RECOMBINANT AAV CAPSID PROTEINS

Description

SEQUENCE LISTING

The content of the electronically submitted Sequence Listing (Name: “404208-VTW-001US_ST26.xml”; Size: 88,030 bytes; Date of Creation: Oct. 1, 2024) submitted in this application is incorporated herein by reference in its entirety.

BACKGROUND

Adeno-associated virus (AAV) possesses unique features that makes it attractive as a vector for delivering foreign DNA into cells for the purposes of gene therapy. For example: AAV infection of cells in culture is non-cytopathic, and natural infection of humans and other animals is silent. Further, because the signals directing AAV replication, genome encapsidation and integration are contained within the inverted terminal repeats (ITRs) of the AAV genome, essentially all of the internal 4.7 kb of the AAV genome (encoding the replication and structural capsid proteins, rep-cap) can be replaced with heterologous nucleic acid sequences, such as a transgene for effecting gene therapy.

Recombinant AAV (rAAV) gene therapy vectors typically consist of a recombinant AAV genome comprising a gene therapy transgene, contained within an AAV capsid. The AAV capsid, which is formed by an assembly of 60 AAV capsid proteins, interacts with the cell surface of target cells and determines the tropism and transduction efficiency of rAAV. For tissue-specific genetic diseases, it would be highly advantageous to have rAAVs that could specifically and efficiently target the tissues in need of gene therapy.

Accordingly, there is a need in the art for tissue specific AAV capsids for use in gene therapy applications.

SUMMARY

Provided herein are recombinant adeno-associated virus (AAV) capsid proteins, compositions (e.g., rAAV) comprising the capsid proteins, nucleic acids encoding the capsid proteins, and methods of making and using the capsid proteins. The recombinant AAV capsid proteins provided herein are engineered to comprise a peptide within a parental AAV capsid protein. In an aspect, the recombinant AAV capsid proteins provided herein are engineered to comprise a peptide within loop IV and/or loop VIII of a parental AAV capsid protein. These recombinant AAV capsid proteins demonstrate significantly increased transduction of muscle cells compared to the parental AAV capsid proteins.

In an aspect, provided herein is a recombinant adeno-associated virus (AAV) capsid protein comprising a peptide and a parental capsid protein, wherein the peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-9. In an aspect, provided herein is a recombinant adeno-associated virus (AAV) capsid protein comprising a peptide and a parental capsid protein, wherein the peptide is comprised within loop IV and/or loop VIII of the parental capsid protein, and wherein the peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-9. In an embodiment, the peptide is comprised within loop IV of the parental capsid protein. In an embodiment, the peptide is comprised within loop VIII of the parental capsid protein.

In an embodiment, the parental capsid protein is a clade A, clade B, clade C, clade D, clade E, clade F, clade G, clade H, clade I, AAVgo. 1, AAV3, AAV4, AAV10, AAV11, AAV12, rh.32, rh32.33, rh.33, rh.34, BAAV, or AAV5 capsid protein, or an engineered variant thereof.

In an embodiment, the parental capsid protein comprises an amino acid sequence that has at least 95% identity to amino acids 138-725 of SEQ ID NO: 11. In an embodiment, the parental capsid protein comprises an amino acid sequence that has at least 99% identity to amino acids 138-725 of SEQ ID NO: 11. In an embodiment, the parental capsid protein comprises the amino acid sequence of amino acids 138-725 of SEQ ID NO: 11.

In an embodiment, the parental capsid protein comprises an amino acid sequence that has at least 95% identity to SEQ ID NO:10 or 11. In an embodiment, the parental capsid protein comprises an amino acid sequence that has at least 99% identity to SEQ ID NO: 10 or 11. In an embodiment, the parental capsid protein comprises the amino acid sequence of SEQ ID NO: 10 or 11.

In an embodiment, the peptide is positioned immediately C-terminal to an amino acid in the parental capsid protein corresponding to amino acid 440, 441, 442, 443, 444, 445, 446, 447, 572, 573, 574, 575, 576, 577, 578, 579, 580, 581, 582, 583, or 584 of SEQ ID NO: 11.

In an embodiment, the peptide is positioned immediately C-terminal to an amino acid in the parental capsid protein corresponding to amino acid 440 of SEQ ID NO: 11.

In an embodiment, the peptide is positioned immediately C-terminal to an amino acid in the parental capsid protein corresponding to amino acid 441 of SEQ ID NO: 11.

In an embodiment, the peptide is positioned immediately C-terminal to an amino acid in the parental capsid protein corresponding to amino acid 442 of SEQ ID NO: 11.

In an embodiment, the peptide is positioned immediately C-terminal to an amino acid in the parental capsid protein corresponding to amino acid 443 of SEQ ID NO: 11.

In an embodiment, the peptide is positioned immediately C-terminal to an amino acid in the parental capsid protein corresponding to amino acid 444 of SEQ ID NO: 11.

In an embodiment, the peptide is positioned immediately C-terminal to an amino acid in the parental capsid protein corresponding to amino acid 445 of SEQ ID NO: 11.

In an embodiment, the peptide is positioned immediately C-terminal to an amino acid in the parental capsid protein corresponding to amino acid 446 of SEQ ID NO: 11.

In an embodiment, the peptide is positioned immediately C-terminal to an amino acid in the parental capsid protein corresponding to amino acid 447 of SEQ ID NO: 11.

In an embodiment, the peptide is positioned immediately C-terminal to an amino acid in the parental capsid protein corresponding to amino acid 572 of SEQ ID NO: 11.

In an embodiment, the peptide is positioned immediately C-terminal to an amino acid in the parental capsid protein corresponding to amino acid 573 of SEQ ID NO: 11.

In an embodiment, the peptide is positioned immediately C-terminal to an amino acid in the parental capsid protein corresponding to amino acid 574 of SEQ ID NO: 11.

In an embodiment, the peptide is positioned immediately C-terminal to an amino acid in the parental capsid protein corresponding to amino acid 575 of SEQ ID NO: 11.

In an embodiment, the peptide is positioned immediately C-terminal to an amino acid in the parental capsid protein corresponding to amino acid 576 of SEQ ID NO: 11.

In an embodiment, the peptide is positioned immediately C-terminal to an amino acid in the parental capsid protein corresponding to amino acid 577 of SEQ ID NO: 11.

In an embodiment, the peptide is positioned immediately C-terminal to an amino acid in the parental capsid protein corresponding to amino acid 578 of SEQ ID NO: 11.

In an embodiment, the peptide is positioned immediately C-terminal to an amino acid in the parental capsid protein corresponding to amino acid 579 of SEQ ID NO: 11.

In an embodiment, the peptide is positioned immediately C-terminal to an amino acid in the parental capsid protein corresponding to amino acid 580 of SEQ ID NO: 11.

In an embodiment, the peptide is positioned immediately C-terminal to an amino acid in the parental capsid protein corresponding to amino acid 581 of SEQ ID NO: 11.

In an embodiment, the peptide is positioned immediately C-terminal to an amino acid in the parental capsid protein corresponding to amino acid 582 of SEQ ID NO: 11.

In an embodiment, the peptide is positioned immediately C-terminal to an amino acid in the parental capsid protein corresponding to amino acid 583 of SEQ ID NO: 11.

In an embodiment, the peptide is positioned immediately C-terminal to an amino acid in the parental capsid protein corresponding to amino acid 584 of SEQ ID NO: 11.

In an embodiment, the recombinant AAV capsid protein comprises: an amino acid sequence that has at least 95% sequence identity to amino acids 194-763 of SEQ ID NO: 12, wherein amino acids 445-482 are ASLEEEWAQVECEVYGRGCPSGSLDESFYDWFERQLGA (SEQ ID NO: 1); an amino acid sequence that has at least 95% sequence identity to amino acids 194-763 of SEQ ID NO: 13, wherein amino acids 578-615 are ASLEEEWAQVECEVYGRGCPSGSLDESFYDWFERQLGA (SEQ ID NO: 1); an amino acid sequence that has at least 95% sequence identity to amino acids 194-734 of SEQ ID NO: 14, wherein amino acids 445-453 are APLTNTVKA (SEQ ID NO: 2); an amino acid sequence that has at least 95% sequence identity to amino acids 194-734 of SEQ ID NO: 15, wherein amino acids 578-586 are APLTNTVKA (SEQ ID NO: 2); an amino acid sequence that has at least 95% sequence identity to amino acids 194-732 of SEQ ID NO: 16, wherein amino acids 445-451 are DDTRHWG (SEQ ID NO: 3); an amino acid sequence that has at least 95% sequence identity to amino acids 194-732 of SEQ ID NO: 17, wherein amino acids 578-584 are DDTRHWG (SEQ ID NO: 3); an amino acid sequence that has at least 95% sequence identity to amino acids 194-732 of SEQ ID NO: 18, wherein amino acids 445-451 are EYHHYNK (SEQ ID NO: 4); an amino acid sequence that has at least 95% sequence identity to amino acids 194-732 of SEQ ID NO: 19, wherein amino acids 578-584 are EYHHYNK (SEQ ID NO: 4); an amino acid sequence that has at least 95% sequence identity to amino acids 194-732 of SEQ ID NO: 20, wherein amino acids 445-451 are QLFPLFR (SEQ ID NO: 5); an amino acid sequence that has at least 95% sequence identity to amino acids 194-732 of SEQ ID NO: 21, wherein amino acids 578-584 are QLFPLFR (SEQ ID NO: 5); an amino acid sequence that has at least 95% sequence identity to amino acids 194-742 of SEQ ID NO: 22, wherein amino acids 445-461 are FNPVTGEVPPRYPLDAR (SEQ ID NO: 6); an amino acid sequence that has at least 95% sequence identity to amino acids 194-742 of SEQ ID NO: 23, wherein amino acids 578-594 are FNPVTGEVPPRYPLDAR (SEQ ID NO: 6); an amino acid sequence that has at least 95% sequence identity to amino acids 194-739 of SEQ ID NO: 24, wherein amino acids 445-458 are SVTEQGAELSNEER (SEQ ID NO: 7); an amino acid sequence that has at least 95% sequence identity to amino acids 194-739 of SEQ ID NO: 25, wherein amino acids 578-591 are SVTEQGAELSNEER (SEQ ID NO: 7); an amino acid sequence that has at least 95% sequence identity to amino acids 194-735 of SEQ ID NO: 26, wherein amino acids 449-454 are RGDLGL (SEQ ID NO: 8); an amino acid sequence that has at least 95% sequence identity to amino acids 194-735 of SEQ ID NO: 27, wherein amino acids 578-584 are RGDLGL (SEQ ID NO: 8); an amino acid sequence that has at least 95% sequence identity to amino acids 194-737 of SEQ ID NO: 28, wherein amino acids 447-453 are ASSLNIA (SEQ ID NO: 9); or an amino acid sequence that has at least 95% sequence identity to amino acids 194-737 of SEQ ID NO: 29, wherein amino acids 580-586 are ASSLNIA (SEQ ID NO: 9).

In an embodiment, the recombinant AAV capsid protein comprises an amino acid sequence that has at least 99% sequence identity to amino acids 194-763 of SEQ ID NO: 12, wherein amino acids 445-482 are ASLEEEWAQVECEVYGRGCPSGSLDESFYDWFERQLGA (SEQ ID NO: 1); an amino acid sequence that has at least 99% sequence identity to amino acids 194-763 of SEQ ID NO: 13, wherein amino acids 578-615 are ASLEEEWAQVECEVYGRGCPSGSLDESFYDWFERQLGA (SEQ ID NO: 1); an amino acid sequence that has at least 99% sequence identity to amino acids 194-734 of SEQ ID NO: 14, wherein amino acids 445-453 are APLTNTVKA (SEQ ID NO: 2); an amino acid sequence that has at least 99% sequence identity to amino acids 194-734 of SEQ ID NO: 15, wherein amino acids 578-586 are APLTNTVKA (SEQ ID NO: 2); an amino acid sequence that has at least 99% sequence identity to amino acids 194-732 of SEQ ID NO: 16, wherein amino acids 445-451 are DDTRHWG (SEQ ID NO: 3); an amino acid sequence that has at least 99% sequence identity to amino acids 194-732 of SEQ ID NO: 17, wherein amino acids 578-584 are DDTRHWG (SEQ ID NO: 3); an amino acid sequence that has at least 99% sequence identity to amino acids 194-732 of SEQ ID NO: 18, wherein amino acids 445-451 are EYHHYNK (SEQ ID NO: 4); an amino acid sequence that has at least 99% sequence identity to amino acids 194-732 of SEQ ID NO: 19, wherein amino acids 578-584 are EYHHYNK (SEQ ID NO: 4); an amino acid sequence that has at least 99% sequence identity to amino acids 194-732 of SEQ ID NO: 20, wherein amino acids 445-451 are QLFPLFR (SEQ ID NO: 5); an amino acid sequence that has at least 99% sequence identity to amino acids 194-732 of SEQ ID NO: 21, wherein amino acids 578-584 are QLFPLFR (SEQ ID NO: 5); an amino acid sequence that has at least 99% sequence identity to amino acids 194-742 of SEQ ID NO: 22, wherein amino acids 445-461 are FNPVTGEVPPRYPLDAR (SEQ ID NO: 6); an amino acid sequence that has at least 99% sequence identity to amino acids 194-742 of SEQ ID NO: 23, wherein amino acids 578-594 are FNPVTGEVPPRYPLDAR (SEQ ID NO: 6); an amino acid sequence that has at least 99% sequence identity to amino acids 194-739 of SEQ ID NO: 24, wherein amino acids 445-458 are SVTEQGAELSNEER (SEQ ID NO: 7); an amino acid sequence that has at least 99% sequence identity to amino acids 194-739 of SEQ ID NO: 25, wherein amino acids 578-591 are SVTEQGAELSNEER (SEQ ID NO: 7); an amino acid sequence that has at least 99% sequence identity to amino acids 194-735 of SEQ ID NO: 26, wherein amino acids 449-454 are RGDLGL (SEQ ID NO: 8); an amino acid sequence that has at least 99% sequence identity to amino acids 194-735 of SEQ ID NO: 27, wherein amino acids 578-584 are RGDLGL (SEQ ID NO: 8); an amino acid sequence that has at least 99% sequence identity to amino acids 194-737 of SEQ ID NO: 28, wherein amino acids 447-453 are ASSLNIA (SEQ ID NO: 9); or an amino acid sequence that has at least 99% sequence identity to amino acids 194-737 of SEQ ID NO: 29, wherein amino acids 580-586 are ASSLNIA (SEQ ID NO: 9).

In an embodiment, the recombinant AAV capsid protein comprises an amino acid sequence that has 100% sequence identity to amino acids 194-763 of SEQ ID NO: 12; an amino acid sequence that has 100% sequence identity to amino acids 194-763 of SEQ ID NO: 13; an amino acid sequence that has 100% sequence identity to amino acids 194-734 of SEQ ID NO: 14; an amino acid sequence that has 100% sequence identity to amino acids 194-734 of SEQ ID NO: 15; an amino acid sequence that has 100% sequence identity to amino acids 194-732 of SEQ ID NO: 16; an amino acid sequence that has 100% sequence identity to amino acids 194-732 of SEQ ID NO: 17; an amino acid sequence that has 100% sequence identity to amino acids 194-732 of SEQ ID NO: 18; an amino acid sequence that has 100% sequence identity to amino acids 194-732 of SEQ ID NO: 19; an amino acid sequence that has 100% sequence identity to amino acids 194-732 of SEQ ID NO: 20; an amino acid sequence that has 100% sequence identity to amino acids 194-732 of SEQ ID NO: 21; an amino acid sequence that has 100% sequence identity to amino acids 194-742 of SEQ ID NO: 22; an amino acid sequence that has 100% sequence identity to amino acids 194-742 of SEQ ID NO: 23; an amino acid sequence that has 100% sequence identity to amino acids 194-739 of SEQ ID NO: 24; an amino acid sequence that has 100% sequence identity to amino acids 194-739 of SEQ ID NO: 25; an amino acid sequence that has 100% sequence identity to amino acids 194-735 of SEQ ID NO: 26; an amino acid sequence that has 100% sequence identity to amino acids 194-735 of SEQ ID NO: 27; an amino acid sequence that has 100% sequence identity to amino acids 194-737 of SEQ ID NO: 28; or an amino acid sequence that has 100% sequence identity to amino acids 194-737 of SEQ ID NO: 29.

In an embodiment, the recombinant AAV capsid protein comprises an amino acid sequence that has at least 95% sequence identity to amino acids 138-763 of SEQ ID NO: 12, wherein amino acids 445-482 are ASLEEEWAQVECEVYGRGCPSGSLDESFYDWFERQLGA (SEQ ID NO: 1); an amino acid sequence that has at least 95% sequence identity to amino acids 138-763 of SEQ ID NO: 13, wherein amino acids 578-615 are ASLEEEWAQVECEVYGRGCPSGSLDESFYDWFERQLGA (SEQ ID NO: 1); an amino acid sequence that has at least 95% sequence identity to amino acids 138-734 of SEQ ID NO: 14, wherein amino acids 445-453 are APLTNTVKA (SEQ ID NO: 2); an amino acid sequence that has at least 95% sequence identity to amino acids 138-734 of SEQ ID NO: 15, wherein amino acids 578-586 are APLTNTVKA (SEQ ID NO: 2); an amino acid sequence that has at least 95% sequence identity to amino acids 138-732 of SEQ ID NO: 16, wherein amino acids 445-451 are DDTRHWG (SEQ ID NO: 3); an amino acid sequence that has at least 95% sequence identity to amino acids 138-732 of SEQ ID NO: 17, wherein amino acids 578-584 are DDTRHWG (SEQ ID NO: 3); an amino acid sequence that has at least 95% sequence identity to amino acids 138-732 of SEQ ID NO: 18, wherein amino acids 445-451 are EYHHYNK (SEQ ID NO: 4); an amino acid sequence that has at least 95% sequence identity to amino acids 138-732 of SEQ ID NO: 19, wherein amino acids 578-584 are EYHHYNK (SEQ ID NO: 4); an amino acid sequence that has at least 95% sequence identity to amino acids 138-732 of SEQ ID NO: 20, wherein amino acids 445-451 are QLFPLFR (SEQ ID NO: 5); an amino acid sequence that has at least 95% sequence identity to amino acids 138-732 of SEQ ID NO: 21, wherein amino acids 578-584 are QLFPLFR (SEQ ID NO: 5); an amino acid sequence that has at least 95% sequence identity to amino acids 138-742 of SEQ ID NO: 22, wherein amino acids 445-461 are FNPVTGEVPPRYPLDAR (SEQ ID NO: 6); an amino acid sequence that has at least 95% sequence identity to amino acids 138-742 of SEQ ID NO: 23, wherein amino acids 578-594 are FNPVTGEVPPRYPLDAR (SEQ ID NO: 6); an amino acid sequence that has at least 95% sequence identity to amino acids 138-739 of SEQ ID NO: 24, wherein amino acids 445-458 are SVTEQGAELSNEER (SEQ ID NO: 7); an amino acid sequence that has at least 95% sequence identity to amino acids 138-739 of SEQ ID NO: 25, wherein amino acids 578-591 are SVTEQGAELSNEER (SEQ ID NO: 7); an amino acid sequence that has at least 95% sequence identity to amino acids 138-735 of SEQ ID NO: 26, wherein amino acids 449-454 are RGDLGL (SEQ ID NO: 8); an amino acid sequence that has at least 95% sequence identity to amino acids 138-735 of SEQ ID NO: 27, wherein amino acids 578-584 are RGDLGL (SEQ ID NO: 8); an amino acid sequence that has at least 95% sequence identity to amino acids 138-737 of SEQ ID NO: 28, wherein amino acids 447-453 are ASSLNIA (SEQ ID NO: 9); or an amino acid sequence that has at least 95% sequence identity to amino acids 138-737 of SEQ ID NO: 29, wherein amino acids 580-586 are ASSLNIA (SEQ ID NO: 9).

In an embodiment, the recombinant AAV capsid protein comprises an amino acid sequence that has at least 99% sequence identity to amino acids 138-763 of SEQ ID NO: 12, wherein amino acids 445-482 are ASLEEEWAQVECEVYGRGCPSGSLDESFYDWFERQLGA (SEQ ID NO: 1); an amino acid sequence that has at least 99% sequence identity to amino acids 138-763 of SEQ ID NO: 13, wherein amino acids 578-615 are ASLEEEWAQVECEVYGRGCPSGSLDESFYDWFERQLGA (SEQ ID NO: 1); an amino acid sequence that has at least 99% sequence identity to amino acids 138-734 of SEQ ID NO: 14, wherein amino acids 445-453 are APLTNTVKA (SEQ ID NO: 2); an amino acid sequence that has at least 99% sequence identity to amino acids 138-734 of SEQ ID NO: 15, wherein amino acids 578-586 are APLTNTVKA (SEQ ID NO: 2); an amino acid sequence that has at least 99% sequence identity to amino acids 138-732 of SEQ ID NO: 16, wherein amino acids 445-451 are DDTRHWG (SEQ ID NO: 3); an amino acid sequence that has at least 99% sequence identity to amino acids 138-732 of SEQ ID NO: 17, wherein amino acids 578-584 are DDTRHWG (SEQ ID NO: 3); an amino acid sequence that has at least 99% sequence identity to amino acids 138-732 of SEQ ID NO: 18, wherein amino acids 445-451 are EYHHYNK (SEQ ID NO: 4); an amino acid sequence that has at least 99% sequence identity to amino acids 138-732 of SEQ ID NO: 19, wherein amino acids 578-584 are EYHHYNK (SEQ ID NO: 4); an amino acid sequence that has at least 99% sequence identity to amino acids 138-732 of SEQ ID NO: 20, wherein amino acids 445-451 are QLFPLFR (SEQ ID NO: 5); an amino acid sequence that has at least 99% sequence identity to amino acids 138-732 of SEQ ID NO: 21, wherein amino acids 578-584 are QLFPLFR (SEQ ID NO: 5); an amino acid sequence that has at least 99% sequence identity to amino acids 138-742 of SEQ ID NO: 22, wherein amino acids 445-461 are FNPVTGEVPPRYPLDAR (SEQ ID NO: 6); an amino acid sequence that has at least 99% sequence identity to amino acids 138-742 of SEQ ID NO: 23, wherein amino acids 578-594 are FNPVTGEVPPRYPLDAR (SEQ ID NO: 6); an amino acid sequence that has at least 99% sequence identity to amino acids 138-739 of SEQ ID NO: 24, wherein amino acids 445-458 are SVTEQGAELSNEER (SEQ ID NO: 7); an amino acid sequence that has at least 99% sequence identity to amino acids 138-739 of SEQ ID NO: 25, wherein amino acids 578-591 are SVTEQGAELSNEER (SEQ ID NO: 7); an amino acid sequence that has at least 99% sequence identity to amino acids 138-735 of SEQ ID NO: 26, wherein amino acids 449-454 are RGDLGL (SEQ ID NO: 8); an amino acid sequence that has at least 99% sequence identity to amino acids 138-735 of SEQ ID NO: 27, wherein amino acids 578-584 are RGDLGL (SEQ ID NO: 8); an amino acid sequence that has at least 99% sequence identity to amino acids 138-737 of SEQ ID NO: 28, wherein amino acids 447-453 are ASSLNIA (SEQ ID NO: 9); or an amino acid sequence that has at least 99% sequence identity to amino acids 138-737 of SEQ ID NO: 29, wherein amino acids 580-586 are ASSLNIA (SEQ ID NO: 9).

In an embodiment, the recombinant AAV capsid protein comprises an amino acid sequence that has 100% sequence identity to amino acids 138-763 of SEQ ID NO: 12; an amino acid sequence that has 100% sequence identity to amino acids 138-763 of SEQ ID NO: 13; an amino acid sequence that has 100% sequence identity to amino acids 138-734 of SEQ ID NO: 14; an amino acid sequence that has 100% sequence identity to amino acids 138-734 of SEQ ID NO: 15; an amino acid sequence that has 100% sequence identity to amino acids 138-732 of SEQ ID NO: 16; an amino acid sequence that has 100% sequence identity to amino acids 138-732 of SEQ ID NO: 17; an amino acid sequence that has 100% sequence identity to amino acids 138-732 of SEQ ID NO: 18; an amino acid sequence that has 100% sequence identity to amino acids 138-732 of SEQ ID NO: 19; an amino acid sequence that has 100% sequence identity to amino acids 138-732 of SEQ ID NO: 20; an amino acid sequence that has 100% sequence identity to amino acids 138-732 of SEQ ID NO: 21; an amino acid sequence that has 100% sequence identity to amino acids 138-742 of SEQ ID NO: 22; an amino acid sequence that has 100% sequence identity to amino acids 138-742 of SEQ ID NO: 23; an amino acid sequence that has 100% sequence identity to amino acids 138-739 of SEQ ID NO: 24; an amino acid sequence that has 100% sequence identity to amino acids 138-739 of SEQ ID NO: 25; an amino acid sequence that has 100% sequence identity to amino acids 138-735 of SEQ ID NO: 26; an amino acid sequence that has 100% sequence identity to amino acids 138-735 of SEQ ID NO: 27; an amino acid sequence that has 100% sequence identity to amino acids 138-737 of SEQ ID NO: 28; or an amino acid sequence that has 100% sequence identity to amino acids 138-737 of SEQ ID NO: 29.

In an embodiment, the recombinant AAV capsid protein comprises an amino acid sequence that has at least 95% sequence identity to amino acids 1-763 of SEQ ID NO: 12, wherein amino acids 445-482 are ASLEEEWAQVECEVYGRGCPSGSLDESFYDWFERQLGA (SEQ ID NO: 1); an amino acid sequence that has at least 95% sequence identity to amino acids 1-763 of SEQ ID NO: 13, wherein amino acids 578-615 are ASLEEEWAQVECEVYGRGCPSGSLDESFYDWFERQLGA (SEQ ID NO: 1); an amino acid sequence that has at least 95% sequence identity to amino acids 1-734 of SEQ ID NO: 14, wherein amino acids 445-453 are APLTNTVKA (SEQ ID NO: 2); an amino acid sequence that has at least 95% sequence identity to amino acids 1-734 of SEQ ID NO: 15, wherein amino acids 578-586 are APLTNTVKA (SEQ ID NO: 2); an amino acid sequence that has at least 95% sequence identity to amino acids 1-732 of SEQ ID NO: 16, wherein amino acids 445-451 are DDTRHWG (SEQ ID NO: 3); an amino acid sequence that has at least 95% sequence identity to amino acids 1-732 of SEQ ID NO: 17, wherein amino acids 578-584 are DDTRHWG (SEQ ID NO: 3); an amino acid sequence that has at least 95% sequence identity to amino acids 1-732 of SEQ ID NO: 18, wherein amino acids 445-451 are EYHHYNK (SEQ ID NO: 4); an amino acid sequence that has at least 95% sequence identity to amino acids 1-732 of SEQ ID NO: 19, wherein amino acids 578-584 are EYHHYNK (SEQ ID NO: 4); an amino acid sequence that has at least 95% sequence identity to amino acids 1-732 of SEQ ID NO: 20, wherein amino acids 445-451 are QLFPLFR (SEQ ID NO: 5); an amino acid sequence that has at least 95% sequence identity to amino acids 1-732 of SEQ ID NO: 21, wherein amino acids 578-584 are QLFPLFR (SEQ ID NO: 5); an amino acid sequence that has at least 95% sequence identity to amino acids 1-742 of SEQ ID NO: 22, wherein amino acids 445-461 are FNPVTGEVPPRYPLDAR (SEQ ID NO: 6); an amino acid sequence that has at least 95% sequence identity to amino acids 1-742 of SEQ ID NO: 23, wherein amino acids 578-594 are FNPVTGEVPPRYPLDAR (SEQ ID NO: 6); an amino acid sequence that has at least 95% sequence identity to amino acids 1-739 of SEQ ID NO: 24, wherein amino acids 445-458 are SVTEQGAELSNEER (SEQ ID NO: 7); an amino acid sequence that has at least 95% sequence identity to amino acids 1-739 of SEQ ID NO: 25, wherein amino acids 578-591 are SVTEQGAELSNEER (SEQ ID NO: 7); an amino acid sequence that has at least 95% sequence identity to amino acids 1-735 of SEQ ID NO: 26, wherein amino acids 449-454 are RGDLGL (SEQ ID NO: 8); an amino acid sequence that has at least 95% sequence identity to amino acids 1-735 of SEQ ID NO: 27, wherein amino acids 578-584 are RGDLGL (SEQ ID NO: 8); an amino acid sequence that has at least 95% sequence identity to amino acids 1-737 of SEQ ID NO: 28, wherein amino acids 447-453 are ASSLNIA (SEQ ID NO: 9); or an amino acid sequence that has at least 95% sequence identity to amino acids 1-737 of SEQ ID NO: 29, wherein amino acids 580-586 are ASSLNIA (SEQ ID NO: 9).

In an embodiment, the recombinant AAV capsid protein comprises an amino acid sequence that has at least 99% sequence identity to amino acids 1-763 of SEQ ID NO: 12, wherein amino acids 445-482 are ASLEEEWAQVECEVYGRGCPSGSLDESFYDWFERQLGA (SEQ ID NO: 1); an amino acid sequence that has at least 99% sequence identity to amino acids 1-763 of SEQ ID NO: 13, wherein amino acids 578-615 are ASLEEEWAQVECEVYGRGCPSGSLDESFYDWFERQLGA (SEQ ID NO: 1); an amino acid sequence that has at least 99% sequence identity to amino acids 1-734 of SEQ ID NO: 14, wherein amino acids 445-453 are APLTNTVKA (SEQ ID NO: 2); an amino acid sequence that has at least 99% sequence identity to amino acids 1-734 of SEQ ID NO: 15, wherein amino acids 578-586 are APLTNTVKA (SEQ ID NO: 2); an amino acid sequence that has at least 99% sequence identity to amino acids 1-732 of SEQ ID NO: 16, wherein amino acids 445-451 are DDTRHWG (SEQ ID NO: 3); an amino acid sequence that has at least 99% sequence identity to amino acids 1-732 of SEQ ID NO: 17, wherein amino acids 578-584 are DDTRHWG (SEQ ID NO: 3); an amino acid sequence that has at least 99% sequence identity to amino acids 1-732 of SEQ ID NO: 18, wherein amino acids 445-451 are EYHHYNK (SEQ ID NO: 4); an amino acid sequence that has at least 99% sequence identity to amino acids 1-732 of SEQ ID NO: 19, wherein amino acids 578-584 are EYHHYNK (SEQ ID NO: 4); an amino acid sequence that has at least 99% sequence identity to amino acids 1-732 of SEQ ID NO: 20, wherein amino acids 445-451 are QLFPLFR (SEQ ID NO: 5); an amino acid sequence that has at least 99% sequence identity to amino acids 1-732 of SEQ ID NO: 21, wherein amino acids 578-584 are QLFPLFR (SEQ ID NO: 5); an amino acid sequence that has at least 99% sequence identity to amino acids 1-742 of SEQ ID NO: 22, wherein amino acids 445-461 are FNPVTGEVPPRYPLDAR (SEQ ID NO: 6); an amino acid sequence that has at least 99% sequence identity to amino acids 1-742 of SEQ ID NO: 23, wherein amino acids 578-594 are FNPVTGEVPPRYPLDAR (SEQ ID NO: 6); an amino acid sequence that has at least 99% sequence identity to amino acids 1-739 of SEQ ID NO: 24, wherein amino acids 445-458 are SVTEQGAELSNEER (SEQ ID NO: 7); an amino acid sequence that has at least 99% sequence identity to amino acids 1-739 of SEQ ID NO: 25, wherein amino acids 578-591 are SVTEQGAELSNEER (SEQ ID NO: 7); an amino acid sequence that has at least 99% sequence identity to amino acids 1-735 of SEQ ID NO: 26, wherein amino acids 449-454 are RGDLGL (SEQ ID NO: 8); an amino acid sequence that has at least 99% sequence identity to amino acids 1-735 of SEQ ID NO: 27, wherein amino acids 578-584 are RGDLGL (SEQ ID NO: 8); an amino acid sequence that has at least 99% sequence identity to amino acids 1-737 of SEQ ID NO: 28, wherein amino acids 447-453 are ASSLNIA (SEQ ID NO: 9); or an amino acid sequence that has at least 99% sequence identity to amino acids 1-737 of SEQ ID NO: 29, wherein amino acids 580-586 are ASSLNIA (SEQ ID NO: 9).

In an embodiment, the recombinant AAV capsid protein comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 12-29. In an embodiment, the amino acid sequence of the AAV capsid protein consists of an amino acid sequence selected from the group consisting of SEQ ID NOs: 12-29.

In an aspect, provided herein is a recombinant adeno-associated virus (AAV) capsid protein comprising a first peptide, a second peptide, and a parental capsid protein, wherein the first peptide is comprised within loop IV of the parental capsid protein and the second peptide is comprised within loop VIII of the parental capsid protein, and wherein the first peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-9, 35, and 36 and the second peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-9, 35, and 36.

In an embodiment, the first peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-9, 35, and 36 and the second peptide comprises the amino acid sequence of SEQ ID NO: 1.

