Capsid variants and methods of using same

Abstract

This disclosure is directed, in part, to variant capsid polypeptides that can be used to deliver a payload.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Application No. 63 / 262,341, filed October 10, 2021, and U.S. Provisional Application No. 63 / 262,330, filed October 8, 2021, which are incorporated by reference herein in their entireties.

[0002] Reference to an electronically submitted sequence listing This application contains a Sequence Listing that has been submitted electronically in XML file format, which is incorporated herein by reference in its entirety. The XML copy, created on October 6, 2022, is named "257394_001302_SeqList.XML" and is 621,812 bytes in size. [Background technology]

[0003] Dependoparvoviruses, such as adeno-associated dependoparvoviruses, e.g., adeno-associated viruses (AAV), are of interest as vectors for delivering various payloads to cells, including human subjects. Summary of the Invention

[0004] The present disclosure provides, in part, improved variant depend parvovirus capsid proteins (e.g., AAV9 variant capsid polypeptides), e.g., VP1, VP2, and / or VP3 variant capsid polypeptides, methods for producing depend parvoviruses, compositions for use therein, and viral particles produced thereby. In some embodiments, the produced viral particles have increased central nervous system (CNS) biodistribution and / or transduction compared to viral particles that do not contain mutations in the capsid proteins.

[0005] In some embodiments, the present disclosure is directed, in part, to a nucleic acid comprising a sequence encoding a variant capsid protein provided herein. In some embodiments, the dependoparvovirus is an adeno-associated dependoparvovirus (AAV). In some embodiments, the AAV is AAV9, e.g., a variant AAV9.

[0006] In some embodiments, the present disclosure is directed, in part, to the variant capsid polypeptides described herein.

[0007] In some embodiments, the disclosure provides, in part, the nucleic acid sequences of SEQ ID NOs: 2, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53 , 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 1 131, 132, 133, 134, 135, 136, 137, 138, or 139, and optionally comprising, e.g., consisting of, SEQ ID NO:2. In some embodiments, the present disclosure is directed, in part, to a dependoparvovirus particle comprising a nucleic acid described herein.

[0008] In some embodiments, the present disclosure is directed, in part, to vectors, e.g., plasmids, that include the nucleic acids described herein. In some embodiments, the present disclosure provides, in part, the nucleic acid sequences of SEQ ID NOs: 3, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 300, 309, 309, 400, 410, 411, 412, 413, 414, 415, 416, 417, 418, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 73, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 2 3, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253 , 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, or 265, a fragment thereof, or a variant thereof having at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% sequence identity thereto.

[0009] In some embodiments, the disclosure is directed, in part, to a dependoparvoviral particle comprising a nucleic acid described herein (e.g., a nucleic acid comprising a sequence encoding a variant capsid polypeptide, e.g., VP1), wherein the coding sequence comprises a charge or mutation provided herein.

[0010] In some embodiments, the disclosure is directed, in part, to a vector comprising a nucleic acid described herein, e.g., a nucleic acid comprising a sequence encoding a variant capsid polypeptide, e.g., a VP1 polypeptide, wherein the coding sequence comprises a charge or mutation provided herein.

[0011] In some embodiments, the disclosure is directed, in part, to a cell, cell-free system, or other translation system that includes a nucleic acid or vector described herein, e.g., a sequence encoding a variant capsid polypeptide, such as VP1, where the variant capsid polypeptide coding sequence includes a charge or mutation provided herein in the coding sequence. In some embodiments, the cell, cell-free system, or other translation system includes a dependoparvovirus particle described herein, e.g., the particle includes a nucleic acid that includes a sequence encoding a variant capsid polypeptide, e.g., a VP1 polypeptide, where the coding sequence includes a charge or mutation provided herein.

[0012] In some embodiments, the disclosure is directed, in part, to a cell, cell-free system, or other translation system that includes a polypeptide described herein, wherein the polypeptide-encoding sequence includes a charge or mutation as provided herein. In some embodiments, the cell, cell-free system, or other translation system includes a dependoparvovirus particle described herein, e.g., the particle includes a nucleic acid that includes a sequence encoding a VP1 polypeptide, wherein the VP1-encoding sequence includes a corresponding charge or mutation as provided herein.

[0013] In some embodiments, the present disclosure is directed, in part, to a method of delivering a payload to a cell, comprising contacting the cell with a dependoparvovirus particle comprising a nucleic acid described herein. In some embodiments, the present disclosure is directed, in part, to a method of delivering a payload to a cell, comprising contacting the cell with a dependoparvovirus particle comprising a variant capsid polypeptide described herein.

[0014] In some embodiments, the present disclosure is directed, in part, to a method of making depend parvovirus particles, the method comprising providing a cell, cell-free system, or other translation system comprising a nucleic acid described herein (e.g., a nucleic acid comprising a sequence encoding a capsid variant provided herein) and cultivating the cell, cell-free system, or other translation system under conditions suitable for the production of depend parvovirus particles, thereby making depend parvovirus particles. In some embodiments, the present disclosure is directed, in part, to a method of making depend parvovirus particles described herein.

[0015] In some embodiments, the present disclosure is directed, in part, to a method of making depend parvovirus particles, the method comprising providing a cell, cell-free system, or other translation system comprising a polypeptide described herein, and cultivating the cell, cell-free system, or other translation system under conditions suitable for the production of depend parvovirus particles, thereby making depend parvovirus particles. In some embodiments, the present disclosure is directed, in part, to a method of making depend parvovirus particles described herein.

[0016] In some embodiments, the present disclosure is directed, in part, to dependoparvovirus particles produced in a cell, cell-free system, or other translation system, wherein the cell, cell-free system, or other translation system comprises a nucleic acid encoding a dependoparvovirus comprising a capsid variant provided herein.

[0017] In some embodiments, the present disclosure is directed, in part, to a method of treating a disease or condition in a subject, comprising administering to the subject a dependoparvovirus particle described herein in an amount effective to treat the disease or condition.

[0018] The present invention is further described with reference to the following numbered embodiments. [Brief explanation of the drawings]

[0019] [Figure 1A] Illustrative AAV serotype alignment. Amino acids present only in the VP1 polypeptide are in normal text, amino acids present only in the VP1 and VP2 polypeptides are in bold, and amino acids present in the VP1, VP2, and VP3 polypeptides are underlined. [Figure 1B] Illustrative AAV serotype alignment. Amino acids present only in the VP1 polypeptide are in normal text, amino acids present only in the VP1 and VP2 polypeptides are in bold, and amino acids present in the VP1, VP2, and VP3 polypeptides are underlined. [Figure 1C] Illustrative AAV serotype alignment. Amino acids present only in the VP1 polypeptide are in normal text, amino acids present only in the VP1 and VP2 polypeptides are in bold, and amino acids present in the VP1, VP2, and VP3 polypeptides are underlined. [Figure 2A] Genomic maps of the plasmids used in Example 2. A) Wild-type AAV9 rep cap plasmid. [Figure 2B] Genomic maps of the plasmids used in Example 2. B) VAR-1 rep cap plasmid. [Figure 2C] Genomic map of the plasmid used in Example 2. C) VAR-1 capsid: packaging plasmid related to the heterologous nucleic acid sequence packaged into the ITR-containing plasmid encoding NLS-eGFP. [Figure 2D] Genomic maps of the plasmids used in Example 2. D) Wild-type AAV9 capsid: packaging plasmid for the heterologous nucleic acid sequence packaged into an ITR-containing plasmid encoding NLS-mCherry. [Figure 3A] Relative transduction (FIG. 3A) and biodistribution (FIG. 3B) for VAR-1 (compared to wild-type AAV9) from the two-capsid NHP experiment described in Example 2. [Figure 3B] (As mentioned above.) [Figure 4A] A) Representative images of VAR-1 and wild-type AAV9 immunofluorescence in the hippocampus and cerebellum. In the hippocampus, the number of cells with VAR-1 GFP expression is approximately 25-fold greater than that with AAV9 mCherry expression. This is also found in the CA3 layer, where VAR-1 GFP can be seen in CA3 pyramidal neurons that show co-staining with the neuronal marker NeuN. In the cerebellum, VAR-1 GFP is expressed in more cells than AAV9 mCherry, with the highest expression in the Purkinje cell layer. [Figure 4B] B) Representative images of VAR-1 and wild-type AAV9 immunofluorescence in the cervical spinal cord, frontal cortex, and caudate nucleus. The number of cells with VAR-1 GFP expression in the spinal cord is 9.4-fold higher than that of AAV9 mCherry. VAR-1-expressing GFP, unlike AAV9 mCherry, is also detected in some neurons (which co-stain with NeuN). In the frontal cortex and caudate, the total number of cells expressing VAR-1 GFP increases compared to AAV9 mCherry (15.9-fold and 4.6-fold increases), which specifically increases neurons by 25-fold and 37-fold (which co-stain with NeuN). [Figure 5] Representative images from an in vitro cell transduction experiment showing transduction of VAR-1 and WT AAV9 in both primary human neurons and the Sh-sy5y cell line. Primary human neurons were treated with virus at a 50K MOI for both VAR-1 and WT AAV9, and Sh-sy5y cells were treated with virus at a 100K MOI. Images were taken from fixed samples using a 20x objective on an EVOS M5000.

[0020] Enumeration of Embodiments 1. A variant capsid polypeptide comprising a polypeptide having at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99% or 100% identity to the VP1, VP2 or VP3 sequence of SEQ ID NO:2.

[0021] 2. The variant capsid polypeptide of embodiment 1, wherein the variant capsid polypeptide is of the same serotype as the polypeptide of SEQ ID NO: 2 (AAV9).

[0022] 3. The variant capsid polypeptide of embodiment 1, wherein the variant capsid polypeptide is of a different serotype compared to the polypeptide of SEQ ID NO: 2 (AAV9).

[0023] 4. The variant capsid polypeptide of any one of the preceding embodiments, wherein the variant capsid polypeptide comprises a mutation corresponding to a mutation at one or more of positions 579, 592, 593, 595, 596, 598, 601, or any combination thereof, compared to SEQ ID NO: 1, and optionally the mutation comprises an insertion, deletion, or substitution.

[0024] 5. The variant capsid polypeptide of any of the preceding embodiments, wherein the variant capsid polypeptide comprises a mutation corresponding to the mutation at position 579 compared to SEQ ID NO:1.

[0025] 6. The variant capsid polypeptide of any of the preceding embodiments, wherein the variant capsid polypeptide comprises a mutation corresponding to the mutation at position 592 compared to SEQ ID NO:1.

[0026] 7. The variant capsid polypeptide of any of the preceding embodiments, wherein the variant capsid polypeptide comprises a mutation corresponding to the mutation at position 593 compared to SEQ ID NO:1.

[0027] 8. The variant capsid polypeptide of any of the preceding embodiments, wherein the variant capsid polypeptide comprises a mutation corresponding to the mutation at position 595 compared to SEQ ID NO:1.

[0028] 9. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a mutation corresponding to the mutation at position 596 compared to SEQ ID NO:1.

[0029] 10. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a mutation corresponding to the mutation at position 598 compared to SEQ ID NO:1.

[0030] 11. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a mutation corresponding to the mutation at position 601 compared to SEQ ID NO:1.

[0031] 12. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579 and 592 compared to SEQ ID NO:1.

[0032] 13. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579 and 593 compared to SEQ ID NO:1.

[0033] 14. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579 and 595 compared to SEQ ID NO:1.

[0034] 15. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579 and 596 compared to SEQ ID NO:1.

[0035] 16. The variant capsid polypeptide of any of the preceding embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579 and 598 compared to SEQ ID NO:1.

[0036] 17. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579 and 601 compared to SEQ ID NO:1.

[0037] 18. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592 and 593 compared to SEQ ID NO:1.

[0038] 19. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592 and 595 compared to SEQ ID NO:1.

[0039] 20. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592 and 596 compared to SEQ ID NO:1.

[0040] 21. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592 and 598 compared to SEQ ID NO:1.

[0041] 22. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592 and 601 compared to SEQ ID NO:1.

[0042] 23. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 593 and 595 compared to SEQ ID NO:1.

[0043] 24. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 593 and 596 compared to SEQ ID NO:1.

[0044] 25. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 593 and 598 compared to SEQ ID NO:1.

[0045] 26. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 593 and 601 compared to SEQ ID NO:1.

[0046] 27. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 595 and 596 compared to SEQ ID NO:1.

[0047] 28. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 595 and 598 compared to SEQ ID NO:1.

[0048] 29. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 595 and 601 compared to SEQ ID NO:1.

[0049] 30. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 596 and 598 compared to SEQ ID NO:1.

[0050] 31. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 596 and 601 compared to SEQ ID NO:1.

[0051] 32. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 598 and 601 compared to SEQ ID NO:1.

[0052] 33. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592 and 593 compared to SEQ ID NO:1.

[0053] 34. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592 and 595 compared to SEQ ID NO:1.

[0054] 35. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592 and 596 compared to SEQ ID NO:1.

[0055] 36. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592 and 598 compared to SEQ ID NO:1.

[0056] 37. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592 and 601 compared to SEQ ID NO:1.

[0057] 38. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 593 and 595 compared to SEQ ID NO:1.

[0058] 39. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 593 and 596 compared to SEQ ID NO:1.

[0059] 40. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 593 and 598 compared to SEQ ID NO:1.

[0060] 41. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 593 and 601 compared to SEQ ID NO:1.

[0061] 42. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 595 and 596 compared to SEQ ID NO:1.

[0062] 43. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 595 and 598 compared to SEQ ID NO:1.

[0063] 44. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 595 and 601 compared to SEQ ID NO:1.

[0064] 45. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 596 and 598 compared to SEQ ID NO:1.

[0065] 46. ​​The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 596 and 601 compared to SEQ ID NO:1.

[0066] 47. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 598 and 601 compared to SEQ ID NO:1.

[0067] 48. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592, 593 and 595 compared to SEQ ID NO:1.

[0068] 49. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592, 593 and 596 compared to SEQ ID NO:1.

[0069] 50. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592, 593 and 598 compared to SEQ ID NO:1.

[0070] 51. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592, 593 and 601 compared to SEQ ID NO:1.

[0071] 52. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592, 595 and 596 compared to SEQ ID NO:1.

[0072] 53. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592, 595 and 598 compared to SEQ ID NO:1.

[0073] 54. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592, 595 and 601 compared to SEQ ID NO:1.

[0074] 55. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592, 596 and 598 compared to SEQ ID NO:1.

[0075] 56. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592, 596 and 601 compared to SEQ ID NO:1.

[0076] 57. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592, 598 and 601 compared to SEQ ID NO:1.

[0077] 58. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 593, 595 and 596 compared to SEQ ID NO:1.

[0078] 59. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 593, 595 and 598 compared to SEQ ID NO:1.

[0079] 60. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 593, 595 and 601 compared to SEQ ID NO:1.

[0080] 61. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 593, 596 and 598 compared to SEQ ID NO:1.

[0081] 62. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 593, 596 and 601 compared to SEQ ID NO:1.

[0082] 63. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 593, 598 and 601 compared to SEQ ID NO:1.

[0083] 64. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 595, 596 and 598 compared to SEQ ID NO:1.

[0084] 65. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 595, 596 and 601 compared to SEQ ID NO:1.

[0085] 66. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 595, 598 and 601 compared to SEQ ID NO:1.

[0086] 67. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 596, 598 and 601 compared to SEQ ID NO:1.

[0087] 68. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 593 and 595 compared to SEQ ID NO:1.

[0088] 69. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 593 and 596 compared to SEQ ID NO:1.

[0089] 70. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 593 and 598 compared to SEQ ID NO:1.

[0090] 71. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 593 and 601 compared to SEQ ID NO:1.

[0091] 72. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 593, 595 and 596 compared to SEQ ID NO:1.

[0092] 73. The variant capsid polypeptide of any of the previous embodiments, wherein the capsid polypeptide comprises mutations corresponding to mutations at positions 579, 593, 595 and 598 compared to SEQ ID NO:1.

[0093] 74. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 593, 595 and 601 compared to SEQ ID NO:1.

[0094] 75. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 595 and 596 compared to SEQ ID NO:1.

[0095] 76. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 595 and 598 compared to SEQ ID NO:1.

[0096] 77. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 595 and 601 compared to SEQ ID NO:1.

[0097] 78. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 593 and 596 compared to SEQ ID NO:1.

[0098] 79. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 593 and 598 compared to SEQ ID NO:1.

[0099] 80. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 593 and 601 compared to SEQ ID NO:1.

[0100] 81. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592, 593, 595 and 596 compared to SEQ ID NO:1.

[0101] 82. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592, 593, 595 and 598 compared to SEQ ID NO:1.

[0102] 83. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592, 593, 595 and 601 compared to SEQ ID NO:1.

[0103] 84. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 593, 595, 596 and 598 compared to SEQ ID NO:1.

[0104] 85. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 593, 595, 596 and 601 compared to SEQ ID NO:1.

[0105] 86. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 595, 596, 598 and 601 compared to SEQ ID NO:1.

[0106] 87. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 593, 595 and 596 compared to SEQ ID NO:1.

[0107] 88. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 593, 595 and 598 compared to SEQ ID NO:1.

[0108] 89. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 593, 595 and 601 compared to SEQ ID NO:1.

[0109] 90. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 593, 595, 596 and 598 compared to SEQ ID NO:1.

[0110] 91. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 593, 595, 596 and 601 compared to SEQ ID NO:1.

[0111] 92. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 595, 596 and 598 compared to SEQ ID NO:1.

[0112] 93. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 595, 596 and 601 compared to SEQ ID NO:1.

[0113] 94. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 593, 596 and 598 compared to SEQ ID NO:1.

[0114] 95. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 593, 596 and 601 compared to SEQ ID NO:1.

[0115] 96. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 593, 595 and 598 compared to SEQ ID NO:1.

[0116] 97. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 593, 595 and 601 compared to SEQ ID NO:1.

[0117] 98. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592, 593, 595, 596 and 598 compared to SEQ ID NO:1.

[0118] 99. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592, 593, 595, 596 and 601 compared to SEQ ID NO:1.

[0119] 100. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 593, 595, 596, 598 and 601 compared to SEQ ID NO:1.

[0120] 101. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 593, 595, 596 and 598 compared to SEQ ID NO:1.

[0121] 102. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 593, 595, 596 and 601 compared to SEQ ID NO:1.

[0122] 103. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592, 593, 595, 596, 598 and 601 compared to SEQ ID NO:1.

[0123] 104. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 593, 595, 596, 598 and 601 compared to SEQ ID NO:1.

[0124] 105. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 595, 596, 598 and 601 compared to SEQ ID NO:1.

[0125] 106. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 593, 596, 598 and 601 compared to SEQ ID NO:1.

[0126] 107. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 593, 595, 598 and 601 compared to SEQ ID NO:1.

[0127] 108. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 593, 595, 596, 598 and 601 compared to SEQ ID NO:1.

[0128] 109. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 596 and 598 compared to SEQ ID NO:1.

[0129] 110. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 596 and 601 compared to SEQ ID NO:1.

[0130] 111. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 598 and 601 compared to SEQ ID NO:1.

[0131] 112. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 593, 596 and 598 compared to SEQ ID NO:1.

[0132] 113. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 593, 596 and 601 compared to SEQ ID NO:1.

[0133] 114. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 593, 598 and 601 compared to SEQ ID NO:1.

[0134] 115. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 595, 596 and 598 compared to SEQ ID NO:1.

[0135] 116. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 595, 596 and 601 compared to SEQ ID NO:1.

[0136] 117. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 595, 598 and 601 compared to SEQ ID NO:1.

[0137] 118. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 596, 598 and 598 compared to SEQ ID NO:1.

[0138] 119. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592, 593, 596 and 598 compared to SEQ ID NO:1.

[0139] 120. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592, 593, 596 and 601 compared to SEQ ID NO:1.

[0140] 121. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592, 593, 598 and 601 compared to SEQ ID NO:1.

[0141] 122. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592, 595, 596 and 598 compared to SEQ ID NO:1.

[0142] 123. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592, 595, 596 and 601 compared to SEQ ID NO:1.

[0143] 124. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592, 595, 598 and 601 compared to SEQ ID NO:1.

[0144] 125. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592, 596, 598 and 601 compared to SEQ ID NO:1.

[0145] 126. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 593, 595, 598 and 601 compared to SEQ ID NO:1.

[0146] 127. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 593, 596, 598 and 601 compared to SEQ ID NO:1.

[0147] 128. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 593, 595, 598 and 601 compared to SEQ ID NO:1.

[0148] 129. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 593, 596, 598 and 601 compared to SEQ ID NO:1.

