATGTT CCGTTGCAAG ACCGGATGTT CCGTTGCAAG ACCGGATGTT CCGTTACAAG ACCGGATGTT CCGTTGCAGG ACCGGATGTT CCGTTGCAAG ACCGGATGTT CCGCTGCAGG ACCGGATGTT CCTCTCCAGG ACCGGATGTT CCTCTCCAGG ACCGGATGTT CCGTTGCAGG ACCGGATGTT CCGTTGCAGG ACCGGATGTT

    CAAATTTGAA CTTACCCGCC CAAATTTGAA CTTACCCGCC CAAATTTGAA CTTACCCGCC CAAATTTGAA CTTACCCGCC CAAATTTGAA CTCACCCGCC CAAATTTGAA CTCACCCGCC CAAATTTGAA CTCACCCGCC TGAATTTGAA CTTACCCGCC TAAGTTCGAA CTCACCCGCC TAAGTTCGAA CTCACCCGCC CAAATTTGAA CTCACCCGCC CAAGTTTGAA CTCACCCGCC
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    42_2

    42_8

    42_15

    42_5b

    42_lb

    42__13

    42_3a

    42_4

    42~5a

    42_10

    42_3b

    42_11

    42_6b

    43_1

    43_5 4 3__12 43__20 43__21 43_23 43_25

    44_1

    44_5

    223_10

    223_2

    223_4

    223_5

    223_6

    223J7

    A3_4

    A3_5

    A3_7

    A3_3

    42_12

    AAV1

    AAV2

    AAV3

    AAV8

    AAV9

    AAV7

    44_2

    Fig. 1AI

    1701 1750 GTCTGGAGCA CGACTTTGGC AAGGTGACAA AGCAGGAAGT CAAAGAGTTC GTCTGGAGCA CGACTTTGGC AAGGTGACAA AGCAGGAAGT CAAAGAGTTC GTCTGGAGCA TGACTTTGGC AAGGTGACAA AGCAGGAAGT CAAAGAGTTC GTCTGGAGCA CGACTTTGGC AAGGTGACAA AGCAGGAAGT CAAAGAGTTC

    GTCTGGAGCA TGACTTTGGC AAGGTGACAA AGCAGGAAGT CAAAGAGTTC GTCTGGAGCA TGACTTTGGC AAGGTGACAA AGCAGGAAGT CAAAGAGTTC

    GTCTGGAGCA TGACTTTGGC AAGGCGACAA AGCAGGAAGT CAAAGAGTTC

    GTCTGGAGCA CGACTTTGGC AAGGTGACAA AGCAGGAAGT CAAAGAGTTC AGCGGGCCTG CCCCTCAGTC GCGGATCCAT CGACGTCAGA CGCGGAAGGA GTCTGGAGCA CGACTTTGGC AAGGTGACCA AGCAGGAAGT CAAAGAGTTC GTCTGGAGCA CGACTTTGGC AAGGTGACCA AGCAGGAAGT CAAAGAGTTC GTCTGGAGCA CGACTTTGGC AAGGTGACCA AGCAGGAAGT CAAAGAGTTC GTCTGGAGCA TGACTTTGGC AAGGTGACGA AGCAGGAAGT CAAAGAGTTC GTCTGGAGCA TGACTTTGGC AAGGTGACGA AGCAGGAAGT CAAAGAGTTC GTCTGGAGCA TGACTTTGGC AAGGTGACGA AGCAGGAAGT CAAAGAGTTC GTCTGGAGCA TGACTTTGGC AAGGTGACGA AGCAGGAAGT CAAAGGGTTC GTCTGGAGCA CGACTTTGGC AAGGTGACAA AGCAGGAAGT CAGAGAGTTC GTCTGGAGCA CGACTTTGGC AAGGTGACAA AGCAGGAAGT CAGAGAGTTC

    GTTTGGATCA TGACTTTGGG AAGGTCACCA AGCAGGAAGT CAAAGACTTT GTTTGGATCA TGACTTTGGG AAGGTCACCA AGCAGGAAGT CAAAGACTTT GTTTGGATCA TGACTTTGGG AAGGTCACCA AGCAGGAAGT CAAAGACTTT GTTTGGATCA TGACTTTGGG AAGGTCACCA AGCAGGAAGT CAAAGACTTT GTCTGGAGCA CGACTTTGGC AAGGTGACAA AGCAGGAAGT CAAAGAGTTC GTCTGGAGCA TGACTTTGGC AAGGTGACAA AGCAGGAAGT CAAAGAGTTC GTCTGGATCA TGACTTTGGG AAGGTCACCA AGCAGGAAGT CAAAGACTTT GTTTGGACCA TGACTTTGGG AAGGTCACCA AACAGGAAGT AAAGGACTTT GTCTGGAGCA CGACTTTGGC AAGGTGACAA AGCAGGAAGT CAAAGAGTTC GTCTGGAGCA CGACTTTGGC AAGGTGACAA AGCAGGAAGT CAAAGAGTTC GTCTGGAGCA CGACTTTGGC AAGGTGACGA AGCAGGAAGT CAAAGAGTTC GTCTGGAGCA CGACTTTGGC AAGGTGACAA AGCAGGAAGT CAGAGAGTTC
35. 35/105

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    Fig. 1AJ

    1751 TTCCGCTGGG TTCCGCTGGG TTCCGCTGGG TTCCGCTGGG CGCAGGATCA CGCAGGATCA CGCAGGATCA CGCAGGATCA CGTGACCGAG CGTGACCGAG CGTGACCGAG CGTGACCGAG GTGGCGCATG GTGGCGCATG GTGGCGCATG GTGGCGCATG 1800 AGTTCTACGT AGTTCTACGT AGTTCTACGT AGTTCTACGT TTCCGCTGGG TTCCGCTGGG CGCAGGATCA CGCAGGATCA CGTGACCGAG CGTGACCGAG GTGGCGCATG GTGGCGCATG AGTTCTACGT AGTTCTACGT TTCCGCTGGG CGCAGGATCA CGTGACCGAG GTGGCGCATG AGTTCTACGT TTCCGCTGGG GCTCCGGTGG TTCCGCTGGG TTCCGCTGGG CGCAGGATCA ACTTTGCCGA CGCAGGATCA CGCAGGATCA CGTGACCGAG CAGGTACCAA CGTGACCGAG CGTGACCGAG GTGGCGCATG AACAAATGTT GTGGCGCATG GTGGCGCATG AGTTCTACGT CTCGTCACGC AGTTCTACGT AGTTCTACGT

    42- 2

    42_8

    42_15 42—5b 42_lb 42-13 42_3a

    42_4

    42_5a

    42-10

    42_3b

    42-il

    42— 6b

    43_1

    43- 5

    43- 12 43-20 43_21 43-23 43-25

    44_1

    44- 5 223_10

    223-2

    223-4

    223-5

    223_6

    223-7

    A3-4

    A3-5

    A3_7

    A3_3

    42-12

    AAV1

    AAV2

    AAV3

    AAV8

    AAV9

    AAV7

    44 2

    TTCCGCTGGG CGCAGGATCA CGTGACCGAG GTGGCGCATG AGTTCTACGT TTCCGCTGGG CGCAGGATCA CGTGACCGAG GTGGCGCATG AGTTCCACGT TTCCGCTGGG CGCAGGATCA* CGTGACCGAG GTGGCGCATG AGTTCCACGT TTCCGCTGGG CGCAGGATCA CGTGACCGAG GTGGCGCATG AGTTCCACGT TTCCGCTGGG CGCAGGATCA CGTGACCGAG GTGGCGCATG AGTTCCACGT TTCCGCTGGG CGCAGGATCA CGTGACCGAG GTGGCGCACG AGTTCTACGT TTCCGCTGGG CGCAGGATCA CGTGACCGAG GTGGCGCACG AGTTCTACGT

    TTCCGGTGGG CTCAAGATCA CGTGACTGAG GTGGAGCATG AGTTCTACGT TTCCGGTGGG CTCAAGATCA CGTGACTGAG GTGGAGCATG AGTTCTACGT TTCCGGTGGG CTCAAGATCA CGTGACTGAG GTGGAGCATG AGTTCTACGT TTCCGGTGGG CTCAAGATCA CGTGACTGAG GTGGAGCATG AGTTCTACGT TTCCGCTGGG CGCAGGATCA CGTGACCGAG GTGGCGCATG AGTTCTACGT TTCCGCTGGG CGCAGGATCA CGTGACCGAG GTGGCGCATG AGTTCTACGT TTCCGGTGGG CAAAGGATCA CGTGGTTGAG GTGGAGCATG AATTCTACGT TTCCGGTGGG CTTCCGATCA CGTGACTGAC GTGGCTCATG AGTTCTACGT TTCCGCTGGG CCAGTGATCA CGTGACCGAG GTGGCGCATG AGTTTTACGT TTCCGCTGGG CCAGTGATCA CGTGACCGAG GTGGCGCATG AGTTTTACGT TTCCGCTGGG CCAGTGATCA CGTGACCGAG GTGGCGCATG AGTTCTACGT TTCCGCTGGG CGCAGGATCA CGTGACCGAG GTGGCGCACG AGTTCTACGT
36. 36/105

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    1801

    Fig. 1AK

    1850

    P40/TAT^

    42_2

    42_8

    42_15

    42_5b

    42_lb

    42_13

    42_3a

    42_4

    42_5a

    42_10

    42_3b

    42_11

    42_6b

    43_1

    43_5

    43_12

    43_20

    43_21

    43_23

    43_25

    44_1

    44_5

    223_10

    223_2

    223_4

    223_5

    223_6

    223_7

    A3_4

    A3_5

    A3_7

    A3_3

    42_12

    AAV1

    AAV2

    AAV3

    AAV8

    AAV9

    AAV7

    44 2

    CAGAAAGGGT

    CAGAAAGGGT

    CAGAAAGGGT

    CAGAAAGGGT

    GGAGCCAACA

    GGAGCCAACA

    GGAGCCAACA

    GGAGCCAACA

    AGAGACCCGC

    AGAGACCCGC

    AGAGACCCGC

    AGAGACCCGC

    CCCCGATGAC

    CCCCGATGAC

    CCCCGATGAC

    CCCCGATGAC

    GCGGATAAAA

    GCGGATAAAA

    GCGGATAAAA

    GCGGATAAAA

    CAGAAAGGGT CAGAAAGGGT GGAGCCAACA GGAGCCAACA AGAGACCCGC AGAGACCCGC CCCCGATGAC CCCCGATGAC GCGGATAAAA GCGGATAAAA CAGAAAGGGT GGAGCCAACA AGAGACCCGC CCCCGATGAC GCGGATAAAA

    CAGAAAGGGT GGAGCCAACA AGAGACCCGC CCCCGATGAC GCGGATAAAA GGGCATAGCG CTGACGTAAA TCACGTCATA GGGGAGTGGT CCTGTATTAG CAGAAAGGGC GGAGCCAGCA AAAGACCCGC CCCCGATGAC GCGGATATAA CAGAAAGGGC GGAGCCAGCA AAAGACCCGC CCCCGATGAC GCGGATATAA CAGAAAGGGC GGAGCCAGCA AAAGACCCGC CCCCGATGAC GCGGATATAA CAGAAAGGGT GGAGCCAACA AGAGACCCGC CCCCGATGAC GCGGATATAA CAGAAAGGGT GGAGCCAACA AGAGACCCGC CCCCGATGAC GCGGATATAA CAGAAAGGGT GGCGCCAACA AGAGACCCGC CCCCGATGAC GCGGATATAA CAGAAAGGGT GGAGCCAACA AGAGACCCGC CCCCGATGAC GCGGATATAA CAGAAAGGGT GGAGCCAACA AGAGACCCGC CCCCGATGAC GCGGATAAAA CAGAAAGGGT GGAGCCAACA AGAGACCCGC CCCCGATGAC GCGGATAAAA

    CAAAAAGGGT GGAGCCAAGA AAAGGCCCGC CCCCGATGAT GTATATATAA CAAAAAGGGT GGAGCCAAGA AAAGGCCCGC CCCCGATGAT GTATATATAA CAAAAAGGGT GGAGCCAAGA AAAGGCCCGC CCCCGATGAT GTATATATAA CAAAAAGGGT GGAGCCAAGA AAAGGCCCGC CCCCGATGAT GTATATATAA CAGAAAGGGT GGAGCCAACA AGAGACCCGC CCCCGATGAC GCGGATAAAA CAGAAAGGGT GGAGCCAACA AAAGACCCGC CCCCGATGAC GCGGATAAAA CAAAAAGGGT GGAGCCAAGA AAAGACCCGC CCCCAGTGAC GCAGATATAA CAGAAAGGGT GGAGCTAAGA AACGCCCCGC CTCCAATGAC GCGGATGTAA CAGAAAGGGC GGAGCCAGCA AAAGACCCGC CCCCGATGAC GCGGATAAAA CAGAAAGGGC GGAGCCAGCA AAAGACCCGC CCCCGATGAC GCGGATAAAA CAGAAAGGGC GGAGCCAGCA AAAGACCCGC CCCCGATGAC GCGGATATAA CAGAAAGGGT GGAGCCAACA AGAGACCCGC CCCCGATGAC GCGGATAAAA

    P40/TATA
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    Fig. 1AI

    42_2

    42_8

    42__15

    42_5b

    42_lb

    42_13

    42_3a

    42_4

    42_5a

    42_10

    42_3b

    42_11

    42_6b

    43_1

    43_5 43..12 43_20 43_21 43_23 43_25 44_1 44_5 223 10 223_2 223_4 223_5 223_6 223_7 A3_4 A3_5 A3_7 A3_3 42_12 AAVl AAV2 AAV3 AAV8 AAV9 AAV7 44 2

    1851 1900 P40RNA

    GCGAGCCCAA GCGGGCCTGC CCCTCAGTCG CGGATCCATC GACGTCAGAC GCGAGCCCAA GCGGGCCTGC CCCTCAGTCG CGGATCCATC GACGTCAGAC GCGAGCCCAA GCGGGCCTGC CCCTCAGTCG CGGATCCATC GACGTCAGAC GCGAGCCCAA GCGGGCCTGC CCCTCAGTCG CGGATCCATC GACGTCAGAC

    GCGAGCCCAA GCGGGCCTGC CCCTCAGTCG CGGATCCATC GACGTCAGAC GCGAGCCCAA GCGGGCCTGC CCCTCAGTCG CGGATCCATC GACGTCAGAC

    GCGAGCCCAA GCGGGCCCGC CCCTCAGTCG CGGATCCATC GACGTCAGAC

    GCGAGCCCAA GCGGGCCTGC CCCTCAGTCG CGGATCCATC GACGTCAGAC CTGTCACGTG AGTGCTTTTG CGACATTTTG C..ATCCATC GACGTCAGAC GCGAGCCCAA GCGGGCCTGC CCCTCAGTCG CGGATCCATC GACGTCAGAC GCGAGCCCAA GCGGGCCTGC CCCTCAGTCG CGGATCCATC GACGTCAGAC GCGAGCCCAA GCGGGCCTGC CCCTCAGTCG CGGATCCATC GACGTCAGAC GCGAGCCCAA GCGGGCCTGC CCCTCAGTCG CGGATCCATC GACGTCAGAC GCGAGCCCAA GCGGGCCTGC CCCTCAGTCG CGGATCCATC GACGTCAGAC GCGAGCCCAA GCGGGCCTGC CCCTCAGTCG CGGATCCATC GACGTCAGAC GCGAGCCCAA GCGGGCCTGC CCCTCAGTCG CGGATCCATC GACGTCAGAC GCGAGCCCAA GCGGGCCTGC CCCTCAGTCG CGGATCCATC GACGTCAGAC GCGAGCCCAA GCGGGCCTGC CCCTCAGTCG CGGATCCATC GACGTCAGAC

    ATGAGCCCAA GCGGGCGCGC GAGTCAGTTG CGCAGCCATC GACGTCAGAC ATGAGCCCAA GCGGGCGCGC GAGTCAGTTG CGCAGCCATC GACGTCAGAC ATGAGCCCAA GCGGGCGCGC GAGTCAGTTG CGCAGCCATC GACGTCAGAC ATGAGCCCAA GCGGGCGCGC GAGTCAGTTG CGCAGCCATC GACGTCAGAC GCGAGCCCAA GCGGGCCTGC CCCTCAGTCG CGGATCCATC GACGTCAGAC GCGAGCCCAA GCGGGCCTGC CCCTCAGTCG CGGATCCATC GACGTCAGAC GTGAGCCCAA ACGGGTGCGC GAGTCAGTTG CGCAGCCATC GACGTCAGAC GCGAGCCAAA ACGGGAGTGC ACGTCACTTG CGCAGCCGAC AACGTCAGAC GCGAGCCCAA GCGGGCCTGC CCCTCAGTCG CGGATCCATC GACGTCAGAC GCGAGCCCAA GCGGGCCTGC CCCTCAGTCG CGGATCCATC GACGTCAGAC GCGAGCCCAA GCGGGCCTGC CCCTCAGTCG CGGATCCATC GACGTCAGAC GCGAGCCCAA GCGGGCCTGC CCCTCAGTCG CGGATCCATC GACGTCAGAC

    P40 RNA
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    Fig. 1AM

    42_2

    42_8

    42JL5

    42_5b

    42_lb

    42_13

    42_3a

    42_4

    42_5a

    42_10

    42_3b

    42_11

    42_6b

    43_1

    43_5

    43J.2

    43_20

    43_21

    43_23

    43_25

    44JL

    44_5

    223^10

    223_2

    223_4

    223_5

    223_6

    223J7

    A3_4

    A3_5

    A3_7

    A3_3

    42_12

    AAVl

    AAV2

    AAV3

    AAV8

    AAV9

    AAV7

    44 2

    1901

    GCGGAAGGAG

    GCGGAAGGAG

    GCGGAAGGAG

    GCGGAAGGAG

    CTCCGGTGGA

    CTCCGGTGGA

    CTCCGGTGGA

    CTCCGGTGGA

    CTTTGCCGAC

    CTTTGCCGAC

    CTTTGCCGAC

    CTTTGCCGAC

    AGGTACCAAA

    AGGTACCAAA

    AGGTACCAAA

    AGGTACCAAA

    1950

    ACAAATGTTC

    ACAAATGTTC

    ACAAATGTTC

    ACAAATGTTC

    GCGGAAGGAG CTCCGGTGGA CTTTGCCGAC AGGTACCAAA ACAAATGTTC GCGGAAGGAG CTCCGGTGGA CTTTGCCGAC AGGTACCAAA ACAAATGTTC

    GCGGAAGGAG CTCCGGTGGA CTTTGCCGAC AGGTACCAAA ACAAATGTTC

    GCGGAAGGAG CTCCGGTGGA CTTTGCCGAC AGGTACCAAA ACAAATGTTC GCGGAAGGAG CTCCGGTGGA CTTTGCCGAC AGGTACCAAA ACAAGTGTTC GCGGAAGGAG CTCCGGTGGA CTTTGCCGAC AGGTACCAAA ACAAATGTTC GCGGAAGGAG CTCCGGTGGA CTTTGCCGAC AGGTACCAAA ACAAATGTTC GCGGAAGGAG CTCCGGTGGA CTTTGCCGAC AGGTACCAAA ACAAATGTTC GCGGAAGGAG CTCCGGTGGA CTTTGCCGAC AGGTACCAAA ACAAATGTTC GCGGAAGGAG CTCCGGTGGA CTTTGCCGAC AGGTACCAAA ACAAATGTTC GCGGAAGGAG CTCCGGTGGA CTTTGCCGAC AGGTACCAAA ACAAATGTTC GCGGAAGGAG CTCCGGTGGA CTTTGCCGAC AGGTACCAAA ACAAATGTTC GCGGAAGGAG CTCCGGTGGA CTTTGCCGAC AGGTACCAAA ACAAATGTTC GCGGAAGGAG CTCCGGTGGA CTTTGCCGAC AGGTACCAAA ACAAATGTTC

    GCGGA. . .AG CTTCGATAAA CTACGCGGGC AGGTACCAAA ACAAATGTTC GCGGA. . .AG CTTCGATAAA CTACGCGGAC AGGTACCAAA ACAAATGTTC GCGGA. . .AG CTTCGATAAA CTACGCGGAC AGGTACCAAA ACAAATGTTC GCGGA. . .AG CTTCGATAAA CTACGCGGAC AGGTACCAAA ACAAATGTTC GCGGAAGGAG CTCCGGTGGA CTTTGCCGAC AGGTACCAAA ACAAATGTTC GCGGAAGGAG CTCCGGTGGA CTTTGCCGAC AGGTACCAAA ACAAATGTTC GCGGA. . .AG CTTCGATCAA CTACGCAGAC AGGTACCAAA ACAAATGTTC GCGGA. . .AG CACCGGCGGA CTACGCGGAC AGGTACCAAA ACAAATGTTC GCGGAAGGAG CTCCGGTGGA CTTTGCCGAC AGGTACCAAA ACAAATGTTC GCGGAAGGAG CTCCGGTGGA CTTTGCCGAC AGGTACCAAA ACAAATGTTC GCGGAAGGAG CTCCGGTGGA CTTTGCCGAC AGGTACCAAA ACAAATGTTC GCGGAAGGAG CTCCGGTGGA CTTTGCCGAC AGGTACCAAA ACAAATGTTC
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    42_2

    42_8

    42_15

    42_5b

    42_lb

    42_13

    42_3a

    42_4 42_5a 42_10 42_3b 42_11 42_6b 43_1 43_5 43^12 ' 43_20 43_21 43_23 43^25 44_1 44_5

    223_10

    223_2

    223_4

    223_5

    223_6

    223_7

    A3_4

    A3~5

    A3_7

    A3_3

    42_12

    AAV1

    AAV2

    AAV3

    AAV8

    AAV9

    AAV7

    44_2

    Fig. IAN

    1951 2000

    TCGTCACGCG GGCATGCTTC AGATGCTGTT TCCCTG.CAA GACATGCGAG TCGTCACGCG GGCATGCTTC AGATGCTGTT TCCCTG.CAA GACATGCGAG TCGTCACGCG GGCATGCTTC AGATGCTGTT TCCCTG.CAA GACATGCGAG TCGTCACGCG GGCATGCTTC AGATGCTGTT TCCCTG.CAA GACATGCGAG

    ........................GAATTC GCCCTT.....GGCTGCGTC

    TCGTCACGCG GGCATGCTTC AGATGCTGTT TCCCTG.CAA GACATGCGAG TCGTCACGCG GGCATGCTTC AGATGCTGCT TCCCTG.CAA GACATGCGAG

    ........................GAATTC GCCCTTTCTA CGGCTGCGTC

    TCGTCACGCG GGCATGCTTC AGATGCTGTT TCCCTG.CAA AACATGCGAG

    ........................GAATTC GCCCTTTCTA CGGCTGCGTC

    ........................GAATTC GCCCTTTCTA CGGCTGCGTC

    TCGTCACGCG GGCATGCTTC AGATGCTGTT TCCCTG.CAA GACATGCGAG TCGTCACGCG GGCATGCTTC AGATGCTGTT TCCCTG.CAA GACATGCGAG TCGTCACGCG GGCATGCTTC AGATGCTGTT TCCCTG.CAA AACGTGCGAG TCGTCACGCG GGCATGCTTC AGACGCTGTT TCCCTG.CAA AACGTGCGAG TCGTCACGCG GGCATGCTCC AGATGCTGTT TCCCTG.CAA AACGTGCGAG TCGTCACGCG GGCATGCTTC AGATGCTGTT TCCCTG.CAA GACATGCGAG TCGTCACGCG GGCATGCTTC AGATGCTGTT TCCCTG.CAA GACATGCGAG TCGTCACGCG GGCATGCTTC AGATGCTGTT TCCCTG.CAA GACATGCGAG TCGTCACGCG GGCATGCTTC AGATGCTGTT TCCCTG.CAA GACATGCGAG' TCGTCACGCG GGCATGCTTC AGATGCTGTT TCCCTG.CAA AACATGCGAG TCGTCACGCG GGCATGCTTC AGATGCTGTT TCCCTG.CAA AACATGCGAG

    TCGTCACGTG

    TCGTCACGTG

    TCGTCACGTG

    TCGTCACGTG

    TCGTCACGCG

    TCGTCACGCG

    TCGTCACGTG

    TCGTCACGTG

    TCGTCACGCG

    TCGTCACGCG

    TCGTCACGCG

    TCGTCACGCG

    GGCATGAATC

    GGCATGAATC

    GGCATGAATC

    GGCATGAATC

    GGCATGCTTC

    GGCATGCTTC

    GGCATGAATC

    GGCATGAATC

    GGCATGCTTC

    GGCATGCTTC

    GGCATGATTC

    GGCATGCTTC

    TGATGCTGTT

    TGATGCTGTT

    TGATGCTGTT

    TGATGCTGTT

    AGATGCTGTT

    AGATGCTGTT

    TGATGCTGTT

    TGATGCTTTT

    AGATGCTGTT

    AGATGCTGCT

    AGATGCTGTT

    AGATGCTGTT

    TCCCTG.TCG

    TCCCTG.TCG

    TCCCTG.TCG

    TCCCTG.TCG

    TCCCTG.CAA

    TCCCTG.CAA

    TCCCTG.CAG

    TCCCTG.TAA

    TCCCTG.CAA

    TCCCTG.CAA

    TCCCTG.CAA

    TCCCTG.CAA

    ACAATGCGAA

    ACAATGCGAA

    ACAATGCGAA

    ACAATGCGAA

    GACATGCGAG

    GACATGCGAG

    ACAATGCGAG

    AACATGCGAG

    AACGTGCGAG

    AACGTGCGAG

    AACGTGCGAG

    AACATGCGAG
40. 40/105

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    42_2

    42_8

    42_15

    42_5b

    42_lb

    42_13

    42_3a

    42_4

    42_5a

    42_10

    42_3b

    42_11

    42_6b

    43_1

    43_5

    43_12

    43_20

    43_21

    43_23

    43_25

    44_1 ⁴⁴„⁵

    223_10

    223_2

    223_4

    223_5

    223_6

    223_7

    A3_4

    A3~5

    A3__7

    A3_3

    42_12

    AAV1

    AAV2

    AAV3

    AAV8

    AAV9

    AAV7

    44 2

    Fig. 1AO

    2001 2050

    AGAATGAATC AGAATTTCAA CATTTGCTTC ACGCACGGGA CCAGAGACTG AGAATGAATC AGAATTTCAA CATTTGCTTC ACGCACGGGA CCAGAGACTG AGAATGAATC AGAATTTCAA CATTTGCTTC ACGCGCGGGA CCAGAGACTG AGAATGAATC AGAATTTCAA CATTTGCTTC ACGCACGGGA CCAGAGACTG

    A.ACTGGACC A. .ATGAGAA CTTTCCCTTC A........A CGATTGCGTC

    AGAATGAATC AGAATTTCAA CATTTGCTTC ACGCACGGGA CCAGAGACTG AGAATGAATC AGAATTTCAG CATTTGCTTC ACGCACGGGA CCAGAGACTG

    A.ACTGGACC A..ATGAGAA CTTTCCCTTC A........A CGATTGCGTC

    AGAATGAATC AGAATTTCAA CATTTGCTTC ACGCACGGGA CCAGAGACTG

    A.ACTGGACC A. .ATGAGAA CTTTCCCTTC A........A CGATTGCGTC

    A.ACTAGACC A. .ATGAGAA CTTTCCCTTC A........A CGATTGCGTC

    AGAATGAATC AGAATTTCAA CATTTGCTTC ACGCACGGGA CCGGAGACTG AGAATGAATC AGAATTTCAA CATTTGCTTC ACGCACGGGA CCAGAGACTG AAAATGAATC AGAATTTCAA CATTTGCTTC ACGCACGGGG TCAGAGACTG AGAATGAATC AGAATTTCAA CATTTGCTTC ACGCACGGGG TCAGAGACTG AGAATGAATC AGAATTTCAA CATTTGCTTC ACGCACGGGG TCAGAGACTG AGAATGAATC AGAATTTCAA CATTTGCTTC ACGCACGGGA CCAGAGACTG AGAATGAATC AGAATTTCAA CATTTGCTTC ACGCACGGGA CCAGAGACTG AGAATGAATC AGAATTTCAA CATTTGCTTC ACGCACGGGA CCAGAGACTG AGAATGAATC AGAATTTCAA CATTTGCTTC ACGCACGGGA CCAGAGACTG AGAATGAATC AGAATTTCAA CATTTGCTTC ACGCACGGGA CCAGAGACTG AGAATGAATC AGAATTTCAA CATTTGCTTC ACGCACGGGA CCAGAGACTG

    AGAATGAATC

    AGAATGAATC

    AGAATGAATC

    AGAATGAATC

    AGAATGAATC

    AGAATGAATC

    AGAATGAATC

    AGAATGAATC

    AGAATGAATC

    AGAATGAATC

    AGAATGAATC

    AGAATGAATC

    AGAATTCAAA

    AGAATTCAAA

    AGAATTCAAA

    AGAATTCAAA

    AGAATTTCAA

    AGAATTTCAA

    AGAATTCAAA

    AAATTTCCAA

    AGAATTTCAA

    AGAATTTCAA

    AGAATTTCAA

    AGAATTTCAA

    TATCTGCTTC

    TATCTGCTTC

    TATCTGCTTC

    TATCTGCTTC

    CATTTGCTTC

    CATTTGCTTC

    TATCTGCTTC

    TGTCTGTTTT

    CATTTGCTTC

    CATTTGCTTC

    CATTTGCTTC

    CATTTGCTTC

    ACACACGGGC

    ACACACGGGC

    ACACACGGGC

    ACACACGGGC

    ACGCACGGGA

    ACGCACGGGA

    ACTCACGGAC

    ACGCATGGTC

    ACACACGGGG

    ACACACGGGG

    ACACACGGGG

    ACGCACGGGA

    AAAAAGACTG

    AAAAAGACTG

    AAAAAGACTG

    AAAAAGACTG

    CCAGAGACTG

    CGAGAGACTG

    AGAAAGACTG

    AAAGAGACTG

    TCAGAGACTG

    TCAGAGACTG

    TCAGAGACTG

    CCAGAGACTG
41. 41/105

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42. 42-2

    42_8

    42JL5 42_5b 42_lb 42_13 42_3a

    42_4

    42_5a

    42— 10 42_3b 42_11 42_6b
43. 43_1

    43_5

    43— 12 43_20 43_21 43_23 43_25
44. 44-1

    44_5

    223_10

    223-2

    223_4

    223-5

    223-6

    223-7

    A3_4

    A3—5

    A3_7

    A3_3

    42-12

    AAV1

    AAV2

    AAV3

    AAV8

    AAV9

    AAV7

    44 2

    2051

    TTCAGAATGT

    TTCAGAATGT

    TTCAGAATGT

    TTCAGAATGT

    GACAAGATGG

    TTCAGAATGT

    TTCAGAATGT

    GACAAGATGG

    TTCAGAATGT

    GACAAGATGG

    GACAAGATGG

    TTCAGAATGT

    TTCAGAATGT

    CTCAGAATGT

    CTCAGAATGT

    CTCAGAATGT

    TTCAGAATGT

    TTCAGAATGT

    TTCAGAATGT

    TTCAGAATGT

    TTCAGAATGT

    TTCAGAATGT

    TTTGGAATGC

    TTTGGAATGC

    TTTGGAATGC

    TTTGGAATGC

    TTCAGAATGT

    TTCAGAGTGC

    TTTAGAGTGC

    TGGGGAATGC

    CTCAGAGTGT

    CTCAGAGTGT

    TTTAGAGTGT

    TTCAGAATGT

    TTCCCCGGCG TGTCAGAATC

    TTCCCCGGCG TGTCAGAATC TTCCCGGGCG TGTCAGAATC TTCCCCGGCG TGTCAGAATC TGATCTGGTG GG..AGGAGG TTCCCCGGCG TGTCAGAATC TTCCCCGGCG TGTCAGAATC TGATCTGGTG GG..AGGAGG TTCCCCGGCG TGTCAGAATC TGATCTGGTG GG..AGGAGG TGATCTGGTG GG. .AGGAGG TTCCCCGGCG TGTCAGAATC TTCCCCGGCG TGTCAGAATC TTCCCCGGTG CATCAGAATC TTCCCCGGTG CATCAGAATC TTCCCCGGTG CATCAGAATC TTCCCCGGCG TGTCAGAATC TTCCCCGGCG TGTCAGAATC TTCCCCGGCG TGTCAGAATC TTCCCCGGCG TGTCAGAATC TTCCCCGGCG TGTCAGAATC TTCCCCGGCG TGTCAGAATC

    TCAACC. . . . 2100 ..GGTCGTCA TCAACC.... ..GGTCGTCA TCAACC.... ..GGTCGTCA TCAACC.... ..GGTCGTCA GCAAGA.... ..TGACGGCC TCAACC.... ..GGTCGTCA TCAACC.... ..GGTCGTCA GCAAGA.... ..TGACGGCC TCAACC.... ..GGTCGTCA GCAAGA.... ..TGACGGCC GCAAGA.. . . ..TGACGGCC TCAACC.... ..GGTCGTCA TCAACC.... ..GGTCGTCA TCAACC.... ..GGTCGTCA TCAACC.... ..GGTCGTCA TCAACC.... ..GGTCGTCA TCAACC.... ..GGTCGTCA TCAACC.... ..GGTCGTCA TCAACC.... ..GGTCGTCA TCAACC.... ..GGTCGTCA TCAACC.... ..GGTCGTCA TCAACC.... ..GGTTGTCA

    TTTCCCG... TTTCCCG... TTTCCCG... TTTCCCG... TTCCCCGGCG TTCCCCGGCG TTTCCCG... TTCCCTGGAA TTCCCCGGCG TTCCCCGGCG TTCCCCGGCG TTCCCCGGCG

    Fig. 1AP

    TGTCAGAATC

    TGTCAGAATC

    TGTCAGAATC

    TGTCAGAATC

    TGTCAGAATC

    TGTCAGAATC

    TGTCAGAATC

    TGTCAGAATC

    TGTCAGAATC

    TGTCAGAATC

    TGTCAGAATC

    TGTCAGAATC

    TCAACCCGTT TCAACCCGTT TCAACCCGTT TCAACCCGTT TCAACC.. . . TCAACC.. . . TCAACCCGTT TCAACCCGTT TCAACC.. . . TCAACC.. .. TCAACC. . . . TCAACC....

    TCTGTCGTCA CCTGTCGTCA TCTGTCGTCA TCTGTCGTCA ..GGTCGTCA ..GGTCGTCA TCTGTCGTCA TCTGTCGTCA ..GGTCGTCA ..GGTCGTCA ..GGTCGTCA ..GGTCGTCA

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    Fig. 1AQ

    2101 2150

    42 2 GAAAGAGGAC GTATCGGAAA CTCTGTGCCA TTCATCATCT GCTGGGG.CG

    GAAAGAGGAC GTATCGGAAA CTCTGTGCCA TTCATCATCT GCTAGGG.CG GAAAGAGGAC GTATCGGAAA CTCTGTGCCA TTCATCATCT GCTGGGG.CG GAAAGAGGAC GTATCGGAAA CTCTGTGCCA TTCATCATCT GCTGGGG.CG .AAGGTCGTG GAGTCCGCCA AG....GCCA TTCATCATCT GCTGGGG.CG GAAAGAGGAC GTATCGGAAA CTCTGTGCCA TTCATCATCT GCTGGGG.CG GAAAGAGGAC GTATCGGAAA CTCTGTGCCA TTCATCATCT GCTGGGG.CG .AAGGTCGTG GAGTCCGCCA AG....GCCA TTCATCATCT GCTGGGG.CG GAAAGAGGAC GTATCGGAAA CTCTGTGCCA TTCATCATCT GCTGGGG.CG AA....GGTC GTGAAGTCCG CCAAG.GCCA TTCATCATCT GCTGGGG.CG AA....GGTC GTGGAGTCCG CCAAG.GCCA TTCATCATCT GCTGGGG.CG GAAAGAGGAC GTATCGGAAA CTCTGTGCCA TTCATCATCT GCTGGGG.CG GAAAGAGGAC GTATCGGAAA CTCTGTGCCA TTCATCATCT GCTGGGG.CG GAAAAAAAAC GTATCAGAAA CTGTGTGCCA TTCATCATCT GCTGGGG.CG GAAAAAAAAC GTATCAGAAA CTGTGTGCCA TTCATCATCT GCTGGGG.CG GAAAAAAAAC GTATCAGAAA CTGTGTGCCA TTCATCATCT GCTGGGG.CG GAAAGAGGAC GTATCGGAAA CTCTGTGCGA TTCATCATCT GCTGGGG.CG GAAAGAGGAC GTATCGGAAA CTCTGTGCGA TTCATCATCT GCTGGGG.CG GAAAGAGGAC GTATCGGAAA CTCTGTGCGA TTCATCATCT GCTGGGG.CG GAAAGAGGAC GTATCGGAAA CTCTGTGCGA TTCATCATCT GCTGGGG.CG GAAAAAAGAC GTATCGGAAA CTCTGTGCGA TTCATCATCT GCTGGGG.CG GAAAAAAGAC GTATCGGAAA CTCTGTGCGA TTCATCATCT GCTGGGG.CG

    42_8

    42_15 42__5b 42JLb 42_13 42_3a 42_4 42_5a 42_10 42_3b 42_11 42_6b 43_1 43_5 43_12 43__20 43_21 43 23 43~25 44_1 44_5 223_10 223_2 223_4 223_5 223_6 223J7 A3_4 GAAAAACG. . A3_5 GAAAAACG. . A3_7 GAAAAACG. . A3_3 GAAAAACG. . 42_12 GAAAGAGGAC AAV1 GAAAGAGGAC AAV2 AAAAGGCG.. AAV3 AAAAGAAGAC AAV8 GAAAGAGGAC AAV9 GAAAGAGGAC AAV7 GAAAAAAGAC 44 2 GAAAAAAGAC .TATCAGAAA CTTTGTTACA .TATCAGAAA CTTTGTTACA .TATCAGAAA CTTTGTTACA .TATCAGAAA CTTTGTTACA GTATCGGAAA CTCTGTGCCA GTATCGGAAA CTCTGTGCCA .TATCAGAAA CTGTGCTACA TTATCAGAAA CTGTGTCCAA GTATCGGAAA CTCTGTGCGA GTATCGGAAA CTCTGTGCGA GTATCGGAAA CTCTGCGCGA GTATCGGAAA CTCTGTGCGA

    TTCATCATAT CATGGGA.AA TTCATCATAT CATGGGA.AA TTCATCATAT CATGGGA.AA TTCATCATAT CATGGGA.AA TTCATCATCT GCTGGGG.CG TTCATCATCT GCTGGGG.CG TTCATCATAT CATGGGA.AA TTCATCATAT CCTGGGA.AG TTCATCATCT GCTGGGG.CG TTCATCATCT GCTGGGG.CG TTCATCATCT GCTGGGG.CG TTCATCATCT GCTGGGGGCG

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    42_2

    42_8

    42_15

    42_5b

    42_lb

    42_13

    42_3a

    42_4

    42_5a

    42__10

    42_3b

    42JL1

    42_6b

    43_1

    43_5

    43_12

    43_20

    43_2l

    43_23

    43_25

    44_1

    44_5

    223_10

    223_2

    223_4

    223^5

    223_6

    223J7

    A3_4

    A3_5

    A3„7

    A3_3

    42_12

    AAV1

    AAV2

    AAV3

    AAV8

    AAV9

    AAV7

    44_2

    Fig. 1AR

    2151 2200 GGCTCCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTGG GGCTCCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTGG GGCTCCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTGG GGCTCCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTGG GGCTCCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTGG GGCTCCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTGG GGCTCCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTGG GGCTCCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTGG GGCTCCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTGG GGCTCCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTGG GGCTCCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTGG GGCTCCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTGG GGCTCCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTGG GGCACCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTGG GGCACCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTGG GGCACCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTGG GGCTCCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTGG GGCTCCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTGG GGCTCCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTGG GGCTCCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTGG GGCACCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTAG GGCACCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTAG

    AGAACCAGAC . .. GCCTGCA CTGCCTGCGA CCTGGTAAAT GTGGACTTGG AGTACCAGAC . .. GCCTGCA CTGCCTGCGA CCTGGTAAAT GTGGACTTGG AGTACCAGAC ...GCCTGCA CTGCCTGCGA CCTGGTAAAT GTGGACTTGG AGTACCAGAC . .. GCCTGCA CTGCCTGCGA CCTGGTAAAT GTGGACTTGG GGCTCCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTGG GGCTCCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTGG GGTGCCAGAC ...GCTTGCA CTGCCTGCGA TCTGGTCAAT GTGGATTTGG GGCACCCGAG ATTGCCTGTT CGGCCTGCGA TTTGGCCAAT GTGGACTTGG GGCTCCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTGG GGCTCCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTGG GGCGCCCGAG ATTGCTTGCT CGGCCTGCGA CCTGGTCAAC GTGGACCTGG GGCACCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTAG

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    42_2

    42_8

    42~15

    42_5b

    42_lb

    42_13

    42_3a

    42_4

    42_5a

    42_10

    42_3b

    42_11

    42_6b

    43_1

    43_5

    43_12

    43_20

    43_21

    43_23

    43_25

    44_1

    44_5

    223JL0

    223_2

    223_4

    223_5

    223_6

    223_7

    A3_4

    A3_5

    A3_7

    A3_3

    42_12

    AAVl

    AAV2

    AAV3

    AAV8

    AAVS

    AAV7

    44_2

    Fig. IAS

    2201 2250

    Rep 78 stop vpl start

    ATGACCGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA ATGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA ATGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA ATGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA ATGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA ATGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA ATGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA ATGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA ATGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA ATGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA ATGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA ATGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA ATGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA ACGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA ACGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA ACGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA ATGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA ATGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA ATGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA ATGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA ATGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA ATGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA

    ATGACTGTAT TTCTGAGCAA TAAATGACTT AAATCAGGTA TGGCTGCTGA ATGACTGTAT TTCTGAGCAA TAAATGACTT AAATCAGGTA TGGCTGCTGA ATGACTGTAT TTCTGAGCAA TAAATGACTT AAATCAGGTA TGGCTGCTGA ATGACTGTAT TTCTGAGCAA TAAATGACTT AAATCAGGTA TGGCTGCTGA ATGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA ATGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA ATGACTGCAT CTTTGAACAA TAAATGATTT AAATCAGGTA TGGCTGCCGA ATGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCTGA ATGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA ATGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA ACGACTGCGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA ATGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA

    Rep78 stop vpl start
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    42/

    42/

    42_15

    42/b

    42_lb

    42_13

    42_3a

    42_4

    42_5a

    42/0

    42_3b

    42_11

    42/b

    43/

    43/

    43/2

    43/0

    43/1

    43/3

    43/5

    44_1

    44/

    223/0

    223/

    223_4

    223/

    223/

    223/

    A3_4

    A3/

    A3_7

    A3_3

    42_12

    AAV1

    AAV2

    AAV3

    AAV8

    AAV9

    AAV7

    44/

    Fig. 1AT

    2251 2300

    Rep68 stop

    TGGTTATCTT CCAGATTGGC TCGAGGACAA CCTCTCTGAG GGCATTCGCG TGGTTATCTT CCAGATTGGC TCGAGGACAA CCTCTCTGAG GGCATTCGCG TGGTTATCTT CCAGATTGGC TCGAGGACAA CCTCTCTGAG GGCATTCGCG TGGTTATCTT CCAGATTGGC TCGAGGACAA CCTCTCTGAG GGCATTCGCG TGGTTATCTT CCAGATTGGC TCGAGGACAA CCTCTCTGAG GGCATTCGCG TGGTTATCTT CCAGATTGGC TCGAGGACAA CCTCTCTGAG GGCATTCGCG TGGTCATCTT CCAGATTGGC TCGAGGACAA CCTCTCTGAG GGCATTCGCG TGGTTATCTT CCAGATTGGC TCGAGGACAA CCTCTCTGAG GGCATTCGCG TGGTTATCTT CCAGATTGGC TCGAGGACAA CCTCTCTGAG GGCATTCGCG TGGTTATCTT CCAGATTGGC TCGAGGACAA CCTCTCTGAG GGCATTCGCG TGGTTATCTT CCAGATTGGC TCGAGGACAA CCTCTCTGAG GGCATTCGCG TGGTTATCTT CCAGATTGGC TCGAGGACAA CCTCTCTGAG GGCATTCGCG TGGTTATCTT CCAGATTGGC TCGAGGACAA CCTCTCTGAG GGCATTCGCG TGGTTATCTT CCAGATTGGC TTGAGGACAA CCTCTCTGAG GGCATTCGCG TGGTTATCTT CCAGATTGGC TTGAGGACAA CCTCTCTGAG GGCATTCGCG TGGTTATCTT CCAGATTGGC TTGAGGACAA CCTCTCTGAG GGCATTCGCG TGGTTATCTT CCAGATTGGC TCGAGGACAA CCTCTCTGAG GGCATTCGCG TGGTTATCTT CCAGATTGGC TCGAGGACAA CCTCTCTGAG GGCATTCGCG TGGTTATCTT CCAGATTGGC TCGAGGACAA CCTCTCTGAG C-GCATTCGCG TGGTTATCTT CCAGATTGGC TCGAGGACAA CCTCTCTGAG GGCATTCGCG TGGTTATCTT CCAGATTGGC TCGAGGACAA CCTCTCTGAG GGCATTCGCG TGGTTATCTT CCAGATTGGC TCGAGGACAA CCTCTCTGAG GGCATTCGCG

    CGGTTATCTT CCAGATTGGC TCGAGGACAC TCTCTCTGAA GGAATCAGAC CGGTTATCTT CCAGATTGGC TCGAGGACAC TCTCTCTGAA GGAATCAGAC CGGTTATCTT CCAGATTGGC TCGAGGACAC TCTCTCTGAA GGAATCAGAC CGGTTATCTT CCAGATTGGC TCGAGGACAC TCTCTCTGAA GGAATCAGAC TGGTTATCTT CCAGATTGGC TCGAGGACAA CCTCTCTGAG GGCATCCGCG TGGTTATCTT CCAGATTGGC TCGAGGACAA CCTCTCTGAG GGCATTCGCG TGGTTATCTT CCAGATTGGC TCGAGGACAC TCTCTCTGAA GGAATAAGAC CGGTTATCTT CCAGATTGGC TCGAGGACAA CCTTTCTGAA GGCATTCGTG TGGTTATCTT CCAGATTGGC TCGAGGACAA CCTCTCTGAG GGCATTCGCG TGGTTATCTT CCAGATTGGC TCGAGGACAA CCTCTCTGAG GGCATTCGCG TGGTTATCTT CCAGATTGGC TCGAGGACAA CCTCTCTGAG GGCATTCGCG TGGTTATCTT CCAGATTGGC TCGAGGACAA CCTCTCTGAG GGCATTCGCG

    Rep 68 stop
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    Fig. 1AU

    2301 2350

    42 2 AGTGGTGGGA CTTGAAACCT GGAGCCCCGA AACCCAAAGC CAACCAGCAA

    42_8 42_15 42_5b 42_lb 42_13 42_3a

    42_4 42_5a 42_10 42_3b 42_11 42_6b 43_1 43-5 43-12 43-20 43_21 43_23 43-25 44_1 44_5 223_10 223_2 223 4 223^5 223-6 223_7

    A3-4 AGTGGTGGAA GCTCAAACCT A3—5 AGTGGTGGAA GCTCAAACCT A3—7 AGTGGTGGAA GCTCAAACCT A3_3 AGTGGTGGAA GCTCAAACCT

    42_12 AGTGGTGGGA CTTGAAACCT

    AAVl AGTGGTGGGA CTTGAAACCT AAV2 AGTGGTGGAA GCTCAAACCT AAV3 AGTGGTGGGC TCTGAAACCT AAV8 AGTGGTGGGC GCTGAAACCT AAV9 AGTGGTGGGC GCTGAAACCT AAV7 AGTGGTGGGA CCTGAAACCT 44 2 AGTGGTGGGA CTTGAAACCT

    AGTGGTGGGA CTTGAAACCT GGAGCCCCGA AACCCAAAGC CAACCAGCAA AGTGGTGGGA CTTGAAACCT GGAGCCCCGA AACCCAAAGC CAACCAGCAA AGTGGTGGGA CTTGAAACCT GGAGCCCCGA AACCCAAAGC CAACCAGCAA AGTGGTGGGA CTTGAGACCT GGAGCCCCGA AACCCAAAGC CAACCAGCAA AGTGGTGGGA CTTGAAACCT GGAGCCCCGA AACCCAAAGC CAACCAGCAA AGTGGTGGGA CTTGAAACCT GGAGCCCCGA AACCCAAAGC CAACCAGCAA AGTGGTGGGA CTTGAAACCT GGAGCCCCGA AACCCAAAGC CAACCAGCAA AGTGGTGGGA CTTGAAACCT GGAGCCCCGA AACCCAAAGC CAACCAGCAA AGTGGTGGGA CTTGAAACCT GGAGCCCCGA AACCCAAAGC CAACCAGCAA AGTGGTGGGA CTTGAAACCT GGAGCCCCGA AACCCAAAGC CAACCAGCAA AGTGGTGGGA CTTGAAACCT GGAGCCCCGA AACCCAAAGC CAACCAGCAA AGTGGTGGGA CTTGAAACCT GGAGCCCCGA AACCCAAAGC CAACCAGCAA AGTGGTGGGA CCTGAAACCT GGAGCCCCGA AACCCAAAGC CAACCAGCAA AGTGGTGGGA CCTGAAACCT GGAGCCCCGA AACCCAAAGC CAACCAGCAA AGTGGTGGGA CCTGAAACCT GGAGCCCCGA AACCCAAAGC CAACCAGCAA AGTGGTGGGA CTTGAAACCT GGAGCCCCGA AACCCAAAGC CAACCAGCAA AGTGGTGGGA CTTGAAACCT GGAGCCCCGA AACCCAAAGC CAACCAGCAA AGTGGTGGGA CTTGAAACCT GGAGCCCCGA AACCCAAAGC CAACCAGCAA AGTGGTGGGA CTTGAAACCT GGAGCCCCGA AACCCAAAGC CAACCAGCAA AGTGGTGGGA CTTGAAACCT GGAGCCCCGA AACCCAAAGC CAACCAGCAA AGTGGTGGGA CTTGAAACCT GGAGCCCCGA AACCCAAAGC CAACCAGCAA

    GGCCCACCAC CGCCGAAACC TAACCAACAA GGCCCACCAC CGCCGAAACC TAACCAACAA GGCCCACCAC CGCCGAAACC TAACCAACAA GGCCCACCAC CGCCGAAACC TAACCAACAA GGAGCCCCGA AACCCAAAGC CAACCAGCAA GGAGCCCCGA AGCCCAAAGC CAACCAGCAA GGCCCACCAC CACCAAAGCC CGCAGAGCGG GGAGTCCCTC AACCCAAAGC GAACCAACAA GGAGCCCCGA AGCCCAAAGC CAACCAGCAA GGAGCCCCGA AGCCCAAAGC CAACCAGCAA GGAGCCCCGA AACCCAAAGC CAACCAGCAA GGAGCCCCGA AACCCAAAGC CAACCAGCAA
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    42_2

    42_8

    42_15 42—5b 42_lb 42_13 42_3a

    42_4

    42_5a 42_10 42_3b 42_11 42_6b

    43_1

    43_5

    43_12 43_20 43_21 43_23 43_25

    44_1

    44—5

    223_10

    223_2

    223-4

    223-5

    223-6

    223-7

    A3_4

    A3-5

    A3_ 7

    A3—3 42_12 AAV1 AAV2 AAV3 AAV8 AAV9 AAV7 44_2

    Fig. 1AV

    2351 2400 AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG

    CACCGGGACG ACAGTAGGGG TCTTGTGCTT CCTGGGTACA AGTACCTCGG CACCGGGACG ACAGTAGGGG TCTTGTGCTT CCTGGGTACA AGTACCTCGG CACCGGGACG ACAGTAGGGG TCTTGTGCTT CCTGGGTACA AGTACCTCGG CACCGGGACG ACAGTAGGGG TCTTGTGCTT CCTGGGTACA AGTACCTCGG AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG CATAAGGACG ACAGCAGGGG TCTTGTGCTT CCTGGGTACA AGTACCTCGG CACCAGGACA ACCGTCGGGG TCTTGTGCTT CCGGGTTACA AATACCTCGG AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG AAGCAGGACA ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG
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    42_2 42_8 42_15 42_5b 42_lb 42_13 42_3a 42_4 42_5a 42_10 42_3b 42_11 42_6b 43_1 43_5 43_12 43_2Q 43_21 43_23 43__25 44_1 44_5 223_10 223_2 223_4 223_5 223_6 223_7 A3_4 ACCCTTCAAC A3_5 ACCCTTCAAC A3_7 ACCCTTCAAC A3_3 ACCCTTCAAC 42_12 ACCCTTCAAC AAV1 ACCCTTCAAC AAV2 ACCCTTCAAC AAV3 ACCCGGTAAC AAV8 ACCCTTCAAC AAV9 ACCCTTCAAC AAV7 ACCCTTCAAC 44 2 ACCCTTCAAC

    Fig. 1AW

    2401 2450 ACCCTTCAAC GGACTCGACA AGGGAGAGCC GGTCAACGAG GCAGACGCCG ACCCTTCAAC GGACTCGACA AGGGGGAGCC CGTCAACGCG GCGGACGCAG ACCCTTCAAC GGACTCGACA AGGGGGAGCC CGTCAACGCG GCGGACGCAG ACCCTTCAAC GGACTCGACA AGGGAGAGCC GGTCAACGAG GCAGACGCCG ACCCTTCAAC GGACTCGACA AGGGAGAGCC GGTCAACGAG GCAGACGCCG ACCCTTCAAC GGACTCGACA AGGGGGAGCC CGTCAACGCG GCGGACGCAG ACCCTTCAAC GGACTCGACA AGGGGGAGCC CGTCAACGCG GCGGACGCAG ACCCTTCAAC GGACTCGACA AGGGAGAGCC GGTCAACGAG GCAGACGCCG ACCCTTCAAC GGACTCGACA AGGGAGAGCC GGTCAACGAG GCAGACGCCG ACCCTTCAAC GGACTCGACA AGGGAGAGCC GGTCAACGAG GCAGACGCCG ACCCTTCAAC GGACTCGACA AGGGAGAGCC GGTCAACGAG GCAGACGCCG ACCCTTCAAC GGACTCGACA AGGGAGAGCC GGTCAACGCG GCGGACGCAG ACCCTTCAAC GGACTCGACA AGGGAGAGCC GGTCAACGAG GCAGACGCCG ACCCTTCAAC GGACTCGACA AGGGGGAGCC CGTCAACGCG GCGGACGCAG ACCCTTCAAC GGACTCGACA AGGGGGAGCC CGTCAACGCG GCGGACGCAG ACCCTTCAAC GGACTCGACA AGGGGGAGCC CGTCAACGCG GCGGACGCAG ACCCTTCAAC GGACTCGACA AGGGGGAGCC CGTCAACGCG GCGGACGCAG ACCCTTCAAC GGACTCGACA AGGGGGAGCC CGTCAACGCG GCGGACGCAG ACCCTTCAAC GGACTCGACA AGGGGGAGCC CGTCAACGCG GCGGACGCAG ACCCTTCAAC GGACTCGACA AGGGGGAGCC CGTCAACGCG GCGGACGCAG ACCCTTCAAC GGACTCGACA AGGGGGAGCC CGTCAACGCG GCGGACGCAG ACCCTTCAAC GGACTCGACA AGGGGGAGCC CGTCAACGCG GCGGACGCAG

    GGACTCGACA AAGGAGAGCC GGACTCGACA AAGGAGAGCC GGACTCGACA AAGGAGAGCC GGACTCGACA AAGGAGAGCC GGACTCGACA AGGGAGAGCC GGACTCGACA AGGGGGAGCC GGACTCGACA AGGGAGAGCC GGACTCGACA AAGGAGAGCC GGACTCGACA AGGGGGAGCC GGACTCGACA AGGGGGAGCC GGACTCGACA AGGGGGAGCC GGACTCGACA AGGGGGAGCC

    GGTCAACGAG GCAGACGCCG GGTCAACGAG GCAGACGCCG GGTCAACGAG GCAGACGCCG GGTCAACGAG GCAGACGCCG GGTCAACGAG GCAGACGCCG CGTCAACGCG GCGGACGCAG GGTCAACGAG GCAGACGCCG GGTCAACGAG GCGGACGCGG CGTCAACGCG GCGGACGCAG CGTCAACGCG GCGGACGCAG CGTCAACGCG GCGGACGCAG CGTCAACGCG GCGGACGCAG
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    Fig. 1AX

    2451 2500

    42_2 CGGCCCTCGA GCACG.ACAA GGCCTACGAC AAGCAGCTCG AGCAGGGGGA 42_8 CGGCCCTCGA GCACG.ACAA GGCCTACGAC CAGCAGCTCA AAGCGGGTGA 42_15 CGGCCCTCGA GCACG.ACAA GGCCTACGAC CAGCAGCTCA AAGCGGGTGA 42_5b CGGCCCTCGA GCACG.ACAA GGCCTACGAC AAGCAGCTCG AGCAGGGGGA 42_lb CGGCCCTCGA GCACG.ACAA GGCCTACGAC AAGCAGCTCG AGCAGGGGGA 42_13 CGGCCCTCGA GCACG.ACAA GGCCTACGAC CAGCAGCTCA AAGCGGGTGA 42_3a CGGCCCTCGA GCACG.ACAA GGCCTACGAC CAGCAGCTCA AAGCGGGTGA 42_4 CGGCCCTCGA GCACG.ACAA GGCCTACGAC AAGCAGCTCG AGCAGGGGGA 42_5a CGGCCCTCGA GCACG.ACAA GGCCTACGAC AAGCAGCTCG AGCAGGGGGA 42_10 CGGCCCTCGA GCACG.ACAA GGCCTACGAC AAGCAGCTCG AGCAGGGGGA 42_3b CGGCCCTCGA GCACG.ACAA GGCCTACGAC AAGCAGCTCG AGCAGGGGGA 42_11 CGGCCCTCGA GCACG.ACAA GGCCTACGAC CAGCAGCTCA AAGCGGGTGA 42_Sb CGGCCCTCGA GCACG.ACAA GGCCTACGAC AAGCAGCTCG AGCAGGGGGA 43_1 CGGCCCTCGA GCACG.ACAA GGCCTACGAC CAGCAGCTCA AAGCGGGTGA 43_5 CGGCCCTCGA GCACG.ACAA GGCCTACGAC CAGCAGCTCA AAGCGGGTGA 43_12 CGGCCCTCGA GCACG.ACAA GGCCTACGAC CAGCAGCTCA AAGCGGGTGA 43_20 CGGCCCTCGA GCACG.ACAA AGCCTACGAC CAGCAGCTCA AAGCGGGTGA 43_2l CGGCCCTCGA GCACG.ACAA AGCCTACGAC CAGCAGCTCA AAGCGGGTGA 43_23 CGGCCCTCGA GCACG.ACAA AGCCTACGAC CAGCAGCTCA AAGCGGGTGA 43_25 CGGCCCTCGA GCACG.ACAA AGCCTACGAC CAGCAGCTCA AAGCGGGTGA 44_1 CGGCCCTCGA GCACG.ACAA GGCCTACGAC CAGCAGCTCA AAGCGGGTGA 44_5 CGGCCCTCGA GCACG.ACAA GGCCTACGAC CAGCAGCTCA AAGCGGGTGA

    223_10 CAA GGCCTACGAC CAGCAGCTCA AAGCGGGTGA

    223_2 CAA GGCCTACGAC CAGCAGCTCA AAGCGGGTGA

    223_4 CAA GGCCTACGAC CAGCAGCTCA AAGCGGGTGA

    223_5 CAA GGCCTACGAC CAGCAGCTCA AAGCGGGTGA

    223_6 CAA GGCCTACGAC CAGCAGCTCA AAGCGGGTGA

    223 7 CAA GGCCTACGAC CAGCAGCTCA AAGCGGGTGA

    A3_4 CGGCCCTCGA GCACG.ACAA AGCCTACGAC CACCAGCTCA AGCAAGGGGA A3_5 CGGCCCTCGA GCACG.ACAA AGCCTACGAC CACCAGCTCA AGCAAGGGGA A3_7 CGGCCCTCGA GCACG.ACAA AGCCTACGAC CACCAGCTCA AGCAAGGGGA A3_3 CGGCCCTCGA GCACG.ACAA AGCCTACGAC CACCAGCTCA AGCAAGGGGA 42_12 CGGCCCTCGA GCACG.ACAA GGCCTACGAC AAGCAGCTCG AGCAGGGGGA AAV1 CGGCCCTCGA GCACG.ACAA GGCCTACGAC CAGCAGCTCA AAGCGGGTGA AAV2 CGGCCCTCGA GCACGTACAA AGCCTACGAC CGGCAGCTCG ACAGCGGAGA AAV3 CAGCCCTCGA ACACG.ACAA AGCTTACGAC CAGCAGCTCA AGGCCGGTGA AAV8 CGGCCCTCGA GCACG.ACAA GGCCTACGAC CAGCAGCTGC AGGCGGGTGA AAV9 CGGCCCTCGA GCACG.GCAA GGCCTACGAC CAGCAGCTGC AGGCGGGTGA AAV7 CGGCCCTCGA GCACG.ACAA GGCCTACGAC CAGCAGCTCA AAGCGGGTGA 44_2 CGGCCCTCGA GCACG.ACAA GGCCTACGAC CAGCAGCTCA AAGCGGGTGA
50. 50/105

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    Fig. 1AY

    2501 42 2 42 8 CAACCCGTAC CAATCCGTAC 42 15 CAATCCGTAC 42 5b CAACCCGTAC 42 lb CAACCCGTAC 42 13 CAATCCGTAC 42 3a CAATCCGTAC 42 4 CAACCCGTAC 42 5a CAACCCGTAC 42 10 CAACCCGTAC 42 3b CAACCCGTAC 42 11 CAATCCGTAC 42 6b CAACCCGTAC 43 1 CAATCCGTAC 43 5 CAATCCGTAC 43 12 CAATCCGTAC 43 20 CAATCCGTAC 43 21 CAATCCGTAC 43 23 CAATCCGTAC 43 25 CAATCCGTAC 44 1 CAATCCGTAC 44 5 CAATCCGTAC 223 10 CAATCCGTAC 223 2 CAATCCGTAC 223 4 CAATCCGTAC 223 5 CAATCCGTAC 223 6 CAATCCGTAC 223 7 CAATCCGTAC A3 4 CAACCCGTAC A3 5 CAACCCGTAC A3 7 CAACCCGTAC A3 3 CAACCCGTAC 42 12 CAACCCGTAC AAV1 CAATCCGTAC AAV2 CAACCCGTAC AAV3 CAACCCGTAC AAV8 CAATCCGTAC AAV9 CAATCCGTAC AAV7 CAATCCGTAC 44 2 CAATCCGTAC

    CTCAAGTACA ACCACGCCGA CTGCGGTATA ACCACGCCGA CTGCGGTATA ACCACGCCGA CTCAAGTACA ACCACGCCGA CTCAAGTACA ACCACGCCGA CTGCGGTATA ACCACGCCGA CTGCGGTATA ACCACGCCGA CTCAAGTACA ACCACGCCGA CTCAAGTACA ACCACGCCGA CTCAAGTACA ACCACGCCGA CTCAAGTACA ACCACGCCGA CTGCGGTATA ACCACGCCGA CTCAAGTACA ACCACGCCGA CTGCGGTATA ACCACGCCGA CTGCGGTATA ACCACGCCGA CTGCGGTATA ACCACGCCGA CTGCGGTATA ATCACGCCGA CTGCGGTATA ATCACGCCGA CTGCGGTATA ATCACGCCGA CTGCGGTATA ATCACGCCGA CTGCGGTATA ACCACGCCGA CTGCGGTATA ACCACGCCGA CTGCGGTATA ACCACGCCGA CTGCGGTATA ACCACGCCGA CTGCGGTATA ACCACGCCGA CTGCGGTATA ACCACGCCGA CTGCGGTATA ACCACGCCGA. CTGCGGTATA ACCACGCCGA CTCAAATACA ACCACGCGGA CTCAAATACA ACCACGCGGA CTCAAATACA ACCACGCGGA CTCAAATACA ACCACGCGGA CTCAAGTACA ACCACGCCGA CTGCGGTATA ACCACGCCGA CTCAAGTACA ACCACGCCGA CTCAAGTACA ACCACGCCGA CTGCGGTATA ACCACGCCGA CTGCGGTATA ACCACGCCGA CTGCGGTATA ACCACGCCGA CTGCGGTATA ACCACGCCGA

    2550

    CGCCGAGTTT CAGGAGCGTC CGCCGAGTTT CAGGAGCGTC CGCCGAGTTT CAGGAGCGTC CGCCGAGTTT CAGGAGCGTC CGCCGAGTTT CAGGAGCGTC CGCCGAGTTT CAGGAGCGTC CGCCGAGTTT CAGGAGCGTC CGCCGAGTTT CAGGAGCGTC CGCCGAGTTT CAGGAGCGTC CGCCGAGTTT CAGGAGCGTC CGCCGAGTTT CAGGAGCGTC CGCCGAGTTT CAGGAGCGTC CGCCGAGTTT CAGGAGCGTC CGCCGAGTTT CAGGAGCGTC CGCCGAGTTT CAGGAGCGTC CGCCGAGTTT CAGGAGCGTC CGCCGAGTTT CAGGAGCGTC CGCCGAGTTT CAGGAGCGTC CGCCGAGTTT CAGGAGCGTC CGCCGAGTTT CAGGAGCGTC CGCCGAGTTT CAGGAGCGTC CGCCGAGTTT CAGGAGCGTC CGCCGAGTTT CAGGAGCGTC CGCCGAGTTT CAGGAGTGTC CGCCGAGTTT CAGGAGCGTC CGCCGAGTTT CAGGAGCGTC CGCCGAGTTT CAGGAGCGTC CGCCGAGTTT CAGGAGCGTC CGCTGAATTT CAGGAGCGTC CGCTGAATTT CAGGAGCGTC CGCTGAATTT CAGGAGCGTC CGCTGAATTT CAGGAGCGTC CGCCGAGTTT CAGGAGCGTC CGCCGAGTTT CAGGAGCGTC CGCGGAGTTT CAGGAGCGCC CGCCGAGTTT CAGGAGCGTC CGCCGAGTTT CAGGAGCGTC CGCCGAGTTT CAGGAGCGTC CGCCGAGTTT CAGGAGCGTC CGCCGAGTTT CAGGAGCGTC
51. 51/105

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    42_2

    42_8

    42_15

    42_5b

    42_lb

    42_13

    42_3a

    42_4

    42_5a

    42_10

    42_3b

    42JL1

    42_6b

    43_1

    43_5

    4 3_1 2 43_20 43_21 43_23 43_25

    44_1

    44 5 223_10 223 2 223_4 223_5 223_6 223_7

    A3_4

    A3_5

    A3_7

    A3_3

    42_12

    AAVl

    AAV2

    AAV3

    AAV8

    AAV9

    AAV7

    44 2

    Fig. 1AZ

    2551 2600

    TTCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG TGCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG TGCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG TTCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG TTCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG TTCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG TTCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG TTCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG TTCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCGG TTCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG TTCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG TTCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG TTCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG TGCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG TGCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG TGCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG TGCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG TGCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG TGCAAGAAGA TACGTCCTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG TGCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG TGCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG TGCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG TTCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG TTCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG TTCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG TTCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG TTCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG TTCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG TTCAAGAAGA TACGTCTTTC GGGGGCAACC TCGGGCGAGC AGTCTTCCAG TTCAAGAAGA TACGTCTTTC GGGGGCAACC TCGGGCGAGC AGTCTTCCAG TTCAAGAAGA TACGTCTTTC GGGGGCAACC TCGGGCGAGC AGTCTTCCAG TTCAAGAAGA TACGTCTTTC GGGGGCAACC TCGGGCGAGC AGTCTTCCAG TTCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG TGCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG TTAAAGAAGA TACGTCTTTT GGGGGCAACC TCGGACGAGC AGTCTTCCAG TTCAAGAAGA TACGTCTTTT GGGGGCAACC TTGGCAGAGC AGTCTTCCAG TGCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG TGCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG TGCAAGAAGA TACGTCATTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG TGCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG
52. 52/105

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    Fig. 1AAA

    42_2

    42__8

    42_15 42_5b 42_lb 42_13 42_3a

    42- 4 42_5a 42_10 42_3b 42-11

    42- 6b

    43- 1

    43- 5 43_12 43_20 43_21 43_23

    43- 25

    44- 1

    44_5

    223—10 223_2 223_4 223_5 223-6 223_7 A3_4 A3_5 A3-7 A3-3 4 2-¹2 AAV1 AAV2 AAV3 AAV8 AAV9 AAV7 44 2

    2601

    GCCAAGAAGC

    GCCAAGAAGC

    GCCAAGAAGC

    GCCAAGAAGC

    GCCAAGAAGC

    GCCAAGAAGC

    GCCAAGAAGC

    GCCAAGAAGC

    GCCAAGAAGC

    GCCAAGAAGC

    GCCAAGAAGC

    GCCAAGAAGC

    GCCAAGAAGC

    GCCAAGAAGC

    GCCAAGAAGC

    GCCAAGAAGC

    GCCAAGAAGC

    GCCAAGAAGC

    GCCAAGAAGC

    GCCAAGAAGC

    GCCAAGAAGC

    GCCAAGAAGC

    GCCAAAAAGC

    GCCAAAAAGC

    GCCAAAAAGC

    GCCAAAAAGC

    GCCAAAAAGC

    GCCAAAAAGC

    GCCAAAAAGA

    GCCAAAAAGA

    GCCAAAAAGA

    GCCAAAAAGA

    GCCAAGAAGC

    GCCAAGAAGC

    GCGAAAAAGA

    GCCAAAAAGA

    GCCAAGAAGC

    GCCAAGAAGC

    GCCAAGAAGC

    GCCAAGAAGC

    GGGTTCTCGA

    GGGTTCTCGA

    GGGTTCTCGA

    GGGTTCTCGA

    GGGTTCTCGA

    GGGTTCTCGA

    GGGTTCTCGA

    GGGTTCTCGA

    GGGTTCTCGA

    GGGTTCTCGA

    GGGTTCTCGA

    GGGTTCTCGA

    GGGTTCTCGA

    GGGTTCTCGA

    GGGTTCTCGA

    GGGTTCTCGA

    GGGTTCTCGA

    GGGTTCTCGA

    GGGTTCTCGA

    GGGTTCTCGA

    GGGTTCTCGA

    GGGTTCTCGA

    GGGTTCTCGA

    GGGTTCTCGA

    GGGTTCTCGA

    GGGTTCTCGA

    GGGTTCTCGA

    GGGTTCTCGA

    GGGTACTCGA

    GGGTACTCGA

    GGGTACTCGA

    GGGTACTCGA

    GGGTTCTCGA

    GGGTTCTCGA

    GGGTTCTTGA

    GGATCCTTGA

    GGGTTCTCGA

    GGGTTCTCGA

    GGGTTCTCGA

    GGGTTCTCGA

    ACCTCTCGGT

    ACCTCTCGGT

    ACCTCTCGGT

    ACCTCTCGGT

    ACCTCTCGGT

    ACCTCTCGGT

    ACCTCTCGGT

    ACCTCTCGGT

    ACCTCTCGGT

    ACCTCTCGGT

    ACCTCTCGGT

    ACCTCTCGGT

    ACCTCTCGGT

    ACCTCTCGGT

    ACCTCTCGGT

    ACCTCTCGGT

    ACCTCTCGGT

    ACCTCTCGGT

    ACCTCTCGGT

    ACCTCTCGGT

    ACCTCTCGGT

    ACCTCTCGGT

    ACCTCTTGGT

    ACCTCTTGGT

    ACCTCTTGGT

    ACCTCTTGGT

    ACCTCTTGGT

    ACCTCTTGGT

    GCCTCTTGGT

    GCCTCTTGGT

    GCCTCTTGGT

    GCCTCTTGGT

    ACCTCTCGGT

    ACCTCTCGGT

    ACCTCTGGGC

    GCCTCTTGGT

    ACCTCTCGGT

    ACCTCTCGGT

    ACCTCTCGGT

    ACCTCTCGGT

    CTGGTTGAGG

    CTGGTTGAGG

    CTGGTTGAGG

    CTGGTTGAGG

    CTGGTTGAGG

    CTGGTTGAGG

    CTGGTTGAGG

    CTGGTTGAGG

    CTGGTTGAGG

    CTGGTTGAGG

    CTGGTTGAGG

    CTGGTTGAGG

    CTGGTTGAGG

    CTGGTTGAGG

    CTGGTTGAGG

    CTGGTTGAGG

    CTGGTTGAGG

    CTGGTTGAGG

    CTGGTTGAGG

    CTGGTTGAGG

    CTGGTTGAGG

    CTGGTTGAGG

    CTGGTTGAGA

    CTGGTTGAGA

    CTGGTTGAGA

    CTGGTTGAGA

    CTGGTTGAGA

    CTGGTTGAGA

    CTGGTTGAGG

    CTGGTTGAGG

    CTGGTTGAGG

    CTGGTTGAGG

    CTGGTTGAGG

    CTGGTTGAGG

    CTGGTTGAGG

    CTGGTTGAGG

    CTGGTTGAGG

    CTGGTTGAGG

    CTGGTTGAGG

    CTGGTTGAGG

    2650

    AAGGCGCTAA

    AAGGCGCTAA

    AAGGCGCTAA

    AAGGCGCTAA

    AAGGCGCTAA

    AAGGCGCTAA

    AAGGCGCTAA

    AAGGCGCTAA

    AAGGCGCTAA

    AAGGCGCTAA

    AAGGCGCTAA

    AAGGCGCTAA

    AAGGCGCTAA

    AAGGCGCTAA

    AAGGCGCTAA

    AAGGCGCTAA

    AAGGCGCTAA

    AAGGCGCTAA

    AAGGCGCTAA

    AAGGCGCTAA

    AAGGCGCTAA

    AAGGCGCTAA

    CGCCAGCTAA

    CGCCAGCTAA

    CGCCAGCTAA

    CGCCAGCTAA

    CGCCAGCTAA

    CGCCAGCTAA

    AAGCTGTTAA

    AAGCTGTTAA

    AAGCTGTTAA

    AAGCTGTTAA

    AAGGCGCTAA

    AAGGCGCTAA

    AACCTGTTAA

    AAGCAGCTAA

    AAGGCGCTAA

    AAGGCGCTAA

    AAGGCGCTAA

    AAGGCGCTAA
53. 53/105

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    Fig. 1AAB

    42_2

    42_8

    42_15 42_5b 42_lb 42—13 42_3a

    42_4 42_5a

    42— 10 42_3b 42_11 42_6b

    4 3_1 43_5

    43- 12 43-20 43-21 43-23 43_25

    44—1

    44_5

    223-10

    223-2 223-4 223-5 223-6 223-7 A3_4 A3-5 A3-7 A3-3 42_12 AAVl AAV2 AAV3 AAV8 AAV9 AAV7 44 2

    2651 2700 vp2 start

    GACGGCTCCT GGAAAGAAGA GACCCATAGA . . .ATCCCCC ..........

    GACGGCTCCT GGAAAGAAGA GACCGGTAGA GCCATCACCC CAGCGTTCTC

    GACGGCTCCT GGAAAGAAGA GACCGGTAGA GCCATCACCC CAGCGTTCTC

    GACGGCTCCT GGAAAGAAGA GACCGGTAGA GCCATCACCC CAGCGTTCTC

    GACGGCTCCT GGAAAGAAGA GACCCATAGA ...ATCCCCC ..........

    GACGGCTCCT GGAAAGAAGA GACCCATAGA . . .ATCCCCC ..........

    GACGGCTCCT GGAAAGAAGA GACCCATAGA . . .ATCCCCC ..........

    GACGGCTCCT GGAAAGAAGA GACCCATAGA . . .ATCCCCC ..........

    GACGGCTCCT GGAAAGAAGA GACCCATAGA . . .ATCCCCC ..........

    GACGGCTCCT GGAAAGAAGA GACCCATAGA ...ATCCCCC ..........

    GACGGCTCCT GGAAAGAAGA GACCCATAGA . . .ATCCCCC ..........

    GACGGCTCCT GGAAAGAAGA GACCCATAGA ...ATCCCCC ..........

    GACGGCTCCT GGAAAGAAGA GACCGGTAGA GCCATCACCC CAGCGTTCTC GACGGCTCCT GGAAAGAAGA GACCGGTAGA GCCATCACCT CAGCGTTCCC GACGGCTCCT GGAAAGAAGA GACCGGTAGA GCCATCACCT CAGCGTTCCC GACGGCTCCT GGAAAGAAGA GACCGGTAGA GCCATCACCT CAGCGTTCCC GACGGCTCCT GGAAAGAAGA GACTGGTAGA GCAGTCGCCA CAAGAG. . .C GACGGCTCCT GGAAAGAAGA GACCGGTAGA GCAGTCGCCA CAAGAG...C GACGGCTCCT GGAAAGAAGA GACCGGTAGA GCAGTCGCCA CAAGAG...C GACGGCTCCT GGAAAGAAGA GACCGGTAGA GCAGTCGCCA CAAGAG. ..C GACGGCTCCT GGAAAGAAGA GACCGGTAGA GCCATCACCC CAGCGTTCTC GACGGCTCCT GGAAAGAAGA GACCGGTAGA GCCATCACCC CAGCC-TTCTC

    GACGGCACCT GGAAAGAAGC GACCGGTAGA CTCGCCA.............

    GACGGCACCT GGAAAGAAGC GACCGGTAGA CTCGCCA.............

    GACGGCACCT GGAAAGAAGC GACCGGTAGA CTCGCCA.............

    GACGGCACCT GGAAAGAAGC GACCGGTAGA CTCGCCA.............

    GACGGCACCT GGAAAGAAGC GACCGGTAGA CTCGCCA.............

    GACGGCACCT GGAAAGAAGC GACCGGTAGA CTCGCCA.............

    GACGGCTCCT GGAAAAAAGA GACCTATAGA GCAGTCTCCT GCAGAA...C GACGGCTCCT GGAAAAAAGA GACCTATAGA GCAGTCTCCT GCAGAA...C GACGGCTCCT GGAAAAAAGA GACCTATAGA GCAGTCTCCT GCAGAA...C GACGGCTCCT GGAAAAAAGA GACCTATAGA GCAGTCTCCT GCAGAA. . . C GACGGCTCCT GGAAAGAAGA GACCGGTAGA GCCATCACCC CAGCGTTCTC GACGGCTCCT GGAAAGAAAC GTCCGGTAGA GCAGTCGCCA CAAGAG. . . C GACGGCTCCG GGAAAAAAGA GGCCGGTAGA GCAGTCTCCT GTGGAG. . .C AACGGCTCCT GGAAAGAAGG GGGCTGTAGA TCAGTCTCCT CAGGAA. . . C GACGGCTCCT GGAAAGAAGA GACCGGTAGA GCCATCACCC CAGCGTTCTC GACGGCTCCT GGAAAGAAGA GACCGGTAGA GCCATCACCC CAGCGTTCTC GACGGCTCCT GGAAAGAAGA GACCGGTAGA GCCGTCACCT CAGCGTTCCC GACGGCTCCT GGAAAGAAGA GACCGGTAGA GCCATCACCC CAGCGTTCTC vp2 start
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    Fig. 1AAC

    42- 2 42_8

    42—15

    42_5b

    42_lb

    42_13

    42_3a

    42_4 4 2-5 a 42_10 42—3b 42-11

    42— 6b

    43- 1

    43_5

    43_12

    43_20

    43_21

    43- 23 43-25

    44- 1

    44-5

    223_10 223-2 223_4 223_5 223_6 223_7 A3-4 A3_5 A3-7 A3- 3 42-12 AAV1 AAV2 AAV3 AAV8 AAV9 AAV7 44-2

    2701

    ..GACTCCTC

    CAGACTCCTC

    CAGACTCCTC

    CAGACTCCTC

    ..GACTCCTC

    ..GACTCCTC

    ..GACTCCTC

    ..GACTCCTC

    ..GACTCCTC

    ..GACTCCTC

    ..GACTCCTC

    ..GACTCCTC

    CAGACTCCTC

    CCGACTCCTC

    CCGACTCCTC

    CCGACTCCTC

    CAGACTCCTC

    CAGACTCCTC

    CAGACTCCTC

    CAGACTCCTC

    CAGACTCCTC

    CAGACTCCTC

    ..GACTCCAC

    ..GACTCCAC

    ..GACTCCAC

    ..GACTCCAC

    .. GACTCCAC

    ..GACTCCAC

    CGGACTCTTC

    CGGACTCTTC

    CGGACTCTTC

    CGGACTCTTC

    CAGACTCCTC

    CAGACTCCTC

    CAGACTCCTC

    CGGACTCATC

    CAGACTCCTC

    CAGACTCCTC

    CCGACTCCTC

    CAGACTCCTC

    CACGGGCATC

    TACGGGCATC

    TACGGGCATC

    TACGGGCATC

    CACGGGCATC

    CACGGGCATC

    CACGGGCATC

    CACGGGCATC

    CACGGGCATC

    CACGGGCATC

    CACGGGCATC

    CACGGGCATC

    TACGGGCATC

    CACGGGCATC

    CACGGGCATC

    CACGGGCATC

    CTCGGGCATC

    CTCGGGCATC

    CTCGGGCATC

    CTCGGGCATC

    TACGGGCATC

    TACGGGCATC

    CTCGGGCATC

    CTCGGGCATC

    CTCGGGCATC

    CTCGGGCATC

    CTCGGGCATC

    CTCGGGCATC

    CTCGGGCATC

    CTCGGGCATC

    CTCGGGCATC

    CTCGGGCATC

    TACGGGCATC

    CTCGGGCATC

    CTCGGGAACC

    ATCTGGTGTT

    TACGGGCATC

    TACGGGCATC

    CACGGGCATC

    TACGGGCATC

    GGCAAGAAAG

    GGCAAGACAG

    GGCAAGACAG

    GGCAAGACAG

    GGCAAGAAAG

    GGCAAGAAAG

    GGCAAGAAAG

    GGCAAGAAAG

    GGCAAGAAAG

    GGCAGGAAAG

    GGCAAGAAAG

    GGCAAGAAAG

    GGCAAGACAG

    GGCAAGAAAG

    GGCAAGAAAG

    GGCAAGAAAG

    GGCAAGACAG

    GGCAAGACAG

    GGCAAGACAG

    GGCAAGACAG

    GGCAAGAAAG

    GGCAAGAAAG

    GGCAAGAAAG

    GGCAAGAAAG

    GGCAAGAAAG

    GGCAAGAAAG

    GGCAAGAAAG

    GGCAAGAAAG

    GGCGAATCAG

    GGCAAATCAG

    GGCAAATCAG

    GGCAAATCAG

    GGCAAGACAG

    GGCAAGACAG

    GGAAAGGCGG

    GGCAAATCGG

    GGCAAGAAAG

    GGCAAGAAAG

    GGCAAGAAAG

    GGCAAGAAAG

    GCCAGCAGCC

    GCCAGCAGCC

    GCCAGCAGCC

    GCCAGCAGCC

    GCCAGCAGCC

    GCCAGCAGCC

    GCCAGCAGCC

    GCCAGCAGCC

    GCCAGCAGCC

    GCCAGCAGCC

    GCCAGCAGCC

    GCCAGCAGCC

    GCCAGCAGCC

    GCCACCAGCC

    GCCACCAGCC

    GCCACCAGCC

    GCCAGCAGCC

    GCCAGCAGCC

    GCCAGCAGCC

    GCCAGCAGCC

    GCCAGCAGCC

    GCCAGCAGCC

    GCCAGCAGCC

    GCCAGCAGCC

    GCCAGCAGCC

    GCCAGCAGCC

    GCCAGCAGCC

    GCCAGCAGCC

    GCCAGCAGCC

    GCCAGCAGCC

    GCCAGCAGCC

    GCCAGCAGCC

    GCCAGCAGCC

    GCCAGCAGCC

    GCCAGCAGCC

    GCAAACAGCC

    GCCAACAGCC

    GCCAACAGCC

    GCCAGCAGCC

    GCCAGCAGCC

    2750

    CGCTAAAAAG

    CGCGAAAAAG

    CGCGAAAAAG

    CGCGAAAAAG

    CGCTAAAAAG

    CGCTAAAAAG

    CGCTAAAAAG

    CGCTAAAAAG

    CGCTAAAAAG

    CGCTAAAAAG

    CGCTAAAAAG

    CGCTAAAAAG

    CGCGAAAAAG

    CGCGAGAAAG

    CGCGAGAAAG

    CGCGAGAAAG

    CGCTAAAAAG

    CGCTAAAAAG

    CGCTAAAAAG

    CGCTAAAAAG

    CGCGAAAAAG

    CGCGAAAAAG

    CGCGAAAAAG

    CGCGAAAAAG

    CGCGAAAAAG

    CGCGAAAAAG

    CGCGAAAAAG

    CGCGAAAAAG

    CGCTAAGAAA

    CGCTAAGAAA

    CGCTAAGAAA

    CGCTAAGAAA

    CGCGAAAAAG

    CGCTAAAAAG

    TGCAAGAAAA

    TGCCAGAAAA

    CGCCAGAAAA

    CGCCAGAAAA

    CGCGAGAAAG

    CGCGAAAAAG
55. 55/105

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    42_2

    42_8

    42_15

    42_5b

    42_lb

    42_13

    42_3a

    42_4

    42_5a

    42_10

    42_3b

    42_11

    42_6b

    43_1

    43_5

    43_12

    43_20

    43_21

    43_23

    43_25

    44_1

    44_5

    223^10

    223_2

    223_4

    223_5

    223_6

    223_7

    A3_4

    A3_5

    A3_7

    A3_3

    42_12

    AAV1

    AAV2

    AAVS

    AAV8

    AAV9

    AAV7

    44_2

    Fig. 1AAD

    2751 2800 AAGCTCAACT TTGGGCAGAC TGGCGACTCA GAGTCAGTGC CCGACCCCCA AGACTCAACT TTGGGCAGAC TGGCGACTCA GAGTCAGTGC CCGACCCTCA AGACTCAACT TTGGGCAGAC TGGCGACTCA GAGTCAGTGC CCGACCCTCA AGACTCAACT TTGGGCAGAC TGGCGACTCA GAGTCAGTGC CCGACCCTCA AGACTCAACT TTGGGCAGAC TGGCGACTCA GAGTCAGTGC CCGACCCTCA AAGCTCAACT TTGGGCAGAC TGGCGACTCA GAGTCAGTGC CCGACCCTCA AAGCTCAACT TTGGGCAGAC TGGCGACTCA GAGTCAGTGC CCGACCCTCA AAGCTCAACT TTGGGCAGAC TGGCGACTCA GAGTCAGTGC CCGACCCTCA AAGCTCAACT TTGGGCAGAC TGGCGACTCA GAGTCAGTGC CCGACCCCCA AAGCTCAACT TTGGGCAGAC TGGCGACTCA GAGTCAGTGC CCGACCCTCA AAGCTCAACT TTGGGCAGAC TGGCGACTCA GAGTCAGTGC CCGACCCTCA AAGCTCAACT TTGGGCAGAC TGGCGACTCA GAGTCAGTGC CCGACCCTCA AGACTCAACT TTGGGCAGAC TGGCGACTCA GAGTCAGTGC CCGACCCTCA AGACTGAACT TTGGGCAGAC TGGCGACTCG GAGTCAGTGC CCGACCCTCA AGACTGAACT TTGGGCAGAC TGGCGACTCG GAGTCAGTGC CCGACCCTCA AGACTGAACT TTGGGCAGAC TGGCGACTCG GAGTCAGTGC CCGACCCTCA AGACTCAATT TTGGTCAGAC TGGCGACTCA GAGTCAGTGC CCGACCCACA AGACTCAATT TTGGTCAGAC TGGCGACTCA GAGTCAGTGC CCGACCCACA AGACTCAATT TTGGTCAGAC TGGCGACTCA GAGTCAGTGC CCGACCCACA AGACTCAATT TTGGTCAGAC TGGCGACTCA GAGTCAGTCC CCGACCCACA AGACTCAACT TTGGGCAGAC TGGCGACTCA GAGTCAGTGC CCGACCCTCA AGACTCAACT TTGGGCAGAC TGGCGACTCA GAGTCAGTGC CCGACCCTCA AGACTCAACT TTGGGCAGAC TGGCGACTCA GAGTCAGTCC CCGACCCTCA AGACTCAACT TTGGGCAGAC TGGCGACTCA GAGTCAGTCC CCGACCCTCA AGACTCAACT TTGGGCAGAC TGGCGACTCA GAGCCAGTCC CCGACCCTCA AGACTCAACT TTGGGCAGAC TGGCGACTCA GAGCCAGTCC CCGACCCTCA AGACTCAACT TTGGGCAGAC TGGCGACTCA GAGTCAGTCC CCGACCCTCA AGACTCAACT TTGGGCAGAC TGGCGACTCA GAGTCAGTCC CCGACCCTCA AGACTCAATT TTGGTCAGAC TGGCGACACA GAGTCAGTCC CAGACCCTCA AGACTCAATT TTGGTCAGAC TGGCGACACA GAGTCAGTCC CAGACCCTCA AGACTCAATT TTGGTCAGAC TGGCGACACA GAGTCAGTCC CAGACCCTCA AGACTCAATT TTGGTCAGAC TGGCGACACA GAGTCAGTCC CAGGCCCTCA AGACTCAACT TTGGGCAGAC TGGCGACTCA GAGTCAGTGC CCGACCCTCA AGACTCAATT TTGGTCAGAC TGGCGACTCA GAGTCAGTCC CCGATCCACA AGATTGAATT TTGGTCAGAC TGGAGACGCA GACTCAGTAC CTGACCCCCA AGACTAAATT TCGGTCAGAC TGGAGACTCA GAGTCAGTCC CAGACCCTCA AGACTCAATT TTGGTCAGAC TGGCGACTCA GAGTCAGTTC CAGACCCTCA AGACTCAATT TTGGTCAGAC TGGCGACTCA GAGTCAGTTC CAGACCCTCA AGACTCAATT TCGGTCAGAC TGGCGACTCA GAGTCAGTCC CCGACCCTCA AGACTCAACT TTGGGCAGAC TGGCGACTCA GAGTCAGTGC CCGACCCTCA
56. 56/105

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    2801

    Fig. 1AAE

    2850

    42._2

    42_8

    42_15

    42_5b

    42_lb

    42_13

    42_3a

    42_4

    42_5a

    42_10

    42_3b

    42_11

    42_6b

    43_1

    43_5

    43_12

    43_20

    43_21

    43^23

    43_25

    44_1

    44_5

    223_l0

    223_2

    223_4

    223_5

    223_6

    223_7

    A3_4

    A3_5

    A3_7

    A3_3

    42_12

    AAVl

    AAV2

    AAV3

    AAV8

    AAV9

    AAV7

    44_2

    42._2

    42_8

    42_15

    42_5b

    42_lb

    42_13

    42_3a

    42_4

    42_5a

    42_10

    42_3b

    42_11

    42_6b

    43_1

    43_5

    43_12

    43_20

    43_21

    43^23

    43_25

    44_1

    44_5

    223_l0

    223_2

    223_4

    223_5

    223_6

    223_7

    A3_4

    A3_5

    A3_7

    A3_3

    42_12

    AAVl

    AAV2

    AAV3

    AAV8

    AAV9

    AAV7

    44_2

    ACCTCTCGGA GAACCTCCCG CCGCGCCCTC AGGTCTGGGA TCTGGTACAA ACCAATCGGA GAACCCCCCG CAGGCCCCTC TGGTCTGGGA TCTGGTACAA ACCAATCGGA GAACCCCCCG CAGGCCCCTC TGGTCTGGGA TCTGGTACAA ACCAATCGGA GAACCCCCCG CAGGCCCCTC TGGTCTGGGA TCTGGTACAA ACCAATCGGA GAACCCCCCG CAGGCCCCTC TGGTCTGGGA TCTGGCACAA ACCAATCGGA GAACCCCCCG CAGGCCCCTC TGGTCTGGGA TCTGGTACAA ACCAATCGGA GAACCCCCCG CAGGCCCCTC TGGTCTGGGA TCTGGTACAA ACCAATCGGA GAACCCCCCG CAGGCCCCTC TGGTCTGGGA TCTGGTACAA ACCTCTCGGA GAACCTCCCG CCGCGCCCTC AGGTCTGGGA TCTGGTACAA ACCAATCGGA GAACCCCCCG CAGGCCCCTC TGGTCTGGGA TCTGGTACAA ACCAATCGGA GAACCCCCCG CAGGCCCCTC TGGTCTGGGA TCTGGTACAA ACCAATCGGA GAACCCCCCG CAGGCCCCTC TGGTCTGGGA TCTGGTACAA ACCAATCGGA GAACCCCCCG CAGGCCCCTC TGGTCTGGGA TCTGGTACAA ACCAATCGGA GAACCACCAG CAGGCCCCTC TGGTCTGGGA TCTGGTACAA ACCAATCGGA GAACCACCAG CAGGCCCCTC TGGTCTGGGA TCTGGTACAA ACCAATCGGA GAACCACCAG CAGGCCCCTC TGGTCTGGGA TCTGGTACAA ACCTCTCGGA GAACCTCCAG CAGCCCCCTC AGGTCTGGGA CCTAATACAA ACCTCTCGGA GAACCTCCAG CAGCCCCCTC AGGTCTGGGA CCTAATACAA ACCTCTCGGA GAACCTCCAG CAGCCCCCTC AGGTCTGGGA CCTAATACAA ACCTCTCGGA GAACCTCCAG CAGCCCCCTC AGGTCTGGGA CCTAATACAA ACCAATCGGA GAACCCCCCG CAGGCCCCTC TGGTCTGGGA TCTGGTACAA ACCAATCGGA GAACCCCCCG CAGGCCCCTC TGGTCTGGGA TCTGGTACAA ACCAATCGGA GAACCACCAG CAGGCCCCTC TGGTCTGGGA TCTGGTACAA ACCAATCGGA GAACCACCAG CAGGCCCCTC TGGTCTGGGA TCTGGTACAA ACCAATCGGA GAACCACCAG CAGGCCCCTC TGGTCTGGGA TCTGGTACAA ACCAATCGGA GAACCACCAG CAGGCCCCTC TGGTCTGGGA TCTGGTACAA ACCAATCGGA GAACCACCAG CAGGCCCCTC TGGTCTGGGA TCTGGTACAA ACCAATCGGA GAACCACCAG CAGGCCCCTC TGGTCTGGGA TCTGGTACAA ACCAATCGGA GAACCCCCCG CAGCCCCCTC TGGTGTGGGA TCTAATACAA ACCAATCGGA GAACCCCCCG CAGCCCCCTC TGGTGTGGGA TCTAATACAA ACCAATCGGA GAACCCCCCG CAGCCCCCTC TGGTGTGGGA TCTAATACAA ACCAATCGGA GAACCCCCCG CAGCCCCCTC TGGTCTGGGA TCTAATACAA ACCAATCGGA GAACCCCCCG CAGGCCCCTC TGGTCTGGGA TCTGGTACAA ACCTCTCGGA GAACCTCCAG CAACCCCCGC TGCTGTGGGA CCTACTACAA GCCTCTCGGA CAGCCACCAG CAGCCCCCTC TGGTCTGGGA ACTAATACGA ACCTCTCGGA GAACCACCAG CAGCCCCCAC AAGTTTGGGA TCTAATACAA ACCTCTCGGA GAACCTCCAG CAGCGCCCTC TGGTGTGGGA CCTAATACAA ACCTCTCGGA GAACCTCCAG CAGCGCCCTC TGGTGTGGGA CCTAATACAA ACCTCTCGGA GAACCTCCAG CAGCGCCCTC TAGTGTGGGA TCTGGTACAG ACCAATCGGA GAACCCCCCG CAGGCCCCTC TGGTCTGGGA TCTGGTACAA

    3». start vp3 start
57. 57/105

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    Fig. 1AAF

    2851 jp3 start codon.

    42_2 TGGCTGCAGG CGGTGGCGCA CCAATGGCAG 42_8 TGGCTGCAGG CGGTGGCGCT CCAATGGCAG 42_15 TGGCTGCAGG CGGTGGCGCT CCAATGGCAG 42_5b TGGCTGCAGG CGGTGGCGCT CCAATGGCAG 42_lb TGGCTGCAGG CGGTGGCGCT CCAATGGCAG 42_13 TGGCTGCAGG CGGTGGCGCT CCAATGGCAG 42_3a TGGCTGCAGG CGGTGGCGCT CCAATGGCAG 42_4 TGGCTGCAGG CGGTGGCGCT CCAATGGCAG 42_5a TGGCTGCAGG CGGTGGCGCA CCAATGGCAG 42_10 TGGCTGCAGG CGGTGGCGCT CCAATGGCAG 42_3b TGGCTGCAGG CGGTGGCGCT CCAATGGCAG 42_11 TGGCTGCAGG CGGTGGCGCT CCAATGGCAG 42_6b TGGCTGCAGG CGGTGGCGCT CCAATGGCAG 43_1 TGGCTGCAGG CGGTGGCGCT CCAATGGCAG 43_5 TGGCTGCAGG CGGTGGCGCT CCAATGGCAG 43_12 TGGCTGCAGG CGGTGGCGCT CCAATGGCAG 43_20 TGGCTTCAGG CGGTGGCGCT CCAATGGCAG 43_21 TGGCTTCAGG CGGTGGCGCT CCAATGGCAG 43_23 TGGCTTCAGG CGGTGGCGCT CCAATGGCAG 43_25 TGGCTTCAGG CGGTGGCGCT CCAATGGCAG 44__1 TGGCTGCAGG CGGTGGCGCT CCAATGGCAG 44_5 TGGCTGCAGG CGGTGGCGCT CCAATGGCAG 223^10 TGGCTGCAGG CGGTGGCGCA CCAATGGCTG 223_2 TGGTTGCAGG CGGTGGCGCA CCAATGGCTG 223_4 TGGCTGCAGG CGGTGGCGCA CCAATGGCTG 223_5 TGGCTGCAGG CGGTGGCGCA CCAATGGCTG 223J5 TGGCTGCAGG CGGTGGCGCA CCAATGGCTG 223_7 TGGCTGCAGG CGGTGGCGCA CCAATGGCTG A3_4 TGGCTTCAGG CGGTGGGGCA CCAATGGCAG A3_5 TGGCTTCAGG CGGTGGGGCA CCAATGGCAG A3_7 TGGCTTCAGG CGGTGGGGCA CCAATGGCAG A3_3 TGGCTTCAGG CGGTGGGGCA CCAATGGCAG 42_12 TGGCTGCAGG CGGTGGCGCT CCAATGGCAG AAV1 TGGCTTCAGG CGGTGGCGCA CCAATGGCAG AAV2 TGGCTACAGG CAGTGGCGCA CCAATGGCAG AAV3 TGGCTTCAGG CGGTGGCGCA CCAATGGCAG AAV8 TGGCTGCAGG CGGTGGCGCA CCAATGGCAG AAV9 TGGCTGCAGG CGGTGGCGCA CCAATGGCAG AAV7 TGGCTGCAGG CGGTGGCGCA CCAATGGCAG 44__2 TGGCTGCAGG CGGTGGCGCT CCAATGGCAG vp3 start codon (cont'd)

    ACAATAACGA

    ACAATAACGA

    ACAATAACGA

    ACAATAACGA

    ACAATAACGA

    ACAATAACGA

    ACAATAACGA

    ACAATAACGA

    ACAATAACGA

    ACAATAACGA

    ACAATAACGA

    ACAATAACGA

    ACAATAACGA

    ACAATAACGA

    ACAATAACGA

    ACAATAACGA

    ACAATAACGA

    ACAATAACGA

    ACAATAACGA

    ACAATAACGA

    ACAATAACGA

    ACAATAACGA

    ACAATAACGA

    ACAATAACGA

    ACAATAACGA

    ACAATAACGA

    ACAATAGCGA

    ACAATAACGA

    ACGATAACGA

    ACAATAACGA

    ACAATAACGA

    ACAATAACGA

    ACAATAACGA

    ACAATAACGA

    ACAATAACGA

    ACAATAACGA

    ACAATAACGA

    ACAATAACGA

    ACAATAACGA

    ACAATAACGA

    2900

    AGGCGCCGAC

    AGGCGCCGAC

    AGGCGCCGAC

    AGGCGCCGAC

    AGGCGCCGAC

    AGGCGCCGAC

    AGGCGCCGAC

    AGGCGCCGAC

    AGGCGCCGAC

    AGGCGCCGAC

    AGGCGCCGAC

    AGGCGCCGAC

    AGGCGCCGAC

    AGGCGCCGAC

    AGGCGCCGAC

    AGGCGCCGAC

    AGGCGCCGAC

    AGGCGCCGAC

    AGGCGCCGAC

    AGGCGCCGAC

    AGGCGCCGAC

    AGGCGCCGAC

    GGGCGCCGAC

    GGGCGCCGAC

    GGGCGCCGAC

    GGGCGCCGAC

    GGGCGCCGAC

    GGGCGCCGAC

    AGGCGCCGAC

    AGGCGCCGAC

    AGGCGCCGAC

    AGGCGCCGAC

    AGGCGCCGAC

    AGGCGCCGAC

    GGGCGCCGAC

    GGGTGCCGAT

    AGGCGCCGAC

    AGGCGCCGAC

    AGGTGCCGAC

    AGGCGCCGAC
58. 58/105

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    Fig. 1AAG

    42 2 2901 GGAGTGGGTA 42 8 GGAGTGGGTA 42 15 GGAGTGGGTA 42 5b GGAGTGGGTA 42 lb GGAGTGGGTA 42 13 GGAGTGGGTA 42 3a GGAGTGGGTA 42 4 GGAGTGGGTA 42 5a GGAGTGGGTA 42 10 GGAGTGGGTA 42 3b GGAGTGGGTA 42 11 GGAGTGGGTA 42 6b GGAGTGGGTA 43 1 GGAGTGGGTA 43 5 GGAGTGGGTA 43 12 GGAGTGGGTA 43 20 GGAGTGGGTA 43 21 GGAGTGGGTA 43 23 GGAGTGGGTA 43 25 GGAGTGGGTA 44 1 GGAGTGGGTA 44 5 GGAGTGGGTA 223 10 GGAGTGGGTA 223 2 GGAGTGGGTA 223 4 GGAGTGGGTA 223 5 GGAGTGGGTA 223 6 GGAGTGGGTA 223-7 GGAGTGGGTA A3 4 GGAGTGGGTA A3 5 GGAGTGGGTA A3 7 GGAGTGGGTA A3 3 GGAGTGGGTA 42—12 GGAGTGGGTA AAVl GGAGTGGGTA AAV2 GGAGTGGGTA AAV3 GGAGTGGGTA AAV8 GGAGTGGGTA AAV9 GGAGTGGGTA AAV7 GGAGTGGGTA AAV10 GGTA AAVll GGTA AAVl 2 GGTA 44 2 GGAGTGGGTA

    ATGCCTCCGG AAATTGGCAT GTTCCTCAGG AAATTGGCAT GTTCCTCAGG AAATTGGCAT GTTCCTCAGG AAATTGGCAT GTTCCTCAGG AAATTGGCAT GTTCCTCAGG AAATTGGCAT GTTCCTCAGG AAATTGGCAT ATGCCTCCGG AAATTGGCAT ATGCCTCCGG AAATTGGCAT ATGCCTCCGG AAATTGGCAT ATGCCTCCGG AAATTGGCAT ATGCCTCCGG AAATTGGCAT GTTCCTCAGG AAATTGGCAT GTTCCTCAGG AAATTGGCAT GTTCCTCAGG AAATTGGCAT GTTCCTCAGG AAATTGGCAT ATTCCTCGGG AAATTGGCAT ATTCCTCGGG AAATTGGCAT ATTCCTCGGG AAATTGGCAT ATTCCTCGGG AAATTGGCAT GTTCCTCAGG AAATTGGCAT GTTCCTCAGG AAATTGGCAT ATGCCTCAGG AAATTGGCAT ATGCCTCAGG AAATTGGCAT ATGCCTCAGG AAATTGGCAT ATGCCTCAGG AAATTGGCAT ATGCCTCAGG AAATTGGCAT ATGCCTCAGG AAATTGGCAT ATTCCTCGGG AAATTGGCAT ATTCCTCGGG AAATTGGCAT ATTCCTCGGG AAATTGGCAT ATTCCTCGGG AAATTGGCAT GTTCCTCAGG AAATTGGCAT ATGCCTCAGG AAATTGGCAT ATTCCTCCGG AAATTGGCAT ATTCCTCAGG AAATTGGCAT GTTCCTCGGG AAATTGGCAT ATTCCTCGGG AAATTGGCAT ATGCCTCAGG AAATTGGCAT ATTCCTCCGG AAATTGGCAT ATTCCTCCGG AAATTGGCAT ATTCCTCCGG AAATTGGCAT GTTCCTCAGG AAATTGGCAT

    2950

    TGCGATTCCA CATGGCTGGG TGCGATTCCA CATGGCTGGG TGCGATTCCA CATGGCTGGG TGCGATTCCA CATGGCTGGG TGCGATTCCA CATGGCTGGG TGCGATTCCA CATGGCTGGG TGCGATTCCA CATAGCTGGG TGCGATTCCA CATGGCTGGG TGCGATTCCA CATGGCTGGG TGCGATTCCA CATGGCTGGG TGCGATTCCA CATGGCTGGG TGCGATTCCA CATGGCTGGG TGCGATTCCA CATGGCTGGG TGCGATTCCA CATGGCTGGG TGCGATTCCA CATGGCTGGG TGCGATTCCA CATGGCTGGG TGCGATTCCA CATGGCTGGG TGCGATTCCA CATGGCTGGG TGCGATTCCA CATGGCTGGG TGCGATTCCA CATGGCTGGG TGCGATTCCA CATGGCTGGG TGCGATTCCA CATGGCTGGG TGCGATTCCA CATGGCTGGG TGCGATTCCA CATGGCTGGG TGCGATTCCA CACGGCTGGG TGCGATTCCA CACGGCTGGG TGCGATTCCA CATGGCTGGG TGCGATTCCA CATGGCTGGG TGCGATTCCA CATGGATGGG TGCGATTCCA CATGGATGGG TGCGATTCCA CATGGATGGG TGCGATTCCA CATGGATGGG TGCGATTCCA CATGGCTGGG TGCGATTCCA CATGGCTGGG TGCGATTCCA CATGGATGGG TGCGATTCCC AATGGCTGGG TGCGATTCCA CATGGCTGGG TGCGATTCCA CATGGCTGGG TGCGATTCCA CATGGCTGGG TGCGATTCCA CATGGCTGGG TGCGATTCCA CATGGCTGGG TGCGATTCCA CATGGCTGGG TGCGATTCCA CATGGCTGGG
59. 59/105

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    FIG. 1AAH

    42_2

    42_8

    42_15

    42_5b

    42_lb

    42_13

    42_3a

    42_4

    42_5a

    42_10

    42_.3b

    42_11

    42_6b

    43_1

    43_5

    43_12

    43_20

    43_21

    43__23

    43_25

    44_I

    44_5

    223_10

    223_2

    223_4

    223_5

    223_6

    223,_7

    A3_4

    A3_5

    A3_7

    A3_3 42_12 AAV1 AAV2 AAV3 AAV8 AAV9 AAV7 AAV10 AAV11 AAV12 44 2

    2951

    CGACAGAGTC

    CGACAGAGTC

    CGACAGAGTC

    CGACAGAGTC

    CGACAGAGTC

    CGACAGAGTC

    CGACAGAGTC

    CGACAGAGTC

    CGACAGAGTC

    CGACAGAGTC

    CGACAGAGTC

    CGACAGAGTC

    CGACAGAGTC

    CGACAGAGTC

    CGACAGAGTC

    CGACAGAGTC

    GGACAGAGTC

    GGACAGAGTC

    GGACAGAGTC

    GGACAGAGTC

    CGACAGAGTC

    CGACAGAGTC

    CGACAGAGTC

    CGACAGAGTC

    CGACAGAGTC

    CGACAGAGTC

    CGACAGAGTC

    CGACAGAGTC

    CGACAGAGTT

    CGACAGAGTT

    CGACAGAGTT

    CGACAGAGTT

    CGACAGAGTC

    CGACAGAGTC

    CGACAGAGTC

    CGACAGAGTC

    CGACAGAGTC

    GGACAGAGTC

    CGACAGAGTC

    CGACAGAGTC

    CGACAGAGTC

    CGACCGAGTC

    CGACAGAGTC

    ATCACCACCA

    ATCACCACCA

    ATCACCACCA

    ATCACCACCA

    ATCACCACCA

    ATCACCACCA

    ATCACCACCA

    ATCACCACCA

    ATCACCACCA

    ATCACCACCA

    ATCACCACCA

    ATCACCACCA

    ATCACCACCA

    ATCACCACCA

    ATCACCACCA

    ATCACCACCA

    ATCACCACCA

    ATCACCACCA

    ATCACCACCA

    ATCACCACCA

    ATCACCACCA

    ATCACCACCA

    ATCACCACCA

    ATCACCACCA

    ATCACCACCA

    ATCACCACCA

    ATCACCACCA

    ATCACCACCA

    ATCACCACCA

    ATCACCACCA

    ATCACCACCA

    ATCACCACCA

    ATCACCACCA

    ATCACCACCA

    ATCACCACCA

    ATCACCACCA

    ATCACCACCA

    ATCACCACCA

    ATTACCACCA

    ATCACCACCA

    ATCACCACCA

    ATTACCACCA

    ATCACCACCA

    GCACCCGCAC

    GCACCCGAAC

    GCACCCGAAC

    GCACCCGAAC

    GCACCCGAAC

    GCACCCGAAC

    GCACCCGAAC

    GCACCCGCAC

    GCACCCGCAC

    GCACCCGCAC

    GCACCCGCAC

    GCACCCGCAC

    GCACCCGAAC

    GCACCCGAAC

    GCACCCGAAC

    GCACCCGAAC

    GCACCCGAAC

    GCACCCGAAC

    GCACCCGAAC

    GCACCCGAAC

    GCACCCGAAC

    GCACCCGAAC

    GCACCCGAAC

    GCACCCGAAC

    GCACCCGAAC

    GCACCCGAAC

    GCACCCGAAC

    GCACCCGAAC

    GCACAAGAAC

    GCACAAGAAC

    GCACAAGAAC

    GCACAAGAAC

    GCACCCGAAC

    GCACCCGCAC

    GCACCCGAAC

    GCACCAGAAC

    GCACCCGAAC

    GCACCCGAAC

    GCACCCGAAC

    GCACCCGAAC

    GCACCCGAAC

    GCACCCGGAC

    GCACCCGAAC

    CTGGGCCCTG

    CTGGGCCCTC

    CTGGGCCCTC

    CTGGGCCCTC

    CTGGGCCCTC

    CTGGGCCCTC

    CTGGGCCCTC

    CTGGGCCCTG

    CTGGGCCCTG

    CTGGGCCCTG

    CTGGGCCCTG

    CTGGGCCCTG

    CTGGGCCCTC

    CTGGGCCCTG

    CTGGGCCCTG

    CTGGGCCCTG

    CTGGGCCCTG

    CTGGGCCCTG

    CTGGGCCCTG

    CTGGGCCCTG

    CTGGGCCCTC

    CTGGGCCCTC

    CTGGGCCCTG

    CTGGGCCCTG

    CTGGGCCCTG

    CTGGGCCCTG

    CTGGGCCCTG

    CTGGGCCCTG

    CTGGGCCCTC

    CTGGGCCCTC

    CTGGGCCCTC

    CTGGGCCCTC

    CTGGGCCCTC

    CTGGGCCTTG

    CTGGGCCCTG

    CTGGGCCCTG

    CTGGGCCCTG

    CTGGGCATTG

    CTGGGCCCTG

    CTGGGTCCTG

    CTGGGCCCTG

    TTGGGCCCTG

    CTGGGCCCTC

    3000

    CCCACCTACA

    CCCACCTACA

    CCCACCTACA

    CCCACCTACA

    CCCACCTACA

    CCCACCTACA

    CCCACCTACA

    CCCACCTACA

    CCCACCTACA

    CCCACCTACA

    CCCACCTACA

    CCCACCTACA

    CCCACCTACA

    CCCACCTACA

    CCCACCTACA

    CCCACCTACA

    CCCACCTACA

    CCCACCTACA

    CCCACCTACA

    CCCACCTACA

    CCCACCTACA

    CCCACCTACA

    CCCACCTACA

    CCCACCTACA

    CCCACCTACA

    CCCACCTACA

    CCCACCTACA

    CCCACCTACA

    CCCACCTACA

    CCCACCTACA

    CCCACCTACA

    CCCACCTACA

    CCCACCTACA

    CCCACCTACA

    CCCACCTACA

    CCCACTTACA

    CCCACCTACA

    CCCACCTACA

    CCCACCTACA

    CCCACCTACA

    CCAACCTACA

    CCCACCTACA

    CCCACCTACA
60. 60/105

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    Fig. 1AAI

    42/

    42/

    4 2/ 5 42/b 42/b 42/3 42/a

    42_4

    42_5a

    42/0

    42_3b

    42/1

    42/b

    43/

    43/

    43/2

    43/0

    43/1

    43/3

    43/5

    44/

    44/

    223/0

    223/

    223/

    223/

    223/

    223/

    A3_4

    A3_5

    A3/

    A3/

    42/2

    AAV1

    AAV2

    AAV3

    AAV8

    AAV9

    AAV7

    AAV10

    AAV11

    AAV12

    44 2

    3001 3050 ACAACCACCT CTACAAGCAG ATATCAA..G TCAGAGCGGG GCT....ACC ACAACCACCT CTACAAGCAA ATCTCCAACG GGACATCGGG AGGAAGCACC ACAACCACCT CTACAAGCAA ATCTCCAACG GGACATCGGG AGGAAGCACC ACAACCACCT CTACAAGCAA ATCTCCAACG GGACATCGGG AGGAAGCACC ACAACCACCT CTACAAGCAA ATCTCCAACG GGACATCGGG AGGAAGCACC ACAACCACCT CTACAAGCAA ATCTCCAACG GGACATCGGG AGGAAGCACC ACAACCACCT CTACAAGCAA ATCTCCAACG GGACATCGGG AGGAAGCACC ACAACCACCT CTACAAGCAG ATATCAA. . . . GTCAGAGCG GGGC. .TACC ACAACCACCT CTACAAGCAG ATATCAA... .GTCAGAGCG GGGC..TACC ACAACCACCT CTACAAGCAG ATATCAA. . G TCAGAGCGGG GCTA. . . .CC ACAACCACCT CTACAAGCAG ATATCAA.. G TCAGAGCGGG GCTA....CC ACAACCACCT CTACAAGCAG ATATCAA. . G TCAGAGCGGG GCTA. . . . CC ACAACCACCT CTACAAGCAA ATCTCCAACG GGACATCGGG AGGAAGCACC ACAACCATCT CTACAAGCAA ATCTCCAACG GGACATCGGG AGGAAGCACT ACAACCATCT CTACAAGCAA ATCTCCAACG GGACATCGGG AGGAAGCACT ACAACCATCT CTACAAGCAA ATCTCCAACG GGACATCGGG AGGAAGCACT ACAACCACCT CTACAAGCAA ATCTCCAACG GCACCTCGGG AGGAAGCACC ACAACCACCT CTACAAGCAA ATCTCCAACG GCACCTCGGG AGGAAGCACC ACAACCACCT CTACAAGCAA ATCTCCAACG GCACCTCGGG AGGAAGCACC ACAACCACCT CTACAAGCAA ATCTCCAACG GCACCTCGGG AGGAAGCACC ACAACCACCT CTACAAGCAA ATCTCCAACG GGACTTCGGG AGGAAGCACC ACAACCACCT CTACAAGCAA ATCTCCAACG GGACTTCGGG AGGAAGCACC ACAACCACCT CTACAAGCAA ATCTCCAGTC AGTCAGCAGG GAG. . .CACC ACAACCACCT CTACAAGCAA ATCTCCAGTC AGTCAGCAGG GAG... CACC ACAACCACCT CTACAAGCAA ATCTCCAGTC AGTCAGCAGG GAG. . . CACC ACAACCACCT CTACAAGCAA ATCTCCAGTC AGTCAGCAGG GAG...CACC ACAACCACCT CTACAAGCAA ATCTCCAGTC AGTCAGCAGG GAG. . .CACC ACAACCACCT CTACAAGCAA ATCTCCAGTC AGTCAGCAGG GAG.. . CACC ATAATCACCT CTACAAGCAA ATCTCCA. . . GCGAATCGGG AGC.. .CACC ATAATCACCT CTACAAGCAA ATCTCCA. . . GCGAATCGGG AGC. . .CACC ATAATCGCCT CTACAAGCAA ATCTCCA. . . GCGAATCGGG AGC. . .CACC ATAATCACCT CTACAAGCAA ATCTCCA.;. GCGAATCGGG AGC...CACC ACAACCACCT CTACAAGCAA ATCTCCAACG GGACATCGGG AGGAAGCACC ATAACCACCT CTACAAGCAA ATCTCCAGTG CTTCAACGGG .GG. .CCAGC ACAACCACCT CTACAAACAA ATTTCCA. . . GCCAATCAGG AGC. . .CTCG ACAACCATCT CTACAAGCAA ATCTCCA. .. GCCAATCAGG AGC...TTCA ACAACCACCT CTACAAGCAA ATCTCCAACG GGACATCGGG AGGAGCCACC ACAACCACCT CTACAAGCAA ATCTCCAATG GAACATCGGG AGGAAGCACC ACAACCACCT CTACAAGCAA ATCTCCAGTG AAACTGCAGG TAG. . . TACC ACAACCACAT CTACAAGCAA ATCTCCAGCG AGACAGGAGC CACCAACGAC ACAACCACCT CTACAAACAA ATCTCCAGCG CTTCAACGGG GGCCAGCAAC ACAACCACCT CTACAAGCAA ATCTCCAGCC AATCGGGTGC CACCAACGAC ACAACCACCT CTACAAGCAA ATCTCCAACG GGACTTCGGG AGGAAGCACC
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    42_2