In an embodiment, the parental capsid protein comprises an amino acid sequence that has at least 95% identity to amino acids 193-725 of SEQ ID NO: 11. In an embodiment, the parental capsid protein comprises an amino acid sequence that has at least 99% identity to amino acids 193-725 of SEQ ID NO:11. In an embodiment, the parental capsid protein comprises the amino acid sequence of amino acids 193-725 of SEQ ID NO: 11. In an embodiment, the parental capsid protein comprises an amino acid sequence that has at least 95% identity to amino acids 138-725 of SEQ ID NO: 11. In an embodiment, the parental capsid protein comprises an amino acid sequence that has at least 99% identity to amino acids 138-725 of SEQ ID NO: 11. In an embodiment, the parental capsid protein comprises the amino acid sequence of amino acids 138-725 of SEQ ID NO: 11. In an embodiment, the parental capsid protein comprises an amino acid sequence that has at least 95% identity to SEQ ID NO: 10 or 11. In an embodiment, the parental capsid protein comprises an amino acid sequence that has at least 99% identity to SEQ ID NO: 10 or 11. In an embodiment, the parental capsid protein comprises the amino acid of SEQ ID NO: 10 or 11.

In an embodiment, (a) the first peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 440, 441, 442, 443, 444, 445, 446, or 447 of SEQ ID NO: 11; and (b) the second peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 572, 573, 574, 575, 576, 577, 578, 579, 580, 581, 582, 583, or 584 of SEQ ID NO: 11.

In an embodiment, the first peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 440 of SEQ ID NO: 11. In an embodiment, the first peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 441 of SEQ ID NO: 11. In an embodiment, the first peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 442 of SEQ ID NO: 11. In an embodiment, the first peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 443 of SEQ ID NO: 11. In an embodiment, the first peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 444 of SEQ ID NO: 11. In an embodiment, the first peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 445 of SEQ ID NO: 11. In an embodiment, the first peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 446 of SEQ ID NO: 11. In an embodiment, the first peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 447 of SEQ ID NO: 11.

In an embodiment, the second peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 572 of SEQ ID NO: 11. In an embodiment, the second peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 573 of SEQ ID NO: 11. In an embodiment, the second peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 574 of SEQ ID NO: 11. In an embodiment, the second peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 575 of SEQ ID NO: 11. In an embodiment, the second peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 576 of SEQ ID NO: 11. In an embodiment, the second peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 577 of SEQ ID NO: 11. In an embodiment, the second peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 578 of SEQ ID NO: 11. In an embodiment, the second peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 579 of SEQ ID NO: 11. In an embodiment, the second peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 580 of SEQ ID NO: 11. In an embodiment, the second peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 581 of SEQ ID NO: 11. In an embodiment, the second peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 582 of SEQ ID NO: 11. In an embodiment, the second peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 583 of SEQ ID NO: 11. In an embodiment, the second peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 584 of SEQ ID NO: 11.

In an embodiment, the recombinant AAV capsid protein comprises: (a) an amino acid sequence that has at least 95% sequence identity to amino acids 194-745 of SEQ ID NO: 30, wherein amino acids 449-454 are RGDLGL (SEQ ID NO: 8) and amino acids 592-597 are RGDLGL (SEQ ID NO: 8); (b) an amino acid sequence that has at least 95% sequence identity to amino acids 194-742 of SEQ ID NO: 31, wherein amino acids 449-454 are RGDLGL (SEQ ID NO: 8) and amino acids 588-594 are RTIGPSV (SEQ ID NO: 35); (c) an amino acid sequence that has at least 95% sequence identity to amino acids 194-742 of SEQ ID NO: 32, wherein amino acids 445-451 are RTIGPSV (SEQ ID NO: 35) and amino acids 589-594 are RGDLGL (SEQ ID NO: 8); (d) an amino acid sequence that has at least 95% sequence identity to amino acids 194-742 of SEQ ID NO: 33, wherein amino acids 445-451 are LSSRLDA (SEQ ID NO: 36) and amino acids 589-594 are RGDLGL (SEQ ID NO: 8); or (e) an amino acid sequence that has at least 95% sequence identity to amino acids 194-744 of SEQ ID NO: 34, wherein amino acids 445-453 are APLTNTVKA (SEQ ID NO: 2) and amino acids 591-596 are RGDLGL (SEQ ID NO: 8).

In an embodiment, the recombinant AAV capsid protein comprises: (a) an amino acid sequence that has at least 99% sequence identity to amino acids 194-745 of SEQ ID NO: 30, wherein amino acids 449-454 are RGDLGL (SEQ ID NO: 8) and amino acids 592-597 are RGDLGL (SEQ ID NO: 8); (b) an amino acid sequence that has at least 99% sequence identity to amino acids 194-742 of SEQ ID NO: 31, wherein amino acids 449-454 are RGDLGL (SEQ ID NO: 8) and amino acids 588-594 are RTIGPSV (SEQ ID NO: 35); (c) an amino acid sequence that has at least 99% sequence identity to amino acids 194-742 of SEQ ID NO: 32, wherein amino acids 445-451 are RTIGPSV (SEQ ID NO: 35) and amino acids 589-594 are RGDLGL (SEQ ID NO: 8); (d) an amino acid sequence that has at least 99% sequence identity to amino acids 194-742 of SEQ ID NO: 33, wherein amino acids 445-451 are LSSRLDA (SEQ ID NO: 36) and amino acids 589-594 are RGDLGL (SEQ ID NO: 8); or (e) an amino acid sequence that has at least 99% sequence identity to amino acids 194-744 of SEQ ID NO: 34, wherein amino acids 445-453 are APLTNTVKA (SEQ ID NO: 2) and amino acids 591-596 are RGDLGL (SEQ ID NO: 8).

In an embodiment, the recombinant AAV capsid protein comprises: (a) an amino acid sequence that has at least 100% sequence identity to amino acids 194-745 of SEQ ID NO: 30; (b) an amino acid sequence that has at least 100% sequence identity to amino acids 194-742 of SEQ ID NO: 31; (c) an amino acid sequence that has at least 100% sequence identity to amino acids 194-742 of SEQ ID NO: 32; (d) an amino acid sequence that has at least 100% sequence identity to amino acids 194-742 of SEQ ID NO: 33; or (e) an amino acid sequence that has at least 100% sequence identity to amino acids 194-744 of SEQ ID NO: 34.

In an embodiment, the recombinant AAV capsid protein comprises: (a) an amino acid sequence that has at least 95% sequence identity to amino acids 138-745 of SEQ ID NO: 30 wherein amino acids 449-454 are RGDLGL (SEQ ID NO: 8) and amino acids 592-597 are RGDLGL (SEQ ID NO: 8); (b) an amino acid sequence that has at least 95% sequence identity to amino acids 138-742 of SEQ ID NO: 31, wherein amino acids 449-454 are RGDLGL (SEQ ID NO: 8) and amino acids 588-594 are RTIGPSV (SEQ ID NO: 35); (c) an amino acid sequence that has at least 95% sequence identity to amino acids 138-742 of SEQ ID NO: 32, wherein amino acids 445-451 are RTIGPSV (SEQ ID NO: 35) and amino acids 589-594 are RGDLGL (SEQ ID NO: 8); (d) an amino acid sequence that has at least 95% sequence identity to amino acids 138-742 of SEQ ID NO: 33, wherein amino acids 445-451 are LSSRLDA (SEQ ID NO: 36) and amino acids 589-594 are RGDLGL (SEQ ID NO: 8); or (e) an amino acid sequence that has at least 95% sequence identity to amino acids 138-744 of SEQ ID NO: 34, wherein amino acids 445-453 are APLTNTVKA (SEQ ID NO: 2) and amino acids 591-596 are RGDLGL (SEQ ID NO: 8).

In an embodiment, the recombinant AAV capsid protein comprises: (a) an amino acid sequence that has at least 99% sequence identity to amino acids 138-745 of SEQ ID NO: 30 wherein amino acids 449-454 are RGDLGL (SEQ ID NO: 8) and amino acids 592-597 are RGDLGL (SEQ ID NO: 8); (b) an amino acid sequence that has at least 99% sequence identity to amino acids 138-742 of SEQ ID NO: 31, wherein amino acids 449-454 are RGDLGL (SEQ ID NO: 8) and amino acids 588-594 are RTIGPSV (SEQ ID NO: 35); (c) an amino acid sequence that has at least 99% sequence identity to amino acids 138-742 of SEQ ID NO: 32, wherein amino acids 445-451 are RTIGPSV (SEQ ID NO: 35) and amino acids 589-594 are RGDLGL (SEQ ID NO: 8); (d) an amino acid sequence that has at least 99% sequence identity to amino acids 138-742 of SEQ ID NO: 33, wherein amino acids 445-451 are LSSRLDA (SEQ ID NO: 36) and amino acids 589-594 are RGDLGL (SEQ ID NO: 8); or (e) an amino acid sequence that has at least 99% sequence identity to amino acids 138-744 of SEQ ID NO: 34, wherein amino acids 445-453 are APLTNTVKA (SEQ ID NO: 2) and amino acids 591-596 are RGDLGL (SEQ ID NO: 8).

In an embodiment, the recombinant AAV capsid protein comprises: (a) an amino acid sequence that has 100% sequence identity to amino acids 138-763 of SEQ ID NO: 30;

- (b) an amino acid sequence that has 100% sequence identity to amino acids 138-763 of SEQ ID NO: 31; (c) an amino acid sequence that has 100% sequence identity to amino acids 138-734 of SEQ ID NO: 32; (d) an amino acid sequence that has 100% sequence identity to amino acids 138-734 of SEQ ID NO: 33; or (e) an amino acid sequence that has 100% sequence identity to amino acids 138-732 of SEQ ID NO: 34.

In an embodiment, the recombinant AAV capsid protein comprises: (a) an amino acid sequence that has at least 95% sequence identity to amino acids 1-745 of SEQ ID NO: 30 wherein amino acids 449-454 are RGDLGL (SEQ ID NO: 8) and amino acids 592-597 are RGDLGL (SEQ ID NO: 8); (b) an amino acid sequence that has at least 95% sequence identity to amino acids 1-742 of SEQ ID NO: 31, wherein amino acids 449-454 are RGDLGL (SEQ ID NO: 8) and amino acids 588-594 are RTIGPSV (SEQ ID NO: 35); (c) an amino acid sequence that has at least 95% sequence identity to amino acids 1-742 of SEQ ID NO: 32, wherein amino acids 445-451 are RTIGPSV (SEQ ID NO: 35) and amino acids 589-594 are RGDLGL (SEQ ID NO: 8); (d) an amino acid sequence that has at least 95% sequence identity to amino acids 1-742 of SEQ ID NO: 33, wherein amino acids 445-451 are LSSRLDA (SEQ ID NO: 36) and amino acids 589-594 are RGDLGL (SEQ ID NO: 8); or (e) an amino acid sequence that has at least 95% sequence identity to amino acids 1-744 of SEQ ID NO: 34, wherein amino acids 445-453 are APLTNTVKA (SEQ ID NO: 2) and amino acids 591-596 are RGDLGL (SEQ ID NO: 8).

In an embodiment, the recombinant AAV capsid protein comprises: (a) an amino acid sequence that has at least 99% sequence identity to amino acids 1-745 of SEQ ID NO: 30 wherein amino acids 449-454 are RGDLGL (SEQ ID NO: 8) and amino acids 592-597 are RGDLGL (SEQ ID NO: 8); (b) an amino acid sequence that has at least 99% sequence identity to amino acids 1-742 of SEQ ID NO: 31, wherein amino acids 449-454 are RGDLGL (SEQ ID NO: 8) and amino acids 588-594 are RTIGPSV (SEQ ID NO: 35); (c) an amino acid sequence that has at least 99% sequence identity to amino acids 1-742 of SEQ ID NO: 32, wherein amino acids 445-451 are RTIGPSV (SEQ ID NO: 35) and amino acids 589-594 are RGDLGL (SEQ ID NO: 8); (d) an amino acid sequence that has at least 99% sequence identity to amino acids 1-742 of SEQ ID NO: 33, wherein amino acids 445-451 are LSSRLDA (SEQ ID NO: 36) and amino acids 589-594 are RGDLGL (SEQ ID NO: 8); or (e) an amino acid sequence that has at least 99% sequence identity to amino acids 1-744 of SEQ ID NO: 34, wherein amino acids 445-453 are APLTNTVKA (SEQ ID NO: 2) and amino acids 591-596 are RGDLGL (SEQ ID NO: 8).

In an embodiment, the recombinant AAV capsid protein comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 30-34. In an embodiment, the amino acid sequence of the recombinant AAV capsid protein consists of an amino acid sequence selected from the group consisting of SEQ ID NOs: 30-34.

In an aspect, provided herein is an isolated polynucleotide encoding a recombinant AAV capsid protein disclosed herein.

In an aspect, provided herein is a vector comprising a polynucleotide disclosed herein.

In an embodiment, the vector is a plasmid or a viral vector. In an embodiment, the viral vector is a retrovirus vector, a herpes virus vector, a baculovirus vector, or an adenovirus vector. In an embodiment, the vector is an expression vector.

In an aspect, provided herein is a recombinant cell comprising a polynucleotide or a vector disclosed herein.

In an aspect, provided herein is a method of producing an AAV capsid protein, the method comprising culturing a recombinant cell disclosed herein under conditions where the polynucleotide is expressed, and the capsid protein is produced.

In an aspect, provided herein is a recombinant adeno-associated virus (rAAV) comprising a capsid comprising one or more recombinant capsid protein disclosed herein; and an rAAV genome.

In an embodiment, the rAAV genome comprises a transgene. In an embodiment, the transgene encodes a polypeptide or non-coding RNA. In an embodiment, the transgene encodes an antibody or a fragment thereof. In an embodiment, the transgene encodes an scFv, nanobody, or VHH.

In an aspect, provided herein is a method of delivering a transgene to a cell, the method comprising contacting the cell with an rAAV disclosed herein, under conditions where the cell is transduced, and the transgene is expressed. In an embodiment, the cell is a muscle cell, microglia, astrocyte, neuron, or cardiomyocyte.

In an aspect, provided herein is a method of delivering a transgene to muscle tissue in a subject in need thereof, the method comprising administering an rAAV disclosed herein. In an embodiment, the subject has a disease associated with muscle tissue.

In an embodiment, the neuromuscular disease or disorder is selected from the group consisting of myopathy, hereditary cardiomyopathy, metabolic myopathy, distal myopathy, muscular dystrophy, congenital myopathy, spinal muscular atrophy (SMA), motor neuron disease, congenital myopathy, congenital muscular dystrophy, motor neuron disease, Duchenne muscular dystrophy, Becker muscular dystrophy, limb-girdle muscular dystrophies, myotonic dystrophy, myotubular myopathy, centronuclear myopathy, nemaline myopathy, selenoprotein N-related myopathy, Pompe disease, glycogen storage disease III, spinal muscular atrophy, amyotrophic lateral sclerosis, Charcot-Marie-Tooth disease, multiple sclerosis, myositis, polymyositis, and dermatomyositis.

In an embodiment, the neurodegenerative disease or disorder is selected from the group consisting of Motor neuron disease (MND), parkinsonism syndrome, Alzheimer's dementia, progressive supranuclear palsy (PSP), Huntington's disease, multiple system atrophy (MSA), spinocerebellar ataxia (SCA), and Friedreich's ataxia.

In an embodiment, the rAAV is administered to the subject intravenously, intraperitoneally, subcutaneously, intramuscularly, intrathecally, or intradermally.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is a series of pictures showing GFP protein expression levels in human myotubes transduced with the recombinant AAV capsid proteins. FIG. 1B is a graph showing quantification of GFP fluorescence in human myotubes following transduction with recombinant AAV capsid proteins that comprise VyPep7, VyPep8, VyPep9, VyPep11, VyPep12, or VyPep13 compared to the parental capsid protein with no peptide insertion.

FIG. 2 is a graph showing the average intensity of GFP expression in myotubes following transduction with recombinant AAV capsid proteins that comprise VYPep14 or VYPep15 in loop IV or loop VIII compared to parental capsid proteins with no peptide insertion.

FIG. 3A is a graph showing the average intensity of GFP expression in myotubes following transduction with recombinant AAV capsid proteins that comprise VYPep14 in loop IV or loop VIII compared to parental capsid proteins with no peptide insertion. FIG. 3B is a graph showing GFP protein expression in human myotubes following transduction with recombinant AAV capsid proteins that comprise VYPep7 in loop IV or loop VIII compared to parental capsid proteins with no peptide insertion.

FIG. 4A is a graph showing the percent positive GFP human astrocytes following transduction with recombinant AAV capsid proteins that comprise peptide insertions in loop IV or loop VIII compared to parental capsid proteins with no peptide insertion, at an MOI of 1×10⁴. FIG. 4B is a graph showing the percent positive GFP human astrocytes following transduction with recombinant AAV capsid proteins that comprise peptide insertions in loop IV or loop VIII compared to parental capsid proteins with no peptide insertion, at an MOI of 1×10⁶.

FIG. 5 is a graph showing the percent positive GFP iPSC-derived motor neurons following transduction with recombinant AAV capsid proteins that comprise VYPep7 inserted in loop IV or loop VIII compared to parental capsid proteins with no peptide insertion.

FIG. 6A is a graph showing the percent GFP-positive astrocytes transduced with recombinant AAV9-GFP capsids, in a time-course experiment. FIG. 6B is a graph showing the percent GFP-positive astrocytes transduced with recombinant AAV5.2-GFP capsids, in a time-course experiment. FIG. 6C is a graph showing the percent GFP-positive astrocytes transduced with recombinant AAV5.2-VYPep7-loop IV-GFP capsids, in a time-course experiment.

FIG. 7 is a graph showing the percentage of GFP-positive NHP-derived astrocytes transduced with recombinant AAV capsids.

FIGS. 8A-B are graphs showing the percent positive GFP cells on either the blood side (endothelial compartment) or the brain side (astrocyte compartment) of the blood brain barrier in a blood brain barrier microfluid model at day 6 (FIG. 8A) and day 11 (FIG. 8B) post-transduction. Cells were transduced at the blood compartment with recombinant AAV capsid proteins comprising VYPep14 or VYPep7 compared to parental capsid proteins with no peptide insertion and transduction levels was assessed at the blood (endothelial) and brain (astrocytes) compartments. FIG. 8C is a graph showing the average intensity of GFP expression in cells on either the blood side or the brain side 6 or 13 days after transduction of astrocytes with recombinant AAV capsid proteins comprising VYPep14 or VYPep7 compared to parental capsid proteins with no peptide insertion, in a blood brain barrier microfluid model.

FIG. 9A is a graph showing the percentage of GFP-positive astrocytes transduced with recombinant AAV capsids. FIG. 9B is a graph showing the full viral titers (viral genomes/mL) of the recombinant AAV capsids. FIG. 9C is a graph the percent of full capsids (dark grey bars) and percent of aggregates (light grey bar) of the recombinant AAV capsids.

DETAILED DESCRIPTION

Definitions

As used herein, the term “AAV” is a standard abbreviation for adeno-associated virus.

As used herein, the term “parental capsid protein” refers to an AAV capsid protein into which a peptide is inserted. A parental capsid protein can be a naturally occurring AAV capsid protein (e.g., of any clade or clone described in Bello et al. Sci. Rep. 2014 4 (6644), 1-11. doi: 10.1038/srep06644 or Gao et al., J Virol. 2004 June; 78 (12): 6381-6388. doi: 10.1128/JVI.78.12.6381-6388.2004) or a non-naturally occurring AAV capsid protein. Suitable non-naturally occurring AAV capsid proteins include, without limitation, chimeric capsid proteins and capsid proteins engineered to contain one or more amino acid insertion, deletion, or substitution relative to a naturally occurring AAV capsid protein.

As used herein, the term “recombinant adeno-associated virus” or “rAAV” refers to an AAV comprising a genome lacking functional rep and cap genes.

As used herein, the term “cap gene” refers to a nucleic acid sequence that encodes a capsid protein. For AAV, the capsid protein may be VP1, VP2, or VP3. VP1, VP2, and/or VP3 capsid proteins assemble into a capsid that surrounds the rAAV genome.

As used herein, the term “rep gene” refers to the nucleic acid sequences that encode the non-structural proteins (e.g., rep78, rep68, rep52, and rep40) required for the replication and production of an AAV.

As used herein, the term “loop IV” refers to the amino acids in an AAV capsid protein corresponding to amino acids 434-466 of SEQ ID NO: 10 or 435-467 of SEQ ID NO: 11. or the corresponding amino acid of a different parental capsid protein. In an embodiment, amino acid 444 of SEQ ID NO: 11 corresponds with amino acid 451 of an AAV2 capsid, amino acid 443 of an AAV5 capsid, or amino acid 444 of an AAV9 capsid.

As used herein, the term “loop VIII” refers to the amino acids in an AAV capsid protein corresponding to amino acids 563-592 of SEQ ID NO: 10 or 564-593 of SEQ ID NO: 11. or the corresponding amino acid of a different parental capsid protein.

As used herein, the term “rAAV genome” refers to a nucleic acid molecule (e.g., DNA and/or RNA) comprising the genome sequence of an rAAV. The skilled artisan will appreciate that where an rAAV genome comprises a transgene (e.g., an antibody heavy chain or light chain coding sequence operably linked to a transcriptional regulatory element), the rAAV genome can be in the sense or antisense orientation relative to the direction of transcription of the transgene.

As used herein, an “isolated polynucleotide” refers to a polynucleotide that has been separated from one or more nucleic acid molecules present in the natural source of the polynucleotide.

As used herein, a “vector” refers to a nucleic acid molecule that is a vehicle for introducing a nucleic acid molecule (e.g., a polynucleotide disclosed herein) into a cell.

As used herein, an “expression vector” refers to a vector comprising transcriptional regulatory elements operably linked to a gene of interest (e.g., a polynucleotide disclosed herein) that facilitate the expression of the gene of interest in a cell and/or a cell free expression system.

As used herein, the term “transgene” refers to a non-AAV nucleic acid sequence that encodes a polypeptide (e.g., an antibody or scFv) or non-coding RNA (e.g., an miRNA, shRNA, siRNA, antisense RNA, gRNA, antagomir, miRNA sponge, RNA aptazyme, or RNA aptamer).

As used herein, the term “transcriptional regulatory element” or “TRE” refers to a cis-acting nucleotide sequence, for example, a DNA sequence, that regulates (e.g., controls, increases, or reduces) transcription of an operably linked nucleotide sequence by an RNA polymerase to form an RNA molecule. A TRE may comprise one or more promoter elements and/or enhancer elements. A skilled artisan would appreciate that the promoter and enhancer elements in a gene may be close in location, and the term “promoter” may refer to a sequence comprising a promoter element and an enhancer element. Thus, the term “promoter” does not exclude an enhancer element in the sequence. The promoter and enhancer elements do not need to be derived from the same gene or species, and the sequence of each promoter or enhancer element may be either identical or substantially identical to the corresponding endogenous sequence in the genome.

As used herein, the term “operably linked” is used to describe the connection between a TRE and a polynucleotide sequence (e.g., a transgene disclosed herein) to be transcribed. Typically, gene expression is placed under the control of a TRE comprising one or more promoter and/or enhancer elements. The transgene is “operably linked” to the TRE if the transcription of the transgene is controlled or influenced by the TRE. The promoter and enhancer elements of the TRE may be in any orientation and/or distance from the transgene, as long as the desired transcriptional activity is obtained. In an embodiment, the TRE is upstream from the transgene.

As used herein, the “percentage identity” between two nucleotide sequences or between two amino acid sequences is calculated by multiplying the number of matches between the pair of aligned sequences by 100, and dividing by the length of the aligned region, including internal gaps. Identity scoring only counts perfect matches and does not consider the degree of similarity of amino acids to one another. When a sequence is described herein as being a certain percentage identical to a reference sequence, the percentage identity to the reference sequence is determined across the full length of the reference sequence.

As used herein, the term “effective amount” in the context of the administration of an AAV to a subject refers to the amount of the AAV that achieves a desired prophylactic or therapeutic effect.

AAV Capsid Proteins

In an aspect, provided herein is a recombinant adeno-associated virus (AAV) capsid protein comprising a peptide and a parental AAV capsid protein. The amino acid sequences of exemplary peptides used in the recombinant AAV capsid proteins disclosed herein are provided in Table 1 below.

TABLE 1

Amino acid sequences of

exemplary peptides

SEQ

Description
ID NO
Amino acid sequence

VYPep1
1
ASLEEEWAQVECEVYGRGC

PSGSLDESFYDWFERQLGA

VYPep7
2
APLTNTVKA

VYPep8
3
DDTRHWG

VYPep9
4
EYHHYNK

VYPep10
5
QLFPLFR

VYPep12
6
FNPVTGEVPPRYPLDAR

VYPep13
7
SVTEQGAELSNEER

VYPep14
8
RGDLGL

VYPep15
9
ASSLNIA

In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 1, and the peptide is comprised within loop IV of the parental capsid protein. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 2, and the peptide is comprised within loop IV of the parental capsid protein. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 3, and the peptide is comprised within loop IV of the parental capsid protein. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 4, and the peptide is comprised within loop IV of the parental capsid protein. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 5, and the peptide is comprised within loop IV of the parental capsid protein. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 6, and the peptide is comprised within loop IV of the parental capsid protein. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 7, and the peptide is comprised within loop IV of the parental capsid protein. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 8, and the peptide is comprised within loop IV of the parental capsid protein. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 9, and the peptide is comprised within loop IV of the parental capsid protein.

In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 1, and the peptide is comprised within loop VIII of the parental capsid protein. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 2, and the peptide is comprised within loop VIII of the parental capsid protein. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 3, and the peptide is comprised within loop VIII of the parental capsid protein. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 4, and the peptide is comprised within loop VIII of the parental capsid protein. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 5, and the peptide is comprised within loop VIII of the parental capsid protein. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 6, and the peptide is comprised within loop VIII of the parental capsid protein. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 7, and the peptide is comprised within loop VIII of the parental capsid protein. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 8, and the peptide is comprised within loop VIII of the parental capsid protein. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 9, and the peptide is comprised within loop VIII of the parental capsid protein.

In an embodiment, the recombinant AAV capsid protein comprises a first peptide within loop IV of the parental capsid protein and a second peptide within loop VIII of the parental capsid protein. In an embodiment, the first peptide and the second peptide are the same peptide. In an embodiment, the first peptide and the second peptide are different peptides. In an embodiment, the first peptide comprises the amino acid sequence of SEQ ID NO: 1 and the second peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 1-9. In an embodiment, the first peptide comprises the amino acid sequence of SEQ ID NO: 2 and the second peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 1-9. In an embodiment, the first peptide comprises the amino acid sequence of SEQ ID NO: 3 and the second peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 1-9. In an embodiment, the first peptide comprises the amino acid sequence of SEQ ID NO: 4 and the second peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 1-9. In an embodiment, the first peptide comprises the amino acid sequence of SEQ ID NO: 5 and the second peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 1-9. In an embodiment, the first peptide comprises the amino acid sequence of SEQ ID NO: 6 and the second peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 1-9. In an embodiment, the first peptide comprises the amino acid sequence of SEQ ID NO: 7 and the second peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 1-9. In an embodiment, the first peptide comprises the amino acid sequence of SEQ ID NO: 8 and the second peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 1-9. In an embodiment, the first peptide comprises the amino acid sequence of SEQ ID NO: 9 and the second peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 1-9.

In an embodiment, the parental capsid protein is a VP1 capsid protein. In an embodiment, the parental capsid protein is a VP2 capsid protein. In an embodiment, the parental capsid protein is a VP3 capsid protein.

In an embodiment, the parental capsid protein is an engineered variant capsid protein comprising amino acid sequences from at least two different AAV capsid proteins. In an embodiment, the parental capsid protein comprises amino acid sequences from an AAV2 capsid protein and an AAV5 capsid protein. In an embodiment, the parental capsid protein comprises a VP1 amino acid sequence from AAV2 and a VP2 and VP3 amino acid sequence from AAV5.

In an embodiment, the parental capsid protein comprises an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% identity to amino acids 193-724 of SEQ ID NO: 10 or amino acids 194-725 of SEQ ID NO: 11. In an embodiment, the parental capsid protein comprises an amino acid sequence that has at least 99% identity amino acids 193-724 of SEQ ID NO: 10 or amino acids 194-725 of SEQ ID NO: 11. In an embodiment, the parental capsid protein comprises an amino acid sequence that has 100% identity to amino acids 193-724 of SEQ ID NO: 10 or amino acids 194-725 of SEQ ID NO: 11.

In an embodiment, the parental capsid protein comprises an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% identity to amino acids 137-724 of SEQ ID NO: 10 or amino acids 138-725 of SEQ ID NO: 11. In an embodiment, the parental capsid protein comprises an amino acid sequence that has at least 99% identity to amino acids 137-724 of SEQ ID NO: 10 or amino acids 138-725 of SEQ ID NO: 11. In an embodiment, the parental capsid protein comprises an amino acid sequence that has 100% identity to amino acids 137-724 of SEQ ID NO: 10 or amino acids 138-725 of SEQ ID NO: 11.

In an embodiment, the parental capsid protein comprises an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% identity to the amino acid sequence of SEQ ID NO: 10 or 11. In an embodiment, the parental capsid protein comprises an amino acid sequence that has at least 99% identity to the amino acid sequence of SEQ ID NO: 10 or 11. In an embodiment, the parental capsid protein comprises an amino acid sequence that has 100% identity to the amino acid sequence of SEQ ID NO: 10 or 11.

In an embodiment, the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 440, 441, 442, 443, 444, 445, 446, 447, 572, 573, 574, 575, 576, 577, 578, 579, 580, 581, 582, 583, or 584 of SEQ ID NO: 11.

In an embodiment, the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 440 of SEQ ID NO: 11.

In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 1 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 440 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 2 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 440 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 3 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 440 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 4 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 440 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 5 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 440 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 6 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 440 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 7 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 440 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 8 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 440 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 9 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 440 of SEQ ID NO: 11.

In an embodiment, the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 441 of SEQ ID NO: 11.

In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 1 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 441 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 2 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 441 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 3 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 441 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 4 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 441 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 5 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 441 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 6 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 441 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 7 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 441 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 8 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 441 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 9 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 441 of SEQ ID NO: 11.

In an embodiment, the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 442 of SEQ ID NO: 11.

In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 1 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 442 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 2 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 442 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 3 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 442 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 4 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 442 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 5 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 442 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 6 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 442 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 7 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 442 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 8 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 442 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 9 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 442 of SEQ ID NO: 11.

In an embodiment, the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 443 of SEQ ID NO: 11

In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 1 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 443 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 2 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 443 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 3 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 443 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 4 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 443 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 5 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 443 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 6 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 443 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 7 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 443 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 8 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 443 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 9 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 443 of SEQ ID NO: 11.

In an embodiment, the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 444 of SEQ ID NO: 11.

In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 1 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 444 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 2 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 444 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 3 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 444 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 4 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 444 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 5 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 444 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 6 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 444 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 7 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 444 of SEQ ID NO: 11, or the corresponding amino acid of a different parental capsid protein. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 8 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 444 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 9 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 444 of SEQ ID NO: 11.

In an embodiment, the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 445 of SEQ ID NO: 11.

In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 1 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 445 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 2 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 445 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 3 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 445 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 4 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 445 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 5 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 445 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 6 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 445 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 7 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 445 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 8 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 445 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 9 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 445 of SEQ ID NO: 11.

In an embodiment, the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 446 of SEQ ID NO: 11.

In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 1 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 446 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 2 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 446 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 3 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 446 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 4 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 446 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 5 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 446 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 6 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 446 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 7 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 446 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 8 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 446 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 9 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 446 of SEQ ID NO: 11.

In an embodiment, the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 447 of SEQ ID NO: 11.

In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 1 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 447 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 2 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 447 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 3 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 447 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 4 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 447 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 5 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 447 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 6 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 447 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 7 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 447 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 8 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 447 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 9 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 447 of SEQ ID NO: 11.

In an embodiment, the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 572 of SEQ ID NO: 11.

In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 1 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 572 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 2 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 572 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 3 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 572 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 4 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 572 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 5 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 572 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 6 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 572 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 7 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 572 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 8 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 572 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 9 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 572 of SEQ ID NO: 11.

In an embodiment, the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 573 of SEQ ID NO: 11.

In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 1 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 573 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 2 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 573 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 3 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 573 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 4 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 573 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 5 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 573 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 6 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 573 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 7 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 573 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 8 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 573 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 9 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 573 of SEQ ID NO: 11.

In an embodiment, the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 574 of SEQ ID NO: 11.

In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 1 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 574 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 2 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 574 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 3 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 574 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 4 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 574 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 5 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 574 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 6 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 574 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 7 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 574 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 8 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 574 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 9 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 574 of SEQ ID NO: 11.

In an embodiment, the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 575 of SEQ ID NO: 11.

In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 1 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 575 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 2 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 575 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 3 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 575 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 4 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 575 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 5 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 575 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 6 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 575 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 7 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 575 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 8 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 575 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 9 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 575 of SEQ ID NO: 11.

In an embodiment, the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 576 of SEQ ID NO: 11.

