Adeno-associated virus capsid

Abstract

Provided herein are recombinant adeno-associated virus (AAV) capsid proteins, compositions comprising the capsid proteins (e.g., rAAV), nucleic acids encoding the capsid proteins, and methods of making and using the capsid proteins. In certain embodiments, the recombinant AAV capsid proteins comprise amino acids 1-734 of SEQ ID NO:2, amino acids 137-734 of SEQ ID NO:2, and / or amino acids 202-734 of SEQ ID NO:2.

Description

[Technical Field]

[0001] Related Applications This application claims the benefit of U.S. Provisional Patent Application No. 63 / 376,470, filed September 21, 2022, the entire disclosure of which is incorporated herein by reference.

[0002] Sequence Listing Reference This application has been submitted electronically in ST.26 format and contains a Sequence Listing, which is incorporated herein by reference in its entirety (a copy of said ST.26, created on September 19, 2023, is entitled "203432_SL.xml" and is 145,517 bytes in size). [Background technology]

[0003] Adeno-associated viruses (AAVs) are small, non-enveloped viruses of the genus Dependovirus within the family Parvoviridae. They package a single-stranded DNA genome of approximately 4.7 kb in length, consisting of the rep and cap genes flanked by inverted terminal repeat regions (ITRs). AAV infection of cells in culture is not cytopathic, and natural infection in humans and other animals is silent, making AAV an ideal delivery system for gene therapy. Furthermore, because 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 replication and structural capsid proteins, rep-cap) can be replaced with heterologous nucleic acid sequences, such as transgenes, to effect gene therapy.

[0004] Recombinant AAV (rAAV) gene therapy vectors typically consist of a recombinant AAV genome containing a gene therapy transgene packaged within an AAV capsid. The AAV capsid, formed by the assembly of 60 AAV capsid proteins, interacts with the cell surface of target cells and determines the tropism and transduction efficiency of the rAAV. In the case of tissue-specific genetic diseases, it is desirable to have an rAAV that can specifically and efficiently target the tissue in need of gene therapy.

[0005] Thus, there is a need in the art for tissue-specific AAV capsids for use in gene therapy applications. Summary of the Invention

[0006] Provided herein are recombinant adeno-associated virus (AAV) capsid proteins, compositions comprising the capsid proteins (e.g., rAAV), nucleic acids encoding the capsid proteins, and methods of making and using the capsid proteins.

[0007] Thus, in one aspect, the present disclosure provides: (i) an amino acid sequence having at least 94% sequence identity to amino acids 1 to 734 of SEQ ID NO: 2, an amino acid sequence having at least 95% sequence identity to amino acids 137 to 734 of SEQ ID NO: 2, and / or an amino acid sequence having at least 96% sequence identity to amino acids 202 to 734 of SEQ ID NO: 2; (ii) an amino acid sequence having at least 96% sequence identity to amino acids 1 to 736 of SEQ ID NO: 4, an amino acid sequence having at least 95% sequence identity to amino acids 138 to 736 of SEQ ID NO: 4, (iii) an amino acid sequence having at least 94% sequence identity to amino acids 1 to 734 of SEQ ID NO: 6, an amino acid sequence having at least 96% sequence identity to amino acids 137 to 734 of SEQ ID NO: 6, and / or an amino acid sequence having at least 97% sequence identity to amino acids 202 to 734 of SEQ ID NO: 6; (iv) an amino acid sequence having at least 91% sequence identity to amino acids 1 to 731 of SEQ ID NO: 8. (v) an amino acid sequence having at least 98% sequence identity to amino acids 1 to 736 of SEQ ID NO: 10, an amino acid sequence having at least 99% sequence identity to amino acids 138 to 736 of SEQ ID NO: 10, and / or an amino acid sequence having at least 99% sequence identity to amino acids 203 to 736 of SEQ ID NO: 10. (vi) an amino acid sequence having at least 96% sequence identity to amino acids 1 to 736 of SEQ ID NO: 12, an amino acid sequence having at least 96% sequence identity to amino acids 137 to 736 of SEQ ID NO: 12, and / or an amino acid sequence having at least 97% sequence identity to amino acids 203 to 736 of SEQ ID NO: 12; (vii) an amino acid sequence having at least 96% sequence identity to amino acids 1 to 736 of SEQ ID NO: 14, an amino acid sequence having at least 95% sequence identity to amino acids 138 to 736 of SEQ ID NO: 14;and / or an amino acid sequence having at least 96% sequence identity to amino acids 204 to 736 of SEQ ID NO: 14, (viii) an amino acid sequence having at least 93% sequence identity to amino acids 1 to 734 of SEQ ID NO: 16, an amino acid sequence having at least 95% sequence identity to amino acids 137 to 734 of SEQ ID NO: 16, and / or an amino acid sequence having at least 97% sequence identity to amino acids 202 to 734 of SEQ ID NO: 16, (ix) an amino acid sequence having at least 95% sequence identity to amino acids 1 to 735 of SEQ ID NO: 18. (x) an amino acid sequence having at least 93% sequence identity to amino acids 137 to 736 of SEQ ID NO: 20, an amino acid sequence having at least 95% sequence identity to amino acids 138 to 735 of SEQ ID NO: 18, and / or an amino acid sequence having at least 96% sequence identity to amino acids 203 to 735 of SEQ ID NO: 18, (x) an amino acid sequence having at least 93% sequence identity to amino acids 1 to 736 of SEQ ID NO: 20, an amino acid sequence having at least 95% sequence identity to amino acids 137 to 736 of SEQ ID NO: 20, and / or an amino acid sequence having at least 96% sequence identity to amino acids 202 to 736 of SEQ ID NO: 20 (xi) an amino acid sequence having at least 96% sequence identity to amino acids 1 to 736 of SEQ ID NO: 22, an amino acid sequence having at least 97% sequence identity to amino acids 137 to 736 of SEQ ID NO: 22, and / or an amino acid sequence having at least 99% sequence identity to amino acids 203 to 736 of SEQ ID NO: 22; (xii) an amino acid sequence having at least 97% sequence identity to amino acids 1 to 736 of SEQ ID NO: 24, an amino acid sequence having at least 96% sequence identity to amino acids 138 to 736 of SEQ ID NO: 24; and / or or an amino acid sequence having at least 97% sequence identity to amino acids 204 to 736 of SEQ ID NO: 24; (xiii) an amino acid sequence having at least 99% sequence identity to amino acids 1 to 735 of SEQ ID NO: 26, an amino acid sequence having at least 99% sequence identity to amino acids 137 to 735 of SEQ ID NO: 26, and / or an amino acid sequence having at least 99% sequence identity to amino acids 202 to 735 of SEQ ID NO: 26; (xiv) an amino acid sequence having at least 92% sequence identity to amino acids 1 to 734 of SEQ ID NO: 28;(xv) an amino acid sequence having at least 92% sequence identity to amino acids 1 to 734 of SEQ ID NO: 30, an amino acid sequence having at least 94% sequence identity to amino acids 137 to 734 of SEQ ID NO: 30, and / or an amino acid sequence having at least 96% sequence identity to amino acids 202 to 734 of SEQ ID NO: 30, (xvi ... xvi) an amino acid sequence having at least 95% sequence identity to amino acids 1 to 735 of SEQ ID NO: 32, an amino acid sequence having at least 95% sequence identity to amino acids 137 to 735 of SEQ ID NO: 32, and / or an amino acid sequence having at least 96% sequence identity to amino acids 202 to 735 of SEQ ID NO: 32; (xvii) an amino acid sequence having at least 96% sequence identity to amino acids 1 to 735 of SEQ ID NO: 34, an amino acid sequence having at least 98% sequence identity to amino acids 137 to 735 of SEQ ID NO: 34, and / or or (xviii) an amino acid sequence having at least 94% sequence identity to amino acids 1 to 735 of SEQ ID NO: 36, an amino acid sequence having at least 96% sequence identity to amino acids 138 to 735 of SEQ ID NO: 36, and / or an amino acid sequence having at least 97% sequence identity to amino acids 203 to 735 of SEQ ID NO: 36, or (xix) an amino acid sequence having at least 94% sequence identity to amino acids 1 to 731 of SEQ ID NO: 38. (xx) an amino acid sequence having at least 94% sequence identity to amino acids 1 to 735 of SEQ ID NO: 40, an amino acid sequence having at least 97% sequence identity to amino acids 137 to 735 of SEQ ID NO: 40, and / or an amino acid sequence having at least 97% sequence identity to amino acids 203 to 735 of SEQ ID NO: 40;(xxi) an amino acid sequence having at least 96% sequence identity to amino acids 1 to 736 of SEQ ID NO: 42, an amino acid sequence having at least 96% sequence identity to amino acids 138 to 736 of SEQ ID NO: 42, and / or an amino acid sequence having at least 96% sequence identity to amino acids 204 to 736 of SEQ ID NO: 42; (xxii) an amino acid sequence having at least 94% sequence identity to amino acids 1 to 736 of SEQ ID NO: 44, an amino acid sequence having at least 96% sequence identity to amino acids 137 to 736 of SEQ ID NO: 44 (xxiii) an amino acid sequence having at least 94% sequence identity to amino acids 1 to 736 of SEQ ID NO: 46, an amino acid sequence having at least 96% sequence identity to amino acids 137 to 736 of SEQ ID NO: 46, and / or an amino acid sequence having at least 97% sequence identity to amino acids 203 to 736 of SEQ ID NO: 46; (xxiv) an amino acid sequence having at least 97% sequence identity to amino acids 1 to 734 of SEQ ID NO: 48 (xxv) an amino acid sequence having at least 94% sequence identity to amino acids 137 to 734 of SEQ ID NO: 48, an amino acid sequence having at least 95% sequence identity to amino acids 137 to 734 of SEQ ID NO: 48, and / or an amino acid sequence having at least 97% sequence identity to amino acids 202 to 734 of SEQ ID NO: 48; (xxv) an amino acid sequence having at least 94% sequence identity to amino acids 1 to 734 of SEQ ID NO: 50, an amino acid sequence having at least 95% sequence identity to amino acids 137 to 734 of SEQ ID NO: 50, and / or an amino acid sequence having at least 97% sequence identity to amino acids 202 to 734 of SEQ ID NO: 48; (xxvi) an amino acid sequence having at least 93% sequence identity to amino acids 1 to 734 of SEQ ID NO: 52, an amino acid sequence having at least 94% sequence identity to amino acids 137 to 734 of SEQ ID NO: 52, and / or an amino acid sequence having at least 96% sequence identity to amino acids 202 to 734 of SEQ ID NO: 52, (xxvii) an amino acid sequence having at least 96% sequence identity to amino acids 1 to 735 of SEQ ID NO: 54,(xxviii) an amino acid sequence having at least 94% sequence identity to amino acids 1 to 735 of SEQ ID NO: 56, an amino acid sequence having at least 95% sequence identity to amino acids 137 to 735 of SEQ ID NO: 56, and / or an amino acid sequence having at least 96% sequence identity to amino acids 202 to 735 of SEQ ID NO: 56; (xxix) an amino acid sequence having at least 84% sequence identity to amino acids 1 to 735 of SEQ ID NO: 58, an amino acid sequence having at least 85% sequence identity to amino acids 137 to 735 of SEQ ID NO: 58, and / or an amino acid sequence having at least 96% sequence identity to amino acids 202 to 735 of SEQ ID NO: 58 (xxx) an amino acid sequence having at least 85% sequence identity to amino acids 1 to 735 of SEQ ID NO: 60, (xxx) an amino acid sequence having at least 90% sequence identity to amino acids 137 to 735 of SEQ ID NO: 60, and / or an amino acid sequence having at least 93% sequence identity to amino acids 202 to 735 of SEQ ID NO: 60, or (xxxi) an amino acid sequence having at least 94% sequence identity to amino acids 1 to 735 of SEQ ID NO: 62, an amino acid sequence having at least 96% sequence identity to amino acids 137 to 735 of SEQ ID NO: 62, and / or an amino acid sequence having at least 97% sequence identity to amino acids 202 to 735 of SEQ ID NO: 62.

[0008] In certain embodiments, the present disclosure provides an amino acid sequence comprising: (i) an amino acid sequence having at least 99% sequence identity to amino acids 1 to 734 of SEQ ID NO:2, an amino acid sequence having at least 99% sequence identity to amino acids 137 to 734 of SEQ ID NO:2, and / or an amino acid sequence having at least 99% sequence identity to amino acids 202 to 734 of SEQ ID NO:2; (ii) an amino acid sequence having at least 99% sequence identity to amino acids 1 to 736 of SEQ ID NO:4, an amino acid sequence having at least 99% sequence identity to amino acids 138 to 736 of SEQ ID NO:4; (iii) an amino acid sequence having at least 99% sequence identity to amino acids 1 to 734 of SEQ ID NO: 6, an amino acid sequence having at least 99% sequence identity to amino acids 137 to 734 of SEQ ID NO: 6, and / or an amino acid sequence having at least 99% sequence identity to amino acids 202 to 734 of SEQ ID NO: 6; (iv) an amino acid sequence having at least 99% sequence identity to amino acids 1 to 731 of SEQ ID NO: 8. (v) an amino acid sequence having at least 99% sequence identity to amino acids 134 to 731 of SEQ ID NO: 8, and / or an amino acid sequence having at least 99% sequence identity to amino acids 199 to 731 of SEQ ID NO: 8; (v) an amino acid sequence having at least 99% sequence identity to amino acids 1 to 736 of SEQ ID NO: 10, an amino acid sequence having at least 99% sequence identity to amino acids 138 to 736 of SEQ ID NO: 10, and / or an amino acid sequence having at least 99% sequence identity to amino acids 203 to 736 of SEQ ID NO: 10. (vi) an amino acid sequence having at least 99% sequence identity to amino acids 1 to 736 of SEQ ID NO: 12, an amino acid sequence having at least 99% sequence identity to amino acids 137 to 736 of SEQ ID NO: 12, and / or an amino acid sequence having at least 99% sequence identity to amino acids 203 to 736 of SEQ ID NO: 12; (vii) an amino acid sequence having at least 99% sequence identity to amino acids 1 to 736 of SEQ ID NO: 14, an amino acid sequence having at least 99% sequence identity to amino acids 138 to 736 of SEQ ID NO: 14;and / or an amino acid sequence having at least 99% sequence identity to amino acids 204 to 736 of SEQ ID NO: 14, (viii) an amino acid sequence having at least 99% sequence identity to amino acids 1 to 734 of SEQ ID NO: 16, an amino acid sequence having at least 99% sequence identity to amino acids 137 to 734 of SEQ ID NO: 16, and / or an amino acid sequence having at least 99% sequence identity to amino acids 202 to 734 of SEQ ID NO: 16, (ix) an amino acid sequence having at least 99% sequence identity to amino acids 1 to 735 of SEQ ID NO: 18. a sequence, an amino acid sequence having at least 99% sequence identity to amino acids 138 to 735 of SEQ ID NO: 18, and / or an amino acid sequence having at least 99% sequence identity to amino acids 203 to 735 of SEQ ID NO: 18; (x) an amino acid sequence having at least 99% sequence identity to amino acids 1 to 736 of SEQ ID NO: 20, an amino acid sequence having at least 99% sequence identity to amino acids 137 to 736 of SEQ ID NO: 20, and / or an amino acid sequence having at least 99% sequence identity to amino acids 202 to 736 of SEQ ID NO: 20 (xi) an amino acid sequence having at least 99% sequence identity to amino acids 1 to 736 of SEQ ID NO: 22, an amino acid sequence having at least 99% sequence identity to amino acids 137 to 736 of SEQ ID NO: 22, and / or an amino acid sequence having at least 99% sequence identity to amino acids 203 to 736 of SEQ ID NO: 22; (xii) an amino acid sequence having at least 99% sequence identity to amino acids 1 to 736 of SEQ ID NO: 24, an amino acid sequence having at least 99% sequence identity to amino acids 138 to 736 of SEQ ID NO: 24, and / or or an amino acid sequence having at least 99% sequence identity to amino acids 204 to 736 of SEQ ID NO: 24; (xiii) an amino acid sequence having at least 99% sequence identity to amino acids 1 to 735 of SEQ ID NO: 26, an amino acid sequence having at least 99% sequence identity to amino acids 137 to 735 of SEQ ID NO: 26, and / or an amino acid sequence having at least 99% sequence identity to amino acids 202 to 735 of SEQ ID NO: 26; (xiv) an amino acid sequence having at least 99% sequence identity to amino acids 1 to 734 of SEQ ID NO: 28;(xv) an amino acid sequence having at least 99% sequence identity to amino acids 137 to 734 of SEQ ID NO: 28, and / or an amino acid sequence having at least 99% sequence identity to amino acids 202 to 734 of SEQ ID NO: 28; (xv) an amino acid sequence having at least 99% sequence identity to amino acids 1 to 734 of SEQ ID NO: 30, an amino acid sequence having at least 99% sequence identity to amino acids 137 to 734 of SEQ ID NO: 30, and / or an amino acid sequence having at least 99% sequence identity to amino acids 202 to 734 of SEQ ID NO: 30; (xv) an amino acid sequence having at least 99% sequence identity to amino acids 137 to 734 of SEQ ID NO: 30, and / or an amino acid sequence having at least 99% sequence identity to amino acids 202 to 734 of SEQ ID NO: 30; xvi) an amino acid sequence having at least 99% sequence identity to amino acids 1 to 735 of SEQ ID NO: 32, an amino acid sequence having at least 99% sequence identity to amino acids 137 to 735 of SEQ ID NO: 32, and / or an amino acid sequence having at least 99% sequence identity to amino acids 202 to 735 of SEQ ID NO: 32; (xvii) an amino acid sequence having at least 99% sequence identity to amino acids 1 to 735 of SEQ ID NO: 34, an amino acid sequence having at least 99% sequence identity to amino acids 137 to 735 of SEQ ID NO: 34, and / or or (xviii) an amino acid sequence having at least 99% sequence identity to amino acids 202 to 735 of SEQ ID NO: 34, (xviii) an amino acid sequence having at least 99% sequence identity to amino acids 1 to 735 of SEQ ID NO: 36, an amino acid sequence having at least 99% sequence identity to amino acids 138 to 735 of SEQ ID NO: 36, and / or an amino acid sequence having at least 99% sequence identity to amino acids 203 to 735 of SEQ ID NO: 36, (xix) an amino acid sequence having at least 99% sequence identity to amino acids 1 to 731 of SEQ ID NO: 38. (xx) an amino acid sequence having at least 99% sequence identity to amino acids 134 to 731 of SEQ ID NO: 38, and / or an amino acid sequence having at least 99% sequence identity to amino acids 199 to 731 of SEQ ID NO: 38; (xx) an amino acid sequence having at least 99% sequence identity to amino acids 1 to 735 of SEQ ID NO: 40, an amino acid sequence having at least 99% sequence identity to amino acids 137 to 735 of SEQ ID NO: 40, and / or an amino acid sequence having at least 99% sequence identity to amino acids 203 to 735 of SEQ ID NO: 40;(xxi) an amino acid sequence having at least 99% sequence identity to amino acids 1 to 736 of SEQ ID NO: 42, an amino acid sequence having at least 99% sequence identity to amino acids 138 to 736 of SEQ ID NO: 42, and / or an amino acid sequence having at least 99% sequence identity to amino acids 204 to 736 of SEQ ID NO: 42; (xxii) an amino acid sequence having at least 99% sequence identity to amino acids 1 to 736 of SEQ ID NO: 44, an amino acid sequence having at least 99% sequence identity to amino acids 137 to 736 of SEQ ID NO: 44 (xxiii) an amino acid sequence having at least 99% sequence identity to amino acids 1 to 736 of SEQ ID NO: 46, an amino acid sequence having at least 99% sequence identity to amino acids 137 to 736 of SEQ ID NO: 46, and / or an amino acid sequence having at least 99% sequence identity to amino acids 203 to 736 of SEQ ID NO: 46; (xxiv) an amino acid sequence having at least 99% sequence identity to amino acids 1 to 734 of SEQ ID NO: 48 (xxv) an amino acid sequence having at least 99% sequence identity to amino acids 137 to 734 of SEQ ID NO: 48, ... and / or an amino acid sequence having at least 99% sequence identity to amino acids 202 to 734 of SEQ ID NO: 48; (xxv) an amino acid sequence having at least 99% sequence identity to amino acids 1 to 734 of SEQ ID NO: 50, an amino acid sequence having at least 99% sequence identity to amino acids 137 to 734 of SEQ ID NO: 50, and / or an amino acid sequence having at least 99% sequence identity to amino acids 202 to 734 of SEQ ID NO: 50; (xxvi) an amino acid sequence having at least 99% sequence identity to amino acids 1 to 734 of SEQ ID NO: 52, an amino acid sequence having at least 99% sequence identity to amino acids 137 to 734 of SEQ ID NO: 52, and / or an amino acid sequence having at least 99% sequence identity to amino acids 202 to 734 of SEQ ID NO: 52, (xxvii) an amino acid sequence having at least 99% sequence identity to amino acids 1 to 735 of SEQ ID NO: 54,(xxviii) an amino acid sequence having at least 99% sequence identity to amino acids 138 to 735 of SEQ ID NO: 54, and / or an amino acid sequence having at least 99% sequence identity to amino acids 203 to 735 of SEQ ID NO: 54; (xxviii) an amino acid sequence having at least 99% sequence identity to amino acids 1 to 735 of SEQ ID NO: 56, an amino acid sequence having at least 99% sequence identity to amino acids 137 to 735 of SEQ ID NO: 56, and / or an amino acid sequence having at least 99% sequence identity to amino acids 202 to 735 of SEQ ID NO: 56; (xxix) an amino acid sequence having at least 99% sequence identity to amino acids 1 to 735 of SEQ ID NO: 58, an amino acid sequence having at least 99% sequence identity to amino acids 137 to 735 of SEQ ID NO: 58, and / or an amino acid sequence having at least 99% sequence identity to amino acids 202 to 735 of SEQ ID NO: 58. (xxx) an amino acid sequence having at least 99% sequence identity to amino acids 1 to 735 of SEQ ID NO: 60, an amino acid sequence having at least 99% sequence identity to amino acids 137 to 735 of SEQ ID NO: 60, and / or an amino acid sequence having at least 99% sequence identity to amino acids 202 to 735 of SEQ ID NO: 60, or (xxxi) an amino acid sequence having at least 99% sequence identity to amino acids 1 to 735 of SEQ ID NO: 62, an amino acid sequence having at least 99% sequence identity to amino acids 137 to 735 of SEQ ID NO: 62, and / or an amino acid sequence having at least 99% sequence identity to amino acids 202 to 735 of SEQ ID NO: 62.