    42_8

    42^15

    42_5b

    42_lb

    42_13

    42J3a

    42_4

    42_5a

    42JL0

    42_3b

    42JL1

    42_6b

    43JL

    43_5

    43_12

    43_20

    43_21

    43_23

    43_25

    44_1

    44^5 223JL0 223_2 223_4 223_5 223J5 223 7

    A3_4

    A3_5

    A3_7

    A3_3 42JL2 AAV1 AAV2 AAV3 AAV8 AAV9 AAV7 AAV10 AAV11 AAV12 44 2

    Fig. 1AAJ

    3051 3100

    AACGACAACC ACTTCTTCGG CTACAGCACC CCCTGGGGCT ATTTTGACTT AACGACAACA CCTACTTCGG CTACAGCACC CCCTGGGGGT ATTTTGACTT AACGACAACA CCTACTTCGG CTACAGCACC CCCTGGGGGT ATTTTGACTT AACGACAACA CCTACTTCGG CTACAGCACC CCCTGGGGGT ATTTTGACTT AACGACAACA CCTACTTCGG CTACAGCACC CCCTGGGGGT ATTTTGACTT AACGACAACA CCTACTTCGG CTACAGCACC CCCTGGGGGT ATTTTGACTT AACGACAACA CCTACTTCGG CTACAGCACC CCCTGGGGGT ATTTTGACTT AACGACAACC ACTTCTTCGG CTACAGCACC CCCTGGGGCT ATTTTGACTT AACGACAACC ACTTCTTCGG CTACAGCACC CCCTGGGGCT ATTTTGACTT AACGACAACC ACTTCTTCGG CTACAGCACC CCCTGGGGCT ATTTTGACTT AACGACAACC ACTTCTTCGG CTACAGCACC CCCTGGGGCT ATTTTGACTT AACGACAACC ACTTCTTCGG CTACAGCACC CCCTGGGGCT ATTTTGACTT AACGACAACA CCTACTTCGG CTACAGCACC CCCTGGGGGT ATTTTGACTT AACGACAACA CCTACTTTGG CTACAGCACC CCCTGGGGGT ATTTTGACTT AACGACAACA CCTACTTTGG CTACAGCACC CCCTGGGGGT ATTTTGACTT AACGACAACA CCTACTTTGG CTACAGCACC CCCTGGGGGT ATTTTGACTT AACGACAACA CCTATTTTGG CTACAGCACC CCCTGGGGGT ATTTTGACTT AACGACAACA CCTATTTTGG CTACAGCACC CCCTGGGGGT ATTTTGACTT AACGACAACA CCTATTTTGG CTACAGCACC CCCTGGGGGT ATTTTGACTT AACGACAACA CCTATTTTGG CTACAGCACC CCCTGGGGGT ATTTTGACTT AACGACAACA CCTACTTCGG CTACAGCACC CCCTGGGGGT ATTTTGACTT AACGACAACA CCTACTTCGG CTACAGCACC CCCTGGGGCT ATTTTGACTT AACGATAACG TCTATTTCGG CTACAGCACC CCCTGGGGGT ATTTTGACTT AACGATAACG TCTATTTCGG CTACAGCACC CCCTGGGGGT ATTTTGACTT AACGATAACG TCTATTTCGG CTACAGCACC CCCTGGGGGT ATTTTGACTT AACGATAACG TCTATTTCGG CTACAGCACC CCCTGGGGGT ATTTTGACTT AACGATAACG TCTATTTCGG CTACAGCACC CCCTGGGGGT ATTTTGACTT AACGATAACG TCTATTTCGG CTACAGCACC CCCTGGGGGT ATTTTGACTT AACGACAACC ACTACTTCGG CTACAGCACC CCCTGGGGGT ATTTTGACTT AACGACAACC ACTACTTCGG CTACAGCACC CCCTGGGGGT ATTTTGACTT AACGACAACC ACTACTTCGG CTACAGCACC CCCTGGGGGT ATTTTGACTT AACGACAACC ACTACTTCGG CTACAGCACC CCCTGGGGGT ATTTTGACTT AACGACAACA CCTACTTCGG CTACAGCACC CCCTGGGGGT ATTTTGACTT AACGACAACC ACTACTTCGG CTACAGCACC CCCTGGGGGT ATTTTGATTT AACGACAATC ACTACTTTGG CTACAGCACC CCTTGGGGGT ATTTTGACTT AACGACAACC ACTACTTTGG CTACAGCACC CCTTGGGGGT ATTTTGACTT AACGACAACA CCTACTTCGG CTACAGCACC CCCTGGGGGT ATTTTGACTT AACGACAACA CCTACTTTGG CTACAGCACC CCCTGGGGGT ATTTTGACTT AACGACAACA CCTACTTCGG CTACAGCACC CCCTGGGGGT ATTTTGACTT

    AACCACTACT TCGGCTACAG C......ACC CCCTGGGGGT ATTTTGACTT . . . GACAACC ACTACTTTGG CTACAGCACC CCCTGGGGGT ATTTTGACTT

    AACCACTACT TCGGCTA......CAGCACC CCTTGGGGGT ATTTTGATTT

    AACGACAACA CCTACTTCGG CTACAGCACC CCCTGGGGGT ATTTTGACTT
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    42 2 3101 TAACAGATTC CACTGCCACT 42 8 TAACAGATTC CACTGCCACT 42 15 TAACAGATTC CACTGCCACT 42 5b TAACAGATTC CACTGCCACT 42 lb TAACAGATTC CACTGCCACT 42 13 TAACAGATTC CACTGCCACT 42 3a TAACAGATTC CACTGCCACT 42 4 CAACAGATTC CACTGCCACT 42 5a CAACAGATTC CACTGCCACT 42 10 CAACAGATTC CACTGCCACT 42 3b CAACAGATTC CACTGCCACT 42 11 CAACAGATTC CACTGCCACT 42 6b TAACAGATTC CACTGCCACT 43 1 CAACAGATTC CACTGCCACT 43 5 CAACAGATTC CACTGCCACT 43 12 CAACAGATTC CACTGCCACT 43 20 CAACAGATTC CACTGTCACT 43 21 CAACAGATTC CACTGTCACT 43 23 CAACAGATTC CACTGTCACT 43_25 CAACAGATTC CACTGTCACT 44 1 TAACAGATTC CACTGCCACT 44 5 TAACAGATTC CACTGCCACT 223 10 CAACAGATTC CATTGCCACT 223 2 CAACAGATTC CATTGCCACT 223 4 CAACAGATTC CATTGCCACT 223 5 CAACAGATTC CATTGCCACT 223 6 CAACAGATTC CATTGCCACT 223 7 CAACAGATTC CATTGCCACT A3 4 TAACAGATTC CACTGTCACT A3 5 TAACAGATTC CACTGTCACT A3 7 TAACAGATTC CACTGTCACT A3 3 TAACAGATTC CACTGTCACT 42_12 TAACAGATTC CACTGCCACT AAVl CAACAGATTC CACTGCCACT AAV2 CAACAGATTC CACTGCCACT AAV3 TAACAGATTC CACTGCCACT AAV8 TAACAGATTC CACTGCCACT AAV9 CAACAGATTC CACTGCCACT AAV7 TAACAGATTC CACTGCCACT AAV10 TAACAGATTC CACTGCCACT AAV11 TAACAGATTC CACTGCCACT AAV12 CAACAGATTC CACTGCCATT 44 2 TAACAGATTC CACTGCCACT

    Fig. 1AAK

    3150

    TCTCACCACG TGACTGGCAG CGACTCATCA TCTCACCACG TGACTGGCAG CGACTCATCA TCTCACCACG TGACTGGCAG CGACTCATCA TCTCACCACG TGACTGGCAG CGACTCATCA TCTCACCACG TGACTGGCAG CGACTCATCA TCTCACCACG TGACTGGCAG CGACTCATCA TCTCACCACG TGACTGGCAG CGACTCATCA TCTCATCACG TGACTGGCAG CGACTCATCA TCTCACCACG TGACTGGCAG CGACTCATCA TCTCACCACG TGACTGGCAG CGACTCATCA TCTCACCACG TGACTGGCAG CGACTCATCA TCTCACCACG TGACTGGCAG CGACTCATCA TCTCACCACG TGACTGGCAG CGACTCATCA TCTCACCACG TGACTGGCAG CGACTCATCA TCTCACCACG TGACTGGCAG CGACTCATCA TCTCACCACG TGACTGGCAG CGACTCATCA TTTCACCACG TGACTGGCAA CGACTCATCA TTTCACCACG TGACTGGCAA CGACTCATCA TTTCACCACG TGACTGGCAA CGACTCATCA TTTCACCACG TGACTGGCAA CGACTCATCA TCTCACCACG TGACTGGCAG CGACTCATCA TCTCACCACG TGACTGGCAG CGACTCATCA TCTCACCACG TGACTGGCAG CGACTTATCA TCTCACCACG TGACTGGCAG CGACTTATCA TCTCACCACG TGACTGGCAG CGACTTATCA TCTCACCACG TGACTGGCAG CGACTTATCA TCTCACCACG TGACTGGCAG CGACTTATCA TCTCACCACG TGACTGGCAG CGACTTATCA TCTCACCACG TGACTGGCAG CGACTCATCA TCTCACCACG TGACTGGCAG CGACTCATCA TCTCACCACG TGACTGGCAG CGACTCATCA TCTCACCACG TGACTGGCAG CGACTCATCA TCTCACCACG TGACTGGCAG CGACTCATCA TTTCACCACG TGACTGGCAG CGACTCATCA TTTCACCACG TGACTGGCAA AGACTCATCA TCTCACCACG TGACTGGCAG CGACTCATTA TTTCACCACG TGACTGGCAG CGACTCATCA TCTCACCACG TGACTGGCAG CGACTCATCA TCTCACCACG TGACTGGCAG CGACTCATCA TTTCACCACG TGACTGGCAG CGACTCATCA TCTCACCACG TGACTGGCAG CGACTCATCA TCTCACCACG TGACTGGCAG CGACTCATCA TCTCACCACG TGACTGGCAG CGACTCATCA
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    Fig. 1AAL

    42 2 3151 ACAACAACTG GGGATTCCGG 42 8 ACAACAACTG GGGATTCCGG 42 15 ACAACAACTG GGGATTCCGG 42 5b ACAACAACTG GGGATTCCGG 42 lb ACAACAACTG GGGATTCCGG 42 13 ACAACAACTG GGGATTCCGG 42 3a ACAACAGCTG GGGATTCCGG 42 4 ACAACAACTG GGGATTCCGG 42 5a ACAACAACCG GGGATTCCGG 42 10 ACAACAACTG GGGATTCCGG 42 3b ACAACAACTG GGGATTCCGG 42 11 ACAACAACTG GGGATTCCGG 42 5b ACAACAACTG GGGATTCCGG 43 1 ACAATAACTG GGGATTCCGG 43 5 ACAATAACTG GGGATTCCGG 43 12 ACAATAACTG GGGATTCCGG 43 20 ACAACAATTG GGGATTCCGG 43 21 ACAACAATTG GGGATTCCGG 43 23 ACAACAATTG GGGATTCCGG 43 25 ACAACAATTG GGGATTCCGG 44 1 ACAACAACTG GGGATTCCGG 44 5 ACAACAACTG GGGATTCCGG 223 10 ACAACAACTG GGGATTCCGG 223 2 ACAACAACTG GGGATTCCGG 223 4 ACAACAACTG GGGATTCCGG 223 5 ACAACAACTG GGGATTCCGG 223 6 ACAACAACTG GGGATTCCGG 223 7 ACAACAACTG GGGATTCCGG A3 4 ACAACAACTG GGGATTTAGA A3 5 ATAACAACTG GGGATTTAGA A3_7 ACAACAACTG GGGATTTAGA A3 3 ACAACAACTG GGGATTTAGA 42_12 ACAACAACTG GGGATTCCGG AAV1 ACAACAATTG GGGATTCCGG AAV2 ACAACAACTG GGGATTCCGA AAV3 ACAACAACTG GGGATTCCGG AAV8 ACAACAACTG GGGATTCCGG AAV9 ACAACAACTG GGGATTCCGG AAV7 ACAACAACTG GGGATTCCGG AAV10 ACAACAACTG GGGATTC AAV11 ACAACAACTG GGGATTC AAV12 ACAACAACTG GGGATTC 44 2 ACAACAACTG GGGATTCCGG

    3200

    CCCAGAAAGC TGCGGTTCAA GTTGTTCAAC CCCAAGAGAC TCAACTTCAA GCTCTTCAAC CCCAAGAGAC TCAACTTCAA GCTCTTCAAC CCCAAGAGAC TCAACTTCAA GCTCTTCAAC CCCAAGAGAC TCAACTTCAA GCTCTTCAAC CCCAAGAGAC TCAACTTCAA GCTCTTCAAC CCCAAGAGAC TCAACTTCAA GCTCTTCAAC CCCAAGAGAC TCAACTTCAA GCTCTTCAAC ' CCCAGAAAGC TGCGGTTCAA GTTGTTCAAC CCCAGAAAGC TGCGGTTCAA GTTGTTCAAC CCCAGAAAGC TGCGGTTCAA GTTGTTCAAC CCCAGAAAGC TGCGGTTCAA GTTGTTCAAC CCCAGAAAGC TGCGGTTCAA GTTGTTCAAC CCCAAGAGAC TCAACTTCAA GCTCTTCAAC CCCAAGAGAC TCAACTTCAA GCTCTTCAAC CCCAAGAGAC TCAACTTCAA GCTCTTCAAC CCCAAAAGAC TCAACTTCAA GCTGTTCAAC CCCAAAAGAC TCAACTTCAA GCTGTTCAAC CCCAAAAGAC TCAACTTCAA GCTGTTCAAC CCCAAAAGAC TCAACTTCAA GCTGTTCAAC CCCAAGAGAC TCAACTTCAA GCTCTTCAAC CCCAAGAGAC CCAACTTCAA GCTCTTCAAC CCCAAGAAGC TCAACTTCAA GCTCTTCAAC CCCAAGAAGC TCAACTTCAA GCTCTTCAAC CCCAAGAAGC TCAACTTCAA GCTCTTCAACCCCAAGAAGC TCAACTTCAA GCTCTTCAAC CCCAAGAAGC TCAACTTCAA GCTCTTCAAC CCCAAGAAGC TCAACTTCAA GCTCTTCAAC CCCAAGAAAC TCAATTTCAA GCTCTTCAAC CCCAAGAAAC TCAATTTCAA GCTCTTCAAC CCCAAGAAAC TCAATTTCAA GCTCTTCAAC CCCAAGAAAC TCAATTTCAA GCTCTTCAAC CCCAAGAGAC TCAACTTCAA GCTCTTCAAC CCCAAGAGAC TCAACTTCAA ACTCTTCAAC CCCAAGAGAC TCAACTTCAA GCTCTTTAAC CCCAAGAAAC TCAGCTTCAA GCTCTTCAAC CCCAAGAGAC TCAGCTTCAA GCTCTTCAAC CCAAAGAGAC TCAACTTCAA GCTGTTCAAC CCCAAGAAGC TGCGGTTCAA GCTCTTCAAC

    CCCAAGAGAC TCAACTTCAA GCTCTTCAAC
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    42 2 42 8 3201 ATCCAGGTCA AGGAGGTCAC ATCCAGGTCA AGGAGGTCAC 42 15 ATCCAGGTCA AGGAGGTCAC 42 5b ATCCAGGTCA AGGAGGTCAC 42 lb ATCCAGGTCA AGGAGGTCAC 42 13 ATCCAGGTCA AGGAGGTCAC 42 3a ATCCAGGTCA AGGAGGTCAC 42 4 ATCCAGGTCA AGGAGGTCAC 42 5a ATCCAGGTCA AGGAGGTCAC 42 10 ATCCAGGTCA AGGAGGTCAC 42' 3b ATCCAGGTCA AGGAGGTCAC 42 11 ATCCAGGTCA AGGAGGTCAC 42 6b ATCCAGGTCA AGGAGGTCAC 43 1 ATCCAGGTCA AGGAGGTCAC 43 5 ATCCAGGTCA AGGAGGTCAC 43 12 ATCCAGGTCA AGGAGGTCAC 43 20 ATCCAGGTCA AGGAAGTCAC 43 21 ATCCAGGTCA AGGAAGTCAC 43 23 ATCCAGGTCA AGGAAGTCAC 43 25 ATCCAGGTCA AGGAAGTCAC 44 1 ATCCAGGTCA AGGAGGTCAC 44 5 ATCCAGGTCA AGGAGGTCAC 223 10 ATCCAGGTCA AGGAGGTCAC 223 2 ATCCAGGTCA AGGAGGTCAC 223 4 ATCCAGGTCA AGGAGGTCAC 223 5 ATCCAGGTCA AGGAGGTCAC 223 6 ATCCAGGTCA AGGAGGTCAC 223 7 ATCCAGGTCA AGGAGGTCAC A3 4 ATCCAAGTCA AGGAGGTCAC A3 5 ATCCAAGTCA AGGAGGTCAC A3J7 ATCCAAGTCA AGGAGGTCAC A3 3 ATCCAAGTCA AGGAGGTCAC 42_12 ATCCAGGTCA AGGAGGTCAC AAVl ATCCAAGTCA AGGAGGTCAC AAV2 ATTCAAGTCA AAGAGGTCAC AAV3 ATCCAAGTTA GAGGGGTCAC AAV8 ATCCAGGTCA AGGAGGTCAC AAV9 ATCCAGGTCA AGGAGGTTAC AAV7 ATCCAGGTCA AGGAGGTCAC 44 2 ATCCAGGTCA AGGAGGTCAC

    Fig. 1AAM

    3250

    GACGAACGAC GGCGTTACGA CCATCGCTAA GCAGAATGAA GGCACCAAGA CCATCGCCAA GCAGAATGAA GGCACCAAGA CCATCGCCAA GCAGAATGAA GGCACCAAGA CCATCGCCAA GCAGAATGAA GGCACCAAGA CCATCGCCAA GCAGAATGAA GGCACCAAGA CCATCGCCAA GCAGAATGAA GGCACCAAGA CCATCGCCAA GCAGAATGAA GGCACCAAGA CCATCGCCAA GACGAACGAC GGCGTTACGA CCATCGCTAA GACGAACGAC GGCGTTACGA CCATCGCCAA GACGAACGAC GGCGTTACGA CCATCGCTAA GACGAACGAC GGCGTTACGA CCATCGCTAA GACGGACGAC GGCGTTACGA CCATCGCTAA GCAGAATGAA GGCACCAAGA CCATCGCCAA GCAGAATGAA GGCACCAAGA CCATCGCCAA GCAGAATGAA GGCACCAAGA CCATCGCCAA GACGAACGAA GGCACCAAGA CCATCGCCAA GACGAACGAA GGCACCAAGA CCATCGCCAA GACGAACGAA GGCACCAAGA CCATCGCCAA GACGAACGAA GGCACCAAGA CCATCGCCAA GCAGAATGAA GGCACCAAGA CCATCGCCAA GCAGAATGAA GGCACCAAGA CCATCGCCAA GACGAATGAC GGTGTCACAA CCATCGCTAA GACGAATGAC GGTGTCACAA CCATCGCTAA GACGAATGAC GGCGTCACAA CCATCGCTAA GACGAATGAC GGCGTCACAA CCATCGCTAA GACGAATGAC GGTGTCACAA CCATCGCTAA GACGAATGAC GGCGTCACAA CCATCGCTAA GCAGAATGAT GGAACCACGA CCATCGCCAA GCAGAATGAT GGAACCACGA CCATCGCCAA GCAGAATGAT GGAACCACGA CCATCGCCAA GCAGAATGAT GGAACCACGA CCATCGCCAA GCAGAATGAA GGCACCAAGA CCATCGCCAA GACGAATGAT GGCGTCACAA CCATCGCTAA GCAGAATGAC GGTACGACGA CGATTGCCAA GCAGAACGAT GGCACGACGA CTATTGCCAA GCAGAATGAA GGCACCAAGA CCATCGCCAA GACGAACGAA GGCACCAAGA CCATCGCCAA GACGAATGAC GGCGTTACGA CCATCGCTAA GCAGAATGAA GGCACCAAGA CCATCGCCAA
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    42_2

    42_8

    42_15

    42_5b

    42_lb

    42_13

    42_3a

    42_4

    42_5a

    42_l0

    42_3b

    42_11

    42_Sb

    43_1

    43_5

    43_12

    43_20

    43_21

    43_23

    43_25

    44_1

    44_5

    223_10

    223_2

    223_4

    223^5

    223_6

    223_7

    A3_4

    A35

    A3J7

    A3_3

    42_12

    AAVl

    AAV2

    AAV3

    AAV8

    AAV9

    AAV7

    44__2

    Fig. 1AAN

    3251 3300 TAACCTTACC AGCACGATTC AGGTCTTCTC GGACTCGGAG TACCAACTGC TAACCTTACC AGCACGATTC AGGTCTTTAC GGACTCGGAA TACCAGCTCC TAACCTTACC AGCACGATTC AGGTCTTTAC GGACTCGGAA TACCAGCTCC TAACCTTACC AGCACGATTC AGGTCTTTAC GGACTCGGAA TACCAGCTCC TAACCTTACC AGCACGATTC AGGTCTTTAC GGACTCGGAA TACCAGCTCC TAACCTTACC AGCACGATTC AGGTCTTTAC GGACTCGGAA TACCAGCTCC TAACCTTACC AGCACGATTC. AGGTCTTTAC GGACTCGGAA TACCAGCTCC TAACCTTACC AGCACGATTC AGGTCTTTAC GGACTCGGAA TACCGGCTCC TAACCTTACC AGCACGATTC AGGTCTTCTC GGACTCGGAG TACCAACTGC TAACCTTACC AGCACGATTC AGGTCTTCTC GGACTCGGAG TACCAACTGC TAACCTTACC AGCACGATTC AGGTCTTCTC GGACTCGGAG TACCAACTGC TAACCTTACC AGCACGATTC AGGTCTTCTC GGACTCGGAG TACCAACTGC TAACCTTACC AGCACGATTC AGGTCTTCTC GGACTCGGAG TACCAACTGC TAACCTTACC AGCACGATTC AGGTGTTTAC GGACTCGGAA TACCAGCTCC TAACCTTACC AGCACGATTC AGGTGTTTAC GGACTCGGAA TACCAGCTCC TAACCTTACC AGCACGATTC AGGTGTTTAC GGACTCGGAA TACCAGCTCC TAATCTCACC AGCACCGTGC AGGTCTTTAC GGACTCGGAG TACCAGTTAC TAATCTCACC AGCACCGTGC GGGTCTTTAC GGACTCGGAG TACCAGTTAC TAATCTCACC AGCACCGTGC AGGTCTTTAC GGACTTGGAG TACCAGTTAC TAATCTCACC AGCACCGTGC AGGTCTTTAC GGACTCGGAG TACCAGTTAC TAACCTTACC AGCACGATTC AGGTCTTTAC GGACTCGGAA TACCAGCTCC TAACCTTACC AGCACGATTC AGGTCTTTAC GGACTCGGAA TACCAGCTCC TAACCTTACC AGCACGGTTC AGGTCTTTTC GGACTCGGAA TATCAACTGC TAACCTTACC AGCACGGTTC AGGTCTTTTC GGACTCGGAA TATCAACTGC TAACCTTACC AGCACGGTTC AGGTCTTTTC GGACTCGGAA TATCAACTGC TAACCTTACC AGCACGGTTC AGGTCTTTTC GGACTCGGAA TATCAACTGC TAACCTTACC AGCACGGTTC AGGTCTTTTC GGACTCGGAA TATCAACTGC TAACCTTACC AGCACGGTTC AGGTCTTTTC GGACCCGGAA TATCAACTGC TAACCTTACC AGCACGGTGC AGGTCTTCAC AGACTCTGAG TACCAGCTGC TAACCTTACC AGCACGGTGC AGGTCTTCAC AGACTCTGAG TACCAGCTGC TAACCTTACC AGCACGGTGC AGGTCTTCAC AGACTCTGAG TACCAGCTGC TAACCTTACC AGCGCGGTGC AGGTCTTCAC AGACTCTGAG TACCAGCTGC TAACCTTACC AGCACGATTC AGGTCTTTAC GGACTCGGAA TACCAGCTCC TAACCTTACC AGCACGGTTC AAGTCTTCTC GGACTCGGAG TACCAGCTTC TAACCTTACC AGCACGGTTC AGGTGTTTAC TGACTCGGAG TACCAGCTCC TAACCTTACC AGCACGGTTC AAGTGTTTAC GGACTCGGAG TATCAGCTCC TAACCTCACC AGCACCATCC AGGTGTTTAC GGACTCGGAG TACCAGCTGC TAACCTTACC AGCACCGTCC AGGTCTTTAC GGACTCGGAG TACCAGCTAC TAACCTTACC AGCACGATTC AGGTATTCTC GGACTCGGAA TACCAGCTGC TAACCTTACC AGCACGATTC AGGTCTTTAC GGACTCGGAA TACCAGCTCC
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    422 42_8

    42_15

    42_5b

    42_lb

    42_13

    42_3a

    42_4

    42_5a

    42_10

    42_3b

    42_1

    42_6b

    43_1

    43_5

    43_12

    43_20

    43_21

    43_23

    43_25

    44_1

    44_5

    223JL0 223_2 223_4 223_5 223_6 223_7 A3_4 A3_5 A3_7 A3_3 42J.2 AAV1 AAV2 AAV3 AAVS AAV9 AAV7 44 2

    Fig. 1 AAO .

    3301 3350 CGTACGTCCT CGGCTCTGCG CACCAGGGCT GCCTCCCTCC GTTCCCTGCG CGTACGTCCT CGGCTCTGCG CACCAGGGCT GCCTGCCTCC GTTCCCGGCG CGTACGTCCT CGGCTCTGCG CACCAGGGCT GCCCGCCTCC GTTCCCGGCG CGTACGTCCT CGGCTCTGCG CACCAGGGCT GCCTGCCTCC GTTCCCGGCG CGTACGTCCT CGGCTCTGCG CACCAGGGCT GCCTGCCTCC GTTCCCGGCG CGTACGTCCT CGGCTCTGCG CACCAGGGCT GCCTGCCTCC GTTCCCGGCG CGTACGTCCT CGGCTCTGCG CACCAGGGCT GCCTGCCTCC GTTCCCGGCG CGTACGTCCT CGGCTCTGCG CACCAGGGCT GCCTGCCTCC GTTCCCGGCG CGTACGTCCT CGGCTCTGCG CACCAGGGCT GCCTCCCTCC GTTCCCTGCG CGTACGTCCT CGGCTCTGCG CACCAGGGCT GCCTCCCTCC GTTCCCTGCG CGTACGTCCT CGGCTCTGCG CACCAGGGCT GCCTCCCTCC GTTCCCTGCG CGTACGTCCT CGGCTCTGCG CACCAGGGCT GCCTCCCTCC GTTCCCTGCG CGTACGTCCT CGGCTCTGCG CACCAGGGCT GCCTCCCTCC GTTCCCTGCG CGTACGTCCC CGGCTCTGCG CACCAGGGCT GCCTCCCTCC GTTCCCGGCG CGTACGTCCT CGGCTCTGCG CACCAGGGCT GCCTCCCTCC GTTCCCGGCG CGTACGTCCT CGGCTCTGCG CACCAGGGCT GCCTCCCTCC GTTCCCGGCG CGTACGTGCT AGGATCCGCT CACCAGGGAT GTCTGCCTCC GTTCCCGGCG CGTACGTGCT AGGATCCGCT CACCAGGGAT GTCTGCCTCC GTTCCCGGCG CGTACGTGCT AGGATCCGCT CACCAGGGAT GTCTGCCTCC GTTCCCGGCG CGTACGTGCT AGGATCCGCT CACCAGGGAT GTCTGCCTCC GTTCCCGGCG CGTACGTCCT CGGCTCTGCG CACCAGGGCT GCCTGCCTCC GTTCCCGGCG CGTACGTCCT CGGCTCTGCG CACCAGGGCT GCCTGCCTCC GTTCCCGGCG CGTACGTCCT CGGCTCCGCG CACCAGGGCT GCCTGCCTCC GTTCCCGGCA CGTACGTCCT CGGCTCCGCG CACCAGGGCT GCCTGCCTCC GTTCCCGGCA CGTACGTCCT CGGCTCCGCG CACCAGGGCT GCCTGCCTCC GTTCCCGGCA CGTACGTCCT CGGCTCCGCG CACCAGGGCT GCCTGCCTCC GTTCCCGGCA CGTACGTCCT CGGCTCCGCG CACCAGGGCT GCCTGCCTCC GTTCCCGGCA CGTACGTCCT CGGCTCCGCG CACCAGGGCT GCCTGCCTCC GTTCCCGGCA CCTACGTCCT CGGTTCGGCT CACCAGGGCT GCCTTCCGCC GTTCCCAGCA CCTACGTCCT CGGTTCGGCT CACCAGGGCT GCCTTCCGCC GTTCCCAGCA CCTACGTCCT CGGTTCGGCT CACCAGGGCT GCCTTCCGCC GTTCCCAGCA CCTACGTCCT CGGTTCGGCT CACCAGGGCT GCCTTCCGCC GTTCCCAGCA CGTACGTCCT CGGCTCTGCG CACCAGGGCT GCCTGCCTCC GTTCCCGGCG CGTACGTCCT CGGCTCTGCG CACCAGGGCT GCCTCCCTCC GTTCCCGGCG CGTACGTCCT CGGCTCGGCG CATCAAGGAT GCCTCCCGCC GTTCCCAGCA CGTACGTGCT CGGGTCGGCG CACCAAGGCT GTCTCCCGCC GTTTCCAGCG CGTACGTTCT CGGCTCTGCC CACCAGGGCT GCCTGCCTCC GTTCCCGGCG CGTACGTCCT AGGCTCTGCC CACCAAGGAT GCCTGCCACC GTTTCCTGCA CGTACGTCCT CGGCTCTGCG CACCAGGGCT GCCTGCCTCC GTTCCCGGCG CGTACGTCCT CGGCTCTGCG CACCAGGGCT GCCTGCCTCC GTTCCCGGCG
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    42_2 42_6

    42-15 42—5b 42-lb 42-13 42-3 a

    42- 4 42—5a 42-10 42—3b 42-1

    42— 6b

    43- 1

    43- 5

    43- 12 43_20 43-21 43-23 43_25

    44- 1

    223_10 223-2 223-4 223_5 223_6 223-7 A3_4 A3-5 A3-7 A3—3 42—12 AAV1 AAV2 AAV3 AAV8 AAV9 AAV7 44 2

    Fig. 1AAP

    3351 3400 GACGTGTTCA TGATTCCTCA GTACGGATAT CTGACTCTAA ACAACGGCAG GACGTCTTCA TGATTCCTCA GTACGGGTAC CTGACTCTGA ACAACGGCAG GACGTCTTCA TGATTCCTCA GTACGGGTAC CTGACTCTGA ACAACGGCAG GACGTCTTCA TGATTCCTCA GTACGGGTAC CTGACTCTGA ACAACGGCAG GACGTCTTCA TGATTCCTCA GTACGGGTAC CTGACTCTGA ACAACGGCAG GACGTCTTCA TGATTCCTCA GTACGGGTAC CTGACTCTGA ACAACGGCAG GACGTCTTCA TGATTCCTCA GTACGGGTAC CTGACTCTGA ACAACGGCAG GACGTCTTCA TGATTCCTCA GTACGGGTAC CTGACTCTGA ACAACGGCAG GACGTGTTCA TGATTCCTCA GTACGGATAT CTGACTCTAA ACAACGGCAG GACGTGTTCA TGATTCCTCA GTACGGATAT CTGACTCTAA ACAACGGCAG GACGTGTTCA TGATTCCTCA GTACGGATAT CTGACTCTAA ACAACGGCAG GACGTGTTCA TGATTCCTCA GTACGGATAT CTGACTCTAA ACAACGGCAG GACGTGTTCA TGATTCCTCA GTACGGATAT CTGACTCTAA ACAACGGCAG GACGTCTTCA TGATTCCTCA GTACGGGTAT CTGACCCTAA ACAATGGCAG GACGTCTTCA TGATTCCTCA GTACGGGTAT CTGACCCTAA ACAATGGCAG GACGTCTTCA TGATTCCTCA GTACGGGTAT CTGACCCTAA ACAATGGCAG GACGTCTTCA CGGTTCCTCA GTACGGCTAT TTAACTTTAA ACAATGGAAG GACGTCTTCA TGGTTCCTCA GTACGGCTAT TTAACTTTAA ACAATGGAAG GACGTCTTCA TGGTTCCTCA GTACGGCTAT TTAACTTTAA ACAATGGAAG GACGTCTTCA TGGTTCCTCA GTACGGCTAT TTAACTTTAA ACAATGGAAG GACGTCTTCA TGATTCCTCA GTACGGGTAC CTGACTCTGA ACAATGGCAG GACGTCTTCA TGATTCCTCA GTACGGGTAC CTGACTCTGA ACAATGGCAG GACGTGTTCA TGATTCCGCA GTACGGATAC CTGACTCTGA ACAATGGCAG GACGTGTTCA TGATTCCGCA GTACGGATAC CTGACTCTGA ACAATGGCAG GACGTGTTCA TGATTCCGCA GTACGGATAC CTGACTCTGA ACAATGGCAG GACGTGTTCA TGATTCCGCA GTACGGATAC CTGACTCTGA ACAATGGCAG GACGTGTTCA TGATTCCGCA GTACGGATAC CTGACTCTGA ACAATGGCAG GACGTGTTCA TGATTCCGCA GTACGGATAC CTGACTCTGA ACAATGGCAG GACGTCTTCA TGATTCCTCA GTACGGCTAC TTGACTCTGA ACAATGGCAG GACGTCTTCA TGATTCCTCA GTACGGCTAC TTGACTCTGA ACAATGGCAG GACGTCTTCA TGATTCCTCA GTACGGCTAC TTGACTCTGA ACAATGGCAG GACGTCTTCA TGATTCCTCA GTACGGCTAC TTGACTCTGA ACAATGGCAG GACGTCTTCA TGATTCCTCA GTACGGGTAC CTGACTCTGA ACAACGGCAG GACGTGTTCA TGATTCCGCA ATACGGCTAC CTGACGCTCA ACAATGGCAG GACGTCTTCA TGGTGCCACA GTATGGATAC CTCACCCTGA ACAACGGGAG GACGTCTTCA TGGTCCCTCA GTATGGATAC CTCACCCTGA ACAACGGAAG GACGTGTTCA TGATTCCCCA GTACGGCTAC CTAACACTCA ACAACGGTAG GACGTCTTCA TGGTTCCTCA GTACGGCTAC CTGACGCTCA ACAATGGAAG GACGTCTTCA TGATTCCTCA GTACGGCTAC CTGACTCTCA ACAATGGCAG GACGTCTTCA TGATTCCTCA GTACGGGTAC CTGACTCTGA ACAATGGCAG
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    42 2 3401 TCAGTCTGTG GGACGTTCCT 42 8 TCAGGCCGTG GGCCGTTCCT 42 15 TCAGGCCGTG GGCCGTTCCT 42 5b TCAGGCCGTG GGCCGTTCCT 42 lb TCAGGCCGTG GGCCGTTCCT 42 13 TCAGGCCGTG GGCCGTTCCT 42 3a TCAGGCCGTG GGCCGTTCCT 42 4 TCAGGCCGTG GGCCGTTCCT 42 5a TCAGTCTGTG GGACGTTCCT 42 10 TCAGTCTGTG GGACGTTCCT 42 3b TCAGTCTGTG GGACGTTCCT 42 11 TCAGTCTGTG GGACGTTCCT 42 6b TCAGTCTGTG GGACGTTCCT 43 1 TCAGGCTGTG GGCCGTTCCT 43 5 TCAGGCTGTG GGCCGTTCCT 43 12 TCAGGCTGTG GGCCGTTCCT 43 20 CCAAGCCCTG GGACGTTCCT 43 21 CCAAGCCCTG GGACGTTCCT 43 23 CCAAGCCCTG GGACGTTCCT 43 25 CCAAGCCCTG GGACGTTCCT 44 1 TCAGGCCGTG GGCCGTTCCT 44 5 TCAGGCCGTG GGCCGTTCCT 223 10 CCAATCGGTA GGCCGTTCCT 223 2 CCAATCGGTA GGCCGTTCCT 223 4 CCAATCGGTA GGCCGTTCCT 223 5 CCAATCGGTA GGCCGTTCCT 223 6 CCAATCGGTA GGCCGTTCCT 223 7 CCAATCGGTA GGCCGTTCCT A3 4 CCAAGCGGTA GGACGTTCTT A3 5 CCAAGCGGTA GGACGTTCTT A3 7 CCAAGCGGTA GGACGTTCTT A3 3 CCAAGCGGTA GGACGTTCTT 42 12 TCAGGCCGTG GGCCGTTCCT AAV1 CCAAGCCGTG GGACGTTCAT AAV2 TCAGGCAGTA GGACGCTCTT AAV3 TCAAGCGGTG GGACGCTCAT AAV8 TCAGGCCGTG GGACGCTCCT AAV9 TCAAGCGTTA GGACGTTCTT AAV7 TCAGTCTGTG GGACGTTCCT 44 2 TCAGGCCGTG GGCCGTTCCT

    Fig. 1AAQ

    3450

    CCTTCTACTG CCTGGAGTAC TTTCCTTCTC CCTTCTACTG CCTGGAGTAC TTTCCTTCTC CCTTCTACTG CCTGGAGTAC TTTCCTTCTC CCTTCTACTG CCTGGAGTAC TTTCCTTCTC CCTTCTACTG CCTGGAGTAC TTTCCTTCTC CCTTCTACTG CCTGGAGTAC TTTCCTTCTC CCTTCTACTG CCTGGAGTAC TTTCCTTCTC CCTTCTACTG CCTGGAGTAC TTTCCTTCTC CCTTCTACTG CCTGGAGTAC TTTCCTTCTC CCTTCTACTG CCTGGAGTAC TTTCCTTCTC CCTTCTACTG CCTGGAGTAC TTTCCTTCTC CCTTCTACTG CCTGGAGTAC TTTCCTTCTC CCTTCTACTG CCTGGAGTAC TTTCCTTCTC CCTTCTACTG CCTGGAATAC TTCCCTTCTC CCTTCTACTG CCTGGAATAC TTCCCTTCTC CCTTCTACTG CCTGGAATAC TTCCCTTCTC CCTTCTACTG TCTGGAGTAT TTCCCATCGC CCTTCTACTG TCTGGAGTAT TTCCCATCGC CCTTCTACTG TCTGGAGTAT TTCCCATCGC CCTTCTACTG TCTGGAGTAT TTCCCATCGC CCTTCTACTG CCTGGAGTAC TTTCCTTCTC CCTTCTACTG CCTGGAGTAC TTTCCTTCTC CCTTCTACTG CCTGGAGTAC TTTCCTTCTC CCTTCTACTG CCTGGAGTAC TTTCCTTCTC CCTTCTACTG CCTGGAGTAC TTTCCTTCTC CCTTCTACTG CCTGGAGTAC TTTCCTTCTC CCTTCTACTG CCTGGAGTAC TTTCCTTCTC CCTTCTACTG CCTGGAGTAC TTTCCTTCTC CATTCTACTG TCTAGAGTAT TTTCCCTCTC CATTCTACTG TCTAGAGTAT TTTCCCTCTC CATTCTACTG TCTAGAGTAT TTTCCCTCTC CATTCTACTG TCTAGAGTAT TTTCCCTCTC CCTTCTACTG CCTGGAGTAC TTTCCTTCTC CCTTTTACTG CCTGGAATAT TTCCCTTCTC CATTTTACTG CCTGGAGTAC TTTCCTTCTC CCTTTTACTG CCTGGAGTAC TTCCCTTCGC CCTTCTACTG CCTGGAATAC TTTCCTTCGC CTTTCTACTG TCTGGAATAC TTCCCTTCTC CCTTCTACTG CCTGGAGTAC TTCCCCTCTC CCTTCTACTG CCTGGAGTAC TTTCCTTCTC
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    42_2

    42_8 42_15 42—5b 42_lb 42_13 42—3a

    42_4 42_5a 42_10

    42— 3b 42_11 4 2-6b

    43-1

    43- 5 43_12 43_20

    43- 21 43-23 43_25

    44_1

    44— 5 223-10

    223 2 223-4 223-5 223-6 223_7 A3-4 A3-5 A3_ 7 A3-3 42-12 AAV1 AAV2 AAV3 AAV8 AAV9 AAV7

    44 2

    Fig. 1AAR

    3451 3500

    AGATGCTGAG AACGGGCAAT AACTTTGAAT TCAGCTACAC CTTTGAGGAA AAATGCTGAG AACGGGCAAC AACTTTGAGT TCAGCTACCA GTTTGAGGAC AAATGCGGAG AACGGGCAAC AACTTTGAGT TCAGCTACCA GTTTGAGGAC AAATGCTGAG AACGGGCAAC AACTTTGAGT TCAGCTACCA GTTTGAGGAC AAATGCTGAG AACGGGCAAC AACTTTGAGT TCAGCTACCA GTTTGAGGAC AAATGCTGAG AACGGGCAAC AACTTTGAGT TCAGCTACCA GTTTGAGGAC AAATGCTGAG AACGGGCAAC AACTTTGAGT TCAGCTACCA GTTTGAGGAC AAATGCTGAG AACGGGCAAC AACTTTGAGT TCAGCTACCA GTTTGAGGAC AGATGCTGAG AACGGGCAAT AACTTTGAAT TCAGCTACCA GTTTGAGGAC AGATGCTGAG AACGGGCAAT AACTTTGAAT TCAGCTACAC CTTTGAGGAA AGATGCTGAG AACGGGCAAT AACTTTGAAT TCAGCTACAC CTTTGAGGAA AGATGCTGAG AACGGGCAAT AACTTTGAAT TCAGCTACAC CTTTGAGGAA AGATGCTGAG AACGGGCAAT AACTTTGAAT TCAGCTACAC CTTTGAGGAA AAATGCTGAG GACGGGCAAC AACTTTGAAT TCAGCTACAC CTTCGAGGAC AAATGCTGAG GACGGGCAAC AACTTTGAAT TCAGCTACAC CTTCGAGGAC AAATGCTGAG GACGGGCAAC AACTTTGAAT TCAGCTACAC CTTCGAGGAC AGATGCTGAG AACCGGCAAC AACTTTGAGT TCAGCTACAC CTTCGAGGAC AGATGCTGAG AACCGGCAAC AACTTTCAGT TCAGCTACAC CTTCGAGGAC AGATGCCGAG AACCGGCAAC AACTTTCAGT TCAGCTACAC CTTCGAGGAC AGATGCTGAG AACCGGCAAC AACTTTCAGT TCAGCTACAC CTTCGAGGAC AAATGCTGAG AACGGGCAAC AACTTTGAGT TCAGCTACCA GTTTGAGGAC AAATGCTGAG AACGGGCAAC AACTTTGAGT TCAGCTACCA GTTTGAGGAC AGATGCTGAG AACGGGCAAC AACTTCACCT TTAGCTACAC CTTCGAGGAC AGATGCTGAG AACGGGCAAC AACTTCACCT TTAGCTACAC CTTCGAGGAC AGATGCTGAG AACGGGCAAC AACTTCACCT TTAGCTACAC CTTCGAGGAC AGATGCTGAG AACGGGCAAC AACTTCACCT TTAGCTACAC CTTCGAGGAC AGATGCTGAG AACGGGCAAC AACTTCACCT TTAGCTACAC CTTCGAGGAC AGATGCTGAG AACGGGCAAC AACTTCACCT TTAGCTACAC CTTCGAGGAC AGATGCTGAG GACGGGAAAC AACTTCACCT TCAGCTACAC TTTTGAAGAC AGATGCTGAG GACGGGAAAC AACTTCACCT TCAGCTACAC TTTTGAAGAC AGATGCTGAG GACGGGAAAC AACTTCACCT TCAGCTACAC TTTTGAAGAC AGATGCTGAG GACGGGAAAC AACTTCACCT TCAGCTACAC TTTTGAAGAC AAATGCTGAG AACGGGCAAC AACTTTGAGT TCAGCTACCA GTTTGAGGAC AGATGCTGAG AACGGGCAAC AACTTTACCT TCAGCTACAC CTTTGAGGAA AGATGCTGCG TACCGGAAAC AACTTTACCT TCAGCTACAC TTTTGAGGAC AGATGCTAAG GACTGGAAAT AACTTCCAAT TCAGCTATAC CTTCGAGGAT AGATGCTGAG AACCGGCAAC AACTTCCAGT TTACTTACAC CTTCGAGGAC AGATGCTGAG AACCGGCAAC AACTTTCAGT TCAGCTACAC TTTCGAGGAC AGATGCTGAG AACGGGCAAC AACTTTGAGT TCAGCTACAG CTTCGAGGAC AAATGCTGAG AACGGGCAAC AACTTTGAGT TCAGCTACCA GTTTGAGGAC
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    42_2

    42_8

    42_15

    42_5b

    42_lb

    42_13

    42_3a

    42~4

    42_5a

    42_10

    42_3b

    42JL1

    42_6b

    43_1

    43_5

    43^12 43_20 43_21 43_23 43_25

    44_1

    44_5 223_10 223_2 223_4 223_5 223J, 223_7

    A3_4

    A3_5

    A3_7

    A3_3

    42_12

    AAVl

    AAV2

    AAV3

    AAVS

    AAV9

    AAV7

    44_2

    Fig. 1AAS

    3501 3550 GTGCCTTTCC ACAGCAGCTA TGCGCACAGC CAGAGCCTGG ACCGGCTGAT GTGCCTTTTC ACAGCAGCTA CGCGCACAGC CAAAGCCTGG ACCGGCTGAT GTGCCTTTTC ACAGCAGCTA CGCGCATAGC CAAAGCCTGG ACCGGCTGAT GTGCCTTTTC ACAGCAGCTA CGCGCACAGC CAAAGCCTGG ACCGGCTGAT GTGCCTTTTC ACAGCAGCTA TGCGCACAGC CAAAGCCTGG ACCGGCTGAT GTGCCTTTTC ACAGCAGCTA TGCGCACAGC CAAAGCCTGG ACCGGCTGAT GTGCCTTTTC ACAGCAGCTA CGCGCACAGC CAAAGCCTGG ACCGGCTGAT GTGCCTTTTC ACAGCAGCTA CGCGCACAGC CAAAGCCTGG ACCGGCTGAT GTGCCCTTTC ACAGCAGCTA CGCGCACAGC CAAAGCCTGG ACCGGCTGAT GTGCCTTTCC ACAGCAGCTA TGCGCACAGC CAGAGCCTGG ACCGGCTGAT GTGCCTTTCC ACAGCAGCTA TGCGCACAGC CAGAGCCTGG ACCGGCTGAT GTGCCTTTCC ACAGCAGCTA TGCGCACAGC CAGAGCCTGG ACCGGCTGAT GTGCCTTTCC ACAGCAGCTA TGCGCATAGC CAGAGCCTGG ACCGGCTGAT GTGCCTTTCC ACAGCAGCTA CGCGCACAGC CAGAGCCTGG ACCGGCTGAT GTGCCTTTCC ACAGCAGCTA CGCGCACAGC CAGAGCCTGG ACCGGCTGAT GTGCCTTTCC ACAGCAGCTA CGCGCACAGC CAGAGCCTGG ACCGGCTGAT GTGCCTTTCC ACAGCAGCTA CGCGCACAGC CAGAGCCTGG ACAGGCTGAT GTGCCTTTCC ACAGCAGCTA CGCGCACAGC CAGAGCCTGG ACAGGCTGAT GTGCCTTTCC ACAGCAGCTA CGCGCACAGC CAGAGCCTGG ACAGGCTGAT GTGCCTTTCC ACAGCAGCTA CGCGCACAGC CAGAGCCTGG ACAGGCTGAT GTGCCTTTTC ACAGCAGCTA CGCGCACAGC CAAAGCCTGG ACCGGCTGAT GTGCCTTTTC ACAGCAGCTA CGCGCACAGC CAAAGCCTGG ACCGGCTGAT GTGCCTTTCC ACAGCAGCTA CGCGCACAGC CAGAGTCTGG ACCGGCTGAT GTGCCTTTCC ACAGCAGCTA CGCGCACAGC CAGAGTCTGG ACCGGCTGAT GTGCCTTTCC ACAGCAGCTA CGCGCACAGC CAGAGTCTGG GCCGGCTGAT GTGCCTTTCC ACAGCAGCTA CGCGCACAGC CAGAGTCTGG GCCGGCTGAT GTGCCTTTCC ACAGCAGCTA CGCGCACAGC CAGAGTCTGG ACCGGCTGAT GTGCCTTTCC ACAGCAGCTA CGCGCACAGC CAGAGTCTGG ACCGGCTGAT GTGCCTTTCC ACAGCAGCTA CGCGCACAGC CAGAGTCTGG ATCGGCTGAT GTGCCTTTCC ACAGCAGCTA CGCGCACAGC CAGAGTCTGG ATCGGCTGAT GTGCCTTTCC ACAGCAGCTA CGCGCACAGC CAGAGTCTGG ATCGGCTGAT GTGCCTTTCC ACAGCAGCTA CGCGCACAGC CAGAGTCTGG ATCGGCTGAT GTGCCTTTTC ACAGCAGCTA CGCGCACAGC CAAAGCCTGG ACCGGCTGAC GTGCCTTTCC ACAGCAGCTA CGCGCACAGC CAGAGCCTGG ACCGGCTGAT GTTCCTTTCC ACAGCAGCTA CGCTCACAGC CAGAGTCTGG ACCGTCTCAT GTACCTTTTC ACAGCAGCTA CGCTCACAGC CAGAGTTTGG ATCGCTTGAT GTGCCTTTCC ACAGCAGCTA CGCCCACAGC CAGAGCTTGG ACCGGCTGAT GTGCCTTTCC ACAGCAGCTA CGCACACAGC CAGAGTCTAG ATCGACTGAT GTGCCTTTCC ACAGCAGCTA CGCACACAGC CAGAGCCTGG ACCGGCTGAT GTGCCTTTTC ACAGCAGCTA CGCGCACAGC CAAAGCCTGG ACCGGCTGAT
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    42_2

    42_8

    42_15

    42_5b

    42_lb

    42_13

    42_3a

    42_4

    42_5a

    42_10

    42_3b

    42_11

    42_6b

    43_1

    43_5

    43_12

    43_20

    43_21

    43_23

    43_25

    44_1

    44_5

    223^10

    223_2

    223_4

    223_5

    223_6

    223_7

    A3_4

    A3_5

    A3_7

    A3_3

    42_12

    AAVl

    AAV2

    AAV3

    AAV8

    AAV9

    AAV7

    44 2

    Fig. 1AAT

    3551 3600 GAATCCCCTC ATCGACCAGT ACCTGTACTA CCTGGCCCGG ACCCAGAGCA GAACCCCCTC ATCGACCAGT ACCTGTACTA CCTGTCTCGG ACTCAGTCCA GAACCCCCTC ATCGACCAGT ACCTGTACTA CCTGTCTCGG ACTCAGTCCA GAACCCCCTC ATCGACCAGT ACCTGTACTA CCTGTCTCGG ACTCAGTCCA GAACCCCCTC ATCGACCAGT ACCTGTACTA CCTGTCTCGG ACTCAGTCCA GAACCCCCTC ATCGACCAGT ACCTGTACTA CCTGTCTCGG ACTCAGTCCA GAACCCCCTC ATCGACCAGT ACCTGTACTA CCTGTCTCGG ACTCAGTCCA GAACCCCCTC ATCGACCAGT ACCTGTACTA CCTGTCTCGG ACTCAGTCCA GAACCCCCTC ATCGACCAGT ACCTGTACTA CCTGTCTCGG ACTCAGTCCA GAATCCCCTC ATCGACCAGT ACCTGTACTA CCTGGCCCGG ACCCAGAGCA GAATCCCCTC ATCGACCAGT ACCTGTACTA CCTGGCCCGG ACCCAGAGCA GAATCCCCTC ATCGACCAGT ACCTGTACTA CCTGGCCCGG ACCCAGAGCA GAATCCCCTC ATCGACCAGT ACCTGTACTA CCTGGCCCGG ACCCAGAGCA GAACCCTCTC ATCGACCAGT ACCTGTATTA CTTATCCAGA ACTCAGTCCA GAACCCTCTC ATCGACCAGT ACCTGTATTA CTTATCCAGA ACTCAGTCCA GAACCCTCTC ATCGACCAGT ACCTGTATTA CTTATCCAGA ACTCAGTCCA GAATCCCCTC ATCGACCAGT ACCTGTACTA CCTGGTCAGA ACGCAAACGA GAATCCCCTC ATCGACCAGT ACCTGTACTA CCTGGTCAGA ACGCAAACGA GAATCCCCTC ATCGACCAGT ACCTGTACTA CCTGGTCAGA ACGCAAACGA GAATCCCCTC ATCGACCAGT ACCTGTACTA CCTGGTCAGA ACGCAAACGA GAACCCCCTC ATCGACCAGT ACCTGTACTA CCTGTCTCGG ACTCAGTCCA GAACCCCCTC ATCGACCAGT ACCTGTACTA CCTGTCTCGG ACTCAGTCCA GAATCCCCTC ATCGACCAGT ACCTGTACTA CTTGGCCAGA ACACAGAGCA GAATCCCCTC ATCGACCAGT ACCTGTACTA CTTGGCCAGA ACACAGAGCA GAATCCCCTC ATCGACCAGT ACCTGTACTA CTTGGCCAGA ACACAGAGCA GAATCCCCTC ATCGACCAGT ACCTGTACTA CTTGGCCAGA ACACAGAGCA GAATCCCCTC ATCGACCAGT ACCTGTACTA CTTGGCCAGA ACACAGAGCA GAATCCCCTC ATCGACCAGT ACCTGTACTA CTTGGCCAGA ACACAGAGCA GAATCCTCTC ATTGACCAGT ACCTGTATTA CCTGAGCAAA ACTCAGGGTA GAATCCTCTC ATTGACCAGT ACCTGTATTA CCTGAGCAAA ACTCAGGGTA GAATCCTCTC ATTGACCAGT ACCTGTATTA CCTGAGCAAA ACTCAGGGTA GAATCCTCTC ATTGACCAGT ACCTGTATTA CCTGAGCAAA ACTCAGGGTA GAACCCCCTC ATCGACCAGT ACCTGTACTA CCTGGCCCGG ACCCAGAGCA GAATCCTCTC ATCGACCAAT ACCTGTATTA CCTGAACAGA ACTCAAA.AT GAATCCTCTC ATCGACCAGT ACCTGTATTA CTTGAGCAGA ACAAACACTC GAATCCTCTT ATTGATCAGT ATCTGTACTA CCTGAACAGA ACGCAAGGAA GAATCCTCTG ATTGACCAGT ACCTGTACTA CTTGTCTCGG ACTCAAACAA GAACCCCCTC ATCGACCAGT ACCTATACTA CCTGGTCAGA ACACAGACAA GAATCCCCTC ATCGACCAGT ACTTGTACTA CCTGGCCAGA ACACAGAGTA GAACCCCCTC ATCGACCAGT ACCTGTACTA CCTGTCTCGG ACTCAGTCCA
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    42-2

    42_8

    42_15 42—5b 42_lb 42_13 4 2_3 a

    42_4

    42-5a 42-10 42—3b 42_11

    42- 6b

    43_1

    43_5

    43- 12 43_20 43-21 43_23 43-25

    44_1

    44_5

    223_10

    223_2

    223-4

    223_5

    223_6

    223_7

    A3_4

    A3_5

    A3—7

    A3_3 42_12

    AAV1

    AAV2

    AAV3

    AAV8

    AAV9

    AAV7

    44 2

    3601

    CTACGG..GG TCCACAAGGG CGGGA...GG TACCGCAGGA CGGGA...GG TACCGCAGGA CGGGA...GG TACCGCAGGA CGGGA...GG TACCGCAGGA CGGGA...GG TACCGCAGGA CGGGA...GG TACCGCAGGA CGGGA...GG TACCGCAGGA CGGGA...GG TACCGCAGGA CTACG. . .GG GTCCACAAGG CTACG.. . GG GTCCACAAGG CTACG. . .GG GTCCACAAGG CTACG. . .GG GTCCACAAGG CAGGA. . .GG AACTCAAGGT CAGGA...GG AACTCAAGGT CAGGA. . . GG AACTCAAGGT

    CT......GG AACTGGAGGG

    CT......GG AACTGGAGGG

    CT......GG AACTGGAGGG

    CT......GG AACTGGAGGG

    CGGGA..-GG TACCGCAGGA CGGGA..-GG TACCGCAGGA ACGCAGGAGG TACTGCTGGC ACGCAGGAGG TACTGCTGGC ACGCAGGAGG TACTGCTGGC ACGCAGGAGG TACTGCTGGC ACGCAGGAGG TACTGCTGGC ACGCAGGAGG TACTGCTGGC CAAG. . . TGG AACAACGCAG CAAG...TGG AACAACGCAG CAAG...TGG AACAACGCAG CAAG. . . TGG AACAACGCAG CTACG...GG GTCCACAAGG CAGTCC . . GG AAGTGCCCAA CAAG. . .TGG AACCACCACG CAACCTCTGG AACAACCAAC CAGGAG. . GC . ACGGCAAAT

    CTGGA......ACTGGGGGA

    ACCCAGGAGG CACAGCTGGC CGGGA...GG TACCGCAGGA

    Fig. 1AAU

    3650

    TCAGGCTGGG

    TCAGGCCGGG

    TCAGGCCGGG

    TCAGGCCGGG

    TCAGGCCGGG

    TCAGGCCGGG

    TCAGGCCGGG

    TCAGGCCGGG

    TCAGGCCGGG

    TCAGGCTGGG

    TCAGGCTGGG

    TCAGGCTGGG

    TCAGGCTGGG

    TCAAGCCGGG

    TCAAGCCGGG

    TCAAGCCGGG

    CCAAGCGGGT

    CCAAGCGGGT

    CCAAGCGGGT

    CCAAGCGGGT

    TCAGGCCGGG

    TCAGGCCGGG

    TCAGGGCGGA

    TCAGGGCGGA

    TCAGGGCGGA

    TCAGGGCGGA

    TCAGGGCGGA

    TCAGGGCGGA

    CCAAGCTGGG

    CCAAGCTGGG

    CCAAGCTGGG

    CCAAGCTGGG

    TCAGGCTGGG

    CCGTGGGTCT

    TCAGGGCGGA

    CCAGGCTGGG

    CCAAGGTGGG

    CCAAGCAGGC

    CCAGGGCGGG

    TCAGGCCGGG

    AGCTGCA.GT TCCA......

    ACTCAGCAGT TGCTATTTTC ACTCAGCAGT TGCTATTTTC ACTCAGCAGT TGCTATTTTC ACTCAGCAGT TGCTATTTTC ACTCAGCAGT TGCTATTTTC ACTCAGCAGT TGCTATTTTC ACTCAGCAGT TGCTATTTTC ACTCAGCAGT TGCTATTTTC

    GAGCTGCAGT TCCA......

    GAGCTGCAGT TCCA......

    GAGCTGCAGT TCCA......

    GAGCTGCAGT TCCA......

    ACTCAGCAAT TGTTATTTTC ACTCAGCAAT TGTTATTTTC ACTCAGCAAT TGTTATTTTC ACGCAGACTC TGGCATTCAG ACGCAGACTC TGGCATTCAG ACGCAGACTC TGGCATTCAG ACGCAGACTC TGGCATTCAG ACTCAGCAGT TGCTATTTTC ACTCAGCAGT TGCTATTTTC AATCGGGAAC TGCAGTTTTA AATCGGGAAC TGCAGTTTTA AATCGGGAAC TGCAGTTTTA AATCGGGAAC TGCAGTTTTA AATCGGGAAC TGCAGTTTTA AATCGGGAAC TGCAGTTTTA CAATCGAGAC TGCAGTTCAG CAATCGAGAC TGCAGTTCAA CAATCGAGAC TGCAGTTCAG CAATCGAGAC TGCAGTTCAG

    GGGCTGCAGT TCCA......

    AACAAGGACT TGCTGTTTAG CAGTCAAGGC TTCAGTTTTC CAATCACGGC TGCTTTTTAG ACGCAGACTC TGGGCTTCAG ACTCAAACTT TGGCATTCAG AATCGGGAAC TGCAGTTTTA ACTCAGCAGT TGCTATTTTC
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    42 2 3651 CCCAACACCA TGGCCGAGCA 42 8 CCTAATAACA TGTCGGCTCA 42 15 CCTAATAACA TGTCGGCTCA 42 5b CCTAATAACA TGTCGGCTCA 42 lb CCTAATAACA TGTCGGCTCA 42 13 CCTAATAACA TGTCGGCTCA 42 3a CCTAATAACA TGTCGGCTCA 42 4 CCTAATAACA TGTCGGCTCA 42 5a CCTAATAACA TGTCGGCTCA 42 10 CCCAACACCA TGGCCGAGCA 42 3b CCCAACACCA TGGCCGAGCA 42 11 CCCAACACCA TGGCCGAGCA 42 6b CCCAACACCA TGGCCGAGCA 43 1 CCCGCAAACA TGTCGGCTCA 43 5 CCCGCAAACA TGTCGGCTCA 43 12 CCCGCAAACA TGTCGGCTCA 43 20 CCTAGCTCAA TGGCCAACCA 43 21 CCTAGCTCAA TGGCCAACCA 43 23 CCTAGCTCAA TGGCCAACCA 43 25 CCTAGCTCAA TGGCCAACCA 44 1 CCTAATAACA TGTCGGCTCA 44 5 CCTAATAACA TGTCGGCTCA 223 10 CCTACCACCA TGGCCGAACA 223 2 CCTACCACCA TGGCCGAACA 223 4 CCTACCACCA TGGCCGAACA 223 5 CCTACCACCA TGGCCGAACA 223 6 CCTACCACCA TGGCCGAACA 223-7 CCTACCACCA TGGCCGAACA A3 4 CCTAGCTCCA TGGCTCAGCA A3 5 CCTAGCTCCA TGGCTCAGCA A3_7 CCTAGCTCCA TGGCTCAGCA A3 3 CCTAGCTCCA TGGCTCAGCA 42 12 CCCAACACCA TGGCCGAGCA AAVl CCAGCTGGCA TGTCTGTTCA AAV2 GCGAGTGACA TTCGGGACCA AAV3 CCTCAGTCTA TGTCTTTGCA AAV8 CCTAATACAA' TGGCCAATCA AAV9 CCTAGCTCAA TGGCCAATCA AAV7 CCTTCAACTA TGGCCGAACA 44 2 CCTAATAACA TGTCGGCTCA

    Fig. 1AAV ' 3700

    ATCAAAGAAC TGGCTGCCCG GACCCTGTTA GGCCAAAAAC TGGCTACCCG GGCCCTGCTA GGCCAAAAAC TGGCTACCCG GGCCCTGCTA GGCCAAAAAC TGGCTACCCG GGCCCTGCTA GGCCAAAAAC TGGCTACCCG GGCCCTGCTA GGCCAAAAAC TGGCTACCCG GGCCCTGCTA GGCCAAAAAC TGGCTACCCG GGCCCTGCTA GGCCAAAAAC TGGCTACCCG GGCCCTGCTA GGCCAAAAAC TGGCTACCCG GGCCCTGCTA ATCAAAGAAC TGGCTGCCCG GACCCTGTTA ATCAAAGAAC TGGCTGCCCG GACCCTGTTA ATCAAAGAAC TGGCTGCCCG GACCCTGTTA ATCAAAGAAC TGGCTGCCCG GACCCTGTTA GGCCAAGAAC TGGCTACCTG GACCGTGTTA GGCCAAGAAC TGGCTACCTG GACCGTGTTA GGCCAAGAAC TGGCTACCTG GACCGTGTTA GGCTAGAAAT TGGGTGCCCG GACCTTGCTA GGCTAGAAAT TGGGTGCCCG GACCTTGCTA GGCTAGAAAT TGGGTGCCCG GACCTTGCTA GGCTAGAAAT TGGGTGCCCG GACCTTGCTA GGCCAAAAAC TGGCTACCCG GGCCCTGCTA GGCCAAAAAC TGGCTACCCG GGCCCTGCTA AGCAAAGAAC TGGCTGCCCG GACCTTGCTT AGCAAAGAAC TGGCTGCCCG GACCTTGCTT AGCAAAGAAC TGGCTGCCCG GACCTTGCTT AGCAAAGAAC TGGCTGCCCG GACCTTGCTT AGCAAAGAAC TGGCTGCCCG GACCTTGCTT AGCAAAGAAC TGGCTGCCCG GACCTTGCTT GGCCAAAAAC TGGCTACCGG GACCCAGCTA GGCCAAAAAC TGGCTACCGG GACCCAGCTA GGCCAAAAAC TGGCTACCGG GACCCAGCTA GGCCAAAAAC TGGCTACCGG GACCCAGCTA ATCAAAGAAC TGGCTGCCCG GACCCTGTTA GCCCAAAAAC TGGCTACCTG GACCCTGTTA GTCTAGGAAC TGGCTTCCTG GACCCTGTTA GGCCAGAAAT TGGCTACCTG GGCCCTGCTA GGCAAAGAAC TGGCTGCCAG GACCCTGTTA GGCTAGAAAC TGGGTACCCG GGCCTTGCTA AGCCAAGAAT TGGTTACCTG GACCTTGCTT GGCCAAAAAC TGGCTACCCG GGCCCTGCTA
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    42_2

    42_8

    42_15

    42_5b

    42_lb

    42_13

    42_3a

    42_4

    42_5a

    42_10

    42_3b

    42_11

    42_6b

    43_1

    43_5

    43„12

    43_20

    43_21

    43_23

    43_25

    44_1

    44_5 223_10 223_2 223_4 223_5 223_6 22 3 7

    A3_4

    A3_5

    A3_7

    A3_3

    42JL2

    AAV1

    AAV2

    AAV3

    AAV8

    AAV9

    AAV7

    44_2

    Fig. 1AAW

    3701 3750

    TCGGCAGCAG AGACTGTCAA AAAACATAGA CAGCAACAAC AACAGTAACT CCGGCAGCAA CGCGTCTCCA CGACACTGTC GCAAAATAAC AACAGCAACT CCGGCAGCAA CGCGTCTCCA CGACACTGTC GCAAAATAAC AACAGCAACT CCGGCAGCAA CGCGTCTCCA CGACACTGTC GCAAAATAAC AACAGCAACT CCGGCAGCAA CGCGTCTCCA CGACAGTGTC GCAAAATAAC AACAGCAACT CCGGCAGCAA CGCGTCTCCA CGACAGTGTC GCAAAATAAC AACAGCAACT CCGGCAGCAA CGCGTCTCCA CGACACTGTC GCAAAATAAC AACAGCAACT CCGGCAGCAA CGCGTCTCCA CGACACTGTC GCAAAATAAC AACAGCAACT CCGGCAGCAA CGCGTCTCCA CGACACTGTC GCAAAATAAC AACAGCAACT TCGGCAGCAG AGACTGTCAA AAAACATAGA CAGCAACAAC AACAGTAACT TCGGCAGCAG AGACTGTCAA AAAACATAGA CAGCAACAAC ACCAGTAACT TCGGCGGCAG AGACTGTCAA AAGACATAGA CAGCAACAAC AACAGTAACT TCGGCAGCAG AGACTGTCAA AAAACATAGA CAGCAACAAC AACAGTAACT CCGTCAGCAA CGAGTTTCCA CGACACTGTC GCAAAACAAC AACAGCAATT CCGTCAGCAA CGAGTTTCCA CGACACTGTC GCAAAACAAC AACAGCAATT CCGTCAGCAA CGAGTTTCCA CGACACTGTC GCAAAACAAC AACAGCAATT CCGGCAGCAG CGCGTCTCCA CGACAACCAA CCAGAACAAC AACAGCAACT CCGGCAGCAG CGCGTCTCCA CGACAACCAA CCAGAGCAAC AACAGCAACT CCGGCAGCAG CGCGTCTCCA CGACAACCAA CCAGAACAAC AACAGCAACT CCGGCAGCAG CGCGTCTCCA CGACAACCAA CCAGAACAAC AACAGCAACT CCGGCAGCAA CGCGTCTCCA CGACACTGTC GCAAAATAAC AACAGCAACT CCGGCAGCAA CGCGTCTCCA CGACACTGTC GCAAAATAAC AACAGCAACT CCGGCAACAG AGAGTATCCA AGACGCTGGA TCAAAATAAC AACAGCAACT CCGGCAACAG AGAGTATCCA AGACGCTGGA TCAAAATAAC AACAGCAACT CCGGCAACAG AGAGTATCCA AGACGCTGGA TCAAAATAAC AACAGCAACT CCGGCAACAG AGAGTATCCA AGACGCTGGA TCAAAATAAC AACAGCAACT CCGGCAACAG AGAGTATCCA AGACGCTGGA TCAAAATAAC AACAGCAACT CCGGCAACAG AGAGTATCCA AGACGCTGGA TCAAAATAAC AACAGCAACT CCGACAGCAG CGAATGTCTA AGACGGCTAA TGACAACAAC AACAGTGAAT CCGACAGCAG CGAATGTCTA AGACGGCTAA TGACAACAAC AACAGTGAAT CCGACAGCAG CGAATGTCTA AGACGGCTAA TGACAACAAC AACAGTGAAT CCGACAGCAG CGAATGTCTA AGACGGCTAA TGACAACAAC AACAGTGAAT TCGGCAGCAG AGACTGTCAA AAAACATAGA CAGCAACAAC AACAGTAACT TCGGCAGCAG CGCGTTTCTA AAACAAAAAC AGACAACAAC AACAGCAATT CCGCCAGCAG CGAGTATCAA AGACATCTGC GGATAACAAC AACAGTGAAT CCGGCAACAG AGACTTTCAA AGACTGCTAA CGACAACAAC AACAGTAACT CCGCCAACAA CGCGTCTCAA CGACAACCGG GCAAAACAAC AATAGCAACT CCGTCAGCAG CGCGTCTCCA CAACCACCAA CCAAAATAAC AACAGCAACT CCGGCAACAA AGAGTCTCCA AAACGCTGGA TCAAAACAAC AACAGCAACT CCGGCAGCAA CGCGTCTCCA CGACACTGTC GCAAAATAAC AACAGCAACT
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    42 2 3751 TTGCCTGGAC CGGGGCCACT 42 8 TTGCTTGGAC CGGTGCCACC 42 15 TTGCTTGGAC CGGTGCCACC 42 5b TTGCTTGGAC CGGTGCCACC 42 lb TTGCTTGGAC CGGTGCCACC 42 13 TTGCTTGGAC CGGTGCCACC 42 3a TTGCTTGGAC CGGTGCCACC 42 4 TTGCTTGGAC CGGTGCCACC 42 5a TTGCTTGGAC CGGTGCCACC 42 10 TTGCCTGGAC CGGGGCCACT 42 3b TTGCCTGGAC CGGGGCCACT 42 11 TTGCCTGGAC CGGGGCCACT 42 6b TTGCCTGGAC CGGGGCCACT 43 1 TTGCTTGGAC CGGTGCCACC 43 5 TTGCTTGGAC CGGTGCCACC 43 12 TTGCTTGGAC CGGTGCCACC 43 20 TTGCCTGGAC GGGAGCTGCC 43 21 TTGCCTGGAC GGGAGCTGCC 43 23 TTGCCTGGAC GGGAGCTGCC 43 25 TTGCCTGGAC GGGAGCTGCC 44 1 TTGCCTGGAC CGGTGCCACC 44 5 TTGCCTGGAC CGGTGCCACC 223 10 TTGCCTGGAC TGGTGCCACA 223 2 TTGCCTGGAC TGGTGCCACA 223 4 TTGCCTGGAC TGGTGCCACA 223 5 TTGCCTGGAC TGGTGCCACA 223 6 TTGCCTGGAC TGGTGCCACA 223_7 TTGCCTGGAC TGGTGCCACA A3 4 TTGCTTGGAC TGCAGCCACC A3 5 TTGCTTGGAC TGCAGCCACC A3-7 TTGCTTGGAC TGCAGCCACC A3 3 TTGCTTGGAC TGCAGCCACC 42 12 TTGCCTGGAC CGGGGCCACT AAVl TTACCTGGAC TGGTGCTTCA AAV2 ACTCGTGGAC TGGAGCTACC AAV3 TTCCTTGGAC AGCGGCCAGC AAV8 TTGCCTGGAC TGCTGGGACC AAV9 TTGCGTGGAC GGGAGCTGCT AAV7 TTGCTTGGAC TGGTGCCACC 44 2 TTGCCTGGAC CGGTGCCACC

    Fig. 1AAX

    3800

    AAATACCATC TGAATGGTAG AAATTCATTA AAGTATCATC TGAATGGCAG AGACTCTCTG AAGTATCATC TGAATGGCAG AGACTCTCTG AAGTATCATC TGAATGGCAG AGACTCTCTG AAGTATCATC TGAATGGCAG AGACTCTCTG AAGTATCATC TGAATGGCAG AGACTCTCTG AAGTATCATC TGAATGGCAG AGACTCTCTG AAGTATCATC TGAATGGCAG AGACTCTCTG AAGTATCATC TGAATGGCAG AGACTCTCTG AAATACCATC TGAATGGTAG AAATTCATTA AAATACCATC TGAATGGTAG AAATTCATTA AAATACCATC TGAATGGTAG AAATTCATTA AAATACCATC TGAATGGTAG AAATTCATTA AAGTATCACC TGAATGGCAG AGACTCCCTG AAGTATCACC TGAATGGCAG AGACTCCCTG AAGTATCACC TGAATGGCAG AGACTCCCTG AAGTTTAAGC TGAACGGCCG AGACTCTCTA AAGTTTAAGC TGAACGGCCG AGACTCTCTA AAGTTTAAGC TGAACGGCCG AGACTCTCTA AAGTTTAAGC TGAACGGCCG AGACTCTCTA AAGTATCATC TGAATGGCAG AGACTCTCTG AAGTATCATC TGAATGGCAG AGACTCTCTG AAATACCATT TAAATGNAAG AAATTCATTG AAATACCATT TAAATGGAAG AAATTCATTG AAATACCATT TAAATGGAAG AAATTCATTG AAATACCATT TAAATGGAAG AAATTCATTG AAATACCATT TAAATGGAAG AAATTCATTG AAATACCATT TAAATGGAAG AAATTCATTG AAATATTACC TGAATGGAAG AAATTCTCTG AAATATTACC CGAATGGAAG AAATTCTCTG AAATATTACC TGAATGGAAG AAATTCTCTG AAATATTACC TGAATGGAAG AAATTCTCTG AAATACCATC TGAATGGTAG AAATTCATTA AAATATAACC TCAATGGGCG TGAATCCATC AAGTACCACC TCAATGGCAG AGACTCTCTG AAATATCATC TCAATGGCCG CGACTCGCTG AAATACCATC TGAATGGAAG AAATTCATTG AAATTCAAGC TGAACGGGAG AGACTCGCTA AAATATCACC TGAACGGGAG AAACTCGTTG AAGTATCATC TGAATGGCAG AGACTCTCTG
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    42_2

    42-8 42_15 42_5b 42_lb 42_13 42—3a

    42- 4 4 2-5 a 42-10 42_3b 42_11

    42— 6b

    43_1

    43- 5

    43- 12 43-20 43-21 43-23 43_25

    44 1

    44- 5 223-10

    223-2 223_4 223_5 223_6 223-7 A3_4 A3—5 A3-7 A3—3 42-12 AAVl AAV2 AAV3 AAV8 AAV9 AAV7

    44 2

    Fig. 1AAY

    3801 3850 ACCAACCCGG GCGTAGCCAT GGCCACCAAC AAGGACGACG AGGACCAGTT GTAAATCCCG GTGTCGCTAT GGCAACGCAC AAGGACGACG AAGAGCGATT GTAAATCCCG GTGTCGCTAT GGCAACGCAC AAGGACGACG AAGAGCGATT GTAAATCCCG GTGTCGCTAT GGCAACGCAC AAGGACGACG AAGAGCGATT GTAAATCCCG GTGTCGCTAT GGCAACGCAC AAGGGCGACG AAGAGCGATT GTAAATCCCG GTGTCGCTAT GGCAACGCAC AAGGGCGACG AAGAGCGATT GTAAATCCCG GTGTCGCTAT GGCAACGCAC AAGGACGACG AAGAGCGATT GTAAATCCCG GTGTCGCTAT GGCAACGCAC AAGGACGACG AAGAGCGATT GTAAATCCCG GTGTCGCTAT GGCAACGCAC AAGGACGACG AAGAGCGATT ACCAACCCGG GCGTAGCCAT GGCCACCAAC AAGGACGACG AGGACCAGTT ACCAACCCGG GCGTAGCCAT GGCCACCAAC AAGGACGACG AGGACCAGTT ACCAACCCGG GCGTAGCCAT GGCCACCAAC AAGGACGACG AGGACCAGTT ACCAACCCGG GCGTAGCCAT GGCCACCAAC AAGGACGACG AGGACCAGTT GTTAATCCCG GCGTTGCCAT GGCTACCCAC AAGGACGACG AGGAGCGCTT GTTAATCCCG GCGTTGCCAT GGCTACCCAC AAGGACGACG AGGAGCGCTT GTTAATCCCG GCGTTGCCAT GGCTACCCAC AAGGACGACG AGGAGCGCTT ATGAATCCGG GCGTGGCAAT GGCTTCCCAC AAGGATGACG ACGACCGCTT ATGAATCCGG GCGTGGCAAT GGCTTCCCAC AAGGATGACG ACGACCGCTT ATGAATCCGG GCGTGGCAAT GGCTTCCCAC AAGGATGACG ACGACCGCTT ATGAATCCGG GCGTGGCAAT GGCTTCCCAC AAGGATGACG ACGACCGCTT GTAAATCCCG GTGTCGCTAT GGCAACCCAC AAGGACGACG AAGAGCGATT GTAAATCCCG GTGTCGCTAT GGCAACCCAC AAGGACGACG AAGAGCGATT GTTAATCCCG GTGTCGCCAT GGCAACCCAC AAGGACGACG AGGAACGCTT GTTAATCCCG GTGTCGCCAT GGCAACCCAC AAGGACGACG AGGAACGCTT GTTAATCCCG GTGTCGCCAT GGCAACCCAC AAGGACGACG AGGAACGCTT GTTAATCCCG GTGTCGCCAT GGCAACCCAC AAGGACGACG AGGAACGCTT GTTAATCCCG GTGTCGCCAT GGCAACCCAC AAGGACGACG AGGAACGCTT GTTAATCCCG GTGTCGCCAT GGCAACCCAC AAGGACGACG AGGAACGCTT GTCAATCCCG GGCCCCCAAT GGCCAGTCAC AAGGACGATG AGGAAAAGTA GTCAATCCCG GGCCCCCAAT GGCCAGTCAC AAGGACGATG AGGAAAAGTA GTCAATCCCG GGCCCCCAAT GGCCAGTCAC AAGGACGATG AGGAAAAGTA GTCAATCCCG GGCCCCCAGT GGCCAGTCAC AAGGACGATG AGGAAAAGTA ACCAACCCGG GCGTAGCCAT GGCCACCAAC AAGGACGACG AGGACCAGTT ATCAACCCTG GCACTGCTAT GGCCTCACAC AAAGACGACG AAGACAAGTT GTGAATCC.. GGCC....AT GGCAAGCCAC AAGGACGATG AAGAAAAGTT GTGAATCCAG GACCAGCTAT GGCCAGTCAC AAGGACGATG AAGAAAAATT GCTAATCCTG GCATCGCTAT GGCAACACAC AAAGACGACG AGGAGCGTTT ATGAATCCTG GCGTGGCTAT GGCATCGCAC AAAGACGACG AGGACCGCTT GTTAATCCCG GCGTCGCCAT GGCAACTCAC AAGGACGACG AGGACCGCTT GTAAATCCCG GTGTCGCTAT GGCAACCCAC AAGGACGACG AAGAGCGATT
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    Fig. 1AAZ

    3851 3900

    42_2 CTTTCCCATC AACGGAGTGC TGGTTTTTGG CGAAACGGGG GCTGCCAACA 42_8 TTTTCCATCC AGCGGAGTCT TGATGTTTGG GAAACAGGGA GCTGGAAA.. 42_15 TTTTCCATCC AGCGGAGTCT TGATGTTTGG GAAACAGGGA GCTGGAAA.. 42_5b TTTTCCATCC AGCGGAGTCT TGATGTTTGG GAAACAGGGA GCTGGAAA.. 42_lb TTTTCCATCC AGCGGAGTCT TGATGTTTGG GAAACAGGGA GCTGGAAA.. 42_13 TTTTCCATCC AGCGGAGTCT TGATGTTTGG GAAACAGGGA GCTGGAAA.. 42__3a TTTTCCATCC AGCGGAGTCT TGATGTTTGG GAAACAGGGA GCTGGAAA.. 42_4 TTTTCCATCC AGCGGAGTCT TGATGTTTGG GAAACAGGGA GCTGGAAA..

    42_5a TTTTCCATCC AGCGGAGTCT TGATGTTTGG GAAACAGGGA GCTGGAAA., 42_10 CTTTCCCATC AACGGAGTGC TGGTTTTTGG CAAAACGGGG GCTGCCAACA 42_3b CTTTCCCATC AACGGAGTGC TGGTTTTTGG CAAAACGGGG GCTGCCAACA 42JL1 CTTTCCCATC AACGGAGTGC TGGTTTTTGG CAAAACGGGG GCTGCCAACA 42_6b CTTTCCCATC AACGGAGTGC TGGTTTTTGG CAAAACGGGG GCTGCCAACA

    43_1 CTTCCCGTCA AGCGGAGTTC TAATGTTTGG CAAGCAGGGG GCTGGAAA.. 43_5 CTTCCCGTCA AGCGGAGTTC TAATGTTTGG CAAGCAGGGG GCTGGAAA..

    43JL2 CTTCCCGTCA AGCGGAGTTC TAATGTTTGG CAAGCAGGGG GCTGGAAA.. 43_20 CTTCCCTTCG AGCGGGGTCC TGATTTTTGG CAAGCAAGGA GCCGGGAA.. 43_21 CTTCCCTTCG AGCGGGGTCC TGATTTTTGG CAAGCAAGGA GCCGGGAA.. 43_23 CTTCCCTTCG AGCGGGGTCC TGATTTTTGG CAAGCAAGGA GCCGGGAA.. 43_25 CTTCCCTTCG AGCGGGGTCC TGATTTTTGG CAAGCAAGGA GCCGGGAA..

    44_1 TTTTCCGTCC AGCGGAGTCT TAATGTTTGG GAAACAGGGA GCTGGAAA.. 44_5 TTTTCCGTCC AGCGGAGTCT TAATGTTTGG GAAACAGGGA GCTGGAAA..

    223_10 CTTCCCTTCG AGCGGAGTTC TAATTTTTGG CAAAACTGGA GCAGCTAATA 223_2 CTCCCCTTCG AGCGGAGTTC TAATTTTTGG CAAAACTGGA GCAGCTAATA 223__4 CTTCCCTTCG AGCGGAGTTC TAATTTTTGG CAAAACTGGA GCAGCTAATA 223_5 CTTCCCTTCG AGCGGAGTTC TAATTTTTGG CAAAACTGGA GCAGCTAATA 223_6 CTTCCCTTCG AGCGGAGTTC TAATTTTTGG CAAAACTGGA GCAGCTAATA 2237 CTTCCCTTCG AGCGGAGTTC TAATTTTTGG CAAAACTGGA GCAGCTAATA A3_4 TTTCCCCATG CACGGAAATC TCATCTTTGG AAAACAAGGC ACAGGAAC. . A3_5 TTTCCCCATG CACGGAAATC TCATCTTTGG AAAACAAGGC ACAGGAAC.. A3_7 TTTCCCCATG CACGGAAATC TCATCTTTGG AAAACAAGGC ACAGGAAC. . A3_3 TTTCCCCATG CACGGAAATC TCATCTTTGG AAAACAAGGC ACAGGAAC.. 42_12 CTTTCCCATC AACGGAGTGC TGGTTTTTGG CAAAACGGGG GCTGCCAACA AAVl CTTTCCCATG AGCGGTGTCA TGATTTTTGG AAAAGAGAGC GCCGGAGC-. AAV2 TTTTCCTCAG AGCGGGGTTC TCATCTTTGG GAAGCAAGGC TCAGAGAA.. AAV3 TTTCCCTATG CACGGCAATC TAATATTTGG CAAAGAAGGG ACAACGGC.. AAV8 TTTTCCCAGT AACGGGATCC TGATTTTTGG CAAACAAAAT GCTGCCAG.. AAV9 CTTTCCATCA AGTGGCGTTC TCATATTTGG CAAGCAAGGA GCCGGGAA. . AAV7 TTTCCCATCC AGCGGAGTCC TGATTTTTGG AAAAACTGGA GCAACTAACA 44_2 TTTTCCGTCC AGCGGAGTCT TAATGTTTGG GAAACAGGGA GCTGGAAA. .
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    42-2

    42-8

    42_15 42—5b 42_lb 42-13 4 2-3 a

    42-4

    42—5a 42_10 42—3b 42-11

    42— 6b

    43_1

    43_5

    43- 12 43-20 43_21 43_23 43-25

    44-1

    44-5

    223-10

    223_2

    223_4

    223_5

    223_6

    223_7

    A3-4

    A3-5

    A3_7

    A3-3 42-12 AAV1 AAV2 AAV3 AAV8 AAV9 AAV7 44 2

    Fig. 1AAAA

    3901 3950

    AGACAACGCT GGAA......AACGTGCTAA TGACCAGCGA GGAGGAGATC

    AGACAACG.T GGACTATAGC AGCGTTATGC TAACCAGTGA GGAAGAAATC AGACAACG.T GGACTATAGC AGCGTTATGC TAACCAGTGA GGAAGAAATC AGACAACG.T GGACTATAGC AGCGTTATGC TAACCAGTGA GGAAGAAATC AGACAACG.T AGACTATAGC AGCGTTATGC TAACCAGTGA GGAAGAAATC AGACAACG.T GGACTATAGC AGCGTTATGC TAACCAGTGA GGAAGAAATC AGACAACG.T GGACTATAGC AGCGTTATGC TAACCAGTGA GGAAGAAATC AGACAACG.T GGACTATAGC AGCGTTATGC TAACCAGTGA GGAAGAAATC AGACAACG.T GGACTATAGC AGCGTTATGC TAACCAGTGA GGAAGAAATC

    AGACAACGCT GGAA...... AACGTGCTAA TGACCAGCGA GGAGGAGATC

    AGACAACGCT GGAA...... AACGTGCTAA TGACCAGCGA GGAGGAGATC

    AGACAACGCT GGAA......AACGTGCTAA TGACCAGCGA GGAGGAGATC

    AGACAACGCT GGAA......AACGTGCTAA TGACCAGCGA GGAGGAGATC

    AGACAATG.T GGACTACAGC AGCGTGATGC TCACCAGCGA AGAAGAAATT AGACAATG.T GGACTACAGC AGCGTGATGC TCACCAGCGA AGAAGAAATT AGACAATG.T GGACTACAGC AGCGTGATGC TCACCAGCGA AGAAGAAATT CGATGGAG.T GGATTACAGC CAAGTGCTGA TTACAGATGA GGAAGAAATC CGATGGAG.T GGATTACAGC CAAGTGCTGA TTACAGATGA GGAAGAAATC CGATGGAG.T GGATTACAGC CAAGTGCTGA TTACAGATGA GGAAGAAATC CGATGGAG.T GGATTACAGC CAAGTGCTGA TTACAGATGA GGAAGAAATC AGACAACG.T GGACTATAGC AGCGTTATGC TAACCAGTGA GGAAGAAATT AGACAACG.T GGACTATAGC AGCGTTATGC TAACCAGTGA GGAAGAAATT

    AAACTACATT AGAA...... AACGTGCTCA TGACAAATGA AGAAGAAATT

    AAACTACATT AGAA...... AACGTGCTCA TGACAAATGA AGAAGAAATT

    AAACTACATT AGAA...... AACGTGCTCA TGACAAATGA AGAAGAAATT

    AAACTACATT AGAA......AACGTGCTCA TGACAAATGA AGAAGAAATT

    AAACTACATT AGAA......AACGTGCTCA TGACAAATGA AGAAGAAATT

    AAACTACATT AGAA...... AACGTGCTCA TGACAAATGA AGAAGAAATT

    TACCAATG.T GGACATTGAA TCAGTGCTTA TTACAGACGA AGAAGAAATC TACCAATG.T GGACATTGAA TCAGTGCTTA TTACAGACGA AGAAGAAATC TACCAATG.T GGACATTGAA TCAGTGCTTA TTACAGACGA AGAAGAAATC TACCAATG.T GGACATTGAA TCAGTGCTTA TTACAGACGA AGAAGAAATC

    AGACAACGCT GGAA...... AACGTGCTAA TGACCAGCGA GGAGGAGATC

    TTCAAACA.C TGCATTGGAC AATGTCATGA TTACAGACGA AGAGGAAATT AACAAATG.T GAACATTGAA AAGGTCATGA TTACAGACGA AGAGGAAATC AAGTAACG.C AGAATTAGAT AATGTAATGA TTACGGATGA AGAAGAGATT AGACAATG.C GGATTACAGC GATGTCATGC TCACCAGCGA GGAAGAAATC CGATGGAG.T CGACTACAGC CAGGTGCTGA TTACAGATGA GGAAGAAATT

    AAACTACATT GGAA......AATGTGTTAA TGACAAATGA AGAAGAAATT

    AGACAACG.T GGACTATAGC AGCGTTATGC TAACCAGTGA GGAAGAAATT
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    42 2 42 8 3951 AAAACCACCA ATCCCGTGGC AAAACCACCA ACCCAGTGGC 42 15 AAAACCACCA ACCCAGTGGC 42 5b AAAACCACCA ACCCAGTGGC 42 lb AAAACCACCA ACCCAGTGGC 42_13 AAAACCACCA ACCCAGTGGC 42 3a AAAACCACCA ACCCAGTGGC 42 4 AAAACCACCA ACCCAGTGGC 42 5a AAAACCACCA ACCCAGTGGC 42 10 AAAACCACCA ATCCCGTGGC 42 3b AAAACCACCA ATCCCGTGGC 42 11 AAAACCACCA ATCCCGTGGC 42 6b AAAACCACCA ATCCCGTGGC 43 1 AAAACTACTA ACCCAGTGGC 43 5 AAAACTACTA ACCCAGTGGC 43 12 AAAACTACTA ACCCAGTGGC 43 20 AAGGCTACCA ACCCCGTGGC 43 21 AAGGCTACCA ACCCCGTGGC 43 23 AAGGCTACCA ACCCCGTGGC 43 25 AAGGCTACCA ACCCCGTGGC 44 1 AAAACCACCA ACCCAGTGGC 44 5 AAAACCACCA ACCCAGTGGC 223 10 CGTCCTACCA ACCCGGTAGC 223 2 CGTCCTACCA ACCCGGTAGC 223 4 CGTCCTACCA ACCCGGTAGC 223 5 CGTCCTACCA ACCCGGTAGC 223 6 CGTCCTACCA ACCCGGTAGC 223 7 CGTCCTACCA ACCCGGTAGC A3 4 AGAACAACTA ATCCTGTGGC A3 5 AGAACGACTA ATCCTGTGGC A3 7 AGAACAACTA ATCCTGTGGC A3 3 AGAACAACTA ATCCTGTGGC 42JL2 AAAACCACCA ATCCCGTGGC AAV1 AAAGCCACTA ACCCTGTGGC AAV2 GGAACAACCA ATCCCGTGGC AAV3 CGTACCACCA ATCCTGTGGC AAVS AAAACCACTA ACCCTGTGGC AAV9 AAAGCCACCA ACCCTGTAGC AAV7 CGTCCTACTA ATCCTGTAGC 44 2 AAAACCACCA ACCCAGTGGC

    Fig. 1AAAB

    4000

    TACAGAAGAA TACGGTGTGG TCTCCAGCAA CACAGAACAG TACGGCGTGG TGGCCGATAA CACAGAACAG TACGGCGTGG TGGCCGATAA CACAGAACAG TACGGCGTGG TGGCCGATAA CACAGAACAG TACGGCGTGG TGGCCGATAA CACAGAACAG TACGGCGTGG TGGCCGATAA CACAGAACAG TACGGCGTGG TGGCCGATAA CACAGAACAG TACGGCGTGG, TGGCCGATAA CACAGAACAG TACGGCGTGG TGGCCGATAA TACAGAAGAA TACGGTGTGG TCTCCAGCAA TACAGAACAG TACGGTGTGG TCTCCAGCAA TACAGAAGAA TACGGTGTGG TCTCCAGCAA TACAGAAGAA TACGGTGTGG TCTCCAGCAA TACAGAGCAG TATGGTGTGG TGGCAGACAA TACAGAGCAG TATGGTGTGG TGGCAGACAA TACAGAGCAG TATGGTGTGG TGGCAGACAA CACAGAAGAA TATGGAGCAG TGGCCATCAA CACAGAAGAA TATGGAGCAG TGGCCATCAA CACAGAAGAA TATGGAGCAG TGGCCATCAA CACAGAAGAA TATGGAGCAG TGGCCATCAA CACGGAACAG TACGGCGTGG TGGCCGATAA CACAGAACAG TACGGCGTGG TGGCCGATAA TACCGAGGAA TACGGGATTG TAAGCAGCAA TACCGAGGAA TACGGGATTG TAAGCAGCAA TACCGAGGAA TACGGGATTG TAAGCAGCAA TACCGAGGAA TACGGGATTG TAAGCAGCAA TACCGAGGAA TACGGGATTG TAAGCAGCAA TACCGAGGAA TACGGGATTG TAAGCAGCAA TACAGAAGAA TACGGACAGG TTGCCACCAA TACAGAACAA TACGGACAGG TTGCCACCAA TACAGAACAA TACGGACAGG TTGCCACCAA TACAGAACAA TACGGACAGG TTGCCACCAA TACAGAAGAA TACGGTGTGG TCTCCAGCAA CACCGAAAGA TTTGGGACCG TGGCAGTCAA TACGGAGCAG TATGGTTCTG TATCTACCAA AACAGAGCAG TATGGAACTG TGGCAAATAA TACAGAGGAA TACGGTATCG TGGCAGATAA CACAGAGGAA TACGGAGCAG TGGCCATCAA CACGGAAGAA TACGGGATAG TCAGCAGCAA CACAGAACAG TACGGCGTGG TGGCCGATAA
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    42 2 4001 CCTGCAATCG 42 8 CCTGCAACAG 42 15 CCTGCAACAG 42 5b CCTGCAACAG 42 lb CCTGCAACAG 42 13 CCTGCAACAG 42 3a CCTGCAACAG 42 4 CCTGCAACAG 42 5a CCTGCAACAG 42 10 CCTGCAATCG 42 3b CCTGCAATCG 42 11 CCTGCAATCG 42 6b CCTGCAATCG 43 1 CCTGCAGCAG 43 5 CCTGCAGCAG 43 12 CCTGCAGCAG 43 20 CAACCAGGCC 43 21 CAACCAGGCC 43 23 CAACCAGGCC 43 25 CAACCAGGCC 44 1 CCTGCAACAG 44 5 CCTGCAACAG 223 10 CTTGCAGGCG 223 2 CTTGCAGGCG 223 4 CTTGCAGGCG 223 5 CTTGCAGGCG 22 3 6 CTTGCAGGCG 223_7 CTTGCAGGCG A3 4 CCATCAGAGT A3 5 CCGTCAGAGT A3 7 CCATCAGAGT A3 3 CCATCAGAGT 42_12 CCTGCAATCG AAVl TTTCCAGAGC AAV2 CCTCCAGAGA AAV3 CTTGCAGAGC AAV8 CTTGCAGCAG AAV 9 CAACCAGGCC AAV7 CTTACAAGCG 44 2 CCTGCAACAG

    Fig. 1AAAC

    TCTACGGCCG GACCCCAGAC CAAAACGCCG CTCCTATTGT CAAAACGCCG CTCCTATTGT CAAAACGCCG CTCCTATTGT CAAAACGCCG CTCCTATTGT CAAAACGCCG CTCCTATTGT CAAAACGCCG CTCCTATTGT CAAAACGCCG CTCCTATTGT CAAAACGCCG CTCCTATTGT TCTACGGCCG GACCCCAGAC TCTACGGCCG GACCCCAGAC TCTACGGCCG GACCCCAGAC TCTACGGCCG GACCCCAGAC ACCAACGGAG CTCCCATTGT ACCAACGGAG CTCCCATTGT ACCAACGGAG CTCCCATTGT GCCAATACGC AGGCGCAGAC GCCAATACGC AGGCGCAGAC GCCAATACGC AGGCGCAGAC GCCAATACGC AGGCGCAGAC CAAAACGCCG CTCCTATTGT CAAAACGCCG CTCCTATTGT GCTAGCACCG CAGCCCAGAC GCTAGCACCG CAGCCCAGAC GCTAGCACCG CAGCCCAGAC GCTAGCACCG CAGCCCAGAC GCTAGCACCG CAGCCCAGAC GCTAGCACCG CAGCCCAGAC CAGGACACCA CAGCTTCCTA CAGAACACCA CAGCTTCCTA CAGAACACCA CAGCTTCCTA CAGAACACCA CAGCTTCCTA TCTACGGCCG GACCCCAGAC AGCAGCACAG ACCCTGCGAC GGCAACAGAC AAGCAGCTAC TCAAATACAG CTCCCACGAC CAAAACACGG CTCCTCAAAT GCTAACACGC AGGCGCAAAC GCTAATACTG CAGCCCAGAC CAAAACGCCG CTCCTATTGT

    4050

    ACAGACTGTC AACAGCCAGG AGGGGCCGTC AACAGTCAAG AGGGGCCGTC AACAGTCAAG AGGGGCCGTC AACAGTCAAG AGGGGCCGTC AACAGTCAAG AGGGGCCGTC AACAGTCAAG AGGGGCCGTC AACAGTCAAG AGGGGCCGTC AACAGTCAAG AGGGGCCGTC AACAGTCAAG ACAGACTGTC AACAGCCAGG ACAGACTGTC AACAGCCAGG ACAGACTGTC AACAGCCAGG ACAGACTGTC AACAGCCAGG GGGAACTGTC AACAGCCAGG GGGAACTGTC AACAGCCAGG GGGAACTGTC AACAGCCAGG CGGACTCGTG CACAACCAGG CGGACTCGTG CACAACCAGG CGGACTCGTG CACAACCAGG CGGACTCGTG CACAACCAGG AGGGGCCGTC AACAGTCAAG AGGGGCCGTC AACAGTCAAG ACAAGTTGTT AACAACCAGG ACAAGTTGTT AACAACCAGG ACAAGTTGTT AACAACCAGG ACAAGTTGTT AACAACCAGG ACAAGTTGTT AACAACCAGG ACAAGTTGTT AACAACCAGG TGGAAGTGTG GACAGCCAGG TGGAAGTGTG GACAGCCAGG TGGAAGTGTG GACAGCCAGG TGGAAGTGTG GACAGCCAGG ACAGACTGTC AACAGCCAGG CGGAGATGTG CATGCTATGG CGCAGATGTC AACACACAAG TGGAACTGTC AATCATCAGG TGGAACTGTC AACAGCCAGG TGGACTTGTG CATAACCAGG ACAAGTTGTC AACAACCAGG AGGGGCCGTC AACAGTCAAG
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    42/

    42/

    42/5

    42/b

    42/b

    42/3

    42/a

    42/

    42/a

    42/0

    42_3b

    42/1

    42/b

    43/

    43/

    43/2

    43/0

    43/1

    43/3

    43/5

    44/

    44/

    223/0

    223/

    223/

    223/

    223/

    223/

    A3/

    A3_5

    A3/

    A3/

    42/2

    AAV1

    AAV2

    AAV3

    AAVS

    AAV9

    AAV7

    44/

    Fig. 1AAAD

    4051 4100 GGGCTCTGCC CGGCATGGTC TGGCAGAACC GGGACGTGTA CCTGCAGGGT GAGCCTTACC TGGCATGGTC TGGCAGAACC GGGACGTGTA CCTGCAGGGT GAGCCTTACC TGGCATGGTC TGGCAGAACC GGGACGTGTA CCTGCAGGGT GAGCCTTACC TGGCATGGTC TGGCAGAACC GGGACGTGTA CCTGCAGGGT GAGCCTTACC TGGCATGGTC TGGCAGAACC GGGACGTGTA CCTGCAGGGT GAGCCTTACC TGGCATGGTC TGGCAGAACC GGGACGTGTA CCTGCAGGGT GAGCCTTACC TGGCATGGTC TGGCAGAACC GGGACGTGTA CCTGCAGGGT GAGCCTTACC TGGCATGGTC TGGCAGAACC GGGACGTGTA CCTGCAGGGT GAGCCTTACC TGGCATGGCC TGGCAGAACC GGGACGTGTA CCTGCAGGGT GGGCTCTGCC CGGCATGGTC TGGCAGAACC GGGACGTGTA CCTGCAGGGT GGGCTCTGCC CGGCATGGTC TGGCAGAACC GGGACGTGTA CCTGCAGGGT GGGCTCTGCC CGGCATGGTC TGGCAGAACC GGGACGTGTA CCTGCAGGGT GGGCTCTGCC CGGCATGGTC TGGCAGAACC GGGACGTGTA CCTGCAGGGT GGGCCTTACC TGGTATGGTC TGGCAAAACC GGGACGTGTA CCTGCAGGGC GGGCCTTACC TGGTATGGTC TGGCAAAACC GGGACGTGTA CCTGCAGGGC GGGCCTTACC TGGTATGGTC TGGCAAAACC GGGACGTGTA CCTGCAGGGC GGGTGATTCC CGGCATGGTG TGGCAGAATA GAGACGTGTA CCTGCAGGGT GGGTGATTCC CGGCATGGTG TGGCAGAATA GAGACGTGTA CCTGCAGGGT GGGTGATTCC CGGCATGGTG TGGCAGAATA GAGACGTGTA CCTGCAGGGT GGGTGATTCC CGGCATGGTG TGGCAGAATA GAGACGTGTA CCTGCAGGGT GAGCCTTACC TGGCATGGTC TGGCAGAACC GGGACGTGTA CCTGCAGGGT GAGCCTTACC TGGCATGGTC TGGCAGAACC GGGACGTGTA CCTGCAGGGT GAGCCTTACC TGGCATGGTC TGGCAGAACC GGGACGTGTA CCTGCAAGGT GAGCCTTACC TGGCATGGTC TGGCAGAACC GGGACGTGTA CCTGCAAGGT GAGCCTTACC TGGCATGGTC TGGCAGAACC GGGACGTGTA CCTGCAAGGT GAGCCTTACC TGGCATGGTC TGGCAGAACC GGGACGTGTA CCTGCAAGGT GAGCCTTACC TGGCATGGTC TGGCAGAACC GGGACGTGTA CCTGCAAGGT GAGCCTTACC TGGCATGGTC TGGCAGAACC GGGACGTGTA CCTGCAAGGT GAATCTTACC TGGAATGGTG TGGCAGGACC GCGATGTCTA TCTTCAAGGT GAATCTTACC TGGAATGGTG TGGCAGGACC GCGATGTCTA TCTTCAAGGT .GAATCTTACC TGGAATGGTG TGGCAGGACC GCGATGTCTA TCTTCAAGGT GAATCTTACC TGGAATGGTG TGGCAGGACC GCGATGTCTA TCTTCAAGGT GGGCTCTGCC CGGCATGGTC TGGCAGAACC GGGACGTGTA CCTGCAGGGT GAGCATTACC TGGCATGGTG TGGCAAGATA GAGACGTGTA CCTGCAGGGT GCGTTCTTCC. AGGCATGGTC TGGCAGGACA GAGATGTGTA CCTTCAGGGG GGGCCTTACC TGGCATGGTG TGGCAAGATC GTGACGTGTA CCTTCAAGGA GGGCCTTACC CGGTATGGTC TGGCAGAACC GGGACGTGTA CCTGCAGGGT GAGTTATTCC TGGTATGGTC TGGCAGAACC GGGACGTGTA CCTGCAGGGC GAGCCTTACC TGGCATGGTC TGGCAGAACC GGGACGTGTA CCTGCAGGGT GAGCCTTACC TGGCATGGTC TGGCAGAACC GGGACGTGTA CCTGCAGGGT
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    42-2

    42-8

    42_15 42_5b 42_lb 42-13 42_3a

    42-4

    42_5a

    42-10

    42-3b

    42- 11 42_6b

    43_1

    43_5

    43_12

    43_20

    43- 21 43-23 4 3-25

    44—1

    44_5

    223_10

    223_2

    223_4

    223_5

    223-6

    223—7

    A3—4

    A3_5

    A3-7

    A3-3

    42_12

    AAV1

    AAV2

    AAV3

    AAV8

    AAV9

    AAV7

    44 2

    Fig. 1AAAE

    4101 4150 CCC.ATCTGG GCCAAAATTC CTCACACGGA CGGCAACTTT CACCCGTCTC CCT.ATCTGG GCCAAGATTC CTCACACGGA CGGCAACTTT CATCCTTCGC CCT.ATCTGG GCCAAGATTC CTCACACGGA CGGCAACTTT CATCCTTCGC CCT.ATCTGG GCCAAGATTC CTCACACGGA CGGCAACTTT CATCCTTCGC CCT.ATCTGG GCCAAGATTC CTCACACGGA CGGCAACTTT CATCCTTCGC CCT.ATCTGG GCCAAGATTC CTCACACGGA CGGCAACTTT CATCCTTCGC CCT.ATCTGG GCCAAGATTC CTCACACGGA CGGCAACTTT CATCCTTCGC CCT.ATCTGG GCCAAGATTC CTCACACGGA CGGCAACTTT CATCCTTCGC CCT.ATCTGG GCCAAGATTC CTCACACGGA CGGCAACTTT CATCCTTCGC CCC.ATCTGG GCCAAAATTC CTCACACGGA CGGCAACTTT CACCCGTCTC CCC.ATCTGG GCCAAAATTC CTCACACGGA CGGCAACTTT CACCCGTCTC CCC.ATCTGG GCCAAAATTC CTCACACGGA CGGCAACTTT CACCCGTCTC CCC.ATCTGG GCCAAAATTC CTCACACGGA CGGCAACTTT CACCCGTCTC CCC.ATCTGG GCCAAAATTC CTCACACGGA CGGCAACTTT CATCCTTCGC CCC.ATCTGG GCCAAAATTC CTCACACGGA CGGCAACTTT CATCCTTCGC CCC.ATCTGG GCCAAAATTC CTCACACGGA CGGCAACTTT CATCCTTCGC CCC.ATCTGG GCCAAAATTC CTCACACGGA CGGCAACTTT CACCCGTCTC CCC.ATCTGG GCCAAAATTC CTCACACGGA CGGCAACTTT CACCCGTCTC CCC.ATCTGG GCCAAAATTC CTCACACGGA CGGCAACTTT CACCCGTCTC CCC.ATCTGG GCCAAAATTC CTCACACGGA CGGCAACTTT CACCCGTCTC CCT.ATCTGG GCCAAGATTC CTCACACGGA CGGAAACTTT CATCCCTCGC CCT.ATCTGG GCCAAGATTC CTCACACGGA CGGAAACTTT CATCCCTCGC CCC.ATTTGG GCCAAGATTC CTCACACGGA CGGCAACTTT CACCCGTCTC CCC.ATTTGG GCCAAGATTC CTCACACGGA CGGCAACTTT CACCCGTCTC CCC.ATTTGG GCCAAGATTC CTCACACGGA CGGCAACTTT CACCCGTCTC CCC.ATTTGG GCCAAGATTC CTCACACGGA CGGCAACTTT CACCCGTCTC CCC.ATTTGG GCCAAGATTC CTCACACGGA CGGCAACTTT CACCCGTCTC CCC.ATTTGG GCCAAGATTC CTCACACGGA CGGCAACTTT CACCCGTCTC CCC.ATTTGG GCCAAAACTC CTCACACGGA CGGACACTTT CATCCTTCTC CCC.ATTTGG GCCAAAACTC CTCACACGGA CGGACACTTT CATCCTTCTC CCC.ATTTGG GCCAAAACTC CTCACACGGA CGGACACTTT CATCCTTCTC CCC.ATTTGG GCCAAAACTC CTCACACGGA CGGACACTTT CATCCTTCTC CCC.ATCTGG GCCAAAATTC CTCACACGGA CGGCAACTTT CACCCGTCTC CCC.ATTTGG GCCAAAATTC CTCACACAGA TGGACACTTT CACCCGTCTC CCC.ATCTGG GCAAAGATTC CACACACGGA CGGACATTTT CACCCCTCTC CCT.ATCTGG GCAAAGATTC CTCACACGGA TGGACACTTT CATCCTTCTC CCC.ATCTGG GCCAAGATTC CTCACACGGA CGGCAACTTC CACCCGTCTC CCCTATTTGG GCTAAAATAC CTCACACAGA TGGCAACTTT CACCCGTCTC CCC.ATCTGG GCCAAGATTC CTCACACGGA TGGCAACTTT CACCCGTCTC CCT.ATCTGG GCCAAGATTC CTCACACGGA CGGAAACTTT CATCCCTCGC
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    42 2 42 8 4151 CCCTGATGGG CGGATTTGGA CGCTGATGGG AGGCTTTGGA 42 15 CGCTGATGGG AGGCTTTGGA 42 5b CGCTGATGGG AGGCTTTGGA 42 lb CGCTGATGGG AGGCTTTGGA 42 13 CGCTGATGGG AGGCTTTGGA 42 3a CGCTGATGGG AGGCTTTGGA 42 4 CGCTGATGGG AGGCTTTGGA 42 5a CGCTGATGGG AGGCTTTGGA 42 10 CCCTGATGGG CGGATTTGGA 42 3b CCCTGATGGG CGGATTTGGA 42 11 CCCTGATGGG CGGATTTGGA 42 6b CCCTGATGGA CGGATTTGGA 43 1 CGCTGATGGG AGGCTTTGGA 43 5 CGCTGATGGG AGGCTTTGGA 43 12 CGCTGATGGG AGGCTTTGGA 43 20 CCCTGATGGG CGGCTTTGGA 43 21 CCCTGATGGG CGGCTTTGGA 43 23 CCCTGATGGG CGGCTTTGGA 43 25 CCCTGATGGG CGGCTTTGGA 44 1 CGCTGATGGG AGGCTTTGGA 44 5 CGCTGATGGG AGGCTTTGGA 223 10 CTCTAATGGG TGGCTTTGGA 223 2 CTCTAATGGG TGGCTTTGGA 223 4 CTCTAATGGG TGGCTTTGGA 223 5 CTCTAATGGG TGGCTTTGGA 223 6 CTCTAATGGG TGGCTTTGGA 223 7 CTCTAATGGG TGGCTTTGGA A3 4 CGCTCATGGG AGGCTTTGGA A3 5 CGCTGATGGG AGGCTTTGGA A3 7 CGCTCATGGG AGGCTTTGGA A3 3 CGCTCATGGG AGGCTTTGGA 42 12 CCCTGATGGG CGGATTTGGA AAVl CTCTTATGGG CGGCTTTGGA AAV2 CCCTCATGGG TGGATTCGGA AAV3 CTCTGATGGG AGGCTTTGGA AAV8 CGCTGATGGG CGGCTTTGGC AAV9 CTCTGATGGG TGGATTTGGA AAV7 CTTTGATGGG CGGCTTTGGA 44 2 CGCTGATGGG AGGCTTTGGA

    Fig. 1AAAF

    4200

    CTCAAACACC CGCCTCCTCA AATTCTCATC CTGAAACACC CGCCTCCTCA GATCCTGATT CTGAAACACC CGCCTCCTCA GATCCTGATT CTGAAACACC CGCCTCCTCA GATCCTGATT CTGAAACACC CGCCTCCTCA GATCCTGATT CTGAAACACC CGCCTCCTCA GATCCTGATT CTGAAACACC CGCCTCCTCA GATCCTGATT CTGAAACACC CGCCTCCTCA GATCCTGATT CTGAAACACC CGCCTCCTCA GATCCTGATT CTCAAACACC CGCCTCCTCA AATTCTCATC CTCAAACACC CGCCTCCTCA AATTCTCATC CTCAAACACC CGCCTCCTCA AATTCTCATC CTCAAACACC CGCCTCCTCA AATTCTCATC CTGAAACACC CGCCTCCTCA GATCCTGGTG CTGAAACACC CGCCTCCTCA GATCCTGGTG CTGAAACACC CGCCTCCTCA GATCCTGGTG CTGAAGCACC CGCCTCCTCA AATTCTCATC CTGAAGCACC CGCCTCCTCA AATTCTCATC CTGAAGCACC CGCCTCCTCA AATTCTCATC CTGAAGCACC CGCCTCCTCA AATTCTCATC CTGAAACACC CGCCTCCTCA GATCCTGATT CTGAAACACC CGCCTCCTCA GATCCTGATT CTGAAACACC CGCCTCCCCA GATCCTGATC CTGAAACACC CGCCTCCCCA GATCCTGATC CTGAAACACC CGCCTCCCCA GATCCTGATC CTGAAACACC CGCCTCCCCA GATCCTGATC CTGAAACACC CGCCTCCCCA GATCCTGATC CTGAAACACC CGCCTCCCCA GATCCTGATC CTGAAACACC CTCCTCCCCA GATCCTGATC CTGAAACACC CTCCTCCCCA GATCCTGATC CTGAAACACC CTCCTCCCCA GATCCTGATC CTGAAACACC CTCCTCCCCA GATCCTGATC CTCAAACACC CGCCTCCTCA AATTCTCATC CTCAAGAACC CGCCTCCTCA GATCCTCATC CTTAAACACC CTCCTCCACA GATTCTCATC CTGAAACATC CGCCTCCTCA AATCATGATC CTGAAACATC CTCCGCCTCA GATCCTGATC CTGAAACACC CACCTCCACA GATTCTAATT CTTAAACATC CGCCTCCTCA GATCCTGATC CTGAAACACC CGCCTCCTCA GATCCTGATT
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    42 2 4201 AAAAACACCC CGGTACCTGC 42 8 AAGAATACAC CTGTTCCCGC 42 15 AAGAATACAC CTGTTCCCGC 42 5b AAGAATACAC CTGTTCCCGC 42 lb AAGAATACAC CTGTTCCCGC 42 13 AAGAATACAC CTGTTCCCGC 42 3a AAGAATACAC CTGTTCCCGC 42 4 AAGAATACAC CTGTTCCCGC 42 5a AAGAATACAC CTGTTCCCGC 42 10 AAAAACACCC CGGTACCTGC 42 3b AAAAACACCC CGGTACCTGC 42 11 AAAAACACCC CGGTACCTGC 42 6b AAAAACACCC CGGTACCTGC 43 1 AAAAACACTC CTGTTCCTGC 43 5 AAAAACACTC CTGTTCCTGC 43 12 AAAAACACTC CTGTTCCTGC 43 20 AAGAACACAC CGGTTCCAGC 43 21 AAGAACACAC CGGTTCCAGC 43 23 AAGAACACAC CGGTTCCAGC 43 25 AAGAACACAC CGGTTCCAGC 44 1 AAGAATACAC CTGTTCCCGC 44 5 AAGAATACAC CTGTTCCCGC 223 10 AAAAACACAC CGGTACCTGC 223 2 AAAAACACGC CGGTACCTGC 223 4 AAAAACACAC CGGTACCTGC 223 5 AAAAACACAC CGGTACCTGC 223 6 AAAAACACAC CGGTACCTGC 223 7 AAAAACACAC CGGTACCTGC A3 4 AAAAACACAC CTGTGCCAGC A3 5 AAAAACACAC CTGTGCCAGC A3 7 AAAAACACAC CTGTGCCAGC A3 3 AAAAACACAC CTGTGCCAGC 42 12 A...A..... AAV1 AAAAACACGC CTGTTCCTGC AAV2 AAGAACACCC CGGTACCTGC AAV3 AAAAATACTC CGGTACCGGC AAV8 AAGAACACGC CTGTACCTGC AAV9 AAAAATACAC CAGTGCCGGC AAV7 AAGAACACTC CCGTTCCCGC 44 2 AAGAATACAC CTGTTCCCGC