In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 1 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 576 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 2 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 576 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 3 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 576 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 4 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 576 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 5 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 576 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 6 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 576 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 7 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 576 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 8 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 576 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 9 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 576 of SEQ ID NO: 11.

In an embodiment, the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 577 of SEQ ID NO: 11.

In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 1 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 577 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 2 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 577 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 3 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 577 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 4 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 577 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 5 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 577 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 6 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 577 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 7 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 577 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 8 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 577 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 9 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 577 of SEQ ID NO: 11.

In an embodiment, the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 578 of SEQ ID NO: 11.

In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 1 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 578 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 2 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 578 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 3 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 578 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 4 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 578 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 5 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 578 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 6 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 578 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 7 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 578 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 8 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 578 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 9 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 578 of SEQ ID NO: 11.

In an embodiment, the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 579 of SEQ ID NO: 11.

In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 1 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 579 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 2 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 579 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 3 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 579 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 4 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 579 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 5 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 579 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 6 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 579 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 7 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 579 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 8 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 579 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 9 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 579 of SEQ ID NO: 11.

In an embodiment, the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 580 of SEQ ID NO: 11.

In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 1 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 580 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 2 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 580 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 3 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 580 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 4 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 580 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 5 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 580 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 6 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 580 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 7 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 580 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 8 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 580 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 9 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 580 of SEQ ID NO: 11.

In an embodiment, the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 581 of SEQ ID NO: 11.

In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 1 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 581 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 2 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 581 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 3 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 581 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 4 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 581 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 5 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 581 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 6 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 581 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 7 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 581 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 8 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 581 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 9 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 581 of SEQ ID NO: 11.

In an embodiment, the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 582 of SEQ ID NO: 11.

In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 1 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 582 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 2 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 582 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 3 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 582 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 4 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 582 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 5 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 582 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 6 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 582 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 7 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 582 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 8 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 582 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 9 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 582 of SEQ ID NO: 11.

In an embodiment, the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 583 of SEQ ID NO: 11.

In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 1 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 583 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 2 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 583 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 3 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 583 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 4 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 583 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 5 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 583 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 6 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 583 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 7 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 583 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 8 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 583 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 9 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 583 of SEQ ID NO: 11.

In an embodiment, the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 584 of SEQ ID NO: 11.

In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 1 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 584 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 2 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 584 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 3 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 584 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 4 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 584 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 5 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 584 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 6 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 584 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 7 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 584 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 8 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 584 of SEQ ID NO: 11. In an embodiment, the peptide comprises the amino acid sequence of SEQ ID NO: 9 and the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 584 of SEQ ID NO: 11.

In an embodiment, the recombinant AAV capsid protein comprises an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 194-763 of SEQ ID NO: 12, wherein amino acids 445-482 are ASLEEEWAQVECEVYGRGCPSGSLDESFYDWFERQLGA (SEQ ID NO: 1); an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 194-763 of SEQ ID NO: 13, wherein amino acids 578-615 are ASLEEEWAQVECEVYGRGCPSGSLDESFYDWFERQLGA (SEQ ID NO: 1); an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 194-734 of SEQ ID NO: 14, wherein amino acids 445-453 are APLTNTVKA (SEQ ID NO: 2); an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 194-734 of SEQ ID NO: 15, wherein amino acids 578-586 are APLTNTVKA (SEQ ID NO: 2); an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 194-732 of SEQ ID NO: 16, wherein amino acids 445-451 are DDTRHWG (SEQ ID NO: 3); an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 194-732 of SEQ ID NO: 17, wherein amino acids 578-584 are DDTRHWG (SEQ ID NO: 3); an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 194-732 of SEQ ID NO: 18, wherein amino acids 445-451 are EYHHYNK (SEQ ID NO: 4); an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 194-732 of SEQ ID NO: 19, wherein amino acids 578-584 are EYHHYNK (SEQ ID NO: 4); an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 194-732 of SEQ ID NO: 20, wherein amino acids 445-451 are QLFPLFR (SEQ ID NO: 5); an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 194-732 of SEQ ID NO: 21, wherein amino acids 578-584 are QLFPLFR (SEQ ID NO: 5); an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 194-742 of SEQ ID NO: 22, wherein amino acids 445-461 are FNPVTGEVPPRYPLDAR (SEQ ID NO: 6); an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 194-742 of SEQ ID NO: 23, wherein amino acids 578-594 are FNPVTGEVPPRYPLDAR (SEQ ID NO: 6); an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 194-739 of SEQ ID NO: 24, wherein amino acids 445-458 are SVTEQGAELSNEER (SEQ ID NO: 7); an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 194-739 of SEQ ID NO: 25, wherein amino acids 578-591 are SVTEQGAELSNEER (SEQ ID NO: 7); an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 194-735 of SEQ ID NO: 26, wherein amino acids 449-454 are RGDLGL (SEQ ID NO: 8); an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 194-735 of SEQ ID NO: 27, wherein amino acids 578-584 are RGDLGL (SEQ ID NO: 8); an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 194-737 of SEQ ID NO: 28, wherein amino acids 447-453 are ASSLNIA (SEQ ID NO: 9); or an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 194-737 of SEQ ID NO: 29, wherein amino acids 580-586 are ASSLNIA (SEQ ID NO: 9).

In an embodiment, the recombinant AAV capsid protein comprises an amino acid sequence that has at least 99% sequence identity to amino acids 194-763 of SEQ ID NO: 12, wherein amino acids 445-482 are ASLEEEWAQVECEVYGRGCPSGSLDESFYDWFERQLGA (SEQ ID NO: 1); an amino acid sequence that has at least 99% sequence identity to amino acids 194-763 of SEQ ID NO: 13, wherein amino acids 578-615 are 13, ASLEEEWAQVECEVYGRGCPSGSLDESFYDWFERQLGA (SEQ ID NO: 1); an amino acid sequence that has at least 99% sequence identity to amino acids 194-734 of SEQ ID NO: 14, wherein amino acids 445-453 are APLTNTVKA (SEQ ID NO: 2); an amino acid sequence that has at least 99% sequence identity to amino acids 194-734 of SEQ ID NO: 15, wherein amino acids 578-586 are APLTNTVKA (SEQ ID NO: 2); an amino acid sequence that has at least 99% sequence identity to amino acids 194-732 of SEQ ID NO: 16, wherein amino acids 445-451 are DDTRHWG (SEQ ID NO: 3); an amino acid sequence that has at least 99% sequence identity to amino acids 194-732 of SEQ ID NO: 17, wherein amino acids 578-584 are DDTRHWG (SEQ ID NO: 3); an amino acid sequence that has at least 99% sequence identity to amino acids 194-732 of SEQ ID NO: 18, wherein amino acids 445-451 are EYHHYNK (SEQ ID NO: 4); an amino acid sequence that has at least 99% sequence identity to amino acids 194-732 of SEQ ID NO: 19, wherein amino acids 578-584 are EYHHYNK (SEQ ID NO: 4); an amino acid sequence that has at least 99% sequence identity to amino acids 194-732 of SEQ ID NO: 20, wherein amino acids 445-451 are QLFPLFR (SEQ ID NO: 5); an amino acid sequence that has at least 99% sequence identity to amino acids 194-732 of SEQ ID NO: 21, wherein amino acids 578-584 are QLFPLFR (SEQ ID NO: 5); an amino acid sequence that has at least 99% sequence identity to amino acids 194-742 of SEQ ID NO: 22, wherein amino acids 445-461 are FNPVTGEVPPRYPLDAR (SEQ ID NO: 6); an amino acid sequence that has at least 99% sequence identity to amino acids 194-742 of SEQ ID NO: 23, wherein amino acids 578-594 are FNPVTGEVPPRYPLDAR (SEQ ID NO: 6); an amino acid sequence that has at least 99% sequence identity to amino acids 194-739 of SEQ ID NO: 24, wherein amino acids 445-458 are SVTEQGAELSNEER (SEQ ID NO: 7); an amino acid sequence that has at least 99% sequence identity to amino acids 194-739 of SEQ ID NO: 25, wherein amino acids 578-591 are SVTEQGAELSNEER (SEQ ID NO: 7); an amino acid sequence that has at least 99% sequence identity to amino acids 194-735 of SEQ ID NO: 26, wherein amino acids 449-454 are RGDLGL (SEQ ID NO: 8); an amino acid sequence that has at least 99% sequence identity to amino acids 194-735 of SEQ ID NO: 27, wherein amino acids 578-584 are RGDLGL (SEQ ID NO: 8); an amino acid sequence that has at least 99% sequence identity to amino acids 194-737 of SEQ ID NO: 28, wherein amino acids 447-453 are ASSLNIA (SEQ ID NO: 9); or an amino acid sequence that has at least 99% sequence identity to amino acids 194-737 of SEQ ID NO: 29, wherein amino acids 580-586 are ASSLNIA (SEQ ID NO: 9).

In an embodiment, the recombinant AAV capsid protein comprises an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 138-763 of SEQ ID NO: 12, wherein amino acids 445-482 are ASLEEEWAQVECEVYGRGCPSGSLDESFYDWFERQLGA (SEQ ID NO: 1); an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 138-763 of SEQ ID NO: 13, wherein amino acids 578-615 are ASLEEEWAQVECEVYGRGCPSGSLDESFYDWFERQLGA (SEQ ID NO: 1); an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 138-734 of SEQ ID NO: 14, wherein amino acids 445-453 are APLTNTVKA (SEQ ID NO: 2); an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 138-734 of SEQ ID NO: 15, wherein amino acids 578-586 are APLTNTVKA (SEQ ID NO: 2); an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 138-732 of SEQ ID NO: 16, wherein amino acids 445-451 are DDTRHWG (SEQ ID NO: 3); an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 138-732 of SEQ ID NO: 17, wherein amino acids 578-584 are DDTRHWG (SEQ ID NO: 3); an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 138-732 of SEQ ID NO: 18, wherein amino acids 445-451 are EYHHYNK (SEQ ID NO: 4); an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 138-732 of SEQ ID NO: 19, wherein amino acids 578-584 are EYHHYNK (SEQ ID NO: 4); an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 138-732 of SEQ ID NO: 20, wherein amino acids 445-451 are QLFPLFR (SEQ ID NO: 5); an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 138-732 of SEQ ID NO: 21, wherein amino acids 578-584 are QLFPLFR (SEQ ID NO: 5); an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 138-742 of SEQ ID NO: 22, wherein amino acids 445-461 are FNPVTGEVPPRYPLDAR (SEQ ID NO: 6); an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 138-742 of SEQ ID NO: 23, wherein amino acids 578-594 are FNPVTGEVPPRYPLDAR (SEQ ID NO: 6); an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 138-739 of SEQ ID NO: 24, wherein amino acids 445-458 are SVTEQGAELSNEER (SEQ ID NO: 7); an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 138-739 of SEQ ID NO: 25, wherein amino acids 578-591 are SVTEQGAELSNEER (SEQ ID NO: 7); an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 138-735 of SEQ ID NO: 26, wherein amino acids 449-454 are RGDLGL (SEQ ID NO: 8); an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 138-735 of SEQ ID NO: 27, wherein amino acids 578-584 are RGDLGL (SEQ ID NO: 8); an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 138-737 of SEQ ID NO: 28, wherein amino acids 447-453 are ASSLNIA (SEQ ID NO: 9); or an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 138-737 of SEQ ID NO: 29, wherein amino acids 580-586 are ASSLNIA (SEQ ID NO: 9).

In an embodiment, the recombinant AAV capsid protein comprises an amino acid sequence that has at least 99% sequence identity to amino acids 138-763 of SEQ ID NO: 12, wherein amino acids 445-482 are ASLEEEWAQVECEVYGRGCPSGSLDESFYDWFERQLGA (SEQ ID NO: 1); an amino acid sequence that has at least 99% sequence identity to amino acids 138-763 of SEQ ID NO: 13, wherein amino 13, acids 578-615 are ASLEEEWAQVECEVYGRGCPSGSLDESFYDWFERQLGA (SEQ ID NO: 1); an amino acid sequence that has at least 99% sequence identity to amino acids 138-734 of SEQ ID NO: 14, wherein amino acids 445-453 are APLTNTVKA (SEQ ID NO: 2); an amino acid sequence that has at least 99% sequence identity to amino acids 138-734 of SEQ ID NO: 15, wherein amino acids 578-586 are APLTNTVKA (SEQ ID NO: 2); an amino acid sequence that has at least 99% sequence identity to amino acids 138-732 of SEQ ID NO: 16, wherein amino acids 445-451 are DDTRHWG (SEQ ID NO: 3); an amino acid sequence that has at least 99% sequence identity to amino acids 138-732 of SEQ ID NO: 17, wherein amino acids 578-584 are DDTRHWG (SEQ ID NO: 3); an amino acid sequence that has at least 99% sequence identity to amino acids 138-732 of SEQ ID NO: 18, wherein amino acids 445-451 are EYHHYNK (SEQ ID NO: 4); an amino acid sequence that has at least 99% sequence identity to amino acids 138-732 of SEQ ID NO: 19, wherein amino acids 578-584 are EYHHYNK (SEQ ID NO: 4); an amino acid sequence that has at least 99% sequence identity to amino acids 138-732 of SEQ ID NO: 20, wherein amino acids 445-451 are QLFPLFR (SEQ ID NO: 5); an amino acid sequence that has at least 99% sequence identity to amino acids 138-732 of SEQ ID NO: 21, wherein amino acids 578-584 are QLFPLFR (SEQ ID NO: 5); an amino acid sequence that has at least 99% sequence identity to amino acids 138-742 of SEQ ID NO: 22, wherein amino acids 445-461 are FNPVTGEVPPRYPLDAR (SEQ ID NO: 6); an amino acid sequence that has at least 99% sequence identity to amino acids 138-742 of SEQ ID NO: 23, wherein amino acids 578-594 are FNPVTGEVPPRYPLDAR (SEQ ID NO: 6); an amino acid sequence that has at least 99% sequence identity to amino acids 138-739 of SEQ ID NO: 24, wherein amino acids 445-458 are SVTEQGAELSNEER (SEQ ID NO: 7); an amino acid sequence that has at least 99% sequence identity to amino acids 138-739 of SEQ ID NO: 25, wherein amino acids 578-591 are SVTEQGAELSNEER (SEQ ID NO: 7); an amino acid sequence that has at least 99% sequence identity to amino acids 138-735 of SEQ ID NO: 26, wherein amino acids 449-454 are RGDLGL (SEQ ID NO: 8); an amino acid sequence that has at least 99% sequence identity to amino acids 138-735 of SEQ ID NO: 27, wherein amino acids 578-584 are RGDLGL (SEQ ID NO: 8); an amino acid sequence that has at least 99% sequence identity to amino acids 138-737 of SEQ ID NO: 28, wherein amino acids 447-453 are ASSLNIA (SEQ ID NO: 9); or an amino acid sequence that has at least 99% sequence identity to amino acids 138-737 of SEQ ID NO: 29, wherein amino acids 580-586 are ASSLNIA (SEQ ID NO: 9).

In an embodiment, the recombinant AAV capsid protein comprises an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 1-763 of SEQ ID NO: 12, wherein amino acids 445-482 are ASLEEEWAQVECEVYGRGCPSGSLDESFYDWFERQLGA (SEQ ID NO: 1); an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 1-763 of SEQ ID NO: 13, wherein amino acids 578-615 are ASLEEEWAQVECEVYGRGCPSGSLDESFYDWFERQLGA (SEQ ID NO: 1); an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 1-734 of SEQ ID NO: 14, wherein amino acids 445-453 are APLTNTVKA (SEQ ID NO: 2); an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 1-734 of SEQ ID NO: 15, wherein amino acids 578-586 are APLTNTVKA (SEQ ID NO: 2); an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 1-732 of SEQ ID NO: 16, wherein amino acids 445-451 are DDTRHWG (SEQ ID NO: 3); an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 1-732 of SEQ ID NO: 17, wherein amino acids 578-584 are DDTRHWG (SEQ ID NO: 3); an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 1-732 of SEQ ID NO: 18, wherein amino acids 445-451 are EYHHYNK (SEQ ID NO: 4); an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 1-732 of SEQ ID NO: 19, wherein amino acids 578-584 are EYHHYNK (SEQ ID NO: 4); an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 1-732 of SEQ ID NO: 20, wherein amino acids 445-451 are QLFPLFR (SEQ ID NO: 5); an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 1-732 of SEQ ID NO: 21, wherein amino acids 578-584 are QLFPLFR (SEQ ID NO: 5); an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 1-742 of SEQ ID NO: 22, wherein amino acids 445-461 are FNPVTGEVPPRYPLDAR (SEQ ID NO: 6); an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 1-742 of SEQ ID NO: 23, wherein amino acids 578-594 are FNPVTGEVPPRYPLDAR (SEQ ID NO: 6); an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 1-739 of SEQ ID NO: 24, wherein amino acids 445-458 are SVTEQGAELSNEER (SEQ ID NO: 7); an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 1-739 of SEQ ID NO: 25, wherein amino acids 578-591 are SVTEQGAELSNEER (SEQ ID NO: 7); an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 1-735 of SEQ ID NO: 26, wherein amino acids 449-454 are RGDLGL (SEQ ID NO: 8); an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 1-735 of SEQ ID NO: 27, wherein amino acids 578-584 are RGDLGL (SEQ ID NO: 8); an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 1-737 of SEQ ID NO: 28, wherein amino acids 447-453 are ASSLNIA (SEQ ID NO: 9); or an amino acid sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% sequence identity to amino acids 1-737 of SEQ ID NO: 29, wherein amino acids 580-586 are ASSLNIA (SEQ ID NO: 9).

In an embodiment, the recombinant AAV capsid protein comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 12-29. In an embodiment, the amino acid sequence of the recombinant AAV capsid protein consists of an amino acid sequence selected from the group consisting of SEQ ID NO: 12-29.

In an embodiment, the peptide is linked (i.e., connected by a peptide bond) directly to the amino acids of the parental AAV capsid protein. In an embodiment, the peptide is linked to the amino acids of the parental AAV capsid protein via an amino acid linker. In an embodiment, the peptide comprises an N-terminal linker. In an embodiment, the peptide comprises a C-terminal linker. In an embodiment, the peptide comprises an N-terminal linker and a C-terminal linker. Suitable linkers include, without limitation, a G linker (AG), GS linker (GS), and a GG linker (GG), TG, GLS, or GQSG.

In an embodiment, the recombinant AAV capsid proteins disclosed herein bind to a protein that is expressed on the cell membrane of a muscle cell. In an embodiment, the recombinant AAV capsid proteins disclosed herein bind to a protein selected from the group consisting of integrin alpha 7 (ITGA7), insulin receptor (INSR/CD220), ADP-ribosyltransferase 1 (ART1), and cadherin 15 (CDH15).

Amino acid sequences of exemplary recombinant AAV capsid proteins provided herein are set forth in Table 2 below.

TABLE 2

Amino acid sequences of exemplary

recombinant AAV capsid proteins

SEQ

ID

Description
NO
Amino acid sequence

AAV5
10
MSFVDHPPDWLEEVGEGLREFLGLEAGPPK

(no peptide

PKPNQQHQDQARGLVLPGYNYLGPGNGLDR

insertion)

GEPVNRADEVAREHDISYNEQLEAGDNPYL

KYNHADAEFQEKLADDTSFGGNLGKAVFQA

KKRVLEPFGLVEEGAKTAPTGKRIDDHFPK

RKKARTEEDSKPSTSSDAEAGPSGSQQLQI

PAQPASSLGADTMSAGGGGPLGDNNQGADG

VGNASGDWHCDSTWMGDRVVTKSTRTWVLP

SYNNHQYREIKSGSVDGSNANAYFGYSTPW

GYFDFNRFHSHWSPRDWQRLINNYWGFRPR

SLRVKIFNIQVKEVTVQDSTTTIANNLTST

VQVFTDDDYQLPYVVGNGTEGCLPAFPPQV

FTLPQYGYATLNRDNTENPTERSSFFCLEY

FPSKMLRTGNNFEFTYNFEEVPFHSSFAPS

QNLFKLANPLVDQYLYRFVSTNNTGGVQFN

KNLAGRYANTYKNWFPGPMGRTQGWNLGSG

VNRASVSAFATTNRMELEGASYQVPPQPNG

MTNNLQGSNTYALENTMIFNSQPANPGTTA

TYLEGNMLITSESETQPVNRVAYNVGGQMA

TNNQSSTTAPATGTYNLQEIVPGSVWMERD

VYLQGPIWAKIPETGAHFHPSPAMGGFGLK

HPPPMMLIKNTPVPGNITSFSDVPVSSFIT

QYSTGQVTVEMEWELKKENSKRWNPEIQYT

NNYNDPQFVDFAPDSTGEYRTTRPIGTRYL

TRPL

AAV5.2 (no
11
MAADGYLPDWLEDTLSEGIRQWWKLKPGPP

peptide

PPKPAERHKDDSRGLVLPGYKYLGPFNGLD

insertion)