[0149] 130. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 595, 596, 598 and 601 compared to SEQ ID NO:1.

[0150] 131. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 595, 598 and 601 compared to SEQ ID NO:1.

[0151] 132. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 596, 598 and 601 compared to SEQ ID NO:1.

[0152] 133. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 595, 596, 598 and 601 compared to SEQ ID NO:1.

[0153] 134. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 593, 598 and 601 compared to SEQ ID NO:1.

[0154] 135. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592, 593, 595, 598 and 601 compared to SEQ ID NO:1.

[0155] 136. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592, 593, 596, 598 and 601 compared to SEQ ID NO:1.

[0156] 137. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592, 595, 596, 598 and 601 compared to SEQ ID NO:1.

[0157] 138. A variant capsid polypeptide, comprising a polypeptide having at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identity to the VP1, VP2, or VP3 sequence of SEQ ID NO: 1; (a) a valine at a position corresponding to Q579 compared to SEQ ID NO: 1; (b) an isoleucine at a position corresponding to Q592 compared to SEQ ID NO: 1; (c) a valine at a position corresponding to T593 compared to SEQ ID NO: 1; (d) an alanine at a position corresponding to W595 compared to SEQ ID NO: 1; (e) a leucine at a position corresponding to V596 compared to SEQ ID NO: 1; (f) a serine at a position corresponding to N598 compared to SEQ ID NO: 1; (g) an alanine at a position corresponding to I601 compared to SEQ ID NO: 1, or (h) Optionally, the variant capsid polypeptide comprises all of (a) through (g), including any combination thereof.

[0158] 139. The variant capsid polypeptide is: (a) a valine at a position corresponding to Q579 compared to SEQ ID NO: 1; (b) an isoleucine at a position corresponding to Q592 compared to SEQ ID NO: 1; (c) a valine at a position corresponding to T593 compared to SEQ ID NO: 1; (d) an alanine at a position corresponding to W595 compared to SEQ ID NO: 1; (e) a leucine at a position corresponding to V596 compared to SEQ ID NO: 1; (f) a serine at a position corresponding to N598 compared to SEQ ID NO: 1; (g) an alanine at a position corresponding to I601 compared to SEQ ID NO: 1, or (h) The variant capsid polypeptide of any of embodiments 1-138, optionally comprising all of (a)-(g), including any combination thereof.

[0159] 140. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579 compared to SEQ ID NO: 1.

[0160] 141. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises an isoleucine at a position corresponding to Q592 compared to SEQ ID NO: 1.

[0161] 142. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to T593 compared to SEQ ID NO: 1.

[0162] 143. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises an alanine at a position corresponding to W595 compared to SEQ ID NO:1.

[0163] 144. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a leucine at a position corresponding to V596 compared to SEQ ID NO:1.

[0164] 145. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a serine at a position corresponding to N598 compared to SEQ ID NO:1.

[0165] 146. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises an alanine at a position corresponding to I601 compared to SEQ ID NO: 1.

[0166] 147. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579 and an isoleucine at a position corresponding to Q592 compared to SEQ ID NO: 1.

[0167] 148. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579 and a valine at a position corresponding to T593 compared to SEQ ID NO: 1.

[0168] 149. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579 and an alanine at a position corresponding to W595 compared to SEQ ID NO: 1.

[0169] 150. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579 and a leucine at a position corresponding to V596 compared to SEQ ID NO: 1.

[0170] 151. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579 and a serine at a position corresponding to N598 compared to SEQ ID NO: 1.

[0171] 152. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579 and an alanine at a position corresponding to I601 compared to SEQ ID NO: 1.

[0172] 153. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises an isoleucine at the position corresponding to Q592 and a valine at the position corresponding to T593 compared to SEQ ID NO: 1.

[0173] 154. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises an isoleucine at the position corresponding to Q592 and an alanine at the position corresponding to W595 compared to SEQ ID NO: 1.

[0174] 155. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises an isoleucine at the position corresponding to Q592 and a leucine at the position corresponding to V596 compared to SEQ ID NO: 1.

[0175] 156. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises an isoleucine at a position corresponding to Q592 and a serine at a position corresponding to N598 compared to SEQ ID NO: 1.

[0176] 157. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises an isoleucine at a position corresponding to Q592 and an alanine at a position corresponding to I601 compared to SEQ ID NO: 1.

[0177] 158. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to T593 and an alanine at a position corresponding to W595 compared to SEQ ID NO: 1.

[0178] 159. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to T593 and a leucine at a position corresponding to V596 compared to SEQ ID NO: 1.

[0179] 160. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to T593 and a serine at a position corresponding to N598 compared to SEQ ID NO: 1.

[0180] 161. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to T593 and an alanine at a position corresponding to I601 compared to SEQ ID NO: 1.

[0181] 162. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises an alanine at a position corresponding to W595 and a leucine at a position corresponding to V596 compared to SEQ ID NO: 1.

[0182] 163. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises an alanine at a position corresponding to W595 and a serine at a position corresponding to N598 compared to SEQ ID NO: 1.

[0183] 164. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises an alanine at a position corresponding to W595 and an alanine at a position corresponding to I601 compared to SEQ ID NO: 1.

[0184] 165. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a leucine at a position corresponding to V596 and a serine at a position corresponding to N598 compared to SEQ ID NO: 1.

[0185] 166. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a leucine at a position corresponding to V596 and an alanine at a position corresponding to I601 compared to SEQ ID NO: 1.

[0186] 167. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a serine at a position corresponding to N598 and an alanine at a position corresponding to I601 compared to SEQ ID NO: 1.

[0187] 168. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, an isoleucine at a position corresponding to Q592, and a valine at a position corresponding to T593 compared to SEQ ID NO: 1.

[0188] 169. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, an isoleucine at a position corresponding to Q592, and an alanine at a position corresponding to W595 compared to SEQ ID NO: 1.

[0189] 170. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, an isoleucine at a position corresponding to Q592, and a leucine at a position corresponding to V596 compared to SEQ ID NO: 1.

[0190] 171. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, an isoleucine at a position corresponding to Q592, and a serine at a position corresponding to N598 compared to SEQ ID NO: 1.

[0191] 172. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, an isoleucine at a position corresponding to Q592, and an alanine at a position corresponding to I601 compared to SEQ ID NO: 1.

[0192] 173. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, a valine at a position corresponding to T593, and an alanine at a position corresponding to W595 compared to SEQ ID NO: 1.

[0193] 174. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, a valine at a position corresponding to T593, and a leucine at a position corresponding to V596 compared to SEQ ID NO: 1.

[0194] 175. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, a valine at a position corresponding to T593, and a serine at a position corresponding to N598 compared to SEQ ID NO: 1.

[0195] 176. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, a valine at a position corresponding to T593, and an alanine at a position corresponding to I601 compared to SEQ ID NO: 1.

[0196] 177. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, an alanine at a position corresponding to W595, and a leucine at a position corresponding to V596 compared to SEQ ID NO: 1.

[0197] 178. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, an alanine at a position corresponding to W595, and a serine at a position corresponding to N598 compared to SEQ ID NO: 1.

[0198] 179. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, an alanine at a position corresponding to W595, and an alanine at a position corresponding to I601 compared to SEQ ID NO: 1.

[0199] 180. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, a leucine at a position corresponding to V596, and a serine at a position corresponding to N598 compared to SEQ ID NO: 1.

[0200] 181. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, a leucine at a position corresponding to V596, and an alanine at a position corresponding to I601 compared to SEQ ID NO: 1.

[0201] 182. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, a serine at a position corresponding to N598, and an alanine at a position corresponding to I601 compared to SEQ ID NO: 1.

[0202] 183. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises an isoleucine at a position corresponding to Q592, a valine at a position corresponding to T593, and an alanine at a position corresponding to W595 compared to SEQ ID NO: 1.

[0203] 184. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises an isoleucine at a position corresponding to Q592, a valine at a position corresponding to T593, and a leucine at a position corresponding to V596 compared to SEQ ID NO: 1.

[0204] 185. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises an isoleucine at a position corresponding to Q592, a valine at a position corresponding to T593, and a serine at a position corresponding to N598 compared to SEQ ID NO: 1.

[0205] 186. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises an isoleucine at a position corresponding to Q592, a valine at a position corresponding to T593, and an alanine at a position corresponding to I601 compared to SEQ ID NO: 1.

[0206] 187. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises an isoleucine at a position corresponding to Q592, an alanine at a position corresponding to W595, and a leucine at a position corresponding to V596 compared to SEQ ID NO: 1.

[0207] 188. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises an isoleucine at a position corresponding to Q592, an alanine at a position corresponding to W595, and a serine at a position corresponding to N598 compared to SEQ ID NO: 1.

[0208] 189. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises an isoleucine at a position corresponding to Q592, an alanine at a position corresponding to W595, and an alanine at a position corresponding to I601 compared to SEQ ID NO: 1.

[0209] 190. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises an isoleucine at a position corresponding to Q592, a leucine at a position corresponding to V596, and a serine at a position corresponding to N598 compared to SEQ ID NO: 1.

[0210] 191. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises an isoleucine at a position corresponding to Q592, a leucine at a position corresponding to V596, and an alanine at a position corresponding to I601 compared to SEQ ID NO: 1.

[0211] 192. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises an isoleucine at a position corresponding to Q592, a serine at a position corresponding to N598, and an alanine at a position corresponding to I601 compared to SEQ ID NO: 1.

[0212] 193. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to T593, an alanine at a position corresponding to W595, and a leucine at a position corresponding to V596 compared to SEQ ID NO: 1.

[0213] 194. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to T593, an alanine at a position corresponding to W595, and a serine at a position corresponding to N598 compared to SEQ ID NO: 1.

[0214] 195. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to T593, an alanine at a position corresponding to W595, and an alanine at a position corresponding to I601 compared to SEQ ID NO: 1.

[0215] 196. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to T593, a leucine at a position corresponding to V596, and a serine at a position corresponding to N598 compared to SEQ ID NO: 1.

[0216] 197. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to T593, a leucine at a position corresponding to V596, and an alanine at a position corresponding to I601 compared to SEQ ID NO: 1.

[0217] 198. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to T593, a serine at a position corresponding to N598, and an alanine at a position corresponding to I601 compared to SEQ ID NO: 1.

[0218] 199. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises an alanine at a position corresponding to W595, a leucine at a position corresponding to V596, and a serine at a position corresponding to N598 compared to SEQ ID NO:1.

[0219] 200. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises an alanine at a position corresponding to W595, a leucine at a position corresponding to V596, and an alanine at a position corresponding to I601 compared to SEQ ID NO:1.

[0220] 201. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises an alanine at a position corresponding to W595, a serine at a position corresponding to N598, and an alanine at a position corresponding to I601 compared to SEQ ID NO:1.

[0221] 202. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a leucine at a position corresponding to V596, a serine at a position corresponding to N598, and an alanine at a position corresponding to I601 compared to SEQ ID NO: 1.

[0222] 203. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, an isoleucine at a position corresponding to Q592, a valine at a position corresponding to T593, and an alanine at a position corresponding to W595, relative to SEQ ID NO: 1.

[0223] 204. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, an isoleucine at a position corresponding to Q592, a valine at a position corresponding to T593, and a leucine at a position corresponding to V596, relative to SEQ ID NO: 1.

[0224] 205. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, an isoleucine at a position corresponding to Q592, a valine at a position corresponding to T593, and a serine at a position corresponding to N598 compared to SEQ ID NO: 1.

[0225] 206. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, an isoleucine at a position corresponding to Q592, a valine at a position corresponding to T593, and an alanine at a position corresponding to I601, relative to SEQ ID NO: 1.

[0226] 207. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, an isoleucine at a position corresponding to Q592, an alanine at a position corresponding to W595, and a leucine at a position corresponding to V596 compared to SEQ ID NO: 1.

[0227] 208. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, an isoleucine at a position corresponding to Q592, an alanine at a position corresponding to W595, and a serine at a position corresponding to N598 compared to SEQ ID NO: 1.

[0228] 209. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, an isoleucine at a position corresponding to Q592, an alanine at a position corresponding to W595, and an alanine at a position corresponding to I601, relative to SEQ ID NO: 1.

[0229] 210. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, an isoleucine at a position corresponding to Q592, an alanine at a position corresponding to W595, and a leucine at a position corresponding to V596, compared to SEQ ID NO: 1.

[0230] 211. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, an isoleucine at a position corresponding to Q592, an alanine at a position corresponding to W595, and a serine at a position corresponding to N598 compared to SEQ ID NO: 1.

[0231] 212. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, an isoleucine at a position corresponding to Q592, an alanine at a position corresponding to W595, and an alanine at a position corresponding to I601, relative to SEQ ID NO: 1.

[0232] 213. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, an isoleucine at a position corresponding to Q592, a valine at a position corresponding to T593, and a leucine at a position corresponding to V596, relative to SEQ ID NO: 1.

[0233] 214. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, an isoleucine at a position corresponding to Q592, a valine at a position corresponding to T593, and a serine at a position corresponding to N598 compared to SEQ ID NO: 1.

[0234] 215. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, an isoleucine at a position corresponding to Q592, a valine at a position corresponding to T593, and an alanine at a position corresponding to I601, relative to SEQ ID NO: 1.

[0235] 216. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises an isoleucine at a position corresponding to Q592, a valine at a position corresponding to T593, an alanine at a position corresponding to W595, and n596s compared to SEQ ID NO: 1.

[0236] 217. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises an isoleucine at a position corresponding to Q592, a valine at a position corresponding to T593, an alanine at a position corresponding to W595, and a serine at a position corresponding to N598 compared to SEQ ID NO: 1.

[0237] 218. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises an isoleucine at a position corresponding to Q592, a valine at a position corresponding to T593, an alanine at a position corresponding to W595, and an alanine at a position corresponding to I601 compared to SEQ ID NO: 1.

[0238] 219. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to T593, an alanine at a position corresponding to W595, a leucine at a position corresponding to V596, and a serine at a position corresponding to N598, compared to SEQ ID NO: 1.

[0239] 220. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to T593, an alanine at a position corresponding to W595, a leucine at a position corresponding to V596, and an alanine at a position corresponding to I601, compared to SEQ ID NO: 1.

[0240] 221. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises an alanine at a position corresponding to W595, a leucine at a position corresponding to V596, a serine at a position corresponding to N598, and an alanine at a position corresponding to I601 compared to SEQ ID NO:1.

[0241] 222. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, an isoleucine at a position corresponding to Q592, a valine at a position corresponding to T593, an alanine at a position corresponding to W595, and a leucine at a position corresponding to V596, relative to SEQ ID NO: 1.

[0242] 223. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, an isoleucine at a position corresponding to Q592, a valine at a position corresponding to T593, an alanine at a position corresponding to W595, and a serine at a position corresponding to N598, relative to SEQ ID NO: 1.

[0243] 224. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, an isoleucine at a position corresponding to Q592, a valine at a position corresponding to T593, an alanine at a position corresponding to W595, and an alanine at a position corresponding to I601, relative to SEQ ID NO: 1.

[0244] 225. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, a valine at a position corresponding to T593, an alanine at a position corresponding to W595, a leucine at a position corresponding to V596, and a serine at a position corresponding to N598, relative to SEQ ID NO: 1.

[0245] 226. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, a valine at a position corresponding to T593, an alanine at a position corresponding to W595, a leucine at a position corresponding to V596, and an alanine at a position corresponding to I601, relative to SEQ ID NO: 1.

[0246] 227. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, an isoleucine at a position corresponding to Q592, an alanine at a position corresponding to W595, a leucine at a position corresponding to V596, and a serine at a position corresponding to N598, relative to SEQ ID NO: 1.

[0247] 228. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, an isoleucine at a position corresponding to Q592, an alanine at a position corresponding to W595, a leucine at a position corresponding to V596, and an alanine at a position corresponding to I601, relative to SEQ ID NO: 1.

[0248] 229. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, an isoleucine at a position corresponding to Q592, a valine at a position corresponding to T593, a leucine at a position corresponding to V596, and a serine at a position corresponding to N598, relative to SEQ ID NO: 1.

[0249] 230. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, an isoleucine at a position corresponding to Q592, a valine at a position corresponding to T593, a leucine at a position corresponding to V596, and an alanine at a position corresponding to I601, relative to SEQ ID NO: 1.

[0250] 231. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, an isoleucine at a position corresponding to Q592, a valine at a position corresponding to T593, an alanine at a position corresponding to W595, and a serine at a position corresponding to N598, relative to SEQ ID NO: 1.

[0251] 232. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, an isoleucine at a position corresponding to Q592, a valine at a position corresponding to T593, an alanine at a position corresponding to W595, and an alanine at a position corresponding to I601, relative to SEQ ID NO: 1.

[0252] 233. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises an isoleucine at a position corresponding to Q592, a valine at a position corresponding to T593, an alanine at a position corresponding to W595, a leucine at a position corresponding to V596, and a serine at a position corresponding to N598, relative to SEQ ID NO: 1.

[0253] 234. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises an isoleucine at a position corresponding to Q592, a valine at a position corresponding to T593, an alanine at a position corresponding to W595, a leucine at a position corresponding to V596, and an alanine at a position corresponding to I601, relative to SEQ ID NO: 1.

[0254] 235. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to T593, an alanine at a position corresponding to W595, a leucine at a position corresponding to V596, a serine at a position corresponding to N598, and an alanine at a position corresponding to I601, compared to SEQ ID NO: 1.

[0255] 236. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, an isoleucine at a position corresponding to Q592, a valine at a position corresponding to T593, an alanine at a position corresponding to W595, a leucine at a position corresponding to V596, and a serine at a position corresponding to N598, relative to SEQ ID NO: 1.

[0256] 237. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, an isoleucine at a position corresponding to Q592, a valine at a position corresponding to T593, an alanine at a position corresponding to W595, a leucine at a position corresponding to V596, and an alanine at a position corresponding to I601, relative to SEQ ID NO: 1.

[0257] 238. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q592, a valine at a position corresponding to T593, an alanine at a position corresponding to W595, a leucine at a position corresponding to V596, a serine at a position corresponding to N598, and an alanine at a position corresponding to I601, relative to SEQ ID NO: 1.

[0258] 239. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, a valine at a position corresponding to T593, an alanine at a position corresponding to W595, a leucine at a position corresponding to V596, a serine at a position corresponding to N598, and an alanine at a position corresponding to I601, relative to SEQ ID NO: 1.

[0259] 240. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, an isoleucine at a position corresponding to Q592, an alanine at a position corresponding to W595, a leucine at a position corresponding to V596, a serine at a position corresponding to N598, and an alanine at a position corresponding to I601, relative to SEQ ID NO: 1.

[0260] 241. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, an isoleucine at a position corresponding to Q592, a valine at a position corresponding to T593, a leucine at a position corresponding to V596, a serine at a position corresponding to N598, and an alanine at a position corresponding to I601, relative to SEQ ID NO: 1.

[0261] 242. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, an isoleucine at a position corresponding to Q592, a valine at a position corresponding to T593, an alanine at a position corresponding to W595, a serine at a position corresponding to N598, and an alanine at a position corresponding to I601, relative to SEQ ID NO: 1.

[0262] 243. The variant capsid polypeptide of any of the preceding embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, an isoleucine at a position corresponding to Q592, a valine at a position corresponding to T593, an alanine at a position corresponding to W595, a leucine at a position corresponding to V596, a serine at a position corresponding to N598, and an alanine at a position corresponding to I601, relative to SEQ ID NO: 1.

[0263] 244. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, an isoleucine at a position corresponding to Q592, a leucine at a position corresponding to V596, and a serine at a position corresponding to N598 compared to SEQ ID NO: 1.

[0264] 245. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, an isoleucine at a position corresponding to Q592, a leucine at a position corresponding to V596, and an alanine at a position corresponding to I601 compared to SEQ ID NO: 1.

[0265] 246. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, an isoleucine at a position corresponding to Q592, a serine at a position corresponding to N598, and an alanine at a position corresponding to I601 compared to SEQ ID NO: 1.

[0266] 247. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, a valine at a position corresponding to T593, a leucine at a position corresponding to V596, and a serine at a position corresponding to N598 compared to SEQ ID NO: 1.

[0267] 248. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, a valine at a position corresponding to T593, a leucine at a position corresponding to V596, and an alanine at a position corresponding to I601, compared to SEQ ID NO: 1.

[0268] 249. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, a valine at a position corresponding to T593, a serine at a position corresponding to N598, and an alanine at a position corresponding to I601, compared to SEQ ID NO: 1.