[0009] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1 to 734 of SEQ ID NO: 2, amino acids 137 to 734 of SEQ ID NO: 2, and / or amino acids 202 to 734 of SEQ ID NO: 2. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 2.

[0010] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1 to 736 of SEQ ID NO: 4, amino acids 138 to 736 of SEQ ID NO: 4, and / or amino acids 204 to 736 of SEQ ID NO: 4. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 4.

[0011] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1 to 734 of SEQ ID NO: 6, amino acids 137 to 734 of SEQ ID NO: 6, and / or amino acids 202 to 734 of SEQ ID NO: 6. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 6.

[0012] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1 to 731 of SEQ ID NO: 8, amino acids 134 to 731 of SEQ ID NO: 8, and / or amino acids 199 to 731 of SEQ ID NO: 8. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 10.

[0013] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1 to 736 of SEQ ID NO: 12, amino acids 137 to 736 of SEQ ID NO: 12, and / or amino acids 203 to 736 of SEQ ID NO: 12. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 12.

[0014] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1 to 736 of SEQ ID NO: 14, amino acids 138 to 736 of SEQ ID NO: 14, and / or amino acids 204 to 736 of SEQ ID NO: 14. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 14.

[0015] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1 to 734 of SEQ ID NO: 16, amino acids 137 to 734 of SEQ ID NO: 16, and / or amino acids 202 to 734 of SEQ ID NO: 16. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 16.

[0016] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1 to 735 of SEQ ID NO: 18, amino acids 138 to 735 of SEQ ID NO: 18, and / or amino acids 203 to 735 of SEQ ID NO: 18. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 18.

[0017] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1 to 736 of SEQ ID NO: 20, amino acids 137 to 736 of SEQ ID NO: 20, and / or amino acids 202 to 736 of SEQ ID NO: 20. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 20.

[0018] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1 to 736 of SEQ ID NO: 22, amino acids 137 to 736 of SEQ ID NO: 22, and / or amino acids 203 to 736 of SEQ ID NO: 22. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 22.

[0019] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1 to 736 of SEQ ID NO: 24, amino acids 138 to 736 of SEQ ID NO: 24, and / or amino acids 204 to 736 of SEQ ID NO: 24. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 24.

[0020] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1 to 735 of SEQ ID NO: 26, amino acids 137 to 735 of SEQ ID NO: 26, and / or amino acids 202 to 735 of SEQ ID NO: 26. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 26.

[0021] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1 to 734 of SEQ ID NO: 28, amino acids 137 to 734 of SEQ ID NO: 28, and / or amino acids 202 to 734 of SEQ ID NO: 28. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 28.

[0022] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1 to 734 of SEQ ID NO: 30, amino acids 137 to 734 of SEQ ID NO: 30, and / or amino acids 202 to 734 of SEQ ID NO: 30. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 30.

[0023] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1 to 735 of SEQ ID NO: 32, amino acids 137 to 735 of SEQ ID NO: 32, and / or amino acids 202 to 735 of SEQ ID NO: 32. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 32.

[0024] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1 to 735 of SEQ ID NO: 34, amino acids 137 to 735 of SEQ ID NO: 34, and / or amino acids 202 to 735 of SEQ ID NO: 34. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 34.

[0025] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1 to 735 of SEQ ID NO: 36, amino acids 138 to 735 of SEQ ID NO: 36, and / or amino acids 203 to 735 of SEQ ID NO: 36. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 36.

[0026] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1 to 731 of SEQ ID NO: 38, amino acids 134 to 731 of SEQ ID NO: 38, and / or amino acids 199 to 731 of SEQ ID NO: 38. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 38.

[0027] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1 to 735 of SEQ ID NO: 40, amino acids 137 to 735 of SEQ ID NO: 40, and / or amino acids 203 to 735 of SEQ ID NO: 40. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 40.

[0028] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1 to 736 of SEQ ID NO: 42, amino acids 138 to 736 of SEQ ID NO: 42, and / or amino acids 204 to 736 of SEQ ID NO: 42. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 42.

[0029] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1 to 736 of SEQ ID NO: 44, amino acids 137 to 736 of SEQ ID NO: 44, and / or amino acids 202 to 736 of SEQ ID NO: 44. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 44.

[0030] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1 to 736 of SEQ ID NO: 46, amino acids 137 to 736 of SEQ ID NO: 46, and / or amino acids 203 to 736 of SEQ ID NO: 46. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 46.

[0031] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1 to 734 of SEQ ID NO: 48, amino acids 137 to 734 of SEQ ID NO: 48, and / or amino acids 202 to 734 of SEQ ID NO: 48. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 48.

[0032] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1 to 734 of SEQ ID NO: 50, amino acids 137 to 734 of SEQ ID NO: 50, and / or amino acids 202 to 734 of SEQ ID NO: 50. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 50.

[0033] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1 to 734 of SEQ ID NO: 52, amino acids 137 to 734 of SEQ ID NO: 52, and / or amino acids 202 to 734 of SEQ ID NO: 52. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 52.

[0034] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1 to 735 of SEQ ID NO: 54, amino acids 138 to 735 of SEQ ID NO: 54, and / or amino acids 203 to 735 of SEQ ID NO: 54. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 54.

[0035] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1 to 735 of SEQ ID NO: 56, amino acids 137 to 735 of SEQ ID NO: 56, and / or amino acids 202 to 735 of SEQ ID NO: 56. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 56.

[0036] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1 to 735 of SEQ ID NO: 58, amino acids 137 to 735 of SEQ ID NO: 58, and / or amino acids 202 to 735 of SEQ ID NO: 58. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 58.

[0037] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1 to 735 of SEQ ID NO: 60, amino acids 137 to 735 of SEQ ID NO: 60, and / or amino acids 202 to 735 of SEQ ID NO: 60. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 60.

[0038] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1 to 735 of SEQ ID NO: 62, amino acids 137 to 735 of SEQ ID NO: 62, and / or amino acids 202 to 735 of SEQ ID NO: 62. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 62.

[0039] In certain embodiments, the recombinant AAV capsid protein of the present disclosure is a variant of 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.

[0040] In another aspect, the disclosure provides an isolated polynucleotide encoding a recombinant AAV capsid protein described herein. In certain embodiments, the isolated polynucleotide has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the nucleic acid sequence set forth in any one of SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, and 61. In certain embodiments, the isolated polynucleotide comprises a nucleic acid sequence set forth in any one of SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, and 61.

[0041] In another aspect, the present disclosure provides a vector comprising the isolated polynucleotide described herein.In certain embodiments, the vector is a plasmid or a viral vector.In certain embodiments, the viral vector is a retroviral vector, a herpesvirus vector, a baculovirus vector, or an adenovirus vector.In certain embodiments, the vector is an expression vector.

[0042] In another aspect, the present disclosure provides a recombinant cell comprising a polynucleotide described in this disclosure or a vector described in this disclosure.

[0043] In another aspect, the present disclosure provides a method of producing a recombinant AAV capsid protein, the method comprising culturing a recombinant cell described in this disclosure under conditions in which the polynucleotide is expressed and the capsid protein is produced.

[0044] In another aspect, the present disclosure provides a recombinant adeno-associated virus (AAV), comprising: (a) a capsid comprising one or more of the recombinant AAV capsid proteins of the present disclosure; and (b) a rAAV genome. In certain embodiments, the rAAV genome comprises a transgene. In certain embodiments, the transgene encodes a polypeptide. In certain embodiments, the transgene encodes an miRNA, shRNA, siRNA, antisense RNA, gRNA, antagomir, miRNA sponge, RNA aptazyme, RNA aptamer, lncRNA, ribozyme, or mRNA. In certain embodiments, the transgene is operably linked to a transcriptional control element.

[0045] In another aspect, the present disclosure provides a method for transducing a cell, the method comprising contacting the cell with an rAAV of the present disclosure under conditions whereby the cell is transduced. In certain embodiments, the present disclosure provides a method for delivering a transgene into a cell, the method comprising contacting the cell with an rAAV of the present disclosure under conditions whereby the cell is transduced and the transgene is expressed. In certain embodiments, the cell is within a subject, and the rAAV is administered to the subject. In certain embodiments, the cell is a muscle cell and / or a liver cell. In certain aspects, the rAAV is administered to the subject intravenously, intraperitoneally, subcutaneously, intramuscularly, intrathecally, or intradermally. In certain embodiments, the subject is selected from the group consisting of a human subject, a canine subject, a feline subject, and an equine subject. In certain embodiments, the subject is a human subject.

[0046] In another aspect, the present disclosure provides a recombinant adeno-associated virus (AAV) for use in medicine, for use as a therapy, or for use as a medicament, the recombinant AAV comprising: (a) a capsid comprising one or more of the recombinant AAV capsid proteins of the present disclosure; and (b) a rAAV genome.

[0047] In another aspect, the present disclosure provides a packaging system for preparing rAAV, the packaging system comprising: (a) a first nucleotide sequence encoding one or more AAV Rep proteins, (b) a second nucleotide sequence encoding a recombinant AAV capsid protein of the disclosure, and (c) a third nucleotide sequence comprising an rAAV genome sequence. In certain embodiments, the packaging system comprises a first vector comprising the first nucleotide sequence and the second nucleotide sequence, and a second vector comprising the third nucleotide sequence.

[0048] In certain embodiments, the packaging system of the present disclosure further comprises a fourth nucleotide sequence comprising one or more helper virus genes. In certain embodiments, the fourth nucleotide sequence is comprised in a third vector. In certain embodiments, the fourth nucleotide sequence comprises one or more genes derived from a virus selected from the group consisting of adenovirus, herpesvirus, vaccinia virus, and cytomegalovirus (CMV).

[0049] In certain embodiments, the first vector, second vector, and / or third vector of the packaging system of the present disclosure is a plasmid.

[0050] In another aspect, the present disclosure provides a method for the recombinant preparation of rAAV, comprising introducing into a cell a packaging system described in this disclosure under conditions whereby rAAV is produced. [Brief explanation of the drawings]

[0051] [Figure 1A] The expression levels of FGF21 (FIG. 1A) or sTGFbR2 (FIG. 1B) in plasma samples from dogs intravenously administered 5×10 vg / kg of vector genomes containing FGF21 and sTGFbR2 coding sequences packaged in CL01, CL03, CL11, CL13, CL27, or AAV8 (control) capsids are shown. Figure 1A shows FGF21 expression assessed by ELISA, and Figure 1B shows sTGFbR2 expression assessed by Western blot. [Figure 1B] The expression levels of FGF21 (FIG. 1A) or sTGFbR2 (FIG. 1B) in plasma samples from dogs intravenously administered 5×10 vg / kg of vector genomes containing FGF21 and sTGFbR2 coding sequences packaged in CL01, CL03, CL11, CL13, CL27, or AAV8 (control) capsids are shown. Figure 1A shows FGF21 expression assessed by ELISA, and Figure 1B shows sTGFbR2 expression assessed by Western blot. DETAILED DESCRIPTION OF THE INVENTION

[0052] Provided herein are recombinant adeno-associated virus (AAV) capsid proteins, compositions comprising the capsid proteins (e.g., rAAV), nucleic acids encoding the capsid proteins, and methods for making and using the capsid proteins. The AAV capsid proteins described herein were isolated from screening in vivo shuffled capsid libraries for AAVs enriched in liver and / or muscle.

[0053] I. Definition As used herein, the term "AAV" is the standard abbreviation for adeno-associated virus.

[0054] As used interchangeably herein, the term "recombinant adeno-associated virus" or "rAAV" refers to an AAV comprising a genome lacking functional rep and cap genes.

[0055] As used herein, the term "cap gene" refers to a nucleic acid sequence that encodes a capsid protein. In the case of AAV, the capsid protein can be VP1, VP2, or VP3. The VP1, VP2, and / or VP3 capsid proteins assemble into a capsid that surrounds the rAAV genome.

[0056] As used herein, the term "rep gene" refers to a nucleic acid sequence that encodes the nonstructural proteins (e.g., rep78, rep68, rep52, and rep40) required for AAV replication and production.

[0057] As used herein, the term "rAAV genome" refers to a nucleic acid molecule (e.g., DNA and / or RNA) comprising the genomic sequence of an rAAV. Those skilled in the art will understand that when the rAAV genome comprises a transgene (e.g., a polypeptide encoding a therapeutic protein operably linked to a transcriptional control element (i.e., payload)), the rAAV genome can be in a sense or antisense orientation relative to the transcriptional direction of the transgene.

[0058] As used herein, an "isolated polynucleotide" refers to a polynucleotide that is separated from one or more nucleic acid molecules that are present in the natural source of the polynucleotide.

[0059] As used herein, the "percentage identity" between two nucleotide sequences or two amino acid sequences is calculated by multiplying the number of matches between the aligned sequence pairs 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 between amino acids.Please note that this length only includes internal gaps, and does not include gaps at the ends of the sequences.

[0060] As used herein, "vector" refers to a nucleic acid molecule that is a vehicle for introducing a nucleic acid molecule (eg, a polynucleotide disclosed herein) into a cell.

[0061] As used herein, "expression vector" refers to a vector that contains transcriptional control elements operably linked to a gene of interest (e.g., a polynucleotide disclosed herein), thereby facilitating expression of the gene of interest in cells and / or cell-free expression systems.

[0062] 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 a non-coding RNA (e.g., an miRNA, shRNA, siRNA, antisense RNA, gRNA, antagomir, miRNA sponge, RNA aptazyme, or RNA aptamer).

[0063] As used herein, the term "transcriptional control element" or "TRE" refers to a cis-acting nucleotide sequence that regulates (e.g., controls, increases, or decreases) the transcription of an operably linked nucleotide sequence by an RNA polymerase to form an RNA molecule. A TRE can include one or more promoter and / or enhancer elements. Those skilled in the art will understand that promoter and enhancer elements within a gene can be positionally contiguous, and the term "promoter" can refer to a sequence that includes promoter and enhancer elements. Thus, the term "promoter" does not exclude enhancer elements within a sequence. The promoter and enhancer elements need not be derived from the same gene or species, and the sequence of each promoter or enhancer element can be either identical or substantially identical to the corresponding endogenous sequence within a genome.

[0064] As used herein, the term "operably linked" is used to describe the connection between a TRE and a polynucleotide sequence to be transcribed (e.g., a transgene disclosed herein). Typically, gene expression is placed under the control of a TRE that includes one or more promoter and / or enhancer elements. A transgene is "operably linked" to a TRE if transcription of the transgene is controlled or influenced by the TRE. The promoter and enhancer elements of the TRE can be in any orientation and / or distance from the transgene, so long as the desired transcriptional activity is obtained. In one embodiment, the TRE is upstream of the transgene.

[0065] As used herein, the term "effective amount" in the context of administering AAV to a subject refers to the amount of AAV that achieves the desired prophylactic or therapeutic effect.

[0066] II. AAV Capsid Proteins In one aspect, the present disclosure provides recombinant adeno-associated virus (AAV) capsid proteins isolated from screening in vivo shuffled capsid libraries for AAVs enriched in liver and / or muscle.

[0067] In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-734 of SEQ ID NO: 2. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-734 of SEQ ID NO: 2. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 202 to 734 of SEQ ID NO:2.

[0068] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1-734 of SEQ ID NO: 2. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 137-734 of SEQ ID NO: 2. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 202-734 of SEQ ID NO: 2. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 2.