KGEPVNEADAAALEHDKAYDRQLDSGDNPY

LKYNHADAEFQERLKEDTSFGGNLGRAVFQ

AKKRVLEPLGLVEEPVKTAPTGKRIDDHFP

KRKKARTEEDSKPSTSSDAEAGPSGSQQLQ

IPAQPASSLGADTMSAGGGGPLGDNNQGAD

GVGNASGDWHCDSTWMGDRVVTKSTRTWVL

PSYNNHQYREIKSGSVDGSNANAYFGYSTP

WGYFDFNRFHSHWSPRDWQRLINNYWGFRP

RSLRVKIFNIQVKEVTVQDSTTTIANNLTS

TVQVFTDDDYQLPYVVGNGTEGCLPAFPPQ

VFTLPQYGYATLNRDNTENPTERSSFFCLE

YFPSKMLRTGNNFEFTYNFEEVPFHSSFAP

SQNLFKLANPLVDQYLYRFVSTNNTGGVQF

NKNLAGRYANTYKNWFPGPMGRTQGWNLGS

GVNRASVSAFATTNRMELEGASYQVPPQPN

GMTNNLQGSNTYALENTMIFNSQPANPGTT

ATYLEGNMLITSESETQPVNRVAYNVGGQM

ATNNQSSTTAPATGTYNLQEIVPGSVWMER

DVYLQGPIWAKIPETGAHFHPSPAMGGFGL

KHPPPMMLIKNTPVPGNITSFSDVPVSSFI

TQYSTGQVTVEMEWELKKENSKRWNPEIQY

TNNYNDPQFVDFAPDSTGEYRTTRPIGTRY

LTRPL

VYPep1,
12
MAADGYLPDWLEDTLSEGIRQWWKLKPGPP

loop IV

PPKPAERHKDDSRGLVLPGYKYLGPFNGLD

insertion

KGEPVNEADAAALEHDKAYDRQLDSGDNPY

LKYNHADAEFQERLKEDTSFGGNLGRAVFQ

AKKRVLEPLGLVEEPVKTAPTGKRIDDHFP

KRKKARTEEDSKPSTSSDAEAGPSGSQQLQ

IPAQPASSLGADTMSAGGGGPLGDNNQGAD

GVGNASGDWHCDSTWMGDRVVTKSTRTWVL

PSYNNHQYREIKSGSVDGSNANAYFGYSTP

WGYFDFNRFHSHWSPRDWQRLINNYWGFRP

RSLRVKIFNIQVKEVTVQDSTTTIANNLTS

TVQVFTDDDYQLPYVVGNGTEGCLPAFPPQ

VFTLPQYGYATLNRDNTENPTERSSFFCLE

YFPSKMLRTGNNFEFTYNFEEVPFHSSFAP

SQNLFKLANPLVDQYLYRFVSTNNASLEEE

WAQVECEVYGRGCPSGSLDESFYDWFERQL

GATGGVQFNKNLAGRYANTYKNWFPGPMGR

TQGWNLGSGVNRASVSAFATTNRMELEGAS

YQVPPQPNGMTNNLQGSNTYALENTMIFNS

QPANPGTTATYLEGNMLITSESETQPVNRV

AYNVGGQMATNNQSSTTAPATGTYNLQEIV

PGSVWMERDVYLQGPIWAKIPETGAHFHPS

PAMGGFGLKHPPPMMLIKNTPVPGNITSFS

DVPVSSFITQYSTGQVTVEMEWELKKENSK

RWNPEIQYTNNYNDPQFVDFAPDSTGEYRT

TRPIGTRYLTRPL

VYPep1,
13
MAADGYLPDWLEDTLSEGIRQWWKLKPGPP

loop VIII

PPKPAERHKDDSRGLVLPGYKYLGPFNGLD

insertion

KGEPVNEADAAALEHDKAYDRQLDSGDNPY

LKYNHADAEFQERLKEDTSFGGNLGRAVFQ

AKKRVLEPLGLVEEPVKTAPTGKRIDDHFP

KRKKARTEEDSKPSTSSDAEAGPSGSQQLQ

IPAQPASSLGADTMSAGGGGPLGDNNQGAD

GVGNASGDWHCDSTWMGDRVVTKSTRTWVL

PSYNNHQYREIKSGSVDGSNANAYFGYSTP

WGYFDFNRFHSHWSPRDWQRLINNYWGFRP

RSLRVKIFNIQVKEVTVQDSTTTIANNLTS

TVQVFTDDDYQLPYVVGNGTEGCLPAFPPQ

VFTLPQYGYATLNRDNTENPTERSSFFCLE

YFPSKMLRTGNNFEFTYNFEEVPFHSSFAP

SQNLFKLANPLVDQYLYRFVSTNNTGGVQF

NKNLAGRYANTYKNWFPGPMGRTQGWNLGS

GVNRASVSAFATTNRMELEGASYQVPPQPN

GMTNNLQGSNTYALENTMIFNSQPANPGTT

ATYLEGNMLITSESETQPVNRVAYNVGGQM

ATNNQSSASLEEEWAQVECEVYGRGCPSGS

LDESFYDWFERQLGATTAPATGTYNLQEIV

PGSVWMERDVYLQGPIWAKIPETGAHFHPS

PAMGGFGLKHPPPMMLIKNTPVPGNITSFS

DVPVSSFITQYSTGQVTVEMEWELKKENSK

RWNPEIQYTNNYNDPQFVDFAPDSTGEYRT

TRPIGTRYLTRPL

VYPep7,
14
MAADGYLPDWLEDTLSEGIRQWWKLKPGPP

loop IV

PPKPAERHKDDSRGLVLPGYKYLGPFNGLD

insertion

KGEPVNEADAAALEHDKAYDRQLDSGDNPY

LKYNHADAEFQERLKEDTSFGGNLGRAVFQ

AKKRVLEPLGLVEEPVKTAPTGKRIDDHF

PKRKKARTEEDSKPSTSSDAEAGPSGSQQL

QIPAQPASSLGADTMSAGGGGPLGDNNQGA

DGVGNASGDWHCDSTWMGDRVVTKSTRTWV

LPSYNNHQYREIKSGSVDGSNANAYFGYST

PWGYFDFNRFHSHWSPRDWQRLINNYWGFR

PRSLRVKIFNIQVKEVTVQDSTTTIANNLT

STVQVFTDDDYQLPYVVGNGTEGCLPAFPP

QVFTLPQYGYATLNRDNTENPTERSSFFCL

EYFPSKMLRTGNNFEFTYNFEEVPFHSSFA

PSQNLFKLANPLVDQYLYRFVSTNNAPLTN

TVKATGGVQFNKNLAGRYANTYKNWFPGPM

GRTQGWNLGSGVNRASVSAFATTNRMELEG

ASYQVPPQPNGMTNNLQGSNTYALENTMIF

NSQPANPGTTATYLEGNMLITSESETQPVN

RVAYNVGGQMATNNQSSTTAPATGTYNLQE

IVPGSVWMERDVYLQGPIWAKIPETGAHFH

PSPAMGGFGLKHPPPMMLIKNTPVPGNITS

FSDVPVSSFITQYSTGQVTVEMEWELKKEN

SKRWNPEIQYTNNYNDPQFVDFAPDSTGEY

RTTRPIGTRYLTRPL

VYPep7,
15
MAADGYLPDWLEDTLSEGIRQWWKLKPGPP

loop VIII

PPKPAERHKDDSRGLVLPGYKYLGPFNGLD

insertion

KGEPVNEADAAALEHDKAYDRQLDSGDNPY

LKYNHADAEFQERLKEDTSFGGNLGRAVFQ

AKKRVLEPLGLVEEPVKTAPTGKRIDDHF

PKRKKARTEEDSKPSTSSDAEAGPSGSQQL

QIPAQPASSLGADTMSAGGGGPLGDNNQGA

DGVGNASGDWHCDSTWMGDRVVTKSTRTWV

LPSYNNHQYREIKSGSVDGSNANAYFGYST

PWGYFDFNRFHSHWSPRDWQRLINNYWGFR

PRSLRVKIFNIQVKEVTVQDSTTTIANNLT

STVQVFTDDDYQLPYVVGNGTEGCLPAFPP

QVFTLPQYGYATLNRDNTENPTERSSFFCL

EYFPSKMLRTGNNFEFTYNFEEVPFHSSFA

PSQNLFKLANPLVDQYLYRFVSTNNTGGVQ

FNKNLAGRYANTYKNWFPGPMGRTQGWNLG

SGVNRASVSAFATTNRMELEGASYQVPPQP

NGMTNNLQGSNTYALENTMIFNSQPANPGT

TATYLEGNMLITSESETQPVNRVAYNVGGQ

MATNNQSSAPLTNTVKATTAPATGTYNLQE

IVPGSVWMERDVYLQGPIWAKIPETGAHFH

PSPAMGGFGLKHPPPMMLIKNTPVPGNITS

FSDVPVSSFITQYSTGQVTVEMEWELKKEN

SKRWNPEIQYTNNYNDPQFVDFAPDSTGEY

RTTRPIGTRYLTRPL

VYPep8,
16
MAADGYLPDWLEDTLSEGIRQWWKLKPGPP

loop IV

PPKPAERHKDDSRGLVLPGYKYLGPFNGLD

insertion

KGEPVNEADAAALEHDKAYDRQLDSGDNPY

LKYNHADAEFQERLKEDTSFGGNLGRAVFQ

AKKRVLEPLGLVEEPVKTAPTGKRIDDHF

PKRKKARTEEDSKPSTSSDAEAGPSGSQQL

QIPAQPASSLGADTMSAGGGGPLGDNNQGA

DGVGNASGDWHCDSTWMGDRVVTKSTRTWV

LPSYNNHQYREIKSGSVDGSNANAYFGYST

PWGYFDFNRFHSHWSPRDWQRLINNYWGFR

PRSLRVKIFNIQVKEVTVQDSTTTIANNLT

STVQVFTDDDYQLPYVVGNGTEGCLPAFPP

QVFTLPQYGYATLNRDNTENPTERSSFFCL

EYFPSKMLRTGNNFEFTYNFEEVPFHSSFA

PSQNLFKLANPLVDQYLYRFVSTNNDDTRH

WGTGGVQFNKNLAGRYANTYKNWFPGPMGR

TQGWNLGSGVNRASVSAFATTNRMELEGAS

YQVPPQPNGMTNNLQGSNTYALENTMIFNS

QPANPGTTATYLEGNMLITSESETQPVNRV

AYNVGGQMATNNQSSTTAPATGTYNLQEIV

PGSVWMERDVYLQGPIWAKIPETGAHFHPS

PAMGGFGLKHPPPMMLIKNTPVPGNITSFS

DVPVSSFITQYSTGQVTVEMEWELKKENSK

RWNPEIQYTNNYNDPQFVDFAPDSTGEYRT

TRPIGTRYLTRPL

VYPep8,
17
MAADGYLPDWLEDTLSEGIRQWWKLKPGPP

loop VIII

PPKPAERHKDDSRGLVLPGYKYLGPFNGLD

insertion

KGEPVNEADAAALEHDKAYDRQLDSGDNPY

LKYNHADAEFQERLKEDTSFGGNLGRAVFQ

AKKRVLEPLGLVEEPVKTAPTGKRIDDHF

PKRKKARTEEDSKPSTSSDAEAGPSGSQQL

QIPAQPASSLGADTMSAGGGGPLGDNNQGA

DGVGNASGDWHCDSTWMGDRVVTKSTRTWV

LPSYNNHQYREIKSGSVDGSNANAYFGYST

PWGYFDFNRFHSHWSPRDWQRLINNYWGFR

PRSLRVKIFNIQVKEVTVQDSTTTIANNLT

STVQVFTDDDYQLPYVVGNGTEGCLPAFPP

QVFTLPQYGYATLNRDNTENPTERSSFFCL

EYFPSKMLRTGNNFEFTYNFEEVPFHSSFA

PSQNLFKLANPLVDQYLYRFVSTNNTGGVQ

FNKNLAGRYANTYKNWFPGPMGRTQGWNLG

SGVNRASVSAFATTNRMELEGASYQVPPQP

NGMTNNLQGSNTYALENTMIFNSQPANPGT

TATYLEGNMLITSESETQPVNRVAYNVGGQ

MATNNQSSDDTRHWGTTAPATGTYNLQEIV

PGSVWMERDVYLQGPIWAKIPETGAHFHPS

PAMGGFGLKHPPPMMLIKNTPVPGNITSFS

DVPVSSFITQYSTGQVTVEMEWELKKENSK

RWNPEIQYTNNYNDPQFVDFAPDSTGEYRT

TRPIGTRYLTRPL

VYPep9,
18
MAADGYLPDWLEDTLSEGIRQWWKLKPGPP

loop IV

PPKPAERHKDDSRGLVLPGYKYLGPFNGLD

insertion

KGEPVNEADAAALEHDKAYDRQLDSGDNPY

LKYNHADAEFQERLKEDTSFGGNLGRAVFQ

AKKRVLEPLGLVEEPVKTAPTGKRIDDHFP

KRKKARTEEDSKPSTSSDAEAGPSGSQQLQ

IPAQPASSLGADTMSAGGGGPLGDNNQGAD

GVGNASGDWHCDSTWMGDRVVTKSTRTWVL

PSYNNHQYREIKSGSVDGSNANAYFGYSTP

WGYFDFNRFHSHWSPRDWQRLINNYWGFRP

RSLRVKIFNIQVKEVTVQDSTTTIANNLTS

TVQVFTDDDYQLPYVVGNGTEGCLPAFPPQ

VFTLPQYGYATLNRDNTENPTERSSFFCLE

YFPSKMLRTGNNFEFTYNFEEVPFHSSFAP

SQNLFKLANPLVDQYLYRFVSTNNEYHHYN

KTGGVQFNKNLAGRYANTYKNWFPGPMGRT

QGWNLGSGVNRASVSAFATTNRMELEGASY

QVPPQPNGMTNNLQGSNTYALENTMIFNSQ

PANPGTTATYLEGNMLITSESETQPVNRVA

YNVGGQMATNNQSSTTAPATGTYNLQEIVP

GSVWMERDVYLQGPIWAKIPETGAHFHPSP

AMGGFGLKHPPPMMLIKNTPVPGNITSFSD

VPVSSFITQYSTGQVTVEMEWELKKENSKR

WNPEIQYTNNYNDPQFVDFAPDSTGEYRTT

RPIGTRYLTRPL

VYPep9,
19
MAADGYLPDWLEDTLSEGIRQWWKLKPGPP

loop VIII

PPKPAERHKDDSRGLVLPGYKYLGPFNGLD

insertion

KGEPVNEADAAALEHDKAYDRQLDSGDNPY

LKYNHADAEFQERLKEDTSFGGNLGRAVFQ

AKKRVLEPLGLVEEPVKTAPTGKRIDDHF

PKRKKARTEEDSKPSTSSDAEAGPSGSQQL

QIPAQPASSLGADTMSAGGGGPLGDNNQGA

DGVGNASGDWHCDSTWMGDRVVTKSTRTWV

LPSYNNHQYREIKSGSVDGSNANAYFGYST

PWGYFDFNRFHSHWSPRDWQRLINNYWGFR

PRSLRVKIFNIQVKEVTVQDSTTTIANNLT

STVQVFTDDDYQLPYVVGNGTEGCLPAFPP

QVFTLPQYGYATLNRDNTENPTERSSFFCL

EYFPSKMLRTGNNFEFTYNFEEVPFHSSFA

PSQNLFKLANPLVDQYLYRFVSTNNTGGVQ

FNKNLAGRYANTYKNWFPGPMGRTQGWNLG

SGVNRASVSAFATTNRMELEGASYQVPPQP

NGMTNNLQGSNTYALENTMIFNSQPANPGT

TATYLEGNMLITSESETQPVNRVAYNVGGQ

MATNNQSSEYHHYNKTTAPATGTYNLQEIV

PGSVWMERDVYLQGPIWAKIPETGAHFHPS

PAMGGFGLKHPPPMMLIKNTPVPGNITSFS

DVPVSSFITQYSTGQVTVEMEWELKKENSK

RWNPEIQYTNNYNDPQFVDFAPDSTGEYRT

TRPIGTRYLTRPL

VYPep10,
20
MAADGYLPDWLEDTLSEGIRQWWKLKPGPP

loop IV

PPKPAERHKDDSRGLVLPGYKYLGPFNGLD

insertion

KGEPVNEADAAALEHDKAYDRQLDSGDNPY

LKYNHADAEFQERLKEDTSFGGNLGRAVFQ

AKKRVLEPLGLVEEPVKTAPTGKRIDDHFP

KRKKARTEEDSKPSTSSDAEAGPSGSQQLQ

IPAQPASSLGADTMSAGGGGPLGDNNQGAD

GVGNASGDWHCDSTWMGDRVVTKSTRTWVL

PSYNNHQYREIKSGSVDGSNANAYFGYSTP

WGYFDFNRFHSHWSPRDWQRLINNYWGFRP

RSLRVKIFNIQVKEVTVQDSTTTIANNLTS

TVQVFTDDDYQLPYVVGNGTEGCLPAFPPQ

VFTLPQYGYATLNRDNTENPTERSSFFCLE

YFPSKMLRTGNNFEFTYNFEEVPFHSSFAP

SQNLFKLANPLVDQYLYRFVSTNNQLFPLF

RTGGVQFNKNLAGRYANTYKNWFPGPMGRT

QGWNLGSGVNRASVSAFATTNRMELEGASY

QVPPQPNGMTNNLQGSNTYALENTMIFNSQ

PANPGTTATYLEGNMLITSESETQPVNRVA

YNVGGQMATNNQSSTTAPATGTYNLQEIVP

GSVWMERDVYLQGPIWAKIPETGAHFHPSP

AMGGFGLKHPPPMMLIKNTPVPGNITSFSD

VPVSSFITQYSTGQVTVEMEWELKKENSKR

WNPEIQYTNNYNDPQFVDFAPDSTGEYRTT

RPIGTRYLTRPL

VYPep10, loop
21
MAADGYLPDWLEDTLSEGIRQWWKLKPGPP

VIII insertion

PPKPAERHKDDSRGLVLPGYKYLGPFNGLD

KGEPVNEADAAALEHDKAYDRQLDSGDNPY

LKYNHADAEFQERLKEDTSFGGNLGRAVFQ

AKKRVLEPLGLVEEPVKTAPTGKRIDDHF

PKRKKARTEEDSKPSTSSDAEAGPSGSQQL

QIPAQPASSLGADTMSAGGGGPLGDNNQGA

DGVGNASGDWHCDSTWMGDRVVTKSTRTWV

LPSYNNHQYREIKSGSVDGSNANAYFGYST

PWGYFDFNRFHSHWSPRDWQRLINNYWGFR

PRSLRVKIFNIQVKEVTVQDSTTTIANNLT

STVQVFTDDDYQLPYVVGNGTEGCLPAFPP

QVFTLPQYGYATLNRDNTENPTERSSFFCL

EYFPSKMLRTGNNFEFTYNFEEVPFHSSFA

PSQNLFKLANPLVDQYLYRFVSTNNTGGVQ

FNKNLAGRYANTYKNWFPGPMGRTQGWNLG

SGVNRASVSAFATTNRMELEGASYQVPPQP

NGMTNNLQGSNTYALENTMIFNSQPANPGT

TATYLEGNMLITSESETQPVNRVAYNVGGQ

MATNNQSSQLFPLFRTTAPATGTYNLQEIV

PGSVWMERDVYLQGPIWAKIPETGAHFHPS

PAMGGFGLKHPPPMMLIKNTPVPGNITSFS

DVPVSSFITQYSTGQVTVEMEWELKKENSK

RWNPEIQYTNNYNDPQFVDFAPDSTGEYRT

TRPIGTRYLTRPL

VYPep12,
22
MAADGYLPDWLEDTLSEGIRQWWKLKPGPP

loop IV

PPKPAERHKDDSRGLVLPGYKYLGPFNGLD

insertion

KGEPVNEADAAALEHDKAYDRQLDSGDNPY

LKYNHADAEFQERLKEDTSFGGNLGRAVFQ

AKKRVLEPLGLVEEPVKTAPTGKRIDDHFP

KRKKARTEEDSKPSTSSDAEAGPSGSQQLQ

IPAQPASSLGADTMSAGGGGPLGDNNQGAD

GVGNASGDWHCDSTWMGDRVVTKSTRTWVL

PSYNNHQYREIKSGSVDGSNANAYFGYSTP

WGYFDFNRFHSHWSPRDWQRLINNYWGFRP

RSLRVKIFNIQVKEVTVQDSTTTIANNLTS

TVQVFTDDDYQLPYVVGNGTEGCLPAFPPQ

VFTLPQYGYATLNRDNTENPTERSSFFCLE

YFPSKMLRTGNNFEFTYNFEEVPFHSSFAP

SQNLFKLANPLVDQYLYRFVSTNNFNPVTG

EVPPRYPLDARTGGVQFNKNLAGRYANTYK

NWFPGPMGRTQGWNLGSGVNRASVSAFATT

NRMELEGASYQVPPQPNGMTNNLQGSNTYA

LENTMIFNSQPANPGTTATYLEGNMLITSE

SETQPVNRVAYNVGGQMATNNQSSTTAPAT

GTYNLQEIVPGSVWMERDVYLQGPIWAKIP

ETGAHFHPSPAMGGFGLKHPPPMMLIKNTP

VPGNITSFSDVPVSSFITQYSTGQVTVEME

WELKKENSKRWNPEIQYTNNYNDPQFVDFA

PDSTGEYRTTRPIGTRYLTRPL

VYPep12,
23
MAADGYLPDWLEDTLSEGIRQWWKLKPGPP

loop VIII

PPKPAERHKDDSRGLVLPGYKYLGPFNGLD

insertion

KGEPVNEADAAALEHDKAYDRQLDSGDNPY

LKYNHADAEFQERLKEDTSFGGNLGRAVFQ

AKKRVLEPLGLVEEPVKTAPTGKRIDDHF

PKRKKARTEEDSKPSTSSDAEAGPSGSQQL

QIPAQPASSLGADTMSAGGGGPLGDNNQGA

DGVGNASGDWHCDSTWMGDRVVTKSTRTWV

LPSYNNHQYREIKSGSVDGSNANAYFGYST

PWGYFDFNRFHSHWSPRDWQRLINNYWGFR

PRSLRVKIFNIQVKEVTVQDSTTTIANNLT

STVQVFTDDDYQLPYVVGNGTEGCLPAFPP

QVFTLPQYGYATLNRDNTENPTERSSFFCL

EYFPSKMLRTGNNFEFTYNFEEVPFHSSFA

PSQNLFKLANPLVDQYLYRFVSTNNTGGVQ

FNKNLAGRYANTYKNWFPGPMGRTQGWNLG

SGVNRASVSAFATTNRMELEGASYQVPPQP

NGMTNNLQGSNTYALENTMIFNSQPANPGT

TATYLEGNMLITSESETQPVNRVAYNVGGQ

MATNNQSSFNPVTGEVPPRYPLDARTTAPA

TGTYNLQEIVPGSVWMERDVYLQGPIWAKI

PETGAHFHPSPAMGGFGLKHPPPMMLIKNT

PVPGNITSFSDVPVSSFITQYSTGQVTVEM

EWELKKENSKRWNPEIQYTNNYNDPQFVDF

APDSTGEYRTTRPIGTRYLTRPL

VYPep13,
24
MAADGYLPDWLEDTLSEGIRQWWKLKPGPP

loop IV

PPKPAERHKDDSRGLVLPGYKYLGPFNGLD

insertion

KGEPVNEADAAALEHDKAYDRQLDSGDNPY

LKYNHADAEFQERLKEDTSFGGNLGRAVFQ

AKKRVLEPLGLVEEPVKTAPTGKRIDDHF

PKRKKARTEEDSKPSTSSDAEAGPSGSQQL

QIPAQPASSLGADTMSAGGGGPLGDNNQGA

DGVGNASGDWHCDSTWMGDRVVTKSTRTWV

LPSYNNHQYREIKSGSVDGSNANAYFGYST

PWGYFDFNRFHSHWSPRDWQRLINNYWGFR

PRSLRVKIFNIQVKEVTVQDSTTTIANNLT

STVQVFTDDDYQLPYVVGNGTEGCLPAFPP

QVFTLPQYGYATLNRDNTENPTERSSFFCL

EYFPSKMLRTGNNFEFTYNFEEVPFHSSFA

PSQNLFKLANPLVDQYLYRFVSTNNSVTEQ

GAELSNEERTGGVQFNKNLAGRYANTYKNW

FPGPMGRTQGWNLGSGVNRASVSAFATTNR

MELEGASYQVPPQPNGMTNNLQGSNTYALE

NTMIFNSQPANPGTTATYLEGNMLITSESE

TQPVNRVAYNVGGQMATNNQSSTTAPATGT

YNLQEIVPGSVWMERDVYLQGPIWAKIPET

GAHFHPSPAMGGFGLKHPPPMMLIKNTPVP

GNITSFSDVPVSSFITQYSTGQVTVEMEWE

LKKENSKRWNPEIQYTNNYNDPQFVDFAPD

STGEYRTTRPIGTRYLTRPL

VYPep13, loop
25
MAADGYLPDWLEDTLSEGIRQWWKLKPGPP

VIII insertion

PPKPAERHKDDSRGLVLPGYKYLGPFNGLD

KGEPVNEADAAALEHDKAYDRQLDSGDNPY

LKYNHADAEFQERLKEDTSFGGNLGRAVFQ

AKKRVLEPLGLVEEPVKTAPTGKRIDDHFP

KRKKARTEEDSKPSTSSDAEAGPSGSQQLQ

IPAQPASSLGADTMSAGGGGPLGDNNQGAD

GVGNASGDWHCDSTWMGDRVVTKSTRTWVL

PSYNNHQYREIKSGSVDGSNANAYFGYSTP

WGYFDFNRFHSHWSPRDWQRLINNYWGFRP

RSLRVKIFNIQVKEVTVQDSTTTIANNLTS

TVQVFTDDDYQLPYVVGNGTEGCLPAFPPQ

VFTLPQYGYATLNRDNTENPTERSSFFCLE

YFPSKMLRTGNNFEFTYNFEEVPFHSSFAP

SQNLFKLANPLVDQYLYRFVSTNNTGGVQF

NKNLAGRYANTYKNWFPGPMGRTQGWNLGS

GVNRASVSAFATTNRMELEGASYQVPPQPN

GMTNNLQGSNTYALENTMIFNSQPANPGTT

ATYLEGNMLITSESETQPVNRVAYNVGGQM

ATNNQSSSVTEQGAELSNEERTTAPATGTY

NLQEIVPGSVWMERDVYLQGPIWAKIPETG

AHFHPSPAMGGFGLKHPPPMMLIKNTPVPG

NITSFSDVPVSSFITQYSTGQVTVEMEWEL

KKENSKRWNPEIQYTNNYNDPQFVDFAPDS

TGEYRTTRPIGTRYLTRPL

VYPep14,
26
MAADGYLPDWLEDTLSEGIRQWWKLKPGPP

loop IV

PPKPAERHKDDSRGLVLPGYKYLGPFNGLD

insertion

KGEPVNEADAAALEHDKAYDRQLDSGDNPY

LKYNHADAEFQERLKEDTSFGGNLGRAVFQ

AKKRVLEPLGLVEEPVKTAPTGKRIDDHF

PKRKKARTEEDSKPSTSSDAEAGPSGSQQL

QIPAQPASSLGADTMSAGGGGPLGDNNQGA

DGVGNASGDWHCDSTWMGDRVVTKSTRTWV

LPSYNNHQYREIKSGSVDGSNANAYFGYST

PWGYFDFNRFHSHWSPRDWQRLINNYWGFR

PRSLRVKIFNIQVKEVTVQDSTTTIANNLT

STVQVFTDDDYQLPYVVGNGTEGCLPAFPP

QVFTLPQYGYATLNRDNTENPTERSSFFCL

EYFPSKMLRTGNNFEFTYNFEEVPFHSSFA

PSQNLFKLANPLVDQYLYRFVSTNNGQSGR

GDLGLTGGVQFNKNLAGRYANTYKNWFPGP

MGRTQGWNLGSGVNRASVSAFATTNRMELE

GASYQVPPQPNGMTNNLQGSNTYALENTMI

FNSQPANPGTTATYLEGNMLITSESETQPV

NRVAYNVGGQMATNNQSSTTAPATGTYNLQ

EIVPGSVWMERDVYLQGPIWAKIPETGAHF

HPSPAMGGFGLKHPPPMMLIKNTPVPGNIT

SFSDVPVSSFITQYSTGQVTVEMEWELKKE

NSKRWNPEIQYTNNYNDPQFVDFAPDSTGE

YRTTRPIGTRYLTRPL

VYPep14,
27
MAADGYLPDWLEDTLSEGIRQWWKLKPGPP

loop VIII

PPKPAERHKDDSRGLVLPGYKYLGPFNGLD

insertion

KGEPVNEADAAALEHDKAYDRQLDSGDNPY

LKYNHADAEFQERLKEDTSFGGNLGRAVFQ

AKKRVLEPLGLVEEPVKTAPTGKRIDDHF

PKRKKARTEEDSKPSTSSDAEAGPSGSQQL

QIPAQPASSLGADTMSAGGGGPLGDNNQGA

DGVGNASGDWHCDSTWMGDRVVTKSTRTWV

LPSYNNHQYREIKSGSVDGSNANAYFGYST

PWGYFDFNRFHSHWSPRDWQRLINNYWGFR

PRSLRVKIFNIQVKEVTVQDSTTTIANNLT

STVQVFTDDDYQLPYVVGNGTEGCLPAFPP

QVFTLPQYGYATLNRDNTENPTERSSFFCL

EYFPSKMLRTGNNFEFTYNFEEVPFHSSFA

PSQNLFKLANPLVDQYLYRFVSTNNTGGVQ

FNKNLAGRYANTYKNWFPGPMGRTQGWNLG

SGVNRASVSAFATTNRMELEGASYQVPPQP

NGMTNNLQGSNTYALENTMIFNSQPANPGT

TATYLEGNMLITSESETQPVNRVAYNVGGQ

MATNNQSSGQSGRGDLGLTTAPATGTYNLQ

EIVPGSVWMERDVYLQGPIWAKIPETGAHF

HPSPAMGGFGLKHPPPMMLIKNTPVPGNIT

SFSDVPVSSFITQYSTGQVTVEMEWELKKE

NSKRWNPEIQYTNNYNDPQFVDFAPDSTGE

YRTTRPIGTRYLTRPL

VYPep15,
28
MAADGYLPDWLEDTLSEGIRQWWKLKPGPP

loop IV

PPKPAERHKDDSRGLVLPGYKYLGPFNGLD

insertion

KGEPVNEADAAALEHDKAYDRQLDSGDNPY

LKYNHADAEFQERLKEDTSFGGNLGRAVFQ

AKKRVLEPLGLVEEPVKTAPTGKRIDDHFP

KRKKARTEEDSKPSTSSDAEAGPSGSQQLQ

IPAQPASSLGADTMSAGGGGPLGDNNQGAD

GVGNASGDWHCDSTWMGDRVVTKSTRTWVL

PSYNNHQYREIKSGSVDGSNANAYFGYSTP

WGYFDFNRFHSHWSPRDWQRLINNYWGFRP

RSLRVKIFNIQVKEVTVQDSTTTIANNLTS

TVQVFTDDDYQLPYVVGNGTEGCLPAFPPQ

VFTLPQYGYATLNRDNTENPTERSSFFCLE

YFPSKMLRTGNNFEFTYNFEEVPFHSSFAP

SQNLFKLANPLVDQYLYRFVSTNNTGASSL

NIAGLSTGGVQFNKNLAGRYANTYKNWFPG

PMGRTQGWNLGSGVNRASVSAFATTNRMEL

EGASYQVPPQPNGMTNNLQGSNTYALENTM

IFNSQPANPGTTATYLEGNMLITSESETQP

VNRVAYNVGGQMATNNQSSTTAPATGTYNL

QEIVPGSVWMERDVYLQGPIWAKIPETGAH

FHPSPAMGGFGLKHPPPMMLIKNTPVPGNI

TSFSDVPVSSFITQYSTGQVTVEMEWELKK

ENSKRWNPEIQYTNNYNDPQFVDFAPDSTG

EYRTTRPIGTRYLTRPL

VYPep15,
29
MAADGYLPDWLEDTLSEGIRQWWKLKPGPP

loop

PPKPAERHKDDSRGLVLPGYKYLGPFNGLD

VIII

KGEPVNEADAAALEHDKAYDRQLDSGDNPY

insertion

LKYNHADAEFQERLKEDTSFGGNLGRAVFQ

AKKRVLEPLGLVEEPVKTAPTGKRIDDHF

PKRKKARTEEDSKPSTSSDAEAGPSGSQQL

QIPAQPASSLGADTMSAGGGGPLGDNNQGA

DGVGNASGDWHCDSTWMGDRVVTKSTRTWV

LPSYNNHQYREIKSGSVDGSNANAYFGYST

PWGYFDFNRFHSHWSPRDWQRLINNYWGFR

PRSLRVKIFNIQVKEVTVQDSTTTIANNLT

STVQVFTDDDYQLPYVVGNGTEGCLPAFPP

QVFTLPQYGYATLNRDNTENPTERSSFFCL

EYFPSKMLRTGNNFEFTYNFEEVPFHSSFA

PSQNLFKLANPLVDQYLYRFVSTNNTGGVQ

FNKNLAGRYANTYKNWFPGPMGRTQGWNLG

SGVNRASVSAFATTNRMELEGASYQVPPQP

NGMTNNLQGSNTYALENTMIFNSQPANPGT

TATYLEGNMLITSESETQPVNRVAYNVGGQ

MATNNQSSTGASSLNIAGLSTTAPATGTYN

LQEIVPGSVWMERDVYLQGPIWAKIPETGA

HFHPSPAMGGFGLKHPPPMMLIKNTPVPGN

ITSFSDVPVSSFITQYSTGQVTVEMEWELK

KENSKRWNPEIQYTNNYNDPQFVDFAPDST

GEYRTTRPIGTRYLTRPL

Amino acid sequences of exemplary recombinant AAV capsid proteins comprising a first and a second peptide (“dual loop capsid proteins”) provided herein are set forth in Table 3 below.

TABLE 3

Amino acid sequences of exemplary recombinant

AAV dual loop capsid proteins

SEQ

ID

Description
NO
Amino acid sequence

AAV5.2-
30
MAADGYLPDWLEDTLSEGIRQWWKL

VYPep14-

KPGPPPPKPAERHKDDSRGLVLPGY

IV-

KYLGPFNGLDKGEPVNEADAAALEH

VYPep14-

DKAYDRQLDSGDNPYLKYNHADAEF

VIII

QERLKEDTSFGGNLGRAVFQAKKRV

LEPLGLVEEPVKTAPTGKRIDDHFP

KRKKARTEEDSKPSTSSDAEAGPSG

SQQLQIPAQPASSLGADTMSAGGGG

PLGDNNQGADGVGNASGDWHCDSTW

MGDRVVTKSTRTWVLPSYNNHQYRE

IKSGSVDGSNANAYFGYSTPWGYFD

FNRFHSHWSPRDWQRLINNYWGFRP

RSLRVKIFNIQVKEVTVQDSTTTIA

NNLTSTVQVFTDDDYQLPYVVGNGT

EGCLPAFPPQVFTLPQYGYATLNRD

NTENPTERSSFFCLEYFPSKMLRTG

NNFEFTYNFEEVPFHSSFAPSQNLF

KLANPLVDQYLYRFVSTNNGQSGRG

DLGLTGGVQFNKNLAGRYANTYKNW

FPGPMGRTQGWNLGSGVNRASVSAF

ATTNRMELEGASYQVPPQPNGMTNN

LQGSNTYALENTMIFNSQPANPGTT

ATYLEGNMLITSESETQPVNRVAYN

VGGQMATNNQSSGQSGRGDLGLTTA

PATGTYNLQEIVPGSVWMERDVYLQ

GPIWAKIPETGAHFHPSPAMGGFGL

KHPPPMMLIKNTPVPGNITSFSDVP

VSSFITQYSTGQVTVEMEWELKKEN

SKRWNPEIQYTNNYNDPQFVDFAPD

STGEYRTTRPIGTRYLTRPL

AAV5.2-
31
MAADGYLPDWLEDTLSEGIRQWWKL

VYPep14-

KPGPPPPKPAERHKDDSRGLVLPGY

IV-

KYLGPFNGLDKGEPVNEADAAALEH

VYPep4-

DKAYDRQLDSGDNPYLKYNHADAEF

VIII

QERLKEDTSFGGNLGRAVFQAKKRV

LEPLGLVEEPVKTAPTGKRIDDHFP

KRKKARTEEDSKPSTSSDAEAGPSG

SQQLQIPAQPASSLGADTMSAGGGG

PLGDNNQGADGVGNASGDWHCDSTW

MGDRVVTKSTRTWVLPSYNNHQYRE

IKSGSVDGSNANAYFGYSTPWGYFD

FNRFHSHWSPRDWQRLINNYWGFRP

RSLRVKIFNIQVKEVTVQDSTTTIA

NNLTSTVQVFTDDDYQLPYVVGNGT

EGCLPAFPPQVFTLPQYGYATLNRD

NTENPTERSSFFCLEYFPSKMLRTG

NNFEFTYNFEEVPFHSSFAPSQNLF

KLANPLVDQYLYRFVSTNNGQSGRG

DLGLTGGVQFNKNLAGRYANTYKNW

FPGPMGRTQGWNLGSGVNRASVSAF

ATTNRMELEGASYQVPPQPNGMTNN

LQGSNTYALENTMIFNSQPANPGTT

ATYLEGNMLITSESETQPVNRVAYN

VGGQMATNNQSSRTIGPSVTTAPAT

GTYNLQEIVPGSVWMERDVYLQGPI

WAKIPETGAHFHPSPAMGGFGLKHP

PPMMLIKNTPVPGNITSFSDVPVSS

FITQYSTGQVTVEMEWELKKENSKR

WNPEIQYTNNYNDPQFVDFAPDSTG

EYRTTRPIGTRYLTRPL

AAV5.2-
32
MAADGYLPDWLEDTLSEGIRQWWKL

VYPep4-

KPGPPPPKPAERHKDDSRGLVLPGY

IV-

KYLGPFNGLDKGEPVNEADAAALEH

VYPep14-

DKAYDRQLDSGDNPYLKYNHADAEF

VIII

QERLKEDTSFGGNLGRAVFQAKKRV

LEPLGLVEEPVKTAPTGKRIDDHFP

KRKKARTEEDSKPSTSSDAEAGPSG

SQQLQIPAQPASSLGADTMSAGGGG

PLGDNNQGADGVGNASGDWHCDSTW

MGDRVVTKSTRTWVLPSYNNHQYRE

IKSGSVDGSNANAYFGYSTPWGYFD

FNRFHSHWSPRDWQRLINNYWGFRP

RSLRVKIFNIQVKEVTVQDSTTTIA

NNLTSTVQVFTDDDYQLPYVVGNGT

EGCLPAFPPQVFTLPQYGYATLNRD

NTENPTERSSFFCLEYFPSKMLRTG

NNFEFTYNFEEVPFHSSFAPSQNLF

KLANPLVDQYLYRFVSTNNRTIGPS

VTGGVQFNKNLAGRYANTYKNWFPG

PMGRTQGWNLGSGVNRASVSAFATT

NRMELEGASYQVPPQPNGMTNNLQG

SNTYALENTMIFNSQPANPGTTATY

LEGNMLITSESETQPVNRVAYNVGG

QMATNNQSSGQSGRGDLGLTTAPAT

GTYNLQEIVPGSVWMERDVYLQGPI

WAKIPETGAHFHPSPAMGGFGLKHP

PPMMLIKNTPVPGNITSFSDVPVSS

FITQYSTGQVTVEMEWELKKENSKR

WNPEIQYTNNYNDPQFVDFAPDSTG

EYRTTRPIGTRYLTRPL

AAV5.2-
33
MAADGYLPDWLEDTLSEGIRQWWKL

VYPep5-

KPGPPPPKPAERHKDDSRGLVLPGY

IV-

KYLGPFNGLDKGEPVNEADAAALEH

VYPep14-

DKAYDRQLDSGDNPYLKYNHADAEF

VIII

QERLKEDTSFGGNLGRAVFQAKKRV

LEPLGLVEEPVKTAPTGKRIDDHFP

KRKKARTEEDSKPSTSSDAEAGPSG

SQQLQIPAQPASSLGADTMSAGGGG

PLGDNNQGADGVGNASGDWHCDSTW

MGDRVVTKSTRTWVLPSYNNHQYRE

IKSGSVDGSNANAYFGYSTPWGYFD

FNRFHSHWSPRDWQRLINNYWGFRP

RSLRVKIFNIQVKEVTVQDSTTTIA

NNLTSTVQVFTDDDYQLPYVVGNGT

EGCLPAFPPQVFTLPQYGYATLNRD

NTENPTERSSFFCLEYFPSKMLRTG

NNFEFTYNFEEVPFHSSFAPSQNLF

KLANPLVDQYLYRFVSTNNLSSRLD

ATGGVQFNKNLAGRYANTYKNWFPG

PMGRTQGWNLGSGVNRASVSAFATT

NRMELEGASYQVPPQPNGMTNNLQG

SNTYALENTMIFNSQPANPGTTATY

LEGNMLITSESETQPVNRVAYNVGG

QMATNNQSSGQSGRGDLGLTTAPAT

GTYNLQEIVPGSVWMERDVYLQGPI

WAKIPETGAHFHPSPAMGGFGLKHP

PPMMLIKNTPVPGNITSFSDVPVSS

FITQYSTGQVTVEMEWELKKENSKR

WNPEIQYTNNYNDPQFVDFAPDSTG

EYRTTRPIGTRYLTRPL

AAV5.2-
34
MAADGYLPDWLEDTLSEGIRQWWKL

VYPep7-

KPGPPPPKPAERHKDDSRGLVLPGY

IV-

KYLGPFNGLDKGEPVNEADAAALEH

VYPep14-

DKAYDRQLDSGDNPYLKYNHADAEF

VIII

QERLKEDTSFGGNLGRAVFQAKKRV

LEPLGLVEEPVKTAPTGKRIDDHFP

KRKKARTEEDSKPSTSSDAEAGPSG

SQQLQIPAQPASSLGADTMSAGGGG

PLGDNNQGADGVGNASGDWHCDSTW

MGDRVVTKSTRTWVLPSYNNHQYRE

IKSGSVDGSNANAYFGYSTPWGYFD

FNRFHSHWSPRDWQRLINNYWGFRP

RSLRVKIFNIQVKEVTVQDSTTTIA

NNLTSTVQVFTDDDYQLPYVVGNGT

EGCLPAFPPQVFTLPQYGYATLNRD

NTENPTERSSFFCLEYFPSKMLRTG

NNFEFTYNFEEVPFHSSFAPSQNLF

KLANPLVDQYLYRFVSTNNAPLTNT

VKATGGVQFNKNLAGRYANTYKNWF

PGPMGRTQGWNLGSGVNRASVSAFA

TTNRMELEGASYQVPPQPNGMTNNL

QGSNTYALENTMIFNSQPANPGTTA

TYLEGNMLITSESETQPVNRVAYNV

GGQMATNNQSSGQSGRGDLGLTTAP

ATGTYNLQEIVPGSVWMERDVYLQG

PIWAKIPETGAHFHPSPAMGGFGLK

HPPPMMLIKNTPVPGNITSFSDVPV

SSFITQYSTGQVTVEMEWELKKENS

KRWNPEIQYTNNYNDPQFVDFAPDS

TGEYRTTRPIGTRYLTRPL

In an embodiment, the parental capsid protein is a clade A, clade B, clade C, clade D, clade E, clade F, clade G, clade H, clade I, AAVgo.1, AAV3, AAV4, AAV10, AAV11, AAV12, rh.32, rh32.33, rh.33, rh.34, BAAV, or AAV5 capsid protein, or an engineered variant thereof.

In an embodiment, the recombinant AAV capsid protein comprises: (a) an amino acid sequence that has 100% sequence identity to amino acids 138-763 of SEQ ID NO: 30;

- (b) an amino acid sequence that has 100% sequence identity to amino acids 138-763 of SEQ ID NO: 31; (c) an amino acid sequence that has 100% sequence identity to amino acids 138-734 of SEQ ID NO: 32; (d) an amino acid sequence that has 100% sequence identity to amino acids 138-734 of SEQ ID NO: 33; or (e) an amino acid sequence that has 100% sequence identity to amino acids 138-732 of SEQ ID NO: 34.

Additional embodiments of the recombinant AAV capsid proteins disclosed herein are listed in Table 4 below.