[0269] 250. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, an alanine at a position corresponding to W595, a leucine at a position corresponding to V596, and a serine at a position corresponding to N598 compared to SEQ ID NO: 1.

[0270] 251. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, an alanine at a position corresponding to W595, a leucine at a position corresponding to V596, and an alanine at a position corresponding to I601, compared to SEQ ID NO: 1.

[0271] 252. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, an alanine at a position corresponding to W595, a serine at a position corresponding to N598, and an alanine at a position corresponding to I601, compared to SEQ ID NO: 1.

[0272] 253. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises an isoleucine at a position corresponding to Q592, a valine at a position corresponding to T593, a leucine at a position corresponding to V596, and a serine at a position corresponding to N598 compared to SEQ ID NO: 1.

[0273] 254. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises an isoleucine at a position corresponding to Q592, a valine at a position corresponding to T593, a leucine at a position corresponding to V596, and an alanine at a position corresponding to I601 compared to SEQ ID NO: 1.

[0274] 255. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises an isoleucine at a position corresponding to Q592, a valine at a position corresponding to T593, a serine at a position corresponding to N598, and an alanine at a position corresponding to I601 compared to SEQ ID NO: 1.

[0275] 256. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises an isoleucine at a position corresponding to Q592, an alanine at a position corresponding to W595, a leucine at a position corresponding to V596, and a serine at a position corresponding to N598 compared to SEQ ID NO: 1.

[0276] 257. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises an isoleucine at a position corresponding to Q592, an alanine at a position corresponding to W595, a leucine at a position corresponding to V596, and an alanine at a position corresponding to I601 compared to SEQ ID NO: 1.

[0277] 258. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises an isoleucine at a position corresponding to Q592, an alanine at a position corresponding to W595, a serine at a position corresponding to N598, and an alanine at a position corresponding to I601 compared to SEQ ID NO: 1.

[0278] 259. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises an isoleucine at a position corresponding to Q592, a leucine at a position corresponding to V596, a serine at a position corresponding to N598, and an alanine at a position corresponding to I601 compared to SEQ ID NO: 1.

[0279] 260. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to T593, an alanine at a position corresponding to W595, a serine at a position corresponding to N598, and an alanine at a position corresponding to I601, compared to SEQ ID NO: 1.

[0280] 261. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to T593, a leucine at a position corresponding to V596, a serine at a position corresponding to N598, and an alanine at a position corresponding to I601 compared to SEQ ID NO: 1.

[0281] 262. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, a valine at a position corresponding to T593, an alanine at a position corresponding to W595, a serine at a position corresponding to N598, and an alanine at a position corresponding to I601, relative to SEQ ID NO: 1.

[0282] 263. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, a valine at a position corresponding to T593, a leucine at a position corresponding to V596, a serine at a position corresponding to N598, and an alanine at a position corresponding to I601, relative to SEQ ID NO: 1.

[0283] 264. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, an alanine at a position corresponding to W595, a leucine at a position corresponding to V596, a serine at a position corresponding to N598, and an alanine at a position corresponding to I601, relative to SEQ ID NO: 1.

[0284] 265. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, an isoleucine at a position corresponding to Q592, an alanine at a position corresponding to W595, a serine at a position corresponding to N598, and an alanine at a position corresponding to I601, relative to SEQ ID NO: 1.

[0285] 266. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, an isoleucine at a position corresponding to Q592, a leucine at a position corresponding to V596, a serine at a position corresponding to N598, and an alanine at a position corresponding to I601, relative to SEQ ID NO: 1.

[0286] 267. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, an alanine at a position corresponding to W595, a leucine at a position corresponding to V596, a serine at a position corresponding to N598, and an alanine at a position corresponding to I601, relative to SEQ ID NO: 1.

[0287] 268. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579, an isoleucine at a position corresponding to Q592, a valine at a position corresponding to T593, a serine at a position corresponding to N598, and an alanine at a position corresponding to I601, relative to SEQ ID NO: 1.

[0288] 268. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q592, a valine at a position corresponding to T593, an alanine at a position corresponding to W595, a serine at a position corresponding to N598, and an alanine at a position corresponding to I601, relative to SEQ ID NO: 1.

[0289] 269. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q592, a valine at a position corresponding to T593, a leucine at a position corresponding to V596, a serine at a position corresponding to N598, and an alanine at a position corresponding to I601, relative to SEQ ID NO: 1.

[0290] 270. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q592, an alanine at a position corresponding to W595, a leucine at a position corresponding to V596, a serine at a position corresponding to N598, and an alanine at a position corresponding to I601, relative to SEQ ID NO: 1.

[0291] 271. A variant capsid polypeptide (e.g., VP1, VP2, or VP3) that is at least, or about, 95, 96, 97, 98, or 99% identical to the capsid polypeptide of SEQ ID NO:2 (e.g., VP1, VP2, or VP3 polypeptide SEQ ID NO:2) and contains at least four, at least five, at least six, and optionally all mutational differences of VAR-1.

[0292] 272. A variant capsid polypeptide (e.g., VP1, VP2, or VP3) having about 1 to about 20 mutations compared to the capsid polypeptide (e.g., VP1, VP2, or VP3) of SEQ ID NO:2, and including at least 4, at least 5, at least 6, and optionally all of the mutational differences of VAR-1.

[0293] 273. The variant capsid polypeptide of embodiment 215, having about 1 to about 10 mutations compared to the capsid polypeptide (e.g., VP1, VP2, or VP3).

[0294] 274. The variant capsid polypeptide of embodiment 215, having about 1 to about 5 mutations compared to the capsid polypeptide (e.g., VP1, VP2, or VP3).

[0295] 275. A variant capsid polypeptide (e.g., VP1, VP2, or VP3) that is at least, or about, 95, 96, 97, 98, or 99% identical to the polypeptide of SEQ ID NO:2 and that comprises a valine at a position corresponding to 596L according to SEQ ID NO:1.

[0296] 276. A variant capsid polypeptide (e.g., VP1, VP2, or VP3) having about 1 to about 20 mutations compared to the capsid polypeptide of SEQ ID NO:2 (e.g., VP1, VP2, or VP3), and comprising a valine at a position corresponding to 596L according to SEQ ID NO:1.

[0297] 277. The variant capsid polypeptide of embodiment 219, having about 1 to about 10 mutations compared to the capsid polypeptide of SEQ ID NO: 2 (e.g., VP1, VP2, or VP3).

[0298] 278. The variant capsid polypeptide of embodiment 219, having about 1 to about 5 mutations compared to the capsid polypeptide of SEQ ID NO: 2 (e.g., VP1, VP2, or VP3).

[0299] 279. A variant capsid polypeptide comprising the VP1, VP2, or VP3 sequence of SEQ ID NO:2.

[0300] 280. A variant capsid polypeptide consisting of the VP1 sequence, VP2 sequence, or VP3 sequence of SEQ ID NO:2.

[0301] 281. The variant capsid polypeptide of any of the previous embodiments, wherein the variant capsid polypeptide is a VP1 polypeptide, a VP2 polypeptide, or a VP3 polypeptide.

[0302] 282. A nucleic acid molecule encoding the capsid variant polypeptide of any one of the preceding embodiments.

[0303] 283. The nucleic acid molecule of embodiment 282, wherein the nucleic acid molecule comprises the sequence of SEQ ID NO: 3, a fragment thereof (e.g., a VP1-encoding fragment, a VP2-encoding fragment, or a VP3-encoding fragment thereof), or a sequence having at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% sequence identity thereto.

[0304] 284. The nucleic acid molecule of embodiment 282 or 283, wherein the fragment encodes a VP2 capsid polypeptide or a VP3 capsid polypeptide.

[0305] 285. The nucleic acid molecule of embodiment 282 or 283, wherein the nucleic acid molecule comprises the sequence SEQ ID NO: 3.

[0306] 286. A viral particle (e.g., an adeno-associated virus ("AAV") particle) comprising a variant capsid polypeptide of any one of the preceding embodiments, or comprising a variant capsid polypeptide encoded by a nucleic acid molecule of any one of embodiments 282-285.

[0307] 287. The viral particle of embodiment 286, comprising a payload (e.g., a heterologous transgene) and a nucleic acid comprising one or more regulatory elements.

[0308] 288. A viral particle described in any one of embodiments 286 to 287, wherein the viral particle exhibits increased central nervous system (CNS) biodistribution compared to wild-type AAV9 (e.g., a viral particle comprising the capsid polypeptide of SEQ ID NO: 1 or encoded by SEQ ID NO: 4), e.g., when measured in a mammal, e.g., a mouse or NHP, e.g., as described herein, and optionally the biodistribution is at least 10-fold, at least 20-fold, at least 32-fold, at least 45-fold, or greater than the biodistribution of viral particles comprising the capsid polypeptide of SEQ ID NO: 1.

[0309] 289. The viral particle of embodiment 288, wherein increased CNS biodistribution is demonstrated upon systemic administration, e.g., intravenous administration, of the viral particle.

[0310] 290. A viral particle according to any of embodiments 286 to 289, wherein the viral particle exhibits greater CNS biodistribution than peripheral nervous system (PNS) biodistribution, optionally with a ratio of CNS biodistribution to PNS biodistribution of at least 10, at least 20, or at least 25, or greater, optionally as measured after systemic administration, e.g., intravenous administration, of the viral particle.

[0311] 291. A viral particle according to any of embodiments 286 to 290, wherein the viral particle exhibits increased transduction in the CNS compared to wild-type AAV9 (e.g., a viral particle comprising the capsid polypeptide of SEQ ID NO: 1 or encoded by SEQ ID NO: 4), e.g., when measured in a mammal, e.g., a mouse or NHP, e.g., as described herein, and optionally, the transduction is at least 10-fold, at least 20-fold, at least 50-fold, at least 60-fold, at least 65-fold, at least 70-fold, at least 75-fold, or greater than the transduction of a viral particle comprising the capsid polypeptide of SEQ ID NO: 1.

[0312] 292. The virus particles are reduced hepatic biodistribution, Decreased splenic biodistribution, Decreased muscle biodistribution, reduced cardiac biodistribution, Decreased liver transduction, or exhibiting one or more, e.g., all, of reduced cardiac transduction; A viral particle described in any of embodiments 286 to 291, wherein, in each case, compared to a wild-type AAV9 (e.g., a viral particle comprising the capsid polypeptide of SEQ ID NO: 1 or encoded by SEQ ID NO: 4), optionally the transduction or biodistribution is at least 1-fold, at least 2-fold, at least 3-fold, at least 4-fold, at least 5-fold, or at least 10-fold lower than the transduction or biodistribution of a viral particle comprising the capsid polypeptide of SEQ ID NO: 1, when measured, for example, in a mammal, such as a mouse or NHP.

[0313] 293. The nucleic acid molecule according to any one of embodiments 282 to 285, wherein the nucleic acid molecule is double-stranded or single-stranded, the nucleic acid molecule is linear or circular, for example, the nucleic acid molecule is a plasmid.

[0314] 294. A method for producing viral particles comprising a variant capsid polypeptide, the method comprising introducing a nucleic acid molecule described in any one of embodiments 282 to 285 or 293 into cells (e.g., HEK293 cells) and recovering the viral particles therefrom.

[0315] 295. A method of delivering a payload (e.g., a nucleic acid) to a cell, comprising contacting the cell with a viral particle comprising a variant capsid polypeptide and a payload of any one of the preceding embodiments, or contacting the cell with a viral particle of any one of embodiments 286-292.

[0316] 296. The method of embodiment 295, wherein the cell is a CNS cell.

[0317] 297. The method of embodiment 296, wherein the CNS cells are neurons, glial cells, astrocytes, oligodendrocytes, endothelial cells, or any combination thereof.

[0318] 298. A method of delivering a payload (e.g., a nucleic acid) to a subject, comprising administering to the subject a viral particle comprising a variant capsid polypeptide and a payload described in any one of the preceding embodiments, or administering to the subject a viral particle described in any one of embodiments 286-292.

[0319] 299. The method of embodiment 298, wherein the viral particles deliver the payload to the CNS.

[0320] 300. The variant capsid polypeptide of any one of the preceding embodiments, the viral particle of any one of embodiments 286-292, or the method of any one of embodiments 294-299, wherein the viral particle (e.g., the viral particle comprising the variant capsid polypeptide) delivers a payload to the CNS with increased biodistribution and / or transduction, e.g., biodistribution compared to viral particles comprising the capsid polypeptide of SEQ ID NO: 1, and optionally the biodistribution is at least 10-fold, at least 20-fold, at least 32-fold, at least 50-fold, at least 75-fold, or more, than the biodistribution and / or transduction of viral particles comprising the capsid polypeptide of SEQ ID NO: 1.

[0321] 301. The variant capsid polypeptide, viral particle, or method of embodiment 300, wherein the one or more cells of the CNS are selected from neurons, glial cells, astrocytes, oligodendrocytes, endothelial cells, or any combination thereof.

[0322] 302. A method of treating a disease or condition in a subject, comprising administering to the subject a viral particle or composition of embodiment 312 in an amount effective to treat the disease or condition, wherein the viral particle is a particle comprising a variant capsid polypeptide of any one of the preceding embodiments, or comprises a variant capsid polypeptide encoded by a nucleic acid molecule of any one of embodiments 282-285 or 293, or is a viral particle of any one of embodiments 286-292.

[0323] 303. The method of embodiment 302, wherein the disease or condition is a disease or condition of the CNS.

[0324] 304. The disease or condition is septum pellucidum defect, acid lipase disease, acid maltase deficiency, acquired epileptic aphasia, acute disseminated encephalomyelitis, attention-deficit hyperactivity disorder (ADHD), Adie pupil, Adie syndrome, adrenoleukodystrophy, agenesis of the corpus callosum, agnosia, Aicardi syndrome, Aicardi-Goutières syndrome disorder, AIDS-neurological complications, Alexander disease, Alpers disease, alternating hemiplegia, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), anencephaly, aneurysm, Angelman syndrome, hemangiomatosis, Angleman syndrome, anoxia , antiphospholipid syndrome, aphasia, apraxia, arachnoid cyst, arachnoiditis, Arnold-Chiari malformation, arteriovenous malformation, Asperger's syndrome, ataxia, ataxia-telangiectasia, ataxia and cerebellar or spinocerebellar degeneration, atrial fibrillation and stroke, attention-deficit hyperactivity disorder, autism spectrum disorder, autonomic dysfunction, back pain, Barth syndrome, Batten disease, Becker's myotonia, Behçet's disease, Bell's palsy, benign essential blepharospasm, benign focal muscular atrophy, benign intracranial hypertension, Bernhard-Roth syndrome, Binswanger's disease, blepharospasm, Bloch-Sulzberger syndrome syndrome, brachial plexus birth injury, brachial plexus injury, Bradbury-Eggleston syndrome, brain and spinal cord tumors (including, but not limited to, those that metastasize to the brain, e.g., metastatic breast cancer), cerebral aneurysm, brain injury, Brown-Séquard syndrome, bulbar palsy, spinal-bulbar muscular atrophy, cerebral autosomal dominant arteriopathy with subcortical infarctions and progressive leukoencephalopathy (CADASIL), Canavan disease, carpal tunnel syndrome, causal pain, cavernoma, cavernous hemangioma, cavernous vascular malformation, central cervical spinal cord syndrome, cervical spinal cord syndrome, central pain syndrome, central pontine myelinolysis, head injury, ceramidase deficiency, cerebellar degeneration, cerebellar hypoplasia, cerebral aneurysm , cerebral arteriosclerosis, cerebral atrophy, cerebral beriberi, cerebral cavernous malformations, cerebral gigantism, cerebral hypoxia, cerebral palsy, cerebro-oculofacial-skeletal syndrome (COFS), Charcot-Marie-Tooth disease, Chiari malformation, cholesterol ester storage disease, chorea, chorea acanthocytosis, chronic inflammatory demyelinating polyneuropathy (CIDP), chronic orthostatic intolerance, chronic pain, Cockayne syndrome type II, Coffin-Lowry syndrome, posterior horn enlargement of the lateral ventricles, coma, complex regional pain syndrome, concentric sclerosis (Balo's sclerosis), congenital bilateral facial nerve palsy, congenital myasthenia, congenital myopathy, congenital cavernous malformations,Corticobasal degeneration, cranial arteritis, craniosynostosis, Cree encephalitis, Creutzfeldt-Jakob disease, chronic progressive external ophthalmoplegia, cumulative trauma disorder, Cushing's syndrome, cytomegalic inclusion disease, cytomegalovirus infection, dancing eyes dancing feet syndrome, Dandy-Walker syndrome, Dawson's disease, Domorsia syndrome, Dejerine-Klumpke palsy, dementia, multi-infarct dementia, semantic dementia, subcortical dementia, dementia with Lewy bodies, demyelination, dentate cerebellar ataxia, Dentatorubral atrophy, dermatomyositis, developmental apraxia, Devic's syndrome, diabetic neuropathy, diffuse sclerosis, distal hereditary motor neuropathy, Dravet syndrome, autonomic neuropathy, dysgraphia, dyslexia, dysphagia, dyspraxia, myoclonic cerebellar dyssynergia, progressive cerebellar dyssynergia, dystonia, early infantile epileptic encephalopathy, Empty-Sella syndrome, encephalitis, encephalitis lethargica, encephalocele, encephalomyelitis, encephalopathy, encephalopathy (familial infantile), trigeminal angiomatosis, epilepsy, epileptic hemiplegia Paralysis, episodic ataxia, Erb's palsy, Erb-Duchenne and Dejurin-Klumpke palsy, essential tremor, extrapontine myelinolysis, Farber disease, Fabry disease, Fahr's syndrome, syncope, familial dysautonomia, familial hemangioma, familial idiopathic basal ganglia calcification, familial periodic paralysis, familial spastic paralysis, Farber disease, febrile seizures, fibromuscular dysplasia, Fisher syndrome, floppy infant syndrome, foot drop, fragile X syndrome, Friedreich's ataxia, frontotemporal dementia, Gorschi syndrome Göttingen's disease, systemic gangliosidosis (GM1, GM2), Gerstmann's syndrome, Gerstmann-Straussler-Scheinker disease, giant axonal neuropathy, giant cell arteritis, giant cell inclusion body disease, globoid cell leukodystrophy, glossopharyngeal neuralgia, glycogen storage disease, Guillain-Barré syndrome, Hallervorden-Spatz syndrome, head injury, headache, persistent hemicrania, hemifacial spasm, alternating hemiplegia, hereditary neuropathies, hereditary spastic paraplegia, hereditary polyneuropathies, herpes zoster Zoster), herpes zoster oticus, Hirayama disease, Holmes-Addie syndrome, holoprosencephaly, HTLV-1-associated myelopathy, Hughes syndrome, Huntington's disease, Hurler syndrome, hydroanencephaly, hydrocephalus, normal pressure hydrocephalus, hydromyelopathy, hyperadrenocorticism, hypersomnia, hypertonia, hypotonia, hypoxia,Immune-mediated encephalomyelitis, inclusion body myositis, incontinentia pigmenti, childhood hypotonia, childhood neuroaxonal dystrophy, childhood phytanic acid storage disease, childhood Refsum's disease, infantile spasms, inflammatory myopathy, foramen occipitalis prolapse, intestinal lipodystrophy, intracranial cyst, intracranial hypertension, Isaacs syndrome, Joubert syndrome, Kearns-Sayre syndrome, Kennedy disease, Kinsbourne syndrome, Kleine-Levin syndrome, Klippel-Feil syndrome, Klippel-Trenaunay syndrome (KTS), Klüver-Bucy syndrome, Korsakoff amnesic syndrome, Krabbe disease, Kugel syndrome Leberg-Welander disease, Kuru, Lambert-Eaton myasthenic syndrome, Landau-Kleffner syndrome, Lateral femoral cutaneous nerve entrapment, Lateral bulbar syndrome, Learning disability, Leigh's disease, Lennox-Gastaut syndrome, Lesch-Nyhan syndrome, Leukodystrophy, Levine-Critchley syndrome, Dementia with Lewy bodies, Lichtheim's disease, Lipid storage disease, Lipoid proteinosis, Lissencephaly, Locked-in syndrome, Lou Gehrig's disease, Lupus - neurological sequelae, Lyme disease - neurological complications, Lysosomal storage disease, Machado-Joseph disease, Megalencephaly, Megalencephaly, Merck Rosenthal syndrome, meningitis, meningitis and encephalitis, Menkes disease, lateral femoral cutaneous neuralgia, metachromatic leukodystrophy, microcephaly, migraine, Miller Fisher syndrome, petit mal seizures, mitochondrial myopathy, mitochondrial DNA depletion syndrome, Moebius syndrome, hemiatrophy, Morvan syndrome, motor neuron disease, moyamoya disease, mucolipidosis, mucopolysaccharidoses, multi-infarct dementia, multifocal motor neuropathy, multiple sclerosis, multiple system atrophy, multiple system atrophy with orthostatic hypotension, muscular dystrophy, congenital myasthenia, myasthenia gravis, demyelinating diffuse sclerosis, spinal cord Myelitis, myoclonic encephalopathy of childhood, myoclonus, myoclonic epilepsy, myopathy, congenital myopathy, thyrotoxic myopathy, myotonia, congenital myotonia, narcolepsy, NARP (neuropathy, ataxia and retinitis pigmentosa), neuroacanthocytosis, neurodegeneration with cerebral iron deposition, neurodegenerative diseases, neurofibromatosis, neuroleptic malignant syndrome, neurological complications of AIDS, neurological complications of Lyme disease, neurological consequences of cytomegalovirus infection, neurological manifestations of Pompe disease, neurological sequelae of lupus, neuromyelitis optica, neuromyotonia,Neuronal ceroid lipofuscinosis, neuronal migration disorder, neuropathic pain, hereditary neuropathies, neuropathy, neurosarcoidosis, neurosyphilis, neurotoxicity, nevus cell nevus, Niemann-Pick disease, O'Sullivan-McLeod syndrome, occipital neuralgia, Ohtahara syndrome, olivopontocerebellar atrophy, opsoclonus-myoclonus, orthostatic hypotension, overuse syndrome, chronic pain, pantothenate kinase-related neurodegeneration, paraneoplastic syndrome, paresthesia, Parkinson's disease, paroxysmal choreoathetosis, paroxysmal hemicrania, Paroxysmal hemicrania Romberg, Pelizaeus-Merzbacher disease, Penner-Shocker type II syndrome, nerve root cyst, peroneal muscular atrophy, periodic paralysis, peripheral neuropathy, periventricular leukomalacia, persistent vegetative state, pervasive developmental disorder, Phelan-McDermid syndrome, phytanic acid storage disease, Pick's disease, compressed nerve, piriformis syndrome, pituitary tumor, polymyositis, Pompe disease, porencephaly, post-polio syndrome, postherpetic neuralgia, post-infectious encephalomyelitis, orthostatic hypotension, postural orthostatic tachycardia syndrome, postural tachycardia syndrome, primary dentate atrophy Atrophy), primary lateral sclerosis, primary progressive aphasia, prion disease, progressive bulbar palsy, progressive facial hemitrophy, progressive gait ataxia, progressive multifocal leukoencephalopathy, progressive muscular atrophy, progressive sclerosing gray matter atrophy, progressive supranuclear palsy, prosopagnosia, pseudobulbar palsy, pseudotorch syndrome, pseudotoxoplasmosis, pseudotumor, psychogenic movement disorder, Ramsay Hunt syndrome type I, Ramsay Hunt syndrome type II, Rasmussen's encephalitis, reflex sympathetic dystrophy syndrome, Refsum's disease, childhood Refsum's disease, repetitive movement disorder, repetitive stress injury, restless legs syndrome, retrovirus-associated myelopathy rheumatoid encephalitis, Rett syndrome, Reye's syndrome, rheumatoid encephalitis, Riley-Day syndrome, sacral nerve root cyst, chorea, salivary gland disease, Sandhoff disease, Schilder's disease, schizencephaly, Seitelberger disease, epilepsy disorder, semantic dementia, septo-optic dysplasia, severe myoclonic epilepsy in infants (SMEI), shaken baby syndrome, shingles, Shy-Drager syndrome, Sjogren's syndrome, sleep apnea, sleeping sickness, Sotos syndrome, spasticity, spina bifida, spinal cord infarction, spinal cord injury, spinal tumor, spinal muscular atrophy, spinocerebellar ataxia, spinocerebellar atrophy, spinocerebellar degeneration, sporadic ataxia,Steele-Richardson-Olszewski syndrome, stiff-person syndrome, striatonigral degeneration, stroke, Sturge-Weber syndrome, subacute sclerosing panencephalitis, subcortical arteriosclerotic encephalopathy, short-lasting unilateral neuralgiform (SUNCT) headache, dysphagia, Sydenham chorea, fainting, syphilitic spinal sclerosis, syringomyelia, syringomyelia, systemic lupus erythematosus, fistula, tardive dyskinesia, intrasacral cyst, Tay-Sachs disease, temporal arteritis, tethered spinal cord syndrome, Thomsen myotonia, thoracic outlet syndrome, thyrotoxic myopathy, painful tics, Todd's palsy, Tourette's syndrome, transient cerebral ischemia 304. The method of embodiment 303, wherein the condition is seizures, transmissible spongiform encephalopathy, transverse myelitis, traumatic brain injury, tremor, trigeminal neuralgia, tropical spastic paraplegia, Troyer syndrome, tuberous sclerosis, cavernous vascular tumors, vasculitic syndromes of the central and peripheral nervous system, vitamin B12 deficiency, von Economo disease, von Hippel-Lindau disease (VHL), von Recklinghausen disease, Wallenberg syndrome, Werdnig-Hoffmann disease, Wernicke-Korsakoff syndrome, West syndrome, whiplash injury, Whipple disease, Williams syndrome, Wilson disease, Wolman disease, or X-linked spinal-bulbar muscular atrophy.