[0069] In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-736 of SEQ ID NO: 4. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 138-736 of SEQ ID NO: 4. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 204 to 736 of SEQ ID NO:4.

[0070] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1-736 of SEQ ID NO: 4. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 138-736 of SEQ ID NO: 4. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 204-736 of SEQ ID NO: 4. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 4.

[0071] In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-734 of SEQ ID NO: 6. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-734 of SEQ ID NO: 6. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 202 to 734 of SEQ ID NO:6.

[0072] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1-734 of SEQ ID NO: 6. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 137-734 of SEQ ID NO: 6. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 202-734 of SEQ ID NO: 6. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 6.

[0073] In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to amino acids 1-731 of SEQ ID NO: 8. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 134-731 of SEQ ID NO:8. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 199 to 731 of SEQ ID NO:8.

[0074] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1-731 of SEQ ID NO: 8. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 134-731 of SEQ ID NO: 8. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 199-731 of SEQ ID NO: 8. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 8.

[0075] In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-736 of SEQ ID NO: 10. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 138-736 of SEQ ID NO: 10. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 203 to 736 of SEQ ID NO: 10.

[0076] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1-736 of SEQ ID NO: 10. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 138-736 of SEQ ID NO: 10. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 203-736 of SEQ ID NO: 10. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 10.

[0077] In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-736 of SEQ ID NO: 12. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-736 of SEQ ID NO: 12. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 203 to 736 of SEQ ID NO:12.

[0078] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1-736 of SEQ ID NO: 12. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 137-736 of SEQ ID NO: 12. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 203-736 of SEQ ID NO: 12. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 12.

[0079] In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-736 of SEQ ID NO: 14. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 138-736 of SEQ ID NO: 14. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 204 to 736 of SEQ ID NO:14.

[0080] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1 to 736 of SEQ ID NO: 14. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 138 to 736 of SEQ ID NO: 14. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 204 to 736 of SEQ ID NO: 14. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 14.

[0081] In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-734 of SEQ ID NO: 16. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-734 of SEQ ID NO: 16. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 202 to 734 of SEQ ID NO:16.

[0082] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1-734 of SEQ ID NO: 16. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 137-734 of SEQ ID NO: 16. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 202-734 of SEQ ID NO: 16. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 16.

[0083] In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-735 of SEQ ID NO: 18. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 138-735 of SEQ ID NO: 18. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 203 to 735 of SEQ ID NO:18.

[0084] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1 to 735 of SEQ ID NO: 18. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 138 to 735 of SEQ ID NO: 18. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 203 to 735 of SEQ ID NO: 18. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 18.

[0085] In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-736 of SEQ ID NO: 20. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-736 of SEQ ID NO: 20. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 202 to 736 of SEQ ID NO:20.

[0086] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1-736 of SEQ ID NO: 20. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 137-736 of SEQ ID NO: 20. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 202-736 of SEQ ID NO: 20. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 20.

[0087] In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-736 of SEQ ID NO: 22. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-736 of SEQ ID NO: 22. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 203 to 736 of SEQ ID NO:22.

[0088] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1-736 of SEQ ID NO: 22. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 137-736 of SEQ ID NO: 22. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 203-736 of SEQ ID NO: 22. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 22.

[0089] In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-736 of SEQ ID NO: 24. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 138-736 of SEQ ID NO: 24. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 204 to 736 of SEQ ID NO:24.

[0090] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1 to 736 of SEQ ID NO: 24. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 138 to 736 of SEQ ID NO: 24. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 204 to 736 of SEQ ID NO: 24. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 24.

[0091] In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-735 of SEQ ID NO: 26. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-735 of SEQ ID NO: 26. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 202 to 735 of SEQ ID NO:26.

[0092] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1-735 of SEQ ID NO: 26. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 137-735 of SEQ ID NO: 26. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 202-735 of SEQ ID NO: 26. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 26.

[0093] In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-734 of SEQ ID NO: 28. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-734 of SEQ ID NO: 28. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 202 to 734 of SEQ ID NO:28.

[0094] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1 to 734 of SEQ ID NO: 28. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 137 to 734 of SEQ ID NO: 28. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 202 to 734 of SEQ ID NO: 28. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 28.

[0095] In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-734 of SEQ ID NO: 30. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-734 of SEQ ID NO: 30. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 202 to 734 of SEQ ID NO:30.

[0096] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1 to 734 of SEQ ID NO: 30. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 137 to 734 of SEQ ID NO: 30. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 202 to 734 of SEQ ID NO: 30. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 30.

[0097] In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-735 of SEQ ID NO: 32. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-735 of SEQ ID NO: 32. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 202 to 735 of SEQ ID NO:32.

[0098] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1-735 of SEQ ID NO: 32. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 137-735 of SEQ ID NO: 32. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 202-735 of SEQ ID NO: 32. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 32.

[0099] In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-735 of SEQ ID NO: 34. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-735 of SEQ ID NO: 34. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 202 to 735 of SEQ ID NO:34.

[0100] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1-735 of SEQ ID NO: 34. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 137-735 of SEQ ID NO: 34. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 202-735 of SEQ ID NO: 34. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 34.

[0101] In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-735 of SEQ ID NO: 36. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 138-735 of SEQ ID NO: 36. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 203 to 735 of SEQ ID NO:36.

[0102] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1-735 of SEQ ID NO: 36. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 138-735 of SEQ ID NO: 36. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 203-735 of SEQ ID NO: 36. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 36.

[0103] In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-731 of SEQ ID NO: 38. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 134-731 of SEQ ID NO: 38. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 199 to 731 of SEQ ID NO:38.

[0104] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1 to 731 of SEQ ID NO: 38. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 134 to 731 of SEQ ID NO: 38. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 199 to 731 of SEQ ID NO: 38. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 38.

[0105] In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-735 of SEQ ID NO: 40. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-735 of SEQ ID NO: 40. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 203 to 735 of SEQ ID NO:40.

[0106] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1-735 of SEQ ID NO: 40. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 137-735 of SEQ ID NO: 40. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 203-735 of SEQ ID NO: 40. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 40.

[0107] In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-736 of SEQ ID NO: 42. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 138-736 of SEQ ID NO: 42. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 204 to 736 of SEQ ID NO:42.

[0108] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1 to 736 of SEQ ID NO: 42. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 138 to 736 of SEQ ID NO: 42. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 204 to 736 of SEQ ID NO: 42. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 42.

[0109] In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-736 of SEQ ID NO: 44. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-736 of SEQ ID NO: 44. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 202 to 736 of SEQ ID NO:44.

[0110] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1-736 of SEQ ID NO: 44. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 137-736 of SEQ ID NO: 44. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 202-736 of SEQ ID NO: 44. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 44.

[0111] In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-736 of SEQ ID NO: 46. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-736 of SEQ ID NO: 46. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 203 to 736 of SEQ ID NO:46.

[0112] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1-736 of SEQ ID NO: 46. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 137-736 of SEQ ID NO: 46. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 203-736 of SEQ ID NO: 46. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 46.

[0113] In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-734 of SEQ ID NO: 48. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-734 of SEQ ID NO: 48. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 202 to 734 of SEQ ID NO:48.

[0114] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1-734 of SEQ ID NO: 48. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 137-734 of SEQ ID NO: 48. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 202-734 of SEQ ID NO: 48. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 48.

[0115] In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-734 of SEQ ID NO: 50. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-734 of SEQ ID NO: 50. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 202 to 734 of SEQ ID NO:50.

[0116] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1-734 of SEQ ID NO: 50. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 137-734 of SEQ ID NO: 50. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 202-734 of SEQ ID NO: 50. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 50.

[0117] In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-734 of SEQ ID NO: 52. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-734 of SEQ ID NO: 52. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 202 to 734 of SEQ ID NO:52.

[0118] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1-734 of SEQ ID NO: 52. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 137-734 of SEQ ID NO: 52. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 202-734 of SEQ ID NO: 52. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 52.

[0119] In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-735 of SEQ ID NO: 54. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 138-735 of SEQ ID NO: 54. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 203 to 735 of SEQ ID NO:54.

[0120] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1-735 of SEQ ID NO: 54. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 138-735 of SEQ ID NO: 54. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 203-735 of SEQ ID NO: 54. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 54.

[0121] In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-735 of SEQ ID NO: 56. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-735 of SEQ ID NO: 56. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 202 to 735 of SEQ ID NO:56.

[0122] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1-735 of SEQ ID NO: 56. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 137-735 of SEQ ID NO: 56. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 202-735 of SEQ ID NO: 56. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 56.

[0123] In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-735 of SEQ ID NO: 58. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-735 of SEQ ID NO: 58. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 202 to 735 of SEQ ID NO:58.

[0124] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1-735 of SEQ ID NO: 58. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 137-735 of SEQ ID NO: 58. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 202-735 of SEQ ID NO: 58. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 58.

[0125] In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-735 of SEQ ID NO: 60. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-735 of SEQ ID NO: 60. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 202 to 735 of SEQ ID NO:60.

[0126] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1-735 of SEQ ID NO: 60. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 137-735 of SEQ ID NO: 60. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 202-735 of SEQ ID NO: 60. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 60.

[0127] In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-735 of SEQ ID NO: 62. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-735 of SEQ ID NO: 62. In certain embodiments, the recombinant AAV capsid protein comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 202 to 735 of SEQ ID NO:62.

[0128] In certain embodiments, the recombinant AAV capsid protein comprises amino acids 1-735 of SEQ ID NO: 62. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 137-735 of SEQ ID NO: 62. In certain embodiments, the recombinant AAV capsid protein comprises amino acids 202-735 of SEQ ID NO: 62. In certain embodiments, the recombinant AAV capsid protein comprises SEQ ID NO: 62.

[0129] In certain embodiments, the recombinant AAV capsid protein is a variant of 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.

[0130] III. Polynucleotides, Vectors, and Methods for Producing AAV Capsids In another aspect, the disclosure provides isolated polynucleotides encoding one or more recombinant AAV capsid proteins described herein.

[0131] In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-734 of SEQ ID NO: 2. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-734 of SEQ ID NO: 2. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 202 to 734 of SEQ ID NO:2.

[0132] In certain embodiments, the isolated polynucleotide encodes amino acids 1-734 of SEQ ID NO: 2. In certain embodiments, the isolated polynucleotide encodes amino acids 137-734 of SEQ ID NO: 2. In certain embodiments, the isolated polynucleotide encodes amino acids 202-734 of SEQ ID NO: 2. In certain embodiments, the isolated polynucleotide encodes SEQ ID NO: 2.

[0133] In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-736 of SEQ ID NO: 4. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 138-736 of SEQ ID NO: 4. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 204 to 736 of SEQ ID NO:4.

[0134] In certain embodiments, the isolated polynucleotide encodes amino acids 1-736 of SEQ ID NO:4. In certain embodiments, the isolated polynucleotide encodes amino acids 138-736 of SEQ ID NO:4. In certain embodiments, the isolated polynucleotide encodes amino acids 204-736 of SEQ ID NO:4. In certain embodiments, the isolated polynucleotide encodes SEQ ID NO:4.

[0135] In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-734 of SEQ ID NO: 6. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-734 of SEQ ID NO: 6. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 202 to 734 of SEQ ID NO:6.

[0136] In certain embodiments, the isolated polynucleotide encodes amino acids 1-734 of SEQ ID NO:6. In certain embodiments, the isolated polynucleotide encodes amino acids 137-734 of SEQ ID NO:6. In certain embodiments, the isolated polynucleotide encodes amino acids 202-734 of SEQ ID NO:6. In certain embodiments, the isolated polynucleotide encodes SEQ ID NO:6.

[0137] In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to amino acids 1-731 of SEQ ID NO: 8. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 134-731 of SEQ ID NO: 8. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 199-731 of SEQ ID NO:8.

[0138] In certain embodiments, the isolated polynucleotide encodes amino acids 1-731 of SEQ ID NO: 8. In certain embodiments, the isolated polynucleotide encodes amino acids 134-731 of SEQ ID NO: 8. In certain embodiments, the isolated polynucleotide encodes amino acids 199-731 of SEQ ID NO: 8. In certain embodiments, the isolated polynucleotide encodes SEQ ID NO: 8.

[0139] In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-736 of SEQ ID NO: 10. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 138-736 of SEQ ID NO: 10. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 203-736 of SEQ ID NO:10.

[0140] In certain embodiments, the isolated polynucleotide encodes amino acids 1-736 of SEQ ID NO: 10. In certain embodiments, the isolated polynucleotide encodes amino acids 138-736 of SEQ ID NO: 10. In certain embodiments, the isolated polynucleotide encodes amino acids 203-736 of SEQ ID NO: 10. In certain embodiments, the isolated polynucleotide encodes SEQ ID NO: 10.

[0141] In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-736 of SEQ ID NO: 12. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-736 of SEQ ID NO: 12. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 203-736 of SEQ ID NO:12.

[0142] In certain embodiments, the isolated polynucleotide encodes amino acids 1-736 of SEQ ID NO: 12. In certain embodiments, the isolated polynucleotide encodes amino acids 137-736 of SEQ ID NO: 10. In certain embodiments, the isolated polynucleotide encodes amino acids 203-736 of SEQ ID NO: 12. In certain embodiments, the isolated polynucleotide encodes SEQ ID NO: 12.

[0143] In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-736 of SEQ ID NO: 14. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 138-736 of SEQ ID NO: 14. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 204 to 736 of SEQ ID NO:14.

[0144] In certain embodiments, the isolated polynucleotide encodes amino acids 1-736 of SEQ ID NO: 14. In certain embodiments, the isolated polynucleotide encodes amino acids 138-736 of SEQ ID NO: 14. In certain embodiments, the isolated polynucleotide encodes amino acids 204-736 of SEQ ID NO: 14. In certain embodiments, the isolated polynucleotide encodes SEQ ID NO: 14.

[0145] In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-734 of SEQ ID NO: 16. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-734 of SEQ ID NO: 16. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 202 to 734 of SEQ ID NO:16.

[0146] In certain embodiments, the isolated polynucleotide encodes amino acids 1-734 of SEQ ID NO: 16. In certain embodiments, the isolated polynucleotide encodes amino acids 137-734 of SEQ ID NO: 16. In certain embodiments, the isolated polynucleotide encodes amino acids 202-734 of SEQ ID NO: 16. In certain embodiments, the isolated polynucleotide encodes SEQ ID NO: 16.

[0147] In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-735 of SEQ ID NO: 18. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 138-735 of SEQ ID NO: 18. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 203 to 735 of SEQ ID NO:18.

[0148] In certain embodiments, the isolated polynucleotide encodes amino acids 1-735 of SEQ ID NO: 18. In certain embodiments, the isolated polynucleotide encodes amino acids 138-735 of SEQ ID NO: 18. In certain embodiments, the isolated polynucleotide encodes amino acids 203-735 of SEQ ID NO: 18. In certain embodiments, the isolated polynucleotide encodes SEQ ID NO: 18.

[0149] In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-736 of SEQ ID NO: 20. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-736 of SEQ ID NO: 20. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 202-736 of SEQ ID NO:20.

[0150] In certain embodiments, the isolated polynucleotide encodes amino acids 1-736 of SEQ ID NO: 20. In certain embodiments, the isolated polynucleotide encodes amino acids 137-736 of SEQ ID NO: 20. In certain embodiments, the isolated polynucleotide encodes amino acids 202-736 of SEQ ID NO: 20. In certain embodiments, the isolated polynucleotide encodes SEQ ID NO: 20.

[0151] In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-736 of SEQ ID NO: 22. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-736 of SEQ ID NO: 22. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 203-736 of SEQ ID NO:22.

[0152] In certain embodiments, the isolated polynucleotide encodes amino acids 1-736 of SEQ ID NO: 22. In certain embodiments, the isolated polynucleotide encodes amino acids 137-736 of SEQ ID NO: 22. In certain embodiments, the isolated polynucleotide encodes amino acids 203-736 of SEQ ID NO: 22. In certain embodiments, the isolated polynucleotide encodes SEQ ID NO: 22.

[0153] In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-736 of SEQ ID NO: 24. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 138-736 of SEQ ID NO: 24. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 204 to 736 of SEQ ID NO:24.

[0154] In certain embodiments, the isolated polynucleotide encodes amino acids 1-736 of SEQ ID NO:24. In certain embodiments, the isolated polynucleotide encodes amino acids 138-736 of SEQ ID NO:24. In certain embodiments, the isolated polynucleotide encodes amino acids 204-736 of SEQ ID NO:24. In certain embodiments, the isolated polynucleotide encodes SEQ ID NO:24.

[0155] In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-735 of SEQ ID NO: 26. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-735 of SEQ ID NO: 26. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 202 to 735 of SEQ ID NO:26.

[0156] In certain embodiments, the isolated polynucleotide encodes amino acids 1-735 of SEQ ID NO: 26. In certain embodiments, the isolated polynucleotide encodes amino acids 137-735 of SEQ ID NO: 26. In certain embodiments, the isolated polynucleotide encodes amino acids 202-735 of SEQ ID NO: 26. In certain embodiments, the isolated polynucleotide encodes SEQ ID NO: 26.

[0157] In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-734 of SEQ ID NO: 28. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-734 of SEQ ID NO: 28. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 202 to 734 of SEQ ID NO:28.

[0158] In certain embodiments, the isolated polynucleotide encodes amino acids 1-734 of SEQ ID NO: 28. In certain embodiments, the isolated polynucleotide encodes amino acids 137-734 of SEQ ID NO: 28. In certain embodiments, the isolated polynucleotide encodes amino acids 202-734 of SEQ ID NO: 28. In certain embodiments, the isolated polynucleotide encodes SEQ ID NO: 28.

[0159] In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-734 of SEQ ID NO: 30. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-734 of SEQ ID NO: 30. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 202 to 734 of SEQ ID NO:30.

[0160] In certain embodiments, the isolated polynucleotide encodes amino acids 1-734 of SEQ ID NO: 30. In certain embodiments, the isolated polynucleotide encodes amino acids 137-734 of SEQ ID NO: 30. In certain embodiments, the isolated polynucleotide encodes amino acids 202-734 of SEQ ID NO: 30. In certain embodiments, the isolated polynucleotide encodes SEQ ID NO: 30.

[0161] In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-735 of SEQ ID NO: 32. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-735 of SEQ ID NO: 32. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 202 to 735 of SEQ ID NO:32.

[0162] In certain embodiments, the isolated polynucleotide encodes amino acids 1-735 of SEQ ID NO: 32. In certain embodiments, the isolated polynucleotide encodes amino acids 137-735 of SEQ ID NO: 32. In certain embodiments, the isolated polynucleotide encodes amino acids 202-735 of SEQ ID NO: 32. In certain embodiments, the isolated polynucleotide encodes SEQ ID NO: 32.

[0163] In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-735 of SEQ ID NO: 34. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-735 of SEQ ID NO: 34. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 202 to 735 of SEQ ID NO:34.

[0164] In certain embodiments, the isolated polynucleotide encodes amino acids 1-735 of SEQ ID NO: 34. In certain embodiments, the isolated polynucleotide encodes amino acids 137-735 of SEQ ID NO: 34. In certain embodiments, the isolated polynucleotide encodes amino acids 202-735 of SEQ ID NO: 34. In certain embodiments, the isolated polynucleotide encodes SEQ ID NO: 34.