TABLE 4

Amino acid sequences of additional

exemplary recombinant AAV capsid

proteins

VYPep1,
37
TAADGYLPDWLEDTLSEGIRQWWKL

loop IV

KPGPPPPKPAERHKDDSRGLVLPGY

insertion

KYLGPFNGLDKGEPVNEADAAALEH

DKAYDRQLDSGDNPYLKYNHADAEF

QERLKEDTSFGGNLGRAVFQAKKRV

LEPLGLVEEPVKTAPTGKRIDDHFP

KRKKARTEEDSKPSTSSDAEAGPSG

SQQLQIPAQPASSLGADTMSAGGGG

PLGDNNQGADGVGNASGDWHCDSTW

MGDRVVTKSTRTWVLPSYNNHQYRE

IKSGSVDGSNANAYFGYSTPWGYFD

FNRFHSHWSPRDWQRLINNYWGFRP

RSLRVKIFNIQVKEVTVQDSTTTIA

NNLTSTVQVFTDDDYQLPYVVGNGT

EGCLPAFPPQVFTLPQYGYATLNRD

NTENPTERSSFFCLEYFPSKMLRTG

NNFEFTYNFEEVPFHSSFAPSQNLF

KLANPLVDQYLYRFVSTNNASLEEE

WAQVECEVYGRGCPSGSLDESFYDW

FERQLGATGGVQFNKNLAGRYANTY

KNWFPGPMGRTQGWNLGSGVNRASV

SAFATTNRMELEGASYQVPPQPNGM

TNNLQGSNTYALENTMIFNSQPANP

GTTATYLEGNMLITSESETQPVNRV

AYNVGGQMATNNQSSTTAPATGTYN

LQEIVPGSVWMERDVYLQGPIWAKI

PETGAHFHPSPAMGGFGLKHPPPMM

LIKNTPVPGNITSFSDVPVSSFITQ

YSTGQVTVEMEWELKKENSKRWNPE

IQYTNNYNDPQFVDFAPDSTGEYRT

TRPIGTRYLTRPL

VYPep1,
38
TAADGYLPDWLEDTLSEGIRQWWKL

loop VIII

KPGPPPPKPAERHKDDSRGLVLPGY

insertion

KYLGPFNGLDKGEPVNEADAAALEH

DKAYDRQLDSGDNPYLKYNHADAEF

QERLKEDTSFGGNLGRAVFQAKKRV

LEPLGLVEEPVKTAPTGKRIDDHFP

KRKKARTEEDSKPSTSSDAEAGPSG

SQQLQIPAQPASSLGADTMSAGGGG

PLGDNNQGADGVGNASGDWHCDSTW

MGDRVVTKSTRTWVLPSYNNHQYRE

IKSGSVDGSNANAYFGYSTPWGYFD

FNRFHSHWSPRDWQRLINNYWGFRP

RSLRVKIFNIQVKEVTVQDSTTTIA

NNLTSTVQVFTDDDYQLPYVVGNGT

EGCLPAFPPQVFTLPQYGYATLNRD

NTENPTERSSFFCLEYFPSKMLRTG

NNFEFTYNFEEVPFHSSFAPSQNLF

KLANPLVDQYLYRFVSTNNTGGVQF

NKNLAGRYANTYKNWFPGPMGRTQG

WNLGSGVNRASVSAFATTNRMELEG

ASYQVPPQPNGMTNNLQGSNTYALE

NTMIFNSQPANPGTTATYLEGNMLI

TSESETQPVNRVAYNVGGQMATNNQ

SSASLEEEWAQVECEVYGRGCPSGS

LDESFYDWFERQLGATTAPATGTYN

LQEIVPGSVWMERDVYLQGPIWAKI

PETGAHFHPSPAMGGFGLKHPPPMM

LIKNTPVPGNITSFSDVPVSSFITQ

YSTGQVTVEMEWELKKENSKRWNPE

IQYTNNYNDPQFVDFAPDSTGEYRT

TRPIGTRYLTRPL

VYPep7,
39
TAADGYLPDWLEDTLSEGIRQWWKL

loop IV

KPGPPPPKPAERHKDDSRGLVLPGY

insertion

KYLGPFNGLDKGEPVNEADAAALEH

DKAYDRQLDSGDNPYLKYNHADAEF

QERLKEDTSFGGNLGRAVFQAKKRV

LEPLGLVEEPVKTAPTGKRIDDHFP

KRKKARTEEDSKPSTSSDAEAGPSG

SQQLQIPAQPASSLGADTMSAGGGG

PLGDNNQGADGVGNASGDWHCDSTW

MGDRVVTKSTRTWVLPSYNNHQYRE

IKSGSVDGSNANAYFGYSTPWGYFD

FNRFHSHWSPRDWQRLINNYWGFRP

RSLRVKIFNIQVKEVTVQDSTTTIA

NNLTSTVQVFTDDDYQLPYVVGNGT

EGCLPAFPPQVFTLPQYGYATLNRD

NTENPTERSSFFCLEYFPSKMLRTG

NNFEFTYNFEEVPFHSSFAPSQNLF

KLANPLVDQYLYRFVSTNNAPLTNT

VKATGGVQFNKNLAGRYANTYKNWF

PGPMGRTQGWNLGSGVNRASVSAFA

TTNRMELEGASYQVPPQPNGMTNNL

QGSNTYALENTMIFNSQPANPGTTA

TYLEGNMLITSESETQPVNRVAYNV

GGQMATNNQSSTTAPATGTYNLQEI

VPGSVWMERDVYLQGPIWAKIPETG

AHFHPSPAMGGFGLKHPPPMMLIKN

TPVPGNITSFSDVPVSSFITQYSTG

QVTVEMEWELKKENSKRWNPEIQYT

NNYNDPQFVDFAPDSTGEYRTTRPI

GTRYLTRPL

VYPep7,
40
TAADGYLPDWLEDTLSEGIRQWWKL

loop VIII

KPGPPPPKPAERHKDDSRGLVLPGY

insertion

KYLGPFNGLDKGEPVNEADAAALEH

DKAYDRQLDSGDNPYLKYNHADAEF

QERLKEDTSFGGNLGRAVFQAKKRV

LEPLGLVEEPVKTAPTGKRIDDHFP

KRKKARTEEDSKPSTSSDAEAGPSG

SQQLQIPAQPASSLGADTMSAGGGG

PLGDNNQGADGVGNASGDWHCDSTW

MGDRVVTKSTRTWVLPSYNNHQYRE

IKSGSVDGSNANAYFGYSTPWGYFD

FNRFHSHWSPRDWQRLINNYWGFRP

RSLRVKIFNIQVKEVTVQDSTTTIA

NNLTSTVQVFTDDDYQLPYVVGNGT

EGCLPAFPPQVFTLPQYGYATLNRD

NTENPTERSSFFCLEYFPSKMLRTG

NNFEFTYNFEEVPFHSSFAPSQNLF

KLANPLVDQYLYRFVSTNNTGGVQF

NKNLAGRYANTYKNWFPGPMGRTQG

WNLGSGVNRASVSAFATTNRMELEG

ASYQVPPQPNGMTNNLQGSNTYALE

NTMIFNSQPANPGTTATYLEGNMLI

TSESETQPVNRVAYNVGGQMATNNQ

SSAPLTNTVKATTAPATGTYNLQEI

VPGSVWMERDVYLQGPIWAKIPETG

AHFHPSPAMGGFGLKHPPPMMLIKN

TPVPGNITSFSDVPVSSFITQYSTG

QVTVEMEWELKKENSKRWNPEIQYT

NNYNDPQFVDFAPDSTGEYRTTRPI

GTRYLTRPL

VYPep8,
41
TAADGYLPDWLEDTLSEGIRQWWKL

loop IV

KPGPPPPKPAERHKDDSRGLVLPGY

insertion

KYLGPFNGLDKGEPVNEADAAALEH

DKAYDRQLDSGDNPYLKYNHADAEF

QERLKEDTSFGGNLGRAVFQAKKRV

LEPLGLVEEPVKTAPTGKRIDDHFP

KRKKARTEEDSKPSTSSDAEAGPSG

SQQLQIPAQPASSLGADTMSAGGGG

PLGDNNQGADGVGNASGDWHCDSTW

MGDRVVTKSTRTWVLPSYNNHQYRE

IKSGSVDGSNANAYFGYSTPWGYFD

FNRFHSHWSPRDWQRLINNYWGFRP

RSLRVKIFNIQVKEVTVQDSTTTIA

NNLTSTVQVFTDDDYQLPYVVGNGT

EGCLPAFPPQVFTLPQYGYATLNRD

NTENPTERSSFFCLEYFPSKMLRTG

NNFEFTYNFEEVPFHSSFAPSQNLF

KLANPLVDQYLYRFVSTNNDDTRHW

GTGGVQFNKNLAGRYANTYKNWFPG

PMGRTQGWNLGSGVNRASVSAFATT

NRMELEGASYQVPPQPNGMTNNLQG

SNTYALENTMIFNSQPANPGTTATY

LEGNMLITSESETQPVNRVAYNVGG

QMATNNQSSTTAPATGTYNLQEIVP

GSVWMERDVYLQGPIWAKIPETGAH

FHPSPAMGGFGLKHPPPMMLIKNTP

VPGNITSFSDVPVSSFITQYSTGQV

TVEMEWELKKENSKRWNPEIQYTNN

YNDPQFVDFAPDSTGEYRTTRPIGT

RYLTRPL

VYPep8,
42
TAADGYLPDWLEDTLSEGIRQWWKL

loop VIII

KPGPPPPKPAERHKDDSRGLVLPGY

insertion

KYLGPFNGLDKGEPVNEADAAALEH

DKAYDRQLDSGDNPYLKYNHADAEF

QERLKEDTSFGGNLGRAVFQAKKRV

LEPLGLVEEPVKTAPTGKRIDDHFP

KRKKARTEEDSKPSTSSDAEAGPSG

SQQLQIPAQPASSLGADTMSAGGGG

PLGDNNQGADGVGNASGDWHCDSTW

MGDRVVTKSTRTWVLPSYNNHQYRE

IKSGSVDGSNANAYFGYSTPWGYFD

FNRFHSHWSPRDWQRLINNYWGFRP

RSLRVKIFNIQVKEVTVQDSTTTIA

NNLTSTVQVFTDDDYQLPYVVGNGT

EGCLPAFPPQVFTLPQYGYATLNRD

NTENPTERSSFFCLEYFPSKMLRTG

NNFEFTYNFEEVPFHSSFAPSQNLF

KLANPLVDQYLYRFVSTNNTGGVQF

NKNLAGRYANTYKNWFPGPMGRTQG

WNLGSGVNRASVSAFATTNRMELEG

ASYQVPPQPNGMTNNLQGSNTYALE

NTMIFNSQPANPGTTATYLEGNMLI

TSESETQPVNRVAYNVGGQMATNNQ

SSDDTRHWGTTAPATGTYNLQEIVP

GSVWMERDVYLQGPIWAKIPETGAH

FHPSPAMGGFGLKHPPPMMLIKNTP

VPGNITSFSDVPVSSFITQYSTGQV

TVEMEWELKKENSKRWNPEIQYTNN

YNDPQFVDFAPDSTGEYRTTRPIGT

RYLTRPL

VYPep9,
43
TAADGYLPDWLEDTLSEGIRQWWKL

loop IV

KPGPPPPKPAERHKDDSRGLVLPGY

insertion

KYLGPFNGLDKGEPVNEADAAALEH

DKAYDRQLDSGDNPYLKYNHADAEF

QERLKEDTSFGGNLGRAVFQAKKRV

LEPLGLVEEPVKTAPTGKRIDDHFP

KRKKARTEEDSKPSTSSDAEAGPSG

SQQLQIPAQPASSLGADTMSAGGGG

PLGDNNQGADGVGNASGDWHCDSTW

MGDRVVTKSTRTWVLPSYNNHQYRE

IKSGSVDGSNANAYFGYSTPWGYFD

FNRFHSHWSPRDWQRLINNYWGFRP

RSLRVKIFNIQVKEVTVQDSTTTIA

NNLTSTVQVFTDDDYQLPYVVGNGT

EGCLPAFPPQVFTLPQYGYATLNRD

NTENPTERSSFFCLEYFPSKMLRTG

NNFEFTYNFEEVPFHSSFAPSQNLF

KLANPLVDQYLYRFVSTNNEYHHYN

KTGGVQFNKNLAGRYANTYKNWFPG

PMGRTQGWNLGSGVNRASVSAFATT

NRMELEGASYQVPPQPNGMTNNLQG

SNTYALENTMIFNSQPANPGTTATY

LEGNMLITSESETQPVNRVAYNVGG

QMATNNQSSTTAPATGTYNLQEIVP

GSVWMERDVYLQGPIWAKIPETGAH

FHPSPAMGGFGLKHPPPMMLIKNTP

VPGNITSFSDVPVSSFITQYSTGQV

TVEMEWELKKENSKRWNPEIQYTNN

YNDPQFVDFAPDSTGEYRTTRPIGT

RYLTRPL

VYPep9,
44
TAADGYLPDWLEDTLSEGIRQWWKL

loop VIII

KPGPPPPKPAERHKDDSRGLVLPGY

insertion

KYLGPFNGLDKGEPVNEADAAALEH

DKAYDRQLDSGDNPYLKYNHADAEF

QERLKEDTSFGGNLGRAVFQAKKRV

LEPLGLVEEPVKTAPTGKRIDDHFP

KRKKARTEEDSKPSTSSDAEAGPSG

SQQLQIPAQPASSLGADTMSAGGGG

PLGDNNQGADGVGNASGDWHCDSTW

MGDRVVTKSTRTWVLPSYNNHQYRE

IKSGSVDGSNANAYFGYSTPWGYFD

FNRFHSHWSPRDWQRLINNYWGFRP

RSLRVKIFNIQVKEVTVQDSTTTIA

NNLTSTVQVFTDDDYQLPYVVGNGT

EGCLPAFPPQVFTLPQYGYATLNRD

NTENPTERSSFFCLEYFPSKMLRTG

NNFEFTYNFEEVPFHSSFAPSQNLF

KLANPLVDQYLYRFVSTNNTGGVQF

NKNLAGRYANTYKNWFPGPMGRTQG

WNLGSGVNRASVSAFATTNRMELEG

ASYQVPPQPNGMTNNLQGSNTYALE

NTMIFNSQPANPGTTATYLEGNMLI

TSESETQPVNRVAYNVGGQMATNNQ

SSEYHHYNKTTAPATGTYNLQEIVP

GSVWMERDVYLQGPIWAKIPETGAH

FHPSPAMGGFGLKHPPPMMLIKNTP

VPGNITSFSDVPVSSFITQYSTGQV

TVEMEWELKKENSKRWNPEIQYTNN

YNDPQFVDFAPDSTGEYRTTRPIGT

RYLTRPL

VYPep10,
45
TAADGYLPDWLEDTLSEGIRQWWKL

loop IV

KPGPPPPKPAERHKDDSRGLVLPGY

insertion

KYLGPFNGLDKGEPVNEADAAALEH

DKAYDRQLDSGDNPYLKYNHADAEF

QERLKEDTSFGGNLGRAVFQAKKRV

LEPLGLVEEPVKTAPTGKRIDDHFP

KRKKARTEEDSKPSTSSDAEAGPSG

SQQLQIPAQPASSLGADTMSAGGGG

PLGDNNQGADGVGNASGDWHCDSTW

MGDRVVTKSTRTWVLPSYNNHQYRE

IKSGSVDGSNANAYFGYSTPWGYFD

FNRFHSHWSPRDWQRLINNYWGFRP

RSLRVKIFNIQVKEVTVQDSTTTIA

NNLTSTVQVFTDDDYQLPYVVGNGT

EGCLPAFPPQVFTLPQYGYATLNRD

NTENPTERSSFFCLEYFPSKMLRTG

NNFEFTYNFEEVPFHSSFAPSQNLF

KLANPLVDQYLYRFVSTNNQLFPLF

RTGGVQFNKNLAGRYANTYKNWFPG

PMGRTQGWNLGSGVNRASVSAFATT

NRMELEGASYQVPPQPNGMTNNLQG

SNTYALENTMIFNSQPANPGTTATY

LEGNMLITSESETQPVNRVAYNVGG

QMATNNQSSTTAPATGTYNLQEIVP

GSVWMERDVYLQGPIWAKIPETGAH

FHPSPAMGGFGLKHPPPMMLIKNTP

VPGNITSFSDVPVSSFITQYSTGQV

TVEMEWELKKENSKRWNPEIQYTNN

YNDPQFVDFAPDSTGEYRTTRPIGT

RYLTRPL

VYPep10,
46
TAADGYLPDWLEDTLSEGIRQWWKL

loop VIII

KPGPPPPKPAERHKDDSRGLVLPGY

insertion

KYLGPFNGLDKGEPVNEADAAALEH

DKAYDRQLDSGDNPYLKYNHADAEF

QERLKEDTSFGGNLGRAVFQAKKRV

LEPLGLVEEPVKTAPTGKRIDDHFP

KRKKARTEEDSKPSTSSDAEAGPSG

SQQLQIPAQPASSLGADTMSAGGGG

PLGDNNQGADGVGNASGDWHCDSTW

MGDRVVTKSTRTWVLPSYNNHQYRE

IKSGSVDGSNANAYFGYSTPWGYFD

FNRFHSHWSPRDWQRLINNYWGFRP

RSLRVKIFNIQVKEVTVQDSTTTIA

NNLTSTVQVFTDDDYQLPYVVGNGT

EGCLPAFPPQVFTLPQYGYATLNRD

NTENPTERSSFFCLEYFPSKMLRTG

NNFEFTYNFEEVPFHSSFAPSQNLF

KLANPLVDQYLYRFVSTNNTGGVQF

NKNLAGRYANTYKNWFPGPMGRTQG

WNLGSGVNRASVSAFATTNRMELEG

ASYQVPPQPNGMTNNLQGSNTYALE

NTMIFNSQPANPGTTATYLEGNMLI

TSESETQPVNRVAYNVGGQMATNNQ

SSQLFPLFRTTAPATGTYNLQEIVP

GSVWMERDVYLQGPIWAKIPETGAH

FHPSPAMGGFGLKHPPPMMLIKNTP

VPGNITSFSDVPVSSFITQYSTGQV

TVEMEWELKKENSKRWNPEIQYTNN

YNDPQFVDFAPDSTGEYRTTRPIGT

RYLTRPL

VYPep12,
47
TAADGYLPDWLEDTLSEGIRQWWKL

loop IV

KPGPPPPKPAERHKDDSRGLVLPGY

insertion

KYLGPFNGLDKGEPVNEADAAALEH

DKAYDRQLDSGDNPYLKYNHADAEF

QERLKEDTSFGGNLGRAVFQAKKRV

LEPLGLVEEPVKTAPTGKRIDDHFP

KRKKARTEEDSKPSTSSDAEAGPSG

SQQLQIPAQPASSLGADTMSAGGGG

PLGDNNQGADGVGNASGDWHCDSTW

MGDRVVTKSTRTWVLPSYNNHQYRE

IKSGSVDGSNANAYFGYSTPWGYFD

FNRFHSHWSPRDWQRLINNYWGFRP

RSLRVKIFNIQVKEVTVQDSTTTIA

NNLTSTVQVFTDDDYQLPYVVGNGT

EGCLPAFPPQVFTLPQYGYATLNRD

NTENPTERSSFFCLEYFPSKMLRTG

NNFEFTYNFEEVPFHSSFAPSQNLF

KLANPLVDQYLYRFVSTNNFNPVTG

EVPPRYPLDARTGGVQFNKNLAGRY

ANTYKNWFPGPMGRTQGWNLGSGVN

RASVSAFATTNRMELEGASYQVPPQ

PNGMTNNLQGSNTYALENTMIFNSQ

PANPGTTATYLEGNMLITSESETQP

VNRVAYNVGGQMATNNQSSTTAPAT

GTYNLQEIVPGSVWMERDVYLQGPI

WAKIPETGAHFHPSPAMGGFGLKHP

PPMMLIKNTPVPGNITSFSDVPVSS

FITQYSTGQVTVEMEWELKKENSKR

WNPEIQYTNNYNDPQFVDFAPDSTG

EYRTTRPIGTRYLTRPL

VYPep12,
48
TAADGYLPDWLEDTLSEGIRQWWKL

loop VIII

KPGPPPPKPAERHKDDSRGLVLPGY

insertion

KYLGPFNGLDKGEPVNEADAAALEH

DKAYDRQLDSGDNPYLKYNHADAEF

QERLKEDTSFGGNLGRAVFQAKKRV

LEPLGLVEEPVKTAPTGKRIDDHFP

KRKKARTEEDSKPSTSSDAEAGPSG

SQQLQIPAQPASSLGADTMSAGGGG

PLGDNNQGADGVGNASGDWHCDSTW

MGDRVVTKSTRTWVLPSYNNHQYRE

IKSGSVDGSNANAYFGYSTPWGYFD

FNRFHSHWSPRDWQRLINNYWGFRP

RSLRVKIFNIQVKEVTVQDSTTTIA

NNLTSTVQVFTDDDYQLPYVVGNGT

EGCLPAFPPQVFTLPQYGYATLNRD

NTENPTERSSFFCLEYFPSKMLRTG

NNFEFTYNFEEVPFHSSFAPSQNLF

KLANPLVDQYLYRFVSTNNTGGVQF

NKNLAGRYANTYKNWFPGPMGRTQG

WNLGSGVNRASVSAFATTNRMELEG

ASYQVPPQPNGMTNNLQGSNTYALE

NTMIFNSQPANPGTTATYLEGNMLI

TSESETQPVNRVAYNVGGQMATNNQ

SSFNPVTGEVPPRYPLDARTTAPAT

GTYNLQEIVPGSVWMERDVYLQGPI

WAKIPETGAHFHPSPAMGGFGLKHP

PPMMLIKNTPVPGNITSFSDVPVSS

FITQYSTGQVTVEMEWELKKENSKR

WNPEIQYTNNYNDPQFVDFAPDSTG

EYRTTRPIGTRYLTRPL

VYPep13,
49
TAADGYLPDWLEDTLSEGIRQWWKL

loop IV

KPGPPPPKPAERHKDDSRGLVLPGY

insertion

KYLGPFNGLDKGEPVNEADAAALEH

DKAYDRQLDSGDNPYLKYNHADAEF

QERLKEDTSFGGNLGRAVFQAKKRV

LEPLGLVEEPVKTAPTGKRIDDHFP

KRKKARTEEDSKPSTSSDAEAGPSG

SQQLQIPAQPASSLGADTMSAGGGG

PLGDNNQGADGVGNASGDWHCDSTW

MGDRVVTKSTRTWVLPSYNNHQYRE

IKSGSVDGSNANAYFGYSTPWGYFD

FNRFHSHWSPRDWQRLINNYWGFRP

RSLRVKIFNIQVKEVTVQDSTTTIA

NNLTSTVQVFTDDDYQLPYVVGNGT

EGCLPAFPPQVFTLPQYGYATLNRD

NTENPTERSSFFCLEYFPSKMLRTG

NNFEFTYNFEEVPFHSSFAPSQNLF

KLANPLVDQYLYRFVSTNNSVTEQG

AELSNEERTGGVQFNKNLAGRYANT

YKNWFPGPMGRTQGWNLGSGVNRAS

VSAFATTNRMELEGASYQVPPQPNG

MTNNLQGSNTYALENTMIFNSQPAN

PGTTATYLEGNMLITSESETQPVNR

VAYNVGGQMATNNQSSTTAPATGTY

NLQEIVPGSVWMERDVYLQGPIWAK

IPETGAHFHPSPAMGGFGLKHPPPM

MLIKNTPVPGNITSFSDVPVSSFIT

QYSTGQVTVEMEWELKKENSKRWNP

EIQYTNNYNDPQFVDFAPDSTGEYR

TTRPIGTRYLTRPL

VYPep13,
50
TAADGYLPDWLEDTLSEGIRQWWKL

loop

KPGPPPPKPAERHKDDSRGLVLPGY

VIII

KYLGPFNGLDKGEPVNEADAAALEH

insertion

DKAYDRQLDSGDNPYLKYNHADAEF

QERLKEDTSFGGNLGRAVFQAKKRV

LEPLGLVEEPVKTAPTGKRIDDHFP

KRKKARTEEDSKPSTSSDAEAGPSG

SQQLQIPAQPASSLGADTMSAGGGG

PLGDNNQGADGVGNASGDWHCDSTW

MGDRVVTKSTRTWVLPSYNNHQYRE

IKSGSVDGSNANAYFGYSTPWGYFD

FNRFHSHWSPRDWQRLINNYWGFRP

RSLRVKIFNIQVKEVTVQDSTTTIA

NNLTSTVQVFTDDDYQLPYVVGNGT

EGCLPAFPPQVFTLPQYGYATLNRD

NTENPTERSSFFCLEYFPSKMLRTG

NNFEFTYNFEEVPFHSSFAPSQNLF

KLANPLVDQYLYRFVSTNNTGGVQF

NKNLAGRYANTYKNWFPGPMGRTQG

WNLGSGVNRASVSAFATTNRMELEG

ASYQVPPQPNGMTNNLQGSNTYALE

NTMIFNSQPANPGTTATYLEGNMLI

TSESETQPVNRVAYNVGGQMATNNQ

SSSVTEQGAELSNEERTTAPATGTY

NLQEIVPGSVWMERDVYLQGPIWAK

IPETGAHFHPSPAMGGFGLKHPPPM

MLIKNTPVPGNITSFSDVPVSSFIT

QYSTGQVTVEMEWELKKENSKRWNP

EIQYTNNYNDPQFVDFAPDSTGEYR

TTRPIGTRYLTRPL

VYPep14,
51
TAADGYLPDWLEDTLSEGIRQWWKL

loop IV

KPGPPPPKPAERHKDDSRGLVLPGY

insertion

KYLGPFNGLDKGEPVNEADAAALEH

DKAYDRQLDSGDNPYLKYNHADAEF

QERLKEDTSFGGNLGRAVFQAKKRV

LEPLGLVEEPVKTAPTGKRIDDHFP

KRKKARTEEDSKPSTSSDAEAGPSG

SQQLQIPAQPASSLGADTMSAGGGG

PLGDNNQGADGVGNASGDWHCDSTW

MGDRVVTKSTRTWVLPSYNNHQYRE

IKSGSVDGSNANAYFGYSTPWGYFD

FNRFHSHWSPRDWQRLINNYWGFRP

RSLRVKIFNIQVKEVTVQDSTTTIA

NNLTSTVQVFTDDDYQLPYVVGNGT

EGCLPAFPPQVFTLPQYGYATLNRD

NTENPTERSSFFCLEYFPSKMLRTG

NNFEFTYNFEEVPFHSSFAPSQNLF

KLANPLVDQYLYRFVSTNNGQSGRG

DLGLTGGVQFNKNLAGRYANTYKNW

FPGPMGRTQGWNLGSGVNRASVSAF

ATTNRMELEGASYQVPPQPNGMTNN

LQGSNTYALENTMIFNSQPANPGTT

ATYLEGNMLITSESETQPVNRVAYN

VGGQMATNNQSSTTAPATGTYNLQE

IVPGSVWMERDVYLQGPIWAKIPET

GAHFHPSPAMGGFGLKHPPPMMLIK

NTPVPGNITSFSDVPVSSFITQYST

GQVTVEMEWELKKENSKRWNPEIQY

TNNYNDPQFVDFAPDSTGEYRTTRP

IGTRYLTRPL

VYPep14,
52
TAADGYLPDWLEDTLSEGIRQWWKL

loop

KPGPPPPKPAERHKDDSRGLVLPGY

VIII

KYLGPFNGLDKGEPVNEADAAALEH

insertion

DKAYDRQLDSGDNPYLKYNHADAEF

QERLKEDTSFGGNLGRAVFQAKKRV

LEPLGLVEEPVKTAPTGKRIDDHFP

KRKKARTEEDSKPSTSSDAEAGPSG

SQQLQIPAQPASSLGADTMSAGGGG

PLGDNNQGADGVGNASGDWHCDSTW

MGDRVVTKSTRTWVLPSYNNHQYRE

IKSGSVDGSNANAYFGYSTPWGYFD

FNRFHSHWSPRDWQRLINNYWGFRP

RSLRVKIFNIQVKEVTVQDSTTTIA

NNLTSTVQVFTDDDYQLPYVVGNGT

EGCLPAFPPQVFTLPQYGYATLNRD

NTENPTERSSFFCLEYFPSKMLRTG

NNFEFTYNFEEVPFHSSFAPSQNLF

KLANPLVDQYLYRFVSTNNTGGVQF

NKNLAGRYANTYKNWFPGPMGRTQG

WNLGSGVNRASVSAFATTNRMELEG

ASYQVPPQPNGMTNNLQGSNTYALE

NTMIFNSQPANPGTTATYLEGNMLI

TSESETQPVNRVAYNVGGQMATNNQ

SSGQSGRGDLGLTTAPATGTYNLQE

IVPGSVWMERDVYLQGPIWAKIPET

GAHFHPSPAMGGFGLKHPPPMMLIK

NTPVPGNITSFSDVPVSSFITQYST

GQVTVEMEWELKKENSKRWNPEIQY

TNNYNDPQFVDFAPDSTGEYRTTRP

IGTRYLTRPL

VYPep15,
53
TAADGYLPDWLEDTLSEGIRQWWKL

loop IV

KPGPPPPKPAERHKDDSRGLVLPGY

insertion

KYLGPFNGLDKGEPVNEADAAALEH

DKAYDRQLDSGDNPYLKYNHADAEF

QERLKEDTSFGGNLGRAVFQAKKRV

LEPLGLVEEPVKTAPTGKRIDDHFP

KRKKARTEEDSKPSTSSDAEAGPSG

SQQLQIPAQPASSLGADTMSAGGGG

PLGDNNQGADGVGNASGDWHCDSTW

MGDRVVTKSTRTWVLPSYNNHQYRE

IKSGSVDGSNANAYFGYSTPWGYFD

FNRFHSHWSPRDWQRLINNYWGFRP

RSLRVKIFNIQVKEVTVQDSTTTIA

NNLTSTVQVFTDDDYQLPYVVGNGT

EGCLPAFPPQVFTLPQYGYATLNRD

NTENPTERSSFFCLEYFPSKMLRTG

NNFEFTYNFEEVPFHSSFAPSQNLF

KLANPLVDQYLYRFVSTNNTGASSL

NIAGLSTGGVQFNKNLAGRYANTYK

NWFPGPMGRTQGWNLGSGVNRASVS

AFATTNRMELEGASYQVPPQPNGMT

NNLQGSNTYALENTMIFNSQPANPG

TTATYLEGNMLITSESETQPVNRVA

YNVGGQMATNNQSSTTAPATGTYNL

QEIVPGSVWMERDVYLQGPIWAKIP

ETGAHFHPSPAMGGFGLKHPPPMML

IKNTPVPGNITSFSDVPVSSFITQY

STGQVTVEMEWELKKENSKRWNPEI

QYTNNYNDPQFVDFAPDSTGEYRTT

RPIGTRYLTRPL

VYPep15,
54
TAADGYLPDWLEDTLSEGIRQWWKL

loop

KPGPPPPKPAERHKDDSRGLVLPGY

VIII

KYLGPFNGLDKGEPVNEADAAALEH

insertion

DKAYDRQLDSGDNPYLKYNHADAEF

QERLKEDTSFGGNLGRAVFQAKKRV

LEPLGLVEEPVKTAPTGKRIDDHFP

KRKKARTEEDSKPSTSSDAEAGPSG

SQQLQIPAQPASSLGADTMSAGGGG

PLGDNNQGADGVGNASGDWHCDSTW

MGDRVVTKSTRTWVLPSYNNHQYRE

IKSGSVDGSNANAYFGYSTPWGYFD

FNRFHSHWSPRDWQRLINNYWGFRP

RSLRVKIFNIQVKEVTVQDSTTTIA

NNLTSTVQVFTDDDYQLPYVVGNGT

EGCLPAFPPQVFTLPQYGYATLNRD

NTENPTERSSFFCLEYFPSKMLRTG

NNFEFTYNFEEVPFHSSFAPSQNLF

KLANPLVDQYLYRFVSTNNTGGVQF

NKNLAGRYANTYKNWFPGPMGRTQG

WNLGSGVNRASVSAFATTNRMELEG

ASYQVPPQPNGMTNNLQGSNTYALE

NTMIFNSQPANPGTTATYLEGNMLI

TSESETQPVNRVAYNVGGQMATNNQ

SSTGASSLNIAGLSTTAPATGTYNL

QEIVPGSVWMERDVYLQGPIWAKIP

ETGAHFHPSPAMGGFGLKHPPPMML

IKNTPVPGNITSFSDVPVSSFITQY

STGQVTVEMEWELKKENSKRWNPEI

QYTNNYNDPQFVDFAPDSTGEYRTT

RPIGTRYLTRPL

AAV5.2-
55
TAADGYLPDWLEDTLSEGIRQWWKL

VYPep14-

KPGPPPPKPAERHKDDSRGLVLPGY

IV-

KYLGPFNGLDKGEPVNEADAAALEH

VYPep14-

DKAYDRQLDSGDNPYLKYNHADAEF

VIII

QERLKEDTSFGGNLGRAVFQAKKRV

LEPLGLVEEPVKTAPTGKRIDDHFP

KRKKARTEEDSKPSTSSDAEAGPSG

SQQLQIPAQPASSLGADTMSAGGGG

PLGDNNQGADGVGNASGDWHCDSTW

MGDRVVTKSTRTWVLPSYNNHQYRE

IKSGSVDGSNANAYFGYSTPWGYFD

FNRFHSHWSPRDWQRLINNYWGFRP

RSLRVKIFNIQVKEVTVQDSTTTIA

NNLTSTVQVFTDDDYQLPYVVGNGT

EGCLPAFPPQVFTLPQYGYATLNRD

NTENPTERSSFFCLEYFPSKMLRTG

NNFEFTYNFEEVPFHSSFAPSQNLF

KLANPLVDQYLYRFVSTNNGQSGRG

DLGLTGGVQFNKNLAGRYANTYKNW

FPGPMGRTQGWNLGSGVNRASVSAF

ATTNRMELEGASYQVPPQPNGMTNN

LQGSNTYALENTMIFNSQPANPGTT

ATYLEGNMLITSESETQPVNRVAYN

VGGQMATNNQSSGQSGRGDLGLTTA

PATGTYNLQEIVPGSVWMERDVYLQ

GPIWAKIPETGAHFHPSPAMGGFGL

KHPPPMMLIKNTPVPGNITSFSDVP

VSSFITQYSTGQVTVEMEWELKKEN

SKRWNPEIQYTNNYNDPQFVDFAPD

STGEYRTTRPIGTRYLTRPL

AAV5.2-
56
TAADGYLPDWLEDTLSEGIRQWWKL

VYPep14-

KPGPPPPKPAERHKDDSRGLVLPGY

IV-

KYLGPFNGLDKGEPVNEADAAALEH

VYPep4-

DKAYDRQLDSGDNPYLKYNHADAEF

VIII

QERLKEDTSFGGNLGRAVFQAKKRV

LEPLGLVEEPVKTAPTGKRIDDHFP

KRKKARTEEDSKPSTSSDAEAGPSG

SQQLQIPAQPASSLGADTMSAGGGG

PLGDNNQGADGVGNASGDWHCDSTW

MGDRVVTKSTRTWVLPSYNNHQYRE

IKSGSVDGSNANAYFGYSTPWGYFD

FNRFHSHWSPRDWQRLINNYWGFRP

RSLRVKIFNIQVKEVTVQDSTTTIA

NNLTSTVQVFTDDDYQLPYVVGNGT

EGCLPAFPPQVFTLPQYGYATLNRD

NTENPTERSSFFCLEYFPSKMLRTG

NNFEFTYNFEEVPFHSSFAPSQNLF

KLANPLVDQYLYRFVSTNNGQSGRG

DLGLTGGVQFNKNLAGRYANTYKNW

FPGPMGRTQGWNLGSGVNRASVSAF

ATTNRMELEGASYQVPPQPNGMTNN

LQGSNTYALENTMIFNSQPANPGTT

ATYLEGNMLITSESETQPVNRVAYN

VGGQMATNNQSSRTIGPSVTTAPAT

GTYNLQEIVPGSVWMERDVYLQGPI

WAKIPETGAHFHPSPAMGGFGLKHP

PPMMLIKNTPVPGNITSFSDVPVSS

FITQYSTGQVTVEMEWELKKENSKR

WNPEIQYTNNYNDPQFVDFAPDSTG

EYRTTRPIGTRYLTRPL

AAV5.2-
57
TAADGYLPDWLEDTLSEGIRQWWKL

VYPep4-

KPGPPPPKPAERHKDDSRGLVLPGY

IV-

KYLGPFNGLDKGEPVNEADAAALEH

VYPep14-

DKAYDRQLDSGDNPYLKYNHADAEF

VIII

QERLKEDTSFGGNLGRAVFQAKKRV

LEPLGLVEEPVKTAPTGKRIDDHFP

KRKKARTEEDSKPSTSSDAEAGPSG

SQQLQIPAQPASSLGADTMSAGGGG

PLGDNNQGADGVGNASGDWHCDSTW

MGDRVVTKSTRTWVLPSYNNHQYRE

IKSGSVDGSNANAYFGYSTPWGYFD

FNRFHSHWSPRDWQRLINNYWGFRP

RSLRVKIFNIQVKEVTVQDSTTTIA

NNLTSTVQVFTDDDYQLPYVVGNGT

EGCLPAFPPQVFTLPQYGYATLNRD

NTENPTERSSFFCLEYFPSKMLRTG

NNFEFTYNFEEVPFHSSFAPSQNLF

KLANPLVDQYLYRFVSTNNRTIGPS

VTGGVQFNKNLAGRYANTYKNWFPG

PMGRTQGWNLGSGVNRASVSAFATT

NRMELEGASYQVPPQPNGMTNNLQG

SNTYALENTMIFNSQPANPGTTATY

LEGNMLITSESETQPVNRVAYNVGG

QMATNNQSSGQSGRGDLGLTTAPAT

GTYNLQEIVPGSVWMERDVYLQGPI

WAKIPETGAHFHPSPAMGGFGLKHP

PPMMLIKNTPVPGNITSFSDVPVSS

FITQYSTGQVTVEMEWELKKENSKR

WNPEIQYTNNYNDPQFVDFAPDSTG

EYRTTRPIGTRYLTRPL

AAV5.2-
58
TAADGYLPDWLEDTLSEGIRQWWKL

VYPep5-

KPGPPPPKPAERHKDDSRGLVLPGY

IV-

KYLGPFNGLDKGEPVNEADAAALEH

VYPep14-

DKAYDRQLDSGDNPYLKYNHADAEF

VIII

QERLKEDTSFGGNLGRAVFQAKKRV

LEPLGLVEEPVKTAPTGKRIDDHFP

KRKKARTEEDSKPSTSSDAEAGPSG

SQQLQIPAQPASSLGADTMSAGGGG

PLGDNNQGADGVGNASGDWHCDSTW

MGDRVVTKSTRTWVLPSYNNHQYRE

IKSGSVDGSNANAYFGYSTPWGYFD

FNRFHSHWSPRDWQRLINNYWGFRP

RSLRVKIFNIQVKEVTVQDSTTTIA

NNLTSTVQVFTDDDYQLPYVVGNGT

EGCLPAFPPQVFTLPQYGYATLNRD

NTENPTERSSFFCLEYFPSKMLRTG

NNFEFTYNFEEVPFHSSFAPSQNLF

KLANPLVDQYLYRFVSTNNLSSRLD

ATGGVQFNKNLAGRYANTYKNWFPG

PMGRTQGWNLGSGVNRASVSAFATT

NRMELEGASYQVPPQPNGMTNNLQG

SNTYALENTMIFNSQPANPGTTATY

LEGNMLITSESETQPVNRVAYNVGG

QMATNNQSSGQSGRGDLGLTTAPAT

GTYNLQEIVPGSVWMERDVYLQGPI

WAKIPETGAHFHPSPAMGGFGLKHP

PPMMLIKNTPVPGNITSFSDVPVSS

FITQYSTGQVTVEMEWELKKENSKR

WNPEIQYTNNYNDPQFVDFAPDSTG

EYRTTRPIGTRYLTRPL

AAV5.2-
59
TAADGYLPDWLEDTLSEGIRQWWKL

VYPep7-

KPGPPPPKPAERHKDDSRGLVLPGY

IV-

KYLGPFNGLDKGEPVNEADAAALEH

VYPep14-

DKAYDRQLDSGDNPYLKYNHADAEF

VIII

QERLKEDTSFGGNLGRAVFQAKKRV

LEPLGLVEEPVKTAPTGKRIDDHFP

KRKKARTEEDSKPSTSSDAEAGPSG

SQQLQIPAQPASSLGADTMSAGGGG

PLGDNNQGADGVGNASGDWHCDSTW

MGDRVVTKSTRTWVLPSYNNHQYRE

IKSGSVDGSNANAYFGYSTPWGYFD

FNRFHSHWSPRDWQRLINNYWGFRP

RSLRVKIFNIQVKEVTVQDSTTTIA

NNLTSTVQVFTDDDYQLPYVVGNGT

EGCLPAFPPQVFTLPQYGYATLNRD

NTENPTERSSFFCLEYFPSKMLRTG

NNFEFTYNFEEVPFHSSFAPSQNLF

KLANPLVDQYLYRFVSTNNAPLTNT

VKATGGVQFNKNLAGRYANTYKNWF

PGPMGRTQGWNLGSGVNRASVSAFA

TTNRMELEGASYQVPPQPNGMTNNL

QGSNTYALENTMIFNSQPANPGTTA

TYLEGNMLITSESETQPVNRVAYNV

GGQMATNNQSSGQSGRGDLGLTTAP

ATGTYNLQEIVPGSVWMERDVYLQG

PIWAKIPETGAHFHPSPAMGGFGLK

HPPPMMLIKNTPVPGNITSFSDVPV

SSFITQYSTGQVTVEMEWELKKENS

KRWNPEIQYTNNYNDPQFVDFAPDS

TGEYRTTRPIGTRYLTRPL

In an embodiment, the recombinant AAV capsid protein comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 37-59. In an embodiment, the amino acid sequence of the recombinant AAV capsid protein consists of an amino acid sequence selected from the group consisting of SEQ ID NOs: 37-59.

Polynucleotides, Vectors, and Methods of Producing AAV Capsid Proteins

In an aspect, provided herein is an isolated polynucleotide encoding a recombinant AAV capsid protein disclosed herein.

In an embodiment, the polynucleotide is optimized, e.g., by codon/RNA optimization, replacement with heterologous signal sequences, and/or elimination of mRNA instability elements. Methods to generate optimized polynucleotides for recombinant expression by introducing codon changes and/or eliminating inhibitory regions in the mRNA can be carried out by adapting the optimization methods described in, e.g., U.S. Pat. Nos. 5,965,726; 6,174,666; 6,291,664; 6,414,132; and 6,794,498, accordingly, all of which are herein incorporated by reference in their entireties. For example, potential splice sites and instability elements (e.g., A/T or A/U rich elements) within the RNA can be mutated without altering the amino acids encoded by the nucleic acid sequences to increase stability of the RNA for recombinant expression. The alterations utilize the degeneracy of the genetic code, e.g., using an alternative codon for an identical amino acid. In an embodiment, it can be desirable to alter one or more codons to encode a conservative mutation, e.g., a similar amino acid with similar chemical structure and properties and/or function as the original amino acid. Such methods can increase expression of the encoded capsid protein relative to the expression of the capsid encoded by polynucleotides that have not been optimized.

In an aspect, provided herein is a vector comprising a polynucleotide disclosed herein. Suitable vectors, include, without limitation, plasmids, viruses, cosmids, artificial chromosomes, linear DNA, and mRNA. In an embodiment, the vector is a plasmid or a viral vector. In an embodiment, the vector is a retrovirus vector, a herpes virus vector, a baculovirus vector, or an adenovirus vector. In an embodiment, the vector is an expression vector.

Vectors (e.g., expression vectors) can be introduced into cells (using any techniques known in the art) for propagation of the vector and/or for expression of an AAV capsid protein encoded by the vector. Accordingly, in another aspect, the instant disclosure provides a recombinant cell comprising a polynucleotide or a vector (e.g., an expression vector) disclosed herein. And further, in another aspect, the instant disclosure provides a method of producing an AAV capsid protein, the method comprising culturing the recombinant cell under conditions whereby the polynucleotide is expressed, and the capsid is produced.

A variety of host cells and expression vector systems can be utilized to express the capsid proteins described herein. In these expression systems, the coding sequences of interest can be produced and subsequently purified. These expression systems also represent cells which can, when transformed or transfected with the appropriate nucleotide coding sequences, express a capsid protein described herein in situ. These include but are not limited to microorganisms such as bacteria (e.g., E. coli and B. subtilis) transformed with, e.g., recombinant bacteriophage DNA, plasmid DNA or cosmid DNA expression vectors containing capsid protein coding sequences; yeast (e.g., Saccharomyces Pichia) transformed with, e.g., recombinant yeast expression vectors containing capsid protein coding sequences; insect cell systems infected with, e.g., recombinant virus expression vectors (e.g., baculovirus) containing capsid protein coding sequences; plant cell systems (e.g., green algae such as Chlamydomonas reinhardtii) infected with, e.g., recombinant virus expression vectors (e.g., cauliflower mosaic virus, CaMV; tobacco mosaic virus, TMV) or transformed with, e.g., recombinant plasmid expression vectors (e.g., Ti plasmid) containing capsid protein coding sequences; or mammalian cell systems (e.g., COS (e.g., COSI or COS), CHO, BHK, MDCK, HEK 293, NS0, PER.C6, VERO, CRL7030, HsS78Bst, HeLa, and NIH 3T3, HEK-293T, HepG2, SP210, R1.1, B-W, L-M, BSC1, BSC40, YB/20, and BMT10 cells) harboring, e.g., recombinant expression constructs containing promoters derived from the genome of mammalian cells (e.g., metallothionein promoter) or from mammalian viruses (e.g., the adenovirus late promoter; the vaccinia virus 7.5K promoter). In an embodiment, cells for expressing the capsid proteins described herein are human cells, e.g., human cell lines. In an embodiment, a mammalian expression vector is pOptiVEC™ or pcDNA3.3. In an embodiment, bacterial cells such as Escherichia coli, or eukaryotic cells (e.g., mammalian cells), are used for the expression of a capsid protein. For example, mammalian cells such as CHO or HEK293 cells, in conjunction with a vector such as the major intermediate early gene promoter element from human cytomegalovirus is an effective expression system for capsid proteins disclosed herein. In an embodiment, insect cells (e.g., Sf9 cells) are used for the expression of a capsid protein.