[0325] 305. The method of any of embodiments 302-304, wherein the subject is a mammal, for example a human.

[0326] 306. A cell, cell-free system, or other translation system comprising a capsid polypeptide, nucleic acid molecule, or viral particle according to any one of the preceding embodiments.

[0327] 307. A method of producing a virus (e.g., an adeno-associated dependent parvovirus (AAV) particle), comprising: providing a cell, cell-free system, or other translation system comprising a nucleic acid according to any one of embodiments 282 to 285 or 293; Cultivating cells, cell-free systems, or other translation systems under conditions suitable for the production of viral particles; This method produces viral particles.

[0328] 308. The method of embodiment 307, wherein the cell, cell-free system, or other translation system comprises a second nucleic acid molecule, at least a portion of which is packaged into the dependoparvovirus particle.

[0329] 309. The method of embodiment 308, wherein the second nucleic acid comprises a heterologous nucleic acid sequence encoding a payload, e.g., a therapeutic product, e.g., as described herein.

[0330] 310. The method of any one of embodiments 307 to 309, wherein the nucleic acid molecule of any one of embodiments 282 to 285 or 293 mediates the production of viral particles that do not contain the nucleic acid or fragment thereof of any one of embodiments 282 to 285 or 293.

[0331] 311. The method of any one of embodiments 307 to 310, wherein the nucleic acid molecule of any one of embodiments 282 to 285 or 293 mediates production of viral particles at a level similar to or at least 10% greater than the level of production mediated by a nucleic acid comprising SEQ ID NO: 4 in an otherwise similar production system.

[0332] 312. A composition, e.g., a pharmaceutical composition, comprising a viral particle according to any one of embodiments 286 to 292 or a viral particle produced by a method according to any one of embodiments 307 to 311, and a pharmaceutically acceptable carrier.

[0333] 313. A variant capsid polypeptide according to any of the preceding embodiments, a nucleic acid molecule according to any of embodiments 282-285 or 293, a viral particle according to any of embodiments 286-292, or a composition according to embodiment 312, for use in treating a disease or condition in a subject.

[0334] 314. A variant capsid polypeptide according to any of the preceding embodiments, a nucleic acid molecule according to any of embodiments 282-285 or 293, a viral particle according to any of embodiments 286-292, or a composition according to embodiment 312, for use in the manufacture of a medicament for use in treating a disease or condition in a subject.

[0335] 315. SEQ ID NOs: 2, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 12 5, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 1 130, 131, 132, 133, 134, 135, 136, 137, 138, or 139. A variant capsid polypeptide comprising a polypeptide having at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99% or 100% identity to a VP1 sequence, VP2 sequence, or VP3 sequence of 00, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, or 139.

[0336] 316. The variant capsid polypeptide of embodiment 315, wherein the variant capsid polypeptide comprises a mutation corresponding to a mutation at one or more of positions 579, 592, 593, 595, 596, 598, 601, or any combination thereof, compared to SEQ ID NO: 1, and optionally the mutation comprises an insertion, deletion, or substitution.

[0337] 317. The variant capsid polypeptide of embodiment 315, wherein the variant capsid polypeptide comprises at least one, at least two, at least three, at least four, at least five, at least six, but not more than seven mutations corresponding to mutations at one or more of positions 579, 592, 593, 595, 596, 598, 601, or any combination thereof, compared to SEQ ID NO: 1, and optionally the mutations comprise insertions, deletions, or substitutions.

[0338] 318. A variant capsid polypeptide, (a) a valine at a position corresponding to Q579 compared to SEQ ID NO: 1; (b) an isoleucine at a position corresponding to Q592 compared to SEQ ID NO: 1; (c) a valine at a position corresponding to T593 compared to SEQ ID NO: 1; (d) an alanine at a position corresponding to W595 compared to SEQ ID NO: 1; (e) a leucine at a position corresponding to V596 compared to SEQ ID NO: 1; (f) a serine at a position corresponding to N598 compared to SEQ ID NO: 1; (g) an alanine at a position corresponding to I601 compared to SEQ ID NO: 1, or (h) optionally, the variant capsid polypeptide comprises a polypeptide comprising all, including combinations, of (a) through (g); Optionally, the variant capsid polypeptide has at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identity to the VP1 sequence, VP2 sequence, or VP3 sequence of SEQ ID NO: 1, with the proviso that the variant capsid polypeptide comprises a combination of (a)-(g), and optionally the variant capsid polypeptide comprises all of (a)-(g).

[0339] 319. A variant capsid polypeptide, (i) a leucine at a position corresponding to V596 compared to SEQ ID NO:1, a serine at a position corresponding to N598 compared to SEQ ID NO:1, and an alanine at a position corresponding to I601 compared to SEQ ID NO:1; (ii) a valine at a position corresponding to Q579 relative to SEQ ID NO:1, a leucine at a position corresponding to V596 relative to SEQ ID NO:1, a serine at a position corresponding to N598 relative to SEQ ID NO:1, and an alanine at a position corresponding to I601 relative to SEQ ID NO:1; (iii) an alanine at a position corresponding to W595 relative to SEQ ID NO:1, a leucine at a position corresponding to V596 relative to SEQ ID NO:1, and a serine at a position corresponding to N598 relative to SEQ ID NO:1; (iv) a valine at a position corresponding to T593 compared to SEQ ID NO:1, an alanine at a position corresponding to W595 compared to SEQ ID NO:1, a leucine at a position corresponding to V596 compared to SEQ ID NO:1, and a serine at a position corresponding to N598 compared to SEQ ID NO:1; (v) an isoleucine at a position corresponding to Q592 relative to SEQ ID NO:1, a valine at a position corresponding to T593 relative to SEQ ID NO:1, and a leucine at a position corresponding to V596 relative to SEQ ID NO:1; (vi) a valine at a position corresponding to T593 compared to SEQ ID NO:1, a leucine at a position corresponding to V596 compared to SEQ ID NO:1, a serine at a position corresponding to N598 compared to SEQ ID NO:1, and an alanine at a position corresponding to I601 compared to SEQ ID NO:1; (vii) a valine at a position corresponding to Q579 compared to SEQ ID NO:1, an alanine at a position corresponding to W595 compared to SEQ ID NO:1, a leucine at a position corresponding to V596 compared to SEQ ID NO:1, and a serine at a position corresponding to N598 compared to SEQ ID NO:1; (viii) a valine at a position corresponding to Q579 compared to SEQ ID NO: 1, or (ix) a polypeptide comprising: a valine at a position corresponding to Q579 compared to SEQ ID NO:1; a valine at a position corresponding to T593 compared to SEQ ID NO:1; an alanine at a position corresponding to W595 compared to SEQ ID NO:1; a leucine at a position corresponding to V596 compared to SEQ ID NO:1; and a serine at a position corresponding to N598 compared to SEQ ID NO:1; Optionally, the variant capsid polypeptide has at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identity to the VP1 sequence, VP2 sequence, or VP3 sequence of SEQ ID NO: 1, provided that the variant capsid polypeptide comprises a set of mutations (i) through (ix).

[0340] 320. A variant capsid polypeptide, comprising a polypeptide having at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identity to the VP1 sequence, VP2 sequence, or VP3 sequence of SEQ ID NO: 2, provided that the variant capsid polypeptide is (i) a mutation between positions 596 and 601 (numbered according to SEQ ID NO: 1), wherein the mutation is Contains LnSnnA, a mutation in which n is any amino acid, optionally n is unmodified as shown in SEQ ID NO: 1; (ii) a mutation between positions 593 and 598 (numbered according to SEQ ID NO: 1), wherein the mutation is Contains n / VnALnS, n is any amino acid, optionally n is unmodified as set forth in SEQ ID NO: 1; Optionally, a mutation wherein the amino acid residue at position 593 is a valine; (iii) a mutation between positions 579 and 601 (numbered according to SEQ ID NO: 1), wherein the mutation is V-(n) 11 -n / In / Vnn / ALnSnnA, n is any amino acid, optionally n is unmodified as set forth in SEQ ID NO: 1; Optionally, the amino acid residue at position 592 is isoleucine; Optionally, the amino acid residue at position 593 is valine; Optionally, a mutation in which the amino acid residue at position 595 is alanine, or (iv) a mutation between positions 579 and 601 (numbered according to SEQ ID NO: 1), wherein the mutation is n / V-(n) 11 -n / In / Vnn / ALnSnnA, n is the wild-type residue shown in SEQ ID NO: 1; Optionally, the amino acid residue at position 579 is a valine; Optionally, the amino acid residue at position 592 is isoleucine; Optionally, the amino acid residue at position 593 is valine; Optionally, the variant capsid polypeptide comprises a mutation where the amino acid residue at position 595 is alanine.

[0341] 321. A variant capsid polypeptide comprising the sequence VVATNHQSAQAQAIVGALQSQGA (SEQ ID NO: 266), or the sequence IVGALQSQGA (SEQ ID NO: 267), or the sequence VGALQS (SEQ ID NO: 268), optionally within a region of the variant capsid polypeptide corresponding to amino acids 550 to 620 according to SEQ ID NO: 1.

[0342] 322. The variant capsid polypeptide of embodiment 321, wherein the capsid polypeptide has more than 95%, more than 96%, more than 97%, more than 98%, or more than 99% sequence identity to the capsid polypeptide of SEQ ID NO: 1.

[0343] 323. The variant capsid polypeptide of embodiment 321, wherein the capsid polypeptide has more than 95%, more than 96%, more than 97%, more than 98%, or more than 99% sequence identity to the capsid polypeptide of SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, or SEQ ID NO:12.

[0344] 324. The variant capsid polypeptide according to any one of embodiments 321 to 323, wherein the sequence VVATNHQSAQAQAIVGALQSQGA (SEQ ID NO: 266) is present at a position corresponding to amino acids 579 to 601 according to SEQ ID NO: 1, or the sequence IVGALQSQGA (SEQ ID NO: 267) is present at a position corresponding to amino acids 592 to 601 according to SEQ ID NO: 1, or the sequence VGALQS (SEQ ID NO: 268).

[0345] 325. Variant capsid polypeptides comprising SEQ ID NOs: 2, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, any one of 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, or 139, optionally 15 or fewer sequences relative to SEQ ID NO:2; SEQ ID NOs: 2, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87 , 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, or 139.

[0346] 326. Variant capsid polypeptides comprising SEQ ID NOs: 2, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, any one of: 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, or 139, optionally comprising a sequence with an edit distance of 15 or less to SEQ ID NO:2; (a) if the mutation set contains fewer than 10 single amino acid mutations, SEQ ID NOs: 2, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83; 70% or more of single amino acid mutations in any one of the mutation sets 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, or 139; (b) When the mutation set contains 10 to 19 single amino acid mutations, SEQ ID NOs: 2, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 80% or more of single amino acid mutations in any one of the sets of mutations 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, or 139; or (c) If the mutation set includes 20 or more single amino acid mutations, SEQ ID NOs: 2, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87 , 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, or 139.

[0347] 327. Variant capsid polypeptides comprising SEQ ID NOs: 2, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 131, 132, 133, 134, 135, 136, 137, 138, or 139, and optionally comprising, e.g., consisting of, the VP1, VP2, or VP3 sequence of SEQ ID NO:2.

[0348] 328. Variant capsid polypeptides, comprising SEQ ID NOs: 2, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84 , 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, or 139.

[0349] 329. A nucleic acid molecule encoding a capsid variant polypeptide according to any one of embodiments 315 to 328.

[0350] 330. The nucleic acid molecule is selected from the group consisting of SEQ ID NOs: 3, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177 , 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219 9, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 33 329. The nucleic acid molecule of embodiment 329, comprising the sequence of 61, 262, 263, 264, or 265, or a fragment thereof (e.g., a VP1-encoding fragment, a VP2-encoding fragment, or a VP3-encoding fragment thereof), or a sequence having at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% sequence identity thereto.

[0351] 331. The nucleic acid molecule of any one of embodiments 329 or 330, wherein the fragment encodes a VP2 capsid polypeptide or a VP3 capsid polypeptide.

[0352] 332. The nucleic acid molecule is selected from the group consisting of SEQ ID NOs: 3, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 0, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 2 05, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 332. The nucleic acid molecule of any one of embodiments 329 to 331, comprising the sequence of 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, or 265.

[0353] 333. A viral particle (e.g., an adeno-associated virus ("AAV") particle) comprising a variant capsid polypeptide described in any one of embodiments 315 to 328, or comprising a variant capsid polypeptide encoded by a nucleic acid molecule described in any one of embodiments 329 to 332.

[0354] 334. A viral particle according to embodiment 19, comprising a payload (e.g., a heterologous transgene) and a nucleic acid comprising one or more regulatory elements.

[0355] 335. The viral particle of any one of embodiments 19-20, wherein the viral particle exhibits increased central nervous system (CNS) biodistribution compared to viral particles comprising wild-type AAV9 (e.g., viral particles comprising the capsid polypeptide of SEQ ID NO: 1 or encoded by SEQ ID NO: 4), e.g., as measured in a mammal, e.g., a mouse or NHP, e.g., as described herein, and optionally, the biodistribution is at least 10-fold, at least 20-fold, at least 32-fold, at least 45-fold, at least 90-fold, or greater than the biodistribution of viral particles comprising a wild-type AAV9 capsid polypeptide (e.g., comprising the capsid polypeptide of SEQ ID NO: 1 or encoded by SEQ ID NO: 4), e.g., as measured by quantification of viral DNA in target tissue (e.g., as described in Examples 1-2).

[0356] 336. The viral particles of embodiment 335, wherein increased CNS biodistribution is demonstrated upon systemic administration, e.g., intravenous administration, of the viral particles.

[0357] 337. A viral particle according to any of embodiments 333-334, wherein the viral particle exhibits higher CNS biodistribution than peripheral nervous system (PNS) biodistribution, optionally with a ratio of CNS biodistribution to PNS biodistribution of at least 10, at least 20, at least 25, at least 50, at least 90, or more, optionally as measured after systemic administration, e.g., intravenous administration, of the viral particle.

[0358] 338. The viral particle of any of embodiments 333-334, wherein the viral particle exhibits increased transduction of the CNS compared to a viral particle comprising a wild-type AAV9 capsid polypeptide (e.g., a viral particle comprising the capsid polypeptide of SEQ ID NO: 1 or encoded by SEQ ID NO: 4), e.g., as measured in a mammal, e.g., a mouse, a rat, or in an NHP, e.g., as described herein, and optionally, the transduction is at least 10-fold, at least 25-fold, at least 50-fold, at least 100-fold, at least 150-fold, at least 200-fold, or at least 220-fold or greater than the transduction of a viral particle comprising a wild-type AAV9 capsid polypeptide (e.g., a viral particle comprising the capsid polypeptide of SEQ ID NO: 1 or encoded by SEQ ID NO: 4), e.g., as measured by quantification of viral transcript mRNA present in target tissue (e.g., as described in Examples 1-3).

[0359] 339. The virus particles are: (a) Decreased hepatic biodistribution, (b) reduced splenic biodistribution; (c) reduced muscle biodistribution; (d) reduced cardiac biodistribution; (e) reduced liver transduction, or (f) exhibiting one or more, e.g., all, of reduced cardiac transduction; A viral particle described in any of embodiments 333 to 334, wherein, in each case, compared to a viral particle comprising a wild-type AAV9 capsid polypeptide (e.g., a viral particle comprising the capsid polypeptide of SEQ ID NO: 1 or encoded by SEQ ID NO: 4), optionally the transduction or biodistribution is at least 1-fold, at least 2-fold, at least 3-fold, at least 4-fold, at least 5-fold, or at least 10-fold lower than the transduction or biodistribution of a viral particle comprising the capsid polypeptide of SEQ ID NO: 1, when measured, for example, in a mammal, such as a mouse or NHP.