[0165] In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-735 of SEQ ID NO: 36. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 138-735 of SEQ ID NO: 36. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 203 to 735 of SEQ ID NO:36.

[0166] In certain embodiments, the isolated polynucleotide encodes amino acids 1-735 of SEQ ID NO: 36. In certain embodiments, the isolated polynucleotide encodes amino acids 138-735 of SEQ ID NO: 36. In certain embodiments, the isolated polynucleotide encodes amino acids 203-735 of SEQ ID NO: 36. In certain embodiments, the isolated polynucleotide encodes SEQ ID NO: 36.

[0167] In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-731 of SEQ ID NO: 38. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 134-731 of SEQ ID NO: 38. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 199-731 of SEQ ID NO:38.

[0168] In certain embodiments, the isolated polynucleotide encodes amino acids 1-731 of SEQ ID NO: 38. In certain embodiments, the isolated polynucleotide encodes amino acids 134-731 of SEQ ID NO: 38. In certain embodiments, the isolated polynucleotide encodes amino acids 199-731 of SEQ ID NO: 38. In certain embodiments, the isolated polynucleotide encodes SEQ ID NO: 38.

[0169] In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-735 of SEQ ID NO: 40. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-735 of SEQ ID NO: 40. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 203-735 of SEQ ID NO:40.

[0170] In certain embodiments, the isolated polynucleotide encodes amino acids 1-735 of SEQ ID NO: 40. In certain embodiments, the isolated polynucleotide encodes amino acids 137-735 of SEQ ID NO: 40. In certain embodiments, the isolated polynucleotide encodes amino acids 203-735 of SEQ ID NO: 40. In certain embodiments, the isolated polynucleotide encodes SEQ ID NO: 40.

[0171] In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-736 of SEQ ID NO: 42. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 138-736 of SEQ ID NO: 42. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 204 to 736 of SEQ ID NO:42.

[0172] In certain embodiments, the isolated polynucleotide encodes amino acids 1-736 of SEQ ID NO: 42. In certain embodiments, the isolated polynucleotide encodes amino acids 138-736 of SEQ ID NO: 42. In certain embodiments, the isolated polynucleotide encodes amino acids 204-736 of SEQ ID NO: 42. In certain embodiments, the isolated polynucleotide encodes SEQ ID NO: 42.

[0173] In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-736 of SEQ ID NO: 44. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-736 of SEQ ID NO: 44. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 202 to 736 of SEQ ID NO:44.

[0174] In certain embodiments, the isolated polynucleotide encodes amino acids 1-736 of SEQ ID NO: 44. In certain embodiments, the isolated polynucleotide encodes amino acids 137-736 of SEQ ID NO: 44. In certain embodiments, the isolated polynucleotide encodes amino acids 202-736 of SEQ ID NO: 44. In certain embodiments, the isolated polynucleotide encodes SEQ ID NO: 44.

[0175] In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-736 of SEQ ID NO: 46. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-736 of SEQ ID NO: 46. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 203-736 of SEQ ID NO:46.

[0176] In certain embodiments, the isolated polynucleotide encodes amino acids 1-736 of SEQ ID NO: 46. In certain embodiments, the isolated polynucleotide encodes amino acids 137-736 of SEQ ID NO: 46. In certain embodiments, the isolated polynucleotide encodes amino acids 203-736 of SEQ ID NO: 46. In certain embodiments, the isolated polynucleotide encodes SEQ ID NO: 46.

[0177] In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-734 of SEQ ID NO: 48. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-734 of SEQ ID NO: 48. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 202 to 734 of SEQ ID NO:48.

[0178] In certain embodiments, the isolated polynucleotide encodes amino acids 1-734 of SEQ ID NO: 48. In certain embodiments, the isolated polynucleotide encodes amino acids 137-734 of SEQ ID NO: 48. In certain embodiments, the isolated polynucleotide encodes amino acids 202-734 of SEQ ID NO: 48. In certain embodiments, the isolated polynucleotide encodes SEQ ID NO: 48.

[0179] In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-734 of SEQ ID NO: 50. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-734 of SEQ ID NO: 50. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 202-734 of SEQ ID NO:50.

[0180] In certain embodiments, the isolated polynucleotide encodes amino acids 1-734 of SEQ ID NO: 50. In certain embodiments, the isolated polynucleotide encodes amino acids 137-734 of SEQ ID NO: 50. In certain embodiments, the isolated polynucleotide encodes amino acids 202-734 of SEQ ID NO: 50. In certain embodiments, the isolated polynucleotide encodes SEQ ID NO: 50.

[0181] In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-734 of SEQ ID NO: 52. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-734 of SEQ ID NO: 52. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 202-734 of SEQ ID NO:52.

[0182] In certain embodiments, the isolated polynucleotide encodes amino acids 1-734 of SEQ ID NO: 52. In certain embodiments, the isolated polynucleotide encodes amino acids 137-734 of SEQ ID NO: 52. In certain embodiments, the isolated polynucleotide encodes amino acids 202-734 of SEQ ID NO: 52. In certain embodiments, the isolated polynucleotide encodes SEQ ID NO: 52.

[0183] In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-735 of SEQ ID NO: 54. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 138-735 of SEQ ID NO: 54. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 203-735 of SEQ ID NO:54.

[0184] In certain embodiments, the isolated polynucleotide encodes amino acids 1-735 of SEQ ID NO: 54. In certain embodiments, the isolated polynucleotide encodes amino acids 138-735 of SEQ ID NO: 54. In certain embodiments, the isolated polynucleotide encodes amino acids 203-735 of SEQ ID NO: 54. In certain embodiments, the isolated polynucleotide encodes SEQ ID NO: 54.

[0185] In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-735 of SEQ ID NO: 56. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-735 of SEQ ID NO: 56. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 202 to 735 of SEQ ID NO:56.

[0186] In certain embodiments, the isolated polynucleotide encodes amino acids 1-735 of SEQ ID NO: 56. In certain embodiments, the isolated polynucleotide encodes amino acids 137-735 of SEQ ID NO: 56. In certain embodiments, the isolated polynucleotide encodes amino acids 202-735 of SEQ ID NO: 56. In certain embodiments, the isolated polynucleotide encodes SEQ ID NO: 56.

[0187] In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-735 of SEQ ID NO: 58. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-735 of SEQ ID NO: 58. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 202 to 735 of SEQ ID NO:58.

[0188] In certain embodiments, the isolated polynucleotide encodes amino acids 1-735 of SEQ ID NO: 58. In certain embodiments, the isolated polynucleotide encodes amino acids 137-735 of SEQ ID NO: 58. In certain embodiments, the isolated polynucleotide encodes amino acids 202-735 of SEQ ID NO: 58. In certain embodiments, the isolated polynucleotide encodes SEQ ID NO: 58.

[0189] In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-735 of SEQ ID NO: 60. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-735 of SEQ ID NO: 60. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 202 to 735 of SEQ ID NO:60.

[0190] In certain embodiments, the isolated polynucleotide encodes amino acids 1-735 of SEQ ID NO: 60. In certain embodiments, the isolated polynucleotide encodes amino acids 137-735 of SEQ ID NO: 60. In certain embodiments, the isolated polynucleotide encodes amino acids 202-735 of SEQ ID NO: 60. In certain embodiments, the isolated polynucleotide encodes SEQ ID NO: 60.

[0191] In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-735 of SEQ ID NO: 62. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-735 of SEQ ID NO: 62. In certain embodiments, the isolated polynucleotide encodes an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 202 to 735 of SEQ ID NO:62.

[0192] In certain embodiments, the isolated polynucleotide encodes amino acids 1-735 of SEQ ID NO: 62. In certain embodiments, the isolated polynucleotide encodes amino acids 137-735 of SEQ ID NO: 62. In certain embodiments, the isolated polynucleotide encodes amino acids 202-735 of SEQ ID NO: 62. In certain embodiments, the isolated polynucleotide encodes SEQ ID NO: 62.

[0193] In certain embodiments, the present disclosure provides an isolated polynucleotide having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a nucleic acid sequence set forth in any one of SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, and 61.

[0194] In certain embodiments, the isolated polynucleotide comprises the nucleic acid sequence set forth in SEQ ID NO: 1. In certain embodiments, the isolated polynucleotide comprises the nucleic acid sequence set forth in SEQ ID NO: 3. In certain embodiments, the isolated polynucleotide comprises the nucleic acid sequence set forth in SEQ ID NO: 5. In certain embodiments, the isolated polynucleotide comprises the nucleic acid sequence set forth in SEQ ID NO: 7. In certain embodiments, the isolated polynucleotide comprises the nucleic acid sequence set forth in SEQ ID NO: 9. In certain embodiments, the isolated polynucleotide comprises the nucleic acid sequence set forth in SEQ ID NO: 11. In certain embodiments, the isolated polynucleotide comprises the nucleic acid sequence set forth in SEQ ID NO: 13. In certain embodiments, the isolated polynucleotide comprises the nucleic acid sequence set forth in SEQ ID NO: 15. In certain embodiments, the isolated polynucleotide comprises the nucleic acid sequence set forth in SEQ ID NO: 17. In certain embodiments, the isolated polynucleotide comprises the nucleic acid sequence set forth in SEQ ID NO: 19. In certain embodiments, the isolated polynucleotide comprises the nucleic acid sequence set forth in SEQ ID NO: 21. In certain embodiments, the isolated polynucleotide comprises the nucleic acid sequence set forth in SEQ ID NO: 23. In certain embodiments, the isolated polynucleotide comprises the nucleic acid sequence set forth in SEQ ID NO: 25. In certain embodiments, the isolated polynucleotide comprises the nucleic acid sequence set forth in SEQ ID NO: 27. In certain embodiments, the isolated polynucleotide comprises the nucleic acid sequence set forth in SEQ ID NO: 29. In certain embodiments, the isolated polynucleotide comprises the nucleic acid sequence set forth in SEQ ID NO: 31. In certain embodiments, the isolated polynucleotide comprises the nucleic acid sequence set forth in SEQ ID NO: 33. In certain embodiments, the isolated polynucleotide comprises the nucleic acid sequence set forth in SEQ ID NO: 35. In certain embodiments, the isolated polynucleotide comprises the nucleic acid sequence set forth in SEQ ID NO: 37. In certain embodiments, the isolated polynucleotide comprises the nucleic acid sequence set forth in SEQ ID NO: 39. In certain embodiments, the isolated polynucleotide comprises the nucleic acid sequence set forth in SEQ ID NO: 41. In certain embodiments, the isolated polynucleotide comprises the nucleic acid sequence set forth in SEQ ID NO: 43.In certain embodiments, the isolated polynucleotide comprises the nucleic acid sequence set forth in SEQ ID NO: 45. In certain embodiments, the isolated polynucleotide comprises the nucleic acid sequence set forth in SEQ ID NO: 47. In certain embodiments, the isolated polynucleotide comprises the nucleic acid sequence set forth in SEQ ID NO: 49. In certain embodiments, the isolated polynucleotide comprises the nucleic acid sequence set forth in SEQ ID NO: 51. In certain embodiments, the isolated polynucleotide comprises the nucleic acid sequence set forth in SEQ ID NO: 53. In certain embodiments, the isolated polynucleotide comprises the nucleic acid sequence set forth in SEQ ID NO: 55. In certain embodiments, the isolated polynucleotide comprises the nucleic acid sequence set forth in SEQ ID NO: 57. In certain embodiments, the isolated polynucleotide comprises the nucleic acid sequence set forth in SEQ ID NO: 59. In certain embodiments, the isolated polynucleotide comprises the nucleic acid sequence set forth in SEQ ID NO: 61.

[0195] In certain embodiments, the isolated polynucleotide consists of the nucleic acid sequence set forth in SEQ ID NO:1. In certain embodiments, the isolated polynucleotide consists of the nucleic acid sequence set forth in SEQ ID NO:3. In certain embodiments, the isolated polynucleotide consists of the nucleic acid sequence set forth in SEQ ID NO:5. In certain embodiments, the isolated polynucleotide consists of the nucleic acid sequence set forth in SEQ ID NO:7. In certain embodiments, the isolated polynucleotide consists of the nucleic acid sequence set forth in SEQ ID NO:9. In certain embodiments, the isolated polynucleotide consists of the nucleic acid sequence set forth in SEQ ID NO:11. In certain embodiments, the isolated polynucleotide consists of the nucleic acid sequence set forth in SEQ ID NO:13. In certain embodiments, the isolated polynucleotide consists of the nucleic acid sequence set forth in SEQ ID NO:15. In certain embodiments, the isolated polynucleotide consists of the nucleic acid sequence set forth in SEQ ID NO:17. In certain embodiments, the isolated polynucleotide consists of the nucleic acid sequence set forth in SEQ ID NO:19. In certain embodiments, the isolated polynucleotide consists of the nucleic acid sequence set forth in SEQ ID NO:21. In certain embodiments, the isolated polynucleotide consists of the nucleic acid sequence set forth in SEQ ID NO:23. In certain embodiments, the isolated polynucleotide consists of the nucleic acid sequence set forth in SEQ ID NO:25. In certain embodiments, the isolated polynucleotide consists of the nucleic acid sequence set forth in SEQ ID NO: 27. In certain embodiments, the isolated polynucleotide consists of the nucleic acid sequence set forth in SEQ ID NO: 29. In certain embodiments, the isolated polynucleotide consists of the nucleic acid sequence set forth in SEQ ID NO: 31. In certain embodiments, the isolated polynucleotide consists of the nucleic acid sequence set forth in SEQ ID NO: 33. In certain embodiments, the isolated polynucleotide consists of the nucleic acid sequence set forth in SEQ ID NO: 35. In certain embodiments, the isolated polynucleotide consists of the nucleic acid sequence set forth in SEQ ID NO: 37. In certain embodiments, the isolated polynucleotide consists of the nucleic acid sequence set forth in SEQ ID NO: 39. In certain embodiments, the isolated polynucleotide consists of the nucleic acid sequence set forth in SEQ ID NO: 41.In certain embodiments, the isolated polynucleotide consists of the nucleic acid sequence set forth in SEQ ID NO:43. In certain embodiments, the isolated polynucleotide consists of the nucleic acid sequence set forth in SEQ ID NO:45. In certain embodiments, the isolated polynucleotide consists of the nucleic acid sequence set forth in SEQ ID NO:47. In certain embodiments, the isolated polynucleotide consists of the nucleic acid sequence set forth in SEQ ID NO:49. In certain embodiments, the isolated polynucleotide consists of the nucleic acid sequence set forth in SEQ ID NO:51. In certain embodiments, the isolated polynucleotide consists of the nucleic acid sequence set forth in SEQ ID NO:53. In certain embodiments, the isolated polynucleotide consists of the nucleic acid sequence set forth in SEQ ID NO:55. In certain embodiments, the isolated polynucleotide consists of the nucleic acid sequence set forth in SEQ ID NO:57. In certain embodiments, the isolated polynucleotide consists of the nucleic acid sequence set forth in SEQ ID NO:59. In certain embodiments, the isolated polynucleotide consists of the nucleic acid sequence set forth in SEQ ID NO:61.

[0196] In certain embodiments, polynucleotides are optimized, for example, by codon / RNA optimization, replacement with a heterologous signal sequence, and / or elimination of mRNA instability elements. Methods for generating polynucleotides optimized for recombinant expression by introducing codon changes into mRNA and / or elimination of inhibitory regions are described, for example, in U.S. Patent Nos. 5,965,726, 6,174,666, 6,291,664, 6,414,132, and 6,794,498, all of which are incorporated herein by reference in their entireties. For example, to increase the stability of RNA for recombinant expression, potential splice sites and instability elements (e.g., A / T or A / U-rich elements) within the RNA can be mutated without changing the amino acids encoded by the nucleic acid sequence. This modification takes advantage of the degeneracy of the genetic code, for example, by using alternative codons for the same amino acid. In certain embodiments, it may be desirable to make conservative mutations, e.g., alter one or more codons to encode a similar amino acid having a similar chemical structure and properties and / or function as the original amino acid. Such methods can increase expression of the encoded capsid protein compared to expression of a capsid encoded by a non-optimized polynucleotide.

[0197] In another aspect, the present disclosure provides a vector comprising the polynucleotide disclosed herein. Suitable vectors include, but are not limited to, plasmids, viruses, cosmids, artificial chromosomes, linear DNA, and mRNA. In certain embodiments, the vector is a plasmid or a viral vector. In certain embodiments, the vector is a retroviral vector, a herpesvirus vector, a baculovirus vector, or an adenovirus vector. In certain embodiments, the vector is an expression vector.

[0198] A vector (e.g., an expression vector) can be introduced into a cell (using any technique known in the art) for propagation of the vector and / or expression of an AAV capsid protein encoded by the vector. Accordingly, in another aspect, the present disclosure provides a recombinant cell comprising a polynucleotide or vector (e.g., an expression vector) disclosed herein. Furthermore, in another aspect, the present disclosure provides a method of producing an AAV capsid protein, the method comprising culturing a recombinant cell under conditions whereby the polynucleotide is expressed and capsid is produced.

[0199] Suitable vectors include, but are not limited to, plasmids, minimal vectors (e.g., minicircle, nanoplasmid™, doggybone, MIDGE vector, etc.), viruses, cosmids, artificial chromosomes, linear DNA, and mRNA. In certain embodiments, the first nucleic acid vector and / or the second nucleic acid vector are DNA plasmids or DNA minimal vectors. Any DNA plasmid or DNA minimal vector capable of accommodating the necessary vector elements can be used as the first nucleic acid vector and the second nucleic acid vector. Suitable DNA minimal vectors include, but are not limited to, linear covalently closed DNA (e.g., ministring DNA), linear covalently closed dumbbell-shaped DNA (e.g., doggybone DNA, dumbbell DNA), minicircle, nanoplasmid™, minimal immunologically defined gene expression (MIDGE), and other vectors known to those skilled in the art. DNA minimal vectors and methods for their production are described, for example, in U.S. Patent Application Nos. 20100233814, 20120282283, 20130216562, 20150218565, 20150218586, 20160008488, 20160215296, 20160355827, 20190185924, 20200277624, and 20210010021, all of which are incorporated herein by reference in their entireties.

