AU2020201242B2 - ADENO-ASSOCIATED VIRUS cy.5 (AAVcy.5) SEQUENCES AND RECOMBINANT AAVs COMPRISING SAME - Google Patents

Abstract

fit\nterwoven\NRPortbl\DCC\FMT\161863 12_.doc-18/l2/2017 ABSTRACT 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

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

This is a divisional of Australian Patent Application No. 2017279564, which in turn is a divisional of Australian Patent Application No. 2015258271, which in turn is a divisional of Australian Patent Application No. 2012238302, which in turn is a divisional of Australian Patent Application No. 2011250837, which in turn is a divisional of Australian Patent Application No. 2008202344, which in turn is a divisional of Australian Patent Application No. 2002361573, 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 non-human 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 According to a first aspect of the invention there is provided a recombinant adeno associated virus (AAV) comprising an AAV capsid comprising vp l proteins having the sequence of amino acids I to 738 of SEQ ID NO: 81 or a sequence at least 95% identical to the full length of amino acids I to 738 of SEQ ID NO: 81, 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 whichdirect expression of the product in a host cell, wherein the gene product is ornithine transcarbamylase, glucose-6-phosphatase, phenylalanine hydroxylase, argininosuccinate synthetase or a dystrophin protein. According to a second aspect of the invention there is provided a recombinant adeno associated virus (AAV) having an AAV capsid comprising AAV vp l proteins, AAV vp2 proteins having a sequence of amino acids 138 to 738 of SEQ ID NO:81 (rh.10) or a sequence at least 95% identical to the full-length of amino acids 138 to 738 of SEQ ID NO: 81, 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, wherein the gene product is ornithine transcarbamylase, glucose-6-phosphatase, phenylalanine hydroxylase, argininosuccinate synthetase or a dystrophin protein. According to a third aspect of the invention there is provided a recombinant adeno associated virus (AAV) having an AAV capsid comprising AAV vp l proteins, AAV vp2 proteins, and AAV vp3 proteins having a sequence of amino acids 204 to 738 of SEQ ID NO:81 (rh.10) or a sequence at least 95% identical to the full-length of amino acids 204 to 738 of SEQ ID NO: 81, 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, wherein the gene product is ornithine transcarbamylase, glucose-6-phosphatase, phenylalanine hydroxylase, argininosuccinate synthetase or a dystrophin protein. According to a fourth aspect of the invention there is provided a composition comprising a pharmaceutically compatible carrier and at least the recombinant AAV according to any one of the first, second or third aspects. According to a fifth aspect of the invention there is provided a method for delivering a transgene product to a subject, said method comprising administering the adeno-associated virus (AAV) according to any one of the first, second or third aspects. 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 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 ofnovel 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. 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 IN 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-filed 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], 42-5b [SEQ ID NO: 29], 42-1 b [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 AAV1O [SEQ ID NO: 117], AAV 1I [SEQ ID NO:

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: C I[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], Fl [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 co filed 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 also suitable for detection, identification and/or isolation of other integrated viral and non viral 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 AAV1, 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 vp1, 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 Fasta, 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 identity 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 identity 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 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 full 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 full-length of the genome, the full-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.

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 well suited for detection of viral sequences which are integrated into the chromosome of a cell, e.g., adeno associated 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 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 involves subjecting a sample containing DNA to 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 predetermined based upon the alignment of the 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 variable 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 of the 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 variable 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 AAVI, AAV2, AAV3, AAV4, AAV5, or AAV6, or that of AAV7, AAV10, AAV11, AAV12, 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 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 N08], 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 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'. However, 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, AAVO, 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, P1 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 anneals 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 (P1 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 (P1 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 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 DrallI, which cleaves at the DrallI 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 (AVIns: 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.1 - rh.37), 6 clones from cynomologous macaques (cy.1 - cy.6), 2 clones from Baboons (bb.1 and bb.2) and 5 clones from Chimps (ch.1 - ch.5). These clones are identified 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, E40RF6. 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 non viral 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 et al., 1995, Nucleic Acid Research, 23:1087-1088, Friezner Degen et al., 1986, J Biol. Chen. 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 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' and3'PCR primers specific for a signature region of the AAV 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 AVIns 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 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 NH 4 SO4 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.

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 ofthe 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: 18 which spans 258 bases]. The AAVI2 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 AAV1O, 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 Clone Source AAV Cap Number Sequence Species Tissue SEQ ID NO (DNA) Rh.1 Clone 9 Rhesus Heart 5 (AAV9) Rh.2 Clone 43.1 Rhesus MLN 39 Rh.3 Clone 43.5 Rhesus MLN 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

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.11 Clone 44.5 Rhesus Liver 47 Rh.12 Clone Rhesus MLN 30 42.1B Rh.13 42.2 Rhesus MLN 9 Rh.14 Clone Rhesus MLN 32 42.3A Rh.15 Clone Rhesus MLN 36 42.3B Rh.16 Clone 42.4 Rhesus MLN 33 Rh.17 Clone Rhesus MLN 34 42.5A Rh.18 Clone Rhesus MLN 29 42.5B Rh.19 Clone Rhesus MLN 38 42.6B 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.30 Clone 223.7 Rhesus Liver 53 Rh.31 Clone Rhesus Liver 48 223.10 Rh.32 Clone C1 Rhesus Spleen, Duo, 19 Kid & Liver Rh.33 Clone C3 Rhesus 20 Rh.34 Clone C5 Rhesus 21 Rh.35 CloneFI Rhesus Liver 22 Rh.36 Clone F3 Rhesus 23 Rh.37 Clone F5 Rhesus 24 Cy.1 Clone 1.3 Cyno Blood 14 Cy.2 Clone Cyno Blood 15 13.3B Cy.3 Clone 24.1 Cyno Blood 16 Cy.4 Clone 27.3 Cyno Blood 17 Cy.5 Clone 7.2 Cyno Blood 18 Cy.6 Clone 16.3 Cyno Blood 10

Table 1 (cont'd) bb.1 Clone 29.3 Baboon Blood 11 bb.2 Clone 29.5 Baboon Blood 13 Ch.1 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 also 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. 1 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, 117-120], 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% identical or homologous to the sequences of the invention, including Fig. 1 and the Sequence Listing [SEQ ID NO:1, 9 - 59, 117-120]. 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. I 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 AAVI, AAV2, or AAV7. However, using the alignment provided herein (obtained using the Clustal W program at default settings), or similar techniques for 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: vp l [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:]. 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 vp1, 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 I 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. I for AAV7] Other fragments of interest may include the AAV 5' inverted terminal repeats ITRs, [nt I to 107 of Fig. 1 for AAV7]; the AAV 3' ITRs [nt 4704 to 4721 of Fig. 1 for AAV7], P19 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.

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: C1 [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], Fl [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], 42-1b [SEQ ID NO:30]; 42-13 [SEQ ID NO: 31], 42-3a

[SEQIDNO: 32],42-4[SEQIDNO:33],42-5a[SEQIDNO:34],42-10[SEQIDNO:35], 42-3b[SEQIDNO:36],42-11[SEQIDNO:37],42-6b[SEQIDNO:38],43-1 [SEQID 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], 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-lB [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], Fl [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

(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. TheAAV 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 vp1 [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; HVR1, 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 501 505; HVR8 is located at aa 513-521; HVR9 is located at 533-554; HVR1O is located at aa 583-596; HVRI1 is located at aa 660-669; HVR12 is located at aa 707-721. Using the 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 HVR 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 displayed below the sequences, starting at 1 for the first residue position. The line 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. Additionally, 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; aa133-165; 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 709 723. Still other desirable fragments include, for example, in AAV7, amino acids I 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. Still 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 I 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 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 sequences. In one embodiment, the rep and cap sequences are expressed from separate sources (e.g., separate vectors, or a host cell 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., HPVI-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 adeno associated virus (AAV) having an AAV serotype 7 (or another novel AAV) capsid, or a portion thereof. Such a method involves culturing a host cell 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 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 cell 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. Still 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 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 P-lactamase, p-galactosidase (LacZ), alkaline phosphatase, thymidine kinase, green fluorescent protein (GFP), chloramphenicol acetyltransferase (CAT), luciferase, membrane bound proteins including, for example, CD2, CD4, CD8, 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 cell 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 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 ofthe 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); Furler, 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 sequences, including promoters which are native, constitutive, inducible and/or tissue specific, 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 5 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 dihydrofolate reductase promoter, the p-actin promoter, the phosphoglycerol kinase (PGK) promoter, and the EFlIa promoter [Invitrogen]. Inducible promoters allow regulation of gene expression 10 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 developmentally, or in a tissue specific manner, or in response to specific transcriptional stimuli. In a further embodiment, 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 p-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 Cell 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 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 plasmid 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-heterologous 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 g to about 100 g DNA, and preferably about 10 to about 50 g DNA to about I X 10 4 cells to about I X 101 cells, and preferably about 105 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 cell 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 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 cell. Another embodiment has the rep and cap sequences transiently expressed in the host cell. 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 comprise one or more of the genes encoding the helper functions, e.g., the adenoviral proteins El, E2a, and E40RF6, 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 polyA 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 X 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 rep68 gene products, leaving the rep52, rep40 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 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 Ela 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 Ela 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, El b, E2a, and/or E40RF6 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, 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 episodes, 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) cells, 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 1, BSC 40, BMT 10, VERO, W138, 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 E40RF6 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.

The preparation of a host cell 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, 5 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 10 throughout the specification. In preferred embodiment, standard transfection techniques are used, e.g., CaPO 4 transfection or electroporation, and/or infection by hybrid adenovirus/AAV vectors into cell lines such as the human embryonic kidney cell line HEK 293 (a human kidney cell line containing functional adenovirus El genes which provides trans-actingEl 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 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 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 or unique AAV serotypes of the invention may be used in constructs containing other viral 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 delivery to other cell types, tissues or organs. Further, vectors based cells, tissues or upon other capsids of the invention may be used for delivery to these or other 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 are well generated with the sequences of the AAV of the invention. Methods for delivery 30 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 AAV mediated delivery of a transgene to a host. This method involves transfecting or infecting a selected host cell with a recombinant viral vector containing a selected transgene under the control of sequences which direct expression thereof and AAV capsid proteins. 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 AAV1, AAV2, AAV3A, AAV3B, AAV4, AAV6, AAV10, AAV 11, and AAV12, or any of the other novel AAV capsids identified herein including, without limitation: A3.1, H2, H6, C1, 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, 43 25, 43-20, 24.1, 42.2, 7.2, 27.3, 16.3, 42.10, 42-3B, 42-11, F1, 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, 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 10" to 1x 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.

B. Therapeutic Transgenes Useful therapeutic products encoded by the transgene include hormones and growth and differentiation factors including, without limitation, 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), platelet derived growth factor (PDGF), insulin growth factors I and II (IGF-I and IGF-II), any one of the transforming growth factor Psuperfamily, including TGF , 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 , interferons a, P, and y, stem cell factor, flk-2/fIt3 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 cofactor 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 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 asjun, fos, max, mad, serum response factor (SRF), AP-1, AP2, myb, MyoD and myogenin, ETS box containing proteins, TFE3, E2F, ATFi, ATF2, ATF3, ATF4, ZF5, NFAT, CREB, HNF 4, 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 transcarbamylase, arginosuccinate synthetase, arginosuccinate lyase, arginase, fumarylacetacetate hydrolase, phenylalanine hydroxylase, alpha-i antitrypsin, glucose-6 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, glutaryl CoA dehydrogenase, insulin, beta glucosidase, 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 P-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, single chain 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 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), Sjbgren'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 ofviral 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 VPI, VP2, VP3, VP4, and VPG. Another viral 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 non human 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 N 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).

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 panleucopeniavirus, 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-family chordopoxvirinae, which encompasses the genera orthopoxvirus (Variola (Smallpox) and Vaccinia (Cowpox)), parapoxvirus, avipoxvirus, capripoxvirus, leporipoxvirus, suipoxvirus, and the sub-family 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.

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 cell 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; shigella; haemophilus; moraxella; H. ducreyi (which causes chancroid); brucella; Franisellatularensis(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 tularemiaa), and viral hemorrhagic fever, all of which are currently classified as

Category A agents; Coxiella burnetti (Q fever); Brucella species (brucellosis), Burkholderia mallei (glanders), Ricinus communis and its toxin(ricin toxin), Clostridiumperfingens and its toxin (epsilon toxin), Staphylococcus species and their toxins (enterotoxin B), all of which are currently classified as Category B agents; and Nipan virus and hantaviruses, which are 5 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 by products, which will prevent and/or treat infection or other adverse reactions with these 10 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 15 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 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 HIV-1 Env is delivered. 10 However, the prime-boost regimens are not limited to immunization for HIV or to delivery of these antigens. For example, priming 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 prime boost regimen can provide a protective immune response to the virus, bacteria or other 15 organism from which the antigen is derived. In another desired embodiment, the prime boost 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 about1I g to 1000 tg 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 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 cross reactive 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 cells 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 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] 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, pig tailed 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 AAV 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.

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 5 variable sequence in the middle. In addition, this region contains a DraIII 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 1, 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, l8as, 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.

Table 1. Sequences for Analysis Sequence # AAV Serotype Size (bp)

I AAV1 258 2 AAV2 255 3 AAV3 255 4 AAV4 246 5 AAV5 258 6 AAV6 258 7 AAV7 258 10 AAV10 255 11 AAV11 258 12 AAV12 255

Table 3. Pairwise Alignment (Percentage of Identity) 5 AAV2 AAV3 AAV4 AAV5 AAV6 AAV7 AAV1O 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 ofthe signature regionfor 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 (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 720 C for I 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

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, the5'primer, AVNs, was GCTGCGTCAACTGGACCAATGAGAAC

[nt 1398-1423 of AAV1, SEQ ID NO:6] and the 3'primer was l8as, 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 Drall 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 DraIII 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 (AVIns: 5' GCTGCGTCAACTGGACCAATGAGAAC 3', nt 1398-1423 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 full-length cap fragments. The PCR products were Topo-cloned according to manufacturer's directions (Invitrogen) and sequence analysis was performed by

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. I- rh.37), 6 clones from cynomologous macaques (cy.1 - cy.6), 2 clones from Baboons (bb.1 and bb.2) and 5 clones from Chimps (ch.1 - 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 splicing 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 cellular 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 cells. In a different experiment, we restricted AAV7 and AAV8 plasmids with Msp I, Ava I and Hael, all 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).

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 AAV3 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 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 large scale 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/00E033 - 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 VP Iclones 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,

68-73 (1998)] with implementation of the method of split decomposition. The analysis depicts homoplasy 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 VPl 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). VPl sequences of the novel AAVs were further characterized with respect to the nature and location of amino acid sequence variation. All 30 VPl 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 three fold-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 I 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 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 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 Clades. 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. pAA V2GFP 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 transplasmid 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 I to linearize the plasid 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 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 P19 promoter. The AAV7 capsid sequences are under the control of the AAV2 P40Opromoter, which is located within the Rep sequences. This plasmid further contains a spacer 5' of the rep ORF. C. ProductionofPseudotypedrAAV 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 pCRAAV7 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, pBG10 plasmid was purchased from Microbix (Canada). A RsrII fragment containing L2 and L3 was deleted from pBHG10, resulting in the first helper plasmid, pAdAF13. Plasmid AdA F1 was constructed by cloning Asp700/SalI fragment with a PmeI/Sgfl deletion, isolating from pBHG10, into Bluescript. MLP, L2, L2 and L3 were deleted in the pAdAF1. Further deletions of a 2.3 kb NruI fragment and, subsequently, a 0.5 kb RsrI/NruI fragment generated helper plasmids pAdAF5 and pAdAF6, respectively. The helper plasmid, termed pAF6, provides the essential helper functions of E2a and E4 ORF6 not provided by the El expressing helper cell, but is deleted of adenoviral capsid proteins and functional El regions). Typically, 50 g of DNA (cis:trans:helper) was transfected onto a 150 mm tissue culture dish. The 293 cells were harvested 72 hours post-transfection, sonicated and treated with 0.5% sodium deoxycholate (37°C for 10 min.) Cell lysates were then subjected to two rounds of a CsCl gradient. Peak fractions containing rAAV vector are collected, pooled and dialyzed against PBS.

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 AAV 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 cell 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 AAVl/7 was employed to produce AAV2 vectors packaged with AAVI, AAV5 and AAV8 capsid proteins. Briefly, 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 I/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 CsC12 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 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 1013 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=1) (n=1)

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) (ii=2)

TBG LacZ 4.18 0.23 0.704+0.43 2.16 0.532 (n1=1) (n=71) (n=2) (n=1) (n=1)

Alb AAT 4.67+0.75 4.77 4.09 5.04 2.02 (n=2) (n=1) (n1=1) (n1=1) (n=-1)

CB AAT 0.567 0.438 2.82 2.78 0.816+ (n1=1 (n=1) (n=1) (n=) 0.679 (n=2)

Table 4 (cont'd).

AAV2/1 AAV2/2 AAV2/5 AAV2/7 | AAV2/8 TBG 8.51+6.65 3.47+2.09 5.26+3.85 6.52+3.08 1.83+0.98 rhCG (n=6) (n=5) (n=4) (n=4) (n=5)

TBG eFIX 1.24+1.29 0.63±0.394 3.74+2.48 4.05 15.8± 15.0 (n=3) (n=6) (n=7) (n=1) (n=5)

Example 6 - Serologic Analysis of Pseudotyped Vectors C57BL/6 mice were injected with vectors of different serotypes of AAVCBA1AT vectors intramuscularly (5 x 1011 GC) and serum samples were collected 34 days later. To test neutralizing and cross-neutralizing activity of sera to each serotype of AAV, sera was analyzed in a transduction based neutralizing antibody assay [Gao, G. P., et al., (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 cells 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 cells] was pre-incubated with heat-inactivated serum from animals that received different serotypes of AAV or from naYve mice. After 1-hour incubation at 370C, 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 Fluoromagin (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 cell line (i.e., 293 cells 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, AAV5 and AAV8 neutralized transduction of the serotype to which the antiserum was generated (AAV5 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).

Table 5. Serological Analysis of New AAV Serotypes.

%Infection on 84-31 cells with AAVCMVEGFP virus: AAV2/1 I 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 11/20 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 AAV2/5 100 100 100 100 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 Serotypes of AAV Vectors In this study, 7 recombinant AAV genomes, AAV2CBhA1AT, AAV2AIbhA1AT, 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 humano antitrypsin (AAT) [Xiao, W., et al., (1999) J Virol 73, 3994-4003] p-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) ProcNatlAcadSci USA 94, 11563-6] and bacterial p-glactosidase (i.e., Lac Z) genes were used as reporter genes. For liver directed 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 p-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 different time points after vector administration. Muscle and liver tissues were harvested at different time points for cryosectioning and Xgal histochemical staining from animalsihat received the lacZ vectors. For the re-administration experiment, C56BL/6 mice initially received AAV2/1, 2/2, 2/5, 2/7 and 2/8CBAIAT 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 U S A 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 al., (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 AAVI, AAV2 and AAV5. Vectors expressing secreted proteins (alpha antitrypsin (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 p-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 AlAT and AAV2/2 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

AAV2/7vectors 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 103). 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 AIAT vectors in nu/nu and C57BL/6 mice and CG vectors in C57BL/6 mice was consistent (See Table 6).

Table 6. Expression of 0-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 cells and overall levels of transgene expression. DNAs extracted from livers of C57BL/6 mice who received the AlAT vectors were analyzed for abundance of vector DNA using real time PCR technology.

The amount of vector DNA found in liver 56 days after injection correlated with the levels of transgene expression (See Table 7). For this experiment, a set of probe and primers targeting the SV40 polyA 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 x1 Genome Copies of Vector.

AAV vectors/Dose Genome Copies per Cell

AAV2/1AlbA1AT 0.6± 0.36

AAV2A1bA1AT 0.003 ±0.001

AAV2/5AlbA1AT 0.83± 0.64

AAV2/7AlbA1AT 2.2± 1.7

AAV2/8AIbA1AT 18 ± 11

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 (1011 genome copies) 56 days after they received intramuscular injections of AlAT vectors of different serotypes. High levels of factor IX expression were obtained 14 days following infusion of AAV2/8 into naYve animals (17±2 pg/ml, n=4) which were not significantly different that what was observed in animals immunized with AAV2/1 (3123 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 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 AAV8 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 AAV8 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., et al., (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 pre existing immunity to the AAV serotypes of the invention, and their tropisms, renders them useful in delivery of therapeutic molecules and other useful molecules.

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 P actin promoter) was selected to drive an easily detectable and quantifiable reporter gene, human c 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 (AAVCBA1AT), 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.10 (44.2) 23±6 53±19 46±11 AAV2/rh.13 (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 CC1OhA1AT minigene for lung specific expression were pseudotyped with capsids of novel AAVs were given to Immune deficient animals (NCR nude) in equal volume (50 pl each of the original preps without dilution) via intratracheal injections as provided in the following table. In Table 9, 50 pl of each original prep per mouse, NCR Nude, detection limit >0.033 pg/ml, Day 28

Table 9

Vector Total GC sg of A1AT/ml pg of A1AT/ml Relative Gene in with 50pl vector with 11 1 " transfer as 50 v ector vector compared to rh.10 (clone 44.2) 2/1 3x1012 2.6+0.5 0.09+0.02 2.2 2/2 5.5x101 <0.03 <0.005 <0.1 2/5 3.6x10' 2 0.65+0.16 0.02+0.004 0.5 2/7 4.2x1012 1+0.53 0.02+0.01 0.5 2/8 7.5x10" 0.9+0.7 0.12+0.09 2.9 2/ch.5 (A.3.1) 9x10' 2 1+0.7 0.01+0.008 0.24 2/rh.8 (43.25) 4.6x10 12 26+21 0.56+0.46 13.7 2/rh.10 (44.2) 2.8x10 12 115138 4.1+1.4 100 2/rh.13 (42.2) 6x10' 7.3+0.8 0.12+0.01 2.9 2/rh.21 (42.10) 2.4x101 2 9+0.9 0.38+0.04 9.3 2/rh.22 (42.11) 2.6x10 12 6+0.4 0.23+0.02 5.6 2/rh.24 (42.13) 1.1xl 1 0.4+0.3 0.4+0.3 1

The vectors were also administered to immune competent animals (C57BL/6) in equal genome copies (1x1O" GC) as shown in the Table 10. (1x10' GC per animal, C57BL/6, day 14, detection limit>0.033 pg/ml)

Table 10 AAV Vector tg of A1AT/mi Relative Gene transfer as with x1 vector compared to rh.10 (clone 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 11 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.10 (44.2) 2.93±1.7 100 2/rh.13 (42.2) 0.45±0.15 15 2/rh.21 (42.10) 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 tropism of clone 44.2 in lung directed gene transfer.

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 Ha. Cross-NAB assay in 8431 cells and adenovirus (Ady) coinfection Infection in 8431 cells (coinfected with Adv) with:

Serum 10 9 GC 10'GC 10 9 GC 1010 GC from rabbit rh.13 rh.21 rh.22 rh.24 immunized with: 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

Table 11b. Cross-NAB assay in 8431 cells andAdv coinfection Infection in 8431 cells (coinfected withAdv) with: 109 GC 101° GC 10°'GC 109 GC 109 GC Serum rh.12 ch.5 rh.8 rh.10 rh.20 from rabbit immunized with: AAV2/42.IB 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 AAV2/42.13 1/5120 ND ND ND 1/2560

Table 12 Titer of rabbit sera Titer after Vector ITiter d21 Boosting 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 10' GC/well 10' GC/well 109 GC/well 109 GC/well 109 GC/well 109 GC/well ch.5 AAV2/1 AAV2/2 AAV2/5 AAV2/7 AAV2/8 AAV2/A3 128 >200 95 56 13 1 #GFU/field 83 >200 65 54 11 1

Table 13b. Infection in 8431 cells (coinfected with Ady) with GFP 10 9 GC/well 10 9 GC/well 109 GC/well 109 GC/well 109 GC/well 109 GC/well 109 GC/well 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 3 13 54 62 10 3 18 #GFU/field 2 12 71 60 14 2 20 1 _ 1_ 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 cis-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 standardCsC12 sedimentation method. To determine the yield TaqMan (Applied Biosystems) analysis was performed using probes and primers targeting the SV40 poly(A) region of the vectors [Gao GP, et aL, Hum Gene Ther. 2000 Oct 10;11(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 C57B/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 retroorbital bleeds and the lipid profile evaluated. The mice were randomly divided into seven groups. The vector was injected via an intraportal injection as previously described ([Chen SJ et al., Mol Therapy 2000; 2(3), 256-2611. 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 100ul PBS was directly injected into the portal vein. Pressure was applied to the injection site to ensure a 5 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 10 plaque measurement and determination of transgene expression.

Table 14 Vector dose n7 Group 1 AAV2/7-TBG-hLDLr lx 1012 gc 12 Group AAV2/7-TBG-hLDLr 3x 10" gc 12 Group 3 AAV2/7-TBG-hLDLr lx 101 gc 12 Group 4 AAV2/8-TBG-hLDLr lx 1012 gc 12 Group 5 AAV2/8-TBG-hLDLr 3x10"gc 12 Group 6 AAV2/8-TBG-hLDLr ix 101 gc 12 Group 7 AAV2/7-TBG- LacZ lx 101 gc 16

C. Serum lipoproteinand liverfunction 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, Schiapparelli 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-HCI Ready Gels (Biorad, Hercules, CA) and transferred to a nitrocellulose membrane (Invitrogen, ). To generate Anti-hLDL receptor antibodies a rabbit was injected intravenously with an AdhLDLr prep (1x10 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 HRP-conjugated anti-rabbit IgG and ECL chemiluminescent detection (ECL Western Blot Detection Kit, Amersham, Arlington Heights, IL). B. Immunocytochemistry For determination of LDL receptor expression in frozen liver sections immunohistochemistry analyses were performed. 1Oum 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 anti rabbit 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 non immune 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. Atheroscleroticplaque 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 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. ClearanceofI125 LDL Two animals per experimental group were tested. A bolus ofI125 labeled LDL (generously provided by Dan Rader, U Penn) was infused slowly through the tail vein over a period of 30 see (1,000,000 counts of [I12s ]-LDL diluted in 100l 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 10pl plasma counted in the gamma counter. Finally the fractional catabolic rate was calculated from the lipoprotein clearance data. 1. Evaluation ofLiver 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 jelly solution. 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% H2 S04 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 ddH2 0 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 IM MgC2 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 plaque area for the AAV2/8 and AAV2/7 mice was observed in treated mice at the first test (2 months), and the effect was observed to persist over the length of the experiment (6 months).

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 AAV1, AAV2, AAV5, AAV7 or AAV8 were constructed to deliver AAV2 5' ITR - liver-specific promoter [LSP] - 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. Nat. Acad. Sci. USA 94: 11563-11566. This model closely mimic the phenotypes of hemophilia B in human. Vectors of different serotypes (AAVI, AAV2, AAV5, AAV7 and AAV8) were delivered as a single intraportal injection into the liver of adult hemophiliac C57B1/6 mice in a dose of xO" GC/mouse for the five different serotypes and one group received an AAV8 vector at a lower dose, 1x10 GC/mouse. Control group was injected with x1" 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.Nat.Acad.Sci.USA, 87:5173-5177 with modifications. Sheep anti canine 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 10") and AAV2/7 constructs, with sustained superphysiology levels cFIX levels (ten-fold higher than the normal level). Expression levels for AAV2/8 (1011) were approximately 10 fold higher

10). The lowest expression levels, than those observed for AAV2/2 and AAV2/8 (1 although still above the therapeutic range, were observed for AAV2/5. 2. In Vitro Activated PartialThromboplastin 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 post injection, 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 (10") 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. HemophiliaB 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.

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" genome copies (GC)/kg. A second dog receives a first injection of AAV2/2.cFIX (2.8x10" GC/kg), followed by a second injection with AAV2/7.cFIX (2.3x1013 GC/kg) at 5 day 1180. A third dog receives a single injection with AAV2/2.cFIX at a dose of 4.6x10 2 GC/cg. The fourth dog receives an injection with AAV2/2.cFIX (2.8x0 2GC/kg) and an injection at day 995 with AAV2/7.cFIX (5x101 GC/kg). The abdomen of hemophilia dogs are aseptically and surgically opened under general anesthesia and a single infusion of vector is administered into the portal vein. The 10 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, 15 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 ofvector 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.

11:\fmht\nterwovn\NRPortbl\DCC\FMT\8872740_I.docx-I6/1[/2015

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.

SEQUENCE LISTING 20 Feb 2020

<110> The Trustees of The University of Pennsylvania Gab, Guangping Wilson, Carnes M. Alvira, Mauricio

<120> A Method of Detecting and/or Identifying Adeno-Associated Virus (AAV} Sequences and Isolating Novel Sequences Identified Thereby

<130> UPN-02735PCT

<150> US 60/350,607 2020201242

<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-associated virus serotype 7

<400> 1 ttggccactc cctctatgcg cgctcgctcg ctcggtgggg cctgcggacc aaaggtccgc 60

agacggcaga gctctgctct gccggcccca ccgagcgagc gagcgcgcat agagggagtg 120

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 cacgctgocc 720

aactggttcg cggtgaccaa gacgcgtaat ggcgccggcg gggggaacaa ggtggtggac 780

gagtgctaca tccccaacta cctcctgccc aagacccagc'ccgagctgca gtgggcgtgg 840

actaacatgg aggagtatat aagcgcgtgt ttgaacctgg ccgaacgcaa acggctcgtg 900

WO 03/042397 PCT/11S02/33629 20 Feb 2020

gcgcagcacc tgacccacgt cagccagacg caggagcaga acaaggagaa tctgaacccc 960

aattctgacg cgcccgtgat caggtcaaaa acctccgcgc gctacatgga gctggtcggg 1020

tggctggtgg accggggcat cacctccgag aagcagtgga tccaggagga ccaggcctcg 1080

tacatctcct tcaa ggccgc ctccaactcg cggtcccaga tcaaggccgc gctggacaat 1140

gccggcaaga tcatggcgct gaccaaatcc gcgcccgact acctggtggg gccctcgctg 1200 2020201242

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 agcaggaaat caaagagttc 1740

ttccgctggg ccagtgatca cgtgaccgag gtggcgcatg agttctacgt cagaaagggc 1800

ggagccagca aaagacccgc ccccgatgac gcggatataa gcgagcccaa gcgggcctgc 1860

ccctcagtcg cggatccatc gacgtcagac gc ggaaggag ctccggtgga ctttgccgac 1920

aggtaccaaa acaaatgttc tcgtcacgcg ggcatgattc agatgctgtt tccctgcaaa 1980

acgtgcgaga iaatgaatca gaatttcaac atttgcttca cacacggagt cagagactgt 2040

ttagagtgtt tccccggcgt gtcagaatct caaccggtcg tcagaaaaaa gacgtatcgg 2100

aaactctgeg 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 cccgactoct ccacgggcat 2700

cggcaagaaa ggccagcagc ccgccagaaa gagactcaat ttcggtcaga ctggcgactc 2760

agagtcagtc cccgaccctc aacctctcgg agaacctcca gcagcgccct ctagtgtggg 2820

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 2020201242

actcatcaac aacaactggg gattccggcc caagaagctg cggttcaagc tcttcaacat 3180

ccaggtcaag gaggtcacga cgaatgacgg cgttacgacc atcgctaata accttaccag 3240

cacgattcag gtattctcgg actcggaata ccagctgccg tacgtcctcg gctctgcgca 3300

ccagggctgc ctgcctccgt tccCggegga 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 3 60 0

tcgggaactg cagttttacc agggcaggcc ttcaactatg gccgaacaag ccaagaattg 3660

gttacctgga ccttgcttcc ggcaacaaag agtctccaaa acgctggatc 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 agatcctgat caagaacact cccgttcccg ctaatcctcc 4200

ggaggtgttt actcctgcca agtttgcttc gttcatcaca cagtacagca ccggacaagt 4260

cagcgtggaa atcgagtggg agctgcagaa ggaaaacagc aagcgctgga accoggagat 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 4 560

aacactgacg tcaccgcggt acccctagtg atggagttgg ccactccctc tatgcgcgct 4 62 0

cgctcgctcg gtggggcctg cggaccaaag gtccgcagac ggcagagctc tgctctgccg 4 680

gccccaccga gcgagcgagc gcgcatagag ggagtggcca a 4721

<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 1 5 10 15

Glu Gly Ile Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro 2020201242

20 25 30

Lys Ala Awl. Gin Gin Lys Gln 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 Gln 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 Ala 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 Ely Gln Gin Pro Ala Arg Lys Arg Leu Asn Phe Gly Gin 165 170 175

Thr Gly Asp Ser Glu Ser Val Pro Asp Pro Gln Pro Leu Gly Glu Pro 180 185 190

Pro Ala Ala Pro Sex 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 Giy 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 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 2020201242

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 Lys Leu Arg Phe Lys Leu Phe Am Ile 305 310 315 320

Gin Val Lys Glu Val Thr Thr Asn Asp Gly Val Thr Thr Ile Ala Asn 325 330 335

Asn Leu Thr Ser Thr Ile Gin Val Phe Ser Asp Ser Glu Tyr Gin Leu 340 345 350

Pro Tyr Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro 355 360 365

Ala Asp Val Phe Met Ile 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 Gln Tyr Leu Tyr Tyr Leu Ala 435 440 445

Arg Thr Gln Ser Asn Pro Gly Gly Thr Ala Giy Asn Arg Giu Leu Gln 450 455 460

Phe Tyr Gin Gly ay Pro Ser Thr Met Ala Glu Gln Ala Lys Asn Trp 465 470 475 480

Leu Pro Gly Pro Cys Phe Arg Gin Gin Arg Val Sex Lys Thr Leu Asp 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 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 Ile 530 535 540 2020201242

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 Ile Val Ser Ser Asn Leu Gln Ala Ala Asn Thr Ala Ala 580 585 590

Gin Thr Gln 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 Net Gly Gly Phe Gly 625 630 635 640

Leu Lys His Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val Pro 645 650 655

Ala Asn Pro Pro Glu Val Phe Thr Pro Ala Lys Phe Ala Ser Phe Ile 660 665 670

Thr Gin Tyr Ser Thr Gly Gin Val Ser Val Glu Ile Glu Trp Glu Leu 675 680 685

Gin Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile 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'Axg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Asn 725 730 735

Leu

<210> 3 <211> 623 <212> PRT <213> rep protein of adeno-associated virus serotype 7 <400> 3 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 2020201242

20 25 30

Lys Glu Trp Glu Lou Pro Pro Asp Ser Asp Met Asp Leu Asn Leu Ile 35 40 45

Giu Gln Ala Pro Lou Thr Val Ala Glu Lys Lou Gln Arg Asp Phe 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 Ile 100 105 110

Arg Glu Lys Leu Val Gln 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 Ile Pro Asn Tyr Leu Leu Pro Lys 145 150 155 160

Thr Gin Pro Glu Lou Gln 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 Asa Leu Asn 195 200 205

Pro Asn Ser Asp Ala Pro Val Ile Arg Ser Lys Thr Ser Ala Arg Tyr 210 215 220

Met Glu Leu Val Gly Trp Leu Val Asp Arg Gly Ile Thr Ser Glu Lys 225 230 235 240

Gin Trp Ile Gln Glu Asp Gln Ala Ser Tyr Ile Ser Phe Asn Ala Ala 245 250 255

Ser Asn Ser Arg Ser Gin Ile 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 2020201242

Leu Pro Ala Asp Ile 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

Gin 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 Net Val Ile 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 Gin Lys Cys Lys Ser Ser Ala Gin 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 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 Gln 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 Ile 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 2020201242

Len Phe Pro Cys Lys Thr Cys Glu Axg 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 Axg 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 Len Asp Asp Cys Val Ser Glu Gin 610 615 620

<210> 4 <211> 4393 <212> DNA <213> adeno-associated virus serotype 8

<400> 4 cagagaggga gtggccaact ccatcactag gggtagcgcg aagcgcctcc cacgctgccg 60

cgtcagcgct gacgtaaatt acgtcatagg agagtggtcc 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

gaatctgato 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

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 2020201242

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 acgtcagacg 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 atctggt caa 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 2640

ttggtcagac tggcgactca gagtcagttc cagaccctca acctctegga gaacctccag 2700

WO 03/042397 PCIMS02/33629 20 Feb 2020

cagcgccctc tggtgtggga cctaatacaa tggctgcagg cggtggcgca ccaatggcag 2760

acaataacga aggcgccgac ggagtgggta gttcctcggg aaattggcat tgcgattcca 2820

catggctggg cgacagagtc atcaccacca gcacccgaac ctgggccctg cccacctaca 2880

acaaccacct ctacaagcaa atctccaacg ggacatcggg aggagccacc aacgacaaca 2940

cctacttcgg ctacagcacc ccctgggggt attttgactt taacagattc cactgccact 3000

tttcaccacg tgactggcag cgactcatca acaacaactg gggattccgg cccaagagac 3060 2020201242

tcagcttcaa gctcttcaac atccaggtca aggaggtcac gcagaatgaa ggcaccaaga 3120

ccatcgccaa taacctcacc agcaccatcc aggtgtttac ggactcggag taccagctgc 3180

cgtacgttct cggctctgcc caccagggct gcctgcctcc gttcceggeg 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 tguggatcct 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

tttggtctct gcg 4393

<210> 5 <211> 4385 <212> DNA <213> adeno-associated virus serotype 9

<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 2020201242

cttttgtgaa ctgggtggcc gagaaggaat gggagctgcc cccggattct gacatggatc 360

ggaatctgat cgagcaggca cccctgaccg tggccgagaa gctgcagcgc gacttcctgg 420

tccaatggcg ccgcgtgagt aaggccccgg aggccctctt ctttgttcag ttcgagaagg 480

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 acgtcagcca gacgcaggag cagaacaagg 840

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

gcaagtegtc cgcccagatc gaccccactc ccgtgatcgt cacctccaac accaacatgt 1500

gcgccgtgat tgacgggaac agcaccacct tcgagcacca gcagcctetc 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

gggtcagaga ctgctcagag tgtttccccg gcgtgtoaga atctcaaccg gtcgtcagaa 1980

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 2020201242

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 2460

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

ccctctggtg 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 3180

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 ggagctgeta aattcaagct gaacgggaga 3660

gactcgctaa tgaatcctgg cgtggctatg gcatcgcaca aagacgacga ggaccgcttc 3720

tttccatcaa gtggcgttct catatttggc aagcaaggag ccgggaacga tggagtcgac 3780

tacagccagg tgctgattac agatgaggaa gaaattaaag ccaccaaccc tgtagccaca 3840

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 2020201242

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 4385

<210> 6 <211> 4718 <212> DNA <213> adeno-associated virus serotype 1

<400> 6 ttgcccactc cctetctgcg cgctcgctcg ctcggtgggg cctgcggacc aaaggtccgc 60

agacggcaga gctctgctct gccggoccca 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

gtacatctcc ttcaaCgccg cttccaactc geggtcccag atcaaggccg ctctggacaa 1140

tgccggcaag atcatggcgc tgaccaaatc cgcgcccgac tacctggtag gccccgctcc 1200

gcccgcggac attaaaacca accgcatcta ccgcatcctg gagctgaacg gctacgaacc 1260

tgcctacgcc ggctccgtct ttctcggctg ggcccagaaa aggttcggga agegcaacac 1320

catctggctg tttgggccgg ccaccacggg caagaccaac atcgcggaag ccatcgccca 1380

cgccgtgccc ttctacggct gcgtcaactg gaccaatgag aactttccct tcaatgattg 1440 2020201242

cgtcgacaag atggtgatct ggtgggagga gggcaagatg acggccaagg tcgtggagtc 1500

cgccaaggcc attctcggcg gcagcaaggt gcgcgtggac caaaagtgca agtcgtccgc 1560

ccagatcgac cccacccccg tgatcgtcac ctccaacacc aacatgtgcg 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 gegggctecc gagattgctt gctcggcctg 2160

cgatctggtc aacgtggacc tggatgactg tgtttctgag caataaatga cttaaaccag 2220

gtatggctgc cgatggttat cttccagatt ggetcgagga 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 caaagegggt gacaatccgt acctgeggta 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 2760

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

WO 03/042397 PCT/11S02/33629 20 Feb 2020

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 2020201242

cgctcaacaa tggcagccaa gccgtgggac gttcatcctt ttactgcctg gaatatttcc 3420

cttctcagat gctgagaacg ggcaacaact ttaccttcag ctacaccttt gaggaagtgc 3480

ctttccacag cagctacgcg cacagccaga gcctggaccg gctgatgaat cctctcatcg 3540

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 catgctatgg 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 cccgaagtgc 4320

agtacacatc caattatgca aaatctgcca acgttgattt tactgtggac aacaatggac 4380

tttatactga gcctcgcccc attggcaccc gttaccttac ccgtcccctg taattacgtg 4440

ttaatcaata aaccggttga ttcgtttcag ttgaactttg gtctcctgtc cttcttatct 4500

tatcggttac catggttata gcttacacat taactgcttg gttgcgcttc gcgataaaag 4560

acttacgtca tcgggttacc cctagtgatg gagttgcoca ctccctctct gcgcgctcgc 4620

tcgctcggtg gggcctgcgg accaaaggtc cgcagacggc agagctctgc tctgccggcc 4680

ccaccgagcg agcgagcgcg cagagaggga gtgggcaa 4718

<210> 7 <211> 4675 <212> DNA <213> adeno-associated virus serotype 2

<400> 7 ttggccactc cctetctgeg cgctcgctcg ctcactgagg ccgggcgacc aaaggtcgcc 60

cgacgcccgg gctttgcccg ggcggcctca gtgagcgagc gagcgcgcag agagggagtg 120

gccaactcca tcactagggg ttcctggagg ggtggagtcg tgacgtgaat tacgtcatag 180

ggttagggag gtcctgtatt agaggtcacg tgagtgtttt gcgacatttt gcgacaccat 240

gtggtcacgc tgggtattta agcccgagtg agcacgcagg gtctccattt tgaagcggga 300 2020201242

ggtttgaacg cgcagccgcc atgccggggt tttacgagat igtgattaag gtccccagcg 360

accttgacgg gcatctgccc ggcatttctg acagctttgt gaactgggtg gccgagaagg 420

aatgggagtt gccgccagat tctgacatgg atctgaatct gattgagcag gcacccctga 480

ccgtggccga gaagctgcag cgcgactttc tgacggaatg gcgccgtgtg agtaaggccc 540

cggaggccct 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 agctccagtg ggcgtggact aatatggaac 840

agtatttaag cgcctgtttg aatctcacgg agcgtaaacg gttggtggcg cagcatctga 900

cgcacgtgtc gcagacgcag gagcagaaca aagagaatca gaatcccaat tctgatgcgc 960

cggtgatcag atcaaaaact tcagccaggt acatggagct ggtcgggtgg ctcgtggaca 1020

aggggattac ctcggagaag cagtggatcc aggaggacca ggcctcatac atctccttca 1080

atgcggcctc caactcgcgg tcccaaatca aggctgcctt ggacaatgcg ggaaagatta 1140

tgagcctgac 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

gttctcgtca cgtgggcatg aatctgatgc tgtttccctg cagacaatgc gagagaatga 1980

atcagaattc aaatatctgc ttcactcacg gacagaaaga ctgtttagag tgctttcccg 2040

tgtcagaatc tcaacccgtt tctgtcgtca aaaaggcgta tcagaaactg tgctacattc 2100

atcatatcat gggaaaggtg ccagacgctt gcactgcctg cgatctggtc aatgtggatt 2160

tggatgactg catctttgaa caataaatga tttaaatcag gtatggctgc cgatggttat 2220 2020201242

cttccagatt ggctcgagga cactctctct gaaggaataa gacagtggtg gaagctcaaa 2280

cctggcccac caccaccaaa gcccgcagag cggcataagg acgacagcag gggtcttgtg 2340

cttcctgggt acaagtacct cggacccttc aacggactcg acaagggaga gccggtcaac 2400

gaggcagacg ccgcggccct cgagcacgta caaagcctac gaccggcagc tcgacagcgg 2460

aganaacccg tacctcaagt acaaccacgc cgacgcggag tttcaggagc gccttaaaga 2520

agatacgtct tttgggggca acctcggacg agcagtcttc caggcgaaaa agagggttct 2580

tgaacctctg ggcctggttg aggaacctgt taagacggct cogggaaaaa agaggccggt 2640

agagcactct cctgtggagc cagactcctc ctcgggaacc ggaaaggcgg gccagcagcc 2700

tgcaagaaaa agattgaatt ttggtcagac tggagacgca gactcagtac ctgaccccca 2760

gcctctcgga cagccaccag cagccccctc tggtctggga actaatacga tggctacagg 2820

cagtggcgca ccaatggcag acaataacga gggcgccgac ggagtgggta attcctccgg 2880

aaattggcat tgcgattcca catggatggg cgacagagtc atcaccacca gcacccgaac 2940

ctgggccctg cccacctaca acaaccacct ctacaaacaa atttccagcc aatcaggagc 3000

ctcgaacgac aatcactact ttggctacag caccccttgg gggtattttg acttcaacag 3060

attccactgc cacttttcac cacgtgactg gcaaagactc atcaacaaca actggggatt 3120

ccgacccaag agactcaact tcaagctott taacattcaa gtcaaagagg tcacgcagaa 3180

tgacggtacg acgacgattg ccaataacct taccagcacg gttcaggtgt ttactgactc 3240

ggagtaccag ctcccgtacg tcctcggctc ggcgcatcaa ggatgcctcc cgccgttccc 3300

agcagacgtc ttcatggtgc cacagtatgg atacctcacc ctgaacaacg ggagtcaggc 3360

agtaggacgc tcttcatttt actgcctgga gtactttcct tctcagatgc tgcgtaccgg 3420

aaacaacttt accttcagct acacttttga ggacgttcct ttccacagca gctacgctca 3480

cagccagagt ctggaccgtc tcatgaatcc tctcatcgac cagtacctgt attacttgag 3540

cagaacaaac actccaagtg gaaccaccac gcagtcaagg cttcagtttt ctcaggccgg 3600

agcgagtgac attcgggacc agtctaggaa ctggcttcct ggaccctgtt accgccagca 3660

gcgagtatca aagacatctg cggataacaa caacagtgaa tactcgtgga ctggagctac 3720

caagtaccac ctcaatggca gagactctct ggtgaatccg gccatggcaa gccacaagga 3780

cgatgaagaa aagttttttc ctcagagcgg ggttctcatc tttgggaagc aaggctcaga 3840

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 2020201242

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 accattggca 4380

ccagatacct gactcgtaat ctgtaattgc ttgttaatca ataaaccgtt taattcgttt 4440

cagttgaact ttggtctctg cgtatttctt tcttatctag tttccatggc tacgtagata 4500

agtagcatgg cgggttaatc attaactaca aggaacccct agtgatggag ttggccactc 4560

cctctatgcg cgctcgctcg ctcactgagg ccgggcgacc aaaggtcgcc cgacgcccgg 4620

gctttgcccg ggcggcctca gtgagcgagd 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 aaggcccogg 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

atttaagcgc ctgtttgaat ctcgcggagc gtaaacggct ggtggcgcag 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 2020201242

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 1980

aaatttccaa tgtctgtttt acgcatggtc aaagagactg tggggaatgc ttccctggaa 2040

tgtcagaatc tcaaccCgtt tctgtcgtca aaaagaagac ttatcagaaa ctgtgtccaa 2100

ttcatcatat cctgggaagg gcacccgaaa 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

cctcaacctc tcggagaacc accagcagcc cccacaagtt tgggatctaa tacaatggct 2820

tcaggcggtg gcgcaccaat ggcagacaat aacgagggtg ccgatggagt gggtaattcc 2880

tcaggaaatt ggcattgcga ttcccaatgg ctgggcgaca gagtcatcac caccagcacc 2940

agaacctggg ccctgcccac ttacaacaac catctctaca agcaaatctc cagccaatca 3000

ggagcttcaa acgacaacca ctactttggc tacagcaccc cttgggggta ttttgacttt 3060

aacagattcc actgccactt ctcaccacgt gactggcagc gactcattaa caacaactrag 3120 2020201242

ggattccggc ccaagaaact cagcttcaag ctcttcaaca tccaagttag aggggtcacg 3180

cagaacgatg gcacgacgac tattgccaat aaccttacca gcacggttca agtgtttacg 3240

gactcggagt atcagctccc gtacgtgctc gggtcggcgc accaaggctg tctcccgccg 3300

tttccagcgg acgtcttcat ggtccctcag tatggatacc tcaccctgaa caacggaagt 3360

caagcggtgg gacgctcatc cttttactgc ctggagtact tcccttcgca gatgctaagg 3420

actggaaata acttccaatt cagctatacc ttcgaggatg taccttttca cagcagctac 3480

gctcacagcc agagtttgga tcgcttgatg aatcctctta ttgatcagta tctgtactac 3540

ctgaacagaa cgcaaggaac aacctctgga acaaccaacc aatcacggct gctttttagc 3600

caggctgggc ctcagtctat gtctttgcag gccagaaatt ggctacctgg gccctgctac 3660

cggcaacaga gactttcaaa gactgctaac gacaacaaca acagtaactt tccttggaca 3720

gcggccagca aatatcatct caatggccgc gactcgctgg tgaatccagg accagctatg 3780

gccagtcaca aggacgatga agaaaaattt ttccctatgc acggcaatct aatatttggc 3840

aaagaaggga caacggcaag taacgcagaa ttagataatg taatgattac ggatgaagaa 3900

gagattcgta ccaccaatcc tgtggcaaca gagcagtatg gaactgtggc aaataacttg 3960

cagagctcaa atacagacc cacgactgga actgtcaatc atcagggggc cttacctggc 4020

atggtgtggc aagatcgtga cgtgtacctt caaggaccta tctgggcaaa gattcctcac 4080

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 4380

cgccctattg gaacccggta tctcacacga aacttgtgaa toctgyttaa tcaataaacc 4440

gtttaattcg tttcagttga actttygctc ttgtgcactt ctttatcttt atcttgtttc 4500

catggctact gcgtagataa gcagcggcct gcggcgcttg cgcttcgcgg tttacaactg 4560

ctggttaata tttaactctc gccatacctc tagtgatgga gttggccact ccctctatgc 4620

gcactcgctc gctcggtggg gcctggcgac caaaggtcgc cagacggacg tgctttgcac 4680

WO 03/042397 PCTIUS02 /33629 20 Feb 2020

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 2020201242

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

gmcctcagt cgcggatcca tcgacgtcag acgcggaagg agctccggtg gactttgccg 540

acaggtacca aaacaaatgt tctcgtcacg cgggcatgct tcagatgctg tttocctgca 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

ttcaacagat tccactgcca cttctcacca cgtgactggc agcgactcat caacaacaac 1740

tggggattcc ggcccagaaa gctgeggttc aagttgttca acatccaggt caaggaggtc 1800

acgacgaacg acggcgttac gaccatcgct aataacctta ccagcacgat tcaggtcttc 1860

tcggactcgg agtaccaact gccgtacgtc ctcggctctg cgcaccaggg ctgcctccct 1920

ccgttccctg cggacgtgtt catgattcct cagtacggat atctgactct aaacaacggc 1980 2020201242

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 acaagacaac gctggaaaac gtgctaatga ccagcgagga ggagatcaaa 2520

accaccaatc ccgtggctac agaagaatac ggtgtggtct ccagcaacct gcaatcgtct 2580

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

cagaaagaaa acagcaaacg ctggaatcca gagattcagt acacctcaaa ttatgccaag 2940

tctaataatg tggaatttgc tgtcaacaac gaaggggttt atactgagcc tcgccccatt 3000

ggcacccgtt acctcacccg taacctgtaa ttgcctgtta atcaataaac cggttaattc 3060

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

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 2020201242

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 960

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 tcccagacct 1680

gagggcgcgg cgggaggttc tccgagaggt tgggggtcgg gcactgactc tgagtcgcca 1740

gtctgcccaa agttgagctt ctttttagcg ggctgctggc ctttettgcc gatgcccgtg 1800

gaggagtcgg gggattctat gggtctcttc tttccaggag ccgtcttagc gccttcctca 1860

accagaccga gaggttcgag aacccgcttc ttggcctgga agactgctcg cccgaggttg 1920

cccccaaaag acgtatcttc ttgaagacgc tcctgaaact cagcgtcggc gtggttgtac 1980

ttgaggtacg ggttgtecce ctgctcgagc tgcttgtcgt aggccttgtc gtgctcgagg 2040

gccgcggcgt ctgcctcgtt gaccggctct cccttgtcga gtccgttgaa gggtccgagg 2 100

tacttgtagc caggaagcac cagaccccgg ccgtcgtcct gcttttgctg gttggctttg 2160

ggtttcgggg ctccaggttt caagtcccac cactcgcgaa tgccctcaga gaggttgtcc 2220

tcgagccaat ctggaagata accatcggca gccatacctg gtttaagtca tttattgctc 2280

agaaacacag tcatccaggt ccacgttgac cagatcgcag gccgagcaag caatctcggg 2340

agcccgcccc agcagatgat gaatggcaca gagtttccga tacgtcctct ttctgacgac 2400

cggttgagat tctgacacgc cagggaaaca ttctgaacag tctctggtcc cgtgcgtgaa 2460

gcaaatgttg aaattctgat tcattctctc gcatgtcttg cagggaaaca gcatctgaag 2520 2020201242

catgcccgcg tgacgagaac atttgttttg gtacctgtcg gcaaagt .cca ccggagctcc 2580

ttccgcgtct gacgtcgatg gatccgcgac tgaggggcag gcccgcttgg gctcgctttt 2640

atccgcgtca tcgggggcgg gcctcttgtt ggctccaccc tttctgacgt agaactcatg 2700

cgccacctcg gtcacgtgat cctgcgccca gcggaagaac tctttgactt cctgctttgt 2760

caccttgcca aagtcctgct ccagacggcg ggtgagttca aatttgaaca tccggtcttg 2820

taacggctgc tggtgctcga aggtggtgct gttcccgtca atcacggcgc acatgttggt 2880

gttggaagtg acgatcacgg gggtgggatc gatctgggcg gacgacttgc acttttggtc 2940

cacgcgcacc ttgCtgCCgC cgagaatggc cttggcggac tccacgacct tggccgtcat 3000

cttgccctcc tcccaccaga tcaccatctt gtcgacgcaa tcgttgaagg gaaagttctc 3060

attggtccag ttgacgcagc cgtagaaagg gcgaattc 3098

<210>. 11 <211> 3121 <212> DNA <213> new AAV serotype, clone 29.3

<400> 11 gaattcgccc ttcgcagaga ccaaagttca 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 cggtgctgta ctgcgtgatg aacgacgcca gcttagcttg actgaaggta 300

gttggaggat ccgcgggaac aggtgtattc ttaatcagga tctgaggagg cgggtgtttc 360

agtccaaagc cccccatcag cggcgaggga tgaaagtttc cgtccgtgtg aggaatcttg 420

gcccagatag gaccctgcag gtacacgtcc cggttctgcc agaccatgcc aggtaaggct 480

ccttgactgt tgacggcccc tacaatagga gcggcgtttt gctgttgcag gttatcggcc 540

accacgccgt actgttctgt ggccactggg ttggtggttt taatttcttc ctcactggtt 600

agcataacgc tgctatagtc cacgttgcct tttccagctc cctgtttccc aaacattaag 660

actccgctgg acggaaaaaa tcgctcttcg tcgtccttgt gggttgccat agcgacaccg 720

ggatttacca gagagtctct gccattcaga tgatacttgg tggcaccggt ccaggcaaag 780

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 1080 2020201242

ggaaagtact ccaggcagta gaaggaggaa cggcccacgg cctgactgcc attgttcaga 1140

gtcaggtacc cgtactgagg aatcatgaag acgtccgccg ggaacggagg caggcagccc 1200

tggcgcgcag agccgaggac gtacgggagc tggtattccg agtccgtaaa gacctgaatc 1260

gtgctggtaa ggttattggc gatggtcttg gtgccttcat tctgcgtgac ctccttgacc 1320

tggatgttga agagcttgaa gttgagtctc ttgggccgga atccccagtt gttgttgatg 1380

agtcgctgcc agtcacgtgg tgagaagtgg cagtggaatc tgttaaagtc aaaatacccc 1440

cagggggtgc tgtagccgaa gtaggtgttg tcgttggtgc ttcctcccga agtcccgttg 1500

gagatttgct tgtagaggtg gttgttgtag gtggggaggg cccaggttcg ggtgctggtg 1560

gtgatgactc tgtcgcccag ccatgtggaa tcgcaatgcc aatttcctga 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

accctttttg acgtagaatt catgctccac ctcaaccacg tgatcetttg 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 2020201242

acagtcgttg aagggaaagt tctcattggt ccagttgacg cagccgtaga agggcgaatt 3120

3121

<210> 12 <211> 3121 <212> DNA <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 gaattctacg tcaaaaaggg 420

tggagccaag aaaagacccg cccccagtga cgcagatata agtgagccca aacgggtgcg 480

cgagtcagtt gcgcagccat cgacgtcaga cgcggaagct tcgatcaact acgcagacag 540

gtaccaaaac aaatgttctc gtcacgcggg catgaatctg atgctgtttc cctgcagaca 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 caggacggcg 960

gccggggtct ggtgcttcct ggctacaagt acctcggacc cttcaacgga ctcgacaagg 1020

gggagcccgt caacgcggcg gacgcagcgg ccctcgagca cgacaaggcc tacgaccagc 1080

agctcaaagc gggtgacaat ccgtacctgc ggtataacca cgccgacgcc gagtttcagg 1140

agcgtctgca agaagatacg tcttttgggg gcaacctcgg gcgagcagtc ttccaggcca 1200

agaagcgggt tctcgaacet 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 tggeagaCaa taacgaaggc gccgacggag 1500

tgggtagttc ctcaggaaat tggcattgcg attccacatg gctgggcgac tgagtcatca 1560 2020201242

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 cgtcctcggc tctgcgcacc 1920

agggctgcct gcctccgttc ccggcggacg tcttcatgat tcctcagtac gggtacctga 1980

ctctgaacaa tggcagtcag gccgtgggcc gttcctcctt ctactgcctg gagtactttC 2040

cttctcaaat 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

gugtggaaat 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/1JS02/33629 20 Feb 2020

3121

<210> 13 <211> 3121 <212> DNA <213> new AAV serotype, clone 29.5

<400> 13 gaattcgccc ttcgcgagac caaagttcaa ctgaaacgaa tcaaccggtt tattgattaa 60

caagcaatta cagattacgg gtgaggtaac gggtgccgat ggggcgaggc tcagaataag 120 2020201242

tgccatctgt gttaacagca aagtccacat ttgtagattt gtagtagttg gaagtgtatt 180

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 420

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 atcat gaaga 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 1440

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

cagatcccag accagagggg cctgcggggg gttctccgat tggttgaggg tcgggcactg 1740 actctgagtc gccagtctgc ccaaagttga gtctcttttt cgcgggctgc tggcctttct 1800

tgccgatgcc cgtagaggag tctggagaac gctggggtga tggctctacc ggtctcttct 1860 ttccaggagc cgtcttagcg ccttcctcaa ccagaccgag aggttcgaga acccgcttct 1920

tggcctggaa gactgctcgc ccgaggttgc ccccaaaaga cgtatcttct tgcagacgct 1980 cctgaaactc ggcgtcggcg tggttatacc gcaggtacgg attgtcaccc gctttgagct 2040 2020201242

gctggtcgta ggccttgtcg tgctcgaggg ccgctgcgtc cgccgcgttg acgggctocc 2100 ccttgtcgag tccgttgaag ggtccgaggt acttgtagcc aggaagcacc agaccccggc 2160 cgtcgtcctg cttttgctgg ttggctttgg gcttcggggc tccaggtttc agcgcccacc 2220

actcgcgaat gccctcagag aggttgtcct cgagccaatc tggaagataa ccatcggcag 2280 ccatacctga tttaaatcat ttattgttca aagatgcagt catccaaatc cacattgacc 2340 agatcgcagg cagtgcaagc gtctggcacc tttcccatga tatgatgaat gtagcacagt 2400 ttctgatacg cctttttgac gacagaaacg ggttgagatt ctgacacggg aaagcactct 2460 aaacagtctt tctgtecgtg agtgaagcag atatttgaat tctgattcat tctctcgcat 2520 tgtctgcagg gaaacagcat cagattcatg cccacgtgac gagaacattt gttttggtac 2580 ctgtctgcgt agttgatcga agcttccgcg tctgacgtcg atggctgcgc aactgactcg 2640 cgcacccgtt tgggctcact tatatctgcg tcactggggg cgggtctttt cttggctcca 2700 ccctttttga cgtagaattc atgctccacc tcaaccacgt gatcctttgc ccaccggaaa 2760 aagtctttga cttcctgctt ggtgaccttc ccaaagtcat gatccagacg gcgggtgagt 2820 tcaaatttga acatccggtc ttgcaacggc tgctggtgtt cgaaggtcgt tgagttcccg 2880 tcaatcacgg cgcacatgtt ggtgttggag gtgacgatca cgggagtcgg gtctatctgg 2940 gccgaggact tgcatttctg gtccacgcgc accttgcttc ctccgagaat ggctttggcc 3000 gactccacga ccttggcggt catcttcccc tcctcccacc agatcaccat cttgtcgaca 3060 cagtcgttga agggaaagtt ctcattggtc cagttgacgc agccgtagaa agggcgaatt 3120 3121

<210> 14 <211> 3131 <212> DNA <213> new AAV serotype, clone 1-3

<400> 14 gcggccgcga attcgccctt ggctgcgtca actggaccaa tgagaacttt cccttcaatg 60 attgcgtcga caagatggtg atctggtggg aggagggcaa gatgacggcc aaggtcgtgg 120 agtccgccaa ggccattctc ggcggcagca aggtgcgcgt ggaccaaaag tgcaagtcgt 180

WO 03/042397 PCT/11S02/33629 20 Feb 2020

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 atgacgogga taaaagcgag cccaagcggg 480

cctgcccctc agtcgcggat ccatcgacgt cagacgcgga aggagctccg gtggactttg 540 2020201242

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 gcttgctogg 780

cctgcgatct ggtcaacgtg gacctggatg 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 agcgtotgca agaagatacg tcttttgggg gcaacctcgg gcgagcagtc 1200

ttccaggcca agaagcgggt tctcgaacct ctcggtctgg ttgaggaagg cgctaagacg 1260

gctcctggaa agaagagacc ggtagagcca tcaccccagc gttctccaga ctcctctacg 1320

ggcatcggoa agaaaggcca acagcccgcc agaaaaagac tcaattttgg tcagactggc 1380

gactcagagt cagttccaga ccctcaacct ctcggagaac ctccagcagc gccctctggt 1440

gtgggaccta atacaatggc tgcaggcggt ggcgcaccaa tggcagacaa taacgaaggc 1500

gccgacggag tgggtagttc ctcgggaaat tggcattgcg attccacatg gctgggcgac 1560

agagtcatca ccaccagcac ccgaacctgg gccctgccca cctacaacaa ccacctctac 1620

aagcaaatct ccaacgggac atcgggagga gccaccaacg acaacaccta cttcggctac 1680

agcaccccct gggggtattt tgactttaac 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

gaggacgtgc ctttccacag cagctacgcc cacagctaga gcttggaccg gctgatgaat 2160

cctctgattg accagtacct gtactacttg tctcggactc aaacaacagg aggcacggca 2220

aatacgcaga ctctgggctt cagccaaggt gggcctaata caatggccaa tcaggcaaag 2280

aactggctgc caggaccctg ttaccgccaa caacgcgtct caacgacaac cgggcaaaac 2340

aacaatagca actttgcctg gactgctggg accaaatacc atctgaatgg aagaaattca 2400

ttggctaatc ctggcatcgc tatggcaaca cacaaagacg acgaggagcg tttttttccc 2460 2020201242

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 accogtctcc 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 caactactac aaatctataa gtgtggactt tgctgttaat 3000

acagaaggcg tgtactctga accccgcccc attggcaccc gttacctcac ccgtaatctg 3060

taattgcctg ttaatcaata aaccggttga ttcgtttcag ttgaactttg gtctctgcga 3120

agggcgaatt 3131

<210> 15 <211> 3127 <212> DNA <213> new AAV serotype, clone 13-3b

<400> 15 gcggccgcga attcgccctt cgcagagacc 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

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 2020201242

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 PCT1US02133629 20 Feb 2020

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 ggt g tttgag 2880

ttcccgtcga tcacggcgca catgttggtg ttggagatga cgatcgcggg agtcgggtct 2940 2020201242

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 540

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

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 1500 2020201242

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 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

tgcgtgaagc aaatgttgaa attctgattc actctctcgc atgtcttgca gggaaaaagc 2520

atctgaagca tgcccgcgtg acgagaacat ttgttttggt acctgtcggc aaagtccacc 2580

ggagctccttccgcgtctga 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

gccgtcatct tgccctcctc ccaccagatc accatcttgt cggcgcaatc gttgaaggga 3060

aagttctcat tggtccagtt gacgcagccg tagaaagggc gaattc 3106

<210> 17 <211> 3102 <212> DNA <213> new MV serotype, clone 27-3

<400> 17 gcggccgcga attcgccctt cgcagagacc aaagttcaac tgaaacgaat caaccggttt 60 2020201242

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

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 ettgttggtg gccatggcta 720

cgcccgggtt ggttaatgaa tttctaccat tcagatggta tttagtggcc ccggtccagg 780

caaagttact gttgttgttg ctgtctatgt tttttgacag tctctgctgc cgataacagg 840

gtccgggcag ccagttcttt gattgctegg 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

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 2020201242

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

tgcgtgaage aaatgttgt.a attctgattc 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

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 ccacgggatt ggtggttttg atctcctcct 600 2020201242

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 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 gtccgagaag acctgaatcg 1250

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 gttgttgttg 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 cggctggccg ttcttgccga 1800

tgcccgtgga ggagtcgggg gattctatgg gtctcttctt tccaggagcc 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 cctgtagcca ggaagcacca gaccccggcc gtcgtcctgc ttttgctggt 2160 tggctttggg tttcggggct ccaggtttca agtcccacca ctcgcgaatg ccctcagaga 2220 ggttgccctc gagccaatct ggaagataac catcggcagc catacctggt ttaagtcatt 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 atgtcttgca ggggaacagc 2520 2020201242

atctgaagca tgcccgcgtg acgagaacat ttgttttggt acctgtcggc aaagtccacc 2580 ggagctcctt ccgcgtctga cgtcgatgga tccgcgactg aggggcaggc ccgcttgggc 2640 tcgcttttat ccgcgtcatc gggggcgggt ctcttgttgg ctccaccctt tctgacgtag 2700 aactcatacg ccacctcggt cacgtgatcc tgcgcccagc ggaagaactc tttgacttcc 27 60 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 gccgtcatcc tgccctcctc ccaccagatc accatcttgt cgacgcaatc gttgaaggga 3060 aagttctcat tggtccagtt gacgcagccg tagaaagggc gaattc 3106

<210> 19 <211> 3105 <212> DNA <213> new AAV serotype, clone Cl

<400> 19 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 cgcgatctcg 780

tcaacgtgga ettggatgac tgtgtttctg agcaataaat gaCttaaacc aggtatggct 840

gctgacggtt atcttccaga ttggctcgag gacaacctct ctgagggcat tcgcgagtgg 900 tgggacctga aacctggagc ccccaagccc aaggccaacc agcagaagca ggacgacggc 960 cggggtctgg tgctteCtgg ctacaagtac ctcggaccct tcaacggact Cgacaagggg 1020

gagcccgtca acgcggcgga cgcagcggcc ctcgagcacg acaaggcCta cgaccagcag 1080 2020201242

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 cOaCCtggtC 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 tgaaaaCtgg caataacttt 2040

gaaatggctt acaactttgg gaaggtgccg ttccactcaa tgtatgctta cagccagagc 2100

ccggacagac tgatgaatcc cctcctggac cagtacctgt ggcacttaca gtcgaccacc 2160

tctggagaga ctctgaatca aggeaatgca 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

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 2020201242

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 gaccaagcgg 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

aagagggtac tcgaaccact 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 2020201242

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 ctgectcett 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 cctectggac 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

<210> 21 <211> 3105 <212> ANA <213> new AAV serotype, clone C5 <400> 21 gaattcgccc ttcgcagaga ccaaagttca actgaaacga atcacacggt ttattgatta 60

actaggcagt tacaaatgat tagtcaaata acgagagcca ataacccgcg gctctgtata 120

cttcccagtt gtatcgggag cccacaacat agaagactgg ttcccacagt ttgaagtaaa 180 2020201242

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 ccgtecgcgt 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

oagctgggcg 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 1380

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

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 2020201242

gttgaagggt ccgaggtact cgtagccagg aagcaccaga ccccggccgt cgtcctgctt 2160

ctgctggttg gccttgggct tgggggctcc aggtttcagg tcccaccact cgcgaatgcc 2220

ctcagagagg ttgtcctcga gccaatctgg aagataaccg tcagcagcca tacctggttt 2280

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 tgcttccgcg tctgacotcg atggctccgc aactgagggg cagguccgct 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 2880

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 V1

<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

ccgccgtctg gaacacgact ttggcaaggt gaccaagcag gaagtcaaag agttcttccg 360

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 2020201242

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 cteggtctgg 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

cctgggceCt 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 1860

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 20 Feb 2020

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 2020201242

accgggacgt gtatctgcag ggtcccatct gggccaaaat tcctcacacg gatggcaact 2700

ttcacccgtc tcctctgatg ggcggttttg gactcaaaca cccgcctcca cagatcctga 2760

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

<210> 23 <211> 3095 <212> DNA <213> new AAV serotype, clone F3

<400> 23 gaattcgccc ttcgcagaga ccaaagttca 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

ctgacttgtc cggtgctgta ctgcgtgatg aaggaggcaa acttggcagg agtaaacacc 300

tccggaggat tagcaggtac aggtgtgttt ttgatcagga tctgtggagg cgggtgtttg 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 cgttgtccag agtcaggtag 1140 ccgtactgag gaatcatgaa gacgtccgcc gggaacggag gcaggcagcc ctggtgcgca 1200 2020201242

gagccgagga cgtacggcag ctggtattcc gagtccgaga agacctgaac cgtgctggta 1260

aggttattag cgatggtcgt gacgccgtca ttcgttgtga cctccttgac ctggatgttg 1320

aggagcttga accgcagctt ettgggccgg 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 tgtctgccat tggtgcgcca ccgcctgcag ccattgtacc agatcccaca 1680

ctagagggcg ctgctggagg ttctccaaga ggttgagggt cggggactga ctctgagtcg 1740

ccagtctgac caaaattgag cttcttttta gcgggctgct ggcctttttt gccgatgccc 1800

gtggaggagt ctggagagcc tatgggtctc ttctttccag gagccgtctt agcgccttcc 1860

tcaaccagac cgagaggttc gagaacccgc ttcttggcct ggaagactgc tcgcccgagg 1920

ttgcccccaa atgacgtatc ttcttgcaga 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 gggctccagg tttcaggtcc caccactcgc gaatgccctc agagaggttg 2220

tcctcgagcc aatctggaag ataaccatcg gcagccatac ctggtttaag tcatttattg 2280

ctcagaaaca cagtcgtcca ggtccacgtt gaccaggtcg caggccgagc aagcaatctc 2340

gggtgcccgc cccagcagat gatgaatcgc acacagcttc cgatacgtct tttttctgac 2400

gaccggttga gattctgaca cgccggggaa acattctaaa cagtctctga ccccgtgcgt 2460

gaagcaaatg ttgaaattct gattcattct ctcgcacgtt ttgcagggaa acagcacctg 2520

aagcatgccc gcgtgacgag aacatttgtt ttggtacctg tcggcaaagt ccaccggagc 2580

tccttccgcg tctgacgtcg atgggtccgt gactgaggga cgggcccgct tgggctcgct 2640

tatatccgcg tcatcggggg cgggtctttt gctggctccg ccctttctga cgtagaactc 2700

WO 03/042397 PCTATS02/33629 20 Feb 2020

atgegtcacc tcagtcacgt gatcactagc ccagcggaag aactctttga cttcctgctt 2760

tgtcaccttq ccaaagtcgt gttccagacg gcgggtgagt tcaaatttga acatccggtc 2820

ctgcaacggt tgctggtgct cgaaggtggt gctgttcccg tcgatcacgg cgcacatgtt 2880

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 2020201242

<210> 24 <211> 3095 <212> DNA <213> new AAV serotype, clone E5

<400> 24 gaattcgccc ttcgcagaga ccaaagttca 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

ctgacttgtc cggtgctgta ctgcgtgatg aaggaggcaa acttggcagg aataaacacc 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 gccggtetag 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

aagagcttga accgcagctt cttgggccgg aatccccagt tgttgttgat gagtcgctgc 1380

cagtcacgtg gtgagaagtg gcagtggaat ctgttaaagt caaaataccc ccagggggtg 1440

ctgtagccga agtagtggtt gtcattggtg gct6ctgagc tgctgctgga gatttgcttg 1500

tagaggtggt tgttgtaggt ggggagggcc caggttctgg tgctggtggt gatgactctg 1560

tcgcccagcc atgtggaatc gcaatgccaa tttcctgagg cattacccac tccgtcggca 1620

ccttcgttat tgtctgccgt tggtgcgcca ccgcctgcag ccattgtacc agatcccaca 1680 2020201242