[0360] 340. The nucleic acid molecule according to any one of embodiments 329 to 332, wherein the nucleic acid molecule is double-stranded or single-stranded, the nucleic acid molecule is linear or circular, for example, the nucleic acid molecule is a plasmid.

[0361] 341. A method for producing viral particles comprising a variant capsid polypeptide, the method comprising introducing a nucleic acid molecule described in any one of embodiments 329-332 or 340 into cells (e.g., HEK293 cells) and recovering the viral particles therefrom.

[0362] 342. A method of delivering a payload (e.g., a nucleic acid) to a cell, comprising contacting the cell with a viral particle comprising a variant capsid polypeptide and a payload described in any one of embodiments 315-328, or contacting the cell with a viral particle described in any one of embodiments 333-339.

[0363] 343. The method of embodiment 342, wherein the cell is a CNS cell.

[0364] 344. The method of embodiment 343, wherein the CNS cells are neurons, glial cells, astrocytes, oligodendrocytes, endothelial cells, or any combination thereof.

[0365] 345. A method of delivering a payload (e.g., a nucleic acid) to a subject, comprising administering to the subject a viral particle comprising a variant capsid polypeptide and a payload described in any one of embodiments 315-328, or administering to the subject a viral particle described in any one of embodiments 333-339.

[0366] 346. The method of embodiment 345, wherein the viral particles deliver the payload to the CNS.

[0367] 347. The variant capsid polypeptide of any one of embodiments 315 to 328, the viral particle of any one of embodiments 333 to 339, or the method of any one of embodiments 341 to 346, wherein the viral particle (e.g., the viral particle comprising the variant capsid polypeptide) delivers a payload to the CNS with increased biodistribution and / or transduction, e.g., biodistribution compared to a viral particle comprising a capsid polypeptide of SEQ ID NO: 1, and optionally the biodistribution is at least 10, at least 20, at least 25, at least 50, at least 90, or more greater than the biodistribution and / or transduction of a viral particle comprising a capsid polypeptide of SEQ ID NO: 1.

[0368] 348. The variant capsid polypeptide, viral particle, or method of embodiment 347, wherein the one or more cells of the CNS are selected from neurons, glial cells, astrocytes, oligodendrocytes, endothelial cells, or any combination thereof.

[0369] 349. A method of treating a disease or condition in a subject, comprising administering to the subject a viral particle described in any one of embodiments 333-339 or 347, or a composition described in embodiment 358, in an amount effective to treat the disease or condition.

[0370] 350. The method of embodiment 349, wherein the disease or condition is a disease or condition of the CNS.

[0371] 351. The disease or condition is septum pellucidum defect, acid lipase disease, acid maltase deficiency, acquired epileptic aphasia, acute disseminated encephalomyelitis, attention-deficit hyperactivity disorder (ADHD), Adie pupil, Adie syndrome, adrenoleukodystrophy, agenesis of the corpus callosum, agnosia, Aicardi syndrome, Aicardi-Goutières syndrome, AIDS-neurological complications, Alexander disease, Alpers disease, alternating hemiplegia, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), anencephaly, aneurysm, Angelman syndrome, hemangiomatosis, Angleman syndrome, anoxia , antiphospholipid syndrome, aphasia, apraxia, arachnoid cyst, arachnoiditis, Arnold-Chiari malformation, arteriovenous malformation, Asperger's syndrome, ataxia, ataxia-telangiectasia, ataxia and cerebellar or spinocerebellar degeneration, atrial fibrillation and stroke, attention-deficit hyperactivity disorder, autism spectrum disorder, autonomic dysfunction, back pain, Barth syndrome, Batten disease, Becker's myotonia, Behçet's disease, Bell's palsy, benign essential blepharospasm, benign focal muscular atrophy, benign intracranial hypertension, Bernhard-Roth syndrome, Binswanger's disease, blepharospasm, Bloch-Sulzberger syndrome syndrome, brachial plexus birth injury, brachial plexus injury, Bradbury-Eggleston syndrome, brain and spinal cord tumors (including, but not limited to, those that metastasize to the brain, e.g., metastatic breast cancer), cerebral aneurysm, brain injury, Brown-Séquard syndrome, bulbar palsy, spinal-bulbar muscular atrophy, cerebral autosomal dominant arteriopathy with subcortical infarctions and progressive leukoencephalopathy (CADASIL), Canavan disease, carpal tunnel syndrome, causal pain, cavernoma, cavernous hemangioma, cavernous vascular malformation, central cervical spinal cord syndrome, cervical spinal cord syndrome, central pain syndrome, central pontine myelinolysis, head injury, ceramidase deficiency, cerebellar degeneration, cerebellar hypoplasia, cerebral aneurysm , cerebral arteriosclerosis, cerebral atrophy, cerebral beriberi, cerebral cavernous malformations, cerebral gigantism, cerebral hypoxia, cerebral palsy, cerebro-oculofacial-skeletal syndrome (COFS), Charcot-Marie-Tooth disease, Chiari malformation, cholesterol ester storage disease, chorea, chorea acanthocytosis, chronic inflammatory demyelinating polyneuropathy (CIDP), chronic orthostatic intolerance, chronic pain, Cockayne syndrome type II, Coffin-Lowry syndrome, posterior horn enlargement of the lateral ventricles, coma, complex regional pain syndrome, concentric sclerosis (Balo's sclerosis), congenital bilateral facial nerve palsy, congenital myasthenia, congenital myopathy, congenital cavernous malformations,Corticobasal degeneration, cranial arteritis, craniosynostosis, Cree encephalitis, Creutzfeldt-Jakob disease, chronic progressive external ophthalmoplegia, cumulative trauma disorder, Cushing's syndrome, cytomegalic inclusion disease, cytomegalovirus infection, dancing eyes dancing feet syndrome, Dandy-Walker syndrome, Dawson's disease, Domorsia syndrome, Dejerine-Klumpke palsy, dementia, multi-infarct dementia, semantic dementia, subcortical dementia, dementia with Lewy bodies, demyelination, dentate cerebellar ataxia, Dentatorubral atrophy, dermatomyositis, developmental apraxia, Devic's syndrome, diabetic neuropathy, diffuse sclerosis, distal hereditary motor neuropathy, Dravet syndrome, autonomic neuropathy, dysgraphia, dyslexia, dysphagia, dyspraxia, myoclonic cerebellar dyssynergia, progressive cerebellar dyssynergia, dystonia, early infantile epileptic encephalopathy, Empty-Sella syndrome, encephalitis, encephalitis lethargica, encephalocele, encephalomyelitis, encephalopathy, encephalopathy (familial infantile), trigeminal angiomatosis, epilepsy, epileptic hemiplegia Paralysis, episodic ataxia, Erb's palsy, Erb-Duchenne and Dejurin-Klumpke palsy, essential tremor, extrapontine myelinolysis, Farber disease, Fabry disease, Fahr's syndrome, syncope, familial dysautonomia, familial hemangioma, familial idiopathic basal ganglia calcification, familial periodic paralysis, familial spastic paralysis, Farber disease, febrile seizures, fibromuscular dysplasia, Fisher syndrome, floppy infant syndrome, foot drop, fragile X syndrome, Friedreich's ataxia, frontotemporal dementia, Gorschi syndrome Göttingen's disease, systemic gangliosidosis (GM1, GM2), Gerstmann's syndrome, Gerstmann-Straussler-Scheinker disease, giant axonal neuropathy, giant cell arteritis, giant cell inclusion body disease, globoid cell leukodystrophy, glossopharyngeal neuralgia, glycogen storage disease, Guillain-Barré syndrome, Hallervorden-Spatz syndrome, head injury, headache, persistent hemicrania, hemifacial spasm, alternating hemiplegia, hereditary neuropathies, hereditary spastic paraplegia, hereditary polyneuropathies, herpes zoster Zoster), herpes zoster oticus, Hirayama disease, Holmes-Addie syndrome, holoprosencephaly, HTLV-1-associated myelopathy, Hughes syndrome, Huntington's disease, Hurler syndrome, hydroanencephaly, hydrocephalus, normal pressure hydrocephalus, hydromyelopathy, hyperadrenocorticism, hypersomnia, hypertonia, hypotonia, hypoxia,Immune-mediated encephalomyelitis, inclusion body myositis, incontinentia pigmenti, childhood hypotonia, childhood neuroaxonal dystrophy, childhood phytanic acid storage disease, childhood Refsum's disease, infantile spasms, inflammatory myopathy, foramen occipitalis prolapse, intestinal lipodystrophy, intracranial cyst, intracranial hypertension, Isaacs syndrome, Joubert syndrome, Kearns-Sayre syndrome, Kennedy disease, Kinsbourne syndrome, Kleine-Levin syndrome, Klippel-Feil syndrome, Klippel-Trenaunay syndrome (KTS), Klüver-Bucy syndrome, Korsakoff amnesic syndrome, Krabbe disease, Kugel syndrome Leberg-Welander disease, Kuru, Lambert-Eaton myasthenic syndrome, Landau-Kleffner syndrome, Lateral femoral cutaneous nerve entrapment, Lateral bulbar syndrome, Learning disability, Leigh's disease, Lennox-Gastaut syndrome, Lesch-Nyhan syndrome, Leukodystrophy, Levine-Critchley syndrome, Dementia with Lewy bodies, Lichtheim's disease, Lipid storage disease, Lipoid proteinosis, Lissencephaly, Locked-in syndrome, Lou Gehrig's disease, Lupus - neurological sequelae, Lyme disease - neurological complications, Lysosomal storage disease, Machado-Joseph disease, Megalencephaly, Megalencephaly, Merck Rosenthal syndrome, meningitis, meningitis and encephalitis, Menkes disease, lateral femoral cutaneous neuralgia, metachromatic leukodystrophy, microcephaly, migraine, Miller Fisher syndrome, petit mal seizures, mitochondrial myopathy, mitochondrial DNA depletion syndrome, Moebius syndrome, hemiatrophy, Morvan syndrome, motor neuron disease, moyamoya disease, mucolipidosis, mucopolysaccharidoses, multi-infarct dementia, multifocal motor neuropathy, multiple sclerosis, multiple system atrophy, multiple system atrophy with orthostatic hypotension, muscular dystrophy, congenital myasthenia, myasthenia gravis, demyelinating diffuse sclerosis, spinal cord Myelitis, myoclonic encephalopathy of childhood, myoclonus, myoclonic epilepsy, myopathy, congenital myopathy, thyrotoxic myopathy, myotonia, congenital myotonia, narcolepsy, NARP (neuropathy, ataxia and retinitis pigmentosa), neuroacanthocytosis, neurodegeneration with cerebral iron deposition, neurodegenerative diseases, neurofibromatosis, neuroleptic malignant syndrome, neurological complications of AIDS, neurological complications of Lyme disease, neurological consequences of cytomegalovirus infection, neurological manifestations of Pompe disease, neurological sequelae of lupus, neuromyelitis optica, neuromyotonia,Neuronal ceroid lipofuscinosis, neuronal migration disorder, neuropathic pain, hereditary neuropathies, neuropathy, neurosarcoidosis, neurosyphilis, neurotoxicity, nevus cell nevus, Niemann-Pick disease, O'Sullivan-McLeod syndrome, occipital neuralgia, Ohtahara syndrome, olivopontocerebellar atrophy, opsoclonus-myoclonus, orthostatic hypotension, overuse syndrome, chronic pain, pantothenate kinase-related neurodegeneration, paraneoplastic syndrome, paresthesia, Parkinson's disease, paroxysmal choreoathetosis, paroxysmal hemicrania, Paroxysmal hemicrania Romberg, Pelizaeus-Merzbacher disease, Penner-Shocker type II syndrome, nerve root cyst, peroneal muscular atrophy, periodic paralysis, peripheral neuropathy, periventricular leukomalacia, persistent vegetative state, pervasive developmental disorder, Phelan-McDermid syndrome, phytanic acid storage disease, Pick's disease, compressed nerve, piriformis syndrome, pituitary tumor, polymyositis, Pompe disease, porencephaly, post-polio syndrome, postherpetic neuralgia, post-infectious encephalomyelitis, orthostatic hypotension, postural orthostatic tachycardia syndrome, postural tachycardia syndrome, primary dentate atrophy Atrophy), primary lateral sclerosis, primary progressive aphasia, prion disease, progressive bulbar palsy, progressive facial hemitrophy, progressive gait ataxia, progressive multifocal leukoencephalopathy, progressive muscular atrophy, progressive sclerosing gray matter atrophy, progressive supranuclear palsy, prosopagnosia, pseudobulbar palsy, pseudotorch syndrome, pseudotoxoplasmosis, pseudotumor, psychogenic movement disorder, Ramsay Hunt syndrome type I, Ramsay Hunt syndrome type II, Rasmussen's encephalitis, reflex sympathetic dystrophy syndrome, Refsum's disease, childhood Refsum's disease, repetitive movement disorder, repetitive stress injury, restless legs syndrome, retrovirus-associated myelopathy rheumatoid encephalitis, Rett syndrome, Reye's syndrome, rheumatoid encephalitis, Riley-Day syndrome, sacral nerve root cyst, chorea, salivary gland disease, Sandhoff disease, Schilder's disease, schizencephaly, Seitelberger disease, epilepsy disorder, semantic dementia, septo-optic dysplasia, severe myoclonic epilepsy in infants (SMEI), shaken baby syndrome, shingles, Shy-Drager syndrome, Sjogren's syndrome, sleep apnea, sleeping sickness, Sotos syndrome, spasticity, spina bifida, spinal cord infarction, spinal cord injury, spinal tumor, spinal muscular atrophy, spinocerebellar ataxia, spinocerebellar atrophy, spinocerebellar degeneration, sporadic ataxia,Steele-Richardson-Olszewski syndrome, stiff-person syndrome, striatonigral degeneration, stroke, Sturge-Weber syndrome, subacute sclerosing panencephalitis, subcortical arteriosclerotic encephalopathy, short-lasting unilateral neuralgiform (SUNCT) headache, dysphagia, Sydenham chorea, fainting, syphilitic spinal sclerosis, syringomyelia, syringomyelia, systemic lupus erythematosus, fistula, tardive dyskinesia, intrasacral cyst, Tay-Sachs disease, temporal arteritis, tethered spinal cord syndrome, Thomsen myotonia, thoracic outlet syndrome, thyrotoxic myopathy, painful tics, Todd's palsy, Tourette's syndrome, transient cerebral ischemia 351. The method of embodiment 350, wherein the condition is seizures, transmissible spongiform encephalopathy, transverse myelitis, traumatic brain injury, tremor, trigeminal neuralgia, tropical spastic paraplegia, Troyer syndrome, tuberous sclerosis, cavernous vascular tumors, vasculitic syndromes of the central and peripheral nervous system, vitamin B12 deficiency, von Economo disease, von Hippel-Lindau disease (VHL), von Recklinghausen disease, Wallenberg syndrome, Werdnig-Hoffmann disease, Wernicke-Korsakoff syndrome, West syndrome, whiplash injury, Whipple disease, Williams syndrome, Wilson disease, Wolman disease, or X-linked spinal-bulbar muscular atrophy.

[0372] 352. The method of any of embodiments 349-351, wherein the subject is a mammal, for example a human.

[0373] 353. The method of any of embodiments 349-352, wherein the viral particle comprises a nucleic acid molecule encoding a therapeutic product effective to treat a disease or condition of the CNS, and a promoter sufficient to drive expression of the therapeutic product.

[0374] 354. A cell, cell-free system, or other translation system comprising a capsid polypeptide, nucleic acid molecule, or viral particle according to any one of the preceding embodiments.

[0375] 355. A method of producing a virus (e.g., an adeno-associated dependent parvovirus (AAV) particle), comprising: Providing a cell, cell-free system, or other translation system comprising a nucleic acid according to any one of embodiments 329-332 or 340; Cultivating cells, cell-free systems, or other translation systems under conditions suitable for the production of viral particles; This method produces viral particles.

[0376] 356. The method of embodiment 355, wherein the cell, cell-free system, or other translation system comprises a second nucleic acid molecule comprising a payload, e.g., a heterologous nucleic acid sequence (e.g., as described herein), encoding a therapeutic product, and at least a portion of the second nucleic acid molecule is packaged into the dependoparvovirus particle.

[0377] 357. The method of any one of embodiments 355-356, wherein the nucleic acid molecule of any one of embodiments 329-332 or 340 mediates the production of viral particles, or fragments thereof, that do not comprise the nucleic acid molecule of any one of embodiments 329-332 or 340, or wherein the nucleic acid molecule of any one of embodiments 329-332 or 340 mediates the production of viral particles at a level similar to or at least 10% greater than the level of production mediated by a nucleic acid comprising SEQ ID NO:4 in an otherwise similar production system.

[0378] 358. A composition, e.g., a pharmaceutical composition, comprising a viral particle according to any one of embodiments 333 to 339, or a viral particle produced by the method according to any one of embodiments 355 to 357, and a pharmaceutically acceptable carrier.

[0379] 359. A variant capsid polypeptide according to any one of embodiments 315 to 328, a nucleic acid molecule according to any one of embodiments 329 to 332 or 340, a viral particle according to any one of embodiments 333 to 339, or a composition according to embodiment 358, for use in treating a disease or condition in a subject.

[0380] 360. A variant capsid polypeptide according to any of embodiments 315-328, a nucleic acid molecule according to any of embodiments 329-332 or 340, a viral particle according to any of embodiments 333-339, or a composition according to embodiment 358, for use in the manufacture of a medicament for use in treating a disease or condition in a subject.

[0381] 361. A viral particle according to any of embodiments 333 to 339, wherein the viral particle exhibits at least a 50-fold increased transduction of cells of the CNS in at least two different NHP species, optionally wherein the species are cynomolgus monkeys and African green monkeys.

[0382] 362. A viral particle according to any of embodiments 333 to 339, wherein the viral particle transduces Purkinje neurons of the cerebellum at a level at least 10-fold or 100-fold greater than a viral particle comprising, for example, a capsid polypeptide of SEQ ID NO: 1 (as measured, for example, by histology, e.g., according to Example 2).

[0383] 363. A viral particle according to any of embodiments 333 to 339, wherein the viral particle transduces CA3 pyramidal neurons of the hippocampus at a level at least 10-fold or 100-fold greater than a viral particle comprising, for example, a capsid polypeptide of SEQ ID NO: 1 (as measured, for example, by histology, e.g., according to Example 2).

[0384] 364. A composition of matter (e.g., virus particles), comprising: (A) a capsid polypeptide, the capsid polypeptide comprising (i) SEQ ID NO: 2 or 14-139, or (ii) a sequence having 70 percent (70%) or more of a set of mutations in SEQ ID NO: 2 or 14-139, and the capsid polypeptide having an edit distance of 15 or less from SEQ ID NO: 2 or 14-139; (B) a heterologous nucleic acid for treating a disorder described herein.

[0385] 365. A composition of matter (e.g., virus particles), comprising: (A) a capsid polypeptide, comprising: (i) SEQ ID NO: 2; or (ii) a capsid polypeptide comprising a sequence having seventy percent (70%) or more of a set of mutations of SEQ ID NO: 2, and having an edit distance of 15 or less from SEQ ID NO: 2; (B) a heterologous nucleic acid for treating a disorder described herein.

[0386] 366. A method for treating a disorder described herein, comprising administering to a subject in need thereof a composition of matter (e.g., a viral particle) described in embodiment 252 or 253, wherein the disorder described herein is treated. DETAILED DESCRIPTION OF THE INVENTION

[0387] The present disclosure is directed, in part, to variant capsid polypeptides that can be used to generate Depend parvoviral particles. In some embodiments, the particles have increased CNS transduction, which can be used to deliver a transgene or molecule of interest to the CNS at a higher transduction efficiency in the CNS compared to Depend parvoviral particles that do not contain the variant capsid polypeptide. Accordingly, provided herein are variant capsid polypeptides, nucleic acid molecules encoding the same, viral particles comprising the variant capsid polypeptides, and methods of using the same.

[0388] definition A, an, the: As used herein, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.

[0389] About, Approximately: As used herein, the terms "about" and "approximately" are intended to mean an acceptable degree of error for the quantity measured, generally given the nature or precision of the measurement. Exemplary degrees of error are within 15 percent (%), typically within 10%, and more typically within 5% of a given value or range of values.