    Fig. 1AAAG

    4250

    TAATCCTCCA GAGGTGTTTA CTCCTGCCAA GGATCCTCCA ACTACCTTCA GTCAAGCCAA GGATCCTCCA ACTACCTTCA GTCAAGCCAA GGATCCTCCA ACTACCTTCA GTCAAGCCAA GGATCCTCCA ACTACCTTCA GTCAAGCCAA GGATCCTCCA ACTACCTTCA GTCAAGCCAA GGATCCTCCA ACTACCTTCA GTCAAGCCAA GGATCCTCCA ACTACCTTCA GTCAAGCCAA GGATCCTCCA ACTACCTTCA GTCAAGCCAA TAATCCTCCA GAGGTGTTTA CTCCTGCCAA TAATCCTCCA GAGGTGTTTA CTCCTGCCAA TAATCCTCCA GAGGTGTTTA CTCCTGCCAA TAATCCTCCA GAGGTGTTTA CTCCTGCCAA GGATCCTCCG ACCACCTTCA GCCAGGCCAA GGATCCTCCG ACCACCTTCA GCCAGGCCAA GGATCCTCCG ACCACCTTCA GCCAGGCCAA GGACCCGCCG CTTACCTTCA ACCAGGCCAA GGACCCGCCG CTTACCTTCA ACCAGGCCAA GGACCCGCCG CTTACCTTCA ACCAGGCCAA GGACCCGCCG CTTACCTTCA ACCAGGCCAA GGATCCTCCA ACTACCTTCA GTCAAGCTAA GGATCCTCCA ACTACCTTCA GTCAAGCTAA TAATCCTCCA GAAGTGTTTA CTCCTGCCAA TAATCCTCCA GAAGTGTTTA CTCCTGCCAA TAATCCTCCA GAAGTGTTTA CTCCTGCCAA TAATCCTCCA GAAGTGTTTA CTCCTGCCAA TAATCCTCCA GAAGTGTTTA CTCCTGCCAA TAATCCTCCA GAAGTGTTTA CTCCTGCCAA GAATCCCGCG ACCACTTTCA CTCCTGGAAA GAATCCCGCG ACCACTTTCA CTCCTGGAAA GAATCCCGCG ACCACTTTCA CTCCTGGAAA GAATCCCGCG ACCACTTTCA CTCCTGGAAA

    GAATCCTCCG GCGGAGTTTT CAGCTACAAA GAATCCTTCG ACCACCTTCA GTGCGGCAAA AAATCCTCCG ACGACTTTCA GCCCGGCCAA GGATCCTCCG ACCACCTTCA ACCAGTCAAA AGATCCTCCT CTTACCTTCA ATCAAGCCAA TAATCCTCCG GAGGTGTTTA CTCCTGCCAA GGATCCTCCA ACTACCTTCA GTCAAGCTAA
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    42_2

    42_8

    42_15

    42_5b

    42_lb

    4 2_13

    42_3a

    42_4

    42_5a

    42_10

    42_3b

    42_11

    42_6b

    43_1

    43_5 4 3_12 43_20 43__21 43_23 43_25

    44_1

    44_5 223_10 223_2 223_4 223_5 223Jo 223J7

    A3_4

    A3_5

    A3_7

    A3_3

    42_12

    AAV1

    AAV2

    AAV3

    AAV8

    AAV9

    AAV7

    44_2

    Fig. 1AAAH

    4251 4300 GTTTGCCTCA TTTATCACGC AGTACAGCAC CGGCCA.GGT CAGCGTGGAG GCTGGCGTCG TTCATCACGC AGTACAGCAC CGGACA.GGT CAGCGTGGAA GCTGGCGTCG TTCATCACGC AGTACAGCAC CGGACA.GGT CAGCGTGGAA GCTGGCGTCG TTCATCACGC AGTACAGCAC CGGACA.GGT CAGCGTGGAA GCTGGCGTCG TTCATCACGC AGTACAGCAC CGGACA.GGT CAGCGTGGAA GCTGGCGTCG TTCATCACGC AGTACAGCAC CGGACA.GGT CAGCGTGGAA GCTGGCGTCG TTCATCACGC AGTACAGCAC CGGACA.GGT CAGCGTGGAA GCCGGCGTCG TTCATCACGC AGTACAGCAC CGGACA.GGT CAGCGTGGAA GCTGGCGTCG TTCATCACGC AGTACAGCAC CGGACA.GGT CAGCGTGGAA GTTTGCCTCA TTTATCACGC AGTACAGCAC CGGCCA.GGT CAGCGTGGAG GTTTGCCTCA TTTATCACGC AGTACAGCAC CGGCCA.GGT CAGCGTGGAG GTTTGCCTCA TTTATCACGC AGTACAGCAC CGGCCA.GGT CAGCGTGGAG GTTTGCCTCA TTTATCACGC AGTACAGCAC CGGCCA.GGT CAGCGTGGAG GCTGGCTTCT TTTATCACGC AGTACAGCAC CGGACA.GGT CAGCGTGGAA GCTGGCTTCT TTTATCACGC AGTACAGCAC CGGACA.GGT CAGCGTGGAA GCTGGCTTCT TTTATCACGC AGTACAGCAC CGGACA.GGT CAGCGTGGAA GCTGAACTCT TTCATCACGC AGTACAGCAC CGGACA.GGT CAGCGTGGAA GCTGAACTCT TTCATCACGC AGTACAGCAC CGGACA.GGT CAGCGTGGAA GCTGAACTCT TTCATCACGC AGTACAGCAC CGGACA.GGT CAGCGTGGAA GCTGAACTCT TTCATCACGC AGTACAGCAC CGGACA.GGT CAGCGTGGAA GCTGGCGTCG TTCATCACGC AGTACAGCAC CGGACA.GGT CAGCGTGGAA GCTGGCGTCG TTCATCACGC AGTACAGCAC CGGACA.GGT CAGCGTGGAA GTTTGCTTCC TTCATCACGC AGTACAGCAC CGGGCA.AGT CAGCGTTGAG GTTTGCTTCC TTCATCACGC AGTACAGCAC CGGGCA.AGT CAGCGTTGAG GTTTGCTTCC TTCATCACGC AGTACAGCAC CGGGCA.AGT CAGCGTTGAG GTTTGCTTCC TTCATCACGC AGTACAGCAC CGGGCA.AGT CAGCGTTGAG GCTTGCTTCC TTCATCACGC AGTACAGCAC CGGGCA.AGT CAGCGTTGAG GATTGCTTCC TTCATCACGC AGTACAGCAC CGGGCA.AGT CAGCGTTGAG GTTTGCTTCG TTCATTACCC AGTATTCCAC CGGACA.GGT CAGCGTGGAA GTTTGCTTCG TTCATTACCC AGTATTCCAC CGGACA.GGT CAGCGTGGAA GTTTGCTTCG TTCATTACCC AGTATTCCAC CGGACA.GGT CAGCGTGGAA GTTTGCTTCG TTCATTACCC AGTATTCCAC CGGACA.GGT CAGCGTGGAA

    GTTTGCTTCA TTCATCACCC AATACTCCAC AGGACA.AGT GAGTGTGGAA GTTTGCTTCC TTCATCACAC AGTACTCCAC GGGACACGGT CAGCGTGGAG GTTTGCTTCA TTTATCACTC AGTACTCCAC TGGACA.GGT CAGCGTGGAA GCTGAACTCT TTCATCACGC AATACAGCAC CGGACA.GGT CAGCGTGGAA GCTGAACTCT TTCATCACGC AGTACAGCAC GGGACA.AGT CAGCGTGGAA GTTTGCTTCG TTCATCACAC AGTACAGCAC CGGACA.AGT CAGCGTGGAA GCTGGCGTCG TTCATCACGC AGTACAGCAC CGGACA.GGT CAGCGTGGAA
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    42_2

    42_8

    42_15 42_5b 42_lb 4 2_13 42_3a 42_4 42_5a 42_10 42_3b 42_11 42_6b 43_1 43_5 43JL2 43_20 43_21 43_23 43_25 44_1 44_5

    223_10 223_2 223_4 223_5 223_6 223_7 A3_4 A3_5 A3_7 A3_3 42JL2 AAV1 AAV2 AAV3 AAV8 AAV9 AAV7 44 2

    Fig. 1AAAI

    4301 4350 ATCGAGTGGG AACTGCAGAA AGAAAACAGC AAACGCTGGA ATCCAGAGAT ATTGAATGGG AGCTGCAGAA AGAGAACAGC AAGCGCTGGA ACCCAGAGAT ATTGAATGGG AGCTGCAGAA AGAGAACAGC AAGCGCTGGA ACCCAGAGAT ATTGAATGGG AGCTGCAGAA AGAGAACAGC AAGCGCTGGA ACCCAGAGAT ATTGAATGGG AGCTGCAGAA AGAGAACAGC AAGCGCTGGA ACCCAGAGAT ATTGAATGGG AGCTGCAGAA AGAGAACAGC AAGCGCTGGA ACCCAGAGAT ATTGAATGGG AGCTGCAGAA AGAGAACAGC AAGCGCTGGA ACCCAGAGAT ATTGAATGGG AGCTGCAGAA AGAGAACAGC AAGCGCTGGA ACCCAGAGAT ATTGAATGGG AGCTGCAGAA AGAGAACAGC AAGCGCTGGA ACCCAGAGAT ATCGAGTGGG AACTGCAGAA AGAAAACAGC AAACGCTGGA ATCCAGAGAT ATCGAGTGGG AACTGCAGAA AGAAAACAGC AAACGCTGGA ATCCAGAGAT ATCGAGTGGG AACTGCAGAA AGAGAACAGC AAACGCTGGA ATCCAGAGAT ATCGAGTGGG AACTGCAGAA AGAAAACAGC AAACGCTGGA ATCCAGAGAT ATCGAATGGG AGCTGCAGAA AGAAAACAGC AAGCGCTGGA ACCCAGAGAT ATCGAATGGG AGCTGCAGAA AGAAAACAGC AAGCGCTGGA ACCCAGAGAT ATCGAATGGG AGCTGCAGAA AGAAAACAGC AAGCGCTGGA ACCCAGAGAT ATCGAGTGGG AGCTGCAGAA AGAAAACAGC AAACGCTGGA ATCCAGAGAT ATCGAGTGGG AGCTGCAGAA AGAAAACAGC AAACGCTGGA ATCCAGAGAT ATCGAGTGGG AGCTGCAGAA AGAAAACAGC AAACGCTGGA ATCCAGAGAT ATCGAGTGGG AGCTGCAGAA AGAAAACAGC AAACGCTGGA ATCCAGAGAT ATTGAATGGG AGCTGCAGAA AGAAAACAGC AAACGCTGGA ACCCAGAGAT ATTGAATGGG AGCTGCAGAA AGAAAACAGC AAACGCTGGA ACCCAGAGAT ATCGAGTGGG AGCTGCAGAA AGAGAACAGC AAGCGCTGGA ACCCAGAGAT ATCGAGTGGG AGCTGCAGAA AGAGAACAGC AAGCGCTGGA ACCCAGAGAT ATCGAATGGG AGCTGCAGAA AGAGAACAGC AAGCGCTGGA ACCCAGAGAT ATCGAATGGG AGCTGCAGAA AGAGAACAGC AAGCGCTGGA ACCCAGAGAT ATCGAGTGGG AGCTGCAGAA AGAGAACAGC AAGCGCTGGA ACCCAGAGAT ATCGAGTGGG AGCTGCAGAA AGAGAACAGC AAGCGCTGGA ACCCAGAGAT ATAGAGTGGG AGCTGCAGAA AGAAAACAGC AAACGCTGGA ACCCAGAAAT ATAGAGTGGG AGCTGCAGAA AGAAAACAGC AAACGCTGGA ACCCGGAAAT ATAGAGTGGG AGCTGCAGAA AGAAAACAGC AAACGCTGGA ACCCAGAAAT ATAGAGTGGG AGCTGCAGAA AGAAAACAGC AAACGCTGGA ACCCAGAAAT

    ATTGAATGGG AGCTGCAGAA AGAAAACAGC AAGCGCTGGA ATCCCGAAGT ATCGAGTGGG AGCTGCAGAA GGAAAACAGC AAACGCTGGA ATCCCGAAAT ATTGAGTGGG AGCTACAGAA AGAAAACAGC AAACGTTGGA ATCCAGAGAT ATTGAATGGG AGCTGCAGAA GGAAAACAGC AAGCGCTGGA ACCCCGAGAT ATCGAGTGGG AGCTGCAGAA AGAAAACAGC AAGCGCTGGA ATCCAGAGAT ATCGAGTGGG AGCTGCAGAA GGAAAACAGC AAGCGCTGGA ACCCGGAGAT ATTGAATGGG AGCTGCAGAA AGAAAACAGC AAACGCTGGA ACCCAGAGAT
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    42_2

    42_8

    42_15

    42_5b

    42_lb

    42_13

    42_3a

    42_4

    42_5a

    42_10

    42_3b

    42_11

    42_6b

    43_1

    43_5

    43_12

    43_20

    43_21

    43_23

    43_25

    44_1

    44_5

    223_10

    223_2

    223_4

    223_5

    223_6

    223_7

    A3_4

    A3_5

    A3_7

    A3_3 42_12 AAV1 AAV2 AAV 3 AAV8 AAV 9 AAV7

    44 2

    Fig. 1AAAJ

    4351 4400 TCAGTACACC TCAAATTATG CCAAGTCTAA TAAT.GTGGA ATTTGCTGTC TCAGTATACT TCCAACTACT ACAAATCTAC AAAT.GTGGA CTTTGCTGTC TCAGTATACT TCCAACTACT ACAAATCTAC AAAT.GTGGA CTTTGCTGTC TCAGTATACT TCCAACTACT ACAAATCTAC AAAT.GTGGA-CTTTGCTGTC TCAGTATACT TCCAACTACT ACAAATCTAC AAAT.GTGGA CTTTGCTGTC TCAGTATACT TCCAACTACT ACAAATCTAC AAAT.GTGGA CTTTGCTGTC TCAGTATACT TCCAACTACT ACAAATCTAC AAAT.GTGGA CTTTGCTGTC TCAGTATACT TCCAACTACT ACAAATCTAC AAAT.GTGGA CTTTGCTGTC TCAGTATACT TCCAACTACT ACAAATCTAC AAAT.GTGGA CTTTGCTGTC TCAGTACACC TCAAATTATG CCAAGTCTAA TAAT.GTGGA ATTTGCTGTC TCAGTACACC TCAAATTATG CCAAGTCTAA TAAT.GTGGA ATTTGCTGTC TCAGTACACC TCAAATTATG CCAAGTCTAA TAAT.GTGGA ATTTGCTGTC TCAGTACACC TCAAATTATG CCAAGTCTAA TAAT.GTGGA ATTTGCTGTC TCAGTATACT TCCAACTACT ACAAATCTAC AAAT.GTGGA CTTTGCTGTC TCAGTATACT TCCAACTACT ACAAATCTAC AAAT.GTGGA CTTTGCTGTC TCAGTATACT TCCAACTACT ACAAATCTAC AAAT.GTGGA CTTTGCTGTC TCAATACACT TCCAACTACT ACAAATCTAC AAAT.GTGGA CTTTGCTGTC TCAATACACT TCCAACTACT ACAAATCTAC AAAT.GTGGA CTTTGCTGTC TCAATACACT TCCAACTACT ACAAATCTAC AAAT.GTGGA CTTTGCTGTC TCAATACACT TCCAACTACT ACAAATCTAC AAAT.GTGGA CTTTGCTGTC TCAATACACT TCCAACTACT ACAAATCTAC AAAT.GTGGA CTTCGCTGTT TCAATACACT TCCAACTACT ACAAATCTAC AAAT.GTGGA CTTTGCTGTT TCAGTACACC TCCAACTTTG ACAAACAGAC TGGA.GTGGA CTTTGCTGTT TCAGTACACC TCCAACTTTG ACAAACAGAC TGGA.GTGGA CTTTGCTGTT TCAGTACACC TCCAACTTTG ACAAACAGAC TGGA.GTGGA CTTTGCTGTT TCAGTACACC TCCAACTTTG ACAAACAGAC TGGA.GTGGA CTTTGCTGTT TCAGTACACC TCCAACTTTG ACAAACAGAC TGGA.GTGGA CTTTGCTGTT TCAGTACACC TCCAACTTTG ACAAACAGAC TGGA.GTGGA CTTTGCTGTT TCAGTACACC TCCAACTACA ACAAGTCGGT GAAT.GTGGA GTTTACCGTG TCAGTACACC TCCAACTACA ACAAGTCGGT GAAT.GTGGA GTTTACCGTG TCAGTACACC TCCAACTACA ACAAGTCGGT GAAT.GTGGA GTTTACCGTG TCAGTACACC TCCAACTACA ACAAGTCGGT GAAT.GTGGA GTTTACCGTG ...GTATACT TCCAACTACT ACAAATCTAC AAAT.GTGGA CTTTGCTGTC GCAGTACACA TCCAATTATG CAAAATCTGC CAAC.GTTGA TTTTACTGTG TCAGTACACT TCCAACTACA ACAAGTCTGT TAATCGTGGA CTT.ACCGTG TCAGTACACT TCCAACTACA ACAAGTCTGT TAAT.GTGGA CTTTACTGTA CCAGTACACC TCCAACTACT ACAAATCTAC AAGT.GTGGA CTTTGCTGTT CCAGTATACT TCAAACTACT ACAAATCTAC AAAT.GTGGA CTTTGCTGTC TCAGTACACC TCCAACTTTG AAAAGCAGAC TGGT.GTGGA CTTTGCCGTT TCAATACACT TCCAACTACT ACAAATCTAC AAAT.GTGGA CTTTGCTGTT
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    Fig. 1AAAK

    42_2

    42_8

    42_15

    42_5b

    42_lb

    42_13

    42_3a

    42_4 42_5a 42JL0 42_3b 4 2_11 42_6b 43_1 43_5 43_12 43_20 43_21 43_23 43_25 44_1 44_5 223_10 223_2

    223_4

    223_5

    223_6

    223_7

    A3_4

    A3_5

    A3_7

    A3_3

    42_12

    AAVl

    AAV2

    AAV3

    AAV8

    AAV 9

    AAV7

    44_2

    4401 4450

    AACAACGAAG GGGTTTATAC TGAGCCTCGC CCCATTGGCA CCCGTTACCT AATACTGAGG GTACTTATTC AGAGCCTCGC CCCATTGGCA CCCGTTACCT AATACTGAGG GTACTTATTC AGAGCCTCGC CCCATTGGCA CCCGTTACCT AATACTGAGG GTACTTATTC AGAGCCTCGC CCCATTGGCA CCCGTTACCT AATACTGAGG GTACTTATTC AGAGCCTCGC CCCATTGGCA CCCGTTACCT AATACTGAGG GTACTTATTC AGAGCCTCGC CCCATTGGCA CCCGTTACCT AATACTGAGG GTACTTATTC AGAGCCTCGC CCCATTGGCA CCCGTTACCT AATACTGAGG GTACTTATTC AGAGCCTCGC CCCATTGGCA CCCGTTACCT AATACTGAGG GTACTTATTC AGAGCCTCGC CCCATTGGCA CCCGTTACCT AACAACGAAG GGGTTTATAC TGAGCCTCGC CCCATTGGCA CCCGTTACCT AACAACGAAG GGGTTTATAC TGAGCCTCGC CCCATTGGCA CCCGTTACCT AACAACGAAG GGGTTTATAC TGAGCCTCGC CCCATTGGCA CCCGTTACCT AACAACGAAG GGGTTTATAC TGAGCCTCGC CCCATTGGCA CCCGTTACCT AATACTGAGG GTACTTATTC AGAGCCTCGC CCCATTGGCA CTCGTTATCT AATACCGAGG GTACTTATTC AGAGCCTCGC CCCATTGGCA CTCGTTATCT AATACTGAGG GTACTTATTC AGAGCCTCGC CCCATTGGCA CTCGTTATCT AACACGGAAG GAGTTTATAG CGAGCCTCGC CCCATTGGCA CCCGTTACCT AACACGGAAG GAGTTTATAG CGAGCCTCGC CCCATTGGCA CCCGTTACCT AACACGGAAG GAGTTTATAG CGAGCCTCGC CCCATTGGCA CCCGTTACCT AACACGGAGG GGGTTTATAG CGAGCCTCGC CCCATTGGCA CCCGTTACCT AACACAGATG GCACTTATTC TGAGCCTCGC CCCATTGGCA CCCGTTACCT AACACAGATG GCACTTATTC TGAGCCTCGC CCCATTGGCA CCCGTTACCT

    GACAGCCAGG GTGTTTACTC TGAGCCT.......................

    GACAGCCAGG GTGTTTACTC TGAGCCT.......................

    GACAGCCAGG GTGTTTACTC TGAGCCT.......................

    GACAGCCAGG GTGTTTACTC TGAGCCT.......................

    GACAGCCAGG GTGTTTACTC TGAGCCT... ....................

    GACAGCCAGG GTGTTTACTC TGAGCCT.......................

    GACGCAAACG GTGTTTATTC TGAACCCCGC CCTATTGGCA CTCGTTACCT GACGCAAACG GTGTTTATTC TGAACCCCGC CCTATTGGCA CTCGTTACCT GACGCAAACG GTGTTTATTC TGAACCCCGC CCTATTGGCA CTCGTTACCT GACGCAAACG GTGTTTATTC TGAACCCCGC CCTATTGGCA CTCGTTACCT

    AATACTGAGG GTACTTATTC AGAGCCTCGC CCCATTGGCA CCCGTTACCT GACAACAATG GACTTTATAC TGAGCCTCGC CCCATTGGCA CCCGTTACCT GATACTAATG GCGTGTATTC AGAGCCTCGC CCCATTGGCA CCAGATACCT GACACTAATG GTGTTTATAG TGAACCTCGC CCTATTGGAA CCCGGTATCT AATACAGAAG GCGTGTACTC TGAACCCCGC CCCATTGGCA CCCGTTACCT AATACCGAAG GTGTTTACTC TGAGCCTCGC CCCATTGGTA CTCGTTACCT GACAGCCAGG GTGTTTACTC TGAGCCTCGC CCTATTGGCA CTCGTTACCT AACACAGATG GCACTTATTC TGAGCCTCGC CCCATCGGCA CCCGTTACCT
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    Fig. 1AAAL

    4451

    VP1-3 stop

    4500

    42_2 42_8 42_15 42_5b 42_lb 4 2_1 3 42_3a 42_4 42_5a 42_10 42_3b 42_11 42_6b 43_1 43_5 43_12 43_20 43_21 43_23 43_25 44__1 44_5 223_10 223_2 223_4 223_5 223_6 223_7 A3_4 A3_5 A3_7 A3_3 42_12 AAVl AAV2 AAV3 AAV8 AAVS AAV7 44_2

    42_2 42_8 42_15 42_5b 42_lb 42_13 42_3a 42_4 42_5a 42_10 42_3b 42_11 42_6b 43_1 43_5 43_12 43_20 43_21 43_23 43_25 44__1 44_5 223_10 223_2 223_4 223_5 223_6 223_7 A3_4 A3_5 A3_7 A3_3 42_12 AAVl AAV2 AAV3 AAV8 AAVS AAV7 44_2

    Poly A signal

    CACCCGTAAC CTGTAATTGC CTGTTAATCA ATAAACCGGT TAATTCGTTT CACCCGTAAC CTGTAATTGC CTGTTAATCA ATAAACCGGC TAATTCGTTT CACCCGTAAC CTGTAATTGC CTGTTAATCA ATAAACCGGT TAATTCGTTT CACCCGTAAC CTGTAATTGC CTGTTAATCA ATAAACCGGT TAATTCGTTT CACCCGTAAC CTGTAATTGC CTGTTAATCA ATAAACCGGT TGATTCGTTT CACCCGTAGC CTGTAATTGC CTGTTAATCA ATAAACCGGT TGATTCGTTT CACCCGTAAC CTGTAATTGC CTGTTAATCA ATAAACCGGT TAATTCGTTT CACCCGTAAC CTGTAATTGC CTGTTAATCA ATAAACCGGT TAATTCGTTT CACCCGTAAC CTGTAATTGC CTGTTAATCA ATAAACCGGT TAATTCGTTT CACCCGTAAC CTGTAATTGC CTGTTAATCA ATAAACCGGT TAATTCGTTT CACCCGTAAC CTGTAATTGC CTGTTAATCA ATAAACCGGT TAATTCGTTT CACCCGTAAC CTGTAATTAC TTGTTAATCA ATAAACCGGT TGATTCGTTT CACCCGTAAC CTGTAATTGC CTGTTAATCA ATAAACCGGT TAATTCGTTT

    CACCCGTAAT CTGTAATTGC TTGTTAATCA ATAAACCGGT ..........

    CACCCGTAAT CTGTAATTGC TTGTTAATCA ATAAACCGGT TAATTCGTTT CACCCGTAAT CTGTAATTGC TTGTTAATCA ATAAACCGGT TAATTCGTTT CACCCGCAAC CTGTAATTAC ATGTTAATCA ATAAACCGGT TAATTCGTTT CACCCGCAAC CTGTAATTAC ATGTTAATCA ATAAACCGGT TAATTCGTTT CACCCGCAAC CTGTAATTAC ATGTTAATCA ATAAACCGGT TAATTCGTTT CACCCGCAAC CTGTAATTAC ATGTTAATCA ATAAACCGGT TAATTCGTTT CACCCGTAAT CTGTAATTGC TCGTTAATCA ATAAACCGGT TGATTCGTTT CACCCGTAAT CTGTAATTGC TTGTTAATCA ATAAACCGGT TGATTCGTTT

    TACCCGGAAC TTGTAATTTC CTGTTAATGA ATAAACCGAT TTATGCGTTT TACCCGGAAC TTGTAATTTC CTGTTAATGA ATAAACCGAT TTATGCGTTT TACCCGGAAC TTGTAATTTC CTGTTAATGA ATAAACCGAT TTATGCGTTT TACCCGGAAC TTGTAATTTC CTGTTAATGA ATAAGCCGAT TTATGCGTTT CACCCGTAAC CTGTAATTGC CTGTTAATCA ATAAACCGGT TAATTCGTTT TACCCGTCCC CTGTAATTAC GTGTTAATCA ATAAACCGGT TGATTCGTTT GACTCGTAAT CTGTAATTGC TTGTTAATCA ATAAACCGTT TAATTCGTTT CACACGAAAC TTGTGAATCC TGGTTAATCA ATAAACCGTT TAATTCGTTT CACCCGTAAT CTGTAATTGC CTGTTAATCA ATAAACCGGT TGATTCGTTT CACCCGTAAT TTGTAATTGC CTGTTAATCA ATAAACCGGT TAATTCGTTT CACCCGTAAT CTGTAATTGC ATGTTAATCA ATAAACCGGT TGATTCGTTT CACCCGTAAT CTGTAATTGC TTGTTAATCA ATAAACCGGT TGATTCGTTT ypl-3 stop

    PolyA signal
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    42_2

    42—8

    42_15 42—5b 42_lb 42_13 42_3 a

    42_4

    42_5 a 42_10 42_3b 42_11 42_6b

    43_1

    43_5

    43_12 43_20 43_21 43_23 43_25

    44-1

    44_5

    223-10

    223_2

    223_4

    223_5

    223-6

    223_7

    A3-4

    A3_5

    A3_7

    A3_3 42-12 AAVl AAV2 AAV 3 AAV8 AAV9 AAV7

    44 2

    Fig. 1AAAM

    4501 4550

    CAGTTGAACT TTGGTCTC.T GCGAAGGGCG AATTC...............

    CAGTTGAACT TTGGTCTC.T GCGAAGGGCG AATTC...............

    CAGTTGAACT TTGGTCTC.T GCGAAGGGCG AATTC...............

    CAGTTGAACT TTGGTCTC.T GCGAAGGGCG AATTCGTTTA AACCTGCAGG

    CAGTTGAACT TTGGTCTC.....AAGGGCG AATTC...............

    CAGTTGAACT TTGGTCTC.T GCGAAGGGCG AATTC...............

    CAGTTGAACT TTGGTCTC.T GCGAAGGGCG AATTC............ ...

    CAGTTGAACT TTGGTCTC.T GCGAAGGGCG AATTC...............

    CAGTTGAACT TTGGTCTC.T GCGAAGGGCG AATTC...............

    CAGTTGAACT TTGGTC.......AAGGGCG AATTC. . .............

    CAGTTGAACT TTGGTCTC.T GCGAAGGGCG AATTC...............

    CAGTTGAACT TTGGTCTC.T GCGAAGGGCG AATTC...............

    CAGTTGAACT TTGGTCTC.T GCGAAGGGCG AATTC...............

    CAGTTGAACT

    CAGTTGAACT

    CAGTTGAACT

    CAGTTGAACT

    CAGTTGAACT

    CAGTTGAACT

    CAGTTGAACT

    CAGTTGAACT

    TTGGTCTC.T TTGGTCTC.T TTGGTCTC.T TTGGTCTC.T TTGGTCTC.T TTGGTCTC.T TTGGTCTC.T TTGGTCTC.T

    CAGTTGAACT

    CAGTTGAACT

    CAGTTGAACT

    CAGTTGAACT

    CAGTTGAACT

    CAGTTGAACT

    CAGTTGAACT

    CAGTTGAACT

    CAGTTGAACT

    CAGTTGAACT

    CAGTTGAACT

    CAGTTGAACT

    TTGGTCTC.T TTGGTCTC.T TTGGTCTC.T TTGGTCTC.T TTGGTCTC.T TTGGTCTCCT TTGGTCTC.T TTGGCTCT.T TTGGTCTC.T TTGGTCTC.T TTGGTCTCCT TTGGTCTC.T

    GCGAAGGGCG AATTCGTTTA AACCTGCAGG

    GCGAAGGGCG AATTC...............

    GCGAAGGGCG AATTC...............

    GCGAAGGGCG AATTC...............

    GCGAAGGGCG AATTC..... . .........

    GCGAAGGGCG AATTC...............

    GCGAAGGGCG AATTC...............

    GCGAAGGGCG AATTC...............

    GCGAAGGGCG AATTCGC.GG CCGCTA....

    GCGAAGGGCG AATTC...............

    GCGAAGGGCG AATTC...............

    GCGAAGGGCG AATTCGT.TT AAACCT....

    GCGAAGGGCG AATTC............. .

    GTCCTTCTTA TCTTATCGGT TACCATGGTT GCGTATTTCT ..TTCTT.AT CTAGTTTCCA GTGCACTTCT TTATCTTTAT CTTGTTTCCA

    GCG...........................

    GCG...........................

    GTGCTTCTTA TCTTATCGGT TTCCATAGCA GCGAAGGGCG AATTC...............
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    Fig. 1AAAN

    4551 4600

    42_2 ..................................................

    42 8 ..................................................

    42_15 ..................................................

    42_5b ACTAGTCCCT TTAGTGAGGG TTAATTCTGA G...................

    42_lb ..................................................

    4213 ..................................................

    42_3a ..................................................

    42_4 ..................................................

    42_5a ..................................................

    4210 ..................................................

    42— 3b ..................................................

    4211 ..................................................

    42_6b ..................................................

    4 31 ..................................................

    43— 5 AC................................................

    43_12 ..................................................

    43_20 ..................................................

    43 21 ..................................................

    43- 23 ..................................................

    4325 ..................................................

    441 .................................-................

    44_5 .............................. - ................223_10 ..................................................

    223_2 ..................................................

    223_4 .............................. ....................

    223—5 ..................................................

    223 6 ..................................................

    223—7 ..................................................

    A3-4 ..................................................

    A3^5 ..................................................

    A3_7 ..................................................

    A3_3 ..................................................

    42—12 ..................................................

    AAVl ATAGCTTACA CATTAACTGC TTGGTTGCGC T...................

    AAV2 TGGCTAC. . . GTAGATAAGT AGC....... ...................

    AAV3 TGGCTACTGC GTAGATAAGC AGCGGCCTGC GGCGCTTGCG CTTCGCGGTT

    AAV8 ..................................................

    AAV9 ..................................................

    AAV7 ACTGGTTACA CATTAACTGC TTGGGTGCGC TTCACGATAA GAACACTGAC

    44— 2 ..................................................
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    Fig. 1AAAO

    4601 4650

    4 2 2 ..................................................

    42 8 ..................................................

    4215 ..................................................

    42_5b ....CTTGGC GTAATCATGG GTCATAG.......................

    42—lb ..................................................

    42_13 ..................................................

    42_3a ..................................................

    424 ..................................................

    42_5a ..................................................

    42—10 ..................................................

    42_3b ..................................................

    4211 ..................................................

    42— 6b ..................................................

    431 ..................................................

    43_5 ..................................................

    43_12 ..................................................

    43— 20 ..................................................

    43 21 ..................................................

    43_23 ..................................................

    43_25 ........................................ ..........

    441 ..................................................

    44—5 ..................................................

    22310 ..................................................

    223 2 ..................................................

    2233 ..................................................

    223—5 ..................................................

    223-6 ..................................................

    22 3 7 ..................................................

    A3_4 ..................................................

    A3-5 ..................................................

    A3—7 ..................................................

    A3_3 ..................................................

    42-12 ..................................................

    AAV1 ....TCGCGA TAAAAGACTT ACGTCATCGG GTTACCCCTA GTGATGGAGT AAV2 ....ATGGCG GGTTAATCAT TAACTACAAG GA.ACCCCTA GTGATGGAGT AAV3 TACAACTGCT GGTTAATATT TAACTCTCGC CATACCTCTA GTGATGGAGT

    AAV8 ..................................................

    AAV9 ..................................................

    AAV7 ......................GTCACCGC GGTACCCCTA GTGATGGAGT

    4 4 2 ..................................................
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    Fig. 1AAAP

    4651 4700

    42 2 ..................................................

    42 8 ..................................................

    4215 ..................................................

    42/b ..................................................

    42/b ..................................................

    42/3 ..................................................

    42/a ..................................................

    42/ ..................................................

    42/a ..................................................

    42/0 ..................................................

    42/b ..................................................

    4211 ..................................................

    42/b ..................................................

    4 31 ..................................................

    43/ ..................................................

    4312 ..................................................

    43/0 ..................................................

    43/1 ..................................................

    43/3 ..................................................

    43/5 ........................................ ..........

    44/ ...................................................

    44/ ..................................................

    223/0 ..................................................

    223/ .........................-........................

    223/ ..............................................* · · ·

    223/ ..................................................

    223 6 .......... ........................................

    22 3 7 ..................................................

    A3_4 ..................................................

    A3/ ..................................................

    A3/ ..................................................

    A3_3 ..................................................

    42 12 ..................................................

    AAV1 TGCCCACTCC CTCTCTGCGC GCTCGCTCGC TCGGTGGGGC CTGCGGACCA AAV2 TGGCCACTCC CTCTCTGCGC GCTCGCTCGC TCACTGAGGC CGGGCGACCA AAV3 TGGCCACTCC CTCTATGCGC ACTCGCTCGC TCGGTGGGGC CTGGCGACCA AAV8 ..................................................

    ..................................................

    AAV7 TGGCCACTCC CTCTATGCGC GCTCGCTCGC TCGGTGGGGC CTGCGGACCA 44/ ..................................................
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    Fig. 1AAAQ

    4701 4750

    4 2 2 ..................................................

    428 ..................................................

    4215 -.................................................

    42— 5b ..................................................

    42_lb ..................................................

    42_13 ........................................ ..........

    42_3a ..................................................

    42_4 ..................................................

    42 5a ..................................................

    42~10 ..................................................

    42_3b .................................₍................

    42_11 ..................................................

    42_6b ..................................................

    4 31 ..................................................

    43_5 ................................................

    43_12 ..................................................

    43_20 ..................................................

    43_21 ..................................................

    43— 23 ..................................................

    43-25 ..................................................

    44_1 ..................................................

    44 5 ..................................................

    22310 ..................................................

    223_2 ..................................................

    223—4 ..................................................

    223—5 ..................................................

    223—6 ..................................................

    223—7 ..................................................

    A3_4 ..................................................

    A3_5 ..................................................

    A3—7 ..................................................

    A3_3 ..................................................

    42_12 ...........-......................................

    AAV1 AAGGTCCGCA GACGGCAGAG CTCTGCTCTG CCGGCCCCAC CGAGCGAGCG

    AAV2 AAGGTCGCCC GACGCCCGGG CTTTGCCCGG GCGGCCTCAG TGAGCGAGCG

    AAV3 AAGGTCGCCA GACGGACGTG CTTTGCACGT CCGGCCCCAC CGAGCGAGCG

    AAV8 ..................................................

    AAV9 ..................................................

    AAV7 AAGGTCCGCA GACGGCAGAG CTCTGCTCTG CCGGCCCCAC CGAGCGAGCG

    44 2 ..................................................
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    Fig. 1AAAR

    4751 4774

    4 2 2 ........................

    42 8 ........................

    42-15 ........................

    42_5b ........................

    42_lb ........................

    4213 ........................

    42_3a ........................

    424 ........................

    42_5a ........................

    42_10 ........................

    42—3b ........................

    42- 11 ........................

    42_6b . .......................

    43— 1 ........................

    43_5 ........................

    43_12 ........................

    43_20 ........................

    43- 21 . ................... . . 4323 ........................

    43_25 .................... ....

    44— 1 ........................

    44_5 ........................

    223-10 .......... ..............

    223_2 ........................

    223—4 ........................

    223—5 ........................

    223_6 ........................

    223_7 ........................

    A3—4 ........................

    A3—5 ........................

    A3_7 .......... ..............

    A3_ 3 ........................

    42—12 ........................

    AAVl AGCGCGCAGA GAGGGAGTGG GCAA AAV2 AGCGCGCAGA GAGGGAGTGG CCAA AAV3 AGTGCGCATA GAGGGAGTGG CCAA

    AAV8 ........................

    AAV9 ........................

    AAV7 AGCGCGCATA GAGGGAGTGG CCAA 44_2 ........................
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    Fig. 2A
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    Fig. 2B
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    Pig. 2C

    OBri AN

    Η Π) d dpi H U dft ^hS^h s

    Pl Pl |Pl Pl Pl <· V « P NN ΠΜΝΝΑ'ί Vi Μ CM WWW N <·

    If) «0 Pl M Bt ffl rt.« m,g ritftrtO Old •irt. rirt, [mflK H, 15w,w.w.w,.l· η I k« 1 η Ip) 4 J f 1*5·*« V < N
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    Fig. 2D
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     Fig. 2E
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     Fig. 2F rtAAAAArtAAAAAAA VW>, lit·* i rt A A rt rt A A A rt A A A A A A A A A rt rt A A A A rt rt A A A A A Art rt A

     4 Φ (4rl Pitl f Η Η Η Η,η,Η'Η Q)t4 ! s e s e a a 3 3 5 5 e s a a «<a s a 5 s s e e «^!s «ws «'«ws _n ^[s 5 Λ. ws;

     (ft^ U fl iiriNNtlN rtinrr ** * * Ί· «ί iq » ** W Μ A

     AAVSCAP a 724 Tuisr ·
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     Fig. 3A

     Met Pro Gly Phe Tyr Glu Ile Val Ile Lys Val Pro Ser Asp Leu Asp 1 5 10 15

     Glu His Leu Pro Gly Ile Ser Asp Ser Phe Val Asn Trp Val Ala Glu 20 25 30

     Lys Glu Trp Glu Leu Pro Pro Asp Ser Asp Met Asp Leu Asn Leu Ile 35 40 45

     Glu Gin Ala Pro Leu Thr Val Ala Glu Lys Leu Gin Arg Asp Phe Leu 50 55 60

     Val Gin Trp Arg Arg Val Ser Lys Ala Pro Glu Ala Leu Phe Phe Val 65 70 75 80

     Gin Phe Glu Lys Gly Glu Ser Tyr Phe His Leu His Val Leu Val Glu 85 90 95

     Thr Thr Gly Val Lys Ser Met Val Leu Gly Arg Phe Leu Ser Gin lie 100 105 110

     Arg Glu Lys Leu Val Gin Thr Ile Tyr Arg Gly Val Glu Pro Thr Leu 115 120 125

     Pro Asn Trp Phe Ala Val Thr Lys Thr Arg Asn Gly Ala Gly Gly Gly 130 135 140

     Asn Lys Val Val Asp Glu Cys Tyr lie Pro Asn Tyr Leu Leu Pro Lys 145 150 155 160

     Thr Gin Pro Glu Leu Gin Trp Ala Trp Thr Asn Met Glu Glu Tyr Ile 165 170 175

     Ser Ala Cys Leu Asn Leu Ala Glu Arg Lys Arg Leu Val Ala Gin His 180 185 190

     Leu Thr His Val Ser Gin Thr Gin Glu Gin Asn Lys Glu Asn Leu Asn 195 200 205

     Pro Asn Ser Asp Ala Pro Val lie Arg Ser Lys Thr Ser Ala Arg Tyr 210 215 220
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     Fig. 3B Met Glu Leu Val Gly Trp Leu Val Asp Arg Gly lie Thr Ser Glu Lys 225 230 235 240 Gln Trp Ile Gln Glu Asp Gln Ala Ser Tyr Ile Ser Phe Asn Ala Ala 245 250 255 Ser Asn Ser Arg Ser Gln lie Lys Ala Ala Leu Asp Asn Ala Gly Lys 260 265 270 Ile Met Ala Leu Thr Lys Ser Ala Pro Asp Tyr Leu Val Gly Pro Ser 275 280 285 Leu Pro Ala Asp lie Lys Thr Asn Arg Ile Tyr Arg Ile Leu Glu Leu 290 295 300 Asn Gly Tyr Asp Pro Ala Tyr Ala Gly Ser Val Phe Leu Gly Trp Ala 305 310 315 320 Gln Lys Lys Phe Gly Lys Arg Asn Thr Ile Trp Leu Phe Gly Pro Ala 325 330 335 Thr Thr Gly Lys Thr Asn Ile Ala Glu Ala Ile Ala His Ala Val Pro 340 345 350 Phe Tyr Gly Cys Val Asn Trp Thr Asn Glu Asn Phe Pro Phe Asn Asp 355 360 365 Cys Val Asp Lys Met Val lie Trp Trp Glu Glu Gly Lys Met Thr Ala 370 375 380 , Lys Val Val Glu Ser Ala Lys Ala Ile Leu Gly Gly Ser Lys Val Arg 385 390 395 400 Val Asp Gln Lys Cys Lys Ser Ser Ala Gln Ile Asp Pro Thr Pro Val 405 410 415 Ile Val Thr Ser Asn Thr Asn Met Cys Ala Val Ile Asp Gly Asn Ser 420 425 430 Thr Thr Phe Glu His Gln Gln Pro Leu Gln Asp Arg Met Phe Lys Phe

     435 440 445
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     Fig. 3C

     Glu Leu Thr Arg Arg Leu Glu His Asp Phe Gly Lys Val Thr Lys Gin 450 455 460

     Glu Val Lys Glu Phe Phe Arg Trp Ala Ser Asp His Val Thr Glu Val 465 470 475 480

     Ala His Glu Phe Tyr Val Arg Lys Gly Gly Ala Ser Lys Arg Pro Ala 485 490 495

     Pro Asp Asp Ala Asp lie Ser Glu Pro Lys Arg Ala Cys Pro Ser Val 500 505 510

     Ala Asp Pro Ser Thr Ser Asp Ala Glu Gly Ala Pro Val Asp Phe Ala 515 520 525

     Asp Arg Tyr Gin Asn Lys Cys Ser Arg His Ala Gly Met Ile Gin Met 530 535 540

     Leu Phe Pro Cys Lys Thr Cys Glu Arg Met Asn Gin Asn Phe Asn Ile 545 550 555 560

     Cys Phe Thr His Gly Val Arg Asp Cys Leu Glu Cys Phe Pro Gly Val 565 570 575

     Ser Glu Ser Gin Pro Val Val Arg Lys Lys Thr Tyr Arg Lys Leu Cys 580 585 590

     Ala Ile His His Leu Leu Gly Arg Ala Pro Glu Ile Ala Cys Ser Ala 595 600 605

     Cys Asp Leu Val Asn Val Asp Leu Asp Asp Cys Val Ser Glu Gin 610 615 620
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     SEQUENCE LISTING <110> The Trustees of The University of Pennsylvania Gad, Guangping Wilson, James M.

     Alvira, Mauricio <120> A Method of Detecting and/or Identifying Adeno-Associated

     Virus (AAV) Sequences and Isolating Novel Sequences Identified Thereby <13 0> UPN-02735PCT <150> US 60/350,607 <151> 2001-11-13 <150> US 60/341,117 <151> 2001-12-17 <150> US 60/377,066 <151> 2002-05-01 <150> US 60/386,675 <151> 2002-06-05 <160> 120 <170> Patentln version 3.1 <210> 1 <211> 4721 <212> DNA <213> adeno-assooiated virus serotype 7 <400> 1

     ttggccactc cctctatgcg cgctcgctcg ctcggtgggg cctgcggacc aaaggtccgc 60 agacggcaga gctctgctct gccggcccca ccgagcgagc gagcgcgcat agagggagtg 12 0 gccaactcca tcactagggg taccgcgaag cgcctcccac gctgccgcgt cagcgctgac 180 gtaaatcacg tcatagggga gtggtcctgt attagctgtc acgtgagtgc ttttgcgaca 240 ttttgcgaca ccacgtggcc atttgaggta tatatggccg agtgagcgag caggatctcc 300 attttgaccg cgaaatttga acgagcagca gccatgccgg gtttctacga gatcgtgatc 360 aaggtgccga gcgacctgga cgagcacctg ccgggcattt ctgactcgtt tgtgaactgg 420 gtggccgaga aggaatggga gctgcccccg gattctgaca tggatctgaa tctgatcgag 480 caggcacccc tgaccgtggc cgagaagctg cagcgcgact tcctggtcca atggcgccgc 540 gtgagtaagg ccccggaggc cctgttcttt gttcagttcg agaagggcga gagctacttc 600 caccttcacg ttctggtgga gaccacgggg gtcaagtcca tggtgctagg ccgcttcctg 660 agtcagattc gggagaagct ggtccagacc atctaccgcg gggtcgagcc cacgctgccc 720 aactggttcg cggtgaccaa gacgcgtaat ggcgccggcg gggggaacaa ggtggtggac 78 0 gagtgctaca tccccaacta cctcctgccc aagacccagc' ccgagctgca gtgggcgtgg 840 actaacatgg aggagtatat aagcgcgtgt ttgaacctgg ccgaacgcaa acggctcgtg 900

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     gcgcagcacc tgacccacgt cagccagacg ' caggagcaga . acaaggagaa l tctgaacccc 960 aattctgacg cgcccgtgat caggtcaaaa acctccgcgc gctacatgga , gctggtcggg 1020 tggctggtgg accggggcat cacctccgag aagcagtgga . tccaggagga . ccaggcctcg 1080 tacatctcct tcaacgccgc ctccaactcg cggtcccaga tcaaggccgc gctggacaat 1140 gccggcaaga tcatggcgct gaccaaatcc gcgcccgact acctggtggg gccctcgctg 1200 cccgcggaca ttaaaaccaa ccgcatctac cgcatcctgg agctgaacgg gtacgatcct 1260 gcctacgccg gctccgtctt tctcggctgg gcccagaaaa agttcgggaa gcgcaacacc 1320 atctggctgt ttgggcccgc caccaccggc aagaccaaca ttgcggaagc catcgcccac 1380 gccgtgccct tctacggctg cgtcaactgg accaatgaga actttccctt caacgattgc 1440 gtcgacaaga tggtgatctg gtgggaggag ggcaagatga cggccaaggt cgtggagtcc 1500 gccaaggcca ttctcggcgg cagcaaggtg cgcgtggacc aaaagtgcaa gtcgtccgcc 1560 cagatcgacc ccacccccgt gatcgtcacc tccaacacca acatgtgcgc cgtgattgac 1620 gggaacagca ccaccttcga gcaccagcag ccgttgcagg accggatgtt caaatttgaa 1680 ctcacccgcc gtctggagca cgactttggc aaggtgacga agcaggaagt caaagagttc 1740 ttccgctggg ccagtgatca cgtgaccgag gtggcgcatg agttctacgt cagaaagggc 1800 ggagccagca aaagacccgc ccccgatgac gcggatataa gcgagcccaa gcgggcctgc 1860 ccctcagtcg cggatccatc gacgtcagac gcggaaggag ctccggtgga ctttgccgac 1920 aggtaccaaa acaaatgttc tcgtcacgcg ggcatgattc agatgctgtt tccctgcaaa 1980 acgtgcgaga gaatgaatca gaatttcaac atttgcttca cacacggggt cagagactgt 2040 ttagagtgtt tccccggcgt gtcagaatct caaccggtcg tcagaaaaaa gacgtatcgg 2100 aaactctgcg cgattcatca tctgctgggg cgggcgcccg agattgcttg ctcggcctgc 2160 gacctggtca acgtggacct ggacgactgc gtttctgagc aataaatgac ttaaaccagg 2220 tatggctgcc gatggttatc ttccagattg gctcgaggac aacctctctg agggcattcg 2280 cgagtggtgg gacctgaaac ctggagcccc gaaacccaaa gccaaccagc aaaagcagga 2340 caacggccgg ggtctggtgc ttcctggcta caagtacctc ggacccttca acggactcga 2400 caagggggag cccgtcaacg cggcggacgc agcggccctc gagcacgaca aggcctacga 2460 ccagcagctc aaagcgggtg acaatccgta cctgcggtat aaccacgccg acgccgagtt 2520 tcaggagcgt ctgcaagaag atacgtcatt tgggggcaac ctcgggcgag cagtcttcca 2580 ggccaagaag cgggttctcg aacctctcgg tctggttgag gaaggcgcta agacggctcc 2640 tgcaaagaag agaccggtag agccgtcacc tcagcgttcc cccgactcct ccacgggcat 2700 cggcaagaaa ggccagcagc ccgccagaaa gagactcaat ttcggtcaga ctggcgactc 2760 agagtcagtc cccgaccctc aacctctcgg agaacctcca gcagcgccct ctagtgtggg 2820

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     atctggtaca gtggctgcag gcggtggcgc accaatggca . gacaataacg ' aaggtgccga 2880 cggagtgggt aatgcctcag gaaattggca ttgcgattcc acatggctgg ' gcgacagagt 2940 cattaccacc agcacccgaa cctgggccct gcccacctac aacaaccacc tctacaagca 3000 aatctccagt gaaactgcag gtagtaccaa cgacaacacc tacttcggct acagcacccc 3060 ctgggggtat tttgacttta acagattcca ctgccacttc tcaccacgtg actggcagcg 3120 actcatcaac aacaactggg gattccggcc caagaagctg cggttcaagc tcttcaacat 3180 ccaggtcaag gaggtcacga cgaatgacgg cgttacgacc atcgctaata accttaccag 3240 cacgattcag gtattctcgg actcggaata ccagctgccg tacgtcctcg gctctgcgca 3300 ccagggctgc ctgcctccgt tcccggcgga cgtcttcatg attcctcagt acggctacct 3360 gactctcaac aatggcagtc agtctgtggg acgttcctcc ttctactgcc tggagtactt 3420 cccctctcag atgctgagaa cgggcaacaa ctttgagttc agctacagct tcgaggacgt 3480 gcctttccac agcagctacg cacacagcca gagcctggac cggctgatga atcccctcat 3540 cgaccagtac ttgtactacc tggccagaac acagagtaac ccaggaggca cagctggcaa 3600 tcgggaactg cagttttacc agggcgggcc ttcaactatg gccgaacaag ccaagaattg 3660 gttacctgga ccttgcttcc ggcaacaaag agtctccaaa aogctggatc aaaacaacaa 3720 cagcaacttt gcttggactg gtgccaccaa atatcacctg aacggcagaa actcgttggt 3780 taatcccggc gtcgccatgg caactcacaa ggacgacgag gaccgctttt tcccatccag 3840 cggagtcctg atttttggaa aaactggagc aactaacaaa actacattgg aaaatgtgtt 3900 aatgacaaat gaagaagaaa ttcgtcctac taatcctgta gccacggaag aatacgggat 3960 agtcagcagc aacttacaag cggctaatac tgcagcccag acacaagttg tcaacaacca 4020 gggagcctta cctggcatgg tctggcagaa ccgggacgtg tacctgcagg gtcccatctg 4080 ggccaagatt cctcacacgg atggcaactt tcacccgtct cctttgatgg gcggctttgg 4140 acttaaacat ccgcctcctc agatqctgat caagaacact cccgttcccg ctaatcctcc 4200 ggaggtgttt actcctgcca agtttgcttc gttcatcaca cagtacagca ccggacaagt 4260 cagcgtggaa atcgagtggg agctgcagaa ggaaaacagc aagcgctgga acccggagat 4320 tcagtacacc tccaactttg aaaagcagac tggtgtggac tttgccgttg acagccaggg 4380 tgtttactct gagcctcgcc ctattggcac tcgttacctc acccgtaatc tgtaattgca 4440 tgttaatcaa taaaccggtt gattcgtttc agttgaactt tggtctcctg tgcttcttat 4500 cttatcggtt tccatagcaa ctggttacac attaactgct tgggtgcgct tcacgataag 4560 aacactgacg tcaccgcggt acccctagtg atggagttgg ccactccctc tatgcgcgct 4620 cgctcgctcg gtggggcctg cggaccaaag gtccgcagac ggcagagctc tgctctgccg 4680 gccccaccga gcgagcgagc gcgcatagag ggagtggcca a 4721

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     2015258271 20 Nov 2015 <210> 2 <211> 737 <212> PRT <213> capsid protein of adeno-associated virus serotpye 7 <400> 2

     Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn leu Ser 15 10 15

     Glu Gly Ile Arg Glu Trp Trp Asp leu lys Pro Gly Ala Pro Lys Pro 20 25 30

     Lys Ala Asn Gin Gin Lys Gin Asp Asn Gly Arg Gly Leu Val Leu Pro 35 40 45

     Gly Tyr lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp lys Gly Glu Pro 50 55 60

     Val Asn Ala Ala Asp Ala Ala Ala leu Glu His Asp Lys Ala Tyr Asp 65 70 75 80

     Gin Gin Leu Lys Ala Gly Asp Asn Pro Tyr leu Arg Tyr Asn His Ala 65 SO 95

     Asp Ala Glu Phe Gin Glu Arg Leu Gin Glu Asp Thr Ser Phe Gly Gly 100 105 110

     Asn Leu Gly Arg Ala Val Phe Gin Ala lys Lys Arg Val Leu Glu Pro 115 120 125

     Leu Gly Leu Val Glu Glu Gly Ala Lys Thr Ala Pro Ala Lys lys Arg 130 135 140

     Pro Val Glu Pro Ser Pro Gin Arg Ser Pro Asp Ser Ser Thr Gly Ile 145 150 155 160

     Gly Lys Lys Gly Gin Gin Pro Ala Arg Lys Arg Leu Asn Phe Gly Gin 165 170 175

     Thr Gly Asp Ser Glu Ser Val Pro Asp Pro Gin Pro Leu Gly Glu Pro . 180 185 190

     Pro Ala Ala Pro Ser Ser Val Gly Ser Gly Thr Val Ala Ala Gly Gly 195 200 205

     Gly Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn 210 215 220

     Ala Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val 225 230 235 240

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     Ile Thr Thr Ser Thr Arg Thr Trp Ala leu Pro Thr Tyr Asn Asn His 245 250 255 leu Tyr lys Gin Ile Ser Ser Glu Thr Ala Gly Ser Thr Asn Asp Asn 260 265 270

     Thr Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg 275 280 285

     Phe His Cys His Phe Ser Pro Arg Asp Trp Gin Arg leu lie Asn Asn 290 295 300

     Asn Trp Gly Phe Arg Pro lys lys leu Arg Phe lys leu Phe Asn lie 305 310 315 320

     Gin Val lys Glu Val Thr Thr Asn Asp Gly Val Thr Thr lie Ala Asn 325 330 335

     Asn leu Thr Ser Thr lie Gin Val Phe Ser Asp Ser Glu Tyr Gin leu 340 345 350

     Pro Tyr Val leu Gly Ser Ala His Gin Gly Cys leu Pro Pro Phe Pro 355 360 365

     Ala Asp Val Phe Met lie Pro Gin Tyr Gly Tyr leu Thr leu Asn Asn 370 375 380

     Gly Ser Gin Ser Val Gly Arg Ser Ser Phe Tyr Cys leu Glu Tyr Phe 385 390 395 400

     Pro Ser Gin Met leu Arg Thr Gly Asn Asn Phe Glu Phe Ser Tyr Ser 405 410 415

     Phe Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gin Ser leu 420 425 430

     Asp Arg leu Met Asn Pro leu Ile Asp Gin Tyr leu Tyr Tyr leu Ala 435 440 445

     Arg Thr Gin Ser Asn Pro Gly Gly Thr Ala Gly Asn Arg Glu leu Gin 450 455 460

     Phe Tyr Gin Gly Gly Pro Ser Thr Met Ala Glu Gin Ala lys Asn Trp 465 470 475 480 leu Pro Gly Pro Cys Phe Arg Gin Gin Arg Val Ser lys Thr leu Asp 485 490 495

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     Gin Asn Asn Asn Ser Asn Phe Ala Trp Thr Gly Ala Thr Lys Tyr His 500 505 510

     Leu Asn Gly Arg Asn Ser Leu Val Asn Pro Gly Val Ala Met Ala Thr 515 520 525

     His Lys Asp Asp Glu Asp Arg Phe Phe Pro Ser Ser Gly Val Leu lie 530 535 540

     Phe Gly Lys Thr Gly Ala Thr Asn Lys Thr Thr leu Glu Asn Val Leu 545 550 555 560

     Met Thr Asn Glu Glu Glu Ile Arg Pro Thr Asn Pro Val Ala Thr Glu 565 570 575

     Glu Tyr Gly lie Val Ser Ser Asn Leu Gin Ala Ala Asn Thr Ala Ala 580 585 590

     Gin Thr Gin Val Val Asn Asn Gin Gly Ala Leu Pro Gly Met Val Trp 595 600 605

     Gin Asn Arg Asp Val Tyr Leu Gin Gly Pro Ile Trp Ala Lys Ile Pro 610 615 620

     His Thr Asp Gly Asn Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly 625 630 635 640

     Leu Lys His Pro Pro Pro Gin Ile Leu lie Lys Asn Thr Pro Val Pro 645 650 655

     Ala Asn Pro Pro Glu Val Phe Thr Pro Ala Lys Phe Ala Ser Phe lie 660 665 670

     Thr Gin Tyr Ser Thr Gly Gin Val Ser Val Glu lie Glu Trp Glu Leu 675 680 685

     Gin Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu lie Gin Tyr Thr Ser 690 695 700

     Asn Phe Glu Lys Gin Thr Gly Val Asp Phe Ala Val Asp Ser Gin Gly 705 710 715 720

     Val Tyr Ser Glu Pro Arg Pro lie Gly Thr Arg Tyr Leu Thr Arg Asn 725 730 735

     Leu

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     Met pro Gly Ehe Tyr Glu lie Val lie Lys Val Pro Ser Asp leu Asp

     1 5 10 15

     Glu His Leu Pro Gly He Ser Asp Ser Phe Val Asn Trp Val Ala Glu 20 25 30

     Lys Glu Trp Glu leu Pro Pro Asp Ser Asp Met Asp leu Asn leu He 35 40 45

     Glu Gin Ala Pro leu Thr Val Ala Glu lys Leu Gin Arg Asp Phe leu 50 55 60 ’

     Val Gin Trp Arg Arg Val Ser lys Ala Pro Glu Ala Leu Phe phe Val 65 70 75 80

     Gin Phe Glu lys Gly Glu Ser Tyr Phe His Leu His Val leu Val Glu 85 90 95

     Thr Thr Gly Val lys Ser Met Val leu Gly Arg Phe Leu Ser Gin lie 100 105 110

     Arg Glu lys Leu Val Gin Thr He Tyr Arg Gly Val Glu Pro Thr Leu 115 120 125

     Pro Asn Trp Phe Ala Val Thr Lys Thr Arg Asn Gly Ala Gly Glv Gly 130 135 140 '

     Asn Lys Val Val Asp Glu Cys Tyr He Pro Asn Tyr Leu leu Ero Lys 145 150 155 160

     Thr Gin Ero Glu Leu Gin Trp Ala Trp Thr Asn Met Glu Glu Tyr He 165 170 175

     Ser Ala Cys Leu Asn Leu Ala Glu Arg Lys Arg Leu Val Ala Gin His 180 185 190

     Leu Thr His Val Ser Gin Thr Gin Glu Gin Asn Lys Glu Asn Leu Asn 195 200 205

     Pro Asn Ser Asp Ala Pro Val He Arg Ser Lys Thr Ser Ala Arg Tyr 210 215 220

     Met Glu Leu Val Gly Trp Leu Val Asp Arg Gly lie Thr Ser Glu Lys 225 230 235 240

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     Gin Trp lie Gin Glu Asp Gin Ala Ser Tyr He Ser Phe Asn Ala Ala 245 250 255

     Ser Asn Ser Arg Ser Gin lie Lys Ala Ala leu Asp Asn Ala Gly Lys 250 265 270

     He Met Ala Leu Thr Lys Ser Ala Pro Asp Tyr Leu Val Gly Pro Ser 275 280 285

     Leu Pro Ala Asp lie Lys Thr Asn Arg He Tyr Arg He Leu Glu Leu 290 295 300

     Asn Gly Tyr Asp Pro Ala Tyr Ala Gly Ser Val Phe Leu Gly Trp Ala 305 310 315 320

     Gin Lys Lys Phe Gly Lys Arg Asn Thr He Trp leu Phe Gly Pro Ala 325 330 335

     Thr Thr Gly Lys Thr Asn He Ala Glu Ala lie Ala His Ala Val Pro 340 345 350

     Phe Tyr Gly Cys Val Asn Trp Thr Asn Glu Asn Phe Pro Phe Asn Asp 355 360 365

     Cys Val Asp Lys Met Val He Trp Trp Glu Glu Gly Lys Met Thr Ala 370 375 380

     Lys Val Val Glu Ser Ala Lys Ala He Leu Gly Gly Ser Lys Val Arg 385 390 395 400

     Val Asp Gin Lys Cys Lys Ser Ser Ala Gin He Asp Pro Thr Pro Val 405 410 415 lie Val Thr Ser Asn Thr Asn Met Cys Ala Val He Asp Gly Asn Ser 420 425 430

     Thr Thr Phe Glu His Gin Gin Pro Leu Gin Asp Arg Met Phe Lys Phe 435 440 445

     Glu Leu Thr Arg Arg Leu Glu His Asp Phe Gly Lys Val Thr Lys Gin 450 455 460

     Glu Val Lys Glu Phe Phe Arg Trp Ala Ser Asp His Val Thr Glu Val 465 470 475 480

     Ala His Glu Phe Tyr Val Arg Lys Gly Gly Ala Ser lys Arg Pro Ala 485 490 495

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     Pro Asp Asp Ala 500 Asp lie Ser Glu Pro 505 Lys Arg Ala Cys Pro 510 Ser Val Ala Asp Pro 515 Ser Thr Ser Asp Ala 520 Glu Gly Ala Pro Val 525 Asp Phe Ala Asp Arg 530 Tyr Gin Asn Lys Cys Ser 535 Arg His Ala Gly 540 Met lie Gin Met Leu Phe 545 Pro Cys Lys Thr 550 Cys Glu Arg Met Asn 555 Gin Asn Phe Asn lie 560 Cys Phe Thr His Gly 565 Val Arg Asp Cys Leu 570 Glu Cys Phe Pro Gly 575 Val Ser Glu Ser Gin 580 Pro Val Val Arg lys 585 Lys Thr Tyr Arg Lys 590 Leu Cys Ala lie His 595 His Leu Leu Gly Arg 600 Ala Pro Glu lie Ala 605 cys Ser Ala Cys Asp Leu Val Asn Val Asp Leu Asp Asp Cys Val Ser Glu Gin

     610 615 620 <210> 4 <211> 4333 <212> DNA <213> adeno-associated virus serotype 8 <400> 4

     cagagaggga gtggccaact ccatcactag gggtagcgcg aagcgcctcc cacgctgccg 60 cgtcagcgct gacgtaaatt acgtcatagg ggagtggtcc tgtattagct gtcacgtgag 120 tgcttttgcg gcattttgcg acaccacgtg gccatttgag gtatatatgg ccgagtgagc 180 gagcaggatc tccattttga ccgcgaaatt tgaacgagca gcagccatgc cgggcttcta 240 cgagatcgtg atcaaggtgc cgagcgacct ggacgagcac ctgccgggca tttctgactc 300 gtttgtgaac tgggtggccg agaaggaatg ggagctgccc ccggattctg acatggatcg 360 gaatctgatc gagcaggcac ccctgaccgt ggccgagaag ctgcagcgcg acttcctggt 420 ccaatggcgc cgcgtgagta aggccccgga ggccctcttc tttgttcagt tcgagaaggg 480 cgagagctac tttcacctgc acgttctggt cgagaccacg ggggtcaagt ccatggtgct 540 aggccgcttc ctgagtcaga ttcgggaaaa gcttggtcca gaccatctac ccgcggggtc 600 gagccccacc ttgcccaact ggttcgcggt gaccaaagac gcggtaatgg cgccggcggg 660 ggggaacaag gtggtggacg agtgctacat ccccaactac ctcctgccca agactcagcc 720 cgagctgcag tgggcgtgga ctaacatgga ggagtatata agcgcgtgct tgaacctggc 780

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     cgagcgcaaa cggctcgtgg cgcagcacct gacccacgtc agccagacgc : aggagcagaa 840 caaggagaat ctgaacccca attctgacgc gcccgtgatc aggtcaaaaa . cctccgcgcg 900 ctatatggag ctggtcgggt ggctggtgga ccggggcatc acctccgaga agcagtggat 960 ccaggaggac caggcctcgt acatctcctt caacgccgcc tccaactcgc ggtcccagat 1020 caaggccgcg ctggacaatg ccggcaagat catggcgctg accaaatccg cgcccgacta 1080 cctggtgggg ccctcgctgc ccgcggacat tacccagaac cgcatctacc gcatcctcgc 1140 tctcaacggc tacgaccctg cctacgccgg ctccgtcttt ctcggctggg ctcagaaaaa 1200 gttcgggaaa cgcaacacca tctggctgtt tggacccgcc accaccggca agaccaacat 1260 tgcggaagcc atcgcccacg ccgtgccctt ctacggctgc gtcaactgga ccaatgagaa 1320 ctttcccttc aatgattgcg tcgacaagat ggtgatctgg tgggaggagg gcaagatgac 1380 ggccaaggtc gtggagtccg ccaaggccat tctcggcggc agcaaggtgc gcgtggacca 1440 aaagtgcaag tcgtccgccc agatcgaccc cacccccgtg atcgtcacct ccaacaccaa 1500 catgtgcgcc gtgattgacg ggaacagcac caccttcgag caccagcagc ctctccagga 1560 ccggatgttt aagttcgaac tcacccgccg tctggagcac gactttggca aggtgacaaa 1620 gcaggaagtc aaagagttct tccgctgggc cagtgatcac gtgaccgagg tggcgcatga 1680 gttttacgtc agaaagggcg gagccagcaa aagacccgcc cccgatgacg cggataaaag 1740 cgagcccaag cgggcctgcc cctcagtcgc ggatccatcg aogtcagacg cggaaggagc 1800 tccggtggac tttgccgaca ggtaccaaaa caaatgttct cgtcacgcgg gcatgcttca 1860 gatgctgttt ccctgcaaaa cgtgcgagag aatgaatcag aatttcaaca tttgcttcac 1920 acacggggtc agagactgct cagagtgttt ccccggcgtg tcagaatctc aaccggtcgt 1980 cagaaagagg acgtatcgga aactctgtgc gattcatcat ctgctggggc gggctcccga 2040 gattgcttgc tcggcctgcg atctggtcaa cgtggacctg gatgactgtg tttctgagca 2100 ataaatgact taaaccaggt atggctgccg atggttatct tccagattgg ctcgaggaca 2160 acctctctga gggcattcgc gagtggtggg cgctgaaacc tggagccccg aagcccaaag 2220 ccaaccagca aaagcaggac gacggccggg gtctggtgct tcctggctac aagtacctcg 2280 gacccttcaa cggactcgac aagggggagc ccgtcaacgc ggcggacgca gcggccctcg 2340 agcacgacaa ggcctacgac cagcagctgc aggcgggtga caatccgtac ctgcggtata 2400 accacgccga cgccgagttt caggagcgtc tgcaagaaga tacgtctttt gggggcaacc 2460 tcgggcgagc agtcttccag gccaagaagc gggttctcga acctctcggt ctggttgagg 2520 aaggcgctaa gacggctcct ggaaagaaga gaccggtaga gccatcaccc cagcgttctc 2580 cagactcctc tacgggcatc ggcaagaaag gccaacagcc cgccagaaaa agactcaatt 2 64 0 ttggtcagac tggcgactca gagtcagttc cagaccctca acctctcgga gaacctccag 2700

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     cagcgccctc tggtgtggga cctaatacaa tggctgcagg cggtggcgca , ccaatggcag 2760 acaataacga aggcgccgac ggagtgggta gttcctcggg aaattggcat tgcgattcca 2820 catggctggg cgacagagtc atcaccacca gcacccgaac ctgggccctg cccacctaca 2380 acaaccacct ctacaagcaa atctccaacg ggacatcggg aggagccacc aacgacaaca 2940 cctacttcgg ctacagcacc ccctgggggt attttgactt taacagattc cactgccact 3000 tttcaccacg tgactggcag cgactcatca acaacaactg gggattccgg cccaagagac 3060 tcagcttcaa gctcttcaac atccaggtca aggaggtcac gcagaatgaa ggcaccaaga 3120 ccatcgccaa taacctcacc agcaccatcc aggtgtttac ggactcggag taccagctgc 3180 cgtacgttct cggctctgcc caccagggct gcctgcctcc gttcccggcg gacgtgttca 3240 tgattcccca gtacggctac ctaacactca acaacggtag tcaggccgtg ggacgctcct 3300 ccttctactg cctggaatac tttccttcgc agatgctgag aaccggcaac aacttccagt 3360 ttacttacac cttcgaggac gtgcctttcc acagcagcta cgcccacagc cagagcttgg 3420 accggctgat gaatcctctg attgaccagt acctgtacta cttgtctcgg actcaaacaa 3480 caggaggcac ggcaaatacg cagactctgg gcttcagcca aggtgggcct aatacaatgg 3540 ccaatcaggc aaagaactgg ctgccaggac cctgttaccg ccaacaacgc gtctcaacga 3600 caaccgggca aaacaacaat agcaactttg cctggactgc tgggaccaaa taccatctga 3660 atggaagaaa ttcattggct aatcctggca tcgctatggc aacacacaaa gacgacgagg 3720 agcgtttttt tcccagtaac gggatcctga tttttggcaa acaaaatgct gccagagaca 3780 atgcggatta cagcgatgtc atgctcacca gcgaggaaga aatcaaaacc actaaccctg 3840 tggctacaga ggaatacggt atcgtggcag ataacttgca gcagcaaaac acggctcctc 3900 aaattggaac tgtcaacagc cagggggcct tacccggtat ggtctggcag aaccgggacg 3960 tgtacctgca gggtcccatc tgggccaaga ttcctcacac ggacggcaac ttccacccgt 4020 ctccgctgat gggcggcttt ggcctgaaac atcctccgcc tcagatcctg atcaagaaca 4080 cgcctgtacc tgcggatcct ccgaccacct tcaaccagtc aaagctgaac tctttcatca 4140 cgcaatacag caccggacag gtcagcgtgg aaattgaatg ggagctgcag aaggaaaaca 4200 gcaagcgctg gaaccccgag atccagtaca cctccaacta ctacaaatct acaagtgtgg 4260 actttgctgt taatacagaa ggcgtgtact ctgaaccccg ccccattggc acccgttacc 4320 tcacccgtaa tctgtaattg cctgttaatc aataaaccgg ttgattcgtt tcagttgaac 4380 tfctggtctct gcg 4393 <210> 5 <211> 4385 <212> DNA <213> adeno-associated virus serotype 9

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     2015258271 20 Nov 2015 <400> 5 cagagaggga gtggccaact ccatcactag gggtaatcgc gaagcgcctc ccacgctgcc 60 gcgtcagcgc tgacgtagat tacgtcatag gggagtggtc ctgtattagc tgtcacgtga 120 gtgcttttgc gacattttgc gacaccacat ggccatttga ggtatatatg gccgagtgag 180 cgagcaggat ctccattttg accgcgaaat ttgaacgagc agcagccatg ccgggcttct 240 acgagattgt gatcaaggtg ccgagcgacc tggacgagca cctgccgggc atttctgact 300 cttttgtgaa ctgggtggcc gagaaggaat gggagctgcc cccggattct gacatggatc 360 ggaatctgat cgagcaggca cccctgaccg tggccgagaa gctgcagcgc gacttcctgg 420 tccaatggcg ccgcgtgagt aaggccccgg aggccctctt ctttgttcag ttcgagaagg 4S0 gcgagagcta ctttcacctg cacgttctgg tcgagaccac gggggtcaag tccatggtgc 540 taggccgctt cctgagtcag attcgggaga agctggtcca gaccatctac cgcgggatcg 600 agccgaccct gcccaactgg ttcgcggtga ccaagacgcg taatggcgcc ggcgggggga 660 acaaggtggt ggacgagtgc tacatcccca actacctcct gcccaagact cagcccgagc 720 tgcagtgggc gtggactaac atggaggagt atataagcgc gtgcttgaac ctggccgagc 780 gcaaacggct cgtggcgcag cacctgaccc acgtcageca gacgeaggag oagaacaagg 340 agaatctgaa ccccaattct gacgcgcccg tgatcaggtc aaaaacctcc gcgcgctaca 900 tggagctggt cgggtggctg gtggaccggg gcatcacctc cgagaagcag tggatccagg 960 aggaccaggc ctcgtacatc tccttcaacg ccgcctccaa ctcgcggtcc cagatcaagg 1020 ccgcgctgga caatgccggc aagatcatgg cgctgaccaa atccgcgccc gactacctgg 1080 taggcccttc acttccggtg gacattacgc agaaccgcat ctaccgcatc ctgcagctca 1140 acggctacga ccctgcctac gccggctccg tctttctcgg ctgggcacaa aagaagttcg 1200 ggaaacgcaa caccatctgg ctgtttgggc cggccaccac gggaaagacc aacatcgcag 1260 aagccattgc ccacgccgtg cccttctacg gctgcgtcaa ctggaccaat gagaactttc 1320 ccttcaacga ttgcgtcgac aagatggtga tctggtggga ggagggcaag atgacggcca 1380 aggtcgtgga gtccgccaag gccattctcg gcggcagcaa ggtgcgcgtg gaccaaaagt 1440 gcaagtcgtc cgcccagatc gaccccactc ccgtgatcgt cacctccaac accaacatgt 1500 gcgccgtgat tgacgggaac agcaccacct tcgagcacca gcagcctctc caggaccgga 1560 tgtttaagtt cgaactcacc cgccgtctgg agcacgactt tggcaaggtg acaaagcagg 1620 aagtcaaaga gttcttccgc tgggccagtg atcacgtgac cgaggtggcg catgagtttt 1680 acgtcagaaa gggcggagcc agcaaaagac ccgcccccga tgacgcggat aaaagcgagc 1740 ccaagcgggc ctgcccctca gtcgcggatc catcgacgtc agacgcggaa ggagctccgg 1800 tggactttgc cgacaggtac caaaacaaat gttctcgtca cgcgggcatg cttcagatgc 1860 tgcttccctg caaaacgtgc gagagaatga atcagaattt caacatttgc ttcacacacg 1920

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     gggtcagaga ctgctcagag tgtttccccg gcgtgtcaga atctcaaccg gtcgtcagaa I960 agaggacgta tcggaaactc tgtgcgattc atcatctgct ggggcgggct cccgagattg 2040 cttgctcggc ctgcgatctg gtcaacgtgg acctggatga ctgtgtttct gagcaataaa 2100 tgacttaaac caggtatggc tgccgatggt tatcttccag attggctcga ggacaacctc 2160 tctgagggca ttcgcgagtg gtgggcgctg aaacctggag ccccgaagcc caaagccaac 2220 cagcaaaagc aggacgacgg ccggggtctg gtgcttcctg gctacaagta cctcggaccc 2280 ttcaacggac tcgacaaggg ggagcccgtc aacgcggcgg acgcagcggc cctcgagcac 2340 ggcaaggcct acgaccagca gctgcaggcg ggtgacaatc cgtacctgcg gtataaccac 2400 gccgacgccg agtttcagga gcgtctgcaa gaagatacgt cttttggggg caacctcggg 24 60 cgagcagtct tccaggccaa gaagcgggtt ctcgaacctc tcggtctggt tgaggaaggc 2520 gctaagacgg ctcctggaaa gaagagaccg gtagagccat caccccagcg ttctccagac 2580 tcctctacgg gcatcggcaa gaaaggccaa cagcccgcca gaaaaagact caattttggt 2640 cagactggcg actcagagtc agttccagac cctcaacctc tcggagaacc tccagcagcg 2700 ccctc-tggtg tgggacctaa tacaatggct gcaggcggtg gcgcaccaat ggcagacaat 2760 aacgaaggcg ccgacggagt gggtaattcc tcgggaaatt ggcattgcga ttccacatgg 2820 ctgggggaca gagtcatcac caccagcacc cgaacctggg cattgcccac ctacaacaac 2880 cacctctaca agcaaatctc caatggaaca tcgggaggaa gcaccaacga caacacctac 2940 tttggctaca gcaccccctg ggggtatttt gacttcaaca gattccactg ccacttctca 3000 ccacgtgact ggcagcgact catcaacaac aactggggat tccggccaaa gagactcaac 3060 ttcaagctgt tcaacatcca ggtcaaggag gttacgacga acgaaggcac caagaccatc 3120 gccaataacc ttaccagcac cgtccaggtc tttacggact cggagtacca gctaccgtac 3130 gtcctaggct ctgcccacca aggatgcctg ccaccgtttc ctgcagacgt cttcatggtt 3240 cctcagtacg gctacctgac gctcaacaat ggaagtcaag cgttaggacg ttcttctttc 3300 tactgtctgg aatacttccc ttctcagatg ctgagaaccg gcaacaactt tcagttcagc 3360 tacactttcg aggacgtgcc tttccacagc agctacgcac acagccagag tctagatcga 3420 ctgatgaacc ccctcatcga ccagtaccta tactacctgg tcagaacaca gacaactgga 3480 actgggggaa ctcaaacttt ggcattcagc caagcaggcc ctagctcaat ggccaatcag 3540 gctagaaact gggtacccgg gccttgctac cgtcagcagc gcgtctccac aaccaccaac 3600 caaaataaca acagcaactt tgcgtggacg ggagctgcta aattcaagct gaacgggaga 3660 gactcgctaa tgaatcctgg cgtggctatg gcatcgcaca aagacgacga ggaccgcttc 3720 tttccatcaa gtggcgttct catatttggc aagcaaggag ccgggaacga tggagtcgac 3780 tacagccagg tgctgattac agatgaggaa gaaattaaag ccaccaaccc tgtagccaca 3840

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     gaggaatacg gagcagtggc catcaacaac caggccgcta acacgcaggc gcaaactgga 3900 cttgtgcata accagggagt tattcctggt atggtctggc agaaccggga cgtgtacctg 3960 cagggcccta tttgggctaa aatacctcac acagatggca actttcaccc gtctcctctg 4020 atgggtggat ttggactgaa acacccacct ccacagattc taattaaaaa tacaccagtg 4080 ccggcagatc ctcctcttac cttcaatcaa gccaagctga actctttcat cacgcagtac 4140 agcacgggac aagtcagcgt ggaaatcgag tgggagctgc agaaagaaaa cagcaagcgc 4200 tggaatccag agatccagta tacttcaaac tactacaaat ctacaaatgt ggactttgct 4260 gtcaatacca aaggtgttta ctctgagcct cgccccattg gtactcgtta cctcacccgt 4320 aatttgtaat tgcctgttaa tcaataaacc ggttaattcg tttcagttga actttggtct 4380

     ctgcg 4395 <210> 6 <211> 4718 <212> DNA <213> adeno-associated virus serotype 1 <400> 6

     ttgcccactc cctctctgcg cgctcgctcg ctcggtgggg cctgcggacc aaaggtccgc 60 agacggcaga gctctgctct gccggcccca ccgagcgagc gagcgcgcag agagggagtg 120 ggcaactcca tcactagggg taatcgcgaa gcgcctccca cgctgccgcg tcagcgctga 180 cgtaaattac gtcatagggg agtggtcctg tattagctgt cacgtgagtg cttttgcgac 240 attttgcgac accacgtggc catttagggt atatatggcc gagtgagcga gcaggatctc 300 cattttgacc gcgaaatttg aacgagcagc agccatgccg ggcttctacg agatcgtgat 360 caaggtgccg agcgacctgg acgagcacct gccgggcatt tctgactcgt ttgtgagctg 420 ggtggccgag aaggaatggg agctgccccc ggattctgac atggatctga atctgattga 480 gcaggcaccc ctgaccgtgg ccgagaagct gcagcgcgac ttcctggtcc aatggcgccg 540 cgtgagtaag gccccggagg ccctcttctt tgttcagttc gagaagggcg agtcctactt 600 ccacctccat attctggtgg agaccacggg ggtcaaatcc atggtgctgg gccgcttcct 660 gagtcagatt agggacaagc tggtgcagac catctaccgc gggatcgagc cgaccctgcc 720 caactggttc gcggtgacca agacgcgtaa tggcgccgga ggggggaaca aggtggtgga 780 cgagtgctac atccccaact acctcctgcc caagactcag cccgagctgc agtgggcgtg 840 gactaacatg gaggagtata taagcgcctg tttgaacctg gccgagcgca aacggctcgt 900 ggcgcagcac ctgacccacg tcagccagac ccaggagcag aacaaggaga atctgaaccc 960 caattctgac gcgcctgtca tccggtcaaa aacctccgcg cgctacatgg agctggtcgg 1020 gtggctggtg gaccggggca tcacctccga gaagcagtgg atccaggagg accaggcctc 1080

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     gtacatctcc ttcaacgccg cttccaactc : gcggtcccag f atcaaggccg ctctggacaa 1140 tgccggcaag atcatggcgc tgaccaaatc cgcgcccgac tacctggtag gccccgctcc 1200 gcccgcggac attaaaacca accgcatcta ccgcatcctg gagctgaacg gctacgaacc 1260 tgcctacgcc ggctccgtct ttctcggctg ggcccagaaa aggttcggga agcgcaacac 132 0 catctggctg tttgggccgg ccaccacggg caagaccaac atcgcggaag ccatcgccca 1380 cgccgtgccc ttctacggct gcgtcaactg gaccaatgag aactttccct tcaatgattg 1440 cgtcgacaag atggtgatct ggtgggagga gggcaagatg acggccaagg tcgtggagtc 1500 cgccaaggcc attctcggcg gcagcaaggt gcgcgtggac caaaagtgca agtcgtccgc 1560 ccagatcgac cccacccccg tgatcgtcac ctccaacacc aaeatgtgcg ccgtgattga 1620 cgggaacagc accaccttcg agcaccagca gccgttgcag gaccggatgt tcaaatttga 1680 actcacccgc cgtctggagc atgactttgg caaggtgaca aagcaggaag tcaaagagtt 1740 cttccgctgg gcgcaggatc acgtgaccga ggtggcgcat gagttctacg tcagaaaggg 1800 tggagccaac aaaagacccg cccccgatga cgcggataaa agcgagccca agcgggcctg 1860 cccctcagtc gcggatccat cgacgtcaga cgcggaagga gctccggtgg actttgccga 1920 caggtaccaa aacaaatgtt ctcgtcacgc gggcatgctt cagatgctgt ttccctgcaa 1980 gacatgcgag agaatgaatc agaatttcaa catttgcttc acgcacggga cgagagactg 2040 ttcagagtgc ttccccggcg tgtcagaatc tcaaccggtc gtcagaaaga ggacgtatcg 2100 gaaactctgt gccattcatc atctgctggg gcgggctccc gagattgctt gctcggcctg 2160 cgatctggtc aacgtggacc tggatgactg tgtttctgag caataaatga cttaaaccag 2220 gtatggctgc cgatggttat cttccagatt ggctcgagga caacctctct gagggcattc 2280 gcgagtggtg ggacttgaaa cctggagccc cgaagcccaa agccaaccag caaaagcagg 2340 acgacggccg gggtctggtg cttcctggct acaagtacct cggacccttc aacggactcg 2400 acaaggggga gcccgtcaac gcggcggacg cagcggccct cgagcacgac aaggcctacg 2460 accagcagct caaagcgggt gacaatccgt acctgcggta taaccacgcc gacgccgagt 2520 ttcaggagcg tctgcaagaa gatacgtctt ttgggggcaa cctcgggcga gcagtcttcc 2580 aggccaagaa gcgggttctc gaacctctcg gtctggttga ggaaggcgct aagacggctc 2640 ctggaaagaa acgtccggta gagcagtcgc cacaagagcc agactcctcc tcgggcatcg 2700 gcaagacagg ccagcagccc gctaaaaaga gactcaattt tggtcagact ggcgactcag 27 60 agtcagtccc cgatccacaa cctctcggag aacctccagc aacccccgct gctgtgggac 2820 ctactacaat ggcttcaggc ggtggcgcac caatggcaga caataacgaa ggcgccgacg 2880 gagtgggtaa tgcctcagga aattggcatt gcgattccac atggctgggc gacagagtca 2940 tcaccaccag cacccgcacc tgggccttgc ccacctacaa taaccacctc tacaagcaaa 3000

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     PCT/US02/33629

     2015258271 20 Nov 2015

     tctccagtgc ttcaacgggg gccagcaacg ' acaaccacta . cttcggctac : agcaccccct 3060 gggggtattt tgatttcaac agattccact gccacttttc accacgtgac : tggcagcgac 3120 tcatcaacaa caattgggga ttccggccca agagactcaa cttcaaactc ttcaacatcc 3180 aagtcaagga ggtcacgacg aatgatggcg tcacaaccat cgctaataac cttaccagca 3240 cggttcaagt cttctcggac tcggagtacc agcttccgta cgtcctcggc tctgcgcacc 3300 agggctgcct ccctccgttc ccggcggacg tgttcatgat tccgcaatac ggctacctga 3360 cgctcaacaa tggcagccaa gccgtgggac gttcatcctt ttactgcctg gaatatttcc 3420 ettctcagat gctgagaacg ggcaacaact ttaccttcag ctacaccttt gaggaagtgc 3480 ctttccacag cagctacgcg cacagccaga gcctggaccg gctgatgaat cctctcatcg 354 0 accaatacct gtattacctg aacagaactc aaaatcagtc cggaagtgcc caaaacaagg 3600 acttgctgtt tagccgtggg tctccagctg gcatgtctgt tcagcccaaa aactggctac 3660 ctggaccctg ttatcggcag cagcgcgttt ctaaaacaaa aacagacaac aacaacagca 3720 attttacctg gactggtgct tcaaaatata acctcaatgg gcgtgaatcc atcatcaacc 3780 ctggcactgc tatggcctca cacaaagacg acgaagacaa gttctttccc atgagcggtg 3840 tcatgatttt tggaaaagag agcgccggag cttcaaacac tgcattggac aatgtcatga 3900 ttacagacga agaggaaatt aaagccacta accctgtggc caccgaaaga tttgggaccg 3960 tggcagtcaa tttccagagc agcagcacag accctgcgac cggagatgtg catgetatgg 4020 gagcattacc tggcatggtg tggcaagata gagacgtgta cctgcagggt cccatttggg 4080 ccaaaattcc tcacacagat ggacactttc acccgtctcc tcttatgggc ggctttggac 4140 tcaagaaccc gcctcctcag atcctcatca aaaacacgcc tgttcctgcg aatcctccgg 4200 cggagttttc agctacaaag tttgcttcat tcatcaccca atactccaca ggacaagtga 4260 gtgtggaaat tgaatgggag ctgcagaaag aaaacagcaa gcgctggaat cccgaagtge 4320 agtacacatc caattatgca aaatctgcca acgttgattt tactgtggac aacaatggac 4380 tttatactga gcctcgcccc attggcaccc gttaccttac ccgtcccctg taattacgtg 4440 ttaatcaata aaccggttga ttcgtttcag ttgaactttg gtctcctgtc ettettatet 4500 tatcggttac catggttata gcttacacat taactgcttg gttgcgcttc gegataaaag 4560 acttacgtca tcgggttacc cctagtgatg gagttgcaca ctccctctct gcgcgctcgc 4 620 tcgctcggtg gggcctgcgg accaaaggtc cgcagacggc agagctctgc tctgccggcc 4680 ccaccgagcg agcgagcgcg cagagaggga gtgggcaa 4718 <210> 7 <211> 4675 <212> DNA <213> adeno-associated virus serotype 2

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015 <400> 7

     ttggccactc cctctctgcg cgctcgctcg ctcactgagg • ccgggcgacc : aaaggtcgcc 60 cgacgcccgg gctttgcccg ggcggcctca gtgagcgagc gagcgcgcag agagggagtg 120 gccaactcca tcactagggg ttcctggagg ggtggagtcg tgacgtgaat taegtcatag 180 ggttagggag gtcctgtatt agaggtcacg tgagtgtttt gcgacatttt gcgacaccat 240 gtggtcacgc tgggtattta agcccgagtg agcacgcagg gtetceattt tgaagcggga 300 ggtttgaacg cgcagccgcc atgccggggt tttacgagat tgtgattaag gtccccagcg 360 accttgacgg gcatctgccc ggcatttctg acagctttgt gaaotgggtg gccgagaagg 420 aatgggagtt gccgccagat tctgacatgg atctgaatct gattgagcag gcacccctga 480 ccgtggccga gaagctgcag egcgaettte tgacggaatg gcgccgtgtg agtaaggcee 540 cggaggccc t tttctttgtg caatttgaga agggagagag ctacttccac atgcacgtgc 600 tcgtggaaac caccggggtg aaatccatgg ttttgggacg tttcctgagt cagattcgcg 660 aaaaactgat tcagagaatt taccgcggga tcgagccgac tttgccaaac tggttcgcgg 720 tcacaaagac cagaaatggc gccggaggcg ggaacaaggt ggtggatgag tgctacatcc 780 ccaattactt gctccccaaa acccagcctg agetccagtg ggcgtggact aatatggaac 840 agtatttaag cgcctgtttg aatctcacgg agcgtaaacg gttggtggcg cagcatctga 900 cgcacgtgtc gcagacgcag gagcagaaca aagagaatca gaatcccaat tctgatgcgc 960 cggtgatcag atcaaaaact teagceaggt acatggagct ggtcgggtgg ctcgtggaca 1020 aggggattac ctcggagaag cagtggatcc aggaggacca ggcctcatac atctccttca 1080 atgcggcctc caactcgcgg tcccaaatca aggctgectt ggacaatgcg ggaaagatta 1140 tgagcetgac taaaaccgcc cccgactacc tggtgggcca gcagcccgtg gaggacattt 1200 ccagcaatcg gatttataaa attttggaac taaacgggta cgatccccaa tatgcggctt 1260 ccgtctttct gggatgggcc acgaaaaagt tcggcaagag gaacaccatc tggctgtttg 1320 ggcctgcaac taccgggaag accaacatcg cggaggccat agcccacact gtgcccttct 1380 acgggtgcgt aaactggacc aatgagaact ttcccttcaa cgactgtgtc gacaagatgg 1440 tgatctggtg ggaggagggg aagatgaccg ccaaggtcgt ggagtcggcc aaagccattc 1500 tcggaggaag caaggtgcgc gtggaccaga aatgcaagtc ctcggcccag atagacccga 1560 ctcccgtgat cgtcacctcc aacaccaaca tgtgcgccgt gattgacggg aactcaacga 1620 ccttcgaaca ccagcagccg ttgcaagacc ggatgttcaa atttgaactc acccgccgtc 1680 tggatcatga ctttgggaag gtcaccaagc aggaagtcaa agactttttc cggtgggcaa 1740 aggatcacgt ggttgaggtg gagcatgaat tctacgtcaa aaagggtgga gccaagaaaa 1800 gacccgcccc cagtgacgca gatataagtg agcccaaacg ggtgcgcgag tcagttgcgc 1860 agccatcgac gtcagacgcg gaagcttcga tcaactacgc agacaggtac caaaacaaat 1920

     WO 03/042397

     PCT/US02/33629 cgtgggcatg aatctgatgc tgtttccctg cagacaatgc gagagaatga 1980 aaatatctgc ttcactcacg gacagaaaga ctgtttagag tgctttcccg 2040 tcaacccgtt tctgtcgtca aaaaggcgta tcagaaactg tgctacattc 2100

     2015258271 20 Nov 2015 gttctcgtca atcagaattc tgtcagaatc atcatatcat tggatgactg cttccagatt cctggcccac cttcctgggt gaggcagacg agacaacccg agatacgtct tgaacctctg agagcactct tgcaagaaaa gcctctcgga cagtggcgca aaattggcat ctgggccctg ctcgaacgac attcoactgc ccgacccaag tgacggtacg ggagtaccag agcagacgtc agtaggacgc aaacaacttt cagccagagt cagaacaaac agcgagtgac gcgagtatca caagtaccac cgatgaagaa

     gggaaaggtg ccagacgctt gcactgcctg cgatctggtc aatgtggatt 2160 catctttgaa caataaatga tttaaatcag gtatggctgc cgatggttat 2220 ggctcgagga cactctctct gaaggaataa gacagtggtg gaagctcaaa 2280 caccaccaaa gcccgcagag cggcataagg acgacagcag gggtcttgtg 2340 acaagtacct cggacccttc aacggactcg acaagggaga gccggtcaac 2400 ccgcggccct cgagcacgta caaagcctac gaccggcagc tcgacagcgg 2460 tacctcaagt acaaccacgc cgacgcggag tttcaggagc gccttaaaga 2520 tttgggggca acctcggacg agcagtcttc caggcgaaaa agagggttct 2580 ggcctggttg aggaacctgt taagacggct ccgggaaaaa agaggccggt 2640 cctgtggagc cagactcctc ctcgggaacc ggaaaggcgg gccagcagcc 2700 agattgaatt ttggtcagac tggagacgca gactcagtac ctgaccccca 2760 cagccaccag cagccccctc tggtctggga actaatacga tggctacagg 2820 ccaatggcag acaataacga gggcgccgac ggagtgggta attcctccgg 2880 tgcgattcca catggatggg cgacagagtc atcaccacca gcacccgaac 2940 cccacctaca acaaccacct ctacaaacaa atttccagcc aatcaggagc 3000 aatcactact ttggctacag caccccttgg gggtattttg acttcaacag 3060 cacttttcac cacgtgactg gcaaagactc atcaacaaca actggggatt 3120 agactcaact tcaagctctt taacattcaa gtcaaagagg tcacgcagaa 3180 acgacgattg ccaataacct taccagcacg gttcaggtgt ttactgactc 3240 ctcccgtacg tcctcggctc ggcgcatcaa ggatgcctcc cgccgttccc 3300 ttcatggtgc cacagtatgg atacctcacc ctgaacaacg ggagtcaggc 3360 tcttcatttt actgcctgga gtactttcct tctcagatgc tgcgtaccgg 3420 accttcagct acacttttga ggacgttcct ttccacagca gctacgctca 3480 ctggaccgtc tcatgaatcc tctcatcgac cagtacctgt attacttgag 3540 actccaagtg gaaccaccac gcagtcaagg cttcagtttt ctcaggccgg 3600 attcgggacc agtctaggaa ctggcttcct ggaccctgtt accgccagca 3660 aagacatctg cggataacaa caacagtgaa tactcgtgga ctggagctac 3720 ctcaatggca gagactctct ggtgaatccg gccatggcaa gccacaagga 3780 aagttttttc ctcagagcgg ggttctcatc tttgggaagc aaggctcaga 3840

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     gaaaacaaat gtgaacattg aaaaggtcat gattacagac gaagaggaaa tcggaacaac 3900 caatcccgtg gctacggagc agtatggttc tgtatctacc aacctccaga gaggcaacag 3960 acaagcagct accgcagatg tcaacacaca aggcgttctt ccaggcatgg tctggcagga 4020 cagagatgtg taccttcagg ggcccatctg ggcaaagatt ccacacacgg acggacattt 4080 tcacccctct cccctcatgg gtggattcgg acttaaacac cctcctccac agattctcat 4140 caagaacacc ccggtacctg cgaatccttc gaccaccttc agtgcggcaa agtttgcttc 4200 cttcatcaca cagtactcca cgggacacgg tcagcgtgga gatcgagtgg gagctgcaga 4260 aggaaaacag caaacgctgg aatcccgaaa ttcagtacac ttccaactac aacaagtctg 4320 ttaatcgtgg acttaccgtg gatactaatg gcgtgtattc agagcctcgc cccattggca 4380 ccagatacct gactcgtaat ctgtaattgc ttgttaatca ataaaccgtt taattcgttt 4440 cagttgaact ttggtctctg cgtatttctt tcttatctag tttccatggc tacgtagata 4500 agtagcatgg cgggttaatc attaactaca aggaacccct agtgatggag ttggccactc 4560 cctctctgcg cgctcgctcg ctcactgagg ccgggcgacc aaaggtcgcc cgacgcccgg 4620 gctttgcccg ggcggcctca gtgagcgagc gagcgcgcag agagggagtg gccaa 4675

     <210> 8 <211> 4726 <212> DNA <213> adeno-associated virus serotype 3 <400> 8

     ttggccactc cctctatgcg cactcgctcg ctcggtgggg cctggcgacc aaaggtcgcc 60 agacggacgt gctttgcacg tccggcccca ccgagcgagc gagtgcgcat agagggagtg 120 gccaactcca tcactagagg tatggcagtg acgtaacgcg aagcgcgcga agcgagacca 180 cgcctaccag ctgcgtcagc agtcaggtga cccttttgcg acagtttgcg acaccacgtg 240 gccgctgagg gtatatattc tcgagtgagc gaaccaggag ctccattttg accgcgaaat 300 ttgaacgagc agcagccatg ccggggttct acgagattgt cctgaaggtc ccgagtgacc 360 tggacgagcg cctgccgggc atttctaact cgtttgttaa ctgggtggcc gagaaggaat 420 gggacgtgcc gccggattct gacatggatc cgaatctgat tgagcaggca cccctgaccg 480 tggccgaaaa gcttcagcgc gagttcctgg tggagtggcg ccgcgtgagt aaggccccgg 540 aggccctctt ttttgtccag ttcgaaaagg gggagaccta cttccacctg cacgtgctga 600 ttgagaccat cggggtcaaa tccatggtgg tcggccgcta cgtgagccag attaaagaga 660 agctggtgac ccgcatctac cgcggggtcg agccgcagct tccgaactgg ttcgcggtga 720 ccaaaacgcg aaatggcgcc gggggcggga acaaggtggt ggacgactgc tacatcccca 780 actacctgct ccccaagacc cagcccgagc tccagtgggc gtggactaac atggaccagt 840

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     atttaagcgc ctgtttgaat ctcgcggagc gtaaacggct ggtggcgcag r catctgacgc 900 acgtgtcgca gacgcaggag cagaacaaag agaatcagaa . ccccaattct . gacgcgccgg 960 tcatcaggtc aaaaacctca gccaggtaca tggagctggt cgggtggctg ' gtggaccgcg 1020 ggatcacgtc agaaaagcaa tggattcagg aggaccaggc ctcgtacatc tccttcaacg 1080 ccgcctccaa ctcgcggtcc cagatcaagg ccgcgctgga caatgcctcc aagatcatga 1140 gcctgacaaa gacggctccg gactacctgg tgggcagcaa cccgccggag gacattacca 1200 aaaatcggat ctaccaaatc ctggagctga acgggtacga tccgcagtac gcggcctccg 1260 tcttcctggg ctgggcgcaa aagaagttcg ggaagaggaa caccatctgg ctctttgggc 1320 cggccacgac gggtaaaacc aacatcgcgg aagccatcgc ccacgccgtg cccttctacg 1380 gctgcgtaaa ctggaccaat gagaactttc ccttcaacga ttgcgtcgac aagatggtga 1440 tctggtggga ggagggcaag atgacggcca aggtcgtgga gagcgccaag gccattctgg 1500 gcggaagcaa ggtgcgcgtg gaccaaaagt gcaagtcatc ggcccagatc gaacccactc 1560 ccgtgatcgt cacctccaac accaacatgt gcgccgtgat tgacgggaac agcaccacct 1620 tcgagcatca gcagccgctg caggaccgga tgtttgaatt tgaacttacc cgccgtttgg 1680 accatgactt tgggaaggtc accaaacagg aagtaaagga ctttttccgg tgggcttccg 1740 atcacgtgac tgacgtggct catgagttct acgtcagaaa gggtggagct aagaaacgcc 1800 ccgcctccaa tgacgcggat gtaagcgagc caaaacggga gtgcacgtca cttgcgcagc 1860 cgacaacgtc agacgcggaa gcaccggcgg actacgcgga caggtaccaa aacaaatgtt 1920 ctcgtcacgt gggcatgaat ctgatgcttt ttccctgtaa aacatgcgag agaatgaatc 198 0 aaatttccaa tgtctgtttt acgcatggtc aaagagactg tggggaatgc ttccctggaa 2040 tgtcagaatc tcaacccgtt tctgtcgtca aaaagaagac ttatcagaaa ctgtgtccaa 2100 ttcatcatat cctgggaagg gcacccgaga ttgcctgttc ggcctgcgat ttggccaatg 2160 tggacttgga tgactgtgtt tctgagcaat aaatgactta aaccaggtat ggctgctgac 2220 ggttatcttc cagattggct cgaggacaac ctttctgaag gcattcgtga gtggtgggct 2280 ctgaaacctg gagtccctca acccaaagcg aaccaacaac accaggacaa ccgtcggggt 2340 cttgtgcttc cgggttacaa atacctcgga cccggtaacg gactcgacaa aggagagccg 2400 gtcaacgagg cggacgcggc agccctcgaa cacgacaaag cttacgacca gcagctcaag 2460 gccggtgaca acccgtacct caagtacaac cacgccgacg ccgagtttca ggagcgtctt 2520 caagaagata cgtcttttgg gggcaacctt ggcagagcag tcttccaggc caaaaagagg 2580 atccttgagc ctcttggtct ggttgaggaa gcagctaaaa cggctcctgg aaagaagggg 2640 gctgtagatc agtctcctca ggaaccggac tcatcatctg gtgttggcaa atcgggcaaa 2700 cagcctgcca gaaaaagact aaatttcggt cagactggag actcagagtc agtcccagac 2760

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     cctcaacctc tcggagaacc accagcagcc cccacaagtt tgggatctaa i tacaatggct 2320 tcaggcggtg gcgcaccaat ggcagacaat aacgagggtg f ccgatggagt ; gggtaattcc 2330 tcaggaaatt ggcattgcga ttcccaatgg ctgggcgaca . gagtcatcac caccagcacc 2940 agaacctggg ccctgcccac ttacaacaac catctctaca agcaaatctc cagccaatca 3000 ggagcttcaa acgacaacca ctactttggc tacagcaccc cttgggggta ttttgacttt 3050 aacagattcc actgccactt ctcaccacgt gactggcagc gactcattaa caacaactgg 3120 ggattccggc ccaagaaact cagcttcaag ctcttcaaca tccaagttag aggggtcacg 3130 cagaacgatg gcacgacgac tattgccaat aaccttacca gcacggttca agtgtttacg 3240 gactcggagt atcagctccc gtacgtgctc gggtcggcgc accaaggctg tctcccgccg 3300 tttccagcgg acgtcttcat ggtccctcag tatggatacc tcaccctgaa caacggaagt 3350 caagcggtgg gacgctcatc cttttactgc ctggagtact tcccttcgca gatgctaagg 3420 actggaaata acttccaatt cagctatacc ttcgaggatg taccttttca cagcagctac 3430 gctcacagcc agagtttgga tcgcttgatg aatcctctta ttgatcagta tctgtactac 3540 ctgaacagaa cgcaaggaac aacctctgga acaaccaacc aatcacggct gctttttagc 3500 caggctgggc ctcagtctat gtctttgcag gccagaaatt ggctacctgg gccctgctac 3560 cggcaacaga gactttcaaa gactgctaac gacaacaaca acagtaactt tccttggaca 3720 gcggccagca aatatcatct caatggccgc gactcgctgg tgaatccagg accagctatg 3730 gccagtcaca aggacgatga agaaaaattt ttccctatgc acggcaatct aatatttggc 3340 aaagaaggga caacggcaag taacgcagaa ttagataatg taatgattac ggatgaagaa 3900 gagattcgta ccaccaatcc tgtggcaaca gagcagtatg gaactgtggc aaataacttg 3960 cagagctcaa atacagctcc cacgactgga actgtcaatc atcagggggc cttacctggc 4020 atggtgtggc aagatcgtga cgtgtacctt caaggaccta tctgggcaaa gattcctcac 4030 acggatggac actttcatcc ttctcctctg atgggaggct ttggactgaa acatccgcct 4140 cctcaaatca tgatcaaaaa tactccggta ccggcaaatc ctccgacgac tttcagcccg 4200 gccaagtttg cttcatttat cactcagtac tccactggac aggtcagcgt ggaaattgag 4260 tgggagctac agaaagaaaa cagcaaacgt tggaatccag agattcagta cacttccaac 4320 tacaacaagt ctgttaatgt ggactttact gtagacacta atggtgttta tagtgaacct 4330 cgccctattg gaacccggta tctcacacga aacttgtgaa tcctggttaa tcaataaacc 4440 gtttaattcg tttcagttga actttggctc ttgtgcactt ctttatcttt atcttgtttc 4500 catggctact gcgtagataa gcagcggcct gcggcgcttg cgcttcgcgg tttacaactg 4560 ctggttaata tttaactctc gccatacctc tagtgatgga gttggccact ccctctatgc 4620 gcactcgctc gctcggtggg gcctggcgac caaaggtcgc cagacggacg tgctttgcac 4 68 0

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015 gtccggcccc accgagcgag cgagtgcgca tagagggagt ggccaa 4726 <210> 9 <211> 3098 <212> DNA <213> new AAV serotype, clone 42.2 <400> 9

     gaattcgccc tttctacggc tgcgtcaact ggaccaatga gaactttccc ttcaacgatt 60 gcgtcgacaa gatggtgatc tggtgggagg agggcaagat gacggccaag gtcgtggagt 120 ccgccaaggc cattctcggc ggcagcaagg tgcgcgtgga ccaaaagtgc aagtcttccg 180 cccagatcga tcccaccccc gtgatcgtca cttccaacac caacatgtgc gctgtgattg 240 acgggaacag caccaccttc gagcaccagc agccgttaca agaccggatg ttcaaatttg 300 aactcacccg ccgtctggag cacgactttg gcaaggtgac aaagcaggaa gtcaaagagt 360 tcttccgctg ggcgcaggat cacgtgaccg aggtggcgca tgagttctac gtcagaaagg 420 gtggagccaa caagagaccc gcccccgatg acgcggataa aagcgagccc aagcgggcct 480 gcccctcagt cgcggatcca tcgacgtcag acgcggaagg agctccggtg gactttgccg 540 acaggtacca aaacaaatgt tctcgtcacg cgggcatgct tcagatgctg tttccctgca 600 agacatgcga gagaatgaat cagaatttca acatttgctt cacgcacggg accagagact 660 gttcagaatg tttccccggc gtgtcagaat ctcaaccggt cgtcagaaag aggacgtatc 720 ggaaactctg tgccattcat catctgctgg ggcgggctcc cgagattgct tgctcggcct 780 gcgatctggt caacgtggac ctggatgacc gtgtttctga gcaataaatg acttaaacca 840 ggtatggctg ccgatggtta tcttccagat tggctcgagg acaacctctc tgagggcatt 900 cgcgagtggt gggacttgaa acctggagcc ccgaaaccca aagccaacca gcaaaagcag 960 gacgacggcc ggggtctggt gcttcctggc tacaagtacc tcggaccctt caacggactc 1020 gacaagggag agccggtcaa cgaggcagac gccgcggccc tcgagcacga caaggcctac 1080 gacaagcagc tcgagcaggg ggacaacccg tacctcaagt acaaccacgc cgacgccgag 1140 tttcaggagc gtcttcaaga agatacgtct tttgggggca acctcgggcg agcagtcttc 1200 caggccaaga agcgggttct cgaacctctc ggtctggttg aggaaggcgc taagacggct 1260 cctggaaaga agagacccat agaatccccc gactcctcca cgggcatcgg caagaaaggc 1320 cagcagcccg ctaaaaagaa gctcaacttt gggcagactg gcgactcaga gtcagtgccc 1380 gacccccaac ctctcggaga acctcccgcc gcgccctcag gtctgggatc tggtacaatg 1440 gctgcaggcg gtggcgcacc aatggcagac aataacgaag gcgccgacgg agtgggtaat 1500 gcctccggaa attggcattg cgattccaca tggctgggcg acagagtcat caccaccagc 1560 acccgcacct gggccctgcc cacctacaac aaccacctct acaagcagat atcaagtcag 1620 agcggggcta ccaacgacaa ccacttcttc ggctacagca ccccctgggg ctattttgac 1680

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     ttcaacagat tccactgcca cttctcacca cgtgactggc agcgactcat caacaacaac 1740 tggggattcc ggcccagaaa gctgcggttc aagttgttca acatc'caggt caaggaggtc 1800 acgacgaacg acggcgttac gaccatcgct aataacctta ccagcacgat tcaggtcttc I860 tcggactcgg agtaccaact gccgtacgtc ctcggctctg cgcaccaggg ctgcctccct 1920 ccgttccctg cggacgtgtt catgattcct cagtacggat atctgactct aaacaacggc 1980 agtcagtctg tgggacgttc ctccttctac tgcctggagt actttccttc tcagatgctg 2040 agaacgggca ataactttga attcagctac acctttgagg aagtgccttt ccacagcagc 2100 tatgcgcaca gccagagcct ggaccggctg atgaatcccc tcatcgacca gtacctgtac 2160 tacctggccc ggacccagag cactacgggg tccacaaggg agctgcagtt ccatcaggct 2220 gggcccaaca ccatggccga gcaatcaaag aactggctgc ccggaccctg ttatcggcag 2280 cagagactgt caaaaaacat agacagcaac aacaacagta actttgcctg gaccggggcc 2340 actaaatacc atctgaatgg tagaaattca ttaaccaacc cgggcgtagc catggccacc 2400 aacaaggacg acgaggacca gttctttccc atcaacggag tgctggtttt tggcgaaacg 2460 ggggctgcca aeaagacaae gctggaaaac gtgctaatga ccagcgagga ggagatcaaa 2520 accaccaatc ccgtggctac agaagaatac gfftgtggtct ccagcaacct gcaatcgtct 2580 acggccggac cccagacaca gactgtcaac agccaggggg ctctgcccgg catggtctgg 2 64 0 cagaaccggg acgtgtacct gcagggtccc atctgggcca aaattcctca cacggacggc 2700 aactttcacc cgtctcccct gatgggcgga tttggactca aacacccgcc tcctcaaatt 2760 cteatcaaaa acaccccggt acctgctaat cctccagagg tgtttactcc tgccaagttt 2820 gcctcattta tcacgcagta cagcaccggc caggtcagcg tggagatcga gtgggaactg 2880 acagcaaacg etggaatcca gagattcagt acacctcaaa ttatgccaag 2940 tctaataatg tggaatttgc tgtcaacaac gaaggggttt atactgagcc tcgccccatt 3000 ggcacccgtt acctcacccg taacctgtaa ttgcctgtta atcaataaac cggttaattc 3 060 gtttcagttg aactttggtc tctgcgaagg gcgaattc 3098 <210> 10 <211> 3098 <212> DNA <213> new AAV serotype, clone 16.3 <400> 10 gaattcgccc ttcgcagaga ccaaagttca actgaaacga atcaaccggt ttattgatta 60 acaagtaatt acaggttacg ggtgaggtaa cgggtgccaa tggggcgagg ctcagtataa 120 accccttcgt tgttgacagc aaattccaca ttattagact tggcataatt tgaggtgtac 180 tgaatctctg gattccagcg tttgctgttt tctttctgca gttcccactc gatctccacg 240

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     ctgacctggc cggtgctgta ctgcgtgata aatgaggcaa actaggcagg ' agtaaacacc 300 cctggaggat tagcaggtac cggggtgttt ttgatgagaa tttgaggagg ^: cgggtgtttg 360 agtccaaatc cgcccatcag gggagacggg tgaaagttgc cgtccgtgtg aggaattttg 420 gcccagatgg gaccctgcag gtacacgtcc cggttctgcc agaccatgcc gggcagagcc 480 ccctggctgt tgacagtctg tgtctggggt ccggccgtag acgattgcag gttgctggag 540 accacaccgt attcttctgt agccacggga ttggtggttt tgatctcctc ctcgctggtc 600 attagcacgt tttccagcgt tgtcttgttg gcagcccccg ttttgccaaa aaccagcact 660 ccgttgatgg gaaagaactg gccctcgtcg tccttgttgg tggccatggc tacgcccggg 720 ttggttaatg aatttctacc attcagatgg tatttagtgg ccccggtcca ggcaaagtta 780 ctgttgttgt tgctgtctat gttttttgac agtctctgct gccgataaca gggtccgggc 840 agccagttct ttgattgctc ggccatggtg ttgggcccag cctgatggaa ctgcagctcc 900 cttgtggacc ccgtagtgct ctgggtccgg gccaggtagt acaggtactg gtcgatgagg 9 60 ggattcatca gccggtccag gctctggctg tgcgcatagc tgctgtggaa aggcacttcc 1020 tcaaaggtgt agctgaattc aaagttattg cccgttctca gcatctgaga aggaaagtac 1080 tccaggcagt agaaggagga acgtcccata gactgactgc cgttgtttag agtcagatat 1140 ccgtactgag gaatcatgaa cacgtccgca gggaacggag ggaggcagcc ctggtgcgca 1200 gagccgagga cgtacggcag ttggtactcc gagtccgaga agacctgaat cgtgctggta 1260 aggttattag cgatggtcgt aacgccgtcg ttcgtcgtga cctccttgac ctggatgttg 1320 aacaacttga accgcagctt tctgggccgg aatccccagt tgttgttgat gagtcgctgc 1380 cagtcacgtg gtgagaagtg gcagtggaat ctgttgaagt caaaatagcc ccagggggtg 1440 ctgtagccga agaagtggtt gtcgttggta gccccgctct gacttgatat ctgcttgtag 1500 aggtggttgt tgtaggtggg cagggcccag gtgcgggtgc tggtggtgat gactctgtcg 1560 cccagccatg tggaatcgca atgccaattt ccggaggcat tacccactcc gtcggcgcct 1620 tcgttattgt ctgccattgg tgcgccaccg cctgcagcca ttgtaccaga tcceagacct 1680 gagggcgcgg cgggaggttc tccgagaggt tgggggtcgg gcactgactc tgagtcgcca 1740 gtctgcccaa agttgagctt ctttttagcg ggctgctggc ctttcttgcc gatgcccgtg 1800 gaggagtcgg gggattctat gggtctcttc tttccaggag ccgtcttagc gccttcctca 1860 accagaccga gaggttcgag aacccgcttc ttggcctgga agactgctcg cccgaggttg 1920 cccccaaaag acgtatcttc ttgaagacgc tcctgaaact cagcgtcggc gtggttgtac 1980 ttgaggtacg ggttgtcccc ctgctcgagc tgcttgtcgt aggccttgtc gtgctcgagg 2040 gccgcggcgt ctgcctcgtt gaccggctct cccttgtcga gtccgttgaa gggtccgagg 2100 tacttgtagc caggaagcac cagaccccgg ccgtcgtcct gcttttgctg gttggctttg 2160

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     ggtttegggg ctecaggttt caagtcccac cactcgcgaa tgccctcaga gaggttgtcc 2220 tcgagccaat ctggaagata accatcggca gccatacctg gtttaagtca tttattgctc 2280 agaaacacag tcatccaggt ccacgttgac eagatcgcag gccgagcaag caatctcggg 2340 agcccgcccc agcagatgat gaatggcaca gagtttccga tacgtcctet ttctgacgac 2400 cggttgagat tctgacacgc cggggaaaca ttctgaacag tctctggtcc egtgegtgaa 2460 gcaaatgttg aaattctgat tcattctctc gcatgtcttg cagggaaaca gcatctgaag 2520 catgcccgcg tgacgagaac atttgttttg gtacctgtcg gcaaagtcca ccggagctcc 2580 ttcegcgtct gacgtcgatg gatecgcgac tgaggggcag gcccgcttgg gctegetttt 2640 atccgcgtca tcgggggcgg gcctcttgtt ggctccaccc tttctgacgt agaactcatg 2700 cgccacctcg gtcacgtgat cctgegceea gcggaagaac tctttgactt cctgctttgt 2760 caccttgcca aagtcctgct ccagacggcg ggtgagttca aatttgaaca tccggtcttg 2820 taacggctgc tggtgctcga aggtggtgct gttcecgtca atcacggcgc acatgttggt 2880 gttggaagtg acgatcacgg gggtgggatc gatctgggcg gacgacttgc acttttggtc 2940 cacgcgcacc ttgetgccgc cgagaatggc ettggcggac tccacgacct tggeegtcat 3000 ettgcectcc tcccaccaga tcaccatctt gtcgacgcaa tcgttgaagg gaaagttetc 3060 attggtccag ttgacgcagc cgtagaaagg gcgaattc 3098