In an insect system, Autographa californica nuclear polyhedrosis virus (AcNPV), for example, can be used as a vector to express foreign genes. The virus grows in Spodoptera frugiperda cells. The capsid protein coding sequence can be cloned individually into non-essential regions (for example the polyhedrin gene) of the virus and placed under control of an AcNPV promoter (for example the polyhedrin promoter).

In mammalian host cells, a number of viral-based expression systems can be utilized. In cases where an adenovirus is used as an expression vector, the capsid protein coding sequence of interest can be ligated to an adenovirus transcription/translation control complex, e.g., the late promoter and tripartite leader sequence. This chimeric gene can then be inserted in the adenovirus genome by in vitro or in vivo recombination. Insertion in a non-essential region of the viral genome (e.g., region E1 or E3) will result in a recombinant virus that is viable and capable of expressing the capsid protein molecule in infected hosts (e.g., see Logan J & Shenk T (1984) PNAS 81 (12): 3655-9, which is herein incorporated by reference in its entirety). Specific initiation signals can also be required for efficient translation of inserted capsid protein coding sequences. These signals include the ATG initiation codon and adjacent sequences. Furthermore, the initiation codon must be in phase with the reading frame of the desired coding sequence to ensure translation of the entire insert. These exogenous translational control signals and initiation codons can be of a variety of origins, both natural and synthetic. The efficiency of expression can be enhanced by the inclusion of appropriate transcription enhancer elements, transcription terminators, etc. (see, e.g., Bitter G et al., (1987) Methods Enzymol. 153:516-544, which is herein incorporated by reference in its entirety). Such mammalian host cells include but are not limited to CHO, VERO, BHK, Hela, MDCK, HEK 293, NIH 3T3, W138, BT483, Hs578T, HTB2, BT20 and T47D, NS0, CRL7030, COS (e.g., COS1 or COS), PER.C6, VERO, HsS78Bst, HEK-293T, HepG2, SP210, R1.1, B-W, L-M, BSC1, BSC40, YB/20, BMT10, and HsS78Bst cells.

For long-term, high-yield production of recombinant proteins, stable expression cells can be generated. For example, cell lines which stably express a capsid protein described herein can be engineered.

In an embodiment, rather than using expression vectors which contain viral origins of replication, host cells can be transformed with a polynucleotide (e.g., DNA or RNA) controlled by appropriate transcriptional regulatory elements (e.g., promoter, enhancer, sequences, transcription terminators, polyadenylation sites, etc.), and a selectable marker. Following the introduction of polynucleotide, engineered cells can be allowed to grow for 1-2 days in an enriched media, and then are switched to a selective media. The selectable marker in the recombinant plasmid confers resistance to the selection and allows cells to stably integrate the plasmid into their chromosomes and grow to form foci which in turn can be cloned and expanded into cell lines. This method can advantageously be used to engineer cell lines which express a capsid protein described herein or a fragment thereof.

A number of selection systems can be used, including but not limited to the herpes simplex virus thymidine kinase (Wigler M et al., (1977) Cell 11 (1): 223-32), hypoxanthineguanine phosphoribosyltransferase (Szybalska E H & Szybalski W (1962) PNAS 48 (12): 2026-2034) and adenine phosphoribosyltransferase (Lowy I et al., (1980) Cell 22 (3): 817-23) genes in tk-, hgprt- or aprt-cells, respectively, all of which are herein incorporated by reference in their entireties. Also, antimetabolite resistance can be used as the basis of selection for the following genes: dhfr, which confers resistance to methotrexate (Wigler M et al., (1980) PNAS 77 (6): 3567-70; O'Hare K et al., (1981) PNAS 78:1527-31); gpt, which confers resistance to mycophenolic acid (Mulligan R C & Berg P (1981) PNAS 78 (4): 2072-6); neo, which confers resistance to the aminoglycoside G-418 (Wu G Y & Wu C H (1991) Biotherapy 3:87-95; Tolstoshev P (1993) Ann Rev Pharmacol Toxicol 32:573-596; Mulligan R C (1993) Science 260:926-932; and Morgan R A & Anderson W F (1993) Ann Rev Biochem 62:191-217; Nabel G J & Felgner P L (1993) Trends Biotechnol 11 (5): 211-5); and hygro, which confers resistance to hygromycin (Santerre R F et al., (1984) Gene 30 (1-3): 147-56), all of which are herein incorporated by reference in their entireties. Methods commonly known in the art of recombinant DNA technology can be routinely applied to select the desired recombinant clone and such methods are described, for example, in Ausubel F M et al., (eds.), Current Protocols in Molecular Biology, John Wiley & Sons, NY (1993); Kriegler M, Gene Transfer and Expression, A Laboratory Manual, Stockton Press, NY (1990); and in Chapters 12 and 13, Dracopoli N C et al., (eds.), Current Protocols in Human Genetics, John Wiley & Sons, NY (1994); Colbère-Garapin F et al., (1981) J Mol Biol 150:1-14, all of which are herein incorporated by reference in their entireties.

AAV Compositions

In one aspect, provided herein is an rAAV composition comprising a capsid comprising a recombinant AAV capsid protein disclosed herein.

In an aspect, provided herein is an rAAV comprising a capsid comprising one or more recombinant capsid protein disclosed herein; and an rAAV genome.

In an embodiment, the rAAV genome comprises a transgene. In an embodiment, the transgene encodes a polypeptide. In an embodiment, the transgene encodes an antibody or a fragment thereof. In an embodiment, the transgene encodes an scFv.

The rAAVs disclosed herein generally comprise a recombinant genome (e.g., an rAAV genome) packaged within the capsid. The rAAV genome can be of any type that is capable of being packaged within an AAV capsid disclosed herein. For example, in an embodiment, the rAAV genome is a single-stranded DNA genome. In an embodiment, the rAAV genome is a self-complementary genome, for example as described in U.S. Pat. No. 7,790,154, which is hereby incorporated by reference in its entirety.

In an embodiment, the rAAV genome comprises a transgene. In an embodiment, the transgene encodes a therapeutic protein. In an embodiment, the transgene encodes an antibody or a fragment thereof (e.g., a Fab, scFv, or full-length antibody). In an embodiment, the transgene encodes an scFv, nanobody, or VHH. In an embodiment, the transgene encodes a non-coding RNA.

In an embodiment, the transgene encodes reporter sequences, which upon expression produce a detectable signal. Such reporter sequences include, without limitation, DNA sequences encoding β-lactamase, β-galactosidase (LacZ), alkaline phosphatase, thymidine kinase, green fluorescent protein (GFP), red fluorescent protein (RFP), 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.

In an embodiment, the rAAV genome comprises a TRE operably linked to the transgene, to control expression of an RNA or polypeptide encoded by the transgene. In an embodiment, the TRE comprises a constitutive promoter. In an embodiment, the TRE is active in any mammalian cell (e.g., any human cell). In an embodiment, the TRE is active in a broad range of human cells. Such TREs may comprise constitutive promoter and/or enhancer elements, including any of those described herein, and any of those known to one of skill in the art. In an embodiment, the TRE comprises an inducible promoter. In an embodiment, the TRE is a tissue-specific TRE, i.e., it is active in specific tissue(s) and/or organ(s). A tissue-specific TRE comprises one or more tissue-specific promoter and/or enhancer elements, and optionally one or more constitutive promoter and/or enhancer elements. Tissue-specific promoter and/or enhancer elements can be isolated from genes specifically expressed in the tissue by methods well known in the art.

Suitable promoters include, e.g., cytomegalovirus promoter (CMV) (Stinski et al. (1985) Journal of Virology 55 (2): 431-441), CMV early enhancer/chicken β-actin (CBA) promoter/rabbit β-globin intron (CAG) (Miyazaki et al. (1989) Gene 79 (2): 269-277), hybrid form of the CBA promoter (CBh) (Gray et al. (2011) Hum Gene Ther. 22 (9): 1143-53), CBSB (Jacobson et al. (2006) Molecular Therapy 13 (6): 1074-1084), human elongation factor 1α promoter (EFla) (Kim et al. (1990) Gene 91 (2): 217-223), human phosphoglycerate kinase promoter (PGK) (Singer-Sam et al. (1984) Gene 32 (3): 409-417), mitochondrial heavy-strand promoter (Lodeiro et al. (2012) PNAS 109 (17): 6513-6518), ubiquitin promoter (Wulff et al. (1990) FEBS Letters 261:101-105).

In an aspect, provided herein is a pharmaceutical composition comprising an rAAV disclosed herein together with a pharmaceutically acceptable excipient, adjuvant, diluent, vehicle or carrier, or a combination thereof. A “pharmaceutically acceptable carrier” includes any material which, when combined with an active ingredient of a composition, allows the ingredient to retain biological activity and without causing disruptive physiological reactions, such as an unintended immune reaction. Pharmaceutically acceptable carriers include water, phosphate buffered saline, emulsions such as oil/water emulsion, and wetting agents. Compositions comprising such carriers are formulated by well-known conventional methods such as those set forth in Remington's Pharmaceutical Sciences, current Ed., Mack Publishing Co., Easton Pa. 18042, USA; A. Gennaro (2000) “Remington: The Science and Practice of Pharmacy”, 20th edition, Lippincott, Williams, & Wilkins; Pharmaceutical Dosage Forms and Drug Delivery Systems (1999) H. C. Ansel et al., 7th ed., Lippincott, Williams, & Wilkins; and Handbook of Pharmaceutical Excipients (2000) A. H. Kibbe et al., 3rd ed. Amer. Pharmaceutical Assoc.

Methods of Use

In an aspect, provided herein is a method of transducing a cell, the method comprising contacting the cell with an rAAV disclosed herein under conditions where the cell is transduced, and the transgene is expressed. In an embodiment, the cell is a muscle cell.

In an embodiment, provided herein is a method for expressing a transgene in a cell, the method generally comprising contacting the cell with such an rAAV under conditions whereby the cell is transduced, and the transgene is expressed. The transgene can encode a polypeptide, such as an antibody or a fragment thereof (e.g., an scFv), as described herein. Accordingly, in an embodiment, provided herein is a method for producing a polypeptide, such as an antibody or a fragment thereof (e.g., an scFv) in a cell, the method generally comprising contacting the cell with such an rAAV under conditions whereby the cell is transduced and the polypeptide, such as an antibody or a fragment thereof (e.g., an scFv), is produced.

In an aspect, provided herein is a method of delivering a transgene to a cell, the method comprising contacting the cell with an rAAV disclosed herein, under conditions where the cell is transduced, and the transgene is expressed. The rAAV disclosed herein can be used to transduce cells in vitro, in vivo and ex vivo. Cells suitable for being transduced by an rAAV disclosed herein include, without limitation, blood, liver, heart, joint tissue, muscle, brain, kidney, or lung cells. In an embodiment, the cell is a muscle cell, microglia, astrocyte, neuron, or cardiomyocyte. In an embodiment, an rAAV provided herein is used to transduce cells in vivo in a subject who has a disease associated with muscle tissue.

In an aspect, provided herein is a method of delivering a transgene to muscle tissue in a subject in need thereof, the method comprising administering an rAAV disclosed to the subject.

In an aspect, provided herein is a method of treating a neuromuscular or neurodegenerative disease or disorder in a subject in need thereof, comprising administering an effective amount of an rAAV disclosed herein to the subject. In an embodiment, the neuromuscular disease is selected from the group consisting of myopathy, hereditary cardiomyopathy, metabolic myopathy, distal myopathy, muscular dystrophy, congenital myopathy, spinal muscular atrophy (SMA), motor neuron disease, congenital myopathy, congenital muscular dystrophy, motor neuron disease, Duchenne muscular dystrophy, Becker muscular dystrophy, limb-girdle muscular dystrophies, myotonic dystrophy, myotubular myopathy, centronuclear myopathy, nemaline myopathy, selenoprotein N-related myopathy, Pompe disease, glycogen storage disease III, spinal muscular atrophy, amyotrophic lateral sclerosis, Charcot-Marie-Tooth disease, multiple sclerosis, myositis, polymyositis, and dermatomyositis.

In an embodiment, the rAAV disclosed herein can be administered to a subject (e.g., a human subject) by all routes suitable for an rAAV, including, without limitation, intravenously, intraperitoneally, subcutaneously, intramuscularly, intrathecally, or intradermally.

In an aspect, provided herein is an rAAV as disclosed herein for use in medicine. In an aspect, provided herein is an rAAV as disclosed herein for use as therapy. In an aspect, provided herein is an rAAV as disclosed herein for use as a medicament.

Adeno-Associated Virus Packaging Systems

In an aspect, provided herein is a packaging system for recombinant preparation of a recombinant adeno-associated virus (rAAV) disclosed herein. Such packaging systems generally comprise: a first nucleotide sequence encoding one or more AAV Rep proteins; a second nucleotide sequence encoding a capsid protein of any recombinant AAV capsid disclosed herein; and a third nucleotide sequence comprising any of AAV genome sequence disclosed herein, wherein the packaging system is operative in a cell for enclosing the AAV genome in the capsid to form the rAAV.

In an embodiment, the packaging system comprises a first vector comprising the first nucleotide sequence encoding the one or more AAV Rep proteins and the second nucleotide sequence encoding the AAV capsid protein, and a second vector comprising the third nucleotide sequence comprising the rAAV genome. As used in the context of a packaging system as described herein, a “vector” refers to a nucleic acid molecule that is a vehicle for introducing nucleic acids into a cell (e.g., a plasmid, a virus, a cosmid, an artificial chromosome).

Any AAV Rep protein can be employed in the packaging systems disclosed herein. In an embodiment of the packaging system, the Rep nucleotide sequence encodes an AAV2 Rep protein. Suitable AAV2 Rep proteins may include, without limitation, Rep 78/68 or Rep 68/52.

In an embodiment, the packaging system further comprises a fourth nucleotide sequence comprising one or more helper virus genes. In an embodiment, the fourth nucleotide sequence comprises adenoviral E2, E4, and VA genes. In an embodiment, the packaging system further comprises a third vector (e.g., a helper virus vector), comprising the fourth nucleotide sequence. The third vector may be an independent third vector, integral with the first vector, or integral with the second vector.

In an embodiment of the packaging system, the helper virus is selected from the group consisting of adenovirus, herpes virus (including herpes simplex virus (HSV)), poxvirus (such as vaccinia virus), cytomegalovirus (CMV), and baculovirus. In an embodiment where the helper virus is adenovirus, the adenovirus genome comprises one or more adenovirus RNA genes selected from the group consisting of E1, E2, E4, and VA. In an embodiment, the adenovirus genome comprises one or more adenovirus RNA genes selected from the group consisting of E2, E4, and VA. In an embodiment where the helper virus is HSV, the HSV genome comprises one or more HSV genes selected from the group consisting of UL5/8/52, ICPO, ICP4, ICP22, and UL30/UL42.

In an embodiment of the packaging system, the first, second, and/or third vector are contained within one or more plasmids. In an embodiment, the first vector and the third vector are contained within a first plasmid. In an embodiment, the second vector and the third vector are contained within a second plasmid.

In an embodiment of the packaging system, the first, second, and/or third vector are contained within one or more recombinant helper viruses. In an embodiment, the first vector and the third vector are contained within a recombinant helper virus. In an embodiment, the second vector and the third vector are contained within a recombinant helper virus.

In an aspect, provided herein is a method for recombinant preparation of an rAAV as described herein, wherein the method comprises transfecting or transducing a cell with a packaging system as described herein under conditions operative for enclosing the rAAV genome in the capsid to form the rAAV as described herein. Exemplary methods for recombinant preparation of an rAAV include transient transfection (e.g., with one or more transfection plasmids containing a first, and a second, and optionally a third vector as described herein), viral infection (e.g., with one or more recombinant helper viruses, such as adenovirus, poxvirus (such as vaccinia virus), herpes virus (including HSV, cytomegalovirus, or baculovirus), containing a first, and a second, and optionally a third vector as described herein), and stable producer cell line transfection or infection (e.g., with a stable producer cell, such as a mammalian or insect cell, containing a Rep nucleotide sequence encoding one or more AAV Rep proteins and/or a Cap nucleotide sequence encoding one or more capsid proteins as described herein, and with a transfer genome as described herein being delivered in the form of a plasmid or a recombinant helper virus).

Accordingly, the instant disclosure provides a packaging system for preparation of an rAAV, wherein the packaging system comprises: a first nucleotide sequence encoding one or more AAV Rep proteins; a second nucleotide sequence encoding an AAV capsid protein disclosed herein; a third nucleotide sequence comprising an rAAV genome sequence described herein; and optionally a fourth nucleotide sequence comprising one or more helper virus genes (e.g., adenoviral E2, E4, and VA genes).

EXAMPLES
Example 1: Production of the Modified Capsids

Recombinant AAV capsids that specifically target muscle cells were developed by inserting a peptide within the amino acid sequence of a parental AAV capsid protein.

a. AAV′2 5 Capsid

A chimeric AAV capsid (AAV5.2, SEQ ID NO: 11) was used as the parental capsid protein to generate recombinant AAV capsid proteins. An AAV capsid is encoded by three viral proteins (VPs), VP1, VP2 and VP3, which are incorporated into a 60-subunit capsid in a 1:1:10 ratio. The AAV5.2 capsid is an engineered variant of AAV2 and AAV5 capsids, which includes a VP1 sequence from AAV2 and a VP2/3 sequence from AAV5.

b. Design of Capsids

The VP1 and VP2 unique sequences are located on the inside of the capsid and contain a phospholipase (PLA2) domain (in VP1) and nuclear localization signal (VP1 and VP2). The VP3 sequence (which is contained in all three VPs) is the primary protein sequence which constitutes the surface topology of the AAV capsid, which in turn dictates tropism and antigenicity. The VP3 topology contains a core eight-stranded (BB to BI)-barrel motif and large loop insertions between the β-strands which form the surface of the capsid. Conformational variations in these nine surface loops (VR-I to VR-IX) define the unique surface features for the distinct AAV serotypes. Accordingly, the peptide insertions described here are inserted in these externally facing loops. Specifically, loops IV and VIII were selected for peptide insertion sites.

Position 443, located at the apex of loop IV on the AAV5 capsid (SEQ ID NO: 10) or position 444 on the AAV5.2 capsid (SEQ ID NO: 11), was selected as an insertion site in loop IV, the peptides were inserted immediately C-terminal to these amino acid positions. Position 576, located at the apex of loop VIII on the AAV5 capsid (SEQ ID NO: 10) or position 577 on the AAV5.2 capsid (SEQ ID NO 11), was selected as the insertion site in loop VIII, the peptides were inserted immediately C-terminal to these amino acid positions. Insertion of a peptide immediately C-terminal to these positions should have minimal effect on capsid integrity because the remaining VP residue interactions remain intact at the base of the capsid.

Nine different peptides (SEQ ID NOs: 1-9; see Table 1) were used to engineer the recombinant AAV capsid proteins. Specifically, polynucleotides encoding capsid proteins comprising a parental AAV5.2 capsid protein with a peptide insertion from Table 1 were synthesized and inserted into a plasmid vector. Each AAV capsid protein was engineered to contain only one peptide insertion, immediately C-terminal to position 444 in loop IV or 577 in loop VIII according to AAV5.2 (SEQ ID NO: 11), i.e., position 443 in loop IV and position 576 in loop VIII of the AAV5 capsid (SEQ ID NO: 10). The amino acid sequences of the resulting recombinant AAV capsid proteins (SEQ ID NOs: 12-29) are disclosed in Table 2.

Example 2: Transduction of Human Muscle Bundles

The ability of the recombinant AAV capsids to target muscle cells was analyzed by transducing muscle cells in human muscle bundles.

Muscle cell transduction was analyzed in a 3D muscle microtissue model, generated using human skeletal myoblasts (CC-2580, Lonza). Briefly, cells were seeded within the hydrogel mixture and an appropriate volume of seeding hydrogel mixture containing cells was added into each muscle chamber of the OMEGAMP device ensuring that the cells were evenly spread within the seeding hydrogel and throughout the chamber. Myoblasts were maintained in myoblast seeding medium for 2 days post seeding. The medium was then replaced with 2 mL of freshly prepared myoblast differentiation medium. AAV transduction of the muscle microtissues was performed at day 11 of differentiation by adding myoblast differentiation medium containing the different AAV capsids, VYAAV-5.2-GFP, AAV-VYPep15-loopIV-GFP, AAV-VYPep14-loopIV-GFP or AAV9-GFP (HEK) at an MOI of 1×10⁶per cell. Medium containing the AAV capsids was replaced with fresh myoblast differentiation medium 2 days post transduction. Myoblast differentiation medium was partially replaced every 2 days until the day of harvest at day 18.