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 tccccettgt cgagtccgtt gaagggtccg 2100

aggtacttgt agccaggaag caccagaccc cggccgtcgt cctgcttttg ctggttggct 2160

ttgggtttcg gggctccagg tttcaggtcc caccactcgc gaatgccctc 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 agatcaccat cttgtcgacg caatcgttga agggaaagtt 3060

ctcattggtc cagttgacgc agcaagggcg aattc 3095

<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 2020201242

tactgaattt cgggattcca gcgtttgctg ttctccttct gcagctccca ctcgatctcc 300

acgctgacct gtcccgtgga atactgtgtg atgaaagaag caaacttggc agaactgaag 360

tttgtgggag gattggctgg aacgggagtg tttttgatca tgatctgagg aggcgggtgt 420

ttgagtccaa aacctcccat cagtggagaa ggatgaaagt gtccatcggt gtgaggaatc 480

ttggcccaaa tgggtccctg caggtacacg tctcgatcct gccacaccat accaggtaac 540

gctccttggt gattgacagt tccagtagtt ggaccagtgt ttgagttttg caaattattt 600

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 1020

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

ccttgatacg ccgagcccag gacatacggg agctggtact ccgagtcagt aaacacctga 1320

accgtgctgg taaggttatt ggcaatcgtc gtcgtaccgt cattctgcgt gacctctttg 1380

acttgaatat taaagagatt 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

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 2020201242

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

ccgtttgggc 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 geggtcatct 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

tcaccaagca ggaagtgaaa gactttttcc ggtgggcaaa ggatcacgtg gttgaggtgg 360

agcatgaatt ctacgtcaaa aagggtggag ctaagaaaag acccgccccc agtgacgcag 420

atataagtga gcccaaacgg gcgcgcgagt cagttgcgca gccatcaacg tcagacgcgg 480

aagettcgat caactacgcg gacaggtacc aaaaacaaat gttctcgtca cgtgggcatg 540

aatctgatgc tgtttccctg cagacaatgc gagagaatga atcagaattc aaatatctgc 600

ttcactcacg gacagaaaga ctgtttagag tgctttcccg tgtcagaatc tcaacccgtt 660 2020201242

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 900

gcccgcagag cggcataagg acgacagcag gggtcttgtg cttcctgggt acaagtacct 960

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 gnacctctgg gcctggttga 1200

ggaacctgtt aagacggctc cgggaaaaaa gaggccggta gagcactctc ctgtggagcc 1260

agactoctcc 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

tggetacagc 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

agctaaaaac tggctgcctg gaccttgcta cagacagcag cgtctgtcaa aacaggcaaa 2280 cgacaacaac aacagcaact ttccctggac tgcagctaca aagtatcatc taaatggccg 2340

ggactcgttg gttaatccag gaccagctat ggccagtcac aaggatgacg aagaaaagtt 2400 tttccccatg catggaaccc tgatatttgg taaacaagga acaaatgcca acgacgcgga 2460 tttggaaaat gtcatgatta cagatgaaga agaaatcagg gccaccaatc ccgtggctac 2520

ggagcagtac gggactgtgt caaataattt gcaaaactca aacactggtc caactactgg 2580 2020201242

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 gcttctttca tcacacagta 2820 ttccacggga caggtcagcg tggagatcga gtgggagctg cagaaggaga acagcaaacg 2880 ctggaatccc gaaattcagt acacttccaa ctacaacaag tctgttaatg tggactttac 2940

tgtggacact aatggtgtgt attcagagcc tcgccccatt ggcaccagat acctgactcg 3000

taatctgtaa ttgcttgtta atcaataaac cgtttaattc gtttcagttg aactttggtc 3060

tctgcgaagg gcgaa 3075

<210> 27 <211> 3128 <212> DNA <213> new AAV serotype, clone 42.8 <400> 27 gaattcgccc tttctacggc tgcgtcaact ggaccaatga gaactttccc ttcaacgatt 60

gcgtogacaa gatggtgatc tggtgggagg agggcaagat gacggccaag gtcgtggagt 120

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 540

acaggtacca aaacaaatgt tctcgtcacg cgggcatgct tcagatgctg. tttccctgca 600

agacatgcga gagaatgaat cagaatttca acatttgCtt cacgcacggg accagagact 660

gttcagaatg tttccccggc gtgtcagaat ctcaaccggt cgtcagaaag aggacgtatc 720

ggaaactctg tgccattcat catctgctag 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 agcagtettc 1200 2020201242

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 ccacatgyct 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 1900

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 eggactcagt 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 ctattgtagg 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 aactcacccg taacctgtaa 3060

ttgcctgtta atcaataaac cggctaattc gtttcagttg aactttggtc tctgcgaagg 3120 2020201242

gcgaattc 3128

<210> 28 <211> 3128 <212> DNA <213> new AAV semotype, 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 ggcgggctec 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 gcageggcce tcgagcacga caaggcctac 1080

gaccagcagc tcaaagcggg tgacaatccg tacctgcggt ataaccacgc cgacgccgag 1140

tttcaggagc gtctgcaaga agatacgtct tttgggggca acctcmcg 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 2020201242

caaatctcca acgggacatc gggaggaagc accaacgaca acacctactt cggctacagc 1680

accccctggg ggtattttga ctttaacaga ttccactgcc acttctcacc acgtgactgg 1740

cagcgactca tcaacaacaa ctggggattc cggcccaaga gactcaactt caagctcttc 1800

aacatccagg tcaaggaggt cacgcagaat gaaggcaoca'agaccatcgc caataacctt 1860

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

aacgtgcctt ttcacagcag 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 ctattgtagg ggccgtcaac 2640

agtcaaggag ccttacctgg catggtctgg cagaaccggg acgtgtacct gcagggtcct 2700

atctgggcca agattectca 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

<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 2020201242

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 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 1140

tttcaggagc gtcttcaaga agatacgtct tttgggggca acctogggeg 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

cagegactca 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 2020201242

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 ctattgtagg 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

gcgaattCgt ttaaacctgc aggactagtc cctttagtga gggttaattc tgagcttggc 3180

gtaatcatgg gtcatag 3197

<210> 30 <211> 2501 <212> DNA <213> new AkV serotype, clone 42.13D

<400> 30 gaattcgccc ttggctgcgt caactggacc aatgagaact ttcccttcaa cgattgcgtc 60

gacaagatgg tgatctggtg ggaggagggc aagatgacgg ccaaggtcgt ggagtccgcc 120

aaggccattc atcatctgct ggggcgggct cccgagattg cttgctcggc ctgcgatctg 180

gtcaacgtgg acctggatga ctgtgtttCt gagcaataaa tgacttaaac caggtatggc 240

WO 03/042397 PCUUS02/33629 20 Feb 2020

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

gotcgagcag ggggacaacc cgtacctcaa gtacaaccac gccgacgccg agtttcagga 540

gcgtcttcaa gaagatacgt cttttggggg caacctcggg cgagcagtct tccaggCcaa 600

gaagcgggtt ctcgaacctc tcggtctggt tgaggaaggc gctaagacgg ctcctggaaa 660 2020201242

gaagagaccc atagaatccc ccgactcctc cacgggcatc ggcaagaaag gccagcagcc 720

cgctaaaaag agactcaact ttgggcagac tggcgactca gagtcagtgc cCgaccctca 780

accaatcgga gaaCCccccg caggcccctc tggtctggga tctggcacaa tggctgCagg 840

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 ccatcgccaa 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 tcagatcctg attaagaata cacctgttcc cgcggatcct ccaactacct tcagtcaagc 2220 20 Feb 2020 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 2020201242

<210> 31 <211> 3113 <212> DNA <213> 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 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 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

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 2020201242

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 acccectcat cgaccagtac 2160

ctgtactacc tgtctcggac tcagtccacg ggaggtaccg caggaactca gcagttgcta 2220

ttttctcagg ccgggcctaa taacatgtcg gctcaggcca aaaactggct accegggccc 2280

tgctaccggc agcaacgcgt ctccacgaca gtgtcgcaaa ataacaacag caactttgct 2340

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 tgtaattgcc tgttaatcaa 3060

taaaccggtt gattcgtttc agttgaactt tggtctctgc gaagggcgaa ttc 3113

<210> 32 <211> 3113 <212> DNA <213> new AAV serotype, clone 42.3a

<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 360 2020201242

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 gcageggccc 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

gaccctcaac caatcggaga accccccgca ggcccctctg gtctgggatc tggtacaatg 1440

gctgcaggcg gtggcgctcc aatggcagac aataacgaag gcgccgacgg agtgggtagt 1500

tcctcaggaa attggcattg cgattccaca tagctgggcg acagagtcat caccaccagc 1560

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 ..

ctgectccgt 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 taacatgteg gctcaggcca aaaactggct acccgggccc 2280

tgctaccggc agcaacgcgt ctccacgaca ctgtcgcaaa ataacaacag caactttgct 2340 2020201242

tggaccggtg ccaccaagta tcatctgaat ggcagagact ctctggtaaa tcccggtgtc 2400

gctatggcaa cgcacaagga cgacgaagag cgattttttc catccagcgg agtcttgatg 2460

tttgggaaac agggagctgg aaaagacaac gtggactata gcagcgttat gctaaccagt 2 52 0

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 aagegotgga acccagagat tcagtatact 2940

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> DNA <213> new AAV sexotype, 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/USO2/33629 20 Feb 2020

caggagcgtc ttcaagaaga tacgtctttt gggggcaacc tcgggcgagc agtcttccag 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 2020201242

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

taattcgttt cagttgaact ttggtctctg cgaagggcga attc 2504

<210> 34 <211> 3106 <212> DNA <213> new AAV semotype, clone 42.5a

<400> 34 gaattcgccc ttctacggct gcgtcaactg gaccaatgag aactttccct tcaacgattg 60

cgtcgacaag atggtgatct ggtgggagga gggcaagatg acggccaagg tcgtggagtc 120 2020201242

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 gctccggtg actttgccga 540

caggtaccaa aacaaatgtt ctcgtcacgc gggcatgctt cagatgctgt ttccctgcaa 600

aacatgcgag aaaatgaatc 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 1090

acaagcagct cgagcagggg gacaacccgt acctcaagta caaccacgcc gacgccgagt 1140

ttcaggagcg tcttcaagaa gatacgtctt ttgggggcaa cctcgggcga gcagtcttcc 1200

gggccaagaa gcgggttctc gaacctctcg gtctggttga ggaaggcgct aagacggctc 1260

ctggaaagaa gagacccata 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 accaccagca 1560

cccgcacctg ggccctgccc acctacaaca accacctcta caagcagata tcaagtcaga 1620

gcggggctac caacgacaac cacttcttcg gctacagcac cccctggggc tattttgact 1680

WO 03/042397 PCTIUS02f33629 20 Feb 2020

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 agtacggata tctgactcta aacaacggca 1980

gtcagtctgt gggacgttcc tccttctact gcctggagta ctttccttct cagatgctga 2040

gaacgggcaa taactttgaa ttcagctacc agtttgagga cgtgcccttt cacagcagct 2100 2020201242

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 cggagtcttg atgtttggga 2460

aacagggagc tggaaaagac aacgtggact atagcagcgt tatgctaacc agtgaggaag 2520

aaatcaaaac caccaaccca gtggccacag aacagtacgg cgtggtggcc gataacctgc 2580

aacagcaaaa cgccgctcct attgtagggg ccgtcaacag tcaaggagcc ttacctggca 2640

tggcctggca gaaccgggac gtgtacctgc agggtcctat ctggyccaag 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 agcaagcgct ggaacccaga gattcagtat acttccaact 2940

actacaaatc tacaaatgtg gactttgctg tcaatactga gggtacttat tcagagcctc 3000

gccccattgg cacccgttac ctcacccgta acctgtaatt gcctgttaat caataaaccg 3060

gttaattcgt ttcagttgaa ctttggtctc tgcgaagggc gaattc 3106

<210> 35 <211> 2489 <212> DNA <213> new A• serotype, clone 42.10

<400> 35 gaattcgccc tttctacggc tgcgtcaact ggaccaatga gaactttccc ttcaacgatt 60

gcgtcgacaa gatggtgatc tggtgggagg agggcaagat gacggccaag gtcgtgaagt 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.

caggagcgtc ttcaagaaga tacgtctttt gggggcaacc tcgggcgagc agtcttccag 600

gccaagaagc gggttctcga acctctcggt ctggttgagg aaggcgctaa gacggctcct 660

ggaaagaaga gacccataga atccoccgac tcctccacgg gcatcggcag gaaaggccag 720 2020201242

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 ctcaccacgt gactggcagc gactcatcaa caacaactgg 1140

ggattccggc ccagaaagct gcggttcaag ttgttcaaca tccaggtcaa ggaggtcacg 1200

acgaacgacg gcgttacgac catcgccaat 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

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

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 2489

<210> 36 <211> 2495 2020201242

<212> DNA <213> new AAV s e r °type, 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 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

caggagcgtc ttcaagaaga tacgtctttt gggggcaacc tcgggcgagc agtcttccag 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 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 catcgctaat aaccttacua 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/TJS02/33629 20 Feb 2020

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 1740

aaataccatc tgaatggtag aaattcatta accaacccgg gcgtagccat ggccaccaac 1800

aaggacgacg aggaccagtt ctttcccatc aacggagtgc tggtttttgg caaaacgggg 18 60 2020201242

gctgccaaca agacaacgct ggaaaacgtg ctaatgacca gcgaggagga gatcaaaacc 1920

accaatcccg tggctacaga acagtacggt gtggtctcca gcaacctgca atcgtctacg 198 0

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

<210> 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 120

ccgccaaggc cattctcggc ggcagcaagg tgcgcgtgga ccaaaagtgc aagtcttccg 180

cccagatcga tcccacccce 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 540

acaggtacca aaacaaatgt tctcgtcacg cgggcatgct tcagatgctg tttccctgca 600

agacatgcga gagaatgaat cagaatttca acatttgctt cacgcacggg accggagact 660

gttcagaatg tttccccggc gtgtcagaat ctcaaccggt cgtcagaa.ag aggacgtatc 720

ggaaact ctg tgccattcat catctgctgg ggcgggctcc cgagattgct tgctcggcct '780

gcgatctggt caacgtggac ctggatgact gtgtttctga gcaataaatg acttaaacca 890

ggtctggttg ccgatggtta tcttccagat tggctcgagg acaacctctc tgagggcatt 900

cgcgagtggt gggacttgaa acctggagcc cc gaaaccca aagccaacca gcaaaagcag 960

gacgacggcc ggggtctggt gcttcctggc tacaagtacc tcggaccctt caacggactc 1020

gacaagg gag agccggtcaa cgcggcggac gcagcg gc cc tcgagcacga caaggcctac 1080 2020201242

gaccagcagc tcaaagcggg tgacaatccg tacctgcggt at aaccacgc cgacgccgag 1140

tttcaggagc gtcttcaaga agatacgtct tttgggggca a cctcgggcg agcagt cttc 1200

c aggcca a ga agcgggttct cgaacctctc ggtctggttg aggaaggcgc taagacggct 1260

ctggaa aga agagaccc at agaatccccc gactcctcca cgggcatcgg caagaaaggc 1320

cagcagc ccg ctaaaaagaa gctcaacttt gggcagactg gcgactcaga gtcagtgccc 1380

gaccctcaac caatcggaga a cc ccccgc a ggcccc tctg gtctgggatc tggtacaatg 1440

gctgcaggcg gtggcgetcc aatggcagac aataac gaag gcgccgacgg agtgggtaat 1500

gcctccggaa attggcattg cgattccaca tggctgggcg acagagtc at caccaccagc 1560

acccgcacct gggccctgcc cacctacaac a.accacctct acaagcagat atcaagtcag 1620

agcggggcta cc aacgacaa ccacttcttc ggctacagca ccccctgggg ctattttgac 1680

ttcaacagat tccactgcca c tt ct ca cc a cgtgactggc agcgactcat caacaacaac 1740

tggggattcc ggcccagaaa gctgcggttc aagttgttca acatccaggt caaggaggtc 1800

acgacgaacg acggcgttac gaccatcgct aataacctta ccagcacgat tcaggtcttc 1860

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 cc acagcagc 2100

tatgcgc aca gccagagcct ggaccggctg atgaatcccc tcatcgacca gtacctgtac 2160

tacctggccc ggacccagag cactacgggg tccacaaggg agctgcagtt ccatcaggct 2220

gggcccaaca ccatggccga gcaatcaaag aactggctgc ccggaccctg ttatcggcgg 2280

cagagactgt caaaagacat agacagcaac aacaacagta actttgcctg gaccgggg cc 2340

actaaatacc atctgaatgg tagaaattca ttaaccaacc cgggcgtagc catggccacc 2400

aacaaggacg acgaggacca gttctttccc atcaacggag tgctggtttt tggcaaaacg 2460

ggggctgcca acaagacaac gctggaaaac gtgctaatga ccagcgagga ggagatcaaa 2520

accaccaatc ccgtggctac agaagaatac ggtgtggtct ccagcaacct gcaatcgtct 2580

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 2020201242

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 tgqcataatt 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 agtetctgct 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

gagccgagga cgtacggcag ttggtactcc gagtccgaga agacctgaat cgtgctggta 1260

aggttattag cgatggtcgt aacgccgtcg tccgtcgtga cctccttgac ctggatgttg 1320

aacaacttga accgcagctt tctgggccgg 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 2020201242

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 gccgtagtc0 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 ccggggaaaa 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 27 60

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

cgcgcacctt gctgccgccg agaatggcct tggcggactc cacgaccttg gccgtcatct 3160

tgccctcctc ccaccagatc accatcttgt cgacgcaatc gttgaaggga aagttctcat 3240

tggtccagtt gacgcagccg tagaaagggc gaattc 3276

<210> 39 <211> 3084 <212> DNA <213> new JthV serotype, clone 43.1

<400> 39 2020201242

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 tetcgtcacg 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 tettccagat 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 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 ccccggctct 1920

gcgcaccagg gctgcctccc tccgttcccg gcggacgtct tcatgattcc tcagtacggg 1980 2020201242

tatctgaccc taaacaatgg cagtcaggct gtgggccgtt cctccttcta ctgcctggaa 2040

tacttccctt ctcaaatgct gaggacgggc aacaactttg aattcagcta caccttcgag 2100

gacgtgcctt tccacagcag ctacgcgcac agccagagcc tggaccggct gatgaaccct 2160

ctcatCgacc agtacctgta ttacttatcc agaactcagt ccacaggagg aactcaaggt 2220

actcagcaat tgttattttc tcaagccggg cccgcaaaca tgtcggctca ggccaagaac 2280

tggctacctg gaccgtgtta ccgtcagcaa cgagtttcca cgacactgtc gcaaaacaac 2340

aacagcaatt ttgcttggac cggtgccacc aagtatcacc tgaatggcag agactccctg 2400

gttaatcccg gcgttgccat ggctacccac aaggacgacg aggagcgctt cttcccgtca 2460

agcggagttc taatgtttgg caagcagggg gctggaaaag acaatgtgga ctacagcagc 2520

gtgatgctca 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

cctcugacca ccttcagcca ggccaagctg gcttctttta tcacgcagta cagcaccgga 2880

caggtcagcg tggaaatcga atgggagctg cagaaagaaa acagcaagcg ctggaaccca 2940

gagattcagt atacttccaa ctactacaaa tctacaaatg tggactttgc tgtcaatact 3000

gagggtactt attcagagcc tcgccccatt ggcactcgtt atctcacccg taatctgtaa 3060

ttgcttgtta atcaataaac cggt 3084

<210> 40 <211> 2370 <212> DNA <213> new AAV serotype, clone 43.5

<400> 40 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 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 2020201242

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 agcocgtcaa 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 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

gacgtgcctt tccacagcag ctacgcgca.c 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 ggtgccacca 2370

<210> 41 <211> 3123 2020201242

<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 gtccgcccag 180

atcgacccca cccccgtgat cgtcacctcc aacaccaaca tgtgcgccgt gattgacggg 240

aacagcacca ccttcgagca ccagcagccg ttgcaggacc ggatgttcaa gttcgaactc 300

acccgccgtc tggagcacga ctttggcaag gtgaccaagc aggaagtcaa agagttcttc 360

cgctgggcgc aggatcacgt gaccgaggtg gcgcatgagt tctacgtcag aaagggcgga 420

gccagcaaaa gacccgcccc cgatgacgcg gatataagcg agcccaagcg ggcctgcccc 480

tcagtcgcgg atccatcgac gtcagacgcg gaaggagctc cggtggactt tgccgacagg 540

taccaaaaca aatgttctcg tcacgcgggc atgctccaga tgctgtttcc ctgcaaaacg 600

tgcgagagaa tgaatcagaa tttcaacatt tgcttcacgc acggggtcag agactgctca 660

gaatgtttcc ccggtgcatc agaatctcaa ccggtcgtca gaaaaaaaac gtatcagaaa 720

ctgtgtgcca ttcatcatct gctggggcgg gcacccgaga ttgcttgctc ggcctgegat 780

ctggtcaacg tggacctgga cgactgtgtt tctgagcaat aaatgactta aaccaggtat 840

ggctgccgat ggttatcttc cagattggct tgaggacaac ctctctgagg gcattcgcga 900

gtggtgggac ctgaaacctg gagccccgaa acccaaagcc aaccagcaaa agcaggacga 960

cggccggggt ctggtgcttc ctggctacaa gtacctcgga cccttcaacg gactcgacaa 1020

gggggagccc gtcaacgcgg cggacgcagc ggccctcgag cacgacaagg cctacgacca 1080

gcagctcaaa gcgggtgaca atccgtacct gcggtataac cacgccgacg ccgagtttca 1140

ggagcgtctg caagaagata cgtcttttgg gggcaacctc gggcgagcag tcttccaggc 1200

caagaagcgg gttctcgaac ctctcggtct ggttgaggaa ggcgctaaga cggctcctgg 1260

aaagaagaga ccggtagagc catcacctca gcgttccccc gactcctcca cgggcatcgg 1320

caagaaaggc caccagcccg cgagaaagag actgaacttt gggcagactg gcgactcgga 1380

gtcagtcccc gaccctcaac caatcggaga accaccagca ggcccctctg gtctgggatc 1440

WO 03/042397 PCTRIS02/33629 20 Feb 2020

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 1740

actcatcaac aataactggg gattccggcc caagagactc aacttcaagc tcttcaacat 1800 2020201242

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

<400> 42 gaattcgccc tttctacggc tgcgtcaact ggaccaatga gaactttccc ttcaacgatt 60

gcgtcgacaa gatggtgatc tggtgggagg agggcaagat gacggccaag gtcgtggagt 120

ccgccaaggc cattctcggc ggcagcaagg tgcgtgtgga ccaaaagtgc aagtcttccg 180

cccagatcga tcccaccccc gtgatcgtca cctccaacac caacatgtgc gccgtgattg 240

acgggaacag cgccaccttc gagcaccagc agccgttgca ggaccggatg ttcaaatttg 300

aactcacccg ccgtctggag catgactttg gcaaggtgac gaagcaggaa gtcaaagagt 360 2020201242

tcttccgctg ggcgcaggat cacgtgaccg aggtggcgca tgagttccac gtcagaaagg 420

gtggagccaa caagagaccc gcccccgatg acgaggatat aagcgagccc aagcgggcct 480

gcccctcagt cgcggatcca tcgacgtcag acgcggaagg agctccggtg gactttgccg 540

acaggtacca aaacaaatgt tctcgtcacg ogggcatgct tcagatgctg tttccctgca 600

agacatgcga gagaatgaat cagaatttca acatttgctt cacgcacggg accagagact 660

gttcagaatg tttccccggc gtgtcagaat ctcaaccggt cgtcagaaag aggacgtatc 720

ggaaactctg tgcgattcat catctgctgg ggcgggctcc cgagattgct tgctcggcct 780

gcgatctggt caacgtggac ctggatgact gtgtttctga gcaataaatg acttaaacca 840

ggtatggctg ccgatggtta tettccagat 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 ggtctggtta aggaaggcgc taagacggct 1260

cctggaaaga agagactggt agagcagtcg ccacaagagc cagactcctc ctcgggcatc 1320

ggcaagacag gccagcagcc cgctaaaaag agactcaatt ttggtcagac tggcgactca 130 0

gagtcagtcc ccgacccaca acctctcgga gaacctccag cagccocctc aggtctggga 1440

cctaatacaa tggcttcagg cggtggcgct ccaatggcag acaataacga aggcgccgac 1500

ggagtgggta attccteggg 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 cggttcctca gtacggctat 1980

ttaactttaa acaatggaag ccaagccctg ggacgttcCt ccttctactg tctggagtat 2040

ttcccatcgc agatgctgag aaccggcaac aactttcagt tcagctacac cttcgaggac 2100

gtgectttcc acagcagcta cgcgcacagc cagagcctgg acaggctgat gaatcccctc 2160

atcgaccagt acctgtacta cctggtcaga acgcaaacga ctggaactgg agggacgcag 2220

actctggcat tcagccaagc gggtcctagc tcaatggcca accaggctag aaattgggtg 2280 2020201242

cceggacctt 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 caygcgcaga ccggactcgt gcacaaccag 2640

ggggtgattc ccggcatggt gtggcagaat agagacgtgt acctgcaggg 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 3120

to 3122

<210> 43 <211> 3117 <212> DNA <213> new PLAY 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 PCMS02/33629 20 Feb 2020

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 ttgcttgctc ggcctgcgat 780

ctggtcaacg tggacctgga tgactgtgtt tctgagcaat aaatgactta aaccaggtat 840 2020201242

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 cgtettttgg 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 tccagcagcc 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 tgcctggacg ggagctgcca agtttaagct gaacggccga gactctctaa tgaatccggg 20 Feb 2020

2400

cgtggcaatg gcttcccaca aggatgacga cgaccgcttc ttcccttcga gcggggtcct 2460

gatttttggc aagcaaggag cegggaacga tggagtggat tacagccaag tgctgattac 2520

agatgaggaa gaaatcaagg ctaccaaccc cgtggccaca gaagaatatg gagcagtggc 2580

catcaacaac caggccgcca atacgcaggc gcagaccgga ctcgtgcaca accagggggt 2640

gattcccggc atggtgtggc agaatagaga cgtgtacctg cagggtccca tctgggccaa 2700

aattcctcac acggacggca actttcaccc gtctcccctg atgggcggct ttggactgaa 2760 2020201242

gcacccgcct cctcaaattc tcatcaagaa cacaccggtt ccagcggacc cgccgcttac 2820

cttcaaccag gccaagctga actctttcat cacgcagtac agcaccggac aggtcagcgt 2880

ggaaatcgag tgggagctgc agaaagaaaa cagcaaacgc tggaatccag agattcaata 2940

cacttccaac tactacaaat ctacaaatgt ggactttgct gtcaacacgg aaggagttta 3000

tagcgagcct cgccccattg gcacccgtta cctcacccgc aacctgtaat tacatgttaa 3060

tcaataaacc ggttaattcg tttcagttga actttggtct ctgcgaaggg cgaattc 3117

<210> 44 <211> 3121 <212> DNA <213> new AAV serotype, clone 93.23

<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 ccgtgattga 240

cgggaacage 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 actttgccga 540

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

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

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 2020201242

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 162 0

tctccaacgg cacctcggga ggaagcacca acgacaacac ctattttggc tacagcaccc 1680

cctgggggta ttttgacttc aacagattcc actgtcactt ttcaccacgt gactggcaac 1740

gactcatcaa caacaattgg ggcttcaggc ccaaaagact caacttcaag ctgttcaaca 1800

tccaggtcaa ggaagtcacg acgaacgaag gcaccaagac catcgccaat aatctcacca 1860

gcaccgtgca ggtctttacg gacttggagt accagttacc gtacgtgcta ggatccgctc 1920

accagggatg tctgcctccg ttcucggcgg 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 cagccaaccg 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

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 2020201242

<213> new AAV serotype, clone 43.25

<400> 45 gaattcgccc tttctacggc tgcgtcaact ggaccaatga gaactttccc ttcaacgatt 60

gcgtcgacaa gatggtgatc tggtgggagg agggcaagat gacggccaag gtcgtggagt 120

ccgccaaggc cattctcggc ggcagcaagg tgcgtgtgga ccaaaagtgc aagtcttccg 180

cccagatcga tcccaccccc gtgatcgtca cctccaacac caacatgtgc gccgtgattg 240

acgggaacag caccaccttc gagcaccagc agccgttgca ggaccggatg ttcaaatttg 300

aactcacccg ccgtctggag catgactttg gcaaggtgac gaagcaggaa gtcaaagggt 360

tcttccgctg ggcgcaggat cacgtgaccg aggtggcgca tgagttccac gtgcgagccc 420

aagcgggcct gcccctcagt cgcggatcca tcgacgtcag accagaaagg gt ggagccaa 480

caagagaccc gcccccgatg acgcggatat aagcggaagg 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 tgcgattcat 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 caaagcctac 1080

gaccagcagc tcaaagcggg tgacaatccg tacctgcggt ataatcacgc cgacgccgag 1140

tttcaggagc gtctgcaaga agatacgtct tttgggggca acctcgggcg agcagtcttc 1200

caggccaaga agcgggttct cgaacctctc ggtctggttg aggaaggcgc taagacggct 1260

cctggaaaga agagaccggt agagcagtcg ccacaagagc cagactcctc ctcgggcatc 1320

ggcaagacag gccagcagcc cgctaaaaag agactcaatt ttggtcagac tggcgactca 1380

gagtcagtcc ccgacccaca acctctcgga gaacctccag cagccccctc aggtctggga 1440 cctaatacaa tggcttcagg cggtggcgct ccaatggcag acaataacga aggcgccgac 20 Feb 2020

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 2020201242

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

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 acctgcaggg 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 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

<400> 46 20 Feb 2020

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 2020201242

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 tttctacggc gtgtcagaat ctcaaccggt cgtcagaaaa 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 1140

tttcaggagc gtctgcaaga agatacgtct tttgggggca acctcgggcg agcagtcttc 1200

caggccaaga agcgggttct cgaacctetc 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 1860

accagcacga ttcaggtctt tacggactcg gaataccagc tcccgtacgt ccteggctct 1920 gcgcaccagg gctgcctgcc tccgttcccg gcggacgtct tcatgattcc tcagtacggg 1980 20 Feb 2020 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 2020201242 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 2880 caggtcagcg tggaaattga atgggagctg cagaaagaaa acagcaaacg ctggaaccca 2940 gagattcaat acacttccaa ctactacaaa tctacaaatg tggacttcgc tgttaacaca 3000 gatggcactt attctgagcc tcgccccatt ggcacccgtt acctcacccg taatctgtaa 3060 ttgetcgtta atcaataaac cggttgattc gtttcagttg aactttggtc tctgcgaagg 3120 gcgaattc 3128

<210> 47 <211> 3128 <212> DNA <213> new AAV serotype, clone 44.5

<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 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 tttcCetgCa 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 2020201242

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 gacccaaCtt caagctcttc 1800

aacatccagg tcaaggaggt cacgcagaat gaaggcacca agaccatcgc caataacctt 1860

accagcacga ttcaggtctt tacggactCg gaataccagc tcccgtacgt cctcggctct 1920

gcgcaccagg getgcctgCC tccgttcccg gcggacgtct tcatgattcc tcagtacggg 1980

tacctgactc tgaacaatgg cagtcaggcc gtgggccgtt Cctccttcta ctgcctggag 2040

tactttcctt ctcaaatgct gagaacgggc aacaactttg agttcagcta ccagtttgag 2100

gaCgtgcctt ttcacagcag ctacgcgcac agccaaagce tggaccggct gatgaacccc 2160

ctcatcgacc agtacctgta ctacctgtct cggactcagt ccacgggagg taccgcagga 2220

actcagcagt tgctattttc tcaggccggg cctaataaca tgtcggctca ggccaaaaac 2280

tggctacccg ggccctgcta ccggcagcaa cgcgtOtCca cgacactgtc gcaaaataac 2340

aacagcaact ttgcctggac cggtgccacc aagtatCatc tgaatggcag agactctctg 2400 gtaaatcccg gtgtcgctat ggcaacccac aaggacgacg aagagcgatt ttttccgtcc 2460 20 Feb 2020 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 2700 atctgggcca agattcctca cacggacgga aactttcatc cctcgccgct gatgggaggc 2760 tttggactga aacacccgcc tcctcagatc ctgattaaga atacacctgt tcccgcggat 2820 2020201242 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> 48 <211> 1933 <212> DNA <213> new AAV serotype, clone 223.10

<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 180

taagacggca cctggaaaga agcgaccggt agactcgcca gactccacct cgggcatcgg 240

caagaaaggc cagcagcccg cgaaaaagag actcaacttt gggcagactg gcgactcaga 300

gtcagtcccc gaccctcaac caatcggaga accaccagca 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

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 2020201242

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 gctgttgaca gccagggtgt 1920

ttactctgag cct 1933

<210> 49 <211> 1933 <212> DNA <213> new AAV serotype, clone 223.2

<400> 49 caaggcctac gaccagcagc tcaaagcggg tgacaatccg tacctgcggt ataaccacgc 60

cgacgccgag tttcaggagt gtcttcaaga agatacgtct tttgggggca acctcgggcg 120

agcagtcttc caggccaaaa agegggttct cgaacctctt ggtctggttg agacgccagc 180

taagacggca cctggaaaga agcgaccggt agactcgcca gactccacct cgggcatcgg 240

caagaaaggc cagcagcccg cgaaaaagag actcaacttt gggcagactg gcgactcaga 300

gtcagtcccc gaccctcaac caatcggaga accaccagca ggcccctctg gtctgggatc 360

tggtacaatg gttgcaggcg 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 20 Feb 2020 ggggtatttt gacttcaaca gattccattg ccacttctca ccacgtgact ggcagcgact 660 tatcaacaac aactggggat tccggcccaa gaagctcaac ttcaagctct tcaacatcca 720 ggtcaaggag gtcacgacga atgacggtgt cacaaccatc gctaataacc ttaccagcac 780 ggttcaggtc ttttcggact cggaatatca actgccgtac gtcctcggct ccgcgcacca 840 gggctgcctg cctccgttcc cggcagacgt gttcatgatt ccgcagtacg gatacctgac 900 tctgaacaat ggcagccaat cggtaggccg ttcctccttc tactgcctgg agtactttcc 960 2020201242 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 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 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 sexotype, 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 gccagtcccc gaccctcaac caatcggaga accaccagca ggcccctctg gtctgggatc 360 20 Feb 2020 tggtacaatg gctgcaggcg gtggcgcacc aatggctgac aataacgagg gcgccgacgg 420 agtgggtaat gcctcaggaa attggcattg cgattccaca cggctgggcg acagagtcat 480 caccaccagc acccgaacct gggccctgcc cacctacaac aaccacctct acaagcaaat 540 ctccagtcag tcagcaggga gcaccaacga taacgtctat ttcggctaca gcacccectg 600 ggggtatttt gacttcaaca gattccattg ccacttctca ccacgtgact ggcagcgact 660 tatcaacaac aactggggat tccggcccaa gaagctcaac ttcaagctct tcaacatcca 720 2020201242 ggtcaaggag gtcacgacga atgacggcgt cacaaccatc gctaataacc ttaccagcac 780 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 tctgggccgg 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 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 gaatgggagc tgcagaaaga gaacagcaag cgctggaacc cagagattca 1860 gtacacctcc aactttgaca aacagactgg agtggacttt gctgttgaca gccagggtgt 1920 ttactctgag cct 1933

<210> 51 <211> 1933 <212> DNA <213> new ?AV serotype, clone 223.5

<400> 51 caaggcctac gaccagcagc tcaaagcggg tgacaatccg tacctgcggt ataaccacgc 60 cgacgccgag tttcaggagc gtcttcaaga agatacgtct tttgggggca acctcgggcg 120 20 Feb 2020 agcagtcttc caggccaaaa agcgggttct cgaacctctt ggtctggttg agacgccagc 180 taagacggca cctggaaaga agcgaccggt agactcgcca gactccacct cmcategg 240 caagaaaggc cagcagcccg cgaaaaagag actcaacttt gggcagactg gcgactcaga 300 gccagtcccc gaccctcaac caatcggaga accaccagca ggcccetctg gtctgggatc 360 tggtacaatg gctgcaggcg gtggcgcacc aatggctgac aataacgagg gcgccgacgg 420 agtgggtaat gcctcaggaa attggcattg cgattccaca cggctgggcg acagagtcat 480 2020201242 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 atgacggcgt cacaaccatc gctaataacc ttaccagcac 780 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 tctgggccgg ctgatgaatc ccctcatcga 1080 ccagtacctg tactacttgg ccagaacaca gagcaacgca ggaggtactg ctggcaatcg 1140 ggaactgcaig ttttatcagg gcggacctac caccatggcc gaacaagcaa agaactggct 1200 gcccggacct tgcttccggc aacagagagt atccaagacg ctggatcaaa ataacaacag 1260 caactttgcc tggactggtg ccacaaaata ccatttaaat ggaagaaatt 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 gaatgggagc tgcagaaaga gaacagcaag cgctggaacc cagagattca 1860 gtacacctcc aactttgaca aacagactgg agtggacttt gctgttgaca gccagggtgt 1920 ttactctgag cct 1933

<210> 52 <211> 1933 <212> DNA <213> new APAr serotype, clone 223.6

<400> 52 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 2020201242

caagaaaggc cagcagcccg cgaaaaagag actcaacttt gggcagactg gcgactcaga 300

gtcagtcccc gaccctcaac caatcggaga accaccagca ggcccctctg gtctgggatc 360

tggtacaatg gctgcaggcg gtggcgcacc aatggctgac aatagcgagg 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

ggttcaggtc ttttcggact cggaatatca actgccgtac gtcctoggct 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 ggaagaaatt 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 cctgccaagc ttgcttcctt catcacgcag tacagcaccg ggcaagtcag 1800 20 Feb 2020 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 2020201242

<400> 53 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

gtcagtcccc gaccctcaac caatcggaga accaccagca 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 560

tatcaacaac aactggggat tccggcccaa gaagctcaac ttcaagctct tcaacatcca 720

ggtcaaggag gtcacgacga atgacggcgt cacaaccatc gctaataacc ttaccagcac 780

ggttcaggtc ttttcggacc 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 ctggatcaam ataacaacag 1260

caactttgcc tggactggtg ccacaaaata ccatttaaat ggaagaaatt cattggttaa 1320

tcccggtgtc gccatggcaa cccacaagga cgacgaggaa cgcttcttcc cttcgagcgg 1380

agttctaatt tttggcaaaa ctggagcagc taataaaact acattagaaa acgtgctcat 1440

gacaaatgaa gaagaaattc gtcctaccaa cccggtagct accgaggaat acgggattgt 1500 aagcagcaac ttgcaggegg ctagcaccgc agcccagaca caagttgtta acaaccaggg 1560 20 Feb 2020 agcattacct 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 2020201242 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 540

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

tagtaaatgt 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

gsgcgtcttc aagaagatac gtctttcggg ggcaacctcg ggcgagcagt cttccaggcC 1200

aaaaagaggg tactcgagcc tcttggtctg gttgaggaag ctgttaagac ggctcctgga 1260 aaaaagagac ctatagagca gtctcctgca gaaccggact cttcctcggg catcggcgaa 1320 20 Feb 2020 tcaggccagc agcccgctaa gaaaagactc aattttggtc agactggcga cacagagtca 1380 gtcccagacc ctcaaccaat cggagaaccc cccgcagccc cctctggtgt gggatctaat 1440 acaatggctt caggcggtgg ggcaccaatg gcagacgata acgaaggcgc cgacggagtg 1500 ggtaattcct cgggaaattg gcattgcgat tccacatgga tgggcgacag agttatcacc 1560 accagcacaa gaacctgggc cctccccacc tacaataatc acctctacaa gcaaatctcc 1620 agcgaatcgg gagccaccaa cgacaaccac tacttcggct acagcacccc ctgggggtat 1684 2020201242 tttgacttta acagattcca ctgtcacttc tcaccacgtg actggcagcg actcatcaac 1740 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 ttcagccaag ctgggcctag ctccatggct cagcaggcca aaaactggct accgggaccc 2280 agctaccgac agcagcgaat gtctaagacg gctaatgaca acaacaacag tgaatttgct 2340 tggactgcag ccaccaaata ttacctgaat ggaagaaatt ctctggtcaa tcccgggccc 2400 ccaatggcca gtcacaagga cgatgaggaa aagtatttcc ccatgcacgg aaatctcatc 2460 tttggaaaac aaggcacagg aactaccaat gtggacattg aatcagtgct tattacagac 2520 gaagaagaaa tcagaacaac taatcctgtg gctacagaac aatacggaca ggttgccacc 2580 aaccatcaga gtcaggacac 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 acccagaaat tcagtacacc 2940 tccaactaca acaagtcggt gaatgtggag tttaccgtgg acgcaaacgg tgtttattct 3000 gaaccccgcc ctattggcac tcgttacctt acccggaact tgtaatttcc tgttaatgaa 3060 taaaccgatt tatgcgtttc agttgaactt tggtctctgc gaagggcgaa ttcgcggccg 3120 cta. 3123

<210> 55 20 Feb 2020

<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 2020201242

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 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 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

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 aacaactggg gatttagacc caagaaactc aatttcaagc tcttcaacat ccaagtcaag 1800 20 Feb 2020 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 2020201242 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 120

tcgtggaatc tgccaaagcc attctgggtg gaagcaaggt tcgtgtggac cagaaatgca 180

ggtcttcggc ccagatcgac ccgactccgg tgattgtcac ctctaacacc aacatgtgcg 240

ccgtgattga cggaaactcg accaccttcg agcaccagca gccgttgcaa gaccggatgt 300

tcaaatttga acttacccgc cgtttggatc atgactttgg gaaggtcacc aagcaggaag 360 tcaaagactt tttccggtgg gctcaagatc acgtgactga ggtggagcat gagttctacg 420 20 Feb 2020 tcaaaaaggg tggagccaag aaaaggcccg cccccgatga tgtatatata aatgagccca 480 agcgggcgcg cgagtcagtt gcgcagccat cgacgtcaga cgcggaagct tcgataaact 540 acgcggacag gtaccaaaac aaatgttctc gtcacgtggg catgaatctg atgctgtttc 600 cctgtcgaca at gcgaaaga atgaatcaga attcaaatat ctgcttcaca cacgggcaaa 660 aagactgttt ggaatgcttt cccgtgtcag aatctcaacc cgtttctgtc gtcagaaaaa 720 cgtatcagaa actttgttac a ttcatcat a tcatgggaaa agtaccagac gcctgcactg 780 2020201242 cctgcgaact ggtaaatgtg gacttggatg actgtatttc tgagcaataa atgacttaaa 840 tcaggtatgg ctgctgacgg ttatcttcca gattggctcg aggacactct ctctgaagga 900 atc agacagt gg tggaagct caaacctggc ccaccaccgc cgaaacctaa ccaacaacac 960 cgggacgaca gtaggggtct tgtgcttcct gggtacaagt acctcggacc cttcaacgga 1020 ctcgacaaag gagagccggt caacgaggc a gacgccgcgg ccctcgagca cgacaaagcc 1080 tacgaccacc agctcaagca aggggacaac ccgtacctca aatacaacca cgcggacgct 1140 gaatttcagg agcgtcttca agaagatacg tatttcgggg gcaacctcgg gcgagcagtc 1200 ttccaggcca aaaagagggt actcgagcct cttggtctgg ttgaggaagc tgttaagacg 1260 gctcctggaa aaaagagacc tatagagcag tctcctgcag aaccggactc ttcctcgggc 1320 a tcgg ca aat 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 gcgaatcggg agccaccaac gacaaccact act tcggcta cagcaccccc 1680 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 caggg ctgcc ttccgccgtt cccagcagac gtcttcatga ttcctcagta cggctacttg 1980 actctgaac a atggcagcca agcggtagga cgttcttcat tc tactgtct agagtatttt 2040 ccctctcaga tgctgaggac gggaaacaac ttcaccttca gctacacttt tgaagacgtg 2100 cctttccaca gcagctacgc gcacagccag agtctggatc ggctgatgaa tcctctcatt 2160 gaccagtacc tgtattacct gagcaaaact cagggtacaa gtggaacaac gcagcaatcg 2220 agactgcagt tcagccaagc tgggcctagc tccatggctc agcaggccaa aaactggcta 2280 ccgggaccca gctaccgaca gcagcgaatg tctaagacgg otaatgacaa caacaacagt 2340 20 Feb 2020 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 2580 gttgccacca accatcagag tcagaacacc acagcttcct atggaagtgt ggacagccag 2640 ggaatcttac ctggaatggt gtggcaggac cgcgatgtct atcttcaagg tcccatttgg 2700 2020201242 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

<400> 57 gaattcgccc tttctacggc tgcgtcaact ggaccaatga aaactttccc ttcaacgatt 60

gcgtcgacaa gatggtgatc tggtgggagg agggaaagat gaccgccaag gtcgtggaat 120

ctgccaaagc cattctgggt ggaggcaagg 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 tacgcggaca 540

ggtaccaaaa caaatgttct cgtcacgtgg gcatgaatct gatgctgttt ccctgtcgac 600

aatgcgaaag aatgaatcag aattcaaata tctgcttcac acacgggcaa aaagactgtt 660

tggaatgctt tcccgtgtca gaatctcaac ccgtttctgt cgtcagaaaa acgtatcaga 720

aactttgtta cattcatcat atcatgggaa aagtaccaga cgcctgcact gcctgcgacc 780

tggtaaatgt ggacttggat gactgtattt ctgagcaata aatgacttaa atcaggtatg 840 gctgctgacg gttatcttcc agattggctc gaggacactc tctctgaagg aatcagacag 900 20 Feb 2020 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 2020201242 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 aucaactggg gatttagacc caagaaactc aatttcaagc tcttcaacat ccaagtcaag 1800 gaggtcacgc agaatgatgg aaccacgacc atcgccaata accttaccag cgcggtgcag 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 ttcagccaag ctgggcctag ctccatggct cagcaggcca aaaactggct accgggaccc 2280 agctaccgac agcagcgaat gtctaagacg gctaatgaca acaacaacag tgaatttgct 2340 tggactgcag ccaccaaata ttacctgaat ggaagaaatt ctctggtcaa tccegggccc 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 2640 cctggaatgg tgtggcagga ccgcgatgtc tatcttcaag gtcccatttg ggccaaaact 2700 cctcacacgg acggacactt tcatccttct ccgctcatgg gaggctttgg actgaaacac 2760 cctcctcccc agatcctgat caaaaacaca cctgtgccag cgaatcccgc gaccactttc 2820 20 Feb 2020 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 2020201242

<210> 58 <211> 2969 <212> DNA <213> new AAV serotype, clone 4 2.12

<400> 58 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 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 acttaaacca 840

ggtatggctg ccgatggtta tcttccagat tggctcgagg acaacctctc tgagggcatc 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 agagaccggt agagccatca ccccagcgtt ctccagactc ctctacgggc 1320 atcggcaaga caggccagca gcccgcgaaa aagagactca actttgggca gactggcgac 1380 20 Feb 2020 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 2020201242 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 gctctgcccg 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 <213> new ANY' serotype, clone 44.2

<400> 59 gaattcgccc tttctacggc tgcgtcaact ggaccaatga gaactttccc ttcaacgatt 60 gcgtcgacaa gatggtgatc tggtgggagg agggcaagat gacggccaag gtcgtggagt 120 20 Feb 2020 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 aaapaggaa gtcagagagt 360 tcttccgctg ggcgcaggat cacgtgaccg aggtggcgca cgagttctac gtcagaaagg 420 gtggagccaa caagagaccc gcccccgatg acgcggataa aagcgagccc aagegggcct 480 2020201242 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 ctcagagtca gtgcccgacc ctcaaccaat cggagaaccc occgcaggcc cctctggtct 1440 gggatctggt acaatggctg caggcggtgg cgctccaatg gcagacaata acgaaggcgc 1500 cgacggagtg ggtagttcct caggaaattg gcattgcgat tccacatggc tgggcgacag 1560 agtcatcacc accagcaccc gaacctgggc cctccccacc tacaacaacc acctctacaa 1620 gcaaatctcc aacgggactt cgggaggaag caccaacgac aacacctact tcggctacag 1680 caccecctgg gggtattttg actttaacag attccactgc cacttctcac cacgtgactg 1740 gcagcgactc atcaacaaca actggggatt ccggcccaag agactcaact tcaagctctt 1800 caacatccag gtcaaggagg tcacgcagaa tgaaggcacc aagaccatcg ccaataacct 1860 taccagcacg attcaggtct ttacggactc ggaataccag ctcccgtacg tcctcggctc 1920 tgcgcaccag ggctgcctgc ctccgttccc ggcggacgtc ttcatgattc ctcagtacgg 1980 gtacctgact ctgaacaatg gcagtcaggc cgtgggccgt tcctccttct actgcctgga 2040 20 Feb 2020 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 2020201242 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 serotype, clone C1VP1

<400> 60

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 1 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 Gin Asp Asp Gly Arg Gly Leu Val Lau 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 Giu His Asp Lys Ala Tyr Asp 20 Feb 2020

65 70 75 80

Gin Gin Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Mn His Ala 85 90 95

Asp Ala Glu Phe Gin Glu Arg Leu Gin Glu Asp Thr Ser Phe Gly Giy 100 105 110

Asn Leu Gly Arg Ala Va1 Phe Gin Ala Lys Lys Arg Val Leu Giu Pro 115 120 125 2020201242

Leu Gly Leu Val Glu Glu Gly Ala Lys Thr Ala Pro Gly Lys Lys Arg 130 135 140

Pro Leu Glu Ser Pro Gln Glu Pro Asp Ser Ser Ser Gly Ile Gly Lys 145 150 155 160

Lys Gly Lys Gin Pro Ala Lys Lys Arg Leu Asn Phe Glu Giu Asp Thr 165 170 175

Gly Ala Giy Asp Gly Pro Pro Glu Gly Ser Asp Thr Ser Ala Met Ser 180 185 190

Ser Asp lie Glu Met Arg Ala Ala Pro Gly Gly Mn Ala Va1 Asp Ala 195 200 205

Gly Gin Gly Ser Asp Gly Val Gly Mn Ala Ser Gly Asp Trp His Cys 210 215 220

Asp Ser Thr Trp Ser Giu Gly Lys Val Thr Thr Thr Ser Thr Arg Thr 225 230 235 240

Trp Val Leu Pro Thr Tyr Asn Asn His Leu Tyr Leu Arg Leu Gly Thr 245 250 255

Thr Ser Asn Ser Asn Thr Tyr Asn Gly Phe Ser Thr Pro TIP Gly Tyr 260 265 270

Phe Asp Phe Asn Arg Phe His Cys His Phe Ser Pro Arg Asp Trp Gln 275 280 285

Arg Leu Ile Asn Asn Asn Trp Gly Leu Arg Pro Lys Ala Met Arg Val 290 295 300

Lys Ile Phe Asn Ile Gin Val Lys Gin Val Thr Thr Sex Asn Gly Glu 305 310 315 320

Thr Thr Val Ala Asn Asn Leu Thr Ser Thr Val Gln Ile Phe Ala Asp 20 Feb 2020

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 Pro Asn Asp Val Phe Met Val Pro Gin Tyr Gly Tyr 355 360 365

Cys Gly Ile Val Thr Gly Glu Asn Gin Asn Gin Thr Asp Arg Asn Ala 370 375 380 2020201242

Phe Tyr Cys Leu Glu Tyr Phe Pro Ser Gin Met Leu Arg Thr Gly Asn 385 390 395 400

Asn Phe Glu Met Ala Tyr Asn Phe Gly Lys Val Pro Phe His Ser Met 405 410 415

Tyr Ala Tyr Ser Gin Sex. Pro 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 Axg Ser Gly Asp Phe 450 455 460

Ala Phe Tyr Arg Lys Asn Trp Leu Pro Gly Pro Cys Val Lys Gln Gin 465 470 475 480

Arg Leu Ser Lys Thr Ala Ser Gln Asn Tyr Lys Ile 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 Ile Ala Pro Gly Pro Pro Met Ala Thr Ala Gly Pro Ser 515 520 525

Asp Gly As Phe Ser Asn Ala Gln Leu Ile 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

Glu Giu Ile Ala Ala Thr Asn Pro Arg Asp Thr Asp Met Phe Gly Gin 565 570 575

Ile Ala Asp Asn Asn Gin Asn Ala Thr Thr Ala Pro Ile Thr Gly Asn 20 Feb 2020

580 585 590

Val Thr Ala Met Giy 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 Ile Gly Gly Phe Giy Leu Lys His Pro 625 630 635 640 2020201242

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 Gln Phe Thr Ser Asn Tyr Gly Asn 690 695 700

Gin Ser Ser Met Leu Trp Ala Pro Asp Thr Thr Giy 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 <21 1 > 733 <212> PRT <213> capsid protein of AAV serotype, clone C2VP1

<400> 61 Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 1 5 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

WO 03/042397 PCITS02/33629

Gin Gin Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala 20 Feb 2020

85 90 95

Asp Ala Glu Phe Gin Glu Arg Leu Gin Glu Asp Thr Ser Phe Gly Gly 100 105 110

Asn Len Gly Arg Ala Val Phe Gin Ala Lys Lys Arg Val Leu Glu Pro 115 120 125

Len Gly Leu Val Glu Glu Gly Ala Lys Thr Ala Pro Gly Lys Lys Arg 130 135 140 2020201242

Pro Leu Glu Sex Pro Gin Glu Pro Asp Ser Ser Ser Gly Ile Gly Lys 145 150 155 160

Lys Gly Lys Gln Pro Ala Lys Lys Arg Len Asn Phe Glu Gin Asp Thr 165 170 175

Gly Ala Gly Asp Gly Pro Pro Glu Gly Ser Asp. Thr Ser Ala Met Ser 160 185 190

Ser Asp Ile Glu Met Arg Ala Ala Pro Gly Gly Asn Ala Val Asp Ala 195 200 205

Gly Gin Gly Sex Asp Gly Val Giy Asn Ala Ser Gly Asp Trp His Cys 210 215 220

Asp Ser Thr Trp Ser Gin Gly Lys Val Thr Thr Thr Ser Thr Arg Thr 225 230 235 240

Trp Val Leu Pro Thr Tyr Asn Asn His Len Tyr Leu Arg Leu Gly Thr 245 250 255

Thr Ser Asn Sex 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 Ile Asn Asn Asn Trp Gly Leu Arg Pro Lys Ala Met Arg Val 290 295 300

Lys Ile Phe Asn Ile Gin Val Lys Glu Val Thr Thr Ser Asn Gly Gin 305 310 315 320

Thr Thr Val Ala Asn Asn Leu Thr Sex Thr Val Gin Ile Phe Ala Asp 325 330 335

Ser Ser Tyr Glu Leu Pro Tyr Val Met Asp Ala Gly Gin Glu Gly Ser 20 Feb 2020

340 345 350

Let Pro Pro Phe Pro Asn Asp Val Phe Met Val Pro Gln Tyr Gly Tyr 355 360 • 365

Cys Gly Ile Val Thr Gly Glu Asn Gin Asn Gin Thr Asp Arg Asn Ala 370 375 380

Phe Tyr Cys Leu Glu Tyr Phe Pro Ser Gln Net Leu Arg Thr Gly Asn 385 390 395 400 2020201242

Asn Phe Glu Met Ala Tyr Asn Phe Giu 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 Gln 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 Gln Gln 465 470 475 480

Arg Phe Ser Lys Thr Ala Ser Gln Asn Tyr Lys Ile 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 Ile Ala Pro Gly Pro Pro Met Ala Thr Ala Gly Pro Ser 515 520 525

Asp Gly Asp Phe Ser Asn Ala Gln Leu Ile Phe Pro Gly Pro Ser Val 530 535 540

Thr Gly Asn Thr Thr Thr Ser Ala Asn Asn Leu Leu Phe Thr Ser Giu 545 550 555 560

Gly Glu Ile Ala Ala Thr Asn Pro Arg Asp Thr Asp Met Phe Gly Gin 565 570 575

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 Ile Pro His Ala Asp Giy 610 615 620

His Phe His Pro Ser Pro Leu Ile Gly Gly Phe Gly Leu Lys His Pro 625 630 635 640

Pro Pro Gln Ile Phe Ile Lys Asn Thr Pro Val Pro Ala Asn Pro Ala 645 650 655 2020201242

Thr Thr Phe Thr Ala Ala Arg Val Asp Ser Phe Ile Thr Gln Tyr Ser 660 665 670

Thr Gly Gln Val Ala Val Gin Ile Glu Trp Glu Ile Glu Lys Glu Arg 675 680 685

Ser Lys Arg Arg Asn Pro 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 1 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 Gin Gin Lys Gin Asp Asp Gly Arg Gly Leu Val Leu Pro 35 40 45

Gly Tyr Glu Tyr Leu Giy Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro 50 55 60

Val Asn Ala Ala Asp Ala Ala Ala Leu Giu His Asp Lys Ala Tyr Asp 65 70 75 80

Gln Gin 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 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 2020201242

Pro Leu Glu Ser Pro Gin Glu Pro Asp Ser Ser Ser Gly Ile Gly Lys 145 150 155 160

Lys Gly Lys Gin Pro Ala Lys Lys Arg Leu Asn Phe Glu Glu Asp Thr 165 170 175

Gly Ala Gly Asp Gly Pro Pro Glu Gly Ser Asp Thr Ser Ala Met Ser 180 185 190

Ser Asp Ile Glu Met Arg Ala Ala Pro Gly Gly Asn Ala Val Asp Ala 195 200 205

Gly Gin Gly Ser Asp Gly Val Gly Asn Ala Ser Gly Asp Trp His Cys 210 215 220

Asp Ser Thr Trp Ser Glu Gly Lys Val Thr Thr Thr Ser Thr Arg Thr 225 230 235 240

Trp Val Leu Pro Thr Tyr Asn Am.]. His Leu Tyr Leu Arg Leu Gly Thr 245 250 255

Thr Ser Asn 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 Gln 275 280 285

Arg Leu Ile Asn Asn Asn Trp Gly Leu Arg Pro Lys Ala Met Arg Val 290 295 -300

Lys Ile Phe Asn Ile Gin Val Lys GIu Val Thr Thr Ser Asn Gly Glu 305 310 315 320

Thr Thr Val Ala Asn Asn Leu Thr Ser Thr Val Gin Ile Phe Ala Asp 325 330 335

Ser Ser Tyr Glu Leu Pro Tyr Val Met Asp Ala Gly Gln 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 Ile Val Thr Gly Glu Asn Gin Asn Gln Thr Asp Arg Asn Ala 370 375 380

Phe Tyr Cys Leu Glu Tyr Phe Pro Ser Gin Met Leu Arg Thr Gly Asn 385 390 395 400

Ala Tyr Asn Phe Glu Lys Val Pro Phe His Ser Met 2020201242

Asn Phe Glu Thr 405 410 415

Tyr Ala His Ser Gin Ser Leu Asp Gly 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 Ile Pro Ala Ser Gly 485 490 495

Gly Asti Ala Leu Leu Lys Tyr Asp Thr His Tyr Thr Leu Asn Asa Arg 500 505 510

Trp Ser Asn Ile Ala Pro Gly Pro Pro Met Ala Thr Ala Gly Pro Ser 515 520 525

Asp Gly Asp Phe Ser Asn Ala Gin Leu Ile 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

Glu Glu Ile Ala Ala Thr Asn Pro Arg Asp Thr Asp Met Phe Gly Gln 565 570 575

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 lie Trp Ala Lys Ile Pro His Ala Asp Gly 20 Feb 2020

610 615 620

His Phe His Pro Ser Pro Lou Ile Gly Gly Phe Gly Leu Lys His Pro 625 630 635 640

Pro Pro Gln 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 Gln Tyr Ser 660 665 670 2020201242

Thr Gly Gin Val Ala Val Gln 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 Cys Gly Asn 690 695 700

Gln 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> 63 <211> 734 <212> PRT <213> capsid protein of AAV serotypo, clone AAV4VP1 <400> 63 Met Thr Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser Glu 1 5 10 15

Giy Val Arg Glu Trp Trp Ala Leu Gin Pro Gly Ala Pro Lys Pro Lys 20 25 30

Ala Asn Gin Gin His Gin Asp Asn Ala Arg Gly Leu Val Leu Pro Gly 35 40 45

Tyr Lys Tyr Leu Gly Pro Gly Asn Giy Leu Asp Lys Gly Glu Pro Val 50 55 60

Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp Gln 65 70 75 80

Gin Leu Lys Ala Gly Asp Asn Pro Tyr Leu Lys Tyr Asn His Ala Asp 85 90 95

Ala Glu Phe Gin Gin Arg Leu Gin Gly Asp Thr Ser Phe Gly Gly Asn 100 105 110

Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro Leu 115 120 125

Gly Leu Val Glu Gin Ala Gly Glu Thr Ala Pro Gly Lys Lys Arg Pro 130 135 140

Leu Ile Glu Ser Pro Gln Gln Pro Asp Ser Ser Thr Gly Ile Gly Lys 145 150 155 160

Lys Gly Lys Gin Pro Ala Lys Lys Lys Leu Val Phe Glu Asp Glu Thr 2020201242

165 170 175

Gly Ala Gly Asp Gly Pro Pro Glu Gly Ser Thr Ser Gly Ala Met Ser 180 185 190

Asp Asp Ser Glu Met Arg Ala Ala Ala Gly Gly Ala Ala Val Glu Gly 195 200 205

Gly Gin Gly Ala Asp Gly Val Gly Asn Ala Ser Gly Asp Trp His Cys 210 215 220

Asp Ser Thr Trp Ser Glu Gly His Val Thr Thr Thr Ser Thr Arg Thr 225 230 235 240

Trp Val Leu Pro Thr Tyr Asn Asn His Leu Tyr Lys Arg Leu Giy Glu 245 250 255

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 Gln • 275 280 285

Arg Leu Ile Asn Asn Asn Trp Gly Met Arg Pro Lys Ala Met Arg Val 290 295 300

Lys Ile Phe Asn Ile Gln 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 Ile Phe Ala Asp 325 330 335

Ser Ser Tyr Glu Leu Pro Tyr Val Met Asp Ala Gly Gln Glu Giy Ser 340 345 350

Leu Pro Pro Phe Pro Asn Asp Val Phe Met Val Pro Gln Tyr Gly Tyr 355 360 365

Cys Gly Leu Val Thr Gly Asn Thr Ser Gin Gin Gin Thr Asp Arg Asn 370 375 380

Ala Phe Tyr Cys Leu Glu Tyr Phe Pro Ser Gln Met Lau Arg Thr Gly 385 390 395 400

Asn Asn Phe Glu Ile Thr Tyr Ser Phe Glu Lys Val Pro Phe His Ser 405 410 415

Met Tyr Ala His Sex Gin Ser Leu Asp Arg Leu Met Asn Pro Leu Ile 2020201242

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 Ile Lys Gln 465 470 475 480

Gin Gly Phe Ser Lys Thr Ala Asn Gin Asn Tyr Lys Ile Pro Ala Thr 485 490 495

Gly Ser Asp Ser Leu Ile 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 Ile Phe Ala Gly Pro Lys 530 535 540

Gin Asn Gly Asn Thr Ala Thr Val Pro Gly Thr Leu Ile 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 Gln 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 Ile Tyr Tyr Gln Gly Pro Ile Trp Ala Lys Ile Pro His Thr Asp 610 615 620

Gly His Phe His Pro Ser Pro Leu Ile Gly Gly Phe Gly Leu Lys His 625 630 635 640

Pro Pro Pro Gin Ile 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 Ile Thr Gln Tyr 660 665 670

Gin Val Ser Val Gin Ile Asp Trp Glu Ile Gin Lys Glu 2020201242

Ser Thr Gly 675 680 685

Arg Her Lys Arg Trp Asn Pro Glu Val Gin Phe Thr Ser Asn Tyr Gly 690 695 700

Gin Gin 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 AAV1 <400> 64 Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 1 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 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 Giu Pro 50 55 60

Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp 65 70 75 BO

Gin Gin Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala 85 90 95

Asp Ala Glu Phe Gin Giu Arg Leu Gin Glu Asp Thr Her 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 Giu Gly Ala Lys Thr Al4 Pro Gly Lys Lys Arg 130 135 140

Pro Val Glu Gln 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 2020201242

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 Sex 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 Asa Phe Lys Leu Phe Asn Ile Gin 305 310 315 320

Val Lys Glu Val Thr Thr Asn Asp Gly Val Thr Thr Ile 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

Ser Gin Met Leu Arg Thr Gly Asn Asn Phe Thr Phe Ser Tyr Thr Phe 405 410 415

Glu Glu Val Pro Phe His Ser Ser Tyr Ala His Ser Gin Ser Leu Asp 420 425 430 2020201242

Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Asn Arg 435 440 445

Thr Gin Asn Gin Ser Gly Ser Ala Gin Asn Lys Asp Leu Leu Phe Ser 450 455 460

Arg Giy Ser Pro Ala Gly Met Ser Val Gin Pro Lys Asn Trp Leu Pro 465 470 475 480

Gly Pro Cys Tyr Arg Gin Gin Arg Val Ser Lys Thr Lys Thr Asp Asn 485 490 495

Asn Asn Ser Asn Phe Thr Trp Thr Gly Ala Sex Lys Tyr Asn Leu Asn 500 505 510

Gly Arg Glu Ser Ile Ile Asn Pro Giy Thr Ala Drift. Ala Ser His Lys 515 520 525

Asp Asp Glu Asp Lys Phe Phe Pro Met Ser Gly Val Met Ile Phe Giy 530 535 540

Lys Glu Ser Ala Gly Ala Ser Asn Thr Ala Leu Asp Asn Val Met lie 545 550 555 560

Thr Asp Glu Glu Glu Ile Lys Ala Thr Asn Pro Val Ala Thr Glu Arg 565 570 575

Phe Gly Thr Val Ala Val Asn Phe Gin Ser Sex Ser Thr Asp Pro Ala 580 585 590

Thr Gly Asp Val His Ala Met Gly Ala Leu Pro Gly Met Val Trp Gln 595 600 605

Asp Arg Asp Val Tyr Leu Gin Gly Pro Ile Trp 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 Asn Pro Pro Pro Gin Ile Leu Ile Lys Asn Thr Pro Val Pro Ala 645 650 655

Asn Pro Pro Ala Glu Phe Ser Ala Thr Lys Phe Ala Ser Phe Ile Thr 660 665 670

Gin Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu Gin 675 680 685 2020201242

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> 65 <211> 736 <212> PRT <213> capsid protein of AAV serotype, clone AAV6VP1

<400> 65 Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 1 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 Gin Gin 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

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 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

Phe 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 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 2020201242

Ala Thr Pro Ala Ala Val Gly Pro Thr Thr Met Ala Ser Gly Gly Gly 195 200 205

Ala Pro Met Ala Asp Awl 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 _Tie 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 Ile 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

Ser Gin Met Leu Arg Thr Gly Asn Asn Phe Thr Phe Ser Tyr Thr Phe 405 410 415

Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gin Ser Leu Asp 420 425 430

Arg Leu Met Asn Pro Leu Ile Asp Gin Tyr Leu Tyr Tyr Leu Asn Arg 435 440 445 2020201242

Thr Gln Asn Gin Ser Gly Ser Ala Gin Asn Lys Asp Leu Leu Phe Ser 450 455 460

Arg Gly Ser Pro Ala Gly Met Ser Val Gin Pro Lys Asn Trp Leu Pro 465 470 475 480

Gly Pro Cys Tyr Arg Gin Gln Arg Val Ser Lys Thr Lys Thr Asp Asn 485 490 495

Asn Asn Ser Asn Phe Thr Trp Thr Gly Ala Ser Lys Tyr Asn Leu Asn 500 505 510

Gly Arg Giu Ser lie Ile Asn Pro Gly Thr Ala Met Ala Ser His Lys 515 520 525

Asp Asp Lys Asp Lys Phe Phe Pro Met Ser Gly Val Met Ile Phe Gly 530 535 540

Lys Glu Ser Ala Gly Ala Ser Asn Thr Ala Leu Asp Asn Val Met Ile 545 550 555 560

Thr Asp Glu Glu Glu Ile Lys Ala Thr Asn Pro Val Ala Thr Glu Arg 565 570 575

Phe Gly Thr Val Ala Val Asn Leu Gin Ser Ser Ser Thr Asp Pro Ala 580 585 590

Thr Gly Asp Val His Val Met Gly Ala Leu Pro Gly Met Val Trp Gin 595 600 605

Asp Arg Asp Val Tyr Leu Gin Gly Pro Ile Trp 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 Ile Leu Ile Lys Asn Thr Pro Val Pro Ala 645 650 655

Asn Pro Pro Ala Glu Phe Ser Ala Thr 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 Mn Pro Glu Val Gin Tyr Thr Ser Asn 690 695 700 2020201242

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 5 10 15

Glu Gly Ile Arg Gin Trp Trp Lys Leu Lys Pro Gly Pro Pro Pro Pro 20 25 30

Lys Pro Mn Gln Gln His Arg Asp Asp Ser Arg Giy 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

Pro Ile Glu Gin Ser Pro Ala Glu Pro Asp Ser Ser Ser Gly Ile Gly 145 150 155 160

Lys Sex Gly Gin Gln 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 2020201242

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 Ile 225 230 235 240

Thr Thr Sex Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu 245 250 255

Tyr Lys Gin Ile Ser Sex Glu Sex Gly Ala Thr Aim 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 Phe Sex Pro Arg Asp Trp Gin Arg Leu Ile Am 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 Gln Asn Asp Gly Thr Thr Thr Ile 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 Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn Gly Ser 370 375 380

Gin Ala Val Gly Arg Sex Sex Phe Tyr Cys Leu Glu Tyr Phe Pro Ser 385 390 395 400

Gin Net Leu Aria Thr Gay 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 Ile Asp Gln 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 2020201242

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 Giu 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 Giu Lys Tyr Phe Pro Met His Gly Asn Leu Ile Phe Gly Lye 530 535 540

Gin Gly Thr Gly Thr Thr Asn Val Asp Ile Giu Ser Val Leu Ile Thr 545 550 555 560

Asp Giu Glu Glu Ile 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 Gl y Ile Leu Pro Gly Met Val Trp Gin Asp 595 600 605

Arg Asp Val Tyr Leu Gln Gly Pro Ile 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 Ile Leu Ile Lys Asn Thr Pro Val Pro Ala Asn 645 650 655

Pro Ala Thr Thr Phe Thr Pro Gly Lys Phe Ala Ser Phe Ile Thr Gln 660 665 670

Tyr Ser Thr Gly Gin Val Ser Val Glu Ile Glu Trp Glu Leu Gln Lys 675 680 685

Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile 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 2020201242

705 710 715 720

Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Lett Thr Arg Asn Leu 725 730 735

<210> 67 <211> 735 <212> PRT <213> capsid protein of AAV serotype, clone A3,7

<400> 67 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 Lau Lys Pro Gly Pro Pro Pro Pro 20 25 30

Lys Pro Asn Gln Gln His Arg Asp Asp Ser Arg Gly Leu Val Leu Pxo 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 Gln 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 Giy Giy 100 105 110

Asn Leu Gly Arg Ala Val Phe Gin Ala Lys Lys Arg Val Lett Glu Pro 115 120 125

Leu Gly Leu Val Glu Glu Ala Val Lys Thr Ala Pro Gly Lys Lys Arg 130 135 140

Pro Ile Glu Gin Ser Pro Ala Glu Pro Asp Ser Ser Ser Giy Ile Gly 145 150 155 160

Lys Ser Gly Gin Gln Pro Ala Lys Lys Arg Leu Asa 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

Ala Ala Pro Ser Gly Val Gay 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 2020201242

210 . 215 220

Ser Gly Asn Trp His Cys Asp Ser Thr Trp Met Gly Asp Arg Val Ile 225 230 235 240

Tbx Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn Arg Leu 245 250 255

Tyr Lys Gln 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 Phe 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 Gln Val 305 310 315 320

Lys Glu Val Thr Gin Asia Asp Gly Thr Thr Thr Ile Ala Asn Asn Leu 325 330 335

Thr Ser Thr 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 Ile 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

Gin Met Leu Arg Thr Gly Asn Asn Phe Thr Phe Ser Tyr Thr Phe Glu 405 410 415

WO 03/042397 PCT/TJS02/33629 20 Feb 2020

Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gin Ser Leu Asp Arg 420 425 430

Leu Met Asn Pro Leu Ile Asp Gin Tyr Leu Tyr Tyr Leu Ser Lys Thr 435 440 445

Gin Gly Thr Ser Gly Thr Thr Gin Gln Ser Arg Leu Gin Phe Ser Gln 450 455 460

Ala Gly Pro Ser Ser Met Ala Gln Gin Ala Lys Asn Trp Leu Pro ay 2020201242

465 470 475 480

Pro Ser Tyr Arg Gin Gln 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 Am./ 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 L ys Tyr Phe Pro Met His Gly Asn Leu Ile Phe Gly Lys 530 535 540

Gin Gly Thr Gly Thr Thr Asn Val Asp Ile Glu Ser Val Leu Ile Thr 545 550 555 560

Asp Glu Glu Glu Ile Arg Thr Thr Asn Pro Val Ala Thz Glu Gin Tyr 565 570 575

Gly Gln Val Ala Thr Asn His Gin Ser Gin Asn Thr Thr Ala Ser Tyr 580 585 590

Gly Ser Val Asp Ser Gin Gly Ile Leu Pro Gly Met Val Trp Gin Asp 595 600 605

Arg Asp Val Tyr Leu Gin Gly Pro Ile 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 Ile Leu Ile Lys Asn Thr Pro Val Pro Ala Asn 645 650 655