[0390] Depend parvovirus capsid: As used herein, the term "depend parvovirus capsid" refers to an assembled viral capsid comprising a depend parvovirus polypeptide. In some embodiments, the depend parvovirus capsid is a functional depend parvovirus capsid, e.g., fully folded and / or assembled and capable of infecting a target cell, or remains stable for at least a threshold period of time (e.g., folded / assembled and / or capable of infecting a target cell).

[0391] Depend parvovirus particle: As used herein, the term "depend parvovirus particle" refers to an assembled viral capsid comprising a depend parvovirus polypeptide and a packaged nucleic acid, e.g., including a payload, one or more components of a depend parvovirus genome (e.g., an entire depend parvovirus genome), or both. In some embodiments, the depend parvovirus particle is a functional depend parvovirus particle, e.g., contains a desired payload, is fully folded and / or assembled, and is capable of infecting a target cell, or remains stable for at least a threshold time (e.g., is folded / assembled and / or is capable of infecting a target cell).

[0392] Depend parvovirus X particle / capsid: As used herein, the term "depend parvovirus X particle / capsid" refers to a depend parvovirus particle / capsid comprising at least one polypeptide or polypeptides encoding a nucleic acid sequence derived from a naturally occurring depend parvovirus X species. For example, a depend parvovirus B particle refers to a depend parvovirus particle comprising at least one polypeptide or polypeptides encoding a nucleic acid sequence derived from a naturally occurring depend parvovirus B sequence. As used in this context, derived from means having at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% identity to the sequence in question. Correspondingly, as used herein, an AAV X particle / capsid refers to an AAV particle / caspid comprising at least one polypeptide or polypeptides encoding a nucleic acid sequence derived from a naturally occurring AAV X serotype. For example, an AAV9 particle refers to an AAV particle that includes at least one polypeptide or polypeptides encoding a nucleic acid sequence derived from a naturally occurring AAV9 sequence.

[0393] Exogenous: As used herein, the term "exogenous" refers to a feature, sequence, or component present in a context (e.g., a nucleic acid, polypeptide, or cell) that does not naturally occur in that context. For example, a nucleic acid sequence comprising an ORF encoding a polypeptide can include an exogenous start codon or a new start codon (e.g., a translation initiation codon) as provided herein. Using the term exogenous in this manner means that the ORF encoding the polypeptide containing the start codon in question at this position does not occur in nature, e.g., does not occur in AAV9, e.g., does not occur in SEQ ID NO: 7. In some embodiments, the exogenous start codon can replace an endogenous start codon. In some embodiments, the exogenous start codon can replace a codon that is not recognized as a start codon by the host cell. Those skilled in the art will readily understand that a sequence (e.g., a start codon) may be exogenous when provided to a first ORF (e.g., does not naturally contain a start codon at the site in question), but may not be exogenous to a second ORF (e.g., naturally contains that particular start codon at the site in question).

[0394] Functional: As used herein in reference to a polypeptide component of a dependoparvovirus capsid (e.g., Cap (e.g., VP1, VP2, and / or VP3) or Rep), the term "functional" refers to a polypeptide that provides at least 50, 60, 70, 80, 90, or 100% of the activity of a naturally occurring version of that polypeptide component (e.g., when present in a host cell). For example, a functional VP1 polypeptide can be stably folded and assembled into a dependoparvovirus capsid (e.g., compatible with packaging and / or secretion). As used herein in reference to a dependoparvovirus capsid or particle, "functional" refers to a capsid or particle that contains one or more of the following production characteristics: it contains a desired payload, is fully folded and / or assembled, and is capable of infecting a target cell, or remains stable (e.g., is folded / assembled and / or is capable of infecting a target cell) for at least a threshold period of time.

[0395] Nucleic Acid: As used herein, in its broadest sense, the term "nucleic acid" refers to any compound and / or substance that is or can be incorporated into an oligonucleotide chain. In some embodiments, nucleic acids are compounds and / or substances that are or can be incorporated into an oligonucleotide chain via a phosphodiester bond. As will be clear from the context, in some embodiments, "nucleic acid" refers to an individual nucleic acid monomer (e.g., nucleotide and / or nucleoside), and in some embodiments, "nucleic acid" refers to an oligonucleotide chain comprising individual nucleic acid monomers or a longer polynucleotide chain comprising many individual nucleic acid monomers. In some embodiments, "nucleic acid" is or comprises RNA, and in some embodiments, "nucleic acid" is or comprises DNA. In some embodiments, a nucleic acid is, comprises, or consists of one or more naturally occurring nucleic acid residues. In some embodiments, a nucleic acid is, comprises, or consists of one or more nucleic acid analogs. In some embodiments, a nucleic acid is, comprises, or consists of one or more modified, synthetic, or non-naturally occurring nucleotides. In some embodiments, a nucleic acid analog differs from a nucleic acid in that it does not utilize a phosphodiester backbone. For example, in some embodiments, a nucleic acid is, comprises, or consists of one or more "peptide nucleic acids," as known in the art and having peptide bonds instead of phosphodiester bonds in the backbone, and are considered within the scope of the present invention. Alternatively, or additionally, in some embodiments, the nucleic acid has one or more phosphorothioate and / or 5'-N-phosphoramidite linkages rather than phosphodiester linkages. In some embodiments, the nucleic acid has a nucleotide sequence that encodes a functional gene product, such as RNA or a protein. In some embodiments, the nucleic acid is partially or completely single-stranded, and in some embodiments, the nucleic acid is partially or completely double-stranded.

[0396] Mutation Set: As used herein, the term "mutation set" refers to the complete set of single amino acid mutations (substitutions, deletions, and / or insertions) in a variant capsid polypeptide sequence relative to a reference sequence (e.g., a wild-type reference sequence). In some embodiments, the reference sequence is wild-type AAV9 (SEQ ID NO: 1). In some cases, a portion of a mutation set (i.e., more than one single amino acid mutation) is referred to collectively; however, even when so referred to, it will be understood that the mutation set is a collection of single amino acid mutations. For example, the insertion of amino acids 1, 2, and 3 between amino acid N at position nn and amino acid W at position ww of the reference sequence may be referred to as "Nnn_3aa_Www_123," with it being understood that each of amino acids 1, 2, and 3 represents a separate single amino acid mutation within the mutation set. Mutation sets for particular variants described herein are found, for example, in the right-most column of Table 1.

[0397] Start codon: As used herein, the term "start codon" refers to any codon recognized by a host cell as a site for initiating translation (e.g., a site that mediates detectable translation initiation). Without wishing to be bound by theory, start codons vary in strength, with strong start codons promoting translation initiation more strongly and weak start codons promoting translation initiation less strongly. The canonical start codon is ATG, which encodes the amino acid methionine, although many non-canonical start codons are also recognized by host cells.

[0398] Variant: As used herein, a "variant" or "variant capsid polypeptide" refers to a polypeptide that differs from a reference sequence (e.g., SEQ ID NO: 1). A variant can include, for example, mutations (e.g., substitutions, deletions, or insertions). In some embodiments, a variant is about or at least 70%, 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a reference sequence. In some embodiments, the reference sequence is a polypeptide comprising SEQ ID NO: 1. In some embodiments, the variant comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 single amino acid mutations relative to a reference sequence (e.g., SEQ ID NO: 1), and optionally further comprises no more than 70, 60, 50, 40, 30, 35, 30, 29, 28, 27, 26, 25, 24, 23, 22, 21, or 20 single amino acid mutations relative to the reference sequence (SEQ ID NO: 1).

[0399] CNS: As used herein, refers to one or more regions of the central nervous system. In some embodiments, the CNS includes one or more of the frontal cortex, temporal cortex, motor cortex, hippocampus, basal ganglia, midbrain, brainstem, cerebellum, and spinal cord.

[0400] PNS: As used herein, refers to one or more regions of the peripheral nervous system that do not include the CNS. In some embodiments, the PNS includes the dorsal root ganglia. In some embodiments, the PNS includes sensory neurons and motor neurons.

[0401] Capsid polypeptides and nucleic acids encoding same The present disclosure is directed, in part, to variant capsid polypeptides and nucleic acids comprising a sequence encoding the variant capsid polypeptide, wherein the variant capsid polypeptide comprises a mutation (insertion, deletion, or substitution) compared to a wild-type sequence. In some embodiments, the wild-type sequence is SEQ ID NO: 1. The present disclosure is directed, in part, to variant capsid polypeptides and nucleic acid molecules encoding the variant capsid polypeptides comprising SEQ ID NO: 1 having one or more mutations compared to SEQ ID NO: 1. The mutations can be, for example, an insertion, deletion, or substitution compared to the wild-type sequence. In some embodiments, the wild-type sequence is SEQ ID NO: 1.

[0402] In some embodiments, the variant capsid polypeptide comprises a mutation corresponding to a mutation at position 579, 592, 593, 595, 596, 598, 601, or any combination thereof, relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises a mutation corresponding to a mutation at position 579 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises a mutation corresponding to a mutation at position 592 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises a mutation corresponding to a mutation at position 593 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises a mutation corresponding to a mutation at position 595 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises a mutation corresponding to a mutation at position 596 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises a mutation corresponding to a mutation at position 598 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises a mutation corresponding to a mutation at position 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579 and 592 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579 and 593 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579 and 595 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579 and 596 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579 and 598 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579 and 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592 and 593 relative to SEQ ID NO:1.In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592 and 595 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592 and 596 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592 and 598 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592 and 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 593 and 595 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 593 and 596 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 593 and 598 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 593 and 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 595 and 596 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 595 and 598 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 595 and 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 596 and 598 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 596 and 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 598 and 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, and 593 relative to SEQ ID NO:1.In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, and 595 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, and 596 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, and 598 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, and 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 593, and 595 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 593, and 596 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 593, and 598 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 593, and 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 595, and 596 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 595, and 598 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 595, and 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 596, and 598 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 596, and 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 596, and 601 relative to SEQ ID NO:1.In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592, 593, and 595 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592, 593, and 596 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592, 593, and 598 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592, 593, and 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592, 595, and 596 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592, 595, and 598 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592, 595, and 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592, 596, and 598 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592, 596, and 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592, 598, and 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 593, 595, and 596 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 593, 595, and 598 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 593, 595, and 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 593, 596, and 598 relative to SEQ ID NO:1.In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 593, 596, and 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 593, 598, and 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 595, 596, and 598 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 595, 596, and 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 595, 598, and 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 596, 598, and 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 593, and 595 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 593, and 596 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 593, and 598 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 593, and 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 596, and 598 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 596, and 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 596, and 601 relative to SEQ ID NO:1.In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 593, 595, and 596 relative to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 593, 595, and 598 relative to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 593, 595, and 601 relative to SEQ ID NO: 1. In some embodiments, the variant. The capsid polypeptide comprises mutations corresponding to mutations at positions 579, 593, 596, and 598 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 593, 596, and 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 593, 598, and 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 595, and 596 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 595, and 598 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 595, and 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 593, and 596 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 593, and 598 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 593, and 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 595, 596, and 598 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 595, 596, and 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 595, 596, and 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 596, 598, and 598 relative to SEQ ID NO:1.In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592, 593, 595, and 596 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592, 593, 595, and 598 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592, 593, 595, and 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592, 593, 596, and 598 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592, 593, 596, and 601 ... In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592, 595, 596, and 598 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592, 595, 596, and 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592, 595, 598, and 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592, 596, 598, and 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 593, 595, 596, and 598 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 593, 595, 596, and 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 593, 595, 598, and 601 relative to SEQ ID NO:1.In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 593, 596, 598, and 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 595, 596, 598, and 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 593, 595, and 596 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 593, 595, and 598 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 593, 595, and 601 ...3, 595, 596, and 598 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 593, 595, 596, and 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 593, 595, 598, and 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 593, 596, 598, and 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 595 ...2, 595, 596, and 598 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 595, 596, and 601 relative to SEQ ID NO:1.In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 595, 598, and 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 596, 598, and 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 595, 596, 598, and 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 593, 596, and 598 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 593, 596, and 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 593, 596, and 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 593, 595, and 598 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 593, 595, and 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592, 593, 595, 596, and 598 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592, 593, 595, 596, and 601 ...8, and 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592, 593, 596, 598, and 601 relative to SEQ ID NO:1.In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592, 595, 596, 598, and 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 593, 595, 596, 598, and 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 593, 595, 596, and 598 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 593, 595, 596, and 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 592, 593, 595, 596, 598, and 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 593, 595, 596, 598, and 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 595, 596, 598, and 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 593, 596, 598, and 601 relative to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to mutations at positions 579, 592, 593, 595 ...

[0403] In some embodiments, the variant capsid polypeptide comprises at least one, at least two, at least three, at least four, at least five, at least six, but not more than seven mutations corresponding to a mutation at one or more of positions 579, 592, 593, 595, 596, 598, 601, or any combination thereof, compared to SEQ ID NO: 1, and optionally the mutation comprises an insertion, deletion, or substitution. In some embodiments, the variant capsid polypeptide comprises at least one mutation corresponding to a mutation at one or more of positions 579, 592, 593, 595, 596, 598, 601, or any combination thereof, compared to SEQ ID NO: 1, and optionally the mutation comprises an insertion, deletion, or substitution. In some embodiments, the variant capsid polypeptide comprises at least two mutations corresponding to mutations at one or more of positions 579, 592, 593, 595, 596, 598, 601, or any combination thereof, compared to SEQ ID NO: 1, where optionally the mutations comprise insertions, deletions, or substitutions. In some embodiments, the variant capsid polypeptide comprises at least three mutations corresponding to mutations at one or more of positions 579, 592, 593, 595, 596, 598, 601, or any combination thereof, compared to SEQ ID NO: 1, where optionally the mutations comprise insertions, deletions, or substitutions. In some embodiments, the variant capsid polypeptide comprises at least four mutations corresponding to mutations at one or more of positions 579, 592, 593, 595, 596, 598, 601, or any combination thereof, compared to SEQ ID NO: 1, where optionally the mutations comprise insertions, deletions, or substitutions. In some embodiments, the variant capsid polypeptide comprises at least five mutations corresponding to mutations at one or more of positions 579, 592, 593, 595, 596, 598, 601, or any combination thereof, compared to SEQ ID NO: 1, and optionally the mutations comprise insertions, deletions, or substitutions.In some embodiments, the variant capsid polypeptide comprises at least six mutations corresponding to mutations at one or more of positions 579, 592, 593, 595, 596, 598, 601, or any combination thereof, relative to SEQ ID NO: 1, where optionally the mutations comprise insertions, deletions, or substitutions. In some embodiments, the variant capsid polypeptide comprises seven mutations corresponding to mutations at one or more of positions 579, 592, 593, 595, 596, 598, 601, or any combination thereof, relative to SEQ ID NO: 1, where optionally the mutations comprise insertions, deletions, or substitutions. In some embodiments, the variant capsid polypeptide comprises seven or fewer mutations corresponding to mutations at one or more of positions 579, 592, 593, 595, 596, 598, 601, or any combination thereof, relative to SEQ ID NO: 1, where optionally the mutations comprise insertions, deletions, or substitutions. In some embodiments, the variant capsid polypeptide comprises seven or fewer mutations compared to SEQ ID NO: 1 corresponding to mutations at one or more of positions 579, 592, 593, 595, 596, 598, 601, or any combination thereof, optionally wherein the mutations comprise insertions, deletions, or substitutions.

[0404] In some embodiments, the mutation corresponding to position 529 is a substitution compared to SEQ ID NO:1. In some embodiments, the substitution is a naturally occurring amino acid. In some embodiments, the substitution is a valine. In some embodiments, the substitution at position 529 of SEQ ID NO:1 is E529V. In some embodiments, the substitution at the position corresponding to E529 of SEQ ID NO:1 is a substitution of a valine at the position corresponding to E529 of SEQ ID NO:1 in a reference capsid sequence other than SEQ ID NO:1, e.g., as described herein.

[0405] In some embodiments, the mutation corresponding to position 530 is a substitution compared to SEQ ID NO:1. In some embodiments, the substitution is a naturally occurring amino acid. In some embodiments, the substitution is an alanine. In some embodiments, the substitution at position 530 is G530A according to SEQ ID NO:1. In some embodiments, the substitution at the position corresponding to G530 in SEQ ID NO:1 is a substitution of an alanine at the position corresponding to G530 in SEQ ID NO:1 in a reference capsid sequence other than SEQ ID NO:1, e.g., as described herein.

[0406] In some embodiments, the mutation corresponding to position 579 is a substitution compared to SEQ ID NO: 1. In some embodiments, the substitution is a naturally occurring amino acid. In some embodiments, the substitution is a valine. In some embodiments, the substitution at position 579 is Q579V according to SEQ ID NO: 1. In some embodiments, the substitution at the position corresponding to Q579 of SEQ ID NO: 1 is a substitution of a valine at the position corresponding to Q579 of SEQ ID NO: 1 in a reference capsid sequence other than SEQ ID NO: 1, e.g., as described herein.

[0407] In some embodiments, the mutation corresponding to position 592 is a substitution compared to SEQ ID NO:1. In some embodiments, the substitution is a naturally occurring amino acid. In some embodiments, the substitution is isoleucine. In some embodiments, the substitution at position 592 is Q592I according to SEQ ID NO:1. In some embodiments, the substitution at the position corresponding to Q592 of SEQ ID NO:1 is a substitution of valine at the position corresponding to Q592 of SEQ ID NO:1 in a reference capsid sequence other than SEQ ID NO:1, e.g., as described herein.

[0408] In some embodiments, the mutation corresponding to position 593 is a substitution compared to SEQ ID NO: 1. In some embodiments, the substitution is a naturally occurring amino acid. In some embodiments, the substitution is a valine. In some embodiments, the substitution at position 593 is T593V according to SEQ ID NO: 1. In some embodiments, the substitution at a position corresponding to T593 in SEQ ID NO: 1 is a substitution of a valine at a position corresponding to T593 in SEQ ID NO: 1 in a reference capsid sequence other than SEQ ID NO: 1, e.g., as described herein.

[0409] In some embodiments, the mutation corresponding to position 595 is a substitution compared to SEQ ID NO:1. In some embodiments, the substitution is a naturally occurring amino acid. In some embodiments, the substitution is an alanine. In some embodiments, the substitution at position 595 is W595A according to SEQ ID NO:1. In some embodiments, the substitution at the position corresponding to W595 of SEQ ID NO:1 is a substitution of a valine at the position corresponding to W595 of SEQ ID NO:1 in a reference capsid sequence other than SEQ ID NO:1, e.g., as described herein.

[0410] In some embodiments, the mutation corresponding to position 596 is a substitution compared to SEQ ID NO:1. In some embodiments, the substitution is a naturally occurring amino acid. In some embodiments, the substitution is a leucine. In some embodiments, the substitution at position 596 is V596L according to SEQ ID NO:1. In some embodiments, the substitution at the position corresponding to V596 of SEQ ID NO:1 is a substitution of valine at the position corresponding to V596 of SEQ ID NO:1 in a reference capsid sequence other than SEQ ID NO:1, e.g., as described herein.

[0411] In some embodiments, the mutation corresponding to position 598 is a substitution compared to SEQ ID NO:1. In some embodiments, the substitution is a naturally occurring amino acid. In some embodiments, the substitution is a serine. In some embodiments, the substitution at position 598 is N598S according to SEQ ID NO:1. In some embodiments, the substitution at the position corresponding to N598 of SEQ ID NO:1 is a substitution of valine at the position corresponding to N598 of SEQ ID NO:1 in a reference capsid sequence other than SEQ ID NO:1, e.g., as described herein.

[0412] In some embodiments, the mutation corresponding to position 601 is a substitution compared to SEQ ID NO: 1. In some embodiments, the substitution is a naturally occurring amino acid. In some embodiments, the substitution is alanine. In some embodiments, the substitution at position 601 is I601A according to SEQ ID NO: 1.

[0413] In some embodiments, the variant capsid polypeptide comprises a polypeptide having at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identity to the VP1, VP2, or VP3 sequence of SEQ ID NO:1, wherein the variant capsid polypeptide comprises: (a) a valine at a position corresponding to Q579 compared to SEQ ID NO:1; (b) an isoleucine at a position corresponding to Q592 compared to SEQ ID NO:1; (c) a valine at a position corresponding to T593 compared to SEQ ID NO:1; (d) an alanine at a position corresponding to W595 compared to SEQ ID NO:1; (e) a leucine at a position corresponding to V596 compared to SEQ ID NO:1; (f) a serine at a position corresponding to N598 compared to SEQ ID NO:1; (g) an alanine at a position corresponding to I601 compared to SEQ ID NO:1; or (h) a combination thereof, optionally wherein the variant capsid polypeptide comprises all of (a)-(g).