[0200] A variety of host cell and expression vector systems can be utilized to express the capsid proteins described herein. Such expression systems represent vehicles in which a coding sequence of interest can be produced and subsequently purified, but also represent cells that, when transformed or transfected with the appropriate nucleotide coding sequence, can express the capsid proteins described herein in situ. These include, for example, microorganisms such as bacteria (e.g., E. coli and B. subtilis) transformed with recombinant bacteriophage DNA, plasmid DNA, or cosmid DNA expression vectors containing the capsid protein coding sequence; yeast (e.g., Saccharomyces Pichia) transformed with recombinant yeast expression vectors containing the capsid protein coding sequence; insect cell systems infected with recombinant virus expression vectors (e.g., baculovirus) containing the capsid protein coding sequence; plant cell systems (e.g., Chlamydomonas spp.) infected with recombinant virus expression vectors (e.g., cauliflower mosaic virus, CaMV; tobacco mosaic virus, TMV) containing the capsid protein coding sequence or transformed with recombinant plasmid expression vectors (e.g., Ti plasmids), for example. reinhardtii); or mammalian cell lines (e.g., COS (e.g., COS1 or COS), CHO, BHK, MDCK, HEK 293, NS0, PER.C6, VERO, CRL7030, HsS78Bst, HeLa, and NIH 3T3, HEK-293T, HepG2, SP210, R1.1, BW, LM, BSC1, BSC40, YB / 20, and BMT10 cells) harboring a recombinant expression construct containing, for example, a promoter derived from the genome of a mammalian cell (e.g., a metallothionein promoter) or a promoter derived from a mammalian virus (e.g., an adenovirus late promoter; a vaccinia virus 7.5K promoter). In certain embodiments, the cells for expressing the capsid proteins described herein are human cells, e.g., human cell lines.In certain embodiments, the mammalian expression vector is pOptiVEC™ or pcDNA3.3. In certain embodiments, bacterial cells such as Escherichia coli or eukaryotic cells (e.g., mammalian cells) are used to express the capsid protein. For example, mammalian cells such as CHO or HEK293 cells combined with a vector such as the major intermediate-early gene promoter element from human cytomegalovirus are effective expression systems for the capsid proteins disclosed herein.

[0201] In bacterial systems, several expression vectors can be advantageously selected depending on the intended use of the expressed capsid protein. For example, when large quantities of capsid protein are to be produced, a vector that directs the expression of high-level fusion protein products that are easily purified may be desirable. Such vectors include, but are not limited to, the E. coli expression vector pUR278 (Ruether U & Mueller-Hill B (1983) EMBO J 2:1791-1794) (the capsid protein coding sequence can be separately ligated into the vector in frame with the lac Z coding region to produce a fusion protein); the pIN vector (Inouye S & Inouye M (1985) Nuc Acids Res 13:3101-3109; Van Heeke G & Schuster SM (1989) J Biol Chem 24:5503-5509), all of which are incorporated herein by reference in their entireties. For example, pGEX vectors can be used to express foreign polypeptides as fusion proteins with glutathione 5-transferase (GST). Generally, such fusion proteins are soluble and can be easily purified from lysed cells by adsorption and binding to matrix glutathione agarose beads, followed by elution in the presence of free glutathione. pGEX vectors are designed to contain thrombin or factor Xa protease cleavage sites so that the cloned target gene product can be released from the GST moiety.

[0202] In insect systems, for example, Autographa californica nuclear polyhedrosis virus (AcNPV) 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 (e.g., the polyhedrin gene) of the virus and placed under control of an AcNPV promoter (e.g., the polyhedrin promoter).

[0203] In mammalian host cells, several virus-based expression systems can be utilized. When 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 into the adenovirus genome by in vitro or in vivo recombination. Insertion into a non-essential region of the viral genome (e.g., region E1 or E3) results in a recombinant virus that is viable and capable of expressing capsid protein molecules in infected hosts (see, e.g., Logan J & Shenk T (1984) PNAS 81(12):3655-9, incorporated herein by reference in its entirety). Specific initiation signals may also be required for efficient translation of the inserted capsid protein coding sequence. 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, incorporated herein by reference in its entirety).

[0204] In addition, a host cell strain can be selected that modulates the expression of the inserted sequences, or modifies and processes the gene product in the specific fashion desired. Such modifications (e.g., glycosylation) and processing (e.g., cleavage) of protein products can be important for the function of the protein. Different host cells have characteristic and specific mechanisms for the post-translational processing and modification of proteins and gene products. An appropriate cell line or host system can be selected to ensure the correct modification and processing of the expressed foreign protein. To this end, eukaryotic host cells that possess the cellular machinery for proper processing of the primary transcript, glycosylation, and phosphorylation of the gene product may be used. Such mammalian host cells include, but are not limited to, CHO, VERO, BHK, Hela, MDCK, HEK 293, NIH 3T3, W138, BT483, Hs578T, HTB2, BT2O and T47D, NS0 (a mouse myeloma cell line that does not endogenously produce any immunoglobulin chains), CRL7O3O, COS (e.g., COS1 or COS), PER.C6, VERO, HsS78Bst, HEK-293T, HepG2, SP210, R1.1, BW, LM, BSC1, BSC40, YB / 20, BMT10, and HsS78Bst cells.

[0205] For long-term, high-yield production of recombinant proteins, stable expression cells can be generated, for example, cell lines that stably express the capsid proteins described herein can be engineered.

[0206] In certain embodiments, rather than using an expression vector containing a viral origin of replication, host cells may be transformed with a polynucleotide (e.g., DNA or RNA) controlled by appropriate transcriptional control elements (e.g., promoter, enhancer, sequence, transcription terminator, polyadenylation site, etc.) and a selectable marker. Following introduction of the polynucleotide, engineered cells are grown in rich medium for 1-2 days and then switched to selective medium. The selectable marker in the recombinant plasmid confers resistance to selection and allows cells to stably integrate the plasmid into their chromosomes and grow to form foci, which can then be cloned and expanded into cell lines. This method can advantageously be used to engineer cell lines that express the capsid proteins or fragments thereof described herein.

[0207] Several selection systems may be used in tk cells, hgprt cells, or aprt cells, respectively, including, but not limited to, herpes simplex virus thymidine kinase (Wigler M et al. (1977) Cell 11(1):223-32), hypoxanthine guanine phosphoribosyltransferase (Szybalska EH & Szybalski W (1962) PNAS 48(12):2026-2034), and adenine phosphoribosyltransferase (Lowy I et al. (1980) Cell 22(3):817-23) genes, all of which are incorporated herein by reference in their entireties. Additionally, antimetabolite resistance is mediated by 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 RC & Berg P (1981) PNAS 78(4):2072-6); neo, which confers resistance to the aminoglycoside G-418 (Wu GY & Wu CH (1991) Biotherapy 3:87-95; Tolstoshev P (1993) Ann Rev Pharmacol Toxicol 32:573-596; Mulligan RC (1993) Science 260:926-932; and Morgan RA & Anderson WF (1993) Ann Rev Biochem 62:191-217; Nabel GJ & Felgner PL (1993) Trends Biotechnol 11(5):211-5); and hygro, which confers resistance to hygromycin, can be used as the basis for selection, all of which are incorporated herein by reference in their entireties.Methods generally known in the field of recombinant DNA technology can be routinely applied to select the desired recombinant clones, and such methods are described, for example, in Ausubel FM 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 Chapters 12 and 13, Dracopoli NC et al. (eds.), Current Protocols in Human Genetics, John Wiley & Sons, NY (1994), Colbere-Garapin F et al. (1981) J Mol Biol 150:1-14, all of which are incorporated herein by reference in their entireties.

[0208] IV.AAV composition In another aspect, the present disclosure provides an rAAV composition comprising a capsid comprising the recombinant AAV capsid proteins disclosed herein.

[0209] In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-734 of SEQ ID NO: 2. In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-734 of SEQ ID NO: 2. In certain embodiments, the rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 202-734 of SEQ ID NO:2.

[0210] In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-736 of SEQ ID NO: 4. In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 138-736 of SEQ ID NO: 4. In certain embodiments, the rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 204 to 736 of SEQ ID NO:4.

[0211] In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-734 of SEQ ID NO: 6. In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-734 of SEQ ID NO: 6. In certain embodiments, the rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 202 to 734 of SEQ ID NO:6.

[0212] In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to amino acids 1-731 of SEQ ID NO: 8. In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 134-731 of SEQ ID NO: 8. In certain embodiments, the rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 199-731 of SEQ ID NO:8.

[0213] In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-736 of SEQ ID NO: 10. In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 138-736 of SEQ ID NO: 10. In certain embodiments, the rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 203-736 of SEQ ID NO:10.

[0214] In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-736 of SEQ ID NO: 12. In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-736 of SEQ ID NO: 12. In certain embodiments, the rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 203-736 of SEQ ID NO:12.

[0215] In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-736 of SEQ ID NO: 14. In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 138-736 of SEQ ID NO: 14. In certain embodiments, the rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 204 to 736 of SEQ ID NO:14.

[0216] In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-734 of SEQ ID NO: 16. In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-734 of SEQ ID NO: 16. In certain embodiments, the rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 202 to 734 of SEQ ID NO:16.

[0217] In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-735 of SEQ ID NO: 18. In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 138-735 of SEQ ID NO: 18. In certain embodiments, the rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 203 to 735 of SEQ ID NO:18.

[0218] In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-736 of SEQ ID NO: 20. In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-736 of SEQ ID NO: 20. In certain embodiments, the rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 202-736 of SEQ ID NO:20.

[0219] In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-736 of SEQ ID NO: 22. In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-736 of SEQ ID NO: 22. In certain embodiments, the rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 203-736 of SEQ ID NO:22.

[0220] In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-736 of SEQ ID NO: 24. In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 138-736 of SEQ ID NO: 24. In certain embodiments, the rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 204 to 736 of SEQ ID NO:24.

[0221] In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-735 of SEQ ID NO: 26. In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-735 of SEQ ID NO: 26. In certain embodiments, the rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 202 to 735 of SEQ ID NO:26.

[0222] In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-734 of SEQ ID NO: 28. In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-734 of SEQ ID NO: 28. In certain embodiments, the rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 202-734 of SEQ ID NO:28.

[0223] In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-734 of SEQ ID NO: 30. In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-734 of SEQ ID NO: 30. In certain embodiments, the rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 202 to 734 of SEQ ID NO:30.

[0224] In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-735 of SEQ ID NO: 32. In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-735 of SEQ ID NO: 32. In certain embodiments, the rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 202 to 735 of SEQ ID NO:32.

[0225] In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-735 of SEQ ID NO: 34. In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-735 of SEQ ID NO: 34. In certain embodiments, the rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 202 to 735 of SEQ ID NO:34.

[0226] In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-735 of SEQ ID NO: 36. In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 138-735 of SEQ ID NO: 36. In certain embodiments, the rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 203 to 735 of SEQ ID NO:36.

[0227] In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-731 of SEQ ID NO: 38. In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 134-731 of SEQ ID NO: 38. In certain embodiments, the rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 199-731 of SEQ ID NO:38.

[0228] In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-735 of SEQ ID NO: 40. In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-735 of SEQ ID NO: 40. In certain embodiments, the rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 203-735 of SEQ ID NO:40.

[0229] In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-736 of SEQ ID NO: 42. In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 138-736 of SEQ ID NO: 42. In certain embodiments, the rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 204 to 736 of SEQ ID NO:42.

[0230] In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-736 of SEQ ID NO: 44. In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-736 of SEQ ID NO: 44. In certain embodiments, the rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 202-736 of SEQ ID NO:44.

[0231] In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-736 of SEQ ID NO: 46. In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-736 of SEQ ID NO: 46. In certain embodiments, the rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 203-736 of SEQ ID NO:46.

[0232] In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-734 of SEQ ID NO: 48. In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-734 of SEQ ID NO: 48. In certain embodiments, the rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 202 to 734 of SEQ ID NO:48.

[0233] In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-734 of SEQ ID NO: 50. In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-734 of SEQ ID NO: 50. In certain embodiments, the rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 202-734 of SEQ ID NO:50.

[0234] In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-734 of SEQ ID NO: 52. In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-734 of SEQ ID NO: 52. In certain embodiments, the rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 202-734 of SEQ ID NO:52.

[0235] In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-735 of SEQ ID NO: 54. In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 138-735 of SEQ ID NO: 54. In certain embodiments, the rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 203-735 of SEQ ID NO:54.

[0236] In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-735 of SEQ ID NO: 56. In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-735 of SEQ ID NO: 56. In certain embodiments, the rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 202 to 735 of SEQ ID NO:56.

[0237] In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-735 of SEQ ID NO: 58. In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-735 of SEQ ID NO: 58. In certain embodiments, the rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 202 to 735 of SEQ ID NO:58.

[0238] In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-735 of SEQ ID NO: 60. In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-735 of SEQ ID NO: 60. In certain embodiments, the rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 202 to 735 of SEQ ID NO:60.

[0239] In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 1-735 of SEQ ID NO: 62. In certain embodiments, an rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 137-735 of SEQ ID NO: 62. In certain embodiments, the rAAV composition comprises a capsid comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to amino acids 202 to 735 of SEQ ID NO:62.

[0240] In another aspect, the present disclosure provides an rAAV comprising a capsid comprising one or more recombinant capsid proteins disclosed herein and an rAAV genome.The rAAV disclosed herein generally comprises a recombinant genome (e.g., rAAV genome) packaged in a capsid.The rAAV genome can be any type that can be packaged in the AAV capsid disclosed herein.For example, in certain embodiments, the rAAV genome is a single-stranded DNA genome.In certain embodiments, the rAAV genome is a self-complementary genome, for example, as described in US7790154, the entire contents of which are incorporated herein by reference.

[0241] In certain embodiments, the rAAV genome comprises a transgene. In certain embodiments, the transgene encodes a polypeptide. In certain embodiments, the transgene encodes a therapeutic protein. In certain embodiments, the transgene encodes an antibody or fragment thereof (e.g., a Fab, scFv, or full-length antibody). In certain embodiments, the transgene encodes an scFv, nanobody, or VHH. In certain embodiments, the transgene encodes a non-coding RNA. In certain embodiments, the transgene comprises one or more sequences encoding an RNA molecule. Suitable RNA molecules include, but are not limited to, miRNA, shRNA, siRNA, antisense RNA, gRNA, antagomir, miRNA sponge, RNA aptazyme, RNA aptamer, mRNA, lncRNA, ribozyme, and synthetic RNA known in the art.

[0242] In certain embodiments, the transgene encodes one or more polypeptides, or fragments thereof. Such transgenes may include the entire coding sequence of a polypeptide or only a fragment of the coding sequence of a polypeptide. In certain embodiments, the transgene encodes a polypeptide useful for treating a disease or disorder in a subject. Suitable polypeptides include β-globin, hemoglobin, tissue plasminogen activator, and clotting factors; colony-stimulating factors (CSF); interleukins, such as IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, and IL-9; growth factors, such as keratinocyte growth factor (KGF), stem cell factor (SCF), fibroblast growth factors (FGFs, such as basic FGF, acidic FGF, and FGF21), hepatocyte growth factor (HGF), insulin-like growth factor (IGF), bone morphogenetic proteins (BMPs), epithelial growth factors (EGFs), and endothelial growth factors (EGFs). factor (EGF), growth differentiation factor-9 (GDF-9), hepatocyte-derived growth factor (HDGF), myostatin (GDF-8), nerve growth factor (NGF), neurotrophins, platelet-derived growth factor (PDGF), thrombopoietin (TPO), transforming growth factor alpha (TGF-a), transforming growth factor beta (TGF-β), and soluble fragments thereof; soluble receptors, such as soluble TNF-a receptor, soluble interleukin receptors (e.g., soluble IL-1 receptor and soluble type II IL-1 receptor), soluble gamma / delta receptors, and the like. T cell receptors, ligand-binding fragments of soluble receptors, etc.; enzymes, such as α-glucosidase, imiglucerase, β-glucocerebrosidase, and alglucerase; enzyme activators, such as tissue plasminogen activator; chemokines, such as IP-10, monokine induced by interferon-gamma (Mig), Groα / IL-8, RANTES, MIP-1α, MIPI-1β, MCP-1, PF-4, etc.; angiogenic agents, such as vascular endothelial growth factors (VEGFs, e.g., VEGF121, VEGF165, VEGF-C, VEGF-2), glioma-derived growth factor, angiogenin, angiogenin-2, etc.; angiogenesis inhibitors, such as soluble VEGF receptors; protein vaccines;Neuroactive peptides, such as nerve growth factor (NGF), bradykinin, cholecystokinin, gastrin, secretin, oxytocin, gonadotropin-releasing hormone, beta-endorphin, enkephalin, substance P, somatostatin, prolactin, galanin, growth hormone-releasing hormone, bombesin, dynorphin, warfarin, neurotensin, motilin, thyrotropin, neuropeptide Y, luteinizing hormone, calcitonin, insulin, glucagon, vasopressin, and adenosine triphosphate (ATP). Angiotensin II, thyrotropin-releasing hormone, vasoactive intestinal peptide, sleep peptide, etc.; thrombolytic agents; atrial natriuretic peptide; relaxin; glial fibrillary acidic protein; follicle-stimulating hormone (FSH); human alpha-1 antitrypsin; leukemia inhibitory factor (LIF); tissue factor; macrophage-activating factor; tumor necrosis factor (TNF); neutrophil chemotactic factor (NCF); tissue inhibitor of metalloproteinases; vasoactive intestinal peptide; angiogenin; angiotrophin; These include, but are not limited to, fibrin, hirudin, IL-1 receptor antagonists, ciliary neurotrophic factor (CNTF), brain-derived neurotrophic factor (BDNF), neurotrophins 3 and 4 / 5 (NT-3 and -4 / 5), glial cell line-derived neurotrophic factor (GDNF), aromatic amino acid decarboxylase (AADC), factor VIII, factor IX, factor X, dystrophin or mini-dystrophin, lysosomal acid lipase, phenylalanine hydroxylase (PAH), glycogen storage disease-related enzymes such as glucose-6-phosphatase, acid maltase, glycogen debranching enzyme, muscle glycogen phosphorylase, liver glycogen phosphorylase, muscle phosphofructokinase, phosphorylase kinase, glucose transporter, aldolase A, β-enolase, glycogen synthase, lysosomal enzymes such as iduronate-2-sulfatase (IS) and arylsulfatase A, and mitochondrial proteins such as frataxin.

[0243] In certain embodiments, the transgene encodes a protein that may be deficient in one or more lysosomal storage diseases. Suitable proteins include α-sialidase, cathepsin A, α-mannosidase, β-mannosidase, glycosylasparaginase, α-fucosidase, α-N-acetylglucosaminidase, β-galactosidase, β-hexosaminidase α-subunit, β-hexosaminidase β-subunit, GM2 activator protein, glucocerebrosidase, saposin C, arylsulfatase A, saposin B, formyl-glycine synthase, β-galactosylceramidase, α-galactosidase A, iduronate sulfatase, α-iduronidase, heparan N-sulfatase, and α-galactosidase. These include, but are not limited to, cetyl-CoA transferase, N-acetylglucosaminidase, β-glucuronidase, N-acetylglucosamine 6-sulfatase, N-acetylgalactosamine 4-sulfatase, galactose 6-sulfatase, hyaluronidase, α-glucosidase, acid sphingomyelinase, acid ceramidase, acid lipase, cathepsin K, tripeptidyl peptidase, palmitoyl-protein thioesterase, cystinosin, sialin, UDP-N-acetylglucosamine, phosphotransferase gamma subunit, mucolipin-1, LAMP-2, NPC1, CLN3, CLN 6, CLN 8, LYST, MYOV, RAB27A, melanophilin, and AP3 β subunit.