At day 18 post differentiation, myoblast differentiation medium was replaced with PBS containing Hoechst 3342 (1:10,000) and the muscle microtissues were imaged using the ImageXpress PICO at 4× magnification. GFP expression from the muscle microtissue was quantified as mean fluorescence intensity using ImageJ and the results were expressed as fold increase in GFP expression from different capsids versus GFP expression from AAV9.

The results summarized in Table 5 below demonstrate that recombinant AAV capsids with a peptide inserted at position 443 in loop IV show improved transduction of muscle cells compared to the parental AAV capsid.

TABLE 5

Quantification of GFP expression

in muscle bundles

Fold increase

GFP expression

Capsid
vs. AAV9

AAV5.2
1.4×

(SEQ ID NO: 11)

AAV5.2-VYPep15-
1.8×

loopIV

SEQ ID NO: 28)

AAV5.2-VYPep14-
4.6×

loopIV

SEQ ID NO: 26)

Example 3: Transduction of Human Myotubes

The transduction efficiency of the recombinant AAV capsids was further analyzed by transducing human myotubes with the capsids.

Human skeletal muscle cells (CC-2580, Lonza) were plated at a cell density of 50,000 cells per well of a 24 well plate. Differentiation of myoblasts was induced when the cells reached 85-90% confluency by replacing myoblast proliferation media with myoblast (low serum) differentiation media. Myotube differentiation was carried out for 7 days with differentiation medium being partially replaced every 2 days. AAV transduction of the myotubes was performed at an MOI of 1×10⁶per cell, mixed with 50 μL of PBS at the start of differentiation and negative controls were treated with 50 μL of PBS only. One day post-transduction, medium was refreshed. For analysis of transduction efficacy, GFP+ cells were monitored overtime with the EVOS FLoid Imaging System (Cat. No. 447116). One-week post-transduction, the transduced myotubes were imaged using the EVOS FLoid Imaging System (Cat. No. 447116) at 20× magnification and later harvested and frozen for further quantitative analyses.

The GFP imaging results shown in FIG. 1A and FIG. 1B, demonstrate that several of the recombinant AAV capsids successfully transduced human myotubes and that some of the capsids showed increased transduction of myotubes when the peptide is inserted in loop IV compared to loop VIII. Further, the results shown in FIG. 2 demonstrate that recombinant AAV capsids comprising VYPep14 or VYPep15 at position 443 in loop IV (AAV5.2-VYPep14-loopIV and AAV5.2-VYPep15-loopIV) or 576 in loop VIII (AAV5.2-VYPep14-loopVIII and AAV5.2-VYPep15-loopVIII) successfully transduced myotubes; and the results shown in FIG. 3A and FIG. 3B demonstrate that the recombinant AAV capsids comprising VYPep14 or VYPep7 at position 443 in loop IV (AAV5.2-VYPep14-loopIV and AAV5.2-VYPep7-loopIV, respectively), show improved transduction of myotubes compared to the parental AAV5.2 capsid.

Example 4: Transduction of Human Astrocytes and Motor Neurons

The transduction efficiency of the recombinant AAV capsids was further analyzed by transducing human astrocytes and motor neurons with the capsids.

Human astrocytes and iPSC-derived motor neurons were plated at a cell density of 50,000 cells per well of a 24 well plate. The astrocytes were transduced with parental AAV9, AAV9 with VYPep14 inserted in loop VIII (AAV9-VYPep14-loopVIII), parental AAV5.2, AAV5.2-VYPep14-loopIV, AAV5.2-VYPep14-loopVIII, AAV5.2-VYPep15-loop VIII, AAV5.2-VYPep7-loopIV, AAV5.2-VYPep7-loopVIII at an MOI of 1×10⁴per cell. The motor neurons were transduced with AAV9, parental AAV5.2, AAV5.2-VYPep7-loopIV, AAV5.2-VYPep7-loop VIII at an 1×10⁶per cell. One day post-transduction, medium was refreshed. For analysis of transduction efficacy of astrocytes, GFP+ cells were monitored overtime with the EVOS FLoid Imaging System (Cat. No. 447116). One-week post-transduction, the transduced astrocytes were imaged using the EVOS FLoid Imaging System (Cat. No. 447116) at 20× magnification and later harvested and frozen for further quantitative analyses. The motor neurons were stained with Hoechst one week post transduction and analyzed for Hoechst and GFP fluorescence. The % positive motor neurons were determined using the cell scoring analysis within the PICO ImageXpress software which scores nuclei positive for both Hoechst and GFP.

GFP expression from the astrocytes was quantified and expressed as percentage of GFP positive cells out of the total number of cells. The results shown in FIG. 4A and FIG. 4B demonstrate that several of the recombinant AAV capsids successfully transduced human astrocytes and that some of the capsids show increased transduction of astrocytes when the peptide is inserted in loop IV compared to loop VIII. Further, the results shown in FIG. 5 demonstrate that recombinant AAV capsids comprising VYPep7 at position 443 in loop IV successfully transduced human motor neurons.

The transduction efficiency of AAV5.2-VYPep7-loop IV in astrocytes was further analyzed at different MOIs over a course of eight days. iPSC-derived astrocytes were seeded at day 0 and transduced 4 days post seeding with AAV5.2-GFP, AAV9-GFP, or AAV5.2-VYPep7-loop IV at 3 different MOIs: 1×10⁴, 1×10⁵, or 1×10⁶. Fluorescence images were acquired at 2—, 4- and 8 days post transduction. The % positive cells were determined using the cell scoring analysis within the PICO ImageXpress software which scores nuclei both positive for Hoechst and GFP. The results in FIGS. 6A-6C show that the transduction efficiency of each AAV capsid increases with increasing MOI, and that AAV5.2-VYPep7-loopIV (FIG. 6C) more efficiently transduced astrocytes compared to the parental AAV9 (FIG. 6A) or AAV5.2 (FIG. 6B).

Example 5: Transduction of Non-Human Primate Astrocytes

The transduction efficiency of the recombinant AAV capsids was further analyzed by transducing non-human primate (NHP) astrocytes.

Primary NHP astrocytes were seeded at day 0 and grown to a 70-90% confluency. Four days post seeding, the cells were transduced at an MOI 1×10⁵and 1×10⁶with mock/negative control, AAV5.2-GFP, AAV9-GFP, AAV5.2-VYPep7-loopIV-GFP, and AAV5.2-VYPep14-loopIV-GFP. Images were acquired at 3 days post transduction. The % positive cells were determined using the cell scoring analysis within the PICO ImageXpress software which scores nuclei positive for both Hoechst and GFP.

The results in FIG. 7 show that the AAV5.2-VYPep7-loopIV capsid is significantly more efficient at transducing NHP astrocytes, compared to the parental AAV5.2 or AAV9 capsids.

Example 6: Transduction of Across the Blood Brain Barrier (BBB)

The ability of the recombinant AAV capsids to permeate the blood brain barrier (BBB) was analyzed using a BBB microfluid model.

The BBB model used for testing of the capsids comprises human cell lines of brain endothelial cells (blood side) and astrocytes (brain side) in a three-lane microfluidic platform that harbors 40 chips in a 384-well plate format (OrganoPlate® 3-lane 40). In each chip, a perfused vessel of brain endothelial cells was grown against an extracellular matrix gel, which was patterned by means of surface tension techniques. Astrocytes were added on the other side of the gel to complete the BBB on-a-chip model. Barrier function of the model was studied using fluorescent barrier integrity assays. The different AAV capsids, VVAAV-5.2-GFP, VYAAV-5.2-GFP, AAV5.2-VYPep7-loopIV-GFP, AAV5.2-VYPep14-loopIV-GFP, AAV5.2-VYPep14-loopVIII-GFP, and AAV9-VYPep14-loop VIII-GFP were added to the chips on the blood side at day 10 post seeding of the endothelial cells at an MOI of 1×10⁶per cell. Medium was replaced with fresh human brain microvascular endothelial cell medium and astrocyte medium on the blood side and the brain side, respectively. At Day 6 post transduction with the AAV5, medium was replaced with PBS containing Hoescht 33342, 1:10,000 (Cat. No. 62249, Thermofisher Scientific) and the Organoplate was imaged using the ImageXpress PICO at 4× magnification.

GFP expression from the cells transduced with AAV5.2-GFP, AAV5.2VYPep7-loopIV, and AAV5.2VYPep14-loopIV was quantified both on the blood side (endothelial) and brain side (astrocytes) and expressed as percentage of GFP positive cells out of the total number of cells at day 6 (FIG. 8A) and day 11 (FIG. 8B). GFP expression from the cells transduced with AAV5.2, AAV9, AAV5.2VYPep14-loopIV, and AAV5.2VYPep14-loopVIII was quantified both from the blood side and brain side at Day 13 post transduction and compared with GFP expression from cells at Day 6 post transduction and results were expressed as average GFP intensity per cell (FIG. 8C). The % positive cells were determined using ImageJ software.

The results in FIG. 8A, FIG. 8B, and FIG. 8C show that the recombinant AAV capsids successfully permeate the BBB and transduce astrocytes on the brain side of the BBB.

Example 7: Transduction Efficiency of Dual Loop Capsids

Recombinant AAV5.2 capsids with two peptide insertions, one in loop IV and one in loop VIII (“dual loop capsids”), were analyzed for their ability to transduce iPSC-derived cortical astrocytes.

The following recombinant AAV5.2 dual loop capsids were designed:

TABLE 6

Dual loop capsids design

Peptide
Peptide

insertion
insertion

in loop
in loop

Capsid
IV*
VIII**

AAV5.2-
VYPep14
VYPep14

VYPep14-
(SEQ ID
(SEQ ID

IV-
NO: 8)
NO: 8)

VYPep14-
RGDLGL
RGDLGL

VIII

(SEQ ID

NO:

30)

AAV5.2-
VYPep14
VYPep4

VYPep14-
(SEQ ID
(SEQ ID

IV-
NO: 8)
NO: 35)

VYPep4-
RGDLGL
RTIGPSV

VIII

(SEQ ID

NO:

31)

AAV5.2-
VYPep4
VYPep14

VYPep4-
(SEQ ID
(SEQ ID

IV-
NO: 35)
NO: 8)

VYPep14-
RTIGPSV
RGDLGL

VIII

(SEQ ID

NO:

32)

AAV5.2-
VYPep5
VYPep14

VYPep5-
(SEQ ID
(SEQ ID

IV-
NO: 36)
NO: 8)

VYPep14-
LSSRLDA
RGDLGL

VIII

(SEQ ID

NO:

33)

AAV5.2-
VYPep7
VYPep14

VYPep7-
(SEQ ID
(SEQ ID

IV-
NO: 2)
NO: 8)

VYPep14-
APLTNTV
RGDLGL

VIII
KA

(SEQ ID

NO:

34)

*The peptide is inserted immediately C-terminal to position 444 in loop IV according to AAV5.2 (SEQ ID NO: 11), i.e., position 443 in loop IV of the AAV5 capsid (SEQ ID NO: 10).

**The peptide is inserted immediately C-terminal to position 577 in loop VIII according to AAV5.2 (SEQ ID NO: 11), i.e., position 576 in loop VIII of the AAV5 capsid (SEQ ID NO: 10).

To test these dual loop capsids, iPSC-derived cortical astrocytes were seeded at day 0 and transduced at 4 days post seeding with AAV5.2-GFP, AAV9-GFP, AAV5.2-VYPep14-IV, AAV5.2-VYPep4-IV, AAV5.2-VYPep7-IV, AAV5.2-VYPep14-IV-VYPep14-VIII-GFP, AAV5.2-VYPep14-IV-VYPep4-VIII-GFP, AAV5.2-VYPep4-IV-VYPep14-VIII-GFP, AAV5.2-VYPep5-IV-VYPep14-VIII-GFP, AAV5.2-VYPep7-IV-VYPep14-VIII-GFP, at MOI 10{circumflex over ( )}5. Images were acquired at 3 days post transduction. The % positive cells were determined using the cell scoring analysis within the PICO ImageXpress software which scores nuclei positive for both Hoechst and GFP. The results in FIG. 9A show that most of the dual loop capsids tested transduce astrocytes more efficiently than the parental AAV5.2 or AAV9 capsids.

The full viral titers, expressed as viral genomes/mL, for AAV5.2-GFP, AAV9-GFP, AAV5.2-VYPep14-IV-VYPep14-VIII-GFP, AAV5.2-VYPep14-IV-VYPep4-VIII-GFP, AAV5.2-VYPep4-IV-VYPep14-VIII-GFP, AAV5.2-VYPep5-IV-VYPep14-VIII-GFP, AAV5.2-VYPep7-IV-VYPep14-VIII-GFP, were determined using the Stunner system (Unchained Labs). The viral titer results are shown in FIG. 9B.

The dual capsid preparations were also tested for full capsids and aggregates. The percentage (%) of full capsids and percentage of aggregation values for AAV5.2-GFP, AAV9-GFP, AAV5.2-VYPep14-IV-VYPep14-VIII-GFP, AAV5.2-VYPep14-IV-VYPep4-VIII-GFP, AAV5.2-VYPep4-IV-VYPep14-VIII-GFP, AAV5.2-VYPep5-IV-VYPep14-VIII-GFP, AAV5.2-VYPep7-IV-VYPep14-VIII-GFP, were determined using the Stunner system (Unchained Labs). The results in FIG. 9C show that the capsids had high percentages of full capsids and low percentages of aggregates.

The invention is not to be limited in scope by the specific embodiments described herein. Indeed, various modifications of the invention in addition to those described will become apparent to those skilled in the art from the foregoing description and accompanying figures. Such modifications are intended to fall within the scope of the appended claims.

All references (e.g., publications or patents or patent applications) cited herein are incorporated herein by reference in their entirety and for all purposes to the same extent as if each individual reference (e.g., publication or patent or patent application) was specifically and individually indicated to be incorporated by reference in its entirety for all purposes. Other embodiments are within the following claims.