[0414] In some embodiments, the variant capsid polypeptide comprises a polypeptide having at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identity to the VP1, VP2, or VP3 sequence of SEQ ID NO:1, with the proviso that the variant capsid polypeptide is (i) a leucine at a position corresponding to V596 compared to SEQ ID NO:1, a serine at a position corresponding to N598 compared to SEQ ID NO:1, and an alanine at a position corresponding to I601 compared to SEQ ID NO:1; (ii) a valine at a position corresponding to Q579 relative to SEQ ID NO:1, a leucine at a position corresponding to V596 relative to SEQ ID NO:1, a serine at a position corresponding to N598 relative to SEQ ID NO:1, and an alanine at a position corresponding to I601 relative to SEQ ID NO:1; (iii) an alanine at a position corresponding to W595 relative to SEQ ID NO:1, a leucine at a position corresponding to V596 relative to SEQ ID NO:1, and a serine at a position corresponding to N598 relative to SEQ ID NO:1; (iv) a valine at a position corresponding to T593 compared to SEQ ID NO:1, an alanine at a position corresponding to W595 compared to SEQ ID NO:1, a leucine at a position corresponding to V596 compared to SEQ ID NO:1, and a serine at a position corresponding to N598 compared to SEQ ID NO:1; (v) an isoleucine at a position corresponding to Q592 relative to SEQ ID NO:1, a valine at a position corresponding to T593 relative to SEQ ID NO:1, and a leucine at a position corresponding to V596 relative to SEQ ID NO:1; (vi) a valine at a position corresponding to T593 compared to SEQ ID NO:1, a leucine at a position corresponding to V596 compared to SEQ ID NO:1, a serine at a position corresponding to N598 compared to SEQ ID NO:1, and an alanine at a position corresponding to I601 compared to SEQ ID NO:1; (vii) a valine at a position corresponding to Q579 compared to SEQ ID NO:1, an alanine at a position corresponding to W595 compared to SEQ ID NO:1, a leucine at a position corresponding to V596 compared to SEQ ID NO:1, and a serine at a position corresponding to N598 compared to SEQ ID NO:1; (viii) a valine at a position corresponding to Q579 compared to SEQ ID NO: 1, or (ix) A valine at a position corresponding to Q579 compared to SEQ ID NO: 1, a valine at a position corresponding to T593 compared to SEQ ID NO: 1, an alanine at a position corresponding to W595 compared to SEQ ID NO: 1, a leucine at a position corresponding to V596 compared to SEQ ID NO: 1, and a serine at a position corresponding to N598 compared to SEQ ID NO: 1.

[0415] In some embodiments, the variant capsid polypeptide comprises a polypeptide having at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identity to the VP1, VP2, or VP3 sequence of SEQ ID NO:1, wherein the variant capsid polypeptide comprises a leucine at a position corresponding to V596 compared to SEQ ID NO:1, a serine at a position corresponding to N598 compared to SEQ ID NO:1, and an alanine at a position corresponding to I601 compared to SEQ ID NO:1.

[0416] In some embodiments, the variant capsid polypeptide comprises a polypeptide having at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identity to the VP1, VP2, or VP3 sequence of SEQ ID NO:1, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579 compared to SEQ ID NO:1, a leucine at a position corresponding to V596 compared to SEQ ID NO:1, a serine at a position corresponding to N598 compared to SEQ ID NO:1, and an alanine at a position corresponding to I601 compared to SEQ ID NO:1.

[0417] In some embodiments, the variant capsid polypeptide comprises a polypeptide having at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identity to the VP1, VP2, or VP3 sequence of SEQ ID NO:1, provided that the variant capsid polypeptide comprises an alanine at a position corresponding to W595 compared to SEQ ID NO:1, a leucine at a position corresponding to V596 compared to SEQ ID NO:1, and a serine at a position corresponding to N598 compared to SEQ ID NO:1.

[0418] In some embodiments, the variant capsid polypeptide comprises a polypeptide having at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identity to the VP1, VP2, or VP3 sequence of SEQ ID NO:1, wherein the variant capsid polypeptide comprises a valine at a position corresponding to T593 compared to SEQ ID NO:1, an alanine at a position corresponding to W595 compared to SEQ ID NO:1, a leucine at a position corresponding to V596 compared to SEQ ID NO:1, and a serine at a position corresponding to N598 compared to SEQ ID NO:1.

[0419] In some embodiments, the variant capsid polypeptide comprises a polypeptide having at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identity to the VP1, VP2, or VP3 sequence of SEQ ID NO:1, wherein the variant capsid polypeptide comprises an isoleucine at a position corresponding to Q592 compared to SEQ ID NO:1, a valine at a position corresponding to T593 compared to SEQ ID NO:1, and a leucine at a position corresponding to V596 compared to SEQ ID NO:1.

[0420] In some embodiments, the variant capsid polypeptide comprises a polypeptide having at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identity to the VP1, VP2, or VP3 sequence of SEQ ID NO:1, wherein the variant capsid polypeptide comprises a valine at a position corresponding to T593 compared to SEQ ID NO:1, a leucine at a position corresponding to V596 compared to SEQ ID NO:1, a serine at a position corresponding to N598 compared to SEQ ID NO:1, and an alanine at a position corresponding to I601 compared to SEQ ID NO:1.

[0421] In some embodiments, the variant capsid polypeptide comprises a polypeptide having at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identity to the VP1, VP2, or VP3 sequence of SEQ ID NO:1, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579 compared to SEQ ID NO:1, an alanine at a position corresponding to W595 compared to SEQ ID NO:1, a leucine at a position corresponding to V596 compared to SEQ ID NO:1, and a serine at a position corresponding to N598 compared to SEQ ID NO:1.

[0422] In some embodiments, the variant capsid polypeptide comprises a polypeptide having at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identity to the VP1, VP2, or VP3 sequence of SEQ ID NO:1, provided that the variant capsid polypeptide comprises a valine at a position corresponding to Q579 compared to SEQ ID NO:1.

[0423] In some embodiments, the variant capsid polypeptide comprises a polypeptide having at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identity to the VP1, VP2, or VP3 sequence of SEQ ID NO:1, wherein the variant capsid polypeptide comprises a valine at a position corresponding to Q579 compared to SEQ ID NO:1, a valine at a position corresponding to T593 compared to SEQ ID NO:1, an alanine at a position corresponding to W595 compared to SEQ ID NO:1, a leucine at a position corresponding to V596 compared to SEQ ID NO:1, and a serine at a position corresponding to N598 compared to SEQ ID NO:1.

[0424] In some embodiments, the variant capsid polypeptide comprises a polypeptide having at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identity to the VP1, VP2, or VP3 sequence of SEQ ID NO:2, with the proviso that the variant capsid polypeptide is (i) a mutation between positions 596 and 601, wherein the mutation is Contains LnSnnA, a mutation in which n is any amino acid, optionally n is unmodified as shown in SEQ ID NO: 1; (ii) a mutation between positions 593 and 598, wherein the mutation is Contains n / VnALnS, n is any amino acid, optionally n is unmodified as set forth in SEQ ID NO: 1; Optionally, a mutation wherein the amino acid residue at position 593 is a valine; (iii) a mutation between positions 579 and 601, wherein the mutation is Contains V-(n)11-n / In / Vnn / ALnSnnA, n is any amino acid, optionally n is unmodified as set forth in SEQ ID NO: 1; Optionally, the amino acid residue at position 592 is isoleucine; Optionally, the amino acid residue at position 593 is valine; Optionally, a mutation in which the amino acid residue at position 595 is alanine, or (iv) a mutation between positions 579 and 601, wherein the mutation is Contains n / V-(n)11-n / In / Vnn / ALnSnnA, n is the wild-type residue shown in SEQ ID NO: 1; Optionally, the amino acid residue at position 579 is a valine; Optionally, the amino acid residue at position 592 is isoleucine; Optionally, the amino acid residue at position 593 is valine; Optionally, the mutation includes one in which the amino acid residue at position 595 is an alanine.

[0425] In some embodiments, the variant capsid polypeptide comprises a polypeptide having at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identity to the VP1, VP2, or VP3 sequence of SEQ ID NO:2, with the proviso that the variant capsid polypeptide comprises a mutation between positions 596 and 601, and the mutation is Contains LnSnnA, n is any amino acid, optionally n is unmodified as shown in SEQ ID NO:1.

[0426] In some embodiments, the variant capsid polypeptide comprises a polypeptide having at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identity to the VP1, VP2, or VP3 sequence of SEQ ID NO:2, with the proviso that the variant capsid polypeptide comprises a mutation between positions 593 and 598, and the mutation is Contains n / VnALnS, n is any amino acid, optionally n is unmodified as set forth in SEQ ID NO: 1, and optionally the amino acid residue at position 593 is valine. In some embodiments, the variant capsid polypeptide comprises a polypeptide having at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identity to the VP1, VP2, or VP3 sequence of SEQ ID NO: 2, with the proviso that the variant capsid polypeptide comprises a mutation between positions 593 and 598, and the mutation is Contains VnALnS, n is any amino acid, optionally n is unmodified as shown in SEQ ID NO:1.

[0427] In some embodiments, the variant capsid polypeptide comprises a polypeptide having at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identity to the VP1, VP2, or VP3 sequence of SEQ ID NO:2, with the proviso that the variant capsid polypeptide comprises a mutation between positions 579 and 601, and the mutation is ... Contains V-(n)11-n / In / Vnn / ALnSnnA, wherein n is any amino acid, optionally n is unmodified as set forth in SEQ ID NO: 1, optionally the amino acid residue at position 592 is isoleucine, optionally the amino acid residue at position 593 is valine, and optionally the amino acid residue at position 595 is alanine. In some embodiments, the variant capsid polypeptide comprises a polypeptide having at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identity to the VP1, VP2, or VP3 sequence of SEQ ID NO: 2, with the proviso that the variant capsid polypeptide comprises a mutation between positions 579 and 601, and the mutation is Contains V-(n)11-In / Vnn / ALnSnnA, n is any amino acid, optionally n is unmodified as set forth in SEQ ID NO: 1, optionally the amino acid residue at position 593 is valine, and optionally the amino acid residue at position 595 is alanine. In some embodiments, the variant capsid polypeptide comprises a polypeptide having at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identity to the VP1, VP2, or VP3 sequence of SEQ ID NO: 2, with the proviso that the variant capsid polypeptide comprises a mutation between positions 579 and 601, and the mutation is Contains V-(n)11-n / IVnn / ALnSnnA, wherein n is any amino acid, optionally n is unmodified as set forth in SEQ ID NO: 1, optionally the amino acid residue at position 592 is isoleucine, and optionally the amino acid residue at position 595 is alanine. In some embodiments, the variant capsid polypeptide comprises a polypeptide having at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identity to the VP1, VP2, or VP3 sequence of SEQ ID NO: 2, with the proviso that the variant capsid polypeptide comprises a mutation between positions 579 and 601, and the mutation is Contains V-(n)11-n / In / VnALnSnnA, n is any amino acid, optionally n is unmodified as set forth in SEQ ID NO: 1, optionally the amino acid residue at position 592 is isoleucine, and optionally the amino acid residue at position 593 is valine. In some embodiments, the variant capsid polypeptide comprises a polypeptide having at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identity to the VP1, VP2, or VP3 sequence of SEQ ID NO: 2, with the proviso that the variant capsid polypeptide comprises a mutation between positions 579 and 601, and the mutation is V-(n)11-IVnn / ALnSnnA, wherein n is any amino acid, optionally n is unmodified as set forth in SEQ ID NO: 1, and optionally the amino acid residue at position 595 is alanine. In some embodiments, the variant capsid polypeptide comprises a polypeptide having at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identity to the VP1, VP2, or VP3 sequence of SEQ ID NO: 2, with the proviso that the variant capsid polypeptide comprises a mutation between positions 579 and 601, and the mutation is Contains V-(n)11-In / VnALnSnnA, n is any amino acid, optionally n is unmodified as set forth in SEQ ID NO: 1, and optionally the amino acid residue at position 593 is valine. In some embodiments, the variant capsid polypeptide comprises a polypeptide having at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identity to the VP1, VP2, or VP3 sequence of SEQ ID NO: 2, with the proviso that the variant capsid polypeptide comprises a mutation between positions 579 and 601, and the mutation is Contains V-(n)11-n / IVnALnSnnA, n is any amino acid, optionally n is unmodified as set forth in SEQ ID NO: 1, and optionally the amino acid residue at position 592 is isoleucine. In some embodiments, the variant capsid polypeptide comprises a polypeptide having at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identity to the VP1, VP2, or VP3 sequence of SEQ ID NO: 2, with the proviso that the variant capsid polypeptide comprises a mutation between positions 579 and 601, and the mutation is V-(n)11-IVnALnSnnA, n is any amino acid, optionally n is unmodified as shown in SEQ ID NO:1.

[0428] In some embodiments, the variant capsid polypeptide comprises a polypeptide having at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identity to the VP1, VP2, or VP3 sequence of SEQ ID NO:2, with the proviso that the variant capsid polypeptide comprises a mutation between positions 579 and 601, and the mutation is ... Contains n / V-(n)11-n / In / Vnn / ALnSnnA, wherein n is the wild-type residue set forth in SEQ ID NO: 1, and optionally the amino acid residue at position 579 is valine, optionally the amino acid residue at position 592 is isoleucine, optionally the amino acid residue at position 593 is valine, and optionally the amino acid residue at position 595 is alanine. In some embodiments, the variant capsid polypeptide comprises a polypeptide having at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identity to the VP1, VP2, or VP3 sequence of SEQ ID NO: 2, with the proviso that the variant capsid polypeptide comprises a mutation between positions 579 and 601, and the mutation is Contains V-(n)11-n / In / Vnn / ALnSnnA, wherein n is the wild-type residue set forth in SEQ ID NO: 1, and optionally the amino acid residue at position 592 is isoleucine, optionally the amino acid residue at position 593 is valine, and optionally the amino acid residue at position 595 is alanine. In some embodiments, the variant capsid polypeptide comprises a polypeptide having at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identity to the VP1, VP2, or VP3 sequence of SEQ ID NO: 2, with the proviso that the variant capsid polypeptide comprises a mutation between positions 579 and 601, and the mutation is Contains n / V-(n)11-In / Vnn / ALnSnnA, wherein n is the wild-type residue set forth in SEQ ID NO: 1, and optionally the amino acid residue at position 579 is valine, optionally the amino acid residue at position 593 is valine, and optionally the amino acid residue at position 595 is alanine. In some embodiments, the variant capsid polypeptide comprises a polypeptide having at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identity to the VP1, VP2, or VP3 sequence of SEQ ID NO: 2, with the proviso that the variant capsid polypeptide comprises a mutation between positions 579 and 601, and the mutation is Contains n / V-(n)11-n / IVnn / ALnSnnA, wherein n is the wild-type residue set forth in SEQ ID NO: 1, and optionally the amino acid residue at position 579 is valine, optionally the amino acid residue at position 592 is isoleucine, and optionally the amino acid residue at position 595 is alanine. In some embodiments, the variant capsid polypeptide comprises a polypeptide having at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identity to the VP1, VP2, or VP3 sequence of SEQ ID NO: 2, with the proviso that the variant capsid polypeptide comprises a mutation between positions 579 and 601, and the mutation is n / V-(n)11-n / In / VnALnSnnA, wherein n is the wild-type residue set forth in SEQ ID NO: 1, and optionally the amino acid residue at position 579 is valine, optionally the amino acid residue at position 592 is isoleucine, and optionally the amino acid residue at position 593 is valine. In some embodiments, the variant capsid polypeptide comprises a polypeptide having at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identity to the VP1, VP2, or VP3 sequence of SEQ ID NO: 2, with the proviso that the variant capsid polypeptide comprises a mutation between positions 579 and 601, and the mutation is Contains V-(n)11-In / Vnn / ALnSnnA, wherein n is the wild-type residue set forth in SEQ ID NO: 1, and optionally the amino acid residue at position 593 is valine, and optionally the amino acid residue at position 595 is alanine. In some embodiments, the variant capsid polypeptide comprises a polypeptide having at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identity to the VP1, VP2, or VP3 sequence of SEQ ID NO: 2, with the proviso that the variant capsid polypeptide comprises a mutation between positions 579 and 601, and the mutation is Contains V-(n)11-n / IVnn / ALnSnnA, wherein n is the wild-type residue set forth in SEQ ID NO: 1, and optionally the amino acid residue at position 592 is isoleucine, and optionally the amino acid residue at position 595 is alanine. In some embodiments, the variant capsid polypeptide comprises a polypeptide having at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identity to the VP1, VP2, or VP3 sequence of SEQ ID NO: 2, with the proviso that the variant capsid polypeptide comprises a mutation between positions 579 and 601, and the mutation is Contains V-(n)11-n / In / VnALnSnnA, and n is the wild-type residue set forth in SEQ ID NO: 1, and optionally the amino acid residue at position 592 is isoleucine, and optionally the amino acid residue at position 593 is valine. In some embodiments, the variant capsid polypeptide comprises a polypeptide having at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identity to the VP1, VP2, or VP3 sequence of SEQ ID NO: 2, with the proviso that the variant capsid polypeptide comprises a mutation between positions 579 and 601, and the mutation is n / V-(n)11-IVnn / ALnSnnA, wherein n is the wild-type residue set forth in SEQ ID NO: 1, and optionally the amino acid residue at position 579 is valine, and optionally the amino acid residue at position 595 is alanine. In some embodiments, the variant capsid polypeptide comprises a polypeptide having at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identity to the VP1, VP2, or VP3 sequence of SEQ ID NO: 2, with the proviso that the variant capsid polypeptide comprises a mutation between positions 579 and 601, and the mutation is n / V-(n)11-In / VnALnSnnA, wherein n is the wild-type residue set forth in SEQ ID NO: 1, and optionally the amino acid residue at position 579 is valine, and optionally the amino acid residue at position 593 is valine. In some embodiments, the variant capsid polypeptide comprises a polypeptide having at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identity to the VP1, VP2, or VP3 sequence of SEQ ID NO: 2, with the proviso that the variant capsid polypeptide comprises a mutation between positions 579 and 601, and the mutation is n / V-(n)11-n / IVnALnSnnA, and n is the wild-type residue set forth in SEQ ID NO: 1, and optionally the amino acid residue at position 579 is valine, and optionally the amino acid residue at position 592 is isoleucine. In some embodiments, the variant capsid polypeptide comprises a polypeptide having at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identity to the VP1, VP2, or VP3 sequence of SEQ ID NO: 2, with the proviso that the variant capsid polypeptide comprises a mutation between positions 579 and 601, and the mutation is V-(n)11-IVnn / ALnSnnA, 1, and optionally, the amino acid residue at position 595 is alanine. In some embodiments, the variant capsid polypeptide comprises a polypeptide having at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identity to the VP1, VP2, or VP3 sequence of SEQ ID NO:2, with the proviso that the variant capsid polypeptide comprises a mutation between positions 579 and 601, and the mutation is Contains V-(n)11-In / VnALnSnnA, 1, and optionally the amino acid residue at position 593 is valine. In some embodiments, the variant capsid polypeptide comprises a polypeptide having at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identity to the VP1, VP2, or VP3 sequence of SEQ ID NO:2, with the proviso that the variant capsid polypeptide comprises a mutation between positions 579 and 601, and the mutation is Contains V-(n)11-n / IVnALnSnnA, 1, and optionally, the amino acid residue at position 592 is isoleucine. In some embodiments, the variant capsid polypeptide comprises a polypeptide having at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identity to the VP1, VP2, or VP3 sequence of SEQ ID NO:2, with the proviso that the variant capsid polypeptide comprises a mutation between positions 579 and 601, and the mutation is n / V-(n)11-IVnALnSnnA, n is the wild-type residue set forth in SEQ ID NO: 1, and optionally, the amino acid residue at position 579 is a valine.