[0244] In certain embodiments, the transgene encodes an antibody or fragment thereof (e.g., a Fab, scFv, or full-length antibody). Suitable antibodies include muromonab-cd3, efalizumab, tositumomab, daclizumab, nebacumab, catumaxomab, edrecolomab, abciximab, rituximab, basiliximab, palivizumab, infliximab, trastuzumab, adalimumab, ibritumomab tiuxetan, omalizumab, cetuximab, bevacizumab, natalizumab, panitumumab, ranibizumab, eculizumab, Certolizumab, ustekinumab, canakinumab, golimumab, ofatumumab, tocilizumab, denosumab, belimumab, ipilimumab, brentuximab vedotin, pertuzumab, raxibacumab, obinutuzumab, alemtuzumab, siltuximab, ramucirumab, vedolizumab, blinatumomab, nivolumab, pembrolizumab, idarucizumab, necitumumab, dinutuximab, secukinumab , mepolizumab, alirocumab, evolocumab, daratumumab, elotuzumab, ixekizumab, reslizumab, olaratumab, bezlotoxumab, atezolizumab, obiltoxaximab, inotuzumab ozogamicin, brodalumab, guselkumab, dupilumab, sarilumab, avelumab, ocrelizumab, emicizumab, benralizumab, gemtuzumab ozogamicin, durvalumab, bros These include, but are not limited to, mab, erenumab, galcanezumab, lanadelumab, mogamulizumab, tildrakizumab, cemiplimab, fremanezumab, ravulizumab, emapalumab, ibalizumab, moxetumomab, caplacizumab, romosozumab, risankizumab, polatuzumab, eptinezumab, leronlimab, sacituzumab, brolucizumab, isatuximab, and teprotumumab.

[0245] In certain embodiments, the transgene encodes a nuclease. Suitable nucleases include zinc finger nucleases (ZFNs) (see, e.g., Porteus, and Baltimore (2003) Science 300:763; Miller et al. (2007) Nat. Biotechnol. 25:778-785; Sander et al. (2011) Nature Methods 8:67-69; and Wood et al. (2011) Science 333:307, each of which is incorporated by reference in its entirety); transcription activator-like effector nucleases (TALENs) (see, e.g., Wood et al. (2011) Science 333:307; Boch et al. (2009) Science 326:1509-1512; Moscou and Bogdanove (2009) Science 326;1501; Christian et al. (2011) Science 333:307; al. (2010) Genetics 186:757-761, Miller et al. (2011) Nat. Biotechnol. 29:143-148, Zhang et al. (2011) Nat. Biotechnol. 29:149-153, and Reyon et al. (2012) Nat. Biotechnol. 30(5):460-465 (each of which is incorporated by reference in its entirety); homing endonucleases; meganucleases (see, e.g., U.S. Patent Publication No. US2014 / 0121115 (incorporated by reference in its entirety)); and RNA-guided nucleases (see, e.g., Makarova et al. (2018) The CRISPR Journal 1(5):325-336, and Adli (2018) Nat. Communications 9:1911 (each of which is incorporated herein by reference in its entirety).

[0246] In certain embodiments, the transgene encodes an RNA-guided nuclease. Suitable RNA-guided nucleases include, but are not limited to, class I and class II clustered regularly interspaced short palindromic repeats (CRISPR)-associated nucleases. Class I is divided into types I, III, and IV, and includes, but is not limited to, type I (Cas3), type IA (Cas8a, Cas5), type IB (Cas8b), type IC (Cas8c), type I-D (Cas10d), type IE (Cse1, Cse2), type IF (Csy1, Csy2, Csy3), type IU (GSU0054), type III (Cas10), type III-A (Csm2), type III-B (Cmr5), type III-C (Csx10 or Csx11), type III-D (Csx10), and type IV (Csf1). Class II is divided into Type II, Type V, and Type VI, and includes, but is not limited to, Type II (Cas9), Type II-A (Csn2), Type II-B (Cas4), Type V (Cpf1, C2c1, C2c3), and Type VI (Ca13a, Cas13b, Cas13c). RNA-guided nucleases also include naturally occurring Class II CRISPR nucleases, such as Cas9 (Type II) or Cas12a / Cpf1 (Type V), as well as other nucleases derived or obtained therefrom. Exemplary Cas9 nucleases that can be used in the present invention include, but are not limited to, S. pyogenes Cas9 (SpCas9), S. aureus Cas9 (SaCas9), N. meningitidis Cas9 (NmCas9), C. jejuni Cas9 (CjCas9), and Geobacillus Cas9 (GeoCas9).

[0247] In certain embodiments, the transgene encodes a reporter sequence that, upon expression, produces a detectable signal. Such reporter sequences include, but are not limited to, 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 (for which high-affinity antibodies exist or can be produced by conventional methods), including, for example, CD2, CD4, CD8, influenza hemagglutinin protein, and others known in the art, and fusion proteins comprising a membrane-bound protein appropriately fused to an antigen tag domain from hemagglutinin or Myc, among others.

[0248] In certain embodiments, the rAAV genome comprises a transcriptional regulatory element (TRE) operably linked to the transgene to control expression of the RNA or polypeptide encoded by the transgene. In certain embodiments, the TRE comprises a constitutive promoter. In certain embodiments, the TRE can be active in any mammalian cell (e.g., any human cell). In certain embodiments, the TRE is active in a wide range of human cells. Such a TRE can comprise a constitutive promoter and / or enhancer element, including any of those described herein and any known to those of skill in the art. In certain embodiments, the TRE comprises an inducible promoter. In certain embodiments, the TRE can be a tissue-specific TRE, i.e., active in a 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. Those skilled in the art will appreciate that tissue-specific promoter and / or enhancer elements can be isolated from genes that are specifically expressed in a tissue by methods well known in the art.

[0249] Suitable promoters include, for example, the cytomegalovirus promoter (CMV) (Stinski et al. (1985) Journal of Virology 55(2):431-441); the CMV early enhancer / chicken β-actin (CBA) promoter / rabbit β-globin intron (CAG) (Miyazaki et al. (1989) Gene 79(2):269-277); SB(Jacobson et al. (2006) Molecular Therapy 13(6):1074-1084); human elongation factor 1 alpha promoter (EF1α) (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 chain promoter (Lodeiro et al. (2012) PNAS 109(17):6513-6518), and ubiquitin promoter (Wulff et al. (1990) FEBS Letters 261:101-105). In certain embodiments, the TRE comprises a cytomegalovirus (CMV) promoter / enhancer, an SV40 promoter, a chicken beta-actin (CBA) promoter, a smCBA promoter, a human elongation factor 1 alpha (EF1α) promoter, a minute virus of mice (MVM) intron containing a transcription factor binding site, a human phosphoglycerate kinase (PGK1) promoter, a human ubiquitin C (Ubc) promoter, a human beta-actin promoter, a human neuron-specific enolase (ENO2) promoter, a human beta-glucuronidase (GUSB) promoter, a rabbit beta-globin element, a human calmodulin 1 (CALM1) promoter, a human ApoE / CI hepatic control region (HCR1), a human alpha 1-antitrypsin (hAAT) promoter, an extended HCR1, an HS-CRM8 element of the hAAT promoter, a human transthyretin (TTR) promoter, and / or a human methyl-CpG binding protein 2 (MeCP2) promoter. Any of the TREs described herein can be combined in any order to drive efficient transcription. For example, a transfer genome can contain a TRE comprising a CMV enhancer, a CBA promoter, and a splice acceptor from exon 3 of the rabbit beta-globin gene (collectively referred to as the CAG promoter).For example, the transfer genome can contain a TRE containing a hybrid of the CMV enhancer and CBA promoter, followed by a splice donor and splice acceptor (collectively referred to as the CASI promoter region). For example, the transfer genome can contain a TRE containing HCR1 and the hAAT promoter (also referred to as the LP1 promoter).

[0250] In certain embodiments, the TRE is liver-specific. Exemplary liver-specific TREs may include, but are not limited to, one or more elements from an ApoA-I promoter, an ApoA-II promoter, an ApoA-IV promoter, an ApoB promoter, an ApoC-I promoter, an ApoC-II promoter, an ApoC-III promoter, an ApoE promoter, an albumin promoter, an α-fetoprotein promoter, a phosphoenolpyruvate carboxykinase 1 (PCK1) promoter, a phosphoenolpyruvate carboxykinase 2 (PCK2) promoter, a transthyretin (TTR) promoter, an α-antitrypsin (AAT or SERPINA1) promoter, a TK (thymidine kinase) promoter, a hemopexin promoter, an alcohol dehydrogenase 6 promoter, a cholesterol 7α-hydroxylase promoter, a factor IX promoter, an α-microglobulin promoter, an SV40 promoter, a CMV promoter, a Rous sarcoma virus-LTR promoter, and an HBV promoter.

[0251] In certain embodiments, the TRE is muscle-specific. Exemplary muscle-specific TREs can include, but are not limited to, one or more elements from the human skeletal α-actin (HSA) promoter, muscle creatine kinase (MCK) promoter, MHCK7 promoter, dMCK promoter, tMCK promoter, CK6 promoter, CK8 promoter, CK8e promoter, human desmin (DES) promoter or a variant thereof, cardiac troponin T (cTnT) promoter, myosin light chain (MLC2v) promoter, human α-myosin heavy chain gene (αMHC) promoter, MLC promoter, human troponin I (TNNI1) promoter, ΔUSEx3 promoter, SPcΔ5-12 promoter, SP-301 promoter, MH promoter, and Sk-CRM4 / DES promoter.

[0252] In certain embodiments, the native promoter of the transgene may be used.When it is desired that the expression of the transgene mimics the natural expression, the native promoter may be preferred.The native promoter can be used when it is necessary to control the expression of the transgene temporally or developmentally, or tissue-specifically, or in response to specific transcriptional stimuli.In further embodiments, other natural expression control elements, such as enhancer elements, polyadenylation sites, or Kozak consensus sequences, can also be used to mimic the natural expression.

[0253] In another aspect, the present disclosure provides a pharmaceutical composition comprising an AAV disclosed herein together with a pharmaceutically acceptable excipient, adjuvant, diluent, vehicle, or carrier, or a combination thereof. A "pharmaceutically acceptable carrier" includes any material that, when combined with the active ingredient of the composition, allows the ingredient to retain its biological activity without eliciting a destructive physiological response, such as an unintended immune response. Pharmaceutically acceptable carriers include water, phosphate-buffered saline, emulsions such as oil / water emulsions, and wetting agents. Compositions containing such carriers are formulated by well-known conventional methods, for example, those described 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. Cansel et al., 7th ed., Lippincott, Williams, & Wilkins; and Handbook of Pharmaceutical Excipients (2000) A.H. Kibbe et al., 3rd ed., American Pharmaceutical Assoc.

[0254] V. How to use In another aspect, the present disclosure provides methods for transducing cells. The methods generally involve contacting cells with a rAAV disclosed herein under conditions whereby the cells are transduced. The rAAV disclosed herein can be used to transduce cells in vitro, in vivo, and ex vivo.

[0255] In another aspect, the present disclosure provides methods for delivering a transgene into a cell. The methods generally involve contacting a cell with an rAAV disclosed herein under conditions whereby the cell is transduced and the transgene is expressed.

[0256] The rAAV disclosed herein may contain a transgene under the control of a TRE. Thus, in certain embodiments, the present disclosure provides a method for expressing a transgene in a cell, generally comprising contacting a cell with such an rAAV under conditions whereby the cell is transduced and the transgene is expressed. The transgene may encode a polypeptide and / or an RNA molecule described herein. Thus, in certain embodiments, the present disclosure provides a method for producing a polypeptide and / or an RNA molecule in a cell, generally comprising contacting a cell with such an rAAV under conditions whereby the cell is transduced and the polypeptide and / or RNA molecule is produced.

[0257] In certain embodiments, the cells are in a subject and the rAAV is administered to the subject. The rAAV disclosed herein can be administered to a subject by any route suitable for the rAAV, including, but not limited to, intravenous, intraperitoneal, subcutaneous, intramuscular, intrathecal, or intradermal administration.

[0258] In certain embodiments, the subject is a member of any mammalian or non-mammalian species. Suitable subjects include, but are not limited to, humans, non-human primates, dogs, cats, ungulates (e.g., horses, cows, swine (e.g., pigs)), birds, rodents (e.g., rats, mice), and other subjects. In certain embodiments, the subject is a dog. In certain embodiments, the subject is a human.

[0259] In another aspect, the present invention provides an rAAV as disclosed herein for use in medicine. In another aspect, the present invention provides an rAAV as disclosed herein for use as a therapy. In another aspect, the present invention provides an rAAV as disclosed herein for use as a medicament.

[0260] VI. Adeno-associated virus packaging systems In another aspect, the present disclosure provides packaging systems for the recombinant preparation of recombinant adeno-associated viruses (rAAVs) disclosed herein. Such packaging systems generally include a first nucleotide sequence encoding one or more AAV Rep proteins, a second nucleotide sequence encoding the capsid protein of any of the AAVs disclosed herein, and a third nucleotide sequence comprising any of the rAAV genome sequences disclosed herein, wherein the packaging system functions within a cell to encapsidate a transfer genome to form an AAV.

[0261] In certain embodiments, a packaging system comprises a first vector comprising a first nucleotide sequence encoding one or more AAV Rep proteins and a second nucleotide sequence encoding an AAV capsid protein, and a second vector comprising a third nucleotide sequence comprising an rAAV genome. As used in the context of the packaging systems described herein, "vector" refers to a nucleic acid molecule that is a vehicle for introducing a nucleic acid into a cell (e.g., a plasmid, a virus, a cosmid, an artificial chromosome, etc.). In certain embodiments of the packaging system, the packaging system further comprises a fourth nucleotide sequence comprising one or more helper virus genes. In certain embodiments, the fourth nucleotide sequence comprises the adenovirus E2, E4, and VA genes. In certain embodiments of the packaging system, the packaging system comprises a third vector (e.g., a helper virus vector) comprising the fourth nucleotide sequence. The third vector can be an independent third vector, integrated with the first vector, or integrated with the second vector.

[0262] In certain embodiments, the packaging system comprises a first vector comprising a first nucleotide sequence encoding one or more AAV Rep proteins, a second nucleotide sequence encoding one or more recombinant AAV capsid proteins disclosed herein, and a third nucleotide sequence comprising any of the rAAV genome sequences disclosed herein, wherein the packaging system functions in a cell to encapsidate the transfer genome to form an AAV. In certain embodiments of the packaging system, the packaging system further comprises a fourth nucleotide sequence comprising one or more helper virus genes. In certain embodiments, the fourth nucleotide sequence comprises the adenovirus E2, E4, and VA genes. In certain embodiments of the packaging system, the packaging system comprises a second vector (e.g., a helper virus vector) comprising the fourth nucleotide sequence. The second vector can be an independent second vector or can be integrated with the first vector.

[0263] Any AAV Rep protein can be used in the packaging system disclosed herein. In certain embodiments of the packaging system, the Rep nucleotide sequence encodes the AAV2 Rep protein. Suitable AAV2 Rep proteins can include, but are not limited to, Rep 78 / 68 or Rep 68 / 52.

[0264] In certain embodiments of the packaging system, the helper virus is selected from the group consisting of adenovirus, herpesvirus (including herpes simplex virus (HSV)), poxvirus (such as vaccinia virus), cytomegalovirus (CMV), and baculovirus. In certain embodiments of the packaging system, when the helper virus is adenovirus, the adenoviral genome comprises one or more adenoviral RNA genes selected from the group consisting of E1, E2, E4, and VA. In certain embodiments of the packaging system, when the helper virus is adenovirus, the adenoviral genome comprises one or more adenoviral RNA genes selected from the group consisting of E2, E4, and VA. In certain embodiments of the packaging system, when 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.

[0265] In certain embodiments of the packaging system, the vectors (eg, the first, second, and / or third vectors) are contained within one or more plasmids.

[0266] In certain embodiments of the packaging system, the first, second, and / or third vectors are contained within one or more recombinant helper viruses. In certain embodiments, the first and third vectors are contained within a recombinant helper virus. In certain embodiments, the second and third vectors are contained within a recombinant helper virus.

[0267] In a further aspect, the present disclosure provides a method for the recombinant preparation of an AAV described herein, comprising transfecting or transducing a cell with a packaging system described herein under conditions that function to encapsidate the rAAV genome to form an rAAV described herein. Exemplary methods for recombinant preparation of rAAV include transient transfection (e.g., with one or more transfection plasmids comprising the first and second vectors described herein, and optionally a third vector), viral infection (e.g., with one or more recombinant helper viruses, e.g., adenovirus, poxvirus (such as vaccinia virus), herpesvirus (including HSV, cytomegalovirus, or baculovirus, comprising the first and second vectors described herein, and optionally a third vector)), and stable producer cell line transfection or infection (e.g., with stable producer cells, such as mammalian or insect cells, comprising Rep nucleotide sequences encoding one or more AAV Rep proteins and / or Cap nucleotide sequences encoding one or more capsid proteins described herein, and with transfer genomes described herein delivered in the form of plasmids or recombinant helper viruses).

[0268] Thus, the present disclosure provides a packaging system for the preparation of rAAV, comprising a first nucleotide sequence encoding one or more AAV Rep proteins, a second nucleotide sequence encoding a capsid protein of any one of the AAVs described herein, a third nucleotide sequence comprising the rAAV genome sequence of any one of the AAVs described herein, and optionally a fourth nucleotide sequence comprising one or more helper virus genes (e.g., adenovirus E2, E4, and VA genes). [Example]

[0269] VII. Working Examples The following examples are offered by way of illustration and not by way of limitation.

[0270] Example 1: Generation of an AAV capsid library and liver and / or muscle enrichment Shuffled capsid libraries were generated using the capsid sequences of AAV1-AAV14, AAVrh8, and AAVrh10 as input. Briefly, nucleic acid molecules encoding each AAV capsid were digested to generate fragments approximately 200-400 base pairs in length, gel extracted, mixed, and assembled by PCR. The assembled shuffled capsids were then digested and ligated into a vector for subsequent virus production. Virus was generated using a standard triple-plasmid transfection technique. Virus was then harvested and collected by precipitation with PEG8000, and non-functional capsids were removed via ultracentrifugation on an iodixanol gradient and buffer exchange of the 40% iodixanol fraction. See, e.g., Zolotukhin et al. (1999) Gene Therapy 6(6):973-985. Nucleic acid encoding a functional capsid was then extracted from the virus preparation using PCR, and the process of virus production was repeated with the functional viral capsid nucleic acid.

[0271] To screen for AAV capsids with liver-specific and / or muscle-specific tropism, two dogs were each injected with 5E12–6E13 vg / kg of AAV virus. Two weeks later, liver tissue was isolated and RNA was extracted to ensure proper infection, double-stranded DNA generation, and capsid production. cDNA was then synthesized from the RNA using second-strand cDNA synthesis, amplified by PCR, digested, and ligated into a vector to generate a liver-specific capsid library. To demonstrate capsid enrichment as a small-scale directed evolution experiment in which liver infectivity served as the selective pressure for the library, a second complete round of capsid nucleic acid extraction, AAV production, and liver infection was performed. The enrichment of individual capsids was determined using sequencing in the original shuffled library and after each round of infection.