     <210>. 11 <211> 3121

     <212> DMA <213> new AAV serotype, clone 29.3 <400> 11 gaattcgcce ttcgeagaga eeaaagttca actgaaacga atcaaccggt ttattgatta 60 acaagcaatt acagattacg ggtgaggtaa cgggtgccga tggggcgagg ctcagaataa 120 gtgccatctg tgttaacagc aaagtccaca tttgtagatt tgtagtagtt ggaagtgtat 180 tgaatctctg ggttccagcg tttgctgttt tctttctgca gctcccattc aatttccacg 240 ctgacctgtc eggtgctgta ctgcgtgatg aacgacgcca gcttagcttg actgaaggta 300 gttggaggat ccgcgggaac aggtgtattc ttaatcagga tctgaggagg cgggtgtttc 360 agtccaaagc cccccatcag eggcgaggga tgaaagtttc cgtccgtgtg aggaatcttg 420 gcccagatag gaccctgeag gtacacgtcc cggttctgce agaccatgcc aggtaaggct 480 ccttgactgt tgacggcccc tacaatagga gcggcgtttt gctgttgcag gttatcggcc 540 aecacgccgt actgttctgt ggccactggg ttggtggttt taatttcttc ctcactggtt 600 agcataacgc tgetatagtc cacgttgcct tttccagete cctgtttccc aaacattaag 660 aeteegctgg acggaaaaaa tegctcttcg tcgtccttgt gggttgccat agcgacaccg 720 ggatttacca gagagtctct gccattcaga tgatacttgg tggcaccggt ccaggcaaag 780

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     ttgctgttgt tattttgcga cagtgtcgtg gagacgcgtt gctgccggta gcagggcccg 840 ggtagccagt ttttggcctg agccgacatg ttattaggcc cggcctgaga aaatagcaac 900 tgctgagttc ctgcggtacc tcccgtggac tgagtccgag acaggtagta caggtactgg 960 tcgatgaggg ggttcatcag ccggtccagg ctttggctgt gcgcgtagct gctgtgaaaa 1020 ggcacgtcct caaactggta gctgaactca aagttgttgc ccgttctcag catttgagaa 108 0 ggaaagtact ccaggcagta gaaggaggaa cggcccacgg cctgactgcc attgttcaga 1140 gtcaggtacc cgtactgagg aatcatgaag acgtccgccg ggaacggagg caggcagccc 1200 tggcgcgcag agccgaggac gtacgggagc tggtattccg agtccgtaaa gacctgaatc 12 60 gtgctggtaa ggttattggc gatggtcttg gtgccttcat tctgcgtgac ctccttgacc 1320 tggatgttga agagcttgaa gttgagtctc ttgggccgga atccccagtt gttgttgatg 1380 agtcgctgcc agtcacgtgg tgagaagtgg cagtggaatc tgttaaagtc aaaatacccc 144 0 cagggggtgc tgtagccgaa gtaggtgttg tcgttggtgc ttcctcccga agtcccgttg 1500 gagatttgct tgtagaggtg gttgttgtag gtggggaggg cccaggttcg ggtgctggtg 1560 gtgatgactc tgtcgcccag ccatgtggaa tcgcaatgcc aattfccctga ggaactaccc 1620 actccgtcgg cgccttcgtt attgtctgcc attggagcgc caccgcctgc agccattgta 1680 ccagatccca gaccagaggg gcctgcgggg ggttctccga ttggttgagg gtcgggcact 1740 gactctgagt cgccagtctg cccaaagttg agtctctttt tcgcgggctg ctggcctttc 1800 ttgccgatgc ccgtagtgga gtctggagaa cgctggggtg atggctctac cggtctcttc 1860 tttccaggag ccgtcttagc gccttcctca accagaccga gaggttcgag aacccgcttc 1920 ttggcctgga agactgctcg tccgaggttg cccccaaaag acgtatcttc ttgcagacgc 1980 tcctgaaact cggcgtcggc gtggttatac cgcaggtacg gattgtcacc cgctttgagc 2040 tgctggtcgt aggccttgtc gtgctcgagg gccgctgcgt ccgccgcgtt gacgggctcc 2100 cccttgtcga gtccgttgaa gggtccgagg tacttgtagc caggaagcac cagaccccgg 2160 ccgtcgtcct gcttttgctg gttggctttg ggcttcgggg ctccaggttt cagcgcccac 2220 cactcgcgaa tgccctcaga gaggttgtcc tcgagccaat ctggaagata accatcggca 2280 gccatacctg atctaaatca tttattgttc aaagatgcag tcatccaaat ccacattgac 2340 cagatcgcag gcagtgcaag cgtctggcac ctttcccatg atatgatgaa tgtagcacag 2400 tttctgatac gcctttttga cgacagaaac gggttgagat tctgacacgg gaaagcactc 2460 taaacagtct ttctgtccgt gagtgaagca gatatttgaa ttctgattca ttctctcgca 2520 ttgtctgcag ggaaacagca tcagattcat gcccacgtga cgagaacatt tgttttggta 2580 cctgtccgcg tagttgatcg aagcttccgc gtctgacgtc gatggctgcg caactgactc 2640 gcgcacccgt ttgggctcac' ttatatctgc gtcactgggg gcgggtcttt tcttggctcc 2700

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     accctttttg acgtagaatt catgctccac ctcaaccacg tgatcctttg cccaccggaa 2760 aaagtctttg acttcctgct tggtgacctt cccaaagtca tgatccagac ggcgggtgag 2820 ttcaaatttg aacatccggt cttgcaacgg ctgctggtgt tcgaaggtcg ttgagttccc 2880 gtcaatcacg gcgcacatgt tggtgttgga ggtgacgatc acgggagtcg ggtctatctg 2940 ggccgaggac ttgcatttct ggtccacgcg caccttgctt cctccgagaa tggctttggc 3000 cgactccacg accttggcgg tcatcttccc ctcctcccac cagatcacca tcttgtcgac 3060 acagtcgttg aagggaaagt tctcattggt ccagttgacg cagccgtaga agggcgaatt 3120

     c 3121 <210> 12 <211> 3121 <212> DHA <213> new AAV serotype, clone 29.4 <400> 12

     gaattcgccc ttctacggct gcgtcaactg gaccaatgag aactttccct tcaacgactg 60 tgtcgacaag atggtgatct ggtgggagga ggggaagatg accgccaagg tcgtggagtc 120 ggccaaagcc attctcggag gaagcaaggt gcgcgtggac cagaaatgca agtcctcggc 180 ccagatagac ccgactcccg tgatcgtcac ctccaacacc aacatgtgcg ccgtgattga 240 cgggaactca acgaccttcg aacaccagca gccgttgcaa gaccggatgt tcaaatttga 300 actcacccgc cgtctggatc atgactttgg gaaggtcacc aagcaggaag tcaaagactt 360 tttccggtgg gcaaaggatc acgtggttga ggtggagcac gaattctaeg tcaaaaaggg 420 tggagccaag aaaagacccg cccccagtga cgcagatata agtgagccca aacgggtgcg 480 cgagtcagtt gcgcagccat cgaogtcaga cgcggaagct tcgatcaact acgcagacag 540 gtaccaaaac aaatgttctc gtcacgcggg catgaatotg atgctgtttc cctgcagaea 600 atgcgagaga atgaatcaga attcaaatat ctgcttcact cacggacaga aagactgttt 660 agagtgcttt cccgtgtcag aatctcaacc cgtttctgtc gtcaaaaagg cgtatcagaa 720 actgtgctac attcatcata tcatgggaaa ggtgccagac gcttgcactg cctgcgatct 780 ggtcgatgtg gatttggatg actgcatctt tgaacaataa atgatttaaa tcaggtatgg 840 ctgccgatgg ttatcttcca gattggctcg aggacaacct ctctgagggc attcgcgagt 900 ggtgggcgct gaaacctgga gccccgaagc ccaaagccaa ccagcaaaag oaggacggcg 960 gccggggtct ggtgcttcct ggctacaagt acctcggacc cttcaacgga ctcgacaagg 1020 gggagcccgt caacgcggcg gacgcagcgg ccctcgagca cgacaaggcc tacgaccagc 1080 agctcaaagc gggtgacaat ccgtaoctgc ggtataacca cgccgacgcc gagtttcagg 1140 agcgtctgca agaagatacg tcttttgggg gcaacctcgg gcgagcagtc ttccaggcca 1200

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     agaagcgggt tctcgaacct ctcggtctgg ttgaggaagg cgctaagacg ' gctcctggaa 1260 agaagagacc ggtagagcca tcaccccagc gttctccaga . ctcctctacg ggcatcggca 1320 agaaaggcca gcagcccgcg aaaaagagac tcaactttgg gcagactggc gactcagagt 1380 cagtgcccga ccctcaacca atcggagaac cccccgcagg cccctctggt ctgggatctg 1440 gtacaatggc tgcaggcggt ggcgctccaa tggcagacaa taacgaaggc gccgacggag 1500 tgggtagttc ctcaggaaat tggcattgcg attccacatg gctgggcgac tgagtcatca 1560 ccaccagcac ccgaacctgg gccctcccca cctacaacaa ccacctctac aagcaaatct 1620 ccaacgggac ttcgggagga agcaccaacg acaacaccta cttcggctac agcaccccct 1680 gggggtattt tgactttaac agattccact gccacttctc accacgtgac tggcagcgac 1740 tcatcaacaa caactgggga ttccggccca agagactcaa cttcaagctc ttcaacatcc 1800 aggtcaagga ggtcacgcag aatgaaggca ccaagaccat cgccaataac cttaccagca 1860 cgattcaggt ctttacggac tcggaatacc agctcccgta cgtcctcgge tctgcgcacc 1920 agggctgcct gcctccgttc ccggcggacg tcttcatgat tcctcagtac gggtacctga 1980 ctctgaacaa tggcagtcag gccgtgggcc gttcctcctt ctactgcctg gagtactttc 2040 cttcteaaat gctgagaacg ggcaacaact ttgagttcag ctaccagttt gaggacgtgc 2100 cttttcacag cagctacgcg cacagccaaa gcctggaccg gctgatgaac cccctcatcg 2160 accagtacct gtactacctg tctcggactc agtccacggg aggtaccgca ggaactcagc 2220 agttgctatt ttctcaggcc gggcctaata acatgtcggc tcaggccaaa aactggctac 2280 ccgggccctg ctaccggcag taacgcgtct ccacgacact gtcgcaaaat aacaacagca 2340 actttgtctg gaccggtgcc accaagtatc atctgaatgg cagagactct ctggtagatc 2400 ccggtgtcgc tatggcaacc cacaaggacg acgaagagcg attttttccg tccagcggag 2460 tcataatgtt tgggaaacag ggagctggaa aagacaacgt ggactatagc agcgtcatgc 2520 taaccagtga ggaagaaatt aaaaccacca acccagtggc cacagaacag tacggcgtgg 2580 tggccgataa cctgcaacag caaaacgccg ctcctattgt aggggccgtc aacagtcaag 2640 gagccttacc tggcatggtc tggcagaacc gggacgtgta cctgcagggt cctacctggg 2700 ccaagattcc tcacacggac ggaaactttc atccctcgcc gctgatggga ggctttggac 2760 tgaaacaccc gcctcctcag atcctgatta agaatacacc tgttcccgcg gatcctccaa 2820 ctaccttcag tcaagctaag ctggcgtcgt tcatcacgca gtacagcacc ggacaggtca 2880 gcgtggaaat tgaatgggag ctgcaggaag aaaacagcaa acgctggaac ccagagattc 2940 aatacacttc caactactac aaatctacaa atgtggactt tgctgttaac acagatggca 3000 cttattctga gcctcgcccc atcggcaccc gttacctcac ccgtaatctg taattgcttg 3060 ttaatcaata aaccggttga ttcgtttcag ttgaactttg gtctctgcga agggcgaatt 3120

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015 c 3121

     <210> <211> <212> <213> 13 3121 DNA new AAV serotype <400> 13

     gaattcgccc ttcgcgagac caaagttcaa ctgaaacgaa tcaaccggtt tattgattaa 60 caagcaatta cagattacgg gtgaggtaac gggtgccgat ggggcgaggc tcagaataag 120 tgccatctgt gttaacagca aagtccacat ttgtagattt gtagtagttg gaagtgtatt 18 0 gaatctctgg gttccagcgt ttgctgtttt ctttctgcag ctcccattca atttccacgc 240 tgacctgtcc ggtgctgtac tgcgtgatga acgacgccag cttagcttga ctgaaggtag 300 ttggaggatc cgcgggaaca ggtgtattct taatcaggat ctgaggaggc gggtgtttca 360 gtccaaagcc tcccatcagc ggcgagggat gaaagtttcc gtccgtgtga ggaatcttgg 42 0 cccagatagg accctgcagg tacacgtccc ggttctgcca gaccatgcca ggtaaggctc 480 cttgactgtt gacggcccct acaataggag cggcgttttg ctgttgcagg ttatcggcca 540 ccacgccgta ctgttctgtg gccactgggt tggtggtttt aatttcttcc tcactggtta 600 gcataacgct gctatagtcc acgttgtctt ttccagctcc ctgtttccca aacattaaga 660 ctccgctgga cggaaaaaat cgctcttcgt cgtccttgtg ggttgccata gcgacaccgg 720 gatttaccag agagtctctg ccattcagat gatacttggt ggcaccggtc caggcaaagt 780 tgctgttgtc attttgcgac agtgtcgtgg agacgcgttg ctgccggtag cagggcccgg 840 gtagccagtt tttggcctga gccgacatgt tattaggccc ggcctgagaa aatagcaact 900 gctgagttcc tgcggtacct cccgtggact gagtccgaga caggtagtac aggtactggt 960 cgatgagggg gttcatcagc cggtccaggc tttggctgtg cgcgtagctg ctgtgaaaag 1020 gcacgtcctc aaactggtag ctgaactcaa agttgttgcc cgttctcagc atttgagaag 1080 gaaagtactc caggcagtag aaggaggaac ggcccacggc ctgactgcca ttgttcagag 1140 tcaggtaccc gtactgagga atcatgaaga cgtccgccgg gaacggaggc aggcagccct 1200 ggtgcgcaga gccgaggacg tacgggagct ggtattccga gtccgtaaag acctgaatcg 1260 tgctggtaag gttattggcg atggtcttgg tgccttcatt ctgcgtgacc tccttgacct 1320 ggatgttgaa gagcttgaag ttgaggctct tgggccggaa tccccagttg ttgttgatga 1380 gtcgctgcca gtcacgtggt gagaagtggc agtggaatct gttaaagtca aaataccccc 144 0 agggggtgct gtagccgaag taggtgttgt cgttggtgct tcctcccgaa gtcccgttgg 1500 agatttgctt gtagaggtgg ttgttgtagg tggggagggc ccaggttcgg gtgctggtgg 1560 tgatgactcc gtcgcccagc catgtggaat cgcaatgcca atttcctgag gaactaccca 1620 ctccgtcggc gccttcgtta ttgtctgcca ttggagcgcc accgcctgca gccattgtac 1680

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     cagatcccag aeeagagggg cctgcggggg gttctccgat tggttgaggg tcgggcactg 1740 actctgagtc gccagtctgc ccaaagttga gtctcttttt cgcgggctgc : tggcctttct 1800 tgccgatgcc cgtagaggag tctggagaac gctggggtga tggctctacc ggtetettet 1860 ttccaggagc cgtcttagcg ccttcctcaa ccagaccgag aggttcgaga acccgcttct 1920 tggcctggaa gactgctcgc ccgaggttgc ccccaaaaga egtatettet tgeagaeget 1980 cctgaaactc ggcgtcggcg tggttatacc gcaggtacgg attgtcaccc getttgaget 2040 gctggtcgta ggccttgtcg tgctcgaggg ccgctgcgtc cgccgcgttg acgggctccc 2100 ccttgtcgag teegttgaag ggtccgaggt aettgtagee aggaagcacc agaccccggc 2160 cgtcgtcctg cttttgctgg ttggctttgg gcttcggggc tccaggtttc agcgcccacc 2220 actcgcgaat gccctcagag aggttgtcct cgagccaatc tggaagataa ccatcggcag 2280 ccatacctga tttaaatcat ttattgttca aagatgeagt catccaaatc cacattgacc 2340 agategcagg cagtgcaagc gtctggcacc tttcccatga tatgatgaat gtagcacagt 2400 ttctgatacg cctttttgac gacagaaacg ggttgagatt ctgacacggg aaagcactct 2460 aaacagtctt tctgtccgtg agtgaagcag atatttgaat tctgattcat tctctcgcat 2520 tgtctgcagg gaaacageat cagattcatg cccacgtgac gagaacattt gttttggtac 2580 ctgtctgcgt agttgatcga agcttccgcg tetgaegteg atggctgcgc aactgactcg 2640 cgcacccgtt tgggctcact tatatctgcg tcactggggg cgggtctttt cttggctcca 2700 ecctttttga egtagaatte atgctccacc tcaaccacgt gatcctttgc ccaccggaaa 2 760 aagtctttga cttcctgctt ggtgaccttc ccaaagtcat gatccagacg gcgggtgagt 2820 tcaaatttga acatccggtc ttgeaaegge tgctggtgtt cgaaggtcgt tgagttcccg 2880 tcaatcacgg cgcacatgtt ggtgttggag gtgaegatea egggagtegg gtctatctgg 2940 gccgaggact tgcatttctg gtccacgcgc accttgcttc ctccgagaat ggctttggcc 3000 gactccacga ccttggcggt catcttcccc tcctcccacc agatcaccat cttgtcgaca 3060 cagtcgttga agggaaagtt ctcattggtc cagttgacgc ageegtagaa agggegaatt 3120 c 3121 <210> 14 <211> 3131 <212> DHA <213> new AAV serotype, clone 1- 3 <400> 14 gcggccgcga attcgccctt ggctgcgtca actggaccaa tgagaacttt cccttcaatg 60 attgegtega caagatggtg atctggtggg aggagggcaa gatgaeggee aaggtcgtgg 120 agtccgccaa ggccattctc ggcggcagca aggtgcgcgt ggaccaaaag tgcaagtcgt 180

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     ccgcccagat cgaccccacc cccgtgatcg tcacctccaa caccaacatg tgcgccgtga 240 ttgacgggaa cagcaccacc ttcgagcacc agcagcctct ccaggaccgg atgtttaagt 300 tcgaactcac ccgccgtctg gagcacgact ttggcaaggt gacaaagcag gaagtcaaag 360 agttcttccg ctgggccagt gatcacgtga ccgaggtggc gcatgagttt tacgtcagaa 420 agggcggagc cagcaaaaga cccgcccccg atgacgcgga taaaagcgag cccaagcggg 480 cctgcccctc agtcgcggat ccatcgacgt cagacgcgga aggagctccg gtggactttg 540 ccgacaggta ccaaaacaaa tgttctcgtc acgcgggcat gcttcagatg ctgtttccct 600 gcaaaacgtg cgagagaatg aatcggaatt tcaacatttg cttcacacac ggggtcagag 660 actgctcaga gtgtttcccc ggcgtgtcag aatctcaacc ggtcgtcaga aagaggacgt 720 atcggaaact ccgtgcgatt catcatctgc tggggcgggc tcccgagatt gcttgctcgg 780 cctgcgatct ggtcaacgtg gaectggatg actgtgtttc tgagcaataa atgacttaaa 840 ccaggtatgg ctgccgatgg ttatcttcca gattggctcg aggacaacct ctctgagggc 900 attcgcgagt ggtgggcgct gaaacctgga gccccgaagc ccaaagccaa ccagcaaaag 960 caggacgacg gccggggtct ggtgcttcct ggctacaagt acctcggacc cttcaacgga 1020 ctcgacaagg gggagcccgt caacgcggcg gacgcagcgg ccctcgagca cgacaaggct 1080 tacgaccagc agctgcaggc gggtgacaat ccgtacctgc ggtataacca cgccgacgcc 114 0 gagtttcagg agcgtctgca agaagatacg tcttttgggg gcaacctcgg gcgagcagtc 1200 ttccaggcca agaagcgggt tctcgaacct ctcggtctgg ttgaggaagg cgctaagacg 1260 gctcctggaa agaagagacc ggtagagcca tcaccccagc gttctccaga ctcctctacg 1320 ggcatcggca agaaaggcca acagcccgcc agaaaaagac tcaattttgg tcagactggc 1380 gaetcagagt cagttccaga eeeteaacct ctcggagaac ctceagcagc gccctctggt 1440 gtgggaccta atacaatggc tgcaggcggt ggcgcaccaa tggcagacaa taacgaaggc 1500 gccgacggag tgggtagttc ctcgggaaat tggcattgcg attccacatg gctgggegac 1560 agagfccatca ccaccagcac qcgaacctgg gccctgccca cctacaacaa ccacctctac 1620 aagcaaatct ccaacgggac atcgggagga gccaccaacg acaacaccta ettcggctae 1680 agcaccccct gggggtattt tgaetttaac agattccact gccacctttc accacgtgac 1740 tggcagcgac tcatcaacaa caactgggga ttccgaccca agagactcag cttcaagctc 1800 ttcaacatcc aggtcaagga ggtcacgcag aatgaaggca ccaagaccat cgccaataac 1860 ctcaccagca ccatccaggt gtttacggac tcggagtacc agctgccgta cgttctcggc 1920 tctgtccacc agggctgcct gcctccgttc ccggcggacg tgttcatgat tccccagtac 1980 ggctacctaa cactcaacaa cggtagtcag gccgtgggac gctcctcctt ctactgcctg 2040 gaatactttc cttcgcagat gctgagaacc ggcaacaact tccagtttac ttacaccttc 2100

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     gaggacgtgc ctttccacag cagctacgcc cacagctaga gcttggaccg gctgatgaat 2160 cctctgattg accagtacct gtactacttg tctcggactc aaacaacagg aggcacggca 2220 aatacgcaga ctctgggctt cagccaaggt gggcctaata caatggccaa tcaggcaaag 228 0 aactggctgc caggaccctg ttaccgccaa caacgcgtct caacgacaac cgggcaaaac 2340 aacaatagca actttgcctg gactgctggg accaaatacc atctgaatgg aagaaattca 2400 ttggctaatc ctggcatcgc tatggcaaca cacaaagacg acgaggagcg tttttttccc 2460 agtaacggga tcctgatttt tggcaaacaa aatgctgcca gagacaatgc ggattacagc 2520 gatgtcatgc tcaccagcga ggaagaaatc aaaaccacta accctgtggc tacagaggaa 2580 tacggtatcg tggcagataa cttgcagcag caaaacacgg ctcctcaaat tggaactgtc 2640 aacagccagg gggccttacc cggtatggtc tggcagaacc gggacgtgta cctgcagggt 2700 cccatctggg ccaagattcc tcacacggac ggcaacttcc acccgtctcc gctgatgggc 2760 ggctttggcc tgaaacatcc tccgcctcag atcctgatca agaacacgcc tgtacctgcg 2820 gatcctccga ccaccttcaa ccagtcaaag ctgaactctt tcatcacgca atacagcacc 2880 ggacaggtca gcgtggaaat tgaatgggag ctgcagaagg aaaacagcaa gcgctggaac 2940 cccgagatcc agtacacctc caaetactac aaatctataa gtgtggactt tgctgttaat 3000 acagaaggcg tgtactctga accccgcccc attggcaccc gttaectcac ccgtaatctg 3060 taattgcctg ttaatcaata aaccggttga ttcgtttcag ttgaactttg gtctctgcga 3120 agggcgaatt c 3131

     <210> 15 <211> 3127

     <212> DNA <213> new AAV serotype, clone 13-3b <400> 15 gcggccgcga attcgccctt cgcagagaec aaagttcaac tgaaacgaat caaccggttt 60 attgattaac atgcaattac agattacggg tgaggtaacg agtgccaata gggcgaggct 120 cagagtaaac accctggctg tcaacggcaa agtccacacc agtctgcttt tcaaagttgg 180 aggtgtactg aatctccggg tcccagcgct tgctgttttc cttctgcagc tcccactcga 240 tttccacgct gacttgtccg gtgctgtact gtgtgatgaa cgaagcaaac ttggcaggag 300 taaacacctc cggaggatta gcgggaacgg gagtgttctt gatcaggatc tgaggaggcg 360 gatgtttaag tccaaagccg cccatcaaag gagacgggtg aaagttgcca tccgtgtgag 420 gaatcttggc ccagatggga ccctgcaggt acacgtcccg gttctgccag accatgccag 480 gtaaggctcc ctggttgttg acaacttgtg tctgggctgc agtattagcc gcttgtaagt 540 tgctgctgac tatcccgtat tcttccgtgg ctacaggatt agtaggacga atttcttctt 600 catttgtcat taacacattt tccaatgtag ttttgttagt tgctccagtt tttccaaaaa 660

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015 tcaggactcc gctggatggg aaaaagcggt cctcgtcgtc cttgtgagtt gccatggcga 720 cgccgggatt aaccaacgag tttctgccgt tcaggtgata tttggtggca ccagtccaag 780 caaagttgct gttgttgttt tgatccagcg ttttggagac cctttgttgc cggaagcagg 840 gtccaggtaa ccaattcttg gcttgttcgg ccatagttga aggcccgccc tggtaaaact 900

     gcagttcccg attgccagct gtgcctcctg ggtcactctg tgttctggcc aggtagtaca 960 agtactggtc gatgagggga ttcatcagcc ggtccaggct ctggctgtgt gcgtagctgc 1020 tgtggaaagg cacgtcctcg aagctgtagc tgaactcaaa gttgttgccc gttctcagca 1080 tctgagaggg gaagtactcc aggcagtaga aggaggaacg tcccacagac tgactgccat 1140 tgttgagagt caggtagccg tactgaggaa tcatgaagac gtccgccggg aacggaggca 1200 ggcagccctg gtgcgcagag ccgaggacgt acggcagctg gtattccgag tccgagaata 1260 cctgaatcgt gctggtaagg ttattagcga tggtcgtaac gccgtcattc gtcgtgacct 1320 ccttgacctg gatgttgaag agcttgaacc gcagcttctt gggccggaat ccccagttgt 1380 tgttgatgag tcgctgccag tcacgtggtg agaagtggca gtggaatctg ttaaagtcaa 1440 aataccccca gggggtgctg tagccgaagt aggtgttgtc gttggtacta cctgcagttt 1500 cactggagat ttgctcgtag aggtggttgt tgtaggtggg cagggcccag gttcgggtgc 1560 tggtggtaat gactctgtcg cccagccatg tggaatcgca atgccaattt cctgaggcat 1620 tacccactcc gtcggcacct tcgttattgt ctgccattgg tgcgccaccg cctgcagcca 1680 ctgtaccaga tcccacacta gagggcgctg ctggaggttc tccgagaggt tgagggtcgg 1740 ggactgactc tgagtcgcca gtctgaccga aattgagtct ctttctggcg ggctgctggc 1800 ccttcttgcc gatgcccgtg gaggagtcgg gggaacgctg aggtgacggc tctaccggtc 1860 tcttctttgc aggagccgtc ttagcgcctt cctcaaccag accgagaggt tcgagaaccc 1920 gcttcttggc ctggaagact gctcgcccga ggttgccccc aaatgacgta tcttcttgca 1980 gacgctcctg aaactcggcg tcggcgtggt tataccgcag gtacgggttg tcacccgcat 2040 tgagctgctg gtcgtaggcc ttgtcgtgct cgagggccgc tgcgtccgcc gcgttgacgg 2100 gctccccctt gtcgagtccg ttgaagggtc cgaggtactt gtagccagga agcaccagac 2160 cccggccgtt gtcctgcttt tgctggttgg ctttgggttt cggggctcca ggtttcaggt 2220 cccaccactc gcgaatgccc tcagagaggt tgtcctcgag ccaatctgga agataaccat 2280 cggcagccat acctgattta aatcatttat tgttcaaaga tgcagtcatc caaatccaca 2340 ttgaccagat cgcaggcagt gcaagcgtct ggcacctttc ccatgatatg atgaatgtag 2400 cacagtttct gatacgcctt tttgacgaca gaaacgggtt tagattctga cacgggaaag 2460 cactctaaac agtctttctg tccgtgagtg aagcagatat ttgaattctg attcattctc 2520 tcgcattgtc tgcagggaaa cagcatcaga ttcatgccca cgtgacgaga acatttgttt 2580

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     tggtacctgt ctgcgtagtt gatcgaagct tccgcgtctg acgtcgatgg ctgcgcaact 2640 gactcgcgca cccgtttggg ctcacttata tctgcgtcac tgggggcggg tcttttcttg 2700 gctccaccct ttttgacgta gaattcatgc tccacctcaa ccacgtaatc ctttgcccac 2760 cggaaaaagt ctttgacttc ctgcttggtg accttcccaa agtcatgatc cagacggcgg 2820 gtgagttcaa atttgaacat ccggtcttgc aacggctgct ggtgttcgaa ggtcgttgag 2880 ttcccgtcga tcacggcgca catgttggtg ttggagatga cgatcgcggg agtcgggtct 2940 atctgggccg aggacttgca tttctggtcc acgcgcacct tgcttcctcc gagaatggct 3000 ttggccgact ccacgacctt ggcggtcatc ttcccctcct cccaccagat caccatcttg 3060 tcgacacagt cgttgaaggg aaagttctca ttggtccagt tgacgcagcc gtagaaaggg 3120

     cgaattc 3127 <210> 16 <211> 3106 <212> DNA <213> new AAV serotype, clone 24-1 <400> 16

     gcggccgcga attcgccctt cgcagagacc aaagttcaac tgaaacgaat caaccggttt 60 attgattaac aagtaattac aggttacggg tgaggtaacg ggtgccaatg gggcgaggct 120 cagtataaac cccttcgttg ttgacagcaa attccacatt attagacttg gcataatttg 180 aggtgtactg aatctctgga ttccagcgtt tgctgttttc tttctgcagt tcccactcga 240 tctccacgct gacctggccg gtgctgtact gcgtgataaa tgaggcaaac ttggcaggag 300 taaacacctc tggaggatta gcaggtaccg gggtgttttt gatgagaatt tgaggaggcg 360 ggtgtttgag tccaaatccg cccatcaggg gagacgggtg aaagttgccg tccgtgtgag 420 gaattttggc ccagatggga ccctgcaggc acacgtcccg gttctgccag accatgccgg 480 gcagagcccc ctggctgttg acagtctgtg tctggggtcc ggccgtagac gattgcaggt 54 0 tgctggagac cacaccgtat tcttctgtag ccacgggatt ggtggttttg atctcctcct 600 cgctggtcat tagcacgttt tccagcgttg tcttgttggc agcccccgtt ttgccaaaaa 660 ccagcactcc gttgatggga aagaactggt cctcgtcgtc cttgttggtg gccatggcta 720 cgcccgggtt ggttaatgaa tttctaccat tcagatggta tttagtggcc ccggtccagg 780 caaagttact gttgttgttg ctgtctatgt tttttgacag tctctgctgc cgataacagg 840 gtccgggcag ccagttcttt gattgctcgg ccatggtgtt gggcccagcc tgatggaact 900 gcagctccct tgtggacccc gtagtgctct gggtccgggc caggtagtac aggtactggt 960 cgatgagggg attcatcagc cggtctaggc tctggctgtg cacatagctg ctgtggaaag 1020 gcacttcctc aaaggtgtag ctgaattcaa agttattgcc cgttctcagc atctgagaag 1080

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     gaaagtactc caggcagtag aaggaggaac gtcccacaga ctgactgccg ttgtttagag 1140 tcagatatcc gtactgagga atcatgaaca cgtccgcagg gaacggaggg aggcagccct 1200 ggtgcgcaga gccgaggacg tacggcagtt ggtactccga gtccgagaag acctgaatcg 1260 tgctggtaag gttattagcg atggtcgtaa cgccgtcgtt cgtcgtgacc tccttgacct 1320 ggatgttgaa caacttgaac cgcagctttc tgggccggaa tccccagttg ttgttgatga 1380 gtcgctgcca gtcacgtggt gagaagtggc agtggaatct gttgaagtca aaatagcccc 1440 agggggtgct gtagctgaag aagtggttgt cgttggtagc cccgctctga cttgatatct 1300 gcttgtagag gtggttgttg taggtgggca gggcccaggt gcgggtgctg gtggtgatga 1560 ctctgtcgcc cagccatgtg gaatcgcaat gccaatttcc ggaggcatta cccactccgt 1620 cggcgccttc gttattgtct gccattggtg cgccaccgcc tgcagccatt gtaccagatc 1680 ccagacctga gggcgcggcg ggaggttctc cgagaggttg ggggtcgggc actgactctg 1740 agtcgccagt ctgcccaaag ttgagcttct ttttagcggg ctgctggcct ttcttgccga 1800 tgcccgtgga ggagtcgggg gattctatgg gtctcttctt tccaggagcc gtcttagcga 1860 cttcctcaac cagaccgaga ggttcgagaa cccgcttctt ggcctggaag actgctcgcc 1920 cgaggttgcc cccaaaagac gtatcttctt gaagacgctc ctgaaactcg gcgtcggcgt 1980 ggttgtactt gaggtacggg ttgtccccct gctcgagctg cttgtcgtag gccttgtcgt 2040 gctcgagggc cgcggcgtct gcctcgttga ccggctctcc cttgtcgagt ccgttgaagg 2100 gtctgaggta cttgtagcca ggaagcacca gaccccggcc gtcgtcc.tgc ttttgctggt 2160 tggctttggg tttcggggct ccaggtttca agtcccacca ctcgcgaatg ccctcagaga 2220 ggttgtcctc gagccaatct ggaagataac catcggcagc catacctggt ttaagtcatt 2280 tattgctcag aaacacagtc atccaggtcc acgttgacca gatcgcaggc cgagcaagca 2340 atctcgggag cccgccccag cagatgatga atggcacaga gtttccgata cgtcctcttt 2400 ctgacgaccg gttgagattc tgacacgccg gggaaacatt ctgaacagtc tctggtcccg 2460 tgcgtgaagc aaatgttgaa attctgattc actctctcgc atgtcttgca gggaaacagc 2520 atctgaagca tgcccgcgtg acgagaacat ttgttttggt acctgtcggc aaagtccacc 2580 ggagctcctt > ccgcgtctga cgtcgatgga ttcgcgactg aggggcaggc ccgcttgggc 2640

     tcgcttttat ccgcgtcatc gggggcgggt ctcttgttgg ccccaccctt tctgacgtag 2700 aacccatgcg ccacctcggt cacgtgatcc tgcgcccagc ggaagaacct tttgacttcc 2760 tgctttgtca ccttgccaaa gttatgctcc agacggcggg tgggttcaaa tttgaacatc 2820 cggtcctgca acggctgctg gtgctcgaag gtggcgctgt tcccgtcaat cacggcgcac 2880 atgttggtgt tggaggtgac ggtcacgggg gtggggtcga tctgggcgga cgacttgcac 2940 ttttggtcca cgcgcacctt gctgccgccg agaatggcct tggcggactc cacgaccttg 3000

     WO 03/042397

     PCT/USO2/33629 gccgtcatct tgccctcctc ccaccagatc accatcttgt cggcgcaatc gttgaaggga 3060 aagttctcat tggtccagtt gacgcagccg tagaaagggc gaattc 3106 <210> 17 <211> 3102 <212> DNA ' <213> new AAV serotype, clone 27-3 <400> 17

     2015258271 20 Nov 2015

     gcggccgcga attcgccctt cgcagagacc aaagttcaac tgaaacgaat caaccggttt 60 attgattaac aagtaattac aggttacggg tgaggtaacg ggtgccaatg gggcgaggct 12 0 cagtataaac cccttcgttg ttgacagcaa attccacatt attagacttg gcataatttg 18 0 aggtgtactg aatctctgga ttccagcgtt tgctgttttc tttctgcagt tcccactcga 24 0 tctccacgct gacctggccg gtgctgtact gcgtgataaa tgaggcaaac ttggcaggag 300 taaacacctc tggaggatta gcaggtaccg gggtgttttt gatgagaatt tgaggaggcg 360 ggtgtttgag tccaaatccg cccatcaggg gagacgggtg aaagttgccg tccgtgtgag 420 gaatttcggc ccagatggga ccctgcaggt acacgtcccg gttctgccag accatgccgg 480 gcagagcccc ctggctgttg acagtctgtg tccggggtcc ggccgtagac gattgcaggt 540 tgctggagac cacaccgtat tcttctgtag ccacgggatt ggtggttttg atctcctcct 600 cgctggtcat tagcacgttt tccagcgttg tcttgttggc agcccccgtt ttgccaaaaa 660 ccagcactcc gttgatggga aggaactggt cctcgtcgtc cttgttggtg gccatggcta 720 cgcccgggtt ggttaatgaa tttctaccat tcagatggta tttagtggcc ccggtccagg 780 caaagttact gttgttgttg ctgtctatgt tttttgacag tctctgctgc cgataacagg 840 gtccgggcag ccagttcttt gattgctcgg ccacggtgtt gggcccagcc tgatggaact 900 gcagctccct tgtggacccc gtagtgctct gggtccgggc caggtagtac aggtactggt 960 cgatgagggg attcatcagc cggtccaggc tctggctgtg cgcatagctg ctgtggaaag 1020 gcacttcctc aaaggtgtag ctgaattcaa agttattgcc cgttctcagc atctgagaag 1080 gaaagtactc caggcagcag aaggaggaac gtcccacaga ctgactgccg ttgtttagag 1140 tcagatatcc gtactgagga atcatgaaca cgtccgcagg gaacggaggg aggcagccct 1200 ggtgcgcaga gccgaggacg tacggcagtt ggtactccga gtccgagaag acctgaatcg 1260 tgctggtaag gttattagcg atggtcgtaa cgccgtcgtt cgtcgtgacc tccttgacct 1320 ggatgttgaa caacttgaac cgcagctttc tgggccggaa tccccagttg ttgttgatga 1380 gtcgctgcca gtcacgtggt gagaagtggc agtggaatct gttgaagtca aaatagcccc 1440 agggggtgct gtagccgaag aagtggttgt cgttggtagc cccgctctga cttgatatct 1500 gcttgtagag gtggttgttg taggtgggca gggcccaggt gcgggtgctg gtggtgatga 1560 ctctgtcgcc cagccatgtg gaatcgcaat gccaatttcc ggaggcatta cccactccgt 1620

     WO 03/042397

     PCT/USO2/33629

     2015258271 20 Nov 2015

     cggcgccttc gttattgtct gccattggtg cgccaccgcc tgcagccatt gtaccagatc 1680 ccagacctga gggcgcggcg ggaggttctc cgagaggttg ggggtcgggc actgactctg 1740 agtcgccagt ctgcccaaag ttgagcttct ttttagcggg ctgctggcct ttcttgccga 1800 tgcccgtgga ggagtcgggg gattctatgg gtctcttctt tccggaagcc gtcttagcgc 1860 cttcctcaac cagaccgaga ggttcgagaa cccgcttctt ggcctggaag actgctcgcc 1920 cgaggttgcc cccaaaagac gtatcttctt gaagacgctc ctgaaactcg gcgtcggcgt 1980 ggttgtactt gaggtacggg ttgtccccct gctcgagctg cttgtcgtag gccttgtcgt 2040 gctcgagggc cgcggcgtct gcctcgttga ccggctctcc cttgtcgagt ccgttgaagg 2100 gtccgaggta cttgtagcca ggaagcacca gaccccggcc gtcgtcctgc ttttgctggt 2160 tggctttggg tttcggggct ccaggtttca agtcccacca ctcgcgaatg ccctcagaga 2220 ggttgtcctc gagccaatct ggaagataac catcggcagc catacctggt ttaagtcatt 2280 tattgctcag aaacacagtc atccaggtcc acgttgacca gatcgcaggc cgagcaagca 2340 atctcgggag cccgccccag cagatgatga atggcacaga gtttccgata cgtcctcttt 2400 ctgacgaccg gttgagattc tgacacgccg gggaaacatt ctgaacagtc tctggtcccg 2460 tgcgtgaags aaatgttgaa attetgat-tc attctctcgc atgtcttgca gggaaacagc 2520 atctgaagca tgcccgcgtg acgagaacat ttgttttggt acctgtcggc aaagtccacc 2580 ggagctcctt ccgcgtctga cgtcgatgga tccgcgactg aggggcaagc ccgcttgggc 2640 tcgcttttat ccgcgtcatc gggggcgggt ctcttgttgg ctccaccctt tctgacgtag 2700 aactcatgcg ccacctcggt cacgtgatcc tgcgcccagc ggaagaactc tttgacttcc 2760 tgctttgtca ccttgccaaa gtcatgctcc agacggcggg tgagttcaaa tttgaacatc 2820 cggtcttgta acggctgctg gtgctcgaag gtggtgctgt tcccgtcaat cacggcgcac 2880 atgttggtgt tggaagtgac gatcacgggg gtgggatcga tctgggcgga cgacttgcac 2940 ttttggtcca cgcgcacctt gctgccgccg agaatggcct tggcggactc cacgaccttg 3000 gccgtcatct tgccctcctc ccaccagatc accatcttgt cgacgcaatc gttgaaggga 3060 aagttctcat tggtccagtt gacgcagccg aagggcgaat tc 3102 <210> 18 <211> 3106 <212> DNA <213> new AAV serotype, clone 7- 2 <400> 18 gcggccgcga attcgccctt cgcagagacc aaagttcaac tgaaacgaat cagccggttt 60 attgattaac aagtaattac aggttacggg tgaggtaacg ggtgccaatg gggcgaggct 120 cagtataaac cccttcgttg ttgacagcaa attccacatt attagacttg gcataatttg 180

     WO 03/042397 PCT/US02/33629

     2015258271 20 Nov 2015

     aggtgtactg aatctctgga ttccagcgtt tgctgttttc ; tttctgcagt tcccactcga 240 tctccacgct gacctggccg gtgctgtact gcgtgataaa tgaggcaaac ttggcaggag 300 taaacacctc tggaggatta gcaggtaccg gggtgttttt gatgagaatt tgaggaggcg 360 ggtgtttgag tccaaatccg cccatcaggg gagacgggtg aaagttgccg tccgtgtgag 420 gaattttggc ccagatggga ccctgcaggt acacgtcccg gttctgccag accatgccgg 480 gcagagcccc ctggctgttg acagtctgtg tctggggtcc ggccgtagac gattgcaggt 540 tgctggagac cacaccgtat tcttctgtag ceacgggatt ggtggttttg atctcctcct 600 cgctggtcat tagcaegttt tccagcgttg tcttgttggc agccecegtt ttgccaaaaa 660 ccagcactcc gttgatggga aagaactggt cctcgtcgtc cttgttggtg gccatggcta 720 cgcccgggtt ggttaatgaa tttctaccat tcagatggta tttagtggcc ccggtccagg 780 caaagttact gttgttgttg ctgtctatgt tttttgacag tctctgctgc cgataacagg 840 gtccgggcag ccagttcttt gattgctcgg ccatggtgtt gggcccagec tgatggaact 900 gcagctccct tgtggacccc gtagtgctct gggtccgggc caggtagtac aggtactggt 960 cgatgagggg attcatcagc cggtccaggc tctggctgtg cgcatagctg ctgtggaaag 1020 gcacttcctc aaaggtgtag ctgaattcaa agttatcgcc cgttctcagc atctgagaag 1080 gaaagtactc caggcagtag aaggaggaac gtcccacaga ctgactgccg ttgtttagag 1140 tcagatatcc gtactgagga atcatgaaca cgtccgcagg gaacggaggg aggcagccct 1200 ggtgcgcaga gccgaggacg tacggcagtt ggtactccga gtcegagaag acctgaatcg 1260 tgctggtaag gttattagcg atggtcgtaa cgccgtcgtt cgtcgtgacc tccttgacct 1320 ggatgttgaa caacttgaac cgcagctttc tgggccggaa tccccagttg ttgttgatga 1380 gtcgctgcca gtcacgtggt gagaagtggc agtggaatct gttgaagtca aaatagcccc 1440 agggggt-gct gtagccgaag aagtggttgt cgttggtage cccgctctga cttgatatct 1500 gcttgtagag gtggttgttg taggtgggca gggcccaggt gcgggtgctg gtggtgatga 1560 ctctgtcgcc cagccatgtg gaatcgcaat gccaatttcc ggaggcatta cccactccgt 1620 cggcgccttc gttattgtct gccattggtg cgeeacegce tgcagceatt gtaccagatc 1680 ccagacctga gggcgcggcg ggaggttctc cgagaggttg ggggtcgggc actgactctg 1740 agtcgccagt ctgcccaaag ttgagcttct ttttagcggg cggctggccg ttcttgccga 1800 tgcccgtgga ggagtcgggg gattctatgg gtctcttctt tccaggagcc gtcttagcgc 18 60 cttcctcaac cagaccgaga ggttcgagaa cccgcttctt ggcctggaag actgctcgcc 1920 cgaggttgcc cccaaaagac gtatcttctt gaagacgctc ctgaaactcg gcgtcggcgt 1980 ggttgtactt gaggtacggg ttgtccccct gctcgagctg cttgtcgtag gccttgtcgt 2040 gctcgagggc cgcggcgtct gcctcgttga ccggctctcc cttgtcgagt ccgttgaagg 2100

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     gtccgaggta cctgtagcca ggaagcacca gaccccggcc gtcgtcctgc ttttgctggt 2160 tggctttggg tttcggggct ccaggtttca agtcccaeca ctcgcgaatg ccctcagaga 2220 ggttgccctc gagccaatct ggaagataac catcggcagc catacctggt ttaagteatt 2280 tattgctcag aaacacagtc atccaggtcc acgttggcca gatcgcaggc cgagcaagca 2340 atctcgggag cccgccccag cagatgatga atggcacaga gtttccgata cgtcctcttt 2400 ctgacgaccg gttgagattc tgacacgccg gggaaacatt ctgaacagtc tctggtcccg 2460 tgcgtgaagc aaatgttgaa attctgattc attctctcgc atgtettgea ggggaacagc 2520 atctgaagca tgcccgcgtg acgagaacat ttgttttggt acctgtcggc aaagtccacc 2580 ggagctcctt ccgcgtctga cgtcgatgga tccgcgactg aggggcaggc ccgcttgggc 2640 tcgcttttat ccgcgtcatc gggggcgggt ctcttgttgg ctccaccctt tetgaegtag 2700 aactcatacg ccacctcggt cacgtgatcc tgcgcccagc ggaagaactc tttgacttcc 27 60 tgctttgtca ccttgccaaa gtcatgctcc agaeggeggg tgagttcaaa tttgaacatc 2820 cggtcttgta acggctgctg gtgctcgaag gtggtgctgt tceegtcaat cacggcgcac 2880 atgttggtgt tggaagtgac gatcacgggg gtgggatcga tctgggcgga cgacttgcac 2940 ttttggtcca cgcgcacctt gctgccgccg agaatggcct tggcggactc cacgaccttg 3000 gccgtcatcc tgccctcctc ccaecagatc accatcttgt cgacgcaatc gttgaaggga 3060 aagttctcat tggtccagtt gacgcagccg tagaaagggc gaattc 310 6

     <210> 19 <211> 3105 <212> DNA <213> new AAV serotype, clone Cl <400> 19

     gaattcgccc ttgctgcgtc aactggacca atgagaaett tcccttcaac gattgegteg ⁶⁰ acaagatggt gatctggtgg gaggagggca agatgaccgc caaggtcgtg gagteegeea 120 aggccattct gggeggaage aaggtgcgcg tggaccaaaa gtgeaagtea tcggcccaga 180 tcgaccccac gcccgtgatc gtcacctcca acaccaacat gtgcgccgtg ategaeggga 240 acagcaccac ettegageac cagcagccgc tgcaggaccg catgttcaag ttegagetea 300 cccgccgtct ggagcacgac tttggcaagg tgaccaagca ggaagtcaaa gagttcttcc 360 gctgggctca ggatcacgtg actgaggtgg egeatgagtt etaegteaga aagggcggag 420 ccaccaaaag acccgccccc agtgacgcgg atataagega gcccaagcgg gcctgcccct 480 cagttgcgga gccatcgacg teagaegegg aagcaccggt ggactttgcg gacaggtacc 540 aaaacaaatg ttctcgtcac gcgggcatgc ttcagatgct gtttccctgc aagacatgcg 600 agagaatgaa tcagaatttc aacgtctgct tcacgcacgg ggtcagagac tgctcagagt 660 gcttccccgg egegteagaa tctcaacccg tegteagaaa aaagaegtat cagaaactgt 720

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     gcgcgattca tcatctgctg gggcgggcac ccgagattgc gtgttcggcc cgcgatctcg 780 tcaacgtgga cttggatgac tgtgtttctg agcaataaat gacttaaacc aggtatggct 840 gctgacggtt atcttccaga ttggctcgag gacaacctct ctgagggcat tcgcgagtgg 900 tgggacctga aacctggagc ccccaagccc aaggccaacc agcagaagca ggacgacggc 960 cggggtctgg tgcttcctgg ctacaagtac ctcggaccct tcaacggact cgacaagggg 1020 gagcccgtca acgcggcgga cgcagcggcc ctcgagcacg acaaggccta cgaccagcag 1080 ctcaaagcgg gtgacaatcc gtacctgcgg tataaccacg ccgacgccga gtttcaggag 1140 cgtctgcaag aagatacgtc ttttgggggc aacctcgggc gagcagtctt ccaggccaag 1200 aagagggtac tcgaacctct gggcctggtt gaagaaggtg ctaagacggc tcctggaaag 1260 aagagaccgt tagagtcacc acaagagccc gactcctcct caggaatcgg caaaaaaggc 1320 aaacaaccag ccaaaaagag actcaacttt gaagaggaca ctggagccgg agacggaccc 1380 cctgaaggat cagataccag cgccatgtct tcagacattg aaatgcgtgc agcaccgggc 1440 ggaaatgctg tcgatgcggg acaaggttcc gatggagtgg gtaatgcctc gggtgattgg 1500 cattgcgatt ccacctggtc tgagggcaag gtcacaacaa cctcgaccag aacctgggtc 1560 ttgcccacct acaacaacca cttgtacctg cggctcggaa caacatcaaa cagcaacacc 1620 tacaacggat tctccacccc ctggggatac tttgacttta acagattcca ctgtcacttc 1680 tcaccacgtg actggcaaag actcatcaac aacaactggg gactacgacc aaaagccatg 1740 cgcgttaaaa tcttcaatat ccaagttaag gaggtcacaa cgtcgaacgg cgagactacg 1800 gtcgctaata accttaccag cacggttcag atatttgcgg actcgtcgta tgagctcccg 1860 tacgtgatgg acgctggaca agagggaagt ctgtctcctt tccccaatga cgtcttcatg 1920 gtgcctcaat atggctactg tggcattgtg actggcgaaa atcagaacca gacggacaga 1980 aatgctttct actgcctgga gtattttcct tcacaaatgc tgagaactgg caataacttt 2040 gaaatggctt acaactttgg gaaggtgccg ttccactcaa tgtatgctta cagccagagc 2100

     ccggacagac tgatgaatcc cctcctggac cagtacctgt ggcacttaca gtcgaccacc 2160 tctggagaga ctctgaatca aggcaatgca gcaaccacat ttggaaaaat caggagtgga 2220 gactttgcct tttacagaaa gaactggctg cctgggcctt gtgttaaaca gcagagactc 2280 tcaaaaactg ccagtcaaaa ttacaagatt cctgccagcg ggggcaacgc tctgttaaag 2340 tatgacaccc actatacctt aaacaaccgc tggagcaaca tagcgcctgg acctccaatg 2400 gcaacagctg gaccttcaga tggggacttc agcaacgccc agctcatctt ccctggacca 2460 tcagtcaccg gaaacacaac aacctcagca aacaatctgt tgtttacatc agaagaagaa 2520 attgctgcca ccaacccaag agacacggac atgtttggtc agattgctga caataatcag 2580 aatgctacaa ctgctcccat aaccggcaac gtgactgcta tgggagtgct tcctggcatg 2640

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     gtgtggcaaa acagagacat ttactaccaa gggccaattt gggccaagat cccacacgcg 2700 gacggacatt ttcatccttc accgctaatt ggcggttttg gactgaaaca tccgcctccc 2760 cagatattta tcaaaaacac ccccgtacct gccaatcctg cgacaacctt cactgcagcc 2820 agagtggact ctttcatcac acaatacagc accggccagg tcgctgttca gattgaatgg 2880 gaaatcgaaa aggaacgctc caaacgctgg aatcctgaag tgcagtttac ttcaaactat 2940 gggaaccagt cttctatgtt gtgggctccc gatacaactg ggaagtatac agagccgcgg 3000 gttattggct ctcgttattt gactaatcat ttgtaactgc ctagttaatc aataaaccgt 3060 gtgattcgtt tcagttgaac tttggtctct gcgaagggcg aattc 3105

     <210> 20 <211> 3105

     <212> DNA <213> new AAV serotype, clone C3 <400> 20 gaattcgccc ttgctgcgtc aactggacca atgagaactt tcccttcaac gattgcgtcg 60 acaagatggt gatctggtgg gaggagggca agatgaccgc caaggtcgtg gagtccgcca 120 aggccattct gggcggaagc aaggtgcgcg tggaccaaaa gtgcaagtca tcggcccaga 180 tcgaccccac gcccgtgatc gtcacctcca acaccaacat gtgcgccgtg atcgacggga 240 acagcaccac cttcgagcac cagcagccgc tgcaggaccg catgttcaag ttcgagctca 300 cccgccgtct ggagcacgac tttggcaagg tgaccaagca ggaagtcaaa gagttcttcc 360 gctgggctca ggatcacgtg actgaggtgg cgcatgagtt ctacgtcaga aagggcggag 420 ccaccaaaag acccgccccc agtgacgcgg atataagcga gcccaagcgg gcctgcccct 480 cagttgcgga gccatcgacg tcagacgcgg aagcaccggt ggactttgcg gacaggtacc 540 aaaacaaatg ttctcgtcac gcgggcatgc ttcagatgct gtttccctgc aagacatgcg 600 agagaatgaa tcagaatttc aacgtctgct tcacgcacgg ggtcagagac tgctcagagt 660 gcttccccgg cgcgtcagaa tctcaacccg tcgtcagaaa aaagacgtat cagaaactgt 720 gcgcgattca tcatctgctg gggcgggcac ccgagattgc gtgttcggcc tgcgatctcg 780 tcaacgtgga cttggatgac tgtgtttctg agcaataaat gacttaaacc aggtatggct 840 gctgacggtt atcttccaga ttggctcgag gacaacctct ctgagggcat tcgcgagtgg 900 tgggacctga aacctggagc ccccaagctc aaggccaacc agcagaagca ggacgacggc 960 cggggtctgg tgcttcctgg ctacaagtac ctcggaccct tccacggact cgacaagggg 1020 gagcccgtca acgcggcgga cgcagcggcc ctcgagcacg acaaggccta cgaccagcag 1080 ctcaaagcgg gtgacaatcc gtacctgcgg tataaccacg ccgacgccga gtttcaggag 1140 cgtctgcaag aagatacgtc ttttgggggc aacctcgggc gagcagtctt ccaggccaag 1200

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     aagagggtac tcgaaccact gggcctggtt gaagaaggtg ctaagacgge tcctggaaag 12 eo aagagaccgt tagagtcacc acaagagccc gactcctcct caggaatcgg caaaaaaggc 1320 aaacaaccag ccaaaaagag actcaacttt gaagaggaca ctggagccgg agacggaccc 1380 cctgaaggat cagataccag cgccatgtct tcagacattg aaatgcgtgc agcaccgggc 1440 ggaaatgctg tcgatgcggg acaaggttcc gatggagtgg gtaatgcctc gggtgattgg 1500 cattgcgatt ccacctggtc tgagggcaag gtcacaacaa cctcgaccag aacctgggtc 1560 ttgcccacct acaacaacca cttgtacctg cggctcggaa caacatcaaa cagcaacacc 1620 tacaacggat tctccacccc ctggggatac tttgacttta acagattcca ctgtcacttc 1680 tcaccacgtg actggcaaag actcatcaac aacaactggg gactacgacc aaaagccatg 1740 cgcgttaaaa tcttqaatat ccaagttaag gaggtcacaa cgtcgaacgg cgagactacg 1800 gtcgctaata accttaccag cacggttcag atatttgcgg actcgtcgta tgagctcccg I860 tacgtgatgg acgctggaca agagggaagt ctgcctcctt tccccaatga cgtcttcatg 1920 gtgcctcaat atggctactg tggcattgtg actggcgaaa atcagaacca gacggacaga 1980 aatgctttct actgcctgga gtattttcct tcacaaatgc tgagaactgg caataacttt 2040 gaaatggctt acaactttga gaaggtgccg ttccactcaa tgtatgctca cagccagagc 2100 ctggacagac tgatgaatcc cctcctggac cagtacctgt ggcacttaca gtcgaccacc 2160 tctggagaga ctctgaatca aggcaatgca gcaaccacat ttggaaaaat caggagtgga 2220 gactttgcct tttacagaaa gaactggctg cctgggcctt gtgttaaaca gcagagattc 2280 tcaaaaactg ccagtcaaaa ttacaagatt cctgccagcg ggggcaacgc tctgttaaag 2340 tatgacaccc actatacctt aaacaaccgc tggagcaaca tagcgcctgg acctccaatg 2400 gcaacagctg gaccttcaga tggggacttc agcaacgccc agctcatctt ccctggacca 2460 tcagtcaccg gaaacacaac aacctcagca aacaatctgt tgtttacatc agaaggagaa 2520 attgctgcca ccaacccaag agacacggac atgtttggtc agattgctga caataatcag 2580 aatgctacaa ctgctcccat aaccggcaac gtgactgcta tgggagtgct tcctggcatg 2640 gtgtggcaaa acagagacat ttactaccaa gggccaattt gggccaagat cccacacgcg 2700 gacggacatt ttcatccttc accgctaatt ggcggttttg gactgaaaca tccgcctccc 2760 cagatattta tcaaaaacac ccccgtacct gccaatcctg cgacaacctt cactgcagcc 2820 agagtggact ctttcatcac acaatacagc accggccagg tcgctgttca gattgaatgg 2880 gaaatcgaaa aggaacgctc caaacgccgg aatcctgaag tgcagtttac ttcaaactat 2940 gggaaccagt cttctatgtt gtgggctccc gatacaactg ggaagtatac agagccgcgg 3000 gttattggct ctcgttattt gactaatcat ttgtaactgc ctagttaatc aataaaccgt 3060 gtgattcgtt tcagttgaac tttggtctct gcgaagggcg aattc 3105

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015 <210> 21 <211> 3105 <212> DNA <213> new AAV serotype, clone C5 <400> 21

     gaattcgccc ttcgcagaga ccaaagttca actgaaacga . atcacacggt ttattgatta 60 actaggcagt tacaaatgat tagtcaaata acgagagcca ataacccgcg gctctgtata 12 0 cttcccagtt gtatcgggag cccacaacat agaagactgg ttcccacagt ttgaagtaaa 1Θ0 ctgcacttca ggattccagc gtttggagcg ttccttttcg atttcccatt caatctgaac 240 agcgacctgg ccggtgctgt attgtgtgat gaaagagtcc actctggctg cagtgaaggt 300 tgtcgcagga taggcaggta cgggggtgtt tttgataaat atctggggag gcggatgttt 360 cagtccaaaa ccgccaatta gcggtgaagg atgaaaatgt ccgtccgcgt gtgggatctt 420 ggcccaaatt ggcccttggt agtaaatgtc tctgttttgc cacaccatgc caggaagcac 480 tcccatagca gtcacgttgc cggttatggg agcagttgta gcattctgat tattgtcagc 540 aatctgacca aacatgtccg tgtctcttgg gttggtggca gcaatttctt cttctgatgt 600 aaacaacaga ttgtttgctg aggttgttgt gtttccggtg actgatggtc cagggaagat 660 gagctgggcg ttgctgaagt ccccatctga aggtccagct gttgccattg gaggtccagg 720 cgctatgttg ctccagcggt tgtttaaggt atagtgggtg tcatacttta acagagcgtt 780 gcccccgctg gcaggaatct tgtaattttg actggcagtt tttgagaatc tctgctgttt 840 aacacaaggc ccaggcagcc agttctttct gtaaaaggca aagtctccac tcctgatttt 900 tccaaatgtg gttgctgcat tgccttgatt cagagtctct ccagaggtgg tcgactgtaa 960 gtgccacagg tactggtcca ggaggggatt catcagtccg tccaggctct ggctgtgagc 1020 atacattgag tggaacggca ccttctcaaa gttgtaagcc gtttcaaagt tattgccagt 1080 tctcagcatt tgtgaaggaa aatactccag gcagtagaaa gcatttctgt ccgtctggtt 1140 ctgattttcg ccagtcacaa tgccacagta gccatattga ggcaccatga agacgtcatt 1200 ggggaaagga ggcagacttc cctcttgtcc agcgtccatc acgtacggga gctcatacga 1260 cgagtccgca aatatctgaa ccgtgctggt aaggttatta gcgaccgtag tctcgccgtt 1320 cgacgttgtg acctccttaa cttggatatt gaagatttta acgcgcatgg cttttggtcg 138 0 tagtccCcag ttgttgttga tgagtctttg ccagtcacgt ggtgagaagt gacagtggaa 1440 tctgttaaag tcaaagtatc cccagggggt ggagaatccg ttgtaggtgt tgctgtttga 1500 tgttgttccg agccgcaggt acaagtggtt gttgtaggtg ggcaagaccc aggttctggt 1560 cgaggttgtt gtgaccttgc cctcagacca ggtggaatcg caatgccaat cacccgaggc 1620 attacccact ccatcggaac cttgtcccgc atcgacagca tttccgcccg gtgctgcacg 1680 catttcaatg tctgaagaca tggcgctggt atctgatcct tcagggggtc cgtctccggc 1740

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     tccagtgtcc tcttcaaagt tgagtctctt tttggctggt tgtttgcctt ttttgccgat 1800 tcctgaggag gagtcgggct cttgtggtga ctctaacggt ctcttctttc caggagccgt ' 1860 cttagcacct tcttcaacca ggcccagagg ttcgagtacc ctcttcttgg cctggaagac 1920 tgctcgcccg aggttgcccc caaaagacgt atcttcttgc agacgctcct gaaactcggc 1980 gtcggcgtgg ttataccgca ggtacggatt gtcacccgct ttgagctgct ggtcgtaggc 2040 cttgtcgtgc tcgagggccg ctgcgtccgc cgcgttgacg ggctccccct tgtcgagtcc 2100 gttgaagggt ccgaggtact cgtagccagg aagcaccaga ccccggccgt cgtcctgctt 2160 ctgctggttg gccttgggct tgggggctcc aggtttcagg tcccaccact cgcgaatgcc 2220 ctcagagagg ttgtcctcga gccaatctgg aagataaccg tcagcagcca tacctggttt 228 0 aagtcattta ttgctcagaa acacagtcat ccaagtccac gttgacgaga tcgcaggccg 2340 aacacgcaat ctcgggtgcc cgccccagca gatgatgaat cgcgcacagt ttctgatacg 2400 tcttttttct gacgacgggt tgagattctg acgcgccggg gaagcactct gagcagtctc 2460 tgaccccgtg cgtgaagcag acgttgaaat tctgattcat tctctcgcat gtcttgcagg 2520 gaaacagcat ctgaagcatg cccgcgtgac gagaacattt gttttggtac ctgtccgcaa 2580 ggtccaccgg tgcttccgsg tctgacgtcg atggctccgc aactgagggg caggcccgct 2640 tgggctcgct tatatccgcg tcactggggg cgggtctttt ggtggctccg ccctttctga 2700 cgtagaactc atgcgccacc tcagtcacgt gatcctgagc ccagcggaag aactctttga 2760 cttcctgctt ggtcaccttg ccaaagtcgt gctccagacg gcgggtgagc tcgaacttga 2820 acatgcggtc ctgcagcggc tgctggtgct cgaaggtggt gctgttcccg tcgatcacgg 288 0 cgcacatgtt ggtgttggag gtgacgatca cgggcgtggg gtcgatctgg gccgatgact 2940 tgcacttttg gtccacgcgc accttgcttc cgcccagaat ggccttggcg gactccacga 3000 ccttggcggt catcttgccc tcctcccacc agatcaccat cttgtcgacg caatcgttga 3060 agggaaagtt ctcattggtc cagttgacgc agcaagggcg aattc 3105

     <210> 22 <211> 3094

     <212> DNA. <213> new AAV serotype, clone FI <400> 22 gaattcgccc ttgctgcgtc aactggacca agagaacttt cccttcaacg attgcgtcga 60 caagatggtg atctggtggg aggagggcaa gatgacggcc aaggtcgtgg agtccgccaa 120 agccattctg ggcggaagca aggtgcgcgt cgaccaaaag tgcaagtcct cggcccagat 180 cgatcccacc cccgtgatcg tcacctccaa caccaacatg tgcgccgtga tcgacgggaa 240 cagcaccacc ttcgagcacc agcagccgtt gcaggaccgg atgttcaaat ttgaactcac 300

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     ccgccgtctg gaacacgact ttggcaaggt gaccaagcag gaagtcaaag agttcttccg 3 60 ctgggctagt gatcacgtga ctgaggtgac gcatgagttc tacgtcagaa agggcggagc 420 cagcaaaaga cccgcccccg atgacgcgga tataagcgag cccaagcggg cctgtccctc 480 agtcacggac ccatcgacgt cagacgcgga aggagctccg gtggactttg ccgacaggta 540 ccaaaacaaa tgttctcgtc acgcgggcat gcttcagatg ctgtttccct gcaaaacgtg 600 cgagagaatg aatcagaatt tcaacatttg cttcacgcac ggggtcagag actgtttaga 660 atgtttcccc ggcgtgtcag aatctcaacc ggtcgtcaga aaaaagacgt atcggaagct 720 gtgtgcgatt catcatctgc tggggcgggc acccgagatt gcttgctcgg cctgcgacct 780 ggtcaacgtg gacctggacg actgtgtttc tgagcaataa atgacttaaa ccgggtatgg 840 ctgccgatgg ttatcttcca gattggctcg aggacaacct ctctgagggc attcgcgagt 900 ggtgggacct gaaacctgga gccccgaaac ccaaagccaa ccagcaaaag caggacgacg 960 gccggggtct ggtgcttcct ggctacaagt acctcggacc cttcaacgga ctcgacaagg 1020 gggagcccgt caacgcggcg gacgcagcgg ccctcgagca cgacaaggcc tacgaccagc 1080 agctcaaagc gggtgacaat ccgtacctgc ggtataacca cgccgacgcc gagtttcagg 1140 agcgtctgca agaagatacg tcatttgggg gcaacctcgg gcgagcagtc ttccaggcca 1200 agaagcgggt tctcgaacct ctcggtctgg ttgaggaagg cgctaagacg gctcctggaa 1260 agaagagacc catagactct ccagactcct ccacgggcat cggcaaaaaa ggccagcagc 1320 ccgctaaaaa gaagctcaat tttggtcaga ctggcgactc agagtcagtc cccgaccctc 1380 aacctcttgg agaacctcca gcagcgccct ctagtgtggg atctggtaca atggctgcag 1440 gcggtggcgc accaatggca gacaataacg aaggtgccga cggagtgggt aatgcctcag 1500 gaaattggca ttgcgattcc acatggctgg gcgacagagt catcaccacc agcaccagaa 1560 cctgggccct ccccacctac aacaaccacc tctacaagca aatctccagc agcagctcag 1620 gagccaccaa tgacaaccac tacttcggct acagcacccc ctgggggtat tttgacttta 1680 acagattcca ctgccacttc tcaccacgtg actggcagcg actcatcaac aacaactggg 1740 gattccggcc caagaagctg cggttcaagc tcttcaacat ccaggtcaag gaggtcacaa 1800 cgaatgacgg cgtcacgacc atcgctaata accttaccag cacggttcag gtcttctcgg 18 60 actcggaata ccagctgccg tacgtcctcg gctctgcgca ccagggctgc ctgcctccgt 1920 tcccggcgga cgtcttcatg attcctcagt acggctacct gactctgaac aacggcagcc 1980 aatcggtggg ccgttcctcc ttctactgcc tggaatattt cccctctcaa atgctgagaa 2040 cgggcaacaa ctttgagttc agttacagct tcgaggacgt gcctttccac agcagctacg 2100 cgcacagcca gagcctagac cggctgatga accctctcat cgaccagtac ctgtactacc 2160 tggcccggac ccagagcacc acgggttcca ccagggaact gcaatttcat caagctgggc 2220

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015 ccaatactat ggccgagcag tcaaagaact ggctgcctgg accctgctat aggcaacagg 2280 gactgtcaaa gaacttggac tttaacaaca acagcaattt tgcctggact gctgccacta 2340 aatatcatct gaatggcaga aactctttga ccaatcctgg cattcccatg gcaaccaaca 2400 aggatgatga ggaccagttc tttcccatca acggggtact ggtttttggc aagacgggag 2460 ctgccaacaa aactacgctg gaaaacgttc tgatgaccag cgaggaggag atcaagacca 2520 ctaaccctgt ggctacagaa gaatacggtg tggtctccag caacctgcag ccgtctacag 2580

     ccgggcctca atcacagact atcaacagcc agggagcact gcctggcatg gtctggcaga 2640 accgggacgt gtatctgcag ggtcccatct gggccaaaat tcctcacacg gatggcaact 2700 ttcacccgtc tcctctgatg ggcggttttg gactcaaaca cccgcctcca cagatcctga 27 60 tcaaaaacac acctgtacct gctaatcctc cggaggtgtt tactcctgcc aagtttgcct 2820 ccttcatcac gcagtacagc accggacaag tcagcgtgga aatcgagtgg gagctgcaga 2880 aagaaaacag caagcgctgg aacccagaaa ttcagtatac ttccaattat gccaagtcta 2940 ataatgttga atttgctgtg aaccctgatg gtgtttatac tgagcctcgc cccattggca 3000 ctcgttacct cccccgtaat ctgtaattgc ttgttaatca ataaaccggt tgattcgttt 3060 cagttgaact ttggtctctg cgaagggcga attc 3094

     <21O> 23 <211> 3095 <212> DNA <213> new AAV serotype, clone F3 <400> 23

     gaattcgcce ttcgeagaga eeaaagttca actgaaacga atcaaccggt ttattgatta 60 acaagcaatt acagattacg ggtgaggtaa cgagtgccaa tggggcgagg ctcagtataa 120 acaccatcag ggttcacagc aaattcaaca ttattagact tggcataatt ggaagtatac 180 tgaatttctg ggttccagcg cttgctgttt tctttctgca gctcccactc gatttccacg 240 ctgaottgtc eggtgctgta ctgcgtgatg aaggaggcaa acttggcagg agtaaacacc 300 teeggaggat tagcaggtae aggtgtgttt ttgatcagga tctgtggagg cgggtgtttg 360 agtccaaaac cgcccatcag aggagaeggg tgaaagttgc catccgtgtg aggaattttg 420 gcccagatgg gaccctgeag atacacgtcc cggttctgce agaccatgcc aggcagtgct 480 ccctggctgt tgatagtctg tgattgaggc ccggctgtag acgactgcag gttgctggag 540 accacaccgt attcttctgt agccacaggg ttagtggtct tgatctcctc ctcgctggtc 600 atcagaacgt tttccagcgt agttttgttg gcagctcccg tcttgccaaa aaccagtacc 660 ccgttgatgg gaaagaactg gtcctcatca tccttgttgg ttgccatggg aatgccagga 720 ttggtcaaag agtttctgcc attcagatga tatttagtgg cagcagtcca ggcaaaattg 780

     WO 03/042397

     PCT/USO2/33629

     2015258271 20 Nov 2015

     ctgttgttgt taaagtccaa gttetttgae agtctctgtt gectatagea . gggtccaggc 840 agccagttct ttgactgctc ggeeatagta ttgggcccag ettgatgaaa , ttgcagttcc 900 ctggtggaac ccgtggtgct ctgggtccgg gccaggtagt acaggtactg gtegatgaga 960 gggttcatca gccggtctag getctggetg tgegegtage tgctgtggaa aggcacgtcc 1020 tcgaagctgt aactgaactc aaagttgttg cccgttctca gcatttgaga ggggaaatat 1080 tccaggcagt agaaggagga aeggeeeaee gattggctgc cgttgtccag agtcaggtag 1140 ccgtactgag gaatcatgaa gaegteegee gggaaeggag gcaggcagcc ctggtgcgca 1200 gagccgagga cgtacggcag etggtattcc gagteegaga agacctgaac cgtgctggta 12 60 aggttattag cgatggtcgt gaegeegtea ttcgttgtga cctccttgac ctggatgttg 1320 aggagcttga accgcagctt ettgggcegg aatccccagt tgttgttgat gagtcgctgc 1380 cagtcacgtg gtgagaagtg geagtggaat ctgttaaagt caaaataccc ccagggggtg 1440 ctgtagccga agtagtggtt gtcattggtg gctcctgagc tgctgctgga gatttgcttg 1500 tagaggtggt tgttgtaggt ggggagggec caggttctgg tgctggtggt gatgactctg 1560 tcgcccagcc atgtggaatc gcaatgeeaa tttcctgagg cattacccac tccgtcggca 1620 ccttcgttat tgtctgccat tggtgegeca eegectgeag ccattgtacc agatcccaca 168 0 ctagagggcg ctgctggagg ttetecaaga ggttgagggt cggggactga ctctgagtcg 1740 ccagtctgac caaaattgag ettcttttta gcgggctgct ggcctttttt gccgatgccc 1800 gtggaggagt ctggagagcc tatgggtcte ttctttccag gageegtett agcgccttcc 1860 tcaaccagac cgagaggttc ga'gaaeeege ttcttggcct ggaagactgc tcgcccgagg 1920 ttgcccccaa atgacgtatc ttettgeaga egetcetgaa actcggcgtc ggcgtggtta 1980 taccgcaggt acggattgtc aeccgctttg agctgctggt egtaggeett gtcgtgctcg 2040 agggccgctg cgtccgccgc gttgacgggc tcccccttgt egagteegtt gaagggtccg 2100 aggtacttgt agccaggaag caeeagaeee cggccgtcgt cctgcttttg ctggttggct 2160 ttgggtttcg gggctccagg ttteaggtee caccactcgc gaatgccctc agagaggttg 2220 tcctcgagcc aatctggaag ataaeeateg gcagccatac ctggtttaag tcatttafctg 2280 ctcagaaaca cagtcgtcca ggtccaegtt gaccaggtcg caggccgagc aagcaatctc 2340 gggtgcccgc cccagcagat gatgaatege acacagcttc egataegtet tttttctgae 2400 gaccggttga gattctgaca cgccggggaa acattctaaa cagtctctga ccccgtgcgt 2460 gaagcaaatg ttgaaattct gattcattet ctcgcacgtt ttgcagggaa acagcacctg 2520 aagcatgccc gcgtgacgag aaeatttgtt ttggtacctg teggcaaagt ccaccggagc 2580 tccttccgcg tetgaegteg atgggtecgt gactgaggga cgggcccgct tgggctcgct 2640 tatatccgcg teateggggg cgggtctttt gctggctccg ecetttctga cgtagaactc 2700

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     atgcgtcacc tcagtcacgt gatcactagc ccagcggaag aactctttga cttcctgctt 2760 tgtcaccttg ccaaagtcgt gttccagacg gcgggtgagt tcaaatttga acatccggtc 2S20 ctgcaacggt tgctggtgct cgaaggtggt gctgttcccg tcgatcacgg cgcacatgtt 2SS0 ggtgttggag gtgacgatca cgggggtggg atcgatctgg gcggacgact tgcacttttg 2940 gtccacgcgc accttgctgc cgccgagaat ggccttggcg gactccacga ccttggccgt 3000 catcttgccc tcctcccacc agatcaccat cttgtcgacg caatcgttga agggaaagtt 3060 ctcattggtc cagttgacgc agcaagggcg aattc 3095

     <210> 24 <211> 3095 <212> DMA <213> new AAV serotype, clone P5 <400> 24

     gaattcgccc ttcgcagaga ccaaagttca actgaaacga atcaaccggt ttattgatta 60 acaagcaatt acagattacg ggtgaggtaa cgagtgccaa tggggcgagg ctcagtataa 12 0 acaccatcag ggttcacagc aaattcaaca ttattagact tggcataatt ggaagtatac 18 0 tgaatttctg ggttccagcg cttgctgttt tctttctgca gctcccactc gatttccacg 240 ctgacttgtc cggtgctgta ctgcgtgatg aaggaggcaa acttggcagg agtaaacacc 300 tccggaggat tagcaggtac aggtgtgttt ttgatcagga tctgtggagg cgggtgttcg 360 agtccaaaac cgcccatcag aggagacggg tgaaagttgc catccgtgtg aggaattttg 420 gcccagatgg gaccctgcag atacacgtcc cggttctgcc agaccatgcc aggcagtgct 480 ccctggctgt tgatagtctg tgattgaggc ccggctgtag acgactgcag gttgctggag 540 accacaccgt attcttctgt agccacaggg ttagtggtct tgatctcctc ctcgctggtc 600 atcagaacgt tttccagcgt agttttgttg gcagctcccg tcttgccaaa aaccagtacc 660 ccgttgatgg gaaagaactg gtcctcatca tccttgttgg ttgccatggg aatgccagga 720 ttggtcaaag agtttctgcc attcagatga tatttagtgg cagcagtcca ggcaaaattg 780 ctgttgttgt taaagtccaa gttctttgac agtctctgtt gcctatagca gggtccaggc 840 agccagttct ttgactgctc ggccatagta ttgggcccag cttgatgaaa ttgcagttcc 900 ctggtggaac ccgtggtgct ctgggtccgg gccaggtagt acaggtactg gtcgatgaga 960 gggttcatca gccggtctag gctctggctg tgcgcgtagc tgctgtggaa aggcacgtcc 1020 tcgaagctgt aactgaactc aaagttgttg cccgttctca gcatttgaga ggggaaatat 1080 tccaggcagt agaaggagga acggcccacc gattggctgc cgttgttcag agtcaggtag 1140 ccgtactgag gaatcatgaa gacgtccgcc gggaacggag gcaggcagcc ctggtgcgca 1200 gagccgagga cgtacggcag ctggtattcc gagtccgaga agacctgaac cgtgctggta 1260 aggttattag cgatggtcgt gacgccgtca ttcgttgtga cctccttgac ctggatgttg 1320

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     aagagcttga accgcagctt cttgggccgg aatccccagt tgttgttgat gagtcgctgc 1380 cagtcacgtg gtgagaagtg gcagtggaat ctgttaaagt caaaataccc ccagggggtg 1440 ctgtagccga agtagtggtt gtcattggtg gctcctgagc tgctgctgga gatttgcttg 1500 tagaggtggt tgttgtaggt ggggagggcc caggttctgg tgctggtggt gatgactctg 1560 tcgcccagcc atgtggaatc gcaatgccaa tttcctgagg cattacccac tccgtcggca 1620 ccttcgttat tgtctgccgt tggtgcgcca ccgcctgcag ccattgtacc agatcccaca 1680 ctagagggcg ctgctggagg ttctccaaga ggttgagggt cggggactga ctctgagtcg 1740 ccagtctgac caaaattgag cttcttttta gcgggctgct ggcctttttt gccgatgccc 1800 gtggaggagt ctggagagtc tatgggtctc ttctttccag gagccgtctt agcgccttcc 1860 tcaaccagac cgagaggttc gagaacccgc ttcttggcct ggaagactgc tcgcccgagg 1920 ttgcccccaa atgacgtatc ttcttgcagg cgctcctgaa actcggcgtc ggcgtggtta 1980 taccgcaggt acggattgtc acccgctttg agctgctggt cgtaggcctt gtcgtgctcg 2040 agggccgctg cgtccgccgc gttgacgggc tcccccttgt cgagtccgtt gaagggtccg 2100 aggtacttgt agccaggaag caccagaccc cggccgtcgt cctgcttttg ctggttggct 2160 ttgggtttcg gggctecagg tttcaggtcc caccaetcgc gaatgccetc agagaggttg 2220 tcctcgagcc aatctggaag ataaccatcg gcagccatac ctggtttaag ccatttattg 2280 ctcagaaaca cagtcgtcca ggtccacgtt gaccaggtcg caggccgagc aggcaatctc 2340 gggtgcccgc cccagcagat gatgaatcgc acacagcttc cgatacgtct tttttctgac 2400 gaccggttga gattctgaca cgccggggaa acattctaaa cagtctctga ccccgtgcgt 2460 gaagcaaatg ttgaaattct gattcattct ctcgcacgtt ttgcagggaa acagcatctg 2520 aagcatgccc gcgtggcgag aacatttgtt ttggtacctg tcggcaaagt ccaccggagc 2580 tccttccgcg tctgacgtcg atgggtccgt gactgaggga caggcccgct tgggctcgct 2640 tatatccgcg tcatcggggg cgggtctttt gctggctccg ccctttctga cgtagaactc 2700 atgcgtcacc tcagtcacgt gatcactagc ccagcggaag aactctttga cttcctgctt 2760 tgtcaccttg ccaaagtcgt gttccagacg gcgggtgagt tcaaatttga acatccggtc 2820 ctgcaacggc tgctggtgct cgaaggtggt gctgttcccg tcgatcacgg cgcgcatgtt 2880 ggtgttggag gtgacgatca cgggggtggg atcgatctgg gcggacgact tgcacttttg 2940 gtccacgcgc accttgctgc cgccgagaat ggccttggcg gactccacga ccttggccgt 3000 catcttgccc tcctcccacc agatcaecat cttgtcgacg caatcgttga agggaaagtt 3060 etcattggtc cagttgacgc agcaagggcg aattc 3095

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015 <210> 25 <211> 3142 <212> DNA <213> new AAV serotype, clone H6 <400> 25

     aaaacgacgg gccagtgatt gtaatacgac tcactatagg gcgaaattga aattagcggc 60 cgcgaattcg cctttcgcag agaccaaagt tcaactgaaa cgaattaaac ggtttattga 120 ttaacaagca attacagatt acgagtcagg tatctggtgc caatggggcg aggctctgaa 180 tacacaccat tagtgtccac agtaaagtcc acattaacag acttgttgta gttggaagtg 240 tactgaattt cgggattcca gcgtttgctg ttctccttct gcagctccca ctcgatctcc 300 acgctgacct gtcccgtgga atactgtgtg atgaaagaag caaacttggc agaactgaag 360 tttgtgggag gattggctgg aacgggagtg tttttgatca tgatctgagg aggcgggtgt 42 0 ttgagtccaa aacctcccat cagtggagaa ggatgaaagt gtccatcggt gtgaggaatc 480 ttggcccaaa tgggtccctg caggtacacg tctcgatcct gccacaccat accaggtaac 540 gctccttggt gattgacagt tccagtagtt ggaccagtgt ttgagttttg caaattattt 60 0 gacacagtcc cgtactgctc cgtagccacg ggattggtgg ccctgatttc ttcttcatct 660 gtaatcatga cattttccaa atccgcgtcg ttggcatttg ttccttgttt accaaatatc 720 agggttccat gcatggggaa aaacttttct tcgtcatcct tgtgactggc catagctggt 780 cctggattaa ccaacgagtc ccggccattt agatgatact ttgtagctgc agtccaggga 840 aagttgctgt tgttgttgtc gtttgcctgt tttgacagac gctgctgtct gtagcaaggt 900 ccaggcagcc agtttttagc ttgaagagac atgttggttg gtccagcttg gctaaacagt 960 agccgagact gctgaagagt tccactattt gtttgtgtct tgttcagata atacaggtac 102 0 tggtcgatca gaggattcat cagccgatcc agactctggc tgtgagcgta gctgctgtgg 1080 aaaggcacgt cttcaaaagt gtagctgaac tgaaagttgt ttccagtacg cagcatctga 1140 gaaggaaagt actccaggca gtaaaaggaa gagcgtccta ccgcctgact cccgttgttc 1200 agggtgaggt atccatactg tgggaccatg aagacgtccg ctggaaacgg cgggaggcat 1260 ccttgatgcg ccgagcccag gacgtacggg agctggtact ccgagtcagt aaacacctga 132 0 acegtgctgg taaggttatt ggcaategte gtcgtaccgt cattctgcgt gacctctttg 1380 acttgaatat taaagagctt gaagttgagt cttttgggcc ggaatccccg gttgttgttg 1440 acgagtcttt gccagtcacg tggtgaaaag tggcagtgga atctgttgaa gtcaaaatac 1500 ccccaggggg tgctgtagcc aaagtagtgg ttgtcgttgc tggctcctga ttggctggag 1560 atttgcttgt agaggtggtt gttgtatgtg ggcagggccc aggttcgggt gctggtggtg 1620 atgactctgt cgcccagcca ttgggaatcg caatgccaat ttcctgagga attacccact 1680 ccatcggcac cctcgttatt gtctgccatt ggtgcgccac tgcctgtagc cattgtagta 1740

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     gatcccagac cagagggggc tgctggtggc tgtccgagag gctgggggtc aggtacggag 1800 tctgcgtctc cagtctgacc aaaatttaat ctttttcttg caggctgctg gcccgctttt 1860 ccggttcccg aggaggagtc tggctccaca ggagagtgct ctaccggcct cttttttccc 1920 ggagccgtct taacaggctc ctcaaccagg cccagaggtt caagaaccct ctttttcgcc 1980 tggaagactg ctcgtccgag gttgccccca aaagacgtat cttctttaag gcgctcctga 2040 aactctgcgt cggcgtggtt gtacttgagg tacgggttgt ctccgctgtc gagctgccgg 2100 tcgtaggcct tgtcgtgctc gagggccgcg gcgtctgcct cgttgaccgg ctcccccttg 2160 tcgagtccgt tgaagggtcc gaggtacttg tacccaggaa gcacaagacc cctgctgtcg 2220 tccttatgcc gctctgcggg ctttggtggt ggtgggccag gtttgagctt ccaccactgt 2280 cttattcctt cagagagagt gtcctcgagc caatctggaa gataaccatc ggcagccata 2340 cctgatttaa atcatttatt gttcagagat gcagtcatcc aaatccacat tgaccagatc 2400 gcaggcagtg caagcgtctg gcacctttcc catgatatga tgaatgtagc acagtttctg 2460 atacgccttt ttgacgacag aaacgggttg agattctgac acgggaaagc actctaaaca 2520 gtctttctgt ccgtgagtga agcagatatt tgaattctga ttcattctct cgcattgtct 2580 gcagggaaac agcatcagat tcatgcccac gtgacgagaa catttgtttt ggtacctgtc 2640 cgcgtagttg atcgaagctt ccgcgtctga cgtcgatggc tgcgcaactg actcgcgcgc 2700 cegtttgggc tcacttatat ctgcgtcact gggggcgggt cttttcttag ctccaccctt 2760 tttgacgtag aattcatgct ccacctcaac cacgtgatcc tttgcccacc ggaaaaagtc 2820 tttcacttcc tgcttggtga cctttccaaa gtcatgatcc agacggcggg taagttcaaa 2880 tttgaacatc cggtcttgca acggctgctg gtgctcgaag gtcgttgagt tcccgtcaat 2940 cacggcgcac atgttggtgt tggaggtgac gatcacggga gtcgggtcta tctgggccga 3000 ggacttgcat ttctggtcca cacgcacctt gcttcctcca agaatggctt tggccgactc 3060 cacgaccttg gcggtcatct tcccctcctc ccaccagatc accatcttgt cgacgcaatg 3120 gtaaaaggaa agttctcatt gg 3142 <210> 26 <211> 3075 <212> DNA <213> new AAV serotype, clone H2 <400> 26 tgagaacttt cctttcaacg attgcgtcgg acaagatggt gatctggtgg gaggagggga 60 agatgaccgc caaggtcgtg gagtcggcca aagccattct tggaggaagc aaggtgcgtg 120 tggaccagaa atgcaagtcc tcggcccaga tagacccgac tcccgtgatc gtcacctcca 180 acaccaacat gtgcgccgtg attgacggga actcaacgac cttcgagcac cagcagccgt 240 tgcaagaccg gatgttcaaa tttgaactta cccgccgtct ggatcatgac tttggaaagg 300

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     tcaccaagca ggaagtgaaa gactttttcc ggtgggcaaa ggatcacgtg gttgaggtgg 360 agcatgaatt ctacgtcaaa aagggtggag ctaagaaaag acccgccccc agtgacgcag 420 atataagtga gcccaaacgg gcgcgcgagt cagttgcgca gc catcaacg tcagacgcgg 480 aagcttcgat caactacgcg gacaggtacc aaaaacaaat gttctcgtca cgtgggcatg 54 0 aatctgatgc tgtttccctg cagacaatgc gagagaatga atcagaattc aaatatctgc 600 ttcactcacg gacagaaaga ctgtttagag tgctttcccg tgtcagaatc tcaacccgtt 660 tctgtcgtca aaaaggcgta tcagaaactg tgctacattc atcatatcat gggaaaggtg 720 ccagacgctt gcactgcctg cgatctggtc aatgtggatt tggatgactg catctctgaa 780 caataaatga tttaaatcag gtatggctgc cgatggttat cctccagatt ggctcgagga 840 cactctctct gaagggataa gacagtggtg gaagctcaaa cctggcccac caccaccaaa SOO gcccgcagag cggcataagg acgacagcag gggtcttgtg cttcctgggt acaagtacct 360 cggacccttc aacggactcg acaaggggga gccggtcaac gaggcagacg ccgcggccct 1020 cgagcacgac aaggcctacg accggcagct cgacagcgga gacaacccgt acctcaagta 1080 caaccacgcc gacgcagagt ttcaggagcg ccttaaagaa gatacgtctt ttgggggcaa 1140 cctcggacga gcagtcttcc aggcgaaaaa gagggttctt gaacctctgg gcctggttga 1200 ggaacctgtt aagacggctc cgggaaaaaa gaggccggta gagcactctc ctgtggagcc 1260 agactcctcc tcgggaaccg gaaaagcggg ccagcggcct gcaagaaaaa gattaaattt 1320 tggtcagact ggagacgcag actccgtacc tgacccccag cctctcggac agccaccagc 1380 agccccctct ggtctgggat ctactacaat ggctacaggc agtggcgcac caatggcaga 1440 caataacgag ggtgccgatg gagtgggtaa ttcctcagga aattggcatt gcgattccca 1500 atggctgggc gacagagtca tcaccaccag cacccgaacc tgggccctgc ccacatacaa 1560 caaccacctc tacaagcaaa tctccagcca atcaggagcc agcaacgaca accactactt 1620 tggctacagc accccctggg ggtattttga cttcaacaga ttccactgcc acttttcacc 1680 acgtgactgg caaagactca tcaacaacaa ctggggattc cggcccaaaa gactcaactt 1740 caagctcttt aatattcaag tcaaagaggt cacgcagaat gacggtacga cgacgattgc 1800 caataacctt accagcacgg ttcaggtgtt tactgactcg gagtaccagc tcccgtacgt 1860 cctgggctcg gcgcatcaag gatgcctccc gccgtttcca gcggacgtct tcatggtccc 1920 acagtatgga tacctcaccc tgaacaacgg gagtcaggcg gtaggacgct cttcctttta 1980 ctgcctggag tactttcctt ctcagatgct gcgtactgga aacaactttc agttcagcta 2040 cacttttgaa gacgtgcctt tccacagcag ctacgctcac agccagagtc tggatcggct 2100 gatgaatcct ctgatcgacc agtacctgta ttatctgaac aagacacaaa caaatagtgg 2160 aactcttcag cagtctcggc tactgtttag ccaagctgga ccaaccaaca tgtctcttca 2220

     WO 03/042397

     PCT/USO2/33629

     2015258271 20 Nov 2015

     agctaaaaac tggctgcctg gaccttgcta cagacagcag cgtctgtcaa aacaggcaaa 2280 cgacaacaac aacagcaact ttccctggac tgcagctaca aagtateate taaatggccg 2340 ggactcgttg gttaatccag gaccagctat ggccagtcac aaggatgacg aagaaaagtt 2400 tttccccatg catggaaccc tgatatttgg taaacaagga acaaatgcca aegaegegga 2460 tttggaaaat gtcatgatta cagatgaaga agaaatcagg gccaccaatc ccgtggctac 2520 ggagcagtac gggactgtgt caaataattt gcaaaactca aacactggtc caactactgg 2590 aactgtcaat cgccaaggag cgttacctgg tatggtgtgg caggatcgag acgtgtacct 2640 gcagggaccc atttgggcca agattcctca caccgatgga cactttcatc cttctccact 2700 gatgggaggt tttggactca aacacccgcc tcctcagatc atgatcaaaa acactcccgt 2760 tccagccaat cctcccacaa acttcagttc tgccaagttt gettetttea tcacacagta 2820 ttccacggga caggtcagcg tggagatcga gtgggagctg cagaaggaga acagcaaacg 2830 ctggaatccc gaaattcagt acacttccaa ctacaacaag tctgttaatg tggactttac 2940 tgtggacact aatggtgtgt attcagagcc tcgccccatt ggcaccagat acctgactcg 3000 taatctgtaa ttgcttgtta ateaataaac cgtttaattc gtttcagttg aactttggtc 3060 tctgcgaagg gcgaa 3075

     <210> 27 <211> 3128 <212> DNA <213> new AAV serotype, clone 42.8 <400> 27

     gaattcgccc tttetaegge tgcgtcaact ggaccaatga gaactttccc ttcaacgatt 60 gcgtcgacaa gatggtgatc tggtgggagg agggcaagat gacggccaag gtcgtggagt 120 ccgccaaggc cattctcggc ggcagcaagg tgcgcgtgga ccaaaagtgc aagtcttccg 180 cccagatcga tcccaccccc gtgategtea cttccaacac eaacatgtge gccgtgattg 240 acgggaacag caccaccttc gagcaccagc agccgttaca agaccggatg ttcaaatttg 300 aactcacccg ccgtctggag cacgactttg gcaaggtgac aaagcaggaa gtcaaagagt 360 tcttccgctg ggcgcaggat cacgtgaccg aggtggcgca tgagttctac gtcagaaagg 420 gtggagccaa caagagaccc gcccccgatg aegeggataa aagcgagccc aagcgggect 480 gcccctcagt cgcggatcca tegaegtcag aegeggaagg agctccggtg gactttgccg 540 acaggtacca aaacaaatgt tctcgtcacg cgggcatgct tcagatgctg tttccctgca 600 agacatgcga gagaatgaat cagaatttca acatttgett cacgcacggg accagagact 660 gttcagaatg tttccccggc gtgtcagaat ctcaaccggt egteagaaag aggaegtate 720 ggaaactctg tgccattcat catctgctag ggcgggctcc egagattget tgctcggcct 780

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     gcgatctggt caacgtggac ctggatgact gtgtttctga gcaataaatg acttaaacca 840 ggtatggctg ccgatggtta tcttccagat tggetegagg acaacctctc tgagggcatt 900 cgcgagtggt gggacttgaa acctggagcc ccgaaaccca aagccaacca gcaaaagcag 960 gacgacggcc ggggtctggt gcttcctggc tacaagtacc tcggaccctt caacggactc 1020 gacaaggggg agcccgtcaa cgcggcggac gcagcggccc tcgagcacga caaggcctac 1080 gaccagcagc teaaageggg tgacaatccg tacctgcggt ataaccacgc cgacgccgag 1140 tttcaggagc gtctgcaaga agataegtet tttgggggca acctcgggcg ageagtette 1200 caggccaaga agcgggttct cgaacctctc ggtctggttg aggaaggege taagaegget 1260 cctggaaaga agagaccggt agagccatca ccccagcgtt ctccagactc ctctacgggc 1320 atcggcaaga caggccagca gcccgcgaaa aagagactca actttgggca gactggcgac 1380 tcagagtcag tgcccgaccc tcaaccaatc ggagaacccc ccgcaggccc ctctggtctg 1440 ggatctggta caatggctgc aggcggtggc gctccaatgg cagacaataa cgaaggcgcc 1500 gacggagtgg gtagttcctc aggaaattgg cattgcgatt ccacatggct gggcgacaga 1560 gtcatcaeca ccagcacccg aacctgggcc ctccccacct acaacaacca cctctacaag 1620 caaatctcca acgggacatc gggaggaagc accaacgaca acacctactt cggctacagc 1680 accccctggg ggtattttga ctttaacaga ttccactgcc acttctcacc acgtgactgg 1740 cagcgactca tcaacaacaa ctggggattc cggcccaaga gactcaactt caagctcttc 1800 aacatccagg tcaaggaggt cacgcagaat gaaggcacca agaccatcgc caataacctt 1860 accagcacga ttcaggtctt tacggactcg gaataccagc tcccgtacgt cctcggctct 1920 gcgcaccagg gctgcctgcc tccgttcccg geggaegtet tcatgattcc teagtaeggg 1980 tacctgactc tgaacaacgg cagtcaggcc gtgggccgtt cctccttcta ctgcctggag 2040 tactttcctt ctcaaatgct gagaaeggge aacaactttg agttcagcta ccagtttgag 2100 gaegtgeett ttcacagcag ctacgcgcac agccaaagcc tggaccggct gatgaacccc 2160 ctcatcgacc agtacctgta ctacctgtct cggactcagt ccacgggagg taccgcagga 2220 actcagcagt tgctattttc teaggeeggg cctaataaca tgteggetea ggccaaaaac 2280 tggctacccg ggccctgcta ccggcagcaa cgcgtctcca cgacactgtc gcaaaataac 2340 aacagcaact ttgcttggac cggtgccacc aagtatcatc tgaatggcag agactctctg 2400 gtaaatcccg gtgtcgctat ggcaacgcac aaggacgacg aagagegatt ttttccatcc 24 60 ageggagtet tgatgtttgg gaaacaggga gctggaaaag acaacgtgga ctatagcagc 2520 gttatgctaa ccagtgagga agaaatcaaa accaccaacc cagtggccac agaacagtac 2580 ggcgtggtgg ccgataacct gcaacagcaa aacgccgctc ctattgtagg ggccgtcaac 2640 agteaaggag ccttacctgg catggtctgg cagaaccggg acgtgtacct gcagggtcct 2700

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     atctgggcca agattcctca cacggacggc aactttcatc cttcgccgct gatgggaggc 2760 tttggactga aacacccgcc tcctcagatc ctgattaaga atacacctgt tcccgcggat 2820 cctccaacta ccttcagtca agccaagctg gcgtcgttca tcacgcagta cagcaccgga 2880 caggtcagcg tggaaattga atgggagctg cagaaagaga acagcaagcg ctggaaccca 2940 gagattcagt atacttccaa ctactacaaa tctacaaatg tggactttgc tgtcaatact 3000 gagggtactt attcagagcc tcgccccatt ggcacccgtt acctcacccg taacctgtaa 3060 ttgcctgtta atcaataaac cggctaattc gtttcagttg aactttggtc tctgcgaagg 3120 gcgaattc 3128

     <210> 28 <211> 3128 <212> DNA <213> new AAV serotype, clone 42.15 <400> 28

     gaattcgccc tttctacggc tgcgtcaact ggaccaatga gaactttccc ttcaacgatt 60 gcgtcgacaa gatggtgatc tggtgggagg agggcaagat gacggccaag gtcgtggagt 120 ccgccaaggc cattctcggc ggcagcaagg tgcgcgtgga ccaaaagtgc aagtcgtccg 180 cccagatcga ccccaccccc gtgatcgtca cctccaacac caacatgtgc gccgtgattg 240 acgggaacag caccaccttc gagcaccagc agccgttgca ggaccggatg ttcaaatttg 300 aactcacccg ccgtctggag catgactttg gcaaggtgac aaagcaggaa gtcaaagagt 360 tcttccgctg ggcgcaggat cacgtgaccg aggtggcgca tgagttctac gtcagaaagg 420 gtggagccaa caagagaccc gcccccgatg acgcggataa aagcgagccc aagcgggcct 480 gcccctcagt cgcggatcca tcgacgtcag acgcggaagg agctccggtg gactttgccg 540 acaggtacca aaacaaatgt tctcgtcacg cgggcatgct tcagatgctg tttccctgca 600 agacatgcga gagaatgaat cagaatttca acatttgctt cacgcgcggg accagagact 660 gttcagaatg tttcccgggc gtgtcagaat ctcaaccggt cgtcagaaag aggacgtatc 720 ggaaactctg tgccattcat catctgctgg ggcgggctcc cgagattgct tgctcggcct 780 gcgatctggt caacgtggac ctggatgact gtgtttctga gcaataaatg acttaaacca 840 ggtatggctg ccgatggtta tcttccagat tggctcgagg acaacctctc tgagggcatt 900 cgcgagtggt gggacttgaa acctggagcc ccgaaaccca aagccaacca gcaaaagcag 960 gacgacggcc ggggtctggt gcttcctggc tacaagtacc tcggaccctt caacggactc 1020 gacaaggggg agcccgtcaa cgcggcggac gcagcggccc tcgagcacga caaggcctac 1080 gaccagcagc tcaaagcggg tgacaatccg tacctgcggt ataaccacgc cgacgccgag 1140 tttcaggagc gtctgcaaga agatacgtct tttgggggca acctcgggcg agcagtcttc 1200 caggccaaga agcgggttct cgaacctctc ggtctggttg aggaaggcgc taagacggct 1260

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     cctggaaaga agagaccggt agagccatca ccccagcgtt ctccagactc ; ctctacgggc 1320 atcggcaaga caggccagca gcccgcgaaa aagagactca actttgggca gactggcgac 1380 tcagagtcag tgcccgaccc tcaaccaatc ggagaacccc ccgcaggccc ctctggtctg 1440 ggatctggta caatggctgc aggcggtggc gctccaatgg cagacaataa cgaaggcgcc 1500 gacggagtgg gtagttcctc aggaaattgg cattgcgatt ccacatggct gggcgacaga 1560 gtcatcacca ccagcacccg aacctgggcc ctccccacct acaacaacca cctctacaag 1620 caaatctcca acgggacatc gggaggaagc accaacgaca acacctactt cggctacagc 1680 accccctggg ggtattttga ctttaacaga ttccactgcc acttctcacc acgtgactgg 1740 cagcgactca tcaacaacaa ctggggattc cggcccaaga gactcaactt caagctcttc 18 00 aacatccagg tcaaggaggt cacgcagaat gaaggcacca agaccatcgc caataacctt 18 60 accagcacga ttcaggtctt tacggactcg gaataccagc tcccgtacgt cctcggctct 1920 gcgcaccagg gctgcccgcc tccgttcccg gcggacgtct tcatgattcc tcagtacggg 1980 tacctgactc tgaacaacgg cagtcaggcc gtgggccgtt cctccttcta ctgcctggag 2040 tactttcctt ctcaaatgcg gagaacgggc aacaactttg agttcagcta ccagtttgag 2100 gacgtgcctt ttc-acagcag ctacgcgcat agccaaagcc tggaccggct gatgaacccc 2160 ctcatcgacc agtacctgta ctacctgtct cggactcagt ccacgggagg taccgcagga 2220 actcagcagt tgctattttc tcaggccggg cctaataaca tgtcggctca ggccaaaaac 2280 tggctacccg ggccctgcta ccggcagcaa cgcgtctcca cgacactgtc gcaaaataac 2340 aacagcaact ttgcttggac cggtgccacc aagtatcatc tgaatggcag agactctctg 2400 gtaaatcccg gtgtcgctat ggcaacgcac aaggacgacg aagagcgatt ttttccatcc 2460 agcggagtct tgatgtttgg gaaacaggga gctggaaaag acaacgtgga ctatagcagc 2520 gttatgctaa ccagtgagga agaaatcaaa accaccaacc cagtggccac agaacagtac 2580 ggcgtggtgg ccgataacct gcaacagcaa aacgccgctc ctatfcgtagg ggccgtcaac 2640 agtcaaggag ccttacctgg catggtctgg cagaaccggg acgtgtacct gcagggtcct 2700 atctgggcca agattcctca cacggacggc aactttcatc cttcgccgct gatgggaggc 2760 tttggactga aacacccgcc tcctcagatc ctgattaaga atacacctgt tcccgcggat 2820 cctccaacta ccttcagtca agccaagctg gcgtcgttca tcacgcagta cagcaccgga 2880 caggtcagcg tggaaattga atgggagctg cagaaagaga acagcaagcg ctggaaccca 2940 gagattcagt atacttccaa ctactacaaa tctacaaatg tggactttgc tgtcaatact 3000 gagggtactt attcagagcc tcgccccatt ggcacccgtt acctcacccg taacctgtaa 3060 ttgcctgtta atcaataaac cggttaattc gtttcagttg aactttggtc tctgcgaagg 3120 gcgaattc 3128

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015 <210> 29 <211> 3197 <212> DNA <213> new AAV serotype, clone 42.5b <400> 29

     gaattcgccc tttctacggc tgcgtcaact ggaccaatga gaactttccc ttcaacgatt 60 gcgtcgacaa gatggtgatc tggtgggagg agggcaagat gacggccaag gtcgtggagt 120 ccgccaaggc cattctcggc ggcagcaagg tgcgcgtgga ccaaaagtgc aagtcgtccg 180 cccagatcga ccccaccccc gtgatcgtca cctccaacac caacatgtgc gccgtgattg 240 acgggaacag caccaccttc gagcaccagc agccgttaca agaccggatg ttcaaatttg 300 aactcacccg ccgtctggag cacgactttg gcaaggtgac aaagcaggaa gtcaaagagt 360 tcttccgctg ggcgcaggat oacgtgaccg aggtggcgca tgagttctac gtcagaaagg 420 gtggagccaa caagagaccc gcccccgatg acgcggataa aagcgagccc aagcgggcct 480 gcccctcagt cgcggatcca tcgacgtcag acgcggaagg agctccggtg gactttgccg 540 acaggtacca aaacaaatgt tctcgtcacg cgggcatgct tcagatgctg tttccctgca 600 agacatgcga gagaatgaat cagaatttca acatttgctt cacgcacggg accagagact 660 gttcagaatg tttccccggc gtgtcagaat ctcaaccggt cgtcagaaag aggacgtatc 720 ggaaactctg tgccattcat catctgctgg ggcgggctcc cgagattgct tgctcggcct 780 gcgatctggt caacgtggac ctggatgact gtgtttctga gcaataaatg acttaaacca 840 ggtatggctg ccgatggtta tcttccagat tggctcgagg acaacctctc tgagggcatt 900 cgcgagtggt gggacttgaa acctggagcc ccgaaaccca aagccaacca gcaaaagcag 960 gacgacggcc ggggtctggt gcttcctggc tacaagtacc tcggaccctt caacggactc 1020 gacaagggag agccggtcaa cgaggcagac gccgcggccc tcgagcacga caaggcctac 1080 gacaagcagc tcgagcaggg ggacaacccg tacctcaagt acaaccacgc cgacgccgag 114 0 tttcaggagc gtcttcaaga agatacgtct tttgggggca acctcgggcg agcagtcttc 1200 caggccaaga agcgggttct cgaacctctc ggtctggttg aggaaggcgc taagacggct 1260 cctggaaaga agagaccggt agagccatca ccccagcgtt ctccagactc ctctacgggc 1320 atcggcaaga caggccagca gcccgcgaaa aagagactca actttgggca gactggcgac 1380 tcagagtcag tgcccgaccc tcaaccaatc ggagaacccc ccgcaggccc ctctggtctg 1440 ggatctggta caatggctgc aggcggtggc gctccaatgg cagacaataa cgaaggcgcc 1500 gacggagtgg gtagttcctc aggaaattgg cattgcgatt ccacatggct gggcgacaga 1560 gtcatcacca ccagcacccg aacctgggcc ctccccacct acaacaacca cctctacaag 1620 caaatctcca acgggacatc gggaggaagc accaacgaca acacctactt cggctacagc 1680 accccctggg ggtattttga ctttaacaga ttccactgcc acttctcacc acgtgactgg 1740

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     cagcgactca tcaacaacaa ctggggattc cggcccaaga gactcaactt caagctcttc 1800 aacatccagg tcaaggaggt cacgcagaat gaaggcacca agaccatcgc caataacctt 1860 accagcacga ttcaggtctt tacggactcg gaataccagc tcccgtacgt cctcggctct 1920 gcgcaccagg gctgcctgcc tccgttcccg gcggacgtct tcatgattcc tcagtacggg 1980 tacctgactc tgaacaacgg cagtcaggcc gtgggccgtt cctccttcta ctgcctggag 2040 tactttcctt ctcaaatgct gagaacgggc aacaactttg agttcagcta ccagtttgag 2100 gacgtgcctt ttcacagcag ctacgcgcac agccaaagcc tggaccggct gatgaacccc 2160 ctcatcgacc agtacctgta ctacctgtct cggactcagt ccacgggagg taccgcagga 2220 actcagcagt tgctattttc tcaggccggg cctaataaca tgtcggctca ggccaaaaac 228 0 tggctacccg ggccctgcta ccggcagcaa cgcgtctcca cgacactgtc gcaaaataac 2340 aacagcaact ttgcttggac cggtgccacc aagtatcatc tgaatggcag agactctctg 2400 gtaaatcccg gtgtcgctat ggcaacgcac aaggacgacg aagagcgatt ttttccatcc 2460 agcggagtct tgatgtttgg gaaacaggga gctggaaaag acaacgtgga ctatagcagc 2520 gttatgctaa ccagtgagga agaaatcaaa accaccaacc cagtggccac agaacagtac 2580 ggcgtggtgg ccgataacct gcaacagcaa aacgccgctc ctattgtagg ggccgtcaac 2640 agtcaaggag ccttacctgg catggtetgg cagaaccggg acgtgtacct gcagggtcct 2700 atctgggcca agattcctca cacggacggc aactttcatc cttcgccgct gatgggaggc 2760 tttggactga aacacccgcc tcctcagatc ctgattaaga atacacctgt tcccgcggat 2820 cctccaacta ccttcagtca agccaagctg gcgtcgttca tcacgcagta cagcaccgga 2880 caggtcagcg tggaaattga atgggagctg cagaaagaga acagcaagcg ctggaaccca 2940 gagattcagt atacttccaa ctactacaaa tctacaaatg tggactttgc tgtcaatact 3000 gagggtactt attcagagcc tcgccccatt ggcacccgtt acctcacccg taacctgtaa 3060 ttgcctgtta atcaataaac cggttaattc gtttcagttg aactttggtc tctgcgaagg 3120 gcgaattcgt ttaaacctgc aggactagtc cctttagtga gggttaattc tgagcttggc 3180 gtaatcatgg gtcatag 3197 <210> 30 <211> 2501 <212> DNA <213> new AAV serotype, clone 42 .lb <400> 30 gaattcgccc ttggctgcgt caactggacc aatgagaact ttcccttcaa cgattgcgtc 60 gacaagatgg tgatctggtg ggaggagggc aagatgacgg ccaaggtcgt ggagtccgcc 120 aaggccattc atcatctgct ggggcgggct cccgagattg cttgctcggc ctgcgatctg 18 0 gtcaacgtgg acctggatga ctgtgtttct gagcaataaa tgacttaaac caggtatggc 240

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     tgccgatggt tatcttccag attggctcga ggacaacctc tctgagggca . ttcgcgagtg 300 gtgggacttg agacctggag ccccgaaacc caaagccaac cagcaaaagc aggacgacgg 360 ccggggtctg gtgcttcctg gctacaagta cctcggaccc ttcaacggac tcgacaaggg 420 agagccggtc aacgaggcag acgccgcggc cctcgagcac gacaaggcct acgacaagca 480 gctcgagcag ggggacaacc cgtacctcaa gtacaaccac gccgacgccg agtttcagga 540 gcgtcttcaa gaagatacgt cttttggggg caacctcggg cgagcagtct tccaggccaa 600 gaagcgggtt ctcgaacctc tcggtctggt tgaggaaggc gctaagacgg ctcctggaaa 660 gaagagaccc atagaatccc ccgactcctc cacgggcatc ggcaagaaag gccagcagcc 720 cgctaaaaag agactcaact ttgggcagac tggcgactca gagtcagtgc ccgaccctca 780 accaatcgga gaaccccccg caggcccctc tggtctggga tctggcacaa tggctgcagg B40 cggtggcgct ccaatggcag acaataacga aggcgccgac ggagtgggta gttcctcagg 900 aaattggcat tgcgattcca catggctggg cgacagagtc atcaccacca gcacccgaac 960 ctgggccctc cccacctaca acaaccacct ctacaagcaa atctccaacg ggacatcggg 1020 aggaagcacc aacgacaaca cctacttcgg ctacagcacc ccctgggggt attttgactt 1080 taacagattc cactgccact tctcaccacg tgactggcag cgactcatca acaacaactg 1140 gggattccgg cccaagagac tcaacttcaa gctcttcaac atccaggtca aggaggtcac 1200 gcagaatgaa ggcaccaaga ceatcgceaa taaccttacc agcacgattc aggtctttac 1260 ggactcggaa taccagctcc cgtacgtcct cggctctgcg caccagggct gcctgcctcc 1320 gttcccggcg gacgtcttca tgattcctca gtacgggtac ctgactctga acaacggcag 1380 tcaggccgtg ggccgttcct ccttctactg cctggagtac tttccttctc aaatgctgag 1440 aacgggcaac aactttgagt tcagctacca gtttgaggac gtgccttttc acagcagcta 1500 tgcgcacagc caaagcctgg accggctgat gaaccccctc atcgaccagt acctgtacta 1560 cctgtctcgg actcagtcca cgggaggtac cgcaggaact cagcagttgc tattttctca 1620 ggccgggcct aataacatgt cggctcaggc caaaaactgg ctacccgggc cctgctaccg 1680 gcagcaacgc gtctccacga cagtgtcgca aaataacaac agcaactttg cttggaccgg 1740 tgccaccaag tatcatctga atggcagaga ctctctggta aatcccggtg tcgctatggc 1800 aacgcacaag ggcgacgaag agcgattttt tccatccagc ggagtcttga tgtttgggaa 1860 acagggagct ggaaaagaca acgtagacta tagcagcgtt atgctaacca gtgaggaaga 1920 aatcaaaacc accaacccag tggccacaga acagtacggc gtggtggccg ataacctgca 1980 acagcaaaac gccgctccta ttgtaggggc cgtcaacagt caaggagcct tacctggcat 2040 ggtctggcag aaccgggacg tgtacctgca gggtcctatc tgggccaaga ttcctcacac 2100 ggacggcaac tttcatcctt cgccgctgat gggaggcttt ggactgaaac acccgcctcc 2160

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015 tcagatcctg attaagaata cacctgttcc cgcggatcct ccaactacct tcagtcaagc 2220 caagctggcg tcgttcatca cgcagtacag caccggacag gtcagcgtgg aaattgaatg 2280 ggagctgcag aaagagaaca gcaagcgctg gaacccagag attcagtata cttccaacta 2340 ctacaaatct acaaatgtgg actttgctgt caatactgag ggtacttatt cagagcctcg 2400 ccccattggc acccgttacc tcacccgtaa cctgtaattg cctgttaatc aataaaccgg 2460 ttgattcgtt tcagttgaac tttggtctca agggcgaatt c 2501 <210> 31 <211> 3113 <2l2> DNA <2l3> new AAV serotype, clone 42.13 <400> 31

     gaattcgccc tttctacggc tgcgtcaact ggaccaatga gaactttccc ttcaacgatt 60 gcgtcgacaa gatggtgatc tggtgggagg agggcaagat gacggccaag gtcgtggagt 120 ccgccaaggc cattctcggc ggcagcaagg tgcgcgtgga ccaaaagtgc aagtcgtccg 180 cccagatcga tcccaccccc gtgatcgtca cttccaacac caacatgtgc gccgtgattg 240 acgggaacag caccaccttc gagcaccagc agccgttaca agaccggatg ttcaaatttg 300 aactcacccg ccgtctggag catgactttg gcaaggtgac aaagcaggaa gtcaaagagt 360 tcttccgctg ggcgcaggat cacgtgaccg aggtggcgca tgagttctac gtcagaaagg 420 gtggagccaa caagagaccc gcccccgatg acgcggataa aagcgagccc aagcgggcct 480 gcccctcagt cgcggatcca tcgacgtcag acgcggaagg agctccggtg gactttgccg 540 acaggtacca aaacaaatgt tctcgtcacg cgggcatgct tcagatgctg tttccctgca 600 agacatgcga gagaatgaat cagaatttca acatttgctt cacgcacggg accagagact 660 gttcagaatg tttccccggc gtgtcagaat ctcaaccggt cgtcagaaag aggacgtatc 720 ggaaactctg tgccattcat catctgctgg ggcgggctcc cgagattgct tgctcggcct 780 gcgatctggt caacgtggac ctggatgact gtgtttctga gcaataaatg act taaacca 840 ggtatggctg ccgatggtta tcttccagat tggctcgagg acaacctctc tgagggcatt 900 cgcgagtggt gggacttgaa acctggagcc ccgaaaccca aagccaacca gcaaaagcag 960 gacgacggcc ggggtctggt gcttcctggc tacaagtacc tcggaccctt caacggactc 1020 gacaaggggg agcccgtcaa cgcggcggac gcagcggccc tcgagcacga caaggcctac 1080 gaccagcagc tcaaagcggg tgacaatccg tacctgcggt ataaccacgc cgacgccgag 1140 tttcaggagc gtcttcaaga agatacgtct tttgggggca acctcgggcg agcagtcttc 1200 caggccaaga agcgggttct cgaacctctc ggtctggttg aggaaggcgc taagacggct 1260 cctggaaaga agagacccat agaatccccc gactcctcca cgggcatcgg caagaaaggc 1320 cagcagcccg ctaaaaagaa gctcaacttt gggcagactg gcgactcaga gtcagtgccc 1380