Pro Ala Thr Thr Phe Thr Pro Gly Lys Phe Ala Ser Phe Ile Thr Gln 660 665 670

Tyr Ser Thr Gly Gin Val Ser Val Gin Ile Gin Trp Glu Leu Gin Lys 675 680 685

Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile 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 2020201242

Ser Glu Pro Arg Pro lie 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 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 Sex Arg Gly Leu Val Len 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 Len 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 Vai Phe Gin Ala Lys Lys Arg Val Leu Glu Pro 115 120 125

Leu Gly Leu Val Giu Gin Ala Val Lys Thr Ala Pro Gly Lys Lys Arg 130 135 140

Pro Ile Glu Gln Ser Pro Ala Glu Pro Asp Ser Ser Ser Gly Ile Gly 145 150 155 160

Glu 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

Ala Ala Pro Ser Gly Val Gly Ser Asn Thr Met Ala Ser Gly Gly Gly 195 200 205

Ala Pro Met Ala Asp Asp Asn Glu Gly Ala Asp Gly Val Gly Asn Ser 210 215 220 2020201242

Ser Gly Asn Trp His Cys Asp Ser Thr Trp Met Gly Asp Arg Val Ile 225 230 235 240

Thr Thr Sex Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu 245 250 255

Tyr Lys Gln 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 Phe 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 Ile Ala Asn Asn Leu 325 330 335

Thr Ser Thr 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 Ile Pro Gin Tyr Gly Tyr Len Thr Leu Asn Asn Gly Ser 370 375 380

Gin Ala Val G11, Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro Ser 385 390 395 400

Gin Met Leu Arg Thr Gly Asn Asn Phe Thr Phe Ser Tyr Thr Phe Glu 405 410 415

Asp Vel Pro Phe His Ser Ser Tyr Ala His Ser Gin Ser Leu Asp Arg 420 425 430

Leu Met Asn Pro Leu Ile Asp Gin Tyr Leu Tyr Tyr Leu Sex Lys Thr 435 440 445

Gin Gly Thr Ser Gly Thr Thr Gin Gin Ser Arg Leu Gln Phe Ser Gln 450 455 460

Ala Gly Pro Ser Ser Met Ala Gin Gin Ala Lys Asn Trp Leu Pro Gly 465 470 475 480 2020201242

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 Ile Phe Giy Lys 530 535 540

Gin Gly Thr Gl y Thr Thr Asn Val Asp Ile Giu Ser Val Leu Ile Thr 545 550 555 560

Asp Glu Glu Glu Ile Arg Thr Thr Asn Pro Val Ala Thr Glu Gin Tyr 565 570 575

Gly Gin Val Ala Thr Asn His Gin Ser Gin Asp Thr Thr Ala Ser Tyr 580 585 590

Gly Ser Val Asp Ser Gin Gly Ile Leu Pro Gly Met Val Trp Gln Asp 595 600 605

Arg Asp Val Tyr Leu Gin Giy Pro Ile 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 Ile Lys Asn Thr Pro Val Pro Ala Asn 645 650 655

Pro Ala Thr Thr Phe Thr Pro Giy Lys Phe Ala Ser Phe lie Thr Gin 660 665 670

Tyr Ser Thr Gly Gin Val Ser Val Giu Ile Glu Trp Giu Leu Gln Lys 675 680 685

Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile 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 Ile Gly Thr Arg Tyr Leu Thr Arg Asn Leu 725 730 735

<210> 69 2020201242

<211> 735 <212> PRT <213> capsid protein of AAV serotype, clone A3.5

<400> 69 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 Gln His Axg Asp Asp Ser Arg Gly Let 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 Gln 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

Pro Ile Glu Gin Ser Pro Ala Glu Pro Asp Ser Ser Ser Gly Ile Gly 145 150 155 160

Lys Ser Gly Gin Gln 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

Ala Ala Pro Ser Giy Val Gly Ser Asn Thr Met Ala Ser Gly Gly Gly 195 200 205

Ala Pro Met Ala Asp Asn Asn Giu Gly Ala Asp Gly Val Gly Asn Ser 210 215 220

Ser Gly Asn Trp His Cys Asp Ser Thr Trp Met Giy Asp Arg Val Ile 225 230 235 240 2020201242

Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu 245 250 255

Tyr Lys Gln 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 Phe 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 Giy Thr Thr Thr Ile Ala Asn Asn Leu 325 330 335

Thr Ser Thr Val Gin Val Phe Thr Asp Ser Glu Tyr Gin Leu Pro Tyr . 340 345 350

Val Leu Gly Sex Ala His Gin Giy Cys Leu Pro Pro Phe Pro Ala Asp 355 360 365

Val Phe Met Ile Pro Gin Tyr Gly Tyr Leu Thr Leu Asn Asn Gly Ser 370 375 380

Gin Ala Val Giy Axg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro Ser 385 390 395 400

Gin Met Leu Arg Thr Giy Asn Asn Phe Thr Phe Ser Tyr Thr Phe Glu 405 410 415

Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu Asp Arg 420 425 430

Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ser Lys Thr 435 440 445

WO 03/042397 PCIMS02/33629 20 Feb 2020

Gin Giy 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 Gln Arg Met Ser Lys Thr Ala Asn Asp Asn. Asn 485 490 495 2020201242

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 Giu Lys Tyr Phe Pro Met His Gly Asn Leu Ile Phe Gly Lys 530 535 540

Gin Gly Thr Gly Thr Thr Asn Val Asp Ile Giu Ser Val Leu Ile Thr 545 550 555 560

Asp Glu Giu Glu Ile Arg Thr Thr Asn Pro Val Ala Thr Glu Gin Tyr 565 570 575

Gly Gln Val Ala Thr Asn Arg Gin Ser Gin Asn Thr Thr Ala Ser Tyr 580 585 590

Gly Ser Val Asp Ser Gin Gly Ile Leu Pro Gly Met Val Trp Gln Asp 595 600 605

Arg Asp Val Tyr Leu Gin Giy Pro Ile Trp Ala Lys Thr Pro His Thr 610 615 620

Asp Gly His Phe His Pro Ser Pro Leu Met Gly Giy Phe Gly Leu Lys 625 630 635 640

His Pro Pro Pro Gin Ile Leu Ile Lys Asn Thr Pro Val Pro Ala Asn 645 650 655

Pro Ala Thr Thr Phe Thr Pro Gly Lys Phe Ala Ser Phe Ile Thr Gin 660 665 670

Tyr Ser Thr Gly Gin Val Ser Val Glu Ile Giu Trp Giu Leu Gin Lys 675 680 685

Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile 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 Ile Gly Thr Arg Tyr Leu Thr Arg Asn Leu 725 730 735

<210> 70 <211> 735 <212> PRT 2020201242

<213> capsid protein of AAV serotype, clone AAV2

<400> 70 Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Thr Leu Ser 5 10 15

Glu Gly Ile Arg Gln Trp Trp Lys Leu Lys Pro Gly Pro Pro Pro Pro 20 25 30

Lys Pro Ala Glu Arg His Lys Asp Asp Ser 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

Arg Gln Leu Asp Ser Gly Asp Asn Pro Tyr Leu Lys Tyr Asn His Ala 85 90 95

Asp Ala Glu Phe Gln Glu Arg Leu Lys 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 Pro Val Lys Thr Ala Pro Gly Lys Lys Arg 130 135 140

Pro Val Glu His Ser Pro Val Glu Pro Asp Ser Ser Ser Gly Thr Gly 145 150 155 160

Lys Ala Gly Gln Gin Pro Ala Arg Lys Arg Leu Asn Phe Gly Gln Thr 165 170 175

Gly Asp Ala Asp Ser Val Pro Asp Pro Gin Pro Leu Gly Gin Pro Pro 180 185 190

WO 03/042397 PCT1US02133629

Ala Ala Pro Ser Gly Leu Gly Thr Asn Thr Met Ala Thr Gly Ser Gly 20 Feb 2020

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 Ile 225 230 235 240

Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu 245 250 255 2020201242

Tyr Lys Gln Ile Ser Ser Gin Ser Gly Ala Ser Asn Asp Asa 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 Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn Asn Trp 290 295 300

Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn Ile Gln Val 305 310 315 320

Lys Glu Val Thr Gln Asn Asp Gly Thr Thr Thr Ile Ala Asn Asn Leu 325 330 335

Thr Ser Thr Val Gln Val Phe Thr Asp Ser Glu Tyr Gln 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 Val Pro Gin Tyr Gly Tyr Leu Thr Leu Asn Asn Gay Ser 370 375 380

Gin Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro Ser 385 390 395 400

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 Ile Asp Gin Tyr Leu Tyr Tyr Leu Ser Arg Thr 435 440 445'

Asn Thr Pro Ser Gly Thr Thr Thr Gin Ser Arg Leu Gin Phe Ser Gin 20 Feb 2020

450 455 460

Ala Gly Ala Ser Asp Ile Arg Asp Gln Ser Arg Asn Trp Leu Pro Gly 465 470 475 480

Pro Cys Tyr Arg Gln Gln Arg Val Ser Lys Thr Ser Ala Asp Asn Asn 485 490 495

Asn Ser Glu Tyr Ser Trp Thr Gly Ala Thr Lys Tyr His Leu Asn Gly 2020201242

500 505 510

Arg Asp Ser Leu Val Asn Pro Gly Pro Ala Met Ala Ser His Lys Asp 515 520 525

Asp Glu Glu Lys Phe Phe Pro Gln Ser Gly Val Leu Ile Phe Gly Lys 530 535 540

Gln Gly Ser Glu Lys Thr Asn Val Asp Ile Glu Lys Val Met Ile Thr 545 550 555 560

Asp Glu Glu Glu Ile Arg Thr Thr Asn Pro Val Ala Thr Glu Gin Tyr 565 570 575

Gly Ser Val Ser Thr Asn Leu Gin Arg Gly Asn Arg Gln Ala Ala Thr 580 585 590

Ala Asp Val Asn Thr Gin Gly Val Leu Pro Gly Met Val Trp Gln Asp 595 600 605

Arg Asp Val Tyr Leu Gin Gly Pro Ile Trp Ala Lys Ile 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 Ile Leu Ile Lys Asn Thr Pro Val Pro Ala Asn 645 650 655

Pro Ser Thr Thr Phe Ser Ala Ala Lys Phe Ala Ser Phe Ile Thr Gin 660 665 670

Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Giu Leu Gin Lys 675 680 685

Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gin Tyr Thr Ser Asn Tyr 690 695 700

Asn Lys Ser Val Asn Val Asp Phe Thr Val Asp Thr Asn Gly Val Tyr 20 Feb 2020

705 710 715 720

Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Asn Leu ' 725 730 735

<210> 71 <211> 736 <212> PICT <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 2020201242

1 5 10 15

Glu Gly Ile Arg Glu Trp Trp Ala Leu Lys Pro Gly Val Pro Gin Pro 20 25 30

Lys Ala Asn Gin Gin His Gin Asp Asn Arg Arg Gly Leu Val Leu Pro 35 40 45

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 55 70 75 80

Gln Gin 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 Gin 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 Gin Ser Pro Gln Glu Pro Asp Ser Ser Ser Gly Val Gly 145 150 155 160

Lys Ser Gly Lys Gin Pro Ala Arg 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 Ala Pro Thr Ser Leu Gly Ser Asn Thr Met Ala Ser Gly Gly Gly 195 200 205

WO 03/042397 PCT/ITS02/33629 20 Feb 2020

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 Gln 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 Gln Ser Gly Ala Ser Asn Asp Asn His Tyr 2020201242

260 265 270

Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe His 275 280 285

Cys His Phe Ser Pro Arg Asp Txp Gin Arg Leu Ile Asn Asn Asn Trp 290 295 300

Gly Phe Arg Pro Lys Lys Leu Ser Phe Lys Leu Phe Asn Ile Gln Val 305 310 315 320

Arg Gly Val Thr Gln Asn Asp Gly Thr Thr Thr Ile Ala Asn Asn Leu 325 330 335

Thr Ser Thr 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 Val 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

Gin Met Leu Arg Thr Gly Asn Asn Phe Gin Phe Ser Tyr Thr Phe Giu 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 Ile Asp Gin Tyr Leu Tyr Tyr Leu Asn Arg Thr 435 440 445

Gin Gly Thr Thr Ser Gly Thr Thr Asn Gin Ser Arg Leu Leu Phe Ser 450 455 460

Gin Ala Gly Pro Gin Ser Met Ser Leu Gin Ala Arg Asn Trp Leu Pro 465 470 475 480

Gly Pro Cys Tyr Arg Gin Gin Arg Lou 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 2020201242

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 Len Asp Asn Val Met Ile 545 550 555 560

Thr Asp Glu Glu Glu Ile Arg Thr Thr Asn Pro Val Ala Thr Glu Gln 565 570 575

Tyr Gly Thr Val Ala Asn Asn Leu Gin Ser Ser Asn Thr Ala Pro Thr 580 585 590

Thr Gly Thr Val Asn His Gin Gly Ala Lou Pro Gly Met Val Trp Gin 595 600 605

Asp Arg Asp Val Tyr Leu Gin Gly Pro Ile Trp 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 Ile Met Ile Lys Asn Thr Pro Val Pro Ala 645 650 655

Asn Pro Pro Thr Thr Phe Ser Pro Ala Lys Phe Ala Sex 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 Giu Asn Ser Lys Arg Trp Asn Pro Giu 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

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 3.3bVP1 <400> 72 Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 1 5 10 15 2020201242

Glu Giy Ile Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro 20 25 30

Lys Ala Asn Gin Gln Lys Gln Asp Asn Gly Arg Gly Leu Val Lau 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 Gln Leu Asn Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala 85 90 95

Asp Ala Giu Phe Gin Glu Axg Len Gin Giu Asp Thr Ser Phe Gly Gly 100 105 110

Asn Lau Gly Arg Ala Val Phe Gin Ala Lys Lys Arg Val Leu Glu Pro 115 120 125

Lau Gly Lau Val Glu Glu Giy Ala Lys Thr Ala Pro Ala Lys Lys Arg 130 135 140

Pro Val Glu Pro Sex Pro Gin Arg Ser Pro Asp Ser Ser Thr Gly Ile 145 150 155 160

Gly Lys Lys Gly Gin Gln 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 Giy 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

Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His 245 250 255

Leu Tyr Glu Gin Ile Ser Ser Glu Thr Ala Gly Ser Thr Asn Asp Asn 2020201242

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 Gln Arg Leu Ile Asn Asn 290 295 300

Asn Trp Gly Phe Arg Pro Lys Lys Leu Arg Phe Lys Leu Phe Asn Ile 305 310 315 320

Gin Val Lys Glu Val Thr Thr Asn Asp Gly Val Thr Thr Ile Ala Asn 325 330 335

Asn Leu Thr Ser Thr Ile Gin Val Phe Ser Asp Ser Glu Tyr Gln 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 Ile 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 Gln Met Leu Arg Thr Giy 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 Asp Pro Giy Gly Thr Ala Gly Asn Arg Glu Leu Gln 450 455 460

Phe Tyr Gin Gly Gly Pio Ser Thr Met Ala Giu Gin Ala Lys Asn Trp 20 Feb 2020

465 470 475 480

Leu Pro Gly Pro Cys Phe Arg Gln Gin Arg Val Ser Lys Thr Leu Asp 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 Asn Ser Leu Val Asn Pro Gly Val Ala Met Ala Thr 515 520 525 2020201242

His Lys Asp Asp Glu Asp Arg Phe Phe Pro Ser Ser Giy Val Leu Ile 530 535 540

Phe Gly Lys Thr Gly Ala Thr Asn Lys Thr Thr Lela 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 Ile Val Sex Ser Asn Leu Gin Ala Ala Asn Thr Ala Ala 580 585 590

Gln Thr Gln Val Val Asn Asn Gin Gly Ala Leu Pro Gly Met Val Trp 595 600 605

Gin Asn Arg Asp Val Tyr Leu Gln 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 Ile Lys Asn Thr Pro Val Pro 645 650 655

Ala Asn Pro Pro Glu Val Phe Thr Pro Ala Lys Phe Ala Ser Phe Ile 660 665 670

Thr Gin Tyr Ser Thr Gly Gin Val Ser Val Glu Ile Glu Trp Glu Leu 675 680 685

Gin Lys Glu Asn Ser Lys Arg Trp Asp Pro Glu Ile Gin Tyr Thr Ser 690 695 700

Asn Phe Glu Lys Gin Thr Gly Val Asp Phe Ala Val Asp Ser Gln Gly 705 710 715 720

Val Tyr Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr A.rg Asn 20 Feb 2020

725 730 735

Leu

<210> 73 <211> 644 <212> PRT <213> capsid protein of AAV serotype, clone 223-4 <400> 73 Lys Ala Tyr Asp Gln Gin Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg 2020201242

1 5 10 15

Tyr Asn His Ala Asp Ala Giu Phe Gin Glu Arg 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 Ara 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 Pro Val Pro Asp Pro Gin Pro Ile 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 Asn Asn His Leu 165 170 175

Tyr Lys Gin Ile 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 Ile Gin 225 230 235 240

Val Lys Glu Val Thr Thr Asn Asp Gly Val Thr Thr Ile Ala Asn Asn 245 250 255

Ser Thr Val Gin Val Phe Ser Asp Ser Glu Tyr Gin Leu Pro 2020201242

Leu Thr 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 Ile Pro Gln 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 Gln Ser Leu Gly 340 345 350

Arg Leu Met Asn Pro Leu Ile Asp Gin Tyr Leu Tyr Tyr Leu Ala Axg 355 360 365

Thr Gin Ser Asn Ala Gly Gly Thr Ala Giy Asn Arg Glu Leu Gin Phe 370 375 380

Tyr Gln Gly Gly Pro Thr Thr Met Ala Giu Gin Ala Lys Asn Trp Leu 385 390 395 400

Pro Giy Pro Cys Phe Arg Gin Gln Arg Val Ser Lys Thr Leu Asp Gin 405 410 415

Asn Asn Asn Ser Asn Phe Ala Trp Thr Giy Ala Thr Lys Tyr His Leu 420 425 430

Asn Gly Arg Asn Sex 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 Ile Arg Pro Thr Asn Pro Val Ala Thr Glu Glu 485 490 495

Tyr Giy Ile Val Ser Ser Asn Leu Gin Ala Ala Ser Thr Ala Ala Gin 500 505 510

Thr Gin Val Val Asn Asn Gln Gly Ala Leu Pro Gly Met Val Trp Gln 2020201242

515 520 525

Asn Arg Asp Val Tyr Leu Gin 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 Ile Thr 580 585 590

Gin Tyr Ser Thr Gly Gin Val Ser Val Glu Ile Glu Trp Glu Leu Gin 595 600 605

Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile G1n Tyr Thr Ser Asn 610 615 620

Phe Asp Lys Gin Thr Giy Val Asp Phe Ala Val Asp Ser Gin Gly Val 625 630 635 640

Tyr Ser Giu Pro

<210> 74 <211> 644 <212> PRT <213> capsid protein of AAV serotype, clone 223.5 <400> 74 Lys Ala Tyr Asp Gin Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg 1 5 10 15

Tyr Asn His Ala Asp Ala Glu Phe Gin Glu Arg Leu Gin Glu Asp Thr 20 25 30

Ser Phe Gly Gly Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg 35 40 45

Val Leu Giu 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 lie Gly 65 70 75 80

Lys Lys Gly Gln Gin Pro Ala Lys Lys Arg Leu Asn Phe Gly Gln Thr 85 90 95 2020201242

Gly Asp Ser Glu Pro Val Pro Asp Pro Gin Pro Ile 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 Giu Gly Ala Asp Gly Val Gly Asn Ala 130 135 140

Sex 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 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 Tie Asn Asn Asn 210 215 220

Trp Gly Phe Arg Pro Lys Lys Leu Asn Phe Lys Leu Phe Awl Ile Gin 225 230 235 240

Val Lys Glu Val Thr Thr Asn Asp Gly Val Thr Thr Ile Ala Asn Asn 245 250 255

Leu Thr Ser Thr Val Gin Val Phe Ser Asp Ser Giu 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 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

Sex Gin Met Leu Arg Thr Gly Asn Asn Phe Thr Phe Ser Tyr Thr Phe 325 330 335

Giu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gin Ser Leu Gly 340 345 350 2020201242

Arg Leu Met Asn Pro Leu Ile 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 Gln 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 Gln 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 Giu 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 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 Val Tyr Leu Gin Gly Pro Ile Trp Ala Lys Ile Pro His 530 535 540

Thr Asp Gly Asn Phe His Pro Ber Pro Leu Net Gly Gly Phe Gly Leu 545 550 555 560

Lys His Pro Pro Pro Gin Ile Leu Ile Lys Awl Thr Pro Val Pro Ala 565 570 575

Asn Pro Pro Giu Val Phe Thr Pro Ala Lys Phe Ala Ser Phe Ile Thr 580 585 590

Gin Tyr Ser Thr Gly Gin Val Ser Val Glu Ile Glu Trp Glu Leu Gln 595 600 605 2020201242

Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Tie 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 Sex Glu Pro

<210> 75 <211> 644 <212> PRT <213> capsid protein of AAV serotype, clone 223.10 <220> <221> MISC FEATURE <222> (434)..(434) <223> can be any amino acid <400> 75 Lys Ala Tyr Asp Gin Gin Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg 1 5 10 15

Tyr Asn His Ala Asp Ala Glu Phe Gin Giu Arg Leu Gln 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 Giu Pro Leu Gly Leu Val Giu 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 Gln 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 Ile Gly Glu Pro Pro 100 105 110

Ala Gly Pro Ser Gly Leu Gly Sex 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 Tie 145 150 155 160

Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu 2020201242

165 170 175

Tyr Lys Gin Ile Ser Sex 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 lie Asn Asn Asn 210 215 220

Trp Gly Phe Arg Pro Lys Lys Leu Asn Phe Lys Leu Phe Asn Ile Gin 225 230 235 2 40

Val Lys Glu Val Thx Thr Asn Asp Gly Val Thr Thr Ile 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 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 Giu Tyr Phe Pro 305 310 315 320

Sex 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

Thr Gln Ser Awl Ala Gly Gly Thr Ala Gly Asn Arg Glu Leu Gin Phe 370 375 380

Tyr Gln Gly Gly Pro Thr Thr Met Ala Glu Gin Ala Lys Asn Trp Leu 385 390 395 400

Pro Gly Pro Cys Phe Aug Gin Gin Arg Val Ser Lys Thr Leu Asp Gln 405 410 415

Asn Asn Asn Ser Asn Phe Ala Trp Thr Gly Ala Thr Lys Tyr His Leu 2020201242

420 425 430

Asn Xaa 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 Tie Arg Pro Thr Asn Pro Val Ala Thr Glu Glu 485 490 435

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

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 Gin 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 Ile Thr 580 585 590

Gin Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu Gin 595 600 605

Lys Glu Asn Ser Lys Arg Trp Asn Pro Giu Ile Gln Tyr Thr Ser Asn 610 615 620

Phe Asp Lys Gln Thr Gly Val Asp Phe Ala Val Asp Sex Gin Gly Val 625 630 635 640

Tyr Ser Glu Pro

<210> 76 <211> 644 <212> PRT <213> capsid protein of AAV serotype, clone 223.2

<400> 76 2020201242

Lys-Ala Tyr Asp Gln Gln 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 Gln Glu Asp Thr 20 25 30

Set Phe Gly Gly Asn Leu Gly Arg Ala Val Phe Gin Ala Lys Lys Arg 35 40 45

Val Len Glu Pro Leu Gly Leu Val Glu Thr Pro Ala Lys Thr Ala Pro 50 55 60

Gly Lys L y s 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 Gln Thr 85 90 95

Gly Asp Ser Glu Ser Val Pro Asp Pro Gin Pro Ile Giy Glu Pro Pro 100 105 110

Ala Gly Pro Ser Giy Leu Gly Ser Gly Thr Met Val Ala Gly Gly Giy 115 120 125

Ala Pro Met Ala Asp _ken Asn Glu Gly Ala Asp Gly Val Gly Asn Ala 130 135 140

Set Gly Asn Trp His Cys Asp Set 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 Gln Ile 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 Ile Gin 225 230 235 240

Val Lys Glu Val Thr Thr Asn Asp Gly Val Thr Thr Ile Ala Asn Asn 245 250 255 2020201242

Leu Thr Ser Thr Val Gin Val Phe Ser Asp Sex 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 Ile Pro Gan Tyr Gly Tyr Leu Thr Leu Asn Asn Gly 290 295 300

Ser Gln Ser Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro 305 310 315 320

Ser Gln 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

Thr Gln 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 Gln Gln 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 Giu Glu Arg Phe Ser 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 Lau Met 465 470 475 480

Thr Asn Glu Giu 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 Thi Ala Ala Gin 500 505 510 2020201242

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 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 Gin Ile Leu Ile Lys Asn Thr Pro Val Pro Ala 565 570 575

Asr, Pro Pro Glu Val Phe Thr Pro Ala Lys Phe Ala Ser Phe Ile Thr 580 585 590

Gin Tyr Ser Thr Gly Gin Val Ser Val Glu Ile 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 Gin Thr Gly Val Asp Phe Ala Val Asp Ser Gln Gly 625 630 635 640

Tyr Ser Glu Pro

<210> 77 <211> 644 <212> PRT <213> capsid protein of AAV serotype, clone 223.7 <400> 77 Lys Ala Tyr Asp Gin Gin Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg 1 5 10 15

Tyr Asn His Ala Asp Ala Glu Phe Gin Glu Arg Leu Gln Glu Asp Thr 20 25 30

Ser Phe Gly Gly Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg 20 Feb 2020

35 40 45

Val Leu Gin 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 Gln Pro Ala Lys Lys Arg Leu Asn Phe Gly Gin Thr 2020201242

85 90 95

Gly Asp Ser Glu Ser Val Pro Asp Pro Gln Pro Ile 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 Aria Val Ile 145 150 155 160

Thr Thr Ser Thr Arg Thr Trp Ala Len Pro Thr Tyr Asn Asn His Leu 165 170 175

Tyr Lys Gin Ile Ser Sex Gln Ser Ala Gly Sex 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 Len Ile Asn Asn Asn 210 215 220

Trp Gly Phe Arg Pro Lys Lys Leu Asn Phe Lys Len Phe Asn Ile Gin 225 230 235 240

Val Lys Glu Val Thr Thr Asn Asp Gly Val Thr Thr Ile Ala Asn Asn 245 250 255

Leu Thr Ser Thr Val Gin Val Phe Ser Asp Pro Gin 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 Net Ile Pro Gin Tyr Gly Tyr Leu Thr Leu Asn Asn Gly 20 Feb 2020

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 Lau 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 Gln Ser Leu Asp 340 345 350 2020201242

Arg Leu Met Asn Pro Leu Ile Asp Gin Tyr Leu Tyr Tyr Leu Ala Arg 355 360 365

Thr Gln 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 Gln Gin Arg Val Ser Lys Thr Leu Asp Gln 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 Sex 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 Ile Arg Pro Thr Asn Pro Val Ala Thr Glu Glu 485 490 495

Tyr Gly lie Val Ser Ser Asn Leu Gln Ala Ala Sex Thr Ala Ala Gln 500 505 510

Thr Gin Val Val Asn Asn Gin Gly Ala Let 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

Thr Asp Gly Asn Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Leu 20 Feb 2020

545 550 555 560

Lys His Pro Pro Pro Gin Ile Leu Tie 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

Gin Tyr Ser Thr Gly Gin Val Ser Val Glu Ile Glu Trp Glu Leu Gin 595 600 605 2020201242

Lys Glu Asn Ser Lys Arg Trp Asn Pro Giu Ile 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> 78 <211> 644 <212> PRT <213> capsid protein of AAV serotype, clone 223.6 <400> 78 Lys Ala Tyr Asp Gin Gin Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg 1 5 10 15

Tyr Asn His Ala Asp Ala Giu Phe Gln Glu Arg Leu Gln 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 Ser Pro Asp Ser Thr Ser Gly Ile Gly 65 70 75 80

Lys Lys Gly Gin Gln Pro Ala Lys Lys Arg Leu Asn Phe Gly Gin Thr 85 90 95

Gly Asp Ser Glu Sex Val Pro Asp Pro Gin Pro Ile Gly Glu Pro Pro 100 105 110

Ala Gly Pro Ser. Gly Leu Gly Sex Gly Thr Met Ala Ala Gly Gly Gly 115 120 125

Ala Pro Met Ala Asp Asn Ser Glu Gly Ala Asp Gly Val Gly Asn Ala 130 135 140

Ser Gly Asn Trio His Cys Asp Ser Thr Trp Leu Giy 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 2020201242

Tyr Lys Gin Ile 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 Tip Gin Arg Leu Ile Asn Asn Asn 210 215 220

Trp Gly Phe Arg Pro Lys Lys Leu Asn Phe Lys Leu Phe Asn Ile Gin 225 230 235 240

Val Lys Glu Val Thr Thr Asn Asp Giy Val Thr Thr Ile Ala Asn Asn 245 250 255

Leu Thr Ser Thr Val Gln 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 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 Gln 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

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 Len 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 2020201242

Asn Gly Arg Asn Ser Leu Val Asn Pro Gly Val Ala Met Ala Thr His 435 440 445

Lys Asp Asp Glu Gin 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 Ile Arg Pro Thr Asn Pro Val Ala Thr Glu Glu 485 490 495

Tyr Gly Ile Val Ser Ser Asn Len Gin Ala Ala Ser Thr Ala Ala Gin 500 505 510

Thr Gin Val Val Asn Asn Gin Gly Ala Len Pro Gly Met Val Trp Gln 515 520 525

Asn Arg Asp Val Tyr Leu Gin 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 Gin Ile Leu Ile Lys Asn Thr Pro Val Pro Ala 565 570 575

Asn Pro Pro Glu Val Phe Thr Pro Ala Lys Leu Ala Ser Phe Ile Thr 580 585 590

Gln Tyr Ser Thr Gly Gin Val Ser Val Glu Ile Glu Tip Glu Len Gln 595 600 605

Lys Glu Asn Ser Lys Arg Trp Asn Pro Giu Ile Gin Tyr Thr Ser Asn 610 615 620

Phe Asp Lys Gan Thr Gly Val Asp Phe Ala Val Asp Ser Gln Gly Val 625 630 635 640

WO 03/042397 PCT/11S02/33629 20 Feb 2020

Tyr Ser 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 2020201242

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 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

Gin Gin Leu Lys Ala Gl y 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 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 Val Glu Pro Sex Pro Gin Arg Ser Pro Asp Ser Ser Thr Gly Ile 145 150 155 160

Gly Lys Lys Gly Gin Gln Pro Ala Lys Lys Arg Leu Asn Phe Gly Gin 165 170 175

Thr Gly Asp Ser Glu Ser Val Pro Asp Pro Gin 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 20 Feb 2020

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 Ile Ser Asn Gly Thr Ser Gly Gly Ser Thr Awl Asp 260 265 270 2020201242

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 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 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 Ile Pro Gin 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

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 Gln Gin Leu Leu 450 455 460

WO 03/042397 PCT/11S02/33629

Phe Ser Gin Ala Gly Pro Asn Asn Met Ser Ala Gin Ala Lys Asn Trp 20 Feb 2020

465 470 475 480

Leu Pro Gly Pro Cys Tyr Arg Gln 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 2020201242

His Lys Asp Asp Glu Giu Arg Phe Phe Pro Ser Ser Gly Val Leu Met 530 535 540

Phe Gly Lys Gln 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

Trp Gin Am.' 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 Gln 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 Gln Tyr Ser Thr Gly Gin Val Ser Val Glu Ile 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

WO 03/042397 PCT/002/33629

Gly Thr Tyr Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg 20 Feb 2020

725 730 735

Asn Leu

<210> 80 <211> 738 <212> PRT <213> capsid protein of AAV serotype, clone 44.5

<400> 80 2020201242

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 1 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 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

Gln Gin Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala 85 90 95

Asp Ala Glu Phe Gln Giu Arg Leu Gin Glu Asp Thr Sex 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 Val Glu Pro Ser Pro Gin Arg Ser . Pro Asp Ser Ser Thr Gly Ile 145 150 155 160

Gly Lys Lys Gly Gln Gin Pro Ala Lys Lys Arg Leu Asn Phe Gly Gln 165 170 175

Thr Gly Asp Ser Glu Ser Val Pro Asp Pro Gin Pro Ile Gly Glu Pro 180 185 190

Pro Ala Gly Pro Ser Gly Len 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

Leu Tyr Lys Gln Ile Ser Asn Gly Thr Ser Gly Gly Ser Thr Asn. Asp 2020201242

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 Ile Asn 290 295 300

Asn Asn Trp Gly Phe Arg Pro Lys Arg Pro Asn Phe Lys Leu Phe Asn 305 310 315 320

Ile 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 Gln 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 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 Gln 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 Gln Tyr Leu Tyr Tyr Leu 435 440 445

Ser Arg Thr Gln 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 Gln Ala Lys Asn Trp 465 470 475 480

Leu Pro Gly Pro Cys Tyr Arg Gin Gln 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 2020201242

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 Giu Ile Lys Thr Thr Asn Pro Val Ala Thr 565 570 575

Glu Gln 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 Gln 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 Lau Ala Ser Phe 660 665 670

Ile Thr Gin Tyr Ser Thr Gly Gin Val Ser Val Glu Ile 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

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 2020201242

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 1 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 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 Lou 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 Gln Leu Lys Ala Gly Asp Awl. 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 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 Val Glu Pro Ser Pro Gin Arg Ser Pro Asp Ser Ser Thr Gly Ile 145 150 155 160

Gly Lys Lys Gly Gin Gln Pro Ala Lys Lys Arg Leu Asn Phe Gly Gln 165 170 175

Thr Gly Asp Ser Glu Ser Val Pro Asp Pro Gin 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 lieu Gly Asp Arg Val 225 230 235 240

Ile Thr Thr Ser Thr Arg Thr Trp Ada Leu Pro Thr Tyr Asn Asn His 245 250 255 2020201242

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 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 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 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 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 Gln Leu Leu 450 455 460

Phe Ser Gln 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 2020201242

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 Gln Gly Ala Gly Lys Asp Asn Val Asp Tyr Ser Ser Val 545 550 555 560

Net 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 Gln Gly Ala Leu Pro Gly Met Val 595 600 605

Trp Gin Asn Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile 610 615 620

Pro His Thr Asp Gly Asn Phe His Pro Ser Pro Leu Met Giy 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 Giy Gln Val Ser Val Glu Ile Glu Trp Glu 675 680 685

Leu Gln Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gin Tyr Thr 690 695 700

Ser Asti 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 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 t clone 29.3VP1 <400> 82 2020201242

Net Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 1 5 10 15 Glu Gly Ile Arg Glu Trp Trp Ala Leu Lys Pro Gly Ala Pro Lys Pro 20 25 30

Lys Ala Asn Gln 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 Ann 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 Val Glu Pro Ser Pro Gln Arg Ser Pro Asp Ser Thr Thr Gly Ile 145 150 155 160

Gly Lys Lys Gly Gin 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 Net 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 2020201242

Leu Tyr Lys Gin lie Ser Asn Gly Thr Ser Gly Gly Ser Thr Pon Asp 260 265 270

Asn Thr Tyr Phe Giy Tyr Sex 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 Gin 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 Arg Gln Gly Cys Leu Pro 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 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 Gin Ser Thr Giy Giy Thr Ala Giy Thr Gin Gin Leu Leu 450 455 460

Phe Ser Gln Ala Gly Pro Awl Asn Met Ser Ala Gin Ala Lys Asn Trp 465 470 475 480

Leu Pro Gly Pro Cys Tyr Arg Gln Gln 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 2020201242

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 Gly 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

Giu Gln 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 Gln Gly Ala Leu Pro Gly Met Val 595 600 605

Trp Gln 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 Gln Val Ser Val Glu Ile Glu Trp Glu 675 680 685

Leu Gin Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln 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

Gly Thr Tyr Ser Glu Pro Axg Pro Ile Gly Thr Arg Tyr Leu Thr Arg 725 730 735

Asn Leu

<210> 83 <211> 738 <212> PRT <213> capsid protein of AAV serotype, clone 29.5VP1 2020201242

<400> 83 Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu ser 1 5 10 15

Giu Gly lie Arg Glu Trp Trp Ala Leu Lys Pro Gly Ala Pro Lys Pro 20 25 30

Lys Ala Am Gln Gin 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

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 Gln Giu 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 Rig 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 Gin Gln Pro Ala Lys Lys Arg Leu Asn Phe Gly Gln 165 170 175

Thr Gly Asp Ser Glu ser Val Pro Asp Pro Gin Pro Ile Gly Glu Pro 180 185 190

WO 03/042397 PCT/ITS02133629

Pro Ala Gly Pro Ser Gly Leu Gly Ser Gly Thr Met Ala Ala Gly Gly 20 Feb 2020

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 2020201242

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 Ile Asn 290 295 300

Asn Asn Trp Gly Phe Arg Pro Lys Ser Lou Asn Phe Lys Leu Phe Asn 305 310 315 320

Ile Gin Val Lys Glu Val Thr Gln 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 Gln 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 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 Asa Asn Phe Glu Phe Ser Tyr 405 410 415

Gin Phe Giu Asp Val Pro Phe His Sex Ser Tyr Ala His Ser Gln Ser 420 425 430

Leu Asp Arg Leu Met Asn Pro Leu Ile Asp Gin Tyr Leu Tyr Tyr Leu 435 440 445

WO 03/042397 PCULTS02/33629

Ser Arg Thr Gin Ser Thr Gly Gly Thr Ala Gly Thr Gin Gin Leu Leu 20 Feb 2020

450 455 460

Phe ser Gin Ala Gly Pro Asn Asn Met Ser Ala Gin Ala Lys Asn Trp 465 470 475 480

Len Pro Gly Pro Cys Tyr Arg Gln Gin Arg Val Ser Thr Thr Leu Ser 485 490 495

Gln Asa Asp Asn Ser Asn Phe Ala Trp Thr Gly Ala Thr Lys Tyr His 500 505 510 2020201242

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 Gin 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 Gln 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 Gln Gly Pro Ile Trp Ala Lys Ile 610 615 620

Pro His Thr Asp Giy As p. 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 Gln Val Ser Val Glu Ile Glu Trp Glu 675 680 685

Leu Gin Lys Glu Asn ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr 690 695 700

Ser Asn Tyr Tyr Lys Ser Thr Asa Val Asp Phe Ala Val Asn Thr Asp 20 Feb 2020

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

<210> 84 <211> 738 2020201242

<212> PRT <213> capsid protein of AAV serotype, clone 42.15 <400> 84 Met Ala Ala. Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 1 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 Gin Gln 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 Giu Glu Gly Ala Lys Thr Ala. Pro Gly Lys Lys Arg 130 135 140

Pro Val Glu Pro Ser Pro Gin Arg Sex Pro Asp Ser Ser Thr Gly Ile 145 150 155 160

Gly Lys Thr 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 Gin 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 let Gly Asp Arg Val 225 230 235 240 2020201242

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 Ile Asn 290 295 300

Asn Asa Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Lou Phe Asn 305 310 315 320

Ile 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 Gln Val Phe Thr Asp Ser Glu Tyr Gin 340 345 350

Leu Pro Tyr Val Leu Gly Ser Ala His Gln Gly Cys Pro 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 Gin Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr 385 390 395 400

Phe Pro Ser Gin Met Arg 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 Gln 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 Gln 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 2020201242

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 Gln 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 Gln 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 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 Gln Ala Lys Leu Ala Ser Phe 660 665 670

Ile Thr Gln Tyr Ser Thr Gly Gin Val Ser Val Glu Ile Giu Trp Glu 675 680 685

Leu Gin Lys Glu Asn Ser Lys Arg Tip 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 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

<210> 85 2020201242

<211> 738 <212> PRT <213> capsid protein of AAV serotype, clone 42.8 <400> 85 Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 1 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 Gin 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

Gin Gin 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 Val Glu Pro Ser Pro Gln Arg Ser Pro Asp Ser Ser Thr Gly Ile 145 150 155 160

Gly Lys Thr Gly Gln Gin Pro Ala Lys Lys Arg Leu Asn Phe Gly Gln 165 170 175

WO 03/042397 Per/002/33629

Thr Ely Asp Ser Glu Ser Val Pro Asp Pro Gln Pro Ile Gly Glu Pro 20 Feb 2020

180 185 190

Pro Ala Gly Pro Ser Gly Leu Gly Ser Gly Thr Met Ala Ala Gly Ely 195 200 205

Gly Ala Pro Met Ala Asp Asn Asn Glu Ely Ala Asp Gly Val Gly Ser 210 215 220

Ser Ser Ely Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val 225 230 235 240 2020201242

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 Ely Thr Ser Ely Gay Ser Thr Asn Asp 260 265 270

Asn Thr Tyr Phe Gly Tyr Sex Thr Pro Trp Ely Tyr Phe Asp Phe Asn 275 280 285

Arg Phe His Cys His Phe Ser Pro Arg Asp Trp Gin 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

lie Gln Val Lys Glu Val Thr Gin Asn Glu Gay Thr Lys Thr Ile Ala 325 330 335

Asn Asn Leu Thr Ser Thr Ile Gin Val Phe Thr Asp Ser Glu Tyr Gln 340 345 350

Leu Pro Tyr Val Leu Ely 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 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 Gln Ser 420 425 430

Leu Asp Arg Leu Met Asn. Pro Len Ile Asp Gln Tyr Leu Tyr Tyr Leu 20 Feb 2020

435 440 445

Ser Arg Thr Gin Ser Thr Gly Gly Thr Ala Gly Thr Gin Gin Leu Leu 450 455 460

Phe Ser Gln 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 Sex Thr Thr Leu Ser 485 490 495 2020201242

Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Gly Ala Thr Lys Tyr His 500 505 510

Leu Asn Gly Arg Asp Ser Len Val Asn Pro Gly Val Ala Met Ala Thr 515 520 525

His Lys Asp Asp Glu Giu Arg Phe Phe Pro Ser Sex Gly Val Leu Met 530 535 540

Phe Gly Lys Gin Gly Ala Gly Lys Asp Asn Val Asp Tyr Ser Sex Val 545 550 555 560

Met Leu Thr Ser Glu Glu Giu Ile Lys Thr Thr Asn Pro Val Ala Thr 565 570 575

Glu Gin Tyr Gly Val Val Ala Asp Asn Leu Gln 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 Gln 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 Len 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 Sex Thr Gly Gin Val Ser Val Glu Ile Glu Trp Glu 675 680 685

Leu Gin Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gin Tyr Thr 20 Feb 2020

690 695 700

Ser Mn 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 2020201242

<210> 86 <211> 733 <212> PRT <213> amino acid of WI serotype, clone 42.13 <400> 86 Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 1 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 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

Gln Gin 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 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 Gln 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 Ile 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 Awl 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 Ile Thr Thr Ser Thr 2020201242

225 230 235 240

Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu Tyr Lys Gln Ile 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 Phe Asn Arg Phe His Cys His 275 280 285

Phe Ser Pro Arg Asp Trp Gin Arg Leu Ile Asn Asn Asn Trp Gly Phe 290 295 300

Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn Ile Gin Val Lys Glu 305 310 315 320

Val Thr Gin Asn Glu Gly Thr Lys Thr Ile Ala Asn Asn Leu Thr Ser 325 330 335

Thr Ile Gin Val Phe Thr Asp Ser Glu Tyr Gln Leu Pro Tyr Val Leu 340 345 350

Gly Ser Ala His Gin Gly Cys Leu Pro Pro Phe Pro Ala Asp Val Phe 355 360 365

Met Ile Pro Gin Tyr Gly Tyr Lei' Thr Leu Asn Asn Gly Ser Gin Ala 370 375 380

Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro Ser Gln Met 385 390 395 400

Leu Arg Thr Gly Asn Asn Phe Glu Phe Ser Tyr Gln 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 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 Gln Arg Val Ser Thr Thr Val Ser Gln Asn Asn Asn Ser 2020201242

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 Sex Glu 545 550 555 560

Glu Glu Ile Lys Thr Thr Asn Pro Val Ala Thr Glu Gln Tyr Gly Val 565 570 575

Val Ala Asp Asa Leu Gin Gin Gin Asn Ala Ala Pro Ile Val Gly Ala 580 585 590

Val Asn Ser Gln Gly Ala Leu Pro Gly Met Val Trp Gln Asn Arg Asp 595 600 605

Val Tyr Leu Gin Gly Pro Ile Trp Ala Lys Ile 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 Ile Leu Ile 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 Gin Tyr Ser 660 665 670

Thr Gly Gin Val Ser Val Glu Ile Glu Trp Glu Leu Gln Lys Glu Asn 675 680 685

Ser Lys Arg Trp Asn Pro Glu Ile 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 Ile Gly Thr Arg Tyr Leu Thr Arg Ser Leu 725 730

<210> 87 2020201242

<211> 733 <212> PRT <213> capsid protein of AAV serotype, clone 42.3A <400> 87 Met Ala Ala Asp Gly His Leu Pro Asp Trp Leu Glu Asp Am Leu Ser 1 5 10 15

Glu Gly Ile Arg Glu Trp Trp Asp Lela Lys Pro Gly Ala Pro Lys Pro 20 25 30

Lys Ala Asn Gin Gin Lys Gin Asp Asp Gly Axg 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 Gln Ala Lys Lys Arg Val Leu Giu 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 Giu Ser Pro Asp Ser Ser Thr Gly Ile 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 Ile 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 Ser Ser 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 2020201242

Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu Tyr Lys Gin Ile 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 Phe Asn Arg Phe His Cys His 275 280 285

Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn Ser Trp Gly Phe 290 295 300

Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn Ile Gin Val Lys Glu 305 310 315 320

Val Thr Gin Asn Giu Gly Thr Lys Thr lie Ala Asn Asn Leu Thr Ser 325 330 335

Thr Ile Gin Val Phe Thr Asp Ser Glu Tyr Gln Leu Pro Tyr Val Leu 340 345 350

Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro Ala Asp Val Phe 355 360 355

Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn Gly Ser Gin Ala 370 375 380

Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro Ser Gln 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 Sex Gin Ser Leu Asp Arg Leu Met 420 425 430

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 Leu Ser Gin Asn Asn Asn Ser 485 490 495 2020201242

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 Ile Lys Thr Thr Asn Pro Val Ala Thr Glu Gin Tier Gly Val 565 570 575

Val Ala Asp Asn Leu Gin Gln Gln Asn Ala Ala Pro Ile Val Gly Ala 580 585 580

Val Asn Ser Gln Gly Ala Leu Pro Gly Met Val Trp Gin Asn Arg Asp 595 600 605

Val Tyr Leu Gin Gly Pro Ile Trp Ala Lys Ile 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 Ile Leu Ile Lys Asn Thr Pro Val Pro Ala Asp Pro Pro 645 650 655

Thr Thr Phe Ser Gin 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 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 Ile 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 2020201242

<400> 88 Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Set 1 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 Gin Gln 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 Gln Gly Asp Asn Pro Tyr Leu Lys Tyr Asn His Ala 85 90 95

Asp Ala Glu Phe Gin Glu Arg Leu Gln 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 Sex . Thr Gly Ile Gly Lys Lys Gly Gin 145 150 155 160

Gln 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 Ile 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 20 Feb 2020

195 200 205

Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn Ala Ser Gay 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 Gin Ile 245 250 255 2020201242

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

Ser Arg Asp Trp Gin Arg Leu Ile Asn Asn Asn Trp Gly Phe Arg Pro 290 295 300

Lys Arg Leu Asn Phe Lys Leu Phe Asn Ile Gln Val Lys Glu Val Thr 305 310 315 320

Gln Asn Glu Gly Thr Lys Thr Ile Ala Asn Asn Leu Thr Ser Thr Ile 325 330 335

Gln Val Phe Thr Asp Ser Glu Tyr Arg 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 Gln Ala Val Gly 370 375 380

Arg Ser Ser Phe Tyr Cys Leu Giu Tyr Phe Pro Ser Gin Met Leu Arg 385 390 395 400

Thr Gly Asn Asn Phe Glu Phe Ser Tyr Gin Phe Glu Asp 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 Gln Tyr Leu Tyr Tyr Leu Ser Arg Thr Gln Ser Thr Gly 435 440 445

Gly Thr Ala Gly Thr Gin Gin Leu Leu Phe Ser Gin Ala Gly Pro Asn 20 Feb 2020

450 455 460

Asn Met Ser Ala Gln Ala Lys Asn Trp Leu Pro Gly Pro Cys Tyr Arg 465 470 475 480

Gln Gin 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 lieu Asn Gly Arg Asp Ser Leu 500 505 510 2020201242

Val Awl 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 Gin Gly Ala Gly 530 535 540

Lys Asp Asn Val Asp Tyr Ser Ser Val Met Leu Thr Ser Glu Glu Glu 545 550 555 560

Ile Lys Thr Thr Asn Pro Val Ala Thr Glu Gln Tyr Gly Val Val Ala 565 570 575

Asp Asn Lou Gin Gin Gln Asn Ala Ala Pro Ile Val Gly Ala Val Asn 580 585 590

Ser Gin Gly Ala Leu Pro Gly Met Val Trp Gln Asn Arg Asp Val Tyr 595 600 605

Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro His Thr Asp Gly Asn Phe 610 615 620

His Pro Ser Pro Leu Met Gly Gly Phe Gly Lou Lys His Pro Pro Pro 625 630 635 640

Gin Ile Leu Ile Lys Asn Thr Pro Val Pro Ala Asp Pro Pro Thr Thr 645 650 655

Phe Ser Gln Ala Lys Pro Ala Ser Phe Ile Thr Gin Tyr Ser Thr Gly 660 665 670

Gln Val Ser Val Giu Ile Glu Trp Glu Leu Gin 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

WO 03/042397 PerfUS02/33629

Asn Val Asp Phe Ala Val Asn Thr Glu Gly Thr Tyr Ser Glu Pro Arg 20 Feb 2020

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> 89 2020201242

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 1 5 10 15

Glu Gly Ile Arg Glu Trp Trp Asp Lou Lys Pro Gly Ala Pro Lys Pro 20 25 30

Lys Ala Asn Gin Gln Lys Gln Asp Asp Gly Arg Gly Leu Val Leu Pro 35 40 45

Gly Tyr Lys Tyr teu 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 L ys Ala Tyr Asp 65 70 75 80

Lys Gln Leu Glu Gin Gly Asp Asa Pro Tyr Lou Lys Tyr Asn His Ala 85 90 95

Asp Ala Glu Phe Gin Glu Arg Lou 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 Axg 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 Gln 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

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 Ile 245 250 255 2020201242

Ser Ser Gin 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 Ile Asn Asn Asn Arg 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 Asa Asp Gly Val Thr Thr Ile Ala Asn Asa 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 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 Gin Phe Glu Asp Val Pro Phe 405 410 415

His Ser Ser Tyr Ala His Ser Gin Ser Leu Asp Arg Leu Net Asa Pro 420 425 430

Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ser Arg Thr Gln Ser Thr Gly 435 440 445

Gly Thr Ala Gly Thr Gin Gin Leu Lett Phe Ser Gln Ala Gly Pro Asn 450 455 460

Asn Met Ser Ala Gln Ala Lys Asn Trp Leu Pro Giy Pro Cys Tyr Arg 465 470 475 480

Gln Gin Arg Val Ser Thr Thr Leu Ser Gin 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 Giu Arg 2020201242

515 520 525

Phe Phe Pro Ser Ser Gly Val Leu Met Phe Gly Lys Gin Gly Ala Gly 530 535 540

Lys Asp Asn Val Asp Tyr Ser Ser Val Met Leu Thr Ser Giu Glu Glu 545 550 555 560

Ile Lys Thr Thr Asn Pro Val Ala Thr Glu Gin Tyr Gly Val Val Ala 565 570 575

ASp Asn Leu Gin Gin Gin Asn Ala Ala Pro Ile Val Gly Ala Val Asn 580 585 590

Ser Gln Gly Ala Leu Pro Gly Met Ala Trp Gin Asn Arg Asp Val Tyr 595 600 605

Leu Gin Gly Pro Ile Trp Ala Lys Ile Pro His Thr Asp Gly Asn Phe 610 615 620

His Pro Ser Pro lieu Met Gly Gly Phe Gly Leu Lys His Pro Pro Pro 625 630 635 640

Gin Ile Leu Ile Lys Asn Thr Pro Val Pro Ala Asp Pro Pro Thr Thr 645 650 655

Phe Ser Gin Ala Lys Leu Ala Ser Phe Ile Thr Gin Tyr Ser Thr Gly 660 665 670

Gin Val Ser Val Glu Ile Glu Trp Glu Leu Gin Lys Glu Asn Ser Lys 675 680 685

Arg Trp Asn Pro Giu Ile Gin 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 Giu Pro Arg 705 710 715 720

Pro Ile Gly Thr Arg Tyr Leu Thr Arg Asn Leu 725 730

<210> 90 <211> 733 <212> PRT <213> capsid protein of AAV serotype, clone 42.1B <400> 90 Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 1 5 10 15 2020201242

Glu Gly Ile Arg Glu Trp Trp Asp Leu Arg Pro Gly Ala Pro Lys Pro 20 25 30

Lys Ala Asn Gin Gin 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 Gin Leu Glu Gin 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 Ile Glu Ser Pro Asp Ser Ser Thr Gly Ile Gly Lys Lys Gly Gin 145 150 155 160

Gln Pro Ala Lys Lys Arg Leu Asn Phe Gly Gin Thr Gly Asp Ser Glu 165 170 175

Ser Val Pro Asp Pro Gin Pro Ile 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 Ser Ser 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 Ile 245 250 255

Sex Asn Gly Thr Ser Gly Gly Ser Thr Asn Asp Asn Thr Tyr Phe Gly 260 265 270 2020201242

Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe His Cys His 275 280 285

Phe Ser Pro Arg Asp Trp Gin Arg Leu Ile Asn Asn Asn Trp Gly Phe 290 295 300

Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn Ile Gln Val Lys Glu 305 ' 310 315 320

Val Thr Gin Asn Glu Gly Thr Lys Thr Ile Ala Asn Asn Leu Thr Ser 325 330 335 Thr Ile Gin Val Phe Thr Asp Ser Glu Tyr Gin Leu Pro Tyr Val Leu 340 345 350

Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro Ala Asp Val Phe 355 360 365

Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn Gly Ser Gin Ala 370 375 380

Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro Ser Gln Met 385 390 395 400

Leu Arg Thr Gly Asn Asn Phe Glu Phe Ser Tyr Gln 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 Ile Asp Gin Tyr Leu Tyr Tyr Leu Sex Arg Thr Gin Ser 435 440 445

Thr Gly Gly Thr Ala Gly Thr Gln Gln Leu Leu Phe Ser Gin Ala Giy 450 455 460

Pro Asn Asn Met Ser Ala Gin Ala Lys Asn Trp Leu Pro Gly Pro Cys 465 470 475 480

WO 03/042397 PCT/111S02/33629 20 Feb 2020

Tyr Arg Gln 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

Giu Arg Phe Phe Pro Ser Ser Gly Val Leu Met Phe Gly Lys Gln Gly 2020201242

530 535 540

Ala Gly Lys Asp Asn Val Asp Tyr Ser Ser Val Met Lau Thr Ser Glu 545 550 555 560

Glu Glu Ile 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 Ile Val Gly Ala 580 585 590

Val Asn Ser Gln Gly Ala Leu Pro Gly Met Val Trp Gin Asn Arg Asp 595 600 605

Val Tyr Leu Gin Gly Pro Ile Trp Ala Lys Ile 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 Ile Leu Ile Lys Asn Thr Pro Val Pro Ala Asp Pro Pro 645 650 655

Thr Thr Phe Ser Gin Ala Lys Leu Ala Ser Phe Ile 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

Ser. Lys Arg Trp Asn. Pro Glu Ile Gin Tyr Thr Ser Asn Tyr Tyr Lys 690 695 700

Sex Thr Awl Val Asp Phe Ala Val Awl. Thr Glu Gly Thr Tyr Ser Glu 705 710 715 720

Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Asn 725 730

<210> 91 <211> 738 <212> PRT <213> capsid protein of AAV serotype, clone 42.55 <400> 91 Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 1 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 Gin Gin Lys Gln Asp Asp Gly Arg Gly Leu Val Leu Pro 2020201242

35 40 45 Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro 50 55 60 Val Asn Giu Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp 65 70 75 80

Lys Gln Leu Giu 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 Bar 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 Val Glu Pro Ser Pro Gin Arg Ser Pro Asp Ser Ser Thr Gly Ile 145 150 155 160

Gly Lys Thr Gly Gin Gin Pro Ala Lys Lys Arg Leu Asn Phe Gly Gin 165 170 175

Thr Gly Asp Ser Glu Ser Val Pro Asp Pro Gin 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

Bar 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

Lau 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 Gln Arg Leu Ile Asn 290 295 300 2020201242

Asn Asn Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn 305 310 315 320 Ile Gin Val Lys Glu Val Thr Gin Asn Glu Gly Thr Lys Thr Ile Ala 325 330 335

Am 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 Ile Pro Gin Tyr Gly Tyr Leu Thr Leu Asn 370 375 380

Asn Gly Sex . 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 Sex Tyr 405 410 415

Gin Phe Glu Asp Val Pro Phe His Ser Set 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 Sex Thr Gly Gly Thr Ala Gly Thr Gin Gin Leu Leu 450 455 460

Phe Ser Gin Ala Gly Pro Am Asn Met Ser Ala Gin Ala Lys Asn Trp 465 470 475 480

Leu Pro Gly Pro Cys Tyr Arg Gin Gin Arg Val Sex Thr Thr Leu Sex 485 490 495

Gin Asn Asn Asn Set Asn Phe Ala Trp Thr Gly Ala Thr Lys Tyr His 500 505 510

Leu Asn Gly Arg Asp Sex Leu Val Asn Pro Gly Val Ala Met Ala Thr 515 520 525

His Lys Asp Asp Glu Glu Arg Phe Phe Pro Sex Ser Gly Val Leu Met 530 535 540

Phe Gly Lys Gin Gly Ala Gly Lys Asp Asn Val Asp Tyr Ser Sex Val 545 550 555 560

Met Leu Thr Ser Glu Glu Glu Ile Lys Thr Thr Asn Pro Val Ala Thr 2020201242

565 570 575

Glu Gln Tyr Gly Val Val Ala Asp Asn Leu Gin Gin Gln Asn Ala Ala 580 585 590

Pro Ile Val Gly Ala Val Asn Ser Gln 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 Ile 610 615 620

Pro His Thr Asp Gly Asn Phe His Pro Sex Pro Leu Met Gly Gly Phe 625 630 635 640

Gly Leu Lys His Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val 645 650 655

Pro Ala Asp Pro Pro Thr Thr Phe Ser Gln Ala Lys ' Leu Ala Sex. Phe 660 665 670

Ile Thr Gin Tyr Ser Thr Gly Gln Val Ser Val Glu Ile 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 Glu 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> 92 <211> 738 <212> PRT <213> capsid protein of AAV serotype, clone 43.1

<400> 92 20 Feb 2020

Met Ala Ala Asp Gly Tyr Leu Pro Asp Txp Leu Glu Asp Asn Leu Ser 1 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 Gin Gln 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 2020201242

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 Asti His Ala 85 90 95

Asp Ala Glu Phe Gin 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 Val Glu Pro Ser Pro Gln Arg Ser Pro Asp Ser Ser Thr Gly Ile 145 150 155 160

Gly Lys Lys Gly His Gln Pro Ala Arg Lys Arg Leu Asn Phe Gly Gin 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

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 Asia Asn His 245 250 255

Leu Tyr Lys Gin Ile Ser Asn Gly Thr Ser Gly Gly Ser Thr Asn Asp 20 Feb 2020

260 265 270

Asn Thr Tyr Phe Giy 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 Giy Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn 305 310 315 320 2020201242

Ile Gln 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 Gln 340 345 350

Leu Pro Tyr Val Pro Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe 355 360 365

Pro Ala Asp Val Phe Met Ile Pro Gin Tyr Gly Tyr Leu Thr Leu Asn 370 375 380

Mn Gly Ser Gln Ala Val Giy 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

Thr Phe Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser 420 425 430

Leu Asp Arg Leu Net Asn Pro Leu Ile Asp Gin Tyr Leu Tyr Tyr Leu 435 440 445

Ser Arg Thr Gin Ser Thr Gly Giy Thr Gln Gly Thr Gin Gln Leu Leu 450 455 460

Phe Ser Gin Ala Gly Pro Ala Asn Met Ser Ala Gin Ala Lys Asn Tip 465 470 475 480

Leu Pro Gly Pro Cys Tyr Arg Gin Gln 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 Axg Phe Phe Pro Ser Ser Gly Val Leu Met 530 535 540

Phe Gly Lys Gln Gly Ala Gly Lye 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 2020201242

Glu Gln Tyr Gly Val Val Ala Asp Asn Leu Gln Gin Thr Asn Gly Ala 580 585 590

Pro Ile Val Gly Thr Val Asn Ser Gln Gly Ala Leu Pro Gly Met Val 595 600 605

Trp Gln 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 L ys His Pro Er° Pro Gin Ile Leu Val 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 Giu Ile Glu Trp Glu 675 680 685

Leu Gin Lys Glu Asn Ser Lys Arg Trp Asn Pro Giu Ile 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 Giu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg 725 730 735

Asn Leu

<210> 93 <211> 738 <212> PRT <213> capsid protein of AAV serotype, clone 43.12

<400> 93 20 Feb 2020

Met Ala Ala Asp Gly Tyr Leu Pro Asp Tip Leu Glu Asp Asn Leu Ser 1 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 2020201242

Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp 65 70 75 BO

Gln 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 Val Glu Pro Ser Pro Gin Arg Ser Pro Asp Ser Ser Thr Gly Ile 145 150 155 160

Gly Lys Lys Gly His Gln Pro Ala Arg Lys Arg Leu Asn Phe Gly Gln 165 170 175

Thr Gly Asp Ser Glu Ser Val Pro Asp Pro Gla 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 Sex . 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 Ile Ser Asn Gly Thr Ser Gly Gly Ser Thr Asn Asp 20 Feb 2020

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 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 2020201242

Ile Gln Val Lys Glu Val Thr Gln Asn Glu Gly Thr Lys Thr Ile Ala 325 330 335

Asn Asn Leu Thr Sex Thr Ile Gin Val Phe Thr Asp Ser Glu Tyr Gin 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 Gin Tyr Gly Tyr lieu Thr Leu Asn 370 375 380

Asn Gly Ser Girt Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Giu Tyr 385 390 395 400

Phe Pro Ser Gin Met Leu Arg Thr Gly Asn Asn Phe Glu Phe Ser Tyr 405 410 415

Thr 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 Lett Tyr Tyr Len 435 440 445

Ser Arg Thr Gin Ser Thr Gly Gly Thr Gin Gly Thr Gin Gin Leu Leu 450 455 460

Phe Sex Gin Ala Gly Pro Ala Asn Met Ser Ala Gin Ala Lys Asn Trp 465 470 475 480

Leu Pro Gly Pro Cys Tyr Arg Gln 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 20 Feb 2020

515 520 525

His Lys Asp Asp Glu Glu Arg Phe Phe Pro Set Sex Gly Val Leu Net 530 535 540

Phe Gly Lys Gln Gly Ala Gly Lys Asp Asa Val Asp Tyr Sex' Sex Val 545 550 555 560

Met Leu Thr Ser Glu Glu Glu Ile Lys Thr Thr Asn Pro Val Ala Thr 565 570 575 2020201242

Glu Gln Tyr Gly Val Val Ala Asp Asn Leu Gln Gln Thr Asn Gly Ala 580 585 590

Pro Ile Val Gly Thr Val Asn Set Gin Gly Ala Leu Pro Gly Met Val 595 600 605

Trp Gln 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 Val 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 Gln Val Ser Val Glu Ile Glu Trp Glu 675 680 685

Leu Gin Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Tie Gin Tyr Thr 690 695 700

Ser Asn Tyr Tyr Lys Ser Thr Asn Val Asp Phe Ala Val Asn Thr Giu 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

<210> 94 <211> 738 <212> PRT <213> capsid protein of AAV serotype, clone 43.5

<400> 94 Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 1 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 Gin Gln Lys Gin Asp Asp Gly Arg Gly Leu Val Leu Pro 35 40 45 2020201242

Gly Tyr Lys Tyr Lou 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 Gln 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 Val Glu Pro Ser Pro Gln Arg Ser Pro 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 Gln 165 170 175

Thr Giy Asp Ser Glu Ser Val Pro Asp Pro Gin Pro Ile Gly Glu Pro 180 185 190

Pro Ala Gly Pro Ser Gly Leu Giy Ser Giy Thr Met Ala Ala Gly Gly 195 200 205

Gly Ala Pro Met Ala Asp Asn Asn Glu Giy 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 Awl Asn His 245 250 255

Leu Tyr Lys Gin Ile Ser Asn Gly Thr Ser Gly Gly Ser Thr Asa 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 Tie Asn 290 295 300

Asn Asn Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn 2020201242

305 310 315 320

Ile 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 Ile Pro Gln 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

Thr 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 Gin Gly Thr Gin Gin Leu Leu 450 455 460

Phe Ser Gin Ala Giy Pro Ala 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 2020201242

565 570 575

Glu Gin Tyr Gly Val Val Ala Asp Asn Leu Gin Gln Thr Asn Gly Ala 580 585 590

Pro Ile Val Gly Thr 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 Pro Pro Gin Ile Leu Val 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 Gln Val Ser Val Glu Tie Glu Trp Glu 675 680 685

Leu Gln 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 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

<210> 95 <211> 738 <212> PRT <213> capsid protein of AAV serotype, clone 3AV8

<400> 95 Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 1 5 10 15

Glu Gly Ile Arg Glu Trp Trp Ala Leu Lys Pro Gly Ala Pro Lys Pro 20 25 30

Lys Ala Asn Gin Gin Lys Gln Asp Asp Gly Arg Gly Leu Val Leu Pro 35 40 45 2020201242

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 G1u His Asp Lys Ala Tyr Asp 65 70 75 80

Gln Gln Leu Gln 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 Sex 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 Val Glu Pro Ser Pro Gin Arg Ser Pro Asp Ser Ser Thr Gly Ile 145 150 155 160

Gly Lys Lys Gly Gln Gln Pro Ala Arg Lys Arg Leu Asn Phe Gly Gin 165 170 175

Thr Gly Asp Ser Giu Ser Val Pro Asp Pro Gin Pro Leu Gly Glu Pro 180 185 190

Pro Ala Ala Pro Ser Gly Val Gly Pro Asn 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 20 Feb 2020

245 250 255

Leu Tyr Lys Gln Ile Ser Asn Gly Thr Ser Gly Gly Ala Thr Asn Asp 260 265 270

Asn Thr Tyr Phe Gly Tyr Ser Thr Pro Trp Giy 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 2020201242

Asn Asn Trp Gly Phe Arg Pro Lys Arg Leu Ser Phe Lys Leu Phe Asn 305 310 315 320

Ile Gin Val Lys Glu Val Thr Gin Asn Giu Gly Thr Lys Thr Ile Ala 325 330 335

Asn Asn Leu Thr Ser Thr Ile Gln 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 Ile Pro Gin 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 Gin Met Leu Arg Thr Gly Asn Asn Phe Gin Phe Thr Tyr 405 410 415

Thr 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 Gln Thr Thr Gly Gly Thr Ala Awl. Thr Gin Thr Leu Gly 450 455 460

Phe Ser Gin Gly Gly Pro Awl Thr Met Ala Asn Gin Ala Lys Asn Trp 465 470 475 480

Leu Pro Gly Pro Cys Tyr Arg Gin Gin Arg Val Ser Thr Thr Thr Gly 485 490 495

WO 03/042397 PCT/ITS02/33629

Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Ala Gly Thr Lys Tyr His 20 Feb 2020

500 505 510

Leu Asn Gly Arg Asn Ser Leu Ala Asn Pro Gly Ile Ala Met Ala Thr 515 520 525

His Lys Asp Asp Glu Giu Arg Phe Phe Pro Ser Asn Gly Ile Leu Ile 530 535 540

Phe Gly Lys Gln Asn Ala Ala Arg Asp Asn Ala Asp Tyr Ser Asp Val 545 550 555 560 2020201242

Met Leu Thr Ser Giu Glu Glu Ile Lys Thr Thr Asn Pro Val Ala Thr 565 570 575

Glu Glu Tyr Gly Ile Val Ala Asp Asn Leu Gln Gin Gln Asn Thr Ala 580 585 590

Pro Gln Ile Gly Thr Val Asn Ser Gin Gly Ala Leu Pro Gly Met Val 595 600 605

Trio 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 Gln Ile Leu Ile Lys Asn Thr Pro Val 645 650 655

Pro Ala Asp Pro Pro Thr Thr Phe Awl Gin Ser Lys Leu Asn Ser Phe 660 665 670

Ile Thr Gln Tyr Ser Thr Gly Gin Val Ser Val Glu Ile Glu Trp Glu 675 680 685

Leu Gln Lys Glu Asn Ser Lys Arg Trp Awl Pro Glu Ile Gln Tyr Thr 690 695 700

Ser Asn Tyr Tyr Lys Ser Thr Ser Val Asp Phe Ala Val Asn Thr Giu 705 710 715 720

Gly Val Tyr Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg 725 730 735

Asn Leu

<210> 96 20 Feb 2020

<211> 736 <212> PRT <213> capsid protein o AAV serotype, clone 43.21 <400> 96 Met. Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 1 5 10 15

Giu Gly Ile Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro 20 25 30 2020201242

Lys Ala Asn Gln 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 Gln Glu Arg Leu Gin 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 Val Giu Gin Ser Pro Gin Giu Pro Asp Ser Ser Bar 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 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

His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val Ile 20 Feb 2020

Ser Gly Asn Trp 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 Ash 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 The Asn Arg 2020201242

275 280 285

Phe His Cys His Phe Ser Pro Arg Asp Trp Gin Arg Leu Ile Asn Asn 290 295 300

Asn Tip Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn Ile 305 310 315 320

Gln Val Lys Giu Val Thr Thr Asn Giu Gly Thr Lys Thr Ile Ala Asn 325 330 335

Asn Leu Thr Ser Thr Val Arg Val Phe Thr 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 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 Gln Met Leu 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 Gln 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 Ser 20 Feb 2020

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 Net Ala Ser His Lys 515 520 525

Asp Asp Asp Asp Arg Phe Phe Pro Sex Ser Gly Val Leu Ile Phe Gly 530 535 540 2020201242

Lys Gln Gly Ala Gly Asn Asp Gly Val Asp Tyr Ser Gin Val Leu Ile 545 550 555 560

Thr Asp Giu Glu Glu Ile Lys Ala Thr Asn Pro Val Ala Thr Glu Glu 565 570 575

Tyr Gly Ala Val Ala Ile Asn Asn Gin Ala Ala Asn Thr Gin Ala Gin 580 585 590

Thr Gly Leu Val His Asn Gln Gly Val Ile Pro Gly Net Val Trp Gin 595 600 605

Asn Arg Asp Val Tyr Leu Gin Gly Pro Ile Trp Ala Lys Ile 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 Gln Ile Leu Ile Lys Asn Thr Pro Val Pro Ala 645 650 655

Asp Pro Pro Leu Thr Phe Asn Gln Ala Lys Leu Asn Ser Phe Ile Thr 660 665 670

Gin Tyr Ser Thr Gly Gin Val Ser Val Glu Ile Giu Trp Glu Leu Gln 675 680 685

Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile 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 Ile Gly Thr Arg Tyr Leu Thr Arg Asn Leu 725 730 735

<210> 97 20 Feb 2020

<211> 736 <212> PAT <213> capsid protein of AA.V serotype, clone 43.25

<400> 97 Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 1 5 10 15

Glu Gly Ile Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro 20 25 30 2020201242

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 Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Am His Ala 85 90 95

Asp Ala Glu Phe Gin 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 Giu 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 Gln 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 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 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

WO 03/042397 PC1711S02/33629 20 Feb 2020

Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thx 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

Thx Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg 275 280 285

Asn 2020201242

Phe His Cys His Phe Ser Pro Arg Asp Trp Gin Arg Leu Ile 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 Ser Glu Tyr Gin Leu 340 345 350

Pro Tyr Val Leu Giy Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro 355 360 365

Ala Asp Val Phe Met Val Pro Gin Tyr Gly Tyr Leu Thr Len Asn Asn 370 375 380

Gly Ser Gln 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 Phe Gln 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 All. Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Val 435 440 445

Arg Thr Gln Thr Thr Gly Thr Gay 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 Gln Gln Arg Val Ser Thr Thr Thr Asn Gin Asn 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 Ile Phe Gly 530 535 540 2020201242

Lys Gln Gly Ala Gly Asn Asp Gly Val Asp Tyr Sex Gin Val Leu Ile 545 550 555 560

Thr Asp Glu Glu Glu Ile Lys Ala Thr Asn Pro Val Ala Thr Giu Glu 565 570 575

Tyr Gly Ala Val Ala Ile Asn Asn Gin Ala Ala Asn Thr Gln Ala Gin 580 585 590

Thr Gly Leu Val His Asn Gln Gly Val Ile Pro Gly Met Val Trp Gin 595 600 605

Asn Arg Asp Val Tyr Leu Gin Gly Pro Ile Trp Ala Lys Ile 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 Ile Leu Ile Lys Asn Thr Pro Val Pro Ala 645 650 655

Asp Pro Pro Leu Thr Phe Asn Gin Ala Lys Leu Asn Sex 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 Tyr Lys Ser Thr Asn Val Asp Phe Ala Val Asn Thr Giu Gly Val 705 710 715 720