[0272] Sequence analysis showed that five capsids were enriched at each stage of virus production and liver infection (Table 1). [Table 1]

[0273] Example 2: Protein expression from liver-enriched capsids in vivo To investigate the properties of the liver-enriched capsids identified in Example 1, rAAV vectors containing a first coding sequence encoding canine FGF21 and a soluble form of canine transforming growth factor beta receptor 2 (sTGFbR2; see, e.g., Davidsohn et al. (2019) Proc. Natl. Acad. Sci. USA 116(47):23505-23511) were packaged into CL01, CL03, CL11, CL13, CL27, or AAV8 capsids. A total of 30 young adult (1-3 years old) naive male and female beagle dogs were inoculated with 5 x 10 CL01-, CL03-, CL11-, CL13-, and CL27-packaged viruses. 12 vg / kg and 1 × 10 13The capsid was administered intravenously at a dose of 0.05 mg / kg (3 dogs per dose per capsid). Two months after administration, plasma samples were isolated from the blood of the dogs, and the expression of FGF21 and sTGFbR2 was measured by ELISA (Fig. 1A) or Western blot (Fig. 1B), respectively. ***

[0274] The present invention is not limited in scope by the specific embodiments described herein. Indeed, various modifications of the present disclosure in addition to those described herein will become apparent to those skilled in the art from the foregoing description and the accompanying drawings. Such modifications are intended to be included within the scope of the appended claims.

[0275] All references (publications or patents or patent applications) cited herein are incorporated by reference in their entirety for all purposes to the same extent as if each individual reference (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 scope of the following claims.

Claims

1. Recombinant adeno-associated virus (AAV) capsid protein, (i) an amino acid sequence having at least 94% sequence identity with amino acids 1 to 734 of SEQ ID NO: 2, an amino acid sequence having at least 95% sequence identity with amino acids 137 to 734 of SEQ ID NO: 2, and / or an amino acid sequence having at least 96% sequence identity with amino acids 202 to 734 of SEQ ID NO: 2 (ii) an amino acid sequence having at least 96% sequence identity with amino acids 1 to 736 of SEQ ID NO: 4, an amino acid sequence having at least 95% sequence identity with amino acids 138 to 736 of SEQ ID NO: 4, and / or an amino acid sequence having at least 96% sequence identity with amino acids 204 to 736 of SEQ ID NO: 4 (iii) an amino acid sequence having at least 94% sequence identity with amino acids 1 to 734 of SEQ ID NO: 6, an amino acid sequence having at least 96% sequence identity with amino acids 137 to 734 of SEQ ID NO: 6, and / or an amino acid sequence having at least 97% sequence identity with amino acids 202 to 734 of SEQ ID NO: 6 (iv) an amino acid sequence having at least 91% sequence identity with amino acids 1 to 731 of SEQ ID NO: 8, an amino acid sequence having at least 91% sequence identity with amino acids 134 to 731 of SEQ ID NO: 8, and / or an amino acid sequence having at least 95% sequence identity with amino acids 199 to 731 of SEQ ID NO: 8 (v) an amino acid sequence having at least 98% sequence identity with amino acids 1 to 736 of SEQ ID NO: 10, an amino acid sequence having at least 99% sequence identity with amino acids 138 to 736 of SEQ ID NO: 10, and / or an amino acid sequence having at least 99% sequence identity with amino acids 203 to 736 of SEQ ID NO: 10 (vi) an amino acid sequence having at least 96% sequence identity with amino acids 1 to 736 of SEQ ID NO: 12, an amino acid sequence having at least 96% sequence identity with amino acids 137 to 736 of SEQ ID NO: 12, and / or an amino acid sequence having at least 97% sequence identity with amino acids 203 to 736 of SEQ ID NO: 12 (vii) an amino acid sequence having at least 96% sequence identity with amino acids 1 to 736 of SEQ ID NO: 14, an amino acid sequence having at least 95% sequence identity with amino acids 138 to 736 of SEQ ID NO: 14, and / or an amino acid sequence having at least 96% sequence identity with amino acids 204 to 736 of SEQ ID NO: 14 (viiii) an amino acid sequence having at least 93% sequence identity with amino acids 1 to 734 of SEQ ID NO: 16, an amino acid sequence having at least 95% sequence identity with amino acids 137 to 734 of SEQ ID NO: 16, and / or an amino acid sequence having at least 97% sequence identity with amino acids 202 to 734 of SEQ ID NO: 16, (ix) an amino acid sequence having at least 95% sequence identity with amino acids 1 to 735 of SEQ ID NO: 18, an amino acid sequence having at least 95% sequence identity with amino acids 138 to 735 of SEQ ID NO: 18, and / or an amino acid sequence having at least 96% sequence identity with amino acids 203 to 735 of SEQ ID NO: 18, (x) an amino acid sequence having at least 93% sequence identity with amino acids 1 to 736 of SEQ ID NO: 20, an amino acid sequence having at least 95% sequence identity with amino acids 137 to 736 of SEQ ID NO: 20, and / or an amino acid sequence having at least 96% sequence identity with amino acids 202 to 736 of SEQ ID NO: 20 (xi) an amino acid sequence having at least 96% sequence identity with amino acids 1 to 736 of SEQ ID NO: 22, an amino acid sequence having at least 97% sequence identity with amino acids 137 to 736 of SEQ ID NO: 22, and / or an amino acid sequence having at least 99% sequence identity with amino acids 203 to 736 of SEQ ID NO: 22 (xi) an amino acid sequence having at least 97% sequence identity with amino acids 1 to 736 of SEQ ID NO: 24, an amino acid sequence having at least 96% sequence identity with amino acids 138 to 736 of SEQ ID NO: 24, and / or an amino acid sequence having at least 97% sequence identity with amino acids 204 to 736 of SEQ ID NO: 24 (xiiii) an amino acid sequence having at least 99% sequence identity with amino acids 1 to 735 of SEQ ID NO: 26, an amino acid sequence having at least 99% sequence identity with amino acids 137 to 735 of SEQ ID NO: 26, and / or an amino acid sequence having at least 99% sequence identity with amino acids 202 to 735 of SEQ ID NO: 26, (xiv) an amino acid sequence having at least 92% sequence identity with amino acids 1 to 734 of SEQ ID NO: 28, an amino acid sequence having at least 94% sequence identity with amino acids 137 to 734 of SEQ ID NO: 28, and / or an amino acid sequence having at least 96% sequence identity with amino acids 202 to 734 of SEQ ID NO: 28, (xv) an amino acid sequence having at least 92% sequence identity with amino acids 1 to 734 of SEQ ID NO: 30, an amino acid sequence having at least 94% sequence identity with amino acids 137 to 734 of SEQ ID NO: 30, and / or an amino acid sequence having at least 96% sequence identity with amino acids 202 to 734 of SEQ ID NO: 30, (xvi) an amino acid sequence having at least 95% sequence identity with amino acids 1 to 735 of SEQ ID NO: 32, an amino acid sequence having at least 95% sequence identity with amino acids 137 to 735 of SEQ ID NO: 32, and / or an amino acid sequence having at least 96% sequence identity with amino acids 202 to 735 of SEQ ID NO: 32, (xvii) an amino acid sequence having at least 96% sequence identity with amino acids 1 to 735 of SEQ ID NO: 34, an amino acid sequence having at least 98% sequence identity with amino acids 137 to 735 of SEQ ID NO: 34, and / or an amino acid sequence having at least 98% sequence identity with amino acids 202 to 735 of SEQ ID NO: 34, (xviiii) an amino acid sequence having at least 94% sequence identity with amino acids 1 to 735 of SEQ ID NO: 36, an amino acid sequence having at least 96% sequence identity with amino acids 138 to 735 of SEQ ID NO: 36, and / or an amino acid sequence having at least 97% sequence identity with amino acids 203 to 735 of SEQ ID NO: 36, (xix) an amino acid sequence having at least 94% sequence identity with amino acids 1 to 731 of SEQ ID NO: 38, an amino acid sequence having at least 95% sequence identity with amino acids 134 to 731 of SEQ ID NO: 38, and / or an amino acid sequence having at least 96% sequence identity with amino acids 199 to 731 of SEQ ID NO: 38, (xx) an amino acid sequence having at least 94% sequence identity with amino acids 1 to 735 of SEQ ID NO: 40, an amino acid sequence having at least 97% sequence identity with amino acids 137 to 735 of SEQ ID NO: 40, and / or an amino acid sequence having at least 97% sequence identity with amino acids 203 to 735 of SEQ ID NO: 40, (xxi) an amino acid sequence having at least 96% sequence identity with amino acids 1 to 736 of SEQ ID NO: 42, an amino acid sequence having at least 96% sequence identity with amino acids 138 to 736 of SEQ ID NO: 42, and / or an amino acid sequence having at least 96% sequence identity with amino acids 204 to 736 of SEQ ID NO: 42, (xxii) an amino acid sequence having at least 94% sequence identity with amino acids 1-736 of SEQ ID NO: 44, an amino acid sequence having at least 96% sequence identity with amino acids 137-736 of SEQ ID NO: 44, and / or an amino acid sequence having at least 97% sequence identity with amino acids 202-736 of SEQ ID NO: 44, (xxiii) an amino acid sequence having at least 94% sequence identity with amino acids 1-736 of SEQ ID NO: 46, an amino acid sequence having at least 96% sequence identity with amino acids 137-736 of SEQ ID NO: 46, and / or an amino acid sequence having at least 97% sequence identity with amino acids 203-736 of SEQ ID NO: 46, (xxiv) an amino acid sequence having at least 94% sequence identity with amino acids 1-734 of SEQ ID NO: 48, an amino acid sequence having at least 95% sequence identity with amino acids 137-734 of SEQ ID NO: 48, and / or an amino acid sequence having at least 97% sequence identity with amino acids 202-734 of SEQ ID NO: 48, (xxv) an amino acid sequence having at least 94% sequence identity with amino acids 1 to 734 of SEQ ID NO: 50, an amino acid sequence having at least 95% sequence identity with amino acids 137 to 734 of SEQ ID NO: 50, and / or an amino acid sequence having at least 95% sequence identity with amino acids 202 to 734 of SEQ ID NO: 50, (xxvi) an amino acid sequence having at least 93% sequence identity with amino acids 1 to 734 of SEQ ID NO: 52, an amino acid sequence having at least 94% sequence identity with amino acids 137 to 734 of SEQ ID NO: 52, and / or an amino acid sequence having at least 96% sequence identity with amino acids 202 to 734 of SEQ ID NO: 52, (xxvii) an amino acid sequence having at least 96% sequence identity with amino acids 1 to 735 of SEQ ID NO: 54, an amino acid sequence having at least 95% sequence identity with amino acids 138 to 735 of SEQ ID NO: 54, and / or an amino acid sequence having at least 96% sequence identity with amino acids 203 to 735 of SEQ ID NO: 54, (xxviiii) an amino acid sequence having at least 94% sequence identity with amino acids 1-735 of SEQ ID NO: 56, an amino acid sequence having at least 95% sequence identity with amino acids 137-735 of SEQ ID NO: 56, and / or an amino acid sequence having at least 96% sequence identity with amino acids 202-735 of SEQ ID NO: 56, (xxix) an amino acid sequence having at least 84% sequence identity with amino acids 1 to 735 of SEQ ID NO: 58, an amino acid sequence having at least 85% sequence identity with amino acids 137 to 735 of SEQ ID NO: 58, and / or an amino acid sequence having at least 85% sequence identity with amino acids 202 to 735 of SEQ ID NO: 58, (xxx) an amino acid sequence having at least 90% sequence identity with amino acids 1 to 735 of SEQ ID NO: 60, an amino acid sequence having at least 92% sequence identity with amino acids 137 to 735 of SEQ ID NO: 60, and / or an amino acid sequence having at least 93% sequence identity with amino acids 202 to 735 of SEQ ID NO: 60, or (xxxi) The recombinant AAV capsid protein comprising an amino acid sequence having at least 94% sequence identity with amino acids 1 to 735 of SEQ ID NO: 62, an amino acid sequence having at least 96% sequence identity with amino acids 137 to 735 of SEQ ID NO: 62, and / or an amino acid sequence having at least 97% sequence identity with amino acids 202 to 735 of SEQ ID NO:

62.

2. (i) an amino acid sequence having at least 99% sequence identity with amino acids 1 to 734 of SEQ ID NO: 2, an amino acid sequence having at least 99% sequence identity with amino acids 137 to 734 of SEQ ID NO: 2, and / or an amino acid sequence having at least 99% sequence identity with amino acids 202 to 734 of SEQ ID NO: 2 (ii) an amino acid sequence having at least 99% sequence identity with amino acids 1 to 736 of SEQ ID NO: 4, an amino acid sequence having at least 99% sequence identity with amino acids 138 to 736 of SEQ ID NO: 4, and / or an amino acid sequence having at least 99% sequence identity with amino acids 204 to 736 of SEQ ID NO: 4 (iii) an amino acid sequence having at least 99% sequence identity with amino acids 1 to 734 of SEQ ID NO: 6, an amino acid sequence having at least 99% sequence identity with amino acids 137 to 734 of SEQ ID NO: 6, and / or an amino acid sequence having at least 99% sequence identity with amino acids 202 to 734 of SEQ ID NO: 6 (iv) an amino acid sequence having at least 99% sequence identity with amino acids 1 to 731 of SEQ ID NO: 8, an amino acid sequence having at least 99% sequence identity with amino acids 134 to 731 of SEQ ID NO: 8, and / or an amino acid sequence having at least 99% sequence identity with amino acids 199 to 731 of SEQ ID NO: 8, (v) an amino acid sequence having at least 99% sequence identity with amino acids 1 to 736 of SEQ ID NO: 10, an amino acid sequence having at least 99% sequence identity with amino acids 138 to 736 of SEQ ID NO: 10, and / or an amino acid sequence having at least 99% sequence identity with amino acids 203 to 736 of SEQ ID NO: 10 (vi) an amino acid sequence having at least 99% sequence identity with amino acids 1 to 736 of SEQ ID NO: 12, an amino acid sequence having at least 99% sequence identity with amino acids 137 to 736 of SEQ ID NO: 12, and / or an amino acid sequence having at least 99% sequence identity with amino acids 203 to 736 of SEQ ID NO: 12 (vii) an amino acid sequence having at least 99% sequence identity with amino acids 1 to 736 of SEQ ID NO: 14, an amino acid sequence having at least 99% sequence identity with amino acids 138 to 736 of SEQ ID NO: 14, and / or an amino acid sequence having at least 99% sequence identity with amino acids 204 to 736 of SEQ ID NO: 14 (viiii) an amino acid sequence having at least 99% sequence identity with amino acids 1 to 734 of SEQ ID NO: 16, an amino acid sequence having at least 99% sequence identity with amino acids 137 to 734 of SEQ ID NO: 16, and / or an amino acid sequence having at least 99% sequence identity with amino acids 202 to 734 of SEQ ID NO: 16 (ix) an amino acid sequence having at least 99% sequence identity with amino acids 1 to 735 of SEQ ID NO: 18, an amino acid sequence having at least 99% sequence identity with amino acids 138 to 735 of SEQ ID NO: 18, and / or an amino acid sequence having at least 99% sequence identity with amino acids 203 to 735 of SEQ ID NO: 18 (x) an amino acid sequence having at least 99% sequence identity with amino acids 1 to 736 of SEQ ID NO: 20, an amino acid sequence having at least 99% sequence identity with amino acids 137 to 736 of SEQ ID NO: 20, and / or an amino acid sequence having at least 99% sequence identity with amino acids 202 to 736 of SEQ ID NO: 20, (xi) an amino acid sequence having at least 99% sequence identity with amino acids 1 to 736 of SEQ ID NO: 22, an amino acid sequence having at least 99% sequence identity with amino acids 137 to 736 of SEQ ID NO: 22, and / or an amino acid sequence having at least 99% sequence identity with amino acids 203 to 736 of SEQ ID NO: 22 (xi) an amino acid sequence having at least 99% sequence identity with amino acids 1 to 736 of SEQ ID NO: 24, an amino acid sequence having at least 99% sequence identity with amino acids 138 to 736 of SEQ ID NO: 24, and / or an amino acid sequence having at least 99% sequence identity with amino acids 204 to 736 of SEQ ID NO: 24 (xiiii) an amino acid sequence having at least 99% sequence identity with amino acids 1 to 735 of SEQ ID NO: 26, an amino acid sequence having at least 99% sequence identity with amino acids 137 to 735 of SEQ ID NO: 26, and / or an amino acid sequence having at least 99% sequence identity with amino acids 202 to 735 of SEQ ID NO: 26, (xiv) an amino acid sequence having at least 99% sequence identity with amino acids 1 to 734 of SEQ ID NO: 28, an amino acid sequence having at least 99% sequence identity with amino acids 137 to 734 of SEQ ID NO: 28, and / or an amino acid sequence having at least 99% sequence identity with amino acids 202 to 734 of SEQ ID NO: 28, (xv) an amino acid sequence having at least 99% sequence identity with amino acids 1 to 734 of SEQ ID NO: 30, an amino acid sequence having at least 99% sequence identity with amino acids 137 to 734 of SEQ ID NO: 30, and / or an amino acid sequence having at least 99% sequence identity with amino acids 202 to 734 of SEQ ID NO: 30, (xvi) an amino acid sequence having at least 99% sequence identity with amino acids 1 to 735 of SEQ ID NO: 32, an amino acid sequence having at least 99% sequence identity with amino acids 137 to 735 of SEQ ID NO: 32, and / or an amino acid sequence having at least 99% sequence identity with amino acids 202 to 735 of SEQ ID NO: 32, (xvii) an amino acid sequence having at least 99% sequence identity with amino acids 1 to 735 of SEQ ID NO: 34, an amino acid sequence having at least 99% sequence identity with amino acids 137 to 735 of SEQ ID NO: 34, and / or an amino acid sequence having at least 99% sequence identity with amino acids 202 to 735 of SEQ ID NO: 34, (xviiii) an amino acid sequence having at least 99% sequence identity with amino acids 1 to 735 of SEQ ID NO: 36, an amino acid sequence having at least 99% sequence identity with amino acids 138 to 735 of SEQ ID NO: 36, and / or an amino acid sequence having at least 99% sequence identity with amino acids 203 to 735 of SEQ ID NO: 36, (xix) an amino acid sequence having at least 99% sequence identity with amino acids 1 to 731 of SEQ ID NO: 38, an amino acid sequence having at least 99% sequence identity with amino acids 134 to 731 of SEQ ID NO: 38, and / or an amino acid sequence having at least 99% sequence identity with amino acids 199 to 731 of SEQ ID NO: 38, (xx) an amino acid sequence having at least 99% sequence identity with amino acids 1 to 735 of SEQ ID NO: 40, an amino acid sequence having at least 99% sequence identity with amino acids 137 to 735 of SEQ ID NO: 40, and / or an amino acid sequence having at least 99% sequence identity with amino acids 203 to 735 of SEQ ID NO: 40, (xxi) an amino acid sequence having at least 99% sequence identity with amino acids 1 to 736 of SEQ ID NO: 42, an amino acid sequence having at least 99% sequence identity with amino acids 138 to 736 of SEQ ID NO: 42, and / or an amino acid sequence having at least 99% sequence identity with amino acids 204 to 736 of SEQ ID NO: 42 (xxii) an amino acid sequence having at least 99% sequence identity with amino acids 1 to 736 of SEQ ID NO: 44, an amino acid sequence having at least 99% sequence identity with amino acids 137 to 736 of SEQ ID NO: 44, and / or an amino acid sequence having at least 99% sequence identity with amino acids 202 to 736 of SEQ ID NO: 44, (xxiii) an amino acid sequence having at least 99% sequence identity with amino acids 1 to 736 of SEQ ID NO: 46, an amino acid sequence having at least 99% sequence identity with amino acids 137 to 736 of SEQ ID NO: 46, and / or an amino acid sequence having at least 99% sequence identity with amino acids 203 to 736 of SEQ ID NO: 46, (xxiv) an amino acid sequence having at least 99% sequence identity with amino acids 1 to 734 of SEQ ID NO: 48, an amino acid sequence having at least 99% sequence identity with amino acids 137 to 734 of SEQ ID NO: 48, and / or an amino acid sequence having at least 99% sequence identity with amino acids 202 to 734 of SEQ ID NO: 48, (xxv) an amino acid sequence having at least 99% sequence identity with amino acids 1 to 734 of SEQ ID NO: 50, an amino acid sequence having at least 99% sequence identity with amino acids 137 to 734 of SEQ ID NO: 50, and / or an amino acid sequence having at least 99% sequence identity with amino acids 202 to 734 of SEQ ID NO: 50, (xxvi) an amino acid sequence having at least 99% sequence identity with amino acids 1 to 734 of SEQ ID NO: 52, an amino acid sequence having at least 99% sequence identity with amino acids 137 to 734 of SEQ ID NO: 52, and / or an amino acid sequence having at least 99% sequence identity with amino acids 202 to 734 of SEQ ID NO: 52, (xxvii) an amino acid sequence having at least 99% sequence identity with amino acids 1 to 735 of SEQ ID NO: 54, an amino acid sequence having at least 99% sequence identity with amino acids 138 to 735 of SEQ ID NO: 54, and / or an amino acid sequence having at least 99% sequence identity with amino acids 203 to 735 of SEQ ID NO: 54, (xxviiii) an amino acid sequence having at least 99% sequence identity with amino acids 1 to 735 of SEQ ID NO: 56, an amino acid sequence having at least 99% sequence identity with amino acids 137 to 735 of SEQ ID NO: 56, and / or an amino acid sequence having at least 99% sequence identity with amino acids 202 to 735 of SEQ ID NO: 56, (xxix) an amino acid sequence having at least 99% sequence identity with amino acids 1 to 735 of SEQ ID NO: 58, an amino acid sequence having at least 99% sequence identity with amino acids 137 to 735 of SEQ ID NO: 58, and / or an amino acid sequence having at least 99% sequence identity with amino acids 202 to 735 of SEQ ID NO: 58, (xxx) an amino acid sequence having at least 99% sequence identity with amino acids 1 to 735 of SEQ ID NO: 60, an amino acid sequence having at least 99% sequence identity with amino acids 137 to 735 of SEQ ID NO: 60, and / or an amino acid sequence having at least 99% sequence identity with amino acids 202 to 735 of SEQ ID NO: 60, or (xxxi) The recombinant AAV capsid protein according to claim 1, comprising an amino acid sequence having at least 99% sequence identity with amino acids 1 to 735 of SEQ ID NO: 62, an amino acid sequence having at least 99% sequence identity with amino acids 137 to 735 of SEQ ID NO: 62, and / or an amino acid sequence having at least 99% sequence identity with amino acids 202 to 735 of SEQ ID NO:

62.

3. The recombinant AAV capsid protein according to claim 1 or 2, comprising amino acids 1 to 734 of SEQ ID NO: 2, amino acids 137 to 734 of SEQ ID NO: 2, and / or amino acids 202 to 734 of SEQ ID NO:

2.

4. The recombinant AAV capsid protein according to claim 3, comprising SEQ ID NO:

2.

5. The recombinant AAV capsid protein according to claim 1 or 2, comprising amino acids 1 to 736 of SEQ ID NO: 4, amino acids 138 to 736 of SEQ ID NO: 4, and / or amino acids 204 to 736 of SEQ ID NO:

4.

6. The recombinant AAV capsid protein according to claim 5, comprising sequence number 4.

7. The recombinant AAV capsid protein according to claim 1 or 2, comprising amino acids 1 to 734 of SEQ ID NO: 6, amino acids 137 to 734 of SEQ ID NO: 6, and / or amino acids 202 to 734 of SEQ ID NO:

6.

8. The recombinant AAV capsid protein according to claim 7, comprising SEQ ID NO:

6.

9. The recombinant AAV capsid protein according to claim 1 or 2, comprising amino acids 1 to 731 of SEQ ID NO: 8, amino acids 134 to 731 of SEQ ID NO: 8, and / or amino acids 199 to 731 of SEQ ID NO:

8.

10. The recombinant AAV capsid protein according to claim 9, comprising SEQ ID NO:

8.

11. The recombinant AAV capsid protein according to claim 1 or 2, comprising amino acids 1 to 736 of SEQ ID NO: 10, amino acids 138 to 736 of SEQ ID NO: 10, and / or amino acids 203 to 736 of SEQ ID NO:

10.

12. The recombinant AAV capsid protein according to claim 11, comprising sequence number 10.

13. The recombinant AAV capsid protein according to claim 1 or 2, comprising amino acids 1 to 736 of SEQ ID NO: 12, amino acids 137 to 736 of SEQ ID NO: 12, and / or amino acids 203 to 736 of SEQ ID NO:

12.

14. The recombinant AAV capsid protein according to claim 13, comprising sequence number 12.

15. The recombinant AAV capsid protein according to claim 1 or 2, comprising amino acids 1 to 736 of SEQ ID NO: 14, amino acids 138 to 736 of SEQ ID NO: 14, and / or amino acids 204 to 736 of SEQ ID NO:

14.

16. The recombinant AAV capsid protein according to claim 15, comprising sequence number 14.

17. The recombinant AAV capsid protein according to claim 1 or 2, comprising amino acids 1 to 734 of SEQ ID NO: 16, amino acids 137 to 734 of SEQ ID NO: 16, and / or amino acids 202 to 734 of SEQ ID NO:

16.

18. The recombinant AAV capsid protein according to claim 17, comprising sequence number 16.

19. The recombinant AAV capsid protein according to claim 1 or 2, comprising amino acids 1 to 735 of SEQ ID NO: 18, amino acids 138 to 735 of SEQ ID NO: 18, and / or amino acids 203 to 735 of SEQ ID NO:

18.

20. The recombinant AAV capsid protein according to claim 19, comprising SEQ ID NO:

18.

21. The recombinant AAV capsid protein according to claim 1 or 2, comprising amino acids 1 to 736 of SEQ ID NO: 20, amino acids 137 to 736 of SEQ ID NO: 20, and / or amino acids 202 to 736 of SEQ ID NO:

20.

22. The recombinant AAV capsid protein according to claim 21, comprising SEQ ID NO:

20.

23. The recombinant AAV capsid protein according to claim 1 or 2, comprising amino acids 1 to 736 of SEQ ID NO: 22, amino acids 137 to 736 of SEQ ID NO: 22, and / or amino acids 203 to 736 of SEQ ID NO:

22.

24. The recombinant AAV capsid protein according to claim 23, comprising SEQ ID NO:

22.

25. The recombinant AAV capsid protein according to claim 1 or 2, comprising amino acids 1 to 736 of SEQ ID NO: 24, amino acids 138 to 736 of SEQ ID NO: 24, and / or amino acids 204 to 736 of SEQ ID NO:

24.

26. The recombinant AAV capsid protein according to claim 25, comprising sequence number 24.

27. The recombinant AAV capsid protein according to claim 1 or 2, comprising amino acids 1 to 735 of SEQ ID NO: 26, amino acids 137 to 735 of SEQ ID NO: 26, and / or amino acids 202 to 735 of SEQ ID NO:

26.

28. The recombinant AAV capsid protein according to claim 27, comprising SEQ ID NO:

26.

29. The recombinant AAV capsid protein according to claim 1 or 2, comprising amino acids 1 to 734 of SEQ ID NO: 28, amino acids 137 to 734 of SEQ ID NO: 28, and / or amino acids 202 to 734 of SEQ ID NO:

28.

30. The recombinant AAV capsid protein according to claim 29, comprising SEQ ID NO:

28.

31. The recombinant AAV capsid protein according to claim 1 or 2, comprising amino acids 1 to 734 of SEQ ID NO: 30, amino acids 137 to 734 of SEQ ID NO: 30, and / or amino acids 202 to 734 of SEQ ID NO:

30.

32. The recombinant AAV capsid protein according to claim 31, comprising sequence number 30.

33. The recombinant AAV capsid protein according to claim 1 or 2, comprising amino acids 1 to 735 of SEQ ID NO: 32, amino acids 137 to 735 of SEQ ID NO: 32, and / or amino acids 202 to 735 of SEQ ID NO:

32.

34. The recombinant AAV capsid protein according to claim 33, comprising SEQ ID NO:

32.

35. The recombinant AAV capsid protein according to claim 1 or 2, comprising amino acids 1 to 735 of SEQ ID NO: 34, amino acids 137 to 735 of SEQ ID NO: 34, and / or amino acids 202 to 735 of SEQ ID NO:

34.

36. The recombinant AAV capsid protein according to claim 35, comprising sequence number 34.

37. The recombinant AAV capsid protein according to claim 1 or 2, comprising amino acids 1 to 735 of SEQ ID NO: 36, amino acids 138 to 735 of SEQ ID NO: 36, and / or amino acids 203 to 735 of SEQ ID NO:

36.

38. The recombinant AAV capsid protein according to claim 37, comprising sequence number 36.

39. The recombinant AAV capsid protein according to claim 1 or 2, comprising amino acids 1 to 731 of SEQ ID NO: 38, amino acids 134 to 731 of SEQ ID NO: 38, and / or amino acids 199 to 731 of SEQ ID NO:

38.

40. The recombinant AAV capsid protein according to claim 39, comprising sequence number 38.

41. The recombinant AAV capsid protein according to claim 1 or 2, comprising amino acids 1 to 735 of SEQ ID NO: 40, amino acids 137 to 735 of SEQ ID NO: 40, and / or amino acids 203 to 735 of SEQ ID NO:

40.

42. The recombinant AAV capsid protein according to claim 41, comprising sequence number 40.

43. The recombinant AAV capsid protein according to claim 1 or 2, comprising amino acids 1 to 736 of SEQ ID NO: 42, amino acids 138 to 736 of SEQ ID NO: 42, and / or amino acids 204 to 736 of SEQ ID NO:

42.

44. The recombinant AAV capsid protein according to claim 43, comprising sequence number 42.

45. The recombinant AAV capsid protein according to claim 1 or 2, comprising amino acids 1 to 736 of SEQ ID NO: 44, amino acids 137 to 736 of SEQ ID NO: 44, and / or amino acids 202 to 736 of SEQ ID NO:

44.

46. The recombinant AAV capsid protein according to claim 45, comprising sequence number 44.

47. The recombinant AAV capsid protein according to claim 1 or 2, comprising amino acids 1 to 736 of SEQ ID NO: 46, amino acids 137 to 736 of SEQ ID NO: 46, and / or amino acids 203 to 736 of SEQ ID NO:

46.

48. The recombinant AAV capsid protein according to claim 47, comprising sequence number 46.

49. The recombinant AAV capsid protein according to claim 1 or 2, comprising amino acids 1 to 734 of SEQ ID NO: 48, amino acids 137 to 734 of SEQ ID NO: 48, and / or amino acids 202 to 734 of SEQ ID NO:

48.

50. The recombinant AAV capsid protein according to claim 49, comprising sequence number 48.

51. The recombinant AAV capsid protein according to claim 1 or 2, comprising amino acids 1 to 734 of SEQ ID NO: 50, amino acids 137 to 734 of SEQ ID NO: 50, and / or amino acids 202 to 734 of SEQ ID NO:

50.

52. The recombinant AAV capsid protein according to claim 51, comprising sequence number 50.

53. The recombinant AAV capsid protein according to claim 1 or 2, comprising amino acids 1 to 734 of SEQ ID NO: 52, amino acids 137 to 734 of SEQ ID NO: 52, and / or amino acids 202 to 734 of SEQ ID NO:

52.

54. The recombinant AAV capsid protein according to claim 53, comprising sequence number 52.

55. The recombinant AAV capsid protein according to claim 1 or 2, comprising amino acids 1 to 735 of SEQ ID NO: 54, amino acids 138 to 735 of SEQ ID NO: 54, and / or amino acids 203 to 735 of SEQ ID NO:

54.

56. The recombinant AAV capsid protein according to claim 55, comprising sequence number 54.

57. The recombinant AAV capsid protein according to claim 1 or 2, comprising amino acids 1 to 735 of SEQ ID NO: 56, amino acids 137 to 735 of SEQ ID NO: 56, and / or amino acids 202 to 735 of SEQ ID NO:

56.

58. The recombinant AAV capsid protein according to claim 57, comprising sequence number 56.

59. The recombinant AAV capsid protein according to claim 1 or 2, comprising amino acids 1 to 735 of SEQ ID NO: 58, amino acids 137 to 735 of SEQ ID NO: 58, and / or amino acids 202 to 735 of SEQ ID NO:

58.

60. The recombinant AAV capsid protein according to claim 59, comprising sequence number 58.

61. The recombinant AAV capsid protein according to claim 1 or 2, comprising amino acids 1 to 735 of SEQ ID NO: 60, amino acids 137 to 735 of SEQ ID NO: 60, and / or amino acids 202 to 735 of SEQ ID NO:

60.

62. The recombinant AAV capsid protein according to claim 61, comprising sequence number 60.

63. The recombinant AAV capsid protein according to claim 1 or 2, comprising amino acids 1 to 735 of SEQ ID NO: 62, amino acids 137 to 735 of SEQ ID NO: 62, and / or amino acids 202 to 735 of SEQ ID NO:

62.

64. The recombinant AAV capsid protein according to claim 63, comprising sequence number 62.

65. The recombinant AAV capsid protein according to claim 1 or 2, wherein the recombinant AAV capsid protein is a variant of 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, rh. 32.33, rh. 33, rh. 34, BAAV, or AAV5 capsid protein.

66. An isolated polynucleotide encoding the recombinant AAV capsid protein described in claim 1.

67. An isolated polynucleotide having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with any one of the nucleic acid sequences described in SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, and 61.

68. The isolated polynucleotide according to claim 66 or 67, comprising the nucleic acid sequence described in any one of SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, and 61.

69. A vector comprising the polynucleotide described in claim 66.

70. A vector comprising the polynucleotide described in claim 67.

71. The vector according to claim 69 or 70, which is a plasmid or a viral vector.

72. The vector according to claim 71, wherein the viral vector is a retroviral vector, a herpesvirus vector, a baculovirus vector, or an adenovirus vector.

73. An expression vector, as described in claim 69 or 70.

74. Recombinant cells comprising the polynucleotide described in claim 66 or the vector described in claim 69 or 70.

75. Recombinant cells comprising the polynucleotide described in claim 67 or the vector described in claim 69 or 70.

76. A method for producing recombinant AAV capsid protein, comprising culturing the recombinant cells described in claim 74 under conditions in which the polynucleotide is expressed and the capsid protein is produced.

77. A method for producing recombinant AAV capsid protein, comprising culturing the recombinant cells described in claim 75 under conditions in which the polynucleotide is expressed and the capsid protein is produced.

78. Recombinant adeno-associated virus (rAAV), (a) A capsid comprising one or more recombinant AAV capsid proteins as described in claim 1, (b) The rAAV comprising an rAAV genome.

79. The rAAV according to claim 78, wherein the rAAV genome includes a transgene.

80. The rAAV according to claim 79, wherein the introduced gene encodes a polypeptide.

81. The rAAV according to claim 79, wherein the introduced gene encodes miRNA, shRNA, siRNA, antisense RNA, gRNA, antagomyl, miRNA sponge, RNA aptazyme, RNA aptamer, lncRNA, ribozyme, or mRNA.

82. The rAAV according to claim 79, wherein the introduced gene is operably linked to a transcriptional regulatory element.

83. A composition for use in a method for transducing cells, comprising the rAAV described in claim 78, wherein the method comprises bringing the cells into contact with the rAAV under conditions that thereby transduce the cells.

84. A composition for use in a method for delivering a transgene into a cell, comprising the rAAV described in claim 78, wherein the method comprises bringing the cell into contact with the rAAV under conditions in which the cell is transduced and the transgene is expressed.

85. The composition according to claim 83, characterized in that the cells are present within the target and the composition is administered to the target.

86. The composition according to claim 84, characterized in that the cells are present in the subject and the composition is administered to the subject.

87. The composition according to claim 85 or 86, wherein the cells are muscle cells and / or liver cells.

88. The composition according to claim 83, characterized in that the composition is administered to the subject intravenously, intraperitoneally, subcutaneously, intramuscularly, intrathecally, or intradermally.

89. The composition according to claim 84, characterized in that the composition is administered to the subject intravenously, intraperitoneally, subcutaneously, intramuscularly, intrathecally, or intradermally.

90. The composition according to claim 88 or 89, wherein the subject is selected from the group consisting of human subjects, dog subjects, cat subjects, and horse subjects.

91. A composition for use in medicine, for use as a therapy, or for use as a drug, comprising the rAAV described in claim 78.

92. A packaging system for the preparation of rAAV, (a) A first nucleotide sequence encoding one or more AAV Rep proteins, (b) A second nucleotide sequence encoding the recombinant AAV capsid protein according to claim 1 or 2, (c) The packaging system comprising a third nucleotide sequence containing the rAAV genome sequence.

93. The packaging system according to claim 92, wherein the packaging system comprises a first vector containing the first nucleotide sequence and the second nucleotide sequence, and a second vector containing the third nucleotide sequence.

94. The packaging system according to claim 93, further comprising a fourth nucleotide sequence containing one or more helper virus genes, wherein the fourth nucleotide sequence is optionally included in the third vector.

95. The packaging system according to claim 94, wherein the fourth nucleotide sequence comprises one or more genes derived from a virus selected from the group consisting of adenovirus, herpesvirus, vaccinia virus, and cytomegalovirus (CMV).

96. The packaging system according to claim 92, wherein the first vector, the second vector, and / or the third vector are plasmids.

97. A method for recombinant preparation of rAAV, comprising introducing the packaging system described in claim 92 into a cell under conditions that thereby produce the rAAV.

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