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     gaccctcaac caatcggaga accccccgca ggcccctctg gtctgggatc tggtacaatg 1440 gctgcaggcg gtggcgctcc aatggcagac aataacgaag gcgccgacgg agtgggtagt 1500 tcctcaggaa attggcattg cgattccaca tggctgggcg acagagtcat caccaccagc 1560 acccgaacct gggccctccc cacctacaac aaccacctct acaagcaaat ctccaacggg 1620 acatcgggag gaagcaccaa cgacaacacc tacttcggct acagcacccc ctgggggtat 1680 tttgacttta acagattcca ctgccacttc tcaccacgtg actggcagcg actcatcaac 1740 aacaactggg gattccggcc caagagactc aacttcaagc tcttcaacat ccaggtcaag 1800 gaggtcacgc agaatgaagg caccaagacc atcgccaata accttaccag cacgattcag 1860 gtctttacgg actcggaata ccagctcccg tacgtcctcg gctctgcgca ccagggctgc 1920 ctgcctccgt tcccggcgga cgtcttcatg attcctcagt acgggtacct gactctgaac 1980 aacggcagtc aggccgtggg ccgttcctcc ttctactgcc tggagtactt tccttctcaa 2040 atgctgagaa cgggcaacaa ctttgagttc agctaccagt ttgaggacgt gccttttcac 2100 agcagctatg cgcacagcca aagcctggac cggctgatga accccctcat cgaccagtac 2160 ctgtactacc tgtctcggac tcagtccacg ggaggtaccg caggaactca gcagttgcta 2220 ttttctcagg ccgggcctaa taacatgtcg gctcaggcca aaaactggct acccgggccc 2280 tgctaccggc agcaacgcgt ctccacgaca gtgtcgcaaa ataacaacag caactttgct 2 340 tggaccggtg ccaccaagta tcatctgaat ggcagagact ctctggtaaa tcccggtgtc 2400 gctatggcaa cgcacaaggg cgacgaagag cgattttttc catccagcgg agtcttgatg 2460 tttgggaaac agggagctgg aaaagacaac gtggactata gcagcgttat gctaaccagt 2520 gaggaagaaa tcaaaaccac caacccagtg gccacagaac agtacggcgt ggtggccgat 2580 aacctgcaac agcaaaacgc cgctcctatt gtaggggccg tcaacagtca aggagcctta 2640 cctggcatgg tctggcagaa ccgggacgtg tacctgcagg gtcctatctg ggccaagatt 2700 cctcacacgg acggcaactt tcatccttcg ccgctgatgg gaggctttgg actgaaacac 2760 ccgcctcctc agatcctgat taagaataca cctgttcccg cggatcctcc aactaccttc 2820 agtcaagcca agctggcgtc gttcatcacg cagtacagca ccggacaggt cagcgtggaa 2880 attgaatggg agctgcagaa agagaacagc aagcgctgga acccagagat tcagtatact 2940 tccaactact acaaatctac aaatgtggac tttgctgtca atactgaggg tacttattca 3000 gagcctcgcc ccattggcac ccgttacctc acccgtagcc tgtaattgec tgttaatcaa 3060 taaaccggtt gattcgtttc agttgaactt tggtctctgc gaagggcgaa ttc 3113 <210> 32 <211> 3113 <212> DNA <213> new AAV serotype, clone 42.3a

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     <400> 32 gaattcgccc tttctacggc tgcgtcaact ggaccaatga gaactttccc ttcaacgatt 60 gcgtcgacaa gatggtgatc tggtgggagg agggcaagat gacggccaag gtcgtggagt 120 ccgccaaggc cattctcggc ggcagcaagg tgcgcgtgga ccaaaagtgc aagtcgtccg 180 cccagatcga tcccaccccc gtgatcgtca cttccaacac caacatgtgc gccgtgattg 240 acgggaacag caccaccttc gagcaccagc agccgttaca agaccggatg ttcaaatttg 300 aactcacccg ccgtctggag catgactttg gcaaggtgac aaagcaggaa gtcaaagagt 3 60 tcttccgctg ggcgcaggat cacgtgaccg aggtggcgca tgagttctac gtcagaaagg 420 gtggagccaa caagagaccc gcccccgatg acgcggataa aagcgagccc aagcgggcct 480 gcccctcagt cgcggatcca tcgacgtcag acgcggaagg agctccggtg gactttgccg 540 acaggtacca aaacaaatgt tctcgtcacg cgggcatgct tcagatgctg cttccctgca 600 agacatgcga gagaatgaat cagaatttca gcatttgctt cacgcacggg accagagact 660 gttcagaatg tttccccggc gtgtcagaat ctcaaccggt cgtcagaaag aggacgtatc 720 ggaaactctg tgccattcat catctgctgg ggcgggctcc cgagattgct tgctcggcct 780 gcgatctggt caacgtggac ctggatgact gtgtttctga gcaataaatg acttaaacca 840 ggtatggctg ccgatggtca tcttccagat tggctcgagg acaacctctc tgagggcatt 900 cgcgagtggt gggacttgaa acctggagcc ccgaaaccca aagccaacca gcaaaagcag 960 gacgacggcc ggggtctggt gcttcctggc tacaagtacc tcggaccctt caacggactc 1020 gacaaggggg agcccgtcaa cgcggcggac gcagcggccc tcgagcacga caaggcctac 1080 gaccagcagc tcaaagcggg tgacaatccg tacctgcggt ataaccacgc cgacgccgag 1140 tttcaggagc gtcttcaaga agatacgtct tttgggggca acctcgggcg agcagtcttc 1200 caggccaaga agcgggttct cgaacctctc ggtctggttg aggaaggc-gc taagacggct 1260 cctggaaaga agagacccat agaatccccc gactcctcca cgggeatcgg caagaaaggc 1320 cagcagcccg ctaaaaagaa gctcaacttt gggcagactg gcgactcaga gtcagtgccc 1380 gaccctcaac caatcggaga accccccgca ggcccctctg gtctgggatc tggtacaatg 1440 gctgcaggcg gtggcgctcc aatggcagac aataacgaag gcgccgacgg agtgggtagt 1500 tcctcaggaa attggcattg cgattccaca tagctgggcg acagagtcat caccaccagc 15 60 acccgaacct gggccctccc cacctacaac aaccacctct acaagcaaat ctccaacggg 1620 acatcgggag gaagcaccaa cgacaacacc tacttcggct acagcacccc ctgggggtat 1680 tttgacttta acagattcca ctgccacttc tcaccacgtg actggcagcg actcatcaac 1740 aacagctggg gattccggcc caagagactc aacttcaagc tcttcaacat ccaggtcaag 1800 gaggtcacgc agaatgaagg caccaagacc atcgccaata accttaccag cacgattcag 1860 gtctttacgg actcggaata ccagctcccg tacgtcctcg gctctgcgca ccagggctgc 1920

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     ctgcctccgt tcccggcgga cgtcttcatg attcctcagt acgggtacct gactctgaac 1980 aacggcagtc aggccgtggg ccgttcctcc ttctactgcc tggagtactt tccttctcaa 2040 atgctgagaa cgggcaacaa ctttgagttc agctaccagt ttgaggacgt gccttttcac 2100 agcagctacg cgcacagcca aagcctggac cggctgatga accccctcat cgaccagtac 2160 ctgtactacc tgtctcggac tcagtccacg ggaggtaccg caggaactca gcagttgcta 2220 ttttctcagg ccgggcctaa taacatgtcg gctcaggcca aaaactggct acccgggccc 2280 tgctaccggc agcaacgcgt ctccacgaca ctgtcgcaaa ataacaacag caactttgct 2340 tggaccggtg ccaccaagta tcatctgaat ggcagagact ctctggtaaa tcccggtgtc 2400 gctatggcaa cgcacaagga cgacgaagag cgattttttc catccagcgg agtcttgatg 2460 tttgggaaac agggagctgg aaaagacaac gtggactata gcagcgttat gctaaccagt 2520 gaggaagaaa tcaaaaccac caacccagtg gccacagaac agtacggcgt ggtggccgat 2580 aacctgcaac agcaaaacgc cgctcctatt gtaggggccg tcaacagtca aggagcctta 2640 cctggcatgg tctggcagaa ccgggacgtg tacctgcagg gtcctatctg ggccaagatt 2700 cctcacacgg acggcaactt tcatccttcg ccgctgatgg gaggctttgg actgaaacac 2760 ccgcctcctc agatcctgat taagaataca cctgttcccg cggatcctcc aactaccttc 2820 agtcaagcca agctggcgtc gttcatcacg cagtacagca ceggaeaggt cagcgtggaa 2880 attgaatggg agctgcagaa agagaacagc aagcgctgga acccagagat tcagtatact 2 94 0 tccaactact acaaatctac aaatgtggac tttgctgtca atactgaggg tacttattca 3000 gagcctcgcc ccattggcac ccgttacctc acccgtaacc tgtaattgcc tgttaatcaa 3060 taaaccggtt aattcgtttc agttgaactt tggtctctgc gaagggcgaa ttc 3113

     <210> 33 <211> 2504

     <212> DMA <213> new AAV serotype, clone 42.4 <400> 33 gaattcgccc tttctacggc tgcgtcaact ggaccaatga gaactttccc ttcaacgatt 60 gcgtcgacaa gatggtgatc tggtgggagg agggcaagat gacggccaag gtcgtggagt 120 ccgccaaggc cattcatcat ctgctggggc gggctcccga gattgcttgc tcggcctgcg 180 atctggtcaa cgtggacctg gatgactgtg tttctgagca ataaatgact taaaccaggt 240 atggctgccg atggttatct tccagattgg ctcgaggaca acctctctga gggcattcgc 300 gagtggtggg acttgaaacc tggagccccg aaacccaaag ccaaccagca aaagcaggac 360 gacggccggg gtctggtgct tcctggctac aagtacctcg gacccttcaa cggactcgac 420 aagggagagc cggtcaacga ggcagacgcc gcggccctcg agcacgacaa ggcctacgac 480 aagcagctcg agcaggggga caacccgtac ctcaagtaca accacgccga cgccgagttt 540

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     caggagcgtc ttcaagaaga tacgtctttt gggggcaacc : tcgggcgagc agtcttccag 600 gccaagaagc gggttctcga acctctcggt ctggttgagg ¹ aaggcgctas l gacggctcct 660 ggaaagaaga gacccataga atcccccgac tcctccacgg gcatcggcaa l gaaaggccag 720 cagcccgcta aaaagaagct caactttggg cagactggcg actcagagtc agtgcccgac 780 cctcaaccaa tcggagaacc ccccgcaggc ccctctggtc tgggatctgg tacaatggct 840 gcaggcggtg gcgctccaat ggcagacaat aacgaaggcg ccgacggagt gggtaatgcc 900 tccggaaatt ggcattgcga ttccacatgg ctgggcgaca gagtcatcac caccagcacc 960 cgcacctggg ccctgcccac ctacaacaac cacctctaca agcagatatc aagtcagagc 1020 ggggctacca acgacaacca cttcttcggc tacagcaccc cctggggcta ttttgacttc 1080 aacagattcc actgccactt ctcatcacgt gactggcagc gactcatcaa caacaactgg 1140 ggattccggc ccaagagact caacttcaag ctcttcaaca tccaggtcaa ggaggtcacg 1200 cagaatgaag gcaccaagac catcgccaat aaccttacca gcacgattca ggtctttacg 1260 gactcggaat accggctccc gtacgtcctc ggctctgcgc accagggctg cctgcctccg 1320 ttcccggcgg acgtcttcat gattcctcag tacgggtacc tgactctgaa caacggcagt 1380 caggccgtgg gccgttcctc cttctactgc ctggagtact ttccttctca aatgctgaga 1440 acgggcaaca actttgagtt cagctaccag tttgaggacg tgccttttca cagcagctac 1500 gcgcacagcc aaagcctgga ccggctgatg aaccccctca tcgaccagta cctgtactac 1560 ctgtctcgga ctcagtccac gggaggtacc gcaggaactc agcagttgct attttctcag 1620 gccgggccta ataacatgtc ggctcaggcc aaaaactggc tacccgggcc ctgctaccgg 1680 cagcaacgcg tctccacgac actgtcgcaa aataacaaca gcaactttgc ttggaccggt 1740 gccaccaagt atcatctgaa tggcagagac tctctggtaa atcccggtgt cgctatggca 1800 acgcacaagg acgacgaaga gcgatttttt ccatccagcg gagtcttgat gtttgggaaa 1860 cagggagctg. gaaaagacaa cgtggactat agcagcgtta tgctaaccag tgaggaagaa 1920 atcaaaacca ccaacccagt ggccacagaa cagtacggcg tggtggccga taacctgcaa 1980 cagcaaaacg ccgctcctat tgtaggggcc gtcaacagtc aaggagcctt acctggcatg 2040 gtctggcaga accgggacgt gtacctgcag ggtcctatct gggccaagat tcctcacacg 2100 gacggcaact ttcatccttc gccgctgatg ggaggctttg gactgaaaca cccgcctcct 2160 cagatcctga ttaagaatac acctgttccc gcggatcctc caactacctt cagtcaagcc 2220 aagccggcgt cgttcatcac gcagtacagc accggacagg tcagcgtgga aattgaatgg 2280 gagctgcaga aagagaacag caagcgctgg aacccagaga ttcagtatac ttccaactac 2340 tacaaatcta caaatgtgga ctttgctgtc aatactgagg gtacttattc agagcctcgc 2400 cccattggca cccgttacct cacccgtaac ctgtaattgc ctgttaatca ataaaccggt 2460

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015 taattcgttt cagttgaact ttggtctctg cgaagggcga attc 2504 <210> 34 <2ll> 3106 <212> DMA <213> new AAV serotype, clone 42.5a <400> 34

     gaattcgccc ttctacggct gcgtcaactg gaccaatgag aactttccct tcaacgattg 60 cgtcgacaag atggtgatct ggtgggagga gggcaagatg acggccaagg tcgtggagtc 120 cgccaaggcc attctcggcg gcagcaaggt gcgcgtggac caaaagtgca agtcgtccgc 180 ccagatcgac cccacccccg tgatcgtcac ctccaacacc aacatgtgcg ccgtgattga 240 cgggaacagc accaccttcg agcaccagca gccgttgcag gaccggatgt tcaaatttga 300 actcacccgc cgtctggagc atgactttgg caaggcgaca aagcaggaag tcaaagagtt 360 cttccgctgg gcgcaggatc acgtgaccga ggtggcgcat gagttctacg tcagaaaggg 420 tggagccaac aagagacccg cccccgatga cgcggataaa agcgagccca agcgggcccg 480 cccctcagtc gcggatccat cgacgtcaga cgcggaagga gctccggtgg actttgccga 540 caggtaccaa aacaaatgtt ctcgtcacgc gggcatgctt cagatgctgt ttccctgcaa 600 aacatgcgag agaatgaatc agaatttcaa catttgcttc acgcacggga ccagagactg 660 ttcagaatgt ttccccggcg tgtcagaatc tcaaccggtc gtcagaaaga ggacgtatcg 720 gaaactctgt gccattcatc atctgctggg gcgggctccc gagattgctt gctcggcctg 780 cgatctggtc aacgtggacc tggatgactg tgtttctgag caataaatga cttaaaccag 840 gtatggctgc cgatggttat cttccagatt ggctcgagga caacctctct gagggcattc 900 gcgagtggtg ggacttgaaa cctggagccc cgaaacccaa agccaaccag caaaagcagg 960 acgacggccg gggtctggtg cttcctggct acaagtacct cggacccttc aacggactcg 1020 acaagggaga gccggtcaac gaggcagacg ccgcggccct cgagcacgac aaggcctacg 1030 acaagcagct cgagcagggg gacaacccgt acctcaagta caaccacgcc gacgccgagt 114 0 ttcaggagcg tcttcaagaa gatacgtctt ttgggggcaa cctcgggcga gcagtcttcc 1200 gggccaagaa gcgggttctc gaacctctcg gtctggttga ggaaggcgct aagacggctc 1260 ctggaaagaa gagaeccata gaatcccccg actcctccac gggcatcggc aagaaaggcc 1320 agcagcccgc taaaaagaag ctcaactttg ggcagactgg cgactcagag tcagtgcccg 1380 acccccaacc tctcggagaa cctcccgccg cgccctcagg tctgggatct ggtacaatgg 1440 ctgcaggcgg tggcgcacca atggcagaca ataacgaagg cgccgacgga gtgggtaatg 1500 cctccggaaa ttggcattgc gattccacat ggctgggcga cagagtcatc accaccagoa 1560 cccgcacctg ggccctgccc acctacaaca accacctcta caagcagata tcaagtcaga 1620 gcggggctac caacgacaac cacttcttcg gctacagcac cccctggggc tattttgact 1680

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     tcaacagatt ccactgccac ttctcaccac gtgactggca gcgactcatc aacaacaacc 1740 ggggattccg gcccagaaag ctgcggttca agttgttcaa catccaggtc aaggaggtca 1800 cgacgaacga cggcgttacg accatcgcta ataaccttac cagcacgatt caggtcttct 1860 cggactcgga gtaccaactg ccgtacgtcc tcggctctgc gcaccagggc tgcctccctc 1920 cgttccctgc ggacgtgttc atgattcctc agtaeggata tctgactcta aacaacggca 1980 gtcagtctgt gggacgttcc tccttctact gcctggagta ctttccttct cagatgctga 2040 gaacgggcaa taactttgaa ttcagctacc agtttgagga cgtgcccttt cacagcagct 2100 acgcgcacag ccaaagcctg gaccggctga tgaaccccct catcgaccag tacctgtact 2160 acctgtctcg gactcagtcc acgggaggta ccgcaggaac tcagcagttg ctattttctc 2220 aggccgggcc taataacatg tcggctcagg ccaaaaactg gctacccggg ccctgctacc 2280 ggcagcaacg cgtctccacg acactgtcgc aaaataacaa cagcaacttt gcttggaccg 2340 gtgccaccaa gtatcatctg aatggcagag actctctggt aaatcccggt gtcgctatgg 2400 caacgcacaa ggacgacgaa gagcgatttt ttccatccag eggagtettg atgtttggga 2460 aacagggagc tggaaaagac aacgtggact atagcagegt tatgctaacc agtgaggaag 2520 aaatcaaaac caccaaccca gtggccacag aacagtacgg cgtggtggcc gataacctgc 2580 aacagcaaaa cgcegctcct attgtagggg ccgtcaacag teaaggagee ttacctggca 2640 tggcctggca gaaccgggac gtgtacctgc agggtcctat ctgggccaag attcctcaca 2700 cggacggcaa ctttcatcct tcgccgctga tgggaggctt tggactgaaa cacccgcctc 2760 ctcagatcct gattaagaat acacctgttc ccgcggatcc tccaactacc ttcagtcaag 2820 ccaagctggc gtcgttcatc acgcagtaca gcaccggaca ggtcagcgtg gaaattgaat 2880 gggagctgca gaaagagaac ageaageget ggaacccaga gattcagtat acttccaact 2940 actacaaatc tacaaatgtg gactttgctg tcaatactga gggtacttat tcagagcctc 3000 gccccattgg cacccgttac ctcacccgta acctgtaatt gcctgttaat caataaaccg 3060 gttaattcgt ttcagttgaa ctttggtctc tgcgaagggc gaatt c 3106 <210 35 <211> 2439 <212> DNA <213> new 1 AAV serotype, clone 42 .10 <400> 35 gaattcgccc tttetaegge tgcgtcaact ggaccaatga gaactttccc ttcaacgatt 60 gcgtcgacaa gatggtgatc tggtgggagg agggcaagat gacggccaag gtcgtgaagt 120 ccgccaaggc cattcatcat ctgctggggc gggctcccga gattgettge tcggcctgcg 18 0 atctggtcaa cgtggacctg gatgactgtg tttctgagca ataaatgact taaaccaggt 240 atggctgccg atggttatct tccagattgg ctcgaggaca acctctctga gggcattcgc 300

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     gagtggtggg acttgaaacc tggagccccg aaacccaaag r ccaaccagca . aaagcaggac 360 gacggccggg gtctggtgct tcctggctac aagtacctcg gacccttcaa . cggactcgac 420 aagggagagc cggtcaacga ggcagacgcc gcggccctcg agcacgacaa ggcctacgac 480 aagcagctcg agcaggggga caacccgtac ctcaagtaca accacgccga cgccgagttt 540 caggagcgtc ttcaagaaga tacgtctttt gggggcaacc tcgggcgagc agtcttccag 600 gccaagaagc gggttctcga acctctcggt ctggttgagg aaggcgctaa gacggctcct 660 ggaaagaaga gacccataga atcccccgac tcctccacgg gcatcggcag gaaaggccag 720 cagcccgcta aaaagaagct caactttggg cagactggcg actcagagtc agtgcccgac 780 cctcaaccaa tcggagaacc ccccgcaggc ccctctggtc tgggatctgg tacaatggct 340 gcaggcggtg gcgctccaat ggcagacaat aacgaaggcg ccgacggagt gggtaatgcc 900 tccggaaatt ggcattgcga ttccacatgg ctgggcgaca gagtcatcac caccagcacc 960 cgcacctggg ccctgcccac ctacaacaac cacctctaca agcagatatc aagtcagagc 1020 ggggctacca acgacaacca cttcttcggc tacagcaccc cctggggcta ttttgacttc 1080 aacagattcc actgccactt ctcaccacgt gactggcagc gactcatcaa caacaactgg 1140 ggattccggc ccagaaagct gcggttcaag ttgttcaaca tccaggtcaa ggaggtcacg 1200 acgaacgacg gcgttacgac catcgccaat aaccttacca gcacgattca ggtettctcg 1260 gactcggagt accaactgcc gtacgtccte ggctctgcgc accagggctg cctccctccg 1320 ttccctgcgg acgtgttcat gattcctcag tacggatatc tgactctaaa caacggcagt 1380 cagtctgtgg gacgttcctc cttctactgc ctggagtact ttccttctca gatgctgaga 1440 acgggcaata actttgaatt cagctacacc tttgaggaag tgcctttcca cagcagctat 1500 gcgcacagcc agagcctgga ccggctgatg aatcccctca tcgaccagta cctgtactac 1560 ctggcccgga cccagagcac tacggggtcc acaagggagc tgcagttcca tcaggctggg 1620 cccaacacca tggccgagca atcaaagaac tggctgcccg gaccctgtta tcggcagcag 1680 agactgtcaa aaaacataga cagcaacaac aacagtaact ttgcctggac cggggccact 1740 aaataccatc tgaatggtag aaattcatta accaacccgg gcgtagccat ggccaccaac 1800 aaggacgacg aggaccagtt ctttcccatc aacggagtgc tggtttttgg caaaacgggg 1860 gctgccaaca agacaacgct ggaaaacgtg ctaatgacca gcgaggagga gatcaaaacc 1920 accaatcccg tggctacaga agaatacggt gtggtctcca gcaacctgca atcgtctacg 1980 gccggacccc agacacagac tgtcaacagc cagggggctc tgcccggcat ggtctggcag 2040 aaccgggacg tgtacctgca gggtcccatc tgggccaaaa ttcctcacac ggacggcaac 2100 tttcacccgt ctcccctgat gggcggattt ggactcaaac acccgcctcc tcaaattctc 2160 atcaaaaaca ccccggtacc tgctaatcct ccagaggtgt ttactcctgc caagtttgcc 2220

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     tcatttatca cgcagtacag caccggccag gtcagcgtgg agatcgagtg ggaactgcag 2280 aaagaaaaca gcaaacgctg gaatccagag attcagtaca cctcaaatta tgccaagtct 2340 aataatgtgg aatttgctgt caacaacgaa ggggtttata ctgagcctcg ccccattggc 2400 acccgttacc tcacccgtaa cctgtaattg cctgttaatc aataaaccgg ttaattcgtt 2460 tcagttgaac tttggtcaag ggcgaattc 2439

     <210> 36 <211> 2495 <212> DNA <213> new AAV serotype, clone 42.3b <400> 36

     gaattcgccc tttctacggc tgcgtcaact agaccaatga gaactttccc ttcaacgatt 60 gcgtcgacaa gatggtgatc tggtgggagg agggcaagat gacggccaag gtcgtggagt 120 ccgccaaggc cattcatcat ctgctggggc gggctcccga gattgcttgc tcggcctgcg 180 atctggtcaa cgtggacctg gatgactgtg tttctgagca ataaatgact taaaccaggt 240 atggctgccg atggttatct tccagattgg ctcgaggaca aoctctctga gggcattcgc 300 gagtggtggg acttgaaacc tggagccccg aaacccaaag ccaaccagca aaagcaggac 360 gaoggccggg gtctggtgct tcctggctac aagtacctcg gacccttcaa cggactcgac 420 aagggagagc cggtcaacga ggcagacgcc gcggccctcg agcacgacaa ggcctacgac 480 aagcagctcg agcaggggga caacccgtac ctcaagtaca accacgccga cgccgagttt 540 caggagcgtc ttcaagaaga tacgtctttt gggggcaacc tcgggcgagc agtcttcoag 600 gccaagaagc gggttctcga acctctcggt ctggttgagg aaggcgctaa gacggctcct 660 ggaaagaaga gacccataga atcccccgac tcctccacgg gcatcggcaa gaaaggccag 720 cagcccgcta aaaagaagct caactttggg cagactggcg actcagagtc agtgcccgac 780 cctcaaccaa tcggagaacc ccccgcaggc ccctctggtc tgggatctgg tacaatggct 840 gcaggcggtg gcgctccaat ggcagacaat aacgaaggcg ccgacggagt gggtaatgcc 900 tccggaaatt ggcattgcga ttccacatgg ctgggcgaca gagtcatcac caccagcacc 960 cgcacctggg ccctgcccac ctacaacaac cacctctaca agcagatato aagtcagagc 1020 ggggctacca acgacaacca cttcttcggc tacagcaccc cctggggcta ttttgacttc 1080 aacagattcc actgccactt ctcaccacgt gactggcagc gactcatcaa caacaactgg 114 0 ggattccggc ccagaaagct gcggttcaag ttgttcaaca tccaggtcaa ggaggtcacg 1200 acgaacgacg gcgttacgac catcgctaat aaccttacca gcacgattca ggtcttctcg 1260 gactcggagt accaactgcc gtacgtcctc ggctctgcgc accagggctg cctccctccg 1320 ttccctgcgg acgtgttcat gattcctcag tacggatatc tgactctaaa caacggcagt 1380 cagtctgtgg gacgttcctc cttctactgc ctggagtact ttccttctca gatgctgaga 1440

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     acgggcaata actttgaatt cagctacacc tttgaggaag tgcctttcca cagcagctat 1500 gcgcacagcc agagcctgga ccggctgatg aatcccctca tcgaccagta cctgtactac 1560 ctggcccgga cccagagcac tacggggtcc acaagggagc tgcagttcca tcaggctggg 1620 cccaacacca tggccgagca atcaaagaac tggctgcccg gaccctgtta tcggcagcag 1680 agactgtcaa aaaacataga cagcaacaac accagtaact ttgcctggac cggggccact 174 0 aaataccatc tgaatggtag aaattcatta accaacccgg gcgtagccat ggccaccaac 1800 aaggacgacg aggaccagtt ctttcccatc aacggagtgc tggtttttgg caaaacgggg 18 60 gctgccaaca agacaacgct ggaaaacgtg ctaatgacca gcgaggagga gatcaaaacc 1920 accaatcccg tggctacaga acagtacggt gtggtctcca gcaacctgca atcgtctacg 1980 gccggacccc agacacagac tgtcaacagc cagggggctc tgcccggcat ggtctggcag 2040 aaccgggacg tgtacctgca gggtcccatc tgggccaaaa ttcctcacac ggacggcaac 2100 tttcacccgt ctcccctgat gggcggattt ggactcaaac acccgcctcc tcaaattctc 2160 atcaaaaaca ccccggtacc tgctaatcct ccagaggtgt ttactcctgc caagtttgcc 2220 tcatttatca cgcagtacag caccggccag gtcagcgtgg agatcgagtg ggaactgcag 2280 aaagaaaaca gcaaacgctg gaatccagag attcagtaca cctcaaatta tgccaagtct 2340 aataatgtgg aatttgctgt caacaacgaa ggggtttata ctgagcctcg ccccattggc 2400 acccgttacc tcacccgtaa cctgtaattg cctgttaatc aataaaccgg ttaattcgtt 2460 tcagttgaac tttggtctct gcgaagggcg aattc 2495 <21O> 37 <211> 3098 <212> DNA <213> new ( AAV serotype, clone 42 :. 11 <400> 37 gaattcgccc tttctacggc tgcgtcaact ggaccaatga gaactttccc ttcaacgatt 60 gcgtcgacaa gatggtgatc tggtgggagg agggcaagat gacggccaag gtcgtggagt 12 0 ccgccaaggc cattctcggc ggcagcaagg tgcgcgtgga ccaaaagtgc aagtcttccg 180 cccagatcga tcccaccccc gtgatcgtca cttccaacac caacatgtgc gccgtgattg 240 acgggaacag caccaccttc gagcaccagc agccgttaca agaccggatg ttcaaatttg 300 aactcacccg ccgtctggag cacgactttg gcaaggtgac aaagcaggaa gtcaaagagt 360 tcttccgctg ggcgcaggat cacgtgaccg aggtggcgca tgagttctac gtcagaaagg 420 gtggagccaa caagagaccc gcccccgatg acgcggataa aagcgagccc aagcgggcct 480 gcccctcagt cgcggatcca tcgacgtcag acgcggaagg agctccggtg gactttgccg 54 0 acaggtacca aaacaaatgt tctcgtcacg cgggcatgct tcagatgctg tttccctgca 600 agacatgcga gagaatgaat cagaatttca acatttgctt cacgcacggg accggagact 660

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     gttcagaatg tttccccggc gtgtcagaat ctcaaccggt ; egteagaaag aggaegtate 720 ggaaactctg tgccattcat catctgctgg ggcgggctcc egagattget tgctcggcct 780 gcgatctggt caacgtggac ctggatgact gtgtttctga gcaataaatg acttaaacca 840 ggtatggctg ccgatggtta tcttccagat tggetegagg acaacctctc tgagggcatt 900 cgcgagtggt gggacttgaa acctggagcc ccgaaaccca aagccaacca gcaaaagcag 960 gacgacggcc ggggtctggt gcttcctggc tacaagtacc tcggaccctt caacggactc 1020 gacaagggag agccggtcaa cgcggcggac gcagcggccc tcgagcacga caaggcctac 1080 gaccageage teaaageggg tgacaatccg tacctgcggt ataaccacgc cgacgccgag 1140 tttcaggagc gtcttcaaga agataegtet tttgggggca acctcgggcg ageagtette 1200 caggccaaga agcgggttct cgaacctctc ggtctggttg aggaaggege taagaegget 1260 cctggaaaga agagacccat agaatccccc gactcctcca cgggcatcgg caagaaaggc 1320 cagcagcccg ctaaaaagaa gctcaacttt gggcagactg gcgactcaga gtcagtgccc 1380 gaccctcaac caatcggaga accccccgca ggcccctctg gtctgggatc tggtacaatg 1440 gctgcaggcg gtggcgctcc aatggcagac aataaegaag gcgccgacgg agtgggtaat 1500 gcctccggaa attggcattg cgattccaca tggctgggcg acagagtcat caccaccagc 1560 accogcacct gggccctgcc cacctacaac aaccacctct acaagcagat atcaagtcag 1620 agcggggcta ccaacgacaa ccacttcttc ggctacagca ccccctgggg ctattttgac 1680 ttcaacagat tccactgcca ettetcaeca cgtgactggc agcgactcat caacaacaac 1740 tggggattcc ggcccagaaa gctgcggttc aagttgttca acatccaggt caaggaggtc 1800 aegaegaaeg acggcgttac gaccatcgct aataacctta ccagcacgat teaggtette 1860 tcggactcgg agtaccaact gccgtacgtc ctcggctctg cgcaccaggg ctgcctccct 1920 ccgttccctg cggacgtgtt catgattcct cagtacggat atctgactct aaacaacggc 1980 agtcagtctg tgggacgttc ctccttctac tgcctggagt actttccttc teagatgetg 2040 agaaegggea ataactttga attcagctac acctttgagg aagtgccttt ccacagcagc 2100 tatgcgcaca gccagagcct ggaccggctg atgaatcccc tcatcgacca gtacctgtac 2160 tacctggccc ggacccagag cactacgggg tccacaaggg agctgcagtt ccatcaggct 2220 gggcccaaca ccatggccga gcaatcaaag aactggctgc ccggaccctg ttateggegg 2280 cagagactgt caaaagacat agacagcaac aacaacagta actttgcctg gaccggggcc 2340 actaaatacc atctgaatgg tagaaattca ttaaccaacc egggegtage catggccacc 2400 aacaaggacg acgaggacca gttctttccc atcaacggag tgctggtttt tggcaaaacg 2460 ggggctgcca acaagacaac gctggaaaac gtgctaatga ccagcgagga ggagatcaaa 2520 accaccaatc ccgtggctac agaagaatac ggtgtggtct ccagcaacct gcaatcgtct 2580

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     acggccggac cccagacaca gactgtcaac agccaggggg ctctgcccgg catggtctgg 2640 cagaaccggg acgtgtacct gcagggtccc atctgggcca aaattcctca cacggacggc 2700 aactttcacc cgtctcccct gatgggcgga tttggactca aacacccgcc tcctcaaatt 2760 ctcatcaaaa acaccccggt acctgctaat cctccagagg tgtttactcc tgccaagttt 2820 gcctcattta tcacgcagta cagcaccggc caggtcagcg tggagatcga gtgggaactg 2880 cagaaagaga acagcaaacg ctggaatcca gagattcagt acacctcaaa ttatgccaag 2940 tctaataatg tggaatttgc tgtcaacaac gaaggggttt atactgagcc tcgccccatt 3000 ggcacccgtt acctcacccg taacctgtaa ttacttgtta atcaataaac cggttgattc 3060 gtttcagttg aactttggtc tctgcgaagg gcgaattc 3098

     <210> 38 <211> 3276 <212> DNA <213> new AAV serotype, clone 42.6a <400> 38

     gaattcgccc ttcgcagaga ccaaagttca actgaaacga attaaccggt ttattgatta 60 acaggcaatt acaggttacg ggtgaggtaa cgggtgccaa tggggcgagg ctcagtataa 120 accccttcgt tgttgacagc aaattccaca ttattagact tggcataatt tgaggtgtac 180 tgaatctctg gattccagcg tttgctgttt tctttctgca gttcccactc gatctccacg 240 ctgacctggc cggtgctgta ctgcgtgata aatgaggcaa acttggcagg agtaaacacc 300 tctggaggat tagcaggtac cggggtgttt ttgatgagaa tttgaggagg cgggtgtttg 360 agtccaaatc cgtccatcag gggagacggg tgaaagttgc cgtccgtgtg aggaattttg 420 gcccagatgg gaccctgcag gtacacgtcc cggttctgcc agaccatgcc gggcagagcc 480 ccctggctgt tgacagtctg tgtctggggt ccggccgtag acgattgcag gttgctggag 540 accacaccgt attcttctgt agccacggga ttggtggttt tgatetcctc ctcgctggtc 600 attagcacgt tttccagcgt tgtcttgttg gcagcccccg ttttgccaaa aaccagcact 660 ccgttgatgg gaaagaactg gtcctcgtcg tccttgttgg tggccatggc tacgcccggg 720 ttggttaatg aatttctacc attcagatgg tatttagtgg ccccggtcca ggcaaagtta 780 ctgttgttgt tgctgtctat gttttttgac agtctctgct gccgataaca gggtccgggc 840 agccagttct ttgattgctc ggccatggtg ttgggcccag cctgatggaa ctgcagctcc 900 cttgtggacc ccgtagtgct ctgggtccgg gccaggtagt acaggtactg gtcgatgagg 960 ggattcatca gccggtccag gctctggcta tgcgcatagc tgctgtggaa aggcacttcc 1020 tcaaaggtgt agctgaattc aaagttattg cccgttctca gcatctgaga aggaaagtac 1080 tccaggcagt agaaggagga acgtcccaca gactgactgc cgttgtttag agtcagatat 1140 ccgtactgag gaatcatgaa cacgtccgca gggaacggag ggaggcagcc ctggtgcgca 1200

     WO 03/042397

     PCT/I/S02/33629

     2015258271 20 Nov 2015

     gagccgagga cgtacggcag ttggtactcc gagtccgaga . agacctgaat cgtgctggta 1260 aggttattag cgatggtcgt aacgccgtcg tccgtcgtga cctccttgac ctggatgttg 1320 aacaacttga accgcagctt tctggggcgg aatccccagt tgttgttgat gagtcgctgc 1380 cagtcacgtg gtgagaagtg gcagtggaat ctgttaaagt caaaataccc ccagggggtg 1440 ctgtagccga agtaggtgtt gtcgttggtg cttcctcccg atgtcccgtt ggagatttgc 1500 ttgtagaggt ggttgttgta ggtggggagg gcccaggttc gggtgctggt ggtgatgact 1560 ctgtcgccca gccatgtgga atcgcaatgc caatttcctg aggaactacc cactccgtcg 1620 gcgccttcgt tattgtctgc cattggagcg ccaccgcctg cagccattgt accagatccc 1680 agaccagagg ggcctgcggg gggttctccg attggttgag ggtcgggcac tgactctgag 1740 tcgccagtct gcccaaagtt gagtctcttt ttcgcgggct gctggcctgt cttgccgatg 1800 cccgtagagg agtctggaga acgctggggt gatggctcta ccggtctctt ctttccagga 1860 gccgtcttag cgccttcctc aaccagaccg agaggttcga gaacccgctt cttggcctgg 1920 aagactgctc gcccgaggtt gcccccaaaa gacgtatctt cttgaagacg ctcctgaaac 1980 tcggcgtcgg cgtggttgta cttgaggtac gggttgtccc cctgctcgag ctgcttgtcg 2040 taggccttgt cgtgctcgag ggccgcggcg tctgcctcgt tgaccggctc tcccttgtcg 2100 agtccgttga agggtccgag gtacttgtag ccaggaagca ccagaccccg gccgtcgtcc 2160 tgcttttgct ggttggcttt gggtttcggg gctccaggtt tcaagtccca ccactcgcga 2220 atgccctcag agaggttgtc ctcgagccaa tctggaagat aaccatcggc agccatacct 2280 ggtttaagtc atttattgct cagaaacaca gtcatccagg tccacgttga ccagatcgca 2340 ggccgagcaa gcaatctcgg gagcccgccc cagcagatga tgaatggcac agagtttccg 2400 atacgtcctc tttctgacga ccggttgaga ttctgacacg ccggggaaac attctgaaca 2460 gtctctggtc ccgtgcgtga agcaaatgtt gaaattctga ttcattctct cgcatgtctt 2520 gcagggaaac agcatctgaa gcatgcccgc gtgacgagaa cacttgtttt ggtacctgtc 2580 ggcaaagtcc accggagctc cttccgcgtc tgacgtcgat ggatgcaaaa tgtcgcaaaa 2640 gcactcacgt gacagctaat acaggaccac tcccctatga cgtgatttac gtcagcgcta 2700 tgcccgcgtg acgagaacat ttgttttggt acctgtcggc aaagtccacc ggagctcctt 2760 ccgcgtctga cgtcgatgga tccgcgactg aggggcaggc ccgcttgggc tcgcttttat 2820 ccgcgtcatc gggggcgggt ctcttgttgg ctccaccctt tctgacgtag aactcatgcg 2880 ccacctcggt cacgtgatcc tgcgcccagc ggaagaactc tttgacttcc tgctttgtca 2940 ccttgccaaa gtcatgctcc agacggcggg tgagttcaaa tttgaacatc cggtcctgca 3000 acggctgctg gtgctcgaag gtggtgctgt tcccgtcaat cacggcgcac atgttggtgt 3060 tggaagtgac gatcacgggg gtgggatcga tctgggcgga agacttgcac ttttggtcca 3120

     WO 03/042397

     PCT/US02/33629 cgcgcacctt gctgccgccg agaatggcct tggcggactc cacgaccttg gccgtcatct 3180 tgccctcctc ccaccagatc accatcttgt cgacgcaatc gttgaaggga aagttctcat 3240 tggtccagtt gacgcagccg tagaaagggc gaattc 3276 <210> 39 <211> 3084 <212> DNA <213> new AAV serotype, clone 43.1 <400> 39

     2015258271 20 Nov 2015

     gaattcgccc tttctacggc tgcatcaact ggaccaatga gaactttccc ttcaacgatt 60 gcgtcgacaa gatggtgatc tggtgggagg agggcaagat gacggccaag gtcgtggagt 120 ccgccaaggc cattctcggc ggcagcaagg tgcgcgtgga ccaaaagtgc aagtcgtccg 180 cccagatcga ccccaccccc gtgatcgtca cctccaacac caacatgtgc gccgtgattg 240 acgggaacag caccaccttc gagcaccagc agccgttgca ggaccggatg ttcaagttcg 300 aactcacccg ccgtctggag cacgactttg gcaaggtgac caagcaggaa gtcaaagagt 360 tcttccgctg ggcgcaggat cacgtgaccg aggtggcgca tgagttctac gtcagaaagg 420 gcggagccag caaaagaccc gcccccgatg acgcggatat aagcgagccc aagcgggcct 480 gcccctcagt cgcggatcca tcgacgtcag acgcggaagg agctccggtg gactttgccg 540 acaggtacca aaacaaatgt tctcgtcacg cgggcatgct tcagatgctg tttccctgca 600 aaacgtgcga gaaaatgaat cagaatttca acatttgctt cacgcacggg gtcagagact 660 gctcagaatg tttccccggt gcatcagaat ctcaaccggt cgtcagaaaa aaaacgtatc 720 agaaactgtg tgccattcat catctgctgg ggcgggcacc cgagattgct tgctcggcct 780 gcgatctggt caacgtggac ctggacgact gtgtttctga gcaataaatg acttaaacca 840 ggtatggctg ccgatggtta tcttccagat tggcttgagg acaacctctc tgagggcatt 900 cgcgagtggt gggacctgaa acctggagcc ccgaaaccca aagccaacca gcaaaagcag 960 gacgacggcc ggggtctggt gcttcctggc tacaagtacc tcggaccctt caacggactc 1020 gacaaggggg agcccgtcaa cgcggcggac gcagcggccc tcgagcacga caaggcctac 1080 gaccagcagc tcaaagcggg tgacaatccg tacctgcggt ataaccacgc cgacgccgag 1140 tttcaggagc gtctgcaaga agatacgtct tttgggggca acctcgggcg agcagtcttc 1200 caggccaaga agcgggttct cgaacctctc ggtctggttg aggaaggcgc taagacggct 1260 cctggaaaga agagaccggt agagccatca cctcagcgtt cccccgactc ctccacgggc 1320 atcggcaaga aaggccacca gcccgcgaga aagagactga actttgggca gactggcgac 1380 tcggagtcag tccccgaccc tcaaccaatc ggagaaccac cagcaggccc ctctggtctg 14 40 ggatctggta caatggctgc aggcggtggc gctccaatgg cagacaataa cgaaggcgcc 1500 gacggagtgg gtagttcctc aggaaattgg cattgcgatt ccacatggct gggcgacaga 1560

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     gtcatcacca ccagcacccg aacctgggcc ctgcccacct acaacaacca tctcta'caag 1620 caaatctcca acgggacatc gggaggaagc actaacgaca acacctactt tggctacagc 1680 accccctggg ggtattttga cttcaacaga ttccactgcc acttctcacc acgtgactgg 1740 cagcgactca tcaacaataa ctggggattc cggcccaaga gactcaactt caagctcttc 1800 aacatccagg tcaaggaggt cacgcagaat gaaggcacca agaccatcgc caataacctt 1860 accagcacga ttcaggtgtt tacggactcg gaataccagc tcccgtacgt ccccggctct 1920 gcgcaccagg gctgcctccc tccgttcccg geggaegtet tcatgattcc teagtaeggg 1980 tatctgaccc taaacaatgg cagtcaggct gtgggccgtt cctccttcta ctgcctggaa 2040 tacttccctt ctcaaatgct gaggaeggge aacaactttg aattcagcta caccttcgag 2100 gaegtgeett tccacagcag ctacgcgcac agccagagcc tggaccggct gatgaaccct 2160 ctcatcgacc agtacctgta ttacttatcc agaactcagt ccacaggagg aactcaaggt 2220 actcagcaat tgttattttc teaageeggg cccgcaaaca tgteggetea ggccaagaac 2280 tggctacctg gaccgtgtta ccgtcagcaa cgagtttcca cgacactgtc gcaaaacaac 2340 aacagcaatt ttgcttggac cggtgccacc aagtatcacc tgaatggcag agactccctg 2400 gttaatcccg gcgttgccat ggctacccac aaggacgacg aggagegett cttcccgtca 2460 ageggagtte taatgtttgg caagcagggg gctggaaaag acaatgtgga ctacagcagc 2520 gtgatgetea ccagcgaaga agaaattaaa actactaacc cagtggctac agagcagtat 2580 ggtgtggtgg cagacaacct gcagcagacc aacggagctc ccattgtggg aactgtcaac 2640 agccaggggg ccttacctgg tatggtctgg caaaaccggg acgtgtacct gcagggcccc 2700 atctgggcca aaattcctca cacggacggc aactttcatc cttcgccgct gatgggaggc 2760 tttggactga aacacccgcc tcctcagatc ctggtgaaaa acactcctgt tcctgcggat 2820 cctccgacca ccttcagcca ggccaagctg gcttctttta tcacgcagta cagcaccgga 2880 caggtcagcg tggaaatega atgggagctg cagaaagaaa acagcaagcg ctggaaccca 2940 gagattcagt atacttccaa ctactacaaa tctacaaatg tggactttgc tgtcaatact 3000 gagggtactt attcagagcc tcgccccatt ggcactcgtt atctcacccg taatctgtaa 3060 ttgcttgtta atcaataaac eggt 3084 <210> 40 <211> 2370 <212> DNA <213> new AAV serotype, clone 43 .5 <400> 40 gaattcgccc tttetaegge tgcgtcaact ggaccaatga gaactttccc ttcaacgatt 60 gcgtcgacaa gatggtgatc tggtgggagg agggcaagat gacggccaag gtcgtggagt 12 0 ccgccaaggc cattctcggc ggcagcaagg tgcgcgtgga ccaaaagtgc aagtcgtccg 18 0

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     cccagatcga ccccaccccc gtgatcgtca cctccaacac caacatgtgc ; gccgtgattg 240 acgggaacag caccaccttc gagcaccagc agccgttgca ggaccggatg ttcaagttcg 300 aactcacccg ccgtctggag cacgactttg gcaaggtgac caagcaggaa gtcaaagagt 360 tcttccgctg ggcgcaggat cacgtgaccg aggtggcgca tgagttctac gtcagaaagg 420 gcggagccag caaaagaccc gcccccgatg acgcggatat aagcgagccc aagcgggcct 480 gcccctcagt cgcggatcca tcgacgtcag acgcggaagg agctccggtg gactttgccg 540 acaggtacca aaacaaatgt tctcgtcacg cgggcatgct tcagacgctg tttccctgca 600 aaacgtgcga gagaatgaat cagaatttca acatttgctt cacgcacggg gtcagagact 660 gctcagaatg tttccccggt gcatcagaat ctcaaccggt cgtcagaaaa aaaacgtatc 720 agaaactgtg tgccattcat catctgctgg ggcgggcacc cgagattgct tgctcggcct 780 gcgatctggt caacgtggac ctggacgact gtgtttctga gcaataaatg acttaaacca 840 ggtatggctg ccgatggtta tcttccagat tggcttgagg acaacctctc tgagggcatt 900 cgcgagtggt gggacctgaa acctggagcc ccgaaaccca aagccaacca gcaaaagcag 960 gacgacggcc ggggtctggt gcttcctggc tacaagtacc tcggaccctt caacggactc 1020 gacaaggggg agcccgtcaa cgcggcggac gcagcggccc tcgagcacga caaggcctac 1080 gaccagcagc tcaaagcggg tgacaatccg tacctgcggt ataaccacgc cgacgccgag 1140 tttcaggage gtctgcaaga agatacgtct tttgggggca acctcgggcg agcagtcttc 1200 caggccaaga agcgggttct cgaacctctc ggtctggttg aggaaggcgc taagacggct 1260 cctggaaaga agagaccggt agagccatca cctcagcgtt cccccgactc ctccacgggc 1320 atcggcaaga aaggccacca gcccgcgaga aagagactga actttgggca gactggcgac 1380 tcggagtcag tccccgaccc tcaaccaatc ggagaaccac cagcaggccc ctctggtctg 1440 ggatctggta caatggctgc aggcggtggc gctccaatgg cagacaataa cgaaggcgcc 1500 gacggagtgg gtagttcctc aggaaattgg cattgcgatt ccacatggct gggcgacaga 1560 gtcatcacca ccagcacccg aacctgggcc ctgcccacct acaacaacca tctctacaag 1620 caaatctcca acgggacatc gggaggaagc actaacgaca acacctactt tggctacagc 1680 accccctggg ggtattttga cttcaacaga ttccactgcc acttctcacc acgtgactgg 1740 cagcgactca tcaacaataa ctggggattc cggcccaaga gactcaactt caagctcttc 1800 aacatccagg tcaaggaggt cacgcagaat gaaggcacca agaccatcgc caataacctt 1860 accagcacga ttcaggtgtt tacggactcg gaataccagc tcccgtacgt cctcggctct 1920 gcgcaccagg gctgcctccc tccgttcccg gcggacgtct tcatgattcc tcagtacggg 1980 tatctgaccc taaacaatgg cagtcaggct gtgggccgtt cctccttcta ctgcctggaa 2040 tacttccctt ctcaaatgct gaggacgggc aacaactttg aattcagcta caccttcgag 2100

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     gacgtgcctt tccacagcag ctacgcgcac agccagagcc tggaccggct gatgaaccct 2160 ctcatcgacc agtacctgta ttacttatcc agaactcagt ccacaggagg aactcaaggt 2220 actcagcaat tgttattttc tcaagccggg cccgcaaaca tgtyggctca ggccaagaac 2280 tggctacctg gaccgtgtta ccgtcagcaa cgagtttcca cgacactgtc gcaaaacaac 2340 aacagcaatt ttgctggacc ggtgccaeca 2370

     <210> 41 <211> 3123 <212> DNA <213> new AAV serotype, clone 43.12 <400> 41

     gaattcgccc ttggctgcgt caactggacc aatgagaact ttcccttcaa cgattgcgtc 60 gacaagatgg tgatctggtg ggaggagggc aagatgacgg ccaaggtcgt ggagtccgcc 120 aaggccattc tcggcggcag caaggtgcgc gtggaccaaa agtgcaagtc gtccgccoag 180 atcgacccca cccccgtgat cgtcacctcc aacaccaaca tgtgcgccgt gattgaeggg 240 aacagcacca ccttcgagca ccagcagccg ttgcaggacc ggatgttcaa gttcgaactc 300 acccgccgtc tggagcacga ctttggcaag gtgaccaagc aggaagteaa agagttetto 360 cgctgggcgc aggatcacgt gaccgaggtg gcgcatgagt tetaegteag aaagggcgga 420 gccagcaaaa gacccgcccc egatgaegeg gatataagcg agcccaagcg ggcctgcccc 480 teagtegegg atccatcgac gtcagacgcg gaaggagctc cggtggactt tgccgacagg 540 taccaaaaca aatgttctcg tcacgcgggc atgctccaga tgctgtttec ctgcaaaacg 60 0 tgcgagagaa tgaatcagaa tttcaacatt tgcttcacgc acggggtcag agactgctoa 660 gaatgtttcc ccggtgcatc agaatctcaa ccggtcgtca gaaaaaaaac gtatoagaaa 720 ctgtgtgcca ttcatcatct gctggggcgg gcaccegaga ttgcttgctc ggcctgcgat 780 ctggtcaacg tggacctgga cgactgtgtt tctgagcaat aaatgaetta aaccaggtat 340 ggctgccgat ggttatcttc cagattggct tgaggacaac ctctctgagg gcattcgcga 900 gtggtgggac ctgaaacctg gagccccgaa acccaaagcc aaccagcaaa ageaggaega 960 cggccggggt ctggtgcttc ctggctacaa gtacotcgga cccttcaacg gactcgacaa 102 0 gggggagccc gteaaegegg cggacgcagc ggccctcgag cacgacaagg cctacgacca 1080 gcagctcaaa gcgggtgaca atccgtacct gcggtataac cacgccgacg ccgagtttca 1140 ggagcgtctg caagaagata cgtcttttgg gggcaacctc gggcgagcag tcttccaggc 1200 caagaagcgg gttctcgaac ctctcggtct ggttgaggaa ggegetaaga cggctcctgg 1260 aaagaagaga ccggtagagc catcacctca gcgttccocc gactcctcca cgggcatcgg 1320 caagaaaggc caccagcccg egagaaagag actgaacttt gggcagactg gcgactcgga 138 0 gtcagtcccc gaccctcaac caatcggaga accaccagca ggcccctctg gtctgggatc 1440

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     tggtacaatg gctgcaggcg gtggcgctcc aatggcagac aataacgaag gcgccgacgg 1500 agtgggtagt tcctcaggaa attggcattg cgattccaca tggctgggcg acagagtcat 1560 caccaccagc acccgaacct gggccctgcc cacctacaac aaccatctct acaagcaaat 1620 ctccaacggg acatcgggag gaagcactaa cgacaacacc tactttggct acagcacccc 1680 ctgggggtat tttgacttca acagattcca ctgccacttc tcaccacgtg actggcagcg 174 0 actcatcaac aataactggg gattccggcc caagagactc aacttcaagc tcttcaacat 1800 ccaggtcaag gaggtcacgc agaatgaagg caccaagacc atcgccaata accttaccag 1860 cacgattcag gtgtttacgg actcggaata ccagctcccg tacgtcctcg gctctgcgca 1920 ccagggctgc ctccctccgt tcccggcgga cgtcttcatg attcctcagt acgggtatct 1980 gaccctaaac aatggcagtc aggctgtggg ccgttcctcc ttctactgcc tggaatactt 2040 cccttctcaa atgctgagga cgggcaacaa ctttgaattc agctacacct tcgaggacgt 2100 gcctttccac agcagctacg cgcacagcca gagcctggac cggctgatga accctctcat 2160 cgaccagtac ctgtattact tatccagaac tcagtccaca ggaggaactc aaggtactca 2220 gcaattgtta ttttctcaag ccgggcccgc aaacatgtcg gctcaggcca agaactggct 2280 acctggaccg tgttaccgtc agcaacgagt ttccacgaca ctgtcgcaaa acaacaacag 2340 caattttgct tggaccggtg ccaccaagta tcacctgaat ggcagagact ccctggttaa 2400 tcccggcgtt gccatggcta cccacaagga cgacgaggag cgcttcttcc cgtcaagcgg 2460 agttctaatg tttggcaagc agggggctgg aaaagacaat gtggactaca gcagcgtgat 2520 gctcaccagc gaagaagaaa ttaaaactac taacccagtg gctacagagc agtatggtgt 2580 ggtggcagac aacctgcagc agaccaacgg agctcccatt gtgggaactg tcaacagcca 2640 gggggcctta cctggtatgg tctggcaaaa ccgggacgtg tacctgcagg gccccatctg 2700 ggccaaaatt cctcacacgg acggcaactt tcatccttcg ccgctgatgg gaggctttgg 2760 actgaaacac ccgcctcctc agatcctggt gaaaaacact cctgttcctg cggatcctcc 2820 gaccaccttc agccaggcca agctggcttc ttttatcacg cagtacagca ccggacaggt 2880 cagcgtggaa atcgaatggg agctgcagaa agaaaacagc aagcgctgga acccagagat 2940 tcagtatact tccaactact acaaatctac aaatgtggac tttgctgtca atactgaggg 3000 tacttattca gagcctcgcc ccattggcac tcgttatctc acccgtaatc tgtaattgct 3060 tgttaatcaa taaaccggtt aattcgtttc agttgaactt tggtctctgc gaagggcgaa 3120

     ttc 3123 <210> 42 <211> 3122 <212> DNA <213> new AAV serotype, clone 43.20

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015 <400> 42

     gaattcgccc tttctacggc tgcgtcaact ggaccaatga gaactttccc ttcaacgatt 60 gcgtcgacaa gatggtgatc tggtgggagg agggcaagat gacggccaag gtcgtggagt 120 ccgccaaggc cattctcggc ggcagcaagg tgcgtgtgga ccaaaagtgc aagtcttccg 18 0 cccagatcga tcccaccccc gtgatcgtca cctccaacac caacatgtgc gccgtgattg 240 acgggaacag cgccaccttc gagcaccagc agccgttgca ggaccggatg tteaaatttg 300 aactcacccg ccgtctggag catgactttg gcaaggtgac gaagcaggaa gtcaaagagt 360 tcttccgctg ggcgcaggat cacgtgaccg aggtggcgca tgagttccac gtcagaaagg 420 gtggagccaa caagagaccc gcccccgatg acgcggatat aagcgagccc aagcgggcct 480 gcccctcagt cgcggatcca tcgacgtcag acgcggaagg agctccggtg gactttgccg 54 0 acaggtacca aaacaaatgt tctcgtcacg cgggcatgct tcagatgctg tttccctgca 600 agacatgcga gagaatgaat cagaatttca acatttgctt cacgcacggg accagagact 660 gttcagaatg tttccccggc gtgtcagaat ctcaaccggt cgtcagaaag aggaogtatc 720 ggaaactctg tgcgattcat catctgctgg ggcgggctcc cgagattgct tgctcggcct 780 gcgatctggt caacgtggac ctggatgact gtgtttctga gcaataaatg acttaaacca 340 ggtatggctg ccgatggtta tcttccagat tggctcgagg acaacctctc tgagggcatt 900 cgcgagtggt gggacttgaa acctggagcc ccgaaaccca aagccaacca gcaaaagcag 960 gacgacggcc ggggtctggt gcttcctggc tacaagtacc tcggaccctt caacggactc 1020 gacaaggggg agcccgtcaa cgcggcggac gcagcggccc tcgagcacga caaagcctac 1080 gaccagcagc tcaaagcggg tgacaatccg tacctgcggt ataatcacgc cgacgccgag 1140 tttcaggagc gtctgcaaga agatacgtct tttgggggca acctcgggcg agcagtcttc 1200 caggccaaga agcgggttct cgaacctctc ggtctggttg aggaaggcgc taagacggct 1260 cctggaaaga agagactggt agagcagtcg ccacaagagc cagactcctc ctcgggcatc 1320 ggcaagacag gccagcagcc cgctaaaaag agactcaatt ttggtcagac tggcgactca 138 0 gagtcagtcc ccgacccaca acctctcgga gaacctccag cagccccctc aggtctggga 1440 cctaatacaa tggcttcagg cggtggcgct ccaatggcag acaataacga aggcgccgac 1500 ggagtgggta attcctcggg aaattggcat tgcgattcca catggctggg ggacagagtc 1560 atcaccacca gcacccgaac ctgggccctg cccacctaca acaaccacct ctacaagcaa 1620 atctccaacg geacetcggg aggaagcacc aacgacaaca cctattttgg ctacagcacc 1680 ccctgggggt attttgactt caacagattc cactgtcact tttcaccacg tgactggcaa 174 0 cgactcatca acaacaattg gggattccgg cccaaaagac tcaacttcaa gctgttcaac 1800 atccaggtca aggaagtcac gacgaacgaa ggcaccaaga ccatcgccaa taatctcacc 1860 agcaccgtgc aggtctttac ggactcggag taccagttac cgtacgtgct aggatccgct 192 0

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     caccagggat gtctgcctcc gttcccggcg gacgtcttca cggttcctca gtacggctat 1980 ttaactttaa acaatggaag ccaagccctg ggacgttcct ccttctactg tctggagtat 2040 ttcccatcgc agatgctgag aaccggcaac aactttcagt tcagctacac cttcgaggac 2100 gtgcctttcc acagcagcta cgcgcacagc cagagcctgg acaggctgat gaatcccctc 2160 atcgaccagt acctgtacta cctggtcaga acgcaaacga ctggaactgg agggacgcag 2220 actctggcat tcagccaagc gggtcctagc tcaatggcca accaggctag aaattgggtg 2280 cccggacctt gctaccggca gcagcgcgtc tccacgacaa ccaaccagaa caacaacagc 2340 aactttgcct ggacgggagc tgccaagttt aagctgaacg gccgagactc tctaatgaat 2400 ccgggcgtgg caatggcttc ccacaaggat gacgacgacc gcttcttccc ttcgagcggg 2460 gtcctgattt ttggcaagca aggagccggg aacgatggag tggattacag ccaagtgctg 2520 attacagatg aggaagaaat caaggctacc aaccccgtgg ccacagaaga atatggagca 2580 gtggccatca acaaccaggc cgccaatacg caggcgcaga ccggactcgt gcacaaccag 2640 ggggtgattc ccggcatggt gtggcagaat agagacgtgt aectgcaggg tcccatctgg 2700 gccaaaattc ctcacacgga cggcaacttt cacccgtctc ccctgatggg cggctttgga 2760 ctgaagcacc cgcctcctca aattctcatc aagaacacac cggttccagc ggacccgccg 2820 cttaccttca accaggccaa gctgaactct ttcatcacgc agtacagcac cggacaggtc 2880 agcgtggaaa tcgagtggga gctgcagaaa gaaaacagca aacgctggaa tccagagatt 2940 caatacactt ccaactacta caaatctaca aatgtggact ttgctgtcaa cacggaagga 3000 gtttatagcg agcctcgccc cattggcacc cgttacctca cccgcaacct gtaattacat 3060 gttaatcaat aaaccggtta attcgtttca gttgaacttt ggtctctgcg aagggcgaat 312 0

     tc 3122 <210> 43 <211> 3117

     <212> DNA <213> new AAV serotype, clone 43. .21 <400> 43 gaattcgccc ttggctgcgt caactggacc aatgagaact ttcccttcaa cgattgcgtc 60 gacaagatgg tgatctggtg ggaggagggc aagatgacgg ccaaggtcgt ggagtccgcc 120 aaggccattc tcggcggcag caaggtgcgt gtggaccaaa agtgcaagtc ttccgcccag 180 atcgatccca cccccgtgat cgtcacctcc aacaccaaca tgtgcgccgt gattgacggg 240 aacagcacca ccttcgagca ccagcagccg ttgcaggacc ggatgttcaa atttgaactc 300 acccgccgtc tggagcatga ctttggcaag gtgacgaagc aggaagtcaa agagttcttc 360 cgctgggcgc aggatcacgt gaccgaggtg gcgcatgagt tccacgtcag aaagggtgga 420

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     gccaacaaga gacccgcccc cgatgacgcg gatataagcg agcccaagcg ggcctgcccc 480 tcagtcgcgg atccatcgac gtcagacgcg gaaggagctc cggtggactt tgccgacagg 540 taccaaaaca aatgttctcg tcacgcgggc atgcttcaga tgctgtttcc ctgcaagaca 600 tgcgagagaa tgaatcagaa tttcaacatt tgcttcacgc acgggaccag agactgttca 660 gaatgtttcc ccggcgtgtc agaatctcaa ccggtcgtca gaaagaggac gtatcggaaa 720 ctctgtgcga ttcatcatct gctggggcgg gctcccgaga ttgettgctc ggcctgcgat 780 ctggtcaacg tggacctgga tgactgtgtt tctgagcaat aaatgactta aaccaggtat 640 ggctgccgat ggttatcttc cagattggct cgaggacaac ctctctgagg gcattcgcga 900 gtggtgggac ttgaaacctg gagccccgaa acccaaagcc aaccagcaaa agcaggacga 960 cggccggggt ctggtgcttc ctggctacaa gtacctcgga cccttcaacg gactcgacaa 1020 gggggagccc gtcaacgcgg cggacgcagc ggccctcgag cacgacaaag cctacgacca 1080 gcagctcaaa gcgggtgaca atccgtacct gcggtataat cacgccgacg ccgagtttca 1140 ggagcgtctg caagaagata cgtcttttgg gggcaacctc gggcgagcag tcttccaggc 1200 caagaagcgg gttctcgaac ctctcggtct ggttgaggaa ggcgctaaga cggctcctgg 1260 aaagaagaga ccggtagagc agtcgccaca agagccagac tcctcctcgg gcatcggcaa 1320 gacaggccag cagcccgcta aaaagagact caattttggt cagactggcg actcagagtc 1380 agtccccgac ccacaacctc tcggagaacc tccagcagc-c ccctcaggtc tgggacctaa 1440 tacaatggct tcaggcggtg gcgctccaat ggcagacaat aacgaaggcg ccgacggagt 1500 gggtaattcc tcgggaaatt ggcattgcga ttccacatgg ctgggggaca gagtcatcac 1560 caccagcacc cgaacctggg ccctgcccac ctacaacaac cacctctaca agcaaatctc 1620 caacggcacc tcgggaggaa gcaccaacga caacacctat tttggctaca gcaccccctg 1680 ggggtatttt gacttcaaca gattccactg tcacttttca ccacgtgact ggcaacgact 1740 catcaacaac aattggggat tccggcccaa aagactcaac ttcaagctgt tcaacatcca 1800 ggtcaaggaa gtcacgacga acgaaggcac caagaccatc gccaataatc tcaccagcac 1860 cgtgcgggtc tttacggact cggagtacca gttaccgtac gtgctaggat ccgctcacca 1920 gggatgtctg cctccgttcc cggcggacgt cttcatggtt cctcagtacg gctatttaac 1980 tttaaacaat ggaagccaag ccctgggacg ttcctccttc tactgtctgg agtatttccc 2040 atcgcagatg ctgagaaccg gcaacaactt tcagttcagc tacaccttcg aggacgtgcc 2100 tttccacagc agctacgcgc acagccagag cctggacagg ctgatgaatc ccctcatcga 2160 ccagtacctg tactacctgg tcagaacgca aacgactgga actggaggga cgcagactct 2220 ggcattcagc caagcgggtc ctagctcaat ggccaaccag gctagaaatt gggtgcccgg 2280 accttgctac cggcagcagc gcgtctccac gacaaccaac cagagcaaca acagcaactt 2340

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     tgcctggacg ggagctgcca agtttaagct gaacggccga gactctctaa tgaatccggg 2400 cgtggcaatg gcttcceaca aggatgacga cgaeegette ttcccttcga gcggggtcct 2460 gatttttggc aagcaaggag ccgggaacga tggagtggat tacagccaag tgctgattac 2520 agatgaggaa gaaatcaagg ctaccaaccc cgtggccaca gaagaatatg gagcagtggc 2580 catcaacaac caggccgcca atacgcaggc gcagaccgga ctcgtgcaca accagggggt 2640 gattcccggc atggtgtggc agaatagaga cgtgtaectg cagggtccca tctgggccaa 2700 aattcctcac acggacggca actttcaccc gtctcccctg atgggcggct ttggactgaa 2760 gcacccgcct ectcaaatte tcatcaagaa eacaceggtt ccagcggacc cgccgcttac 2820 cttcaaccag gccaagctga actctttcat cacgcagtac agcaccggac aggtcagcgt 2880 ggaaategag tgggagctgc agaaagaaaa cagcaaacgc tggaatccag agattcaata 2940 cacttccaac tactacaaat ctacaaatgt ggactttgct gtcaacacgg aaggagttta 3000 tagcgagcct cgccccattg gcacccgtta cctcacccgc aacctgtaat tacatgttaa 3060 tcaataaacc ggttaattcg tttcagttga actttggtet ctgcgaaggg cgaattc 3117

     <210> 44 <211> 3121 <212> DNA <213> new AAV serotype, clone 43.23 <400> 44

     gaattcgccc ttctacggct gcgtcaactg gaccaatgag aactttccct tcaacgattg 60 cgtcgacaag atggtgatct ggtgggagga gggcaagatg acggccaagg tcgtggagtc 120 cgccaaggcc attctcggcg gcagcaaggt gcgtgtggac caaaagtgca agtcttccgc 180 ccagatcgat cccacccccg tgatcgtcac ctccaacacc aacatgtgcg cegtgattga 240 cgggaacagc accaccttcg agcaccagca gccgttgcag gaccggatgt tcaaatttga 300 actcacccgc cgtctggagc atgactttgg caaggtgacg aagcaggaag tcaaagagtt 360 cttccgctgg gcgcaggatc acgtgaccga ggtggcgcat gagttccacg tcagaaaggg 420 tggcgccaac aagagacccg cccccgatga cgcggatata agcgagccca agcgggcctg 480 cccctcagtc gcggatccat cgacgtcaga cgcggaagga gctccggtgg actttgecga 54 0 caggtaccaa aacaaatgtt ctcgtcacgc gggcatgctt cagatgctgt ttccctgcaa 600 gacatgcgag agaatgaatc agaatttcaa catttgcttc acgcacggga ccagagactg 660 ttcagaatgt ttccccggcg tgtcagaatc tcaaccggtc gtcagaaaga ggacgtatcg 720 gaaactctgt gcgattcatc atctgctggg gcgggctccc gagattgctt gctcggcctg 780 egatetggtc aacgtggacc tggatgactg tgtttctgag caataaatga cttaaaccag 840 gtatggctgc cgatggttat cttccagatt ggctcgagga caacctctct gagggcattc 900 gcgagtggtg ggacttgaaa cctggagccc cgaaacccaa agccaaccag caaaagcagg 960

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     acgacggccg gggtctggtg cttcctggct acaagtacct cggacccttc aacggactcg 1020 acaaggggga gcccgtcaac gcggcggacg cagcggccct cgagcacgac aaagcctacg 1080 accagcagct caaagcgggt gacaatccgt acctgcggta taatcacgcc gacgccgagt 1140 ttcaggagcg tctgcaagaa gatacgtcct ttgggggcaa cctcgggcga gcagtcttcc 1200 aggccaagaa gcgggttctc gaacctctcg gtctggttga ggaaggcgct aagacggctc 1260 ctggaaagaa gagaccggta gagcagtcgc cacaagagcc agactcctcc tcgggcatcg 1320 gcaagacagg ccagcagccc gctaaaaaga gactcaattt tggtcagact ggcgactcag 1380 agtcagtccc cgacccacaa cctctcggag aacctccagc agccccctca ggtctgggac 1440 ctaatacaat ggcttcaggc ggtggcgctc caatggcaga caataacgaa ggcgccgacg 1500 gagtgggtaa ttcctcggga aattggcatt gcgattccac atggctgggg gacagagtca 1560 tcaccaccag cacccgaacc tgggccctgc ccacctacaa caaccacctc tacaagcaaa 1620 tctccaacgg cacctcggga ggaagcacca acgacaacac ctattttggc tacagcaccc 1680 cctgggggta ttttgacttc aacagattcc actgtcactt ttcaccacgt gactggcaac 1740 gactcatcaa caacaattgg ggattccggc ccaaaagact caacttcaag ctgttcaaca 1800 tccaggtcaa ggaagtcacg acgaacgaag gcaccaagac catcgccaat aatctcacca 1860 gcaccgtgca ggtctttacg gacttggagt accagttacc gtacgtgcta ggatccgctc 1920 accagggatg tctgcctccg ttcccggcgg acgtcttcat ggttcctcag tacggctatt 1980 taactttaaa caatggaagc caagccctgg gacgttcctc cttctactgt ctggagtatt 2040 tcccatcgca gatgccgaga accggcaaca actttcagtt cagctacacc ttcgaggacg 2100 tgcctttcca cagcagctac gcgcacagcc agagcctgga caggctgatg aatcccctca 2160 tcgaccagta cctgtactac ctggtcagaa cgcaaacgac tggaactgga gggacgcaga 2220 ctctggcatt cagccaagcg ggtcctagct caatggccaa ccaggctaga aattgggtgc 2280 ccggaccttg ctaccggcag cagcgcgtct ccacgacaac caaccagaac aacaacagca 2340 actttgcctg gacgggagct gccaagttta agctgaacgg ccgagactct ctaatgaatc 2400 cgggcgtggc aatggcttcc cacaaggatg acgacgaccg cttcttccct tcgagcgggg 2460 tcctgatttt tggcaagcaa ggagccggga acgatggagt ggattacagc caagtgctga 2520 ttacagatga ggaagaaatc aaggctacca accccgtggc cacagaagaa tatggagcag 2580 tggccatcaa caaccaggcc gccaatacgc aggcgcagac cggactcgtg cacaaccagg 2640 gggtgattcc cggcatggtg tggcagaata gagacgtgta cctgcagggt cccatctggg 2700 ccaaaattcc tcacacggac ggcaactttc acccgtctcc cctgatgggc ggctttggac 2760 tgaagcaccc gcctcctcaa attctcatca agaacacacc ggttccagcg gacccgccgc 2820 ttaccttcaa ccaggccaag ctgaactctt tcatcacgca gtacagcacc ggacaggtca 2880

     WO 03/042397

     PCT/U SO2/33629

     2015258271 20 Nov 2015

     gcgtggaaat cgagtgggag ctgcagaaag aaaacagcaa acgctggaat ccagagattc 2940 aatacacttc caactactac aaatctacaa atgtggactt tgctgtcaac acggaaggag 3000 tttatagcga gcctcgcccc attggcaccc gttacctcac ccgcaacctg taattacatg 3060 ttaatcaata aaccggttaa ttcgtttcag ttgaactttg gtctctgcga agggcgaatt 3120 c 3121

     <210> 45 <211> 3122 <212> DNA <213> new AAV serotype, clone 43.25 <400> 45

     gaattcgccc tttetaegge tgcgtcaact ggaccaatga gaactttccc ttcaacgatt 60 gcgtcgacaa gatggtgatc tggtgggagg agggcaagat gacggccaag gtcgtggagt 12 0 ccgccaaggc cattctcggc ggcagcaagg tgcgtgtgga ccaaaagtgc aagtcttccg 180 cccagatcga tcccaccccc gtgategtea cctccaacac eaacatgtge gccgtgattg 240 acgggaacag caccaccttc gagcaccagc ageegttgea ggaccggatg ttcaaatttg 300 aactcacccg ccgtctggag catgactttg gcaaggtgac gaagcaggaa gtcaaagggt 360 tcttccgctg ggcgcaggat cacgtgaccg aggtggcgca tgagttccac gtgcgagccc 420 aagcgggect gcccctcagt cgcggatcca tegaegtcag accagaaagg gtggagccaa 480 caagagaccc gcccccgatg aegeggatat aageggaagg agctccggtg gactttgccg 54 0 acaggtacca aaacaaatgt tctcgtcacg cgggcatgct tcagatgctg tttccctgca 60 0 agacatgcga gagaatgaat cagaatttca acatttgett cacgcacggg accagagact 660 gttcagaatg tttccccggc gtgtcagaat ctcaaccggt egteagaaag aggaegtate 720 ggaaactctg tgcgattcat catctgctgg ggcgggctcc egagattget tgctcggcct 780 gcgatctggt caacgtggac ctggatgact gtgtttctga gcaataaatg acttaaacca 840 ggtatggctg ccgatggtta tcttccagat tggetegagg acaacctctc tgagggcatt 900 cgcgagtggt gggacttgaa acctggagcc ccgaaaccca aagccaacca gcaaaagcag 960 gacgacggcc ggggtctggt gcttcctggc tacaagtacc tcggaccctt caacggactc 1020 gacaaggggg agcccgtcaa cgcggcggac gcagcggccc tegagcaega caaagcctac 1080 gaccagcagc teaaageggg tgacaatccg tacctgcggt ataatcacgc cgacgccgag 1140 tttcaggagc gtctgcaaga agataegtet tttgggggca acctcgggcg ageagtette 1200 caggccaaga agcgggttct cgaacctctc ggtctggttg aggaaggege taagaegget 1260 cctggaaaga agagaccggt agagcagtcg ccacaagagc cagactcctc ctcgggcatc 1320 ggcaagacag gccagcagcc egetaaaaag agactcaatt ttggtcagac tggcgactca 1380 gagtcagtcc ccgacccaca acctctcgga gaacctccag cagccccctc aggtctggga 1440

     S3

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     cctaatacaa tggcttcagg cggtggcgct ccaatggcag acaataacga aggcgccgac 1500 ggagtgggta attcctcggg aaattggcat tgcgattcca catggctggg ggacagagtc 1560 atcaccacca gcacccgaac ctgggccctg cccacctaca acaaccacct ctacaagcaa 1620 atctccaacg gcacctcggg aggaagcacc aacgacaaca cctattttgg ctacagcacc 1680 ccctgggggt attttgactt caacagattc cactgtcact tttcaccacg tgactggcaa 1740 cgactcatca acaacaattg gggattccgg cccaaaagac tcaacttcaa gctgttcaac 1800 atccaggtca aggaagtcac gacgaacgaa ggcaccaaga ccatcgccaa taatctcacc 1860 agcaccgtgc aggtctttac ggactcggag taccagttac cgtacgtgct aggatccgct 1920 caccagggat gtctgcctcc gttcccggcg gacgtcttca tggttcctca gtacggctat 1980 ttaactttaa acaatggaag ccaagccctg ggacgttcct ccttctactg tctggagtat 2040 ttcccatcgc agatgctgag aaccggcaac aactttcagt tcagctacac cttcgaggac 2100 gtgcctttcc acagcagcta cgcgcacagc cagagcctgg acaggctgat gaatcccctc 2160 atcgaccagt acctgtacta cctggtcaga acgcaaacga ctggaactgg agggacgcag 2220 actctggcat tcagccaagc gggtcctagc tcaatggcca accaggctag aaattgggtg 2280 cccggacctt gctaccggca gcagcgcgtc tccacgacaa ccaaccagaa caacaacagc 2340 aactttgeet ggacgggagc tgccaagttt aagctgaacg gccgagactc tctaatgaat 2400 ccgggcgtgg caatggcttc ccacaaggat gacgacgacc gcttcttccc ttcgagcggg 2460 gtcctgattt ttggcaagca aggagccggg aacgatggag tggattacag ccaagtgctg 2520 attacagatg aggaagaaat caaggctacc aaccccgtgg ccacagaaga atatggagca 2580 gtggccatca acaaccaggc cgccaatacg caggcgcaga ccggactcgt gcacaaccag 2640 ggggtgattc ccggcatggt gtggcagaat agagacgtgt acctgcaggg tcccatctgg 2700 gccaaaattc ctcacacgga cggcaacttt cacccgtctc ccctgatggg cggctttgga 27 60 ctgaagcacc cgcctcctca aattctcatc aagaacacac cggttccagc ggacccgccg 2820 cttaccttca accaggccaa gctgaactct ttcatcacgc agtacagcac cggacaggtc 2880 agcgtggaaa tcgagtggga gctgcagaaa gaaaacagca aacgctggaa tccagagatt 2940 caatacactt ccaactacta caaatctaca aatgtggact ttgctgtcaa cacggagggg 3000 gtttatagcg agcctcgccc cattggcacc cgttacctca cccgcaacct gtaattacat 3060 gttaatcaat aaaccggtta attcgtttca gttgaacttt ggtctctgcg aagggcgaat 3120

     tc 3122 <210> 46 <211> 3128 <212> DNA <213> new AAV serotype, clone 44.1

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     <400> 46 gaattcgccc tttctacggc tgcgtcaact ggaccaatga . gaactttccc ; ttcaacgatt 60 gcgtcgacaa gatgttgatc tggtgggagg agggcaagat gacggccaag gtcgtggagt 120 ccgccaaggc cattctcggc ggcagcaaag tgcgcgtgga ccaaaagtgc aagccgtccg 180 cccagatcga ccccaccccc gtgatcgtca cctccaacac caacatgtgc gccgtgattg 240 acgggaacag caccaccttc gagcaccagc agccgttgcg ggaccggatg ttcaagtttg 300 aactcacccg ccgtctggag cacgactttg gcaaggtgac aaagcaggaa gtcagagagt 360 tcttccgctg ggcgcaggat cacgtgaccg aggtggcgca cgagttctac gtcagaaagg 420 gtggagccaa caagagaccc gcccccgatg acgcggataa aagcgagccc aagcgggcct 480 gcccctcagt cgcggatcca tcgacgtcag acgcggaagg agctccggtg gactttgccg 540 acaggtacca aaacaaatgt tctcgtcacg cgggcatgct tcagatgctg tttccctgca 600 aaacatgcga gagaatgaat cagaatttca acatttgctt cacgcacggg accagagact 660 gttcagaatg tttccccggc gtgtcagaat ctcaaccggt cgtcagaaaa aagacgtatc 720 ggaaactctg tgcgattcat catctgctgg ggcgggcacc cgagattgct tgctcggcct 780 gcgatctggt caacgtggac ctagatgact gtgtttctga gcaat aaatg acttaaacca 840 ggtatggctg ccgatggtta tcttccagat tggctcgagg acaacctctc tgagggcatt 900 cgcgagtggt gggacttgaa acctggagcc ccgaaaccca aagccaacca gcaaaagcag 960 gacgacggcc ggggtctggt gcttcctggc tacaagtacc tcggaccctt caacggactc 1020 gacaaggggg agcccgtcaa cgcggcggac gcagcggccc tcgagcacga caaggcctac 1080 gaccagcagc tcaaagcggg tgacaatccg tacctgcggt ataaccacgc cgacgccgag 1140 tttcaggagc gtctgcaaga agatacgtct tttgggggca acctcgggcg agcagtcttc 1200 caggccaaga agcgggttct cgaacctctc ggtctggttg aggaaggcgc taagacggct 1260 cctggaaaga agagaccggt agagccatca ccccagcgtt ctccagactc ctctacgggc 1320 atcggcaaga aaggccagca gcccgcgaaa aagagactca actttgggca gactggcgac 1380 tcagagtcag tgcccgaccc tcaaccaatc ggagaacccc ccgcaggccc ctctggtctg 1440 ggatctggta caatggctgc aggcggtggc gctccaatgg cagacaataa cgaaggcgcc 1500 gacggagtgg gtagttcctc aggaaattgg cattgcgatt ccacatggct gggcgacaga 1560 gtcatcacca ccagcacccg aacctgggcc ctccccacct acaacaacca cctctacaag 1620 caaatctcca acgggacttc gggaggaagc accaacgaca acacctactt cggctacagc 1680 accccctggg ggtattttga ctttaacaga ttccactgcc acttctcacc acgtgactgg 1740 cagcgactca tcaacaacaa ctggggattc cggcccaaga gactcaactt caagctcttc 1800 aacatccagg tcaaggaggt cacgcagaat gaaggcacca agaccatcgc caataacctt i860 accagcacga ttcaggtctt tacggactcg gaataccagc tcccgtacgt cctcggctct 1920

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     gcgcaccagg gctgcctgcc tccgttcccg gcggacgtct tcatgattcc tcagtacggg 1980 tacctgactc tgaacaatgg cagtcaggcc gtgggccgtt cctccttcta ctgcctggag 2040 tactttcctt ctcaaatgct gagaacgggc aacaactttg agttcagcta ccagtttgag 2100 gacgtgcctt ttcacagcag ctacgcgcac agccaaagcc tggaccggct gatgaacccc 2160 ctcatcgacc agtacctgta ctacctgtct cggactcagt ccacgggagg taccgcagga 2220 actcagcagt tgctattttc tcaggccggg cctaataaca tgtcggctca ggccaaaaac 2280 tggctacccg ggccctgcta ccggcagcaa cgcgtctcca cgacactgtc gcaaaataac 2340 aacagcaact gtaaatcccg gtgtcgctat ggcaacccac aaggacgacg aagagcgatt 2400 ttgcctggac cggtgccacc aagtatcatc tgaatggcag agactctctg ttttccgtcc 2460 agcggagtct taatgtttgg gaaacaggga gctggaaaag acaacgtgga ctatagcagc 2520 gttatgctaa ccagtgagga agaaattaaa accaccaacc cagtggccac ggaacagtac 2580 ggcgtggtgg ccgataacct gcaacagcaa aacgccgctc ctattgtagg ggccgtcaac 2640 agtcaaggag ccttacctgg catggtctgg cagaaccggg acgtgtacct gcagggtcct 2700 atctgggcca agattcctca cacggacgga aactttcatc cctcgccgct gatgggaggc 2760 tttggactga aacacccgcc tcctcagatc ctgattaaga atacacctgt tcccgcggat 2820 cctccaacta ccttcagtca agctaagctg gcgtcgttca tcacgcagta cagcaccgga 2830 caggtcagcg tggaaattga atgggagctg cagaaagaaa acagcaaacg ctggaaccca 2940 gagattcaat acacttccaa ctactacaaa tctacaaatg tggacttcgc tgttaacaca 3 000 gatggcactt attctgagcc tcgccccatt ggcacccgtt acctcacccg taatctgtaa 3060 ttgctcgtta atcaataaac cggttgattc gtttcagttg aactttggtc tctgcgaagg 3120

     gcgaattc 3128 <210> 47 <211> 3128

     <212> DNA <213> new AAV serotype, clone 44 1.5 <400> 47 gaattcgccc tttctacggc tgcgtcaact ggaccaatga gaactttccc ttcaacgatt 60 gcgtcgacaa gatggtgatc tggtgggagg agggcaagat gacggccaag gtcgtggagt 120 ccgccaaggc cattctcggc ggcagcaaag tgcgcgtgga ccaaaagtgc aagtcgtccg 180 cccagatcga ccccaccccc gtgatcgtca cctccaacac caacatgtgc gccgtgattg 24 0 acgggaacag caccaccttc gagcaccagc agccgttgca ggaccggatg ttcaagtttg 300 aactcacccg ccgtctggag cacgactttg gcaaggtgac aaagcaggaa gtcagagagt 360 tcttccgctg ggcgcaggat cacgtgaccg aggtggcgca cgagttctac gtcagaaagg 420 gtggagccaa caagagaccc gcccccgatg acgcggataa aagcgagccc aagcgggcct 480

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     gcccctcagt cgcggatcca tcgacgtcag acgcggaagg agctccggtg gactttgccg 540 acaggtacca aaacaaatgt tctcgtcacg cgggcatgct tcagatgctg tttccctgca 600 aaacatgcga gagaatgaat cagaatttca acatttgctt cacgcacggg accagagact 660 gttcagaatg tttccccggc gtgtcagaat ctcaaccggt tgtcagaaaa aagacgtatc 720 ggaaactctg tgcgattcat catctgctgg ggcgggcacc cgagattgct tgctcggcct 780 gcgatctggt caacgtggac ctagatgact gtgtttctga gcaataaatg acttaaacca 840 ggtatggctg ccgatggtta tcttccagat tggctcgagg acaacctctc tgagggcatt 900 cgcgagtggt gggacttgaa acctggagcc ccgaaaccca aagccaacca gcaaaagcag 960 gacgacggcc ggggtctggt gcttcctggc tacaagtacc tcggaccctt caacggactc 1020 gacaaggggg agcccgtcaa cgcggcggac gcagcggccc tcgagcacga caaggcctac 1080 gaccagcagc tcaaagcggg tgacaatccg tacctgcggt ataaccacgc cgacgccgag 114 0 tttcaggagc gtctgcaaga agatacgtct tttgggggca acctcgggcg agcagtcttc 1200 caggccaaga agcgggttct cgaacctctc ggtctggttg aggaaggcgc taagacggct 1260 cctggaaaga agagaccggt agagccatca ccccagcgtt ctccagactc ctctacgggc 1320 atcggcaaga aaggccagca gcccgcgaaa aagagactca actttgggca gactggcgac 1380 tcagagtcag tgcccgaccc tcaaccaatc ggagaacccc ccgcaggccc ctctggtctg 1440 ggatctggta caatggctgc aggaggtggc gctccaatgg cagacaataa cgaaggcgcc 1500 gacggagtgg gtagttcctc aggaaattgg cattgcgatt ccacatggct gggcgacaga 1560 gtcatcacca ccagcacccg aacctgggcc ctccccacct acaacaacca cctctacaag 1620 caaatctcca acgggacttc gggaggaagc accaacgaca acacctactt cggctacagc 1680 accccctggg ggtattttga ctttaacaga ttccactgcc acttctcacc acgtgactgg 1740 cagcgactca tcaacaacaa ctggggattc cggcccaaga gacccaactt caagctcttc 1800 aacatccagg tcaaggaggt cacgcagaat gaaggcacca agaccatcgc caataacctt 1860 accagcacga ttcaggtctt tacggactcg gaataccagc tcccgtacgt cctcggctct 1920 gcgcaccagg gctgcctgcc tccgttcccg gcggacgtct tcatgattcc tcagtacggg 1980 tacctgactc tgaacaatgg cagtcaggcc gtgggccgtt cctccttcta ctgcctggag 2040 tactttcctt ctcaaatgct gagaacgggc aacaactttg agttcagcta ccagtttgag 2100 gacgtgcctt ttcacagcag ctacgcgcac agccaaagcc tggaccggct gatgaacccc 2160 ctcatcgacc agtacctgta ctacctgtct cggactcagt ccacgggagg taccgcagga 2220 actcagcagt tgctattttc tcaggccggg cctaataaca tgtcggctca ggccaaaaac 228 0 tggctacccg ggccctgcta ccggcagcaa cgcgtctcca cgacactgtc gcaaaataac 2340 aacagcaact ttgcctggac cggtgccacc aagtatcatc tgaatggcag agactctctg 2400

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     gtaaatcccg gtgtcgctat ggcaacccac aaggacgacg aagagcgatt ttttccgtcc 2460 agcggagtct taatgtttgg gaaacaggga gctggaaaag acaacgtgga ctatagcagc 2520 gttatgctaa ccagtgagga agaaattaaa accaccaacc cagtggccac agaacagtac 2580 ggcgtggtgg ccgataacct gcaacagcaa aacgccgctc ctattgtagg ggccgtcaac 2640 agtcaaggag ccttacctgg catggtctgg cagaaccggg acgtgtacct gcagggtcct 270 0 atctgggcca agattcctca cacggacgga aactttcatc cctcgccgct gatgggaggc 2760 tttggactga aacacccgce tcctcagatc ctgattaaga atacacctgt tcccgcggat 2820 cctccaacta ccttcagtca agctaagctg gcgtcgttca tcacgcagta cagcaccgga 2880 caggtcagcg tggaaattga atgggagctg cagaaagaaa acagcaaacg ctggaaccca 2940 gagattcaat acacttccaa ctactacaaa tctacaaatg tggactttgc tgttaacaca 3000 gatggcactt attctgagcc tcgccccatt ggcacccgtt acctcacccg taatctgtaa 3060 ttgcttgtta atcaataaac cggttgattc gtttcagttg aactttggtc tctgcgaagg 3120 gcgaattc 3128

     <210> <211> <212> <213> 48 1933 DNA new AAV Serotype, clone 223 <220> <221> misc feature <222> (1302) . . (1302) <223> can be a, c, g or t

     <400> 48

     caaggcctac gaccagcagc tcaaagcggg tgacaatccg tacctgcggt ataaccacgc 60 cgacgccgag tttcaggagc gtcttcaaga agatacgtct tttgggggca acctcgggcg 120 agcagtcttc caggccaaaa agcgggttct cgaacctctt ggtctggttg agacgccagc 130 taagacggca cctggaaaga agcgaccggt agactcgcca gactccacct cgggcatcgg 240 caagaaaggc cagcagcccg cgaaaaagag actcaacttt gggcagactg gcgactcaga 300 gtcagtcccc gaccctcaac caatcggaga acc&ccagca ggcccctctg gtctgggatc 360 tggtacaatg gctgcaggcg gtggcgcacc aatggctgac aataacgagg gcgccgacgg 420 agtgggtaat gcctcaggaa attggcattg cgattccaca tggctgggcg acagagtcat 480 caccaccagc acccgaacct gggccctgcc cacctacaac aaccacctct acaagcaaat 540 ctccagtcag tcagcaggga gcaccaacga taacgtctat ttcggctaca gcaccccctg 600 ggggtatttt gacttcaaca gattccattg ccacttctca ccacgtgact ggcagcgact 660 tatcaacaac aactggggat tccggcccaa gaagctcaac ttcaagctct tcaacatcca 720 ggtcaaggag gtcacgacga atgacggtgt cacaaccatc gctaataacc ttaccagcac 780

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     ggttcaggtc ttttcggact cggaatatca actgccgtac gtcctcggct ccgcgcacca 840 gggctgcctg cctccgttcc cggcagacgt gttcatgatt ccgcagtacg gatacctgac 900 tctgaacaat ggcagccaat cggtaggccg ttcctccttc tactgcctgg agtactttcc 960 ttctcagatg ctgagaacgg gcaacaactt cacctttagc tacaccttcg aggacgtgcc 1020 tttccacagc agctacgcgc acagccagag tctggaccgg ctgatgaatc ccctcatcga 1080 ccagtacctg tactacttgg ccagaacaca gagcaacgca ggaggtactg ctggcaatcg 1140 ggaactgcag ttttatcagg gcggacctac caccatggcc gaacaagcaa agaactggct 1200 gcccggacct tgcttccggc aacagagagt atccaagacg ctggatcaaa ataacaacag 1260 caactttgcc tggactggtg ccacaaaata ccatttaaat gnaagaaatt cattggttaa 1320 tcccggtgtc gccatggcaa cccacaagga cgacgaggaa cgcttcttcc cttcgagcgg 1380 agttctaatt tttggcaaaa ctggagcagc taataaaact acattagaaa acgtgctcat 1440 gacaaatgaa gaagaaattc gtcctaccaa cccggtagct accgaggaat acgggattgt 1500 aagcagcaac ttgcaggcgg ctagcaccgc agcccagaca caagttgtta acaaccaggg 1560 agccttacct ggcatggtct ggcagaaccg ggacgtgtac ctgcaaggtc ccatttgggc 1620 caagattcct cacacggacg gcaactttca cccgtctcct ctaatgggtg gctttggact 1680 gaaacacccg cctccccaga tcctgatcaa aaacacaccg gtacctgcta atcctccaga 1740 agtgtttact cctgccaagt ttgcttcctt catcacgcag tacagcaccg ggcaagtcag 1800 cgttgagatc gagtgggagc tgcagaaaga gaacagcaag cgctggaacc cagagattca 1860 gtacacctcc aactttgaca aacagactgg agtggacttt gctgttgaea gccagggtgt 1920 ttactctgag cct 1933

     <210> 49 <211> 1933

     <212> DNA <213> new AAV serotype, clone 223.2 <400> 49 caaggcctac gaccagcagc teaaageggg tgacaatccg tacctgcggt ataaccacgc 60 cgacgccgag tttcaggagt gtcttcaaga agataegtet tttgggggca acctcgggcg 120 ageagtette caggccaaaa agcgggttct cgaacctctt ggtctggttg agacgccagc 180 taagaeggea cctggaaaga agcgaccggt agactcgcca gactccacct cgggcatcgg 240 caagaaaggc cagcagcccg egaaaaagag actcaacttt gggcagactg gcgactcaga 300 gtcagtcccc gaccctcaac caatcggaga accaccagca ggcccctctg gtctgggatc 360 tggtacaatg gttgcaggcg gtggcgcacc aatggctgac aataaegagg gcgccgacgg 420 agtgggtaat gcctcaggaa attggcattg cgattccaca tggctgggcg acagagtcat 480 caccaccagc acccgaacct gggccctgcc cacctacaac aaccacctct acaagcaaat 540

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     ctccagtcag tcagcaggga gcaccaacga taacgtctat ttcggctaca gcaccccctg 600 ggggtatttt gacttcaaca gattccattg ccacttctca ccacgtgact ggcagogact 660 tatcaacaac aactggggat tccggcccaa gaagctcaac ttcaagctct tcaacatcca 720 ggtcaaggag gtcacgacga atgacggtgt cacaaccatc gctaataacc ttaccagcac 780 ggttcaggtc ttttcggact cggaatatca actgccgtac gtcctcggct ccgcgoacca 840 gggctgcctg cctccgttcc cggcagacgt gttcatgatt ccgcagtacg gatacctgac 900 tctgaacaat ggcagccaat cggtaggccg ttcctccttc tactgcctgg agtactttcc 960 ttctcagatg ctgagaacgg gcaacaactt cacctttagc tacaccttcg aggacgtgcc 1020 tttccacagc agctacgcgc acagccagag tctggaccgg ctgatgaatc ccctcatcga 1080 ccagtacctg tactacttgg ccagaacaca gagcaacgca ggaggtactg ctggcaatcg 1140 ggaactgcag ttttatcagg gcggacctac caccatggcc gaacaagcaa agaactggct 1200 gcccggacct tgcttccggc aacagagagt atccaagacg ctggatcaaa ataacaacag 1260 caactttgcc tggactggtg ccacaaaata ccatttaaat ggaagaaatt cattggttaa 1320 tcccggtgtc gccatggcaa cccacaagga cgacgaggaa cgcttctccc cttcgagcgg 1380 agttctaatt tttggcaaaa ctggagcagc taataaaact acattagaaa acgtgctcat 1440 gacaaatgaa gaagaaattc gtcctaccaa cccggtagst aocgaggaat acgggattgt 1500 aagcagcaac ttgcaggcgg ctagcaccgc agcccagaca caagttgtta acaaccaggg 1560 agccttacct ggcatggtct ggcagaaccg ggacgtgtac ctgcaaggtc ccatttgggc 162 0 caagattcct cacacggacg gcaactttca cccgtctcct ctaatgggtg gctttggact 1680 gaaacacccg cctccccaga tcctgatcaa aaacacgccg gtacctgcta atcctccaga 1740 agtgtttact cctgccaagt ttgcttcctt catcacgcag tacagcaccg ggcaagtcag 1800 cgttgagatc gagtgggagc tgcagaaaga gaacagcaag cgctggaacc cagagattca 1860 gtacacctcc aactttgaca aacagactgg agtggacttt gctgttgaca gccagggtgt 1920 ttactctgag cct 1933 <210> 50 <211> 1933 <212> DNA <213> new AAV serotype, clone 223.4 <400> 50 caaggcctac gaccagcagc tcaaagcggg tgacaatccg tacctgcggt ataaccacgc 60 cgacgccgag tttcaggagc gtcttcaaga agatacgtct tttgggggca acctcgggcg 120 agcagtcttc caggccaaaa agcgggttct cgaacctctt ggtctggttg agacgccagc 180 taagacggca cctggaaaga agcgaccggt agactcgcca gactccacct cgggcatcgg 240 caagaaaggc cagcagcccg cgaaaaagag actcaacttt gggcagactg gcgactcaga 300

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     gccagtcccc gaccctcaac caatcggaga accaccagca ggcccctctg gtctgggatc 360 tggtacaatg gctgcaggcg gtggcgcacc aatggctgac aataaegagg gcgccgacgg 420 agtgggtaat gcctcaggaa attggcattg cgattccaca cggctgggcg acagagtcat 4S0 caccaccagc acccgaacct gggccctgcc cacctacaac aaccacctct acaagcaaat 540 ctccagtcag tcagcaggga gcaccaacga taaegtetat ttcggctaca gcaccccctg 600 ggggtatttt gacttcaaca gattccattg ccacttctca ccacgtgact ggcagcgact 660 tatcaacaac aactggggat tccggcccaa gaagctcaac ttcaagctct tcaacatcca 720 ggtcaaggag gteaegaega atgaeggegt cacaaccatc gctaataacc ttaccagcac 780 ggttcaggtc ttttcggact eggaatatea actgccgtac gtcctcggct ccgcgcacca 840 gggctgcctg cctccgttcc cggcagacgt gttcatgatt ccgcagtacg gatacctgac 900 tctgaacaat ggcagccaat cggtaggccg ttcctccttc tactgcctgg agtactttcc 960 ttctcagatg ctgagaacgg gcaacaactt cacctttagc tacaccttcg aggaegtgee 1020 tttccacagc agctacgcgc acagccagag tctgggccgg ctgatgaatc ccctcatcga 1080 ccagtacctg tactaettgg ccagaacaca gagcaacgca ggaggtactg ctggcaatcg 114 0 ggaactgcag ttttatcagg gcggacctac caccatggcc gaacaagcaa agaactggct 1200 gcccggacct tgcttccggc aacagagagt atccaagacg ctggatcaaa ataacaacag 1260 caactttgcc tggactggtg ccacaaaata ccatttaaat ggaagaaatt cattggttaa 1320 tcccggtgtc gccatggcaa cccacaagga egaegaggaa cgcttcttcc ettegagegg 1380 agttctaatt tttggcaaaa ctggagcagc taataaaact acattagaaa acgtgctcat 1440 gacaaatgaa gaagaaattc gtcctaccaa cccggtagct accgaggaat acgggattgt 1500 aagcagcaac ttgeaggegg ctagcaccgc agcccagaca caagttgtta acaaccaggg 1560 agccttacct ggcatggtct ggcagaaccg ggacgtgtac ctgcaaggtc ccatttgggc 1620 caagattcct cacacggacg gcaactttca cccgtctcct ctaatgggtg gctttggact 1680 gaaacacccg cctccccaga tcctgatcaa aaacacaccg gtacctgcta atcctccaga 1740 agtgtttact cctgccaagt ttgcttcctt catcacgcag tacagcaccg ggcaagtcag 1800 cgttgagate gaatgggagc tgcagaaaga gaacagcaag cgctggaacc cagagattca 1860 gtacacctcc aactttgaca aacagactgg agtggacttt gctgttgaca gccagggtgt 1920 ttactctgag cct 1933

     <210> 51 <211> 1933 <212> DNA <213> new AAV serotype, clone 223.5 <400> 51 caaggcctac gaccagcagc tcaaagcggg tgacaatccg tacctgcggt ataaccacgc 60

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     cgacgccgag tttcaggagc gtcttcaaga agataegtet tttgggggca acctcgggcg 120 agcagtcttc caggccaaaa agegggttct cgaacctctt ggtctggttg agacgccagc 180 taagacggca cctggaaaga agcgaccggt agactcgcca gactccacct cgggcatcgg 240 caagaaaggc cagcagcccg egaaaaagag actcaacttt gggcagactg gcgactcaga 300 gccagtcccc gaccctcaac caatcggaga accaccagca ggcccctctg gtctgggatc 360 tggtacaatg gctgcaggcg gtggcgcacc aatggctgac aataaegagg gcgccgacgg 420 agtgggtaat gcctcaggaa attggcattg cgattccaca cggctgggcg acagagtcat 480 caccaccagc acccgaacct gggccctgcc cacctacaac aaccacctct acaagcaaat 540 ctccagtcag tcagcaggga gcaccaacga taaegtetat ttcggctaca gcaccccctg 600 ggggtatttt gacttcaaca gattccattg ccacttctca ccacgtgact ggcagegact 660 tatcaacaac aactggggat tccggcccaa gaagctcaac ttcaagctct tcaacatcca 720 ggtcaaggag gteaegaega atgaeggegt cacaaccatc gctaataacc ttaccagcac 780 ggttcaggtc ttttcggact eggaatatea actgccgtac gtcctcggct ccgcgcacca 840 gggctgcctg cctccgttcc cggcagacgt gttcatgatt ccgcagtacg gatacctgac 900 tctgaacaat ggcagccaat cggtaggccg ttcctcettc tactgcctgg agtactttcc 960 ttetcagatg ctgagaacgg gcaacaaett cacctttagc tacaccttcg aggaegtgee 1020 tttccacagc agctacgcgc acagccagag tctgggccgg ctgatgaatc ccctcatcga 1080 ccagtacctg tactacttgg ccagaacaca gagcaacgca ggaggtactg ctggcaatcg 1140 ggaactgcag ttttateagg gcggacctac caccatggcc gaacaagcaa agaactggct 1200 gcccggacct tgcttccggc aacagagagt atccaagacg ctggatcaaa ataacaacag 1260 caactttgcc tggactggtg ccacaaaata ccatttaaat ggaagaaatt cattggttaa 1320 tcccggtgtc gccatggcaa cccacaagga egaegaggaa cgcttcttcc ettegagegg 1380 agttctaatt tttggcaaaa ctggagcagc taataaaact acattagaaa acgtgctcat 1440 gacaaatgaa gaagaaattc gtcctaccaa cccggtagct accgaggaat acgggattgt 1500 aagcagcaac ttgeaggegg ctagcaccgc agcccagaca caagttgtta acaaccaggg 1560 agccttacct ggcatggtct ggcagaaccg ggacgtgtac ctgcaaggtc ccatttgggc 1620 caagattcct cacacggaeg gcaactttca cccgtctcct ctaatgggtg gctttggact 1680 gaaacacccg cctccccaga tcctgatcaa aaacacaccg gtacctgcta atcctccaga 1740 agtgtttact cctgccaagt ttgcttcctt catcacgcag tacagcaccg ggcaagtcag 1800 cgttgagate gaatgggagc tgcagaaaga gaacagcaag cgctggaacc cagagattca 1860 gtacacctcc aactttgaca aacagactgg agtggacttt gctgttgaca gccagggtgt 1920 ttactctgag ect 1933

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015 <210> 52 <211> 1933 <212> DNA <213> new AAV serotype, clone 223.6 <400> 52

     caaggcctac gaccagcagc tcaaagcggg tgacaatccg tacctgcggt ataaccacgc 60 cgacgccgag tttcaggage gtcttcaaga agatacgtct tttgggggca acctcgggcg 120 agcagtcttc caggecaaaa agcgggttct cgaacctctt ggtctggttg agacgccagc 180 taagacggca cctggaaaga agcgaccggt agactcgcca gactccacct cgggcatcgg 240 caagaaaggc cagcagcccg egaaaaagag actcaacttt gggcagactg gcgactcaga 300 gtcagtcccc gaccctcaac caatcggaga accaccagca ggcccctctg gtctgggatc 360 tggtacaatg gctgcaggcg gtggcgcacc aatggctgac aatagegagg gcgccgacgg 420 agtgggtaat gcctcaggaa attggcattg cgattccaca tggctgggcg acagagtcat 480 caccaccagc acccgaacct gggccctgcc cacctacaac aaccacctct acaagcaaat 540 ctccagtcag tcagcaggga gcaccaacga taaegtetat ttcggctaca gcaccccctg 600 ggggtatttt gacttcaaca gattccattg ccacttctca ccacgtgact ggcagcgact 660 tatcaacaac aactggggat tccggcccaa gaagctcaac ttcaagctct tcaacatcca 720 ggtcaaggag gteaegaega atgacggtgt cacaaccatc gctaataace ttaccagcac 780 ggttcaggtc ttttcggact eggaatatea actgccgtac gtcctcggct ccgcgcacca 340 gggctgcctg cctccgttcc eggcagaegt gttcatgatt ccgcagtacg gatacctgac 900 tctgaacaat ggcagccaat cggtaggccg ttcctccttc tactgcctgg agtactttcc 960 ttctcagatg ctgagaacgg gcaacaactt cacctttagc tacaccttcg aggaegtgee 1020 tttccacagc agctacgcgc acagccagag tctggaccgg ctgatgaatc ccctcatcga 1080 ccagtacctg tactacttgg ccagaacaca gagcaacgca ggaggtactg ctggcaatcg 1140 ggaactgcag ttttatcagg gcggacctac caccatggcc gaacaagcaa agaactggct 1200 gcccggacct tgcttccggc aacagagagt atccaagacg ctggatcaaa ataacaacag 1260 caactttgcc tggactggtg ccacaaaata ccatttaaat ggaagaaatt cattggttaa 1320 tcccggtgtc gccatggcaa cccacaagga egaegaggaa cgcttcttcc ettegagegg 1380 agttctaatt tttggcaaaa ctggagcagc taataaaact acattagaaa acgtgctcat 1440 gacaaatgaa gaagaaattc gtcctaccaa cccggtagct accgaggaat acgggattgt 1500 aagcagcaac ttgeaggegg ctagcaccgc agcccagaca caagttgtta acaaccaggg 1560 agccttacct ggcatggtct ggcagaaccg ggacgtgtac ctgcaaggtc ccatttgggc 1620 caagattcct cacacggacg gcaactttca cccgtctcct ctaatgggtg gctttggact 168 0 gaaacacccg cctccccaga tcctgatcaa aaacacaccg gtacctgcta atcctccaga 1740

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015 agtgtttact cctgccaagc ttgcttcctt catcacgcag tacagcaccg ggcaagtcag 1800 cgttgagatc gagtgggagc tgcagaaaga gaacagcaag cgctggaacc cagagattca 1860 gtacacctcc aactttgaca aacagactgg agtggacttt gctgttgaca gccagggtgt 1920 ttactctgag cct 1933 <210> 53 <211> 1933 <212> DNA <213> new AAV serotype, clone 223.7 <400> 53

     caaggcctac gaccagcagc teaaageggg tgacaatccg tacctgcggt ataaccacgc 60 cgacgccgag tttcaggagc gtcttcaaga agataegtet tttgggggca acctcgggcg 120 ageagtette caggccaaaa agcgggttct cgaacctctt ggtctggttg agacgccagc 180 taagaeggea cctggaaaga agcgaccggt agactcgcca gactccacct cgggcatcgg 240 caagaaaggc cagcagcccg egaaaaagag actcaacttt gggcagactg gcgactcaga 300 gtcagtcccc gaccctcaac caatcggaga accaccagca ggcccctctg gtctgggatc 360 tggtacaatg gctgcaggcg gtggcgcacc aatggctgac aataaegagg gcgccgacgg 420 agtgggtaat gcctcaggaa attggcattg cgattccaca tggctgggcg acagagtcat 480 caccaccagc acccgaacct gggccctgcc cacctacaac aaccacctct acaagcaaat 540 ctccagtcag tcagcaggga gcaccaacga taaegtetat ttcggctaca gcaccccctg 600 ggggtatttt gacttcaaca gattccattg ccacttctca ccacgtgact ggcagcgact S60 tatcaacaac aactggggat tccggcccaa gaagctcaac ttcaagctct tcaacatcca 720 ggtcaaggag gteaegaega atgaeggegt cacaaccatc gctaataacc ttaccagcac 780 ggttcaggtc ttttcggacc eggaatatea actgccgtac gtcctcggct ccgcgcacca 840 gggctgcctg cctccgttcc eggcagaegt gttcatgatt ccgcagtacg gatacctgac 900 tctgaacaat ggcagccaat cggtaggccg ttcctccttc tactgcctgg agtactttcc 960 ttctcagatg ctgagaacgg gcaacaactt cacctttagc tacaccttcg aggacgtgcc 1020 tttccacagc agctacgcgc acagccagag tctggaccgg ctgatgaatc ccctcatcga 1080 ccagtacctg tactacttgg ccagaacaca gagcaacgca ggaggtactg ctggcaatcg 1140 ggaactgcag ttttatcagg gcggacctac caccatggcc gaacaagcaa agaactggct 1200 gcccggacct tgcttccggc aacagagagt atccaagacg ctggatcaaa ataacaacag 1260 caactttgcc tggactggtg ccacaaaata ccatttaaat ggaagaaatt cattggttaa 1320 tcccggtgtc gccatggcaa cccacaagga egaegaggaa cgcttcttcc ettegagegg 1380 agttctaatt tttggcaaaa ctggagcagc taataaaact acattagaaa acgtgctcat 1440 gacaaatgaa gaagaaattc gtcctaccaa cccggtagct accgaggaat acgggattgt 1500

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     aagcagcaac ttgcaggcgg ctagcaccgc agcccagaca caagttgtta acaaccaggg 1560 agccttacct ggcatggtct ggcagaaccg ggacgtgtac ctgcaaggtc ccatttgggc 1620 caagattcct cacacggacg gcaactttca cccgtctcct ctaatgggtg gctttggact 1680 gaaacacccg cctccccaga tcctgatcaa aaacacaccg gtacctgcta atcctccaga 1740 agtgtttact cctgccaaga ttgcttcctt catcacgcag tacagcaccg ggcaagtcag 1800 cgttgagatc gagtgggagc tgcagaaaga gaacagcaag cgctggaacc cagagattca 1860 gtacacctcc aactttgaca aacagactgg agtggacttt gctgttgaca gccagggtgt 1920 ttactctgag cct 1933

     <210> 54 <211> 3123 <212> DNA <213> new AAV serotype, clone A3.4 <400> 54

     gaattcgccc tttctacggc tgcgtcaact ggaccaatga aaactttccc ttcaacgatt 60 gcgtcgacaa gatggtgatc tggtgggagg agggaaagat gaccgccaag gtcgtggaat 120 ctgccaaagc cattctgggt ggaagcaagg ttcgtgtgga ccagaaatgc aagtcttcgg 180 cccagatcga cccgactccg gtgattgtca cctctaacac caacatgtgc gccgtgattg 240 acggaaactc gaccaccttc gagcaccagc agccgttgca agaccggatg ttcaaatttg 300 aacttacccg ccgtttggat catgactttg ggaaggtcac caagcaggaa gtcaaagact 360 ttttccggtg ggctcaagat cacgtgactg aggtggagca tgagttctac gtcaaaaagg 420 gtggagccaa gaaaaggccc gcccccgatg atgtatatat aaatgagccc aagcgggcgc 480 gcgagtcagt tgcgcagcca tcgacgtcag acgcggaagc ttcgataaac tacgcgggca 54 0 ggtaccaaaa caaatgttct cgtcacgtgg gcatgaatct gatgctgttt ccctgtcgac 600 aatgcgaaag aatgaatcag aattcaaata tctgcttcac acacgggcaa aaagactgtt 660 tggaatgctt tcccgtgtca gaatctcaac ccgtttctgt cgtcagaaaa acgtatcaga 720 aactttgtta cattcatcat atcatgggaa aagaaccaga cgcctgcact gcctgcgacc 780 tggtaaatgt ggacttggat gactgtattt ctgagcaata aatgacttaa atcaggtatg 840 gctgctgacg gttatcttcc agattggctc gaggacactc tctctgaagg aatcagacag 900 tggtggaagc tcaaacctgg cccaccaccg ccgaaaccta accaacaaca ccgggacgac 960 agtaggggtc ttgtgcttcc tgggtacaag tacctcggac ccttcaacgg actcgacaaa 1020 ggagagccgg tcaacgaggc agacgccgcg gccctcgagc acgacaaagc ctacgaccac 1080 cagctcaagc aaggggacaa cccgtacctc aaatacaacc acgcggacgc tgaatttcag 1140 gagcgtcttc aagaagatac gtctttcggg ggcaacctcg ggcgagcagt cttccaggcc 1200 aaaaagaggg tactcgagcc tcttggtctg gttgaggaag ctgttaagac ggctcctgga 1260