Tyr Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Asn Leu 725 730 735

<210> 98 20 Feb 2020

<211> 736 <212> PRT <213> capsid protein of ARV serotype, clone 43.23 <400> 98 Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 1 5 10 15

Glu Gly Ile Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro 20 Z5 30 2020201242

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 Gin Leu Lys Ala Gly Asp Asn Pro Tyr Lou Arg Tyr Awl. His Ala 85 90 95

Asp Ala Glu Fhe Gin Glu Arg Leu Gln Glu Asp Thr Ser Phe Gly Gly 100 105 110

Asn Lou 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 Val Glu Gln Ser Pro Gln Glu Pro Asp Ser Ser Ser Gly Ile Gly 145 150 155 160

Lys Thr Gly Gin Gln Pro Ala Lys Lys Arg Leu Asn Phe Gly Gin 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 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

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 2020201242

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 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 Gln Ala Leu Gly Arg Ser Ser Phe Tyr Cys Leu Gla 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 Gln 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 Gln Thr Leu Ala Phe Ser 450 455 46D

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 Gln Asn 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 Ale Ser His Lys 515 520 525

Asp Asp Asp Asp Arg Phe Phe Pro Ser Ser Gly Val Leu Ile Phe Gly 530 535 540 2020201242

Lys Gin Gly Ala Gly Asn Asp Gly Val Asp Tyr Ser Gln Val Leu Ile 545 550 555 560

Thr Asp Glu Glu Glu Ile Lys Ala Thr Asia Pro Val Ala Thr Glu Glu 565 570 575

Tyr Gly Ala Val Ala Ile Asn Asn Gin Ala Ala Asn Thr Gln Ala Gln 580 585 590

Thr Gly Leu Val His Asn Gln Gly Val Ile Pro Gly Met Val Trp Gin 595 600 605

Asn Arg Asp Val Tyr Leu Gin Gly Pro Ile Trp Ala Lys Ile 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 Gln Ile Leu Ile Lys Asn Thr Pro Val Pro Ala 645 650 655

Asp Pro Pro Leu Thr Phe Asn Gin Ala Lys Leu Asn Ser Phe Tie Thr 660 665 670

Gln 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 Tyr Lys Ser Thr Asn Val Asp Phe Ala Val Asn Thr Glu Gly Val 705 710 715 720

Tyr ear Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Asa Leu 725 730 735

<210> 99 20 Feb 2020

<211> 736 <212> PRT <213> capsid protein of AAV serotype, clone 43.20 <400> 99 Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 1 5 10 15

Glu Gly Ile Arg Giu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro 20 25 30 Lys Ala Asn Gin Gln Lys Gin Asp Asp Gly Arg Gly Leu Val Lou Pro 2020201242

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 Lou Lys Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala 85 90 95

Asp Ala Glu Phe Gin Glu Arg Lou Gin Glu Asp Thr Ser Phe Gly Gly 100 105 110

Asn I,eu Gly Arg Ala Val Phe Gin Ala Lys Lys Arg Val Leu Giu Pro 115 120 125

Leu Gly Leu Val Giu Glu Gly Ala Lys Thr Ala Pro Gly Lys Lys Arg 130 135 140

Leu 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 Lou Asn Phe Gly Gin Thr 165 170 175

Gly Asp Ser Giu Ser Val Pro Asp Pro Gln Pro Leu Gly Glu Pro Pro 180 185 190

Ala 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

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 As Phe Asn Arg 275 280 285

Phe His Cys His Phe Ser Pro Arg Asp'Trp Gln Arg Leu Ile Asn Asn 2020201242

290 295 300

Asa Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn Ile 305 310 315 320

Gln 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 Pro Pro Phe Pro 355 360 365

Ala Asp Val Phe Thr Val Pro Gin Tyr Gly Tyr Leu Thr Leu Asn Asn 370 375 380

Gly Ser Gin Ala Leu Giy Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe 385 390 395 400

Pro Ser Gln Met Leu 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 Mn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Val 435 440 445

Axg Thr Gin Thr Thr Gly Thr Gly Gly Thr Gin Thr Leu Ala Phe Ser 450 455 460

Gin Ala Giy Pro Ser Ser Met Ala Asn Gin Ala Arg Asn Trp Val Pro 465 470 475 480

Gly Pro Cys Tyr Arc! Gln Gin Arg Val Ser Thr Thr Thr Asn Gin Asn 485 490 495

Asn Asn Ser Asn Phe Ala Trp Thr Gly Ala Ala Lys Phe Lys Leu Asn 20 Feb 2020

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 Ile Phe Gly 530 535 540

Lys Gin Gly Ala Gly Asn Asp Gly Val Asp Tyr Ser Gln Val Leu Ile 545 550 555 560 2020201242

Thr Asp Glu Glu Glu Ile Lys Ala Thr Asn Pro Val Ala Thr Glu Glu 565 570 575

Tyr Gly Ala Val Ala Ile Asn Asn Gin Ala Ala Asn Thr Gin Ala Gin 580 585 590

Thr Gly Leu Val His Asn Gin Gly Val Ile Pro Gly Met Val Trp Gin 595 600 605

Asn Arg Asp Val Tyr Leu Gin Gly,Pro Ile Trp Ala Lys Ile 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 Gln Ile Leu Ile Lys Asn Thr Pro Val Pro Ala 645 650 655

Asp Pro Pro Leu Thr Phe Asn Gin Ala Lys Leu Asn Ser Phe Ile Thr 660 665 670

Gln 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 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 Ile 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 ANV9

400> 100 Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 1 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 Gin Gln Lys Gln Asp Asp Gly Arg Gly Leu Val Leu Pro 35 40 45 2020201242

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 Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala 85 90 95

Asp Ala Gin Phe Gin Gin Arg Leu Gln Glu Asp Thr Ser Phe Gly Giy 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 Val Glu Gin Ser Pro Gln Glu Pro Asp Ser Ser Ser Gly Ile Gly 145 150 155 160

Lys Ser Giy Gin Gin Pro Ala Lys Lys Arg Leu Asn Phe Giy Gln Thr 165 170 175

Gly Asp Ser Glu Ser Val Pro Asp Pro Gin 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 Lau Pro Thr Tyr Asn Asn His Leu 245 250 255

Ser Asn Gly Thr Ser Gly Gly Ser Thr Asn Asp Asn 20 Feb 2020

Tyr Lys Gln Ile 260 265 270

Thr Tyr Phe Giy 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 2020201242

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 Gln Gly Cys Leu Pro Pro Phe Pro 355 360 365

Ala Asp Val Phe Net Val Pro Gln 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 Phe Gln Phe Sex 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 Net Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Val 435 440 445

Arg Thr Gln Thr Thr Gly Thr Gly Gly Thr Gln Thr Leu Ala Phe Ser 450 455 460

Gln Ala Giy Pro Ser Ser Met Ala Asn Gln 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

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 20 Feb 2020

515 520 525

Asp Asp Glu Asp Arg Phe Phe Pro Ser Ser Gly Val Leu Ile Phe Gly 530 535 540

Lys Gin Giy Ala Gly Asn Asp Gly Val Asp Tyr Ser Gin Val Leu Ile 545 550 555 560

Thr Asp Glu Glu Glu Ile Lys Ala Thr Asn Pro Val Ala Thr Glu Giu 2020201242

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 Gln Gly Val Ile Pro Gly Met Val Trp Gln 595 600 605

Asn Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile 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 Ile Leu Ile Lys Asn Thr Pro Val Pro Ala 645 650 655

Asp Pro Pro Leu Thr Phe Asn Gin Ala L ys Leu Asn Ser Phe Ile Thr 660 665 670

Gin Tyr Ser Thr Gly Gin Val Ser Val Giu Ile Glu Trp Glu Leu Gln 675 680 685

Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gin Tyr Thr Ser Asn 690 695 700

Tyr Tyr Lys Ser Thr Asn Val Asp Phe Ala Vai Asn Thr Glu Gly Val 705 710 715 720

Tyr Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Asn Leu 725 730 735

<210> 101 <211> 728 <212> PRT <213> capsid protein of AAV serotype, clone 24.1 <400> 101 Net Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 1 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 Gin Gin Lys Gin Asp Asp Gly Arg Gly Leu Val Leu Pro 35 40 45

Gly Tyr Lys Tyr Leu Arg 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 2020201242

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 Axg Leu Gln 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 Ile Glu Ser Pro Asp Ser Ser Thr Gly Ile Gly Lys Lys Gly Gin 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 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

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 Ile 245 250 255

Ser Ser Gin Ser Gly Ala Thr Asn Asp Asn His Phe Phe Ser 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 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 2020201242

Thr Asn Asp G1y Val Thr Thr Ile Ala Asn Asn Leu Thr Sex 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 Gln 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 Lau Met Asn Pro 420 425 430

Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ala Arg Thr Gin Ser Thr Thr 435 440 445

Gly Ser Thr Arg Glu Leu Gln Phe His Gin Ala Gly Pro Asn Thr Met 450 455 460

Ala Glu Gin Ser Lys Am Trp Leu Pro Gly Pro Cys Tyr Axg Gin Gln 465 470 475 480

Arg Leu Ser Lys Asn Ile Asp Ser Asn Asn Ran Sex 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 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 Ile Lys Thr 545 550 555 560

Thr Asn Pro Val Pas. 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 2020201242

Asn Ser Gln Gly 580 585 590

Ala Leu Pro Gly Met Val Trp Gln Asn Arg Asp Val Cys 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 Gin Tyr Ser Thr Gly Gln Val Ser 660 665 670

Val Glu Ile Glu Trp Glu Leu Gin Lys Glu Asn Ser Lys Arg Trp Asn 675 680 6B5

Pro Glu Ile Gln Tyr Thr Ser Asn Tyr Ala Lys Ser Asn Asn VS1 Glu 690 695 700

Phe Ala Val Asn Asn Glu Gly Val Tyr Thr Glu Pro Arg Pro Ile Gly 705 710 715 720

Thr. Arg Tyr Leu Thr Arg Asn Leu 725

<210> 102 <211> 728 <212> PRT <213> capsid protein of ANV serotype, clone 42.2REAI <400> 102 Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 1 5 10 15

Glu Gly Ile Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro 20 Feb 2020

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 lieu Glu His Asp Lys Ala Tyr Asp 65 70 75 80 2020201242

Lys Gln Leu Glu Gln Gly Asp Asn Pro Tyr Leu Lys Tyr Asn His Ala 85 90 95

Asp Ala Glu Phe Gin Giu Arg Lau 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 Giu Ser Pro Asp Ser Ser Thr Gly Ile Gly Lys Lys Gly Gin 145 150 155 160

Gln Pro Ala Lys L ys 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

Asp Asn Asn Giu 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 Gin Ile 245 250 255

Ser Ser Gin 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 Ser 20 Feb 2020

His Cys His Phe 275 280 285

Pro Arg Asp Trp Gln Arg Leu Ile 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

Thr Asn Asp Gly Val Thr Thr Ile Ala Asn Asn Leu Thr Ser Thr Ile 2020201242

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 Giy 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 Ala His Ser Gln 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 Gln 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

Pro Ile Asn Gly Val Leu Val Phe Gly Glu Thr Gly Ala Ala Asn Lys 20 Feb 2020

530 535 540

Thr Thr Leu Glu Asn Val Leu Met Thr Ser Glu Glu Glu Ile 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 Gln Thr Gin Thr Val Asn Ser Gin Gly 2020201242

580 585 590

Ala Leu Pro Gly Met Val Trp Gin 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 Gin Tyr Ser Thr Gly Gin Val Ser 660 665 670

Val Giu Ile Glu Trp Giu Leu Gln Lys Glu Asn Ser Lys Arg Trp Asn 675 680 685

Pro Glu Ile Gin Tyr Thr Ser Asn Tyr Ala Lys Sex Asn Asn Val Glu 650 695 700

Phe Ala Val Asn Asn Glu Gly Val Tyr Thr Glu Pro Arg Pro Ile Gly 705 710 715 720

Thr Ara Tyr Leu Thr Arg Asn Leu 725

<210> 103 <211> 728 <212> PRT <213> capsid protein of ANV serotype, clone 7.2VP1 <400> 103 Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Gly Asn Leu Ser 1 5 10 15

Glu Gly Ile Arg Giu 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 Lem Pro 35 40 45

Gly Tyr Arg 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 2020201242

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 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 Ile Glv Lys Asn Gly Gin 145 150 155 160

Pro 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

Asp Asn Asn Glu Gly Ala Asp Gly Val Giy 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 Gin 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 Gin Arg Leu Ile Asn Asn Asn Txp 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 2020201242

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 Gln Tyr Gly Tyr Leu Thr Leu Asn Asn Gly Ser Gin Ser Val Gly 370 375 380

Arg Ser Ser Phe Tyr Cys Len 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 Ser. Tyr Ala 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 Net 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

Pro Ile Asn Gly Val Leu Val Phe Gly Lys Thr Gly Ala Ala Asn Lys 530 535 540

WO 03/042397 PCIALTS02133629 20 Feb 2020

Thr Thr Leu Glu Asn Val Leu Met Thr Ser Glu Glu Glu Ile 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 Gln Thr Gln Thr Val Asn Ser Gin Gly 580 585 590

Ala Leu Pro Gly Met Val Trp Gln Asn Arg Asp Val Tyr Leu Gln Gly 2020201242

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 Giu Val Phe Thr Pro 645 650 655 '

Ala Lys Phe Ala Ser Phe Ile Thr Gin Tyr Ser Thr Gly Gin 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 Tie 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 Ile Gly 705 710 715 720

Thr Arg Tyr Leu Thr Arg Asn Leu 725

<210> 104 <211> 728 <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 1 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 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 Gln Leu Glu Gln Gly Asp Asn Pro Tyr Leu Lys Tyr Asn His Ala 2020201242

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 Giu Glu Gly Ala Lys Thr Ala Ser 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

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 Tyx Lys Gin Ile 245 250 255

Ser Ser Gin 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 Gin Arg Leu Ile Asn Asn Asn Trp Gly Phe Arg Fro 20 Feb 2020

290 295 300

Arg Lys Leu Arg Phe Lys Leu Phe Asn Ile Gin Val Lys Glu Val Thr 305 310 315 320

Thr Am 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 Len Gly Ser 2020201242

340 345 350

Ala His Gin 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 Gin Ser Val Gly 370 375 380

Arg Ser Ser Phe Cys 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 Gin Set Len 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 Gln Pile His Gin Ala Gly Pro Asn Thr Val 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 Aen 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 Net Ala Thr Asn Lys Asp Asp Gin Asp Gin Phe Leu 515 520 525

Pro Ile Asn Gly Val Len 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

Thr Asn Pro Val Ala Thr Glu Glu Tyr Gly Val Val Ser Ser Asn Leu 565 570 575

Gan Ser Ser Thr Ala Gly Pro Arg Thr Gin Thr Val Asn Ser Gin Gly 580 585 590

Ala Leu Pro Giy Met Val Trp Gin Asn Arg Asp Val Tyr Leu Gin Giy 2020201242

595 600 605

Pro Ile Trp Ala Glu Ile Pro His Thr Asp Gly Asn Phe His Pro Ser 610 615 620

Pro Lou Met Gly Gly Phe Gly Leu Lys His Pro Pro Pro Gin 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 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 Pro Arg Pro Ile Gly 705 710 715 720

Thr Arg Tyr Leu Thr Arc 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 Lou Ser 1 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 Gin Gin Lys Gin Asp Asp Gly Arg Gly Leu Val Leu Pro 35 40 45

WO 03/042397 Pei/002/33629 20 Feb 2020

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 Giu Gin Gly Asp Asn Pro Tyr Leu Lys Tyr Awl His Ala 85 90 95

Asp Ala Glu Phe Gin Glu Arg Leu Gin Glu Asp Thr Set Phe Gly Gly 2020201242

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 Gln 145 150 155 160

Gln 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

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 Mel' Pro Thr Tyr Asn Asn His Leu Tyr Lys Gin Ile 245 250 255

Set Ser Gin 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 Ile 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

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 2020201242

Ala His Gin 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 Gin Ser Met 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 Sex Tyr Thr Phe Glu Glu Val Pro The 405 410 415

His Ser Ser Tyr Ala 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 Gln Sex 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 Giu Gln Ser Lys Asn Trp Leu Pro Gly Pro Cys Tyr Arg Gin 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 Gin 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 Giu Ile 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 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 Gln Gly 595 600 605 2020201242

Pro Ile Trp Ala Lys Ile Pro His Thr Asp Gly Asa 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 Gly Val Phe Thr Pro 645 650 655

Ala Leu Phe Ala Ser Phe Ile Thr Gin Tyr Ser Thr Gly Gin Val Ser 660 665 670

Val Glu Ile Glu Trp Giu Leu Gin Lys Giu 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 Pro Arg Pro Ile Gly 705 710 715 720

Thr Arg Tyr Leu Thr Arg Asn Leu 725

<210> 106 <211> 728 <212> PRT <213> capsid protein of AM' serotype, clone 42.10 <400> 106 Net Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asa Leu Ser 1 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 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 2020201242

Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro 115 120 125

Leu Gly lieu 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 Arg L ys Gly Gin 145 150 155 160

Gin 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 Ile 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 Ile 245 250 255

Ser Ser Gin 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 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 Gln Val Lys Glu Val Thr 305 310 315 320

Thr Asn Asp Gly Val Thr Thr Ile Ala Apn Asn Leu Thr Ser Thr Ile 325 330 335

Gln Val Phe Ser Asp Ser Glu Tyr Gin Leu Pro Tyr Val Leu Gly Set 340 345 350

Ala His Gin Gly Cys Leu Pro Pro Phe Pro Ala Asp Val Phe Met Ile 2020201242

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 Set 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 Gln Ser Leu Asp Arg Leu Met Asn Pro 420 425 430

Leu Ile Asp Gin Tyr Leu Tyr Tyr Lea Ala Arg Thr Gin Ser Thr Thr 435 440 445

Gly Ser. Thr Arg Glu Leu Gin Phe His Gln Ala Gly Pro Asn Thr Met 450 455 460

Ala Glu Gin Sex Lys Asn Trp Leu Pro Gly Pro Cys Tyr Arg Gin 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 Sex 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 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 Ile Lys Thr 545 550 555 560

Thr Asn Pro Val Ala Thr Glu Glu Tyr Gly Val Val Ser Ser Pon Leu 20 Feb 2020

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 Awl Arg Asp Val Tyr Leu Gin Gly 595 600 605

Pro Ile Trp Ala Lys Ile Pro His Thr Asp Gly Asn Phe His Pro Ser 610 615 620 2020201242

Pro Leu Met Gly Gly Phe Gly Leu Lys His Pro Pro Pro Gln Ile Lou 625 630 635 640

Ile Lys Awl Thr Pro Val Pro Ala Asn Pro Pro Glu Val Phe Thr Pro 645 650 655

Ala Lys Phe Ala Ser Phe 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 Pro Arg Pro Ile Gly 705 710 715 720

Thr Arg Tyr Lou Thr Arg Asn Leu 725

<210> 107 <211> 728 <212> PRT <213> capsid protein of ANAT serotype, clone 42.3B <400> 107 Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 1 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 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 Gln 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 2020201242

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 Ile Gly Lys Lys Gly Gin 145 150 155 160

Gin Pro Ala Lys Lys Lys Len Asn Phe Gly Gin Thr Gly Asp Ser Glu 165 170 175

Ser Val Pro Asp Pro Gin Pro Ile 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 Ile 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 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 Lau Thr Sex. Thr Ile 325 330 335

Gin Val Phe Ser Asp Ser Glu Tyr Gin Leu Pro Tyr Val Leu Gly Sex. 340 345 350

Ala His Gin 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 Gin Ser Val Gly 2020201242

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 Ala His Ser Gln Ser Leu Asp Arg Leu Met Asn Pro 420 425 430

Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ala Arg Thr Gin Ser Thr Thr 435 440 445

Gly Ser Thr Arg Glu Lou Gln 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 Thr Sex Asn Phe Ala Trp 485 490 495

Thr Gly Ala Thr Lys Tyr His Leu Asn Gly Arg Asn Sex 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 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 Giu Glu Glu Ile Lys Thr 545 550 555 560

Thr Asn Pro Val Ala Thr Glu Gln 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 Gln Asn Arg Asp Val Tyr Leu Gin Gly 595 600 605

Pro Ile Trp Ala Lys Ile Pro His Thr Asp Gly Asn Phe His Pro Ser 610 615 620 2020201242

Pro Leu Met Gly Gly Phe Gly Leu Lys His Pro Pro Pro Gin 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 Gin Tyr Ser Thr Gly Gln Val Ser 660 665 670

Val Glu Tie Glu Trp Glu Leu Gln Lys Glu Asn Ser Lys Aria Trp Asn 675 680 685

Pro Giu Ile Gin Tyr Thr Ser Asn Tyr Ala Lys Ser Asn Asn Val Glu 690 695 700

Phe Ala Val Asn Asn Giu Gly Val Tyr Thr Glu Pro Arg Pro Ile Gly 705 710 715 720

Thr Arg Tyr Leu Thr Arg Asn Leu 725

<210> 108 <211> 728 <212> PRT <213> capsid protein of AAV serotype, clone 42.11 <400> 108 Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 1 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 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 Giu 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 Gln Glu Arg Leu Gin G1u Asp Thr Ser Phe Gly Gly 100 105 110

Asn lieu Gly Arg Ala Val Phe Gin Ala Lys Lys Arg Val Leu Glu Pro 2020201242

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 Lau Asn Phe Gly Gin Thr Gly Asp Ser Glu 165 170 175

Ser Val Pro Asp Pro Gin Pro Ile Gly Glu Pro Pro Ala Gly Pro Ser 180 185 190

Gly Lau 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 Ile 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 Gin Arg Leu Ile Asn Asn Asti Trp Gly Phe Arg Pro 290 295 300

Arg Lys lieu 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 Awl Asn Leu Thr Ser Thr Ile 20 Feb 2020

325 330 335

Gln 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 ay Tyr Leu Thr Leu Asn Asn Gly Ser Gln Ser Val Gly 370 375 380 2020201242

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 Ala His Ser Gln Ser Leu Asp Arg lieu Met Asn Pro 420 425 430

Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ala Arg Thr Gln 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 Gln Ser Lys Asn Trp Leu Pro Gly Pro Cys Tyr Arg Arg Gin 465 470 475 480

Arg lieu Ser Lys Asp 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 Let 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 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 Ile Lys Thr 545 550 555 560

Thr Asn Pro Val Ala Thr Giu Glu Tyr Gly Val Val Ser Ser Asn 565 570 575

Gln Ser Ser Thr Ala Gly Pro Gin Thr Gin Thr Val Asn Ser Gln Gly 580 585 590

Ala lieu Pro Gly Met Val Trp Gin Awl Arg Asp Val Tyr Leu Gin 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 Gin Ile Leu 2020201242

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 Gin Tyr Ser Thr Gly Gin Val Ser 660 665 670

Val Glu Ile Glu Trp Glu Leu Gln Lys Giu Asn Ser Lys Arg Trp Asn 675 680 685

Pro Giu 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 Pro Arg Pro Ile Gly 705 710 715 720

Thr Arg Tyr Leu Thr Arg Asn Leu 725

<210> 109 <211> 729 <212> PRT <213> capsid protein of AAV serotype, clone F1VP1

<400> 109

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 1 5 10 15

Glu Gly Ile Arg Glu Txp Tip 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 20 Feb 2020

85 90 95

Asp Ala Glu Phe Gin Glu Arg Leu Gin Gin 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 2020201242

Pro Ile Asp 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

Sex. Val Gly Ser Sly Thr Met Ala Ala Gly Gly Sly Ala Pro Met Ala 195 200 205

Asp Asn Asn Glu Gly Ala Asp Gly Val Sly 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 Lou Pro Thr Tyr Asn Asn His Len Tyr Lys Gln Ile 245 250 255

Ser Ser Ser Ser. Ser Gly Ala Thr Asn Asp Asn His Tyr Phe Gly Tyr 260 265 270

Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe His Cys His Phe 275 280 285

Ser Pro Arg Asp Trp Gin Arg Len Tie Asn Asn Asn Trp Gly Phe Arg 290 295 300

Pro Lys Lys Leu Arg Phe Lys Len Phe Asn Ile Gin Val Lys Glu Val 305 310 315 320

Thr Thr Asn Asp Gly Val Thr Thr Ile Ala Asn Asn Leu Thr Ser Thr 325 330 335

Leu Pro Tyr Val leu Giy 20 Feb 2020

Val Gln Val Phe Ser Asp Ser Giu Tyr Gln 340 345 350

Ser Ala His Gin Gly Cys Leu Pro Pro Phe Pro Ala Asp Val Phe Met 355 360 365

Ile Pro Gin Tyr Gly Tyi Leu Thr Leu Asn Asn Gly Ser Gln Ser Val 370 375 380

Gly Arg Ser Ser Phe Tyr Cys Len Glu Tyr Phe Pro Ser Gln Met Leu 2020201242

385 390 395 400

Arg Thr Gly Asn Asn Phe Glu Phe Ser Tyr Set Phe Glu Asp Val Pro 405 410 415

Phe His Ser Ser Tyr Ala His Ser Gin Ser Len Asp Arg Leu Met Asn 420 425 430

Pro Leu Tie Asp Gin Tyr Leu Tyr Tyr Len Ala Arg Thr Gin Ser Thr 435 440 445

Thr Gly Ser Thr Arg Giu Len Gin Phe His Gam Ala Gly Pro Asn Thr 450 455 460

Met Ala Glu Gin Ser Lys Asn Trp Len. Pro Gly Pro Cys Tyr Arg Gin 465 470 475 480

Gln Gly Leu Ser Lys Asn Len Asp Phe Asn Asn Asn Ser Asn Phe Ala 485 490 495

Trp Thr Ala Ala Thr Lys Tyr His Len Asn Gly Arg Asn Sex . Leu Thr 500 505 510

Asn Pro Giy Ile Pro Met Ala Thr Asn Lys Asp Asp Gin Asp Gin Phe 515 520 525

Phe Pro Ile Asn Gly Val Leu Val Phe Gly Lys Thr Gly Ala Ala Asn 530 535 540

Lys Thr Thr Len Glu Asn Val Leu Met Thr Ser Glu Glu Gin Ile Lys 545 550 555 560

Thr Thr Asn Pro Val Ala Thr Gin Glu Tyr Gly Val Val Ser Ser Asn 565 570 575

Leu Gln Pro 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 20 Feb 2020

595 600 605

Gly Pro Ile Trp Ala Lys Ile 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 Ile Lys Asn Thr Pro Val Pr6 Ala Asn Pro Pro Glu Val Phe Thr 645 650 655 2020201242

Pro Ala Lys Phe Ala Ser Phe Ile Thr Gin Tyr Ser Thr Gly Gin Val 660 665 670

Ser Val Glu Ile Giu Trp Glu Leu Gin . Lys Giu Asn Ser Lys Arg Trp 675 680 685

Asn Pro Giu Ile 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 Len Pro Arg Asn Leu 725

<210> 110 <211> 729 <212> PRT <213> capsid protein of AAV serotype, clone F5VP1@3 <400> 110 MetAla Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 1 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 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 Gln 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 2020201242

Pro Ile Asp 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 Sex Glu 165 170 175

Ser Val Pro Asp Pro Gln Pro Leu Gly Glu Pro Pro Ala Ala Pro Ser 180 185 190

Ser Val Gly Ser Gly Thr Met Ala Ala Gly Gly Gly Ala Pro Thr 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 Ile 245 250 255

Ser Ser Ser Ser Ser Gly Ala Thr Asn Asp Asn His Tyr Phe Gly Tyr 260 265 270

Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe His Cys His Phe 275 280 285

Sex Pro Arg Asp Trp Gin Arg Leu Ile Asn Asn Asn Trp Gly Phe Arg 290 295 300

Pro Lys Lys Leu Arg Phe Lys Leu Phe Asn Ile Gin Val Lys Glu Val 305 310 315 320

Thr Thr Asn Asp Gly Val Thr Thr Ile Ala Asn Asn Leu Thr Ser Thr 325 330 335

Val Gln Val Phe Ser Asp Ser Glu Tyr Gln Leu Pro Tyr Val Leu Gly 340 345 350

WO 03/042397 PCT/ITS02/33629 20 Feb 2020

Ser Ala His Gin Gly Cys Leu Pro Pro Phe Pro Ala Asp Val Phe Met 355 360 365

Ile 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 2020201242

Arg Thr Gly Asn Asn Phe Giu 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 Ile Asp Gin Tyr Leu Tyr Tyr Leu Ala Arg Thr Gln Ser Thr 435 440 445

Thr Gly Ser Thr Arg Glu Leu Gin Phe His Gin Ala Gly Pro Asn Thr 450 455 460

Mot Ala Glu Gin Ser Lys Asn Trp Leu Pro Gly Pro Cys Tyr Arg Gin 465 470 475 480

Gin Arg 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 Ile Pro Met Ala Thr Asn Lys Asp Asp Glu Asp Gin Phe 515 520 525

Phe Pro Ile 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 Ile 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 Gln 580 585 590

Gly Ala Leu Pro Gly Met Val Trp Gln Asn Axg 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 Glu His Pro Pro Pro Gin Ile 625 630 635 640

Len Ile Lys Asn Thr Pro Val Pro Ala Asn Pro Pro Glu Val Phe Thr 645 650 655 2020201242

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 Gln Lys Glu Asn Ser Lys Arg Trp 675 680 685

Asn Pro Glu Ile Gln Tyr Thr Ser Asn Tyr Ala Lys Ser Asn Asn Val 690 695 700

Gin 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> 111 <211> 729 <212> PRT <213> capsid protein of ARV serotype, clone F3VP1 <400> 111 Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 1 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 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 Len Asp Lys Gly Glu Pro 50 55 60

Val Asn Ala Ala Asp Ala Ala Ala Leu Giu His Asp Lys Ala Tyr Asp 65 70 75 80

Gin Gln 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 Gln Glu Asp Thr Ser Phe Gly Gly 20 Feb 2020

100 105 110

Asn Leu Gly Arg Ala Val Phe Gin Ala Lys Lys Arg Val Lau 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 Gly Ser Pro Asp Ser Ser Thr Gly Ile Gly Lys Lys Gly Gin 145 150 155 160 2020201242

Gin Pro Ala Lys Lys Lys Leu Asn Phe Gly Gin Thr Gly Asp Sex Glu 165 170 175

Ser Val Pro Asp Pro Gin Pro Leu Gly Glu Pro Pro Ala Ala Pro Ser 180 185 190

Ser Val 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 Sex 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 Ile 245 250 255

Ser Sex Ser Ser Ser Gly Ala Thr Asn Asp Asn His Tyr Phe Gly Tyr 260 265 270

Sex Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe His Cys His Phe 275 280 285

Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn Asn Trp Gly Phe Arg 290 295 300

Pro Lys Lys Leu Arg Phe Lys Leu Leu Asn Ile Gin Val Lys Giu Val 305 310 315 320

Thr Thr Asn Asp Gly Val Thr Thr Ile Ala Asn Asn Leu Thr Ser Thr 325 330 335

Val Gin Val Phe Ser Asp Sex Giu Tyr Gin Leu Pro Tyr Val Leu Gly 340 345 350

Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro Ala Asp Val Phe Met 20 Feb 2020

355 360 365

Ile Pro Gin Tyr Gly Tyr Leu Thr Leu Asp Asn Sly 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 Awl Phe Glu Phe Ser Tyr Ser Phe Giu Asp Val Pro 2020201242

405 410 415

Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu Asp Arg Leu Met Asn 420 425 430

Pro Lau Ile 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

Gln Arg Leu Ser Lys Asn Leu Asp Phe Asn Asn Asn Sex 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 Ile Pro Met Ala Thr Asn Lys Asp Asp Glu Asp Gin Phe 515 520 525

Phe Pro Ile 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 Ile Lys 545 550 555 560

Thr Thr Asn Pro Val Ala Thr Glu Giu Tyr Gly Val Val Ser Ser Asn 565 570 575

Leu Gin Ser Ser Thr Ala Gly Pro Gin Ser Gln Thr Ile Asn Ser Gin 580 585 590

Gly Ala Leu Pro Gly Met Val Trp Gln Asn Arg Asp Val Tyr Leu Gln 595 600 605

WO 03/042397 PCTATS02/33629

Gly Pro lie Trp Ala Lys Ile Pro His Thr Asp Sly Asn Phe His Pro 20 Feb 2020

610 615 620

Ser Pro Leu Met Gly Gly Phe Gly Leu Lys 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 2020201242

Ser Val Glu Ile Glu Trp Glu Leu Gin Lys Glu Asn Ser Lys Arg Trp 675 680 685

Asn Pro Giu Ile 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 42.65 <400> 112 Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Her 1 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 Gin Gin Lys Gin Asp Asp Gly Arg Sly lieu 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 Giu 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 Gln Glu Asp Thr Sex Phe Gly Gly 100 105 110

WO 03/042397 PCT/ITS02/33629 20 Feb 2020

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 Val Giu Pro Ser Pro Gin Arg Ser Pro Asp Ser Ser Thr Gly Ile 145 150 155 160 2020201242

Gly Lys Thr Gly Gin Gln Pro Ala Lys Lys Arg Leu Asn Phe Gly Gin 165 170 175

Thr Gly Asp Ser Glu Ser Val Pro Asp Pro Gin Pro Ile Gly Giu 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

Leu Tyr Lys Gin Tie Ser Asn Gly Thr Sex 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 Ile Asn 290 295 300

Asn Asn Trp Gly Phe Arg Pro Arg Lys Leu Arg Phe Lys Leu Phe Asn 305 310 315 320

Ile Gin Val Lys Glu Val Thr Thr Asp Asp Gly Val Thr Thr Ile Ala 325 330 335

Asn Asn Leu Thr Ser Thr Ile Gin Val Phe Ser Asp Ser Glu Tyr Gln 340 345 350

Leu Pro Tyr Val Leu Gly Ser Ala His Gin Gly Cys Leu Pro Pro Phe 355 360 365

WO 03/042397 PCTTUS02/33629 20 Feb 2020

Pro Ala Asp Val Phe Met Ile Pro Gin Tyr Gly Tyr Leu Thr Leu Asn 370 375 380

Asn Gly Ser Gin Ser Val Gly Arg Sex 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 2020201242

Thr Phe Glu Glu 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 Gln Tyr Leu Tyr Tyr Leu 435 440 445

Ala Arg Thr Gln Ser Thr Thr Gly Sex Thr Arg Glu Leu Gin Phe His 450 455 460

Gin Ala Giy Pro Asn Thr Met Ala Glu Gln Ser Lys Asn Trp Leu Pro 465 470 475 480

Gly Pro Cys Tyr Arg Gin Gin Arg Leu Sex Lys Asn Ile Asp Ser Asn 485 490 495

Asn Asn Ser Asn Phe Ala Trp Thr Gly Ala Thr Lys Tyr His Lett Asn 500 505 510

Gly Arg Asn Ser Leu Thr Asn Pro Gly Val Ala Net Ala Thr Asn Lys 515 520 525

Asp Asp Glu Asp Gin Phe Phe Pro Ile 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

Sex Glu Glu Glu Ile 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 Gln Thr 580 585 590

Gin Thr Val Asn Ser Gin Gly Ala Leu Pro Gly Net Val Trp Gin Asn 595 600 605

Arg Asp Val Tyr Leu Gin Gly Pro Ile Trp Ala Lys Ile Pro His Thr 610 615 620

Asp Gly Asn Phe His Pro Ser Pro Leu Met Asp GLy Phe Gly Leu Lys 625 630 635 640

His Pro Pro Pro Gln Ile Leu Tie Lys Asn Thr Pro Val Pro Ala Asn 645 650 655

Pro Pro Glu Val Phe Thr Pro Ala Lys Phe Ala Ser Phe Ile Thr Gln 660 665 670 2020201242

Tyr Ser Thr Gly Gln Val ser Val Glu Ile Glu Trp Glu Leu Gin Lys 675 680 685

Glu Asn Ser Lys Arg Trp Awl Pro Glu Ile Gin Tyr Thr ser Asn Tyr 690 695 700

Ala Lys Ser Asn Asn Val Glu Phe Ala Val Asn Asn Glu Gly Val Tyr 705 710 715 720

Thr Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Asn Leu 725 730 735

<210> 113 <211> 685 <212> PRT <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 1 5 10 15

Giu Gly Ile Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro 20 25 30

Lys Ala Asn Gin 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 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 20 Feb 2020

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 Ile 145 150 155 160

Gly Lys Thr Gly Gin Gin Pro Ala Lys Lys Arg Lau Asn Phe Gly Gin 165 170 175 2020201242

Thr Gly Asp Ser Glu Ser Val Pro Asp Pro Gin Pro Tie 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 lieu 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 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 Giu 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 Gln Gly Cys Leu Pro Pro Phe 355 360 365

Pro Ala Asp Val Phe Met Ile Pro Gin Tyr Gly Tyr Leu Thr Leu Asn 20 Feb 2020

370 375 380

Asn Gly Ser Gin Ala Val Gly Arg Ser Ser Phe Tyr Cys Lau Glu Tyr 385 390 395 400

Phe Pro Ser Gin Met Leu Arg Thr Gly Asn Asn Phe G1u Phe Ser Tyr 405 410 415

Gln Phe Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gin Ser 420 425 430 2020201242

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 Asn Ser Asn Phe Ala Trp Thr Gly Ala Thr Lys Tyr His Ieu 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 Ile Am Gly Val Leu Val Phe Gly 530 535 540

Lys Thr Gly Ala Ala Asn Lys Thr Thr Leu Glu Asa Val Leu Met Thr 545 550 555 560

Sex Glu Glu Glu Ile 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 Gln Gly Ala Leu Pro Gly Met Val Trp Gin Asn 595 600 605

Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro His Thr 610 615 620

Asp Gly Asn Phe His Pro Ser Pro Leu Met Gly Gly Phe Sly Leu Lys 20 Feb 2020

625 630 635 640

His Pro Pro Pro Gin Ile Leu Ile Lys Tyr Thr Ser Asn Tyr Tyr Lys 645 650 655

Ser Thr Asn Val Asp Phe Ala Val Asn Thr Glu Sly Thr Tyr Ser Glu 660 665 670

Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Asn Leu 675 680 685 2020201242

<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 1 5 10 15

Gly Leu Arg Glu Phe Let Gly Leu Glu Ala Gly Pro Pro Lys Pro Lys 20 25 30

Pro ken Gin Gin His Gin Asp Gin Ala Arg Gly Leu Val Leu Pro Gly 35 40 45

Tyr Asn Tyr Leu Gly Pro Gly Asn Sly Leu Asp Arg Gly Giu Pro Val 50 55 60

Asn Arg Ala Asp Glu Val Ala Arg Glu His Asp Ile Ser Tyr Am Glu 65 70 75 80

Gin Leu Glu Ala Gly Asp Asn Pro Tyr Leu Lys Tyr Asn His Ala Asp 85 90 95

Ala Glu Phe Gln Glu Lye Leu Ala Asp Asp Thr Ser Phe Gly Sly 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 Sly Ala Lys Thr Ala Pro Thr Gly Lys Arg Ile 130 135 140

Asp Asp His Phe Pro Lys Arg Lys Lys Ala Arg Thr Glu Glu Asp Ser 145 150 155 160

Lys Pro Ser Thr Ser Ser Asp Ala Glu Ala Gly Pro Ser Gly Ser Gin 165 170 175

Gin Leu Gin Ile Pro Ala Gin Pro Ala Ser Ser Leu Gly Ala Asp Thr 180 185 190

Met Ser Ala Gly Gly Gly Gly Pro Leu Gly Asp Asn Asn Gln Gly Ala 195 200 205

Asp Gly Val Gly Asn Ala Ser Gly Asp Trp His Cys Asp Ser Thr Trp 210 215 220 2020201242

Met Gly Asp Arg Val Val Thr Lys Ser Thr Arg Thr Trp Val Leu Pro 225 230 235 240

Ser Tyr Asn Asn His Gin Tyr Arg Glu Ile Lys Ser Gly Ser Val Asp 245 250 255

Giy Ser Asn Ala Asn Ala Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr 260 265 270

Phe Asp Phe Asn Arg Phe His Ser His Trp Ser Pro Arg Asp Trp Gin 275 280 285

Arg Len Ile Asn Asn Tyr Trp Gly Phe Arg Pro Arg Ser Leu Arg Val 290 295 300

Lys Ile Phe Asn Ile Gin Val Lys Glu Val Thr Val Gin Asp Ser Thr 305 310 315 320

Thr Thr Ile Ala Asn Asn Leu Thr Ser Thr Val Gin Val Phe Thr Asp 325 330 335

Asp Asp Tyr Gln Leu Pro Tyr Val Val Gly Asn Gly Thr Glu Gly Cys 340 345 350

Leu Pro Ala Phe Pro Pro Gln Val Phe Thr Leu Pro Gln Tyr Gly Tyr 355 360 365

Ala Thr Leu Asn Arg Asp Asn Thr Glu Awl Pro Thr Glu Arg Ser Ser 370 375 380

Phe Phe Cys Leu Glu Tyr Phe Pro Ser Lys Met Leu Arg Thr Gly Asn 385 390 395 400

Asn Phe Glu Phe Thr Tyr Asn Phe Glu Glu Val Pro Phe His Ser Ser 405 410 415

Phe Ala Pro Ser Gin Asn Leu Phe Lys Leu Ala Asn Pro Leu Val Asp 420 425 430

Gin Tyr Leu Tyr Arg Phe Val Ser Thr Asn Asn Thr Gly Gly Val Gin 435 440 445

Phe Asn Lys Asn Leu Ala Gly Arg Tyr Ala Asn Thr Tyr Lys Asn Trp 450 455 460

Phe Pro Gly Pro Met Gly Arg Thr Gin Gly Trp Asn Leu Gly Ser Gly 465 470 475 480 2020201242

Val Asn Arg Ala Sex' Val Ser Ala Phe Ala Thr Thr Asn Arg Met Glu 485 490 495

Leu Glu Gly Ala Sex Tyr Gin Val Pro Pro Gln Pro Asn Gly Met Thr 500 505 510

Asn Asn Leu Gin Gly Ser Asn Thr Tyr Ala Leu Giu Asn Thr Met Ile 515 520 525

Phe Asn Sex Gin Pro Ala Asn Pro Gly Thr Thr Ala Thr Tyr Leu Glu 530 535 540

Gly Asn Met Leu Ile Thr Ser Glu Sex Glu Thr Gin Pro Val Asn Arg 545 550 555 560

Val Ala Tyr Asn Val Gly Gly Gln Met Ala Thr Asn Asn Gin Sex Ser 555 570 575

Thr Thr Ala Pro Ala Thr Gly Thr Tyr Asn Leu Gln Glu Ile Val Pro 580 585 590

Gly Ser Val Trp Met Glu Arg Asp Val Tyr lieu Gin Gly Pro Ile Trp 595 600 605

Ala Lys Ile Pro Glu Thr Gly Ala His Phe His Pro Ser Pro Ala Met 610 615 620

Gly Gly Phe Gly Leu Lys His Pro Pro Pro Met Met Leu Ile Lys Asn 625 630 635 640

Thr Pro Val Pro Gly Asn Ile Thr Ser Phe Ser Asp Val Pro Val Ser 645 650 655

Ser Phe Ile Thr Gin Tyr Ser Thr Gly Gin Val Thr Val Glu Met Glu 660 665 670

Trp Glu Leu Lys Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln 675 680 685

Tyr Thr Asn Asn Tyr Asn Asp'Pro Gin Phe Val Asp Phe Ala Pro Asp 690 695 700

Ser Thr Gly Glu Tyr Arg Thr Thr Arg Pro Ile Gly Thr Arg Tyr Ieu 705 710 715 720

Thr Arg Pro lieu 2020201242

<210> 115 <211> 9 <212> DNA <213> DraIII restriction enzyme site

<400> 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

accagcaccc gaacctgggt cctgcccacc tacaacaacc acatctacaa gcaaatctcc 120

agcgagacag gagccaccaa cgacaaccac tacttcggct acagcacccc ctgggggtat 180

tttgacttta acagattcca ctgccacttt tcaccacgtg actggcagcg actcatcaac 240

aacaactggg gattc 255

<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 gctacagcac cccctggggg 180

tattttgact ttaacagatt ccactgccac ttctcaccac gtgactggca gcgactcatc 240

aacaacaact ggggattc 258

<210> 119 <211> 255 <212> DNA <213> adeno-associated virus serotype 12

<400> 119 ggtaattcct ccggaaattg gcattgcgat tccacatggc tgggcgaccg agtcattacc 60 2020201242

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 A3.1vp1

<400> 120 atggctgccg atggttatct tccagattgg ctcgaggaca ctctctctga aggaatcaga 60

cagtggtgga agctcaaacc tggcccacca 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 tacgtctttc 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 accetcaacc aatcggagaa ccccccgcag ccccctctgg tgtgggatct 600

aatacaatgg cttcaggcgg tggggcacca atggcagaca ataacgaagg 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

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 2020201242

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 tgygaggctt tggactgaaa 1920 caccctcctc cccagatcct gatcaaaaac acacctgtgc cagcgaatcc cgcgaccact 1980 ttcactcctg gaaagtttgc ttcgttcatt acccagtatt ccaccggaca ggtcagcgtg 2040 gaaatagagt gggagctgca gaaagaaaac agcaaacgct ggaacccaga aattcagtac 2100 acctccaact acaacaagtc ggtgaatgtg gagtttaccg tggacgcaaa cggtgtttat 2160 tctgaacccc gccctattgg cactcgttac cttacccgga acttg 2205

Claims (2)

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 I to 738 of SEQ ID NO: 81 or a sequence at least 95% identical to the full length of amino acids I to 738 of SEQ ID NO: 81, 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, wherein the gene product is ornithine transcarbamylase, glucose-6 phosphatase, phenylalanine hydroxylase, argininosuccinate synthetase or a dystrophin protein.

2. The recombinant AAV according to claim 1, wherein the sequence of the vp l proteins is at least 97% identical to the full length of amino acids I to 738 of SEQ ID NO: 81.

3. The recombinant AAV according to claim 1, wherein the sequence of the vp l proteins is at least 99% identical to the full-length of amino acids 1 to 738 of SEQ ID NO: 81.

4. The recombinant AAV according to claim 1, wherein the sequence of the vp I proteins is the full-length of amino acids I to 738 of SEQ ID NO: 81.

5. A recombinant adeno-associated virus (AAV) having an AAV capsid comprising AAV vp Iproteins, AAV vp2 proteins having a sequence of amino acids 138 to 738 of SEQ ID NO:81 (rh.10) or a sequence at least 95% identical to the full-length of amino acids 138 to 738 of SEQ ID NO: 81, 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, wherein the gene product is ornithine transcarbamylase, glucose 6-phosphatase, phenylalanine hydroxylase, argininosuccinate synthetase or a dystrophin protein.

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: 81.

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: 81.

8. The recombinant AAV according to claim 5, wherein the sequence of the vp2 proteins is the full-length of amino acids 138 to 738 of SEQ ID NO: 81.

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:81 (rh.10) or a sequence at least 95

% identical to the full-length of amino acids 204 to 738 of SEQ ID NO: 81, 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, wherein the gene product is ornithine transcarbamylase, glucose 6-phosphatase, phenylalanine hydroxylase, argininosuccinate synthetase or a dystrophin protein.

10. The recombinant AAV according to claim 9, wherein the sequence of the vp3 proteins is at least 97% identical to the full length of amino acids 204 to 738 of SEQ ID NO: 81.

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: 81.

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: 81.

13. The recombinant AAV according to any one of claims 1 to 12, wherein the AAV ITR is from AAV2.

14. A composition comprising a pharmaceutically compatible carrier and at least the recombinant AAV according to any one of claims 1 to 13. 15. A method for delivering a transgene product to a subject, said method comprising administering the adeno-associated virus (AAV) according to any one of claims I to 13.

16. The recombinant AAV according to any one of claims I to 13, wherein the gene product is ornithine transcarbamylase.

17. The recombinant AAV according to any one of claims I to 13, wherein the gene product is glucose-6-phosphatase.

18. The recombinant AAV according to any one of claims I to 13, wherein the gene product is phenylalanine hydroxylase.

19. The recombinant AAV according to any one of claims I to 13, wherein the gene product is argininosuccinate synthetase.

20. The recombinant AAV according to any one of claims I to 13, wherein the gene product is a dystrophin protein.

WO 03/042397 20 Feb 2020

FIG . 1A

1 50 42_2 42_8 42_15 42 5b 42 1b. 2020201242

4213 42:3a 42_4 42_5a 42_10 42 3b 42:11 42_6b 43_1 43_5 43J2 43_20 43 21 43 23 43:25 44 1 44y5 22310 223_2 223 4 223-5 223 6 2237 A3 4 A3^5 A3 7 A3_3 42_12 AAV1 TTGCCCACTC CCTCTCTGCG CGCTCGCTCG CTCGGTGGGG CCTGCGGACC AAV2 TTGGCCACTC CCTCTCTGCG CGCTCGCTCG CTCACTGAGG CCGGGCGACC AAV3 TTGGCCACTC CCTCTATGCG CACTCGCTCG CTCGGTGGGG CCTGGCGACC AAV8 AAV9 AAV7 TTGGCCACTC CCTCTATGCG CGCTCGCTCG CTCGGTGGGG CCTGCGGACC 44 2

1/105

Fig. IB

51 100

Rep binding site 42 2 42 8 42_15 2020201242

42_5b 42_1b 42_13 42 3a 42 4 42 5a 42 10 42_3b 42_11 42_6b 1 43_5 43_12 43_20 43 21 43u23 43 25 44_1 44_5 223_10 223_2 223 4 2235 2236 223_7 A3_4 A3 5 A3 7 A3_3 42_12 AAV1 AAAGGTCCGC AGACGGCAGA GCTCTGCTCT GCCGGCCCCA CCGAGCGAGC AAV2 AAAGGTCGCC CGACGCCCGG GCTTTGCCCG GGCGGCCTCA GTGAGCGAGC AAV3 AAAGGTCGCC AGACGGACGT GCTTTGCACG TCCGGCCCCA CCGAGCGAGC AAVB AAV9 AAV7 AAAGGTCCGC AGACGGCAGA GCTCTGCTCT GCCGGCCCCA CCGAGCGAGC 44 2

Rep binding site

2/105

Fig. 1C

101

Rep binding site 150 ITRS 42_2 42_8 42 15 2020201242

42_5b 42—lb 42_13 4213a 42_4 42_5a 42_10 42 3b 42 11 42:0 43_1 435 43_12 43_20 43 21 4323 43:25 44_1 44_5 223_10 223_2 223_4 223_5 223 6 2237 A3 4 A3-5 A3_7 A3_3 42_12 AAV1 GAGCGCGCAG AGAGGGAGTG GGCAACTCCA TCACTAGGGG TAATCGCGAA AAV2 GAGCGCGCAG AGAGGGAGTG GCCAACTCCA TCACTAGGGG TTC AAV3 GAGTGCGCAT AGAGGGAGTG GCCAACTCCA TCACTAGAGG T AAV8 CAG AGAGGGAGTG GCCAACTCCA TCACTAGGGG TAG.CGCGAA AAV9 CAG AGAGGGAGTG GCCAACTCCA TCACTAGGGG TAATCGCGAA AAV7 GAGCGCGCAG' AGAGGGAGTG GC1AACTCCA TCACTAGGGG TA.CCGCGAA 44 2 ep binding site TRS

3/105

Fig. 1D

151 200 4 2 2 42 8 42_15 4 2_5b 4 2 lb 4 2 13 4 2 3a 2020201242

42 4 42_5a 4210 42 3b 4 2 11 42_6b 43 1 435 ' 43 12 4320 43_21 4323 43_ _25 4 4 1 44 5 223_10 223 2 22344 2 2 3—R 2236 _ 22377 A3 4 A3 - 5 A37 A3 3 4 2 12 AAV- 1 GCGCCTCCCA CGCTGCCGCG TCAGCGCTGA CGTAAATTAC GTCATAGGGG AAV2 GAGGGGTGGA CTG GTCGTGACGT GAATTACGTC ATAGGGT TAG AAV3 ATG GCAGTGACGT AACGCGAAGC GCGCGAAGCG AGACCACGCC AAV8 GCGCCTCCCACGCTGCCGCG TCAGCGCTGA CGTAAATTAC GTCATAGGGG AAV9 GCGCCTCCCA CGCTGCCGCG TCAGCGCTGA CGTAGATTAC GTCATAGGGG AAV7 GCGCCTCCCA CGCTGCCGCG TCAGCGCTGA CGTAAATCAC GTCATAGGGG 44 2

Fig. 1E

201 250 Ebox/USF YY1 4 2_2 42_8 42_15 42 5b 42 lb 2020201242

42:13 42_3a 424 42_5a 42_10 42 3b 42 11 4 2 6b 43_1 4 3 5 4 3 12 43 20 43_2121 43 23 43:25 441 44-5 22 3 -170 22i 2 22 3 4 22 3 5 223 - 6 2237 A3^4 A3 5 A37 A3_3 42_12 AAV1 AGTGGTCCTG TATTAGCTGT CACGTGAGTG CTTTTGCGAC ATTTTGCGAC AAV2 GGAGGTCCTG TATTAGAGGT CACGTGAGT. GTTTTGCGAC ATTTTGCGAC AAV3 T AC CAGCTG CGTCAGCAGT CAGGTGACC. CTTTTGCGAC AGTTTGCGAC AAV8 AGTGGTCCTG TAT TAGCTGT CACGTGAGTG CTTTTGCGGC ATTTTGCGAC AAV9 AGTGGTCCTG TATTAGCTGT CACGTGAGTG CTTTTGCGAC ATTTTGCGAC AAV7 AGTGGTCCTG TATTAGCTGT CACGTGAGTG CTTTTGCGAC ATTTTGCGAC _ 44 2

Ebox/USF YY1

5/105

Fig. 1F

251 300

P5/TATA

42 2 428 2020201242

42 15 42 5b 42_1b 4213 42:3a 42_4 42_5a 42_10 42 3b 42 11 42:6b 43 1 43 5 43_12 43 20 4321 43:23 43_25 44 1 44 5 223_TO 223 2 223_4 223 5 223_6 2237 A3 4 A3 5 A3_7 A3J 42_12 AAV1 ACCACGTGGC CATTTAGGGT ATATATGGCC GAGTGAGC.G AGCAGGATCT AAV2 ACCATGTGGT CACGCTGGGT ATTTAAGCCC GAGTGAGC.A CGCAGGGTCT 110, AAV3 ACCACGTGGC CGCTGAGGGT ATATATTCTC GAGTGAGC GA ACCAGGAGCT AAVB ACCACGTGGC CATTTGAGGT ATATATGGCC GAGTGAGC.G AGCAGGATCT AAV9 ACCACATGGC CATTTGAGGT ATATATGGCC GAGTGAGC.G AGCAGGATCT AAV7 ACCACGTGGC CATTTGAGGT ATATATGGCC GAGTGAGC.G AGCAGGATC,f 44_2 P5/TAT.

6/105

Fig. 1G

301 350 YY1/P5 RNA Rep78/68 start 42_2 4 42_8 42 15 42_5b 2020201242

42 lb 4213 42_3a 42_4 42 5a 42__10 42 3b 42 11 42 6b 43_1 43_5 43_12 43_20 4321 43 23 43T25 44 1 445 223_10 223_2 223 4 223_5 223 6 223`7 A3_4 A3_5 A3 7 A3 3 42_12 ARV 1 CCATTTTGAC .CGCGAAATT TGAACGAGCA GCAGCCATGC CGGGCTTCTA AAV2 CCATTTTGAA GCGGGAGGTT TGAACGCGCA GCCGCCATGC CGGGGTTTTA AAV3 CCATTTTGAC .CGCGAAATT TGAACGAGCA GCAGCCATGC CGGGGTTCTA AAVB CCATTTTGAC .CGCGAAATT TGAACGAGCA GCAGCCATGC CGGGCTTCTA AAV9 CCATTTTGAC .CGCGAAATT TGAACGAGCA GCAGCCATGC CGGGCTTCTA AAV7 CCATTTT AC .CGCGAAATT TGAACGAGCA GCAGCCATGC CGGGTTTCTA 44 2 4 YY1/P5 RNA Rep78/68 start

7/105

Fig. 1H

351 400 42_2 42_8 42 15 42_5b 42 lb 2020201242

42_13 42 3a 4 425a 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 Yo 2n 2 223_4 223_5 223 6 223 7 A3 4 A3_5 A3_7 A3_3 42 12 AAVI CGAGATCGTG ATCAAGGTGC CGAGCGACCT GGACGAGCAC CTGCCGGGCA AAV2 CGAGATTGTG ATTAAGGTCC CCAGCGACCT TGACGGGCAT CTGCCCGGCA AAV3 CGAGATTGTC CTGAAGGTCC CGAGTGACCT GGACGAGCGC CTGCCGGGCA AAV8 CGAGATCGTG ATCAAGGTGC CGAGCGACCT GGACGAGCAC CTGCCGGGCA AAV9 CGAGATTGTG ATCAAGGTGC CGAGCGACCT GGACGAGCAC CTGCCGGGCA AAV7 CGAGATCGTG ATCAAGGTGC CGAGCGACCT GGACGAGCAC CTGCCGGGCA 44 2

8 /105

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Fig. 11

401 450 42 2 42 8 42_15 42_5b 42_ lb 42_13 2020201242

423a 42 4 42_5a 42_10 42_3b 42_11 42_6b 43 1 43 5 43_12 43 20 43—_21 43_23 4325 44_1 _ 44_5 223_10 223_2 223 4 223__5 223_6 _ 223 7 A3_ 4 A35 _ A3_7 A3_3 42_12 AAV1 TTTCTGACTC GTTTGTGAGC TGGGTGGCCG AGAAGGAATG GGAGCTGCCC AAV2 T TT CT GACAG CTTTGTGAAC TGGGTGGCCG AGAAGGAATG GGAGTTGCCG AAV3 TT TC TAACTC GTTTGTTAAC TGGGTGGCCG AGAAGGAATG GGACGTGCCG AAVB TTTCTGACTC GTTTGTGAAC TGGGTGGCCG AGAAGGAATG GGAGCTGCCC AAV9 TTTCTGACTC TTTTGTGAAC TGGGTGGCCG AGAAGGAATG GGAGCTGCCC AAV7 TTTCTGACTC GTTTGTGAAC TGGGTGGCCG AGAAGGAATG GGAGCTGCCC 44 2 '

9 /105

Fig. 1J

451 500 42_2 42_8 42 15 42 5b 42_-1b 42_13 2020201242

42 3a 0 4 42_5a 42_10 42 3b 42 11 42-6b 43_1 435 43_12 43_20 43-21 43_23 43_25 a 1 445 22310 223_2 223 4 2235 2236 223 7 A3 4 A3 5 A37 A3 3 42_12 AAV1 CCGGATTCTG ACATGGATCT GAATCTGATT GAGCAGGCAC CCCTGACCGT AAV2 CCAGATTCTG ACATGGATCT GAATCTGATT GAGCAGGCAC CCCTGACC GT AAV3 CCGGATTCTG ACATGGATCC GAATCTGATT GAGCAGGCAC CCCTGACCGT AAV8 CCGGATTCTG ACATGGATCG GAATCTGATC GAGCAGGCAC CCCTGACCGT AAV9 CCGGATTCTG ACATGGATCG GAATCTGATC GAGCAGGCAC CCCTGACCGT AAV7 CCGGATTCTG ACATGGATCT GAATCTGATC GAGCAGGCAC CCCTGACCGT 44 2

Fig. 1K

501 550 42_2 42 8 42 15 4 2 5b 42-1b 4 2 13 2020201242

4 213a 42_4 42_5a 4 2 10 42 3b 4 2 11 42 6b 43_1 43_5 4 312 4320 4 3 21 4 3 23 4325 471_1 44_5 2 2 3_10 2232 223 4 2235 2236 6 2237 A3^4 A3 5 A37 A3_3 4 2 12 AAV1 GGCCGAGAAG CTGCAGCGCG ACTTCCTGGT CCAATGGCGC CGCGTGAGTA AAV2 GGCCGAGAAG CTGCAGCGCG ACT TTCT GAC GGAGTGGCGC CGT GT GAGTA AAV3 GpcCGAAAAG CTTCAGCGCG AGTTCCTGGT GGAGTGGCGC CGCGTGAGTA AAV8 GGCCGAGAAG CTGCAGCGCG ACTTCCTGGT CCAATGGCGC CGCGTGAGTA AAV9 GGCCGAGAAG CTGTAGCGCG ACTTCCTGGT CCAATGGCGC CGCGTGAGTA AAV7 GGCCGAGAAG CTGCAGCGCG ACTTCCTGGT CCAATGGCGC CGCGTGAGTA 44 2

11/105

Fig.

551 600 42_2 4 2 8 42 15 42 5b 42-1b 42 13 2020201242

4 2-3 a 42_4 42_5a 42 10 4 2 3b 4 2 11 4 2:6b 4 3 1 4 3 5 43 Y2 4320 43 21 4323 43:25 4 4 1 44 - 5 223_50 223 2 22 3_ 4 2 2 3- 5 2236 223_ A3 4 A3_-5 A3-7 A3 3 42 12 AAV1 AGGCCCCGGA GGCCCTCTTC TTTGTTCAGT TCGAGAAGGG CGAGTCCTAC AAV2 AGGCCCCGGA GGCCCTTTTC TTTGTGCAAT TTGAGAAGGG AGAGAGCTAC AAV3 AGGCCCCGGA GGCCCTCTTT TTTGTCCAGT TCGAAAAGGG GGAGACCTAC AAV8 AGGCCCCGGA GGCCCTCTTC TTTGTTCAGT TCGAGAAGGG CGAGAGCTAC AAV9 AGGCCCCGGA GGCCCTCTTC TTTGTTCAGT TCGAGAAGGG CGAGAGCTAC AAV7 AGGCCCCGGA GGCCCTGTTC TTTGTTCAGT TCGAGAAGGG CGAGAGCTAC 4 42

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PC1'41502/33629 WO 03/042397 20 Feb 2020

Fig. 1M

601 650 422 42_8 42 1 5 4 2 5b 42 lb 42_13 2020201242

4 2 3a #ff 4 423a 42 1 0 4 2 3b 421-11 42_ 6b 43 1 435 4 3 T2 4320 4 3 21 4 3 23 4325 44 1 445 22 3 TO 223_2 2234 2235 223 6 2237 A3 4 A3 5 A3 7 A3 3 42 12 AAV1 TTCCACCTCC ATATTCTGGT GGAGACCACG GGGGTCAAAT CCATGGTGCT WW2 TTC CACAT GC ACGT GC TCGT GGAAACCACC GGGGTGAAAT CCATGGTT TT AAV3 T TC CAC CTGC AC GTGCTGAT TGAGACCATC GGGGTCAAAT CCATGGTGGT AAV8 TTTCACCTGC ACGTTCTGGT CGAGACCACG GGGGTCAAGT CCATGGTGCT AAV9 TTTCACCTGC ACGTTCTGGT CGAGACCACG GGGGTCAAGT CCAT GGTGCT AAV 7 TTCCACCTTC ACGTTCTGGT GGAGACCACG GGGGTCAAGT CCATGGTGCT 44 2

13/105

Fig. IN

651 700 42_2 42 8 42_15 42 5b 42 lb 42_13 42_3a 2020201242

42_4 42_5a 42 10 42_3b 42_11 42_6b 4-5 _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 A37 A3 3 42_12 AAV1 GGGCCGCTTC CTGAGTCAGA TTAGGGACAA GCT.GGTGCA GACCATCTAC AAV2 GGGACGTTTC CTGAGTCAGA TTCGGGAAAA ACT..GATTC AGAGAATTTA AAV3 CGGCCGCTAC GTGAGCCAGA TTAAAGAGAA GCT..GGTGA CCCGCATCTA AAV8 AGGCCGCTTC CTGAGTCAGA TTCGGGAAAA GCTTGGTCCA GACCATCTAC AAV9 AGGCCGCTTC CTGAGTCAGA TTCGGGAGAA GCT.GGTCCA GACCATCTAC AAV7 AGGCCGCTTC CTGAGTCAGA TTCGGGAGAA GCT....G.. GTCCAGACCA 44 2

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WO 03/042397 20 Feb 2020

Fig. 10

701 750 42_2 42_8 42_15 42_5b 42 lb 42_13 42_3a 2020201242

42_4 42_5a 42-10 42 3b 42 11 42_6b

43 5 43_12 43 20 43 21 43 23 4325 44_1 445 223_10 223_2 223_4 223 5 223 6 223=7 A34 A3 5 A3 7 A3 3 42 12 AAV1 C.GCGGGATC GAGCCG.ACC CTGCCCAACT GGTTCGCGGT GACCAA.GAC AAV2 CCGCGGGATC GAGCCG.ACT TTGCCAAACT GGTTCGCGGT CACAAA...G AAV3 CCGCGGGGTC GAGCCG.CAG CTTCCGAACT GGTTCGCGGT GACCAA...A AAV8 CCGCGGGGTC GAGCCCCACC TTGCCCAACT GGTTCGCGGT GACCAAAGAC AAV9 C.GCGGGATC GAGCCG.ACC CTGCCCAACT GGTTCGCGGT GACCAA.GAC AAV7 TCTACCGCGG GGTCGAGCCC ACGCTGCCCA ACTGGTTCGC GGTGACCAAG 44 2

15/105

Fig. 11D

751 BOO 42_2 42_8 42J5 42 5b 42 1b 42 13 2020201242

42 3a 42_4 42 5a 42_10 42-3b 42-11 42_6b 43_1 43_5 43_12 43_20 43 21 4323 43 25 a 1 44 5 223_10 223_2 223 4 2235 2236 2237 A3_^4 A3_5 A3-7 A3_3 42_12 AAV1 GCG.TAATGG CGCCGGAGGG GGG.AACAAG GTGGTGGACG AGTGCTACAT AAV2 ACCAGAAATG GCGCCGGAGG CGGGAACAAG GTGGTGGATG AGTGCTACAT AAV3 ACGCGAAATG GCGCCGGGGG CGGGAACAAG GTGGTGGACG ACTGCTACAT AAVB GCGGTAATGG CGCCGGCGGG GGGGAACAAG GTGGTGGACG AGTGCTACAT AAV9 GCGGTAATGG CGCCGGCGGG GGG.AACAAG GTGGTGGACG AGTGCTACAT AAV7 ACGCGTAATG GCGCCGGCGG GGGGAACAAG GTGGTGGACG AGTGCTACAT 44 2

16/105

Fig. 1Q

801 850 42 2 42u8 42_15 42 5b 421b 42_13 42 3a 2020201242

zff 4 42_5a 42_10 42 3b 42-11 42 6b 43_1 43_5 43_12 , 43^20 43 21 93 23 43:25 44 1 44 5 223J0 223_2 223 4 223_5 223 6 223_7 A3_4 A3_5 A3 7 A3 3 42 12 AAV1 CCCCAACTAC CTCCTGCCCA AGACTCAGCC CGAGCTGCAG TGGGCGTGGA AAV2 CCCCAATTAC TTGCTCCC CA AAACCCAGCC TGAGCTCCAG TGGGCGTGGA AAV3 CCCCAACTAC C TGC TCCC CA AGACCCAGCC CGAGCTCCAG TGGGCGTGGA AAV8 CCCCAACTAC CTCCTGCCCA AGACTCAGCC CGAGCTGCAG TGGGCGTGGA AAV9 CCCCAACTAC CTCCTGCCCA AGACTCAGCC CGAGCTGCAG TGGGCGTGGA AAV7 CCCCAACTAC CTCCTGCCCA AGACCCAGCC CGAGCTGCAG TGGGCGTGGA 44 2

17/105

WO 03/042397 PCT/U S02/33629 20 Feb 2020

Fig. 1R

851 900

P19/TATA P19 RNA 42 2 42 8 42_15 2020201242

42_5b 42 lb 4213 42:3a 42_4 42 5a 42__10 42 3b 42_11 42_6b 43 1 435 43_12 43 20 43_21 43 23 43_25 a 1 44_5 223_10 223_2 223_4 223 5 223:6 2237 A3 4 A3_5 A3 7 A3 3 42 i2 AAV1 CTAACATGGA GGAGTATATA AGCGCCTGTT TGAACCTGGC CGAGCGCAAA AAV2 CTAATATGGA ACAGTATTTA AGCGCCTGTT TGAATCTCGC GGAGCGTAAA AAV3 CTAACATGGA CCAGTATTTA AGCGCCTGTT TGAATCTCGC GGAGCGTAAA AAV8 CTAACATGGA GGAGTATATA AGCGCGTGCT TGAACCTGGC CGAGCGCAAA AAV9 CTAACATGGA GGAGTATATA AGCGCGTGCT TGAACCTGGC CGAGCGCAAA AAV7 CTAACATGGA GGAGTATATA AGCGCGTGTT TGAACCTGGCArGAACGCAAA 44 2 A P19/TATA P19 RNA

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WO 03/042397 20 Feb 2020

Fig. 18

901 950 42_2 42:8 42_15 42 5b 421b 42_13 42_3a 2020201242

42_4 42_5a 42 10 42_3b 42_11 42 6b 43 1 43_5 43_12 43_20 43 21 43 23 4325 - 4711 44_5 223_10 223 2 2234 2235 223_6 2237 A3 4 A3 5 A3-7 A3_3 42_12 AAV1 CGGCTCGTGG CGCAGCACCT GACCCACGTC AGCCAGACCC AGGAGCAGAA AAV2 CGGTTGGTGG CGCAGCATCT GACGCACGTG TCGCAGACGC AGGAGCAGAA AAV3 CGGCTGGTGG CGCAGCATCT GACGCACGTG TCGCAGACGC AGGAGCAGAA AAV8 CGGCTCGTGG CGCAGCACCT GACCCACGTC AGCCAGACGC AGGAGCAGAA AAV9 CGGCTCGTGG CGCAGCACCT GACCCACGTC AGCCAGACGC AGGAGCAGAA AAV7 CGGCTCGTGG CGCAGCACCT GACCCACGTC AGCCAGACGC AGGAGCAGAA 44 2

19/105

Fig. 1T

951 1000 42 2 42 8 42_15 42 5b 42-1b 42_13 2020201242

42_3a 424 42 5a 4210 42 3b 42-11 42:6b 43 1 435 43 12 43 20 43-21 4323 43_25 a 1 44_5 223 I. 0 22'§ 2 223_4 223_5 223_6 22317 A3 4 A3_5 A:3=7 A3 3 42 1.