Claims

1. A recombinant adeno-associated virus (AAV) capsid protein comprising a peptide and a parental capsid protein, wherein the peptide is comprised within loop IV and/or loop VIII of the parental capsid protein, and wherein the peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-9.
2. The recombinant AAV capsid protein of claim 1, wherein the parental capsid protein is a clade A, clade B, clade C, clade D, clade E, clade F, clade G, clade H, clade I, AAVgo.1, AAV3, AAV4, AAV10, AAV11, AAV12, rh.32, rh32.33, rh.33, rh.34, BAAV, or AAV5 capsid protein, or an engineered variant thereof.
3. The recombinant AAV capsid protein of claim 1, wherein the parental capsid protein comprises an amino acid sequence that has at least 95% identity to amino acids 193-725 of SEQ ID NO: 11.
4. The recombinant AAV capsid protein of claim 1, wherein the parental capsid protein comprises an amino acid sequence that has at least 99% identity to amino acids 193-725 of SEQ ID NO: 11.
5. The recombinant AAV capsid protein of claim 1, wherein the parental capsid protein comprises the amino acid sequence of amino acids 193-725 of SEQ ID NO: 11.
6. The recombinant AAV capsid protein of claim 1, wherein the parental capsid protein comprises an amino acid sequence that has at least 95% identity to amino acids 138-725 of SEQ ID NO: 11.
7. The recombinant AAV capsid protein of claim 1, wherein the parental capsid protein comprises an amino acid sequence that has at least 99% identity to amino acids 138-725 of SEQ ID NO: 11.
8. The recombinant AAV capsid protein of claim 1, wherein the parental capsid protein comprises the amino acid sequence of amino acids 138-725 of SEQ ID NO: 11.
9. The recombinant AAV capsid protein of claim 1, wherein the parental capsid protein comprises an amino acid sequence that has at least 95% identity to SEQ ID NO: 10 or 11.
10. The recombinant AAV capsid protein of claim 1, wherein the parental capsid protein comprises an amino acid sequence that has at least 99% identity to SEQ ID NO: 10 or 11.
11. The recombinant AAV capsid protein of claim 1, wherein the parental capsid protein comprises the amino acid of SEQ ID NO: 10 or 11.
12. The recombinant AAV capsid protein of any one of claims 1-11, wherein the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 440, 441, 442, 443, 444, 445, 446, 447, 572, 573, 574, 575, 576, 577, 578, 579, 580, 581, 582, 583, or 584 of SEQ ID NO: 11.
13. The recombinant AAV capsid protein of claim 12, wherein the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 440 of SEQ ID NO: 11.
14. The recombinant AAV capsid protein of claim 12, wherein the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 441 of SEQ ID NO: 11.
15. The recombinant AAV capsid protein of claim 12, wherein the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 442 of SEQ ID NO: 11.
16. The recombinant AAV capsid protein of claim 12, wherein the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 443 of SEQ ID NO: 11.
17. The recombinant AAV capsid protein of claim 12, wherein the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 444 of SEQ ID NO: 11.
18. The recombinant AAV capsid protein of claim 12, wherein the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 445 of SEQ ID NO: 11.
19. The recombinant AAV capsid protein of claim 12, wherein the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 446 of SEQ ID NO: 11.
20. The recombinant AAV capsid protein of claim 12, wherein the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 447 of SEQ ID NO: 11.
21. The recombinant AAV capsid protein of claim 12, wherein the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 572 of SEQ ID NO: 11.
22. The recombinant AAV capsid protein of claim 12, wherein the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 573 of SEQ ID NO: 11.
23. The recombinant AAV capsid protein of claim 12, wherein the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 574 of SEQ ID NO: 11.
24. The recombinant AAV capsid protein of claim 12, wherein the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 575 of SEQ ID NO: 11.
25. The recombinant AAV capsid protein of claim 12, wherein the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 576 of SEQ ID NO: 11.
26. The recombinant AAV capsid protein of claim 12, wherein the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 577 of SEQ ID NO: 11.
27. The recombinant AAV capsid protein of claim 12, wherein the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 578 of SEQ ID NO: 11.
28. The recombinant AAV capsid protein of claim 12, wherein the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 579 of SEQ ID NO: 11.
29. The recombinant AAV capsid protein of claim 12, wherein the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 580 of SEQ ID NO: 11.
30. The recombinant AAV capsid protein of claim 12, wherein the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 581 of SEQ ID NO: 11.
31. The recombinant AAV capsid protein of claim 12, wherein the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 582 of SEQ ID NO: 11.
32. The recombinant AAV capsid protein of claim 12, wherein the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 583 of SEQ ID NO: 11.
33. The recombinant AAV capsid protein of claim 12, wherein the peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 584 of SEQ ID NO: 11.
34. The recombinant AAV capsid protein of claim 1, comprising: (a) an amino acid sequence that has at least 95% sequence identity to amino acids 194-763 SEQ ID NO: 12, wherein of amino acids 445-482 are ASLEEEWAQVECEVYGRGCPSGSLDESFYDWFERQLGA (SEQ ID NO: 1);(b) an amino acid sequence that has at least 95% sequence identity to amino acids 194-763 of SEQ ID NO: 13, wherein amino acids 578-615 are ASLEEEWAQVECEVYGRGCPSGSLDESFYDWFERQLGA (SEQ ID NO: 1);(c) an amino acid sequence that has at least 95% sequence identity to amino acids 194-734 of SEQ ID NO: 14, wherein amino acids 445-453 are APLTNTVKA (SEQ ID NO: 2);(d) an amino acid sequence that has at least 95% sequence identity to amino acids 194-734 of SEQ ID NO: 15, wherein amino acids 578-586 are APLTNTVKA (SEQ ID NO: 2);(e) an amino acid sequence that has at least 95% sequence identity to amino acids 194-732 of SEQ ID NO: 16, wherein amino acids 445-451 are DDTRHWG (SEQ ID NO: 3);(f) an amino acid sequence that has at least 95% sequence identity to amino acids 194-732 of SEQ ID NO: 17, wherein amino acids 578-584 are DDTRHWG (SEQ ID NO: 3);(g) an amino acid sequence that has at least 95% sequence identity to amino acids 194-732 of SEQ ID NO: 18, wherein amino acids 445-451 are EYHHYNK (SEQ ID NO: 4);(h) an amino acid sequence that has at least 95% sequence identity to amino acids 194-732 of SEQ ID NO: 19, wherein amino acids 578-584 are EYHHYNK (SEQ ID NO: 4);(i) an amino acid sequence that has at least 95% sequence identity to amino acids 194-732 of SEQ ID NO: 20, wherein amino acids 445-451 are QLFPLFR (SEQ ID NO: 5);(j) an amino acid sequence that has at least 95% sequence identity to amino acids 194-732 of SEQ ID NO: 21, wherein amino acids 578-584 are QLFPLFR (SEQ ID NO: 5);(k) an amino acid sequence that has at least 95% sequence identity to amino acids 194-742 of SEQ ID NO: 22, wherein amino acids 445-461 are FNPVTGEVPPRYPLDAR (SEQ ID NO: 6);(l) an amino acid sequence that has at least 95% sequence identity to amino acids 194-742 of SEQ ID NO: 23, wherein amino acids 578-594 are FNPVTGEVPPRYPLDAR (SEQ ID NO: 6);(m) an amino acid sequence that has at least 95% sequence identity to amino acids 194-739 of SEQ ID NO: 24, wherein amino acids 445-458 are SVTEQGAELSNEER (SEQ ID NO: 7);(n) an amino acid sequence that has at least 95% sequence identity to amino acids 194-739 of SEQ ID NO: 25, wherein amino acids 578-591 are SVTEQGAELSNEER (SEQ ID NO: 7);(o) an amino acid sequence that has at least 95% sequence identity to amino acids 194-735 of SEQ ID NO: 26, wherein amino acids 449-454 are RGDLGL (SEQ ID NO: 8);(p) an amino acid sequence that has at least 95% sequence identity to amino acids 194-735 of SEQ ID NO: 27, wherein amino acids 578-584 are RGDLGL (SEQ ID NO: 8);(q) an amino acid sequence that has at least 95% sequence identity to amino acids 194-737 of SEQ ID NO: 28, wherein amino acids 447-453 are ASSLNIA (SEQ ID NO: 9); or(r) an amino acid sequence that has at least 95% sequence identity to amino acids 194-737 of SEQ ID NO: 29, wherein amino acids 580-586 are ASSLNIA (SEQ ID NO: 9).
35. The recombinant AAV capsid protein of claim 1, comprising: (a) an amino acid sequence that has at least 99% sequence identity to amino acids 194-763 SEQ ID NO: 12, wherein amino acids 445-482 are ASLEEEWAQVECEVYGRGCPSGSLDESFYDWFERQLGA (SEQ ID NO: 1);(b) an amino acid sequence that has at least 99% sequence identity to amino acids 194-763 of of SEQ ID NO: 13, wherein amino acids 578-615 are ASLEEEWAQVECEVYGRGCPSGSLDESFYDWFERQLGA (SEQ ID NO: 1);(c) an amino acid sequence that has at least 99% sequence identity to amino acids 194-734 of SEQ ID NO: 14, wherein amino acids 445-453 are APLTNTVKA (SEQ ID NO: 2);(d) an amino acid sequence that has at least 99% sequence identity to amino acids 194-734 of SEQ ID NO: 15, wherein amino acids 578-586 are APLTNTVKA (SEQ ID NO: 2);(e) an amino acid sequence that has at least 99% sequence identity to amino acids 194-732 of SEQ ID NO: 16, wherein amino acids 445-451 are DDTRHWG (SEQ ID NO: 3);(f) an amino acid sequence that has at least 99% sequence identity to amino acids 194-732 of SEQ ID NO: 17, wherein amino acids 578-584 are DDTRHWG (SEQ ID NO: 3);(g) an amino acid sequence that has at least 99% sequence identity to amino acids 194-732 of SEQ ID NO: 18, wherein amino acids 445-451 are EYHHYNK (SEQ ID NO: 4);(h) an amino acid sequence that has at least 99% sequence identity to amino acids 194-732 of SEQ ID NO: 19, wherein amino acids 578-584 are EYHHYNK (SEQ ID NO: 4);(i) an amino acid sequence that has at least 99% sequence identity to amino acids 194-732 of SEQ ID NO: 20, wherein amino acids 445-451 are QLFPLFR (SEQ ID NO: 5);(j) an amino acid sequence that has at least 99% sequence identity to amino acids 194-732 of SEQ ID NO: 21, wherein amino acids 578-584 are QLFPLFR (SEQ ID NO: 5);(k) an amino acid sequence that has at least 99% sequence identity to amino acids 194-742 of SEQ ID NO: 22, wherein amino acids 445-461 are FNPVTGEVPPRYPLDAR (SEQ ID NO: 6);(l) an amino acid sequence that has at least 99% sequence identity to amino acids 194-742 of SEQ ID NO: 23, wherein amino acids 578-594 are FNPVTGEVPPRYPLDAR (SEQ ID NO: 6);(m) an amino acid sequence that has at least 99% sequence identity to amino acids 194-739 of SEQ ID NO: 24, wherein amino acids 445-458 are SVTEQGAELSNEER (SEQ ID NO: 7);(n) an amino acid sequence that has at least 99% sequence identity to amino acids 194-739 of SEQ ID NO: 25, wherein amino acids 578-591 are SVTEQGAELSNEER (SEQ ID NO: 7);(o) an amino acid sequence that has at least 99% sequence identity to amino acids 194-735 of SEQ ID NO: 26, wherein amino acids 449-454 are RGDLGL (SEQ ID NO: 8);(p) an amino acid sequence that has at least 99% sequence identity to amino acids 194-735 of SEQ ID NO: 27, wherein amino acids 578-584 are RGDLGL (SEQ ID NO: 8);(q) an amino acid sequence that has at least 99% sequence identity to amino acids 194-737 of SEQ ID NO: 28, wherein amino acids 447-453 are ASSLNIA (SEQ ID NO: 9); or(r) an amino acid sequence that has at least 99% sequence identity to amino acids 194-737 of SEQ ID NO: 29, wherein amino acids 580-586 are ASSLNIA (SEQ ID NO: 9).
36. The recombinant AAV capsid protein of claim 1, comprising: (a) an amino acid sequence that has 100% sequence identity to amino acids 194-763 of SEQ ID NO: 12;(b) an amino acid sequence that has 100% sequence identity to amino acids 194-763 of SEQ ID NO: 13;(c) an amino acid sequence that has 100% sequence identity to amino acids 194-734 of SEQ ID NO: 14;(d) an amino acid sequence that has 100% sequence identity to amino acids 194-734 of SEQ ID NO: 15;(e) an amino acid sequence that has 100% sequence identity to amino acids 194-732 of SEQ ID NO: 16;(f) an amino acid sequence that has 100% sequence identity to amino acids 194-732 of SEQ ID NO: 17;(g) an amino acid sequence that has 100% sequence identity to amino acids 194-732 of SEQ ID NO: 18;(h) an amino acid sequence that has 100% sequence identity to amino acids 194-732 of SEQ ID NO: 19;(i) an amino acid sequence that has 100% sequence identity to amino acids 194-732 of SEQ ID NO: 20;(j) an amino acid sequence that has 100% sequence identity to amino acids 194-732 of SEQ ID NO: 21;(k) an amino acid sequence that has 100% sequence identity to amino acids 194-742 of SEQ ID NO: 22;(l) an amino acid sequence that has 100% sequence identity to amino acids 194-742 of SEQ ID NO: 23;(m) an amino acid sequence that has 100% sequence identity to amino acids 194-739 of SEQ ID NO: 24;(n) an amino acid sequence that has 100% sequence identity to amino acids 194-739 of SEQ ID NO: 25;(o) an amino acid sequence that has 100% sequence identity to amino acids 194-735 of SEQ ID NO: 26;(p) an amino acid sequence that has 100% sequence identity to amino acids 194-735 of SEQ ID NO: 27;(q) an amino acid sequence that has 100% sequence identity to amino acids 194-737 of SEQ ID NO: 28; or(r) an amino acid sequence that has 100% sequence identity to amino acids 194-737 of SEQ ID NO: 29.
37. The recombinant AAV capsid protein of claim 1, comprising: (a) an amino acid sequence that has at least 95% sequence identity to amino acids 138-763 SEQ ID NO: 12, wherein amino acids 445-482 are of ASLEEEWAQVECEVYGRGCPSGSLDESFYDWFERQLGA (SEQ ID NO: 1);(b) an amino acid sequence that has at least 95% sequence identity to amino acids 138-763 SEQ amino acids 578-615 are ID NO: 13, wherein of ASLEEEWAQVECEVYGRGCPSGSLDESFYDWFERQLGA (SEQ ID NO: 1);(c) an amino acid sequence that has at least 95% sequence identity to amino acids 138-734 of SEQ ID NO: 14, wherein amino acids 445-453 are APLTNTVKA (SEQ ID NO: 2);(d) an amino acid sequence that has at least 95% sequence identity to amino acids 138-734 of SEQ ID NO: 15, wherein amino acids 578-586 are APLTNTVKA (SEQ ID NO: 2);(e) an amino acid sequence that has at least 95% sequence identity to amino acids 138-732 of SEQ ID NO: 16, wherein amino acids 445-451 are DDTRHWG (SEQ ID NO: 3);(f) an amino acid sequence that has at least 95% sequence identity to amino acids 138-732 of SEQ ID NO: 17, wherein amino acids 578-584 are DDTRHWG (SEQ ID NO: 3);(g) an amino acid sequence that has at least 95% sequence identity to amino acids 138-732 of SEQ ID NO: 18, wherein amino acids 445-451 are EYHHYNK (SEQ ID NO: 4);(h) an amino acid sequence that has at least 95% sequence identity to amino acids 138-732 of SEQ ID NO: 19, wherein amino acids 578-584 are EYHHYNK (SEQ ID NO: 4);(i) an amino acid sequence that has at least 95% sequence identity to amino acids 138-732 of SEQ ID NO: 20, wherein amino acids 445-451 are QLFPLFR (SEQ ID NO: 5);(j) an amino acid sequence that has at least 95% sequence identity to amino acids 138-732 of SEQ ID NO: 21, wherein amino acids 578-584 are QLFPLFR (SEQ ID NO: 5);(k) an amino acid sequence that has at least 95% sequence identity to amino acids 138-742 of SEQ ID NO: 22, wherein amino acids 445-461 are FNPVTGEVPPRYPLDAR (SEQ ID NO: 6);(l) an amino acid sequence that has at least 95% sequence identity to amino acids 138-742 of SEQ ID NO: 23, wherein amino acids 578-594 are FNPVTGEVPPRYPLDAR (SEQ ID NO: 6);(m) an amino acid sequence that has at least 95% sequence identity to amino acids 138-739 of SEQ ID NO: 24, wherein amino acids 445-458 are SVTEQGAELSNEER (SEQ ID NO: 7);(n) an amino acid sequence that has at least 95% sequence identity to amino acids 138-739 of SEQ ID NO: 25, wherein amino acids 578-591 are SVTEQGAELSNEER (SEQ ID NO: 7);(o) an amino acid sequence that has at least 95% sequence identity to amino acids 138-735 of SEQ ID NO: 26, wherein amino acids 449-454 are RGDLGL (SEQ ID NO: 8);(p) an amino acid sequence that has at least 95% sequence identity to amino acids 138-735 of SEQ ID NO: 27, wherein amino acids 578-584 are RGDLGL (SEQ ID NO: 8);(q) an amino acid sequence that has at least 95% sequence identity to amino acids 138-737 of SEQ ID NO: 28, wherein amino acids 447-453 are ASSLNIA (SEQ ID NO: 9); or(r) an amino acid sequence that has at least 95% sequence identity to amino acids 138-737 of SEQ ID NO: 29, wherein amino acids 580-586 are ASSLNIA (SEQ ID NO: 9).
38. The recombinant AAV capsid protein of claim 1, comprising: (a) an amino acid sequence that has at least 99% sequence identity to amino acids 138-763 SEQ ID NO: 12, wherein amino acids 445-482 are of ASLEEEWAQVECEVYGRGCPSGSLDESFYDWFERQLGA (SEQ ID NO: 1);(b) an amino acid sequence that has at least 99% sequence identity to amino acids 138-763 of SEQ ID NO: 13, wherein amino acids 578-615 are ASLEEEWAQVECEVYGRGCPSGSLDESFYDWFERQLGA (SEQ ID NO: 1);(c) an amino acid sequence that has at least 99% sequence identity to amino acids 138-734 of SEQ ID NO: 14, wherein amino acids 445-453 are APLTNTVKA (SEQ ID NO: 2);(d) an amino acid sequence that has at least 99% sequence identity to amino acids 138-734 of SEQ ID NO: 15, wherein amino acids 578-586 are APLTNTVKA (SEQ ID NO: 2);(e) an amino acid sequence that has at least 99% sequence identity to amino acids 138-732 of SEQ ID NO: 16, wherein amino acids 445-451 are DDTRHWG (SEQ ID NO: 3);(f) an amino acid sequence that has at least 99% sequence identity to amino acids 138-732 of SEQ ID NO: 17, wherein amino acids 578-584 are DDTRHWG (SEQ ID NO: 3);(g) an amino acid sequence that has at least 99% sequence identity to amino acids 138-732 of SEQ ID NO: 18, wherein amino acids 445-451 are EYHHYNK (SEQ ID NO: 4);(h) an amino acid sequence that has at least 99% sequence identity to amino acids 138-732 of SEQ ID NO: 19, wherein amino acids 578-584 are EYHHYNK (SEQ ID NO: 4);(i) an amino acid sequence that has at least 99% sequence identity to amino acids 138-732 of SEQ ID NO: 20, wherein amino acids 445-451 are QLFPLFR (SEQ ID NO: 5);(j) an amino acid sequence that has at least 99% sequence identity to amino acids 138-732 of SEQ ID NO: 21, wherein amino acids 578-584 are QLFPLFR (SEQ ID NO: 5);(k) an amino acid sequence that has at least 99% sequence identity to amino acids 138-742 of SEQ ID NO: 22, wherein amino acids 445-461 are FNPVTGEVPPRYPLDAR (SEQ ID NO: 6);(l) an amino acid sequence that has at least 99% sequence identity to amino acids 138-742 of SEQ ID NO: 23, wherein amino acids 578-594 are FNPVTGEVPPRYPLDAR (SEQ ID NO: 6);(m) an amino acid sequence that has at least 99% sequence identity to amino acids 138-739 of SEQ ID NO: 24, wherein amino acids 445-458 are SVTEQGAELSNEER (SEQ ID NO: 7);(n) an amino acid sequence that has at least 99% sequence identity to amino acids 138-739 of SEQ ID NO: 25, wherein amino acids 578-591 are SVTEQGAELSNEER (SEQ ID NO: 7);(o) an amino acid sequence that has at least 99% sequence identity to amino acids 138-735 of SEQ ID NO: 26, wherein amino acids 449-454 are RGDLGL (SEQ ID NO: 8);(p) an amino acid sequence that has at least 99% sequence identity to amino acids 138-735 of SEQ ID NO: 27, wherein amino acids 578-584 are RGDLGL (SEQ ID NO: 8);(q) an amino acid sequence that has at least 99% sequence identity to amino acids 138-737 of SEQ ID NO: 28, wherein amino acids 447-453 are ASSLNIA (SEQ ID NO: 9); or(r) an amino acid sequence that has at least 99% sequence identity to amino acids 138-737 of SEQ ID NO: 29, wherein amino acids 580-586 are ASSLNIA (SEQ ID NO: 9).
39. The recombinant AAV capsid protein of claim 1, comprising: (a) an amino acid sequence that has 100% sequence identity to amino acids 138-763 of SEQ ID NO: 12;(b) an amino acid sequence that has 100% sequence identity to amino acids 138-763 of SEQ ID NO: 13;(c) an amino acid sequence that has 100% sequence identity to amino acids 138-734 of SEQ ID NO: 14;(d) an amino acid sequence that has 100% sequence identity to amino acids 138-734 of SEQ ID NO: 15;(e) an amino acid sequence that has 100% sequence identity to amino acids 138-732 of SEQ ID NO: 16;(f) an amino acid sequence that has 100% sequence identity to amino acids 138-732 of SEQ ID NO: 17;(g) an amino acid sequence that has 100% sequence identity to amino acids 138-732 of SEQ ID NO: 18;(h) an amino acid sequence that has 100% sequence identity to amino acids 138-732 of SEQ ID NO: 19;(i) an amino acid sequence that has 100% sequence identity to amino acids 138-732 of SEQ ID NO: 20;(j) an amino acid sequence that has 100% sequence identity to amino acids 138-732 of SEQ ID NO: 21;(k) an amino acid sequence that has 100% sequence identity to amino acids 138-742 of SEQ ID NO: 22;(l) an amino acid sequence that has 100% sequence identity to amino acids 138-742 of SEQ ID NO: 23;(m) an amino acid sequence that has 100% sequence identity to amino acids 138-739 of SEQ ID NO: 24;(n) an amino acid sequence that has 100% sequence identity to amino acids 138-739 of SEQ ID NO: 25;(o) an amino acid sequence that has 100% sequence identity to amino acids 138-735 of SEQ ID NO: 26;(p) an amino acid sequence that has 100% sequence identity to amino acids 138-735 of SEQ ID NO: 27;(q) an amino acid sequence that has 100% sequence identity to amino acids 138-737 of SEQ ID NO: 28; or(r) an amino acid sequence that has 100% sequence identity to amino acids 138-737 of SEQ ID NO: 29.
40. The recombinant AAV capsid protein of claim 1, comprising: (a) an amino acid sequence that has at least 95% sequence identity to amino acids 1-763 of SEQ ID NO: 12, wherein amino acids 445-482 are ASLEEEWAQVECEVYGRGCPSGSLDESFYDWFERQLGA (SEQ ID NO: 1);(b) an amino acid sequence that has at least 95% sequence identity to amino acids 1-763 of SEQ ID NO: 13, wherein amino acids 578-615 are ASLEEEWAQVECEVYGRGCPSGSLDESFYDWFERQLGA (SEQ ID NO: 1);(c) an amino acid sequence that has at least 95% sequence identity to amino acids 1-734 of SEQ ID NO: 14, wherein amino acids 445-453 are APLTNTVKA (SEQ ID NO: 2);(d) an amino acid sequence that has at least 95% sequence identity to amino acids 1-734 of SEQ ID NO: 15, wherein amino acids 578-586 are APLTNTVKA (SEQ ID NO: 2);(e) an amino acid sequence that has at least 95% sequence identity to amino acids 1-732 of SEQ ID NO: 16, wherein amino acids 445-451 are DDTRHWG (SEQ ID NO: 3);(f) an amino acid sequence that has at least 95% sequence identity to amino acids 1-732 of SEQ ID NO: 17, wherein amino acids 578-584 are DDTRHWG (SEQ ID NO: 3);(g) an amino acid sequence that has at least 95% sequence identity to amino acids 1-732 of SEQ ID NO: 18, wherein amino acids 445-451 are EYHHYNK (SEQ ID NO: 4);(h) an amino acid sequence that has at least 95% sequence identity to amino acids 1-732 of SEQ ID NO: 19, wherein amino acids 578-584 are EYHHYNK (SEQ ID NO: 4);(i) an amino acid sequence that has at least 95% sequence identity to amino acids 1-732 of SEQ ID NO: 20, wherein amino acids 445-451 are QLFPLFR (SEQ ID NO: 5);(j) an amino acid sequence that has at least 95% sequence identity to amino acids 1-732 of SEQ ID NO: 21, wherein amino acids 578-584 are QLFPLFR (SEQ ID NO: 5);(k) an amino acid sequence that has at least 95% sequence identity to amino acids 1-742 of SEQ ID NO: 22, wherein amino acids 445-461 are FNPVTGEVPPRYPLDAR (SEQ ID NO: 6);(l) an amino acid sequence that has at least 95% sequence identity to amino acids 1-742 of SEQ ID NO: 23, wherein amino acids 578-594 are FNPVTGEVPPRYPLDAR (SEQ ID NO: 6);(m) an amino acid sequence that has at least 95% sequence identity to amino acids 1-739 of SEQ ID NO: 24, wherein amino acids 445-458 are SVTEQGAELSNEER (SEQ ID NO: 7);(n) an amino acid sequence that has at least 95% sequence identity to amino acids 1-739 of SEQ ID NO: 25, wherein amino acids 578-591 are SVTEQGAELSNEER (SEQ ID NO: 7);(o) an amino acid sequence that has at least 95% sequence identity to amino acids 1-735 of SEQ ID NO: 26, wherein amino acids 449-454 are RGDLGL (SEQ ID NO: 8);(p) an amino acid sequence that has at least 95% sequence identity to amino acids 1-735 of SEQ ID NO: 27, wherein amino acids 578-584 are RGDLGL (SEQ ID NO: 8);(q) an amino acid sequence that has at least 95% sequence identity to amino acids 1-737 of SEQ ID NO: 28, wherein amino acids 447-453 are ASSLNIA (SEQ ID NO: 9); or(r) an amino acid sequence that has at least 95% sequence identity to amino acids 1-737 of SEQ ID NO: 29, wherein amino acids 580-586 are ASSLNIA (SEQ ID NO: 9).
41. The recombinant AAV capsid protein of claim 1, comprising: (a) an amino acid sequence that has at least 99% sequence identity to amino acids 1-763 of SEQ ID NO: 12, wherein amino acids 445-482 are ASLEEEWAQVECEVYGRGCPSGSLDESFYDWFERQLGA (SEQ ID NO: 1);(b) an amino acid sequence that has at least 99% sequence identity to amino acids 1-763 of SEQ ID NO: 13, wherein amino acids 578-615 are ASLEEEWAQVECEVYGRGCPSGSLDESFYDWFERQLGA (SEQ ID NO: 1);(c) an amino acid sequence that has at least 99% sequence identity to amino acids 1-734 of SEQ ID NO: 14, wherein amino acids 445-453 are APLTNTVKA (SEQ ID NO: 2);(d) an amino acid sequence that has at least 99% sequence identity to amino acids 1-734 of SEQ ID NO: 15, wherein amino acids 578-586 are APLTNTVKA (SEQ ID NO: 2);(e) an amino acid sequence that has at least 99% sequence identity to amino acids 1-732 of SEQ ID NO: 16, wherein amino acids 445-451 are DDTRHWG (SEQ ID NO: 3);(f) an amino acid sequence that has at least 99% sequence identity to amino acids 1-732 of SEQ ID NO: 17, wherein amino acids 578-584 are DDTRHWG (SEQ ID NO: 3);(g) an amino acid sequence that has at least 99% sequence identity to amino acids 1-732 of SEQ ID NO: 18, wherein amino acids 445-451 are EYHHYNK (SEQ ID NO: 4);(h) an amino acid sequence that has at least 99% sequence identity to amino acids 1-732 of SEQ ID NO: 19, wherein amino acids 578-584 are EYHHYNK (SEQ ID NO: 4);(i) an amino acid sequence that has at least 99% sequence identity to amino acids 1-732 of SEQ ID NO: 20, wherein amino acids 445-451 are QLFPLFR (SEQ ID NO: 5);(j) an amino acid sequence that has at least 99% sequence identity to amino acids 1-732 of SEQ ID NO: 21, wherein amino acids 578-584 are QLFPLFR (SEQ ID NO: 5);(k) an amino acid sequence that has at least 99% sequence identity to amino acids 1-742 of SEQ ID NO: 22, wherein amino acids 445-461 are FNPVTGEVPPRYPLDAR (SEQ ID NO: 6);(l) an amino acid sequence that has at least 99% sequence identity to amino acids 1-742 of SEQ ID NO: 23, wherein amino acids 578-594 are FNPVTGEVPPRYPLDAR (SEQ ID NO: 6);(m) an amino acid sequence that has at least 99% sequence identity to amino acids 1-739 of SEQ ID NO: 24, wherein amino acids 445-458 are SVTEQGAELSNEER (SEQ ID NO: 7);(n) an amino acid sequence that has at least 99% sequence identity to amino acids 1-739 of SEQ ID NO: 25, wherein amino acids 578-591 are SVTEQGAELSNEER (SEQ ID NO: 7);(o) an amino acid sequence that has at least 99% sequence identity to amino acids 1-735 of SEQ ID NO: 26, wherein amino acids 449-454 are RGDLGL (SEQ ID NO: 8);(p) an amino acid sequence that has at least 99% sequence identity to amino acids 1-735 of SEQ ID NO: 27, wherein amino acids 578-584 are RGDLGL (SEQ ID NO: 8);(q) an amino acid sequence that has at least 99% sequence identity to amino acids 1-737 of SEQ ID NO: 28, wherein amino acids 447-453 are ASSLNIA (SEQ ID NO: 9); or(r) an amino acid sequence that has at least 99% sequence identity to amino acids 1-737 of SEQ ID NO: 29, wherein amino acids 580-586 are ASSLNIA (SEQ ID NO: 9).
42. The recombinant AAV capsid protein of claim 1, comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 12-29.
43. The recombinant AAV capsid protein of claim 1, wherein the amino acid sequence of the recombinant AAV capsid protein consists of an amino acid sequence selected from the group consisting of SEQ ID NOs: 12-29.
44. A recombinant adeno-associated virus (AAV) capsid protein comprising a first peptide, a second peptide, and a parental capsid protein, wherein the first peptide is comprised within loop IV of the parental capsid protein and the second peptide is comprised within loop VIII of the parental capsid protein, and wherein the first peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-9, 35, and 36 and the second peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-9, 35, and 36.
45. The recombinant AAV capsid protein of claim 44, wherein the first peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-9, 35, and 36 and the second peptide comprises the amino acid sequence of SEQ ID NO: 1.
46. The recombinant AAV capsid protein of claim 44, wherein the first peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-9, 35, and 36 and the second peptide comprises the amino acid sequence of SEQ ID NO: 2.
47. The recombinant AAV capsid protein of claim 44, wherein the first peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-9, 35, and 36 and the second peptide comprises the amino acid sequence of SEQ ID NO: 3.
48. The recombinant AAV capsid protein of claim 44, wherein the first peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-9, 35, and 36 and the second peptide comprises the amino acid sequence of SEQ ID NO: 4.
49. The recombinant AAV capsid protein of claim 44, wherein the first peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-9, 35, and 36 and the second peptide comprises the amino acid sequence of SEQ ID NO: 5.
50. The recombinant AAV capsid protein of claim 44, wherein the first peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-9, 35, and 36 and the second peptide comprises the amino acid sequence of SEQ ID NO: 6.
51. The recombinant AAV capsid protein of claim 44, wherein the first peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-9, 35, and 36 and the second peptide comprises the amino acid sequence of SEQ ID NO: 7.
52. The recombinant AAV capsid protein of claim 44, wherein the first peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-9, 35, and 36 and the second peptide comprises the amino acid sequence of SEQ ID NO: 8.
53. The recombinant AAV capsid protein of claim 44, wherein the first peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-9, 35, and 36 and the second peptide comprises the amino acid sequence of SEQ ID NO: 9.
54. The recombinant AAV capsid protein of claim 44, wherein the first peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-9, 35, and 36 and the second peptide comprises the amino acid sequence of SEQ ID NO: 35.
55. The recombinant AAV capsid protein of claim 44, wherein the first peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-9, 35, and 36 and the second peptide comprises the amino acid sequence of SEQ ID NO: 36.
56. The recombinant AAV capsid protein of any one of claims 45-55, wherein the parental capsid protein is a clade A, clade B, clade C, clade D, clade E, clade F, clade G, clade H, clade I, AAVgo.1, AAV3, AAV4, AAV10, AAV11, AAV12, rh.32, rh32.33, rh.33, rh.34, BAAV, or AAV5 capsid protein, or an engineered variant thereof.
57. The recombinant AAV capsid protein of any one of claims 45-55, wherein the parental capsid protein comprises an amino acid sequence that has at least 95% identity to amino acids 193-725 of SEQ ID NO: 11.
58. The recombinant AAV capsid protein of any one of claims 45-55, wherein the parental capsid protein comprises an amino acid sequence that has at least 99% identity to amino acids 193-725 of SEQ ID NO:11.
59. The recombinant AAV capsid protein of any one of claims 45-55, wherein the parental capsid protein comprises the amino acid sequence of amino acids 193-725 of SEQ ID NO: 11.
60. The recombinant AAV capsid protein of any one of claims 45-55, wherein the parental capsid protein comprises an amino acid sequence that has at least 95% identity to amino acids 138-725 of SEQ ID NO: 11.
61. The recombinant AAV capsid protein of any one of claims 45-55, wherein the parental capsid protein comprises an amino acid sequence that has at least 99% identity to amino acids 138-725 of SEQ ID NO: 11.
62. The recombinant AAV capsid protein of any one of claims 45-55, wherein the parental capsid protein comprises the amino acid sequence of amino acids 138-725 of SEQ ID NO: 11.
63. The recombinant AAV capsid protein of any one of claims 45-55, wherein the parental capsid protein comprises an amino acid sequence that has at least 95% identity to SEQ ID NO: 10 or 11.
64. The recombinant AAV capsid protein of any one of claims 45-55, wherein the parental capsid protein comprises an amino acid sequence that has at least 99% identity to SEQ ID NO: 10 or 11.
65. The recombinant AAV capsid protein of any one of claims 45-55, wherein the parental capsid protein comprises the amino acid of SEQ ID NO: 10 or 11.
66. The recombinant AAV capsid protein of any one of claims 45-65, wherein: (a) the first peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 440, 441, 442, 443, 444, 445, 446, or 447 of SEQ ID NO: 11; and(b) the second peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 572, 573, 574, 575, 576, 577, 578, 579, 580, 581, 582, 583, or 584 of SEQ ID NO: 11.
67. The recombinant AAV capsid protein of any one of claims 45-65, wherein the first peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 440 of SEQ ID NO: 11.
68. The recombinant AAV capsid protein of any one of claims 45-65, wherein the first peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 441 of SEQ ID NO: 11.
69. The recombinant AAV capsid protein of any one of claims 45-65, wherein the first peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 442 of SEQ ID NO: 11.
70. The recombinant AAV capsid protein of any one of claims 45-65, wherein the first peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 443 of SEQ ID NO: 11.
71. The recombinant AAV capsid protein of any one of claims 45-65, wherein the first peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 444 of SEQ ID NO: 11.
72. The recombinant AAV capsid protein of any one of claims 45-65, wherein the first peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 445 of SEQ ID NO: 11.
73. The recombinant AAV capsid protein of any one of claims 45-65, wherein the first peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 446 of SEQ ID NO: 11.
74. The recombinant AAV capsid protein of any one of claims 45-65, wherein the first peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 447 of SEQ ID NO: 11.
75. The recombinant AAV capsid protein of any one of claims 45-74, wherein the second peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 572 of SEQ ID NO: 11.
76. The recombinant AAV capsid protein of any one of claims 45-74, wherein the second peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 573 of SEQ ID NO: 11.
77. The recombinant AAV capsid protein of any one of claims 45-74, wherein the second peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 574 of SEQ ID NO: 11.
78. The recombinant AAV capsid protein of any one of claims 45-74, wherein the second peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 575 of SEQ ID NO: 11.
79. The recombinant AAV capsid protein of any one of claims 45-74, wherein the second peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 576 of SEQ ID NO: 11.
80. The recombinant AAV capsid protein of any one of claims 45-74, wherein the second peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 577 of SEQ ID NO: 11.
81. The recombinant AAV capsid protein of any one of claims 45-74, wherein the second peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 578 of SEQ ID NO: 11.
82. The recombinant AAV capsid protein of any one of claims 45-74, wherein the second peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 579 of SEQ ID NO: 11.
83. The recombinant AAV capsid protein of any one of claims 45-74, wherein the second peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 580 of SEQ ID NO: 11.
84. The recombinant AAV capsid protein of any one of claims 45-74, wherein the second peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 581 of SEQ ID NO: 11.
85. The recombinant AAV capsid protein of any one of claims 45-74, wherein the second peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 582 of SEQ ID NO: 11.
86. The recombinant AAV capsid protein of any one of claims 45-74, wherein the second peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 583 of SEQ ID NO: 11.
87. The recombinant AAV capsid protein of any one of claims 45-74, wherein the second peptide is positioned immediately C-terminal to an amino acid in the parental capsid corresponding to amino acid 584 of SEQ ID NO: 11.
88. The recombinant AAV capsid protein of claim 45, comprising: (a) an amino acid sequence that has at least 95% sequence identity to amino acids 194-745 of SEQ ID NO: 30, wherein amino acids 449-454 are RGDLGL (SEQ ID NO: 8) and amino acids 592-597 are RGDLGL (SEQ ID NO: 8);(b) an amino acid sequence that has at least 95% sequence identity to amino acids 194-742 of SEQ ID NO: 31, wherein amino acids 449-454 are RGDLGL (SEQ ID NO: 8) and amino acids 588-594 are RTIGPSV (SEQ ID NO: 35);(c) an amino acid sequence that has at least 95% sequence identity to amino acids 194-742 of SEQ ID NO: 32, wherein amino acids 445-451 are RTIGPSV (SEQ ID NO: 35) and amino acids 589-594 are RGDLGL (SEQ ID NO: 8);(d) an amino acid sequence that has at least 95% sequence identity to amino acids 194-742 of SEQ ID NO: 33, wherein amino acids 445-451 are LSSRLDA (SEQ ID NO: 36) and amino acids 589-594 are RGDLGL (SEQ ID NO: 8); or(e) an amino acid sequence that has at least 95% sequence identity to amino acids 194-744 of SEQ ID NO: 34, wherein amino acids 445-453 are APLTNTVKA (SEQ ID NO: 2) and amino acids 591-596 are RGDLGL (SEQ ID NO: 8).
89. The recombinant AAV capsid protein of claim 45, comprising: (a) an amino acid sequence that has at least 99% sequence identity to amino acids 194-745 of SEQ ID NO: 30, wherein amino acids 449-454 are RGDLGL (SEQ ID NO: 8) and amino acids 592-597 are RGDLGL (SEQ ID NO: 8);(b) an amino acid sequence that has at least 99% sequence identity to amino acids 194-742 of SEQ ID NO: 31, wherein amino acids 449-454 are RGDLGL (SEQ ID NO: 8) and amino acids 588-594 are RTIGPSV (SEQ ID NO: 35);(c) an amino acid sequence that has at least 99% sequence identity to amino acids 194-742 of SEQ ID NO: 32, wherein amino acids 445-451 are RTIGPSV (SEQ ID NO: 35) and amino acids 589-594 are RGDLGL (SEQ ID NO: 8);(d) an amino acid sequence that has at least 99% sequence identity to amino acids 194-742 of SEQ ID NO: 33, wherein amino acids 445-451 are LSSRLDA (SEQ ID NO: 36) and amino acids 589-594 are RGDLGL (SEQ ID NO: 8); or(e) an amino acid sequence that has at least 99% sequence identity to amino acids 194-744 of SEQ ID NO: 34, wherein amino acids 445-453 are APLTNTVKA (SEQ ID NO: 2) and amino acids 591-596 are RGDLGL (SEQ ID NO: 8).
90. The recombinant AAV capsid protein of claim 45, comprising: (a) an amino acid sequence that has at least 100% sequence identity to amino acids 194-745 of SEQ ID NO: 30;(b) an amino acid sequence that has at least 100% sequence identity to amino acids 194-742 of SEQ ID NO: 31;(c) an amino acid sequence that has at least 100% sequence identity to amino acids 194-742 of SEQ ID NO: 32;(d) an amino acid sequence that has at least 100% sequence identity to amino acids 194-742 of SEQ ID NO: 33; or(e) an amino acid sequence that has at least 100% sequence identity to amino acids 194-744 of SEQ ID NO: 34.
91. The recombinant AAV capsid protein of claim 45, comprising: (a) an amino acid sequence that has at least 95% sequence identity to amino acids 138-745 of SEQ ID NO: 30 wherein amino acids 449-454 are RGDLGL (SEQ ID NO: 8) and amino acids 592-597 are RGDLGL (SEQ ID NO: 8);(b) an amino acid sequence that has at least 95% sequence identity to amino acids 138-742 of SEQ ID NO: 31, wherein amino acids 449-454 are RGDLGL (SEQ ID NO: 8) and amino acids 588-594 are RTIGPSV (SEQ ID NO: 35);(c) an amino acid sequence that has at least 95% sequence identity to amino acids 138-742 of SEQ ID NO: 32, wherein amino acids 445-451 are RTIGPSV (SEQ ID NO: 35) and amino acids 589-594 are RGDLGL (SEQ ID NO: 8);(d) an amino acid sequence that has at least 95% sequence identity to amino acids 138-742 of SEQ ID NO: 33, wherein amino acids 445-451 are LSSRLDA (SEQ ID NO: 36) and amino acids 589-594 are RGDLGL (SEQ ID NO: 8); or(e) an amino acid sequence that has at least 95% sequence identity to amino acids 138-744 of SEQ ID NO: 34, wherein amino acids 445-453 are APLTNTVKA (SEQ ID NO: 2) and amino acids 591-596 are RGDLGL (SEQ ID NO: 8).
92. The recombinant AAV capsid protein of claim 45, comprising: (a) an amino acid sequence that has at least 99% sequence identity to amino acids 138-745 of SEQ ID NO: 30 wherein amino acids 449-454 are RGDLGL (SEQ ID NO: 8) and amino acids 592-597 are RGDLGL (SEQ ID NO: 8);(b) an amino acid sequence that has at least 99% sequence identity to amino acids 138-742 of SEQ ID NO: 31, wherein amino acids 449-454 are RGDLGL (SEQ ID NO: 8) and amino acids 588-594 are RTIGPSV (SEQ ID NO: 35);(c) an amino acid sequence that has at least 99% sequence identity to amino acids 138-742 of SEQ ID NO: 32, wherein amino acids 445-451 are RTIGPSV (SEQ ID NO: 35) and amino acids 589-594 are RGDLGL (SEQ ID NO: 8);(d) an amino acid sequence that has at least 99% sequence identity to amino acids 138-742 of SEQ ID NO: 33, wherein amino acids 445-451 are LSSRLDA (SEQ ID NO: 36) and amino acids 589-594 are RGDLGL (SEQ ID NO: 8); or(e) an amino acid sequence that has at least 99% sequence identity to amino acids 138-744 of SEQ ID NO: 34, wherein amino acids 445-453 are APLTNTVKA (SEQ ID NO: 2) and amino acids 591-596 are RGDLGL (SEQ ID NO: 8).
93. The recombinant AAV capsid protein of claim 45, comprising: (a) an amino acid sequence that has 100% sequence identity to amino acids 138-763 of SEQ ID NO: 30;(b) an amino acid sequence that has 100% sequence identity to amino acids 138-763 of SEQ ID NO: 31;(c) an amino acid sequence that has 100% sequence identity to amino acids 138-734 of SEQ ID NO: 32;(d) an amino acid sequence that has 100% sequence identity to amino acids 138-734 of SEQ ID NO: 33; or(e) an amino acid sequence that has 100% sequence identity to amino acids 138-732 of SEQ ID NO: 34.
94. The recombinant AAV capsid protein of claim 45, comprising: (a) an amino acid sequence that has at least 95% sequence identity to amino acids 1-745 of SEQ ID NO: 30 wherein amino acids 449-454 are RGDLGL (SEQ ID NO: 8) and amino acids 592-597 are RGDLGL (SEQ ID NO: 8);(b) an amino acid sequence that has at least 95% sequence identity to amino acids 1-742 of SEQ ID NO: 31, wherein amino acids 449-454 are RGDLGL (SEQ ID NO: 8) and amino acids 588-594 are RTIGPSV (SEQ ID NO: 35);(c) an amino acid sequence that has at least 95% sequence identity to amino acids 1-742 of SEQ ID NO: 32, wherein amino acids 445-451 are RTIGPSV (SEQ ID NO: 35) and amino acids 589-594 are RGDLGL (SEQ ID NO: 8);(d) an amino acid sequence that has at least 95% sequence identity to amino acids 1-742 of SEQ ID NO: 33, wherein amino acids 445-451 are LSSRLDA (SEQ ID NO: 36) and amino acids 589-594 are RGDLGL (SEQ ID NO: 8); or(e) an amino acid sequence that has at least 95% sequence identity to amino acids 1-744 of SEQ ID NO: 34, wherein amino acids 445-453 are APLTNTVKA (SEQ ID NO: 2) and amino acids 591-596 are RGDLGL (SEQ ID NO: 8).
95. The recombinant AAV capsid protein of claim 45, comprising: (a) an amino acid sequence that has at least 99% sequence identity to amino acids 1-745 of SEQ ID NO: 30 wherein amino acids 449-454 are RGDLGL (SEQ ID NO: 8) and amino acids 592-597 are RGDLGL (SEQ ID NO: 8);(b) an amino acid sequence that has at least 99% sequence identity to amino acids 1-742 of SEQ ID NO: 31, wherein amino acids 449-454 are RGDLGL (SEQ ID NO: 8) and amino acids 588-594 are RTIGPSV (SEQ ID NO: 35);(c) an amino acid sequence that has at least 99% sequence identity to amino acids 1-742 of SEQ ID NO: 32, wherein amino acids 445-451 are RTIGPSV (SEQ ID NO: 35) and amino acids 589-594 are RGDLGL (SEQ ID NO: 8);(d) an amino acid sequence that has at least 99% sequence identity to amino acids 1-742 of SEQ ID NO: 33, wherein amino acids 445-451 are LSSRLDA (SEQ ID NO: 36) and amino acids 589-594 are RGDLGL (SEQ ID NO: 8); or(e) an amino acid sequence that has at least 99% sequence identity to amino acids 1-744 of SEQ ID NO: 34, wherein amino acids 445-453 are APLTNTVKA (SEQ ID NO: 2) and amino acids 591-596 are RGDLGL (SEQ ID NO: 8).
96. The recombinant AAV capsid protein of claim 45, comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 30-34.
97. The recombinant AAV capsid protein of claim 45, wherein the amino acid sequence of the recombinant AAV capsid protein consists of an amino acid sequence selected from the group consisting of SEQ ID NOs: 30-34.
98. An isolated polynucleotide encoding the recombinant AAV capsid protein of any one of claims 1-97.
99. A vector comprising the polynucleotide of claim 98.
100. The vector of claim 99, which is a plasmid or a viral vector.
101. The vector of claim 100, wherein the viral vector is a retrovirus vector, a herpes virus vector, a baculovirus vector, or an adenovirus vector.
102. The vector of any one of claims 99-101, which is an expression vector.
103. A recombinant cell comprising the polynucleotide of claim 98 or the vector of any one of claims 99-102.
104. A method of producing a recombinant AAV capsid protein, the method comprising culturing the recombinant cell of claim 103 under conditions where the polynucleotide is expressed, and the capsid protein is produced.
105. A recombinant adeno-associated virus (rAAV) comprising: (a) a capsid comprising one or more of the recombinant AAV capsid protein of any one of claims 1-97; and(b) an rAAV genome.
106. The rAAV of claim 105, wherein the rAAV genome comprises a transgene.
107. The rAAV of claim 106, wherein the transgene encodes a polypeptide or a non-coding RNA.
108. The rAAV of claim 106 or 107, wherein the transgene encodes an antibody or a fragment thereof.
109. The rAAV of claim 108, wherein the transgene encodes an scFv, a nanobody, or a VHH.
110. A method of delivering a transgene to a cell, the method comprising contacting the cell with the rAAV of any one of claims 105-109, under conditions where the cell is transduced, and the transgene is expressed.
111. The method of claim 110, wherein the cell is a muscle cell, microglia, astrocyte, neuron, or cardiomyocyte.
112. A method of delivering a transgene to muscle tissue in a subject in need thereof, the method comprising administering the rAAV of any one of claims 105-109 to the subject.
113. The method of claim 112, wherein the subject has a disease associated with muscle tissue.
114. A method of treating a neuromuscular or neurodegenerative disease or disorder in a subject in need thereof, comprising administering an effective amount of an rAAV of any one of claims 105-109 to the subject.
115. The method of claim 114, wherein the neuromuscular disease or disorder is selected from the group consisting of myopathy, hereditary cardiomyopathy, metabolic myopathy, distal myopathy, muscular dystrophy, congenital myopathy, spinal muscular atrophy (SMA), motor neuron disease, congenital myopathy, congenital muscular dystrophy, motor neuron disease, Duchenne muscular dystrophy, Becker muscular dystrophy, limb-girdle muscular dystrophies, myotonic dystrophy, myotubular myopathy, centronuclear myopathy, nemaline myopathy, selenoprotein N-related myopathy, Pompe disease, glycogen storage disease III, spinal muscular atrophy, amyotrophic lateral sclerosis, Charcot-Marie-Tooth disease, multiple sclerosis, myositis, polymyositis, and dermatomyositis.
116. The method of claim 114, wherein the neurodegenerative disease or disorder is selected from the group consisting of Motor neuron disease (MND), parkinsonism syndrome, Alzheimer's dementia, progressive supranuclear palsy (PSP), Huntington's disease, multiple system atrophy (MSA), spinocerebellar ataxia (SCA), and Friedreich's ataxia.
117. The method of any one of claims 112-116, wherein the rAAV is administered to the subject intravenously, intraperitoneally, subcutaneously, intramuscularly, intrathecally, or intradermally.

CROSS REFERENCE TO RELATED APPLICATIONS

This This application is a continuation of International Patent Application No. PCT/IB2023/000175, filed Apr. 4, 2023, which claims priority to U.S. Patent Application Ser. No. 63/366,428, filed Jun. 15, 2022, and U.S. Patent Application Ser. No. 63/362,419, filed Apr. 4, 2022, the entire disclosures of which are hereby incorporated herein by reference.

Provisional Applications (2)

	Number	Date	Country
	63366428	Jun 2022	US
	63362419	Apr 2022	US

Continuations (1)

	Number	Date	Country
Parent	PCT/IB2023/000175	Apr 2023	WO
Child	18907094		US

RECOMBINANT AAV CAPSID PROTEINS

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CROSS REFERENCE TO RELATED APPLICATIONS

Provisional Applications (2)

Continuations (1)