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     aaaaagagac ctatagagca gtctcctgca gaaccggact cttcctcggg catcggcgaa 1320 tcaggccagc agcccgctaa gaaaagactc aattttggtc agactggcga cacagagtca 1380 gtcccagacc ctcaaccaat cggagaaccc cccgcagccc cctctggtgt gggatctaat 1440 acaatggctt caggcggtgg ggcaccaatg gcagacgata aegaaggege egaeggagtg 1500 ggtaattcct cgggaaattg gcattgcgat tccacatgga tgggcgacag agttatcacc 1560 accagcacaa gaacctgggc cctccccacc tacaataatc acctctacaa gcaaatctcc 1620 agegaategg gagccaccaa cgacaaccac taettegget acagcacccc ctgggggtat 1680 tttgacttta acagattcca ctgtcacttc tcaccacgtg actggcagcg actcatcaac 174 0 aacaactggg gatttagacc caagaaactc aatttcaagc tcttcaacat ccaagtcaag 1800 gaggteaege agaatgatgg aaccacgacc atcgccaata accttaccag cacggtgcag I860 gtcttcacag actctgagta ccagctgccc tacgtcctcg gtteggetea ccagggctgc 1920 cttccgccgt tcccagcaga cgtcttcatg attcctcagt aeggetaett gactctgaac 1980 aatggcagcc aagcggtagg aegttettea ttctactgtc tagagtattt tccctctcag 2040 atgetgagga cgggaaacaa cttcaccttc agctacactt ttgaagacgt gcctttccac 2100 ageagetaeg cgcacagcca gagtctggat cggctgatga atcctctcat tgaccagtac 2160 ctgtattacc tgageaaaac tcagggtaca agtggaacaa cgcagcaatc gagactgcag 2220 ttcagccaag ctgggcctag ctccatggct cagcaggcca aaaactggct accgggaccc 2280 agctaccgac ageagegaat gtctaagacg gctaatgaca acaacaacag tgaatttgct 2340 tggactgcag ccaccaaata ttacctgaat ggaagaaatt ctctggtcaa tcccgggccc 2400 ccaatggcca gtcacaagga egatgaggaa aagtatttcc ccatgcacgg aaatctcatc 2460 tttggaaaac aaggcacagg aactaccaat gtggacattg aatcagtgct tattacagac 2520 gaagaagaaa tcagaacaac taatcctgtg gctacagaac aatacggaca ggttgccacc 2580 aaccatcaga gtcaggacac cacagcttce tatggaagtg tggacagcca gggaatetta 2640 cctggaatgg tgtggcagga ccgcgatgtc tatcttcaag gtcccatttg ggccaaaact 2700 cctcacacgg acggacactt tcatccttct ccgctcatgg gaggctttgg actgaaacac 2760 cctcctcccc agatcctgat caaaaacaca cctgtgccag cgaatcccgc gaccactttc 2820 actcctggaa agtttgcttc gttcattacc cagtattcca ccggacaggt cagcgtggaa 2880 atagagtggg agctgcagaa agaaaacagc aaacgctgga acccagaaat tcagtacacc 2940 tccaactaca acaagtcggt gaatgtggag tttaccgtgg acgcaaacgg tgtttattct 3000 gaaccccgcc ctattggcac tcgttacctt acccggaact tgtaatttcc tgttaatgaa 3060 taaaccgatt tatgcgtttc agttgaactt tggtctctgc gaagggcgaa ttcgcggccg 3120

     eta 3123

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015 <210> 55 <211> 3113 <212> DNA <213> new AAV serotype, clone A3.5 <400> 55

     gaattcgccc tttctacggc tgcgtcaact ggaccaatga aaactttccc ttcaacgatt 60 gcgtcgacaa gatggtgatc tggtgggagg agggaaagat gaccgccaag gtcgtggaat 120 ctgccaaagc cattctgggt ggaagcaagg ttcgtgtgga ccagaaatgc aagtcttcgg 180 cccagatcga cccgactccg gtgattgtca cctctaacac caacatgtgc gccgtgattg 240 acggaaactc gaccaccttc gagcaccagc agccgttgca agaccggatg ttcaaatttg 300 aacttacccg ccgtttggat catgactttg ggaaggtcac caagcaggaa gtcaaagact 360 ttttccggtg ggctcaagat cacgtgactg aggtggagca tgagttc tac gtcaaaaagg 420 gtggagccaa gaaaaggccc gcccccgatg atgtatatat aaatgagccc aagcgggcgc 480 gcgagtcagt tgcgcagcca tcgacgtcag acgcggaagc ttcgataaac tacgcggaca 540 ggtaccaaaa caaatgttct cgtcacgtgg gcatgaatct gatgctgttt ccctgtcgac 600 aatgcgaaag aatgaatcag aattcaaata tctgcttcac acacgggcaa aaagactgtt 660 tggaatgctt tcccgtgtca gaatctcaac ccgttcctgt cgtcagaaaa acgtatcaga 720 aactttgtta cattcatcat atcatgggaa aagtaccaga cgcctgcact gcctgcgacc 730 tggtaaatgt ggacttggat gactgtattt ctgagcaata aatgacttaa atcaggtatg 840 gctgctgacg gttatcttcc agattggctc gaggacactc tctctgaagg aatcagacag 900 tggtggaagc tcaaacctgg cccaccaccg ccgaaaccta accaacaaca ccgggacgac 960 agtaggggtc ttgtgcttcc tgggtacaag tacctcggac ccttcaacgg actcgacaaa 1020 ggagagccgg tcaacgaggc agacgccgcg gccctcgagc acgacaaagc ctacgaccac 1080 cagctcaagc aaggggacaa cccgtacctc aaatacaacc acgcggacgc tgaatttcag 1140 gagcgtcttc aagaagatac gtctttcggg ggcaacctcg ggcgagcagt cttccaggcc 1200 aaaaagaggg tactcgagcc tcttggtctg gttgaggaag ctgttaagac ggctcctgga 1260 aaaaagagac ctatagagca gtctcctgca gaaccggact cttcctcggg catcggcaaa 1320 tcaggccagc agcccgctaa gaaaagactc aattttggtc agactggcga cacagagtca 1380 gtcccagacc ctcaaccaat cggagaaccc cccgcagccc cctctggtgt gggatctaat 1440 acaatggctt caggcggtgg ggcaccaatg gcagacaata acgaaggcgc cgacggagtg 1500 ggtaattcct cgggaaattg gcattgcgat tccacatgga tgggcgacag agttatcacc 1560 accagcacaa gaacctgggc cctccccacc tacaataatc acctctacaa gcaaatctcc 1620 agcgaatcgg gagccaccaa cgacaaccac tacttcggct acagcacccc ctgggggtat 1680 tttgacttta acagattcca ctgtcacttc tcaccacgtg actggcagcg actcatcaat 1740

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     aacaactggg gatttagacc caagaaactc aatttcaagc tcttcaacat ccaagtcaag 1800 gaggtcacgc agaatgatgg aaccacgacc atcgccaata accttaccag cacggtgcag 1860 gtcttcacag actctgagta ccagctgccc tacgtcctcg gttcggctca ccagggctgc 1920 cttccgccgt tcccagcaga cgtcttcatg attcctcagt acggctactt gactctgaac 1980 aatggcagcc aagcggtagg acgttcttca ttctactgtc tagagtattt tccctctcag 2040 atgctgagga cgggaaacaa cttcaccttc agctacactt ttgaagacgt gcctttccac 2100 agcagctacg cgcacagcca gagtctggat cggctgatga atcctctcat tgaccagtac 2160 ctgtattacc tgagcaaaac tcagggtaca agtggaacaa cgcagcaatc gagactgcag 2220 ttcaaccaag ctgggcctag ctccatggct cagcaggcca aaaactggct accgggaccc 2280 agctaccgac agcagcgaat gtctaagacg gctaatgaca acaacaacag tgaatttgct 2340 tggactgcag ccaccaaata ttacccgaat ggaagaaatt ctctggtcaa tcccgggccc 2400 ccaatggcca gtcacaagga cgatgaggaa aagtatttcc ccatgcacgg aaatctcatc 2460 tttggaaaac aaggcacagg aactaccaat gtggacattg aatcagtgct tattacagac 2520 gaagaagaaa tcagaacgac taatcctgtg gctacagaac aatacggaca ggttgccacc 2580 aaccgtcaga gtcagaacac cacagcttcc tatggaagtg tggacagcca gggaatctta 2640 cctggaatgg tgtggcagga ccgcgatgtc tatcttcaag gtcccatttg ggccaaaact 2700 cctcacacgg acggacactt tcatccttct ccgctcatgg gaggctttgg actgaaacac 2760 cctcctcccc agatcctgat caaaaacaca cctgtgccag cgaatcccgc gaccactttc 2820 actcctggaa agtttgcttc gttcattacc cagtattcca ccggacaggt cagcgtggaa 2880 atagagtggg agctgcagaa agaaaacagc aaacgctgga acccggaaat tcagtacacc 2940 tccaactaca acaagtcggt gaatgtggag tttaccgtgg acgcaaacgg tgtttattct 3000 gaaccccgcc ctattggcac tcgttacctt acccggaact tgtaatttcc tgttaatgaa 3060 taaaccgatt tatgcgtttc agttgaactt tggtctctgc gaagggcgaa ttc 3113 <210> 56 <211> 3122 <212> DNA <213> new AAV serotype, clone A3 .7 <400> 56 agcggccgcg aattcgccct ttctacggct gcgtcaactg gaccaatgaa aactttccct 60 tcaacgattg cgtcgacaag atggtgatct ggtgggagga gggaaagatg accgccaagg 12 0 tcgtggaatc tgccaaagcc attctgggtg gaagcaaggt tcgtgtggac cagaaatgca 180 ggtcttcggc ccagatcgac ccgactccgg tgattgtcac ctctaacacc aaeatgtgcg 240 ccgtgattga cggaaactcg accaccttcg agcaccagca gccgttgcaa gaccggatgt 300 tcaaatttga acttacccgc cgtttggatc atgactttgg gaaggtcacc aagcaggaag 360

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     tcaaagactt tttccggtgg gctcaagatc acgtgactga ggtggagcat gagttctacg 420 tcaaaaaggg tggagceaag aaaaggcccg cccccgatga tgtatatata aatgagccca 480 agcgggcgcg cgagtcagtt gcgcagccat egacgtcaga cgcggaagct tcgataaact 54 0 acgcggacag gtaccaaaac aaatgttctc gtcacgtggg catgaatctg atgctgtttc 600 cctgtcgaca atgcgaaaga atgaatcaga attcaaatat ctgcttcaca cacgggcaaa 660 aagactgttt ggaatgcttt cccgtgtcag aatctcaacc cgtttctgtc gtcagaaaaa 720 cgtatcagaa actttgttac atteateata tcatgggaaa agtaccagac gcctgcactg 780 cctgcgacct ggtaaatgtg gaettggatg actgtatttc tgagcaataa atgacttaaa 840 tcaggtatgg ctgctgacgg ttatcttcca gattggctcg aggacactct ctctgaagga 900 atcagacagt ggtggaagct caaacctggc ccaccaccgc cgaaacctaa ccaacaacac 960 cgggacgaca gtaggggtct tgtgcttcct gggtacaagt acctcggacc cttcaacgga 1020 ctcgacaaag gagagccggt eaacgaggea gacgccgcgg ccctcgagca cgacaaagcc 1080 tacgaccacc agctcaagca aggggacaac ccgtacctca aatacaacca cgcggacgct 1140 gaatttcagg agcgtcttca agaagatacg tctttcgggg gcaacctcgg gcgagcagtc 1200 ttccaggcca aaaagagggt actcgagcct cttggtctgg ttgaggaagc tgttaagacg 1260 gctectggaa aaaagagacc tatagagcag tctcctgcag aaccggactc ttcctcggge 1320 atcggcaaat caggccagca gcccgctaag aaaagactca attttggtca gactggcgac 1380 acagagtcag tcccagaccc tcaaccaatc ggagaacccc ccgcagcccc ctctggtgtg 1440 ggatctaata caatggcttc aggcggtggg gcaccaatgg cagacaataa cgaaggcgcc 1500 gacggagtgg gtaattcctc gggaaattgg cattgcgatt ccacatggat gggcgacaga 1560 gttatcacca ccagcacaag aacctgggcc ctccccacct acaataatcg cctctacaag 1620 caaatctcca gegaatcggg agccaccaac gacaaccact acttcggcta cagcaccccc 168 0 tgggggtatt ttgactttaa cagattccac tgtcacttct caccacgtga ctggcagcga 1740 ctcatcaaca acaactgggg atttagaccc aagaaactca atttcaagct cttcaacatc 1800 caagtcaagg aggtcacgca gaatgatgga accacgacca tcgccaataa ccttaccagc 1860 acggtgcagg tcttcacaga ctctgagtac cagctgccct acgtcctcgg ttcggctcac 1920 cagggctgec ttccgccgtt cccagcagac gtcttcatga ttcctcagta cggctacttg 1980 actctgaaca atggcagcca agcggtagga cgttcttcat tctactgtct agagtatttt 2040 ccctctcaga tgctgaggac gggaaacaac ttcaccttca gctacacttt tgaagacgtg 2100 cctttccaca gcagctaege gcacagccag agtctggatc ggctgatgaa tcctctcatt 2160 gaccagtacc tgtattacct gagcaaaact cagggtacaa gtggaacaac gcagcaatcg 2220 agactgcagt tcagccaagc tgggcctagc tccatggctc agcaggccaa aaactggcta 2280

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     ccgggaccca gctaccgaca gcagcgaatg tctaagacgg ctaatgacaa caacaacagt 2340 gaatttgctt ggactgcagc caccaaatat tacctgaatg gaagaaattc tctggtcaat 2400 cccgggcccc caatggccag tcacaaggac gatgaggaaa agtatttccc catgcacgga 2460 aatctcatct ttggaaaaca aggcacagga actaccaatg tggacattga atcagtgctt 2520 attacagacg aagaagaaat cagaacaact aatcctgtgg ctacagaaca atacggacag 2 58 0 gttgccacca accatcagag tcagaacacc acagcttcct atggaagtgt ggacagccag 2640 ggaatcttac ctggaatggt gtggcaggac cgcgatgtct atcttcaagg tcccatttgg 2700 gccaaaactc ctcacacgga cggacacttt catccttctc cgctcatggg aggctttgga 2760 ctgaaacacc ctcctcccca gatcctgatc aaaaacacac ctgtgccagc gaatcccgcg 2820 accactttca ctcctggaaa gtttgcttcg ttcattaccc agtattccac cggacaggtc 2880 agcgtggaaa tagagtggga gctgcagaaa gaaaacagca aacgctggaa cccagaaatt 2940 cagtacacct ccaactacaa caagtcggtg aatgtggagt ttaccgtgga cgcaaacggt 3000 gtttattctg aaccccgccc tattggcact cgttacctta cccggaactt gtaatttcct 3060 gttaatgaat aaaccgattt atgcgtttca gttgaacttt ggtctctgcg aagggcgaat 3120 tc 3122

     <210> 57 <211> 3123 <212> DNA <213> new AAV serotype, clone A3.3 <4 00> 57

     gaattcgcce tttetaegge tgcgtcaact ggaccaatga aaactttccc ttcaaegatt 60 gcgtcgacaa gatggtgatc tggtgggagg agggaaagat gaccgccaag gtcgtggaat 120 ctgccaaagc cattctgggt ggaggcaagg ttcgtgtgga ccagaaatgc aagtettegg 180 cccagatcga cccgactccg gtgattgtca cctctaacac caacatgtgc gccgtgattg 240 acggaaactc gaccaccttc gagcaccagc ageegttgea agaccggatg ttcaaatttg 300 aacttacccg ccgtttggat catgactttg ggaaggtcac caagcaggaa gtcaaagact 360 ttttccggtg ggctcaagat cacgtgactg aggtggagca tgagttctac gtcaaaaagg 420 gtggagccaa gaaaaggccc gcccccgatg atgtatatat aaatgagccc aagcgggcgc 480 gegagteagt tgcgcagcca tegaegteag aegeggaage ttcgataaac tacgcggaca 540 ggtaccaaaa caaatgttct cgtcacgtgg gcatgaatct gatgctgttt ccctgtcgac 600 aatgegaaag aatgaatcag aattcaaata tctgcttcac acacgggcaa aaagactgtt 660 tggaatgett tcccgtgtca gaatctcaac ccgtttctgt cgtcagaaaa acgtatcaga 72 0 aactttgtta cattcatcat atcatgggaa aagtaccaga cgcctgcact gcctgcgacc 780 tggtaaatgt ggacttggat gactgtattt ctgagcaata aatgacttaa atcaggtatg 840

     100

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     gctgctgacg gttatcttcc agattggctc gaggacactc : tctctgaagg aatcagacag 900 tggtggaagc tcaaacctgg cccaccaccg ccgaaaccta accaacaaca . ccgggacgac 960 agtaggggtc ttgtgcttcc tgggtacaag tacctcggac ccttcaacgg ' actcgacaaa 1020 ggagagccgg tcaacgaggc agacgccgcg gccctcgagc acgacaaagc ; ctacgaccac 10B0 cagctcaagc aaggggacaa cccgtacctc aaatacaacc acgcggacgc tgaatttcag 114 0 gagcgtcttc aagaagatac gtctttcggg ggcaacctcg ggcgagcagt cttccaggcc 1200 aaaaagaggg tactcgagcc tcttggtctg gttgaggaag ctgttaagac ggctcctgga 1260 aaaaagagac ctatagagca gtctcctgca gaaccggact cttcctcggg catcggcaaa 1320 tcaggccagc agcccgctaa gaaaagactc aattttggtc agactggcga cacagagtca 1380 gtcccaggcc ctcaaccaat cggagaaccc cccgcagccc cctctggtgt gggatctaat 1440 acaatggctt caggcggtgg ggcaccaatg gcagacaata acgaaggcgc cgacggagtg 1500 ggtaattcct cgggaaattg gcattgcgat tccacatgga tgggcgacag agttatcacc 1560 accagcacaa gaacctgggc cctccccacc tacaataatc acctctacaa gcaaatctcc 1620 agcgaatcgg gagccaccaa cgacaaccac tacttcggct acagcacccc ctgggggtat 1680 tttgacttta acagattcca ctgtcacttc tcaccacgtg actggcagcg actcatcaac 1740 aacaactggg gatttagacc caagaaactc aatttcaagc tcttcaacat ccaagtcaag 1B00 gaggtcacgc agaatgatgg aaccacgacc atcgccaata accttaccag cgcggtgcag 18 60 gtcttcacag actctgagta ccagctgccc tacgtcctcg gttcggctca ccagggctgc 1920 cttccgccgt tcccagcaga cgtcttcatg attcctcagt acggctactt gactctgaac 1980 aatggcagcc aagcggtagg acgttcttca ttctactgtc tagagtattt tccctctcag 2040 atgctgagga cgggaaacaa cttcaccttc agctacactt ttgaagacgt gcctttccac 2100 agcagctacg cgcacagcca gagtctggat cggctgatga atcctctcat tgaccagtac 2160 ctgtattacc tgagcaaaac tcagggtaca agtggaacaa cgcagcaatc gagactgcag 2220 ttcagccaag ctgggcctag ctccatggct cagcaggcca aaaactggct accgggaccc 2280 agctaccgac agcagcgaat gtctaagacg gctaatgaca acaacaacag tgaatttgct 2340 tggactgcag ccaccaaata ttacctgaat ggaagaaatt ctctggtcaa tcccgggccc 2400 ccagtggcca gtcacaagga cgatgaggaa aagtatttcc ccatgcacgg aaatctcatc 2460 tttggaaaac aaggcacagg aactaccaat gtggacattg aatcagtgct tattacagac 2520 gaagaagaaa tcagaacaac taatcctgtg gctacagaac aatacggaca ggttgccacc 2580 aaccatcaga gtcagaacac cacagcttcc tatggaagtg tggacagcca gggaatctta 2 64 0 cctggaatgg tgtggcagga ccgcgatgtc tatcttcaag gtcccatttg ggccaaaact 2700 cctcacacgg acggacactt tcatccttct ccgctcatgg gaggctttgg actgaaacac 2760

     101

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     cctcctcccc agatcctgat caaaaacaca cctgtgccag cgaatcccgc gaccactttc 2820 actcctggaa agtttgcttc gttcattacc cagtattcca cctgacaggt cagcgtggaa 2880 atagagtggg agctgcagaa agaaaacagc aaacgctgga acccagaaat tcagtacacc 2940 tccaactaca acaagtcggt gaatgtggag tttaccgtgg acgcaaacgg tgtttattct 3000 gaaccccgcc ctattggcac tcgttacctt acccggaact tgtaatttcc tgttaatgaa 3060 taagccgatt tatgcgtttc agttgaactt tggtctctgc gaagggcgaa ttcgtttaaa 3120 cct 3123

     <210> 58 <211> 2969 <212> DNA <213> new AAV serotype, clone 42.12 <400> 58

     gaattcgccc tttetaegge tgcgtcaact ggaccaatga gaactttccc ttcaacgatt 60 gcgtcgacaa gatggtgatc tggtgggagg agggcaagat gacggccaag gtcgtggagt 12 0 ccgccaaggc cattctcggc ggcagcaagg tgcgcgtgga ccaaaagtgc aagtcgtccg 180 cccagatcga ccccaccccc gtgategtea cctccaacac eaacatgtge gccgtgattg 240 acgggaacag caccaccttc gagcaccagc agccgttaca agaccggatg ttcaaatttg 300 aactcacccg ccgtctggag cacgactttg gcaaggtgac aaagcaggaa gtcaaagagt 360 tcttccgctg ggcgcaggat cacgtgaccg aggtggcgca tgagttctac gtcagaaagg 420 gtggagccaa caagagaccc gcccccgatg aegeggataa aagcgagccc aagcgggect 480 gcccctcagt cgcggatcca tegaegtcag aegeggaagg agctccggtg gactttgccg 540 acaggtacca aaacaaatgt tctcgtcacg cgggcatgct tcagatgctg tttccctgca 600 agacatgcga gagaatgaat cagaatttca acatttgctt cacgcacggg accagagact 660 gttcagaatg tttccccggc gtgtcagaat ctcaaccggt egteagaaag aggaegtate 720 ggaaactctg tgccattcat catctgctgg ggcgggctcc egagattget tgctcggcct 780 gcgatctggt caacgtggac ctggatgact gtgtttctga gcaataaatg acttaaacca 840 ggtatggctg ccgatggtta tcttccagat tggetegagg acaacctctc tgagggcatc 900 cgcgagtggt gggacttgaa acctggagcc ccgaaaccca aageeaacca gcaaaagcag 960 gacgacggcc ggggtctggt gcttcctggc tacaagtacc tcggaccctt caacggactc 1020 gacaagggag agccggtcaa cgaggcagac gccgcggccc tegagcaega caaggcctac 1080 gacaagcagc tcgagcaggg ggacaacccg tacctcaagt acaaccacgc cgacgccgag 1140 tttcaggagc gtcttcaaga agataegtet tttgggggca acctcgggcg ageagtette 1200 caggccaaga agcgggttct cgaacctctc ggtctggttg aggaaggege taagaegget 1260 cctggaaaga agagaccggt agagccatca ccccagcgtt ctccagactc ctctacgggc 1320

     102

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     atcggcaaga caggccagca gcccgcgaaa aagagactca actttgggca gactggcgac 1380 tcagagtcag tgcccgaccc tcaaccaatc ggagaacccc ccgcaggccc ctctggtctg 1440 ggatctggta caatggctgc aggcggtggc gctccaatgg cagacaataa cgaaggcgcc 1500 gacggagtgg gtagttcctc aggaaattgg cattgcgatt ccacatggct gggcgacaga 1560 gtcatcacca ccagcacccg aacctgggcc ctccccacct acaacaacca cctctacaag 1620 caaatctcca acgggacatc gggaggaagc accaacgaca acacctactt cggctacagc 1680 accccctggg ggtattttga ctttaacaga ttccactgcc acttctcacc acgtgactgg 1740 cagcgactca tcaacaacaa ctggggattc cggcccaaga gactcaactt caagctcttc 1800 aacatccagg tcaaggaggt cacgcagaat gaaggcacca agaccatcgc caataacctt 1860 accagcacga ttcaggtctt tacggactcg gaataccagc tcccgtacgt cctcggctct 1920 gcgcaccagg gctgcctgcc tccgttcccg gcggacgtct tcatgattcc tcagtacggg 1980 tacctgactc tgaacaacgg cagtcaggcc gtgggccgtt cctccttcta ctgcctggag 2040 tactttcctt ctcaaatgct gagaacgggc aacaactttg agttcagcta ccagtttgag 2100 gacgtgcctt ttcacagcag ctacgcgcac agccaaagcc tggaccggct gacgaacccc 2160 ctcatcgacc agtacctgta ctacctggcc cggacccaga gcactacggg gtccacaagg 2220 gggctgcagt tccatcaggc tgggcccaac accatggccg agcaatcaaa gaactggctg 2280 cccggaccct gttatcggca gcagagactg tcaaaaaaca tagacagcaa caacaacagt 2340 aactttgcct ggaccggggc cactaaatac catctgaatg gtagaaattc attaaccaac 2400 ccgggcgtag ccatggccac caacaaggac gacgaggacc agttctttcc catcaacgga 2460 gtgctggttt ttggcaaaac gggggctgcc aacaagacaa cgctggaaaa cgtgctaatg 2520 accagcgagg aggagatcaa aaccaccaat cccgtggcta cagaagaata cggtgtggtc 2580 tccagcaacc tgcaatcgtc tacggccgga ccccagacac agactgtcaa cagccagggg 2640 gctetgcccg gcatggtctg gcagaaccgg gacgtgtacc tgcagggtcc catctgggcc 2700 aaaattcctc acacggacgg caactttcac ccgtctcccc tgatgggcgg atttggactc 2760 aaacacccgc ctcctcaaat tctcatcaag tatacttcca actactacaa atctacaaat 2820 gtggactttg ctgtcaatac tgagggtact tattcagagc ctcgccccat tggcacccgt 2880 tacctcaccc gtaacctgta attgcctgtt aatcaataaa ccggttaatt cgtttcagtt 2940 gaactttggt ctctgcgaag ggcgaattc 2969

     <210> 59 <211> 3129 <212> DNA <2l3> new AAV serotype, clone 44.2 <400> 59 gaattcgccc tttctacggc tgcgtcaact ggaccaatga gaactttccc ttcaacgatt 60

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     gcgtcgacaa gatggtgatc tggtgggagg agggcaagat gacggccaag gtcgtggagt 120 ccgccaaggc cattctcggc ggcagcaaag tgcgcgtgga ccaaaagtgc aagtcgtccg 180 cccagatcga ccccaccccc gtgatcgtca cctccaacac caacatgtgc gccgtgattg 240 acgggaacag caccaccttc gagcaccagc agccgttgca ggaccggatg ttcaagtttg 300 aactcacccg ccgtctggag cacgactttg gcaaggtgac aaagcaggaa gtcagagagt 360 tcttccgctg ggcgcaggat cacgtgaccg aggtggcgca cgagttctac gtcagaaagg 420 gtggagccaa caagagaccc gcccccgatg acgcggataa aagcgagccc aagcgggcct 480 gcccctcagt cgcggatcca tcgacgtcag acgcggaagg agctccggtg gactttgccg 540 acaggtacca aaacaaatgt tctcgtcacg cgggcatgct tcagatgctg tttccctgca 600 aaacatgcga gagaatgaat cagaatttca acatttgctt cacgcacggg accagagact 660 gttcagaatg tttccccggc gtgtcagaat ctcaaccggt cgtcagaaaa aagacgtatc 720 ggaaactctg tgcgattcat catctgctgg gggcgggcac ccgagattgc ttgctcggcc 780 tgcgatctgg tcaacgtgga cctagatgac tgtgtttctg agcaataaat gacttaaacc 840 aggtatggct gccgatggtt atcttccaga ttggctcgag gacaacctct ctgagggcat 900 tcgcgagtgg tgggacttga aacctggagc cccgaaaccc aaagccaacc agcaaaagca 960 ggacgacggc cggggtctgg tgcttcctgg ctacaagtac ctcggaccct tcaacggact 1020 cgacaagggg gagcccgtca acgcggcgga cgcagcggcc ctcgagcacg acaaggccta 1080 cgaccagcag ctcaaagcgg gtgacaatcc gtacctgcgg tataaccacg ccgacgccga 1140 gtttcaggag cgtctgcaag aagatacgtc ttttgggggc aacctcgggc gagcagtctt 1200 ccaggccaag aagcgggttc tcgaacctct cggtctggtt gaggaaggcg ctaagacggc 1260 tcctggaaag aagagaccgg tagagccatc accccagcgt tctccagact cctctacggg 1320 catcggcaag aaaggccagc agcccgcgaa aaagagactc aactttgggc agactggcga 1380 cteagagtca gtgcccgacc ctcaaccaat cggagaaccc cccgcaggcc cctctggtct 1440 gggatctggt acaatggctg caggcggtgg cgctccaatg gcagacaata acgaaggcgc 1500 cgacggagtg ggtagttcct caggaaattg gcattgcgat tccacatggc tgggcgacag 1560 agtcatcacc accagcaccc gaacctgggc cctccccacc tacaacaacc acctctacaa 162 0 gcaaatctcc aacgggactt cgggaggaag caccaacgac aacacctact tcggctacag 1680 caccccctgg gggtattttg actttaacag attccactgc cacttctcac cacgtgactg 1740 gcagcgactc atcaacaaca actggggatt ccggcccaag agactcaact tcaagctctt 1800 caacatccag gtcaaggagg tcacgcagaa tgaaggcacc aagaccatcg ccaataacct I860 taccagcacg attcaggtct ttacggactc ggaataccag ctcccgtacg tcctcggctc 1920 tgcgcaccag ggctgcctgc ctccgttccc ggcggacgtc ttcatgattc ctcagtacgg 198 0

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     gtacctgact ctgaacaatg gcagtcaggc cgtgggccgt tcctccttct actgcctgga 2040 gtactttcct tctcaaatgc tgagaacggg caacaacttt gagttcagct accagtttga 2100 ggacgtgcct tttcacagca gctacgcgca cagccaaagc ctggaccggc tgatgaaccc 2160 cctcatcgac cagtacctgt actacctgtc tcggactcag tccacgggag gtaccgcagg 2220 aactcagcag ttgctatttt ctcaggccgg gcctaataac atgtcggctc aggccaaaaa 2280 ctggctaccc gggccctgct accggcagca acgcgtctcc acgacactgt cgcaaaataa 2340 caacagcaac tttgcctgga ccggtgccac caagtatcat ctgaatggca gagactctct 2400 ggtaaatccc ggtgtcgcta tggcaaccca caaggacgac gaagagcgat tttttccgtc 2460 cagcggagtc ttaatgtttg ggaaacaggg agctggaaaa gacaacgtgg actatagcag 2520 cgttatgcta accagtgagg aagaaattaa aaccaccaac ccagtggcca cagaacagta 2580 cggcgtggtg gccgataacc tgcaacagca aaacgccgct cctattgtag gggccgtcaa 2640 cagtcaagga gccttacctg gcatggtctg gcagaaccgg gacgtgtacc tgcagggtcc 2700 tatctgggcc aagattcctc acacggacgg aaactttcat ccctcgccgc tgatgggagg 2760 ctttggactg aaacacccgc ctcctcagat cctgattaag aatacacctg ttcccgcgga 2820 tcctccaact accttcagtc aagctaagct ggcgtcgttc atcacgcagt acagcaccgg 2880 acaggtcagc gtggaaattg aatgggagct gcagaaagaa aacagcaaac gctggaaccc 2940 agagattcaa tacacttcca actactacaa atctacaaat gtggactttg ctgttaacac 3000 agatggcact tattctgagc ctcgccccat cggcacccgt tacctcaccc gtaatctgta 3060 attgcttgtt aatcaataaa ccggttgatt cgtttcagtt gaactttggt ctctgcgaag 3120

     ggcgaattc 3129 <210> 60 <211> 733 <212> PRT <213> capsid protein of AAV 3erotype, cions C1VP1 <400> 60

     Met 1 Ala Ala Asp Gly 5 Tyr Leu Pro Asp Trp 10 Leu Glu Asp Asn Leu 15 Ser GlU Gly He Arg 20 Glu Trp Trp Asp Leu 25 Lys Pro Gly Ala Pro 30 Lys Pro Lys Ala Asn 35 Gin Gin Lys Gin Asp 40 Asp Gly Arg Gly Leu 45 Val Leu Pro Gly Tyr 50 Lys Tyr Leu Gly pro 55 Phe Asn Gly Leu Asp 60 Lys Gly Glu Pro

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     Val Asn Ala Ala Asp 65

     Gin Gin Leu Lys Ala 85

     Asp Ala Glu Phe Gin 100

     Asn Leu Gly Arg Ala 115

     Leu Gly Leu Val Glu 130

     Pro Leu Glu Ser Pro 145

     Lys Gly Lys Gin Pro 165

     Gly Ala Gly Asp Gly 180

     Ser Asp lie Glu Met 195

     Gly Gin Gly Ser Asp 210

     Asp Ser Thr Trp Ser 225

     Trp Val Leu Pro Thr 245

     Thr Ser Asn Ser Asn 260

     Phe Asp Phe Asn Arg 275

     Arg Leu lie Asn Asn 290

     Lys He Phe Asn lie 305

     Ala Ala Ala Leu 70

     Gly Asp Asn Pro Tyr 90

     Glu Arg Leu Gin Glu 105

     Val Phe Gin Ala Lys 120

     Glu Gly Ala Lys Thr 135

     Gin Glu Pro Asp Ser 150

     Ala Lys Lys Arg Leu 170

     Pro Pro Glu Gly Ser 185

     Arg Ala Ala Pro Gly 200

     Gly Val Gly Asn Ala 215

     Glu Gly Lys Val Thr 230

     Tyr Asn Asn His Leu 250

     Thr Tyr Asn Gly Phe 265

     Phe His Cys His Phe 280

     Asn Trp Gly Leu Arg 295

     Gin Val Lys Glu Val 310

     His Asp Lys Ala Tyr Asp 75 80

     Leu Arg Tyr Asn His Ala 95

     Asp Thr Ser Phe Gly Gly 110

     Lys Arg Val Leu Glu Pro 125

     Ala Pro Gly Lys Lys Arg 140

     Ser Ser Gly He Gly Lys 155 160

     Asn Phe Glu Glu Asp Thr 175

     Asp Thr ser Ala Met Ser 190

     Gly Asn Ala Val Asp Ala 205

     Ser Gly Asp Trp His Cys 220

     Thr Thr Ser Thr Arg Thr 235 240

     Tyr Leu Arg Leu Gly Thr 255

     Ser Thr Pro Trp Gly Tyr 270 '

     Ser Pro Arg Asp Trp Gin 285

     Pro Lys Ala Met Arg Val 300

     Thr Thr Ser Asn Gly Glu 315 320
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     Thr Thr Val Ala Asn Asn Leu Thr Ser Thr Val Gin lie Phe Ala Asp 325 330 335

     Ser Ser Tyr Glu Leu Pro Tyr Val Met Asp Ala Gly Gin Glu Gly Ser 340 345 350

     Leu Ser Pro Phe Ero Asn Asp Val Phe Met Val Pro Gin Tyr Gly Tyr 355 360 365

     Cys Gly lie Val Thr Gly Glu Asn Gin Asn Gin Thr Asp Arg Asn Ala

     370 375

     Ehe Tyr Cys Leu Glu Tyr Phe Pro 385 390

     Asn Phe Glu Met Ala Tyr Asn Phe 405

     Tyr Ala Tyr Ser Gin Ser Pro Asp 420

     380

     Ser Gin Met Leu Arg Thr Gly Asn 395 400

     Gly Lys Val Pro Phe His Ser Met 410 415

     Arg Leu Met Asn Pro Leu Leu Asp 425 430

     Gin Tyr Leu Trp His Leu Gin Ser 435 440

     Thr Thr Ser Gly Glu Thr Leu Asn 445

     Gin Gly Asn Ala Ala Thr Thr Phe 450 455

     Gly Lys lie Arg Ser Gly Asp Ehe 460

     Ala Phe Tyr Arg Lys Asn Trp Leu 465 470

     Pro Gly Pro cys Val Lys Gin Gin 475 480

     Arg Leu Ser Lys Thr Ala Ser Gin 485

     Asn Tyr Lys He Pro Ala Ser Gly 490 495

     Gly Asn Ala Leu Leu Lys Tyr Asp 500

     Thr His Tyr Thr Leu Asn Asn Arg 505 510

     Trp Ser Asn Ile Ala Pro Gly Pro 515 520

     Ero Met Ala Thr Ala Gly Ero Ser 525

     Asp Gly Asp Phe Ser Asn Ala Gin 530 535

     Leu Ile Ehe Ero Gly Ero Ser Val 540

     Thr Gly Asn Thr Thr Thr Ser Ala 545 550

     Asn Asn Leu Leu phe Thr Ser Glu 555 560

     Glu Glu lie Ala Ala Thr Asn Pro 565

     Arg Asp Thr Asp Met Ehe Gly Gin 570 575
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     Ile Ala Asp Asn Asn Gin Asn Ala Thr Thr Ala Pro Ile Thr Gly Asn 580 585 590 Val Thr Ala Met Gly Val Leu Pro Gly Met Val Trp Gin Asn Arg Asp 595 600 605 Ile Tyr Tyr Gin Gly Pro Ile Trp Ala Lys lie Pro His Ala Asp Gly 610 615 620 His Phe His Pro Ser Pro Leu lie Gly Gly Phe Gly Leu Lys His Pro 625 630 635 640 Pro Pro Gin Ile Phe Ile Lys Asn Thr Pro Val Pro Ala Asn Pro Ala 645 650 655 Thr Thr Phe Thr Ala Ala Arg Val Asp Ser Phe Ile Thr Gin Tyr Ser 660 665 670 Thr Gly Gin Val Ala Val Gin Ile Glu Trp Glu Ile Glu Lys Glu Arg 675 680 685 Ser Lys Arg Trp Asn Pro Glu Val Gin Phe Thr Ser Asn Tyr Gly Asn 690 695 700 Gin Ssr Ser Met Leu Trp Ala Pro Asp Thr Thr Gly Lys Tyr Thr Glu 705 710 715 720 Pro Arg Val Ile Gly Ser Arg Tyr Leu Thr Asn His Leu

     725 730 <210> 61 <211> 733 <212> PRT <213> capsid protein of AAV serotype, clone G2VP1 <400> 61

     Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 15 10 15

     Glu Gly Ile Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Leu 20 25 30

     Lys Ala Asn Gin Gin Lys Gin Asp Asp Gly Arg Gly Leu Val Leu Pro 35 40 45

     Gly Tyr Lys Tyr Leu Gly Pro Phe His Gly Leu Asp Lys Gly Glu Pro 50 55 60

     Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp 65 70 75 80
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     Gin Gin Leu Lys Ala 85 Gly Asp Asn Pro Tyr 90 Leu Arg Tyr Asn His 95 Ala Asp Ala Glu Phe 100 Gin Glu Arg Leu Gin 105 Glu Asp Thr Ser Phe 110 Gly Gly As η Leu Gly 115 Arg Ala Val Phe Gin 120 Ala Lys Lys Arg val 125 Leu Glu Pro Leu Gly 130 Leu Val Glu Glu Gly 135 Ala Lys Thr Ala Pro 140 Gly Lys Lys Arg Pro 145 Leu Glu Ser Pro Gin 150 Glu Pro Asp Ser Ser 155 Ser Gly lie Gly Lys 160 Lys Gly Lys Gin Pro 165 Ala Lys Lys Arg Leu 170 Asn Phe Glu Glu Asp 175 Thr Gly Ala Gly Asp Gly Pro Pro Glu Gly Ser Asp. Thr Ser Ala Met Ser

     1B0 185 190

     Ser Asp lie 195 Glu Met Arg Ala Ala 200 Pro Gly Gly Asn Ala 205 Val Asp Ala Gly Gin 210 Gly Ser Asp Gly Val 215 Gly Asn Ala Ser Gly Asp 220 Tip His Cys Asp 225 Ser Thr Trp Ser Glu 230 Gly Lys Val Thr Thr 235 Thr Ser Thr Arg Thr 240 Trp Val Leu Pro Thr 245 Tyr Asn Asn His Leu 250 Tyr Leu Arg leu Gly 255 Thr Thr Ser Asn Ser 260 Asn Thr Tyr Asn Gly 265 Phe Ser Thr Pro Trp 270 Gly Tyr Phe Asp Phe 275 Asn Arg Phe His Cys 280 His Phe Ser Pro Arg 285 Asp Trp Gin Arg Leu 290 lie Asn Asn Asn Trp 295 Gly leu Arg Pro Lys 300 Ala Met Arg Val Lys 3 05 He Phe Asn lie Gin 310 Val Lys Glu Val Thr 315 Thr Ser Asn Gly Glu 320 Thr Thr Val Ala Asn 325 Asn Leu Thr Ser Thr 330 Val Gin Lie Phe Ala 335 Asp
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     Ser ser Tyr Glu Leu Pro Tyr Val Met Asp Ala Gly Gin Glu Gly Ser 340 345 350

     Leu Pro Pro Phe Pro Asn Asp Val Phe Met Val Pro Gin Tyr Gly Tyr 355 360 365

     Cys Gly lie Val Thr Gly Glu Asn Gin Asn Gin Thr Asp Arg Asn Ala 370 375 300

     Phe Tyr Cys Leu Glu Tyr Phe Pro Ser Gin Met Leu Arg Thr Gly Asn 3S5 390 395 400

     Asn Phe Glu Met Ala Tyr Asn Phe Glu Lys Val Pro Phe His Ser-Met 405 410 415

     Tyr Ala His Ser Gin Ser Leu Asp Arg Leu Met Asn Pro Leu Leu Asp 420 425 430

     Gin Tyr Leu Trp His Leu Gin Ser Thr Thr Ser Gly Glu Thr Leu Asn 435 440 445

     Gin Gly Asn Ala Ala Thr Thr Phe Gly Lys lie Arg Ser Gly Asp Phe 450 455 460

     Ala Phe Tyr Arg Lys Asn Trp Leu Pro Gly Pro Cys Val Lys Gin Gin 465 470 475 480

     Arg Phe Ser Lys Thr Ala Ser Gin Asn Tyr Lys lie Pro Ala Ser Gly 485 490 495

     Gly Asn Ala Leu Leu Lys Tyr Asp Thr His Tyr Thr Leu Asn Asn Arg 500 505 510

     Trp Ser Asn Xie Ala Pro Gly Pro Pro Met Ala Thr Ala Gly Pro Ser 515 520 525

     Asp Gly Asp Phe Ser Asn Ala Gin Leu lie Phe Pro Gly Pro Ser Val 530 535 540

     Thr Gly Asn Thr Thr Thr Ser Ala Asn Asn Leu Leu Phe Thr Ser Glu 545 550 555 560

     Gly Glu lie Ala Ala Thr Asn Pro Arg Asp Thr Asp Met Phe Gly Gin 565 570 575 lie Ala Asp Asn Asn Gin Asn Ala Thr Thr Ala Pro lie Thr Gly Asn 580 585 590
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     Val Thr Ala Met Gly Val Leu Pro Gly Met Val Trp Gin Asn Arg Asp 595 600 605

     Ile Tyr Tyr Gin Gly Pro Ile Trp Ala Lys Ile Pro His Ala Asp Gly 610 615 620

     His Phe His Pro Ser Pro Leu lie Gly Gly Phe Gly Leu Lys His Pro 625 630 635 640

     Pro Pro Gin Ile Phe Ile Lys Asn Thr Pro Val Pro Ala Asn Pro Ala 645 650 655

     Thr Thr Phe Thr Ala Ala Arg Val Asp Ser Phe He Thr Gin Tyr Ser 660 665 670

     Thr Gly Gin Val Ala Val Gin Ile Glu Trp Glu lie Glu Lys Glu Arg 675 6B0 6S5

     Ser Lys Arg Arg Asn Fro Glu Val Gin Phe Thr Ser Asn Tyr Gly Asn 690 695 700

     Gin Ser Ser Met Leu Trp Ala Pro Asp Thr Thr Gly Lys Tyr Thr Glu 705 710 715 720

     Pro Arg Val Ile Gly Ser Arg Tyr Leu Thr Asn His Leu 725 730 <210> 62 <211> 733 <212> PRT <213> capsid protein of AAV serotype, clone C5VP102 <400> 62

     Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 15 10 15

     Glu Gly Ile Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro 20 25 30

     Lys Ala Asn Gin Gin Lys Gin Asp Asp Gly Arg Gly Leu Val Leu Pro 35 40 45

     Gly Tyr Glu Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu pro 50 55 60

     Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp 65 70 75 80

     Gin Gin Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala 85 90 95
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     Asp

     Asn

     Leu

     Pro

     145

     Lys

     Gly ser

     Gly

     Asp

     225

     Trp

     Thr

     Phe

     Arg

     Lys

     305

     Thr

     Ser

     Ala Glu Phe Gin Glu Arg Leu Gin Glu Asp Thr Ser Phe Gly Gly 100 105 110

     Leu Gly Arg Ala Val Phe Gin Ala Lys Lys Arg Val Leu Glu Pro 115 120 125

     Gly Leu Val Glu Glu Gly Ala Lys Thr Ala Pro Gly Lys Lys Arg 130 135 140

     Leu Glu Ser Pro Gin Glu Pro Asp Ser Ser ser Gly He Gly Lys 150 155 160

     Gly Lys Gin Pro Ala Lys Lys Arg Leu Asn Phe Glu Glu Asp Thr 165 170 175

     Ala Gly Asp Gly Pro Pro Glu Gly Ser Asp Thr Ser Ala Met Ser 180 185 190

     Asp He Glu Met Arg Ala Ala Pro Gly Gly Asn Ala Val Asp Ala 195 200 205

     Gin Gly Ser Asp Gly Val Gly Asn Ala Ser Gly Asp Trp His Cys 210 215 220

     Ser Thr Trp Ser Glu Gly Lys Val Thr Thr Thr Ser Thr Arg Thr 230 235 240

     Val Leu Pro Thr Tyr Asn Asn His Leu Tyr Leu Arg Leu Gly Thr 245 250 255

     Ser Asn Ser Asn Thr Tyr Asn Gly Phe Ser Thr Pro Trp Gly Tyr 260 265 270

     Asp Phe Asn Arg Phe His Cys His Phe Ser Pro Arg Asp Trp Gin 275 280 285

     Leu lie Asn Asn Asn Trp Gly Leu Arg Pro Lys Ala Met Arg Val 290 295 300 lie Phe Asn He Gin Val Lys Glu Val Thr Thr Ser Asn Gly Glu 310 315 320

     Thr Val Ala Asn Asn Leu Thr Ser Thr Val Gin lie Phe Ala Asp 325 330 335

     Ser Tyr Glu Leu Pro Tyr Val Met Asp Ala Gly Gin Glu Gly Ser 340 345 350
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     Leu Pro

     Cys Gly 370

     Phe Tyr 385

     Asn Phe

     Tyr Ala

     Gln Tyr

     Gln Gly 450

     Ala Phe 4 65

     Arg Phe

     Gly Asn

     Trp Ser

     Asp Gly 530

     Thr Gly 545

     Glu Glu

     Ile Ala

     Val Thr

     Pro Phe 355 lie Val

     Cys Leu

     Glu Thr

     His Ser 420

     Leu Trp 435

     Asn Ala

     Tyr Arg

     Ser Lys

     Ala Leu 500

     Asn Ile 515

     Asp Phe

     Asn Thr

     Ile Ala

     Asp Asn 580

     Ala Met 595

     Pro Asn Asp Val Phe 360

     Thr Gly Glu Asn Gln 375

     Glu Tyr Phe Pro Ser 390

     Ala Tyr Asn Phe Glu 405

     Gln Ser Leu Asp Gly 425

     His Leu Gln Ser Thr 440

     Ala Thr Thr Phe Gly 455

     Lys Asn Trp Leu Pro 470

     Thr Ala Ser Gln Asn 485

     Leu Lys Tyr Asp Thr 505

     Ala Pro Gly Pro Pro 520

     Ser Asn Ala Gln Leu 535

     Thr Thr Ser Ala Asn 550

     Ala Thr Asn Pro Arg 565

     Asn Gln Asn Ala Thr 585

     Gly Val Leu Pro Gly 600

     Met Val Pro Gln Tyr Gly Tyr 365

     Asn Gln Thr Asp Arg Asn Ala 380

     Gln Met Leu Arg Thr Gly Asn 395 400

     Lys Val Pro Phe His Ser Met 410 415

     Leu Met Asn Pro Leu Leu Asp 430

     Thr Ser Gly Glu Thr Leu Asn 445

     Lys He Arg Ser Gly Asp Phe 460

     Gly Pro Cys Val Lys Gln Gln 475 480

     Tyr Lys lie Pro Ala Ser Gly 490 495

     His Tyr Thr Leu Asn Asn Arg 510

     Met Ala Thr Ala Gly Pro Ser 525 lie Phe Pro Gly Pro Ser Val 540

     Asn Leu Leu Phe Thr Ser Glu 555 560

     Asp Thr Asp Met Phe Gly Gln 570 575

     Thr Ala Pro Ile Thr Gly Asn 590

     Met Val Trp Gln Asn Arg Asp 605
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     Ile Tyr Tyr Gin Gly Pro lie Trp Ala Lys lie Pro His Ala Asp Gly 610 615 620

     His Phe His Pro Ser Pro Leu lie Gly Gly Phe Gly Leu Lys His Pro 625 630 635 640

     Pro Pro Gin Ile Phe Ile Lys Asn Thr Pro Val Pro Ala Tyr pro Ala 645 650 655

     Thr Thr Phe Thr Ala Ala Arg Val Asp Ser Phe lie Thr Gin Tyr Ser 660 665 67 0

     Thr Gly Gin Val Ala Val Gin lie Glu Trp Glu Ile Glu Lys Glu Arg 675 680 685

     Ser Lys Arg Trp Asn Pro Glu Val Gin Phe Thr Ser Asn Cys Gly Asn 690 695 700

     Gin Ser Ser Met Leu Trp Ala Pro Asp Thr Thr Gly Lys Tyr Thr Glu 705 710 715 720

     Pro Arg val lie Gly Ser Arg Tyr Leu Thr Asn His Leu 725 730 <210> 63 <211> 734 <212> PRT <213> capsid protein of AAV serotype, clone AAV4VP1 <400> 63

     Met 1 Thr Asp Gly Tyr Leu 5 Pro Asp Trp Leu 10 Glu Asp Asn Leu Ser 15 Glu Gly Val Arg Glu 20 Trp Trp Ala Leu Gin 25 Pro Gly Ala Pro Lys 30 Pro Lys Ala Asn Gin 35 Gin His Gin Asp Asn 40 Ala Arg Gly Leu Val 45 Leu Pro Gly Tyr Lys 50 Tyr Leu Gly Pro Gly 55 Asn Gly Leu Asp Lys 60 Gly Glu Pro Val Asn 65 Ala Ala Asp Ala Ala 70 Ala Leu Glu His Asp 75 Lys Ala Tyr Asp Gin 80 Gin Leu Lys Ala Gly Asp 85 Asn Pro Tyr Leu 90 Lys Tyr Asn His Ala 95 Asp Ala GlU Phe Gin 100 Gin Arg Leu Gin Gly 105 Asp Thr Ser Phe Gly 110 Gly Asn
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     Leu Gly Arg 115 Ala Val Phe Gin Ala 120 Lys Lys Arg Val Leu 125 Glu Pro Leu Gly Leu 130 Val Glu Gin Ala Gly 135 Glu Thr Ala Pro Gly 140 Lys Lys Arg Pro Leu 145 He Glu Ser Pro Gin 150 Gin Pro Asp Ser Ser 155 Thr Gly He Gly Lys 160 Lys Gly Lys Gin Pro 165 Ala Lys Lys Lys Leu 170 Val Phe Glu Asp Glu 175 Thr Gly Ala Gly Asp 180 Gly Pro Pro Glu Gly 185 Ser Thr Ser Gly Ala 190 Met Ser Asp Asp Ser 195 Glu Met Arg Ala Ala 2 00 Ala Gly Gly Ala Ala 205 Val Glu Gly Gly Gin 210 Gly Ala Asp Gly Val 215 Gly Asn Ala Ser Gly Asp 220 Trp His Cys Asp 225 Ser Thr Trp Ser Glu 230 Gly His Val Thr Thr 235 Thr Ser Thr Arg Thr 240 Trp Val Leu Pro Thr 245 Tyr Asn Asn His Leu 250 Tyr Lys Arg Leu Gly 255 Glu Ser Leu Gin Ser Asn Thr Tyr Asn Gly Phe Ser Thr Pro Trp Gly Tyr

     260 265 270

     Phe Asp Phe Asn Arg Phe His Cys His Phe Ser Pro Arg Asp Trp Gin 275 280 285

     Arg Leu lie Asn Asn Asn Trp Gly Met Arg Pro Lys Ala Met Arg Val 290 295 300

     Lys He Phe Asn He Gin Val Lys Glu Val Thr Thr Ser Asn Gly Glu 305 310 315 320

     Thr Thr Val Ala Asn Asn Leu Thr Ser Thr Val Gin lie Phe Ala Asp 325 330 335

     Ser Ser Tyr Glu Leu Pro Tyr Val Met Asp Ala Gly Gin Glu Gly Ser 340 345 350

     Leu Pro Pro Phe Pro Asn Asp Val Phe Met Val Pro Gin Tyr Gly Tyr 355 360 365
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     Cys Gly Leu Val Thr Gly Asn Thr Ser Gin Gin Gin Thr Asp Arg Asn

     370 375 380

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     Ala Phe Tyr Cys Leu Glu Tyr Phe Pro Ser Gin Met Leu Arg Thr Gly 385 390 395 400

     Asn Asn Phe Glu lie Thr Tyr Ser Phe Glu Lys Val Pro Phe His Ser 405 410 415

     Met Tyr Ala His Ser Gin Ser Leu Asp Arg Leu Met Asn Pro Leu lie 420 425 430

     Asp Gin Tyr Leu Trp Gly Leu Gin Ser Thr Thr Thr Gly Thr Thr Leu 435 440 445

     Asn Ala Gly Thr Ala Thr Thr Asn Phe Thr Lys Leu Arg Pro Thr Asn 450 455 460

     Phe Ser Asn Phe Lys Lys Asn Trp Leu Pro Gly Pro Ser lie Lys Gin 465 470 475 480

     Gin Gly Phe Ser Lys Thr Ala Asn Gin Asn Tyr Lys lie Pro Ala Thr 435 490 495

     Gly Ser Asp Ser Leu He Lys Tyr Glu Thr His Ser Thr Leu Asp Gly 500 505 510

     Arg Trp Ser Ala Leu Thr Pro Gly Pro Pro Met Ala Thr Ala Gly Pro 515 520 525

     Ala Asp Ser Lys Phe Ser Asn Ser Gin Leu lie Phe Ala Gly Pro Lys 530 535 540

     Gin Asn Gly Asn Thr Ala Thr Val Pro Gly Thr Leu He Phe Thr Ser 545 550 555 560

     Glu Glu Glu Leu Ala Ala Thr Asn Ala Thr Asp Thr Asp Met Trp Gly 565 570 575

     Asn Leu Pro Gly Gly Asp Gin Ser Asn Ser Asn Leu Pro Thr Val Asp 580 585 590

     Arg Leu Thr Ala Leu Gly Ala Val Pro Gly Met Val Trp Gin Asn Arg 595 600 605

     Asp lie Tyr Tyr Gin Gly Pro He Trp Ala Lys lie Pro His Thr Asp 610 615 620
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     Gly His Phe His Pro Ser Pro Leu Ile Gly Gly Phe Gly Leu Lys His 625 630 635 640

     Pro Pro Pro Gln lie Phe Ile Lys Asn Thr Pro Val Pro Ala Asn Pro 645 650 655

     Ala Thr Thr Phe Ser Ser Thr Pro Val Asn Ser Phe lie Thr Gln Tyr 660 665 670

     Ser Thr Gly Gln Val Ser Val Gln Ile Asp Trp Glu Ile Gln Lys Glu 675 680 685

     Arg Ser Lys Arg Trp Asn Pro Glu Val Gln Phe Thr Ser Asn Tyr Gly 690 695 700

     Gln Gln Asn Ser Leu Leu Trp Ala Pro Asp Ala Ala Gly Lys Tyr Thr 705 710 715 720

     Glu Pro Arg Ala Ile Gly Thr Arg Tyr Leu Thr His His Leu 725 730

     <210 64 <211> 736 <212> PRT <213> capsid protein of AAV serotype, clone AAVl <400> 64 Met Ala i Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser

     15 10 15

     Glu Gly lie Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro 20 25 30

     Lys Ala Asn Gln Gln Lys Gln Asp Asp Gly Arg Gly Leu Val Leu Pro 35 40 45

     Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro 50 55 60

     Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp 65 70 75 80

     Gln Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala 85 90 95

     Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr Ser Phe Gly Gly 100 105 110

     Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro 115 120 125
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     Leu Gly Leu Val Glu Glu Gly Ala Lys Thr Ala Pro Gly Lys Lys Arg 130 135 140

     Pro Val Glu Gin Ser Pro Gin Glu Pro Asp Ser Ser Ser Gly He Gly

     145 150

     Lys Thr Gly Gin Gin Pro Ala Lys 165

     Gly Asp Ser Glu ser Val Pro Asp 180

     Ala Thr Pro Ala Ala Val Gly Pro 195 200

     Ala Pro Met Ala Asp Asn Asn Glu 210 215

     155 160

     Lys Arg Leu Asn Phe Gly Gin Thr 170 175

     Pro Gin Pro Leu Gly Glu Pro Pro 185 190

     Thr Thr Met Ala Ser Gly Gly Gly 205

     Gly Ala Asp Gly Val Gly Asn Ala 220

     Ser Gly Asn Trp His Cys Asp Ser 225 230

     Thr Trp Leu Gly Asp Arg Val lie 235 240

     Thr Thr Ser Thr Arg Thr Trp Ala 245

     Leu Pro Thr Tyr Asn Asn His Leu 250 255

     Tyr Lys Gin He Ser Ser Ala Ser 2 60

     Thr Gly Ala Ser Asn Asp Asn His 265 270

     Tyr Phe Gly Tyr Ser Thr Pro Trp 275 280

     Gly Tyr Phe Asp Phe Asn Arg Phe 285

     His cys His Phe Ser Pro Arg Asp 290 295

     Trp Gin Arg Leu lie Asn Asn Asn 300

     Trp Gly Phe Arg Pro Lys Arg Leu 305 . 310

     Asn Phe Lys Leu Phe Asn He Gin 315 320

     Val Lys Glu Val Thr Thr Asn Asp 325

     Gly Val Thr Thr He Ala Asn Asn 330 335

     Leu Thr Ser Thr Val Gin Val Phe 340

     Ser Asp Ser Glu Tyr Gin Leu Pro 345 350

     Tyr Val Leu Gly Ser Ala His Gin 355 360

     Gly Cys Leu Pro Pro Phe Pro Ala 365

     Asp Val Phe Met He Pro Gin Tyr 370 375

     Gly Tyr Leu Thr leu Asn Asn Gly 380
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     Ser Gin Ala Val Gly 385

     Ser Gin Met Leu Arg 405

     Glu Glu Val Pro Phe 420

     Arg Leu Met Asn Pro 435

     Thr Gin Asn Gin Ser 450

     Arg Gly Ser Pro Ala 4 65

     Gly Pro Cys Tyr Arg 485

     Asn Asn Ser Asn Phe 500

     Gly Arg Glu ser Ile 515

     Asp Asp Glu Asp Lys 530

     Lys Glu Ser Ala Gly 545

     Thr Asp Glu Glu Glu 565

     Phe Gly Thr Val Ala 580

     Thr Gly Asp Val His 595

     Asp Arg Asp Val Tyr 610

     Thr Asp Gly His Phe 625

     Arg Ser Ser Phe Tyr 390

     Thr Gly Asn Asn Phe 410

     His Ser Ser Tyr Ala 425

     Leu lie Asp Gin Tyr 440

     Gly Ser Ala Gin Asn 455

     Gly Met Ser Val Gin 470

     Gin Gin Arg Val Ser 490

     Thr Trp Thr Gly Ala 505

     Ile Asn Pro Gly Thr 520

     Phe Phe Pro Met Ser 535

     Ala Ser Asn Thr Ala 550

     Ile Lys Ala Thr Asn 570

     Val Asn Phe Gin Ser 585

     Ala Met Gly Ala Leu 600

     Leu Gin Gly Pro Ile 615

     His Pro Ser Pro Leu 630

     Cys Leu Glu Tyr Phe Pro 395 400

     Thr Phe Ser Tyr Thr Phe 415

     His Ser Gin Ser Leu Asp 430

     Leu Tyr Tyr Leu Asn Arg 445

     Lys Asp leu Leu Phe Ser 460

     Pro Lys Asn Trp Leu Pro 475 480

     Lys Thr Lys Thr Asp Asn 495

     Ser Lys Tyr Asn Leu Asn 510

     Ala Met Ala Ser His Lys 525

     Gly Val Met Ile Phe Gly 540

     Leu Asp Asn Val Met lie 555 560

     Pro Val Ala Thr Glu Arg 575

     Ser Ser Thr Asp Pro Ala 590

     Pro Gly Met Val Trp Gin 605

     Trp Ala lys lie Pro His 620

     Met Gly Gly Phe Gly Leu 635 640
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     Lys Asn Pro Pro Pro 645 Gin Ile Leu He Lys Asn Thr Pro Val 650 Pro Ala 655 Asn Pro Pro Ala Glu 660 Phe Ser Ala Thr Lys Phe Ala Ser Phe 665 670 Ile Thr Gin Tyr Ser Thr Gly 675 Gin Val Ser Val Glu lie Glu Trp Glu 680 685 Leu Gin Lys Glu Asn ser Lys 690 Arg Trp Asn Pro Glu Val Gin Tyr Thr 695 700 Ser Asn Tyr 705 Ala Lys Ser Ala Asn Val Asp Phe Thr Val Asp Asn Asn 710 715 Gly Leu 720 Tyr Thr Glu Pro Arg 725 <2l0> 65 <211> 736 <212> PRT Pro lie Gly Thr Arg Tyr Leu Thr Arg 730 Pro Leu 735 <213> capsid protein of AAV serotype, clone AAV6VP1 <400> 65 Met 1 Ala Ala Asp Gly 5 Tyr Leu Pro Asp Trp Leu Glu Asp A3n 10 Leu Ser 15 Glu Gly Ile Arg Glu 20 Trp Trp Asp Leu Lys Pro Gly Ala Pro 25 30 Lys Pro Lys Ala Asn Gin Gin 35 Lys Gin Asp Asp Gly Arg Gly Leu Val 40 45 Leu Pro Gly Tyr Lys Tyr Leu 50 Gly Pro Phe Asn Gly Leu Asp Lys Gly 55 60 Glu Pro Val 65 Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala 70 75 Tyr Asp 80 Gin Gin Leu Lys Ala 85 Gly Asp Asn Pro Tyr Leu Arg Tyr Asn 90 His Ala 95 Asp Ala Glu Phe Gin 100 Glu Arg Leu Gin Glu Asp Thr Ser Phe 105 110 Gly Gly Asn Leu Gly Arg Ala 115 Val Phe Gin Ala Lys Lys Arg Val Leu 120 125 Glu Pro Phe Gly Leu Val Glu 130 Glu Gly Ala Lys Thr Ala Pro Gly Lys 135 140 Lys Arg
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     Pro Val Glu Gin Ser Pro Gin Glu Pro Asp Ser Ser Ser Gly Ile Gly 145 150 155 160

     Lys Thr Gly Gin Gin Pro Ala Lys Lys Arg Leu Asn Phe Gly Gin Thr 165 ' 170 175

     Gly Asp Ser Glu Ser Val Pro Asp Pro Gin Pro Leu Gly Glu Pro Pro 180 185 190

     Ala Thr Pro Ala Ala Val Gly Pro Thr Thr Met Ala Ser Gly Gly Gly 195 200 205

     Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn Ala 210 215 220

     Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val Ile 225 230 235 240

     Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu 245 250 255

     Tyr Lys Gin Ile Ser Ser Ala Ser Thr Gly Ala Ser Asn Asp Asn His 260 265 270

     Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe 275 280 285

     His Cys His Phe Ser Pro Arg Asp Trp Gin Arg Leu Ile Asn Asn Asn 290 295 300

     Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn Ile Gin 305 310 315 320

     Val Lys Glu Val Thr Thr Asn Asp Gly Val Thr Thr lie Ala Asn Asn 325 330 335

     Leu Thr Ser Thr Val Gin Val Phe Ser Asp Ser Glu Tyr Gin Leu Pro 340 345 350

     Tyr Val Leu Gly Ser Ala His Gin Gly Cys Leu Pro Pro Phe Pro Ala 355 360 365

     Asp Val Phe Met lie Pro Gin Tyr Gly Tyr Leu Thr leu Asn Asn Gly 370 375 380

     Ser Gin Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro 385 390 395 400
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     Ser Gln Met Leu Arg 405 Thr Gly Asn . Asn . Phe 410 ! Thr : Phe ! Ser Tyr • Thr Phe 415 Glu Asp Val Pro 420 Phe His Ser Ser Tyr 425 Ala His Ser Gln Ser 430 Leu i Asp Arg Leu Met 435 Asn Pro Leu Ile Asp 440 Gln Tyr Leu . Tyr Tyr 445 Leu Asn . Arg Thr Gln 450 Asn Gln Ser Gly Ser 455 Ala Gln Asn Lys Asp 4 60 Leu Leu Phe Ser Arg 465 Gly Ser Pro Ala Gly 470 Met Ser Val Gln Pro 475 Lys Asn Trp Leu Pro 480 Gly Pro Cys Tyr Arg 485 Gln Gln Arg Val Ser 490 Lys Thr Lys Thr Asp 495 Asn Asn Asn Ser Asn 500 Phe Thr Trp Thr Gly 505 Ala Ser Lys Tyr Asn 510 Leu Asn Gly Arg Glu 515 Ser Ile lie Asn Pro 520 Gly Thr Ala Met Ala 525 Ser His Lys Asp Asp 530 Lys Asp Lys Phe Phe 535 Pro Met Ser Gly Val 540 Met lie Phe Gly Lys 545 Glu Ser Ala Gly Ala 550 Ser Asn Thr Ala Leu 555 Asp Asn Val Met Ile 560 Thr Asp Glu Glu Glu 565 Ile Lys Ala Thr Asn 57 0 Pro Val Ala Thr Glu 575 Arg Phe Gly Thr Val 580 Ala Val Asn Leu Gln 585 Ser Ser Ser Thr Asp 590 Pro Ala Thr Gly Asp 595 Val His Val Met Gly 600 Ala Leu Pro Gly Met 605 Val Trp Gln Asp Arg 610 Asp Val Tyr Leu Gln 615 Gly Pro Ile Trp Ala 620 Lys Ile Pro His Thr 625 Asp Gly His Phe His 630 Pro Ser Pro Leu Met 635 Gly Gly Phe Gly Leu 640 Lys His Pro Pro Pro Gln Ile Leu lie Lys . Asn Thr Pro Val Pro . Ala

     645 650 655
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     Asn pro Pro Ala Glu Phe Ser Ala Thr Lys Phe Ala Ser Phe Ile Thr 660 665 670

     Gin Tyr Ser 675 Thr Gly Gin Val Ser 680 Val Glu lie Glu Trp ’ 685 Glu Leu Gin Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Val Gin Tyr Thr Ser Asn 690 695 700 Tyr Ala Lys Ser Ala Asn Val Asp Phe Thr Val Asp Asn Asn Gly Leu 705 710 715 720 Tyr Thr Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Pro Leu 725 730 735 <210> 66 <211> 735 <212> PRT <213> capsid protein of AAV serotype, clone A3.3 <400> 66 Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Thr Leu Ser 1 5 10 15 Glu Gly Ile Arg Gin Trp Trp Lys Leu Lys Pro Gly Pro Pro Pro Pro 20 25 30 Lys Pro Asn Gin Gin His Arg Asp Asp Ser Arg Glv Leu Val Leu Pro 35 40 45 Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro 50 55 60 Val Asn Glu Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp 65 70 75 80 His Gin Leu Lys Gin Gly Asp Asn Pro Tyr Leu Lys Tyr Asn His Ala 85 90 95 Asp Ala Glu Phe Gin Glu Arg Leu Gin Glu Asp Thr Ser Phe Gly Gly 100 105 110 Asn Leu Gly Arg Ala Val Phe Gin Ala Lys Lys Arg Val Leu Glu Pro 115 120 125

     Leu Gly Leu Val Glu Glu Ala Val Lys Thr Ala Pro Gly Lys Lys Arg 130 135 . 140
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     Pro lie Glu Gin Ser Pro Ala Glu Pro Asp Ser Ser Ser Gly Ile Gly

     145 150 155 160

     2015258271 20 Nov 2015

     Lys Ser Gly Gin Gin Pro Ala Lys Lys Arg Leu Asn Phe Gly Gin Thr 165 170 175

     Gly Asp Thr Glu Ser Val Pro Gly Pro Gin Pro Ile Gly Glu Pro Pro 180 185 190

     Ala Ala Pro Ser Gly Val Gly Ser Asn Thr Met Ala Ser Gly Gly Gly 195 200 205

     Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn Ser 210 215 220

     Ser Gly Asn Trp His Cys Asp Ser Thr Trp Met Gly Asp Arg Val lie 225 230 235 240

     Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His leu 245 250 255

     Tyr lys Gin Ile Ser Ser Glu Ser Gly Ala Thr Asn Asp Asn His Tyr . 260 265 270

     Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe His 275 280 285

     Cys His Ehe Ser Pro Arg Asp Trp Gin Arg Leu Ile Asn Asn Asn Trp 290 295 300

     Gly Phe Arg Pro Lys Lys Leu Asn Phe Lys Leu Phe Asn Ile Gin Val 305 310 315 320

     Lys Glu Val Thr Gin Asn Asp Gly Thr Thr Thr lie Ala Asn Asn Leu 325 330 335

     Thr Ser Ala Val Gin Val Phe Thr Asp Ser Glu Tyr Gin Leu pro Tyr 340 345 350

     Val leu Gly Ser Ala His Gin Gly Cys Leu Pro Pro Phe Pro Ala Asp 355 360 365

     Val Phe Met lie Pro Gin Tyr Gly Tyr leu Thr leu Asn Asn Gly Ser 370 375 380

     Gin Ala Val Gly Arg Ser Ser Phe Tyr Cys leu Glu Tyr Phe Pro Ser 385 390 395 400
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     Gin Met Leu Arg Thr Gly Asn Asn Phe Thr Phe Ser Tyr Thr Phe Glu 405 ' 410 415

     Asp Val Pro Phe His Ser ser Tyr Ala His Ser Gin Ser Leu Asp Arg 420 425 430

     Leu Met Asn Pro Leu lie Asp Gin Tyr Leu Tyr Tyr Leu Ser Lys Thr 435 440 445

     Gin Gly Thr Ser Gly Thr Thr Gin Gin Ser Arg Leu Gin Phe Ser Gin 450 455 460

     Ala Gly Pro Ser Ser Met Ala Gin Gin Ala Lys Asn Trp Leu Pro Gly 465 470 475 480

     Pro Ser Tyr Arg Gin Gin Arg Met Ser Lys Thr Ala Asn Asp Asn Asn 485 490 495

     Asn Ser Glu Phe Ala Trp Thr Ala Ala Thr Lys Tyr Tyr Leu Asn Gly 500 505 510

     Arg Asn Ser Leu Val Asn Pro Gly Pro Pro Val Ala Ser His Lys Asp 515 520 525

     Asp Glu Glu Lys Tyr Phe Pro Met His Gly Asn Leu He Phe Gly Lys 530 535 540

     Gin Gly Thr Gly Thr Thr Asn Val Asp lie Glu Ser Val Leu lie Thr 545 550 555 560

     Asp Glu Glu Glu lie Arg Thr Thr Asn Pro Val Ala Thr Glu Gin Tyr 565 570 575

     Gly Gin Val Ala Thr Asn His Gin Ser Gin Asn Thr Thr Ala Ser Tyr 580 585 590

     Gly Ser Val Asp Ser Gin Gly lie Leu Pro Gly Met Val Trp Gin Asp 595 600 605

     Arg Asp Val Tyr Leu Gin Gly Pro lie Trp Ala Lys Thr Pro His Thr 610 615 620

     Asp Gly His Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Leu Lys 625 630 635 640

     His Pro Pro Pro Gin lie Leu lie Lys Asn Thr Pro Val Pro Ala Asn 645 650 655
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     Pro Ala Thr Thr Phe Thr Pro Gly Lys Phe Ala Ser Phe lie Thr Gin

     660 665 670

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     Tyr ser Thr Gly Gin Val Ser Val Glu He Glu Trp Glu Leu Gin Lys 675 680 685

     Glu Asn Ser Lys Arg Trp Asn Pro Glu lie Gin Tyr Thr Ser Asn Tyr 690 695 700

     Asn Lys Ser Val Asn Val Glu Phe Thr Val Asp Ala Asn Gly Val Tyr 705 710 715 720

     Ser Glu Pro Arg Pro He Gly Thr Arg Tyr Leu Thr Arg Asn Leu 725 730 735 <210> 67 <211> 735 <212> PBT <213> capsid protein of AAV serotype, clone A3.7 <400> 67

     Met 1 Ala Ala Asp Gly 5 Tyr Leu Pro Asp Trp 10 Leu Glu Asp Thr Leu 15 Ser Glu Gly He Arg 20 Gin Trp Trp Lys Leu 25 Lys Pro Gly Pro Pro 30 Pro Pro Lys Pro Asn 35 Gin Gin His Arg Asp 40 Asp Ser Arg Gly Leu 45 Val Leu Pro Gly Tyr 50 Lys Tyr Leu Gly Pro 55 Phe Asn Gly Leu Asp 60 Lys Gly Glu Pro Val 65 Asn Glu Ala Asp Ala 70 Ala Ala Leu Glu His 75 Asp Lys Ala Tyr Asp 80 His Gin Leu Lys Gin 85 Gly Asp Asn Pro Tyr 90 Leu Lys Tyr Asn His 95 Ala Asp Ala Glu Phe 100 Gin Glu Arg Leu Gin 105 Glu Asp Thr Ser Phe 110 Gly Gly Asn Leu Gly Arg 115 Ala Val Phe Gin 120 Ala Lys Lys Arg Val 125 Leu Glu Pro Leu Gly 130 Leu Val Glu Glu Ala 135 Val Lys Thr Ala Pro 140 Gly Lys Lys Arg Pro 145 He Glu Gin Ser Pro 150 Ala Glu Pro Asp Ser 155 Ser Ser Gly He Gly 160
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     Lys Ser Gly Gin Gin 165 pro Ala Lys Lys Arg Leu Asn Phe Gly Gin Thr 170 175 Gly Asp Thr Glu 180 Ser val Pro Asp Pro 185 Gin Pro lie Gly Glu Pro Pro 190 Ala Ala Fro 195 Ser Gly Val Gly Ser 200 Asn Thr Met Ala Ser Gly Gly Gly 205 Ala Pro 210 Met Ala Asp Asn Asn 215 Glu Gly Ala Asp Gly Val Gly Asn Ser 220 Ser 225 Gly Asn Trp His Cys 230 Asp Ser Thr Trp Met Gly Asp Arg Val lie 235 240 Thr Thr Ser Thr Arg 245 Thr Trp Ala Leu Pro Thr Tyr Asn Asn Arg Leu 250 255 Tyr Lys Gin lie 2 60 Ser Ser Glu Ser Gly 265 Ala Thr Asn Asp Asn His Tyr 270 Phe Gly Tyr 275 Ser Thr Pro Trp Gly 280 Tyr Phe Asp Phe Asn Arg Phe His 285 cys His 290 Phe Ser Pro Arg Asp 295 Trp Gin Arg Leu lie Asn Asn Asn Trp 300 Gly 305 Phe Arg Pro Lys Lys 310 Leu Asn Phe Lys Leu Phe Asn Ile Gin Val 315 320 Lys Glu Val Thr Gin 325 Asn Asp Gly Thr Thr Thr lie Ala Asn Asn Leu 330 335 Thr Ser Thr Val 340 Gin Val Phe Thr Asp 345 Ser Glu Tyr Gin Leu Pro Tyr 350 val Leu Gly 355 Ser Ala His Gin Gly 360 Cys Leu Pro Pro Phe Pro Ala Asp 365 val Phe 370 Met lie Pro Gin Tyr 375 Gly Tyr Leu Thr Leu Asn Asn Gly Ser 380 Gin 385 Ala val Gly Arg Ser 390 Ser Phe Tyr Cys Leu Glu Tyr Phe Pro Ser 395 400 Gin Met Leu Arg Thr Gly Asn Asn Phe Thr Phe Ser Tyr Thr Phe Glu

     405 410 415
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     Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gin Ser Leu Asp Arg 420 425 430

     Leu Met Asn Pro Leu lie Asp Gin Tyr Leu Tyr Tyr Leu Ser Lys Thr 435 440 445

     Gin Gly Thr Ser Gly Thr Thr Gin Gin Ser Arg Leu Gin Phe Ser Gin 450 455 460

     Ala Gly Pro Ser Ser Met Ala Gin Gin Ala Lys Asn Trp Leu pro Gly 465 470 475 480

     Pro Ser Tyr Arg Gin Gin Arg Met Ser Lys Thr Ala Asn Asp Asn Asn 485 490 495

     Asn Ser Glu Phe Ala Trp Thr Ala Ala Thr Lys Tyr Tyr Leu Asn Gly 500 505 510

     Arg Asn Ser Leu Val Asn Pro Gly Pro Pro Met Ala Ser His Lys Asp 515 520 525

     Asp Glu Glu Lys Tyr Phe Pro Met His Gly Asn Leu lie Phe Gly Lys 530 ' 535 540

     Gin Gly Thr Gly Thr Thr Asn Val Asp He Glu Ser Val Leu lie Thr 545 550 555 560

     Asp Glu Glu Glu He Arg Thr Thr Asn Pro Val Ala Thr Glu Gin Tyr 565 570 575

     Gly Gin Val Ala Thr Asn His Gin Ser Gin Asn Thr Thr Ala Ser Tyr 580 585 590

     Gly Ser Val Asp Ser Gin Gly lie Leu Pro Gly Met Val Trp Gin Asp 595 600 605

     Arg Asp Val Tyr Leu Gin Gly Pro He Trp Ala lys Thr Pro His Thr 610 615 620

     Asp Gly His Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Leu Lys 625 630 635 640

     His Pro Pro Pro Gin He Leu He Lys Asn Thr Pro Val Pro Ala Asn 645 650 655

     Pro Ala Thr Thr Phe Thr Pro Gly Lys Phe Ala Ser Phe lie Thr Gin 660 665 670
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     Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu Gln. lys 675 680 6B5

     Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr Ser Asn Tyr 690 695 700

     Asn Lys Ser Val Asn Val Glu Phe Thr Val Asp Ala Asn Gly Val Tyr

     705 710 715 720 Ser Glu Pro Arg Pro ile Gly Thr Arg Tyr Leu Thr Arg Asn Leu 725 730 735

     <210> 68 <211> 735 <212> PRT <213> capsid protein of AAV serotype, clone A3.4

     <400> 68

     Met 1 Ala Ala Asp Gly 5 Tyr Leu Pro Asp Trp 10 Leu Glu Asp Thr Leu 15 Ser Glu Gly Ile Arg 20 Gln Trp Trp Lys Leu 25 Lys Pro Gly Pro Pro 30 Pro Pro Lys Pro Aen 35 Gln Gln His Arg Asp 40 Asp Ser Arg Gly Leu 45 Val Leu Pro Gly Tyr 50 Lys Tyr Leu Gly Pro 55 Phe Asn Gly Leu Asp 60 Lys Gly Glu Pro Val 65 Asn Glu Ala Asp Ala 70 Ala Ala Leu Glu His 75 Asp Lys Ala Tyr Asp 80 His Gln Leu Lys Gln 85 sly Asp Asn Pro Tyr 90 Leu Lys Tyr Asn His 95 Ala Asp Ala Glu Phe 100 Gln Glu Arg Leu Gln 105 Glu Asp Thr Ser Phe no Gly Gly Asn Leu Gly Arg 115 Ala Val Phe Gln 120 Ala Lys Lys Arg Val 125 Leu Glu Pro Leu Gly 130 Leu Val Glu Glu Ala 135 Val Lys Thr Ala Pro 14 0 Gly Lys Lys Arg Pro 145 Ile Glu Gln Ser Pro 150 Ala Glu Pro Asp Ser 155 Ser Ser Gly lie Gly 160 Glu Ser sly Gln Gln Pro Ala Lys Lys Arg Leu Asn Phe Gly Gln Thr

     165 170 175
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     Thr Glu Ser Val Pro Asp Pro Gln Pro Ile Gly Glu Pro Pro

     180 185 190

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     Gly Asp

     Ala Ala

     Ala Pro 210

     Ser Gly 225

     Thr Thr

     Tyr Lys

     Phe Gly

     Cys His 290

     Gly Phe 305

     Lys Glu

     Thr Ser

     Val Leu

     Val Phe 370

     Gln Ala 385

     Gln Met

     Pro ser Gly Val Gly Ser Asn Thr Met Ala ser Gly Gly Gly 195 200 205

     Met Ala Asp Asp Asn Glu Gly Ala Asp Gly Val Gly Asn Ser 215 220

     Asn Trp His Cys Asp Ser Thr Trp Met Gly Asp Arg Val lie 230 235 240

     Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu 245 250 255

     Gln Ile Ser Ser Glu Ser Gly Ala Thr Asn Asp Asn His Tyr 260 265 270

     Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe His 275 280 285

     Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn Asn Trp 295 300

     Arg Pro Lys Lys Leu Asn Phe Lys Leu Phe Asn Ile Gln Val 310 315 320

     Val Thr Gln Asn Asp Gly Thr Thr Thr Ile Ala Asn Asn Leu 325 330 335

     Thr Val Gln Val Phe Thr Asp Ser Glu Tyr Gln Leu Pro Tyr 340 345 350

     Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro Ala Asp 355 360 365

     Met lie Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn Gly ser 375 380

     Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro Ser 390 395 400

     Leu Arg Thr Gly Asn Asn Phe Thr Phe Ser Tyr Thr Phe Glu 405 410 415

     Pro Phe His ser Ser Tyr Ala His Ser Gln Ser Leu Asp Arg 420 425 430

     Asp Val
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     Leu Met Asn 435 Pro Leu lie Asp Gin 440 Tyr Leu i Tyr Tyr Leu 445 Ser Lys Thr Gin Gly 450 Thr Ser Gly Thr Thr 455 Gin Gin Ser Arg Leu 460 . Gin Phe Ser Gin Ala 465 Gly Pro Ser Ser Met 470 Ala Gin Gin Ala Lys 475 Asn Trp Leu Pro Gly 480 Pro Ser Tyr Arg Gin 485 Gin Arg Met Ser Lys 490 Thr Ala Asn Asp Asn Asn 495 Asn Ser Glu Phe 500 Ala Trp Thr Ala Ala 505 Thr Lys Tyr Tyr Leu 510 Asn Gly Arg Asn Ser 515 Leu Val Asn Pro Gly 520 Pro Pro Met Ala Ser 525 His Lys Asp Asp Glu 530 Glu Lys Tyr Phe Pro 535 Met His Gly Asn Leu 540 lie Phe Gly Lys Gin 545 Gly Thr Gly Thr Thr 550 Asn Val Asp He Glu 555 Ser Val Leu lie Thr 560 Asp Glu Glu Glu lie 565 Arg Thr Thr Asn Pro 570 Val Ala Thr Glu Gin Tyr 575 Gly Gin Val Ala 580 Thr Asn His Gin Ser 585 Gin Asp Thr Thr Ala 590 Ser Tyr Gly Ser Val 595 Asp Ser Gin Gly lie 600 Leu Pro Gly Met Val 605 Trp Gin Asp Arg Asp 610 Val Tyr Leu Gin Gly 615 Pro He Trp Ala Lys 620 Thr Pro His Thr Asp 625 Gly His Phe His Pro 630 Ser Pro Leu Met Gly 635 Gly Phe Gly Leu Lys 64 0 His Pro Pro Pro Gin 645 He Leu He Lys Asn 650 Thr Pro Val pro Ala Asn 655 Pro Ala Thr Thr 660 Phe Thr Pro Gly Lys 665 Phe Ala Ser Phe lie 670 Thr Gin Tyr Ser Thr Gly Gin Val Ser val Glu He Glu Trp Glu Leu Gin Lys

     675 680 685
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     Glu Asn Ser Lys Arg Trp Asn Pro Glu lie Gin Tyr Thr Ser Asn Tyr 690 695 700

     Asn Lys Ser Val Asn Val Glu Phe Thr Val Asp Ala Asn Gly Val Tyr

     705 710 715 720 Ser Glu Pro Arg Pro He Gly Thr Arg Tyr Leu Thr Arg 725 730 <210> 69 <211> 735 <212> PRT <213> capsid protein of AAV serotype, clone A3.5 <400> 69 Asn Leu 735 Met Ala Ala 1 Asp Gly Tyr 5 Leu Pro Asp Trp Leu Glu Asp 10 Thr Leu Ser 15 Glu Gly He Arg Gin Trp 20 Trp Lys Leu Lys Pro Gly Pro 25 Pro Pro Pro 30 Lys Pro Asn 35 Gin Gin His Arg Asp Asp Ser Arg Gly Leu 40 45 Val Leu pro Gly Tyr Lys 50 Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys 55 60 Gly Glu Pro Val Asn Glu 65 Ala Asp Ala 70 Ala Ala Leu Glu His Asp Lys 75 Ala Tyr Asp SO His Gin Leu Lys Gin Gly 85 Asp Asn Pro Tyr Leu Lys Tyr 90 Asn His Ala 95 Asp Ala Glu Phe Gin Glu 100 Arg Leu Gin Glu Asp Thr Ser 105 Phe Gly Gly 110 Asn Leu Gly 115 Arg Ala Val Phe Gin Ala Lys Lys Arg Val 120 125 Leu Glu Pro Leu Gly Leu 130 Val Glu Glu Ala Val Lys Thr Ala Pro Gly 135 140 Lys Lys Arg

     Pro He Glu Gin Ser Pro Ala Glu Pro Asp Ser Ser Ser Gly Ile Gly 145 150 155 160

     Lys Ser Gly Gin Gin Pro Ala Lys Lys Arg Leu Asn Phe Gly Gin Thr 165 170 175

     Gly Asp Thr Glu Ser Val Pro Asp Pro Gin Pro Ile Gly Glu Pro Pro 180 185 190
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     Ala Ala

     Ala Pro 210

     Ser Gly 225

     Thr Thr

     Tyr Lys

     Phe Gly

     Cys His 290

     Gly Phe 305

     Lys Glu

     Thr Ser

     Thr Val Gin 340

     Pro Ser Gly 195

     Met Ala Asp

     Asn Trp His

     Ser Thr Arg 245

     Gin lie Ser 260

     Tyr Ser Thr 275

     Phe Ser Pro

     Arg Pro Lys

     Val Thr Gin 325

     Val Gly Ser 200 Asn Thr Asn Asn 215 Glu Gly Ala Cys 230 Asp Ser Thr Trp Thr Trp Ala Leu Pro 250 Ser Glu Ser Gly 265 Ala Pro Trp Gly 280 Tyr Phe Arg Asp 295 Trp Gin Arg Lys 310 Leu Asn Phe Lys Asn Asp Gly Thr Thr 330 Val Phe Thr Asp Ser

     345

     Met Ala Ser Gly Gly Gly 205

     Asp Gly Val Gly Asn Ser 220

     Met Gly Asp Arg Val lie 235 240

     Thr Tyr Asn Asn His Leu 255

     Thr Asn Asp Asn His Tyr 270

     Asp Phe Asn Arg Phe His 285

     Leu lie Asn Asn Asn Trp 300

     Leu Phe Asn lie Gin Val 315 320

     Thr lie Ala Asn Asn Leu 335

     Glu Tyr Gin Leu Pro Tyr 350

     Val Leu

     Gly Ser Ala 355

     His Gin Gly Cys Leu 360

     Pro Pro Phe Pro Ala Asp 365

     Val Phe 37 0

     Met lie Pro

     Gin Tyr Gly Tyr Leu 375

     Thr Leu Asn Asn Gly Ser 3S0

     Gin Ala 385

     Val Gly Arg

     Ser Ser Phe Tyr Cys 390

     Leu Glu Tyr Phe Pro Ser 395 400

     Gin Met

     Leu Arg Thr 405

     Gly Asn Asn Phe Thr 410

     Phe Ser Tyr Thr Phe Glu 415

     Asp Val

     Pro Phe His 420

     Ser Ser Tyr Ala His 425

     Ser Gin Ser Leu Asp Arg 430

     Asn Pro Leu 435 lie Asp Gin Tyr Leu 440

     Tyr Tyr Leu Ser Lys Thr 445

     Leu Met
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     Gin Gly Thr Ser Gly Thr Thr Gin Gin Ser Arg Leu Gin Phe Asn Gin 450 455 460

     Ala Gly Pro Ser Ser Met Ala Gin Gin Ala Lys Asn Trp Leu Pro Gly 465 470 475 480

     Pro Ser Tyr Arg Gin Gin Arg Met Ser Lys Thr Ala Asn Asp Asn Asn 485 490 495

     Asn Ser Glu Phe Ala Trp Thr Ala Ala 'Thr Lys Tyr Tyr Pro Asn Gly 500 505 510

     Arg Asn Ser Leu Val Asn Pro Gly Pro Pro Met Ala Ser His Lys Asp 515 520 525

     Asp Glu Glu Lys Tyr Phe Pro Met His Gly Asn Leu lie Phe Gly lys 530 535 540

     Gin Gly Thr Gly Thr Thr Asn Val Asp lie Glu Ser Val Leu lie Thr 545 550 555 560

     Asp Glu Glu Glu lie Arg Thr Thr Asn Pro Val Ala Thr Glu Gin Tyr 565 570 575

     Gly Gin Val Ala Thr Asn Arg Gin Ser Gin Asn Thr Thr Ala Ser Tyr 580 585 590

     Gly Ser Val Asp Ser Gin Gly He Leu Pro Gly Met Val Trp Gin Asp 595 600 605

     Arg Asp Val Tyr Leu Gin Gly Pro lie Trp Ala Lys Thr Pro His Thr 610 615 620

     Asp Gly His Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Leu Lys 625 630 635 640

     His Pro Pro Pro Gin lie Leu He Lys Asn Thr Pro Val Pro Ala Asn 645 650 655

     Pro Ala Thr Thr Phe Thr Pro Gly Lys Phe Ala Ser Phe He Thr Gin 660 665 670

     Tyr Ser Thr Gly Gin Val Ser Val Glu He Glu Trp Glu Leu Gin Lys 675 680 685

     Glu Asn Ser Lys Arg Trp Asn Pro Glu lie Gin Tyr Thr Ser Asn Tyr 690 695 700
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     Asn Lys Ser Val· Asn Val Glu Phe Thr Val Asp Ala Asn Gly Val Tyr 705 710 715 720

     Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Asn Leu 725 730 735 <210> 70 <211> 735 <212> PRT <213> capsid protein of AAV serotype, clone AAV2 <400> 70

     Met 1 Ala Ala Asp Gly 5 Tyr Leu Pro Asp Trp 10 Leu Glu Asp Thr Leu 15 Ser Glu Gly Ile Arg 20 Gin Trp Trp Lys Leu 25 Lys Pro Gly Pro Pro 30 Pro Pro Lys Pro Ala 35 Glu Arg His Lys Asp 40 Asp Ser Arg Gly Leu 45 Val Leu Pro Gly Tyr 50 Lys Tyr Leu Gly Pro 55 Phe Asn Gly Leu Asp 60 Lys Gly Glu Pro Val 65 Asn Glu Ala Asp Ala 70 Ala Ala Leu Glu His 75 Asp Lys Ala Tyr Asp 80 Arg Gin Leu Asp Ser 85 Gly Asp Asn Pro Tyr 90 Leu Lys Tyr Asn His 95 Ala Asp Ala Glu Phe 100 Gin Glu Arg Leu Lys 105 Glu Asp Thr Ser Phe 110 Gly Gly Asn Leu Gly 115 Arg Ala Val Phe Gin 120 Ala Lys Lys Arg Val 125 Leu Glu Pro Leu Gly 130 Leu Val Glu Glu Pro 135 Val Lys Thr Ala Pro 140 Gly Lys Lys Arg Pro 145 Val Glu His Ser Pro 150 Val Glu Pro Asp Ser 155 Ser Ser Gly Thr Gly 160 Lys Ala Gly Glu Gin 165 Pro Ala Arg Lys Arg 170 Leu Asn Phe Gly Gin 175 Thr Gly Asp Ala Asp 180 Ser Val Pro Asp Pro 185 Gin Pro Leu Gly Gin 190 Pro Pro
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     Ala Ero Ser Gly Leu Gly Thr Asn Thr Met Ala Thr Gly Ser Gly

     135 200 205

     Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn Ser

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     Ala

     Ala

     Ser

     225

     Thr

     Tyr

     Ehe

     Cys

     Gly

     305

     Lys

     Thr

     Val

     Val

     Gin

     385

     Gin

     Asp

     Leu

     210 215

     Gly Asn Trp His Cys Asp Ser 230

     Thr Ser Thr Arg Thr Trp Ala 245

     Lys Gin lie Ser Ser Gin Ser 260

     Gly Tyr Ser Thr Ero Trp Gly 275 280

     His Phe Ser Ero Arg Asp Trp 290 235

     Phe Arg Ero Lys Arg Leu Asn 310

     Glu Val Thr Gin Asn Asp Gly 325

     Ser Thr Val Gin Val Ehe Thr 340

     Leu Gly Ser Ala His Gin Gly 355 360

     Phe Met Val Ero Gin Tyr Gly 370 375

     Ala Val Gly Arg Ser Ser Ehe 390

     Met Leu Arg Thr Gly Asn Asn 405

     Val Ero Phe His Ser Ser Tyr 420

     Met Asn Pro Leu Ile Asp Gin 435 440

     220

     Thr Trp Met Gly Asp Arg Val Ile 235 240

     Leu Pro Thr Tyr Asn Asn His Leu 250 255

     Gly Ala Ser Asn Asp Asn His Tyr 265 270

     Tyr Phe Asp Phe Asn Arg Phe His 285

     Gin Arg Leu Ile Asn Asn Asn Trp 300

     Phe Lys Leu Phe Asn Ile Gin Val 315 320

     Thr Thr Thr lie Ala Asn Asn Leu 330 335

     Asp Ser Glu Tyr Gin Leu Pro Tyr 345 350

     Cys Leu Pro Pro Ehe Pro Ala Asp 365

     Tyr Leu Thr Leu Asn Asn Gly Ser 380

     Tyr Cys Leu Glu Tyr Ehe Pro Ser 395 400

     Phe Thr Phe Ser Tyr Thr Ehe Glu 410 415

     Ala His Ser Gin Ser Leu Asp Arg 425 430

     Tyr Leu Tyr Tyr Leu Ser Arg Thr 445'
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     Asn Thr 450 Pro Ser ¹ Gly Thr Thr 455 Thr Gln . Ser Arg Leu Gln 460 i Phe s Ser Gln Ala 465 Gly Ala Ser Asp Ile 470 Arg Asp Gln Ser Arg 475 Asn Trp 1 Leu l Pre i Gly 480 Pro Cys Tyr Arg Gln 485 Gln Arg Val Ser Lys 490 Thr Ser Ala Asp Asn 495 . Asn Asn Ser Glu Tyr 500 Ser Trp Thr Gly Ala 505 Thr Lys Tyr His Leu 510 Asn Gly Arg Asp Ser 515 Leu Val Asn Pro Gly 520 Pro Ala Met Ala Ser 525 His Lys Asp Asp Glu 530 Glu Lys Phe Phe Pro 535 Gln Ser Gly Val Leu Ile 540 Phe Gly Lys Gln 545 Gly Ser Glu Lys Thr 550 Asn Val Asp Ile Glu 555 Lys Val Met Ile Thr 560 Asp Glu Glu Glu Ile 565 Arg Thr Thr Asn Pro 570 val Ala Thr Glu Gln 575 Tyr Gly Ser Val Ser 580 Thr Asn Leu Gln Arg 585 Gly Asn Arg Gln Ala 590 Ala Thr Ala Asp Val 595 Asn Thr Gln Gly Val 600 Leu Pro Gly Met Val 605 Trp Gln Asp Arg Asp 610 Val Tyr Leu Gln Gly 615 Pro Ile Trp Ala Lys Ile 620 Pro His Thr Asp 625 Gly His Phe His Pro 630 Ser Pro Leu Met Gly 635 Gly Phe Gly Leu Lys 640 His Pro Pro Pro Gln 645 Ile Leu Ile Lys Asn 650 Thr Pro Val Pro Ala 655 Asn Pro Ser Thr Thr 660 Phe Ser Ala Ala Lys 665 Phe Ala Ser Phe lie 670 Thr Gln Tyr Ser Thr 675 Gly Gln Val Ser Val 680 Glu Ile Glu Trp Glu 685 Leu Gln Lys Glu Asn 690 Ser Lys . Arg Trp Asn 695 Pro Glu Ile Gln Tyr Thr 700 Ser Asn Tyr
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     Asn Lys Ser Val Asn Val Asp Phe Thr Val Asp Thr Asn Gly Val Tyr 705 710 715 720

     Ser Glu Pro Arg Pro He Gly Thr Arg Tyr Leu Thr Arg Asn Leu ' 725 730 735 <210> 71 <211> 736 <212> PRT <213> capsid protein of AAV serotype, clone AAV3 <400> 71

     Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 1 5 10 15 o oo GlU Gly Ile Arg Glu Trp Trp Ala Leu Lys Pro Gly Val Pro Gln pro in 20 25 30 CM in Lys Ala Asn Gln Gln His Gln Asp Asn Arg Arg Gly Leu Val Leu Pro o 35 40 45 CM Gly Tyr Lys Tyr Leu Gly Pro Gly Asn Gly Leu Asp Lys Gly Glu Pro 50 55 60 val Asn Glu Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp 65 70 75 80 Gln Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Lys Tyr Asn His Ala 85 90 95 Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr Ser Phe Gly Gly 100 105 110 Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Ile Leu Glu Pro 115 120 125 Leu Gly Leu Val Glu Glu Ala Ala Lys Thr Ala Pro Gly Lys Lys Gly 130 135 140 Ala Val Asp Gln Ser Pro Gln Glu Pro Asp Ser Ser Ser Gly Val Gly 145 150 155 160 Lys Ser Gly Lys Gln Pro Ala Arg Lys Arg Leu Asn Phe Gly Gln Thr 165 170 175 Gly Asp Ser Glu Ser Val Pro Asp Pro Gln Pro Leu Gly Glu Pro Pro 180 185 190 Ala Ala Pro Thr Ser Leu Gly Ser Asn Thr Met Ala Ser Gly Gly Gly

     195 200 205
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     Ala Pro 210 Met Ala Asp Asn Asn 215 Glu . Gly Ala . Asp . Gly Val Gly Asn Ser 220 Ser 225 Gly Asn Trp His Cys 230 Asp Ser Gin Trp Leu 235 Gly Asp Arg Val . He 240 Thr Thr Ser Thr Arg 245 Thr Trp Ala Leu Pro 250 Thr Tyr Asn Asn His 255 Leu Tyr Lys Gin lie 2 60 Ser Ser Gin Ser Gly 265 Ala Ser Asn Asp Asn His 270 Tyr Phe Gly Tyr 275 Ser Thr Pro Trp Gly 280 Tyr Phe Asp Phe Asn Arg Phe 285 His Cys His 290 Phe Ser Pro Arg Asp 295 Trp Gin Arg Leu lie 300 Asn Asn Asn Trp Gly 305 Phe Arg Pro lys Lys 310 Leu Ser Phe Lys Leu 315 Phe Asn He Gin Val 32 0 Arg Gly Val Thr Gin 325 Asn Asp Gly Thr Thr 330 Thr lie Ala Asn Asn 335 Leu Thr Ser Thr Val 340 Gin Val Phe Thr Asp 345 Ser Glu Tyr Gin Leu Pro 350 Tyr Val Leu Gly 355 Ser Ala His Gin Gly 3 60 Cys Leu Pro Pro Phe Pro Ala 365 Asp Val Ehe 370 Met Val Pro Gin Tyr 375 Gly Tyr Leu Thr Leu 38 0 Asn Asn Gly Ser Gin 385 Ala Val Gly Arg Ser 390 Ser Phe Tyr Cys Leu 395 Glu Tyr Phe Pro Ser 400 Gin Met Leu Arg Thr 405 Gly Asn Asn Ehe Gin 410 Phe Ser Tyr Thr Phe 415 Glu Asp Val Pro Ehe 420 His Ser Ser Tyr Ala 425 His Ser Gin Ser Leu Asp 430 Arg Leu Met Asn 435 Pro Leu He Asp Gin 440 Tyr Leu Tyr Tyr Leu Asn Arg 445 Thr Gin Gly Thr Thr Ser Gly Thr Thr Asn Gin Ser . Arg Leu Leu Ehe Ser

     450 455 460
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     Gin Ala Gly Pro Gin Ser Met Ser Leu Gin Ala Arg Asn Trp Leu Pro

     465 470 475_; 480

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     Gly Pro Cys Tyr Arg Gin Gin Arg Leu Ser Lys Thr Ala Asn Asp Asn 485 490 495

     Asn Asn Ser Asn Phe Pro Trp Thr Ala Ala Ser Lys Tyr His Leu Asn 500 505 510

     Gly Arg Asp Ser Leu Val Asn Pro Gly Pro Ala Met Ala Ser His Lys 515 520 525

     Asp Asp Glu Glu Lys Phe Phe Pro Met His Gly Asn Leu Ile Phe Gly 530 535 540

     Lys Glu Gly Thr Thr Ala Ser Asn Ala Glu Leu Asp Asn Val Met Ile 545 550 555 560

     Thr Asp Glu Glu Glu lie Arg Thr Thr Asn Pro Val Ala Thr Glu Gin 565 570 575

     Tyr Gly Thr Val Ala Asn Asn Leu Gin Ser Ser Asn Thr Ala Pro Thr 580 535 590

     Thr Gly Thr Val Asn His Gin Gly Ala Leu Pro Gly Met Val Trp Gin 595 600 605

     Asp Arg Asp Val Tyr Leu Gin Gly Pro lie Tip Ala Lys Ile Pro His 610 615 620

     Thr Asp Gly His phe His Pro Ser Pro Leu Met Gly Gly phe Gly Leu 625 630 635 ' 640

     Lys His Pro Pro Pro Gin lie Met lie Lys Asn Thr Pro Val Pro Ala 645 650 655

     Asn Pro Pro Thr Thr Phe Ser Pro Ala Lys Phe Ala Ser Phe Ile Thr 660 665 670

     Gin Tyr Ser Thr Gly Gin Val Ser Val Glu Ile Glu Trp Glu Leu Gin 675 680 685

     Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gin Tyr Thr Ser Asn 690 695 700

     Tyr Asn Lys Ser Val Asn Val Asp Phe Thr Val Asp Thr Asn Gly Val 705 710 715 720
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     Tyr Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Asn Leu 725 730 735 <210> 72 <211> 737 <212> PRT <213> capsid protein of AAV serotype, clone 3.3bVPl <400> 72

     Met 1 Ala Ala Asp Gly 5 Tyr Leu Pro Asp Trp 10 Leu Glu Asp Asn Leu 15 Ser Glu Gly lie Arg 20 Glu Trp Trp Asp Leu 25 Lys Pro Gly Ala Pro 30 Lys Pro Lys Ala Asn 35 Gln Gln Lys Gln Asp 40 Asn Gly Arg Gly Leu 45 Val Leu Pro Gly Tyr 50 Lys Tyr Leu Gly Pro 55 Phe Asn Gly Leu Asp 60 Lys Gly Glu Pro Val 65 Asn Ala Ala Asp Ala 70 Ala Ala Leu Glu His 75 Asp Lys Ala Tyr Asp 80 Gln Gln Leu Asn Ala 85 Gly Asp Asn Pro Tyr 90 Leu Arg Tyr Asn His 95 Ala Asp Ala Glu Phe 100 Gln Glu Arg Leu Gln 105 Glu Asp Thr Ser Phe 110 Gly siy Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro

     115 120 125

     Leu Gly 130 Leu Val Glu Glu Gly 135 Ala Lys Thr Ala Pro 140 Ala Lys Lys Arg Pro 145 Val Glu Pro Ser Pro 150 Gln Arg Ser Pro Asp 155 ser Ser Thr Gly Ile 160 Gly Lys Lys Gly Gln 165 Gln Pro Ala Arg Lys 170 Arg Leu Asn Phe Gly 175 Gln Thr Gly Asp Ser 180 Glu Ser Val Pro Asp 185 Pro Gln Pro Leu Gly 190 Glu Pro pro Ala Ala 195 Pro Ser Ser Val Gly 200 Ser Gly Thr Val Ala 205 Ala Gly Gly
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     Gly Ala 210 Pro Met Ala Asp Asn 215 Asn Glu Gly Ala Asp 220 , Gly Val . Gly ' Asn Ala 225 Ser Gly Asn Trp His 2 30 Cys Asp Ser Thr Trp 235 Leu Gly ' Asp Arg Val 240 Ile Thr Thr Ser Thr 245 Arg Thr Trp Ala Leu 250 Pro Thr Tyr Asn Asn 255 His Leu Tyr Glu Gin 260 Ile Ser Ser Glu Thr 265 Ala Gly Ser Thr Asn 270 Asp Asn Thr Tyr Phe 275 Gly Tyr Ser Thr Pro 280 Trp Gly Tyr Phe Asp 285 Phe Asn Arg Phe His 290 Cys His Phe Ser Pro 295 Arg Asp Trp Gin Arg 300 Leu Ile Asn Asn Asn 305 Trp Gly Phe Arg Pro 310 Lys Lys Leu Arg Phe 315 Lys Leu Phe Asn Ile 320 Gin Val Lys Glu Val 325 Thr Thr Asn Asp Gly 330 Val Thr Thr Ile Ala 335 Asn Asn Leu Thr Ser 340 Thr Ile Gin Val Phe 345 Ser Asp Ser Glu Tyr 350 Gin Leu Pro Tyr Val 355 Leu Gly Ser Ala His 360 Gin Gly Cys Leu Pro 365 Pro Phe Pro Ala Asp 370 Val Phe Met Ile Pro 375 Gin Tyr Gly Tyr Leu 380 Thr Leu Asn Asn Gly 385 Ser Gin Ser Val Gly Arg 390 Ser Ser Phe Tyr 395 Cys Leu Glu Tyr Phe 400 Pro Ser Gin Met Leu 405 Arg Thr Gly Asn Asn 410 Phe Glu Phe Ser Tyr 415 Ser Phe Glu Asp Val 420 Pro Phe His Ser Ser 425 Tyr Ala His Ser Gin 430 Ser Leu Asp Arg Leu 435 Met Asn Pro Leu Ile 440 Asp Gin Tyr Leu Tyr 445 Tyr Leu Ala Arg Thr Gin Ser Asp Pro Gly Gly Thr Ala Gly . Asn . Arg Glu Leu Gin

     450 455 460
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     Asn Phe 705

     Phe Tyr 4 65

     Leu Pro

     Gin Asn

     Leu Asn.