2 AAV1 CAAGGAGAAT CTGAACCC CA ATTCTGACGC GCCGGTCATC CGGTCAAAAA AAV2 CAAAGAGAAT CAGAATC C CA ATTCTGATGC GCCCGTGATC AGGTCAAAAA AAV3 CAAAGAGAAT CAGAACC C CA ATTCTGACGC GCCGGTCATC AGGTCAAAAA AAVB CAAGGAGAAT CTGAACCCCA ATTCTGACGC GCCCGT GATC AG GT CAAAAA AAV9 CAAGGAGAAT CTGAACCCCA ATTCTGACGC GCCCGTGATC AGGTCAAAAA AAV7 CAAGGAGAAT CTGAACCCCA ATTCTGACGC GCCCGTGATC AGGTCAAAAA 44 2

20/105

PCTALS02/33629 WO 03/042397 20 Feb 2020

Fig. 1U

1001 1050

Rep52/ tart codon 42_2 42_8 42_15 42_5b 42 lb 2020201242

42_13 42 3a 4214 42_5a 42u10 42 - 3b 42 - 11 42:6b 43 1 43 5 43 12 4320 43-21 4323 43:25 44_1 44_5 223_10 223_2 2234 223 5 223_6 223=7 A3_4 A35 A3_7 A3_3 42_12 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 Rep 52/40 start

Fig. 1V

1051 1100 42 2 42 8 42_15 42 5b 42-1b 42 13 2020201242

42:3a 42_4 42_5a 42_10 42_3b 42 11 42:6b 43_1_ 43_5 43_52 43_20 43 _23. 43 23 4325 4i1 44_5 223_10 223_2_ 223_4_ 223_5_ 223 6 223= _7 A3 4 A3 5 A3-7 A3_3 42_12 AA.V1 ACCTCCGAGA AGCAGTGGAT CCAGGAGGAC CAGGCCTCGT ACATCTCCTT AAV2 ACCTCGGAGA AGCAGTGGAT CCAGGAGGAC CAGGCCTCGT ACATCTCC TT AAV3 ACGTCAGAAA AGCAGTGGAT TCAGGAGGAC CAGGCCTCGT ACATCTCCTT AAV8 ACCTCCGAGA AGCAGTGGAT CCAGGAGGAC CAGGCCTCGT ACATCTCCTT AAV9 ACCTCCGAGA AGCAGTGGAT CCAGGAGGAC CAGGCCTCGT ACATCTCCTT AAV7 ACCTCCGAGA AGCAGTGGAT CCAGGAGGAC CAGGCCTCGT ACATCTCCTT 44 2

22/105

Fig. 1W

1101 1150 42_2 428 42_15 42 5b 4 2 lb 42_13 42 3a 2020201242

42 4 423a 42_1 0 4 2 3b 42 11 42__6b 43 1 435 4 3 T2 43) 0 4321 43 23 43_25 44 1 445 223_10 2 23 2 223 4 223:5 2 23 6 2237 A3 4 A3 5 A3 7 A3_3 4 2 12 AAV1 CAACGCCGCT TCCAACTCGC GGTCCCAGAT CAAGGCCGCT CTGGACAATG AAV2 CAATGCGGCC TCCAACTCGC GGTCCCAGAT CAAGGCTGCC TTGGACAATG AAV3 CAACGCCGCC TCCAACTCGC GGTCCCAGAT CAAGGCCGCG CTGGACAATG AAVB CAACGCCGCC TCCAACTCGC GGTCCCAGAT CAAGGCCGCG CTGGACAATG AAV9 CAACGCCGCC TCCAACTCGC GGTCCCAGAT CAAGGCCGCG CTGGACAATG AAV7 CAACGCCGCC TCCAACTCGC GGTCCCAGAT CAAGGCCGCG CT GGACAATG 4 42

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WO 03/042397 20 Feb 2020

Fig. 1X

1151 1200 42 2 428 42_15 42 5b 42 lb 42 13 2020201242

42 3a 42 4 423a 4210 42 3b 42 11 4 2 6b 4 -3- 1 43_5 43_12 4320 4 3_21 43_23 43_2 5 44 1 445 223_10 223_2 223 4 223-5 223 6 223_7 A3 4 A3=5 A3 7 A3 3 42_12 AAV1 CCGGCAAGAT CAT GGCGCTG ACCAAATCCG CGCCCGAC TA CCTGGTAGGC AAV2 CGGGAAAGAT TAT GAGCC T G ACTAAAACCG CCCCCGACTA CCTGGTGGGC AAV3 CCTCCAA GAT CATGAGCCTG ACAAAGACGG CTCCGGACTA CCTGGTGGGC AAV8 CCGGCAAGAT CATGGCGCTG ACCAAATCCG CGCCCGACTA CC TGGTGGGG AAV9 CCGGCAAGAT CATGGCGCTG ACCAAATCCG CGCCCGACTA CCTGGTAGGC AAV7 CCGGCAAGAT CATGGCGCTG ACCAAATCCG CGCCCGACTA CC TGGTGGGG 44 2

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WO 03/042397 20 Feb 2020

Fig, 1Y

1201 1250 42 2 42 8 42_15 42 5b 42 lb 42 13 42:3a 2020201242

424 42_5a 42 10 42_3b 42:11 42_6b GA ATTCGCCCTT TCTACGGCTG 43 1 435 43_12 43_20 43 21 43_23 43:25 44_1 44_5 223_10 223_2 223_4 223_5 223_6 223u7 A3 4 A3:5 A3_7 A3 3 42_12 AAV1 CCCGCTCCGC CCGCGGACAT TAAAACCAAC CGCATCTACC GCATCCTGGA AAV2 CAGCAGCCCG TGGAGGACAT TT CCAGCAAT CGGATTTATA AAATTTTGGA AAV3 AGCAAC C C GC CGGAGGACAT TACCAAAAAT CGGATCTACC AAAT C CT GGA AAV8 CCCTCGCTGC CCGCGGACAT TACCCAGAAC CGCATCTACC GCATCCTCGC AAV9 CCTTCACTTC CGGTGGACAT TACGCAGAAC CGCATCTACC GCATCCTGCA AAV7 CCCTCGCTGC CCGCGGACAT TAAAACCAAC CGCATCTACC GCATCCTGGA 44 2

25/105

WO 03/042397 20 Feb 2020

Fig, 1Z

1251 1300 42_2 42_8 42_15 42 5b 42 lb 42_13 42 3a 2020201242

eff 4 42_3a 42 10 42^3b 42 11 42 6b CGTCAACTGG ACCAATGAGA ACTTTCCCTT CAACGATTGC GTCGACAAGA 1 43_5 43 12 43 20 43 21 4323 43 25 a 1 44 5 223_10 223_2 2234 4 223:5 2236 223 7 A3_4 A315 A3 7 A3 3 42_12 AAV1 GCTGAACGGC TACGACCCTG CCTACGCCGG CTCCGTCTTT CTCGGCTGGG AAV2 ACTAAACGGG TACGATCCCC AATATGCGGC TTCCGTCTTT CTGGGATGGG AAV3 GCTGAACGGG TAC GATCCGC AGTACGCGGC CTCCGTCTTC CTGGGCTGGG AAV8 TCTCAACGGC TACGACCCTG CCTACGCCGG CTCCGTCTTT CTCGGCTGGG AAV9 GC T CAACGGC TACGACCCTG CCTACGCCGG CTCCGTCTTT CTCGGCTGGG AAV7 GCTGAACGGG TACGAT CC TG CCTACGCCGG CTCCGTCTTT CTCGGCTGGG 44 2

26/105

Fig. IAA

1301 1350 42_2 42_8 42_15 42 5b 42 lb 42 13 42:3a 2020201242

42_4 42_5a 42_10 42 3b 4211 42_6b TGGTGATCTG GTGGGAGGAG GGCAAGATGA CGGCCAAGGT CGTGGAGTCC 43 1 435 43_1- 2 43_20 43_21 43-23 43_25 a 1 44 5 223_10 223 2 223^4 2235 223 - 6 223-7 A3 4 A3 5 A37 A3_- 3 42_12 AAV1 CCCAGAAAAG GTTCGGGAAG CGCAACACCA TCTGGCTGTT TGGGCCGGCC AAV2 CCACGAAAAA GTTCGGCAAG AGGAACACCA TCTGGCTGTT TGGGCCTGCA AAV3 CGCAAAAGAA GTTCGGGAAG AGGAACACCA TCTGGCTCTT TGGGCCGGCC AAV8 CTCAGAAAAA GTTCGGGAAA CGCAACACCA TCTGGCTGTT TGGACCCGCC AAV9 CACAAAAGAA GTTCGGGAAA CGCAACACCA TCTGGCTGTT TGGGCCGGCC AAV7 CCCAGAAAAA GTTCGGGAAG CGCAACACCA TCTGGCTGTT TGGGCCCGCC 44 2

27/105

WO 03/042397 20 Feb 2020

Fig. 1AB

1351 1400

42 2 GAA TTCGCCCTTT 42 8 GAA TTCGCCCTTT 42_15 GAA TTCGCCCTTT 42 5b GAA TTCGCCCTTT 42—lb 2020201242

42_13 GAA TTCGCCCTTT 42-3a GAA TTCGCCCTTT 4 42_5a GA ATTCGCCCTT 42 10 42-3b 42_11 GAA TTCGCCCTTT 42 6b GCCAAGGCCA TTCTCGGCGG CAGCAAGGTG CGCGTGGACC AAAAGTGCAA 43_1 GAA TTCGCCCTTT 43_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_10 223 223_ 4 223 - 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 AGACCAACAT CGCGGAAGCC ATCGCCCACG CCGTGCCCTT AAVB ACCACCGGCA AGACCAACAT TGCGGAAGCC ATCGCCCACG CCGTGCCCTT AAV9 ACCACGGGAA AGACCAACAT CGCAGAAGCC ATTGCCCACG CCGTGCCCTT AAV7 ACCACCGGCA AGACCAACAT TGCGGAAGCC ATCGCCCACG CCGTGCCCTT 44 2 GA ATTCGCCCTT

28/105

WO 03/042397 20 Feb 2020

Fig. 1AC

1401 1450 42 2 .CTACGGCTG CGTCAACTGG ACCAATGAGA ACTTTCCCTT CAACGATTGC 42_`8 .CTACGGCTG CGTCAACTGG ACCAATGAGA ACTTTCCCTT CAACGATTGC 42_15 .CTACGGCTG CGTCAACTGG ACCAATGAGA ACTTTCCCTT CAACGATTGC 42_5b .CTACGGCTG CGTCAACTGG ACCAATGAGA ACTTTCCCTT CAACGATT GC 42-1b 42 13 .CTACGGCTG CGTCAACTGG ACCAATGAGA ACTTTCCCTT CAACGATTGC 42:3a .CTACGGCTG CGTCAACTGG ACCAATGAGA ACTTTCCCTT CAACGATTGC 2020201242

42_4 425a .CTACGGCTG CGTCAACTGG ACCAATGAGA ACTTTCCCTT CAACGATTGC 42 10 42`3b • 42-11 .CTACGGCTG CGTCAACTGG ACCAATGAGA ACTTTCCCTT CAACGATT GC 42 6b GTCTTCCGC CCAGATCGAT CCCACCCCCG TGATCGTCAC TTCCAACACC 43 1 .CTACGGCTG CATCAACTGG ACCAATGAGA ACTTTCCCTT CAACGATTGC 43_5 .CTACGGCTG CGTCAACTGG ACCAATGAGA ACTTTCCCTT CAACGATTGC 43_12 GGCTG CGTCAACTGG ACCAATGAGA ACTTTCCCTT CAACGATTGC 43_`20 .CTACGGCTG. CGTCAACTGG ACCAATGAGA ACTTTCCCTT CAACGATTGC 43 21 GGCTG CGTCAACTGG ACCAATGAGA ACTTTCCCTT CAACGATTGC 43:23 .CTACGGCTG CGTCAACTGG ACCAATGAGA ACTTTCCCTT CAACGATTGC 43_25 .CTACGGCTG CGTCAACTGG ACCAATGAGA ACTTTCCCTT CAACGATTGC 44_1 .CTACGGCTG CGTCAACTGG ACCAATGAGA ACTTTCCCTT CAACGATTGC 445 .CTACGGCTG CGTCAACTGG ACCAATGAGA ACTTTCCCTT CAACGATTGC 223_10 223_2 223_4 223 5 223_6 223_7 A3 4 TCTACGGCTG CGTCAACTGG ACCAATGAAA ACTTTCCCTT CAACGATTGC A3`5 TCTACGGCTG CGTCAACTGG ACCAATGAAA ACTTTCCCTT CAACGATT GC A37 TCTACGGCTG CGTCAACTGG ACCAATGAAA ACTTTCCCTT CAACGATTGC A3_3 TCTACGGCTG CGTCAACTGG ACCAATGAAA ACTTTCCCTT CAACGATTGC 42_1_2 CTACGGCTG CGTCAACTGG ACCAATGAGA ACTTTCCCTT CAACGATTGC AAV1 .CTACGGCTG CGTCAACTGG ACCAATGAGA ACTTTCCCTT CAATGATTGC AAV2 .CTACGGCTG CGTAAACTGG ACCAATGAGA ACTTTCCCTT CAACGACTGT AAV3 .CTACGGCTG CGTAAA.CTGG ACCAATGAGA ACTTTCCCTT CAACGATTGC AAV8 .CTACGGCTG CGTCAACTGG ACCAATGAGA ACTTTCCCTT CAATGATTGC AAV9 .CTACGGCTG CGTCAACTGG ACCAATGAGA ACTTTCCCTT CAACGATTGC AAV7 .CTACGGCTG CGTCAACTGG ACCAATGAGA ACTTTCCCTT CAACGATTGC 44_2 TCTACGGCTG CGTCAACTGG ACCAATGAGA ACTTTCCCTT CAACGATTGC

29/105

Fig. lAD

1451 1500 42_2 GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGCAAGATGA CGGCCAAGGT 42_8 GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGCAAGATGA CGGCCAAGGT 42_15 GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGCAAGATGA CGGCCAAGGT 42 5b GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGCAAGATGA CGGCCAAGGT 42 lb 42 13 GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGCAAGATGA CGGCCAAGGT 42:3a GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGCAAGATGA CGGCCAAGGT 2020201242

42_4 42 5a GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGCAAGATGA CGGCCAAGGT 4210 42_3b 42_11 GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGCAAGATGA CGGCCAAGGT 42_6b AACATGTGCG CCGTGATTGA CGGGAACAGC ACCACCTTCG AGCACCAGCA 43 1 GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGCAAGATGA CGGCCAAGGT 43 5 GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGCAAGATGA CGGCCAAGGT 43_12 GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGCAAGATGA CGGCCAAGGT 43 20 GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGCAAGATGA CGGCCAAGGT 431)1 GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGCAAGATGA CGGCCAAGGT 4323 GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGCAAGATGA CGGCCAAGGT 43__25 GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGCAAGATGA CGGCCAAGGT 44_1 GTCGACAAGA TGTTGATCTG GTGGGAGGAG GGCAAGATGA CGGCCAAGGT 44_5 GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGCAAGATGA CGGCCAAGGT 223_10 223 2 223 4 223_5 223_6 223:7 A3 4 GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGAAAGATGA CCGCCAAGGT A3 5 GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGAAAGATGA CCGCCAAGGT A3-7 GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGAAAGATGA CCGCCAAGGT A3 3 GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGAAAGATGA CCGCCAAGGT 42.52 GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGCAAGATGA CGGCCAAGGT AAV1 GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGCAAGATGA CGGCCAAGGT AAV2 GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGGAAGATGA CCGCCAAGGT AAV3 GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGCAAGATGA CGGCCAAGGT AAV8 GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGCAAGATGA CGGCCAAGGT AAV9 GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGCAAGATGA CGGCCAAGGT AAV7 GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGCAAGATGA CGGCCAAGGT 44 2 GTCGACAAGA TGGTGATCTG GTGGGAGGAG GGCAAGATGA CGGCCAAGGT

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Fig. 1AE

1501 1550 42_2 CGTGGAGTCC GCCAAGGCCA TTCTCGGCGG CAGCAAGGTG CGCGTGGACC 42_8 CGTGGAGTCC GCCAAGGCCA TTCTCGGCGG CAGCAAGGTG CGCGTGGACC 42_15 CGTGGAGTCC GCCAAGGCCA TTCTCGGCGG CAGCAAGGTG CGCGTGGACC 42 5b CGTGGAGTCC GCCAAGGCCA TTCTCGGCGG CAGCAAGGTG CGCGTGGACC 42 lb 42:13 CGTGGAGTCC GCCAAGGCCA TTCTCGGCGG CAGCAAGGTG CGCGTGGACC 423a CGTGGAGTCC GCCAAGGCCA TTCTCGGCGG CAGCAAGGTG CGCGTGGACC 2020201242

4 42_-5-a CGTGGAGTCC GCCAAGGCCA TTCTCGGCGG CAGCAAGGTG CGCGTGGACC 42 10 42 3b 4211 CGTGGAGTCC GCCAAGGCCA TTCTCGGCGG CAGCAAGGTG CGCGTGGACC 42 - 6b GCCGTTGCAG GACCGGATGT TCAAATTTGA ACTCACCCGC CGTCTGGAGC 43- 1 CGTGGAGTCC GCCAAGGCCA TTCTCGGCGG CAGCAAGGTG CGCGTGGACC 43_5 CGTGGAGTCC GCCAAGGCCA TTCTCGGCGG CAGCAAGGTG CGCGTGGACC 43_12 CGTGGAGTCC GCCAAGGCCA TTCTCGGCGG CAGCAAGGTG CGCGTGGACC 43 20 CGTGGAGTCC GCCAAGGCCA TTCTCGGCGG CAGCAAGGTG CGTGTGGACC 4321 CGTGGAGTCC GCCAAGGCCA TTCTCGGCGG CAGCAAGGTG CGTGTGGACC 4323 CGTGGAGTCC GCCAAGGCCA TTCTCGGCGG CAGCAAGGTG CGTGTGGACC 43-25 CGTGGAGTCC GCCAAGGCCA TTCTCGGCGG CAGCAAGGTG CGTGTGGACC 4 -4 1 CGTGGAGTCC GCCAAGGCCA TTCTCGGCGG CAGCAAAGTG CGCGTGGACC 44 5 CGTGGAGTCC GCCAAGGCCA TTCTCGGCGG CAGCAAAGTG CGCGTGGACC 223_10 223 2 223_4 223_5 223 6 2237 A3 4 CGTGGAATCT GCCAAAGCCA TTCTGGGTGG AAGCAAGGTT CGTGTGGACC A3 5 CGTGGAATCT GCCAAAGCCA TTCTGGGTGG AAGCAAGGTT CGTGTGGACC A3-7 CGTGGAATCT GCCAAAGCCA TTCTGGGTGG AAGCAAGGTT CGTGTGGACC A3 3 CGTGGAATCT GCCAAAGCCA TTCTGGGTGG AAGCAAGGTT CGTGTGGACC 42_12 CGTGGAGTCC GCCAAGGCCA TTCTCGGCGG CAGCAAGGTG CGCGTGGACC AAV1 CGTGGAGTCC GCCAAGGCCA TTCTCGGCGG CAGCAAGGTG CGCGTGGACC AAV2 CGTGGAGTCG GCCAAAGCCA TTCTCGGAGG AAGCAAGGTG CGCGTGGACC AAV3 CGTGGAGAGC GCCAAGGCCA TTCTGGGCGG AAGCAAGGTG CGCGTGGACC AAV8 CGTGGAGTCC GCCAAGGCCA TTCTCGGCGG CAGCAAGGTG CGCGTGGACC AAV9 CGTGGAGTCC GCCAAGGCCA TTCTCGGCGG CAGCAAGGTG CGCGTGGACC AAV7 CGTGGAGTCC GCCAAGGCCA TTCTCGGCGG CAGCAAGGTG CGCGTGGACC 44 2 CGTGGAGTCC GCCAAGGCCA TTCTCGGCGG CAGCAAAGTG CGCGTGGACC

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Fig. IAF

1551 1600 42 2 AAAAGTGCAA GTCTTCCGCC CAGATCGATC CCACCCCCGT GATCGTCACT 42-8 AAAAGTGCAA GTCTTCCGCC CAGATCGATC CCACCCCCGT GATCGTCACT 4215 AAAAGTGCAA GTCGTCCGCC CAGATCGACC CCACCCCCGT GATCGTCACC 42-5b AAAAGTGCAA GTCGTCCGCC CAGATCGACC CCACCCCCGT GATCGTCACC 42 lb 42_13 AAAAGTGCAA GTCGTCCGCC CAGATCGATC CCACCCCCGT GATCGTCACT 42_3a AAAAGTGCAA GTCGTCCGCC CAGATCGATC CCACCCCCGT GATCGTCACT 2020201242

4-2- 4 425a AAAAGTGCAA GTCGTCCGCC CAGATCGACC CCACCCCCGT GATCGTCACC 42_10 42 3b 42_11 AAAAGTGCAA GTCTTCCGCC CAGATCGATC CCACCCCCGT GATCGTCACT 42µ_6b ATGACTTTGG CAAGGTGACA AAGCAGGAAG TCAAAGAGTT CTTCCGCTGG 43 1 AAAAGTGCAA GTCGTCCGCC CAGATCGACC CCACCCCCGT GATCGTCACC 43 5 AAAAGTGCAA GTCGTCCGCC CAGATCGACC CCACCCCCGT GATCGTCACC 43_12 AAAAGTGCAA GTCGTCCGCC CAGATCGACC CCACCCCCGT GATCGTCACC 43 20 AAAAGTGCAA GTCTTCCGCC CAGATCGATC CCACCCCCGT GATCGTCACC 43 21 AAAAGTGCAA GTCTTCCGCC CAGATCGATC CCACCCCCGT GATCGTCACC 43-23 AAAAGTGCAA GTCTTCCGCC CAGATCGATC CCACCCCCGT GATCGTCACC 43-25 AAAAGTGCAA GTCTTCCGCC CAGATCGATC CCACCCCCGT GATCGTCACC 44 1 AAAAGTGCAA GCCGTCCGCC CAGATCGACC CCACCCCCGT GATCGTCACC 44 5 AAAAGTGCAA GTCGTCCGCC CAGATCGACC CCACCCCCGT GATCGTCACC 223_10 22-31_2 223__4 223_5 223 6 2237 A34 AGAAATGCAA GTCTTCGGCC CAGATCGACC CGACTCCGGT GATTGTCACC A3 5 AGAAATGCAA GTCTTCGGCC CAGATCGACC CGACTCCGGT GATTGTCACC A3 7 AGAP.ATGCAG GTCTTCGGCC CAGATCGACC CGACTCCGGT GATTGTCACC A3 3 AGAAATGCAA GTCTTCGGCC CAGATCGACC CGACTCCGGT GATTGTCACC 42_12 AAAAGTGCAA GTCGTCCGCC CAGATCGACC CCACCCCCGT GATCGTCACC AAV1 AAAAGTGCAA GTCGTCCGCC CAGATCGACC CCACCCCCGT GATCGTCACC AGAAATGCAA GTCCTCGGCC CAGATAGACC CGACTCCCGT GATCGTCACC AAV3 AAAAGTGCAA GTCATCGGCC CAGATCGAAC CCACTCCCGT GATCGTCACC AAV8 AATAAGTGCAA GTCGTCCGCC CAGATCGACC CCACCCCCGT GATCGTCACC AAV9 AAAAGTGCAA GTCGTCCGCC CAGATCGACC CCACTCCCGT GATCGTCACC AAV7 AAAAGTGCAA GTCGTCCGCC CAGATCGACC CCACCCCCGT GATCGTCACC 44_2 AAAAGTGCAA GTCGTCCGCC CAGATCGACC CCACCCCCGT GATCGTCACC

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Fig. lAG

1601 1650 42_2 TCCAACACCA ACATGTGCGC TGTGATTGAC GGGAACAGCA CCACCTTCGA 42_8 TCCAACACCA ACATGTGCGC CGTGATTGAC GGGAACAGCA CCACCTTCGA 42 1.5 TCCAACACCA ACATGTGCGC CGTGATTGAC GGGAACAGCA CCACCTTCGA 42_5b TCCAACACCA ACATGTGCGC CGTGATTGAC GGGAACAGCA CCACCTTCGA 42 lb 42 13 TCCAACACCA ACATGTGCGC CGTGATTGAC GGGAACAGCA CCACCTTCGA 2020201242

42 3a TCCAACACCA ACATGTGCGC CGTGATTGAC GGGAACAGCA CCACCTTCGA 4214 42_5a TCCAACACCA ACATGTGCGC CGTGATTGAC GGGAACAGCA CCACCTTCGA 42_10 42 3b 42 11 TCCAACACCA ACATGTGCGC CGTGATTGAC GGGAACAGCA CCACCTTCGA 4216b GCGCAGGATC ACGTGACCGA GGTGGCGCAT GAGTTCTACG TCAGAAAGGG 43 1 TCCAACACCA ACATGTGCGC CGTGATTGAC GGGAACAGCA CCACCTTCGA 43 5 TCCAACACCA ACATGTGCGC CGTGATTGAC GGGAACAGCA CCACCTTCGA 43 12 TCCAACACCA ACATGTGCGC CGTGATTGAC GGGAACAGCA CCACCTTCGA 4320 TCCAACACCA ACATGTGCGC CGTGATTGAC GGGAACAGCG CCACCTTCGA 43-21 TCCAACACCA ACATGTGCGC CGTGATTGAC GGGAACAGCA CCACCTTCGA 4323 TCCAACACCA ACATGTGCGC CGTGATTGAC GGGAACAGCA CCACCTTCGA 43125 TCCAACACCA ACATGTGCGC CGTGATTGAC GGGAACAGCA CCACCTTCGA 44 1 TCCAACACCA ACATGTGCGC CGTGATTGAC GGGAACAGCA CCACCTTCGA 44_5 TCCAACACCA ACATGTGCGC CGTGATTGAC GGGAACAGCA CCACCTTCGA 223_10 223_2 223_4 223 5 223_6 223D A3^4 TCTAACACCA ACATGTGCGC CGTGATTGAC GGAAACTCGA CCACCTTCGA A3 5 TCTAACACCA ACATGTGCGC CGTGATTGAC GGAAACTCGA CCACCTTCGA A3-7 TCTAACACCA ACATGTGCGC CGTGATTGAC GGAAACTCGA CCACCTTCGA A33 TCTAACACCA ACATGTGCGC CGTGATTGAC GGAAACTCGA CCACCTTCGA 42_12 TCCAACACCA ACATGTGCGC CGTGATTGAC GGGAACAGCA CCACCTTCGA AAV1 TCCAACACCA ACATGTGCGC CGTGATTGAC GGGAACAGCA CCACCTTCGA AAV2 TCCAACACCA ACATGTGCGC CGTGATTGAC GGGAACTCAA CGACCTTCGA AAV3 TCCAACACCA ACATGTGCGC CGTGATTGAC GGGAACAGCA CCACCTTCGA AAV8 TCCAACACCA ACATGTGCGC CGTGATTGAC GGGAACAGCA CCACCTTCGA AAV9 TCCAACACCA ACATGTGCGC CGTGATTGAC GGGAACAGCA CCACCTTCGA AAV7 TCCAACACCA ACATGTGCGC CGTGATTGAC GGGAACAGCA CCACCTTCGA 44_2 TCCAACACCA ACATGTGCGC CGTGATTGAC GGGAACAGCA CCACCTTCGA

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Fig. lAH

1651 1700 42_2 GCACCAGCAG CCGTTACAAG ACCGGATGTT CAAATTTGAA CTCACCCGCC 42_8 GCACCAGCAG CCGTTACAAG ACCGGATGTT CAAATTTGAA CTCACCCGCC 42_15 GCACCAGCAG CCGTTGCAGG ACCGGATGTT CAAATTTGAA CTCACCCGCC 42 5b GCACCAGCAG CCGTTACAAG ACCGGATGTT CAAATTTGAA CTCACCCGCC 42 1b 42 13 GCACCAGCAG CCGTTACAAG ACCGGATGTT CAAATTTGAA CTCACCCGCC 42=3a GCACCAGCAG CCGTTACAAG ACCGGATGTT CAAATTTGAA CTCACCCGCC 2020201242

42_4 42 5a GCACCAGCAG CCGTTGCAGG ACCGGATGTT CAAATTTGAA CTCACCCGCC 42-10 42_3b 42 11 GCACCAGCAG CCGTTACAAG ACCGGATGTT CAAATTTGAA CTCACCCGCC 42 6h TGGAGCCAAC AAGAGACCCG CCCCCGATGA CGCGGATAAA AGCGAGCCCA GCACCAGCAG CCGTTGCAGG ACCGGATGTT CAAGTTCGAA CTCACCCGCC 43_5 GCACCAGCAG CCGTTGCAGG ACCGGATGTT CAAGTTCGAA CTCACCCGCC 43_12 GCACCAGCAG CCGTTGCAGG ACCGGATGTT CAAGTTCGAA CTCACCCGCC 43_20 GCACCAGCAG CCGTTGCAGG ACCGGATGTT CAAATTTGAA CTCACCCGCC 43_21 GCACCAGCAG CCGTTGCAGG ACCGGATGTT CAAATTTGAA CTCACCCGCC 43 23 GCACCAGCAG CCGTTGCAGG ACCGGATGTT CAAATTTGAA CTCACCCGCC 43^25 GCACCAGCAG CCGTTGCAGG ACCGGATGTT CAAATTTGAA CTCACCCGCC 1 GCACCAGCAG CCGTTGCGGG ACCGGATGTT CAAGTTTGAA CTCACCCGCC 44_5 GCACCAGCAG CCGTTGCAGG ACCGGATGTT CAAGTTTGAA CTCACCCGCC 223_10 223_2 223 4 223 5 223-6 223 7 A3 4 GCACCAGCAG CCGTTGCAAG ACCGGATGTT CAAATTTGAA CTTACCCGCC A3 5 GCACCAGCAG CCGTTGCAAG ACC GGATGTT CAAATTTGAA CTTACCCGCC A3=7 GCACCAGCAG CCGTTGCAAG ACCGGATGTT CAAATTTGAA CTTACCCGCC A3 3 GCACCAGCAG CCGTTGCAAG ACCGGATGTT CAAATTTGAA CTTACCCGCC 42_12 GCACCAGCAG CCGTTACAAG ACCGGATGTT CAAATTTGAA CTCACCCGCC AHV1 GCACCAGCAG CCGTTGCAGG ACCGGATGTT CAAATTTGAA CTCACCCGCC AAV2 ACACCAGCAG CCGTTGCAAG ACCGGATGTT CAAATTTGAA CTCACCCGCC AAV3 GCATCAGCAG CCGCTGCAGG ACCGGATGTT TGAATTTGAA CTTACCCGCC AAV8 GCACCAGCAG CCTCTCCAGG ACCGGATGTT TAAGTTCGAA CTCACCCGCC AAV9 GCACCAGCAG CCTCTCCAGG ACCGGATGTT TAAGTTCGAA CTCACCCGCC AAV7 GCACCAGCAG CCGTTGCAGG ACCGGATGTT CAAATTTGAA CTCACCCGCC 44 2 GCACCAGCAG CCGTTGCAGG ACCGGATGTT CAAGTTTGAA CTCACCCGCC

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PCT/U502/33629 WO 03/042397 20 Feb 2020

Fig. 1AI

1701 1750 42 2 GTCTGGAGCA CGACTTTGGC AAGGTGACAA AGCAGGAAGT CAAAGAGTTC 42y8 GTCTGGAGCA CGACTTTGGC AAGGTGACAA AGCAGGAAGT CAAAGAGTTC 42_15 GTCTGGAGCA TGACTTTGGC AAGGTGACAA AGCAGGAAGT CAAAGAGTTC 42 5b GTCTGGAGCA CGACTTTGGC AAGGTGACAA AGCAGGAAGT CAAAGAGTTC 42-1b 42 13 GTCTGGAGCA TGACTTTGGC AAGGTGACAA AGCAGGAAGT CAAAGAGTTC 42 3a GTCTGGAGCA TGACTTTGGC AAGGTGACAA AGCAGGAAGT CAAAGAGTTC 2020201242

4214 42_5a GTCTGGAGCA TGACTTTGGC AAGGCGACAA AGCAGGAAGT CAAAGAGTTC 42 10 42 3b 4211 GTCTGGAGCA CGACTTTGGC AAGGTGACAA AGCAGGAAGT CAAAGAGTTC 42 6b AGCGGGCCTG CCCCTCAGTC GCGGATCCAT CGACGTCAGA CGCGGAAGGA 43_1 GTCTGGAGCA CGACTTTGGC AAGGTGACCA AGCAGGAAGT CAAAGAGTTC 43_5 GTCTGGAGCA CGACTTTGGC AAGGTGACCA AGCAGGAAGT CAAAGAGTTC 43_12 GTCTGGAGCA CGACTTTGGC AAGGTGACCA AGCAGGAAGT CAAAGAGTTC 3 20 4 GTCTGGAGCA TGACTTTGGC AAGGTGACGA AGCAGGAAGT CAAAGAGTTC 4321 A GTCTGGAGCA TGACTTTGGC AAGGTGACGA AGCAGGAAGT CAAAGAGTTC 43 23 GTCTGGAGCA TGACTTTGGC AAGGTGACGA AGCAGGAAGT CAAAGAGTTC 43 25 GTCTGGAGCA TGACTTTGGC AAGGTGACGA AGCAGGAAGT CAAAGGGTTC 44 1 GTCTGGAGCA CGACTTTGGC AAGGTGACAA AGCAGGAAGT CAGAGAGTTC 44 5 GTCTGGAGCA CGACTTTGGC AAGGTGACAA AGCAGGAAGT CAGAGAGTTC 223_10 223_2 2234 223 5 223_6 223-7 A34 GTTTGGATCA TGACTTTGGG AAGGTCACCA AGCAGGAAGT CAAAGACTTT A3 5 GTTTGGATCA TGACTTTGGG AAGGTCACCA AGCAGGAAGT CAAAGACTTT A317 GTTTGGATCA TGACTTTGGG AAGGTCACCA AGCAGGAAGT CAAAGACTTT A33 GTTTGGATCA TGACTTTGGG AAGGTCACCA AGCAGGAAGT CAAAGACTTT 42_12 GTCTGGAGCA CGACTTTGGC AAGGTGACAA AGCAGGAAGT CAAAGAGTTC AAV1 GTCTGGAGCA TGACTTTGGC AAGGTGACAA AGCAGGAAGT CAAAGAGTTC AAV2 GTCTGGATCA TGACTTTGGG AAGGTCACCA AGCAGGAAGT CAAAGACTTT AAV3 GTTTGGACCA TGACTTTGGG AAGGTCACCA AACAGGAAGT AAAGGACTTT AAV8 GTCTGGAGCA CGACTTTGGC AAGGTGACAA AGCAGGAAGT CAAAGAGTTC AAV9 GTCTGGAGCA CGACTTTGGC AAGGTGACAA AGCAGGAAGT CAAAGAGTTC AAV7 GTCTGGAGCA CGACTTTGGC AAGGTGACGA AGCAGGAAGT CAAAGAGTTC 44 2 GTCTGGAGCA CGACTTTGGC AAGGTGACAA AGCAGGAAGT CAGAGAGTTC

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Fig. 1AJ

1751 1800 42 2 TTCCGCTGGG CGCAGGATCA CGTGACCGAG GTGGCGCATG AGTTCTACGT 42 8 TTCCGCTGGG CGCAGGATCA CGTGACCGAG GTGGCGCATG AGTTCTACGT 42_15 TTCCGCTGGG CGCAGGATCA CGTGACCGAG GTGGCGCATG AGTTCTACGT 42 5b TTCCGCTGGG CGCAGGATCA CGTGACCGAG GTGGCGCATG AGTTCTACGT 42—lb 42 13 TTCCGCTGGG CGCAGGATCA CGTGACCGAG GTGGCGCATG AGTTCTACGT 2020201242

42 3a TTCCGCTGGG CGCAGGATCA CGTGACCGAG GTGGCGCATG AGTTCTACGT 4i_4 42 5a TTCCGCTGGG CGCAGGATCA CGTGACCGAG GTGGCGCATG AGTTCTACGT 42 10 42 3b 42 11 TTCCGCTGGG CGCAGGATCA CGTGACCGAG GTGGCGCATG AGTTCTACGT 42_6b GCTCCGGTGG ACTTTGCCGA CAGGTACCAA AACAAATGTT CTCGTCACGC 4 -3- 1 TTCCGCTGGG CGCAGGATCA CGTGACCGAG GTGGCGCATG AGTTCTACGT 43_5 TTCCGCTGGG CGCAGGATCA CGTGACCGAG GTGGCGCATG AGTTCTACGT 43 12 TTCCGCTGGG CGCAGGATCA CGTGACCGAG GTGGCGCATG AGTTCTACGT 43 20 TTCCGCTGGG CGCAGGATCA CGTGACCGAG GTGGCGCATG AGTTCCACGT 43-21 TTCCGCTGGG CGCAGGATCA CGTGACCGAG GTGGCGCATG AGTTCCACGT 4323 TTCCGCTGGG CGCAGGATCA CGTGACCGAG GTGGCGCATG AGTTCCACGT 4325 TTCCGCTGGG CGCAGGATCA CGTGACCGAG GTGGCGCATG AGTTCCACGT 44 1 TTCCGCTGGG CGCAGGATCA CGTGACCGAG GTGGCGCACG AGTTCTACGT 44 5 TTCCGCTGGG CGCAGGATCA CGTGACCGAG GTGGCGCACG AGTTCTACGT 223_10 223 2 223W4 223_5 223_6 223-7 A3 r4 TTCCGGTGGG CTCAAGATCA CGTGACTGAG GTGGAGCATG AGTTCTACGT A3 r5 TTCCGGTGGG CTCAAGATCA CGTGACTGAG GTGGAGCATG AGTTCTACGT A37 TTCCGGTGGG CTCAAGATCA CGTGACTGAG GTGGAGCATG AGTTCTACGT A3_3 TTCCGGTGGG CTCAAGATCA CGTGACTGAG GTGGAGCATG AGTTCTACGT 42_12 TTCCGCTGGG CGCAGGATCA CGTGACCGAG GTGGCGCATG AGTTCTACGT AAV1 TTCCGCTGGG CGCAGGATCA CGTGACCGAG GTGGCGCATG AGTTCTACGT AAV2 TTCCGGTGGG CAAAGGATCA CGTGGTTGAG GTGGAGCATG AATTCTACGT AAV3 TTCCGGTGGG CTTCCGATCA CGTGACTGAC GTGGCTCATG AGTTCTACGT AAVS TTCCGCTGGG CCAGTGATCA CGTGACCGAG GTGGCGCATG AGTTTTACGT AAV9 TTCCGCTGGG CCAGTGATCA CGTGACCGAG GTGGCGCATG AGTTTTACGT AAV7 TTCCGCTGGG CCAGTGATCA CGTGACCGAG GTGGCGCATG AGTTCTACGT 44_2 TTCCGCTGGG CGCAGGATCA CGTGACCGAG GTGGCGCACG AGTTCTACGT

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Fig. 1AK

1801 1850 P40 TAT

42_2 CAGAAAGGGT GGAGCCAACA AGAGACCCGC CCCCGATGAC GC GGA AAAA 42_8 CAGAAAGGGT GGAGCCAACA AGAGACCCGC CCCCGATGAC GCGGA AAAA 42 15 CAGAAAGGGT GGAGCCAACA AGAGACCCGC CCCCGATGAC GCGGATAAAA 4215b CAGAAAGGGT GGAGCCAACA AGAGACCCGC CCCCGATGAC GCGGATAAAA 42 lb 2020201242

42_13 CAGAAAGGGT GGAGCCAACA AGAGACCCGC CCCCGATGAC GCGGATAAAA 42_3a CAGAAAGGGT GGAGCCAACA AGAGACCCGC CCCCGATGAC GCGGATAAAA 42_4 42_5a CAGAAAGGGT GGAGCCAACA AGAGACCCGC CCCCGATGAC GCGGATAAAA 42 10 42 3b 42:11 CAGAAAGGGT GGAGCCAACA AGAGACCCGC CCCCGATGAC GCGGATAAAA 42_6b GGGCATAGCG CTGACGTAAA. TCACGTCATA GGGGAGTGGT C CTGTAT TAG 43 1 CAGAAAGGGC GGAGCCAGCA AAAGACCCGC CCCCGATGAC GCGGATATAA 43 5 CAGAAAGGGC GGAGCCAGCA AAAGACCCGC CCCCGATGAC GCGGATATAA 43 12 CAGAAAGGGC GGAGCCAGCA AGAGACCCGC CCCCGATGAC GCGGATATAA 43W20 CAGAAAGGGT GGAGCCAACA AGAGACCCGC CCCCGATGAC GCGGATATAA 43:21 CAGAAAGGGT GGAGCCAACA AGAGACCC GC CCCCGATGAC GCGGATATAA 43_23 CAGAA.AGGGT GGAGCCAACA AGAGACCCGC CCCCGATGAC GCGGATATAA 43_25 CAGAAAGGGT GGAGCCAACA AGAGACCCGC CCCCGATGAC GCGGATATAA 44 1 CAGAAAGGGT GGAGCCAACA AGAGACCCGC CCCCGATGAC GCGGATAAAA 44 5 CAGAAAGGGT GGAGCCAACA AGAGACCCGC CCCCGATGAC GCGGATAAAA 223_10 223_2 223_4 2235 223_6 223W7 A3_4 CAAAAAGGGT GGAGCCAAGA AAAGGCCCGC CCCCGATGAT GTATATATAA A3-5 CAAAAAGGGT GGAGCCAAGA AAAGGCC CGC CCCCGATGAT GTATATATAA A3 7 CAAAAAGGGT GGAGCCAAGA AAAGGCCCGC CCCCGATGAT GTATATATAA A3_3 CAAAAAGGGT GGAGCCAAGA AAAGACCCGC CCCCGATGAT GTATATATAA 42_12 CAGAAAGGGT GGAGCCAACA AGAGACCCGC CCCCGATGAC GCGGATAAAA AAV1 CAGAAAGGGT GGAGCCAACA AAAGACCCGC CCCCGATGAC GCGGATAAAA AAV2 CAAAAAGGGT GGAGCCAAGA AAAGACCCGC CCCCAGTGAC GCAGATATAA AAV3 CAGAAAGGGT GGAGCTAAGA AACGCCCCGC CTCCAAT GAC GCGGATGTAA AAV8 CAGAAAGGGC GGAGCCAGCA AAAGACCCGC CCCCGATGAC GCGGATAAAA AA.V 9 CAGAAAGGGC GGAGCCAGCA AGAGACCCGC CCCCGATGAC GCGGATAAAA AAV7 CAGAAAGGGC GGAGCCAGCA AGAGACCCGC CCCCGATGAC GCGGATATAA 44 2 CAGAAAGGGT GGAGCCAACA AGAGACCCGC CCCCGATGAC GCGGAIA,,, P40/TA A

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Fig. 1AL

1851 2900 P40 RNA 42 2 GCGAGCCCAA GCGGGCCTGC CCCTCAGTCG CGGATCC ATC GACGTCAGAC 42 8 GCGAGCCCAA GCGGGCCTGC CCCTCAGTCG CGGATCCATC GACGTCAGAC 42 15 GCGAGCCCAA GCGGGCCTGC CCCTCAGTCG CGGATCCATC GACGTCAGAC 42 5b GCGAGCCCAA GCGGGCCTGC CCCTCAGTCG CGGATCCATC GACGTCAGAC 42—lb 2020201242

4213 GCGAGCCCAA GCGGGCCTGC CCCTCAGTCG CGGATCCATC GACGTCAGAC 42 3a GCGAGCCCAA GCGGGCCTGC CCCTCAGTCG CGGATCCATC GACGTCAGAC 42_4 42_5a GCGAGCCCAA GCGGGCCCGC CCCTCAGTCG CGGATCCATC GACGTCAGAC 42_10 42 3b 4211 GCGAGCCCAA GCGGGCCTGC CCCTCAGTCG CGGATCCATC GACGTCAGAC 42:6b CTGTCACGTG AGTGCTTTTG CGACATTTTG C..ATCCATC GACGTCAGAC 43_1 GCGAGCCCAA GCGGGCCTGC CCCTCAGTCG CGGATCCATC GACGTCAGAC 43_5 GCGAGCCCAA GCGGGCCTGC CCCTCAGTCG CGGATCCATC GACGTCAGAC 43_12 GCGAGCCCAA GCGGGCCTGC CCCTCAGTCG CGGATCCATC GACGTCAGAC 43_20 GCGAGCCCAA GCGGGCCTGC CCCTCAGTCG CGGATCCATC GACGTCAGAC 43 21 GCGAGCCCAA GCGGGCCTGC CCCTCAGTCG CGGATCCATC GACGTCAGAC 43_23 GCGAGCCCAA GCGGGCCTGC CCCTCAGTCG CGGATCCATC GACGTCAGAC 43125 GCGAGCCCAA GCGGGCCTGC CCCTCAGTCG CGGATCCATC GACGTCAGAC 44 1 GCGAGCCCAA GCGGGCCTGC CCCTCAGTCG CGGATCCATC GACGTCAGAC 44u5 GCGAGCCCAA GCGGGCCTGC CCCTCAGTCG CGGATCCATC GACGTCAGAC 223 10 223 2 2234 223 5 2236 223:7 A3_4 ATGAGCCCAA GCGGGCGCGC GAGTCAGTTG CGCAGCCATC GACGTCAGAC A3_5 ATGAGCCCAA GCGGGCGCGC GAGTCAGTTG CGCAGCCATC GACGTCAGAC A3 7 ATGAGCCCAA GCGGGCGCGC GAGTCAGTTG CGCAGCCATC GACGTCAGAC A3 3 ATGAGCCCAA GCGGGCGCGC GAGTCAGTTG CGCAGCCATC GACGTCAGAC 4212 GCGAGCCCAA GCGGGCCTGC CCCTCAGTCG CGGATCCATC GACGTCAGAC AAV1 GCGAGCCCAA GCGGGCCTGC CCCTCAGTCG CGGATCCATC GACGTCAGAC AAV2 GTGAGCCCAA ACGGGTGCGC GAGTCAGTTG CGCAGCCATC GACGTCAGAC AAV3 GCGAGCCAAA ACGGGAGTGC ACGTCACTTG CGCAGCCGAC AACGTCAGAC AAVB GCGAGCCCAA GCGGGCCTGC CCCTCAGTCG CGGATCCATC GACGTCAGAC AAV9 GCGAGCCCAA GCGGGCCTGC CCCTCAGTCG CGGATCCATC GACGTCAGAC AAV7 GCGAGCCCAA GCGGGCCTGC CCCTCAGTCG CGGATCCATC GACGTCAGAC 44 2 GCGAGCCCAA GCGGGCCTGC CCCTCAGTCG CGGATCCATC GACGTCAGAC

P40 RNA

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Fig. IAM

1901 1950 42 2 GCGGAAGGAG CTCCGGTGGA CTTTGCCGAC AGGTACCAAA ACAAATGTTC 42 8 GCGGAAGGAG CTCCGGTGGA CTTTGCCGAC AGGTACCAAA ACAAATGTTC 42 15 GCGGAAGGAG CTCCGGTGGA CTTTGCCGAC AGGTACCAAA ACAAATGTTC 42 5b GCGGAAGGAG CTCCGGTGGA CTTTGCCGAC AGGTACCAAA ACAAATGTTC 42:1b 42x13 GCGGAAGGAG CTCCGGTGGA CTTTGCCGAC AGGTACCAAA ACAAATGTTC 42 3a GCGGAAGGAG CTCCGGTGGA CTTTGCCGAC AGGTACCAAA ACAAATGTTC 2020201242

42 5a GCGGAAGGAG CTCCGGTGGA CTTTGCCGAC AGGTACCAAA ACAAATGTTC 4210 42 3b 4211 GCGGAAGGAG CTCCGGTGGA CTTTGCCGAC AGGTACCAAA ACAAATGTTC 42 6b GCGGAAGGAG CTCCGGTGGA CTTTGCCGAC AGGTACCAAA ACAAGTGTTC 43 1 GCGGAAGGAG CTCCGGTGGA CTTTGCCGAC AGGTACCAAA ACAAATGTTC 43 5 GCGGAAGGAG CTCCGGTGGA CTTTGCCGAC AGGTACCAAA ACAAATGTTC 43 12 GCGGAAGGAG CTCCGGTGGA CTTTGCCGAC AGGTACCAAA. ACAAATGTTC 4320 GCGGAAGGAG CTCCGGTGGA CTTTGCCGAC AGGTACCAAA ACAAATGTTC 43_21 GCGGAAGGAG CTCCGGTGGA CTTTGCCGAC AGGTACCAAA ACAAATGTTC 43 23 GCGGAAGGAG CTCCGGTGGA CTTTGCCGAC AGGTACCAAA ACAAATGTTC 43=25 GCGGAAGGAG CTCCGGTGGA CTTTGCCGAC AGGTACCAAA ACAAATGTTC 44 1 GCGGAAGGAG CTCCGGTGGA CTTTGCCGAC AGGTACCAAA ACAAATGTTC 44x5 GCGGAAGGAG CTCCGGTGGA CTTTGCCGAC AGGTACCAAA ACAAATGTTC 223_10 223_2 223_4 223 5 2236 223y7 A3 4 GCGGA...AG CTTCGATAAA CTACGCGGGC AGGTACCAAA ACAAATGTTC A3-5 GCGGA...AG CTTCGATAAA CTACGCGGAC AGGTACCAAA ACAAATGTTC A3 7 GCGGA...AG CTTCGATAAA CTACGCGGAC AGGTACCAAA ACAAATGTTC A3_3 GCGGA...AG CTTCGATAAA CTACGCGGAC AGGTACCAAA ACAAATGTTC 42_12 GCGGAAGGAG CTCCGGTGGA CTTTGCCGAC AGGTACCAAA ACAAATGTTC AAV1 GCGGAAGGAG CTCCGGTGGA CTTTGCCGAC AGGTACCAAA ACAAATGTTC AAV2 GCGGA...AG CTTCGATCAA CTACGCAGAC AGGTACCAAA ACAAATGTTC AAV3 GCGGA...AG CACCGGCGGA CTACGCGGAC AGGTACCAAA ACAAATGTTC AAVB GCGGAAGGAG CTCCGGTGGA CTTTGCCGAC AGGTACCAAA ACAAATGTTC AAV9 GCGGAAGGAG CTCCGGTGGA CTTTGCCGAC AGGTACCAAA ACAAATGTTC AAV7 GCGGAAGGAG CTCCGGTGGA CTTTGCCGAC AGGTACCAAA ACAAATGTTC 44_2 GCGGAAGGAG CTCCGGTGGA CTTTGCCGAC AGGTACCAAA ACAAATGTTC

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Fig. IAN

1951 2000 42_2 TCGTCACGCG GGCATGCTTC AGATGCTGTT TCCCTG.CAA GACATGCGAG 42_8 TCGTCACGCG GGCATGCTTC AGATGCTGTT TCCCTG.CAA GACATGCGAG 42 15 TCGTCACGCG GGCATGCTTC AGATGCTGTT TCCCTG.CAA GACATGCGAG 42 5b TCGTCACGCG GGCATGCTTC AGATGCTGTT TCCCTG.CAA GACATGCGAG 421b GAATTC GCCCTT.... .GGCTGCGTC 42y13 TCGTCACGCG GGCATGCTTC AGATGCTGTT TCCCTG.CAA GACATGCGAG 42 3a TCGTCACGCG GGCATGCTTC AGATGCTGCT TCCCTG.CAA 2020201242

GACATGCGAG 4&4 GAATTC GCCCTTTCTA CGGCTGCGTC 42 5a TCGTCACGCG GGCATGCTTC AGATGCTGTT TCCCTG.CAA AACATGCGAG 42 10 GAATTC GCCCTTTCTA CGGCTGCGTC 42-3b GAATTC GCCCTTTCTA CGGCTGCGTC 42 11 TCGTCACGCG GGCATGCTTC AGATGCTGTT TCCCTG.CAA GACATGCGAG 42 6b TCGTCACGCG GGCATGCTTC AGATGCTGTT TCCCTG.CAA GACATGCGAG 43- 1 TCGTCACGCG GGCATGCTTC AGATGCTGTT TCCCTG.CAA AACGTGCGAG 43_5 TCGTCACGCG GGCATGCTTC AGACGCTGTT TCCCTG.CAA AACGTGCGAG 43 12 TCGTCACGCG GGCATGCTCC AGATGCTGTT TCCCTG.CAA AACGTGCGAG 43y20 TCGTCACGCG GGCATGCTTC AGATGCTGTT TCCCTG.CAA GACATGCGAG 43-21 TCGTCACGCG GGCATGCTTC AGATGCTGTT TCCCTG.CAA GACATGCGAG 4323 TCGTCACGCG GGCATGCTTC AGATGCTGTT TCCCTG.CAA GACATGCGAG 4325 TCGTCACGCG GGCATGCTTC AGATGCTGTT TCCCTG.CAA GACATGCGAG 44 1 TCGTCACGCG GGCATGCTTC AGATGCTGTT TCCCTG.CAA AACATGCGAG 44x5 TCGTCACGCG GGCATGCTTC AGATGCTGTT TCCCTG.CAA AACATGCGAG 223 10 223_2 223_4 223_5 223u6 223-7 A3 4 TCGTCACGTG GGCATGAATC TGATGCTGTT TCCCTG.TCG ACAATGCGAA A3 5 TCGTCACGTG GGCATGAATC TGATGCTGTT TCCCTG.TCG ACAATGCGAA A3-7 TCGTCACGTG GGCATGAATC TGATGCTGTT TCCCTG.TCG ACAATGCGAA A3 3 TCGTCACGTG GGCATGAATC TGATGCTGTT TCCCTG.TCG ACAATGCGAA 42_12 TCGTCACGCG GGCATGCTTC AGATGCTGTT TCCCTG.CAA GACATGCGAG AAV1 TCGTCACGCG GGCATGCTTC AGATGCTGTT TCCCTG.CAA GACATGCGAG AAV2 TCGTCACGTG GGCATGAATC TGATGCTGTT TCCCTG.CAG ACAATGCGAG AAV3 TCGTCACGTG GGCATGAATC TGATGCTTTT TCCCTG.TAA AACATGCGAG AAV8 TCGTCACGCG GGCATGCTTC AGATGCTGTT TCCCTG.CAA AACGTGCGAG AAV9 TCGTCACGCG GGCATGCTTC AGATGCTGCT TCCCTG.CAA AACGTGCGAG AAV7 TCGTCACGCG GGCATGATTC AGATGCTGTT TCCCTG.CAA AACGTGCGAG 44 2 TCGTCACGCG GGCATGCTTC AGATGCTGTT TCCCTG.CAA AACATGCGAG

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Fig. 1A0

2001 2050 42 2 AGAATGAATC AGAATTTCAA CATTTGCTTC ACGCACGGGA CCAGAGACTG 42_8 AGAATGAATC AGAATTTCAA CATTTGCTTC ACGCACGGGA CCAGAGACTG 42 15 AGAATGAATC AGAATTTCAA CATTTGCTTC ACGCGCGGGA CCAGAGACTG 42 5b AGAATGAATC AGAATTTCAA CATTTGCTTC ACGCACGGGA CCAGAGACTG 42 lb A.ACTGGACC A..ATGAGAA CTTTCCCTTC A A CGATTGCGTC 42 13 AGAATGAATC AGAATTTCAA CATTTGCTTC ACGCACGGGA CCAGAGACTG 4213a AGAATGAATC AGAATTTCAG CATTTGCTTC ACGCACGGGA CCAGAGACTG 2020201242

42_4 A.ACTGGACC A..ATGAGAA CTTTCCCTTC A A CGATTGCGTC 42 5a AGAATGAATC AGAATTTCAA CATTTGCTTC ACGCACGGGA CCAGAGACTG 4210 A.ACTGGACC A..ATGAGAA CTTTCCCTTC A A CGATTGCGTC 42 3b A.ACTAGACC A..ATGAGAA CTTTCCCTTC A A CGATTGCGTC 42 11 AGAATGAATC AGAATTTCAA CATTTGCTTC ACGCACGGGA CCGGAGACTG 42:6b AGAATGAATC AGAATTTCAA CATTTGCTTC ACGCACGGGA CCAGAGACTG 43_1 AGAATGAATC AGAATTTCAA CATTTGCTTC ACGCACGGGG TCAGAGACTG 43_5 AGAATGAATC AGAATTTCAA CATTTGCTTC ACGCACGGGG TCAGAGACTG 43_12 AGAATGAATC AGAATTTCAA CATTTGCTTC ACGCACGGGG TCAGAGACTG 43 20 AGAATGAATC AGAATTTCAA CATTTGCTTC ACGCACGGGA CCAGAGACTG 43x21 AGAATGAATC AGAATTTCAA CATTTGCTTC ACGCACGGGA CCAGAGACTG 43123 AGAATGAATC AGAATTTCAA CATTTGCTTC ACGCACGGGA CCAGAGACTG 43_25 AGAATGAATC AGAATTTCAA CATTTGCTTC ACGCACGGGA CCAGAGACTG 44 1 AGAATGAATC AGAATTTCAA CATTTGCTTC ACGCACGGGA CCAGAGACTG 44 5 AGAATGAATC AGAATTTCAA CATTTGCTTC ACGCACGGGA CCAGAGACTG 223_10 223_2 223 4 223:5 223 6 223_7 A34 AGAATGAATC AGAATTCAAA TATCTGCTTC ACACACGGGC AAAAAGACTG A35 AGAATGAATC AGAATTCAAA TATCTGCTTC ACACACGGGC AAAAAGACTG A3-7 AGAATGAATC AGAATTCAAA TATCTGCTTC ACACACGGGC AAAAAGACTG A3 3 AGAATGAATC AGAATTCAAA TATCTGCTTC ACACACGGGC AAAAAGACTG 42_12 AGAATGAATC AGAATTTCAA CATTTGCTTC ACGCACGGGA CCAGAGACTG AAV1 AGAATGAATC AGAATTTCAA CATTTGCTTC ACGCACGGGA CCAGAGACTG AAV2 AGAATGAATC AGAATTCAAA TATCTGCTTC ACTCACGGAC AGAAAGACTG AAV3 AGAATGAATC AAATTTCCAA TGTCTGTTTT ACGCATGGTC AAAGAGACTG AAV8 AGAATGAATC AGAATTTCAA CATTTGCTTC ACACACGGGG TCAGAGACTG AAV9 AGAATGAATC AGAATTTCAA CATTTGCTTC ACACACGGGG TCAGAGACTG AAV7 AGAATGAATC AGAATTTCAA CATTTGCTTC ACACACGGGG TCAGAGACTG 44_2 AGAATGAATC AGAATTTCAA CATTTGCTTC ACGCACGGGA CCAGAGACTG

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Fig. lAP

2051 2100 422 TTCAGAATGT TTCCCCGGCG TGTCAGAATC TCAACC.... ..GGTCGTCA

42_8 TTCAGAATGT TTCCCCGGCG TGTCAGAATC TCAACC.... ..GGTCGTCA 42 15 TTCAGAATGT TTCCCGGGCG TGTCAGAATC TCAACC.... ..GGTCGTCA 42 5b TTCAGAATGT TTCCCCGGCG TGTCAGAATC TCAACC.... ..GGTCGTCA 421b GACAAGATGG TGATCTGGTG GG..AGGAGG GCAAGA.... ..TGACGGCC 42x13 TTCAGAATGT TTCCCCGGCG TGTCAGAATC TCAACC.... ..GGTCGTCA 2020201242

42:3a TTCAGAATGT TTCCCCGGCG TGTCAGAATC TCAACC.... ..GGTCGTCA 42_4 GACAAGATGG TGATCTGGTG GG..AGGAGG GCAAGA.... ..TGACGGCC 42 5a TTCAGAATGT TTCCCCGGCG TGTCAGAATC TCAACC. ..GGTCGTCA 42 10 GACAAGATGG TGATCTGGTG GG..AGGAGG GCAAGA. ..TGACGGCC 42-3b GACAAGATGG TGATCTGGTG GG..AGGAGG GCAAGA.... ..TGACGGCC 42^11 TTCAGAATGT TTCCCCGGCG TGTCAGAATC TCAACC.... ..GGTCGTCA 42 6b TTCAGAATGT TTCCCCGGCG TGTCAGAATC TCAACC. ..GGTCGTCA 43 1 CTCAGAATGT TTCCCCGGTG CATCAGAATC TCAACC. ..GGTCGTCA 43y5 CTCAGAATGT TTCCCCGGTG CATCAGAATC TCAACC.... ..GGTCGTCA 43 12 CTCAGAATGT TTCCCCGGTG CATCAGAATC TCAACC.... ..GGTCGTCA 4320 TTCAGAATGT TTCCCCGGCG TGTCAGAATC TCAACC.... ..GGTCGTCA 43 21 TTCAGAATGT TTCCCCGGCG TGTCAGAATC TCAACC.... ..GGTCGTCA 43_23 TTCAGAATGT TTCCCCGGCG TGTCAGAATC TCAACC.... ..GGTCGTCA 43:25 TTCAGAATGT TTCCCCGGCG TGTCAGAATC TCAACC.... ..GGTCGTCA 44 1 TTCAGAATGT TTCCCCGGCG TGTCAGAATC TCAACC.... ..GGTCGTCA 44 5 TTCAGAATGT TTCCCCGGCG TGTCAGAATC TCAACC.... ..GGTTGTCA 223_10 223_2 223_4 223 5 223 6 223_7 A3^4 TTTGGAATGC TTTCCCG... TGTCAGAATC TCAACCCGTT TCTGTCGTCA A315 TTTGGAATGC TTTCCCG... TGTCAGAATC TCAACCCGTT CCTGTCGTCA A3 7 TTTGGAATGC TTTCCCG... TGTCAGAATC TCAACCCGTT TCTGTCGTCA A3_3 TTTGGAATGC TTTCCCG... TGTCAGAATC TCAACCCGTT TCTGTCGTCA 42 12 TTCAGAATGT TTCCCCGGCG TGTCAGAATC TCAACC.... ..GGTCGTCA AAV1 TTCAGAGTGC TTCCCCGGCG TGTCAGAATC TCAACC.... ..GGTCGTCA AAV2 TTTAGAGTGC TTTCCCG... TGTCAGAATC TCAACCCGTT TCTGTCGTCA AAV3 TGGGGAATGC TTCCCTGGAA TGTCAGAATC TCAACCCGTT TCTGTCGTCA AAV8 CTCAGAGTGT TTCCCCGGCG TGTCAGAATC TCAACC.... ..GGTCGTCA AAV9 CTCAGAGTGT TTCCCCGGCG TGTCAGAATC TCAACC.... ..GGTCGTCA AAV7 TTTAGAGTGT TTCCCCGGCG TGTCAGAATC TCAACC.... ..GGTCGTCA 44_2 TTCAGAATGT TTCCCCGGCG TGTCAGAATC TCAACC.... ..GGTCGTCA

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Fig. 1AQ

2101 2150 42 2 GAAAGAGGAC GTATCGGAAA CTCTGTGCCA TTCATCATCT GCTGGGG.CG

42 8 GAAAGAGGAC GTATCGGAAA CTCTGTGCCA TTCATCATCT GCTAGGG.CG 42_15 GAAAGAGGAC GTATCGGAAA CTCTGTGCCA TTCATCATCT GCTGGGG.CG 42 5b GAAAGAGGAC GTATCGGAAA CTCTGTGCCA TTCATCATCT GCTGGGG.CG 42 lb .AAGGTCGTG GAGTCCGCCA AG....GCCA TTCATCATCT GCTGGGG.CG GTATCGGAAA CTCTGTGCCA TTCATCATCT 2020201242

4213 GAAAGAGGAC GCTGGGG.CG 42=3a GAAAGAGGAC GTATCGGAAA CTCTGTGCCA TTCATCATCT GCTGGGG.CG 42_4 .AAGGTCGTG GAGTCCGCCA AG....GCCA TTCATCATCT GCTGGGG.CG 42 5a GAAAGAGGAC GTATCGGAAA CTCTGTGCCA TTCATCATCT GCTGGGG.CG 42_-10 AA....GGTC GTGAAGTCCG CCAAG.GCCA TTCATCATCT GCTGGGG.CG 42-3b AA....GGTC GTGGAGTCCG CCAAG.GCCA TTCATCATCT GCTGGGG.CG 42_11 GAAAGAGGAC GTATCGGAAA CTCTGTGCCA TTCATCATCT GCTGGGG.CG 4216b GAAAGAGGAC GTATCGGAAA CTCTGTGCCA TTCATCATCT GCTGGGG.CG 43_1 GAAAAAAAAC GTATCAGAAA CTGTGTGCCA TTCATCATCT GCTGGGG.CG 435 GAAAAAAAAC GTATCAGAAA CTGTGTGCCA TTCATCATCT GCTGGGG.CG 43_12 GAARAAAAAC GTATCAGAAA CTGTGTGCCA TTCATCATCT GCTGGGG.CG 43 20 GAAAGAGGAC GTATCGGAAA CTCTGTGCGA TTCATCATCT GCTGGGG.CG 43 21 GAAAGAGGAC GTATCGGAAA CTCTGTGCGA TTCATCATCT GCTGGGG.CG 43=23 GAAAGAGGAC GTATCGGAAA CTCTGTGCGA TTCATCATCT GCTGGGG.CG 43_25 GAAAGAGGAC GTATCGGAAA CTCTGTGCGA TTCATCATCT GCTGGGG.CG 44_1 GAAAAAAGAC GTATCGGAAA CTCTGTGCGA TTCATCATCT GCTGGGG.CG 44 5 GAAAAAAGAC GTATCGGAAA CTCTGTGCGA TTCATCATCT GCTGGGG.CG 223 10 223_2 223_4 223 5 223=6 2237 A3_4 GAAAAACG .TATCAGAAA CTTTGTTACA TTCATCATAT CATGGGA.AA A35 GAAAAACG .TATCAGAAA CTTTGTTACA TTCATCATAT CATGGGA.AA A3_7 GAAAAACG .TATCAGAAA CTTTGTTACA TTCATCATAT CATGGGA.AA A3_3 GAAAAACG .TATCAGAAA CTTTGTTACA TTCATCATAT CATGGGA.AA GAAAGAGGAC GTATCGGAAA CTCTGTGCCA TTCATCATCT GCTGGGG.CG AAV1 GAAAGAGGAC GTATCGGAAA CTCTGTGCCA TTCATCATCT GCTGGGG.CG AAV2 AAAAGGCG .TATCAGAAA CTGTGCTACA TTCATCATAT CATGGGA.A.A AAV3 AAAAGAAGAC TTATCAGAAA CTGTGTCCAA TTCATCATAT CCTGGGA.AG AAV8 GAAAGAGGAC GTATCGGAAA CTCTGTGCGA TTCATCATCT GCTGGGG.CG AAV9 GAAAGAGGAC GTATCGGAAA CTCTGTGCGA TTCATCATCT GCTGGGG.CG AAV7 GAAAAAAGAC GTATCGGAAA CTCTGCGCGA TTCATCATCT GCTGGGG.CG 44 2 GAAAAAAGAC GTATCGGAAA CTCTGTGCGA TTCATCATCT GCTGGGGGCG

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Fig. 1AR

2151 2200 42 2 GGCTCCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTGG 42_^8 GGCTCCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTGG 42_15 GGCTCCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTGG 42 5b GGCTCCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTGG 42 lb GGCTCCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTGG 4213 GGCTCCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTGG 42:3a GGCTCCCGAG ATTGCTTGCT CGGCCTGCGA 2020201242

TCTGGTCAAC GTGGACCTGG 42_4 GGCTCCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTGG 42_5a GGCTCCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTGG 42_10 GGCTCCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTGG 42_3h GGCTCCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTGG 42 11 GGCTCCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTGG 42 6b GGCTCCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTGG 43 1 GGCACCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTGG 43:5 GGCACCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTGG 43_12 GGCACCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTGG 43 20 GGCTCCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTGG 4321 GGCTCCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTGG 4323 GGCTCCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTGG 43_25 GGCTCCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTGG 44_1 GGCACCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTAG 44_5 GGCACCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTAG 223_10 223_2 223 4 223:5 223_6 223 7 A3^4 AGAACCAGAC ...GCCTGCA CTGCCTGCGA CCTGGTAAAT GTGGACTTGG A3 5 AGTACCAGAC ...GCCTGCA CTGCCTGCGA CCTGGTAAAT GTGGACTTGG A3-7 AGTACCAGAC ...GCCTGCA CTGCCTGCGA CCTGGTAAAT GTGGACTTGG A3 3 AGTACCAGAC ...GCCTGCA CTGCCTGCGA CCTGGTAAAT GTGGACTTGG 42_12 GGCTCCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTGG AAV1 GGCTCCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTGG AAV2 GGTGCCAGAC ...GCTTGCA CTGCCTGCGA TCTGGTCAAT GTGGATTTGG AAV3 GGCACCCGAG ATTGCCTGTT CGGCCTGCGA TTTGGCCAAT GTGGACTTGG AAV8 GGCTCCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTGG AAV9 GGCTCCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTGG AAV7 GGCGCCCGAG ATTGCTTGCT CGGCCTGCGA CCTGGTCAAC GTGGACCTGG 44 2 GGCACCCGAG ATTGCTTGCT CGGCCTGCGA TCTGGTCAAC GTGGACCTAG

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Fig. lAS

2201 2250

Reg 78 sto p Vp 1 start 42_2 ATGACCGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA 42_8 ATGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA 42 Y5 ATGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA 42 5b ATGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA 42 lb ATGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA 2020201242

42 - 13 ATGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA 42:3a ATGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA 42_4 ATGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA 42 5a ATGACTGTGT 'TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA 42 10 ATGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA 42-3b ATGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA 42_- 11 ATGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA 42 6b ATGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA 43 1 ACGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA ACGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA 43_12 ACGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA 43_20 ATGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA 43_21 ATGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA 43:23 ATGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA 43_25 ATGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA 44 1 ATGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA 44 5 ATGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA 223 10 223_2 223_4 223_5 223_6 223_7 A3_4 ATGACTGTAT TTCTGAGCAA TAAATGACTT AAATCAGGTA TGGCTGCTGA A3_5 ATGACTGTAT TTCTGAGCAA TAAATGACTT AAATCAGGTA TGGCTGCTGA A3_7 ATGACTGTAT TTCTGAGCAA TAAATGACTT AAATCAGGTA TGGCTGCTGA A3_3 ATGACTGTAT TTCTGAGCAA TAAATGACTT AAATCAGGTA TGGCTGCTGA 42_12 ATGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA AAV1 ATGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA AAV2 ATGACTGCAT CTTTGAACAA TAAATGATTT AAATCAGGTA TGGCTGCCGA AAV3 ATGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCTGA AAV8 ATGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA AAV9 ATGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA AAV7 ACGACTGCGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA 44 2 ATGACTGTGT TTCTGAGCAA TAAATGACTT AAACCAGGTA TGGCTGCCGA Rep78 stop vpl start

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Fig. 1AT

2251 2300 1268 stop 42_2 TGGTTATCTT CCAGATTGGC TCGAGGACAA CCTCTCTGAG GGCATTCGCG 42_8 TGGTTATCTT CCAGATTGGC TCGAGGACAA CCTCTCTGAG GGCATTCGCG 42_15 TGGTTATCTT CCAGATTGGC TCGAGGACAA CCTCTCTGAG GGCATTCGCG 42_5b TGGTTATCTT CCAGATTGGC TCGAGGACAA CCTCTCTGAG GGCATTCGCG 42-1b TGGTTATCTT CCAGATTGGC TCGAGGACAA CCTCTCTGAG GGCATTCGCG 2020201242

42_13 TGGTTATCTT CCAGATTGGC TCGAGGACAA CCTCTCTGAG GGCATTCGCG 42_3a TGGTCATCTT CCAGATTGGC TCGAGGACAA CCTCTCTGAG GGCATTCGCG 4 TGGTTATCTT CCAGATTGGC TCGAGGACAA CCTCTCTGAG GGCATTCGCG 42_5a TGGTTATCTT CCAGATTGGC TCGAGGACAA CCTCTCTGAG GGCATTCGCG 42_10 TGGTTATCTT CCAGATTGGC TCGAGGACAA CCTCTCTGAG GGCATTCGCG 42 3b TGGTTATCTT CCAGATTGGC TCGAGGACAA CCTCTCTGAG GGCATTCGCG 42 11 TGGTTATCTT CCAGATTGGC TCGAGGACAA CCTCTCTGAG GGCATTCGCG 4276b TGGTTATCTT CCAGATTGGC TCGAGGACAA CCTCTCTGAG GGCATTCGCG 43_1 TGGTTATCTT CCAGATTGGC TTGAGGACAA CCTCTCTGAG GGCATTCGCG 43_5 TGGTTATCTT CCAGATTGGC TTGAGGACAA CCTCTCTGAG GGCATTCGCG 43_12 TGGTTATCTT CCAGATTGGC TTGAGGACAA CCTCTCTGAG GGCATTCGCG 43_20 TGGTTATCTT CCAGATTGGC TCGAGGACAA CCTCTCTGAG GGCATTCGCG 43_21 TGGTTATCTT CCAGATTGGC TCGAGGACAA CCTCTCTGAG GGCATTCGCG 43_23 TGGTTATCTT CCAGATTGGC TCGAGGACAA CCTCTCTGAG GGCATTCGCG 43 25 TGGTTATCTT CCAGATTGGC TCGAGGACAA CCTCTCTGAG GGCATTCGCG 4T 1 TGGTTATCTT CCAGATTGGC TCGAGGACAA CCTCTCTGAG GGCATTCGCG 44_5 TGGTTATCTT CCAGATTGGC TCGAGGACAA CCTCTCTGAG GGCATTCGCG 223_10 223_2 223_4 223_5 223_6 223_7 A3_4 CGGTTATCTT CCAGATTGGC TCGAGGACAC TCTCTCTGAA GGAATCAGAC A3_5 CGGTTATCTT CCAGATTGGC TCGAGGACAC TCTCTCTGAA GGAATCAGAC A3^7 CGGTTATCTT CCAGATTGGC TCGAGGACAC TCTCTCTGAA GGAATCAGAC A3_3 CGGTTATCTT CCAGATTGGC TCGAGGACAC TCTCTCTGAA GGAATCAGAC 42_12 TGGTTATCTT CCAGATTGGC TCGAGGACAA CCTCTCTGAG GGCATCCGCG AAV1 TGGTTATCTT CCAGATTGGC TCGAGGACAA CCTCTCTGAG GGCATTCGCG AAV2 TGGTTATCTT CCAGATTGGC TCGAGGACAC TCTCTCTGAA GGAATAAGAC AAV3 CGGTTATCTT CCAGATTGGC TCGAGGACAA CCTTTCTGAA GGCATTCGTG AAV8 TGGTTATCTT CCAGATTGGC TCGAGGACAA CCTCTCTGAG GGCATTCGCG AAV9 TGGTTATCTT CCAGATTGGC TCGAGGACAA CCTCTCTGAG GGCATTCGCG AAV7 TGGTTATCTT CCAGATTGGC TCGAGGACAA CCTCTCTGAG GGCATTCGCG 44_2 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 AGTGGTGGGA CTTGAAACCT GGAGCCCCGA AACCCAAAGC CAACCAGCAA 42_15 AGTGGTGGGA CTTGAAACCT GGAGCCCCGA AACCCAAAGC CAACCAGCAA 42_5b AGTGGTGGGA CTTGAAACCT GGAGCCCCGA AACCCAAAGC CAACCAGCAA 42 lb AGTGGTGGGA CTTGAGACCT GGAGCCCCGA AACCCAAAGC CAACCAGCAA 42:13 AGTGGTGGGA CTTGAAACCT GGAGCCCCGA AACCCAAAGC CAACCAGCAA 2020201242