     His Lys 530

     Phe Gly 545

     Met Thr

     Glu Tyr

     Gin Thr

     Gin Asn 610

     His Thr 625

     Leu Lys

     Ala Asn

     Thr Gin

     Gin Lys 690

     Gin Gly Gly Pro 470 ι Ser Thr Met Ala 1 Glu Gin Ala 475 i Lys i Asn Trp 480 Gly Pro Cys 485 Phe Arg Gin Gin Arg 490 Val Ser Lys Thr Leu Asp 4 95 Asn Asn 500 Ser Asn Phe Ala Trp Thr 505 1 Gly Ala Thr Lys 510 Tyr His Gly 515 Arg Asn Ser Leu val 520 Asn Pro Gly Val Ala 525 Met Ala Thr Asp Asp Glu Asp Arg 535 Phe Phe Pro Ser Ser Gly 540 Val Leu Ile Lys Thr Gly Ala 550 Thr Asn Lys Thr Thr 555 Leu Glu Asn Val Leu 560 Asn Glu Glu 565 Glu Ile Arg Pro Thr 570 Asn Pro Val Ala Thr 575 Glu Gly Ile 580 Val Ser Ser Asn Leu Gin 585 Ala Ala Asn Thr 590 Ala Ala Gin 595 Val Val Asn Asn Gin 600 Gly Ala Leu Pro Gly 605 Met Val Trp Arg Asp Val Tyr Leu 615 Gin Gly Ero lie Trp Ala 620 Lys Ile Pro Asp Gly Asn Phe 630 His Pro Ser Pro Leu 635 Met Gly Gly Phe Gly 640 His Pro Pro 645 Pro Gin lie Leu lie 650 Lys Asn Thr Pro Val 655 Pro Pro Pro 660 Glu Val Phe Thr Pro Ala 665 Lys Phe Ala Ser 670 Phe Ile Tyr 675 Ser Thr Gly Gin Val 680 Ser Val Glu Ile Glu 685 Trp Glu Leu Glu Asn Ser Lys Arg 695 Trp Asp Pro Glu Ile Gin 700 Tyr Thr Ser Glu Lys Gin Thr Gly Val . Asp Phe . Ala ' Val Asp Ser Gin Gly

     710 715 720
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     Val Tyr Ser Glu Pro Arg Pro lie Gly Thr Arg Tyr Leu Thr Arg Asn 725 730 735

     Leu <210> 73 <211> 644 <212> PRT <213> capsid protein of AAV serotype, clone 223-4 <400> 73

     Lys 1 Ala Tyr Asp Gin 5 Gin Leu Lys Ala Gly 10 ASp Asn Ero Tyr Leu 15 Arg Tyr Asn His Ala 20 ASp Ala GlU Phe Gin 25 Glu Arg Leu Gin Glu 30 Asp Thr Ser Phe Gly 35 Gly Asn Leu Gly Arg 40 Ala Val Phe Gin Ala 45 Lys Lys Arg Val Leu 50 Glu Pro Leu Gly Leu 55 Val Glu Thr Pro Ala 60 Lys Thr Ala pro Gly 65 Lys Lys Arg Pro Val 70 Asp Ser Pro Asp Ser 75 Thr Ser Gly lie Gly 80 Lys Lys Gly Gin Gin 85 pro Ala Lys Lys Arg 90 Leu Asn Phe Gly Gin 95 Thr Gly Asp Ser Glu 100 Pro Val Pro ASp Pro 105 Gin Pro lie Gly Glu 110 Pro Pro Ala Gly Pro 115 Ser Gly Leu Gly Ser 120 Gly Thr Met Ala Ala 125 Gly Gly Gly Ala Pro 130 Met Ala Asp Asn Asn 135 Glu Gly Ala Asp Gly 140 Val Gly Asn Ala Ser 145 Gly Asn Trp His Cys 150 Asp Ser Thr Arg Leu 155 Gly Asp Arg Val He 160 Thr Thr Ser Thr Arg 165 Thr Trp Ala Leu Pro 170 Thr Tyr Asn Asn His 175 Leu Tyr Lys Gin lie 180 Ser Ser Gin Ser Ala 185 Gly Ser Thr Asn Asp 190 Asn Val Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe

     195 200 205
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     His Cys His Phe Ser Pro Arg Asp Trp Gin Arg leu He Asn Asn Asn 210 215 220

     Trp Gly Phe Arg Pro lys lys leu Asn Phe lys leu Phe Asn lie Gin 225 230 235 240

     Val Lys Glu Val Thr Thr Asn Asp Gly Val Thr Thr He Ala Asn Asn 245 250 255

     Leu Thr Ser Thr Val Gin Val Phe Ser Asp Ser Glu Tyr Gin Leu Pro 260 265 270

     Tyr Val Leu Gly Ser Ala His Gin Gly Cys Leu Pro Pro Phe Pro Ala 275 280 285

     Asp Val Phe Met He Pro Gin Tyr Gly Tyr Leu Thr Leu Asn Asn Gly 290 295 300

     Ser Gin Ser Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro 305 310 315 320

     Ser Gin Met Leu Arg Thr Gly Asn Asn Phe Thr Phe ser Tyr Thr Phe 325 330 335

     Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gin Ser Leu Gly 340 345 350

     Arg Leu Met Asn Pro Leu He Asp Gin Tyr Leu Tyr Tyr Leu Ala Arg 355 360 365

     Thr Gin Ser Asn Ala Gly Gly Thr Ala Gly Asn Arg Glu Leu Gin Phe 370 375 380

     Tyr Gin Gly Gly Pro Thr Thr Met Ala Glu Gin Ala lys Asn Trp Leu 385 390 395 400

     Pro Gly Pro cys Phe Arg Gin Gin Arg Val Ser Lys Thr Leu Asp Gin 405 410 415

     Asn Asn Asn Ser Asn Phe Ala Trp Thr Gly Ala Thr Lys Tyr His Leu 420 425 430

     Asn Gly Arg Asn Ser Leu Val Asn Pro Gly Val Ala Met Ala Thr His 435 440 445

     Lys Asp Asp Glu Glu Arg Phe Phe Pro Ser Ser Gly Val Leu He Phe 450 455 460
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     Gly Lys Thr Gly Ala Ala Asn Lys Thr Thr Leu Glu Asn Val Leu Met 465 470 475 480

     Thr Asn Glu Glu Glu Ile Arg Pro Thr Asn Pro Val Ala Thr Glu Glu 485 490 495

     Tyr Gly Ile Val Ser Ser Asn Leu Gin Ala Ala Ser Thr Ala Ala Gin 500 505 510

     Thr Gin Val Val Asn Asn Gin Gly Ala Leu Pro Gly Met Val Trp Gin 515 520 525 Asn Arg Asp 530 Val Tyr Leu Gin Gly Pro 535 Ile Trp Ala Lys lie Pro His 540 Thr 545 Asp Gly Asn Phe His Pro Ser Pro 550 Leu Met Gly Gly Phe Gly Leu 555 560 Lys His Pro Pro Pro Gin Ile Leu lie 565 Lys Asn Thr Pro Val Pro Ala 570 575 Asn Pro Pro Glu Val Phe Thr Pro Ala 580 585 Lys phe Ala Ser Phe lie Thr 590 Gin Tyr Ser 595 Thr Gly Gin Val Ser Val 600 Glu Ile Glu Trp Glu Leu Gin 605 Lys Glu Asn 610 Ser Lys Arg Trp Asn Pro 615 Glu lie Gin Tyr Thr Ser Asn 620 Phe Asp Lys Gin Thr Gly Val Asp Phe Ala Val Asp Ser Gin Gly Val 625 630 635 640 Tyr Ser Glu Pro <210> 74 <211> 644 <212> PRT <213> capsid protein of AAV serotype, clone 223.5 <400> 74 Lys 1 Ala Tyr Asp Gin Gin Leu Lys Ala 5 Gly Asp Asn Pro Tyr Leu Arg 10 15 Tyr Asn His Ala Asp Ala Glu Phe Gin 20 25 Glu Arg Leu Gin Glu Asp Thr 30 Ser Phe Gly 35 Gly Asn Leu Gly Arg Ala 40 Val Phe Gin Ala Lys Lys Arg 45
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     Val leu Glu Pro leu Gly leu Val Glu Thr Pro Ala Lys Thr Ala Pro

     50 55 60

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     Gly Lys Lys Arg Pro Val Asp Ser Pro Asp Ser Thr Ser Gly Ile Gly 65 70 75 80 lys lys Gly Gln Gln Pro Ala lys Lys Arg Leu Asn Phe Gly Gln Thr 85 90 95

     Gly Asp Ser Glu Pro Val Pro Asp Pro Gln Pro lie Gly Glu Pro Pro 100 105 110

     Ala Gly Pro Ser Gly leu Gly Ser Gly Thr Met Ala Ala Gly Gly Gly 115 120 125

     Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn Ala 130 135 140

     Ser Gly Asn Trp His Cys Asp Ser Thr Arg leu Gly Asp Arg Val Ile 145 150 155 160

     Thr Thr ser Thr Arg Thr Trp Ala leu Pro Thr Tyr A3n Asn His Leu 165 170 175

     Tyr Lys Gln lie ser Ser Gln Ser Ala Gly Ser Thr Asn Asp Asn Val 180 185 190

     Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe 195 200 205

     His cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn Asn 210 215 220 '

     Trp Gly Phe Arg Pro lys Lys Leu Asn Phe Lys Leu Phe Asn Ile Gln 225 230 235 240

     Val lys Glu Val Thr Thr Asn Asp Gly Val Thr Thr lie Ala Asn Asn 245 250 255

     Leu Thr Ser Thr Val Gln Val Phe Ser Asp Ser Glu Tyr Gln leu Pro 260 265 270

     Tyr Val leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro Ala 275 280 285

     Asp Val Phe Met lie Pro Gln Tyr Gly Tyr leu Thr Leu Asn Asn Gly 290 295 300
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     Ser 305 Gin Ser Val Gly Arg 310 Ser Ser Phe Tyr Cys 315 Leu Glu i Tyr Phe i Pro 320 Ser Gin Met Leu Arg 325 Thr Gly Asn Asn Phe 330 Thr Phe Ser Tyr Thr 335 Phe Glu Asp Val Pro 340 Phe His ser Ser Tyr 345 Ala His Ser Gin Ser 350 Leu Gly Arg Leu Met 355 Asn Pro Leu He Asp 360 Gin Tyr Leu Tyr Tyr 365 Leu Ala Arg Thr Gin 370 Ser Asn Ala Gly Gly 375 Thr Ala Gly Asn Arg 380 GlU Leu Gin Phe Tyr 385 Gin Gly Gly Pro Thr 390 Thr Met Ala Glu Gin 395 Ala Lys Asn Trp Leu 400 Pro Gly pro Cys Phe 405 Arg Gin Gin Arg Val 410 Ser Lys Thr Leu Asp 415 Gin Asn. A3n Asn Ser 420 Asn Phe Ala Trp Thr 425 Gly Ala Thr Lys Tyr 430 His Leu Asn Gly Arg 435 Asn Ser Leu Val Asn 440 Pro Gly Val Ala Met 445 Ala Thr His Lys Asp 450 Asp Glu GlU Arg Phe 455 Phe Pro Ser Ser Gly 460 Val Leu lie Phe Gly 4 05 Lys Thr Gly Ala Ala 470 Asn Lys Thr Thr Leu 475 Glu Asn Val Leu Met 480 Thr Asn Glu Glu Glu 485 lie Arg Pro Thr Asn 490 Pro Val Ala Thr Glu 495 Glu Tyr Gly lie Val 500 Ser Ser Asn Leu Gin 505 Ala Ala Ser Thr Ala 510 Ala Gin Thr Gin Val 515 Val Asn Asn Gin Gly 520 Ala Leu Pro Gly Met 525 Val Trp Gin Asn Arg 530 Asp Val Tyr Leu Gin 535 Gly Pro He Trp Ala 540 Lys He Pro His Thr 545 Asp Gly Asn Phe His 550 Pro Ser Pro Leu Met 555 Gly Gly Phe Gly Leu 560
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     Lys His Pro Pro Pro Gin lie Leu lie Lys Asn Thr Pro Val Pro Ala 565 570 575

     Asn Pro Pro Glu Val Phe Thr Pro Ala Lys Phe Ala Ser Phe He Thr 580 585 590

     Gin Tyr Ser Thr Gly Gin Val Ser Val Glu He Glu Trp Glu Leu Gin 595 600 605 lys Glu Asn Ser Lys Arg Trp Asn Pro Glu lie Gin Tyr Thr Ser Asn 610 615 620

     Phe Asp Lys Gin Thr Gly Val Asp Phe Ala Val Asp Ser Gin Gly Val 625 630 635 640

     Tyr Ser Glu Pro <210> 75 <211> 644 <212> PRT <213> capsid protein of AAV s <220>

     <221> MISC_FEATURB <222> (434) . .(434) <223> can be any amino acid <400> 75 erotype, clone 223.10

     Lys 1 Ala Tyr Asp Gin 5 Gin Leu lys Tyr Asn His Ala 20 Asp Ala Glu Phe Ser Phe Gly 35 Gly Asn Leu Gly Arg 40 Val Leu 50 Glu Pro Leu Gly Leu 55 Val Gly 65 lys Lys Arg Pro Val 70 Asp Ser lys Lys Gly Gin Gin 85 Pro Ala Lys Gly Asp Ser Glu 100 Ser Val Pro Asp

     Ala Gly Asp Asn Pro Tyr Leu Arg 10 15

     Gin Glu Arg Leu Gin Glu Asp Thr 25 30

     Ala Val Phe Gin Ala Lys Lys Arg 45

     Glu Thr Pro Ala Lys Thr Ala Pro 60

     Pro Asp Ser Thr Ser Gly lie Gly 75 80

     Lys Arg Leu Asn Phe Gly Gin Thr 90 95

     Pro Gin Pro lie Gly Glu Pro Pro 105 110
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     Ala Gly Pro Ser Gly Leu Gly Ser Gly Thr Met Ala Ala Gly Gly Gly 115 120 125

     Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn Ala 130 135 140

     Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val lie 145 150 155 160

     Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu 165 170 175

     Tyr Lys Gin lie Ser Ser Gin Ser Ala Gly Ser Thr Asn Asp Asn Val 180 185 190

     Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe 195 200 205

     His Cys His Phe Ser Pro Arg Asp Trp Gin Arg Leu ile Asn Asn Asn 210 215 220

     Trp Gly Phe Arg Pro Lys Lys Leu Asn Phe Lys Leu Phe Asn lie Gin 225 230 235 240

     Val Lys Glu Val Thr Thr Asn Asp Gly Val Thr Thr lie Ala Asn Asn 245 250 255

     Leu Thr Ser Thr Val Gin Val Phe Ser Asp Ser Glu Tyr Gin Leu Pro 260 265 270

     Tyr Val Leu Gly Ser Ala His Gin Gly Cys Leu Pro Pro Phe Pro Ala 275 280 285

     Asp Val Phe Met Ila Pro Gin Tyr Gly Tyr Leu Thr Leu Asn Asn Gly 290 295 300

     Ser Gin Ser Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro 305 310 315 320

     Ser Gin Met Leu Arg Thr Gly Asn Asn Phe Thr Phe Ser Tyr Thr Phe 325 330 335

     Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gin Ser Leu Asp 340 345 350

     Arg Leu Met Asn Pro Leu Ile Asp Gin Tyr Leu Tyr Tyr Leu Ala Arg 355 360 365
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     Thr Gin 370 Ser Asn Ala Gly Gly 375 Thr Ala Gly Asn . Arg Glu 380 1 Leu . Gin i Phe Tyr 385 Gin Gly Gly Pro Thr 390 Thr Met Ala Glu . Gin 395 Ala Lys Asn Trp Leu 400 Pro Gly Pro Cys Phe 405 Arg Gin Gin Arg Val 410 Ser Lys Thr Leu Asp 415 Gin Asn Asn Asn Ser 420 Asn Phe Ala Trp Thr 425 Gly Ala Thr Lys Tyr 430 His Leu Asn Xaa Arg 435 Asn Ser Leu Val Asn 440 Pro Gly Val Ala Met 445 Ala Thr His Lys Asp 4 50 Asp Glu Glu Arg Phe 455 Phe Pro Ser Ser Gly Val 460 Leu Ile Phe Gly 465 Lys Thr Gly Ala Ala 470 Asn Lys Thr Thr Leu 475 Glu Asn Val Leu Met 480 Thr Asn Glu Glu Glu 485 Ile Arg Pro Thr Asn 490 Pro Val Ala Thr Glu 495 Glu Tyr Gly Ile Val 500 Ser Ser Asn Leu Gin 505 Ala Ala Ser Thr Ala 510 Ala Gin Thr Gin Val 515 Val Asn Asn Gin Gly 520 Ala Leu Pro Gly Met 525 Val Trp Gin Asn Arg 530 Asp Val Tyr Leu Gin 535 Gly Pro Ile Trp Ala Lys 540 Ile Pro His Thr 545 Asp Gly Asn Phe His 550 Pro Ser Pro Leu Met 555 Gly Gly Phe Gly Leu 560 Lys His Pro Pro Pro 565 Gin Ile Leu Ile Lys 570 Asn Thr pro Val Pro 575 Ala Asn Pro Pro Glu 580 Val Phe Thr Pro Ala 585 Lys Phe Ala Ser Phe 590 Ile Thr Gin Tyr Ser 595 Thr Gly Gin Val Ser 600 Val Glu Ile Glu Trp 605 Glu Leu Gin Lys Glu 610 Asn Ser Lys Arg Trp 615 Asn Pro Glu Ile Gin Tyr 620 Thr Ser . Asn
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     Phe Asp Lys Gin Thr Gly Val Asp Phe Ala Val Asp Ser Gin Gly Val

     625 630 635 640

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     Tyr Ser Glu Pro <210 76 <211> 644 <212> PRT <213> capsid protein of AAV serotype, clone 223.2

     <400 Lys Al a 1 76 Tyr Asp Gin Gin Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg 5 10 15 Tyr Asn His Ala Asp Ala Glu Phe Gin Glu Cys Leu Gin Glu Asp Thr 20 25 30 Ser Phe Gly Gly Asn Leu Gly Arg Ala Val Phe Gin Ala Lys Lys Arg 35 40 45 Val Leu Glu Pro Leu Gly leu Val Glu Thr Pro Ala Lys Thr Ala Pro 50 55 60 Gly Lys Lys Arg Pro Val Asp Sar Pro Asp Ser Thr Ser Gly He Gly 65 70 75 80 Lys Lys Gly Gin Gin Pro Ala lys lys Arg Leu Asn Phe Gly Gin Thr 85 90 95 Gly Asp Ser Glu Ser Val Pro Asp Pro Gin Pro lie Gly Glu Pro Pro 100 105 110 Ala Gly Pro Ser Gly Leu Gly Ser Gly Thr Met Val Ala Gly Gly Gly 115 120 125 Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn Ala 130 135 140 Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val lie 145 150 155 160 Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu 165 170 175 Tyr lys Gin lie Ser Ser Gin Ser Ala Gly Ser Thr Asn Asp Asn Val 180 185 190 Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe 195 200 205
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     His Cys His Phe Ser 210

     Trp Gly Phe Arg Pro 225

     Val Lys Glu Val Thr 245

     Leu Thr Ser Thr Val 260

     Tyr Val Leu Gly Ser 275

     Asp Val Phe Met Ile 290

     Ser Gln Ser Val Gly 305

     Ser Gln Met Leu Arg 325

     Glu Asp Val Pro Phe 340

     Arg Leu Met Asn Pro 355

     Thr Gln Ser Asn Ala 370

     Tyr Gln Gly Gly Pro 385

     Pro Gly Pro Cys Phe 405

     Asn Asn Asn Ser Asn 420

     Asn Gly Arg Asn Ser 435

     Lys Asp Asp Glu Glu 450

     Pro Arg Asp Trp Gln Arg 215

     Lys Lys Leu Asn Phe Lys 230 235

     Thr Asn Asp Gly Val 250

     Gln Val Phe Ser Asp 2 65

     Ala His Gln Gly Cys 280

     Pro Gln Tyr Gly Tyr 295

     Arg Ser Ser Phe Tyr 310 '

     Thr Gly Asn Asn Phe 330

     His Ser Ser Tyr Ala 345

     Leu Ile Asp Gln Tyr 360

     Gly Gly Thr Ala Gly 375

     Thr Thr Met Ala Glu 390

     Arg Gln Gln Arg Val 410

     Phe Ala Trp Thr Gly 425

     Leu Val Asn Pro Gly 440

     Arg Phe Ser Pro Ser 455

     Leu Ile Asn Asn Asn 220

     Leu Phe Asn lie Gln 240

     Thr Thr Ile Ala Asn Asn 255

     Ser Glu Tyr Gln Leu Pro 270

     Leu Pro Pro Phe Pro Ala 285

     Leu Thr Leu Asn Asn Gly 300

     Cys Leu Glu Tyr Phe Pro 315 320

     Thr Phe Ser Tyr Thr Phe 335

     His Ser Gln Ser Leu Asp 350

     Leu Tyr Tyr Leu Ala Arg 365

     Asn Arg Glu Leu Gln Phe 380

     Gln Ala Lys Asn Trp Leu 395 400

     Ser Lys Thr Leu Asp Gln 415

     Ala Thr Lys Tyr His Leu 430

     Val Ala Met Ala Thr His 445

     Ser Gly Val Leu Ile Phe 460
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     Gly Lys Thr Gly Ala Ala Asn Lys Thr Thr Leu Glu Asn Val Leu Met 465 470 475 480

     Thr Asn Glu Glu Glu Ile Arg Pro Thr Asn Pro Val Ala Thr Glu Glu 485 490 495

     Tyr Gly Ile Val Ser Ser Asn Leu Gln Ala Ala Ser Thr Ala Ala Gln 500 505 510

     Thr Gln Val Val Asn Asn Gln Gly Ala Leu Pro Gly Met Val Trp Gln 515 520 525

     Asn Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala lys Ile Pro His 530 535 540

     Thr Asp Gly Asn Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Leu 545 550 555 560

     Lys His Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val Pro Ala 565 570 575

     Asn Pro Pro Glu Val Phe Thr Pro Ala Lys Phe Ala Ser Phe Ils Thr 580 585 590

     Gln Tyr Ser Thr Gly Gln Val Ser Val Glu lie Glu Trp Glu Leu Gln 595 600 605

     Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr Ser Asn 610 615 620

     Phe Asp Lys Gln Thr Gly Val Asp Phe Ala Val Asp Ser Gln Gly Val 625 630 635 640

     Tyr Ser Glu Pro <2l0> 77 <211> 644 <212> PRT <213> capsid protein of AAV serotype, clone 223.7 <400> 77

     Lys Ala Tyr Asp Gln Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg 15 10 15

     Tyr Asn His Ala Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr 20 25 30
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     Ser Phe Gly Gly Asn Leu Gly Arg Ala Val Phe Gin Ala Lys Lys Arg 35 40 45

     Val leu Glu Pro Leu Gly Leu Val Glu Thr Pro Ala Lys Thr Ala Pro 50 55 60

     Gly Lys Lys Arg Pro Val Asp Ser Pro Asp Ser Thr Ser Gly Ile Gly 65 70 75 80

     Lys lys Gly Gin Gin Pro Ala Lys Lys Arg Leu Asn Phe Gly Gin Thr 85 90 95

     Gly Asp Ser Glu Ser Val Pro Asp Pro Gin Pro lie Gly Glu Pro Pro 100 105 110

     Ala Gly Pro Ser Gly Leu Gly Ser Gly Thr Met Ala Ala Gly Gly Gly 115 120 125

     Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn Ala 130 135 140

     Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val Ile 145 150 155 160

     Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu 165 170 175

     Tyr Lys Gin lie Ser Ser Gin Ser Ala Gly Ser Thr Asn Asp Asn Val 180 185 190

     Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe 195 200 205

     His Cys His Phe Ser Pro Arg Asp Trp Gin Arg Leu Ile Asn Asn Asn 210 215 220

     Trp Gly Phe Arg Pro Lys Lys Leu Asn Phe lys leu Phe Asn lie Gin 225 230 235 240

     Val lys Glu Val Thr Thr Asn Asp Gly Val Thr Thr lie Ala Asn Asn 245 250 255 leu Thr Ser Thr Val Gin Val Phe Ser Asp Pro Glu Tyr Gin leu Pro 260 265 270

     Tyr Val Leu Gly Ser Ala His Gin Gly Cys Leu Pro Pro Phe Pro Ala 275 280 285
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     Asp Val Phe Met Ile Pro Gin Tyr Gly Tyr Leu Thr Leu Asn Asn Gly 290 295 300

     Ser Gin Ser Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro 305 310 315 320

     Ser Gin Met Leu Arg Thr Gly Asn Asn Phe Thr Phe Ser Tyr Thr Phe 325 330 335

     Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gin Ser Leu Asp 340 345 350

     Arg Leu Met Asn Pro Leu He Asp Gin Tyr Leu Tyr Tyr Leu Ala Arg 355 360 365

     Thr Gin Ser Asn Ala Gly Gly Thr Ala Gly Asn Arg Glu Leu Gin Phe 370 375 380

     Tyr Gin Gly Gly Pro Thr Thr Met Ala Glu Gin Ala Lys Asn Trp Leu 385 390 395 400

     Pro Gly Pro Cys Phe Arg Gin Gin Arg Val Ser Lys Thr Leu Asp Gin 405 410 415

     Asn Asn Asn Ser Asn Phe Ala Trp Thr Gly Ala Thr Lys Tyr His Leu 420 425 430

     Asn Gly Arg Asn Ser Leu Val Asn Pro Gly Val Ala Met Ala Thr His 435 440 445

     Lys Asp Asp Glu Glu Arg Phe Phe Pro Ser Ser Gly Val Leu Ile Phe 450 455 460

     Gly Lys Thr Gly Ala Ala Asn Lys Thr Thr Leu Glu Asn Val Leu Met 465 470 475 480

     Thr Asn Glu Glu Glu lie Arg Pro Thr Asn Pro Val Ala Thr Glu Glu 485 490 495

     Tyr Gly Ile Val Ser ser Asn Leu Gin Ala Ala Ser Thr Ala Ala Gin 500 505 510

     Thr Gin Val Val Asn Asn Gin Gly Ala Leu Pro Gly Met Val Trp Gin 515 520 525

     Asn Arg Asp Val Tyr Leu Gin Gly Pro Ile Trp Ala Lys Ile Pro His 530 535 540
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     Thr Asp Gly Asn Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Leu 545 550 555 560

     Lys His Pro Pro Pro Gln Ile Leu lie Lys Asn Thr Pro Val Pro Ala 565 570 575

     Asn Pro Pro Glu Val Phe Thr Pro Ala Lys Ile Ala Ser Phe Ile Thr 580 585 590

     Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu Gln 595 600 605

     Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu lie Gln Tyr Thr Ser Asn 610 615 620

     Phe Asp Lys Gln Thr Gly Val Asp Phe Ala Val Asp Ser Gln Gly Val 625 630 635 640

     Tyr Ser Glu Pro <210> 78 <211> 644 <212> PRT <213> capsid protein of AAV <400> 78 irotype, clone 223.6

     Lys 1 Ala Tyr Asp Gln 5 Gln Leu Lys _Tyr Asn His Ala 20 Asp Ala Glu Phe Ser Phe Gly 35 Gly Asn Leu Gly Arg 40 Val Leu 50 Glu Pro Leu Gly Leu 55 Val Gly 65 Lys Lys Arg Pro Val 70 Asp Ser Lys Lys Gly Gln Gln 85 Pro Ala Lys Gly Asp Ser Glu 100 Ser Val Pro Asp Ala Gly Pro 115 Ser Gly Leu Gly Ser 120

     Ala Gly Asp Asn Pro Tyr Leu Arg 10 15

     Gln Glu Arg Leu Gln Glu Asp Thr 25 30

     Ala Val Phe Gln Ala Lys Lys Arg 45

     Glu Thr Pro Ala Lys Thr Ala Pro 60

     Pro Asp Ser Thr Ser Gly Ile Gly 75 80

     Lys Arg Leu Asn Phe Gly Gln Thr 90 95

     Pro Gln Pro Ile Gly Glu Pro pro 105 110

     Gly Thr Met Ala Ala Gly Gly Gly 125
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     Ala i Pro 130 Met Ala . Asp Asn Ser 135 Glu i Gly Ala . Asp Gly Val Gly Asn Ala 140 Ser 145 Gly Asn Trp His Cys 150 Asp Ser Thr Trp Leu Gly Asp 155 Arg Val He 160 Thr Thr Ser Thr Arg 165 Thr Trp Ala Leu Pro 170 Thr Tyr Asn Asn His Leu 175 Tyr Lys Gin lie 180 Ser . Ser Gin Ser Ala 185 Gly Ser Thr Asn Asp 190 Asn Val Tyr Phe Gly 195 Tyr Ser Thr Pro Trp 200 Gly Tyr Phe Asp Ehe 205 Asn Arg Phe His Cys 210 His Phe Ser Pro Arg 215 Asp Trp Gin Arg Leu He 220 Asn Asn Asn Trp 225 Gly Ehe Arg Pro Lys 230 Lys Leu Asn Phe Lys Leu Phe 235 Asn He Gin 240 Val Lys Glu Val Thr 245 Thr Asn Asp Gly Val 2 50 Thr Thr lie Ala Asn Asn 255 Leu Thr Ser Thr 260 Val Gin Val Phe Ser 2 65 Asp Ser Glu Tyr Gin 270 Leu Pro Tyr Val Leu 275 Gly Ser Ala His Gin 280 Gly Cys Leu Pro Pro 285 Ehe Pro Ala Asp Val 230 Phe Met He Pro Gin 235 Tyr Gly Tyr Leu Thr Leu 300 Asn Asn Gly Ser 305 Gin Ser Val Gly Arg 310 Ser Ser Phe Tyr Cys Leu Glu 315 Tyr Phe Pro 320 Ser Gin Met Leu Arg 325 Thr Gly Asn Asn Phe 330 Thr Ehe Ser Tyr Thr Phe 335 Glu Asp Val Pro 340 Ehe His Ser Ser Tyr 345 Ala His Ser Gin Ser 350 Leu Asp Arg Leu Met 355 Asn Pro Leu He Asp 360 Gin Tyr Leu Tyr Tyr 365 Leu . Ala Arg Thr Gin 370 Ser Asn Ala Gly Gly 375 Thr . Ala Gly . Asn Arg Glu 380 Leu Gin Phe
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     Gly Gly Pro Thr Thr Met Ala Glu Gin Ala Lys Asn Trp Leu

     390 395 400

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     Tyr Gin 385

     Pro Gly

     Asn Asn

     Asn Gly

     Lys Asp 450

     Gly Lys 465

     Thr Asn

     Tyr Gly

     Thr Gin

     Asn Arg 530

     Thr Asp 545

     Lys His

     Asn Pro

     Gin Tyr

     Lys Glu 610

     Pro Cys Phe Arg Gin Gin Arg Val Ser Lys Thr Leu Asp Gin 405 410 415

     Asn Ser Asn Phe Ala Trp Thr Gly Ala Thr Lys Tyr His Leu 420 425 430

     Arg Asn Ser Leu Val Asn Pro Gly Val Ala Met Ala Thr His 435 440 445

     Asp Glu Glu Arg Phe Phe Pro Ser Ser Gly Val Leu lie Phe 455 460

     Thr Gly Ala Ala Asn Lys Thr Thr Leu Glu Asn Val Leu Met 470 475 480

     Glu Glu Glu lie Arg Pro Thr Asn Pro Val Ala Thr Glu Glu 485 490 495

     He Val Ser Ser Asn Leu Gin Ala Ala Ser Thr Ala Ala Gin 500 505 510

     Val Val Asn Asn Gin Gly Ala Leu Pro Gly Met Val Trp Gin 515 520 525

     Asp Val Tyr Leu Gin Gly Pro lie Trp Ala Lys lie Pro His 535 540

     Gly Asn Phe His Pro Ser Pro Leu Met Gly Gly phe Gly Leu 550 555 560

     Pro Pro Pro Gin lie Leu lie Lys Asn Thr Pro Val Pro Ala 565 570 575

     Pro Glu Val Phe Thr Pro Ala Lys Leu Ala Ser Phe lie Thr 580 585 590

     Ser Thr Gly Gin Val Ser Val Glu lie Glu Trp Glu Leu Gin 595 600 605

     Asn Ser Lys Arg Trp Asn Pro Glu lie Gin Tyr Thr Ser Asn 615 620

     Lys Gin Thr Gly Val Asp Phe Ala Val Asp Ser Gin Gly Val 630 635 640

     Phe Asp

     625
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     Tyr Sei : Glu Pro <210> 79 <211> 738 <212> PRT <213> capsid protein of AAV serotype, clone 44.1 <400> 79 Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 1 5 10 15 Glu Gly lie Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro 20 25 30 Lys Ala Asn Gln Gln Lys Gln Asp Asp Gly Arg Gly Leu Val Leu Pro 35 40 45 Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro 50 55 60 Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp 65 70 75 80 Gln Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala 85 90 95 Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr Ser Phe Gly Gly 100 105 110 Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro 115 120 125 leu Gly Leu Val Glu Glu Gly Ala Lys Thr Ala Ere Gly Lys Lys Arg 130 135 140 Pro Val Glu Pro Ser Pro Gln Arg Ser Pro Asp Ser Ser Thr Gly Ile 145 150 155 160 Gly Lys Lys Gly Gln Gln Pro Ala Lys Lys Arg Leu Asn Phe Gly Gln 165 170 175 Thr Gly Asp Ser Glu Ser Val Pro Asp Pro Gln Pro Ile Gly Glu Pro 180 185 190 Pro Ala Gly Pro Ser Gly Leu Gly Ser Gly Thr Met Ala Ala Gly Gly

     195 200 205
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     Gly Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Ser 210 215 220

     Ser Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val 225 230 235 240

     Ile Thr- Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His 245 250 255

     Leu Tyr Lys Gln Xie Ser Asn Gly Thr Ser Gly Gly Ser Thr Asn Asp 260 265 270

     Asn Thr Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn 275 280 285

     Arg Phe His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn 290 295 300

     Asn Asn Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn 305 310 . 315 320

     Ile Gln Val Lys Glu Val Thr Gln Asn Glu Gly Thr Lys Thr Ile Ala 325 330 335

     Asn Asn Leu Thr Ser Thr Ile Gln Val Phe Thr Asp Ser Glu Tyr Gln 340 345 350 '

     Leu Pro Tyr Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe 355 360 365

     Pro Ala Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn 370 375 380

     Asn Gly Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr 385 390 395 400

     Phe Pro Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Glu Phe Ser Tyr 405 410 415

     Gln Phe Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser 420 425 430

     Leu Asp Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu 435 440 445

     Ser Arg Thr Gln Ser Thr Gly Gly Thr Ala Gly Thr Gln Gln Leu Leu 450 455 460
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     Phe Ser Gin Ala Gly Pro Asn Asn Met Ser Ala Gin Ala Lys Asn Trp 465 470 475 480

     Leu Pro Gly Pro Cys Tyr Arg Gin Gin Arg Val Ser Thr Thr Leu Ser 485 490 495

     Gin Asn Asn Asn Ser Asn Phe Ala Trp Thr Gly Ala Thr Lys Tyr His 500 505 510

     Leu Asn Gly Arg Asp Ser Leu Val Asn Pro Gly Val Ala Met Ala Thr 515 520 525

     His Lys Asp Asp Glu Glu Arg Phe Phe Pro Ser Ser Gly Val Leu Met 530 535 540

     Phe Gly Lys Gin Gly Ala Gly Lys Asp Asn Val Asp Tyr Ser Ser Val 545 550 555 560

     Met Leu Thr Ser Glu Glu Glu lie Lys Thr Thr Asn Pro Val Ala Thr 565 570 575

     Glu Gin Tyr Gly Val Val Ala Asp Asn Leu Gin Gin Gin Asn Ala Ala 580 585 590

     Pro lie Val Gly Ala Val Asn Ser Gin Gly Ala Leu Pro Gly Met Val 595 600 605

     Trp Gin Asn Arg Asp Val Tyr Leu Gin Gly Pro lie Trp Ala Lys Ile 610 615 620

     Pro His Thr Asp Gly Asn Phe His Pro Ser Pro Leu Met Gly Gly Phe 625 630 635 640

     Gly Leu Lys His Pro Pro Pro Gin lie Leu lie lys Asn Thr Pro Val 645 650 655

     Pro Ala Asp Pro Pro Thr Thr Phe Ser Gin Ala Lys Leu Ala ser Phe 660 665 670

     Ile Thr Gin Tyr Ser Thr Gly Gin Val Ser Val Glu lie Glu Trp Glu 675 680 685

     Leu Gin Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu lie Gin Tyr Thr 690 695 700

     Ser Asn Tyr Tyr Lys Ser Thr Asn Val Asp Phe Ala Val Asn Thr Asp 705 710 715 720
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     Gly Thr Tyr Ser Glu Pro Arg Pro lie Gly Thr Arg Tyr Leu Thr Arg 725 730 735

     Asn Leu <210> 80 <211> 738 <212> PRT <213> capsid protein of AAV serotype, clone 44,5 <400> 80

     Met 1 Ala Ala Asp Gly 5 Tyr Leu Pro Asp Trp 10 Leu Glu Asp Asn Leu 15 . Ser Glu Gly lie Arg 20 Glu Trp Trp Asp Leu 25 Lys Pro Gly Ala Pro 30 Lys Pro Lys Ala Asn 35 Gin Gin Lys Gin Asp 40 Asp Gly Arg Gly Leu 45 Val Leu Pro Gly Tyr 50 Lys Tyr Leu Gly Pro 55 Phe Asn Gly Leu Asp 60 Lys Gly Glu Pro Val 65 Asn Ala Ala Asp Ala 70 Ala Ala Leu Glu Kis 75 Asp Lys Ala Tyr Asp 80 Gin Gin Leu Lys Ala 85 Gly Asp Asn Pro Tyr 90 Leu Arg Tyr Asn His 95 Ala Asp Ala Glu Phe 100 Gin Glu Arg Leu Gin 105 Glu Asp Thr Ser Phe 110 Gly Gly Asn Leu Gly 115 Arg Ala Val Phe Gin 120 Ala Lys Lys Arg Val 125 Leu Glu Pro Leu Gly 130 Leu Val Glu Glu Gly 135 Ala Lys Thr Ala Pro 14 0 Gly Lys Lys Arg Pro 145 Val Glu Pro Ser Pro 150 Gin Arg Ser Pro Asp 155 Ser Ser Thr Gly lie 160 Gly Lys Lys Gly Gin 165 Gin Pro Ala Lys Lys 170 Arg Leu Asn Phe Gly 175 Gin Thr Gly Asp Ser 180 Glu Ser Val Pro Asp 185 Pro Gin Pro lie Gly 190 Glu Pro Pro Ala Gly 195 Pro Ser Gly Leu Gly 200 Ser Gly Thr Met Ala 205 Ala Gly Gly
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     Gly Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Ser 210 215 220

     Ser Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val 225 230 235 240 lie Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His 245 250 255

     Leu Tyr Lys Gin Ile Ser Asn Gly Thr Ser Gly Gly Ser Thr Asn Asp 260 265 270

     Asn Thr Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn 275 200 285

     Arg Phe His Cys His Phe Ser Pro Arg Asp Trp Gin Arg Leu lie Asn 290 , 295 300

     Asn Asn Trp Gly Phe Arg Pro Lys Arg Pro Asn Phe Lys Leu Phe Asn 305 310 315 320 lie Gin Val Lys Glu Val Thr Gin Asn Glu Gly Thr Lys Thr Ile Ala 325 330 335

     Asn Asn Leu Thr Ser Thr Ile Gin Val Phe Thr Asp Ser Glu Tyr Gin . 340 345 350

     Leu Pro Tyr Val Leu Gly Ser Ala His Gin Gly Cys Leu Pro Pro Phe 355 360 365

     Pro Ala Asp Val Phe Met lie Pro Gin Tyr Gly Tyr Leu Thr Leu Asn 370 375 380

     Asn Gly Ser Gin Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr 385 390 395 400

     Phe Pro Ser Gin Met Leu Arg Thr Gly Asn Asn Phe Glu Phe Ser Tyr 405 410 415

     Gin Phe Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gin Ser 420 425 430

     Leu Asp Arg Leu Met Asn Pro Leu Ile Asp Gin Tyr Leu Tyr Tyr Leu 435 440 445

     Ser Arg Thr Gin Ser Thr Gly Gly Thr Ala Gly Thr Gin Gin Leu Leu 450 455 460
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     Phe Ser Gin Ala Gly Pro Asn Asn Met Ser Ala Gin Ala Lys Asn Trp 465 470 475 480

     Leu Pro Gly Pro Cys Tyr Arg Gin Gin Arg Val Ser Thr Thr Leu Ser 485 490 495

     Gin Asn Asn Asn Ser Asn Phe Ala Trp Thr Gly Ala Thr Lys Tyr His 500 505 510

     Leu Asn Gly Arg Asp Ser Leu Val Asn Pro Gly Val Ala Met Ala Thr 515 520 525

     His Lys Asp Asp Glu Glu Arg Phe Phe Pro Ser Ser Gly Val Leu Met 530 535 540

     Phe Gly Lys Gin Gly Ala Gly Lys Asp Asn Val Asp Tyr Ser Ser Val 545 550 555 560

     Met Leu Thr Ser Glu Glu Glu Ile Lys Thr Thr Asn Pro Val Ala Thr 565 570 575

     Glu Gin Tyr Gly Val Val Ala Asp Asn Leu Gin Gin Gin Asn Ala Ala 580 585 590

     Pro Ile Val Gly Ala Val Asn Ser Gin Gly Ala Leu Pro Gly Met Val 595 600 605

     Tip Gin Asn Arg Asp Val Tyr Leu Gin Gly Pro Ile Trp Ala Lys Ile 610 615 620

     Pro His Thr Asp Gly Asn Phe His Pro Ser Pro Leu Met Gly Gly Phe 625 630 635 640

     Gly Leu Lys His Pro Pro Pro Gin Ile Leu Ile Lys Asn Thr Pro Val 645 650 655

     Pro Ala Asp Pro Pro Thr Thr Phe Ser Gin Ala Lys leu Ala Ser Phe 660 665 670

     Ile Thr Gin Tyr Ser Thr Gly Gin Val Ser Val Glu lie Glu Trp Glu 675 680 685

     Leu Gin Lys Glu Asn Ser lys Arg Trp Asn Pro Glu Ile Gin Tyr Thr 690 695 700

     Ser Asn Tyr Tyr Lys Ser Thr Asn Val Asp Phe Ala Val Asn Thr Asp 705 710 715 720
165. 165

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     Gly Thr Tyr Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr leu Thr Arg 725 730 735

     Asn Leu <210> 81 <211> 738 <212> PRT <213> capsid protein of AAV serotype, clone 44.2

     <400> 81 Met 1 Ala Ala Asp Gly 5 Tyr Leu Pro Asp Trp 10 leu Glu Asp Asn Leu Ser 15 Glu Gly lie Arg 20 Glu Trp Trp Asp Leu 25 Lys Pro Gly Ala Pro 30 Lys Pro Lys Ala Asn 35 Gln Gln Lys Gln Asp 40 Asp Gly Arg Gly Leu 45 Val Leu Pro Gly Tyr 50 lys Tyr Leu Gly Pro 55 Phe Asn Gly Leu Asp 60 Lys Gly Glu Pro Val 65 Asn Ala Ala Asp Ala 70 Ala Ala Leu Glu His 75 Asp Lys Ala Tyr Asp 80 Gln Gln Leu Lys Ala 85 Gly Asp Asn Pro Tyr SO Leu Arg Tyr Asn His Ala 95 Asp Ala Glu Phe 100 Gln Glu Arg Leu Gln 105 Glu Asp Thr Ser Phe 110 Gly Gly Asn Leu Gly 115 Arg Ala Val Phe Gln 120 Ala Lys Lys Arg Val 125 Leu Glu Pro Leu Gly 130 Leu Val Glu Glu Gly 135 Ala Lys Thr Ala Pro 140 Gly Lys Lys Arg Pro 145 Val Glu Pro Ser Pro 150 Gln Arg Ser Pro Asp 155 Ser Ser Thr Gly lie 160 Gly lys Lys Gly Gln 165 Gln Pro Ala Lys Lys 170 Arg Leu Asn Phe Gly Gln 175 Thr Gly Asp Ser 180 Glu Ser Val Pro Asp 185 Pro Gln Pro Ile Gly 190 Glu Pro Pro Ala Gly 195 Pro Ser Gly Leu Gly 200 Ser Gly Thr Met Ala 205 Ala Gly Gly
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     Gly Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Ser 210 215 220

     Ser Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val 225 230 235 240

     Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His 245 250 255

     Leu Tyr Lys Gin lie Ser Asn Gly Thr Ser Gly Gly Ser Thr Asn Asp 260 265 270

     Asn Thr Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn 275 280 285

     Arg Phe His Cys His Phe Ser Pro Arg Asp Trp Gin Arg Leu lie Asn 290 295 300

     Asn Asn Trp Gly Phe Arg Pro Lys Arg Leu Asn Ehe Lys Leu Phe Asn 305 310 315 320

     Ile Gin Val Lys Glu Val Thr Gin Asn Glu Gly Thr Lys Thr He Ala 325 330 335

     Asn Asn Leu Thr Ser Thr He Gin Val Phe Thr Asp Ser Glu Tyr Gin 340 345 350

     Leu Pro Tyr Val Leu Gly Ser Ala His Gin Gly Cys Leu Ero Pro Phe 355 360 365

     Pro Ala Asp Val Phe Met Ile Pro Gin Tyr Gly Tyr Leu Thr Leu Asn 370 375 380

     Asn Gly Ser Gin Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr 385 390 395 400

     Phe Pro Ser Gin Met Leu Arg Thr Gly Asn Asn Phe Glu Phe Ser Tyr 405 410 415

     Gin Phe Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gin Ser 420 425 430

     Leu Asp Arg Leu Met Asn Pro Leu He Asp Gin Tyr Leu Tyr Tyr Leu 435 440 445

     Ser Arg Thr Gin Ser Thr Gly Gly Thr Ala Gly Thr Gin Gin Leu Leu 450 455 460
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     Ehe Ser 465

     Leu Ero

     Gin Asn

     Leu Asn

     His Lys 530

     Ehe Gly 545

     Met Leu

     Glu Gin

     Pro lie

     Trp Gin 610

     Ero His 625

     Gly Leu

     Pro Ala

     He Thr

     Leu Gin 690

     Gin Ala Gly Pro Asn Asn Met Ser Ala Gin Ala Lys Asn Trp 470 475 480

     Gly Pro Cys Tyr Arg Gin Gin Arg Val Ser Thr Thr Leu Ser 485 490 495

     Asn Asn Ser Asn Ehe Ala Trp Thr Gly Ala Thr Lys Tyr His 500 505 510

     Gly Arg Asp Ser Leu Val Asn Pro Gly Val Ala Met Ala Thr 515 520 525

     Asp Asp Glu Glu Arg Ehe Phe Pro Ser Ser Gly Val Leu Met 535 540

     Lys Gin Gly Ala Gly Lys Asp Asn Val Asp Tyr Ser Ser Val 550 555 560

     Thr Ser Glu Glu Glu He Lys Thr Thr Asn Ero Val Ala Thr 565 570 575

     Tyr Gly Val Val Ala Asp Asn Leu Gin Gin Gin Asn Ala Ala 580 585 590

     Val Gly Ala Val Asn Ser Gin Gly Ala Leu Ero Gly Met Val 595 600 605

     Asn Arg Asp Val Tyr Leu Gin Gly Pro lie Trp Ala Lys He 615 620

     Thr Asp Gly Asn Phe His Pro Ser Ero Leu Met Gly Gly Phe 630 635 640

     Lys His Ero Pro Pro Gin lie Leu He Lys Asn Thr Pro Val 645 650 655

     Asp Pro Pro Thr Thr Phe Ser Gin Ala Lys Leu Ala Ser Phe 660 665 670

     Gin Tyr Ser Thr Gly Gin Val Ser Val Glu He Glu Trp Glu 675 680 685

     Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu lie Gin Tyr Thr 695 700

     Tyr Tyr Lys Ser Thr Asn Val Asp Phe Ala Val Asn Thr Asp 710 715 720

     Ser Asn

     705
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     Gly Thr Tyr Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg 725 730 735

     Asn Leu <210> 82 <211> 738 <212> PRT <213> capsid protein of AAV serotype, clone 29.3VP1 <400> 82

     Met 1 Ala Ala Asp Gly 5 Tyr Leu Pro Asp Trp 10 Leu Glu Asp Asn Leu 15 Ser Glu Gly lie Arg 20 Glu Trp Trp Ala Leu 25 Lys Pro Gly Ala Pro 30 Lys Pro lys Ala Asn 35 Gin Gin Lys Gin Asp 40 Asp Gly Arg Gly Leu 45 Val Leu Pro Gly Tyr 50 Lys Tyr Leu Gly Pro 55 Phe Asn Gly Leu Asp 60 Lys Gly Glu Pro Val 65 Asn Ala Ala Asp Ala 70 Ala Ala leu Glu His 75 Asp Lys Ala Tyr Asp 80 Gin Gin Leu Lys Ala 85 Gly Asp Asn Pro Tyr 90 Leu Arg Tyr Asn His S5 Ala Asp Ala Glu Phe 100 Gin Glu Arg Leu Gin 105 Glu Asp Thr Ser Phe 110 Gly Gly Asn Leu Gly 115 Arg Ala Val Phe Gin 120 Ala Lys Lys Arg Val 125 Leu Glu Pro Leu Gly 130 Leu Val Glu Glu Gly 135 Ala Lys Thr Ala Pro 140 Gly Lys Lys Arg Pro 145 Val Glu Pro Ser Pro 150 Gin Arg Ser Pro Asp 155 Ser Thr Thr Gly Ile 160 Gly Lys Lys Gly Gin 165 Gin Pro Ala Lys Lys 170 Arg Leu Asn Phe Gly 175 Gin Thr Giy Asp Ser 180 Glu Ser Val Pro Asp 185 Pro Gin Pro Ile Gly 190 Glu Pro Pro Ala Gly 195 Pro Ser Gly Leu Gly 200 Ser Gly Thr Met Ala 205 Ala Gly Gly
169. 169

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     Gly Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Ser 210 215 220

     Ser Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val 225 230 235 240

     Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His 245 250 255

     Leu Tyr Lys Gln lie Ser Asn Gly Thr Ser Gly Gly Ser Thr Asn Asp 260 265 270

     Asn Thr Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn 275 280 285

     Arg Phe His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu lie Asn 290 295 300

     Asn Asn Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn 305 310 315 320

     Ils Gln Val Lys Glu Val Thr Gln Asn Glu Gly Thr Lys Thr lie Ala 325 330 “ ' 335

     Asn Asn Leu Thr Ser Thr Ile Gln Val Phe Thr Asp Ser Glu Tyr Gln 340 345 350

     Leu Pro Tyr Val Leu Gly Ser Ala Arg Gln Gly Cys Leu Pro Pro Phe 355 360 365

     Pro Ala Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn 370 375 380

     Asn Gly Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr 385 390 395 400

     Phe Pro Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Glu Phe Ser Tyr 405 410 415

     Gln Phe Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser 420 425 430

     Leu Asp Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu 435 440 445

     Ser Arg Thr Gln Ser Thr Gly Gly Thr Ala Gly Thr Gln Gln Leu Leu 450 455 460
170. 170

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     Phe Ser 4 65

     Leu Pro

     Gln Asn

     Leu Asn

     His Lys 530

     Phe Gly 545

     Met Leu

     Glu Gln

     Pro Ile

     Trp Gln 610

     Pro His 625

     Gly Leu pro Ala

     Ile Thr

     Leu Gln 690

     Gln , Ala Gly Pro 470 Asn . Asn 1 Met Ser Ala 475 . Gln Ala Lys Asn Trp 480 Gly Pro Cys 485 Tyr Arg Gln . Gln Arg 490 Val Ser Thr Thr Leu Ser 495 Asn Asn 500 Ser Asn Phe Ala Trp 505 Thr Gly Ala Thr Lys 510 Tyr His Gly 515 Arg Asp Ser Leu Val 520 Asn Pro Gly Val Ala 525 Met Ala Thr Asp Asp Glu Glu Arg 535 Phe Phe Pro Ser Ser Gly 540 Val Leu Met Lys Gln Gly Ala 550 Gly Lys Gly Asn Val 555 Asp Tyr Ser Ser Val 560 Thr Ser Glu 565 Glu Glu Ile Lys Thr 570 Thr Asn Pro Val Ala Thr 575 Tyr Gly 580 Val Val Ala Asp Asn 585 Leu Gln Gln Gia Asn 590 Ala Ala Val 595 Gly Ala Val Asn Ser 600 Gln Gly Ala Leu Pro 605 Gly Met Val Asn Arg Asp Val Tyr 615 Leu Gln Gly Pro lie Trp 620 Ala Lys Ile Thr Asp Gly Asn 630 Phe His Pro Ser Pro 635 Leu Met Gly Gly Phe 640 Lys His Pro 645 Pro Pro Gln lie Leu 650 lie Lys Asn Thr Pro Val 655 Asp Pro 6 60 Pro Thr Thr Phe Ser 665 Gln Ala Lys Leu Ala 670 Ser Phe Gln 675 Tyr Ser Thr Gly Gln 680 Val Ser Val Glu lie 685 Glu Trp Glu Lys Glu Asn Ser Lys 695 Arg Trp , Asn Pro Glu lie 700 Gln Tyr Thr Tyr Tyr Lys Ser 710 Thr Asn Val . Asp Phe . 715 Ala Val Asn Thr Asp 720

     Ser Asn

     705
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     Gly Thr Tyr Ser Glu Pro Arg Pro lie Gly Thr Arg Tyr Leu Thr Arg

     725 730 735

     2015258271 20 Nov 2015

     Asn. Leu <210> 83 <211> 738 <212> PRT <213> capsid protein of AAV serotype, clone 29.5VP1 <400> 83

     Met 1 Ala Ala Asp Gly 5 Tyr Leu Pro Asp Trp 10 Leu Glu Asp Asn Leu 15 Ser Glu Gly He Arg 20 Glu Trp Trp Ala Leu 25 Lys Pro Gly Ala Pro 30 Lys Pro Lys Ala Asn 35 Gin Gin Lys Gin Asp 40 Asp Gly Arg Gly Leu 45 Val Leu Pro Gly Tyr 50 Lys Tyr Leu Gly Pro 55 Phe Asn Gly Leu Asp 60 Lys Gly Glu Pro Val 65 Asn Ala Ala Asp Ala 70 Ala Ala Leu Glu His 75 Asp Lys Ala Tyr Asp 80 Gin Gin Leu Lys Ala 85 Gly Asp Asn Pro Tyr 90 Leu Arg Tyr Asn His 95 Ala Asp Ala Glu Phe 100 Gin Glu Arg Leu Gin 105 Glu Asp Thr Ser Phe 110 Gly Gly Asn Leu Gly Arg 115 Ala Val Phe Gin 120 Ala Lys Lys Arg Val 125 Leu Glu Pro Leu Gly 130 Leu val Glu Glu Gly 135 Ala Lys Thr Ala Pro 140 Gly Lys Lys Arg Pro 145 Val Glu Pro Ser Pro 150 Gin Arg Ser Pro Asp 155 Ser Ser Thr Gly lie 160 Gly Lys Lys Gly Gin 165 Gin Pro Ala Lys Lys 170 Arg Leu Asn Phe Gly 175 Gin Thr Gly Asp Ser 180 Glu Ser val Pro Asp 185 Pro Gin Pro lie Gly 190 Glu Pro
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     Pro Ala Gly Pro Ser Gly Leu Gly Ser Gly Thr Met Ala Ala Gly Gly 195 200 205

     Gly Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Ser 210 215 220

     Ser Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Gly Val 225 230 235 240

     Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn. Asn His 245 250 255

     Leu Tyr Lys Gin Ile Ser Asn Gly Thr Ser Gly Gly Ser Thr Asn Asp 260 265 270

     Asn Thr Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn 275 280 285

     Arg Phe His Cys His Phe Ser Pro Arg Asp Trp Gin Arg Leu lie Asn 290 295 300

     Asn Asn Trp Gly Phe Arg Pro Lys Ser Leu Asn Phe Lys Leu Phe Asn 305 310 315 320 lie Gin Val Lys Glu Val Thr Gin Asn Glu Gly Thr Lys Thr Ile Ala 325 330 335

     Asn Asn Leu Thr Ser Thr Ile Gin Val Phe Thr Asp Ser Glu Tyr Gin 340 345 350

     Leu Pro Tyr Val Leu Gly Ser Ala His Gin Gly Cys Leu Pro Pro Phe 355 360 365

     Pro Ala Asp Val Phe Met lie Pro Gin Tyr Gly Tyr Leu Thr Leu Asn 370 375 380

     Asn Gly Ser Gin Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr 385 390 395 400

     Phe Pro Ser Gin Met Leu Arg Thr Gly Asn Asn Phe Glu Phe Ser Tyr 405 410 415

     Gin Phe Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gin Ser 420 425 430

     Leu Asp Arg Leu Met Asn Pro Leu lie Asp Gin Tyr Leu Tyr Tyr Leu 435 440 445
173. 173

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     Leu Gin 690

     Ser Arg 450

     Phe Ser 4 65

     Leu Pro

     Gin Asn

     Leu Asn

     His Lys 530

     Phe Gly 545

     Met Leu

     Glu Gin

     Pro lie

     Trp Gin 610

     Pro His 625

     Gly Leu

     Pro Ala lie Thr

     Thr Gin Ser Thr Gly 455 Gly Thr Ala Gly Thr Gin Gin 460 l Leu Leu Gin Ala Gly Pro 470 Asn Asn Met Ser Ala 475 Gin Ala . Lys Asn Trp 480 Gly Pro Cys 485 Tyr Arg Gin Gin Arg 490 Val Ser Thr Thr Leu Ser 495 Asp Asn 500 Ser Asn Phe Ala Trp 505 Thr Gly Ala Thr Lys 510 Tyr His Gly 515 Arg Asp Ser Leu Val 520 Asn Pro Gly val Ala 525 Met Ala Thr Asp Asp Glu Glu Arg 535 Phe Phe Pro Ser Ser 540 Gly Val Leu Met Lys Gin Gly Ala 550 Gly Lys Asp Asn Val 555 Asp Tyr Ser Ser Val 560 Thr Ser Glu 565 Glu Glu He Lys Thr 570 Thr Asn Pro Val Ala Thr 575 Tyr Gly 580 Val Val Ala Asp Asn 585 Leu Gin Gin Gin Asn 590 Ala Ala Val 595 Gly Ala Val Asn Ser 600 Gin Gly Ala Leu Pro 605 Gly Met Val Asn Arg Asp Val Tyr 615 Leu Gin Gly Pro lie 620 Trp Ala Lys lie Thr Asp Gly Asn 630 Phe His Pro Ser Pro 635 Leu Met Gly Gly Phe 640 Lys His Pro 645 Pro Pro Gin lie Leu 650 He Lys Asn Thr Pro Val 655 Asp Pro 660 Pro Thr Thr Phe Ser 665 Gin Ala Lys Leu Ala 670 Ser Phe Gin 675 Tyr Ser Thr Gly Gin 680 Val Ser Val Glu He 685 Glu Trp Glu Lys Glu Asn Ser Lys . Arg Trp . Asn Pro Glu lie Gin Tyr Thr

     695 700
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     Ser Asn Tyr Tyr Lys Ser Thr Asn Val Asp Phe Ala Val Asn Thr Asp 705 710 715 720

     Gly Thr Tyr Ser Glu Pro Arg Pro lie Gly Thr Arg Tyr Leu Thr Arg 725 730 735

     Asn Leu <210> 84 <211> 738 <212> PRT <213> capsid protein of AAV serotype, clone 42.15 <400> 84

     Met Ala 1 Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 15 5 10 Glu Gly lie Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Ero Lys pro 20 25 30 Lys Ala Asn Gin Gin Lys Gin Asp Asp Gly Arg Gly Leu Val Leu Pro 35 40 45 Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Fro 50 55 60 Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp 65 70 75 80 Gin Gin Leu Lys Ala Gly Asp Asn Ero Tyr Leu Arg Tyr Asn His Ala 85 90 95 Asp Ala Glu Phe Gin Glu Arg Leu Gin Glu Asp Thr Ser Ehe Gly Gly 100 105 110 Asn Leu Gly Arg Ala Val Ehe Gin Ala Lys Lys Arg Val Leu Glu Pro 115 120 125 Leu Gly Leu Val Glu Glu Gly Ala Lys Thr Ala Pro Gly Lys Lys Arg 130 135 140 Ero Val Glu Ero Ser Pro Gin Arg Ser Ero Asp Ser Ser Thr Gly Ile 145 150 155 160 Gly Lys Thr Gly Gin Gin Ero Ala Lys Lys Arg Leu Asn Phe Gly Gin 165 170 175 Thr Gly Asp Ser Glu Ser Val Pro Asp Pro Gin Pro lie Gly Glu Ero 180 185 190
175. 175

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     Pro Ala Gly 195 Pro Ser Gly Leu Gly 200 Ser Gly Thr Met ; Ala 205 Ala i Gly Gly Gly Ala 210 Pro Met Ala Asp Asn Asn 215 , Glu . Gly ' Ala . Asp 220 Gly Val , Gly Ser Ser 225 Ser Gly Asn Trp His 230 Cys Asp Ser Thr Trp 235 Leu Gly Asp Arg Val 240 Ile Thr Thr Ser Thr 245 Arg Thr Trp Ala Leu 250 Pro Thr Tyr Asn Asn His 255 Leu Tyr Lys Gln 260 lie Ser Asn Gly Thr 265 Ser Gly Gly Ser Thr 270 Asn Asp Asn. Thr Tyr 275 Phe Gly Tyr Ser Thr 280 Pro Trp Gly Tyr Phe 285 Asp Phe Asn Arg Phe 290 His Cys His Phe Ser Pro 295 Arg Asp Trp Gln 300 Arg Leu lie Asn Asn 305 Asn Trp Gly Phe Arg 310 Pro Lys Arg Leu Asn 315 Phe Lys Leu Phe Asn 320 lie Gln Val Lys Glu 325 Val Thr Gln Asn Glu 330 Gly Thr Lys Thr lie Ala 335 Asn Asn Leu Thr 340 Ser Thr Ile Gln Val 345 Phe Thr Asp Ser Glu 350 Tyr Gln Leu Pro Tyr 355 Val Leu Gly Ser Ala 3 60 His Gln Gly Cys Pro 365 Pro Pro Phe Pro Ala 370 Asp Val Phe Met lie Pro 375 Gln Tyr Gly Tyr 380 Leu Thr Leu Asn Asn 385 Gly Ser Gln Ala Val 390 Gly Arg Ser Ser Phe 395 Tyr Cys Leu Glu Tyr 400 Phe Pro Ser Gln Met 405 Arg Arg Thr Gly Asn 410 Asn Phe Glu Phe Ser Tyr 415 Gln Phe Glu Asp . 420 Val Pro Phe His Ser 425 Ser Tyr Ala His Ser 430 Gln Ser Leu Asp Arg Leu Met Asn Pro Leu Ile . Asp Gln Tyr Leu Tyr Tyr Leu

     435 440 445
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     Ser Arg Thr Gin Ser Thr Gly Gly Thr Ala Gly Thr Gin Gin Leu Leu

     450 455 460

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     Phe Ser Gin Ala Gly Pro Asn Asn Met Ser Ala Gin Ala Lys Asn Trp 465 470 475 480

     Leu Pro Gly Pro Cys Tyr Arg Gin Gin Arg Val Ser Thr Thr Leu Ser 485 490 495

     Gin Asn Asn Asn Ser Asn Phe Ala Trp Thr Gly Ala Thr Lys Tyr His 500 505 510

     Leu Asn Gly Arg Asp Ser Leu Val Asn Pro Gly Val Ala Met Ala Thr 515 520 525

     His Lys Asp Asp Glu Glu Arg Phe Phe Pro Ser Ser Gly Val Leu Met 530 535 540

     Phe Gly Lys Gin Gly Ala Gly Lys Asp Asn Val Asp Tyr Ser Ser Val 545 550 555 560

     Met Leu Thr Ser Glu Glu Glu lie Lys Thr Thr Asn Pro Val Ala Thr 565 570 575

     Glu Gin Tyr Gly Val Val Ala Asp Asn Leu Gin Gin Gin Asn Ala Ala 580 585 590

     Pro Ile Val Gly Ala Val Asn Ser Gin Gly Ala Leu Pro Gly Met Val 595 600 605

     Trp Gin Asn Arg Asp Val Tyr Leu Gin Gly Pro Ile Trp Ala Lys lie 610 615 620

     Pro His Thr Asp Gly Asn Phe His Pro ser Pro Leu Met Gly Gly Phe 625 630 635 640

     Gly Leu Lys His Pro Pre Pro Gin lie Leu lie Lys Asn Thr Pro Val 645 650 655

     Pro Ala Asp Pro Pro Thr Thr Phe Ser Gin Ala Lys Leu Ala ser Phe 660 665 670

     Ile Thr Gin Tyr Ser Thr Gly Gin Val Ser Val Glu lie Glu Trp Glu 675 680 685

     Leu Gin Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu lie Gin Tyr Thr 690 695 700
177. 177

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     Ser Asn Tyr Tyr Lys Ser Thr Asn Val Asp Phe Ala Val Asn Thr Glu

     705 710 715 720

     2015258271 20 Nov 2015

     Gly Thr Tyr Ser Glu Pro Arg Pro lie Gly Thr Arg Tyr Leu Thr Arg 725 730 735

     Asn Leu <210> 85 <211> 738 <212> PRT <213> capsid protein of AAV serotype, clone 42.8 <400> 85

     Met 1 Ala Ala Asp Gly 5 Tyr Leu Pro Asp Trp 10 Leu Glu Asp Asn Leu 15 Ser GlU sly lie Arg 20 Glu Trp Trp Asp Leu 25 Lys Pro Gly Ala Pro 30 Lys Pro Lys Ala Asn 35 Gin Gin Lys Gin Asp 40 Asp Gly Arg Gly Leu 45 Val Leu Pro Gly Tyr 50 Lys Tyr Leu Gly Pro 55 Phe Asn Gly Leu Asp 60 Lys Gly Glu Pro Val 65 Asn Ala Ala Asp Ala 70 Ala Ala Leu Glu His 75 Asp Lys Ala Tyr Asp 80 Gin Gin Leu Lys Ala 85 Gly Asp Asn Pro Tyr 90 Leu Arg Tyr Asn His 95 Ala Asp Ala Glu Phe 100 Gin Glu Arg Leu Gin 105 Glu Asp Thr Ser Phe 110 Gly Gly Asn Leu Gly 115 Arg Ala Val Phe Gin 120 Ala Lys Lys Arg Val 125 Leu Glu Pro Leu Gly 130 Leu Val Glu Glu Gly 135 Ala Lys Thr Ala Pro 140 Gly Lys Lys Arg Pro 145 Val Glu Pro Ser Pro 150 Gin Arg Ser Pro Asp 155 Ser Ser Thr Gly lie 160 Gly Lys Thr Gly Gin 165 Gin Pro Ala Lys Lys 170 Arg Leu Asn Phe Gly 175 Gin
178. 178

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     Thr Gly Asp Ser 180 Glu Ser Val Pro ' Asp 185 Pro , Gln . Pro , lie Gly 190 Glu Pro Pro Ala Gly 195 Pro Ser Gly Leu Gly 200 Ser Gly Thr Met Ala 205 Ala Gly Gly Gly Ala 210 Pro Met Ala Asp Asn 215 Asn Glu Gly Ala Asp 220 Gly Val Gly Ser Ser 225 Ser Gly Asn Trp His 230 Cys Asp Ser Thr Trp 235 Leu Gly Asp Arg Val 240 Ile Thr Thr Ser Thr 245 Arg Thr Trp Ala Leu 250 Pro Thr Tyr Asn Asn 255 His Leu Tyr Lys Gln 260 lie Ser Asn Gly Thr 265 Ser Gly Gly Ser Thr 270 Asn Asp Asn Thr Tyr 275 Phe Gly Tyr Ser Thr 260 Pro Trp Gly Tyr Phe 285 Asp Phe Asn Arg Phe 290 His Cys His Phe Ser 295 Pro Arg Asp Trp Gln 300 Arg Leu Ile Asn Asn 305 Asn Trp Gly Phe Arg 310 Pro Lys Arg Leu Asn 315 Phe Lys Leu Phe Asn 320 Ile Gln Val Lys Glu 325 Val Thr Gln Asn Glu 330 Gly Thr Lys Thr Ile 335 Ala Asn Asn Leu Thr 340 Ser Thr Ile Gln Val 345 Phe Thr Asp Ser Glu 350 Tyr Gln Leu Pro Tyr 355 Val Leu Gly Ser Ala 360 His Gln Gly Cys Leu 365 Pro Pro Phe Pro Ala 370 Asp Val Phe Met Ile 375 Pro Gln Tyr Gly Tyr 380 Leu Thr Leu Asn Asn 365 Gly Ser Gln Ala Val 390 Gly Arg Ser Ser Phe 395 Tyr Cys Leu Glu Tyr 400 Phe Pro Ser Gln Met 4 05 Leu Arg Thr Gly Asn 410 Asn Phe Glu Phe Ser 415 Tyr Gln Phe Glu Asp 420 Val Pro Phe His Ser 425 Ser Tyr Ala His Ser 430 Gln Ser
179. 179

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     Leu Asp Arg Leu Met 435 Asn Pro Leu Ile 440 ; Asp Gln Tyr Leu Tyr Tyr Leu 445 Ser Arg Thr Gln Ser 450 Thr Gly 455 Gly Thr Ala Gly Thr Gln Gln Leu Leu 460 Phe Ser Gln Ala Gly 465 Pro Asn 470 Asn Met Ser Ala Gln Ala Lys Asn Trp 475 480 Leu Pro Gly Pro Cys 485 Tyr Arg Gln Gln Arg val Ser Thr Thr Leu Ser 490 495 Gln Asn Asn Asn Ser 500 Asn Phe Ala Trp 505 Thr Gly Ala Thr Lys Tyr His 510 Leu Asn Gly Arg Asp 515 Ser Leu Val Asn 520 Pro Gly Val Ala Met Ala Thr 525 His Lys Asp Asp Glu 530 Glu Arg 535 Phe Phe Pro Ser Ser Gly Val Leu Met 540 Phe Gly Lys Gln Gly 545 Ala Gly 550 Lys Asp Asn val Asp Tyr Ser ser Val 555 560 Met leu Thr Ser Glu 565 Glu Glu lie Lys Thr Thr Asn Pro Val Ala Thr 570 575 Glu Gln Tyr Gly Val 580 Val Ala Asp Asn 585 Leu Gln Gln Gln Asn Ala Ala 590 Pro He Val Gly Ala 595 Val Asn ser Gln 600 Gly Ala Leu Pro Gly Met Val 605 Trp Gln Asn Arg Asp 610 Val Tyr 615 Leu Gln Gly Pro lie Trp Ala Lys Ile 620 Pro His Thr Asp Gly 625 Asn Phe 630 His Pro Ser Pro Leu Met Gly Gly Phe 635 640 Gly Leu Lys His Pro 645 Pro Pro Gln lie Leu lie Lys Asn Thr Pro Val 650 655 Pro Ala Asp Pro Pro 660 Thr Thr Phe Ser 665 Gln Ala Lys Leu Ala Ser Phe 670 lie Thr Gln Tyr Ser Thr Gly Gln Val Ser val Glu Ile Glu Trp Glu

     675 680 685
180. 180

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     Leu Gin Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu lie Gin Tyr Thr 690 695 700

     Ser Asn Tyr Tyr Lys Ser Thr Asn Val Asp Phe Ala Val Asn Thr Glu 705 710 715 720

     Gly Thr Tyr Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg 725 730 735

     Asn Leu <21O> 86 <211> 733 <212> PRT <213> amino acid of AAV serotype, clone 42.13 <400> 86

     Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 15 10 15

     Glu Gly Ile Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro 20 25 30

     Lys Ala Asn Gin Gin Lys Gin Asp Asp Gly Arg Gly Leu Val Leu Pro 35 40 45

     Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro

     50 55 60

     Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp lys Ala Tyr Asp 65 70 75 80

     Gin Gin Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala 85 90 95

     Asp Ala Glu Phe Gin Glu Arg Leu Gin Glu Asp Thr Ser Phe Gly Gly 100 105 110

     Asn Leu Gly Arg Ala Val Phe Gin Ala Lys Lys Arg Val Leu Glu Pro 115 120 125

     Leu Gly Leu Val Glu Glu Gly Ala Lys Thr Ala Pro Gly Lys Lys Arg 130 135 140

     Pro lie Glu Ser Pro Asp Ser Ser Thr Gly Ile Gly Lys Lys Gly Gin 145 150 155 160

     Gin Pro Ala Lys Lys Lys Leu Asn Phe Gly Gin Thr Gly Asp Ser Glu 165 170 175
181. 181

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     Ser Val Ero Asp 180 Pro Gin Pro Ile Gly 185 Glu Pro Ero Ala Gly 190 Pro Ser Gly Leu Gly 195 Ser Gly Thr Met Ala 200 Ala Gly Gly Gly Ala 205 Pro Met Ala Asp Asn 210 Asn Glu Gly Ala Asp 215 Gly Val Gly Ser Ser 220 Ser Gly Asn Trp His 225 Cys Asp Ser Thr Trp 230 Leu Gly Asp Arg Val 235 Ile Thr Thr Ser Thr 240 Arg Thr Trp Ala Leu 245 Pro Thr Tyr Asn Asn 250 His Leu Tyr Lys Gin 255 Ile Ser Asn Gly Thr 260 Ser Gly Gly Ser Thr 265 Asn Asp Asn Thr Tyr 270 Phe Gly Tyr Ser Thr 275 Pro Trp Gly Tyr Phe 280 Asp Phe Asn Arg Phe 285 His Cys His Phe Ser 290 Pro Arg Asp Trp Gin 2 95 Arg Leu Ile Asn Asn 300 Asn Trp Gly Phe Arg 305 Pro Lys Arg Leu Asn 310 Phe Lys Leu Phe Asn 315 lie Gin Val Lys Glu 320 Val Thr Gin Asn Glu 325 Gly Thr Lys Thr Ile 330 Ala Asn Asn Leu Thr 335 Ser Thr lie Gin Val 340 Phe Thr Asp Ser Glu 345 Tyr Gin Leu Pro Tyr 350 Val Leu Gly Ser Ala 355 His Gin Gly Cys Leu 360 Pro Pro Phe Pro Ala 365 Asp Val Phe Met lie 370 Pro Gin Tyr Gly Tyr 375 Leu Thr Leu Asn Asn 380 Gly Ser Gin Ala Val 385 Gly Arg Ser Ser Phe 390 Tyr Cys Leu Glu Tyr 395 Phe Pro Ser Gin Met 400 Leu Arg Thr Gly Asn 4 05 Asn Ehe Glu Phe Ser 410 Tyr Gin Phe Glu Asp 415 Val Pro Phe His Ser Ser Tyr Ala His Ser Gin Ser Leu Asp Arg Leu Met

     420 425 430
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     Asn Pro Leu Ile Asp Gin Tyr Leu Tyr Tyr Leu Ser Arg Thr Gin Ser 435 440 445

     Thr Gly Gly Thr Ala Gly Thr Gin Gin Leu Leu Phe Ser Gin Ala Gly 450 455 460

     Pro Asn Asn Met Ser Ala Gin Ala Lys Asn Trp Leu Pro Gly Pro Cys 465 470 475 480

     Tyr Arg Gin Gin Arg Val Ser Thr Thr Val Ser Gin Asn Asn Asn Ser 485 490 495

     Asn Phe Ala Trp Thr Gly Ala Thr Lys Tyr His Leu Asn Gly Arg Asp 500 505 510

     Ser Leu Val Asn Pro Gly Val Ala Met Ala Thr His Lys Gly Asp Glu 515 520 525

     Glu Arg Phe Phe Pro Ser Ser Gly Val Leu Met Phe Gly Lys Gin Gly 530 535 540

     Ala Gly Lys Asp Asn Val Asp Tyr Ser Ser Val Met leu Thr Ser Glu 545 550 555 560

     Glu Glu Ile Lys Thr Thr Asn Ero Val Ala Thr Glu Gin Tyr Gly Val 565 570 575

     Val Ala Asp Asn Leu Gin Gin Gin Asn Ala Ala Pro Ile Val Gly Ala 580 585 590

     Val Asn Ser Gin Gly Ala leu Ero Gly Met Val Trp Gin Asn Arg Asp 595 600 605

     Val Tyr leu Gin Gly Pro Ile Trp Ala Lys lie Pro His Thr Asp Gly 610 615 620

     Asn Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Leu Lys His Ero 625 630 635 640

     Pro Ero Gin Ile Leu lie lys Asn Thr Ero Val Ero Ala Asp Ero Pro 645 650 655

     Thr Thr Phe Ser Gin Ala lys Leu Ala Ser Phe lie Thr Gin Tyr Ser 660 665 670

     Thr Gly Gin Val Ser Val Glu Ile Glu Trp Glu Leu Gin Lys Glu Asn 675 680 685
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     Ser Lys Arg Trp 690 Asn Pro Glu 695 He Gin Tyr Thr Ser Asn Tyr Tyr Lys 700 Ser Thr Asn Val Asp Phe Ala Val Asn Thr Glu Gly Thr Tyr Ser Glu 705 710 715 720 Pro Arg Pro lie Gly Thr Arg Tyr Leu Thr Arg Ser Leu 725 730 <210> 87 <211> 733 <212> PRT <213> capsid protein of AAV serotype, clone 42.3A <400> 87 Met 1 Ala Ala Asp Gly His Leu 5 Pro Asp Trp Leu Glu Asp Asn Leu Ser 10 15 Glu Gly He Arg 20 Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys pro 25 30 Lys Ala Asn Gin 35 Gin Lys Gin Asp Asp Gly Arg Gly Leu Val Leu pro 40 45 Gly Tyr Lys Tyr 50 Leu Gly Pro 55 Phe Asn Gly Leu Asp Lys Gly Glu Pro 60 Val 65 Asn Ala Ala Asp Ala Ala 70 Ala Leu Slu His Asp Lys Ala Tyr Asp 75 80 Gin Gin Leu Lys Ala Gly Asp 85 Asn Pro Tyr Leu Arg Tyr Asn His Ala 90 95 Asp Ala Glu Phe 100 Gin Glu Arg Leu Gin Glu Asp Thr Ser Phe Glv Gly 105 110 Asn Leu Gly Arg 115 Ala Val Phe Gin Ala Lys Lys Arg Val Leu Glu pro 120 125 Leu Gly Leu Val 130 Glu Glu Gly 135 Ala Lys Thr Ala Pro Gly Lys Lys Arg 140 Pro 145 He Glu Ser pro Asp Ser 150 Ser Thr Gly lie Gly Lys Lys Gly Gin 155 160 Gin Pro Ala Lys Lys Lys Leu 165 Asn Phe Gly Gin Thr Gly Asp Ser Glu 170 175 Ser Val Pro Asp 180 Pro Gin Pro He Gly Glu Pro Pro Ala Gly Pro Ser 185 190
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     Gly Leu Gly Ser Gly Thr Met Ala Ala Gly Gly Gly Ala Pro Met Ala 195 200 205

     Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Ser Ser Ser Gly Asn Trp 210 215 220

     His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val lie Thr Thr Ser Thr 225 230 235 240

     Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu Tyr Lys Gin lie 245 250 255

     Ser Asn Gly Thr Ser Gly Gly Ser Thr Asn Asp Asn Thr Tyr Phe Gly . 260 265 270

     Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Ehe Asn Arg Ehe His Cys His 275 280 285

     Phe ser Pro Arg Asp Trp Gin Arg Leu lie Asn Asn Ser Trp Gly Phe 290 295 300

     Arg Pro Lys Arg Leu Asn. Phe Lys Leu Phe Asn He Gin Val Lys Glu 305 310 315 320

     Val Thr Gin Asn Glu Gly Thr Lys Thr He Ala Asn Asn Leu Thr Ser 325 330 335

     Thr lie Gin Val Phe Thr Asp Ser Glu Tyr Gin Leu Pro Tyr Val Leu 340 345 350

     Gly Ser Ala His Gin Gly Cys Leu Ero Pro Phe Ero Ala Asp Val Phe 355 360 3S5

     Met He Pro Gin Tyr Gly Tyr Leu Thr Leu Asn Asn Gly Ser Gin Ala 370 375 380

     Val Gly Arg Ser Ser Ehe Tyr Cys Leu Glu Tyr Phe Pro Ser Gin Met 385 390 395 400

     Leu Arg Thr Gly Asn Asn Phe Glu Phe Ser Tyr Gin Phe Glu Asp Val 405 410 415

     Pro Phe His Ser Ser Tyr Ala His Ser Gin Ser Leu Asp Arg Leu Met 420 425 430

     Asn Pro Leu He Asp Gin Tyr leu Tyr Tyr leu Ser Arg Thr Gin ser 435 440 445
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     Thr Gly Gly Thr Ala Gly Thr Gln Gln Leu Leu Phe Ser Gln Ala Gly 450 455 460

     Pro Asn Asn Met Ser Ala Gln Ala Lys Asn Trp Leu Pro Gly Pro Cys 465 470 475 480

     Tyr Arg Gln Gln Arg Val Ser Thr Thr Leu Ser Gln Asn Asn Asn Ser 485 490 495

     Asn Phe Ala Trp Thr Gly Ala Thr Lys Tyr His Leu Asn Gly Arg Asp 500 505 510

     Ser Leu Val Asn Pro Gly Val Ala Met Ala Thr His Lys Asp Asp Glu 515 520 525

     Glu Arg Phe Phe Pro Ser Ser Gly Val Leu Met Phe Gly Lys Gln Gly 530 535 540

     Ala Gly Lys Asp Asn Val Asp Tyr Ser Ser Val Met Leu Thr Ser Glu 545 550 555 560

     Glu Glu lie Lys Thr Thr Asn Pro Val Ala Thr Glu Gln Tyr Gly Val 565 570 575

     Val Ala Asp Asn Leu Gln Gln Gln Asn Ala Ala Pro Ile Val Gly Ala 580 585 5S0

     Val Asn Ser Gln Gly Ala Leu Pro Gly Met Val Trp Gln Asn Arg Asp 595 600 605

     Val Tyr Leu Gln Gly Pro lie Trp Ala Lys lie Pro His Thr Asp Gly 610 615 620

     Asn Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Leu Lys His Pro 625 630 635 640

     Pro Pro Gln lie Leu lie Lys Asn Thr Pro Val Pro Ala Asp Pro Pro 645 650 655

     Thr Thr Phe Ser Gln Ala Lys Leu Ala Ser Phe Ile Thr Gln Tyr Ser 660 665 670

     Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu Gln Lys Glu Asn 675 680 685

     Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr Ser Asn Tyr Tyr Lys 690 695 700
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     Ser Thr Asn Val Asp Phe Ala Val Asn Thr Glu Gly Thr Tyr Ser Glu 705 710 715 720

     Pro Arg Pro lie Gly Thr Arg Tyr Leu Thr Arg Asn Leu 725 730 <210> 88 .

     <211> 731 <212> PRT <213> capsid protein of AAV serotype, clone 42.4 <400> 88

     Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp 10 Leu Glu Asp Asn Leu Ser 15 1 5 Glu Gly lie Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro 20 25 30 Lys Ala Asn Gin Gin Lys Gin Asp Asp Gly Arg Gly Leu Val Leu Pro 35 40 45 Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro 50 55 60 Val Asn Glu Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp 65 70 75 80 Lys Gin Leu Glu Gin Gly Asp Asn Pro Tyr Leu Lys Tyr Asn His Ala 85 90 95 Asp Ala Glu phe Gin Glu Arg Leu Gin Glu Asp Thr Ser Phe Gly Gly 100 105 110 Asn Leu Gly Arg Ala Val Phe Gin Ala Lys Lys Arg Val Leu Glu Pro 115 120 125 Leu Gly Leu Val Glu Glu Gly Ala Lys Thr Ala Pro Gly Lys Lys Arg 130 135 140 Pro lie Glu Ser Pro Asp Ser Ser Thr Gly lie Gly Lys Lys Gly Gin 145 150 155 160 Gin Pro Ala Lys Lys Lys Leu Asn Phe Gly Gin Thr Gly Asp Ser Glu 165 170 175 Ser Val Pro Asp Pro Gin Pro lie Gly Glu Pro Pro Ala Gly Pro Ser 180 185 190
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     Gly leu Gly Ser Gly Thr Met Ala Ala Gly Gly Gly Ala Pro Met Ala 195 200 205

     Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn Ala Ser Gly Asn Trp

     210 215

     His Cys Asp Ser Thr Trp leu Gly 225 230

     Arg Thr Trp Ala leu Pro Thr Tyr 245

     Ser Ser Gln Ser Gly Ala Thr Asn 260

     Thr Pro Trp Gly Tyr Phe Asp Phe 275 280

     Ser Arg Asp Trp Gln Arg Leu lie 290 295

     220

     Asp Arg Val Ile Thr Thr Ser Thr 235 240

     Asn Asn His Leu Tyr Lys Gln Ile 250 255

     Asp Asn His Phe Phe Gly Tyr Ser 265 270

     Asn Arg Phe His Cys His Phe Ser 285

     Asn Asn Asn Trp Gly Phe Arg Pro 300 lys Arg Leu Asn Phe Lys leu Phe 305 310

     Asn Ile Gln Val Lys Glu Val Thr 315 320

     Gln Asn Glu Gly Thr Lys Thr Ile 325

     Ala Asn Asn Leu Thr Ser Thr Ile 330 335

     Gln Val Phe Thr Asp Ser Glu Tyr 340

     Arg leu Pro Tyr Val Leu Gly Ser 345 350

     Ala His Gln Gly Cys leu Pro Pro 355 360

     Phe Pro Ala Asp Val Phe Met Ile 365

     Pro Gln Tyr Gly Tyr leu Thr leu 370 375

     Asn Asn Gly Ser Gln Ala Val Gly 380

     Arg Ser Ser Phe Tyr Cys leu Glu 385 390

     Tyr Phe Pro Ser Gln Met Leu Arg 395 400

     Thr Gly Asn Asn Phe Glu Phe Ser 405

     Tyr Gln Phe Glu Asp Val Pro Phe 410 415

     His Ser Ser Tyr Ala His Ser Gln 420

     Ser Leu Asp Arg Leu Met Asn Pro 425 430

     Leu Ile Asp Gln Tyr leu Tyr Tyr 435 440 leu Ser Arg Thr Gln Ser Thr Gly 445
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     Gly Thr Ala Gly Thr Gin Gin Leu 450 455

     Leu Phe Ser Gin Ala Gly Pro Asn 460

     Asn Met Ser Ala Gin Ala Lys 465 470

     Gin Gin Arg Val Ser Thr Thr 485

     Ala Trp Thr Gly Ala Thr Lys 500

     Val Asn Pro Gly Val Ala Met 515

     Phe Phe Pro Ser Ser Gly Val 530 535

     Lys Asp Asn Val Asp Tyr Ser 545 550 lie Lys Thr Thr Asn Pro Val 565

     Asp Asn Leu Gin Gin Gin Asn 580

     Ser Gin Gly Ala Leu Pro Gly 595

     Leu Gin Gly Pro lie Trp Ala 610 615

     His Pro Ser Pro leu Met Gly 625 630

     Gin Ile leu Ile Lys Asn Thr 645

     Phe Ser Gin Ala Lys Pro Ala 660

     Gin Val Ser Val Glu lie Glu 675

     Arg Trp Asn Pro Glu Ile Gin 690 695

     Asn Trp Leu Pro Gly Pro Cys Tyr Arg 475 480

     Leu Ser Gin Asn Asn Asn Ser Asn Phe 490 495

     Tyr His leu Asn Gly Arg Asp Ser Leu 505 510

     Ala Thr His lys Asp Asp Glu Glu Arg 520 525

     Leu Met Phe Gly Lys Gin Gly Ala Gly 540

     Ser Val Met Leu Thr Ser Glu Glu Glu 555 560

     Ala Thr Glu Gin Tyr Gly Val Val Ala 570 575

     Ala Ala Pro Ile Val Gly Ala Val Asn 585 590

     Met Val Trp Gin Asn Arg Asp Val Tyr 600 605

     Lys lie Pro His Thr Asp Gly Asn Phe 620

     Gly Phe Gly Leu Lys His Pro Pro Pro 635 640

     Pro Val Pro Ala Asp Pro Pro Thr Thr 650 655

     Ser Phe Ile Thr Gin Tyr Ser Thr Gly 665 670

     Trp Glu Leu Gin Lys Glu Asn Ser Lys 680 685

     Tyr Thr Ser Asn Tyr Tyr Lys Ser Thr 700
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     Asn Val Asp Phe Ala Val Asn Thr Glu Gly Thr Tyr Ser Glu Pro Arg 705 710 715 720

     Pro Ile Gly Thr Arg Tyr Leu Thr Arg Asn Leu 725 730 <210> 89 <211> 731 <212> PRT <213> capsid protein of AAV serotype, clone 42.5A

     <400> Met Ala 1 89 Ala Asp Gly 5 Tyr Leu Pro Asp Trp 10 leu Glu Asp Asn leu Ser 15 Glu Gly Ile Arg Glu Trp Trp Asp Leu lys Pro Gly Ala Pro Lys Pro 20 25 30 Lys Ala Asn Gin Gin lys Gin Asp ASp Gly Arg Gly Leu Val Leu Pro 35 40 45 Gly Tyr Lys Tyr leu Gly Pro Phe Asn Gly Leu Asp lys Gly Glu Pro 50 55 60 Val Asn Glu Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp 65 70 75 80 Lys Gin Leu Glu Gin Gly Asp Asn Pro Tyr Leu Lys Tyr Asn His Ala 85 90 95 Asp Ala Glu Phe Gin Glu Arg Leu Gin Glu Asp Thr Ser Phe Gly Gly 100 105 110 Asn Leu Gly Arg Ala Val Phe Arg Ala lys Lys Arg Val Leu Glu Pro 115 120 125 Leu Gly Leu Val Glu Glu Gly Ala Lys Thr Ala Pro Gly Lys Lys Arg 130 135 140 Pro Ile Glu Ser Pro Asp Ser Ser Thr Gly Ile Gly Lys Lys Gly Gin 145 150 155 160 Gin Pro Ala lys lys Lys Leu Asn Phe Gly Gin Thr Gly Asp Ser Glu 165 170 175 Ser Val Pro Asp Pro Gin Pro Leu Gly Glu Pro Pro Ala Ala Pro Ser 180 185 190 Gly Leu Gly Ser Gly Thr Met Ala Ala Gly Gly Gly Ala Pro Met Ala

     195 200 205
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     Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn Ala Ser Gly Asn Trp 210 215 220

     His 225 Cys Asp Ser Thr Trp 230 Leu Gly Asp Arg Val 235 Ile Thr Thr Ser Thr 240 Arg Thr Trp Ala Leu 245 Pro Thr Tyr Asn Asn 250 His Leu Tyr Lys Gin 255 . Ile Ser Ser Gin Ser 260 Gly Ala Thr Asn Asp 265 Asn His Phe Ehe Gly 270 Tyr Ser Thr Pro Trp 275 Gly Tyr Phe Asp Ehe 280 Asn Arg Phe His Cys 285 His Phe Ser Pro Arg 290 Asp Trp Gin Arg Leu 295 Ile Asn Asn Asn Arg 300 Gly Phe Arg Pro Arg 305 Lys Leu Arg Phe Lys 310 Leu Phe Asn Ile Gin 315 Val Lys Glu Val Thr 320 Thr Asn Asp Gly Val 325 Thr Thr Ile Ala Asn 330 Asn Leu Thr Ser Thr 335 lie Gin Val Phe Ser 340 Asp Ser Glu Tyr Gin 345 Leu Pro Tyr Val Leu 350 Gly Ser Ala His Gin 355 Gly Cys Leu Pro Pro 360 Phe Pro Ala Asp Val 365 Phe Met Ile Ero Gin 370 Tyr Gly Tyr Leu Thr 375 Leu Asn Asn Gly Ser 380 Gin Ser val Gly Arg 385 Ser Ser Phe Tyr Cys 390 Leu Glu Tyr Phe Pro 395 Ser Gin Met Leu Arg 400 Thr Gly Asn Asn Phe 405 Glu Phe Ser Tyr Gin 410 Phe Glu Asp Val Pro 415 Phe His Ser Ser Tyr 420 Ala His Ser Gin Ser 425 Leu Asp Arg Leu Met 430 Asn Pro Leu Ile Asp 435 Gin Tyr Leu Tyr Tyr 440 Leu Ser Arg Thr Gin 445 Ser Thr Gly Gly Thr 450 Ala Gly Thr Gin Gin 4 55 Leu Leu Phe Ser Gin 460 Ala Gly Pro . Asn
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     Asn Met Ser Ala Gln Ala Lys Asn Trp Leu Pro Gly Pro Cys Tyr Arg 465 470 475 480

     Gln Gln Arg Val Ser Thr Thr Leu Ser Gln Asn Asn Asn Ser Asn Phe 485 490 495

     Ala Trp Thr Gly Ala Thr Lys Tyr His Leu Asn Gly Arg Asp Ser Leu 500 505 510

     Val Asn Pro Gly Val Ala Met Ala Thr His Lys Asp Asp Glu Glu Arg 515 520 525

     Phe Phe Pro Ser Ser Gly Val Leu Met Phe Gly Lys Gln Gly Ala Gly 530 535 540

     Lys Asp Asn Val Asp Tyr Ser Ser Val Met Leu Thr Ser Glu Glu Glu 54 5 550 555 560

     Ile Lys Thr Thr Asn Pro Val Ala Thr Glu Gln Tyr Gly Val Val Ala 565 570 575

     Asp Asn Leu Gln Gln Gln Asn Ala Ala Pro Ile Val Gly Ala Val Asn 580 585 590

     Ser Gln Gly Ala Leu Pro Gly Met Ala Trp Gln Asn Arg Asp Val Tyr 5 9 5 6 0 0 605

     Leu Gln Gly Pro lie Trp Ala Lys Ile Pro His Thr Asp Gly Asn Phe 610 615 620

     His Pro Ser Pro Leu Met Gly Gly Phe Gly Leu Lys His Pro Pro Pro 625 630 635 640

     Gln Ile Leu Ile Lys Asn Thr Pro Val Pro Ala Asp Pro Pro Thr Thr 645 650 655

     Phe Ser Gln Ala Lys Leu Ala Ser Phe lie Thr Gln Tyr Ser Thr Gly 660 665 670

     Gln Val Ser Val Glu Ile Glu Trp Glu Leu Gln Lys Glu Asn Ser Lys 675 680 685

     Arg Trp Asn Pro Glu Ile Gln Tyr Thr Ser Asn Tyr Tyr Lys Ser Thr 690 695 700

     Asn Val Asp Phe Ala Val Asn Thr Glu Gly Thr Tyr Ser Glu Pro Arg 7 05 710 715 720
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     Pro lie Gly Thr Arg Tyr Leu Thr Arg Asn Leu 725 730 <210> 90 <211> 733 <212> PRT <213> capsid protein of AAV serotype, clone 42.IB <400> 90

     Met 1 Ala Ala Asp Gly 5 Tyr Leu Pro Asp Trp 10 Leu Glu Asp Asn leu 15 . Ser Glu Gly lie Arg 20 Glu Trp Trp Asp Leu 25 Arg Pro Gly Ala Pro 30 Lys Pro lys Ala Asn 35 Gin Gin Lys Gin Asp 40 Asp Gly Arg Gly Leu 45 Val Leu Pro Gly Tyr 50 lys Tyr leu Gly Pro 55 Phe Asn Gly Leu Asp 60 Lys Gly Glu Pro Val 65 Asn Glu Ala Asp Ala 70 Ala Ala leu Glu His 75 Asp Lys Ala Tyr Asp 80 Lys Gin leu Glu Gin 85 Gly Asp Asn Pro Tyr 90 Leu Lys Tyr Asn His 95 Ala Asp Ala Glu Phe 100 Gin Glu Arg Leu Gin 105 Glu Asp Thr Ser Phe 110 Gly Gly Asn leu Gly 115 Arg Ala Val Phe Gin 120 Ala Lys Lys Arg Val 125 Leu Glu Pro Leu Gly 130 leu Val Glu GlU Gly 135 Ala Lys Thr Ala Pro 140 Gly Lys Lys Arg Pro 145 He Glu Ser Pro Asp 150 Ser Ser Thr sly lie 155 Gly iys Lys Gly Gin 160 Gin Pro Ala lys Lys 165 Arg leu Asn Phe sly 170 Gin Thr Gly Asp Ser 175 Glu Ser Val Pro Asp 180 Pro Gin Pro lie Gly 185 Glu Pro Pro Ala Gly 190 Pro Ser Gly leu Gly 195 Ser Gly Thr Met Ala 200 Ala Gly Gly Gly Ala 205 Pro Met Ala Asp Asn 210 Asn Glu Gly Ala Asp 215 Gly Val Gly Ser Ser 220 Ser Gly Asn Trp
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     His 225 Cys Asp Ser ' Thr Trp 230 Leu , Gly Asp Arg Val 235 Ile ! Thr : Thr ' Ser Thr 240 Arg Thr Trp Ala Leu 245 Ero Thr Tyr Asn Asn 250 His Leu i Tyr Lys Gin Ile 255 Ser Asn Gly Thr 260 Ser Gly Gly Ser Thr 2 65 Asn Asp Asn Thr Tyr 270 Phe Gly Tyr Ser Thr 275 Ero Trp Gly Tyr Phe 280 Asp Phe Asn Arg Phe 285 His Cys His Ehe Ser 2 90 Ero Arg Asp Trp Gin 295 Arg Leu lie Asn Asn 300 Asn Trp Gly Phe Arg 305 Pro lys Arg Leu Asn 310 Phe Lys Leu Phe Asn 315 lie Gin Val Lys Glu 320 Val Thr Gin Asn Glu 325 Gly Thr Lys Thr Ile 330 Ala Asn Asn Leu Thr 335 Ser Thr Ile Gin Val 340 Phe Thr Asp Ser Glu 345 Tyr Gin Leu Pro Tyr 350 Val Leu Gly Ser Ala 3 55 His Gin Gly Cys Leu 360 Ero Pro Phe Ero Ala 365 Asp Val Ehe Met lie 370 Ero Gin Tyr Gly Tyr 375 Leu Thr Leu Asn Asn 380 Gly Ser Gin Ala Val 385 Gly Arg Ser Ser Phe 390 Tyr Cys Leu Glu Tyr 395 Phe Pro Ser Gin Met 400 leu Arg Thr Gly Asn 405 Asn Phe Glu Phe Ser 410 Tyr Gin Phe Glu Asp 415 Val Pro Phe His Ser 420 Ser Tyr Ala His Ser 425 Gin Ser Leu Asp Arg 430 Leu Met Asn Pro leu 435 Ile Asp Gin Tyr Leu 440 Tyr Tyr Leu Ser Arg 445 Thr Gin Ser Thr Gly 450 Gly Thr Ala Gly Thr 455 Gin Gin Leu leu Phe 460 Ser Gin Ala Gly Pro Asn Asn Met Ser Ala Gin Ala Lys Asn Trp Leu Ero Gly Ero Cys

     465 470 475 480
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     Tyr Arg Gin Gin Arg Val Ser Thr Thr Val Ser Gin Asn Asn Asn Ser 485 490 495

     Asn Phe Ala Trp Thr Gly Ala Thr Lys Tyr His Leu Asn Gly Arg Asp 500 505 510

     Ser Leu Val Asn Pro Gly Val Ala Met Ala Thr His Lys Gly Asp Glu 515 520 525

     Glu Arg Phe Phe Pro Ser Ser Gly Val Leu Met Phe Gly Lys Gin Gly 530 535 540

     Ala Gly Lys Asp Asn Val Asp Tyr Ser Ser Val Met Lsu Thr Ser Glu 545 550 555 560

     Glu Glu lie Lys Thr Thr Asn Pro Val Ala Thr Glu Gin Tyr Gly Val 565 570 575

     Val Ala Asp Asn Leu Gin Gin Gin Asn Ala Ala Pro lie Val Gly Ala 580 585 590

     Val Asn Ser Gin Gly Ala Leu Pro Gly Met Val Trp Gin Asn Arg Asp 595 600 605

     Val Tyr Leu Gin Gly Pro He Trp Ala Lys He Pro His Thr Asp Gly 610 615 620

     Asn Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly leu Lys His Pro 625 630 635 640

     Pro Pro Gin He Leu He Lys Asn Thr Pro Val Pro Ala Asp Pro Pro 645 650 655

     Thr Thr Phe Ser Gin Ala Lys Leu Ala Ser Phe lie Thr Gin Tyr Ser 660 665 670

     Thr Gly Gin Val Ser Val Glu lie Glu Trp Glu Leu Gin Lys Glu Asn 675 680 685

     Ser Lys Arg Trp Asn Pro Glu He Gin Tyr Thr Ser Asn Tyr Tyr Lys 690 695 700

     Ser Thr Asn Val Asp Phe Ala Val Asn Thr Glu Gly Thr Tyr Ser Glu 705 710 715 720

     Pro Arg Pro He Gly Thr Arg Tyr Leu Thr Arg Asn Leu 725 730
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     Met 1 Ala Ala Asp Gly 5 Tyr Leu Pro Asp Trp 10 Leu Glu Asp Asn . Leu 15 . Ser Glu Gly He Arg 20 Glu Trp Trp Asp Leu 25 Lys Pro Gly Ala Pro 30 Lys Pro lys Ala Asn 35 Gin Gin Lys Gin Asp 40 Asp Gly Arg Gly Leu 45 Val Leu Pro Gly Tyr 50 Lys Tyr Leu Gly Pro 55 Phe Asn Gly Leu Asp 60 Lys Gly Glu Pro Val 65 Asn Glu Ala Asp Ala 70 Ala Ala Leu Glu His 75 Asp Lys Ala Tyr Asp 80 lys Gin leu Glu Gin 85 Gly Asp Asn Pro Tyr 90 Leu Lys Tyr Asn His 95 Ala Asp Ala Glu Phe 100 Gin Glu Arg Leu Gin 105 Glu Asp Thr Ser Phe 110 Gly Gly Asn leu Gly Arg 115 Ala Val Phe Gin 120 Ala Lys Lys Arg Val 125 Leu Glu Pro Leu Gly 130 Leu Val Glu Glu Gly 135 Ala Lys Thr Ala Pro 140 Gly Lys Lys Arg Pro 145 Val Glu Pro Ser Pro 150 Gin Arg Ser Pro Asp 155 Ser Ser Thr Gly He 160 Gly Lys Thr Gly Gin 165 Gin Pro Ala Lys Lys 170 Arg Leu Asn Phe Gly 175 Gin Thr Gly Asp Ser 180 Glu Ser Val Pro Asp 185 Pro Gin Pro lie Gly 190 Glu Pro Pro Ala Gly 195 Pro Ser Gly Leu Gly 200 Ser Gly Thr Met Ala 205 Ala Gly Gly Gly Ala 210 Pro Met Ala Asp Asn 215 Asn Glu Gly Ala Asp 220 Gly Val Gly Ser Ser 225 Ser Gly Asn Trp His 230 Cys Asp Ser Thr Trp 235 Leu Gly Asp Arg Val 240 lie Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His

     245 250 255
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     Leu Tyr Lys Gin 2 60 Ile Ser Asn Gly Thr 265 Ser Gly Gly Ser Thr 270 Asn Asp Asn Thr Tyr 275 Phe Gly Tyr Ser Thr 280 Pro Trp Gly Tyr Phe 285 Asp Phe Asn Arg Phe 290 His Cys His Phe Ser 295 Pro Arg Asp Trp Gin Arg 300 Leu Ile Asn Asn 305 Asn Trp Gly Phe Arg 310 Pro Lys Arg Leu Asn 315 Phe Lys Leu Phe Asn 320 Ile Gin Val Lys Glu 325 Val Thr Gin Asn Glu 330 Gly Thr Lys Thr Ile 335 Ala Asn Asn Leu Thr 340 Ser Thr Ile Gin Val 345 Phe Thr Asp Ser Glu 350 _Tyr Gin Leu Pro Ty_r 355 Val Leu Gly Ser Ala 360 His Gin Gly Cys Leu 365 Pro Pro Phe Pro Ala 370 Asp Val Phe Met Ile 375 Pro Gin Tyr Gly Tyr 380 Leu Thr Leu Asn Asn 385 Gly Ser Gin Ala Val 390 Gly Arg Ser Ser Phe 395 Tyr Cys Leu Glu Tyr 400 Phe Pro Ser Gin Met 405 Leu Arg Thr Gly Asn 410 Asn Phe Glu Phe Ser 415 Tyr Gin Phe Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gin Ser

     420 425 430

     Leu Asp Arg Leu Met Asn. Pro Leu Ile Asp Gin Tyr leu Tyr Tyr Leu 435 440 445

     Ser Arg Thr Gin Ser Thr Gly Gly Thr Ala Gly Thr Gin Gin Leu Leu 450 455 460

     Phe Ser Gin Ala Gly Pro Asn Asn Met Ser Ala Gin Ala Lys Asn Trp 465 470 475 480

     Leu Pro Gly Pro Cys Tyr Arg Gin Gin Arg Val Ser Thr Thr Leu Ser 485 490 495

     Gin Asn Asn Asn Ser Asn Phe Ala Trp Thr Gly Ala Thr Lys Tyr His 500 505 510
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     Leu Asn Gly 515 Arg Asp Ser Leu Val Asn 520 . Pro Gly Val Ala Met 525 ; Ala Thr His Lys 530 Asp Asp Glu Glu Arg 535 Phe Phe Pro Ser Ser 540 Gly Val Leu Met Phe 545 Gly Lys Gln Gly Ala 550 Gly Lys Asp Asn Val Asp 555 Tyr Ser Ser Val 560 Met Leu Thr Ser Glu 565 Glu Glu lie Lys Thr 570 Thr Asn Pro Val Ala Thr 575 Glu Gln Tyr Gly 580 Val Val Ala Asp Asn 585 Leu Gln Gln Gln Asn 590 Ala Ala Pro lie Val 595 Gly Ala Val Asn Ser 600 Gln Gly Ala Leu Pro Gly 605 Met Val Trp Gln 610 Asn Arg Asp Val Tyr 615 Leu Gln Gly Pro Ile 620 Trp Ala Lys Ile Pro 625 His Thr Asp Gly Asn 630 Phe His Pro Ser Pro Leu 635 Met Gly Gly Phe 640 Gly Leu Lys His Pro 645 Pro Pro Gln Ile Leu 650 Ile Lys Asn Thr Pro Val 655 Pro Ala Asp Pro 660 Pro Thr Thr Phe Ser 665 Gln Ala Lys ^L Leu Ala 670 Ser Phe Ile Thr Gln 675 Tyr Ser Thr Gly Gln 680 Val Ser Val Glu Ile Glu 685 Trp Glu Leu Gln 690 Lys Glu Asn Ser Lys 695 Arg Trp Asn Pro Glu 700 Ile Gln Tyr Thr Ser 705 Asn Tyr Tyr Lys Ser 710 Thr Asn Val Asp Phe Ala 715 Val Asn Thr Glu 720 Gly Thr Tyr Ser Glu 725 Pro Arg Pro lie Gly 730 Thr Arg Tyr Leu Thr Arg 735

     Asn Leu <210> 92 <211> 738 <212> PRT <213> capsid protein of AAV serotype, clone 43.1
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     Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 15 10 15

     Glu Gly Ile Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro 20 25 30

     Lys Ala Asn Gin Gin Lys Gin Asp Asp Gly Arg Gly Leu Val Leu Pro 35 40 45

     Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro 50 55 60

     Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp lys Ala Tyr Asp 65 70 75 80

     Gin Gin Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala 85 90 95

     Asp Ala Glu Phe Gin Glu Arg Leu Gin Glu Asp Thr Ser Phe Gly Gly 100 105 110

     Asn Leu Gly Arg Ala Val Phe Gin Ala Lys Lys Arg Val Leu Glu Pro

     Leu Gly Leu Val Glu Glu Gly Ala Lys Thr Ala Pro Gly Lys Lys Arg 130 135 140

     Pro Val Glu Pro Ser Pro Gin Arg Ser Ero Asp Ser Ser Thr Gly Ile 145 150 155 160

     Gly Lys Lys Gly His Gin Pro Ala Arg Lys Arg Leu Asn Phe Gly Gin 165 170 175

     Thr Gly Asp Ser Glu Ser Val Pro Asp Pro Gin Pro lie Gly Glu Pro 180 185 190

     Pro Ala Gly Pro Ser Gly Leu Gly Ser Gly Thr Met Ala Ala Gly Gly 195 200 205

     Gly Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Ser 210 215 220

     Ser Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val 225 230 235 . 240

     Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His 245 250 255
199. 199

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     Leu . Tyr Lys Gln 260 . Ile Ser Asn i Gly Thr 265 Ser Gly Gly - Ser Thr 270 ' Asn Asp Asn Thr Tyr 275 Phe Gly Tyr Ser Thr 280 Pro Trp Gly Tyr Phe 285 Asp Phe Asn Arg Phe 290 His Cys His Phe Ser 295 Pro Arg Asp Trp Gln 300 Arg Leu Ile Asn Asn 305 Asn Trp Gly Phe Arg 310 Pro Lys Arg Leu Asn 315 Phe Lys Leu Phe Asn 320 Ile Gln Val Lys Glu 325 Val Thr Gln Asn Glu 330 Gly Thr Lys Thr lie 335 Ala Asn Asn Leu Thr 340 Ser Thr Ile Gln Val 345 Phe Thr Asp Ser Glu 350 Tyr Gln Leu Pro Tyr 3 55 Val Pro Gly Ser Ala 360 His Gln Gly Cys Leu 365 Pro Pro Phe Pro Ala 370 Asp Val Phe Met lie 375 Pro Gln Tyr Gly Tyr 380 Leu Thr Leu Asn Asn 385 Gly Ser Gln Ala Val 390 Gly Arg Ser Ser Phe 395 Tyr Cys Leu Glu Tyr 400 Phe Pro Ser Gln Met 405 Leu Arg Thr Gly Asn 410 Asn Phe Glu Phe Ser 415 Tyr Thr Phe Glu Asp 420 Val Pro Phe His Ser 425 ser Tyr Ala His Ser 430 Gln Ser Leu Asp Arg 435 Leu Met Asn pro Leu 440 lie Asp Gln Tyr Leu 445 Tyr Tyr Leu Ser Arg 450 Thr Gln Ser Thr Gly 455 Gly Thr Gln Gly Thr 4 60 Gln Gln Leu Leu Phe 4 65 Ser Gln Ala Gly Pro 470 Ala Asn Met Ser Ala 475 Gln Ala Lys Asn Trp 480 Leu pro Gly Pro Cys 485 Tyr Arg Gln Gln Arg 490 Val Ser Thr Thr Leu 495 Ser Gln Asn Asn Asn 500 Ser Asn Phe Ala Trp 505 Thr Gly Ala Thr Lys 510 Tyr His Leu Asn Gly Arg Asp Ser Leu Val Asn Pro Gly Val Ala Met Ala Thr

     515 520 525
200. 200

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     His Lys 530 Asp Asp Glu Glu Arg 535 Phe Phe Pro Ser Ser 540 Gly Val Leu , Met Phe 545 Gly Lys Gln Gly Ala 550 Gly Lys Asp Asn Val 555 Asp Tyr Ser Ser Val 560 Met Leu Thr Ser Glu 565 Glu Glu lie Lys Thr 57 0 Thr Asn Pro Val Ala 575 Thr Glu Gln Tyr Gly 580 Val Val Ala Asp Asn 585 Leu Gln Gln Thr Asn 590 Gly Ala Pro Ile Val 595 Gly Thr Val Asn Ser 600 Gln Gly Ala Leu Pro 605 Gly Met Val Trp Gln 610 Asn Arg Asp Val Tyr 615 leu Gln Gly Ero lie 620 Trp Ala Lys Ile Pro 625 His Thr Asp Gly Asn 630 Phe His pro Ser Ero 635 Leu Met Gly Gly Phe 640 Gly Leu lys His Ero 645 Ero Pro Gln lie Leu 650 Val Lys Asn Thr Pro 655 Val Pro Ala Asp Pro 660 Pro Thr Thr Phe Ser 665 Gln Ala Lys Leu Ala 670 Ser Ehe Ile Thr Gln 675 Tyr Ser Thr Gly Gln 680 Val Ser Val Glu Ile 685 Glu Trp Glu Leu Gln 690 Lys Glu Asn Ser Lys 695 Arg Trp Asn Ero Glu 700 lie Gln IPyr Thr Ser 705 Asn Tyr Tyr iys Ser 710 Thr Asn Val Asp Phe 715 Ala Val Asn Thr Glu 720 Gly Thr Tyr Ser Glu 725 Ero Arg Pro Ile Gly 730 Thr Arg Tyr Leu Thr . 735 Arg

     Asn Leu <210> 93 <211> 738 <212> PRT <213> capsid protein oi AAV serotype, clone 43.12
201. 201

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     <400> Met Ala 1 93 Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 5 10 15 Glu Gly He Arg Glu 20 Trp Trp Asp Leu Lys Pro Glj 25 ' Ala Pro Lys Pro 30 Lys Ala Asn Gin Gin 35 Lys Gin Asp Asp Gly Arg Gly 40 ’ Leu Val Leu Pro 45 Gly Tyr 50 Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp 55 60 Lys Gly Glu Pro Val Asn 65 Ala Ala Asp Ala Ala Ala Leu Glu His Asp 70 75 Lys Ala Tyr Asp 80 Gin Gin Leu Lys Ala 85 Gly Asp Asn Pro Tyr Leu Arg 90 Tyr Asn His Ala 95 Asp Ala Glu Phe Gin 100 Glu Arg Leu Gin Glu Asp Thr 105 Ser Phe Gly Gly 110 Asn Leu Gly Arg Ala 115 Val Phe Gin Ala Lys Lys Arg 120 Val Leu Glu Pro 125 Leu Gly 130 Leu Val Glu Glu Gly Ala Lys Thr Ala Pro 135 140 Gly Lys Lys Arg Pro Val 145 Glu Pro Ser Pro Gin Arg Ser Pro Asp Ser 150 155 Ser Thr Gly lie 160 Gly Lys Lys Gly His 165 Gin Pro Ala Arg Lys Arg Leu 170 Asn Phe Gly Gin 175 Thr Gly Asp Ser Glu 180 Ser Val Pro Asp Pro Gin Pro 185 lie Gly Glu Pro 190 Pro Ala Gly Pro Ser 195 Gly Leu Gly Ser Gly Thr Met 200 Ala Ala Gly Gly 205 Gly Ala 210 Pro Met Ala Asp Asn Asn Glu Gly Ala Asp 215 220 Gly Val Gly Ser Ser Ser 225 Gly Asn Trp His Cys Asp Ser Thr Trp Leu 230 235 Gly Asp Arg Val 240 lie Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His

     245 250 255
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     Leu . Tyr Lys Gin 2 60 lie Ser Asn . Gly Thr 265 Ser Gly Gly Ser Thr 270 Asn ι Asp Asn Thr Tyr 275 Phe Gly Tyr Ser Thr 280 Pro Trp Gly Tyr Phe 285 Asp Phe Asn Arg Phe 290 His Cys His Phe Ser 295 Pro Arg Asp Trp Gin Arg 300 Leu Ile Asn Asn 305 Asn Trp Gly Phe Arg 310 Pro Lys Arg Leu Asn 315 Phe lys Leu Phe Asn 320 lie Gin Val Lys Glu 325 Val Thr Gin Asn Glu 330 Gly Thr Lys Thr Ile 335 Ala Asn Asn Leu Thr 340 Ser Thr Ile Gin Val 345 Phe Thr Asp Ser Glu 350 Tyr Gin Leu Pro Tyr 355 Val Leu Gly Ser Ala 3 60 His Gin Gly Cys Leu 365 Pro Pro Phe Pro Ala 370 Asp Val Ehe Met Ile 375 Pro Gin Tyr Gly Tyr 380 Leu Thr Leu Asn Asn 385 Gly Ser Gin Ala Val 390 Gly Arg Ser Ser Phe 395 Tyr Cys Leu Glu Tyr 400 Phe Ero Ser Gin Met 405 Leu Arg Thr Gly Asn 410 Asn Ehe Glu Phe Ser 415 Tyr Thr Phe Glu Asp 420 Val Pro Phe His Ser 425 Ser Tyr Ala His Ser 430 Gin Ser Leu Asp Arg 435 Leu Met Asn Pro Leu 440 Ile Asp Gin Tyr Leu 445 Tyr Tyr Leu Ser Arg 45C Thr Gin Ser Thr Gly 455 Gly Thr Gin Gly Thr 4 60 Gin Gin Leu Leu Phe 465 Ser Gin Ala Gly Pro 470 Ala Asn Mfet Ser Ala 475 Gin Ala Lys Asn Trp 480 Leu Pro Gly Pro Cys 485 Tyr Arg Gin Gin Arg 490 Val Ser Thr Thr Leu 495 Ser Gin Asn Asn Asn 500 Ser Asn Phe Ala Trp 505 Thr Gly Ala Thr Lys 510 Tyr His
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     Leu Asn Gly Arg 515 Asp Ser Leu Val 520 Asn Pro Gly Val Ala 525 Met Ala . Thr His Lys 530 Asp Asp Glu Glu Arg 535 Phe Phe Pro Ser Ser 540 Gly Val Leu • Met Phe 545 Gly Lys Gin Gly Ala 550 Gly Lys Asp Asn Val 555 Asp Tyr Ser Ser Val 560 Met Leu Thr Ser Glu 565 Glu Glu He Lys Thr 570 Thr Asn Pro Val Ala 575 Thr Glu Gin Tyr Gly 580 Val Val Ala Asp Asn 585 Leu Gin Gin Thr Asn 590 Gly Ala Pro lie Val 595 Gly Thr Val Asn Ser 600 Gin Gly Ala Leu Pro 605 Gly Met Val Trp Gin 610 Asn Arg Asp Val Tyr 615 Leu Gin Gly Pro lie 620 Trp Ala Lys He Pro 625 His Thr Asp Gly Asn 630 Phe His Pro Ser Pro 635 Leu Met Gly Gly Phe 640 Gly Leu Lys His Pro 645 Pro Pro Gin lie Leu 650 Val Lys Asn Thr Pro 655 Val Pro Ala Asp Pro 660 Ero Thr Thr Phe Ser 665 Gin Ala Lys Leu Ala 670 Ser Phe lie Thr Gin 675 Tyr Ser Thr Gly Gin 680 Val Ser Val Glu lie 685 Glu Trp Glu Leu Gin 690 Lys Glu Asn Ser Lys 695 Arg Trp Asn Fro Glu 700 lie Gin Tyr Thr Ser 7 05 Asn Tyr Tyr Lys Ser 710 Thr Asn Val Asp Phe 715 Ala Val Asn Thr Glu 720 Gly Thr Tyr Ser Glu Pro Arg Pro He Gly Thr Arg Tyr Leu Thr Arg

     725 730 735

     Asn Leu <210> 94 <211> 738 <212> PRT <213> capsid protein of AAV serotype, clone 43.5
204. 204

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     <400> Met Ala 1 94 Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 5 10 15 Glu Gly Ile Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro 20 25 30 Lys Ala Asn Gln Gln Lys Gln Asp Asp Gly Arg Gly Leu Val Leu Pro 35 40 45 Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro 50 55 60 Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp 65 70 75 80 Gln Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala 85 90 95 Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr Ser Phe Gly Gly 100 105 110 Asn Leu Gly Arg Ala Val Phe Gln Ala Ly3 Lys Arg Val Leu Glu Pro 115 120 125 Leu Gly Leu Val Glu Glu Gly Ala Lys Thr Ala Pro Gly Lys Lys Arg 130 135 140 Pro Val Glu Pro Ser Pro Gln Arg Ser Pro Asp Ser Ser Thr Gly lie 145 150 155 160 Gly Lys Lys Gly His Gln Pro Ala Arg Lys Arg Leu Asn Phe Gly Gln 165 170 175 i Thr Gly Asp ser Glu Ser Val Pro Asp pro Gln 1 Pro Ile Gly Glu Pro 180 185 190 Pro Ala Gly Pro Ser Gly Leu Gly Ser Gly Thr Met Ala Ala Gly Gly 195 200 205 Gly Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Ser 210 215 220 Ser ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val 2 25 230 235 240 Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His 245 250 255
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     Leu Tyr Lys

     Asn Thr Tyr 275

     Arg Phe His 290

     Asn Asn Trp 305

     Ile Gln Val

     Asn Asn Leu

     Leu Pro Tyr 355

     Pro Ala Asp 370

     Asn Gly Ser 385

     Phe Pro Ser

     Thr Phe Glu

     Leu Asp Arg 435

     Ser Arg Thr 450

     Phe Ser Gln 4 65

     Leu Pro Gly

     Gln Ile Ser Asn Gly Thr Ser Gly Gly Ser Thr Asn Asp 260 265 270

     Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn 280 285

     Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn 295 300

     Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys leu Phe Asn 310 315 320 lys Glu Val Thr Gln Asn Glu Gly Thr lys Thr Ile Ala 325 330 335

     Thr Ser Thr Ile Gln Val Phe Thr Asp Ser Glu Tyr Gln 340 345 350

     Val Leu Gly Ser Ala His Gln Gly cys Leu Pro Pro Phe 360 365

     Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn 375 380

     Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr 390 395 400

     Gln Met Leu Arg Thr Gly Asn Asn Phe Glu Phe Ser Tyr 405 410 415

     Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser 420 425 430 leu Met Asn Pro Leu lie Asp Gln Tyr Leu Tyr Tyr Leu 440 445

     Gln Ser Thr Gly Gly Thr Gin Gly Thr Gln Gln Leu Leu 455 460

     Ala Gly Pro Ala Asn Met Ser Ala Gln Ala Lys Asn Trp 470 475 480

     Pro Cys Tyr Arg Gln Gln Arg Val Ser Thr Thr Leu Ser 485 490 495

     Asn Ser Asn Phe Ala Trp Thr Gly Ala Thr Lys Tyr His 500 505 510

     Gln Asn Asn
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     Leu Asn Gly 515 Arg Asp Ser Leu Val 520 Asn Pro , Gly Val Ala 525 Met Ala . Thr His Lys 530 Asp Asp Glu Glu Arg 535 Phe Phe Pro Ser Ser 540 Gly Val Leu . Met Phe 545 Gly Lys Gin Gly Ala 550 Gly Lys Asp Asn Val 555 Asp Tyr Ser Ser Val 560 Met Leu Thr Ser Glu 565 Glu Glu Ile Lys Thr 570 Thr Asn Pro Val Ala 575 Thr Glu Gin Tyr Gly 580 Val val Ala Asp Asn 585 Leu Gin Gin Thr Asn 590 Gly Ala Pro Ile Val 595 Gly Thr Val Asn Ser 600 Gin Gly Ala Leu Pro 605 Gly Met Val Trp Gin 610 Asn Arg Asp Val Tyr 615 Leu Gin Gly Pro Ile 620 Trp Ala Lys lie Pro S25 His Thr Asp Gly Asn 630 Phe His Pro Ser Pro 635 Leu Met Gly Gly Phe 640 Gly Leu Lys His Pro 645 Pro Pro Gin Ile Leu 650 Val Lys Asn Thr Pro 655 Val Pro Ala Asp Pro 660 Pro Thr Thr Phe Ser 665 Gin Ala Lys Leu Ala 670 Ser Phe Ile Thr Gin 675 Tyr Ser Thr Gly Gin 68 0 Val Ser Val Glu lie 685 Glu Trp Glu Leu Gin 690 Lys Glu Asn Ser Lys 695 Arg Trp Asn Pro Glu 700 Ile Gin Tyr Thr Ser 705 Asn Tyr Tyr Lys Ser 710 Thr Asn val Asp Phe 715 Ala Val Asn Thr Glu 720 Gly Thr Tyr Ser Glu Pro Arg Pro Ile Gly Thr . Arg Tyr Leu Thr . Arg

     725 730 735

     Asn Leu <210> 95 <2ll> 738 <212> PRT <213> capsid protein of AAV serotype, clone AAV8
207. 207

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     Met Ala 1

     Glu Gly

     Lys Ala

     Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 5 10 15 lie Arg Glu Trp Trp Ala Leu Lys Ero Gly Ala Pro Lys Pro 20 25 30

     Asn Gin Gin Lys Gin Asp Asp Gly Arg Gly leu Val Leu Pro 35 40 45

     Gly Tyr 50

     Val Asn 65

     Gin Gin

     Asp Ala

     Asn Leu

     Leu Gly 130

     Pro Val 145

     Gly Lys

     Thr Gly

     Pro Ala

     Gly Ala 210

     Ser Ser 225

     Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp lys Gly Glu Pro 55 60

     Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp 70 75 80

     Leu Gin Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala 85 90 95

     Glu Phe Gin Glu Arg Leu Gin Glu Asp Thr Ser Phe Gly Gly 100 105 110

     Gly Arg Ala Val Phe Gin Ala Lys Lys Arg Val Leu Glu Pro 115 120 125

     Leu Val Glu Glu Gly Ala Lys Thr Ala Pro Gly Lys Lys Arg 135 140

     Glu Pro Ser Pro Gin Arg Ser Pro Asp Ser Ser Thr Gly lie 150 155 160

     Lys Gly Gin Gin Pro Ala Arg Lys Arg Leu Asn Phe Gly Gin 165 170 175

     Asp Ser Glu Ser Val Pro Asp Ero Gin Pro leu Gly Glu Pro 180 185 190

     Ala Pro Ser Gly Val Gly Ero Asn Thr Met Ala Ala Gly Gly 195 200 205

     Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Ser 215 220

     Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val 230 235 240
208. 208

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     Ile Thr Thr Ser Thr 245 Arg Thr Trp Ala Leu 250 . Pro Thr : Tyr Asn . Asn 255 l His 1 Leu Tyr Lys Gln 260 Ile Ser Asn Gly Thr 265 Ser Gly Gly Ala Thr 270 Asn . Asp Asn Thr Tyr 275 Phe Gly Tyr Ser Thr 280 Pro Trp Gly Tyr Phe 285 Asp Phe Asn Arg Phe 290 His Cys His Phe Ser 295 Pro Arg Asp Trp Gln 3 00 Arg Leu lie Asn Asn 305 Asn Trp Gly Phe Arg 310 Pro Lys Arg Leu Ser 315 Phe Lys Leu Phe Asn 320 Ile Gln Val Lys Glu 325 Val Thr Gln Asn Glu 330 Gly Thr Lys Thr Ile 335 Ala Asn Asn Leu Thr 340 Ser Thr Ile Gln Val 345 Phe Thr Asp Ser Glu 350 Tyr Gln Leu Pro Tyr 355 Val Leu Gly Ser Ala 360 His Gln Gly Cys Leu 365 Pro Pro Phe Pro Ala 370 Asp Val Phe Met Ile 375 Pro Gln Tyr Gly Tyr 380 Leu Thr Leu Asn Asn 385 Gly Ser Gln Ala Val 390 Gly Arg Ser Ser Phe 395 Tyr Cys Leu Glu Tyr 400 Phe Pro Ser Gln Met 405 Leu Arg Thr Gly Asn 410 Asn Phe Gln Phe Thr 415 Tyr Thr Phe Glu Asp 420 Val Pro Phe His Ser 425 Ser Tyr Ala His Ser 430 Gln Ser Leu Asp Arg 435 Leu Met Asn Pro Leu 440 lie Asp Gln Tyr Leu 445 Tyr Tyr Leu Ser Arg 450 Thr Gln Thr Thr Gly 455 Gly Thr Ala Asn Thr 460 Gln Thr Leu Gly Phe 465 Ser Gln Gly Gly Pro 470 Asn Thr Met Ala Asn 475 Gln Ala Lys Asn Trp 480 Leu Pro Gly Pro Cys 485 Tyr Arg Gln Gln Arg 490 Val Ser Thr Thr Thr 495 Gly
209. 209

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     Gin Asn Asn Asn 500 Ser Asn Phe Ala Trp 505 Thr Ala . Gly Thr Lys 510 Tyr His Leu Asn Gly 515 Arg Asn Ser Leu Ala 520 Asn Pro Gly Ile Ala 525 Met Ala Thr His Lys 530 Asp Asp Glu Glu Arg 535 Phe Phe Pro Ser Asn 540 Gly Ile Leu lie Phe 545 Gly Lys Gin Asn Ala 550 Ala Arg Asp Asn Ala 555 Asp Tyr Ser Asp Val 560 Met Leu Thr Ser Glu 565 Glu Glu Ile Lys Thr 570 Thr Asn Pro Val Ala 575 Thr Glu Glu Tyr Gly 580 Ile Val Ala Asp Asn 585 Leu Gin Gin Gin Asn 590 Thr Ala Pro Gin Ile 595 Gly Thr Val Asn Ser 600 Gin Gly Ala Leu Pro 605 Gly Met Val Trp Gin 610 Asn Arg Asp Val Tyr 615 Leu Gin Gly Pro lie 620 Trp Ala Lys lie Pro 625 His Thr Asp Gly Asn 630 Phe His Pro Ser Pro 635 Leu Met Gly Gly Phe 640 Gly Leu Lys His Pro 645 Pro Pro Gin Ile Leu 650 Ile Lys Asn Thr Pro 655 Val Pro Ala Asp Pro 660 Pro Thr Thr Phe Asn 665 Gin Ser Lys Leu Asn 670 Ser Phe η β j-S Thr Gin 67 5 Tyr Ser Thr Gly Gin 680 Val Ser Val Glu Ile 685 Glu Trp Glu Leu Gin 690 Lys Glu Asn Ser Lys 695 Arg Trp Asn Pro Glu 700 Ile Gin Tyr Thr Ser 705 Asn Tyr Tyr Lys Ser 710 Thr Ser Val Asp Phe 715 Ala Val Asn Thr Glu 720 Gly Val Tyr Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr . Arg

     725 730 735

     Asn Leu
210. 210

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     <211>

     <212>

     <213>

     <4 0 0>

     Met Ala 1

     736

     PRT capsid protein of AAV serotype, clone 43,21

     Ala Pro 210

     Glu Gly

     Lys Ala

     Gly Tyr 50

     Val Asn 65

     Gin Gin.

     Asp Ala

     Asn Leu

     Leu Gly 130

     Pro Val 145

     Lys Thr

     Gly Asp

     Ala Ala

     Ala Asp Gly 5 Tyr Leu Pro Asp Trp 10 Leu . Glu . Asp lie Arg 20 Glu Trp Trp Asp Leu 25 Lys Pro Gly Ala Asn 35 Gin Gin Lys Gin Asp 40 Asp Gly Arg Gly Leu 45 Lys Ty_r Leu Gly Pro 55 Phe Asn Gly Leu Asp 60 lys Ala Ala Asp Ala 70 Ala Ala Leu Glu His 75 Asp lys Leu Lys Ala 85 Gly Asp Asn Pro Tyr 90 Leu Arg Tyr Glu Phe 100 Gin Glu Arg Leu Gin 105 Glu Asp Thr Ser Gly Arg 115 Ala Val Phe Gin 120 Ala Lys Lys Arg Val 125 Leu Val Glu Glu Gly 135 Ala Lys Thr Ala Pro 140 Gly Glu Gin Ser Pro 150 Gin Glu Pro Asp Ser 155 Ser Ser Gly Gin Gin 165 Pro Ala lys Lys Arg 17 0 Leu Asn Phe Ser Glu 180 Ser Val Pro Asp pro 185 Gin Pro Leu Gly Pro 195 Ser Gly Leu Gly Pro 200 Asn Thr Met Ala Ser 205 Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val

     215 220

     Asn Leu Ser 15

     Pro Lys Pro 30

     Val Leu Pro

     Gly Glu Pro

     Ala Tyr Asp 80

     Asn His Ala 95

     Phe Gly Gly 110

     Leu Glu Pro

     Lys Lys Arg

     Gly He Gly 160

     Gly Gin Thr 175

     Glu Pro Pro 190

     Gly Gly Gly

     Gly Asn Ser
211. 211

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     Ser Gly Asn Trp His Cys 225 230

     Thr Thr Ser Thr Arg 245

     Tyr Lys Gin Ile Ser 260

     Thr Tyr Phe Gly Tyr 275

     Phe His Cys His Phe 2 90

     Asn Trp Gly Phe Arg 305

     Gin Val Lys Glu Val 325

     Asn Leu Thr Ser Thr 340

     Pro Tyr Val Leu Gly 355

     Ala Asp Val Ehe Met 370

     Gly Ser Gin Ala Leu 385

     Ero Ser Gin Met Leu 405

     Ehe Glu Asp Val Pro 420

     Asp Arg Leu Met Asn 435

     Arg Thr Gin Thr Thr 450

     Gin Ala Gly Pro Ser 465

     Asp Ser Thr

     Thr Trp Ala Leu Pro 250

     Asn Gly Thr Ser Gly 265

     Ser Thr Pro Trp Gly 280

     Ser Pro Arg Asp Trp 295

     Pro Lys Arg Leu Asn 310

     Thr Thr Asn Glu Gly 330

     Val Arg Val Phe Thr 345

     Ser Ala His Gin Gly 360

     Val Pro Gin Tyr Gly 375

     Gly Arg Ser Ser Phe 390

     Arg Thr Gly Asn Asn 410

     Phe His Ser Ser Tyr 425

     Pro Leu lie Asp Gin 440

     Gly Thr Gly Gly Thr 455

     Ser Met Ala Asn Gin 470

     Leu Gly Asp Arg Val lie 235 240

     Thr Tyr Asn Asn His Leu 255

     Gly Ser Thr Asn Asp Asn 270

     Tyr Phe Asp Phe Asn Arg 285

     Gin Arg Leu Ile Asn Asn 300

     Phe Lys Leu Phe Asn lie 315 320

     Thr Lys Thr lie Ala Asn 335

     Asp Ser Glu Tyr Gin Leu 350

     Cys Leu Pro Pro Phe Pro 365

     Tyr Leu Thr Leu Asn Asn 380

     Tyr Cys Leu Glu Tyr Ehe 395 400

     Phe Gin Phe Ser Tyr Thr 415

     Ala His Ser Gin Ser Leu 430

     Tyr Leu Tyr Tyr Leu Val 445

     Gin Thr Leu Ala Phe Ser 460

     Ala Arg Asn Trp Val Pro 475 480
212. 212

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     Gly Pro Cys Tyr Arg Gin Gin Arg Val Ser Thr Thr Thr Asn Gin Ser 485 490 495

     Asn Asn Ser Asn Phe Ala Trp Thr Gly Ala Ala Lys Phe Lys Leu Asn 500 505 510

     Gly Arg Asp Ser Leu Met Asn Pro Gly Val Ala Met Ala Ser His Lys 515 520 525

     Asp Asp Asp Asp Arg Phe Phe Pro Ser Ser Gly Val Leu lie Phe Gly 530 535 540

     Lys Gin Gly Ala Gly Asn Asp Gly val Asp Tyr Ser Gin Val Leu lie 545 550 555 560

     Thr Asp Glu Glu Glu He Lys Ala Thr Asn Pro Val Ala Thr Glu Glu 565 570 575

     Tyr Gly Ala val Ala He Asn Asn Gin Ala Ala Asn Thr Gin Ala Gin 580 585 590

     Thr Gly Leu Val His Asn Gin Gly Val He Pro Gly Mat Val Trp Gin 595 600 605

     Asn Arg Asp Val Tyr Leu Gin Gly Pro lie Trp Ala Lys lie Pro His 610 615 620

     Thr Asp Gly Asn Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Leu 625 630 635 640

     Lys His Fro Pro Pro Gin He Leu He Lys Asn Thr Pro Val Pro Ala 645 650 655

     Asp Pro Pro Leu Thr Phe Asn Gin Ala Lys Leu Asn Ser Phe He Thr 660 665 670

     Gin Tyr Ser Thr Gly Gin Val Ser Val Glu He Glu Trp Glu Leu Gin 675 680 685

     Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu He Gin Tyr Thr Ser Asn 690 695 700

     Tyr Tyr Lys Ser Thr Asn Val Asp Phe Ala Val Asn Thr Glu Gly Val 705 710 715 720

     Tyr Ser Glu Pro Arg Pro He Gly Thr Arg Tyr Leu Thr Arg Asn Leu 725 730 735
213. 213

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     Met Ala 1 Ala Asp Gly 5 Tyr Leu . Pro Asp Trp 10 1 Leu Glu Asp Asn . Leu Ser 15 Glu Gly Ile Arg 20 Glu Trp Trp Asp Leu 25 Lys Pro Gly Ala Pro 30 Lys Pro Lys Ala Asn 35 Gin Gin Lys Gin Asp 40 Asp Gly Arg Gly Leu Val 45 Leu Pro Gly Tyr 50 Lys Tyr Leu Gly Pro 55 Phe Asn Gly Leu Asp Lys Gly 60 Glu Pro Val Asn 65 Ala Ala Asp Ala 70 Ala Ala Leu Glu His 75 Asp Lys Ala Tyr Asp 80 Gin Gin Leu Lys Ala 85 Gly Asp Asn Pro Tyr 90 Leu Arg Tyr Asn His Ala 95 Asp Ala Glu Phe 100 Gin Glu Arg Leu Gin 105 Glu Asp Thr Ser Phe 110 Gly Gly Asn Leu Gly 115 Arg Ala Val Phe Gin 120 Ala Lys Lys Arg Val Leu 125 . Glu Pro Leu Gly 130 Leu Val Glu Glu Gly 135 Ala Lys Thr Ala Pro Gly Lys 140 Lys Arg Pro Val 145 Glu Gin Ser Pro 150 Gin Glu Pro Asp Ser 155 Ser Ser Gly Ile Gly 160 Lys Thr Gly Gin Gin 1S5 pro Ala Lys Lys Arg 170 Leu Asn Phe Gly Gin Thr 175 Gly Asp Ser Glu 180 Ser Val Pro Asp Pro 185 Gin Pro Leu Gly Glu 190 Pro Pro Ala Ala Pro 195 Ser Gly Leu Gly Pro 200 Asn Thr Met Ala Ser Gly 205 Gly Gly Ala Pro 210 Met Ala Asp Asn Asn 215 Glu Gly Ala Asp Gly Val Gly 220 Asn Ser Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg ' Val Ile

     225 230 235 240
214. 214

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     Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu

     245 250 255

     2015258271 20 Nov 2015

     Tyr Lys Gin Ile Ser Asn Gly Thr Ser Gly Gly Ser Thr Asn Asp Asn 260 265 270

     Thr Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg 275 280 285

     Phe His Cys His Phe Ser Pro Arg Asp Trp Gin Arg Leu Ile Asn Asn 290 295 300

     Asn Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn lie 305 310 315 320

     Gin Val Lys Glu Val Thr Thr Asn Glu Gly Thr Lys Thr Ile Ala Asn 325 330 335

     Asn Leu Thr Ser Thr Val Gin Val Phe Thr Asp Ser Glu Tyr Gin Leu 340 345 350

     Pro Tyr Val Leu Gly Ser Ala His Gin Gly Cys Leu Ero Ero Ehe Ero 355 360 365

     Ala Asp Val Phe Met Val Pro Gin Tyr Gly Tyr Leu Thr Leu Asn Asn 370 375 380

     Gly Ser Gin Ala Leu Gly Arg Ser Ser Phe Tyr Cvs Leu Glu Tyr Phe 385 390 395 400

     Pro Ser Gin Met Leu Arg Thr Gly Asn Asn Phe Gin Phe Ser Tvr Thr 405 410 415

     Phe Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gin Ser Leu 420 425 430

     Asp Arg Leu Met Asn Pro Leu lie Asp Gin Tyr Leu Tyr Tyr Leu Val 435 440 445

     Arg Thr Gin Thr Thr Gly Thr Gly Gly Thr Gin Thr Leu Ala Phe Ser 450 455 460

     Gin Ala Gly Pro Ser Ser Met Ala Asn Gin Ala Arg Asn Trp Val Pro 465 470 475 480

     Gly Pro Cys Tyr Arg Gin Gin Arg Val Ser Thr Thr Thr Asn Gin Asn 485 490 495
215. 215

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     Asn Asn Ser Asn Phe Ala Trp Thr Gly Ala Ala Lys Phe Lys Leu Asn 500 505 510

     Gly Arg Asp Ser Leu Met Asn Pro Gly Val Ala Met Ala Ser His Lys 515 520 525

     Asp Asp Asp Asp Arg Phe Phe Pro Ser Ser Gly Val leu lie phe Gly 530 535 540

     Lys Gin Gly Ala Gly Asn Asp Gly Val Asp Tyr Ser Gin Val Leu He 545 550 555 560

     Thr Asp Glu Glu Glu lie Lys Ala Thr Asn Pro Val Ala Thr Glu Glu 565 570 575

     Tyr Gly Ala Val Ala lie Asn Asn Gin Ala Ala Asn Thr Gin Ala Gin 580 585 590

     Thr Gly Leu Val His Asn Gin Gly Val He Pro Gly Met Val Trp Gin 595 600 605

     Asn Arg Asp Val Tyr Leu Gin Gly Pro lie Trp Ala Lys He Pro His 610 615 620

     Thr Asp Gly Asn Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Leu 625 630 635 640

     Lys His Pro Pro Pro Gin Tie Leu lie Lys Asn Thr Pro Val Pro Ala 645 650 655

     Asp Pro Pro Leu Thr Phe Asn Gin Ala Lys Leu Asn Ser Phe He Thr 660 665 670

     Gin Tyr Ser Thr Gly Gin Val Ser val Glu He Glu Trp Glu Leu Gin 675 680 685

     Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu He Gin Tyr Thr ser Asn 690 695 700

     Tyr Tyr Lys ser Thr Asn Val Asp Phe Ala Val Asn Thr Glu Gly val 705 710 715 720

     Tyr Ser Glu Pro Arg Pro He Gly Thr Arg Tyr Leu Thr Arg Asn Leu 725 730 735
216. 216

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     2015258271 20 Nov 2015 <210> 98 <211> 736 <212> PRT <213> capsid protein of AAV serotype, clone 43.23

     <400> Met Ala 1 98 Ala Asp Gly Tyr leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 5 10 15 Glu Gly Ile Arg Glu Trp Trp Asp 20 Leu Lys 25 Pro Gly Ala Pro Lys pro 30 Lys Ala Asn Gln Gln Lys Gln Asp 35 40 Asp Gly Arg Gly Leu Val Leu Pro 45 Gly Tyr 50 Lys Tyr Leu Gly Pro Phe 55 Asn Gly Leu Asp Lys Gly Glu pro 60 Val Asn 65 Ala Ala Asp Ala Ala Ala 70 Leu Glu His Asp Lys Ala Tyr Asp 75 80 Gln Gln Leu Lys Ala Gly Asp Asn 85 Pro Tyr 90 Leu Arg Tyr Asn His Ala 95 Asp Ala Glu Phe Gln Glu Arg Leu 100 Gln Glu 105 Asp Thr Ser Phe Gly Gly 110 ~ Asn Leu Gly Arg Ala Val Phe Gln 115 120 Ala Lys Lys Arg Val Leu Glu Pro 125 Leu Gly 13 0 Leu Val Glu Glu Gly Ala 135 Lys Thr Ala Pro Gly Lys Lys Arg 140 Pro Val 145 Glu Gln Ser Pro Gln Glu 150 Pro Asp Ser Ser Ser Gly Ile Gly 155 160 Lys Thr Gly Gln Gln Pro Ala Lys 165 Lys Arg 170 Leu Asn Phe Gly Gln Thr 175 Gly Asp Ser Glu Ser Val Pro Asp 180 Pro Gln 185 Pro Leu Gly Glu Pro Pro 190 Ala Ala Pro Ser Gly Leu Gly Pro 195 200 Asn Thr Met Ala Ser Gly Gly Gly 205 Ala Pro 210 Met Ala Asp Asn Asn Glu 215 Gly Ala Asp Gly Val Gly Asn Ser 220 Ser Gly 225 Asn Trp His Cys Asp Ser 230 Thr Trp Leu Gly Asp Arg Val Ile 235 240
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     Thr Thr Ser Thr Arg Thr Trp Ala leu Pro Thr Tyr Asn Asn His Leu 245 250 255

     Tyr Lys Gin Ile Ser Asn Gly Thr Ser Gly Gly Ser Thr Asn Asp Asn 260 265 270

     Thr Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg 275 280 285

     Phe His cys His Phe Ser Pro Arg Asp Trp Gin Arg leu Ile Asn Asn 290 295 300

     Asn Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys leu Phe Asn Ile 305 310 315 320

     Gin Val Lys Glu Val Thr Thr Asn Glu Gly Thr Lys Thr Ile Ala Asn 325 330 335

     Asn Leu Thr Ser Thr Val Gin Val Phe Thr Asp Leu Glu Tyr Gin Leu 340 345 350

     Pro Tyr Val Leu Gly Ser Ala His Gin Gly Cys Leu Pro Pro Phe Pro ' 355 360 365

     Ala Asp Val Phe Met Val Pro Gin Tyr Gly Tyr Leu Thr Leu Asn Asn 370 375 380

     Gly Ser Gin Ala Leu Gly Arg Ser Ser Phe Tyr Cys leu Glu Tyr Phe 385 390 395 400

     Pro Ser Gin Met Pro Arg Thr Gly Asn Asn Phe Gin Phe Ser Tyr Thr 405 410 415

     Phe Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gin Ser Leu 420 425 430

     Asp Arg Leu Met Asn Pro Leu Ile Asp Gin Tyr Leu Tyr Tyr Leu Val 435 440 445

     Arg Thr Gin Thr Thr Gly Thr Gly Gly Thr Gin Thr leu Ala Phe Ser 450 455 460

     Gin Ala Gly Pro Ser Ser Met Ala Asn Gin Ala Arg Asn Trp Val Pro 465 470 475 480

     Gly Pro Cys Tyr Arg Gin Gin Arg val Ser Thr Thr Thr Asn Gin Asn 485 490 495
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     Asn. Asn Ser Asn Phe Ala Trp Thr Gly Ala Ala Lys Phe Lys Leu Asn 500 505 510

     Gly Arg Asp Ser Leu Met Asn Pro Gly Val Ala Met Ala Ser His Lys 515 520 525

     Asp Asp Asp Asp Arg Phe Phe Pro Ser Ser Gly Val Leu lie Phe Gly 530 535 540

     Lys Gin Gly Ala Gly Asn Asp Gly Val Asp Tyr Ser Gin Val Leu lie 545 550 555 560

     Thr Asp Glu Glu Glu He Lys Ala Thr Asn Pro Val Ala Thr Glu Glu 565 570 575

     Tyr Gly Ala Val Ala lie Asn Asn Gin Ala Ala Asn Thr Gin Ala Gin 580 585 590

     Thr Gly Leu Val His Asn Gin Gly Val He Pro Gly Met Val Trp Gin 5 9 5 600 605

     Asn Arg Asp Val Tyr Leu Gin Gly Pro He Trp Ala Lys Ils Pro His 610 615 620

     Thr Asp Gly Asn Phe His Pro Ser Pro Leu Met Gly Gly phe Gly Leu 625 630 635 640

     Lys His Pro Pro Pro Gin He Leu lie Lys Asn Thr Pro Val Pro Ala 645 650 655

     Asp Pro Pro Leu Thr Phe Asn Gin Ala Lys Leu Asn Ser Phe He Thr 660 665 670

     Gin Tyr Ser Thr Gly Gin Val Ser Val Glu lie Glu Trp Glu Leu Gin 675 680 685

     Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu He Gin Tyr Thr Ser Asn 690 695 700

     Tyr Tyr Lys Ser Thr Asn Val Asp Phe Ala Val Asn Thr Glu Gly Val 705 710 715 720

     Tyr Ser Glu Pro Arg Pro He Gly Thr Arg Tyr Leu Thr Arg Asn Leu 725 730 735
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     2015258271 20 Nov 2015 <210> 99 <211> 736 <212> PRT <213> capsid protein of AAV serotype, clone 43.20

     <400> Met Ala 1 99 Ala Asp Gly Tyr 5 Leu Pro Asp Trp 10 Leu Glu Asp Asn Leu Ser 15 Glu Gly Ile Arg Glu Trp 20 Trp Asp Leu 25 Lys Pro Gly Ala Pro Lys Pro 30 Lys Ala Asn 35 Gln Gln Lys Gln Asp 40. Asp Gly Arg Gly Leu 45 Val Leu Pro Gly Tyr 50 Lys Tyr Leu Gly Pro 55 Phe Asn Gly Leu Asp Lys 60 Gly Glu Pro Val Asn 65 Ala Ala Asp Ala 70 Ala Ala Leu Glu His Asp Lys 75 Ala Tyr Asp 80 Gln Gln Leu Lys Ala Gly Asp 85 Asn Pro Tyr 90 Leu Arg Tyr Asn His Ala 95 Asp Ala Glu Phe Gln Glu 100 Arg Leu Gln 105 Glu Asp Thr Ser Phe Gly Gly 110 Asn Leu Gly 115 Arg Ala Val Phe Gln 120 Ala Lys Lys Arg Val 125 Leu Glu Pro Leu Gly 130 Leu Val Glu Glu Gly 135 Ala Lys Thr Ala Pro Gly 140 Lys Lys Arg Leu Val 145 Glu Gln Ser Pro 150 Gln Glu Pro Asp Ser Ser Ser 155 Gly Ile Gly 160 Lys Thr Gly Gln Gln Pro 165 Ala Lys Lys Arg 170 Leu Asn Phe Gly Gln Thr 175 Gly Asp Ser Glu Ser Val 180 Pro Asp Pro 185 Gln Pro Leu Gly Glu Pro Pro 190 Ala Ala Pro 195 Ser Gly Leu Gly Pro 200 Asn Thr Met Ala Ser 205 Gly Gly Gly Ala Pro 210 Met Ala Asp Asn Asn 215 Glu Gly Ala Asp Gly Val 220 Gly Asn ser Ser Gly 225 Asn Trp His Cys 230 Asp Ser Thr Trp Leu Gly Asp 235 Arg Val lie 240
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     Thr Thr Ser Thr Arg 245 Thr Trp Ala Leu Pro 250 Thr Tyr Asn . Asn . His 255 Leu Tyr Lys Gln. Ile 260 Ser Asn Gly Thr Ser 265 Gly Gly Ser Thr Asn 270 Asp Asn Thr Tyr Phe 275 Gly Tyr Ser Thr Pro 280 Trp Gly Tyr Phe ASp 285 Phe Asn Arg Phe His 290 Cys His Phe Ser Pro 295 Arg Asp' Trp Gln Arg 3 00 Leu Ile Asn Asn Asn 305 Trp Gly Phe Arg Pro 310 Lys Arg Leu Asn Phe 315 Lys Leu Phe Asn Ile 320 Gln Val Lys Glu Val 325 Thr Thr Asn Glu Gly 330 Thr Lys Thr Ile Ala 335 Asn Asn Leu Thr Ser 340 Thr Val Gln Val Phe 345 Thr Asp Ser Glu Tyr 350 Gln Leu Pro Tyr Val 355 Leu Gly Ser Ala His 360 Gln Gly Cys Leu Pro 365 Pro Phe Pro Ala Asp 370 Val Phe Thr Val Pro 375 Gln Tyr Gly Tyr Leu 380 Thr Leu Asn Asn Gly 385 Ser Gln Ala Leu Glv 390 Arg Ser Ser Phe Tyr 395 Cys Leu Glu Tyr Phe 400 Pro Ser Gln Met Leu 405 Arg Thr Gly Asn Asn 410 Phe Gln Phe Ser Tyr 415 Thr Phe Glu Asp Val 420 Pro Phe His Ser Ser 425 Tyr Ala His Ser Gln 430 Ser Leu Asp Arg Leu 435 Met Asn Pro Leu lie 440 Asp Gln Tyr Leu Tyr 445 Tyr Leu Val Arg Thr 450 Gln Thr Thr Gly Thr 455 Gly Gly Thr Gln Thr 460 Leu Ala Phe Ser Gln 465 Ala Gly Pro Ser Ser 470 Met Ala Asn Gln Ala 475 Arg Asn Trp Val Pro 480 Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Thr Thr Thr . Asn Gln Asn

     485 490 495
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     Asn Asn Ser Asn 500 Phe Ala Trp Thr Gly 505 Ala Ala Lys Phe Lys 510 Leu Asn Gly Arg Asp 515 Ser Leu Met Asn Pro 520 Gly Val Ala Met Ala 525 Ser His Lys Asp Asp 530 Asp Asp Arg Phe Phe 535 Pro Ser Ser Gly Val 540 Leu lie Phe Gly Lys 545 Gln Gly Ala Gly Asn 550 Asp Gly Val Asp Tyr 555 Ser Gln Val Leu Ile 560 Thr Asp Glu Glu Glu 565 Ile Lys Ala Thr Asn 570 Pro Val Ala Thr Glu 575 Glu Tyr sly Ala Val 580 Ala Ile Asn Asn Gln 585 Ala Ala Asn Thr Gln 590 Ala Gln Thr Gly Leu 595 Val His Asn Gln Gly 600 Val lie Pro Gly Met 605 Val Trp Gln Asn Arg 610 Asp Val Tyr Leu Gln 615 Gly. Pro Ile Trp Ala 620 Lys Ile Pro His Thr 625 Asp Gly Asn Phe His 630 Pro Ser Pro Leu Met 635 Gly Gly Phe Gly Leu 640 Lys His Pro Pro Pro 645 Gln lie Leu lie Lys 650 Asn Thr Pro Val Pro 655 Ala Asp Pro Pro Leu 660 Thr Phe Asn Gln Ala 665 Lys Leu Asn Ser Phe 670 Ile Thr Gln Tyr Ser 675 Thr Gly Gln Val Ser 680 Val Glu Ile Glu Trp 685 Glu Leu Gln Lys Glu 690 Asn Ser Lys Arg Trp 695 Asn Pro Glu lie Gln 700 Tyr Thr Ser Asn Tyr 705 Tyr Lys Ser Thr Asn 710 Val Asp Phe Ala Val 715 Asn Thr Glu Gly Val 720 Tyr Ser Glu Pro Arg Pro lie Gly Thr Arg Tyr Leu Thr . Arg . Asn Leu

     725 730 735 <210> 100 <211> 736 <212> PRT <213> capsid protein of AAV serotype, clone AAV9
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     400> 100

     Met Ala Ala Asp Gly Tyr leu Pro Asp Trp Leu Glu Asp Asn leu Ser 15 10 15

     Glu Gly Ile Arg Glu Trp Trp Asp Leu lys Pro Gly Ala Pro lys Pro 20 25 30 lys Ala Asn Gln Gln Lys Gln Asp Asp Gly Arg Gly Leu Val Leu Pro 35 40 45

     Gly Tyr Lys Tyr leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro 50 55 60

     Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp lys Ala Tyr Asp 65 70 75 80

     Gln Gln leu lys Ala Gly Asp Asn Ero Tyr leu Arg Tyr Asn His Ala 85 90 95

     Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr Ser Phe Gly Gly 100 105 110

     Asn Leu Gly Arg Ala Val phe Gln Ala Lys Lys Arg Val Leu Glu Ero 115 120 125

     Leu Gly Leu Val Glu Glu Gly Ala lys Thr Ala Pro Gly lys lys Arg 130 135 140

     Ero Val Glu Gln Ser Pro Gln Glu Pro Asp Ser Ser Ser Gly lie Gly 145 150 155 160

     Lys Ser Gly Gln Gln Pro Ala Lys lys Arg leu Asn Phe Gly Gln Thr 165 170 175

     Gly Asp Ser Glu Ser Val pro Asp Pro Gln Pro leu Gly Glu Pro Pro 180 185 190

     Glu Ala Pro Ser Gly leu Gly Pro Asn Thr Met Ala Ser Gly Gly Gly 195 200 205

     Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn Ser 210 215 220

     Ser Gly Asn Trp His Cys Asp Ser Thr Trp leu Gly Asp Arg Val Ile 225 230 235 240

     Thr Thr Ser Thr Arg Thr Trp Ala leu Pro Thr Tyr Asn Asn His leu 245 250 255
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     Tyr Lys Gin lie Ser Asn Gly Thr Ser Gly Gly Ser Thr Asn Asp Asn

     260 265 270

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     Thr Tyr Ehe Gly Tyr Ser Thr Ero Trp Gly Tyr Phe Asp Ehe Asn Arg 275 280 265

     Ehe His Cys His Ehe Ser Ero Arg Asp Trp Gin Arg leu Ile Asn Asn 290 295 300

     Asn Trp Gly Ehe Arg Ero Lys Arg Leu Asn Ehe Lys leu Ehe Asn lie 305 310 315 320

     Gin Val Lys Glu Val Thr Thr Asn Glu Gly Thr Lys Thr lie Ala Asn 325 330 335

     Asn Leu Thr Ser Thr Val Gin Val Ehe Thr Asp Ser Glu Tyr Gin Leu 340 345 350

     Ero Tyr Val Leu Gly Ser Ala His Gin Gly Cys Leu Ero Ero Phe Pro 355 360 365

     Ala Asp Val Ehe Met Val Ero Gin Tyr Gly Tyr Leu Thr Leu Asn Asn 370 375 380

     Gly Ser Gin Ala Leu Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe 385 390 395 400

     Pro Ser Gin Met Leu Arg Thr Gly Asn Asn Ehe Gin Phe Ser Tyr Thr 405 410 415

     Ehe Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gin Ser Leu 420 425 430

     Asp Arg Leu Met Asn Ero Leu Ile Asp Gin Tyr Leu Tyr Tyr Leu Val 435 440 445

     Arg Thr Gin Thr Thr Gly Thr Gly Gly Thr Gin Thr Leu Ala Phe Ser 450 455 460

     Gin Ala Gly Pro Ser Ser Met Ala Asn Gin Ala Arg Asn Trp Val Ero 465 470 475 480

     Gly Ero Cys Tyr Arg Gin Gin Arg Val Ser Thr Thr Thr Asn Gin Asn 485 490 495

     Asn Asn Ser Asn Ehe Ala Trp Thr Gly Ala Ala Lys Phe Lys Leu Asn 500 505 510
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     Gly Arg Asp Ser Leu Met Asn Pro Gly Val Ala Met Ala ser His Lys 515 520 525

     Asp Asp 530 Glu Asp Arg Phe Phe 535 Pro Ser Ser Gly Val 540 Leu lie Phe : Gly Lys 545 Gin Gly Ala Gly Asn 550 Asp Gly Val Asp Tyr 555 ser Gin Val Leu He 560 Thr Asp Glu Glu Glu 565 lie Lys Ala Thr Asn 570 Pro Val Ala Thr Glu 575 Glu Tyr Gly Ala Val 580 Ala lie Asn Asn Gin 585 Ala Ala Asn Thr Gin. 590 Ala Gin Thr Gly Leu 595 Val His Asn Gin Gly 600 Val lie Pro Gly Met 605 Val Trp Gin Asn Arg 610 Asp Val Tyr Leu Gin 615 Gly Pro He Trp Ala 620 Lys He Pro His Thr 62-5 Asp Gly Asn Phe His 630 Pro Ser Pro Leu Met 635 Gly Gly Phe Gly Leu 640 Lys His Pro Pro Pro 645 Gin He Leu He Lys 650 Asn Thr Pro Val Pro 655 Ala Asp Pro Pro Leu 6 60 Thr Phe Asn Gin Ala 665 Lys Leu Asn Ser Phe 670 lie Thr Gin Tyr Ser 675 Thr Gly Gin Val Ser 680 Val Glu He Glu Trp 685 Glu Leu Gin Lys Glu 690 Asn Ser Lys Arg Trp 695 Asn Pro Glu lie Gin 700 Tyr Thr Ser Asn Tyr 705 Tyr Lys Ser Thr Asn 710 Val Asp Phe Ala Val 715 Asn Thr Glu Gly Val 720 Tyr Ser Glu Pro Arg 725 Pro lie Gly Thr Arg 730 Tyr Leu Thr Arg Asn 735 Leu

     <210> 101 <211> 728 <212> PRT <213> capsid protein of AAV serotype, clone 24.1 <400> 101

     Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 15 10 15
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     Glu Gly lie Arg Glu Trp Trp Asp Leu Lys Ero Gly Ala Ero Lys Ero 20 25 30

     Lys Ala Asn Gin Gin Lys Gin Asp Asp Gly Arg Gly Leu Val Leu Ero 35 40 45

     Gly Tyr Lys Tyr Leu Arg Ero phe Asn Gly Leu Asp Lys Gly Glu Pro 50 55 60

     Val Asn Glu Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp 65 70 75 80

     Lys Gin Leu Glu Gin Gly Asp Asn Pro Tyr Leu Lys Tyr Asn His Ala 85 90 95

     Asp Ala Glu Phe Gin Glu Arg Leu Gin Glu Asp Thr Ser phe Gly Gly 100 105 110

     Asn Leu Gly Arg Ala Val Phe Gin Ala Lys Lys Arg Val Leu Glu Pro 115 120 125

     Leu Gly Leu Val Glu Glu Val Ala Lys Thr Ala Pro Gly Lys Lys Arg 130 135 140

     Pro lie Glu Ser Pro Asp Ser Ser Thr Gly lie Gly Lys Lys Gly Gin 145 150 155 160

     Gin Pro Ala Lys Lys Lys Leu Asn Phe Gly Gin Thr Gly Asp Ser Glu 165 170 175

     Ser Val Pro Asp Pro Gin Pro Leu Gly Glu Pro pro Ala Ala Pro Ser 180 185 190

     Gly Leu Gly Ser Gly Thr Met Ala Ala Gly Gly Gly Ala Ero Met Ala 195 200 205

     Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn Ala Ser Gly Asn Trp 210 215 220

     His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val lie Thr Thr Ser Thr 225 230 235 240

     Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu Tyr Lys Gin He 245 250 255

     Ser Ser Gin Ser Gly Ala Thr Asn Asp Asn His Phe Phe Ser Tyr ser 260 265 270
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     Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe His Cys His Phe Ser

     275 280 285

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     Pro Arg Asp Trp Gin Arg Leu Ile Asn Asn Asn Trp Gly Phe Arg Pro 290 295 300

     Arg Lys Leu Arg Phe Lys Leu Phe Asn Ile Gin Val Lys Glu Val Thr 305 310 315 320

     Thr Asn Asp Gly Val Thr Thr Ile Ala Asn Asn Leu Thr Ser Thr Ile 325 330 335

     Gin Val Phe Ser Asp Ser Glu Tyr Gin Leu Pro Tyr Val Leu Gly Ser 340 345 350

     Ala His Gin Gly Cys Leu Pro Pro Phe Pro Ala Asp Val Phe Met Ile 355 360 365

     Pro Gin Tyr Gly Tyr Leu Thr Leu Asn Asn Gly Ser Gin Ser Val Gly 370 375 380

     Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro Ser Gin Met Leu Arg 385 390 395 400

     Thr Gly Asn Asn Phe Glu Phe Ser Tyr Thr Phe Glu Glu Val Pro Phe 405 410 415

     His Ser Ser Tyr Val His Ser Gin Ser Leu Asp Arg Leu Met Asn Pro 420 425 430

     Leu Ile Asp Gin Tyr Leu Tyr Tyr Leu Ala Arg Thr Gin Ser Thr Thr 435 440 445

     Gly Ser Thr Arg Glu Leu Gin Phe His Gin Ala Gly Pro Asn Thr Met 450 455 460

     Ala Glu Gin Ser Lys Asn Trp Leu Pro Gly Pro Cys Tyr Arg Gin Gin 465 470 475 480

     Arg Leu Ser Lys Asn Ile Asp Ser Asn Asn Asn Ser Asn Phe Ala Trp 485 490 495

     Thr Gly Ala Thr Lys Tyr His Leu Asn Gly Arg Asn Ser Leu Thr Asn 500 505 510

     Pro Gly Val Ala Met Ala Thr Asn Lys Asp Asp Glu Asp Gin Phe Phe 515 520 525
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     Pro lie 530 Asn Gly Val Leu Val Phe 535 Gly Lys Thr Gly Ala Ala Asn Lys 540 Thr Thr Leu Glu Asn Val Leu Met Thr Ser Glu Glu Glu lie Lys Thr 545 550 555 560 Thr Asn Pro Val Ala Thr Glu Glu Tyr Gly Val Val Ser Ser Asn Leu 565 570 575 Gin Ser Ser Thr Ala Gly Pro Gin Thr Gin Thr Val Asn Ser Gin Gly 580 585 590 Ala Leu Pro Gly Met Val Trp Gin Asn Arg Asp Val Cys Leu Gin Gly 595 600 605 Pro lie Trp Ala Lys lie Pro His Thr Asp Gly Asn Phe His Pro Ser 610 615 620 Pro Leu Met Gly Gly Phe Gly Leu Lys His Pro Pro Pro Gin lie Leu 625 630 635 640 lie Lys Asn Thr Pro Val pro Ala Asn Pro Pro Glu Val Phe Thr Pro 645 650 655 Ala Lys Phe Ala Ser Phe lie Thr Gin Tyr Ser Thr Gly Gin Val Ser 660 665 670 Val Glu lie Glu Trp Glu Leu Gin Lys Glu Asn Ser Lys Arg Trp Asn 675 680 685 Pro Glu lie Gin Tyr Thr Ser Asn Tyr Ala Lys Ser Asn Asn Val Glu 690 695 700 Phe Ala Val Asn Asn Glu Gly Val Tyr Thr Glu Pro Arg Pro He Gly 705 710 715 720 Thr Arg Tyr Leu Thr Arg Asn Leu

     725 <210> 102 <211> 728 <212> PRT <213> capsid protein of AAV serotype, clone 42.2REAL <400> 102

     Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 15 10 15
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     Glu Gly Ile Arg Glu Trp Trp Asp leu lys Pro Gly Ala Pro lys Pro 20 25 30 lys Ala Asn Gln Gln lys Gln Asp Asp Gly Arg Gly leu Val leu Pro 35 40 45

     Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly leu Asp lys Gly Glu Pro 50 55 60

     Val Asn Glu Ala Asp Ala Ala Ala leu Glu His Asp lys Ala Tyr Asp 65 70 75 80

     Lys Gln leu Glu Gln Gly Asp Asn Pro Tyr Leu lys Tyr Asn His Ala 85 90 95

     Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr Ser Phe. Gly Gly 100 105 110

     Asn leu Gly Arg Ala Val Phe Gln Ala lys Lys Arg Val leu Glu Pro 115 120 125 leu Gly leu Val Glu Glu Gly Ala lys Thr Ala Pro Gly lys lys Arg

     130

     135 140

     Pro lie Glu Ser Pro Asp 145 150

     Ser Ser Thr Gly lie Gly Lys Lys Gly Gln 155 160

     Gln Pro Ala lys lys lys 165

     Leu Asn Phe Gly Gln Thr Gly Asp Ser Glu 170 175

     Ser Val Pro Asp Pro Gln 180

     Pro Leu Gly Glu Pro Pro Ala Ala Pro Ser 185 190

     Gly leu Gly Ser Gly Thr 195

     Met Ala Ala Gly Gly Gly Ala Pro Met Ala 200 205

     Asp Asn Asn Glu Gly Ala 210

     Asp Gly Val Gly Asn Ala Ser Gly Asn Trp 215 220

     His Cys Asp Ser Thr Trp 225 230

     Leu Gly Asp Arg Val Ile Thr Thr Ser Thr 235 240

     Arg Thr Trp Ala leu Pro 245

     Thr Tyr Asn Asn His Leu Tyr Lys Gln lie 250 255

     Ser Ser Gln Ser Gly Ala 260

     Thr Asn Asp Asn His Phe Phe Gly Tyr Ser 265 270
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     Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe His Cys His Phe Ser 275 280 285

     Pro Arg Asp Trp Gin Arg Leu lie Asn Asn Asn Trp Gly Phe Arg Pro 290 295 300

     Arg Lys Leu Arg Phe Lys Leu Phe Asn Ile Gin Val Lys Glu Val Thr 305 310 315 320

     Thr Asn Asp Gly Val Thr Thr Ile Ala Asn Asn Leu Thr Ser Thr Ile 325 330 335

     Gin Val Phe Ser Asp Ser Glu Tyr Gin Leu Pro Tyr Val Leu Gly Ser 340 345 350

     Ala His Gin Gly Cys Leu Pro Pro Phe Pro Ala Asp Val Phe Met lie 355 360 365

     Pro Gin Tyr Gly Tyr Leu Thr Leu Asn Asn Gly Ser Gin Ser Val Gly 370 375 380

     Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro Ser Gin Met Leu Arg 385 390 395 400

     Thr Gly Asn Asn Phe Glu Phe Ser Tyr Thr Ehe Glu Glu Val Pro Phe 405 410 415

     His Ser Ser Tyr Ala His Ser Gin Ser Leu Asp Arg Leu Met Asn Ero 420 425 430

     Leu Ile Asp Gin Tyr Leu Tyr Tyr Leu Ala Arg Thr Gin Ser Thr Thr 435 440 445

     Gly Ser Thr Arg Glu Leu Gin Ehe His Gin Ala Gly Ero Asn Thr Met 450 455 460

     Ala Glu Gin Ser Lys Asn Trp Leu Pro Gly Pro Cys Tyr Arg Gin Gin 465 470 475 480

     Arg Leu Ser Lys Asn Ile Asp Ser Asn Asn Asn Ser Asn Phe Ala Trp 485 490 495

     Thr Gly Ala Thr Lys Tyr His Leu Asn Gly Arg Asn Ser Leu Thr Asn 500 505 510

     Pro Gly Val Ala Met Ala Thr Asn Lys Asp Asp Glu Asp Gin Ehe Ehe 515 520 525
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     Ero lie Asn Gly Val Leu Val Ehe Gly Glu Thr Gly Ala Ala Asn Lys 530 535 540

     Thr Thr Leu Glu Asn Val Leu Met Thr Ser Glu Glu Glu lie Lys Thr 545 550 555 560

     Thr Asn Pro Val Ala Thr Glu Glu Tyr Gly Val Val Ser Ser Asn Leu 565 570 575

     Gin Ser Ser Thr Ala Gly Ero Gin Thr Gin Thr Val Asn Ser Gin Gly 5S0 585 590

     Ala Leu Pro Gly Met Val Trp Gin Asn Arg Asp Val Tyr Leu Gin Gly 595 600 605

     Pro lie Trp Ala Lys He Pro His Thr Asp Gly Asn Phe His Pro Ser 610 615 620

     Ero Leu Met Gly Gly Phe Gly Leu Lys His Pro Pro Pro Gin lie Leu 625 630 635 640 lie lys Asn Thr Ero Val Ero Ala Asn Pro Pro Glu Val Ehe Thr Ero 645 650 655

     Ala Lys Phe Ala Ser Phe Xie Thr Gin Tyr Ser Thr Gly Gin Val Ser 660 665 670

     Val Glu He Glu Trp Glu Leu Gin Lys Glu Asn Ser Lys Arg Trp Asn 675 680 685

     Pro Glu lie Gin Tyr Thr Ser Asn Tyr Ala Lys Ser Asn Asn Val Glu 690 695 700

     Ehe Ala Val Asn Asn Glu Gly Val Tyr Thr Glu Pro Arg Pro Xie Gly 705 710 715 720

     Thr Arc Tvr Leu Thr Arg Asn Leu 725 <210> 103 <211> 728 <212> ERT <213> capsid protein of AAV serotype, clone 7.2VP1 <400> 103

     Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Gly Asn leu Ser 15 10 15

     Glu Gly lie Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro 20 25 30
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     Lys Ala Asn 35 Gin Gin Lys Gin Asp 40 Asp Gly Arg Gly ' Leu 45 l Val leu Pro Gly Tyr 50 Arg Tyr Leu Gly Ero 55 Phe Asn Gly Leu Asp 60 Lys Gly Glu i Ero Val 65 Asn Glu Ala Asp Ala 70 Ala Ala Leu Glu His 75 Asp Lys Ala Tyr Asp 80 Lys Gin Leu Glu Gin 85 Gly Asp Asn Ero Tyr 90 Leu Lys Tyr Asn His 95 Ala Asp Ala Glu Ehe 100 Gin GlU Arg Leu Gin 105 Glu Asp Thr Ser Ehe 110 Gly Gly Asn Leu Gly Arg 115 Ala val Phe Gin 120 Ala Lys Lys Arg Val 125 Leu Glu Pro Leu Gly 130 Leu Val Glu Glu Gly 135 Ala lys Thr Ala Ero 140 Gly Lys Lys Arg Ero 145 lie Glu Ser Pro Asp 150 Ser Ser Thr Gly lie 155 Gly Lys Asn Gly Gin 160 Ero Pro Ala Lys Lys 165 Lys Leu Asn Ehe Gly 170 Gin Thr Gly Asp Ser 175 Glu Ser Val Pro Asp 180 Pro Gin Ero Leu Gly 185 Glu Ero Pro Ala Ala 190 Ero Ser Gly Leu Gly iss Ser Gly Thr Met Ala 200 Ala Gly Gly Gly Ala 205 Ero Met Ala Asp Asn 210 Asn Glu Gly Ala Asp 215 Gly Val Gly Asn Ala 220 Ser Gly Asn Trp His 225 Cys Asp Ser Thr Trp 230 Leu Gly Asp Arg Val 235 lie Thr Thr Ser Thr 240 Arg Thr Trp Ala Leu 245 Pro Thr Tyr Asn Asn 250 His Leu Tyr Lys Gin 255 Ile Ser Ser Gin Ser 260 Gly Ala Thr Asn Asp 2 65 Asn His Ehe Ehe Gly 270 Tyr Ser Thr Pro Trp Gly Tyr Ehe Asp Ehe Asn Arg Ehe His cys His Ehe Ser

     275 280 285
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     Pro Arg Asp Trp Gin Arg leu lie Asn Asn Asn Trp Gly Phe Arg Pro 290 295 300

     Arg lys leu Arg Phe lys leu Phe Asn He Gin Val lys Glu Val Thr 305 310 315 320

     Thr Asn Asp Gly Val Thr Thr He Ala Asn Asn leu Thr Ser Thr He 325 330 335

     Gin Val Phe ser Asp ser Glu Tyr Gin leu Pro Tyr Val leu Gly ser 340 345 350

     Ala His Gin Gly Cys leu Pro Pro Phe Pro Ala Asp Val Phe Met He 355 360 365

     Pro Gin Tyr Gly Tyr leu Thr Leu Asn Asn Gly Ser Gin Ser Val Gly 370 375 380

     Arg Ser ser Phe Tyr Cys leu Glu Tyr Phe Pro Ser Gin Met leu Arg 385 390 395 400

     Thr Gly Asp Asn Phe Glu Phe Ser Tyr Thr Phe Glu Glu Val Pro Phe 405 410 415

     His Ser Sex Tyr Ala His Ser Gin Ser Leu Asp Arg leu Met Asn Pro 420 425 430 leu He Asp Gin Tyr Leu Tyr Tyr leu Ala Arg Thr Gin Ser Thr Thr 435 440 445

     Gly Ser Thr Arg Glu Leu Gin Phe His Gin Ala Gly Pro Asn Thr Met 450 455 460

     Ala Glu Gin Ser Lys Asn Trp Leu Pro Gly Pro Cys Tyr Arg Gin Gin 465 470 475 480

     Arg leu Ser Lys Asn lie Asp Ser Asn Asn Asn Ser Asn Phe Ala Trp 485 490 495

     Thr Gly Ala Thr lys Tyr His leu Asn Gly Arg Asn Ser leu Thr Asn 500 505 510

     Pro Gly Val Ala Met Ala Thr Asn lys Asp Asp Glu Asp Gin Phe Phe 515 520 525

     Pro He Asn Gly Val leu Val Phe Gly lys Thr Gly Ala Ala Asn lys 530 535 540
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     Thr 545 Thr Leu Glu Asn Val 550 Leu Met Thr Ser Glu Glu Glu 555 He Lys Thr 560 Thr Asn Pro Val Ala Thr Glu Glu Tyr Gly Val Val Ser Ser Asn Leu 565 570 575 Gin ser Ser Thr Ala Gly Ero Gin Thr Gin Thr Val Asn Ser Gin Gly 580 585 590 Ala Leu Ero Gly Met Val Trp Gin Asn Arg Asp val Tyr Leu Gin Gly 595 600 605 Pro He Trp Ala Lys He Ero His Thr Asp Gly Asn Ehe His Pro Ser 610 615 620 Pro Leu Met Gly Gly Ehe Gly Leu Lys His Pro Pro Pro Gin He Leu 625 630 635 640 He Lys Asn Thr Ero Val Pro Ala Asn Pro Pro GlU Val Phe Thr Pro 645 650 655 Ala Lys Ehe Ala Ser Ehe He Thr Gin Tyr Ser Thr Gly Gin Val Ser 660 665 670 Val Glu He Glu Trp Glu Leu Gin Lys Glu Asn Ser Lys Arg Trp Asn 675 680 685 Pro GlU lie Gin Tyr Thr Ser Asn Tyr Ala Lys Ser Asn Asn Val Glu 690 695 700 Phe Ala Val Asn Asn Glu Gly Val Tyr Thr Glu Pro Arg Pro lie Gly 705 710 715 720 Thr Arg Tyr Leu Thr Arg Asn Leu

     725 <210> 104 <211> 720 <212> PRT <213> capsid protein of AAV serotype, clone 27.3VP1 <400> 104

     Met Ala Ala Asp Gly Tyr leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 15 10 15

     Glu Gly lie Arg Glu Trp Trp Asp Leu Lys Ero Gly Ala Ero Lys Ero 20 25 30
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     Lys Ala Asn Gin Gin 35 Lys Gin Asp Asp 40 Gly Arg Gly Leu Val Leu Pro 45 Gly Tyr Lys Tyr Leu 50 Gly Pro Phe Asn 55 Gly leu Asp Lys Gly Glu Pro 60 Val Asn Glu Ala Asp 65 Ala 70 Ala Ala leu Glu His Asp Lys Ala Tyr Asp 75 80 Lys Gin Leu Glu Gin 85 Gly Asp Asn Pro Tyr Leu lys Tyr Asn His Ala 90 95 Asp Ala Glu Phe Gin 100 Glu Arg Leu Gin 105 Glu Asp Thr Ser Phe Gly Gly 110 Asn Leu Gly Arg Ala 115 Val Phe Gin Ala 120 lys lys Arg Val Leu Glu Pro 125 Leu Gly Leu Val Glu 130 Glu Gly Ala Lys 135 Thr Ala Ser Gly lys Lys Arg 140 Pro lie Glu Ser Pro 145 Asp 150 Ser Ser Thr Gly Ile Gly Lys Lys Gly Gin 155 160 Gin Pro Ala lys Lys 165 Lys Leu Asn Phe Gly Gin Thr Gly Asp Ser Glu 170 175 Ser Val Pro Asp Pro 180 Gin Pro leu Gly 185 Glu Pro Pro Ala Ala Pro Ser 190 Gly Leu Gly Ser Gly 195 Thr Met Ala Ala 200 Gly Gly Gly Ala Pro Met Ala 205 Asp Asn Asn Glu Gly 210 Ala Asp Gly Val 215 Gly Asn Ala Ser Gly Asn Trp 220 His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val Ile Thr Thr Ser Thr

     225 230 235 240

     Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu Tyr Lys Gin lie 245 250 255

     Ser Ser Gin Ser Gly Ala Thr Asn Asp Asn His Phe Ehe Gly Tyr Ser 260 265 270

     Thr Pro Trp Gly Tyr Phe Asp Ehe Asn Arg Phe His Cys His Phe Ser 275 280 285
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     Pro Arg Asp Trp Gin Arg Leu lie Asn Asn Asn Trp Gly Phe Arg Pro 290 295 300

     Arg Lys Leu Arg Phe Lys Leu Phe Asn He Glu Val Lys Glu Val Thr 305 310 315 320

     Thr Asn Asp Gly Val Thr Thr He Ala Asn Asn Leu Thr Ser Thr He 325 330 335

     Gin Val Phe Ser Asp Ser Glu Tyr Gin Leu Pro Tyr Val Leu Gly Ser 340 345 350

     Ala His Gin Gly Cys Leu Pro Pro Phe Pro Ala Asp Val Phe Met He 355 360 365

     Pro Gin Tyr Gly Tyr Leu Thr Leu Asn Asn Gly Ser Gin Ser Val Gly 370 375 380

     Arg Ser Ser Phe Cys Cys Leu Glu Tyr Phe Pro Ser Gin Met Leu Arg 385 390 395 400

     Thr Gly Asn Asn Phe Glu Phe Ser Tyr Thr Phe Glu Glu Val Pro Phe 405 410 415

     His Ser Ser Tyr Ala His Ser Gin Ser Leu Asp Arg Leu Met Asn Pro 420 425 430

     Leu lie Asp Gin Tyr Leu Tyr Tyr Leu Ala Arg Thr Gin Ser Thr Thr 435 440 445

     Gly Ser Thr Arg Glu Leu Gin Phe His Gin Ala Gly Ero Asn Thr Val 450 455 460

     Ala Glu Glu Ser Lys Asn Trp Leu Ero Gly Pro Cys Tyr Arg Gin Gin 465 470 475 480

     Arg Leu Ser Lys Asn He Asp Ser Asn Asn Asn Ser Asn Phe Ala Trp 485 490 495

     Thr Gly Ala Thr Lys Tyr His Leu Asn Gly Arg Asn Ser Leu Thr Asn 500 505 510

     Pro Gly Val Ala Met Ala Thr Asn Lys Asp Asp Glu Asp Gin Phe Leu 515 520 525

     Pro He Asn Gly Val Leu Val Phe Gly Lys Thr Gly Ala Ala Asn Lys 530 535 540
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     Thr Thr leu Glu Asn Val leu Met Thr Ser Glu Glu Glu lie lys Thr 545 550 555 560

     Thr Asn Pro Val Ala Thr Glu Glu Tyr Gly Val Val Ser Ser Asn leu 565 570 575

     Gln Ser Ser Thr Ala Gly Pro Arg Thr Gln Thr Val Asn Ser Gln Gly 500 585 590

     Ala Leu Pro Gly Met Val Trp Gln Asn Arg Asp Val Tyr leu Gln Gly 595 600 605

     Pro lie Trp Ala Glu lie Pro His Thr Asp Gly Asn Phe His Pro Ser 610 615 620

     Pro leu Met Gly Gly Phe Gly Leu lys His Pro Pro Pro Gln lie leu 625 630 635 640 lie lys Asn Thr Pro Val Pro Ala Asn Pro Pro Glu Val Phe Thr Pro 645 650 655

     Ala lys Phe Ala Ser Phe Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser 660 665 670

     Val Glu lie Glu Trp Glu Leu Gln lys Glu Asn Ser Lys Arg Trp Asn 675 680 685

     Pro Glu lie Gln Tyr Thr Ser Asn Tyr Ala lys Ser Asn Asn Val Glu 690 695 700

     Phe Ala Val Asn Asn Glu Gly Val Tyr Thr Glu Pro Arg Pro lie Gly 705 710 715 720

     Thr Arg Tyr Leu Thr Arg Asn Leu 725 <210> 105 <211> 728 <212> PRT <213> capsid protein of AAV serotype, clone 16.3VP1 <400> 105

     Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 15 10 15

     Glu Gly lie Arg Glu Trp Trp Asp leu lys Pro Gly Ala Pro Lys Pro 20 25 30 lys Ala Asn Gln Gln Lys Gln Asp Asp Gly Arg Gly Leu Val Leu Pro 35 40 45
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     Gly Tyr lys Tyr leu Gly Pro phe Asn Gly leu Asp lys Gly Glu Pro

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     Val Asn Glu Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp 65 70 75 80

     Lys Gin Leu Glu Gin Gly Asp Asn Pro Tyr Leu Lys Tyr Asn His Ala 85 90 95

     Asp Ala Glu Phe Gin Glu Arg leu Gin Glu Asp Thr Ser Phe Gly Gly - 100 105 110

     Asn Leu Gly Arg Ala Val Phe Gin Ala Lys Lys Arg Val Leu Glu Pro 115 120 125 leu Gly Leu Val Glu Glu Gly Ala Lys Thr Ala Pro Gly Lys Lys Arg 130 135 140

     Pro Ile Glu Ser Pro Asp Ser Ser Thr Gly Ile Gly Lys lys Gly Gin 145 150 155 160

     Gin Pro Ala Lys Lys Lys Leu Asn Phe Gly Gin Thr Gly Asp Ser Glu 165 170 175

     Ser Val Pro Asp Pro Gin Pro Leu Gly Glu Ero Ero Ala Ala Pro Ser 180 185 190

     Gly Leu Gly Ser Gly Thr Met Ala Ala Gly Gly Gly Ala Pro Met Ala 195 200 205

     Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn Ala Ser Gly Asn Trp 210 215 220

     His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val Ile Thr Thr Ser Thr 225 230 235 240

     Arg Thr Trp Ala Leu Ero Thr Tyr Asn Asn His Leu Tyr Lys Gin Ile 245 250 255

     Ser Ser Gin Ser Gly Ala Thr Asn Asp Asn His Ehe Ehe Gly Tyr Ser 260 265 270

     Thr Ero Trp Gly Tyr Ehe Asp Ehe Asn Arg Ehe His Cys His Ehe Ser 275 280 285

     Pro Arg Asp Trp Gin Arg Leu Ile Asn Asn Asn Tip Gly Phe Arg Pro 290 295 300
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     Arg Lys Leu Arg Phe Lys Leu Phe Asn Ile Gln Val Lys Glu Val Thr 305 310 315 320

     Thr Asn Asp Gly Val Thr Thr Ile Ala Asn Asn Leu Thr Ser Thr Ile 325 330 335

     Gln Val Phe Ser Asp Ser Glu Tyr Gln Leu Pro Tyr Val Leu Gly Ser 340 345 350

     Ala His Gln Gly Cys Leu Pro Pro Phe Pro Ala Asp Val Phe Met Ile 355 360 365

     Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn Gly Ser Gln Ser Met Gly 370 375 380

     Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro Ser Gln Met Leu Arg 385 390 395 400

     Thr Gly Asn Asn Phe Glu Phe Ser Tyr Thr Phe Glu Glu Val Pro Phe 405 410 415

     His Ser Ser Tyr Ala His Ser Gln Ser Leu Asp Arg Leu Met Asn Pro 420 425 430

     Leu lie Asp Gln Tyr Leu Tyr Tyr Leu Ala Arg Thr Gln Sex Thr Thr 435 440 445

     Gly Ser Thr Arg Glu Leu Gln Phe His Gln Ala Gly Ero Asn Thr Met 450 455 460

     Ala Glu Gln Ser Lys Asn Trp Leu Pro Gly Pro Cys Tyr Arg Gln Gln 465 470 475 480

     Arg Leu Ser Lys Asn Ile Asp Ser Asn Asn Asn Ser Asn Phe Ala Trp 485 490 495

     Thr Gly Ala Thr Lys Tyr His Leu Asn Gly Arg Asn Ser Leu Thr Asn 500 505 510

     Pro Gly Val Ala Met Ala Thr Asn Lys Asp Asp Glu Gly Gln Phe Phe 515 520 525

     Pro Ile Asn Gly Val Leu Val Phe Gly Lys Thr Gly Ala Ala Asn Lys 530 535 540

     Thr Thr Leu Glu Asn Val Leu Met Thr Ser Glu Glu Glu lie Lys Thr 545 550 555 560
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     Thr Asn Pro Val Ala Thr Glu Glu Tyr Gly Val Val Ser Ser Asn Leu 565 570 575

     Gin Ser Ser Thr Ala Gly Pro Gin Thr Gin Thr Val Asn Ser Gin Gly 580 585 590

     Ala Leu Pro Gly Met Val Trp Gin Asn Arg Asp Val Tyr Leu Gin Gly 595 600 605 pro Ile Trp Ala Lys lie Pro His Thr Asp Gly Asn Ehe His Ero Ser 610 615 620

     Pro Leu Met Gly Gly Phe Gly Leu Lys His Ero Pro Ero Gin Ile Leu 625 630 635 640 lie Lys Asn Thr Pro Val Pro Ala Asn Pro Pro Gly Val Phe Thr Ero 645 650 655

     Ala Leu Phe Ala Ser Phe lie Thr Gin Tyr Ser Thr Gly Gin Val Ser 660 665 670

     Val Glu Ile Glu Trp Glu Leu Gin Lys Glu Asn Ser Lys Arg Trp Asn 675 680 685

     Ero Glu Ile Gin Tyr Thr Ser Asn Tyr Ala Lys Ser Asn Asn Val Glu 690 695 700

     Phe Ala Val Asn Asn Glu Gly Val Tyr Thr Glu Pro Arg Pro lie Gly 705 710 715 720

     Thr Arg Tyr Leu Thr Arg Asn Leu 725 <210> 106 <211> 728 <212> PRT <213> capsid protein of AAV serotype, clone 42.10 <400> 106

     Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 15 10 15

     Glu Gly Ile Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro 20 25 30

     Lys Ala Asn Gin Gin Lys Gin Asp Asp Gly Arg Gly leu Val Leu Pro 35 40 45
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     Gly Tyr 50 lys Tyr Leu i Gly Ero 55 Phe Asn l Gly Leu i Asp Lys Gly Glu Ero 60 Val 65 Asn Glu Ala Asp Ala 70 Ala Ala Leu Glu His 75 Asp i Lys Ala . Tyr ' Asp 80 lys Gin Leu Glu Gin 85 Gly Asp Asn Ero Tyr 90 Leu Lys Tyr Asn . His 95 Ala Asp Ala Glu Phe 100 Gin Glu Arg Leu Gin 105 Glu Asp Thr Ser Phe 110 Gly Gly Asn leu Gly 115 Arg Ala Val Phe Gin Ala 120 Lys Lys Arg Val Leu 125 Glu Ero leu Gly 13 0 Leu Val Glu Glu Gly 135 Ala Lys Thr Ala Ero 140 Gly Lys Lys Arg Pro 145 lie Glu Ser Pro Asp 150 Ser Ser Thr Gly lie 155 Gly Arg Lys Gly Gin 160 Gin Pro Ala Lys Lys 165 Lys Leu Asn Phe Gly 170 Gin Thr Gly Asp Ser 175 Glu Ser Val Pro Asp 130 Pro Gin Ero He Gly 185 Glu Pro Ero Ala Gly 190 Pro Ser Gly leu Gly 195 Ser Gly Thr Met Ala Ala 200 Gly Gly Gly Ala Ero 205 Met Ala Asp Asn 210 Asn Glu Gly Ala Asp 215 Gly Val Gly Asn Ala 220 Ser Gly Asn Trp His 225 Cys Asp Ser Thr Trp 230 Leu Gly Asp Arg Val 235 lie Thr Thr Ser Thr 240 Arg Thr Trp Ala Leu 245 Ero Thr Tyr Asn Asn 250 His Leu Tyr Lys Gin 255 lie Ser Ser Gin Ser 260 Gly Ala Thr Asn Asp 2 65 Asn His Ehe Phe Gly 270 Tyr Ser Thr Pro Trp 275 Gly Tyr Phe Asp Phe Asn 2B0 Arg Ehe His Cys His 285 Ehe Ser Pro Arg Asp Trp Gin Arg Leu lie Asn Asn . Asn Trp Gly Ehe . Arg Ero

     290 295 300
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     Arg Lys Leu Arg Phe Lys Leu Phe Asn Ile Gln Val Lys Glu Val Thr 305 310 315 320

     Thr Asn Asp Gly Val Thr Thr Ile Ala Asn Asn Leu Thr Ser Thr lie 325 330 335

     Gln Val Phe Ser Asp Ser Glu Tyr Gln Leu Pro Tyr Val Leu Gly Ser 340 345 350

     Ala His Gln Gly Cys Leu Pro Pro Phe Pro Ala Asp Val Phe Met Ile 355 360 365

     Pro Gln Tyr Gly Tyr Leu Thr leu Asn Asn Gly Ser Gln Ser Val Gly 370 375 380

     Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro Ser Gln Met Leu Arg 385 390 395 400

     Thr Gly Asn Asn Phe Glu Phe Ser Tyr Thr Phe Glu Glu Val Pro Phe 405 410 415

     His Ser Ser Tyr Ala His Ser Gln Ser Leu Asp Arg Leu Met Asn Pro 420 425 430

     Leu He Asp Gln Tyr Leu Tyr Tyr Leu Ala Arg Thr Gln Ser Thr Thr 435 440 445

     Gly Ser Thr Arg Glu Leu Gln Phe His Gln Ala Gly Pro Asn Thr Met 450 455 460

     Ala Glu Gln Ser Lys Asn Trp Leu Pro Gly Pro Cys Tyr Arg Gln Gln 465 470 475 480

     Arg Leu Ser Lys Asn lie Asp Ser Asn Asn Asn Ser Asn Phe Ala Trp 485 490 495

     Thr Gly Ala Thr Lys Tyr His Leu Asn Gly Arg Asn Ser Leu Thr Asn 500 505 510

     Pro Gly Val Ala Met Ala Thr Asn Lys Asp Asp Glu Asp Gln Phe Phe 515 520 525

     Pro lie Asn Gly Val Leu Val Phe Gly Lys Thr Gly Ala Ala Asn Lys 530 535 540

     Thr Thr Leu Glu Asn Val Leu Met Thr Ser Glu Glu Glu Ile Lys Thr 545 550 555 560
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     Thr Asn Pro Val Ala Thr Glu Glu Tyr Gly Val Val Ser Ser Asn leu 565 570 575

     Gln Ser Ser Thr Ala Gly Pro Gln Thr Gln Thr Val Asn Ser Gln Gly 580 585 590

     Ala Leu Pro Gly Met val Trp Gln Asn Arg Asp Val Tyr Leu Gln Gly 595 600 605

     Pro Ile Trp Ala Lys Ile Pro His Thr Asp Gly Asn Phe His Pro Ser 610 615 620

     Pro Leu Met Gly Gly Phe Gly Leu Lys His Pro Pro Pro Gln Ile Leu 625 630 635 640

     Ile Lys Asn Thr Pro Val Pro Ala Asn Pro Pro Glu Val Phe Thr Pro 645 650 655

     Ala Lys Phe Ala Ser Phe Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser 660 665 670

     Val Glu Ile Glu Trp Glu Leu Gln Lys Glu Asn Ser Lys Arg Trp Asn 675 680 685

     Pro Glu Ile Gln Tyr Thr Ser Asn Tyr Ala Lys Ser Asn Asn Val Glu 690 695 700

     Phe Ala Val Asn Asn Glu Gly Val Tyr Thr Glu Ere Arg Pro Ile Gly 705 710 715 720

     Thr Arg Tyr Leu Thr Arg Asn Leu 725 <210> 107 <211> 728 <212> PRT <213> capsid protein of AAV serotype, clone 42.3B <400> 107

     Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Aan Leu Ser 15 10 15

     Glu Gly lie Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro 20 25 30

     Lys Ala Asn Gln Gln Lys Gln Asp Asp Gly Arg Gly Leu Val Leu Pro 35 40 45

     Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro 50 55 60
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     Val Asn Glu Ala Asp 65 lys Gin leu Glu Gl:

     Θ5

     Asp Ala Glu Phe Gin 100

     Asn leu Gly Arg Ala 115

     Leu Gly Leu Val Glu 130

     Pro lie Glu Ser Pro 145

     Gin Pro Ala Lys lys 165

     Ser Val Pro Asp Pro 180

     Gly Leu Gly Ser Gly 195

     Asp Asn Asn Glu Gly 210

     His Cy3 Asp Ser Thr 225

     Arg Thr Trp Ala Leu 245

     Ser Ser Gin Ser Gly 260

     Thr Pro Trp Gly Tyr 275

     Pro Arg Asp Trp Gin 290

     Arg Lys Leu Arg Phe 305

     Ala Ala Ala Leu Glu 70

     Gly Asp Asn Pro Tyr 90

     Glu Arg Leu Gin Glu 105

     Val Phe Gin Ala Lys 120

     Glu Gly Ala Lys Thr 135

     Asp Ser Ser Thr Gly 150

     His Asp Lys Ala Tyr Asp 75 80 leu Lys Tyr Asn His Ala 95

     Asp Thr Ser Phe Gly Gly ' 110 lys Arg Val Leu Glu Pro 125

     Ala Pro Sly lys Lys Arg 140

     Ile Gly Lys Lys Gly Gin 155 160

     Lys Leu Asn Phe Gly Gin 170

     Gin Pro Ile Gly Glu Pro 185

     Thr Met Ala Ala Gly Gly 200

     Ala Asp Gly Val Gly Asn 215

     Trp Leu Gly Asp Arg Val 230 235

     Pro Thr Tyr Asn Asn His 250

     Ala Thr Asn Asp Asn His 265

     Phe Asp Phe Asn Arg Phe 280

     Arg Leu lie Asn Asn Asn 295

     Lys Leu Phe Asn Ile Gin 310 315

     Thr Sly Asp Ser Glu 175

     Pro Ala Gly Pro Ser 190

     Gly Ala Pro Met Ala 205

     Ala Ser Gly Asn Trp 220 lie Thr Thr Ser Thr 240

     Leu Tyr Lys Gin lie 255

     Phe Phe Gly Tyr Ser 270

     His Cys His Phe Ser 285

     Trp Sly Phe Arg Pro 300

     Val Lys Glu Val Thr 320
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     Thr Asn Asp Gly Val Thr Thr lie Ala Asn Asn Leu Thr Ser Thr He 325 330 335

     Gin Val Phe Ser Asp Ser Glu Tyr Gin Leu Ero Tyr Val Leu Gly Ser 340 345 350

     Ala His Gin Gly Cys Leu Ero Pro Ehe Ero Ala Asp Val Ehe Met He 355 360 365

     Ero Gin Tyr Gly Tyr Leu Thr Leu Asn Asn Gly Ser Gin Ser Val Gly 370 375 380

     Arg Ser Ser Ehe Tyr Cys Leu Glu Tyr Ehe Ero Ser Gin Met Leu Arg 385 390 395 400

     Thr Gly Asn Asn Ehe Glu Phe Ser Tyr Thr Ehe Glu Glu Val Ero Phe 405 410 415

     His Ser Ser Tyr Ala His Ser Gin Ser Leu Asp Arg Leu Met Asn Ero 420 425 430

     Leu He Asp Gin Tyr Leu Tyr Tyr Leu Ala Arg Thr Gin Ser Thr Thr 435 440 445

     Gly Ser Thr Arg Glu Leu Gin Ehe His Gin Ala Gly Ero Asn Thr Met 450 455 460

     Ala Glu Gin Ser Lys Asn Trp Leu Ero Gly Ero Cys Tyr Arg Gin Gin 465 470 475 480

     Arg Leu Ser Lys Asn He Asp Ser Asn Asn Thr Ser Asn Ehe Ala Trp 485 490 495

     Thr Gly Ala Thr Lys Tyr His Leu Asn Gly Arg Asn Ser Leu Thr Asn 500 505 510

     Ero Gly Val Ala Met Ala Thr Asn Lys Asp Asp Glu Asp Gin Ehe Ehe 515 520 525

     Ero lie Asn Gly Val Leu Val Ehe Gly Lys Thr Gly Ala Ala Asn Lys 530 535 540

     Thr Thr Leu Glu Asn Val Leu Met Thr Ser Glu Glu Glu lie Lys Thr 545 550 555 560

     Thr Asn Ero Val Ala Thr Glu Gin Tyr Gly Val Val Ser Ser Asn Leu 565 570 575
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     Gin Ser Ser Thr 5Θ0 Ala Gly Pro Gin Thr Gin Thr 585 Val Asn Ser Gin Gly 590 Ala Leu Pro Gly 595 Met Val Trp Gin 600 Asn Arg Asp Val Tyr Leu Gin Gly 605 Pro lie Trp Ala 610 lys He Pro 615 His Thr Asp Gly Asn Phe His Pro Ser 620 Pro 625 Leu Met Gly Gly Phe Gly 630 Leu lys His Pro 635 Pro Pro Gin lie Leu 640 lie Lys Asn Thr Pro Val Pro 645 Ala Asn Pro Pro 650 Glu Val Phe Thr Pro 655 Ala Lys Phe Ala 660 Ser Phe lie Thr Gin Tyr Ser 665 Thr Gly Gin Val ser 670 Val Glu lie Glu 675 Trp Glu Leu Gin 680 Lys Glu Asn Ser lys Arg Trp Asn 685 Pro Glu He Gin 630 Tyr Thr ser 695 Asn Tyr Ala Lys Ser Asn Asn Val Glu 700 Phe Ala Val Asn Asn Glu Gly Val Tyr Thr Glu 705 710 715 Thr Arg Tyr leu Thr Arg Asn leu 725 <210> 100 <211> 720 <212> PRT <213> capsid protein of AAV serotype, clone <400> 108 Pro Arg Ero lie Gly 720 : 42.11 Met 1 Ala Ala Asp Gly Tyr Leu 5 Pro Asp Trp Leu 10 Glu Asp Asn Leu Ser 15 Glu Gly lie Arg 20 Glu Trp Trp Asp Leu Lys Pro 25 Gly Ala Pro Lys Pro 30 Lys Ala Asn Gin 35 Gin Lys Gin Asp 40 Asp Gly Arg Gly Leu Val Leu Pro 45 Gly Tyr Lys Tyr Leu Gly Pro Phe . Asn Gly Leu . P-sp Lys Gly Glu Pro

     50 55 60
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     Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp lys Ala Tyr Asp

     65 70 75 80

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     Gln Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala 85 90 95

     Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr Ser Phe Gly Gly 100 105 110

     Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro 115 120 125

     Leu Gly Leu Val Glu Glu Gly Ala Lys Thr Ala Pro Gly Lys Lys Arg 130 135 140

     Pro Ile Glu Ser Pro Asp Ser Ser Thr Gly lie Gly Lys Lys Gly Gln 145 150 155 160

     Gln Pro Ala Lys Lys Lys Leu Asn Phe Gly Gln Thr Gly Asp Ser Glu 165 170 175

     Ser Val Pro Asp Pro Gln Pro lie Gly Glu Pro Pro Ala Gly Pro Ser 180 185 190

     Gly Leu Gly Ser Gly Thr Met Ala Ala Gly Gly Gly Ala Pro Met Ala 195 200 205

     Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn Ala Ser Gly Asn Trp 210 215 220

     His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val Ile Thr Thr Ser Thr 225 230 235 240

     Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu Tyr Lys Gln lie 245 250 255

     Ser Ser Gln Ser Gly Ala Thr Asn Asp Asn His Phe Phe Gly Tyr Ser 260 265 270

     Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe His Cys His Phe Ser 275 280 285

     Pro Arg Asp Trp Gln Arg Leu lie Asn Asn Asn Trp Gly Phe Arg Pro 290 295 300

     Arg Lys Leu Arg Phe Lys Leu Phe Asn Ile Gln Val Lys Glu Val Thr 305 310 315 320
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     Thr Asn Asp

     Gin Val Phe

     Ala His Gin 355

     Pro Gin Tyr 370

     Arg Ser Ser 385

     Thr Gly Asn

     His Ser Ser

     Gly Val Thr Thr Ile Ala Asn Asn Leu Thr Ser Thr Ile 325 330 335

     Ser Asp Ser Glu Tyr Gin Leu Pro Tyr Val Leu Gly Ser

     340 345

     Gly Cys Leu Pro Pro Phe 360

     Gly Tyr Leu Thr Leu Asn 375

     Phe Tyr Cys Leu Glu Tyr 390

     Asn Phe Glu Phe Ser Tyr 405

     Tyr Ala His Ser Gin Ser 420 425

     350

     Pro Ala Asp Val Phe Met Ile 365

     Asn Gly Ser Gin Ser Val Gly 380

     Phe Pro Ser Gin Met Leu Arg 395 400

     Thr Phe Glu Glu Val Pro Phe 410 415

     Leu Asp Arg Leu Met Asn Pro 430

     Leu Ile Asp 435

     Gin Tyr Leu Tyr Tyr Leu 440

     Ala Arg Thr Gin Ser Thr Thr 445

     Gly Ser Thr 450

     Arg Glu Leu Gin Phe His 455

     Gin Ala Glv Ero Asn Thr Met 460

     Ala Glu Gin 465

     Ser Lys Asn Trp Leu Pro 470

     Gly Ero Cys Tyr Arg Arg Gin 475 480

     Arg Leu Ser

     Lys Asp Ile Asp Ser Asn 485

     Asn Asn Ser Asn Ehe Ala Trp 490 495

     Thr Gly Ala

     Thr Lys Tyr His Leu Asn 500 505

     Gly Arg Asn Ser Leu Thr Asn 510

     Pro Gly Val 515

     Ala Met Ala Thr Asn Lys 520

     Asp Asp Glu Asp Gin Ehe Ehe 525

     Pro Ile Asn 530

     Gly Val Leu Val Phe Gly 535

     Lys Thr Gly Ala Ala Asn Lys 540

     Thr Thr Leu 545

     Glu Asn Val Leu Met Thr 550

     Ser Glu Glu Glu lie Lys Thr 555 560

     Thr Asn Pro

     Val Ala Thr Glu Glu Tyr 565

     Gly Val Val Ser Ser Asn Leu 570 575
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     Gin Ser Ser Thr Ala Gly Pro Gin Thr Gin Thr Val Asn Ser Gin Gly 580 585 530

     Ala Leu Pro Gly Met Val Trp Gin Asn Arg Asp Val Tyr Leu Gin Gly 595 600 605

     Ero lie Trp Ala lys Ile Pro His Thr Asp Gly Asn Ehe His Pro Ser 610 615 620

     Ero leu Met Gly Gly Phe Gly Leu lys His Pro Ero Ero Gin Ile Leu 625 630 635 640

     Ile lys Asn Thr Pro Val Pro Ala Asn Pro Pro Glu Val Phe Thr Ero 645 650 655

     Ala lys Phe Ala Ser Ehe Ile Thr Gin Tyr Ser Thr Gly Gin Val Ser 660 665 670

     Val Glu Ile Glu Trp Glu Leu Gin lys Glu Asn Ser Lys Arg Trp Asn 675 680 685

     Pro Glu Ile Gin Tyr Thr Ser Asn Tyr Ala Lys Ser Asn Asn Val Glu 690 695 700

     Phe Ala Val Asn Asn Glu Gly Val Tyr Thr Glu Ero Arg Pro lie Gly 705 . 710 715 720

     Thr Arg Tyr Leu Thr Arg Asn Leu 725 <210> 109 <211> 729 <212> PRT <2'13> capsid protein of AAV serotype, clone PlVPl <400> 109

     Met 1 Ala Ala Asp Gly 5 Tyr leu Pro Asp Trp 10 leu Glu Asp Asn leu 15 Ser Glu Gly Ile Arg 20 Glu Trp Trp Asp leu 25 lys Pro Gly Ala Ero 30 lys Pro lys Ala Asn 35 Gin Gin lys Gin Asp 40 Asp Gly Arg Gly leu 45 Val leu Pro Gly Tyr 50 lys Tyr leu Gly Pro 55 Phe Asn Gly leu Asp 60 lys Gly Glu Pro Val 65 Asn Ala Ala Asp Ala 70 Ala Ala leu Glu His 75 Asp lys Ala Tyr Asp 80
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     Gln i Gln . Leu Lys Ala Gly Asp 85 i Asn i Pre i Tyr Leu Arg Tyr Asn His Ala 90 95 Asp Ala Glu Phe 100 Gln Glu Arg Leu Gln 105 Glu . Asp i Thr Ser Phe 110 Gly Gly Asn Leu Gly 115 Arg Ala Val Phe Gln 120 Ala Lys Lys Arg Val Leu 125 Glu Pro Leu Gly 130 Leu Val Glu Glu Gly 135 Ala Lys Thr Ala Pro Gly Lys 140 Lys Arg Pro 145 lie Asp Ser pro Asp 150 Ser Ser Thr Gly lie 155 Gly Lys Lys Gly Gln 160 Gln Pro Ala Lys Lys 165 Lys Leu Asn Phe Gly 170 Gln Thr Gly Asp Ser Glu 175 Ser Val Pro Asp 180 Pro Gln Pro Leu Gly 185 Glu Pro Pro Ala Ala 190 Pro Ser Ser Val Gly 195 Ser Gly Thr Met Ala 200 Ala Gly Gly Gly Ala Pro 205 Met Ala Asp Asn 210 Asn Glu Gly Ala Asp 215 Gly Val Gly Asn Ala Ser Gly 220 Asn Trp Kis 225 Cys Asp ser Thr Trp 230 Leu Gly Asp Arg Val 235 Ile Thr Thr Ser Thr 240 Arg Thr Trp Ala Leu 245 Pro Thr Tyr Asn Asn 250 His Leu Tyr Lys Gln lie 255 Ser Ser Ser Ser 260 Ser Gly Ala Thr Asn 2 65 Asp Asn His Tyr Phe 270 Gly Tyr Ser Thr Pro 275 Trp Gly Tyr Phe Asp 230 Phe Asn Arg Phe His Cys 285 His Phe Ser Pro 290 Arg Asp Trp Gln Arg 2 95 Leu lie Asn Asn Asn Trp Gly 300 Phe Arg Pro 305 Lys Lys Leu Arg Phe 310 Lys Leu Phe Asn lie 315 Gln Val Lys Glu Val 320 Thr Thr Asn Asp Gly Val Thr Thr lie . Ala Asn . Asn Leu Thr Ser Thr

     325 330 335
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     Val Gin Val Phe Ser Asp Ser Glu Tyr Gin leu Pro Tyr Val leu Gly 340 345 350

     Ser Ala His Gin Gly Cys leu Pro Pro Phe Pro Ala Asp Val Phe Met 355 360 365 lie Pro Gin Tyr Gly Tyr Leu Thr Leu Asn Asn Gly Ser Gin Ser Val 370 375 380

     Gly Arg Ser Ser Phe Tyr Cys leu Glu Tyr Phe Pro Ser Gin Met leu 385 390 395 400

     Arg Thr Gly Asn Asn Phe Glu Phe Ser Tyr Ser Phe Glu Asp Val Pro 405 410 415

     Phe His Ser Ser Tyr Ala His Ser Gin Ser leu Asp Arg leu Met Asn 420 425 430

     Pro leu He Asp Gin Tyr leu Tyr Tyr Leu Ala Arg Thr Gin Ser Thr 435 440 445

     Thr Gly Ser Thr Arg Glu Leu Gin Phe His Gin Ala Gly Pro Asn Thr 450 455 460

     Met Ala Glu Gin Ser Lys Asn Trp Leu Pro Gly Pro Cys Tyr Arg Gin 465 470 475 480

     Gin Gly Leu Ser Lys Asn Leu Asp Phe Asn Asn Asn Ser Asn Phe Ala 485 490 495

     Trp Thr Ala Ala Thr Lys Tyr His Leu Asn Gly Arg Asn Ser Leu Thr 500 505 510

     Asn Pro Gly He Pro Met Ala Thr Asn Lys Asp Asp Glu Asp Gin Phe 515 520 525

     Phe Pro He Asn Gly Val Leu Val Phe Gly Lys Thr Gly Ala Ala Asn 530 535 540

     Lys Thr Thr Leu Glu Asn Val Leu Met Thr Ser Glu Glu Glu He Lys 545 550 555 560

     Thr Thr Asn Pro Val Ala Thr Glu Glu Tyr Gly Val Val Ser Ser Asn 565 570 575

     Leu Gin Pro Ser Thr Ala Gly Pro Gin Ser Gin Thr lie Asn Ser Gin 580 585 590
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     Gly Ala Leu Pro Gly Met Val Trp Gin Asn Arg Asp Val Tyr Leu Gin 595 600 605

     Gly Pro Ile Trp Ala Lys lie Pro His Thr Asp Gly Asn Phe His Pro 610 615 620

     Ser Pro Leu Met Gly Gly Phe Gly Leu Lys His Pro Pro Pro Gin Ile 625 630 635 640

     Leu lie Lys Asn Thr Pro Val Pro Ala Asn Pro Pro Glu Val Phe Thr 645 650 655

     Pro Ala Lys Phe Ala Ser Phe Ile Thr Gin Tyr Ser Thr Gly Gin Val 660 665 670

     Ser Val Glu lie Glu Trp Glu Leu Gin Lys Glu Asn Ser Lys Arg Trp 675 680 685

     Asn Pro Glu He Gin Tyr Thr Ser Asn Tyr Ala Lys Ser Asn Asn Val 690 695 700

     Glu Phe Ala Val Asn Pro Asp Gly Val Tyr Thr Glu Pro Arg Pro Ile 705 710 715 720

     Gly Thr Arg Tyr Leu Pro Arg Asn Leu 725 <210> 110 <211> 729 <212> PRT <213> capsid protein of AAV serotype, clone F5VP1@3 <400> 110

     Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 15 10 15

     Glu Gly Ile Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro 20 25 30

     Lys Ala Asn Gin Gin Lys Gin Asp Asp Gly Arg Gly Leu Val Leu Pro 35 40 45

     Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro 50 55 60

     Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp 65 70 75 80

     Gin Gin Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala 85 90 95
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     Asp Ala Glu Phe 100 Gin Glu . Arg Leu Gin 105 . Glu Asp i Thr Ser Ehe 110 : Gly Gly Asn Leu Gly 115 Arg Ala Val Phe Gin 120 Ala Lys Lys Arg Val 125 Leu Glu Ero Leu Gly 130 Leu Val Glu Glu Gly 135 Ala Lys Thr Ala Pro Gly 140 Lys Lys Arg Pro 145 lie Asp Ser Pro Asp 150 Ser Ser Thr Gly He 155 Gly Lys Lys Gly Gin 160 Gin Pro Ala Lys Lys 165 Lys Leu Asn Phe Gly 170 Gin Thr Gly Asp Ser Glu 175 Ser Val Pro Asp 180 Pro Gin Ero Leu Gly 185 GlU Pro Ero Ala Ala 190 Ero Ser Ser Val Gly 195 Ser Gly Thr Met Ala 200 Ala Gly Gly Gly Ala 205 Pro Thr Ala Asp Asn 210 Asn Glu Gly Ala Asp 215 Gly Val Gly Asn Ala Ser 220 Gly Asn Trp His 225 Cys Asp Ser Thr Trp 230 Leu Gly Asp Arg Val 235 He Thr Thr Ser Thr 240 Arg Thr Trp Ala Leu 245 Pro Thr Tyr Asn Asn 250 His Leu Tyr Lys Gin lie 255 Ser Ser Ser Ser 260 Ser Gly Ala Thr Asn 2 65 Asp Asn His Tyr Phe 270 Gly Tyr Ser Thr Pro 275 Trp Gly Tyr Ehe Asp 280 Phe Asn Arg Phe His 285 Cys His Ehe Ser Pro 290 Arg Asp Trp Gin Arg 295 Leu He Asn Asn Asn Trp 300 Gly Phe Arg Pro 305 Lys Lys Leu Arg Phe 310 Lys Leu Ehe Asn He 315 Gin Val Lys Glu Val 320 Thr Thr Asn Asp Gly 325 Val Thr Thr He Ala 330 Asn Asn Leu Thr Ser Thr 335 Val Gin Val Phe Ser Asp Ser Glu Tyr Gin Leu Ero Tyr Val Leu Gly

     340 345 350
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     Gly Ala Leu 595

     Ser Ala His 355

     Ile Pro Gin 370

     Gly Arg Ser 385

     Arg Thr Gly

     Phe His Ser

     Pro Leu lie 435

     Thr Gly Ser 450

     Met Ala Glu 4 65

     Gin Arg Leu

     Trp Thr Ala

     Asn Pro Gly 515

     Ehe Pro Ile 530

     Lys Thr Thr 545

     Thr Thr Asn

     Leu Gin Ser

     Gin Gly Cys Leu . Pro 360 Pro , Phe : Pro < Ala . Asp 365 i Val . Phe Met Tyr Gly Tyr Leu 375 Thr Leu Asn Asn Gly 380 Ser Gin Ser : Val Ser Phe Tyr 390 Cys Leu Glu Tyr Phe 395 Pro Ser Gin Met Leu 400 Asn Asn Phe 405 Glu Phe Ser Tyr 410 Ser Phe Glu Asp Val 415 Pro Ser 420 Tyr Ala His Ser Gin 425 Ser Leu Asp Arg Leu 430 Met Asn Asp Gin Tyr Leu Tyr 440 Tyr Leu Ala Arg Thr 445 Gin Ser Thr Thr Arg Glu Leu 4 55 Gin Phe His Gin Ala 460 Gly Pro Asn Thr Gin Ser Lys 470 Asn Trp Leu Pro Gly 475 Pro Cys Tyr Arg Gin 480 Ser Lys Asn 485 Leu Asp Phe Asn 490 Asn Asn Ser Asn Phe 495 Ala Ala 500 Thr Lys Tyr His Leu 505 Asn Gly Arg Asn Ser 510 Leu Thr Ile Pro Met Ala Thr 520 Asn Lys Asp Asp Glu 525 Asp Gin Phe Asn Gly Val Leu 535 Val Phe Gly Lys Thr 540 Gly Ala Ala Asn Leu Glu Asn 550 Val Leu Met Thr Ser 555 Glu Glu Glu Ile Lvs 560 Pro Val Ala 565 Thr Glu Glu Tyr 570 Gly Val Val Ser Ser 575 Asn Ser 580 Thr Ala Gly Pro Gin 585 Ser Gin Thr Ile Asn 590 Ser Gin Pro Gly Met Val Trp Gin Asn Arg Asp Val Tyr Leu Gin

     600 605
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     Gly Pro Ile Trp Ala Lys lie Pro His Thr Asp Gly Asn Phe His Pro 610 615 620 Ser Ero leu Met Gly Gly Phe Gly Leu Glu His Pro Pro Pro Gin Ile 625 630 635 640 Leu Ile Lys Asn Thr Pro Val Pro Ala Asn Pro Pro Glu Val Phe Thr 645 650 655 Pro Ala Lys Phe Ala Ser Phe Ile Thr Gin Tyr Ser Thr Gly Gin Val 660 665 670 Ser Val Glu Ile Glu Trp Glu Leu Gin Lys Glu Asn Ser Lys Arg Trp 675 680 685 Asn Pro Glu lie Gin Tyr Thr Ser Asn Tyr Ala Lys Ser Asn Asn Val 690 695 700 Glu Phe Ala Val Asn Pro Asp Gly Val Tyr Thr Glu Pro Arg Pro lie 705 710 715 720 Gly Thr Arg Tyr Leu Thr Arg Asn Leu

     725 <210> 111 <211> 729 <212> PRT <213> capsid protein of AAV serotype, clone P3VP1 <400> 111

     Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 15 10 15

     Glu Gly lie Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Ero Lys Pro 20 25 30

     Lys Ala Asn Gin Gin Lys Gin Asp Asp Gly Arg Gly Leu Val Leu Pro 35 40 45

     Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly leu Asp Lys Gly Glu Ero 50 55 60

     Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp 65 70 75 80

     Gin Gin Leu Lys Ala Gly Asp Asn Ero Tyr Leu Arg Tyr Asn His Ala 85 90 95
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     Asp

     Asn

     Leu

     Ero

     145

     Gln

     Ser

     Ser

     Asp

     His

     225

     Arg

     Ser

     Ser

     Ser

     Ero

     305

     Thr

     Val

     Ala Glu Phe 100

     Leu Gly Arg 115

     Gly Leu Val 130

     Ile Gly Ser

     Pro Ala Lys

     Val Ero Asp 180

     Val Gly Ser 195

     Asn Asn Glu 210

     Cys Asp Ser

     Thr Trp Ala

     Ser Ser Ser 260

     Thr Ero Trp 275

     Ero Arg Asp 290

     Lys Lys Leu

     Thr Asn Asp

     Gln Val Ehe 340

     Gln Glu Arg Leu Gln Glu Asp Thr Ser Ehe Gly Gly 105 110

     Ala Val Ehe Gln Ala Lys Lys Arg Val Leu Glu Ero

     120

     125

     Glu Glu Gly Ala Lys Thr 135

     Pro Asp Ser Ser Thr Gly 150

     Lys Lys Leu Asn Phe Gly 165 170

     Pro Gln Pro Leu Gly Glu 185

     Gly Thr Met Ala Ala Gly 200

     Gly Ala Asp Gly Val Gly 215

     Thr Trp Leu Gly Asp Arg 230

     Leu Ero Thr Tyr Asn Asn 245 250

     Ser Gly Ala Thr Asn Asp 265

     Gly Tyr Phe Asp Phe Asn 280

     Trp Gln Arg Leu Ile Asn 295

     Arg Ehe Lys Leu Leu Asn 310

     Gly Val Thr Thr lie Ala 325 330

     Ser Asp Ser Glu Tyr Gln 345

     Ala Pro Gly Lys Lys Arg 140

     Ile Gly Lys Lys Gly Gln 155 160

     Gln Thr Gly Asp Ser Glu 175

     Ero Pro Ala Ala Pro Ser 190

     Gly Gly Ala Pro Met Ala 205

     Asn Ala Ser Gly Asn Trp 220

     Val Ile Thr Thr Ser Thr 235 240

     His Leu Tyr Lys Gln Ile 255

     Asn His Tyr Ehe Gly Tyr 270

     Arg Phe His Cys His Phe 235

     Asn Asn Trp Gly Ehe Arg 300

     Ile Gln Val Lys Glu Val 315 320

     Asn Asn Leu Thr Ser Thr 335

     Leu Pro Tyr Val Leu Gly 350
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     Ser Ala His 355 Gin Gly Cys leu Pro Pro Ehe Pro Als 360 l Asp Val Ehe Met 365 Ile Pro Gin Tyr Gly Tyr leu Thr leu Asp Asn Glj ’ Ser Gin Ser Val 370 375 380 Gly Arg Ser Ser Phe Tyr Cys leu Glu Tyr Ehe Pro Ser Gin Met leu 385 390 395 400 Arg Thr Gly Asn Asn Ehe Glu Phe Ser Tyr Ser Phe Glu Asp Val Pro 405 410 415 Phe His Ser Ser Tyr Ala His Ser Gin Ser leu Asp Arg leu Met Asn 420 425 430 Pro leu lie Asp Gin Tyr leu Tyr Tyr leu Ala Arg Thr Gin Ser Thr 435 440 445 Thr Gly Ser Thr Arg Glu leu Gin Phe His Gin Ala Gly Ero Asn Thr 450 455 460 Met Ala Glu Gin Ser lys Asn Trp leu Ero Gly Ero Cys Tyr Arg Gin 465 470 475 480 Gin Arg leu Ser lys Asn Leu Asp Ehe Asn Asn Asn Ser Asn Phe Ala 485 490 495 Trp Thr Ala Ala Thr lys Tyr His leu Asn Gly Arg Asn Ser leu Thr 500 505 510 Asn Pro Gly lie Pro Met Ala Thr Asn lys Asp Asp Glu Asp Gin Phe 515 520 525 Phe Ero lie Asn Gly Val leu Val Phe Gly lys Thr Gly Ala Ala Asn 530 535 540 lys Thr Thr leu Glu Asn Val leu Met Thr Ser Glu Glu Glu lie lys 545 550 555 560 Thr Thr Asn Pro Val Ala Thr Glu Glu Tyr Gly Val Val Ser Ser Asn 565 570 575 leu Gin Ser Ser Thr Ala Gly Pro Gin Ser Gin Thr Ile Asn Ser Gin 580 585 590 Gly Ala leu Pro Gly Met Val Trp Gin Asn Arg Asp ' Val Tyr leu Gin 595 600 605
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     Gly Pro lie Trp Ala Lys lie Pro His Thr Asp Gly Asn Phe His Pro 610 615 620 Ser Pro Leu Met Gly Gly Phe Gly leu Lys His Pro Pro Pro Gln lie 625 630 635 640 Leu Ile Lys Asn Thr Pro Val Pro Ala Asn Pro Pro Glu Val Phe Thr 645 650 655 Pro Ala Lys Phe Ala Ser Phe lie Thr Gln Tyr Ser Thr Gly Gln Val 660 665 670 Ser Val Glu Ile Glu Trp Glu Leu Gln Lys Glu Asn Ser Lys Arg Trp 675 680 685 Asn Pro Glu lie Gln Tyr Thr Ser Asn Tyr Ala Lys Ser Asn Asn Val 690 695 700 Glu Phe Ala Val Asn Pro Asp Gly val Tyr Thr GlU Pro Arg Pro Ile 705 710 715 720 Gly Thr Arg Tyr Leu Thr Arg Asn Leu

     725 <210> 112 <211> 735 <212> PRT <213> capsid protein of AAV serotype, clone 42.6B <400> 112

     Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 15 10 15

     Glu Gly lie Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro 20 25 30

     Lys Ala Asn Gln Gln Lys Gln Asp Asp Gly Arg Gly Leu Val Leu Pro 35 40 45

     Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro 50 55 60

     Val Asn Glu Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp 65 70 75 80

     Lys Gln Leu Glu Gln Gly Asp Asn Pro Tyr Leu Lys Tyr Asn His Ala 85 90 95

     Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr Ser Phe Gly Gly 100 105 110
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     Asn Leu Gly 115 Arg Ala Val Phe Gln 120 . Ala Lys Lys Arg Val 125 . Leu Glu Pro Leu Gly 130 Leu Val Glu Glu Gly 135 Ala Lys Thr Ala Pro Gly 140 Lys Lys Arg Pro 145 Val Glu Pro Ser Pro 150 Gln Arg Ser Pro Asp 155 Ser Ser Thr Gly Ile 160 Gly Lys Thr Gly Gln 165 Gln Pro Ala Lys Lys 170 Arg Leu Asn Phe Gly Gln 175 Thr Gly Asp Ser ieo Glu Ser Val Pro Asp 185 Pro Gln Pro Ile Gly 190 Glu Pro Pro Ala Gly 195 Pro Ser Gly Leu Gly 200 Ser Gly Thr Met Ala 205 Ala Gly Gly Gly Ala 210 Pro Met Ala Asp Asn 215 Asn Glu Gly Ala Asp Gly 220 Val Gly Ser Ser 225 Ser Gly Asn Trp His 230 Cys Asp Ser Thr Trn 235 Leu Gly Asp Arg Val 240 Ile Thr Thr Ser Thr 245 Arg Thr Trp Ala Leu 250 Pro Thr Tyr Asn Asn His 255 Leu Tyr Lys Gln 260 lie Ser Asn Gly Thr 265 Ser Gly Gly Ser Thr 270 Asn Asp Asn Thr Tyr 275 Phe Gly Tyr Ser Thr 280 Pro Trp Gly Tyr Phe 285 Asp Phe Asn Arg Phe 290 His Cys His Phe Ser 295 Pro Arg Asp Trp Gln Arg 300 Leu Ile Asn Asn 305 Asn Trp Gly Phe Arg 310 Pro Arg Lys Leu Arg 315 Phe Lys Leu Phe Asn 320 lie Gln Val Lys Glu 325 Val Thr Thr Asp Asp 330 Gly Val Thr Thr lie Ala 335 Asn Asn Leu Thr 340 Ser Thr Ile Gln Val 345 Phe Ser Asp Ser Glu 350 Tyr Gln Leu Pro Tyr 355 Val Leu Gly Ser Ala 360 His Gln Gly Cys Leu 3 65 pro Pro Phe
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     Pro Ala 370 . Asp Val Phe Met lie 375 Pro Gin Tyr Gly Tyr Leu 380 i Thr ' Leu Asn Asn 385 Gly Ser Gin Ser Val 390 Gly Arg Ser Ser Phe 395 Tyr Cys Leu . Glu . Tyr 400 Phe Pro Ser Gin Met 405 Leu Arg Thr Gly Asn 410 Asn Ehe Glu Phe Ser 415 Tyr Thr Phe Glu Glu 420 Val Pro Phe His Ser 425 Ser Tyr Ala His Ser 430 Gin Ser Leu Asp Arg 435 Leu Met Asn Pro Leu 440 He Asp Gin Tyr Leu 445 Tyr Tyr Leu Ala Arg 450 Thr Gin Ser Thr Thr 455 Gly Ser Thr Arg Glu Leu 460 Gin Ehe His Gin 4 65 Ala Gly Pro Asn Thr 470 Met Ala Glu Gin Ser 475 Lys Asn Trp Leu Pro 480 Gly Pro Cys Tyr Arg 485 Gin Gin Arg Leu Ser 490 Lys Asn He Asp Ser 495 Asn Asn Asn Ser Asn 500 Phe Ala Trp Thr Gly 505 Ala Thr Lys Tyr His 510 Leu Asn Gly Arg Asn 515 Ser Leu Thr Asn Pro 520 Gly Val Ala Met Ala 525 Thr Asn Lys Asp Asp 530 Glu Asp Gin Phe Phe 535 Pro He Asn Gly Val Leu 540 Val Phe Gly Lys 545 Thr Gly Ala Ala Asn 550 Ays Thr Thr Leu Glu 555 Asn Val Leu Met Thr 560 Ser Glu Glu Glu lie 565 Lys Thr Thr Asn Pro 570 Val Ala Thr Glu Glu 575 Tyr Gly val Val Ser 580 Ser Asn Leu Gin Ser 585 Ser Thr Ala Gly Ero 590 Gin Thr Gin Thr Val 595 Asn Ser Gin Gly Ala 600 Leu Pro Gly Met val 605 Trp Gin Asn Arg Asp Val Tyr Leu Gin Gly Pro He Trp . Ala Lys He Ero His ¹ Thr

     610 615 620
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     Asp 625 Gly Asn Phe His Pro 630 Ser Pro Leu Met Asp 635 GLy Phe Gly Leu Lys 640 His Pro Pro Pro Gln 645 Ile Leu Ile Lys Asn 650 Thr Ero Val Ero Ala 655 Asn Pro Pro Glu Val 660 Phe Thr Pro Ala Lys 665 Phe Ala Ser Phe lie 670 Thr Gln Tyr Ser Thr 675 Gly Gln Val Ser Val 680 Glu Ile Glu Trp Glu 685 Leu Gln Lys Glu Asn 690 Ser Lys Arg Trp Asn 695 Ero Glu Ile Gln Tyr 700 Thr Ser Asn Tyr Ala 705 Lys Ser Asn Asn Val 710 Glu Ehe Ala Val Asn 715 Asn Glu Gly Val Tyr 720 Thr Glu Pro Arg Pro 725 lie Gly Thr Arg Tyr 730 Leu Thr Arg Asn Leu 735

     <210 113 <211> 685 <212> ERT <213> capsid protein of AAV serotype, clone 42.12 <400> 113

     Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 15 10 15

     Glu Gly Ile Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro 20 25 30

     Lys Ala Asn Gln Gln Lys Gln Asp Asp Gly Arg Gly Leu Val Leu Pro 35 40 45 ,

     Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro 50 55 60

     Val Asn Glu Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp 65 70 75 80

     Lys Gln Leu Glu Gln Gly Asp Asn Pro Tyr Leu Lys Tyr Asn His Ala 85 90 95

     Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr Ser Phe Gly Gly 100 105 110
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     Asn . Leu . Gly 115 Arg Ala Val Ehe Gin 120 . Ala . Lys , Lys Arg Val 125 . Leu Glu Ero Leu Gly 130 Leu Val Glu Glu Gly 135 Ala Lys Thr Ala Era 140 , Gly ' Lys Lys Arg Ero 145 Val Glu Ero Ser Ero 150 Gin Arg Ser Pro Asp 155 Ser Ser Thr Gly lie 160 Gly Lys Thr Gly Gin 165 Gin Ero Ala Lys Lys 170 Arg Leu Asn Phe Gly 175 Gin Thr Gly Asp Ser 180 Glu Ser Val Ero Asp 185 Ero Gin Pro He Gly 190 Glu Ero Ero Ala Gly 195 Ero Ser Gly Leu Gly 200 Ser Gly Thr Met Ala 205 Ala Gly Gly Gly Ala 210 Ero Met Ala Asp Asn 215 Asn Glu Gly Ala Asp 220 Gly Val Gly Ser Ser 225 Ser Gly Asn Trp His 230 Cys Asp Ser Thr Trp 235 Leu Gly Asp Arg Val 240 Xie Thr Thr Ser Thr 245 Arg Thr Trp Ala Leu 250 Pro Thr Tyr Asn Asn 255 His Leu Tyr Lys Gin 260 lie Ser Asn Gly Thr 265 Ser Gly Gly Ser Thr 270 Asn Asp Asn Thr Tyr 275 Ehe Gly Tyr Ser Thr 280 Ero Trp Gly Tyr Phe 285 Asp Ehe Asn Arg Ehe 290 His Cys His Ehe Ser 295 Ero Arg Asp Trp Gin 300 Arg Leu lie Asn Asn 305 Asn Trp Gly Ehe Arg 310 Ero Lys Arg Leu Asn 315 Phe Lys Leu Phe Asn 320 lie Gin Val Lys Glu 325 Val Thr Gin Asn Glu 330 Gly Thr Lys Thr lie 335 Ala Asn Asn Leu Thr 340 Ser Thr lie Gin Val 345 Phe Thr . Asp Ser Glu 350 Tyr Gin Leu Ero Tyr Val Leu Gly Ser Ala His Gin Gly Cys Leu Ero Ero Ehe

     355 360 365
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     Pro Ala Asp Val Phe Met Ile Pro Gin Tyr Gly Tyr Leu Thr Leu Asn

     370 375 380

     2015258271 20 Nov 2015

     Asn Gly Ser Gin Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr 385 390 395 400

     Phe Pro Ser Gin Met Leu Arg Thr Gly Asn Asn Phe Glu Phe Ser Tyr 405 410 415

     Gin Phe Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gin Ser 420 425 430

     Leu Asp Arg Leu Thr Asn Pro Leu lie Asp Gin Tyr Leu Tyr Tyr Leu 435 440 445

     Ala Arg Thr Gin Ser Thr Thr Gly Ser Thr Arg Gly Leu Gin Phe His 450 455 460

     Gin Ala Gly Pro Asn Thr Met Ala Glu Gin Ser Lys Asn Trp Leu Pro 465 470 475 480

     Gly Pro Cys Tyr Arg Gin Gin Arg Leu Ser Lys Asn Ile Asp Ser Asn 485 490 495

     Asn A.sn Ser Asn Phe Ala Trp Thr Gly Ala Thr Lys Tyr His Leu Asn 500 505 510

     Gly Arg Asn Ser Leu Thr Asn Pro Gly Val Ala Met Ala Thr Asn Lys 515 520 525

     Asp Asp Glu Asp Gin Phe Phe Pro lie Asn Gly Val Leu Val Phe Gly 530 535 540

     Lys Thr Gly Ala Ala Asn Lys Thr Thr Leu Glu Asn Val Leu Met Thr 545 550 555 560

     Ser Glu Glu Glu lie Lys Thr Thr Asn Pro Val Ala Thr Glu Glu Tyr 565 570 575

     Gly Val Val Ser Ser Asn Leu Gin Ser Ser Thr Ala Gly Pro Gin Thr 580 585 590

     Gin Thr Val Asn Ser Gin Gly Ala Leu Pro Gly Met Val Trp Gin Asn 595 600 605

     Arg Asp Val Tyr Leu Gin Gly Pro Ile Trp Ala Lys lie Pro His Thr 610 615 620
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     Asp 625 Gly Asn Phe His Pro 630 Ser Pro Leu Met Gly 635 Gly Phe Gly Leu Lys 640 His Pro Pro Pro Gin 645 He Leu He Lys Tyr 650 Thr Ser Asn Tyr Tyr 655 Lys Ser Thr Asn Val 660 Asp Phe Ala Val Asn 665 Thr Glu Gly Thr Tyr 670 Ser Glu Pro Arg Pro lie Gly Thr Arg Tyr Leu Thr Arg Asn Leu

     675 680 685 <210> 114 <211> 724 <212> PRT <213> capsid protein of AAV serotype, clone AAV5CAP <400> 114

     Met Ser Phe Val Asp His Pro Pro Asp Trp Leu Glu Glu Val Gly Glu 15 10 15

     Gly Leu Arg Glu Phe Leu Gly Leu Glu Ala Gly Pro Pro Lys Pro Lys 20 25 30

     Pro Asn Gin Gin His Gin Asp Gin Ala Arg Sly Leu Val leu pro Gly 35 40 45

     Tyr Asn Tyr Leu Gly Pro Gly Asn Gly Leu Asp Arg Gly Glu Pro Val 50 55 60

     Asn Arg Ala Asp Glu Val Ala Arg Glu His Asp lie Ser Tyr Asn Glu 65 70 75 80

     Gin Leu Glu Ala Gly Asp Asn Pro Tyr Leu Lys Tyr Asn His Ala Asp 85 SO 95

     Ala Glu Phe Gin Glu Lys leu Ala Asp Asp Thr Ser Phe Gly Gly Asn 100 105 110

     Leu Gly lys Ala Val Phe Gin Ala Lys Lys Arg Val Leu Glu Pro Phe 115 120 125

     Gly Leu Val Glu Glu Gly Ala Lys Thr Ala Pro Thr Gly Lys Arg lie 130 135 140

     Asp Asp His Phe Pro Lys Arg Lys Lys Ala Arg Thr Glu Glu Asp Ser 14 5 150 155 160

     Lys Pro Ser Thr Ser Ser Asp Ala Glu Ala Gly Pro Ser Gly Ser Gin 165 170 175
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     Gln lie Pro Ala Gln Pro Ala Ser Ser Leu Gly Ala Asp Thr

     180 185 190

     2015258271 20 Nov 2015

     Gln Leu

     Met Ser

     Asp Gly 210

     Met Gly 225

     Ser Tyr

     Gly Ser

     Phe Asp

     Arg Leu 290

     Lys lie 305

     Thr Thr

     Asp Asp

     Leu Pro

     Ala Thr 370

     Ehe Ehe 385

     Asn Ehe

     Ala Gly Gly Gly Gly Pro Leu Gly Asp Asn Asn Gln Gly Ala 195 200 205

     Val Gly Asn Ala Ser Gly Asp Trp His Cys Asp Ser Thr Trp 215 220

     Asp Arg Val Val Thr Lys Ser Thr Arg Thr Trp Val Leu Pro 230 235 240

     Asn Asn His Gln Tyr Arg Glu He Lys Ser Gly Ser Val Asp 245 250 255

     Asn Ala Asn Ala Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr 260 265 270

     Phe Asn Arg Phe His Ser His Trp Ser pro Arg Asp Trp Gln 275 280 285

     Ile Asn Asn Tyr Trp Gly Phe Arg Pro Arg Ser Leu Arg Val 295 300

     Ehe Asn Ile Gln Val Lys Glu Val Thr Val Gln Asp Ser Thr 310 315 320

     Ile Ala Asn Asn Leu Thr Ser Thr Val Gln Val Phe Thr Asp 325 330 335

     Tyr Gln Leu Pro Tyr Val Val Gly Asn Gly Thr Glu Gly Cys 340 345 350

     Ala Phe Pro Pro Gln Val Phe Thr Leu Ero Gln Tyr Gly Tyr 355 360 365

     Leu Asn Arg Asp Asn Thr Glu Asn Ero Thr Glu Arg Ser Ser 375 380

     Cys Leu Glu Tyr Phe Pro Ser Lys Met Leu Arg Thr Gly Asn 390 395 400

     Glu Phe Thr Tyr Asn Phe Glu Glu Val Pro Phe His Ser Ser 405 410 415

     Pro Ser Gln Asn Leu Phe Lys Leu Ala Asn Pro leu Val Asp 420 425 430

     Phe Ala
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     Gin Tyr Leu Tyr Arg Ehe Val Ser Thr Asn Asn Thr Gly Gly Val Gin

     435 440 445

     Ehe Asn lys Asn Leu Ala Gly Arg Tyr Ala Asn Thr Tyr Lys Asn Trp

     2015258271 20 Nov 2015

     450 455

     Ehe Ero Gly Pro Met Gly Arg Thr 465 470

     Val Asn Arg Ala Ser Val Ser Ala 485 leu Glu Gly Ala Ser Tyr Gin Val 500

     Asn Asn Leu Gin Gly Ser Asn Thr 515 520

     4 60

     Gin Gly Trp Asn Leu Gly Ser Gly 475 480

     Phe Ala Thr Thr Asn Arg Met Glu 490 495

     Pro Pro Gin Pro Asn Gly Met Thr 505 510

     Tyr Ala Leu Glu Asn Thr Met lie 525

     Phe Asn Sex Gin Pro Ala Asn Ero 530 535

     Gly Thr Thr Ala Thr Tyr Leu Glu 540

     Gly Asn Met leu Ile Thr Ser Glu 545 550

     Ser Glu Thr Gin Pro Val Asn Arg 555 560

     Val Ala Tyr Asn Val Gly Gly Gin 565

     Met Ala Thr Asn Asn Gin Ser Ser 570 575

     Thr Thr Ala Ero Ala Thr Gly Thr 580

     Tyr Asn Leu Gin Glu lie Val Pro 585 590

     Gly ser Val Trp Met Glu Arg Asp 595 600

     Val Tyr Leu Gin Gly Pro Ile Trp 605

     Ala Lys Ile Pro Glu Thr Gly Ala 610 615

     His Phe His Pro Ser Pro Ala Met 620

     Gly Gly Phe Gly Leu Lys His Pro 625 630

     Pro Pro Met Met Leu Ile Lys Asn 635 640

     Thr Pro Val Pro Gly Asn Ile Thr 645

     Ser Ehe Ser Asp Val Pro Val Ser 650 655

     Ser Phe lie Thr Gin Tyr Ser Thr 660

     Gly Gin Val Thr Val Glu Met Glu 665 670

     Trp Glu Leu Lys Lys Glu Asn Ser 675 680

     Lys Arg Trp Asn Pro Glu Ile Gin 685
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     Tyr Thr Asn Asn Tyr Asn Asp Pro Gin Phe Val Asp Phe Ala Pro Asp

     690 695 700

     2015258271 20 Nov 2015

     Ser Thr Gly Glu Tyr Arg Thr Thr Arg Pro lie Gly Thr Arg Tyr leu 705 710 715 720

     Thr Arg Pro leu <210> 115 <211> 9 <212> DNA <213> Drain restriction enzyme site <4 00> 115 caccacgtc 9 <210> 116 <211> 28 <212> DNA <213> AV2cas <400> 116 cgcagagacc aaagttcaac tgaaacga 28 <210> 117 <211> 255 <212> DNA <213> adeno-associated virus serotype 10 <400> 117

     ggtaattcct ccggaaattg gcattgcgat tccacatggc tgggcgacag agtcatcacc 60 120 18 0 240 255 accagcaccc agcgagacag tttgacttta aacaac-tggg gaacctgggt cctgcccacc taoaacaacc aoatctacaa gcaaatctcc gagccaccaa cgacaaccac tacttcggct acagcacccc actggcagcg ctgggggtat actcatcaac acagattcca gat to ctgccacttt tcaccacgtg <210> 118 <211> 258 <212> DNA <213> adeno-associated virus serotype 11 <400> 118 ggtaattcct ccggaaattg gcattgcgat tccacatggc tgggcgacag agtcatcacc 60 accagcaccc gaacctgggc cctgccaacc tacaacaacc acctctacaa acaaatctcc 120 agcgcttcaa cgggggccag caacgacaac cactactttg gctacagcae cccctggggg 18 0
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     PCT/US02/33629

     2015258271 20 Nov 2015 tattttgact ttaacagatt ccactgccac ttctcaccac gtgactggca gcgactcatc 240 aacaacaact ggggattc 258 <21O> 119 <211> 255 <212> DNA <213> adeno-associated virus serotype 12 <400> 119 ggtaattcct ccggaaattg gcattgcgat tccacatggc tgggcgaccg agtcattacc 60 accagcaccc ggacttgggc cctgcccacc tacaacaacc acctctacaa gcaaatctcc 120 agccaatcgg gtgccaccaa cgacaaccac tacttcggct acagcacccc ttgggggtat 180 tttgatttca acagattcca ctgccatttc tcaccacgtg actggcagcg actcatcaac 240 aacaactggg gattc 255 <210> 120 <211> 2205 <212> DNA <213> adeno-associated virus serotype, clone A3.1vpl <400> 120

     atggctgccg atggttatct tccagattgg ctcgaggaca ctctctctga aggaatcaga 60 cagtggtgga agctcaaacc tggcccaeca ccgccgaaac ctaaccaaca acaccgggac 120 gacagtaggg gtcttgtgct tcctgggtac aagtacctcg gacccttcaa cggactcgac 180 aaaggagagc cggtcaacga ggcagacgcc gcggccctcg agcacgacaa agcctacgac 240 caccagctca agcaagggga caacccgtac ctcaaataca accacgcgga cgctgaattt 300 caggagcgtc ttcaagaaga taegtettte gggggcaacc tcgggcgagc agtcttccag 360 gccaaaaaga gggtactcga gcctcttggt ctggttgagg aagctgttaa gacggctcct 420 ggaaaaaaga gacctataga gcagtctcct gcagaaccgg actcttcctc gggcatcggc 480 aaatcaggcc agcagcccgc taagaaaaga ctcaattttg gtcagactgg cgacacagag 540 tcagtcccag accctcaacc aatcggagaa ccccccgcag ccccctctgg tgtgggatct 600 aatacaatgg cttcaggcgg tggggcacca atggcagaca ataaegaagg cgccgacgga 660 gtgggtaatt cctcgggaaa ttggcattgc gattccacat ggatgggcga cagagttatc 720 accaccagca caagaacctg ggccctcccc acctacaata atcacctcta caagcaaatc 780 tccagcgaat cgggagccac caacgacaac cactacttcg gctacagcac cccctggggg 840 tattttgact ttaacagatt ccactgtcac ttctcaccac gtgactggca gcgactcatc 900 aacaacaact ggggatttag acccaagaaa ctcaatttca agctcttcaa catccaagtc 960 aaggaggtca cgcagaatga tggaaccacg accatcgcca ataaccttac cagcacggtg 1020
268. 268

     WO 03/042397

     PCT/US02/33629

     2015258271 20 Nov 2015

     caggtcttca cagactctga gtaccagctg ccctacgtcc tcggttcggc tcaccagggc 1080 tgccttccgc cgttcccagc agacgtcttc atgattcctc agtacggcta cttgactctg 1140 aacaatggca gccaagcggt aggacgttct tcattctact gtctagagta ttttccctct 1200 cagatgctga ggacgggaaa caacttcacc ttcagctaca cttttgaaga cgtgcctttc 1260 cacagcagct acgcgcacag ccagagtctg gatcggctga tgaatcctct cattgaccag 1320 tacctgtatt acctgagcaa aactcagggt acaagtggaa caacgcagca atcgagactg 1380 cagttcagcc aagctgggcc tagctccatg gctcagcagg ccaaaaactg gctaccggga 1440 cccagctacc gacagcagcg aatgtctaag acggctaatg acaacaacaa cagtgaattt 1500 gcttggactg cagccaccaa atattacctg aatggaagaa attctctggt caatcccggg 1560 cccccaatgg ccagtcacaa ggacgatgag gaaaagtatt tccccatgca cggaaatctc 1620 atctttggaa aacaaggcac aggaactacc aatgtggaca ttgaatcagt gcttattaca 1680 gacgaagaag aaatcagaac aactaatcct gtggctacag aacaatacgg acaggttgcc 1740 accaaccatc agagtcagaa caccacagct tcctatggaa gtgtggacag ccagggaatc 1800 ttacctggaa tggtgtggca ggaccgcgat gtctatcttc aaggtcccat ttgggccaaa 1860 actcctcaca cggacggaca ctttcatcct tctccgctca tgggaggctt tggactgaaa 1920 caccctcctc cccagatcct gatcaaaaac acacctgtgc cagcgaatcc cgcgaccact 1980 ttcactcctg gaaagtttgc ttcgttcatt acccagtatt ccaecggaca ggtcagcgtg 2040 gaaatagagt gggagctgca gaaagaaaac agcaaacgct ggaacccaga aattcagtac 2100 acctccaact acaacaagtc ggtgaatgtg gagtttaccg tggacgcaaa cggtgtttat 2160 tctgaacccc gccctattgg cactcgttac cttacccgga acttg 2205
269. 269