42_3a AGTGGTGGGA CTTGAAACCT GGAGCCCCGA AACCCAAAGC CAACCAGCAA 42_4 AGTGGTGGGA CTTGAAACCT GGAGCCCCGA AACCCAAAGC CAACCAGCAA 42_5a AGTGGTGGGA CTTGAAACCT GGAGCCCCGA AACCCAAAGC CAACCAGCAA 42_10 AGTGGTGGGA CTTGAAACCT GGAGCCCCGA AACCCAAAGC CAACCAGCAA 42_3b AGTGGTGGGA CTTGAAACCT GGAGCCCCGA AACCCAAAGC CAACCAGCAA 42_11 AGTGGTGGGA CTTGAAACCT GGAGCCCCGA AACCCAAAGC CAACCAGCAA 42-6b AGTGGTGGGA CTTGAAACCT GGAGCCCCGA AACCCAAAGC CAACCAGCAA 1 AGTGGTGGGA CCTGAAACCT GGAGCCCCGA AACCCAAAGC CAACCAGCAA 43_5 AGTGGTGGGA CCTGAAACCT GGAGCCCCGA AACCCAAAGC CAACCAGCAA 43_1.2 AGTGGTGGGA CCTGAAACCT GGAGCCCCGA AACCCAAAGC CAACCAGCAA 43 20 AGTGGTGGGA CTTGAAACCT GGAGCCCCGA AACCCAAAGC CAACCAGCAA 4321 AGTGGTGGGA CTTGAAACCT GGAGCCCCGA AACCCAAAGC CAACCAGCAA 43_23 AGTGGTGGGA CTTGAAACCT GGAGCCCCGA AACCCAAAGC CAACCAGCAA 43_25 AGTGGTGGGA CTTGAAACCT GGAGCCCCGA AACCCAAAGC CAACCAGCAA 44 1 AGTGGTGGGA CTTGAAACCT GGAGCCCCGA AACCCAAAGC CAACCAGCAA 445 AGTGGTGGGA CTTGAAACCT GGAGCCCCGA AACCCAAAGC CAACCAGCAA 223_10 223_2 2234 223_5 223 6 223_7 A3 4 AGTGGTGGAA GCTCAAACCT GGCCCACCAC CGCCGAAACC TAACCAACAA A3 5 AGTGGTGGAA GCTCAAACCT GGCCCACCAC CGCCGAAACC TAACCAACAA A3:7 AGTGGTGGAA GCTCAAACCT GGCCCACCAC CGCCGAAACC TAACCAACAA A3_3 AGTGGTGGAA GCTCAAACCT GGCCCACCAC CGCCGAAACC TAACCAACAA 42_12 AGTGGTGGGA CTTGAAACCT GGAGCCCCGA AACCCAAAGC CAACCAGCAA AAV1 AGTGGTGGGA CTTGAAACCT GGAGCCCCGA AGCCCAAAGC CAACCAGCAA AAV2 AGTGGTGGAA GCTCAAACCT GGCCCACCAC CACCAAAGCC CGCAGAGCGG AAV3 AGTGGTGGGC TCTGAAACCT GGAGTCCCTC AACCCAAAGC GAACCAACAA AAV8 AGTGGTGGGC GCTGAAACCT GGAGCCCCGA AGCCCAAAGC CAACCAGCAA AAV9 AGTGGTGGGC GCTGAAACCT GGAGCCCCGA AGCCCAAAGC CAACCAGCAA AAV7 AGTGGTGGGA CCTGAAACCT GGAGCCCCGA AACCCAAAGC CAACCAGCAA 44 2 AGTGGTGGGA CTTGAAACCT GGAGCCCCGA AACCCAAAGC CAACCAGCAA

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Fig. lAV

2351 2400 42_2 AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG 42 8 AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG 42_15 AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG 42 5b AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG 4 2 lb AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG 42 13 AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG 4 2 3a AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG 2020201242

42- 4 AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG 42_5a AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG 42_10 AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG 4 2 3b AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG 4 2 11 AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG 42--_6b AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG 43_1 AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG 4 3_5 AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG 43_12 AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG 43_2 0 AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG 43 21 AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG 4323 AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG 4325 AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG 4-4- 1 AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG 445 AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG 223_10 223_2 223 4 22355 22366 2237 A3 4 CACCGGGACG ACAGTAGGGG TCTTGTGCTT CCTGGGTACA AGTACCTCGG A3_5 CACCGGGACG ACAGTAGGGG TCTTGTGCTT CCTGGGTACA AGTACCTCGG A3 7 CACCGGGACG ACAGTAGGGG TCTTGTGCTT CCTGGGTACA AGTACCTCGG A3_3 CACCGGGACG ACAGTAGGGG TCTTGTGCTT CCTGGGTACA AGTACCTCGG 425.2 AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG ATM AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG AAV2 CATAAGGACG ACAGCAGGGG TCTTGTGCTT CCTGGGTACA AGTACCTCGG AAV3 CAC CAGGACA ACCGTCGGGG TCTTGTGCTT CCGGGTTACA AATACCTCGG AAV8 AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG AAV9 AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG AAV7 AAGCAGGACA ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG 44 2 AAGCAGGACG ACGGCCGGGG TCTGGTGCTT CCTGGCTACA AGTACCTCGG

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Fig. lAW

2401 2450 422 ACCCTTCAAC GGACTCGACA AGGGAGAGCC GGTCAACGAG GCAGACGCCG 42_8 ACCCTTCAAC GGACTCGACA AGGGGGAGCC CGTCAACGCG GCGGACGCAG 4255 ACCCTTCAAC GGACTCGACA AGGGGGAGCC CGTCAACGCG GCGGACGCAG 42_5b ACCCTTCAAC GGACTCGACA AGGGAGAGCC GGTCAACGAG GCAGACGCCG 42 lb ACCCTTCAAC GGACTCGACA AGGGAGAGCC GGTCAACGAG GCAGACGCCG 42_13 ACCCTTCAAC GGACTCGACA AGGGGGAGCC CGTCAACGCG GCGGACGCAG 42-3a ACCCTTCAAC GGACTCGACA AGGGGGAGCC CGTCAACGCG GCGGACGCAG 2020201242

42_4 ACCCTTCAAC GGACTCGACA AGGGAGAGCC GGTCAACGAG GCAGACGCCG 42 ACCCTTCAAC GGACTCGACA AGGGAGAGCC GGTCAACGAG GCAGACGCCG 42_10 ACCCTTCAAC GGACTCGACA AGGGAGAGCC GGTCAACGAG GCAGACGCCG 42 3b ACCCTTCAAC GGACTCGACA AGGGAGAGC C GGTCAACGAG GCAGACGC CG 42=11 ACCCTTCAAC GGACTCGACA AGGGAGAGCC G GT CAACGCG GCGGACGCAG 42 6b ACCCTTCAAC GGACTCGACA AGGGAGAGCC GGTCAACGAG GCAGACGCCG 43_1 ACCCTTCAAC GGACTC GACA AGGGGGAGCC CGTCAACGCG GCGGACGCAG 43 5 ACCCTT CAAC GGACTCGACA AGGGGGAGCC CGTCAACGCG GCGGACGCAG 43_12 ACCCTTCAAC GGACTCGACA AGGGGGAGCC CGTCAACGCG GCGGACGCAG 43 20 ACCCTTCAAC GGACTCGACA AGGGGGAGCC CGTCAACGCG GCGGACGCAG 43-21 ACCCTTCAAC GGACTCGACA AGGGGGAGCC CGTCAACGCG GCGGACGCAG 43_23 ACCCTTCAAC GGACTCGACA AGGGGGAGCC CGTCAACGCG GCGGACGCAG 43-25 ACCCTTCAAC GGACTCGACA AGGGGGAGCC CGTCAACGCG GCGGACGCAG 4i 1 ACCCTTCAAC GGACTCGACA AGGGGGAGCC CGTCAACGCG GCGGACGCAG 44 5 ACCCTTCAAC GGACTCGACA AGGGGGAGCC CGTCAACGCG GCGGACGCAG I 223 0 22.7_2 223_4 223_5 223_6 223_7 A3_4 ACCCTT CAAC GGACTCGACA AAGGAGAGCC GGTCAACGAG GCAGACGCCG A3^5 ACCCTTCAAC GGAC TCGACA AAGGAGAGCC GGTCAACGAG GCAGACGCCG A3_7 ACCCTTCAAC GGACTCGACA AAGGAGAGCC GGTCAACGAG GCAGACGCCG A3_3 ACCCTTCAAC GGACTCGACA AAGGAGAGCC GGTCAACGAG GCAGACGCCG 42_12 ACCCTT CAAC GGACTCGACA AGGGAGAGCC GGTCAACGAG GCAGACGCCG AAV1 ACCCTTCAAC GGACTCGACA AGGGGGAGCC CGT CAACGCG GCGGACGCAG AAV2 ACCCTTCAAC GGACTCGACA AGGGAGAGCC GGTCAACGAG GCAGACGCCG AAV3 ACCCGGTAAC GGACTCGACA AAGGAGAGCC GGTCAACGAG GCGGACGCGG AAV8 ACCCTTCAAC GGACTCGACA AGGGGGAGCC CGTCAACGCG GCGGACGCAG AAV9 ACCCTTCAAC GGACTCGACA AGGGGGAGCC CGTCAACGCG GCGGACGCAG AAV7 ACCCTTCAAC GGACTCGACA AGGGGGAGCC CGTCAACGCG GCGGACGCAG 44 2 ACCCTTCAAC GGACTCGACA AGGGGGAGCC CGTCAACGCG GCGGACGCAG

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WO 03/042397 PCULTS02/33629 20 Feb 2020

Fig. lAX

2451 2500 42 2 CGGCCCTCGA GCACG.ACAA GGCCTACGAC AAGCAGCTCG AGCAGGGGGA 424_8 CGGCCCTCGA GCACG.ACAA GGCCTACGAC CAGCAGCTCA AAGCGGGTGA 42_15 CGGCCCTCGA GCACG.ACAA GGCCTACGAC CAGCAGCTCA AAGCGGGTGA 4215b 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 2020201242

42_4 CGGCCCTCGA GCACG.ACAA GGCCTACGAC AAGCAGCTCG AGCAGGGGGA 42_3a CGGCCCTCGA GCACG.ACAA GGCCTACGAC AAGCAGCTCG AGCAGGGGGA 42_10 CGGCCCTCGA GCACG.ACAA GGCCTACGAC AAGCAGCTCG AGCAGGGGGA 42 3b CGGCCCTCGA GCACG.ACAA GGCCTACGAC AAGCAGCTCG AGCAGGGGGA 4211 CGGCCCTCGA GCACG.ACAA GGCCTACGAC CAGCAGCTCA AAGCGGGTGA 42_^ 6b CGGCCCTCGA GCACG.ACAA GGCCTACGAC AAGCAGCTCG AGCAGGGGGA 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 21 CGGCCCTCGA GCACG.ACAA AGCCTACGAC CAGCAGCTCA AAGCGGGTGA 43__23 CGGCCCTCGA GCACG.ACAA AGCCTACGAC CAGCAGCTCA AAGCGGGTGA 43_25 CGGCCCTCGA GCACG.ACAA AGCCTACGAC CAGCAGCTCA AAGCGGGTGA 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_52 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 AAVB 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

50/105

WO 03/042397 20 Feb 2020

Fig. 'AY

2501 2550 42_2 CAACCCGTAC CTCAAGTACA ACCACGCCGA CGCCGAGTTT CAGGAGCGTC 428 CAATCCGTAC CTGCGGTATA ACCACGCCGA CGCCGAGTTT CAGGAGCGTC 42_15 CAATCCGTAC CTGCGGTATA ACCACGCCGA CGCCGAGTTT CAGGAGCGTC 42 5b CAACCCGTAC CTCAAGTACA ACCACGCCGA CGCCGAGTTT CAGGAGCGTC 42 1b CAACCCGTAC CTCAAGTACA ACCACGCCGA CGCCGAGTTT CAGGAGCGTC 42 13 CAATCCGTAC CTGCGGTATA ACCACGCCGA CGCCGAGTTT CAGGAGCGTC 42:3a CAATCCGTAC C TGCGGTATA ACCACGCCGA CGCCGAGTTT CAGGAGCGTC 2020201242

42_4 CAACCCGTAC CTCAAGTACA ACCACGCCGA CGCCGAGTTT CAGGAGCGTC 42_5a CAACCCGTAC CTCAAGTACA ACCACGCCGA CGCCGAGTTT CAGGAGCGTC 42 10 CAACCCGTAC CTCAAGTACA ACCACGCCGA CGCCGAGTTT CAGGAGCGTC 42^3b CAACCCGTAC CTCAAGTACA ACCACGCCGA CGCCGAGTTT CAGGAGCGTC 4211 CAATCCGTAC CTGCGGTATA ACCACGCCGA CGCCGAGTTT CAGGAGCGTC 42 6b CAACCCGTAC CTCAAGTACA ACCACGCCGA CGCCGAGTTT CAGGAGCGTC 1 CAATCCGTAC CTGCGGTATA ACCACGCCGA CGCCGAGTTT CAGGAGCGTC 43_5 CAATCCGTAC CTGCGGTATA ACCACGCCGA CGCCGAGTTT CAGGAGCGTC 43_12 CAATCCGTAC CTGCGGTATA ACCACGCCGA CGCCGAGTTT CAGGAGCGTC 43:20 CAATCCGTAC CTGCGGTATA ATCACGCCGA CGCCGAGTTT CAGGAGCGTC 432121 CAATCCGTAC CTGCGGTATA ATCACGCCGA CGCCGAGTTT CAGGAGCGTC 43:23 CAATCCGTAC CTGCGGTATA ATCACGCCGA CGCCGAGTTT CAGGAGCGTC 43_25 CAATCCGTAC CTGCGGTATA ATCACGCCGA CGCCGAGTTT CAGGAGCGTC 44_1 CAATCCGTAC CT GCGGTATA ACCACGCCGA CGCCGAGTTT CAGGAGCGTC 44_5 CAATCCGTAC CTGCGGTATA ACCACGCCGA CGCCGAGTTT CAGGAGCGTC 223_10 CAATCCGTAC C TGCGGTATA ACCACGCCGA CGCCGAGTTT CAGGAGCGTC 223_2 CAATCCGTAC CTGCGGTATA ACCACGCCGA CGCCGAGTTT CAGGAGT GTC 223_4 CAATCCGTAC CTGCGGTATA ACCACGCCGA CGCCGAGTTT CAGGAGCGTC 223 5 CAATCCGTAC CTGCGGTATA ACCACGCCGA CGCCGAGTTT CAGGAGCGTC 223~6 CAATCCGTAC CTGCGGTATA ACCACGCCGA CGCCGAGTTT CAGGAGCGTC 223:7 CAATCCGTAC CTGCGGTATA ACCACGCCGA CGCCGAGTTT CAGGAGCGTC A3 4 CAACCCGTAC CTCAAATACA ACCACGCGGA CGCTGAATTT CAGGAGCGTC A3_5 CAACCCGTAC CTCAAATACA ACCACGCGGA CGCTGAAT TT CAGGAGCGTC A3-7 CAACCCGTA.0 CT CAAATACA ACCACGCGGA CGCTGAAT TT CAGGAGCGTC A3_3 CAACCCGTAC CTCAAATACA ACCACGCGGA CGCTGAATTT CAGGAGCGTC 42_12 CAACCCGTAC CTCAAGTACA ACCACGCCGA CGCCGAGTTT CAGGAGCGTC AAV1 CAATCCGTAC CTGCGGTATA ACCACGCCGA CGCCGAGTTT CAGGAGCGTC AAV2 CAACCCGTAC CTCAAGTACA ACCACGCC GA CGCGGAGTTT CAGGAGCGCC AAV3 CAACCCGTAC CTCAAGTACA ACCACGCCGA CGCCGAGTTT CAGGAGCGTC AAV8 CAATCCGTAC CTGCGGTATA ACCACGCCGA CGCCGAGTTT CAGGAGCGTC AAV9 CAATCCGTAC CTGCGGTATA ACCACGCCGA CGCCGAGTTT CAGGAGCGTC AAV7 CAATCCGTAC CTGCGGTATA ACCACGCCGA CGCCGAGTTT CAGGAGCGTC 44_2 CAATCCGTAC CTGCGGTATA ACCACGCCGA CGCCGAGTTT CAGGAGCGTC

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Fig. 1AZ

2551 2600 42 2 TTCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG 42 8 TGCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG 42 15 TGCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG 42_5b TTCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG 42 lb TTCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG 42:13 TTCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG 42_3a TTCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG 2020201242

42_4 TTCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG 42_5a TTCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCGG 42_10 TTCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG 42 3b TTCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG 42:11 TTCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG 42_6b TTCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG 431, TGCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG 43_5 TGCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG 43 TGCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG 43_ 20 TGCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG 43_21 TGCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG 43-23 TGCAAGAAGA TACGTCCTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG 43_25 TGCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG 41_ 1 TGCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG 44_5 TGCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG 223_10 TTCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG 223 2 TTCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG 223_4 TTCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG 223 5 TTCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG 223:6 TTCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG 223_7 TTCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG A3_4 TTCAAGAAGA TACGTCTTTC GGGGGCAACC TCGGGCGAGC AGTCTTCCAG A3_5 TTCAAGAAGA TACGTCTTTC GGGGGCAACC TCGGGCGAGC AGTCTTCCAG A3_7 TTCAAGAAGA TACGTCTTTC GGGGGCAACC TCGGGCGAGC AGTCTTCCAG A3_3 TTCAAGAAGA TACGTCTTTC GGGGGCAACC TCGGGCGAGC AGTCTTCCAG 4212 TTCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG AAV1 TGCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG AAV2 TTAAAGAAGA TACGTCTTTT GGGGGCAACC TCGGACGAGC AGTCTTCCAG AAV3 TTCAAGAAGA TACGTCTTTT GGGGGCAACC TT GGCAGAGC AGTCTTCCAG AAV8 TGCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG AAV9 TGCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG AAV7 TGCAAGAAGA TACGTCAT TT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG 44_2 TGCAAGAAGA TACGTCTTTT GGGGGCAACC TCGGGCGAGC AGTCTTCCAG

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Fig. lAAA

2 601 2 650 4 2 2 GCCAAGAAGC GGGTTCTCGA ACCTCTCGGT CTGGTTGAGG AAGGCGCTAA 4 2 8 GCCAAGAAGC GGGTTCTCGA ACCTCTCGGT CTGGTTGAGG AAGGCGCTAA 4 2 15 GCCAAGAAGC GGGTTCTCGA ACCTCTCGGT CTGGTTGAGG AAGGCGCTAA 42 5b GCCAAGAAGC GGGTTCTCGA ACCTCTCGGT CTGGTTGAGG AAGGCGCTAA 42_1b GCCAAGAAGC GGGTTCTCGA ACCTCTCGGT CTGGTTGAGG AAGGCGCTAA 421313 GCCAAGAAGC GGGTTCTCGA ACCTCTCGGT CTGGTTGAGG AAGGCGCTAA 42_ GCCAAGAAGC GGGTTCTCGA ACCTCTCGGT CTGGTTGAGG AAGGCGCTAA 2020201242

42_4 GCCAAGAAGC GGGTTCTCGA ACCTCTCGGT CTGGTTGAGG AAGGCGCTAA 42_5a GCCAAGAAGC GGGTTCTCGA ACCTCTCGGT CTGGTTGAGG AAGGCGCTAA 4 2 10 GCCAAGAAGC GGGTTCTCGA ACCTCTCGGT CTGGTTGAGG AAGGCGCTAA 42 3b GCCAAGAAGC GGGTTCTCGA ACCTCTCGGT CTGGTTGAGG AAGGCGCTAA 4 211 GCCAAGAAGC GGGTTCTCGA ACCTCTCGGT CTGGTTGAGG AAGGCGCTAA 4 2 6b GCCAAGAAGC GGGTTCTCGA ACCTCTCGGT CTGGTTGAGG AAGGCGCTAA 45 1 GCCAAGAAGC GGGTTCTCGA ACCTCTCGGT CTGGTTGAGG AAGGCGCTAA 435 GCCAAGAAGC GGGTTCTCGA ACCTCTCGGT CTGGTTGAGG AAGGCGCTAA 4 3 12 GCCAAGAAGC GGGTTCTCGA ACCTCTCGGT CTGGTTGAGG AAGGCGCTAA 4 3 2 0 GCCAAGAAGC GGGTTCTCGA ACCTCTCGGT CTGGTTGAGG AAGGCGCTAA 4 3-21 GCCAAGAAGC GGGTTCTCGA ACCTCTCGGT CTGGTTGAGG AAGGCGCTAA 4 3 23 GCCAAGAAGC GGGTTCTCGA ACCTCTCGGT CTGGTTGAGG AAGGCGCTAA 43_25 GCCAAGAAGC GGGTTCTCGA ACCTCTCGGT CTGGTTGAGG AAGGCGCTAA 44 1 GCCAAGAAGC GGGTTCTCGA ACCTCTCGGT CTGGTTGAGG AAGGCGCTAA 445 GCCAAGAAGC GGGTTCTCGA ACCTCTCGGT CTGGTTGAGG AAGGCGCTAA 223_10 GCCAAAAAGC GGGTTCTCGA ACCTCTTGGT CTGGTTGAGA CGCCAGCTAA 223 _2 GCCAAAAAGC GGGTTCTCGA ACCTCTTGGT CTGGTTGAGA CGCCAGCTAA 22 3 4 GCCAAAAAGC GGGTTCTCGA ACCTCTTGGT CTGGTTGAGA CGCCAGCTAA 2235GC CAA_AAAGC GGGTTCTCGA. ACCTCTTGGT CTGGTTGAGA CGCCAGCTAA 2 2 3:6 GCCAAAAAGC GGGTTCTCGA ACCTCTTGGT CTGGTTGAGA. CGCCAGCTAA 223_77 GC CAAAAAGC GGGTTCTCGA ACCTCTTGGT CTGGTTGAGA CGCCAGCTAA A3_4 GCCAAAAAGA GGGTACTCGA GCCTCTTGGT CTGGTTGAGG AAGCTGTTAA A3 5 GCCAAAAAGA GGGTACTCGA GCCTCTTGGT CTGGTTGAGG AAGCTGTTAA A3 7 GCCAAAAAGA GGGTACTCGA GCCTCTTGGT CTGGTTGAGG AAGCTGTTAA A3_-3 GCCAAAAAGA GGGTACTCGA. GCCTCTTGGT CTGGTTGAGG AAGCTGTTAA 42_12 GCCAAGAAGC GGGTTCTCGA ACCTCTCGGT CTGGTTGAGG AAGGCGCTAA AAV1 GCCAAGAAGC GGGTTCTCGA ACCTCTCGGT CTGGTTGAGG AAGGCGCTAA AAV2 GCGAAAAAGA GGGTTCTTGA ACCTCTGGGC CTGGTTGAGG AACCTGTTAA AAV3 GCCAAAAAGA GGATCCTTGA GCCTCTTGGT CTGGTTGAGG AAGCAGCTAA AAV8 GCCAAGAAGC GGGTTCTCGA ACCTCTCGGT CTGGTTGAGG AAGGCGCTAA AAV9 GCCAAGAAGC GGGTTCTCGA ACCTCTCGGT CTGGTTGAGG AAGGCGCTAA AAV7 GCCAAGAAGC GGGTTCTCGA ACCTCTCGGT CTGGTTGAGG AAGGCGCTAA 4 4 2 GCCAAGAAGC GGGTTCTCGA ACCTCTCGGT CTGGTTGAGG AAGGCGCTAA

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Fig. lAAB

2651 2700

IR2 start 42 2 GACGGCTCCT GGAAAGAAGA GACCCATAGA ...ATCCCCC 42_8 GACGGCTCCT GGAAAGAAGA GACCGGTAGA GCCATCACCC CAGCGTTCTC 42_15 GACGGCTCCT GGAAAGAAGA' GACCGGTAGA GCCATCACCC CAGCGTTCTC 42 5b GACGGCTCCT GGAAAGAAGA GACCGGTAGA GCCATCACCC CAGCGTTCTC 2020201242

42—lb GACGGCTCCT GGAAAGAAGA GACCCATAGA ...ATCCCCC 42W13 GACGGCTCCT GGAAAGAAGA GACCCATAGA ...ATCCCCC 42-3a GACGGCTCCT GGAAAGAAGA GACCCATAGA ...ATCCCCC 42- 4 GACGGCTCCT GGAAAGAAGA GACCCATAGA ...ATCCCCC 42 GACGGCTCCT GGAAAGAAGA GACCCATAGA ...ATCCCCC 42 10 GACGGCTCCT GGAAAGAAGA GACCCATAGA ...ATCCCCC 42-3b GACGGCTCCT GGAAAGAAGA GACCCATAGA ...ATCCCCC 42_11 GACGGCTCCT GGAAAGAAGA GACCCATAGA ...ATCCCCC 42_6b GACGGCTCCT GGAAAGAAGA GACCGGTAGA GCCATCACCC CAGCGTTCTC 43 1 GACGGCTCCT GGAAAGAAGA GACCGGTAGA GCCATCACCT CAGCGTTCCC 43-5 GACGGCTCCT GGAAAGAAGA GACCGGTAGA GCCATCACCT CAGCGTTCCC 4312 GACGGCTCCT GGAAAGAAGA GACCGGTAGA GCCATCACCT CAGCGTTCCC 43x20 GACGGCTCCT GGAAAGAAGA GACTGGTAGA GCAGTCGCCA CAAGAG...0 4321 GACGGCTCCT GGAAAGAAGA GACCGGTAGA GCAGTCGCCA CAAGAG...0 43)3 GACGGCTCCT GGAAAGAAGA GACCGGTAGA GCAGTCGCCA CAAGAG...0 43x25 GACGGCTCCT GGAAAGAAGA GACCGGTAGA GCAGTCGCCA CAAGAG...0 44_1 GACGGCTCCT GGAAAGAAGA GACCGGTAGA GCCATCACCC CAGCGTTCTC 44_5 GACGGCTCCT GGAAAGAAGA GACCGGTAGA GCCATCACCC CAGCGTTCTC 223_10 GACGGCACCT GGAAAGAAGC GACCGGTAGA CTCGCCA 22 -312 GACGGCACCT GGAAAGAAGC GACCGGTAGA CTCGCCA 2234 GACGGCACCT GGAAAGAAGC GACCGGTAGA CTCGCCA 2235 GACGGCACCT GGAAAGAAGC GACCGGTAGA CTCGCCA 22316 GACGGCACCT GGAAAGAAGC GACCGGTAGA CTCGCCA 223_7 GACGGCACCT GGAAAGAAGC GACCGGTAGA CTCGCCA A3 u4 GACGGCTCCT GGAAAAAAGA GACCTATAGA GCAGTCTCCT GCAGAA...0 A3 5 GACGGCTCCT GGAAAAAAGA GACCTATAGA GCAGTCTCCT GCAGAA...0 A3 7 GACGGCTCCT GGAAAAAAGA GACCTATAGA GCAGTCTCCT GCAGAA...0 A33 GACGGCTCCT GGAAAAAAGA GACCTATAGA GCAGTCTCCT GCAGAA...0 42_12 GACGGCTCCT GGAAAGAAGA GACCGGTAGA GCCATCACCC CAGCGTTCTC AAV1 GACGGCTCCT GGAAAGAAAC GTCCGGTAGA GCAGTCGCCA CAAGAG...0 GACGGCTCCG GGAAAAAAGA GGCCGGTAGA GCACTCTCCT GTGGAG...0 AAV3 AACGGCTCCT GGAAAGAAGG GGGCTGTAGA TCAGTCTCCT CAGGAA...0 AAV8 GACGGCTCCT GGAAAGAAGA GACCGGTAGA GCCATCACCC CAGCGTTCTC AAV9 GACGGCTCCT GGAAAGAAGA GACCGGTAGA GCCATCACCC CAGCGTTCTC AAV7 GACGGCTCCT GCAAAGAAGA GACCGGTAGA GCCGTCACCT CAGCGTTCCC 44_2 GACGGCTCCT GGAAAGAAGA GACCGGTAGA GCCATCACCC CAGCGTTCTC vp2 start

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Fig. 1AAC

2701 2750 42_2 ..GACTCCTC CACGGGCATC GGCAAGAAAG GCCAGCAGCC CGCTAAAAAG 428 CAGACTCCTC TACGGGCATC GGCAAGACAG GCCAGCAGCC CGCGAAAAAG 42 15 CAGACTCCTC TACGGGCATC GGCAAGACAG GCCAGCAGCC CGCGAAAAAG 42 5b CAGACTCCTC TACGGGCATC GGCAAGACAG GCCAGCAGCC CGCGAAAAAG 42 —lb ..GACTCCTC CACGGGCATC GGCAAGAAAG GCCAGCAGCC CGCTAAAAAG 42 13 ..GACTCCTC CACGGGCATC GGCAAGAAAG GCCAGCAGCC CGCTAAAAAG 2020201242

421.3a ..GACTCCTC CACGGGCATC GGCAAGAAAG GCCAGCAGCC CGCTAAAAAG 42_4 ..GACTCCTC CACGGGCATC GGCAAGAAAG GCCAGCAGCC CGCTAAAAAG 42_5a ..GACTCCTC CACGGGCATC GGCAAGAAAG GCCAGCAGCC CGCTAAAAAG 42_10 ..GACTCCTC CACGGGCATC GGCAGGAAAG GCCAGCAGCC CGCTAAAAAG 42 3b ..GACTCCTC CACGGGCATC GGCAAGAAAG GCCAGCAGCC CGCTAAAAAG 42 11 ..GACTCCTC CACGGGCATC GGCAAGAAAG GCCAGCAGCC CGCTAAAAAG 42:6b CAGACTCCTC TACGGGCATC GGCAAGACAG GCCAGCAGCC CGCGAAAAAG 43 1 CCGACTCCTC CACGGGCATC GGCAAGAAAG GCCACCAGCC CGCGAGAAAG 435 CCGACTCCTC CACGGGCATC GGCAAGAAAG GCCACCAGCC CGCGAGAAAG 43 12 CCGACTCCTC CACGGGCATC GGCAAGAAAG GCCACCAGCC CGCGAGAAAG 4320 CAGACTCCTC CTCGGGCATC GGCAAGACAG GCCAGCAGCC CGCTAAAAAG 4321 — CAGACTCCTC CTCGGGCATC GGCAAGACAG GCCAGCAGCC CGCTAAAAAG 43 23 CAGACTCCTC CTCGGGCATC GGCAAGACAG GCCAGCAGCC CGCTAAAAAG 43_25 CAGACTCCTC CTCGGGCATC GGCAAGACAG GCCAGCAGCC CGCTAAAAAG 44 1 CAGACTCCTC TACGGGCATC GGCAAGAAAG GCCAGCAGCC CGCGAAAAAG 44^5 CAGACTCCTC TACGGGCATC GGCAAGAAAG GCCAGCAGCC CGCGAAAAAG 223_10 ..GACTCCAC CTCGGGCATC GGCAAGAAAG GCCAGCAGCC CGCGAAAAAG 2232 ..GACTCCAC CTCGGGCATC GGCAAGAAAG GCCAGCAGCC CGCGAAAAAG 223_ 4 ..GACTCCAC CTCGGGCATC GGCAAGAAAG GCCAGCAGCC CGCGAAAAAG 223 5 ..GACTCCAC CTCGGGCATC GGCAAGAAAG GCCAGCAGCC CGCGAAAAAG 22316 ..GACTCCAC CTCGGGCATC GGCAAGAAAG GCCAGCAGCC CGCGAAAAAG 223_7 ..GACTCCAC CTCGGGCATC GGCAAGAAAG GCCAGCAGCC CGCGAAAAAG A3 4 CGGACTCTTC CTCGGGCATC GGCGAATCAG GCCAGCAGCC CGCTAAGAAA A3=5 CGGACTCTTC CTCGGGCATC GGCAAATCAG GCCAGCAGCC CGCTAAGAAA A3 7 CGGACTCTTC CTCGGGCATC GGCAAATCAG GCCAGCAGCC CGCTAAGAAA A3 3 CGGACTCTTC CTCGGGCATC GGCAAATCAG GCCAGCAGCC CGCTAAGAAA 42_12 CAGACTCCTC TACGGGCATC GGCAAGACAG GCCAGCAGCC CGCGAAAAAG AAV1 CAGACTCCTC CTCGGGCATC GGCAAGACAG GCCAGCAGCC CGCTAAAAAG AAV2 CAGACTCCTC CTCGGGAACC GGAAAGGCGG GCCAGCAGCC TGCAAGAAAA AAV3 CGGACTCATC ATCTGGTGTT GGCAAATCGG GCAAACAGCC TGCCAGAAAA AAV8 CAGACTCCTC TACGGGCATC GGCAAGAAAG GCCAGCAGCC CGCCAGAAAA AAV9 CAGACTCCTC TACGGGCATC GGCAAGAAAG GCCAGCAGCC CGCCAGAAAA AAV7 CCGACTCCTC CACGGGCATC GGCAAGAAAG GCCAGCAGCC CGCCAGAAAG 442 CAGACTCCTC TACGGGCATC GGCAAGAAAG GCCAGCAGCC CGCGAAAAAG

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Fig. LAAD

2751 2800 42_2 AAGCTCAACT TTGGGCAGAC TGGCGACTCA GAGTCAGTGC CCGACCCCCA 42_8 AGACTCAACT TTGGGCAGAC TGGCGACTCA GAGTCAGTGC CCGACCCTCA 42 15 AGACTCAACT TTGGGCAGAC TGGCGACTCA GAGTCAGT GC CCGACCCTCA 42_5b AGACTCAACT TTGGGCAGAC TGGCGACTCA GAG TCAGTGC CCGACCCTCA 42-1b AGAC TCAACT TTGGGCAGAC TGGCGACTCA GAGTCAGTGC CCGACCCTCA 13 4213 AAGCTCAACT TTGGGCAGAC TGGCGACTCA GAGTCAGTGC CCGACCCTCA 42:3a AAGCTCAACT TTGGGCAGAC TGGCGACTCA GAGTCAGTGC CCGACCC TCA 2020201242

42_4 AAGCTCAACT TTGGGCAGAC TGGCGACTCA GAGTCAGTGC CCGACCCTCA 42_5a AAGCTCAACT TTGGGCAGAC TGGCGACTCA GAGTCAGTGC CCGACCCCCA 42 10 AAGCTCAACT TTGGGCAGAC TGGCGACT CA GAGTCAGT GC CCGACCCTCA 42 3b AAGCTCAACT TTGGGCAGAC TGGCGACTCA GAGTCAGTGC CCGACCCTCA 42:11 AAGCTCAACT TTGGGCAGAC TGGCGACTCA GAGTCAGTGC CCGACCCTCA 42_6b AGACTCAACT TTGGGCAGAC TGGCGACTCA GAGTCAGTGC CCGACCCTCA 43 1 AGACTGAACT TTGGGCAGAC TGGCGACTCG GAGTCAGTCC CCGACCCTCA 43 5 AGACTGAACT TTGGGCAGAC TGGCGACTCG GAGTCAGTCC CCGACCCTCA 4312 AGACTGAACT TTGGGCAGAC TGGCGACTCG GAGTCAGTCC CCGACCCTCA 43_20 AGACTCAATT TTGGTCAGAC TGGCGACTCA GAGTCAGTCC CCGACCCACA 43^21 AGACTCAATT TTGGTCAGAC TGGCGACTCA GAGTCAGTCC CCGACCCACA 43 23 AGACTCAATT TTGGTCAGAC TGGCGACTCA GAGTCAGTCC CCGACCCACA 43 25 AGACTCAATT TTGGTCAGAC TGGCGACTCA GAGTCAGTCC CCGACCCACA 44 1 AGACTCAACT TTGGGCAGAC TGGCGACTCA GAGTCAGTGC CCGACCCTCA 44 5 AGACTCAACT TTGGGCAGAC TGGCGACTCA GAGTCAGTGC CCGACCCT CA 223_10 AGACTCAACT TTGGGCAGAC TGGCGACTCA GAGTCAGTCC CCGACCCTCA 223_2 AGACTCAACT TTGGGCAGAC TGGCGACTCA GAGTCAGTCC CCGACCCTCA 223 4 AGACTCAACT TTGGGCAGAC TGGCGACTCA GAGCCAGTCC CCGACCCTCA 2235 AGACTCAACT TTGGGCAGAC TGGCGACTCA GAGCCAGTCC CCGACCCTCA 223:6 AGACTCAACT TTGGGCAGAC TGGCGACTCA GAGTCAGTCC CCGACCCT CA 223_7 AGACTCAACT TTGGGCAGAC TGGCGACTCA GAGTCAGTCC CCGACCCTCA A3_4 AGACTCAATT TTGGTCAGAC TGGCGACACA GAGTCAGTCC CAGACCCTCA A3_5 AGACTCAATT TTGGTCAGAC TGGCGACACA GAGTCAGTCC CAGACCC TCA A3^7 AGACTCAATT TTGGTCAGAC TGGCGACACA GAGTCAGTCC CAGACCCTCA A3_3 AGACTCAAT T TTGGTCAGAC TGGCGACACA GAGTCAGTCC CAGACCCTCA 42_12 AGACTCAACT TTGGGCAGAC TGGCGACTCA GAGTCAGTGC CCGACCCTCA AF,V1 AGACTCAATT TTGGTCAGAC TGGCGACTCA GAGTCAGTCC CCGATCCACA AAV2 AGATTGAATT TTGGTCAGAC TGGAGACGCA GACTCAGTAC CTGACCCCCA AAV3 AGACTAAATT TCGGTCAGAC T GGAGAC T CA GAGTCAGTCC CAGACCCTCA AAV8 AGACTCAATT TTGGTCAGAC TGGCGACTCA GAGTCAGTTC CAGACCCTCA AAV9 AGACTCAATT TTGGTCAGAC TGGCGACTCA GAGTCAGTTC CAGACCCTCA AAV7 AGACTCAATT TCGGTCAGAC TGGCGACT CA GAGTCAGTCC CCGACCCTCA 44 2 AGACTCAACT TTGGGCAGAC TGGCGACTCA GAGTCAGTGC CCGACCCTCA

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PCT/ITS02/33629 WO 03/042397 20 Feb 2020

Fig. lAAE

2801 2850 3 start 42 2 ACCTCTCGGA GAACCTCCCG CCGCGCCCTC AGGTCTGGGA TCTGGTAC 42 ^8 ACCAATCGGA GAACCCCCCG CAGGCCCCTC TGGTCTGGGA TCTGGTAC 42_15 ACCAATCGGA GAACCCCCCG CAGGCCCCTC TGGTCTGGGA TCTGGTACAA 42A5b ACCAATCGGA GAACCCCCCG CAGGCCCCTC TGGTCTGGGA TCTGGTACAA 42 A lb ACCAATCGGA GAACCCCCCG CAGGCCCCTC TGGTCTGGGA TCTGGCACAA ACCAATCGGA GAACCCCCCG CAGGCCCCTC TGGTCTGGGA TCTGGTACAA 2020201242

42 13 423a ACCAATCGGA GAACCCCCCG CAGGCCCCTC TGGTCTGGGA TCTGGTACAA 42_4 ACCAATCGGA GAACCCCCCG CAGGCCCCTC TGGTCTGGGA TCTGGTACAA 42_5a ACCTCTCGGA GAACCTCCCG CCGCGCCCTC AGGTCTGGGA TCTGGTACAA 42_10 ACCAATCGGA GAACCCCCCG CAGGCCCCTC TGGTCTGGGA TCTGGTACAA 42'3b ACCAATCGGA GAACCCCCCG CAGGCCCCTC TGGTCTGGGA TCTGGTACAA 42^11 ACCAATCGGA GAACCCCCCG CAGGCCCCTC TGGTCTGGGA TCTGGTACAA 42=6b ACCAATCGGA GAACCCCCCG CAGGCCCCTC TGGTCTGGGA TCTGGTACAA 43_1 ACCAATCGGA GAACCACCAG CAGGCCCCTC TGGTCTGGGA TCTGGTACAA 43_5 ACCAATCGGA GAACCACCAG CAGGCCCCTC TGGTCTGGGA TCTGGTACAA 43 12 ACCAATCGGA GAACCACCAG CAGGCCCCTC TGGTCTGGGA TCTGGTACAA 4320A ACCTCTCGGA GAACCTCCAG CAGCCCCCTC AGGTCTGGGA CCTAATACAA 43 A 21 ACCTCTCGGA GAACCTCCAG CAGCCCCCTC AGGTCTGGGA CCTAATACAA 43 23 ACCTCTCGGA GAACCTCCAG CAGCCCCCTC AGGTCTGGGA CCTAATACAA. 43=25 ACCTCTCGGA GAACCTCCAG CAGCCCCCTC AGGTCTGGGA CCTAATACAA 44_1 ACCAATCGGA GAACCCCCCG CAGGCCCCTC TGGTCTGGGA TCTGGTACAA 44_5 ACCAATCGGA GAACCCCCCG CAGGCCCCTC TGGTCTGGGA TCTGGTACAA 223_10 ACCAATCGGA GAACCACCAG CAGGCCCCTC TGGTCTGGGA TCTGGTACAA 223_2 ACCAATCGGA GAACCACCAG CAGGCCCCTC TGGTCTGGGA TCTGGTACAA 223 4 ACCAATCGGA GAACCACCAG CAGGCCCCTC TGGTCTGGGA TCTGGTACAA 223`5 ACCAATCGGA GAACCACCAG CAGGCCCCTC TGGTCTGGGA TCTGGTACAA 223=6 ACCAATCGGA GAACCACCAG CAGGCCCCTC TGGTCTGGGA TCTGGTACAA 223_'7 ACCAATCGGA GAACCACCAG CAGGCCCCTC TGGTCTGGGA TCTGGTACAA A3 4 ACCAATCGGA GAACCCCCCG CAGCCCCCTC TGGTGTGGGA TCTAATACAA A3=5 ACCAATCGGA GAACCCCCCG CAGCCCCCTC TGGTGTGGGA TCTAATACAA A37 ACCAAT CGGA GAACCCCCCG CAGCCCCCTC TGGTGTGGGA TCTAATACAA A33 ACCAATCGGA GAACCCCCCG CAGCCCCCTC TGGTGTGGGA TCTAATACAA 42_12 ACCAATCGGA GAACCCCCCG CAGGCCCCTC TGGTCTGGGA TCTGGTACAA AAY1 ACCTCTCGGA GAACCTCCAG CAACCCCCGC TGCTGTGGGA CCTACTACAA AAV2 GCCTCTCGGA CAGCCACCAG CAGCCCCCTC TGGTCTGGGA ACTAA.TACGA AAV3 ACCTCTCGGA GAACCACCAG CAGCCCCCAC AAGTTTGGGA TCTAATACAA AAV8 ACCTCTCGGA GAACCTCCAG CAGCGCCCTC TGGTGTGGGA CCTAATACAA AAV9 ACCTCTCGGA GAACCTCCAG CAGCGCCCTC TGGTGTGGGA CCTAATACAA AAV7 ACCTCTCGGA GAACCTCCAG CAGCGCCCTC TAGTGTGGGA TCTGGTACAG 44_2 A ACCAATCGGA GAACCCCCCG CAGGCCCCTC TGGTCTGGGA TCTGGTACM 110- vp 3 start

Fig. lAAF

2851 2900 4(0 start codon 42_2 IGCTGCAGG CGGTGGCGCA CCAATGGCAG ACAATAACGA AGGCGCCGAC 42_8 T GCTGCAGG CGGTGGCGCT CCAATGGCAG ACAATAACGA AGGCGCCGAC 42_15 TGGCTGCAGG CGGTGGCGCT CCAATGGCAG ACAATAACGA AGGCGCCGAC 42_5b TGGCTGCAGG CGGTGGCGCT CCAATGGCAG ACAATAACGA AGGCGCCGAC 42_1b TGGCTGCAGG CGGTGGCGCT CCAATGGCAG ACAATAACGA AGGCGCCGAC 2020201242

4213 TGGCTGCAGG CGGTGGCGCT CCAATGGCAG ACAATAACGA AGGCGCCGAC 42_3a TGGCTGCAGG CGGTGGCGCT CCAATGGCAG ACAATAACGA AGGCGCCGAC 42_4 TGGCTGCAGG CGGTGGCGCT CCAATGGCAG ACAATAACGA AGGCGCCGAC 42_5a TGGCTGCAGG CGGTGGCGCA CCAATGGCAG ACAATAACGA AGGCGCCGAC 42_10 TGGCTGCAGG CGGTGGCGCT CCAATGGCAG ACAATAACGA AGGCGCCGAC 42 3b TGGCTGCAGG CGGTGGCGCT CCAATGGCAG ACAATAACGA AGGCGCCGAC 42^11 TGGCTGCAGG CGGTGGCGCT CCAATGGCAG ACAATAACGA AGGCGCCGAC 42- 6b TGGCTGCAGG CGGTGGCGCT CCAATGGCAG ACAATAACGA AGGCGCCGAC 1 TGGCTGCAGG CGGTGGCGCT CCAATGGCAG ACAATAACGA AGGCGCCGAC 435 TGGCTGCAGG CGGTGGCGCT CCAATGGCAG ACAATAACGA AGGCGCCGAC 43 1.2 TGGCTGCAGG CGGTGGCGCT CCAATGGCAG ACAATAACGA AGGCGCCGAC 43 20 TGGCTTCAGG CGGTGGCGCT CCAATGGCAG ACAATAACGA AGGCGCCGAC 4321 TGGCTTCAGG CGGTGGCGCT CCAATGGCAG ACAATAACGA AGGCGCCGAC 43_23 TGGCTTCAGG CGGTGGCGCT CCAATGGCAG ACAATAACGA AGGCGCCGAC 43_25 TGGCTTCAGG CGGTGGCGCT CCAATGGCAG ACAATAACGA AGGCGCCGAC 44 1 TGGCTGCAGG CGGTGGCGCT CCAATGGCAG ACAATAACGA AGGCGCCGAC 44 5 TGGCTGCAGG CGGTGGCGCT CCAATGGCAG ACAATAACGA AGGCGCCGAC 223_10 TGGCTGCAGG CGGTGGCGCA CCAATGGCTG ACAATAACGA GGGCGCCGAC 223_2 TGGTTGCAGG CGGTGGCGCA CCAATGGCTG ACAATAACGA GGGCGCCGAC 223_4 TGGCTGCAGG CGGTGGCGCA CCAATGGCTG ACAATAACGA GGGCGCCGAC 223_5 TGGCTGCAGG CGGTGGCGCA CCAATGGCTG ACAATAACGA GGGCGCCGAC 223_6 TGGCTGCAGG CGGTGGCGCA CCAATGGCTG ACAATAGCGA GGGCGCCGAC 223 ^7 TGGCTGCAGG CGGTGGCGCA CCAATGGCTG ACAATAACGA GGGCGCCGAC A3 4 TGGCTTCAGG CGGTGGGGCA CCAATGGCAG ACGATAACGA AGGCGCCGAC A3_5 TGGCTTCAGG CGGTGGGGCA CCAATGGCAG ACAATAACGA AGGCGCCGAC A3 7 TGGCTTCAGG CGGTGGGGCA CCAATGGCAG ACAATAACGA AGGCGCCGAC A3 3 TGGCTTCAGG CGGTGGGGCA CCAATGGCAG ACAATAACGA AGGCGCCGAC 42 12 TGGCTGCAGG CGGTGGCGCT CCAATGGCAG ACAATAACGA AGGCGCCGAC AAV1 TGGCTTCAGG CGGTGGCGCA CCAATGGCAG ACAATAACGA AGGCGCCGAC AAV2 TGGCTACAGG CAGTGGCGCA CCAATGGCAG ACAATAACGA GGGCGCCGAC AAV3 TGGCTTCAGG CGGTGGCGCA CCAATGGCAG ACAATAACGA GGGTGCCGAT AAV8 TGGCTGCAGG CGGTGGCGCA CCAATGGCAG ACAATAACGA AGGCGCCGAC AAV9 TGGCTGCAGG CGGTGGCGCA CCAATGGCAG ACAATAACGA AGGCGCCGAC AAV7 TGGCTGCAGG CGGTGGCGCA CCAATGGCAG ACAATAACGA AGGTGCCGAC 44 2 TGGCTGCAGG CGGTGGCGCT CCAATGGCAG ACAATAACGA AGGCGCCGAC vp3 start codon (cont'd)

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WO 03/042397 PCT/U.S02/33629 20 Feb 2020

Fig. lAAG

2901 2950 422 GGAGTGGGTA ATGCCTCCGG AAATTGGCAT TGCGATTCCA CATGGCTGGG 428 GGAGTGGGTA GTTCCTCAGG AAATTGGCAT TGCGATTCCA CATGGCTGGG 4 2 15 GGAGTGGGTA GTTCCTCAGG AAATTGGCAT TGCGATTCCA CATGGCTGGG 42 5b GGAGTGGGTA GTTCCTCAGG AAATTGGCAT TGCGATTCCA CATGGCTGGG 42-1b GGAGTGGGTA GTTCCTCAGG AAATTGGCAT TGCGATTCCA CATGGCTGGG 4 2 13 GGAGTGGGTA GTTCCTCAGG AAATTGGCAT TGCGATTCCA CATGGCTGGG 2020201242

4 2-_3 a GGAGTGGGTA GTTCCTCAGG AAATTGGCAT TGCGATTCCA CATAGCTGGG 42_4 GGAGTGGGTA ATGCCTCCGG AAATTGGCAT TGCGATTCCA CATGGCTGGG 42_5a GGAGTGGGTA ATGCCTCCGG AAATTGGCAT TGCGATTCCA CATGGCTGGG 42 10 GGAGTGGGTA ATGCCTCCGG AAATTGGCAT TGCGATTCCA CATGGCTGGG 4 2 -3 b GGAGTGGGTA ATGCCTCCGG AAATTGGCAT TGCGATTCCA CATGGCTGGG 4 2 11 GGAGTGGGTA ATGCCTCCGG AAATTGGCAT TGCGATTCCA CATGGCTGGG 4 2 6b GGAGTGGGTA GTTCCTCAGG AAATTGGCAT TGCGATTCCA CATGGCTGGG 1 GGAGTGGGTA GTTCCTCAGG AAATTGGCAT TGCGATTCCA CATGGCTGGG 435 GGAGTGGGTA GTTCCTCAGG AAATTGGCAT TGCGATTCCA CATGGCTGGG 43_12 GGAGTGGGTA GTTCCTCAGG AAATTGGCAT TGCGATTCCA CATGGCTGGG 43 2 0 GGAGTGGGTA ATTCCTCGGG AAATTGGCAT TGCGATTCCA CATGGCTGGG 43121 GGAGTGGGTA ATTCCTCGGG AAATTGGCAT TGCGATTCCA CATGGCTGGG 43_2 3 GGAGTGGGTA ATTCCTCGGG AAATTGGCAT TGCGATTCCA CAT GGCTGGG 43 25 GGAGTGGGTA ATTCCTCGGG AAATTGGCAT TGCGATTCCA CATGGCTGGG a 1 GGAGTGGGTA GTTCCTCAGG AAATTGGCAT TGCGATTCCA CATGGCTGGG 44 5 GGAGTGGGTA GTTCCTCAGG AAATTGGCAT TGCGATTCCA CATGGCTGGG 223_10 GGAGTGGGTA ATGCCTCAGG AAATTGGCAT TGCGATTCCA CATGGCTGGG 223 _2 GGAGTGGGTA ATGCCTCAGG AAATTGGCAT TGCGATTCCA CATGGCTGGG 223_9 GGAGTGGGTA ATGCCTCAGG AAATTGGCAT TGCGATTCCA CACGGCTGGG 223_5 GGAGTGGGTA ATGCCTCAGG AAATTGGCAT TGCGATTCCA CACGGCTGGG 223_6 GGAGTGGGTA ATGCCTCAGG AAATTGGCAT TGCGATTCCA CATGGCTGGG 223 7 GGAGTGGGTA ATGCCTCAGG AAATTGGCAT TGCGATTCCA CATGGCTGGG A3_4 GGAGTGGGTA ATTCCTCGGG AAATTGGCAT TGCGATTCCA CATGGATGGG A3_5 GGAGTGGGTA ATTCCTCGGG AAATTGGCAT TGCGATTCCA CAT GGATGGG A3_7 GGAGTGGGTA ATTCCTCGGG AAATTGGCAT TGCGATTCCA CAT GGATGGG A3_3 GGAGTGGGTA ATTCCTCGGG AAATTGGCAT TGCGATTCCA CATGGATGGG 42_12 GGAGTGGGTA GTTCCTCAGG AAATTGGCAT TGCGAT TCCA CAT GGCTGGG AAV1 GGAGTGGGTA ATGCCTCAGG AAATTGGCAT TGCGATTCCA CATGGCTGGG AAV2 GGAGTGGGTA ATTCCTCCGG AAATTGGCAT TGCGATTCCA CATGGATGGG AAV3 GGAGTGGGTA ATTCCTCAGG AAATTGGCAT TGCGATTCCC AATGGCTGGG AAVB GGAGTGGGTA GT TCCTCGGG AAATTGGCAT TGCGATTCCA CATGGCTGGG AAV9 GGAGTGGGTA ATTCCTCGGG AAATTGGCAT TGCGATTCCA CATGGCTGGG AAV7 GGAGTGGGTA ATGCCTCAGG AAATTGGCAT TGCGATTCCA CATGGCTGGG AAV1 0 GGTA ATTCCTCCGG AAATTGGCAT TGCGATTCCA CATGGCTGGG AAV11 GGTA ATTCCTCCGG AAATTGGCAT TGCGATTCCA CATGGCTGGG AAV1 2 GGTA ATTCCTCCGG AAATTGGCAT TGCGATTCCA CATGGCTGGG 442 GGAGTGGGTA GTTCCTCAGG AAATTGGCAT TGCGATTCCA CATGGCTGGG

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FIG. 1AAH

2951 3000 42 2 CGACAGAGTC ATCACCACCA GCACCCGCAC CTGGGCCCTG CCCACCTACA 428 CGACAGAGTC ATCACCACCA GCACCCGAAC CT GGGCCCTC CCCACCTACA 42 15 CGACAGAGTC ATCACCACCA GCACCCGAAC CTGGGCCCTC CCCACCTACA 425b CGACAGAGTC ATCACCACCA GCACCCGAAC CTGGGCCCTC CCCACCTACA 2020201242

42 lb CGACAGAGTC ATCACCACCA GCACCCGAAC CTGGGCCCTC CCCACCTACA 42_ ' 13 CGACAGAGTC ATCACCACCA GCACCCGAAC CTGGGCCCTC CCCACCTACA 42 3 a CGACAGAGTC ATCACCACCA GCACCCGAAC CTGGGCCCTC CCCACCTACA 4 -2- 4 CGACAGAGTC ATCACCACCA GCACCCGCAC CTGGGCCCTG CC CACCTACA 42_5a CGACAGAGTC ATCACCACCA GCACCCGCAC CTGGGCCCTG CCCACCTACA 42 10 CGACAGAGTC ATCACCACCA GCACCCGCAC CTGGGCCCTG CCCACCTACA 42 3b CGACAGAGTC ATCACCACCA GCACCCGCAC CTGGGCCCTG CCCACCTACA 4211 CGACAGAGTC ATCACCACCA GCACCCGCAC CTGGGCCCTG CCCACCTACA 42_6b CGACAGAGTC ATCACCACCA GCACCCGAAC CTGGGCCCTC CCCACCTACA 43_1 CGACAGAGTC ATCACCACCA GCACCCGAAC CTGGGCCCTG CCCACCTACA 43_5 CGACAGAGTC ATCACCACCA GCACCCGAAC CTGGGCCCTG CCCACCTACA 43 12 CGACAGAGTC ATCACCACCA GCACCCGAAC CTGGGCCCTG CCCACCTACA 43 20 GGACAGAGTC ATCACCACCA GCACCCGAAC CTGGGCCCTG CCCACCTACA 43:21 GGACAGAGTC ATCACCACCA. GCACCCGAAC CTGGGCCCTG CCCACCTACA 43_23 GGACAGAGTC ATCACCACCA GCACCCGAAC CTGGGCCCTG CCCACCTACA 43_25 GGACAGAGTC ATCACCACCA GCACCCGAAC CTGGGCCCTG CCCACCTACA 44 1 CGACAGAGTC ATCACCACCA GCACCCGAAC CTGGGCCCTC CCCACCTACA 44 5 CGACAGAGTC ATCACCACCA GCACCCGAAC CTGGGCCCTC CCCACCTACA 223=1:0 CGACAGAGTC ATCACCACCA GCACCCGAAC CTGGGCCCTG CCCACCTACA 223 2 CGACAGAGTC ATCACCACCA GCACCCGAAC CTGGGCCCTG CCCACCTACA 2234 CGACAGAGTC ATCACCACCA GCACCCGAAC CTGGGCCCTG CCCACCTACA 223=5 CGACAGAGTC ATCACCACCA GCACCCGAAC CTGGGCCCTG CCCACCTACA 223^6 CGACAGAGTC ATCACCACCA GCACCCGAAC CTGGGCCCTG CCCACCTACA 223_7 CGACAGAGTC ATCACCACCA GCACCCGAAC CTGGGCCCTG CCCACCTACA A3 4 CGACAGAGTT ATCACCACCA GCACAAGAAC CTGGGCCCTC CCCACCTACA A3^5 CGACAGAGTT ATCACCACCA GCACAAGAAC CTGGGCCCTC CCCACCTACA A37 CGACAGAGTT ATCACCACCA GCACAAGAAC CTGGGCCCTC CCCACCTACA A3_3 CGACAGAGTT ATCACCACCA GCACAAGAAC CTGGGCCCTC CCCACCTACA 42_12 CGACAGAGTC ATCACCACCA GCACCCGAAC CTGGGCCCTC CCCACCTACA AAV1 CGACAGAGTC ATCACCACCA GCACCCGCAC CTGGGCCTTG CCCACCTACA AAV2 CGACAGAGTC ATCACCACCA GCACCCGAAC CTGGGCCCTG CCCACCTACA AAV3 CGACAGAGTC ATCACCACCA GCACCAGAAC CTGGGCCCTG CCCACTTACA AAV8 CGACAGAGTC ATCACCACCA GCACCCGAAC CTGGGCCCTG CCCACCTACA AAV9 GGACAGAGTC ATCACCACCA GCACCCGAAC CTGGGCATTG CCCACCTACA AAV7 CGACAGAGTC ATTACCACCA GCACCCGAAC CTGGGCCCTG CCCACCTACA AAV10 CGACAGAGTC ATCACCACCA GCACCCGAAC CTGGGTCCTG CCCACCTACA AAV11 CGACAGAGTC ATCACCACCA GCACCCGAAC CTGGGCCCTG CCAACCTACA AAV12 CGACCGAGTC ATTACCACCA GCACCCGGAC TTGGGCCCTG CCCACCTACA 44_2 CGACAGAGTC ATCACCACCA GCACCCGAAC CTGGGCCCTC CCCACCTACA

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Fig. lAAI

3001 3050 42 2 ACAACCACCT CTACAAGCAG ATATCAA..G TCAGAGCGGG GCT....ACC 42 8 ACAACCACCT CTACAAGCAA ATCTCCAACG GGACATCGGG AGGAAGCACC 42_15 ACAACCACCT CTACAAGCAA ATCTCCAACG GGACATCGGG AGGAAGCACC 42 5b ACAACCACCT CTACAAGCAA ATCTCCAACG GGACATCGGG AGGAAGCACC 42 1b ACAACCACCT CTACAAGCAA ATCTCCAACG GGACATCGGG AGGAAGCACC 42-13 ACAACCACCT CTACAAGCAA ATCTCCAACG GGACATCGGG AGGAAGCACC 2020201242

42 3a ACAACCACCT CTACAAGCAA ATCTCCAACG GGACATCGGG AGGAAGCACC 42_ 4 ACAACCACCT CTACAAGCAG ATATCAA... .GTCAGAGCG GGGC..TACC 42_5a ACAACCACCT CTACAAGCAG ATATCAA... .GTCAGAGCG GGGC..TACC 42 10 ACAACCACCT CTACAAGCAG ATATCAA..G TCAGAGCGGG GCTA....CC 42-3b ACAACCACCT CTACAAGCAG ATATCAA..G TCAGAGCGGG GCTA....CC 42 11 ACAACCACCT CTACAAGCAG ATATCAA..G TCAGAGCGGG GCTA....CC 42 6b ACAACCACCT CTACAAGCAA ATCTCCAACG GGACATCGGG AGGAAGCACC 43_1 ACAACCATCT CTACAAGCAA ATCTCCAACG GGACATCGGG AGGAAGCACT 43_5 ACAACCATCT CTACAAGCAA ATCTCCAACG GGACATCGGG AGGAAGCACT 43_12 ACAACCATCT CTACAAGCAA ATCTCCAACG GGACATCGGG AGGAAGCACT 43_20 ACAACCACCT CTACAAGCAA ATCTCCAACG GCACCTCGGG AGGAAGCACC 43_21 ACAACCACCT CTACAAGCAA ATCTCCAACG GCACCTCGGG AGGAAGCACC 43 23 ACAACCACCT CTACAAGCAA ATCTCCAACG GCACCTCGGG AGGAAGCACC 4325 ACAACCACCT CTACAAGCAA ATCTCCAACG GCACCTCGGG AGGAAGCACC a 1 ACAACCACCT CTACAAGCAA ATCTCCAACG GGACTTCGGG AGGAAGCACC 44~5 ACAACCACCT CTACAAGCAA ATCTCCAACG GGACTTCGGG AGGAAGCACC 223_10 ACAACCACCT CTACAAGCAA ATCTCCAGTC AGTCAGCAGG GAG...CACC 223_2 ACAACCACCT CTACAAGCAA ATCTCCAGTC AGTCAGCAGG GAG...CACC 2234 4 ACAACCACCT CTACAAGCAA ATCTCCAGTC AGTCAGCAGG GAG...CACC 223:5 ACAACCACCT CTACAAGCAA ATCTCCAGTC AGTCAGCAGG GAG...CACC 223 6 ACAACCACCT CTACAAGCAA ATCTCCAGTC AGTCAGCAGG GAG...CACC 223 7 ACAACCACCT CTACAAGCAA ATCTCCAGTC AGTCAGCAGG GAG...CACC A3-4 ATAATCACCT CTACAAGCAA ATCTCCA... GCGAATCGGG AGC...CACC A3_5 ATAATCACCT CTACAAGCAA ATCTCCA... GCGAATCGGG AGC...CACC A3 7 ATAATCGCCT CTACAAGCAA ATCTCCA... GCGAATCGGG AGC...CACC A3 3 ATAATCACCT CTACAAGCAA ATCTCCA.:. GCGAATCGGG AGC...CACC 42_12 ACAACCACCT CTACAAGCAA ATCTCCAACG GGACATCGGG AGGAAGCACC AAV1 ATAACCACCT CTACAAGCAA ATCTCCAGTG CTTCAACGGG .GG..CCAGC AAV2 ACAACCACCT CTACAAACAA ATTTCCA... GCCAATCAGG AGC...CTCG AAV3 ACAACCATCT CTACAAGCAA ATCTCCA... GCCAATCAGG AGC...TTCA AAV8 ACAACCACCT CTACAAGCAA ATCTCCAACG GGACATCGGG AGGAGCCACC AAV9 ACAACCACCT CTACAAGCAA ATCTCCAATG GAACATCGGG AGGAAGCACC AAV7 ACAACCACCT CTACAAGCAA ATCTCCAGTG AAACTGCAGG TAG...TACC AAV10 ACAACCACAT CTACAAGCAA ATCTCCAGCG AGACAGGAGC CACCAACGAC AAV11 ACAACCACCT CTACAAACAA ATCTCCAGCG CTTCAACGGG GGCCAGCAAC AAV12 ACAACCACCT CTACAAGCAA ATCTCCAGCC AATCGGGTGC CACCAACGAC 44_2 ACAACCACCT CTACAAGCAA ATCTCCAACG GGACTTCGGG AGGAAGCACC

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Fig. lAAJ

3051 3100 42_2 AACGACAACC ACTTCTTCGG CTACAGCACC CCCTGGGGCT ATTTTGACTT 42_^ 8 AACGACAACA CCTACTTCGG CTACAGCACC CCCTGGGGGT ATTTTGACTT 42_15AACGACAACA CCTACTTCGG CTACAGCACC CCCTGGGGGT ATTTTGACTT 42_5b AACGACAACA CCTACTTCGG CTACAGCACC CCCTGGGGGT ATTTTGACTT 42 lb AACGACAACA CCTACTTCGG CTACAGCACC CCCTGGGGGT ATTTTGACTT 4213 AACGACAACA CCTACTTCGG CTACAGCACC CCCTGGGGGT ATTTTGACTT 42_3a AACGACAACA CCTACTTCGG CTACAGCACC CCCTGGGGGT ATTTTGACTT 2020201242

4 AACGACAACC ACTTCTTCGG CTACAGCACC CCCTGGGGCT ATTTTGACTT 42_3a AACGACAACC ACTTCTTCGG CTACAGCACC CCCTGGGGCT ATTTTGACTT 42^10 AACGACAACC ACTTCTTCGG CTACAGCACC CCCTGGGGCT ATTTTGACTT 42_ ^ 3b AACGACAACC ACTTCTTCGG CTACAGCACC CCCTGGGGCT ATTTTGACTT 42 11 AACGACAACC ACTTCTTCGG CTACAGCACC CCCTGGGGCT ATTTTGACTT 42_6b AACGACAACA CCTACTTCGG CTACAGCACC CCCTGGGGGT ATTTTGACTT 6. 1 AACGACAACA CCTACTTTGG CTACAGCACC CCCTGGGGGT ATTTTGACTT 43_^5 AACGACAACA CCTACTTTGG CTACAGCACC CCCTGGGGGT ATTTTGACTT 43_12 AACGACAACA CCTACTTTGG CTACAGCACC CCCTGGGGGT ATTTTGACTT 43_20 AACGACAACA CCTATTTTGG CTACAGCACC CCCTGGGGGT ATTTTGACTT 43-21 AACGACAACA CCTATTTTGG CTACAGCACC CCCTGGGGGT ATTTTGACTT 43^23 AACGACAACA CCTATTTTGG CTACAGCACC CCCTGGGGGT ATTTTGACTT 43-25 AACGACAACA CCTATTTTGG CTACAGCACC CCCTGGGGGT ATTTTGACTT 44_1 AACGACAACA CCTACTTCGG CTACAGCACC CCCTGGGGGT ATTTTGACTT 44_5 AACGACAACA CCTACTTCGG CTACAGCACC CCCTGGGGGT ATTTTGACTT 223_10 AACGATAACG TCTATTTCGG CTACAGCACC CCCTGGGGGT ATTTTGACTT 223 2 AACGATAACG TCTATTTCGG CTACAGCACC CCCTGGGGGT ATTTTGACTT 223_4 AACGATAACG TCTATTTCGG CTACAGCACC CCCTGGGGGT ATTTTGACTT 223^5 AACGATAACG TCTATTTCGG CTACAGCACC CCCTGGGGGT ATTTTGACTT 223 6 AACGATAACG TCTATTTCGG CTACAGCACC CCCTGGGGGT ATTTTGACTT 223 7 AACGATAACG TCTATTTCGG CTACAGCACC CCCTGGGGGT ATTTTGACTT A3__4 AACGACAACC ACTACTTCGG CTACAGCACC CCCTGGGGGT ATTTTGACTT A3 5 AACGACAACC ACTACTTCGG CTACAGCACC CCCTGGGGGT ATTTTGACTT A3 7 AACGACAACC ACTACTTCGG CTACAGCACC CCCTGGGGGT ATTTTGACTT A3 ^3 AACGACAACC ACTACTTCGG CTACAGCACC CCCTGGGGGT ATTTTGACTT 42_12 AACGACAACA CCTACTTCGG CTACAGCACC CCCTGGGGGT ATTTTGACTT AXV 1 AACGACAACC ACTACTTCGG CTACAGCACC CCCTGGGGGT ATTTTGATTT AAV2 AACGACAACC ACTACTTTGG CTACAGCACC CCTTGGGGGT ATTTTGACTT AAV3 AACGACAACC ACTACTTTGG CTACAGCACC CCTTGGGGGT ATTTTGACTT AAV8 AACGACAACA CCTACTTCGG CTACAGCACC CCCTGGGGGT ATTTTGACTT AAV9 AACGACAACA CCTACTTTGG CTACAGCACC CCCTGGGGGT ATTTTGACTT AAV7 AACGACAACA CCTACTTCGG CTACAGCACC CCCTGGGGGT ATTTTGACTT AAV10 AACCACTACT TCGGCTACAG C ACC CCCTGGGGGT ATTTTGACTT AAV11 ...GACAACC ACTACTTTGG CTACAGCACC CCCTGGGGGT ATTTTGACTT AAV12 AACCACTACT TCGGCTA... . . . CAGCACC CCTTGGGGGT ATTTTGATTT 44_2 AACGACAACA CCTACTTCGG CTACAGCACC CCCTGGGGGT ATTTTGACTT

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Fig. 1AAK

3101 3150 42 2 TAACAGATTC CACTGCCACT TCTCACCACG TGACTGGCAG CGACTCATCA 428 TAACAGATTC CACTGCCACT TCTCACCACG TGACTGGCAG CGACTCATCA 42 15 TAACAGATTC CACTGCCACT TCTCACCACG TGACTGGCAG CGACTCATCA 42 ^5b TAACAGATTC CACTGCCACT TCTCACCACG TGACTGGCAG CGACTCATCA 42 lb TAACAGATTC CACTGCCACT TCTCACCACG TGACTGGCAG CGACTCATCA 42 ^13 TAACAGATTC CACTGCCACT TCTCACCACG TGACTGGCAG CGACTCATCA 42:3a 2020201242

TAACAGATTC CACTGCCACT TCTCACCACG TGACTGGCAG CGACTCATCA 42_4 CAACAGATTC CACTGCCACT TCTCATCACG TGACTGGCAG CGACTCATCA 42_5a CAACAGATTC CACTGCCACT TCTCACCACG TGACTGGCAG CGACTCATCA 42^10 CAACAGATTC CACTGCCACT TCTCACCACG TGACTGGCAG CGACTCATCA 42`3b CAACAGATTC CACTGCCACT TCTCACCACG TGACTGGCAG CGACTCATCA 4211 CAACAGATTC CACTGCCACT TCTCACCACG TGACTGGCAG CGACTCATCA 42 ^ 6b TAACAGATTC CACTGCCACT TCTCACCACG TGACTGGCAG CGACTCATCA 431 CAACAGATTC CACTGCCACT TCTCACCACG TGACTGGCAG CGACTCATCA 43 W5 CAACAGATTC CACTGCCACT TCTCACCACG TGACTGGCAG CGACTCATCA 43 12 CAACAGATTC CACTGCCACT TCTCACCACG TGACTGGCAG CGACTCATCA 43_ ^20 CAACAGATTC CACTGTCACT TTTCACCACG TGACTGGCAA CGACTCATCA 43 23. CAACAGATTC CACTGTCACT TTTCACCACG TGACTGGCAA CGACTCATCA 9323 CAACAGATTC CACTGTCACT TTTCACCACG TGACTGGCAA CGACTCATCA 43_25 CAACAGATTC CACTGTCACT TTTCACCACG TGACTGGCAA CGACTCATCA 44_1 TAACAGATTC CACTGCCACT TCTCACCACG TGACTGGCAG CGACTCATCA 44_5 TAACAGATTC CACTGCCACT TCTCACCACG TGACTGGCAG CGACTCATCA 223_10 CAACAGATTC CATTGCCACT TCTCACCACG TGACTGGCAG CGACTTATCA 223 2 CAACAGATTC CAT TGCCACT TCTCACCACG TGACTGGCAG CGACTTATCA 223~_4 CAACAGATTC CATTGCCACT TCTCACCACG TGACTGGCAG CGACTTATCA 223 5 CAACAGATTC CATTGCCACT TCTCACCACG TGACTGGCAG CGACTTATCA 223:6 CAACAGATTC CATTGCCACT TCTCACCACG TGACTGGCAG CGACTTATCA 223 ^7 CAACAGATTC CAT TGCCACT TCTCACCACG TGACTGGCAG CGACTTATCA A3 4 TAACAGATTC CACTGTCACT TCTCACCACG TGACTGGCAG CGACTCATCA A3-5 TAACAGATTC CACTGTCACT TCTCACCACG TGACTGGCAG CGACTCATCA A3 7 TAACAGATTC CACTGTCACT TCTCACCACG TGACTGGCAG CGACTCATCA A3 3 TAACAGATTC CACTGTCACT TCTCACCACG TGACTGGCAG CGACTCATCA 42_12 TAACAGATTC CACT GCCACT TCTCACCACG TGACTGGCAG CGACTCATCA AAV1 CAACAGATTC CACTGCCACT TTTCACCACG TGACTGGCAG CGACTCATCA AAV2 CAACAGATTC CACTGCCACT TTTCACCACG TGACTGGCAA AGACTCATCA AAV3 TAACAGATTC CACTGCCACT TCTCACCACG TGACTGGCAG CGACTCATTA AAV8 TAACAGATTC CACTGCCACT TTTCACCACG TGACTGGCAG CGACTCATCA AAV9 CAACAGATTC CACTGCCACT TCTCACCACG TGACTGGCAG CGACTCATCA AAV7 TAACAGATTC CACTGCCACT TCTCACCACG TGACTGGCAG CGACTCATCA AAV10 TAACAGATTC CACTGCCACT TTTCACCACG TGACTGGCAG CGACTCATCA AAV11 TAACAGATTC CACTGCCACT TCTCACCACG TGACTGGCAG CGACTCATCA AAV12 CAACAGATTC CACTGCCATT TCTCACCACG TGACTGGCAG CGACTCATCA 44^2 TAACAGATTC CACTGCCACT TCTCACCACG TGACTGGCAG CGACTCATCA

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Fig. lAAL

3151 3200 42_2 ACAACAACTG GGGATTCCGG CCCAGAAAGC TGCGGTTCAA GTTGTTCAAC 42_8 ACAACAACTG GGGATTCCGG CCCAAGAGAC TCAACTTCAA GCTCTTCAAC 42 15 ACAACAACTG GGGATTCCGG CCCAAGAGAC TCAACTTCAA GCTCTTCAAC 42_5b ACAACAACTG GGGATTCCGG CCCAAGAGAC TCAACTTCAA GCTCTTCAAC 42—lb ACAACAACTG GGGATTCCGG CCCAAGAGAC TCAACTTCAA GCTCTTCAAC 42^13 ACAACAACTG GGGATTCCGG CCCAAGAGAC TCAACTTCAA GCTCTTCAAC 42 3a ACAACAGCTG GGGATTCCGG CCCAAGAGAC TCAACTTCAA GCTCTTCAAC 2020201242

42- 4 ACAACAACTG GGGATTCCGG CCCAAGAGAC TCAACTTCAA GCTCTTCAAC 42_5a ACAACAACCG GGGATTCCGG CCCAGAAAGC TGCGGTTCAA GTTGTTCAAC 42^10 ACAACAACTG GGGATTCCGG CCCAGAAAGC TGCGGTTCAA GTTGTTCAAC 42 3b ACAACAACTG GGGATTCCGG CCCAGAAAGC TGCGGTTCAA GTTGTTCAAC 42 11 ACAACAACTG GGGATTCCGG CCCAGAAAGC TGCGGTTCAA GTTGTTCAAC 42:6b ACAACAACTG GGGATTCCGG CCCAGAAAGC TGCGGTTCAA GTTGTTCAAC 43 1 ACAATAACTG GGGATTCCGG CCCAAGAGAC TCAACTTCAA GCTCTTCAAC 43 5 ACAATAACTG GGGATTCCGG CCCAAGAGAC TCAACTTCAA GCTCTTCAAC 43_12 ACAATAACTG GGGATTCCGG CCCAAGAGAC TCAACTTCAA GCTCTTCAAC 43 20 ACAACAATTG GGGATTCCGG CCCAAAAGAC TCAACTTCAA GCTGTTCAAC 43^21 ACAACAATTG GGGATTCCGG CCCAAAAGAC TCAACTTCAA GCTGTTCAAC 43:23 ACAACAATTG GGGATTCCGG CCCAAAAGAC TCAACTTCAA GCTGTTCAAC 4325 ACAACAATTG GGGATTCCGG CCCAAAAGAC TCAACTTCAA GCTGTTCAAC 44 1 ACAACAACTG GGGATTCCGG CCCAAGAGAC TCAACTTCAA GCTCTTCAAC 44_5 ACAACAACTG GGGATTCCGG CCCAAGAGAC CCAACTTCAA GCTCTTCAAC 223_10 ACAACAACTG GGGATTCCGG CCCAAGAAGC TCAACTTCAA GCTCTTCAAC 223_2 ACAACAACTG GGGATTCCGG CCCAAGAAGC TCAACTTCAA GCTCTTCAAC 223 4 ACAACAACTG GGGATTCCGG CCCAAGAAGC TCAACTTCAA GCTCTTCAAC- 2235 ACAACAACTG GGGATTCCGG CCCAAGAAGC TCAACTTCAA GCTCTTCAAC 223-6 ACAACAACTG GGGATTCCGG CCCAAGAAGC TCAACTTCAA GCTCTTCAAC 223 7 ACAACAACTG GGGATTCCGG CCCAAGAAGC TCAACTTCAA GCTCTTCAAC A3 4 ACAACAACTG GGGATTTAGA CCCAAGAAAC TCAATTTCAA GCTCTTCAAC A3 5 ATAACAACTG GGGATTTAGA CCCAAGAAAC TCAATTTCAA GCTCTTCAAC A3^7 ACAACAACTG GGGATTTAGA CCCAAGAAAC TCAATTTCAA GCTCTTCAAC A3_^3 ACAACAACTG GGGATTTAGA CCCAAGAAAC TCAATTTCAA GCTCTTCAAC 42_12 ACAACAACTG GGGATTCCGG CCCAAGAGAC TCAACTTCAA GCTCTTCAAC AAV1 ACAACAATTG GGGATTCCGG CCCAAGAGAC TCAACTTCAA ACTCTTCAAC AAV2 ACAACAACTG GGGATTCCGA CCCAAGAGAC TCAACTTCAA GCTCTTTAAC AAV3 ACAACAACTG GGGATTCCGG CCCAAGAAAC TCAACTTCAA GCTCTTCAAC AAV8 ACAACAACTG GGGATTCCGG CCCAAGAGAC TCAACTTCAA GCTCTTCAAC AAV9 ACAACAACTG GGGATTCCGG CCAAAGAGAC TCAACTTCAA GCTGTTCAAC AAV7 ACAACAACTG GGGATTCCGG CCCAAGAAGC TGCGGTTCAA GCTCTTCAAC AAV10 ACAACAACTG GGGATTC AAV11 ACAACAACTG GGGATTC AAV12 ACAACAACTG GGGATTC 44 2 ACAACAACTG GGGATTCCGG CCCAAGAGAC TCAACTTCAA GCTCTTCAAC

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WO 03/042397 PCIYUS02/33629 20 Feb 2020

Fig. 1AAM

3201 3250 42 2 ATCCAGGTCA AGGAGGTCAC GACGAACGAC GGCGTTACGA CCATCGCTAA 42 8 ATCCAGGTCA AGGAGGTCAC GCAGAATGAA GGCACCAAGA CCATCGCCAA 42 175 ATCCAGGTCA AGGAGGTCAC GCAGAATGAA GGCACCAAGA CCATCGCCAA 92 5b ATCCAGGTCA AGGAGGTCAC GCAGAATGAA GGCACCAAGA CCATCGCCAA 42-1b ATCCAGGTCA AGGAGGTCAC GCAGAATGAA GGCACCAAGA CCATCGCCAA 42^13 ATCCAGGTCA AGGAGGTCAC GCAGAATGAA GGCACCAAGA CCATCGCCAA 42__3a ATCCAGGTCA AGGAGGTCAC GCAGAATGAA GGCACCAAGA CCATCGCCAA 2020201242

4 -f4 ATCCAGGTCA AGGAGGTCAC GCAGAATGAA. GGCACCAAGA CCATCGCCAA 42 5a ATCCAGGTCA AGGAGGTCAC GACGAACGAC GGCGTTACGA CCATCGCTAA 4210 ATCCAGGTCA AGGAGGTCAC GACGAACGAC GGCGTTACGA CCATCGCCAA ATCCAGGTCA AGGAGGTCAC GACGAACGAC GGCGTTACGA CCATCGCTAA 4211 ATCCAGGTCA AGGAGGTCAC GACGAACGAC GGCGTTACGA CCATCGCTAA 4216b ATCCAGGTCA AGGAGGTCAC GACGGACGAC GGCGTTACGA CCATCGCTAA 93 1 ATCCAGGTCA AGGAGGTCAC GCAGAATGAA GGCACCAAGA CCATCGCCAA 43 5 ATCCAGGTCA AGGAGGTCAC GCAGAATGAA GGCACCAAGA CCATCGCCAA 43 12 ATCCAGGTCA AGGAGGTCAC GCAGAATGAA GGCACCAAGA CCATCGCCAA. 43 20 ATCCAGGTCA AGGAGGTCAC GACGAACGAA GGCACCAAGA CCATCGCCAA 43:21 ATCCAGGTCA AGGAAGTCAC GACGAACGAA GGCACCAAGA CCATCGCCAA 43_23 ATCCAGGTCA AGGAAGTCAC GACGAACGAA GGCACCAAGA CCATCGCCAA 43_25 ATCCAGGTCA AGGAAGTCAC GACGAACGAA GGCACCAAGA CCATCGCCAA 44_1 ATCCAGGTCA AGGAGGTCAC GCAGAATGAA GGCACCAAGA CCATCGCCAA 44_5 ATCCAGGTCA AGGAGGTCAC GCAGAAT GAA GGCACCAAGA CCATCGCCAA 223_30 ATCCAGGTCA AGGAGGTCAC GACGAATGAC GGT GTCAC AA CCATCGCTAA 223 2 ATCCAGGTCA AGGAGGTCAC GACGAATGAC GGCGTCACAA CCATCGCTAA 2234 ATCCAGGTCA AGGAGGTCAC GACGAATGAC GGCGTCACAA CCATCGCTAA 223=5 ATCCAGGTCA AGGAGGTCAC GACGAATGAC GGCGTCACAA CCATCGCTAA 2236 ATCCAGGTCA AGGAGGTCAC GACGAATGAC GGTGTCACAA CCATCGCTAA 223_7 ATCCAGGTCA AGGAGGTCAC GACGAATGAC GGCGTCACAA CCATCGCTAA A3-4 ATCCAAGTCA AGGAGGTCAC GCAGAATGAT GGAACCACGA CCATCGCCAA A3 5 ATCCAGGTCA AGGAGGTCAC GCAGAATGAT GGAACCACGA CCATCGCCAA A3_-7 ATCCAAGTCA AGGAGGTCAC GCAGAATGAT GGAACCAC GA CCATCGCCAA A3_3 ATCCAAGTCA AGGAGGTCAC GCAGAATGAT GGAACCACGA CCATCGCCAA 42_12 ATCCAGGTCA AGGAGGTCAC GCAGAATGAA GGCACCAAGA CCATCGCCAA AAV1 ATCCAGGTCA AGGAGGTCAC GACGAA.T GAT GGCGTCACAA CCATCGCTAA AAV2 ATTCAAGTCA AGGAGGTCAC GCAGAAT GAC GGTACGACGA CGATTGCCAA AAV3 ATCCAAGT TA GAGGGGT CAC GCAGAAC GAT GGCACGACGA CGATTGCCAA AAV8 ATCCAGGTCA AGGAGGTCAC GCAGAATGAA GGCACCAAGA CCATCGCCAA AAV9 ATCCAGGTCA AGGAGGTTAC GACGAACGAA GGCACCAAGA CCATCGCCAA AAV7 ATCCAGGTCA AGGAGGTCAC GACGAATGAC GGCGTTACGA CCATCGCTAA 44_2 ATCCAGGTCA AGGAGGTCAC GCAGAATGAA GGCACCAAGA CCATCGCCAA

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Fig. 1AAN

3251 3300 42_2 TAACCTTACC AGCACGATTC AGGTCTTCTC GGACTCGGAG TACCAACTGC 42_8 TAACCTTACC AGCACGATTC AGGTCTTTAC GGACTCGGAA TACCAGCTCC 42_15 TAACCTTACC AGCACGATTC AGGTCTTTAC GGACTCGGAA TACCAGCTCC 42 5b TAACCTTACC AGCACGATTC AGGTCTTTAC GGACTCGGAA TACCAGCTCC 42 lb TAACCTTACC AGCACGATTC AGGTCTTTAC GGACTCGGAA TACCAGCTCC 42 13 TAACCTTACC AGCACGATTC AGGTCTTTAC GGACTCGGAA TACCAGCTCC 42:3a TAACCTTACC AGCACGATTC, AGGTCTTTAC GGACTCGGAA TACCAGCTCC 2020201242

42_4 TAACCTTACC AGCACGATTC AGGTCTTTAC GGACTCGGAA TACCGGCTCC 42 5a TAACCTTACC AGCACGATTC AGGTCTTCTC GGACTCGGAG TACCAACTGC 42 10 TAACCTTACC AGCACGATTC AGGTCTTCTC GGACTCGGAG TACCAACTGC 42 3b TAACCTTACC AGCACGATTC AGGTCTTCTC GGACTCGGAG TACCAACTGC 42_11 TAACCTTACC AGCACGATTC AGGTCTTCTC GGACTCGGAG TACCAACTGC 42 6b TAACCTTACC AGCACGATTC AGGTCTTCTC GGACTCGGAG TACCAACTGC 431 TAACCTTACC AGCACGATTC AGGTGTTTAC GGACTCGGAA TACCAGCTCC 43 5 TAACCTTACC AGCACGATTC AGGTGTTTAC GGACTCGGAA TACCAGCTCC 43_12 TAACCTTACC AGCACGATTC AGGTGTTTAC GGACTCGGAA TACCAGCTCC 43 20 TAATCTCACC AGCACCGTGC AGGTCTTTAC GGACTCGGAG TACCAGTTAC 43 21 TAATCTCACC AGCACCGTGC GGGTCTTTAC GGACTCGGAG TACCAGTTAC 43:23 TAATCTCACC AGCACCGTGC AGGTCTTTAC GGACTTGGAG TACCAGTTAC 43_25 TAATCTCACC AGCACCGTGC AGGTCTTTAC GGACTCGGAG TACCAGTTAC 44 1 TAACCTTACC AGCACGATTC AGGTCTTTAC GGACTCGGAA TACCAGCTCC 44y5 TAACCTTACC AGCACGATTC AGGTCTTTAC GGACTCGGAA TACCAGCTCC 22310 TAACCTTACC AGCACGGTTC AGGTCTTTTC GGACTCGGAA TATCAACTGC 223_2 TAACCTTACC AGCACGGTTC AGGTCTTTTC GGACTCGGAA TAT CAACTGC 223 4 TAACCTTACC AGCACGGTTC AGGTCTTTTC GGACTCGGAA TATCAACTGC 223'5 TAACCTTACC AGCACGGT TO AGGTCTTTTC GGACTCGGAA TATCAACTGC 223:6 TAACCTTACC AGCACGGTTC AGGTCTTTTC GGACTCGGAA TATCAACTGC 223_7 TAACCTTACC AGCACGGTTC AGGTCTTTTC GGACCCGGAA TATCAACTGC A3 4 TAACCTTACC AGCACGGTGC AGGTCTTCAC AGACTCTGAG TACCAGCTGC A3 5 TAACCTTACC AGCACGGTGC AGGTCTTCAC AGACTCTGAG TACCAGCTGC A3-7 TAACCTTACC AGCACGGTGC AGGTCTTCAC AGACTCTGAG TACCAGCTGC A3 3 TAACCTTACC AGCGCGGTGC AGGTCTTCAC AGACTCTGAG TACCAGCTGC 42_32 TAACCTTACC AGCACGATTC AGGTCTTTAC GGACTCGGAA TACCAGCTCC AAV1 TAACCTTACC AGCACGGTTC AAGTCTTCTC GGACTCGGAG TACCAGCTTC AAV2 TAACCTTACC AGCACGGTTC AGGTGTTTAC TGACTCGGAG TACCAGCTCC AAV3 TAACCT TACO AGCACGGTTC AAGTGTTTAC GGACTCGGAG TATCAGCTCC AAV8 TAACCTCACC AGCACCATCC AGGTGTTTAC GGACTCGGAG TACCAGCTGC AAV9 TAACCTTACC AGCACCGTCC AGGTCTTTAC GGACTCGGAG TACCAGCTAC AAV7 TAACCTTACC AGCACGATTC AGGTATTCTC GGACTCGGAA TACCAGCTGC 44 2 TAACCTTACC AGCACGATTC AGGTCTTTAC GGACTCGGAA TACCAGCTCC

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Fig. IAA°

3301 3350 42_2 CGTACGTCCT CGGCTCTGCG CACCAGGGCT GCCTCCCTCC GTTCCCTGCG 42_^8 CGTACGTCCT CGGCTCTGCG CACCAGGGCT GCCTGCCTCC GTTCCCGGCG 42 1.5 CGTACGTCCT CGGCTCTGCG CACCAGGGCT GCCCGCCTCC GTTCCCGGCG 42 5b CGTACGTCCT CGGCTCTGCG CACCAGGGCT GCCTGCCTCC GTTCCCGGCG 42 ^1b CGTACGTCCT CGGCTCTGCG CACCAGGGCT GCCTGCCTCC GTTCCCGGCG 42 13 CGTACGTCCT CGGCTCTGCG CACCAGGGCT GCCTGCCTCC GTTCCCGGCG CGTACGTCCT CGGCTCTGCG CACCAGGGCT GCCTGCCTCC GTTCCCGGCG 2020201242

42 3a 42 4 CGTACGTCCT CGGCTCTGCG CACCAGGGCT GCCTGCCTCC GTTCCCGGCG 42 3a CGTACGTCCT CGGCTCTGCG CACCAGGGCT GCCTCCCTCC GTTCCCTGCG 42^10 CGTACGTCCT CGGCTCTGCG CACCAGGGCT GCCTCCCTCC GTTCCCTGCG 42 3b CGTACGTCCT CGGCTCTGCG CACCAGGGCT GCCTCCCTCC GTTCCCTGCG 42 1 CGTACGTCCT CGGCTCTGCG CACCAGGGCT GCCTCCCTCC GTTCCCTGCG 42 6b CGTACGTCCT CGGCTCTGCG CACCAGGGCT GCCTCCCTCC GTTCCCTGCG zff 1 CGTACGTCCC CGGCTCTGCG CACCAGGGCT GCCTCCCTCC GTTCCCGGCG 43_5 CGTACGTCCT CGGCTCTGCG CACCAGGGCT GCCTCCCTCC GTTCCCGGCG 43 12 CGTACGTCCT CGGCTCTGCG CACCAGGGCT GCCTCCCTCC GTTCCCGGCG 43^20 CGTACGTGCT AGGATCCGCT CACCAGGGAT GTCTGCCTCC GTTCCCGGCG 43 21 CGTACGTGCT AGGATCCGCT CACCAGGGAT GTCTGCCTCC GTTCCCGGCG 43_23 CGTACGTGCT AGGATCCGCT CACCAGGGAT GTCTGCCTCC GTTCCCGGCG 43 25 CGTACGTGCT AGGATCCGCT CACCAGGGAT GTCTGCCTCC GTTCCCGGCG 44 1 CGTACGTCCT CGGCTCTGCG CACCAGGGCT GCCTGCCTCC GTTCCCGGCG 44 5 CGTACGTCCT CGGCTCTGCG CACCAGGGCT GCCTGCCTCC GT TCCCGGCG 223 1.0 CGTACGTCCT CGGCTCCGCG CACCAGGGCT GCCTGCCTCC GTTCCCGGCA 223 2 CGTACGTCCT CGGCTCCGCG CACCAGGGCT GCCTGCCTCC GTTCCCGGCA 223 4 CGTACGTCCT CGGCTCCGCG CACCAGGGCT GCCTGCCTCC GTTCCCGGCA 2231-5 CGTACGTCCT CGGCTCCGCG CACCAGGGCT GCCTGCCTCC GTTCCCGGCA 223_6 CGTACGTCCT CGGCTCCGCG CACCAGGGCT GCCTGCCTCC GTTCCCGGCA 223_7 CGTACGTC CT CGGCTCCGCG CACCAGGGCT GCCTGCCTCC GTTCCCGGCA A3_4 CCTACGTCCT CGGTTCGGCT CACCAGGGCT GCCTTCCGCC GTTCCCAGCA A3_5 CCTACGTCCT CGGTTCGGCT CACCAGGGCT GCCTTCCGCC GT TCCCAGCA A3^7 CCTACGTCCT CGGTTCGGCT CACCAGGGCT GCCTTCCGCC GTTCCCAGCA A3_3 CCTACGTCCT CGGTTCGGCT CACCAGGGCT GCCTTCCGCC GTTCCCAGCA 42_12 CGTACGTCCT CGGCTCTGCG CACCAGGGCT GCCTGCCTCC GTTCCCGGCG ATIV1 CGTACGTCCT CGGCTCTGCG CACCAGGGCT GCCTCCCTCC GTTCCCGGCG AAV2 CGTACGTCCT CGGCTCGGCG CAT CAAGGAT GCCTCCCGCC GTTCCCAGCA AAV3 CGTACGTGCT CGGGTCGGCG CACCAAGGCT GTCTCCCGCC GTTTCCAGCG AAV8 CGTACGTT CT CGGCTCTGCC CACCAGGGCT GCCTGCCTCC GTTCCCGGCG AAV9 CGTACGTCCT AGGCTCTGCC CACCAAGGAT GCCTGCCACC GTTTCCTGCA AAV7 CGTACGTCCT CGGCTCTGCG CACCAGGGCT GCCTGCCTCC GTTCCCGGCG 44 2 CGTACGTCCT CGGCTCTGCG CACCAGGGCT GCCTGCCTCC GT TCCCGGCG

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Fig. lAAP

3351 3400 42 2 GACGTGTTCA TGATTCCTCA GTACGGATAT CTGACTCTAA ACAACGGCAG 42 ^8 GACGTCTTCA TGATTCCTCA GTACGGGTAC CTGACTCTGA ACAACGGCAG 42 15 GACGTCTTCA TGATTCCTCA GTACGGGTAC CTGACTCTGA ACAACGGCAG 42 ^5b GACGTCTTCA TGATTCCTCA GTACGGGTAC CTGACTCTGA ACAACGGCAG 42-1b GACGTCTTCA TGATTCCTCA GTACGGGTAC CTGACTCTGA ACAACGGCAG 4213 GACGTCTTCA TGATTCCTCA GTACGGGTAC CTGACTCTGA ACAACGGCAG 4213a GACGTCTTCA TGATTCCTCA GTACGGGTAC CTGACTCTGA ACAACGGCAG 2020201242

42_4 GACGTCTTCA TGATTCCTCA GTACGGGTAC CTGACTCTGA ACAACGGCAG 42 5a GACGTGTTCA TGATTCCTCA GTACGGATAT CTGACTCTAA ACAACGGCAG 4210 GACGTGTTCA TGATTCCTCA GTACGGATAT CTGACTCTAA ACAACGGCAG 42_3b GACGTGTTCA TGATTCCTCA GTACGGATAT CTGACTCTAA ACAACGGCAG 421 GACGTGTTCA TGATTCCTCA GTACGGATAT CTGACTCTAA ACAACGGCAG 42_ ^ 6b GACGTGTTCA TGATTCCTCA GTACGGATAT CTGACTCTAA ACAACGGCAG 43 1 GACGTCTTCA TGATTCCTCA GTACGGGTAT CTGACCCTAA ACAATGGCAG 43:5 GACGTCTTCA TGATTCCTCA GTACGGGTAT CTGACCCTAA ACAATGGCAG 43 12 GACGTCTTCA TGATTCCTCA GTACGGGTAT CTGACCCTAA ACAATGGCAG 43 20 GACGTCTTCA CGGTTCCTCA GTACGGCTAT TTAACTTTAA ACAATGGAAG 43 21 GACGTCTTCA TGGTTCCTCA GTACGGCTAT TTAACTTTAA ACAATGGAAG 4323 GACGTCTTCA TGGTTCCTCA GTACGGCTAT TTAACTTTAA ACAATGGAAG 4325 GACGTCTTCA TGGTTCCTCA GTACGGCTAT TTAACTTTAA ACAATGGAAG 44 1 GACGTCTTCA TGATTCCTCA GTACGGGTAC CTGACTCTGA ACAATGGCAG 44 ^5 GACGTCTTCA TGATTCCTCA GTACGGGTAC CTGACTCTGA ACAATGGCAG 223_30 GACGTGTTCA TGATTCCGCA GTACGGATAC CTGACTCTGA ACAATGGCAG 223_2 GACGTGTTCA TGATTCCGCA GTACGGATAC CTGACTCTGA ACAATGGCAG 223_4 GACGTGTTCA TGATTCCGCA GTACGGATAC CTGACTCTGA ACAATGGCAG 223 5 GACGTGTTCA TGATTCCGCA GTACGGATAC CTGACTCTGA ACAATGGCAG 223 6 GACGTGTTCA TGATTCCGCA GTACGGATAC CTGACTCTGA ACAATGGCAG 2237 GACGTGTTCA TGATTCCGCA GTACGGATAC CTGACTCTGA ACAATGGCAG A3__4 GACGTCTTCA TGATTCCTCA GTACGGCTAC TTGACTCTGA ACAATGGCAG A3 5 GACGTCTTCA TGATTCCTCA GTACGGCTAC TTGACTCTGA ACAATGGCAG A3 7 GACGTCTTCA TGATTCCTCA GTACGGCTAC TTGACTCTGA ACAATGGCAG A3:3 GACGTCTTCA TGATTCCTCA GTACGGCTAC TTGACTCTGA ACAATGGCAG 42_12 GACGTCTTCA TGATTCCTCA GTACGGGTAC CTGACTCTGA ACAACGGCAG AAV1 GACGTGTTCA TGATTCCGCA ATACGGCTAC CTGACGCTCA ACAATGGCAG AAV2 GACGTCTTCA TGGTGCCACA GTATGGATAC CTCACCCT GA ACAACGGCAG AAV3 GACGTCTTCA TGGTCCCTCA GTATGGATAC CT CACCCT GA ACAACGGAAG AAV8 GACGTGTTCA TGATTCCCCA GTACGGCTAC CTGACGCTCA ACAACGGTAG AAV9 GACGTCTTCA TGGTTCCTCA GTACGGCTAC CTGACGCTCA ACAATGGAAG AAV7 GACGTCTTCA TGATTCCTCA GTACGGCTAC CTGACTCTCA ACAATGGCAG 44 2 GACGTCTTCA TGATTCCTCA GTACGGGTAC CTGACTCTGA ACAATGGCAG

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Fig. IAA()

3401 3450 42_2 TCAGTCTGTG GGACGTTCCT CCTTCTACTG CCTGGAGTAC TTTCCTTCTC 4 2 8 TCAGGCCGTG GGCCGTTCCT CCTTCTACTG CCTGGAGTAC TTTCCTTCTC 42_15 TCAGGCCGTG GGCCGTTCCT CCTTCTACTG CCTGGAGTAC TTTCCTTCTC 42 5b TCAGGCCGTG GGCCGTTCCT CCTTCTACTG CCTGGAGTAC TTTCCTTCTC 42 lb TCAGGCCGTG GGCCGTTCCT CCTTCTACTG CCTGGAGTAC TTTCCTTCTC 4 2 13 TCAGGCCGTG GGCCGTTCCT CCTTCTACTG CCTGGAGTAC TTTCCTTCTC 2020201242

4 2 3a TCAGGCCGTG GGCCGTTCCT CCTTCTACTG CCTGGAGTAC TTTCCTTCTC 42- 4 TCAGGCCGTG GGCCGTTCCT CCTTCTACTG CCTGGAGTAC TTTCCTTCTC 42 -5-a TCAGTCTGTG GGACGTTCCT CCTTCTACTG CCTGGAGTAC TTTCCTTCTC 4 2 10 TCAGTCTGTG GGACGTTCCT CCTTCTACTG CCTGGAGTAC TTTCCTTCTC 42-313 TCAGTCTGTG GGACGTTCCT CCTTCTACTG CCTGGAGTAC TTTCCTTCTC 42 11 TCAGTCT GTG GGACGTTCCT CCTTCTACTG CCTGGAGTAC TTTCCTTCTC 4 2-- 6b TCAGTCTGTG GGACGTTCCT CCTTCTACTG CCTGGAGTAC TTTCCTTCTC 4 3 1 TCAGGCT GTG GGCCGTTCCT CCTTCTACTG CCTGGAGTAC TTCCCTTCTC 4 3 5 TCAGGCTGTG GGCCGTTCCT CCTTCTACTG CCTGGAGTAC TTCCCTTCTC 43_12 TCAGGCTGTG GGCCGTTCCT CCTTCTACTG C C TGGAATAC TTCCCTTCTC 43 2 0 CCAAGCCCTG GGACGTTCCT CCTTCTACTG TCTGGAGTAT TTCCCATCGC 4 3 21 CCAAGCCCTG GGACGTTCCT CCTTCTACTG TCTGGAGTAT TTCCCATCGC 43 23 CCAAGCCCTG GGACGTTCCT CC TTCTACTG TCTGGAGTAT TTCCCATCGC 4 3_25 CCAAGCCCTG GGACGTTCCT CCTTCTACTG TCTGGAGTAT TTCCCATCGC 44 1 TCAGGCCGTG GGCCGTTCCT CCTTCTACTG CCTGGAGTAC TTTCCTTCTC 4 4 5 TCAGGCCGTG GGCCGTTCCT CCTTCTACTG CCTGGAGTAC TTTCCTTCTC 22350 CCAATCGGTA GGCCGTTCCT CCTTCTACTG CCTGGAGTAC TTTCCTTCTC 223 2 CCAATCGGTA GGCCGTTCCT CCTTCTACTG CCTGGAGTAC TTTCCTTCTC 22 3 4 CCAATCGGTA GGCCGTTCCT CCTTCTACTG CCTGGAGTAC TTTCCTTCTC 2 23 5 CCAATCGGTA GGCCGTTCCT CCTTCTACTG CCTGGAGTAC TTTCCTTCTC 223 6 CCAATCGGTA GGCCGTTCCT CCTTCTACTG CCTGGAGTAC TTTCCTTCTC 223-7 CCAATCGGTA GGCCGTTCCT CCTTCTACTG CCTGGAGTAC TTTCCTTCTC A3^4 CCAAGCGGTA GGACGTTCTT CATTCTACTG TCTAGAGTAT TTTCCCTCTC A3-5 CCAAGCGGTA GGACGTTCTT CATTCTACTG TCTAGAGTAT TTTCCCTCTC A3 7 CCAAGCGGTA GGACGTTCTT CATTCTACTG TCTAGAGTAT TTTCCCTCTC A3 3 CCAAGCGGTA GGACGTTCTT CATTCTACTG TCTAGAGTAT TTTCCCTCTC 4252 TCAGGCCGTG GGCCGTTCCT CCTTCTACTG CCTGGAGTAC TTTCCTTCTC AAV1 CCAAGCCGTG GGACGTTCAT CCTTTTACTG CCTGGAATAT TTCCCTTCTC AAV2 TCAGGCAGTA GGACGCTCTT CATTTTACTG CCTGGAGTAC TTTCCTTCTC AAV3 TCAAGCGGTG GG-ACGCTCAT CCTTTTACTG CCTGGAGTAC TTCCCTTCGC AAV8 TCAGGCCGTG GGACGCTCCT CCTTCTACTG CCTGGAGTAC TTTCCTTCGC AAV9 TCAAGCGT TA GGACGTTCTT CT TTCTACTG TCTGGAATAC TTCCCTTCTC AAV7 TCAGTCTGTG GGACGTTCCT CCTTCTACTG CCTGGAGTAC TTCCCCTCTC 44 2 TCAGGCCGTG GGCCGTTCCT CCTTCTACTG CCTGGAGTAC TTTCCTTCTC

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Fig. 1AAR

3451 3500 42_2 AGATGCTGAG AACGGGCAAT AACTTTGAAT TCAGCTACAC CTTTGAGGAA 42 8 AAATGCTGAG AACGGGCAAC AACTTTGAGT TCAGCTACCA GTTTGAGGAC 42 15 AAATGCGGAG AACGGGCAAC AACTTTGAGT TCAGCTACCA GTTTGAGGAC 42 5b AAATGCTGAG AACGGGCAAC AACTTTGAGT TCAGCTACCA GTTTGAGGAC 42-1b AAATGCTGAG AACGGGCAAC AACTTT GAGT TCAGCTACCA GTTTGAGGAC 42 13 AAATGCT GAG AACGGGCAAC AACTTTGAGT TCAGCTACCA GTTTGAGGAC 2020201242

42_3a AGATGCTGAG AACGGGCAAC AACTTTGAGT TCAGCTACCA GTTTGAGGAC 4-f4 AAATGCTGAG AACGGGCAAC AACTTTGAGT TCAGCTACCA GTTTGAGGAC 42_5a AGATGCTGAG AACGGGCAAT AACTTTGAAT TCAGCTACCA GTTTGAGGAC 42W10 AGATGCTGAG AACGGGCAAT AACTTTGAAT TCAGCTACAC CTTTGAGGAA 42 3b AGATGCTGAG AACGGGCAAT AACTTTGAAT TCAGCTACAC CTTTGAGGAA 42-11 AGATGCTGAG AACGGGCAAT AACTTTGAAT TCAGCTACAC CTTTGAGGAA 42 6b AGATGCTGAG AACGGGCAAT AACTTTGAAT TCAGCTACAC CTTTGAGGAA 43 1 AGATGCTGAG GACGGGCAAC AACTTTGAAT TCAGCTACAC CTTCGAGGAC 43_5 AGATGCTGAG GACGGGCAAC AACTTTGAAT TCAGCTACAC CTTCGAGGAC 43_12 AAATGCTGAG GACGGGCAAC AACTTTGAAT TCAGCTACAC CTTCGAGGAC 43_20 AGATGCTGAG AACCGGCAAC AACTTTCAGT TCAGCTACAC CTTCGAGGAC 43-21 AGATGCTGAG AACCGGCAAC AACTTTCAGT TCAGCTACAC CTTCGAGGAC 4323 AGATGCCGAG AACCGGCAAC AACTTTCAGT TCAGCTACAC CTTCGAGGAC 43125 AGATGCTGAG AACCGGCAAC AACTTTCAGT TCAGCTACAC CTTCGAGGAC 44_1 AAATGCTGAG AACGGGCAAC AACTTTGAGT TCAGCTACCA GTTTGAGGAC 44_5 AAATGCTGAG AACGGGCAAC AACTTTGAGT TCAGCTACCA GTTTGAGGAC 223_10 AGATGCTGAG AACGGGCAAC AACTTCACCT TTAGCTACAC CTTCGAGGAC 223_2 AGATGCTGAG AACGGGCAAC AACTTCACCT TTAGCTACAC CTTCGAGGAC 223 4 AGATGCTGAG AACGGGCAAC AACTTCACCT TTAGCTACAC CTTCGAGGAC 2235 AGATGCTGAG AACGGGCAAC AACTTCACCT TTAGCTACAC CTTCGAGGAC 223 6 AGATGCTGAG AACGGGCAAC AACTTCACCT TTAGCTACAC CTTCGAGGAC 223-7 AGATGCTGAG AACGGGCAAC AACTTCACCT TTAGCTACAC CTTCGAGGAC A3 4 AGATGCTGAG GACGGGAAAC AACTT CACCT TCAGCTACAC TTTTGAAGAC A3 5 AGATGCTGAG GACGGGAAAC AACTTCACCT TCAGCTACAC TTTTGAAGAC A3-7 AGATGCTGAG GACGGGAAAC AACTTCACCT TCAGCTACAC TTTTGAAGAC A3 3 AGATGCTGAG GACGGGAAAC AACTTCACCT TCAGCTACAC TTTTGAAGAC 42_12 AAATGCTGAG AACGGGCAAC AACTTTGAGT TCAGCTACCA GTTTGAGGAC AAV1 AGATGCTGAG AACGGGCAAC AAC TT TACC T TCAGCTACAC CTTTGAGGAA AAV2 AGATGC TGCG TACCGGAAAC AACTT TACCT TCAGCTACAC TTTTGAGGAC AAV3 AGATGCTAAG GAC TGGAAAT AACT TCCAAT TCAGCTATAC CTTCGAGGAT AAV8 AGATGCTGAG AACCGGCAAC AAC TTCCAGT T TACT TACAC CTTCGAGGAC AAV9 AGATGCTGAG AACCGGCAAC AACTTTCAGT TCAGCTACAC TTTCGAGGAC AAV7 AGATGCT GAG AACGGGCAAC AACTTTGAGT TCAGCTACAG CTTCGAGGAC 44_2 AAATGCTGAG AACGGGCAAC AACTTTGAGT TCAGCTACCA GTTTGAGGAC

Fig. 1AAS

3501 3550 42 2 GTGCCTTTCC ACAGCAGCTA TGCGCACAGC CAGAGCCTGG ACCGGCTGAT 42_8 GTGCCTTTTC ACAGCAGCTA CGCGCACAGC CAAAGCCTGG ACCGGCTGAT 42_15 GTGCCTTTTC ACAGCAGCTA CGCGCATAGC CAAAGCCTGG ACCGGCT GAT 42 5b GTGCCTTTTC ACAGCAGCTA CGCGCACAGC CAAAGCCTGG ACCGGCTGAT 42-1b GTGCCTTTTC ACAGCAGCTA TGCGCACAGC CAAAGCCTGG ACCGGCTGAT 42^13 GTGCCTTTTC ACAGCAGCTA TGCGCACAGC CAAAGCCTGG ACCGGCTGAT 42_3a 2020201242

GTGCCTTTTC ACAGCAGCTA CGCGCACAGC CAAAGCCTGG ACCGGCTGAT 4 GTGCCTTTTC ACAGCAGCTA CGCGCACAGC CAAAGCCTGG ACCGGCTGAT 42_3a GTGCCCTTTC ACAGCAGCTA CGCGCACAGC CAAAGCCTGG ACCGGCTGAT 42^10 GTGCCTTTCC ACAGCAGCTA TGCGCACAGC CAGAGCCTGG ACCGGCTGAT 42 3b GTGCCTTTCC ACAGCAGCTA TGCGCACAGC CAGAGCCTGG ACCGGCTGAT 42 11 GTGCCTTTCC ACAGCAGCTA TGCGCACAGC CAGAGCCTGG ACCGGCTGAT 42_6b GTGCCTTTCC ACAGCAGCTA TGCGCATAGC CAGAGCCTGG ACCGGCTGAT 43 1 GTGCCTTTCC ACAGCAGCTA CGCGCACAGC CAGAGCCTGG ACCGGCTGAT 43 5 GTGCCTTTCC ACAGCAGCTA CGCGCACAGC CAGAGCCTGG ACCGGCTGAT 43 12 GTGCCTTTCC ACAGCAGC TA CGCGCACAGC CAGAGCCTGG ACCGGCTGAT 4320 GTGCCTTTCC ACAGCAGCTA CGCGCACAGC CAGAGCCTGG ACAGGCTGAT 43-21 GTGCCTTTCC ACAGCAGCTA CGCGCACAGC CAGAGCCTGG ACAGGCTGAT 43 23 GTGCCTTTCC ACAGCAGCTA CGCGCACAGC CAGAGCCTGG ACAGGCTGAT 43=25 GTGCCTTTCC ACAGCAGCTA CGCGCACAGC CAGAGCCTGG ACAGGCTGAT 44 1 GTGCCTTTTC ACAGCAGCTA CGCGCACAGC CAAAGCCTGG ACCGGCTGAT 445 GTGCCTTTTC ACAGCAGCTA CGCGCACAGC CAAAGCCTGG ACCGGCTGAT 223_10 GTGCCTTTCC ACAGCAGCTA CGCGCACAGC CAGAGTCTGG ACCGGCTGAT 223_2 GTGCCTTTCC ACAGCAGCTA CGCGCACAGC CAGAGTCTGG ACCGGCTGAT 223 4 GTGCCTTTCC ACAGCAGCTA CGCGCACAGC CAGAGTCTGG GCCGGCTGAT 2235 GTGCCTTTCC ACAGCAGCTA CGCGCACAGC CAGAGTCTGG GCCGGCTGAT 223=6 GTGCCTTTCC ACAGCAGCTA CGCGCACAGC CAGAGTCTGG ACCGGCTGAT 223 7 GTGCCTTTCC ACAGCAGCTA CGCGCACAGC CAGAGTCTGG ACCGGCTGAT A3_4 GTGCCTTTCC ACAGCAGCTA CGCGCACAGC CAGAGTCTGG ATCGGCTGAT A3 5 GTGCCTTTCC ACAGCAGCTA CGCGCACAGC CAGAGTCTGG ATCGGCTGAT A3-7 GTGCCTTTCC ACAGCAGCTA CGCGCACAGC CAGAGTCTGG ATCGGCTGAT A3 3 GTGCCTTTCC ACAGCAGCTA CGCGCACAGC CAGAGTCTGG ATCGGCTGAT 42_12 GTGCCTTTTC ACAGCAGCTA CGCGCACAGC CAAAGCCTGG ACCGGCTGAC AAV1 GTGCCTTTCC ACAGCAGCTA CGCGCACAGC CAGAGCCTGG ACCGGCTGAT AAV2 GTTCCTTTCC ACAGCAGCTA CGCTCACAGC CAGAGTCTGG ACCGTCTCAT AAV3 GTACCTTTTC ACAGCAGCTA CGCTCACAGC CAGAGTTTGG ATCGCTTGAT AAV8 GTGCCTTTCC ACAGCAGCTA CGCCCACAGC CAGAGCTTGG ACCGGCTGAT AAV9 GTGCCTTTCC ACAGCAGCTA CGCACACAGC CAGAGTCTAG ATCGACTGAT AAV7 GTGCCTTTCC ACAGCAGCTA CGCACACAGC CAGAGCCTGG ACCGGCTGAT 44 2 GTGCCTTTTC ACAGCAGCTA CGCGCACAGC CAAAGCCTGG ACCGGCTGAT

Fig. lAAT

3551 3600 42 2 GAATCCCCTC ATCGACCAGT ACCTGTACTA CCTGGCCCGG ACCCAGAGCA ^8 42_ GAACCCCCTC ATCGACCAGT ACCTGTACTA CCTGTCTCGG ACTCAGTCCA 42 15 GAACCCCCTC ATCGACCAGT ACCTGTACTA CCTGTCTCGG ACTCAGTCCA 42 5b GAACCCCCTC ATCGACCAGT ACCTGTACTA CCTGTCTCGG ACTCAGTCCA 421b GAACCCCCTC ATCGACCAGT ACCTGTACTA CCTGTCTCGG ACTCAGTCCA 42_13 GAACCCCCTC ATCGACCAGT ACCTGTACTA CCTGTCTCGG ACTCAGTCCA 2020201242

42 3a GAACCCCCTC AT CGACCAGT ACCTGTACTA CCTGTCTCGG ACTCAGTCCA 4 GAACCCCCTC ATCGACCAGT ACCTGTACTA CCTGTCTCGG ACTCAGTCCA 42-5-a GAACCCCCTC ATCGACCAGT ACCTGTACTA CCTGTCTCGG ACTCAGTCCA 42^10 GAATCCCCTC ATCGACCAGT ACCTGTACTA CCTGGCCCGG ACCCAGAGCA 42 3b GAATCCCCTC ATCGACCAGT ACCTGTACTA CCTGGCCCGG ACCCAGAGCA 42-11 GAATCCCCTC ATCGACCAGT ACCTGTACTA CCTGGCCCGG ACCCAGAGCA 42 6b GAATCCCCTC ATCGACCAGT ACCTGTACTA CCTGGCCCGG ACCCAGAGCA 431 GAACCCTCTC ATCGACCAGT ACCTGTATTA CTTATCCAGA ACTCAGTCCA 43 5 GAACCCTCTC ATCGACCAGT ACCTGTATTA CTTATCCAGA ACTCAGTCCA 43 12 GAACCCTCTC ATCGACCAGT ACCTGTATTA CTTATCCAGA ACTCAGTCCA 43^20 GAATCCCCTC ATCGACCAGT ACCTGTACTA CCTGGTCAGA ACGCAAACGA 43-21 GAATCCCCTC ATCGACCAGT ACCTGTACTA CCTGGTCAGA ACGCAAACGA 43_23 GAATCCCCTC ATCGACCAGT ACCTGTACTA CCTGGTCAGA ACGCAAACGA 43_25 GAATCCCCTC ATCGACCAGT ACCTGTACTA CCTGGTCAGA ACGCAAACGA 44 1 GAACCCCCTC ATCGACCAGT ACCTGTACTA CCTGTCTCGG ACTCAGTCCA 44 5 GAACCCCCTC ATCGACCAGT ACCTGTACTA CCTGTCTCGG ACTCAGTCCA 223_10 GAATCCC CTC ATCGACCAGT ACCTGTACTA CTTGGCCAGA ACACAGAGCA 2n 2 GAATCCCCTC ATCGACCAGT ACCTGTACTA CTTGGCCAGA ACACAGAGCA 2234 GAATCCCCTC ATCGACCAGT ACCTGTACTA CTTGGCCAGA ACACAGAGCA 2235 GAATCCCCTC ATCGACCAGT ACCTGTACTA CTTGGCCAGA ACACAGAGCA 223^6 GAATCCCCTC ATCGACCAGT ACCTGTACTA CTTGGCCAGA ACACAGAGCA 223_7 GAATCCCCTC ATCGACCAGT ACCTGTACTA CTTGGCCAGA ACACAGAGCA A3 A4 GAATCCTCTC ATTGACCAGT ACCTGTATTA CCTGAGCAAA ACTCAGGGTA A3 5 GAATCCTCTC ATTGACCAGT ACCTGTATTA CCTGAGCAAA ACTCAGGGTA A3^7 GAATCCTCTC AT TGACCAGT ACCTGTATTA CCTGAGCAAA ACTCAGGGTA A3^3 GAATCCTCTC ATTGACCAGT ACCTGTATTA CCTGAGCAA ACTCAGGGTA 42_12 GAACCCCCTC ATCGACCAGT ACCTGTACTA CCTGGCCCGG ACCCAGAGCA AAV1 GAATCCTCTC ATCGACCAAT ACCTGTATTA CCTGAACAGA ACTCAAA.AT AAV2 GAATCCTCTC ATCGACCAGT ACCTGTATTA CTT GA.GCAGA ACAAACACTC AAV3 GAATCCTCTT AT T GAT CAGT ATCTGTACTA CCTGAACAGA ACGCAAGGAA AAVB GAATCCTCTG ATTGACCAGT ACCTGTACTA CTTGTCTCGG ACTCAAACAA AAV9 GAACCCCCTC ATCGACCAGT AC CTATACTA CCTGGTCAGA ACACAGACAA AAV7 GAATCCCCTC ATCGACCAGT ACTTGTACTA CCTGGCCAGA ACACAGAGTA 44 2 GAACCCCCTC ATCGACCAGT ACCTGTACTA CCTGTCTCGG ACTCAGTCCA

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Fig. lAAU

3601 3650 42 2 CTACGG GG TCCACAAGGG AGCTGCA. GT TCCA TCAGGCTGGG 42__8 CGGGA GG TACCGCAGGA ACTCAGCAGT TGCTATTTTC TCAGGCCGGG 42_55 CGGGA GG TACCGCAGGA ACTCAGCAGT TGCTATTTTC TCAGGCCGGG 42_5b CGGGA GG TACCGCAGGA ACTCAGCAGT TGCTATTTTC TCAGGCCGGG 42 lb CGGGA GG TACCGCAGGA ACTCAGCAGT TGCTATTTTC TCAGGCCGGG 42_13 CGGGA GG TACCGCAGGA ACTCAGCAGT TGCTATTTTC TCAGGCCGGG 2020201242

42 3a CGGGA GG TACCGCAGGA ACTCAGCAGT TGCTATTTTC TCAGGCCGGG 42_4 CGGGA GG TACCGCAGGA ACTCAGCAGT TGCTATTTTC TCAGGCCGGG 42_5a CGGGA GG TACCGCAGGA ACTCAGCAGT TGCTATTTTC TCAGGCCGGG 42_10 CTACG GG GTCCACAAGG GAGCTGCAGT TCCA TCAGGCTGGG 42_3b CTACG GG GTCCACAAGG GAGCTGCAGT TCCA. TCAGGCTGGG 42 ^11 CTACG GG GTCCACAAGG GAGCTGCAGT TCCA TCAGGCTGGG 42 Eb CTACG GG GTCCACAAGG GAGCTGCAGT TCCA TCAGGCTGGG 0_1 CAGGA GG AACTCAAGGT ACTCAGCAAT TGTTATTTTC TCAAGCCGGG 43_5 CAGGA GG AACTCAAGGT ACTCAGCAAT TGTTATTTTC TCAAGCCGGG 43_12 CAGGA GG AACTCAAGGT ACTCAGCAAT TGTTATTTTC TCAAGCCGGG 43^20 CT GG AACTGGAGGG ACGCAGACTC TGGCATTCAG CCAAGCGGGT 43 21 CT GG AACTGGAGGG ACGCAGACTC TGGCATTCAG CCAAGCGGGT 43__23 CT GG AACTGGAGGG ACGCAGACTC TGGCATTCAG CCAAGCGGGT 43-25 CT GG AACTGGAGGG ACGCAGACTC TGGCATTCAG CCAAGCGGGT 44_1 CGGGA...GG TACCGCAGGA ACTCAGCAGT TGCTATTTTC TCAGGCCGGG 44_5 CGGGA...GG TACCGCAGGA ACTCAGCAGT TGCTATTTTC TCAGGCCGGG 223_TO ACGCAGGAGG TACTGCTGGC AATCGGGAAC TGCAGTTTTA TCAGGGCGGA 223_2 ACGCAGGAGG TACTGCTGGC AATCGGGAAC TGCAGTTTTA TCAGGGCGGA 223_4 ACGCAGGAGG TACTGCTGGC AATCGGGAAC TGCAGTTTTA TCAGGGCGGA 223_5 ACGCAGGAGG TACTGCTGGC AATCGGGAAC TGCAGTTTTA TCAGGGCGGA 223_6 ACGCAGGAGG TACTGCTGGC AATCGGGAAC TGCAGTTTTA TCAGGGCGGA 223_7 ACGCAGGAGG TACTGCTGGC AATCGGGAAC TGCAGTTTTA TCAGGGCGGA A3_4 CAAG...TGG AACAACGCAG CAATCGAGAC TGCAGTTCAG CCAAGCTGGG A3 5 CAAG...TGG AACAACGCAG CAATCGAGAC TGCAGTTCAA CCAAGCTGGG A3 7 CAAG...TGG AACAACGCAG CAATCGAGAC TGCAGTTCAG CCAAGCTGGG A3 3 CAAG...TGG AACAACGCAG CAATCGAGAC TGCAGTTCAG CCAAGCTGGG 42_12 CTACG...GG GTCCACAAGG GGGCTGCAGT TCCA TCAGGCTGGG AAV1 CAGTCC..GG AAGTGCCCAA AACAAGGACT TGCTGTTTAG CCGTGGGTCT AAV2 CAAG...TGG AACCACCACG CAGTCAAGGC TTCAGTTTTC TCAGGCCGGA AAV3 CAACCTCTGG AACAACCAAC CAATCACGGC TGCTTTTTAG CCAGGCTGGG AAV8 CAGGAG..GC .ACGGCAAAT ACGCAGACTC TGGGCTTCAG CCAAGGTGGG AAV9 CTGGA ACTGGGGGA ACTCAAACTT TGGCATTCAG CCAAGCAGGC AAV7 ACCCAGGAGG CACAGCTGGC AATCGGGAAC TGCAGTTTTA CCAGGGCGGG 44 2 CGGGA...GG TACCGCAGGA ACTCAGCAGT TGCTATTTTC TCAGGCCGGG

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Fig. 1AAV

3651 3700 42 2 CCCAACACCA TGGCCGAGCA ATCAAAGAAC TGGCTGCCCG GACCCTGTTA 42=8 CCTAATAACA TGTCGGCTCA GGCCAAAAAC TGGCTACCCG GGCCCTGCTA 42_15 CCTAATAACA TGTCGGCTCA GGCCAAAAAC TGGCTACCCG GGCCCTGCTA 42 5b CCTAATAACA TGTCGGCTCA GGCCAAAAAC TGGCTACCCG GGCCCTGCTA 42 lb CCTAATAACA TGTCGGCTCA GGCCAAAAAC TGGCTACCCG GGCCCTGCTA 42-13 CCTAATAACA TGTCGGCTCA GGCCAAAAAC TGGCTACCCG GGCCCTGCTA 2020201242

42 3a CCTAATAACA TGTCGGCTCA GGCCAAAAAC TGGCTACCCG GGCCCTGCTA 0 4 CCTAATAACA TGTCGGCTCA GGCCAAAAAC TGGCTACCCG GGCCCTGCTA 42_5a CCTAATAACA TGTCGGCTCA GGCCAAAAAC TGGCTACCCG GGCCCTGCTA 42_10 CCCAACACCA TGGCCGAGCA ATCAAAGAAC TGGCTGCCCG GACCCTGTTA 42 3b CCCAACACCA TGGCCGAGCA ATCAAAGAAC TGGCTGCCCG GACCCTGTTA 42:11 CCCAACACCA TGGCCGAGCA ATCAAAGAAC TGGCTGCCCG GACCCTGTTA 426b CCCAACACCA TGGCCGAGCA ATCAAAGAAC TGGCTGCCCG GACCCTGTTA 43 1 CCCGCAAACA TGTCGGCTCA GGCCAAGAAC TGGCTACCTG GACCGTGTTA 4315 CCCGCAAACA TGTCGGCTCA GGCCAAGAAC TGGCTACCTG GACCGTGTTA 43_12 CCCGCAAACA TGTCGGCTCA GGCCAAGAAC TGGCTACCTG GACCGTGTTA 43_20 CCTAGCTCAA TGGCCAACCA GGCTAGAAAT TGGGTGCCCG GACCTTGCTA 43_21 CCTAGCTCAA TGGCCAACCA GGCTAGAAAT TGGGTGCCCG GACCTTGCTA 43_23 CCTAGCTCAA TGGCCAACCA GGCTAGAAAT TGGGTGCCCG GACCTTGCTA 43:25 CCTAGCTCAA TGGCCAACCA GGCTAGAAAT TGGGTGCCCG GACCTTGCTA 44_1 CCTAATAACA TGTCGGCTCA GGCCAAAAAC TGGCTACCCG GGCCCTGCTA 94_5 CCTAATAACA TGTCGGCTCA GGCCAAAAAC TGGCTACCCG GGCCCTGCTA 22310 CCTACCACCA TGGCCGAACA AGCAAAGAAC TGGCTGCCCG GACCTTGCTT 2232 CCTACCACCA TGGCCGAACA AGCAAAGAAC TGGCTGCCCG GACCTTGCTT 223 4 CCTACCACCA TGGCCGAACA AGCAAAGAAC TGGCTGCCCG GACCTTGCTT 223^5 CCTACCACCA TGGCCGAACA AGCAAAGAAC TGGCT GCCCG GACCTTGCT T 223:6 CCTACCACCA TGGCCGAACA AGCAAAGAAC TGGCTGCCCG GACCTTGCTT 223_7 CCTACCACCA TGGCCGAACA AGCAAAGAAC TGGCTGCCCG GACCTTGCTT A3_4 CCTAGCTCCA. TGGCTCAGCA GGCCAAAAAC TGGCTACCGG GACCCAGCTA A3_5 CCTAGCTCCA TGGCTCAGCA GGCCAAAAAC TGGCTACCGG GACCCAGCTA A3 7 CCTAGCTCCA TGGCTCAGCA GGCCAAAAAC TGGCTACCGG GACCCAGCTA A3_^3 CCTAGCTCCA TGGCTCAGCA GGCCAAAAAC TGGCTACCGG GACCCAGCTA 42_12 CCCAACACCA TGGCCGAGCA ATCAAAGAAC TGGCTGCCCG GACCCTGTTA AAV1 CCAGCT GGCA TGTCTGTTCA GCCCAAAAAC TGGCTACCTG GACCCTGTTA AAV2 GCGAGTGACA TTCGGGACCA GT C TAGGAAC TGGCTTCCTG GACCCTGTTA AAV3 CCTCAGTCTA. TGTCTTTGCA GGCCAGAAAT TGGCTACCTG GGCCCTGCTA AAV8 CCTAATACAA TGGCCAATCA GGCAAAGAAC TGGCTGCCAG GACCCTGTTA AAV9 CCTAGCTCAA TGGCCAATCA GGCTAGAAAC TGGGTACCCG GGCCCTGCTA AAV7 CCTTCAACTA TGGCCGAACA AGCCAAGAAT TGGTTACCTG GACCTTGCTT 44_2 CCTAATAACA TGTCGGCTCA GGCCAAAAAC TGGCTACCCG GGCCCTGCTA

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Fig. lAAW

3701 3750 42_2 TCGGCAGCAG AGACTGTCAA AAAACATAGA CAGCAACAAC AACAGTAACT 42_8 CCGGCAGCAA CGCGTCTCCA CGACACTGTC GCAAAATAAC AACAGCAACT 4 2 15 CCGGCAGCAA CGC GTCTCCA CGACACTGTC GCAAAATAAC AACAGCAACT 4 2_5b CCGGCAGCAA CGCGTCTCCA CGACACTGTC GCAAAATAAC AACAGCAACT 4 2 lb CCGGCAGCAA CGCGTCTCCA CGACAGTGTC GCAAAATAAC AACAGCAACT 4 2 13 CCGGCAGCAA CGCGTCTCCA CGACAGTGTC GCAAAATAAC AACAGCAACT 2020201242

42 3a CCGGCAGCAA CGCGTCTCCA CGACACTGTC GCAAAATAAC AACAGCAACT 42- 4 CCGGCAGCAA CGCGTCTCCA CGACACTGTC GCAAAATAAC AACAGCAACT 4 2_5 a CCGGCAGCAA CGCGTCTCCA CGACACTGTC GCAAAATAAC AACAGCAACT 42_10 TCGGCAGCAG AGACTGTCAA AAAACATAGA CAGCAACAAC AACAGTAACT 42 3b TCGGCAGCAG AGACTGTCAA AAAACATAGA CAGCAACAAC ACCAGTAACT 4 2 11 TCGGCGGCAG AGACTGTCAA AAGACATAGA CAGCAACAAC AACAGTAACT 4 2 6b TCGGCAGCAG AGACTGTCAA AAAACATAGA CAGCAACAAC AACAGTAACT 43 1 CCGTCAGCAA CGAGTTTCCA CGACACTGTC GCAAAACAAC AACAGCAAT T 43__5 CCGTCAGCAA CGAGTTTCCA CGACACTGTC GCAAAACAAC AACAGCAATT 43 12 CCGTCAGCAA CGAGTTTCCA CGACACTGTC GCAAAACAAC AACAGCAATT 4320 CCGGCAGCAG CGCGTCTCCA CGACAACCAA CCAGAACAAC AACAGCAACT 43 21 CCGGCAGCAG CGCGTCTCCA CGACAAC CAA CCAGAGCAAC AACAGCAACT 4323 CCGGCAGCAG CGCGTCTCCA CGACAAC CAA CCAGAACAAC AACAGCAACT 4 3=2 5 CCGGCAGCAG CGCGTCTCCA C GACAACCAA CCAGAACAAC AACAGCAACT 44 1 CCGGCAGCAA CGCGTCTCCA CGACACTGTC GCAAAATAAC AACAGCAACT 445 CCGGCAGCAA CGCGTCTCCA CGACACTGTC GCAAAATAAC AACAGCAACT 2 2 3_10 CCGGCAACAG AGAGTATCCA AGACGCTGGA TCAAAATAAC AACAGCAACT 2232 CCGGCAACAG AGAGTATCCA AGACGCTGGA TCAAAATAAC AACAGCAACT 2234 CCGGCAACAG AGAGTATCCA AGACGCTGGA TCAAAATAAC AACAGCAACT 2235 CCGGCAACAG AGAGTATCCA AGACGCTGGA TCAAAATAAC AACAGCAACT 223 6 CCGGCAACAG AGAGTATCCA AGACGCTGGA TCAAAATAAC AACAGCAACT 2237 CCGGCAACAG AGAGTATCCA AGACGCTGGA TCAAAATAAC AACAGCAACT A3=4 CCGACAGCAG CGAATGTCTA AGACGGCTAA TGACAACAAC AACAGTGAAT A3_5 CCGACAGCAG CGAATGTCTA AGACGGCTAA TGACAACAAC AACAGTGAAT A3 7 CCGACAGCAG CGAATGTCTA AGACGGCTAA TGACAACAAC AACAGTGAAT A3 3 CCGACAGCAG CGAATGTCTA AGACGGCTAA TGACAACAAC AACAGTGAAT 42_12 TCGGCAGCAG AGACTGTCAA AAAACATAGA CAGCAACAAC AACAGTAACT AAV1 TCGGCAGCAG CGCGTTTCTA AAACAAAAAC AGACAACAAC AACAGCAATT AAV2 CC GCCAGCAG C GAG TAT CAA AGACAT C T GC GGATAACAAC AAC A G T GAAT AAV3 CCGGCAACAG AGACT TTCAA AGACTGCTAA CAGCAACAAC AACAGTAACT AAV8 CCGCCAACAA CGCGTCTCAA CGACAACCGG GCAAAACAAC AACAGCAACT AAV9 CCGTCAGCAG CGCGTCTCCA CAACCAC CAA CCAAAATAAC AACAGCAACT AAV7 CC GG CAACAA AGAGTCTCCA AAACGCTGGA TCAAAACAAC AACAGCAACT 442 CCGGCAGCAA CGCGTCTCCA CGACACTGTC GCAAAATAAC AACAGCAACT

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PCT/ITS02/33629 WO 03/042397 20 Feb 2020

Fig. lAAX

3751 3800 42 2 TTGCCTGGAC CGGGGCCACT AAATACCATC TGAATGGTAG AAATTCATTA 42-8 TTGCTTGGAC CGGTGCCACC AAGTATCATC TGAATGGCAG AGACTCTCTG 42 15 TTGCTTGGAC CGGTGCCACC AAGTATCATC TGAATGGCAG AGACTCTCTG 42_5b TTGCTTGGAC CGGTGCCACC AAGTATCATC TGAATGGCAG AGACTCTCTG 421b T TGCTTGGAC CGGTGCCACC AAGTATCATC TGAATGGCAG AGACTCTCTG 42 13 TTGCTTGGAC CGGTGCCACC AAGTATCATC TGAATGGCAG AGACTCTCTG 42 3a TTGCTTGGAC CGGTGCCACC AAGTATCATC TGAATGGCAG AGACTCTCTG 2020201242

42- 4 TTGCTTGGAC CGGTGCCACC AAGTATCATC T GAATGGCAG AGACTCTCTG 42 3a TTGCTTGGAC CGGTGCCACC AAGTATCATC TGAATGGCAG AGACTCTCTG 4210 TTGCCTGGAC CGGGGCCACT AAATACCATC TGAATGGTAG AAATTCATTA 42 3b TTGCCTGGAC CGGGGCCACT AAATACCATC TGAATGGTAG AAATTCATTA 42-11 TTGCCTGGAC CGGGGCCACT AAATACCATC TGAATGGTAG AAATTCATTA 42^6b TTGCCTGGAC CGGGGCCACT AAATACCATC T GMT GGTAG AAATTCATTA 4j1 TTGCTTGGAC CGGTGCCACC AAGTATCACC TGAATGGCAG AGACTCCCTG 43 5 TTGCTTGGAC CGGTGCCACC AAGTATCACC TGAATGGCAG AGACTCCCTG 4 3 12 TTGCTTGGAC CGGT GCCACC AAGTATCACC TGAATGGCAG AGACTCCCTG 43 _-2 TTGCCTGGAC GGGAGCTGCC AAGTTTAAGC TGAACGGCCG AGACTCTCTA 4321 TTGCCTGGAC GGGAGCTGCC AAGTTTAAGC TGAACGGCCG AGACTCTCTA 43 23 TTGCCTGGAC GGGAGCTGCC AAGTTTAAGC TGAACGGCCG AGACTCTCTA 43 25 TTGCCTGGAC GGGAGCTGCC AAGTTTAAGC TGAACGGCCG AGACTCTCTA 44 - 1 TTGCCTGGAC CGGTGCCACC AAGTATCATC T GMT GGCAG AGACTCTCTG 445 TTGCCTGGAC CGGTGCCACC AAGTATCATC TGAATGGCAG AGACTCTCTG 22 3 io TTGCCTGGAC TGGTGCCACA AAATACCATT TAAATGNAAG AAATTCATTG 223_22 TTGCCTGGAC TGGTGCCACA AAATACCATT TAAATGGAAG AAATTCATTG 223 4 TTGCCTGGAC TGGTGCCACA AAATACCATT TAAATGGAAG AAATTCATTG 2235 TTGCCTGGAC TGGTGCCACA AAATACCATT TAAATGGAAG AAATTCATTG 2236 TTGCCTGGAC TGGTGCCACA AAATACCATT TAAATGGAAG AAATTCATTG 223__7 TTGCCTGGAC TGGTGCCACA AAATACCAT T TAAATGGAAG AAATTCATTG A3 4 TTGCTTGGAC TGCAGCCACC AAATATTACC TGAATGGAAG AAATTCTCTG A3_5 TTGCTTGGAC TGCAGCCACC AAATATTACC CGAATGGAAG AAATTCTCTG A3 7 TTGCTTGGAC TGCAGCCACC AAATATTACC TGAATGGAAG AAATTCTCTG A3 3 TTGCTTGGAC TGCAGCCACC AAATATTACC TGAATGGAAG AAATTCTCTG 42_12 TTGCCTGGAC CGGGGCCACT AAATACCATC TGAATGGTAG AAATTCATTA AAV1 TTACCTGGAC TGGT GCTT CA AAATATAACC TCAATGGGCG TGAATCCATC AC TCGTGGAC TGGAGCTACC AAGTACCACC TCAATGGCAG AGACTCTCTG AAV3 TTCCTTGGAC AGCGGCCAGC A.A_ATAT CAT C TCAATGGCCG CGACTCGCTG AAV8 TTGCCTGGAC TGCTGGGACC AAATACCATC TGAATGGAAG AAATTCATTG AAV 9 TTGCGTGGAC GGGAGCTGCT AAAT TCAAGC TGAACGGGAG AGACTCGCTA AAV7 TTGCTTGGAC TGGTGCCACC AAATATCACC TGAACGGCAG AAACTCGTTG 442 TTGCCTGGAC CGGTGCCACC AAGTATCATC TGAATGGCAG AGACTCTCTG

WO 03/042397 20 Feb 2020

Fig. 1AAY

3801 3850 42_2 ACCAACCCGG GCGTAGCCAT GGCCACCAAC AAGGACGACG AGGACCAGTT 42_8 GTAAATCCCG GTGTCGCTAT GGCAACGCAC AAGGACGACG AAGAGCGATT 42_15 GTAAATCCCG GTGTCGCTAT GGCAACGCAC AAGGACGACG AAGAGCGATT 42 5b GTAAATCCCG GTGTCGCTAT GGCAACGCAC AAGGACGACG AAGAGCGATT 42lb GTAAATCCCG GTGTCGCTAT GGCAACGCAC AAGGGCGACG AAGAGCGATT 4213 13 GTAAATCCCG GTGTCGCTAT GGCAACGCAC AAGGGCGACG AAGAGCGATT 4213a GTAAATCCCG GTGTCGCTAT GGCAACGCAC AAGGACGACG AAGAGCGATT 2020201242

42_4 GTAAATCCCG GTGTCGCTAT GGCAACGCAC AAGGACGACG AAGAGCGATT 42_5a GTAAATCCCG GTGTCGCTAT GGCAACGCAC AAGGACGACG AAGAGCGATT 42 10 ACCAACCCGG GCGTAGCCAT GGCCACCAAC AAGGACGACG AGGACCAGTT 42 3b ACCAACCCGG GCGTAGCCAT GGCCACCAAC AAGGACGACG AGGACCAGTT 42:11 ACCAACCCGG GCGTAGCCAT GGCCACCAAC AAGGACGACG AGGACCAGTT 42_6b ACCAACCCGG GCGTAGCCAT GGCCACCAAC AAGGACGACG AGGACCAGTT 43_1 GTTAATCCCG GCGTTGCCAT GGCTACCCAC AAGGACGACG AGGAGCGCTT 43_5 GTTAATCCCG GCGTTGCCAT GGCTACCCAC AAGGACGACG AGGAGCGCTT 4312 GTTAATCCCG GCGTTGCCAT GGCTACCCAC AAGGACGACG AGGAGCGCTT 4320 ATGAATCCGG GCGTGGCAAT GGCTTCCCAC AAGGATGACG ACGACCGCTT 4321 ATGAATCCGG GCGTGGCAAT GGCTTCCCAC AAGGATGACG ACGACCGCTT 4323 ATGAATCCGG GCGTGGCAAT GGCTTCCCAC AAGGATGACG ACGACCGCTT 43_25 ATGAATCCGG GCGTGGCAAT GGCTTCCCAC AAGGATGACG ACGACCGCTT 471L1 GTAAATCCCG GTGTCGCTAT GGCAACCCAC AAGGACGACG AAGAGCGATT 44_5 GTAAATCCCG GTGTCGCTAT GGCAACCCAC AAGGACGACG AAGAGCGATT 223_10 GTTAATCCCG GTGTCGCCAT GGCAACCCAC AAGGACGACG AGGAACGCTT 223 2 GTTAATCCCG GTGTCGCCAT GGCAACCCAC AAGGACGACG AGGAACGCTT 223__4 GTTAATCCCG GTGTCGCCAT GGCAACCCAC AAGGACGACG AGGAACGCTT 223-5 GTTAATCCCG GTGTCGCCAT GGCAACCCAC AAGGACGACG AGGAACGCTT 223 6 GTTAATCCCG GTGTCGCCAT GGCAACCCAC AAGGACGACG AGGAACGCTT 223:7 GTTAATCCCG GTGTCGCCAT GGCAACCCAC AAGGACGACG AGGAACGCTT A3_4 GTCAATCCCG GGCCCCCAAT GGCCAGTCAC AAGGACGATG AGGAAAAGTA A3 5 GTCAATCCCG GGCCCCCAAT GGCCAGTCAC AAGGACGATG AGGAAAAGTA A3_7 GTCAATCCCG GGCCCCCAAT GGCCAGTCAC AAGGACGATG AGGAAAAGTA A33 GTCAATCCCG GGCCCCCAGT GGCCAGTCAC AAGGACGATG AGGAAAAGTA 42_12 ACCAACCCGG GCGTAGCCAT GGCCACCAAC AAGGACGACG AGGACCAGTT AAV1 ATCAACCCTG GCACTGCTAT GGCCTCACAC AAAGACGACG AGGACCAGTT AAV2 GTGAATCC.. GGCC....AT GGCAAGCCAC AAGGACGATG AAGAAAAGTT AAV3 GTGAATCCAG GACCAGCTAT GGCCAGTCAC AAGGACGATG AAGAAAAATT AAV8 GCTAATCCTG GCATCGCTAT GGCAACACAC AAAGACGACG AGGAGCGTTT AAV9 ATGAATCCTG GCGTGGCAAT GGCATCGCAC AAAGACGACG AGGACCGCTT AAV7 GTTAATCCCG GCGTCGCCAT GGCAACTCAC AAGGACGACG AGGACCGCTT 44_2 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 YA5 TTTTCCATCC AGCGGAGTCT TGATGTTTGG GAAACAGGGA GCTGGAAA.. 42 5b TTTTCCATCC AGCGGAGTCT TGATGTTTGG GAAACAGGGA GCTGGAAA.. 42Alb TTTTCCATCC AGCGGAGTCT TGATGTTTGG GAAACAGGGA GCTGGAAA.. 42A13 TTTTCCATCC AGCGGAGTCT TGATGTTTGG GAAACAGGGA GCTGGAAA.. 2020201242

423a TTTTCCATCC AGCGGAGTCT TGATGTTTGG GAAACAGGGA GCTGGAAA.. 42_4 TTTTCCATCC AGCGGAGTCT TGATGTTTGG GAAACAGGGA GCTGGAAA.. 42A 5a TTTTCCATCC AGCGGAGTCT TGATGTTTGG GAAACAGGGA GCTGGAAA.. 42 10 CTTTCCCATC AACGGAGTGC TGGTTTTTGG CAAAACGGGG GCTGCCAACA 42 3b CTTTCCCATC AACGGAGTGC TGGTTTTTGG CAAAACGGGG GCTGCCAACA 4211 A CTTTCCCATC AACGGAGTGC TGGTTTTTGG CAAAACGGGG GCTGCCAACA 426b CTTTCCCATC AACGGAGTGC TGGTTTTTGG CAAAACGGGG GCTGCCAACA 43_1 CTTCCCGTCA AGCGGAGTTC TAATGTTTGG CAAGCAGGGG GCTGGAAA.. 43_5 CTTCCCGTCA AGCGGAGTTC TAATGTTTGG CAAGCAGGGG GCTGGAAA.. 43_12 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.. TTTTCCGTCC AGCGGAGTCT TAATGTTTGG GAAACAGGGA GCTGGAAA.. 44_5 TTTTCCGTCC AGCGGAGTCT TAATGTTTGG GAAACAGGGA GCTGGAAA.. 22310 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 A314 TTTCCCCATG CACGGAAATC TCATCTTTGG AAAACAAGGC ACAGGAAC.. A3_5 TTTCCCCATG CACGGAAATC TCATCTTTGG AAAACAAGGC ACAGGAAC.. A3A7 TTTCCCCATG CACGGAAATC TCATCTTTGG AAAACAAGGC ACAGGAAC.. A3 3 TTTCCCCATG CACGGAAATC TCATCTTTGG AAAACAAGGC ACAGGAAC.. 42_12 CTTTCCCATC AACGGAGTGC TGGTTTTTGG CAAAACGGGG GCTGCCAACA AAV1 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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Fig. 1AAAA

3901 3950 42 2 AGACAACGCT GGAA AACGTGCTAA TGACCAGCGA GGAGGAGATC 428 AGACAACG.T GGACTATAGC AGCGTTATGC TAACCAGTGA GGAAGAAATC 42 15 AGACAACG.T GGACTATAGC AGCGTTATGC TAACCAGTGA GGAAGAAATC 42_5b AGACAACG.T GGACTATAGC AGCGTTATGC TAACCAGTGA GGAAGAAATC 42-1b AGACAACG.T AGACTATAGC AGCGTTATGC TAACCAGTGA GGAAGAAATC 42 13 AGACAACG.T GGACTATAGC AGCGTTATGC TAACCAGTGA GGAAGAAATC 2020201242

42 3a AGACAACG.T GGACTATAGC AGCGTTATGC TAACCAGTGA GGAAGAAATC AGACAACG.T GGACTATAGC AGCGTTATGC TAACCAGTGA GGAAGAAATC 42_5a AGACAACG.T GGACTATAGC AGCGTTATGC TAACCAGTGA GGAAGAAATC 42 -10 AGACAACGCT GGAA AACGTGCTAA TGACCAGCGA GGAGGAGATC 42 3b AGACAACGCT GGAA AACGTGCTAA TGACCAGCGA GGAGGAGATC 42 11 AGACAACGCT GGAA AACGTGCTAA TGACCAGCGA GGAGGAGATC 42-6b AGACAACGCT GGAA AACGTGCTAA TGACCAGCGA GGAGGAGATC 43_1 AGACAATG.T GGACTACAGC AGCGTGATGC TCACCAGCGA AGAAGAAATT 43_5 AGACAATG.T GGACTACAGC AGCGTGATGC TCACCAGCGA AGAAGAAATT 43 12 AGACAATG.T GGACTACAGC AGCGTGATGC TCACCAGCGA AGAAGAAATT 4320 CGATGGAG.T GGATTACAGC CAAGTGCTGA TTACAGATGA GGAAGAAATC 4321 CGATGGAG.T GGATTACAGC CAAGTGCTGA TTACAGATGA GGAAGAAATC 4323 CGATGGAG.T GGATTACAGC CAAGTGCTGA TTACAGATGA GGAAGAAATC 43 25 CGATGGAG.T GGATTACAGC CAAGTGCTGA TTACAGATGA GGAAGAAATC 44_1 AGACAACG.T GGACTATAGC AGCGTTATGC TAACCAGTGA GGAAGAAATT 44 5 AGACAACG.T GGACTATAGC AGCGTTATGC TAACCAGTGA GGAAGAAATT 223 TO AAACTACATT AGAA AACGTGCTCA TGACAAATGA AGAAGAAATT 223_2 AAACTACATT AGAA AACGTGCTCA TGACAAATGA AGAAGAAATT 223_4 AAACTACATT AGAA AACGTGCTCA TGACAAATGA AGAAGAAATT 223_5 AAACTACATT AGAA AACGTGCTCA TGACAAATGA AGAAGAAATT 223_6 AAACTACATT AGAA AACGTGCTCA TGACAAATGA AGAAGAAATT 223_7 AAACTACATT AGAA AACGTGCTCA TGACAAATGA AGAAGAAATT A3 4 TACCAATG.T GGACATTGAA TCAGTGCTTA TTACAGACGA AGAAGAAATC A3 5 TACCAATG.T GGACATTGAA TCAGTGCTTA TTACAGACGA AGAAGAAATC A3_^7 TACCAATG.T GGACATTGAA TCAGTGCTTA TTACAGACGA AGAAGAAATC A3_3 TACCAATG.T GGACATTGAA TCAGTGCTTA TTACAGACGA AGAAGAAATC 42_52 AGACAACGCT GGAA AACGTGCTAA TGACCAGCGA GGAGGAGATC AAV1 TTCAAACA.0 TGCATTGGAC AATGTCATGA TTACAGACGA AGAGGAAATT AAV2 AACAAATG.T GGACATTGAA AAGGTCATGA TTACAGACGA AGAGGAAATC AAV3 AAGTAACG.0 AGAATTAGAT. AATGTAATGA TTACAGATGA AGAAGAGATT AAV8 AGACAATG.0 GGATTACAGC GATGTCATGC TCACCAGCGA GGAAGAAATC AAV9 CGATGGAG.T CGACTACAGC CAGGTGCTGA TTACAGATGA GGAAGAAATT AAV7 AAACTACATT GGAA AATGTGTTAA TGACAAATGA AGAAGAAATT 44_2 AGACAACG.T GGACTATAGC AGCGTTATGC TAACCAGTGA GGAAGAAATT

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Fig. 1AAAB

3951 4000 42 2 AAAACCACCA ATCCCGTGGC TACAGAAGAA TACGGTGTGG TCTCCAGCAA 42 8 AAAACCACCA ACCCAGTGGC CACAGAACAG TACGGCGTGG TGGCCGATAA 42 15 AAAACCACCA ACCCAGTGGC CACAGAACAG TACGGCGTGG TGGCCGATAA 42 5b AAAACCACCA ACCCAGTGGC CACAGAACAG TACGGCGTGG TGGCCGATAA 42-1b AAAACCACCA ACCCAGTGGC CACAGAACAG TACGGCGTGG TGGCCGATAA 42^13 AAAACCACCA ACCCAGTGGC CACAGAACAG TACGGCGTGG TGGCCGATAA 42 3a AAAACCACCA ACCCAGTGGC CACAGAACAG TACGGCGTGG TGGCCGATAA 2020201242

42- 4 AAAACCACCA ACCCAGTGGC CACAGAACAG TACGGCGTGG TGGCCGATAA 42_5a AAAACCACCA ACCCAGTGGC CACAGAACAG TACGGCGTGG TGGCCGATAA 42_10 AAAACCACCA ATCCCGTGGC TACAGAAGAA TACGGTGTGG TCTCCAGCAA 42 3b AAAACCACCA ATCCCGTGGC TACAGAACAG TACGGTGTGG TCTCCAGCAA 42 11 AAAACCACCA ATCCCGTGGC TACAGAAGAA TACGGTGTGG TCTCCAGCAA 42_ ^6b AAAACCACCA ATCCCGTGGC TACAGAAGAA TACGGTGTGG TCTCCAGCAA 4 -3- 1 AAAACTACTA ACCCAGTGGC TACAGAGCAG TATGGTGTGG TGGCAGACAA 43_5 AAAACTACTA ACCCAGTGGC TACAGAGCAG TATGGTGTGG TGGCAGACAA 43 12 AAAACTACTA ACCCAGTGGC TACAGAGCAG TATGGTGTGG T GGCAGACAA 4320 AAGGCTACCA ACCCCGTGGC CACAGAAGAA TATGGAGCAG TGGCCATCAA 43__21 AAGGCTACCA ACCCCGTGGC CACAGAAGAA TATGGAGCAG TGGCCATCAA 43_23 AAGGCTACCA ACCCCGTGGC CACAGAAGAA TATGGAGCAG TGGCCATCAA 43_25 AAGGCTACCA ACCCCGTGGC CACAGAAGAA TATGGAGCAG TGGCCATCAA 4 -4- 1 AAAACCACCA ACCCAGTGGC CACGGAACAG TACGGCGTGG TGGCCGATAA 44_5 AAAACCACCA ACCCAGTGGC CACAGAACAG TACGGCGTGG TGGCCGATAA 223_10 CGTCCTACCA ACCCGGTAGC TACCGAGGAA TACGGGATTG TAAGCAGCAA 223_2 CGTCCTACCA ACCCGGTAGC TACCGAGGAA TACGGGATTG TAAGCAGCAA 223_4 CGTCCTACCA ACCCGGTAGC TACCGAGGAA TACGGGATTG TAAGCAGCAA 223 5 CGTCCTACCA ACCCGGTAGC TACCGAGGAA TACGGGATTG TAAGCAGCAA 223=6 CGTCCTACCA ACCCGGTAGC TACCGAGGAA TACGGGATTG TAAGCAGCAA 2237 CGTCCTACCA ACCCGGTAGC TACCGAGGAA TACGGGATTG TAAGCAGCAA A3 4 AGAACAACTA ATCCTGTGGC TACAGAACAA TACGGACAGG TTGCCACCAA A3 5 AGAAC GAC TA ATCCTGTGGC TACAGAACAA TACGGACAGG TTGCCACCAA A3-7 AGAACAACTA ATCCTGTGGC TACAGAACAA TACGGACAGG TTGCCACCAA -- Ai 3 AGAACAACTA ATCCTGTGGC TACAGAACAA TACGGACAGG TTGCCACCAA 4212 AAAACCACCA ATCCCGTGGC TACAGAAGAA TACGGTGTGG TCTCCAGCAA AAV1 AAAACCACTA ACCCTGTGGC CAC C GAAAGA TT T GGGACCG TGGCAGT CAA AAV2 GGAACAACCA ATCCCGTGGC TACGGAGCAG TATGGTTCTG TAT C TACCAA AAV3 CGTACCACCA ATCCTGTGGC AACAGAGCAG TAT GGAAC TG TGGCAAATAA AAV8 AAAACCACTA ACCCTGTGGC TACAGAGGAA TACGGTATCG TGGCAGATAA AAV9 AAAGC CAC CA ACC CTGTAGC CACAGAGGAA TACGGAGCAG TGGCCATCAA AAV7 CGTCCTACTA ATCCTGTAGC CAC GGAAGAA TACGGGATAG TAAGCAGCAA 44_2 AAAACCACCA ACCCAGTGGC CACAGAACAG TACGGCGTGG TGGCCGATAA

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WO 03/042397 20 Feb 2020

Fig. lAAAC

4001 4050 42_2 CCTGCAATCG TCTACGGCCG GACCCCAGAC ACAGACTGTC AACAGCCAGG 428 CCTGCAACAG CAAAACGCCG CTCCTATTGT AGGGGCCGTC AACAGTCAAG 42_15 CCTGCAACAG CAAAACGCCG CTCCTATTGT AGGGGCCGTC AACAGTCAAG 42 5b CCTGCAACAG CAAAACGCCG CTCCTATTGT AGGGGCCGTC AACAGTCAAG 42 lb CCTGCAACAG CAAAACGCCG CTCCTATTGT AGGGGCCGTC AACAGTCAAG 42^_13 CCTGCAACAG CAAAACGCCG CTCCTATTGT AGGGGCCGTC AACAGTCAAG 42_3a CCTGCAACAG CAAAACGCCG CTCCTATTGT AGGGGCCGTC AACAGTCAAG 2020201242

CCTGCAACAG CAAAACGCCG CTCCTATTGT AGGGGCCGTC AACAGTCAAG 42_5a CCTGCAACAG CAAAACGCCG CTCCTATTGT AGGGGCCGTC AACAGTCAAG 42_10 CCTGCAATCG TCTACGGCCG GACCCCAGAC ACAGACTGTC AACAGCCAGG 42 3b CCTGCAATCG TCTACGGCCG GACCCCAGAC ACAGACTGTC AACAGCCAGG 42 11 CCTGCAATCG TCTACGGCCG GACCCCAGAC ACAGACTGTC AACAGCCAGG 42=4 CCTGCAATCG TCTACGGCCG GACCCCAGAC ACAGACTGTC AACAGCCAGG 43_1 CCTGCAGCAG ACCAACGGAG CTCCCATTGT GGGAACTGTC AACAGCCAGG 43_5 CCTGCAGCAG ACCAACGGAG CTCCCATTGT GGGAACTGTC AACAGCCAGG 43_12 CCTGCAGCAG ACCAACGGAG CTCCCATTGT GGGAACTGTC AACAGCCAGG 43 20 CAACCAGGCC GCCAATACGC AGGCGCAGAC CGGACTCGTG CACAACCAGG 43 ^21 CAACCAGGCC GCCAATACGC AGGCGCAGAC CGGACTCGTG CACAACCAGG 43-23 CAACCAGGCC GCCAATACGC AGGCGCAGAC CGGACTCGTG CACAACCAGG 43 25 CAACCAGGCC GCCAATACGC AGGCGCAGAC CGGACTCGTG CACAACCAGG 44 1 CCTGCAACAG CAAAACGCCG CTCCTATTGT AGGGGCCGTC AACAGTCAAG 44 5 CCTGCAACAG CAAAACGCCG CTCCTATTGT AGGGGCCGTC AACAGTCAAG 223 10 CTTGCAGGCG GCTAGCACCG CAGCCCAGAC ACAAGTTGTT AACAACCAGG 223 2 CTTGCAGGCG GCTAGCACCG CAGCCCAGAC ACAAGTTGTT AACAACCAGG 223 ^4 CTTGCAGGCG GCTAGCACCG CAGCCCAGAC ACAAGTTGTT AACAACCAGG 223-5 CTTGCAGGCG GCTAGCACCG CAGCCCAGAC ACAAGTTGTT AACAACCAGG 223_6 CTTGCAGGCG GCTAGCACCG CAGCCCAGAC ACAAGTTGTT AACAACCAGG 223 7 CTTGCAGGCG GCTAGCACCG CAGCCCAGAC ACAAGTTGTT AACAACCAGG A3 ^4 CCATCAGAGT CAGGACACCA CAGCTTCCTA TGGAAGTGTG GACAGCCAGG A35 CCGTCAGAGT CAGAACACCA CAGCTTCCTA TGGAAGTGTG GACAGCCAGG A3 7 CCATCAGAGT CAGAACACCA CAGCTTCCTA TGGAAGTGTG GACAGCCAGG A3_3 CCATCAGAGT CAGAACACCA CAGCTTCCTA TGGAAGTGTG GACAGCCAGG 42_12 CCTGCAATCG TCTACGGCCG GACCCCAGAC ACAGACTGTC AACAGCCAGG AAV1 TTTCCAGAGC AGCAGCACAG ACCCTGCGAC CGGAGATGTG CATGCTATGG AAV2 CCTCCAGAGA GGCAACAGAC AAGCAGCTAC CGCAGATGTC AACACACAAG AAV3 CTTGCAGAGC TCAAATACAG CTCCCACGAC TGGAACTGTC AATCATCAGG AAV8 CTTGCAGCAG CAAAACACGG CTCCTCAAAT TGGAACTGTC AACAGCCAGG AAV9 CAACCAGGCC GCTAACACGC AGGCGCAAAC TGGACTTGTG CATAACCAGG AAV7 CTTACAAGCG GCTAATACTG CAGCCCAGAC ACAAGTTGTC AACAACCAGG 44 2 CCTGCAACAG CAAAACGCCG CTCCTATTGT AGGGGCCGTC AACAGTCAAG

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Fig. 1AAAD

4051 4100 42_2 GGGCTCTGCC CGGCATGGTC TGGCAGAACC GGGACGTGTA CCTGCAGGGT 42_8 GAGCCTTACC TGGCATGGTC TGGCAGAACC GGGACGTGTA CCTGCAGGGT 42_15 GAGCCTTACC TGGCATGGTC TGGCAGAACC GGGACGTGTA CCTGCAGGGT 42 5b GAGCCTTACC TGGCATGGTC TGGCAGAACC GGGACGTGTA CCTGCAGGGT 42-1b GAGCCTTACC TGGCATGGTC TGGCAGAACC GGGACGTGTA CCT GCAGGGT 42^13 GAGCCTTACC TGGCATGGTC TGGCAGAACC GGGACGTGTA CCTGCAGGGT 42—_3a GAGCCTTACC TGGCATGGTC TGGCAGAACC GGGACGTGTA CCTGCAGGGT 2020201242

42_4 GAGCCTTACC TGGCATGGTC TGGCAGAACC GGGACGTGTA CCTGCAGGGT 42_5a GAGCCTTACC TGGCATGGCC TGGCAGAACC GGGACGTGTA CCTGCAGGGT 42 10 GGGCTCTGCC CGGCATGGTC TGGCAGAACC GGGACGTGTA CCTGCAGGGT 42^3b GGGCTCTGCC CGGCATGGTC TGGCAGAACC GGGACGTGTA CCTGCAGGGT 42 11 GGGCTCTGCC CGGCATGGTC TGGCAGAACC GGGACGTGTA CCTGCAGGGT 42-6b GGGCTCTGCC CGGCATGGTC TGGCAGAACC GGGACGTGTA CCT GCAGGGT 43_1 GGGCCTTACC TGGTATGGTC TGGCAAAACC GGGACGTGTA CCT GCAGGGC 43_5 GGGCCTTACC TGGTATGGTC TGGCAAAACC GGGACGTGTA CCTGCAGGGC 43 T2 GGGCCTTACC TGGTATGGTC TGGCAAAACC GGGACGTGTA CCTGCAGGGC 43W20 GGGTGATTCC CGGCATGGTG TGGCAGAATA GAGACGTGTA CCTGCAGGGT 43_21 GGGTGATTCC CGGCATGGTG TGGCAGAATA GAGACGTGTA CCTGCAGGGT 43_23 GGGTGATTCC CGGCATGGTG TGGCAGAATA GAGACGTGTA CCTGCAGGGT 43_25 GGGTGATTCC CGGCATGGTG TGGCAGAATA GAGACGTGTA CCTGCAGGGT 44 1 GAGCCTTACC TGGCATGGTC TGGCAGAACC GGGACGTGTA CCTGCAGGGT 44 5 GAGCCTTACC TGGCATGGTC TGGCAGAACC GGGACGTGTA CCTGCAGGGT 223 JO GAGCCTTACC TGGCATGGTC TGGCAGAACC GGGACGTGTA CCTGCAGGGT 223 2 GAGCCTTACC TGGCATGGTC TGGCAGAACC GGGACGTGTA CCTGCAAGGT 223 4 GAGCCTTACC TGGCATGGTC TGGCAGAACC GGGACGTGTA CCTGCAAGGT 223 5 GAGCCTTACC TGGCATGGTC TGGCAGAACC GGGACGTGTA CCTGCAAGGT 223_6 GAGCCTTACC TGGCATGGTC TGGCAGAACC GGGACGTGTA CCTGCAAGGT 223 7 GAGCCTTACC TGGCATGGTC TGGCAGAACC GGGACGTGTA CCTGCAAGGT A3_^4 GAATCTTACC TGGAATGGTG TGGCAGGACC GCGATGTCTA TCTTCAAGGT A3 5 GAATCTTACC TGGAATGGTG TGGCAGGACC GCGATGTCTA TCTTCAAGGT A3_7 GAATCTTACC TGGAATGGTG TGGCAGGACC GCGATGTCTA TCTTCAAGGT A33 GAATCTTACC TGGAATGGTG TGGCAGGACC GCGATGTCTA TCTTCAAGGT 42_12 GGGCTCTGCC CGGCATGGTC TGGCAGAACC GGGACGTGTA CCTGCAGGGT AAV1 GAGCATTACC TGGCATGGTG TGGCAAGATA GAGACGTGTA CCT GCAGGGT GCGTTCTTCC. AGGCATGGTC TGGCAGGACA GAGATGTGTA CCT TCAGGGG AAV3 GGGCCTTACC TGGCATGGTG TGGCAAGATC GTGACGTGTA CCTTCAAGGA AAV8 GGGCCTTACC CGGTATGGTC TGGCAGAACC GGGACGTGTA CCTGCAGGGT AAV9 GAGTTATT CC TGGTATGGTC TGGCAGAACC GGGACGTGTA OCT GCAGGGC AAV7 GAGCCTTACC TGGCATGGTC TGGCAGAACC GGGACGTGTA OCT GCAGGGT 44 2 GAGCCTTACC TGGCATGGTC TGGCAGAACC GGGACGTGTA CCTGCAGGGT

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Fig. 1AAAE

4101 4150 42 2 CCC.ATCTGG GCCAAAATTC CTCACACGGA CGGCAACTTT CACCCGTCTC 42 8 CCT.ATCTGG GCCAAGATTC CTCACACGGA CGGCAACTTT CATCCTTCGC 42_15 CCT.ATCTGG GCCAAGATTC CTCACACGGA CGGCAACTTT CATCCTTCGC 42_5b CCT.ATCTGG GCCAAGATTC CTCACACGGA CGGCAACTTT CATCCTTCGC 42-1b CCT.ATCTGG GCCAAGATTC CTCACACGGA CGGCAACTTT CATCCTTCGC 42 13 CCT.ATCTGG GCCAAGATTC CTCACACGGA CGGCAACTTT CATCCTTCGC 42 3a CCT.ATCTGG GCCAAGATTC CTCACACGGA CGGCAACTTT CATCCTTCGC 2020201242

47 4 CCT.ATCTGG GCCAAGATTC CTCACACGGA CGGCAACTTT CATCCTTCGC 42_5a CCT.ATCTGG GCCAAGATTC CTCACACGGA CGGCAACTTT CATCCTTCGC 42 10 CCC.ATCTGG GCCAAAATTC CTCACACGGA CGGCAACTTT CACCCGTCTC 42 3b CCC.ATCTGG GCCAAAATTC CTCACACGGA CGGCAACTTT CACCCGTCTC 42_11 CCC.ATCTGG GCCAAAATTC CTCACACGGA CGGCAACTTT CACCCGTCTC 42 6b CCC.ATCTGG GCCAAAATTC CTCACACGGA CGGCAACTTT CACCCGTCTC 43_1 CCC.ATCTGG GCCAAAATTC CTCACACGGA CGGCAACTTT CATCCTTCGC 435 CCC.ATCTGG GCCAAAATTC CTCACACGGA CGGCAACTTT CATCCTTCGC 43_12 CCC.ATCTGG GCCAAAATTC CTCACACGGA CGGCAACTTT CATCCTTCGC 43_20 CCC.ATCTGG GCCAAAATTC CTCACACGGA CGGCAACTTT CACCCGTCTC 43 21 CCC.ATCTGG GCCAAAATTC CTCACACGGA CGGCAACTTT CACCCGTCTC 4323 CCC.ATCTGG GCCAAAATTC CTCACACGGA CGGCAACTTT CACCCGTCTC 43_25 CCC.ATCTGG GCCAAAATTC CTCACACGGA CGGCAACTTT CACCCGTCTC 44 1 CCT.ATCTGG GCCAAGATTC CTCACACGGA CGGAAACTTT CATCCCTCGC 44W5 CCT.ATCTGG GCCAAGATTC CTCACACGGA CGGAAACTTT CATCCCTCGC 223_10 CCC.ATTTGG GCCAAGATTC CTCACACGGA CGGCAACTTT CACCCGTCTC 223_2 CCC.ATTTGG GCCAAGATTC CTCACACGGA CGGCAACTTT CACCCGTCTC 223_4 CCC.ATTTGG GCCAAGATTC CTCACACGGA CGGCAACTTT CACCCGTCTC 223_5 CCC.ATTTGG GCCAAGATTC CTCACACGGA CGGCAACTTT CACCCGTCTC 223 6 CCC.ATTTGG GCCAAGATTC CTCACACGGA CGGCAACTTT CACCCGTCTC 2237 CCC.ATTTGG GCCAAGATTC CTCACACGGA CGGCAACTTT CACCCGTCTC A3:4 CCC.ATTTGG GCCAAAACTC CTCACACGGA CGGACACTTT CATCCTTCTC A3_5 CCC.ATTTGG GCCAAAACTC CTCACACGGA CGGACACTTT CATCCTTCTC A3 7 CCC.ATTTGG GCCAAAACTC CTCACACGGA CGGACACTTT CATCCTTCTC A3 3 CCC.ATTTGG GCCAAAACTC CTCACACGGA CGGACACTTT CATCCTTCTC 42_12 CCC.ATCTGG GCCAAAATTC CTCACACGGA CGGCAACTTT CACCCGTCTC AAV1 CCC.ATTTGG GCCAAAATTC CTCACACAGA TGGACACTTT CACCCGTCTC AAV2 CCC.ATCTGG GCAAAGATTC CACACACGGA CGGACATTTT CACCCCTCTC AAV3 CCT.ATCTGG GCAAAGATTC CTCACACGGA TGGACACTTT CATCCTTCTC AAV8 CCC.ATCTGG GCCAAGATTC CTCACACGGA CGGCAACTTC CACCCGTCTC AAV9 CCCTATTTGG GCTAAAATAC CTCACACAGA TGGCAACTTT CACCCGTCTC AAV7 CCC.ATCTGG GCCAAGATTC CTCACACGGA TGGCAACTTT CACCCGTCTC 44 2 CCT.ATCTGG GCCAAGATTC CTCACACGGA CGGAAACTTT CATCCCTCGC

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Fig. lAAAF

4151 4200 42_2 CCCTGATGGG CGGATTTGGA CTCAAACACC CGCCTCCTCA AATTCTCATC 4 2 8 CGCTGATGGG AGGCTTTGGA CTGAAACACC CGCCTCCTCA GATCCTGATT 42_15 CGCTGATGGG AGGCTTTGGA CTGAAACACC CGCCTCCTCA GATCCTGATT 42 5b CGCTGATGGG AGGCTTTGGA CTGAAACACC CGCCTCCTCA GATCCTGATT 42 lb CGCTGATGGG AGGCTTTGGA CTGAAACACC CGCCTCCTCA GATCCTGATT 4213 CGCTGATGGG AGGCTTTGGA CTGAAACACC CGCCTCCTCA GATCCTGATT 42-3a CGCTGATGGG AGGCTTTGGA CTGAAACACC CGCCTCCTCA GATCCTGATT 2020201242

4 CGCTGATGGG AGGCTTTGGA CTGAAACACC CGCCTCCTCA GATCCTGATT 42 CGCTGATGGG AGGCTTTGGA CTGAAACACC CGCCTCCTCA GATCCTGATT 42_10 CCCTGATGGG CGGATTTGGA CTCAAACACC CGCCTCCTCA AATTCTCATC 4 2 3b CCCTGATGGG CGGATTTGGA CTCAAACACC CGCCTCCTCA AATTCTCATC 4 2 11 CCCTGATGGG CGGATTTGGA CTCAAACACC CGCCTCCTCA AATTCTCATC 42_6b 6b CCCTGATGGA CGGATTTGGA CTCAAACACC CGCCTCCTCA AATTCTCATC 43- 1 CGCTGATGGG AGGCTTTGGA CTGAAACACC CGCCTCCTCA GATCCTGGTG 4 3 5 CGCTGATGGG AGGCTTTGGA CT GAAACACC CGCCTCCTCA GATCCTGGTG 4 3 T2 CGCTGATGGG AGGCTTTGGA CTGAAACACC CGCCTCCTCA GATCCTGGTG 43_20 CCCTGATGGG CGGCTTTGGA CTGAAGCACC CGCCTCCTCA AATTCTCATC 4 3 21 CCCTGATGGG CGGCTTTGGA CTGAAGCACC CGCCTCCTCA AATTCTCATC 4 3 23 CCCTGATGGG CGGCTTTGGA CTGAAGCACC CGCCTCCTCA AATTCTCATC 4 3 25 CCCTGATGGG CGGCTTTGGA CTGAAGCACC CGCCTCCTCA AATTCTCATC 441_1 CGCTGATGGG AGGCTTTGGA CTGAAACACC CGCCTCCTCA GATCCTGATT 445 CGCTGATGGG AGGCTTTGGA CTGAAACACC CGCCTCCTCA GATCCTGATT I 22 3 0 CTCTAATGGG TGGCTTTGGA CTGAAACACC CGCCTCCCCA GATCCTGATC 223 2 CTCTAATGGG TGGCTTTGGA CTGAAACACC CGCCTCCCCA GATCCTGATC 22 3 4 CTCTAATGGG TGGCTTTGGA CTGAAACACC CGCCTCCCCA GATCCTGATC 2235 CTCTAATGGG TGGCTTTGGA CTGAAACACC CGCCTCCCCA GATCCTGATC 2 2 3 6 CTCTAATGGG TGGCTTTGGA CTGAAACACC CGCCTCCCCA GATCCTGATC 2237 CTCTAATGGG TGGCTTTGGA CTGAAACACC CGCCTCCCCA GATCCTGATC A3 4 CGCTCATGGG AGGCTTTGGA CTGAAACACC CTCCTCCCCA GATCCTGATC A3 5 CGCTCATGGG AGGCTTTGGA CTGAAACACC CTCCTCCCCA GATCCTGATC A3_7 CGCTCATGGG AGGCTTTGGA CTGAAACACC CTCCTCCCCA GAT CCTGATC A3_3 CGCTCATGGG AGGCTTTGGA CTGAAACACC CTCCTCCCCA GATCCTGATC 42_12 CCCTGATGGG CGGATTTGGA CTCAAACACC CGCCTCCTCA AATTCTCATC AHV1 CTCTTATGGG CGGCTTTGGA CTCAAGAACC CGCCTCCTCA GAT CCTCAT C AAV2 CCCTCATGGG TGGATTCGGA CTTAAACACC CTCCTCCACA GATTCTCATC AAV3 CTCTGATGGG AGGCTTTGGA CTGAAACATC CGCCTCCTCA AATCATGATC AAVB CGCTGATGGG CGGCTTTGGC CTGAAACATC CTCCGCCTCA GATCCTGATC AAV9 CTCTGATGGG TGGATTTGGA CTGAAACACC CACCTCCACA GAT TC TAAT T AAV7 CTTTGATGGG CGGCTTTGGA CTGAAACATC CGCCTCCTCA GATCCTGATC 44 2 CGCTGATGGG AGGCTTTGGA CTGAAACACC CGCCTCCTCA GATCCTGATT

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Fig. lAAAG

4201 4250 42_2 AAAAACACCC CGGTACCTGC TAATCCTCCA GAGGTGTTTA CT CC TGCCAA 42_8 AAGAATACAC CTGTTCCCGC GGATCCTCCA ACTACCTTCA GTCAAGCCAA 42_15 AAGAATACAC CTGTTCCCGC GGATCCTCCA ACTACCTTCA Gfi CAAGCCAA 42_5b AAGAATACAC CTGTTCCCGC GGATCCTCCA ACTACCTTCA GTCAAGCCAA 42 lb AAGAATACAC CTGTTCCCGC GGATCCTCCA ACTACCTTCA GTCAAGCCAA 42 13 AAGAATACAC CTGTTCCCGC GGATCCTCCA ACTACCTTCA GTCAAGCCAA 4 2 3a AAGAATACAC CTGTTCCCGC GGATCCTCCA ACTACCTTCA GTCAAGCCAA 2020201242

4L4 AAGAATACAC CTGTTCCCGC GGATCCTCCA ACTACCTTCA GTCAAGCCAA 42_5a AAGAATACAC CTGTTCCCGC GGATCCTCCA ACTACCTTCA GTCAAGCCAA 42_10 AAAAACACCC CGGTACCTGC TAATCCTCCA GAGGTGTTTA CTCCTGCCAA 4 2 3b AAAAACACCC CGGTACCTGC TAATCCTCCA GAGGTGTTTA CTCCTGCCAA 42 11 AAAAACACCC CGGTACCTGC TAATCCTCCA GAGGT GTTTA CTCCTGCCAA 42_6b AAAAACACCC CGGTACCTGC TAATCCTCCA GAGGTGTTTA CTCCTGCCAA 431 AAAAACACTC CTGTTCCTGC GGATCCTCCG ACCACCTTCA GCCAGGCCAA 435 AAAAACACTC CTGTTCCTGC GGATCCTCCG ACCACCTTCA GCCAGGCCAA 43 1.2 AAAAACACTC CTGTTCCTGC GGATCCTCCG ACCACCTTCA GCCAGGCCAA 4320 _ AAGAACACAC CGGTTCCAGC GGACCCGCCG CTTACCTTCA ACCAGGCCAA 4 3 21 AAGAACACAC CGGTTCCAGC GGACCCGCCG CTTACCTTCA ACCAGGCCAA 4323 AAGAACACAC CGGTTCCAGC GGACCCGCCG CTTACCTTCA ACCAGGCCAA 4325 AAGAACACAC CGGTTCCAGC GGACCCGCCG CTTACCTTCA ACCAGGCCAA 1 AAGAATACAC CTGTTCCCGC GGATCCTCCA ACTACCTTCA GTCAAGCTAA 44_5 AAGAATACAC CTGTTCCCGC GGATCCTCCA ACTACCTTCA GTCAAGCTAA 2 2 3_10 AAAAACACAC CGGTACCTGC TAATCCTCCA GAAGTGTTTA CTCCTGCCAA 2 232 AAAAACACCC CGGTACCTGC TAATCCTCCA GAAGTGTTTA CTCCT GCCAA 2 2 3__4 AAAAACACAC CGGTACCTGC TAATCCTCCA GAAGTGTTTA CTCCTGCCAA 223 5 AAAAACACAC CGGTACCTGC TAATCCTCCA GAAGTGTTTA CTCCTGCCAA 223 6 AAAAACACAC CGGTACCTGC TAATCCTCCA GAAGTGTTTA CTCCTGCCAA 22- 37 AAAAACACAC CGGTACCTGC TAATCCTCCA GAAGTGTTTA CTCCTGCCAA A3 4 AAAAACACAC CTGTGCCAGC GAATCCCGCG ACCACTTTCA CTCCTGGAAA A3_5 AAAAACACAC CTGTGCCAGC GAATCCCGCG ACCACTTTCA CTCCTGGAAA A37 AAAAACACAC CTGTGCCAGC GAATCCCGCG ACCACTTTCA CTCCTGGAAA A3_3 AAAAACACAC CTGTGCCAGC GAATCCCGCG ACCACTTTCA CTCCTGGAAA 42_12 A A AAV1 AAAAACACCC CTGTTCCTGC GAATCCTCCG GCGGAGTTTT CAGCTACAAA AAV2 AAAAACACCC CGGTACCTGC GAATCCTTCG ACCACCTTCA GTGCGGCAAA AAV3 AAAAATACTC CGGTACCGGC AAATCC TCCG ACCACTTTCA GCCCGGCCAA AAV8 AAGAACACGC CGGTACCTGC GGATCCTCCG ACCACCTTCA ACCAGTCAAA AAV9 AAAAATACAC CAGTGCCGGC AGATCCTCCT CTTACCTTCA AT CAAGCCAA AAV7 AAGAACACTC CCGTTCCCGC TAATCCTCCG GAGGTGTTTA CTCCTGCCAA 44 2 AAGAATACAC CTGTTCCCGC GGATCCTCCA ACTACCTTCA GTCAAGCTAA

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Fig. 1AAAH

4251 4300 42_2 GTTTGCCTCA TTTATCACGC AGTACAGCAC CGGCCA. GGT CAGCGTGGAG 42 8 GCTGGCGTCG TTCATCACGC AGTACAGCAC CGGACA GGT CAGCGTGGAA 42 15 GCTGGCGTCG TTCATCACGC AGTACAGCAC CGGACA. GGT CAGCGTGGAA 42 5b GCTGGCGTCG TTCATCACGC AGTACAGCAC CGGACA. GGT CAGCGTGGAA 42:1b GCTGGCGTCG TTCATCACGC AGTACAGCAC CGGACA GGT CAGCGTGGAA 4213 GCTGGCGTCG TTCATCACGC AGTACAGCAC CGGACA. GGT CAGCGTGGAA 42_3a GCTGGCGTCG TTCATCACGC AGTACAGCAC CGGACA. GGT CAGCGTGGAA 2020201242

42 4 GCCGGCGTCG TTCATCACGC AGTACAGCAC CGGACA. GGT CAGCGTGGAA 42_5a GCTGGCGTCG TTCATCACGC AGTACAGCAC CGGACA. GGT CAGCGTGGAA 42_10 GTTTGCCTCA TTTATCACGC AGTACAGCAC CGGCCA. GGT CAGCGTGGAG 42 3b GTTTGCCTCA TTTATCACGC AGTACAGCAC CGGCCA . GGT CAGCGTGGAG 42 11 GTTTGCCTCA TTTATCACGC AGTACAGCAC CGGCCA. GGT CAGCGTGGAG 42 6b GTTTGCCTCA TTTATCACGC AGTACAGCAC CGGCCA. GGT CAGCGTGGAG 1 GCTGGCTTCT TTTATCACGC AGTACAGCAC CGGACA GGT CAGCGTGGAA 43_5 GCTGGCT TOT TTTATCACGC AGTACAGCAC CGGACA. GGT CAGCGTGGAA 43 12 GCTGGCTTCT TTTATCACGC AGTACAGCAC CGGACA. GGT CAGCGTGGAA 43_20 GCTGAACTCT TTCATCACGC AGTACAGCAC CGGACA. GGT CAGCGTGGAA 43 21 GCTGAACTCT TTCATCACGC AGTACAGCAC CGGACA. GGT CAGCGTGGAA 4323 GCTGAACTCT TTCATCACGC AGTACAGCAC CGGACA. GGT CAGCGTGGAA 43 25 GOT GAACTCT TTCATCACGC AGTACAGCAC CGGACA. GGT CAGCGTGGAA 4T 1 GOT GGCGTCG TTCATCACGC AGTACAGCAC CGGACA. GGT CAGCGTGGAA 445 GCTGGCGTCG TTCATCACGC AGTACAGCAC CGGACA GGT CAGCGTGGAA 223_10 GTTTGCT TCC TTCATCACGC AGTACAGCAC CGGGCA.AGT CAGCGTTGAG 223_2 GTTTGCTTCC TTCATCACGC AGTACAGCAC CGGGCA .AGT CAGCGTTGAG 223 4 GTTTGCTTCC TTCATCACGC AGTACAGCAC CGGGCA.AGT CAGCGTTGAG 223_5 GTTTGCTTCC TTCATCACGC AGTACAGCAC CGGGCA.AGT CAGCGTTGAG 223_6 GCTT GCT T CC TTCATCACGC AGTACAGCAC CGGGCA .AGT CAGCGTTGAG 2237 GAT TGCT T CC TTCATCACGC AGTACAGCAC CGGGCA.AGT CAGCGTTGAG A3 4 GTTTGCTTCG TTCATTACCC AGTATTCCAC CGGACA. GGT CAGCGTGGAA A3 5 GTTTGCTTCG TTCATTACCC AGTATTCCAC CGGACA. GGT CAGCGTGGAA A3-7 GTTTGCTTCG TTCATTACCC AGTATTCCAC CGGACA G GT CAGCGTGGAA A3 3 GTTTGCTTCG TTCATTACCC AGTATTCCAC CGGACA. GGT CAGCGTGGAA 42 12 AAV1 GTTTGCTTCA TTCATCACCC AATACTCCAC AGGACA.AGT GAGTGTGGAA AAV2 GTTTGCTTCC TTCATCACAC AGTACTCCAC GGGACACGGT CAGCGTGGAG AAV3 GTTTGCTTCA TTTATCACTC AGTACTCCAC TGGACA.GGT CAGCGTGGAA AAV8 GCTGAACTCT TTCATCACGC AATACAGCAC CGGACA.GGT CAGCGTGGAA AAV9 GCTGAACTCT TTCATCACGC AGTACAGCAC GGGACA.AGT CAGCGTGGAA AAV7 GTTTGCTTCG TTCATCACAC AGTACAGCAC CGGACA.AGT CAGCGTGGAA 44_2 GCTGGCGTCG TTCATCACGC AGTACAGCAC CGGACA.GGT CAGCGTGGAA

WO 03/042397 PCT/002/33629 20 Feb 2020

Fig. lAAAI

4301 4350 422 ATCGAGTGGG AACTGCAGAA AGAAAACAGC AAACGCTGGA ATCCAGAGAT 428 ATTGAATGGG AGCTGCAGAA AGAGAACAGC AAGCGCTGGA ACCCAGAGAT 4 2 T. 5 ATTGAATGGG AGCTGCAGAA AGAGAACAGC AAGCGCTGGA ACCCAGAGAT 42 5b ATTGAATGGG AGCTGCAGAA AGAGAACAGC AAGCGCTGGA ACCCAGAGAT 42—lb ATTGAATGGG AGCTGCAGAA AGAGAACAGC AAGCGCTGGA ACCCAGAGAT 42 - 13 AT T GAATGGG AGCTGCAGAA AGAGAACAGC AAGCGCTGGA ACCCAGAGAT 42=3a ATTGAATGGG AGCTGCAGAA AGAGAACAGC AAGCGCTGGA ACCCAGAGAT 2020201242

424 ATTGAAT GGG AGCT GCAGAA AGAGAACAGC AAGCGCTGGA ACCCAGAGAT 4 2 3a ATTGAATGGG AGCTGCAGAA AGAGAACAGC AAGCGCTGGA ACCCAGAGAT 4210 ATCGAGTGGG AACTGCAGAA AGAAAACAGC AAACGCTGGA ATCCAGAGAT 42 3b ATCGAGTGGG AACTGCAGAA AGAAAACAGC AAACGCTGGA ATCCAGAGAT 42-11 11 ATCGAGTGGG AACTGCAGAA AGAGAACAGC AAACGCTGGA AT CCAGAGAT 42_ ATCGAGTGGG AACTGCAGAA AGAAAACAGC AAACGCTGGA ATCCAGAGAT 431 ATCGAATGGG AGCTGCAGAA AGAAAACAGC AAGCGCTGGA ACCCAGAGAT 435 ATCGAATGGG AGCTGCAGAA AGAAAACAGC AAGCGCTGGA ACC CAGAGAT 43 T.2 ATCGAATGGG AGCTGCAGAA AGAAAACAGC AAGCGCTGGA ACCCAGAGAT 432 20 ATCGAGTGGG AGCTGCAGAA AGAAAACAGC AAACGCTGGA ATCCAGAGAT 4 3-2 1 ATCGAGT GGG AGCTGCAGAA AGAAAACAGC AAACGCTGGA ATCCAGAGAT 4323 ATCGAGTGGG AGCTGCAGAA AGAAAACAGC AAACGCTGGA ATCCAGAGAT 4325 ATCGAGTGGG AGCTGCAGAA AGAAAACAGC AAACGCTGGA ATCCAGAGAT 471 4 ATTGAATGGG AGCTGCAGAA AGAAAACAGC AAACGCTGGA ACCCAGAGAT 44_5 ATTGAATGGG AGCTGCAGAA AGAAAACAGC AAACGCTGGA ACCCAGAGAT 2 2 3_1 0 ATCGAGTGGG AGCTGCAGAA AGAGAACAGC AAGCGCTGGA ACCCAGAGAT 2232 ATCGAGTGGG AGCTGCAGAA AGAGAACAGC AAGCGCTGGA ACCCAGAGAT 2 23 4 ATCGAATGGG AGCTGCAGAA AGAGAACAGC AAGCGCTGGA ACCCAGAGAT 2235 ATCGAAT GGG AGCTGCAGAA AGAGAACAGC AAGCGCTGGA ACCCAGAGAT 223 6 ATCGAGTGGG AGCTGCAGAA AGAGAACAGC AAGCGCTGGA ACCCAGAGAT 2237 ATCGAGTGGG AGCTGCAGAA AGAGAACAGC AAGCGCTGGA ACCCAGAGAT A3-4 ATAGAGTGGG AGCTGCAGAA AGAAAACAGC AAACGCTGGA ACC CAGAAAT A3 3 ATAGAGTGGG AGCTGCAGAA AGAAAACAGC AAACGCTGGA AC C C GGAAAT A3-7 ATAGAGTGGG AGCTGCAGAA AGAAAACAGC AAACGCTGGA ACCCAGAGAT A3 3 ATAGAGTGGG AGCT GCAGAA AGAAAACAGC AAACGCTGGA ACCCAGAGAT 42_12 AAV1 AT T GAAT GGG AGCTGCAGAA AGAAAACAGC AAGCGCTGGA ATCCCGAAGT AAV2 ATCGAGTGGG AGCTGCAGAA GGAAAACAGC AAACGCTGGA ATCCCGAAAT AAV3 ATTGAGTGGG AGCTACAGAA AGAAAACAGC AAACGTTGGA ATCCAGAGAT AAV 8 AT T GAAT G GG AGCTGCAGAA GGAAAACAGC AAGCGCTGGA AC C C CGAGAT AAV9 ATCGAGTGGG AGCTGCAGAA AGAAAACAGC AAGCGCTGGA ATCCAGAGAT AAV 7 ATCGAGTGGG AGCTGCAGAA GGAAAACAGC AAGCGCTGGA ACC CGGAGAT 442 ATTGAATGGG AGCTGCAGAA AGAAAACAGC AAACGCTGGA ACCCAGAGAT

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Fig. 1AAAJ

4351 4400 42 2 TCAGTACACC TCAAATTATG CCAAGTCTAA TAAT . GTGGA ATTTGCTGTC 42 8 TCAGTATACT TCCAACTACT ACAAATCTAC AAAT . GT GGA CTTTGCTGTC 42_15 TCAGTATACT TCCAACTACT ACAAATCTAC AAAT . GTGGA CTTTGCTGTC 42_5b TCAGTATACT TCCAACTACT ACAAATCTAC AAAT . GT GGA •CTTTGCTGTC 42 lb TCAGTATACT TCCAACTACT ACAAATCTAC AAAT GTGGA CTTTGCTGTC 42-13 TCAGTATACT TCCAACTACT ACAAATCTAC AAAT GTGGA CTTTGCTGTC 42 3a TCAGTATACT TCCAACTACT ACAAATCTAC AAAT . GTGGA CTTTGCTGTC 2020201242

4ff 4 TCAGTATACT TCCAACTACT ACAAATCTAC AAAT . GTGGA CTTTGCTGTC 425a TCAGTATACT TCCAACTACT ACAAATCTAC AAAT GTGGA CTTTGCTGTC 42 10 TCAGTACACC TCAAATTATG CCAAGTCTAA TAAT . GTGGA ATTTGCTGTC 42 3b TCAGTACACC TCAAATTATG CCAAGTCTAA TAATCGTGGA ATTTGCTGTC 42:11 TCAGTACACC TCAAATTATG CCAAGTCTAA TAAT . GTGGA ATTTGCTGTC 42_6b TCAGTACACC TCAAATTATG CCAAGTCTAA TAATCGTGGA ATTTGCTGTC 43_1 TCAGTATACT TCCAACTACT ACAAATCTAC AAAT . GTGGA CTTTGCTGTC 43_5 TCAGTATACT TCCAACTACT ACAAATCTAC AAAT . GTGGA CTTTGCTGTC 43_12 TCAGTATACT TCCAACTACT ACAAATCTAC AAAT . GTGGA CTTTGCTGTC 43_20 TCAATACACT TCCAACTACT ACAAATCTAC AAAT . GTGGA CTTTGCTGTC 43 21 TCAATACACT TCCAACTACT ACAAATCTAC AAAT . GTGGA CTTTGCTGTC 43:23 TCAATACACT TCCAACTACT ACAAATCTAC AAAT . GTGGA CTTTGCTGTC 43_25 TCAATACACT TCCAACTACT ACAAATCTAC AAAT GTGGA CTTTGCTGTC 44_1 TCAATACACT TCCAACTACT ACAAATCTAC AAAT . GT GGA CTTCGCTGTT 44_5 TCAATACACT TCCAACTACT ACAAATCTAC AAAT . GTGGA CTTTGCTGTT 223_10 TCAGTACACC TCCAACTTTG ACAAACAGAC TGGA . GT GGA CTTTGCTGTT 223_2 TCAGTACACC TCCAACTTTG ACAAACAGAC TGGA. GTGGA CTTTGCTGTT 223 4 TCAGTACACC TCCAACTTTG ACAAACAGAC TGGA GTGGA CTTTGCTGTT 223 5 TCAGTACACC TCCAACTTTG ACAAACAGAC TGGA . GTGGA CTTTGCTGTT 223 6 TCAGTACACC TCCAACTTTG ACAAACAGAC TGGA. GTGGA CTTTGCTGTT 223:7 TCAGTACACC TCCAACTT TG ACAAACAGAC TGGA GTGGA OTTTGCTGTT A3_4 TCAGTACACC TCCAACTACA ACAAGTCGGT GAAT . GT GGA GTTTACCGTG A3 5 TCAGTACACC TCCAACTACA ACAAGTCGGT GAAT GTGGA GTTTACCGTG A3 7 TCAGTACACC TCCAACTACA ACAAGTCGGT GAAT GTGGA GTTTACCGTG A3 3 TCAGTACACC TCCAACTACA ACAAGTCGGT GAAT GTGGA GTTTACCGTG 42_12 . . . GTATACT TCCAACTACT ACAAATCTAC AAAT . GTGGA CTTTGCTGTC AAV1 GCAGTACACA TCCAATTATG CAAAAT CT GC CAAC . GTTGA TTTTACTGTG AAV2 TCAGTACACT TCCAACTACA ACAAGTCT GT TAATCGTGGA CTT.ACCGTG AAV3 TCAGTACACT TCCAACTACA ACAAGTC T GT TAAT . GT GGA CTTTACTGTA AAV8 CCAGTACACC TCCAACTACT ACAAATCTAC AAGT. GTGGA CTTTGCTGTT AAV 9 CCAGTATAcT TCAAACTACT ACAAATCTAC AAAT . GTGGA CTTTGCTGTC AAV7 TCAGTACACC TCCAACTTTG ACAAACAGAC TGGT GTGGA CTTTGCCGTT 44 2 TCAATACACT TCCAACTACT ACAAATCTAC AAAT . GTG GA CTTTGCTGTT

88/105

Fig. lAAAK

4401 4450 42_2 AACAACGAAG GGGTTTATAC TGAGCCTCGC CCCATTGGCA CCCGTTACCT 42_8 AATACTGAGG GTACTTATTC AGAGCCTCGC CCCATTGGCA CCCGTTACCT 42_15 AATACTGAGG GTACTTATTC AGAGCCTCGC CCCATTGGCA CCCGTTACCT 42 5b AATACTGAGG GTACTTATTC AGAGCCTCGC CCCATTGGCA CCCGTTACCT 42-1b AATACTGAGG GTACTTATTC AGAGCCTCGC CCCATTGGCA CCCGTTACCT 4213 AATACTGAGG GTACTTATTC AGAGCCTCGC CCCATTGGCA CCCGTTACCT 42:3a AATACTGAGG GTACTTATTC AGAGCCTCGC CCCATTGGCA CCCGTTACCT 2020201242

424 AATACTGAGG GTACTTATTC AGAGCCTCGC CCCATTGGCA CCCGTTACCT 42 5a AATACTGAGG GTACTTATTC AGAGCCTCGC CCCATTGGCA CCCGTTACCT 4 2 10 AACAACGAAG GGGTTTATAC TGAGCCTCGC CCCATTGGCA CCCGTTACCT 4 2 3b AACAACGAAG GGGTTTATAC TGAGCCTCGC CCCATTGGCA CCCGTTACCT 4 2 11 AACAACGAAG GGGTTTATAC TGAGCCTCGC CCCATTGGCA CCCGTTACCT 42-6b AACAACGAAG GGGTTTATAC TGAGCCTCGC CCCATTGGCA CCCGTTACCT 43_1 AATACTGAGG GTACTTATTC AGAGCCTCGC CCCATTGGCA CTCGTTATCT 43_5 AATACCGAGG GTACTTATTC AGAGCCTCGC CCCATTGGCA CTCGTTATCT 43_12 AATACTGAGG GTACTTATTC AGAGCCTCGC CCCATTGGCA CTCGTTATCT 43 20 AACACGGAAG GAGTTTATAG CGAGCCTCGC CCCATTGGCA CCCGTTACCT 4321 AACACGGAAG GAGTTTATAG CGAGCCTCGC CCCATTGGCA CCCGTTACCT 4 3 23 AACACGGAAG GAGTTTATAG CGAGCCTCGC CCCATTGGCA CCCGTTACCT 4 3 25 AACACGGAGG GGGTTTATAG CGAGCCTCGC CCCATTGGCA CCCGTTACCT 471_1 AACACAGATG GCACTTATTC TGAGCCTCGC CCCATTGGCA CCCGTTACCT 44_5 AACACAGATG GCACTTATTC TGAGCCTCGC CCCATTGGCA CCCGTTACCT 223_10 GACAGCCAGG GTGTTTACTC TGAGCCT 223_2 GACAGCCAGG GTGTTTACTC TGAGCCT 223 4 GACAGCCAGG GTGTTTACTC TGAGCCT 22355 GACAGCCAGG GTGTTTACTC TGAGCCT 223=6 GACAGCCAGG GTGTTTACTC TGAGCCT 22387 GACAGCCAGG GTGTTTACTC TGAGCCT A3 4 GACGCAAACG GTGTTTATTC TGAACCCCGC CCTATTGGCA CTCGTTACCT A3 5 GACGCAAACG GTGTTTATTC TGAACCCCGC CCTATTGGCA CTCGTTACCT A3 7 GACGCAAACG GTGTTTATTC TGAACCCCGC CCTATTGGCA CTCGTTACCT A3 3 GACGCAAACG GTGTTTATTC TGAACCCCGC CCTATTGGCA CTCGTTACCT 42_12 AATACTGAGG GTACTTATTC AGAGCCTCGC CCCATTGGCA CCCGTTACCT AAV1 GACAACAATG GACTTTATAC TGAGCCTCGC CCCATTGGCA CCCGTTACCT AAV2 GATACTAATG GCGTGTATTC AGAGCCTCGC CCCATTGGCA CCAGATACCT AAV 3 GACACTAATG GT GTT TATAG TGAACCTCGC CCTATTGGAA CCCGGTATCT AAV8 AATACAGAAG GCGTGTACTC TGAACCCCGC CCCATTGGCA CCCGTTACCT AAV9 AATACCGAAG GTGTTTACTC TGAGCCTCGC CCCATTGGTA CTCGTTACCT AAV7 GACAGCCAGG GTGTTTACTC TGAGCCTCGC CCTATTGGCA CTCGTTACCT 44 2 AACACAGATG GCACTTATTC TGAGCCTCGC CCCATCGGCA CCCGTTACCT

89/105

Fig. 1AAAL

4451 4500 VP1-3 stop Poly A signal 42_2 CACCCGTAAC CTGTAATTGC CTGTTAATCA ATAAACCGGT TAATTCGTTT 42 8 CACCCGTAAC CTGTAATTGC CTGTTAATCA ATAAACCGGC TAATTCGTTT 42 15 CACCCGTAAC CTGTAATTGC CTGTTAATCA ATAAACCGGT TAATTCGTTT 42 5b CACCCGTAAC CTGTAATTGC CTGTTAATCA ATAAACCGGT TAATTCGTTT 42—lb CACCCGTAAC CTGTAATTGC CTGTTAATCA ATAAACCGGT TGATTCGTTT 42 13 CACCCGTAGC CTGTAATTGC CTGTTAATCA ATAAACCGGT TGATTCGTTT 2020201242

42:3a CACCCGTAAC CTGTAATTGC CTGTTAATCA ATAAACCGGT TAATTCGTTT 42_4 CACCCGTAAC CTGTAATTGC CTGTTAATCA ATAAACCGGT TAATTCGTTT 42_5a CACCCGTAAC CTGTAATTGC CTGTTAATCA ATAAACCGGT TAATTCGTTT 42_10 CACCCGTAAC CTGTAATTGC CTGTTAATCA ATAAACCGGT TAATTCGTTT 42 3b CACCCGTAAC CTGTAATTGC CTGTTAATCA ATAAACCGGT TAATTCGTTT 42W11 CACCCGTAAC CTGTAATTAC TTGTTAATCA ATAAACCGGT TGATTCGTTT 42:6t) CACCCGTAAC CTGTAATTGC CTGTTAATCA ATAAACCGGT TAATTCGTTT 43_1 CACCCGTAAT CTGTAATTGC TTGTTAATCA ATAAACCGGT 43_5 CACCCGTAAT CTGTAATTGC TTGTTAATCA ATAAACCGGT TAATTCGTTT 43_12 CACCCGTAAT CTGTAATTGC TTGTTAATCA ATAAACCGGT TAATTCGTTT 43_20 CACCCGCAAC CTGTAATTAC ATGTTAATCA ATAAACCGGT TAATTCGTTT 43-21 CACCCGCAAC CTGTAATTAC ATGTTAATCA ATAAACCGGT TAATTCGTTT 43 23 CACCCGCAAC CTGTAATTAC ATGTTAATCA ATAAACCGGT TAATTCGTTT 43:25 CACCCGCAAC CTGTAATTAC ATGTTAATCA ATAAACCGGT TAATTCGTTT 44 1 CACCCGTAAT CTGTAATTGC TCGTTAATCA ATAAACCGGT TGATTCGTTT 44 5 CACCCGTAAT CTGTAATTGC TTGTTAATCA ATAAACCGGT TGATTCGTTT 223_10 223_2 223 4 2235 223:6 223 7 A3 4 TACCCGGAAC TTGTAATTTC CTGTTAATGA ATAAACCGAT TTATGCGTTT A3_5 TACCCGGAAC TTGTAATTTC CTGTTAATGA ATAAACCGGT TTATGCGTTT A3 7 TACCCGGAAC TTGTAATTTC CTGTTAATGA ATAAACCGGT TTATGCGTTT A3_3 TACCCGGAAC TTGTAATTTC CTGTTAATGA ATAAGCCGAT TTATGCGTTT 42_12 CACCCGTAAC CTGTAATTGC CTGTTAATCA ATAAACCGGT TAATTCGTTT AAV1 TACCCGTCCC CTGTAATTAC GTGTTAATCA ATAAACCGGT TGATTCGTTT AAV2 GACTCGTAAT CTGTAATTGC TTGTTAATCA ATAAACCGTT TAATTCGTTT AAV3 CACACGAAAC TTGTGAATCC TGGTTAATCA ATAAACCGTT TAATTCGTTT AAV8 CACCCGTAAT CTGTAATTGC CTGTTAATCA ATAAACCGGT TGATTCGTTT AAV9 CACCCGTAAT TTGTAATTGC CTGTTAATCA ATAAACCGGT TAATTCGTTT AAV7 CACCCGTAAT CTGTAATTGC ATGTTAATCA ATAAACCGGT TGATTCGTTT 44 2 CACCCGTAAT CTGTAATTGC TTGTTAATCA ATAAACCGGT TGATTCGTTT vp1-3 stop PolyA signal

90/105

Fig. lAAAM

4501 4550

42_2 CAGTTGAACT TTGGTCTC.T GCGAAGGGCG AATTC 42_8 CAGTTGAACT TTGGTCTC.T GCGAAGGGCG AATTC 42_15 CAGTTGAACT TTGGTCTC.T GCGAAGGGCG AATTC 42 5b CAGTTGAACT TTGGTCTC.T GCGAAGGGCG AATTCGTTTA AACCTGCAGG 42 lb CAGTTGAACT TTGGTCTC.. ...AAGGGCG AATTC 4213 CAGTTGAACT TTGGTCTC.T GCGAAGGGCG AATTC 2020201242

42_3a CAGTTGAACT TTGGTCTC.T GCGAAGGGCG AATTC 4 CAGTTGAACT TTGGTCTC.T GCGAAGGGCG AATTC 42_5a CAGTTGAACT TTGGTCTC.T GCGAAGGGCG AATTC 42__10 CAGTTGAACT TTGGTC.... ...AAGGGCG AATTC 42_3b CAGTTGAACT TTGGTCTC.T GCGAAGGGCG AATTC 42 11 CAGTTGAACT TTGGTCTC.T GCGAAGGGCG AATTC 42:6b CAGTTGAACT TTGGTCTC.T GCGAAGGGCG AATTC 43_1 43_5 CAGTTGAACT TTGGTCTC.T GCGAAGGGCG AATTCGTTTA AACCTGCAGG 43_12 CAGTTGAACT TTGGTCTC.T GCGAAGGGCG AATTC 43_20 CAGTTGAACT TTGGTCTC.T GCGAAGGGCG AATTC 43_21 CAGTTGAACT TTGGTCTC.T GCGAAGGGCG AATTC 43 23 CAGTTGAACT TTGGTCTC.T GCGAAGGGCG AATTC..... 43 25 CAGTTGAACT TTGGTCTC.T GCGAAGGGCG AATTC 44 1 CAGTTGAACT TTGGTCTC.T GCGAAGGGCG AATTC 44 5 CAGTTGAACT TTGGTCTC.T GCGAAGGGCG AATTC 223_10 223_2 223 4 223_5 223-6 223 7 A3 4 CAGTTGAACT TTGGTCTC.T GCGAAGGGCG AATTCGC.GG CCGCTA.... A3 5 CAGTTGAACT TTGGTCTC.T GCGAAGGGCG AATTC A3 7 CAGTTGAACT TTGGTCTC.T GCGAAGGGCG AATTC A3_3 CAGTTGAACT TTGGTCTC.T GCGAAGGGCG AATTCGT.TT AAACCT.... 42_12 CAGTTGAACT TTGGTCTC.T GCGAAGGGCG AATTC AAV1 CAGTTGAACT TTGGTCTCCT GTCCTTCTTA TCTTATCGGT TACCATGGTT AAV2 CAGTTGAACT TTGGTCTC.T GCGTATTTCT ..TTCTT.AT CTAGTTTCCA AAV3 CAGTTGAACT TTGGCTCT.T GTGCACTTCT TTATCTTTAT CTTGTTTCCA AAV6 CAGTTGAACT TTGGTCTC.T GCG AAV9 CAGTTGAACT TTGGTCTC.T GCG AAV7 CAGTTGAACT TTGGTCTCCT GTGCTTCTTA TCTTATCGGT TTCCATAGCA 44 2 CAGTTGAACT TTGGTCTC.T GCGAAGGGCG AATTC

91/105

•

Fig. lAAAN

4551 4600 42_2 42_8 42_15 42 5b ACTAGTCCCT TTAGTGAGGG TTAATTCTGA G 42lb 42_13 42-3a 2020201242

/ff 4 42_5a 42_10 42-3b 42-11 42-6b 1 43_5 AC 43_12 43 20 43_21 43 23 43-25 1 44_5 223 1.0 2n 2 223_4 223 5 223_6 223-7 A3_4 A3 5 A3_7 A3_3 42_12 AAV1 ATAGCTTACA CATTAACTGC TTGGTTGCGC T AAV2 TGGCTAC... GTAGATAAGT AGC AAV3 TGGCTACTGC GTAGATAAGC AGCGGCCTGC GGCGCTTGCG CTTCGCGGTT AAV8 AAV9 AAV7 ACTGGTTACA CATTAACTGC TTGGGTGCGC TTCACGATAA GAACACTGAC 44 2

Fig. 1AAA0

4601 4650 42_2 42_8 42_15 42 5b ....CTTGGC GTAATCATGG GTCATAG. 42 1b 42_13 42 3a 2020201242

42_4 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 2237 A3_4 A3_5 A3 7 A313 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 44 2

Fig. lAAAP

4651 4700 42 2 42 8 42 15 42 5b 42 lb 42-13 42 3a 2020201242

42 4 42 42_10 42 3b 4211 426b 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 TGCCCACTCC CTCTCTGCGC GCTCGCTCGC TCGGTGGGGC CTGCGGACCA AAV2 TGGCCACTCC CTCTCTGCGC GCTCGCTCGC TCACTGAGGC CGGGCGACCA AAV3 TGGCCACTCC CTCTATGCGC ACTCGCTCGC TCGGTGGGGC CTGGCGACCA AAV8 AAV9 AAV7 TGGCCACTCC CTCTATGCGC GCTCGCTCGC TCGGTGGGGC CTGCGGACCA 44 2

94/105

Fig. lAAAQ

4701 4750 42_2 42_8 42 Y5 42_5b 42 lb 42_13 42:3a 2020201242

42_4 42 5a 4210 42 3b 42 11 42:6b 43_1 43_5 4312 43_20 43 21 431)3 43_25 44_1 44_5 223_10 223_2 223 4 2235 2236 2237 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

95/105

Fig. 1AAAR

4751 4774 42_2 428 42 15 42_5b 42 lb 2020201242

42 13 42 3a 42 4 423a 42_10 42 3b 4211 42:6b 43_1 43_5 43_12 43_20 43_21 43_23 ,4325 44_1 44_5 22310 223_2 223_4 2235 5 223:6 2237 A3 4 A3_5 A3 7 A3 3 42_12 PLAV1 AGCGCGCAGA GAGGGAGTGG GCAA AAV2 AGCGCGCAGA GAGGGAGTGG CCAA AAV3 AGT GC GCATA GAGGGAGTGG CCAA AAV8 AAV9 AAV7 AGCGCGCATA GAGGGAGTGG CCAA 44 2

96/105

Fig. 2A

... ... i ... Iiillri goi ll imiiiimiiiiiiiiilhri p iiiii 2020201242

100111100111111111001110Ma ,, , 1 /0111100111101111110111101 1 Kom l41-0im . l pidiogrid 1 0.- iil I .! Ifilh

11 1" 11111 11 11 1 1 1 1 11 1 1111411 6 111 11 111111111111 .ig 1111111191111211111 d 11 I1 111 1

IMII I IHMIIII 1 IIIIMMII ILIr 11 W il 181lit 110111 114111 liqu 1111611 il 11 11- 11 1 1 1 1 1 0 ' 11 -1 11 1 1 1 IIIINII 11111 1 HM 1101 0 11111 111111111111111191111 11

11111111 111 111 11111111111111111111111111 1111111 1"li n 1141111111 11

110111111 ad0111111011 1.11

IIMIHMI .1,0011111011111111101MO

1111111 15 1 iiirpoloillimmillii Huila 55X 1 hilmilli!!!!uompillp, i ig l;'';111 ki 5 iNiPIE ;;It'24:441;ict?'11 fr;V;AtIv.V411g1,4111 "h 'i 2 " 711,. 97/105

Fig. 2B

1..C.f.D.1,NW,E.WWWWV.t.t.O.V.V.M.7MOMMOVWNNOMAM.1.....WWWWWOINNNNNNMMMMMt., WW.MOIMMOIMMMMMM AAAAA rfM4AMAMV10101.707010,07mOlmeteth0.7%...00,101M07010101011,7tha VINNMNPINNMNOIMMMKNOIMNINOMNnONNOMPINVIMMMNNOMMPIftVINNMPINrINCINNIINVI

miiiiiiiiiiiiiiiiiiiiiiii iiiiiiiiiiiiiiiiiiiiiiii illi 2020201242

ii

1 1 1 1 I 1 1 1 11111111 11111111111 111111111111111111 1 IIm! 1 i

i biiiit) 111 iiii iiiill 11111111 1001 1 1 hiiiiiiiiii dlihil,b,; 11 ii 01 00#14,

11111111111111111111111111111111111111111011111101. 11111118 i glih I ggggggri .0 giggeg11110111111111111 Iiirrlhihd9dhhhPHIPIPr li "1 "" "BM08 grim guigligtillig. Illii wng i 1111 mei88Fq 11 4 4111111 1iiii Iiii111111110110111101111011111°:

;1111 IN 2 111 g DI 11111 I i li i 11 1§ ill /11 illi li I 1 !II:1111 11 I 11 1 1 li I I,ail /L :.-' ill lil11 11IlllilI! il 1/1ill I amt 191 1; 11 1 111111/11111/11i1111.11111111.1111111dli -1111411$opillum111111.$111..mildinhou, thiiimillowillimillimiiiiiiiimcillilliiiii !milmillimaiimiimAiliiiillialliiimagl iimil1101111111iiiiiiiiiiipla 1111 . 1 I... " 1111 . . .....11 . „.. ,...1. . apt W® 11111 1111111111111111111111111i111111111111111 1 1111111111111 111111111 1111 1111111111111 1111111 11 III Im111U - 41. 8 .41.11811 E..iii°11111. 8 1 0 ( 0 MO Til!!!!!!!!1111111111111111111111111111/1111111111111P "Ag"M"P"A"PAIffC1%CCH.4"PnI4PV:Ig4PPP:011"WV"ITIA 181141 "11111q4flarnRaVlgrOVV V4TANWP!MEWILOP 0:0; Nt.t.10 NO

98/105

•

so1/66 .Nob 5 !1 ig-g M0,45#115E9RWnegYX555Y6TIWOIRRN5

11 1 111111 1 1111 ilicIli iiiiiii t tit" 2020201242

1 111 1111 11 111 1 1 111111111 11 mill! 1111 111111

11111111 III 1 1 11111111111 1 111111 MI 11111111-i.

1 1101111111111 1111111111111111 1 1 1111111111111.: 11111 1 /111 1 1 1 11 1 1111111111111 111111 11 1 111111111111111

11 111 11111 11 1111 111111111 111 1 1 i ll 1 111111 11111111rm. • Fod! ffilro iiiiiiililliiiiiiiiiiiiiiiiiiiiiiiiilliiiiiiiiiiiiiii v11111101199911111111;119 111 11 1 111 1111 111 2

1111 Willi 11 1111111 1.111111.11111„pr

111111111 mmm mm 1 111111111111111:111:1111111: mmmm mm 111 1111111111 1 1 1 10110101mmullh 1

1 111 1111 0 iiiii 11111 ifilliiiiiiiilliliiilill 1 1 1 1 1 1

$1111111111111111illili I 111111111011111111111 1 tlaa pc: az i a a ala al 1. Lat.11 la gill 1 1111 H l 1111/111111111211 1 i l/

11104 gi..1110111L liii111111111111 1111.1.111111&11111i AAAAAAAAAAAAAAAA &&&&&& A &&&&&&&&&&&& AWWWWWWAAAAAAAAA &&& WAAAAAWUWWWWWWAAAAAAAAAAAWWAAAAAAAAAOOMMOIMAAAAAAAAAAWWWW MM01000WWWblibletOMMMUNIRMMOIMMKWWMKMMMOMMMAAAAAAUIWWWWWWWAA.41AMOI

az •BIa

6Z9a/ZOSI1/13c1 L6CZ170/E0 OM

Fig. 2D

211222:SMITAT4SMSOMV=222Sgigg:=22122P=ggPVIMISF WOMMMMOWWWWMWMWOMMMMWMTNmMWMMMMOMMOMMMWMOMOMWMMMMWMWMOMM

Ififillil pli filf111111 gi 1 1 111 111 1 111111r 1 li Ili 11111.111 1 1 11 11111 11114. 1111 11 2020201242

p $ 1 1 1 1111- 1 1111 111111111111111 1 1 111 1 111 1 1 1 11 111 '4' lj :1121 pil 1l 11111 . 111111111111 1-111N411 111 1 4/ 111 . 111 1111IIIIIPP11111410111,11 IL

1111111111111111111111111111,111111111111111111111111:

4111141111111111111111111111111111111111111111111111°.

101 111 1 1 11 11 1m Illin ta ' N EE mallE111111111111111

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4 11111 1 11 1 Ild 11111111111111111111 1111 111/11 °

1 1 111 1 1 1 11 11111/1111111111111 111111111 111111 1 11.611.14.11 ill Jill .. III A Rill i 1 11111 04111illiiliiiiliffliiiliiiiiiilili1111141141116 .1111 .k. ii-ii ' A 66660666'666W ' 6 '''' iiii'iiii"6il il, '

MAIMPhhdONENNT4PMAPOWr 111 1 111111111111 1 1111 /111 1111 1 4 111111111/11111111111h I 1111111111111111111111111111111111/11111111111111111 11111111111111 / 111 ill...1116.11111111111101

1 11111 111 1111 1 111 1 1 11111 1 1111111 1 1 1 1 111111 1 1 10 1 11 il li Y"Ug -111rE-1 p pep ppp; ppeppp. i"m"1 iliiiii i illipiiiglilA ' iii6iii 11111111111111111111511111 111111111110111111 Dii% AI v

5115105115gigg41:44g4=44CIP m GL i,, . a mm V07 . , M W Nt....R W I

100/105

Fig. 2E

NNNMMM4000WMWWOOWOV.Onnt.Nr.0.1,04.4*ON NMMminVINI,r.nNe.b.b.mmMVAPn f•M1i+ntr FAiy ....... m ......

1111111111/1" 1 :::111111111 11111111111111111111 11111111 i mm; 11 di 1 Mieriii 5 2020201242

Im "" ' g " 1 "" 1

111-011111111 0AMOM IN

11 1 1 1111111EIPMI IM 1 'ii lip re glmiliiIIII11101111 ilitil 1111P111111 111'11111HAH11 dhilliFOR . IROMMP i 11 N

1I ill 1111111111

g 1

gm

° 14' 111 1111 11 1111111111 1111111111111111 1 1111111111111111111 it 110111111:11111111111111111 g 4111 1111Eupooccpc ilillillicii " "m5 cil .c. ..c licEli 4

11 11114111111111111111111111 1 01 1

1111111111126 191111lliiiilliliiiiiiiiiIiiiiiily "11191461 1 iiiilliiiiiiii11111111111 1111111. 11

11111110101101111100 il l011 0H6 011110111100 11ilii hhmhbi . ll111111 11111 1 U14161..14 . . 11

11111111111111111111111111111111111111111111111111111 111 1111 01111111 111111111111111101111111111111111 0

Irdifi gill IIIIMINNIIIMMil millmaliNiggGrong4wifigNiom .01 a i.,6i 1:' S , in : -

101/105

Fig. 2F 2020201242

M00,W w 0MMNIMW ....... VmmaimammCMTIHHilMcamomImmiwwW00000140CMM0114M4 elmmmOMMeimmmnmra.VVVVV,Pmehmmmommommmmmommmmmmeimmmarlmolamnimmmr4

4,7141401414404140ONIIIIvigAQAg4AAA04ANNOAANAARONAAAARNAARAAAA. .....o.-m.;;.snwe-i-m-H.N-ovwg-ggnng-me...2.:4.m rm. g ;p3;o1112glmig.tann 0101n00..4 T44;;.v.w4v.w44.w„wvelm.0 44s5d.el riu;01 A m4. 4 NO 4 4 4444 Nm144gpl,”nn d 4 r: M

102/105

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 2020201242

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 Ile 100 105 110

Arg Glu Lys Leu Val Gln 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 Ile 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 Gln Asn Lys Glu Asn Leu Asn 195 200 205

Pro Asn Ser Asp Ala Pro Val Ile Arg Ser Lys Thr Ser Ala Arg Tyr 210 215 220

103/105

WO 031042397 PCT/1JS02/33629 20 Feb 2020

Fig. 3B

Met Glu Leu Val Gly Trp Leu Val Asp Arg Gly Ile Thr Ser Glu Lys 225 230 235 240

Gin Trp Ile Gln Glu Asp Gin Ala Ser Tyr Ile Ser Phe Asn Ala Ala 245 250 255

Ser Asn Ser Arg Ser Gin Ile Lys Ala Ala Leu Asp Asn Ala Gly Lys 2020201242

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 Ile 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

Gin 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 Ile Trp Trp Glu Glu Gly Lys Met Thr Ala 370 375 380

Lys Val Val Glu Ser Ala Lys Ala Ile Leu Gly ply Ser Lys Val Arg 385 390 395 400

Val Asp Gin 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 Gin Gin Pro Leu Gin 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

Giu Val Lys Glu Phe Phe Arg Trp Ala Ser Asp His Val Thr Giu Val 465 470 475 480 2020201242

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 Gilt Val 565 570 575

Ser Glu Ser Gln 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 Gln 610 615 620

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