[0429] In some embodiments, the variant capsid polypeptide comprises a mutation corresponding to a Q579V mutation compared to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises a mutation corresponding to a Q592I mutation compared to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises a mutation corresponding to a T593V mutation compared to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises a mutation corresponding to a W595A mutation compared to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises a mutation corresponding to a V596L mutation compared to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises a mutation corresponding to a N598S mutation compared to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises a mutation corresponding to a I601A mutation compared to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to Q579V and Q592I mutations compared to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to Q579V and T593V mutations compared to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to Q579V and W595A mutations compared to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to Q579V and V596L mutations compared to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to Q579V and N598S mutations compared to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to Q579V and I601A mutations compared to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to Q592I and T593V mutations compared to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to Q592I and W595A mutations compared to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to Q592I and V596L mutations compared to SEQ ID NO:1.In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q592I and N598S mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q592I and I601A mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the T593V and W595A mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the T593V and V596L mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the T593V and N598S mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the T593V and I601A mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the W595A and V596L mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the W595A and N598S mutations compared to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the W595A and I601A mutations compared to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the V596L and N598S mutations compared to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the V596L and I601A mutations compared to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the N598S and I601A mutations compared to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, Q592I, and T593V mutations compared to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, Q592I, and W595A mutations compared to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, Q592I, and V596L mutations compared to SEQ ID NO:1.In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, Q592I, and N598S mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, Q592I, and I601A mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, T593V, and W595A mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, T593V, and V596L mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, T593V, and N598S mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, T593V, and I601A mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, W595A, and V596L mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, W595A, and N598S mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, W595A, and I601A mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, V596L, and N598S mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, V596L, and I601A mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, N598S, and I601A mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q592I, T593V, and W595A mutations relative to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q592I, T593V, and V596L mutations relative to SEQ ID NO: 1.In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q592I, T593V, and N598S mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q592I, T593V, and I601A mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q592I, W595A, and V596L mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q592I, W595A, and N598S mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q592I, W595A, and I601A mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q592I, V596L, and N598S mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q592I, V596L, and I601A mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q592I, N598S, and I601A mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the T593V, W595A, and V596L mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the T593V, W595A, and N598S mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the T593V, W595A, and I601A mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the T593V, V596L, and N598S mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the T593V, V596L, and I601A mutations relative to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the T593V, N598S, and I601A mutations relative to SEQ ID NO: 1.In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the W595A, V596L, and N598S mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the W595A, V596L, and I601A mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the W595A, N598S, and I601A mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the V596L, N598S, and I601A mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, Q592I, T593V, and W595A mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, Q592I, T593V, and V596L mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, Q592I, T593V, and N598S mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, Q592I, T593V, and I601A mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, Q592I, W595A, and V596L mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, Q592I, W595A, and N598S mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, Q592I, W595A, and I601A mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, Q592I, W595A, and V596L mutations relative to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, Q592I, W595A, and N598S mutations relative to SEQ ID NO: 1.In some embodiments, the variant capsid polypeptide comprises mutations corresponding to Q579V, Q592I, W595A, and I601A mutations relative to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to Q579V, Q592I, T593V, and V596L ... In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, Q592I, T593V, and N598S mutations relative to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, Q592I, T593V, and I601A mutations relative to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q592I, T593V, W595A, and N596S mutations relative to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q592I, T593V, W595A, and N598S mutations relative to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q592I, T593V, W595A, and I601A mutations relative to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the T593V, W595A, V596L, and N598S mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the T593V, W595A, V596L, and I601A mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the W595A, V596L, N598S, and I601A mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, Q592I, V596L, and N598S mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, Q592I, V596L, and I601A mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, Q592I, N598S, and I601A mutations compared to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, T593V, V596L, and N598S mutations relative to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, T593V, V596L, and I601A mutations relative to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, T593V, N598S, and I601A mutations relative to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, W595A, V596L, and N598S mutations relative to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, W595A, V596L, and I601A mutations relative to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, W595A, N598S, and I601A mutations relative to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q592I, T593V, V596L, and N598S mutations relative to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q592I, T593V, V596L, and I601A mutations relative to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q592I, T593V, N598S, and I601A mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q592I, W595A, V596L, and N598S mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q592I, W595A, V596L, and I601A mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q592I, W595A, N598S, and I601A mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q592I, V596L, N598S, and I601A mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the T593V, W595A, N598S, and I601A mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the T593V, V596L, N598S, and I601A mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, Q592I, T593V, W595A, and V596L mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, Q592I, T593V, W595A, and N598S mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, Q592I, T593V, W595A, and I601A mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, T593V, W595A, V596L, and N598S mutations relative to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, T593V, W595A, V596L, and I601A mutations relative to SEQ ID NO: 1.In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, Q592I, W595A, V596L, and N598S mutations relative to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, Q592I, W595A, V596L, and I601A mutations relative to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, Q592I, T593V, V596L, and N598S mutations relative to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, Q592I, T593V, V596L, and I601A mutations relative to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, Q592I, T593V, W595A, and N598S mutations relative to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, Q592I, T593V, W595A, and I601A mutations relative to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q592I, T593V, W595A, V596L, and N598S mutations relative to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q592I, T593V, W595A, V596L, and I601A mutations relative to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the T593V, W595A, V596L, N598S, and I601A mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, T593V, W595A, N598S, and I601A mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, T593V, V596L, N598S, and I601A mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, W595A, V596L, N598S, and I601A mutations compared to SEQ ID NO: 1.In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, Q592I, W595A, N598S, and I601A mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, Q592I, V596L, N598S, and I601A mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, W595A, V596L, N598S, and I601A mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, Q592I, T593V, N598S, and I601A mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q592V, T593V, W595A, N598S, and I601A mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q592V, T593V, V596L, N598S, and I601A mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q592V, W595A, V596L, N598S, and I601A mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, Q592I, T593V, W595A, V596L, and N598S mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, Q592I, T593V, W595A, V596L, and I601A mutations relative to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q592V, T593V, W595A, V596L, N598S, and I601A mutations relative to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, T593V, W595A, V596L, N598S, and I601A mutations relative to SEQ ID NO: 1.In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, Q592I, W595A, V596L, N598S, and I601A mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, Q592I, T593V, V596L, N598S, and I601A mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, Q592I, T593V, W595A, N598S, and I601A mutations compared to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises mutations corresponding to the Q579V, Q592I, T593V, W595A, V596L, N598S, and I601A mutations compared to SEQ ID NO: 1.

[0430] In some embodiments, the variant capsid polypeptide comprises: (a) a sequence comprising any one of SEQ ID NOs: 2-139; (b) a sequence having at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to, or comprising a set of mutations in, any one of SEQ ID NOs: 2 or 14-139; or (c) a sequence comprising a set of mutations in any one of SEQ ID NOs: 2 or 14-139, and having at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 single amino acid mutations relative to any one of SEQ ID NOs: 2 or 14-139, and optionally having fewer than 70, 60, 50, 40, 35, 30, or 20 single amino acid mutations relative to any one of SEQ ID NOs: 2 or 14-139.

[0431] In some embodiments, the disclosure provides variant capsid polypeptides (and nucleic acids encoding the variant capsid polypeptides) that include at least one mutational difference relative to any variant capsid polypeptide in Table 1, or that include at least one mutation that corresponds to a mutational difference relative to any variant capsid polypeptide in Table 1. In some embodiments, the disclosure provides variant capsid polypeptides (and nucleic acids encoding the capsid polypeptides) that include at least two mutational differences relative to any variant capsid polypeptide in Table 1, or that include at least two mutations that correspond to two mutational differences relative to any variant capsid polypeptide in Table 1. In some embodiments, the disclosure provides variant capsid polypeptides (and nucleic acids encoding the capsid polypeptides) that include at least three mutational differences relative to any variant capsid polypeptide in Table 1, or that include at least three mutations that correspond to the three mutational differences relative to any variant capsid polypeptide in Table 1. In some embodiments, the disclosure provides variant capsid polypeptides (and nucleic acids encoding the capsid polypeptides) that include at least four mutational differences relative to any variant capsid polypeptide in Table 1, or that include at least four mutations that correspond to the four mutational differences relative to any variant capsid polypeptide in Table 1. In some embodiments, the disclosure provides variant capsid polypeptides (and nucleic acids encoding the capsid polypeptides) that include at least five mutational differences relative to any variant capsid polypeptide in Table 1, or that include at least five mutations that correspond to the five mutational differences relative to any variant capsid polypeptide in Table 1. In some embodiments, the disclosure provides variant capsid polypeptides (and nucleic acids encoding the capsid polypeptides) that include at least six mutational differences relative to any variant capsid polypeptide in Table 1, or that include at least six mutations that correspond to the six mutational differences relative to any variant capsid polypeptide in Table 1.In some embodiments, the disclosure provides variant capsid polypeptides (and nucleic acids encoding the capsid polypeptides) that comprise at least seven mutational differences relative to any of the variant capsid polypeptides in Table 1, or that comprise at least seven mutations that correspond to the seven mutational differences relative to any of the variant capsid polypeptides in Table 1.

[0432] In some embodiments, the disclosure provides variant capsid polypeptides (and nucleic acids encoding the capsid polypeptides) that include all of the mutational differences associated with any of the variant capsid polypeptides in Table 1, or that include mutations that correspond to all of the mutational differences associated with any of the variant capsid polypeptides in Table 1.

[0433] In any of the above-described aspects, where a mutational difference associated with any variant capsid polypeptide in Table 1, or a number of mutational differences corresponding to the mutational difference of any variant capsid polypeptide in Table 1, is specified, it will be understood that the mutation may be selected from any of the mutational differences associated with that variant capsid polypeptide. Thus, for example, with respect to the VAR-1 mutational differences (Q579V, Q592I, T593V, W595A, V596L, N598S, I601A), if a variant capsid includes one of the mutational differences, it may be Q579V, Q592I, T593V, W595A, V596L, N598S, or I601A. Similarly, if the variant capsid contains two of the mutation differences, those two are Q579V and Q592I, Q579V and T593V, Q579V and W595A, Q579V and V596L, Q579V and N598S, Q579V and I601A, Q592I and T593V, Q592I and W595A, Q592I and V596L, Q592 It may also be I and N598S, Q592I and I601A, T593V and W595A, T593V and V596L, T593V and N598S, T593V and I601A, W595A and V596L, W595A and N598S, W595A and I601A, V596L and N598S, V596L and I601A, N598S and I601A. Similarly, if a variant contains three of the mutational differences, those three are Q579V, Q592I, and T593V, Q579V, Q592I, and W595A, Q579V, Q592I, and V596L, Q579V, Q592I, and N598S, Q579V, Q592I, and I601A, Q592I, T593V, and W595A, Q592I, T593V, and V596L. 96L, Q592I and T593V and N598S, Q592I and T593V and I601A, T593V and W595A and V596L, T593V and W595A and N598S, T593V and W595A and I601A, W595A and V596L and N598S, W595A and V596L and I601A, V596L and N598S and I601A.Similarly, if a variant contains four of the mutational differences, those four are Q579V and Q592I and T593V and W595A, Q579V and Q592I and T593V and V596L, Q579V and Q592I and T593V and N598S, Q579V and Q592I and T593V and I601A, Q592I and T593V and and W595A and V596L, Q592I and T593V and W595A and N598S, Q592I and T593V and W595A and I601A, T593V and W595A and V596L and N598S, T593V and W595A and V596L and I601A, W595A and V596L and N598S and I601A. Similarly, if a variant includes five of the mutational differences, those five may be Q579V and Q592I and T593V and W595A and V596L; Q579V and Q592I and T593V and W595A and N598S; Q579V and Q592I and T593V and W595A and I601A; Q592I and T593V and W595A and V596L and N598S; Q592I and T593V and W595A and V596L and I601A; T593V and W595A and V596L and N598S and I601A. Similarly, if a variant contains six of the mutational differences, those six are: Q579V and Q592I and T593V and W595A and V596L and N598S; Q579V and Q592I and T593V and W595A and V596L and I601A; Q592I and T593V and W595A and V596L and N598S and I601A; Q579V and It may be T593V and W595A and V596L and N598S and I601A, Q579V and Q592I and W595A and V596L and N598S and I601A, Q579V and Q592I and T593V and V596L and N598S and I601A, Q579V and Q592I and T593V and W595A and N598S and I601A. Similarly, if the variant includes seven of the mutational differences, those seven may be Q579V and Q592I and T593V and W595A and V596L and N598S and I601A.

[0434] In some embodiments, the variant capsid polypeptide comprises one or more mutational differences, e.g., as described herein, e.g., as described in Table 1, e.g., has at least 80%, at least 85%, at least 90%, 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 a reference AAV serotype (e.g., as described herein, e.g., SEQ ID NO: 1). In some embodiments, the variant capsid polypeptide comprises one or more mutational differences as described in Table 1, or corresponding to one or more mutational differences as described in Table 1. In some embodiments, the variant capsid polypeptide is at least 90%, at least 95%, 96%, 97%, 98%, 99%, or 100% identical to a reference AAV serotype described herein, except for the mutational differences as described in Table 1, or corresponding to the mutational differences as described in Table 1. In some embodiments, the variant capsid polypeptides described herein are at least 90%, at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the capsid polypeptide of SEQ ID NO: 1 (e.g., the VP1, VP2, or VP3 sequence of SEQ ID NO: 1), except for the mutational differences in Table 1, or corresponding mutational differences in Table 1, contained within such capsid polypeptide. In some embodiments, the variant capsid polypeptides described herein are at least 90%, at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the capsid polypeptide of SEQ ID NO: 5 (e.g., the VP1, VP2, or VP3 sequence of SEQ ID NO: 5), except for the mutational differences in Table 1, or corresponding mutational differences in Table 1, contained within such capsid polypeptide. In some embodiments, the variant capsid polypeptides described herein are at least 90%, at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the capsid polypeptide of SEQ ID NO: 7 (e.g., the VP1, VP2, or VP3 sequence of SEQ ID NO: 7), except for the mutational differences of Table 1 contained within such capsid polypeptide, or mutational differences corresponding to the mutational differences of Table 1.In some embodiments, the variant capsid polypeptides described herein are at least 90%, at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the capsid polypeptide of SEQ ID NO: 9 (e.g., the VP1, VP2, or VP3 sequence of SEQ ID NO: 9), except for the mutational differences in Table 1, or corresponding mutational differences, contained within such capsid polypeptide. In some embodiments, the variant capsid polypeptides described herein are at least 90%, at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the capsid polypeptide of SEQ ID NO: 11 (e.g., the VP1, VP2, or VP3 sequence of SEQ ID NO: 11), except for the mutational differences in Table 1, or corresponding mutational differences, contained within such capsid polypeptide. In some embodiments, the variant capsid polypeptides described herein are at least 90%, at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the capsid polypeptide of SEQ ID NO: 12 (e.g., the VP1, VP2, or VP3 sequence of SEQ ID NO: 12), except for the mutational differences in Table 1 contained within such capsid polypeptide, or mutational differences corresponding to the mutational differences in Table 1.

[0435] In some embodiments, the variant capsid polypeptide comprises the sequence VVATNHQSAQAQAIVGALQSQGA (SEQ ID NO: 266), or comprises the sequence IVGALQSQGA (SEQ ID NO: 267), or comprises the sequence VGALQS (SEQ ID NO: 268). In some embodiments, the variant capsid polypeptide comprises the sequence VVATNHQSAQAQAIVGALQSQGA (SEQ ID NO: 266), or comprises the sequence IVGALQSQGA (SEQ ID NO: 267), or comprises the sequence VGALQS (SEQ ID NO: 268), optionally within a region of the variant capsid polypeptide corresponding to amino acids 550 to 620 according to SEQ ID NO: 1.

[0436] In some embodiments, the variant capsid polypeptide comprises the sequence VVATNHQSAQAQAIVGALQSQGA (SEQ ID NO: 266). In some embodiments, the variant capsid polypeptide comprises the sequence IVGALQSQGA (SEQ ID NO: 267). In some embodiments, the variant capsid polypeptide comprises the sequence VGALQS (SEQ ID NO: 268). In some embodiments, the variant capsid polypeptide comprises the sequence VVATNHQSAQAQAIVGALQSQGA (SEQ ID NO: 266), optionally within a region of the variant capsid polypeptide corresponding to amino acids 550-620 according to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises the sequence IVGALQSQGA (SEQ ID NO: 267) or comprises the sequence VGALQS (SEQ ID NO: 268), optionally within a region of the variant capsid polypeptide corresponding to amino acids 550-620 according to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises the sequence VGALQS (SEQ ID NO: 268), optionally within a region of the variant capsid polypeptide corresponding to amino acids 550 to 620 according to SEQ ID NO: 1.

[0437] In some embodiments, the variant capsid polypeptide comprises the sequence VVATNHQSAQAQAIVGALQSQGA (SEQ ID NO: 266), wherein the capsid polypeptide has greater than 95%, greater than 96%, greater than 97%, greater than 98%, or greater than 99% sequence identity to the capsid polypeptide of SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises the sequence IVGALQSQGA (SEQ ID NO: 267), wherein the capsid polypeptide has greater than 95%, greater than 96%, greater than 97%, greater than 98%, or greater than 99% sequence identity to the capsid polypeptide of SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises the sequence VGALQS (SEQ ID NO: 268), wherein the capsid polypeptide has greater than 95%, greater than 96%, greater than 97%, greater than 98%, or greater than 99% sequence identity to the capsid polypeptide of SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises the sequence VVATNHQSAQAQAIVGALQSQGA (SEQ ID NO:266), wherein the capsid polypeptide has greater than 95%, greater than 96%, greater than 97%, greater than 98%, or greater than 99% sequence identity to the capsid polypeptide of SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, or SEQ ID NO: 12. In some embodiments, the variant capsid polypeptide comprises the sequence IVGALQSQGA (SEQ ID NO:267), wherein the capsid polypeptide has greater than 95%, greater than 96%, greater than 97%, greater than 98%, or greater than 99% sequence identity to the capsid polypeptide of SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, or SEQ ID NO:12. In some embodiments, the variant capsid polypeptide comprises the sequence VGALQS (SEQ ID NO:268), wherein the capsid polypeptide has greater than 95%, greater than 96%, greater than 97%, greater than 98%, or greater than 99% sequence identity to the capsid polypeptide of SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, or SEQ ID NO:12.In some embodiments, the variant capsid polypeptide comprises the sequence VVATNHQSAQAQAIVGALQSQGA (SEQ ID NO:266), wherein the sequence VVATNHQSAQAQAIVGALQSQGA (SEQ ID NO:266) is present at a position corresponding to amino acids 579-601 according to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises the sequence IVGALQSQGA (SEQ ID NO:267), wherein the sequence IVGALQSQGA (SEQ ID NO:267) is present at a position corresponding to amino acids 592-601 according to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises the sequence VGALQS (SEQ ID NO:268), wherein the sequence VGALQS (SEQ ID NO:268) is present at a position corresponding to amino acids 592-601 according to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises the sequence VVATNHQSAQAQAIVGALQSQGA (SEQ ID NO:266), wherein the capsid polypeptide has greater than 95%, greater than 96%, greater than 97%, greater than 98%, or greater than 99% sequence identity to the capsid polypeptide of SEQ ID NO: 1, and wherein the sequence VVATNHQSAQAQAIVGALQSQGA (SEQ ID NO:266) is present at a position corresponding to amino acids 579-601 according to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises the sequence IVGALQSQGA (SEQ ID NO:267), wherein the capsid polypeptide has greater than 95%, greater than 96%, greater than 97%, greater than 98%, or greater than 99% sequence identity to the capsid polypeptide of SEQ ID NO: 1, and wherein the sequence IVGALQSQGA (SEQ ID NO:267) is present at a position corresponding to amino acids 592-601 according to SEQ ID NO:1. In some embodiments, the variant capsid polypeptide comprises the sequence VGALQS (SEQ ID NO:268), wherein the capsid polypeptide has greater than 95%, greater than 96%, greater than 97%, greater than 98%, or greater than 99% sequence identity to the capsid polypeptide of SEQ ID NO:1, and wherein the sequence VGALQS (SEQ ID NO:268) is present at a position corresponding to amino acids 592 to 601 according to SEQ ID NO:1.In some embodiments, the variant capsid polypeptide comprises the sequence VVATNHQSAQAQAIVGALQSQGA (SEQ ID NO: 266), wherein the capsid polypeptide has greater than 95%, greater than 96%, greater than 97%, greater than 98%, or greater than 99% sequence identity to the capsid polypeptide of SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, or SEQ ID NO: 12, and wherein the sequence VVATNHQSAQAQAIVGALQSQGA (SEQ ID NO: 266) is present at a position corresponding to amino acids 579-601 according to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises the sequence IVGALQSQGA (SEQ ID NO:267), wherein the capsid polypeptide has greater than 95%, greater than 96%, greater than 97%, greater than 98%, or greater than 99% sequence identity to the capsid polypeptide of SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, or SEQ ID NO:12, and wherein the sequence IVGALQSQGA (SEQ ID NO:267) is present at a position corresponding to amino acids 592-601 according to SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises the sequence VGALQS (SEQ ID NO:268), wherein the capsid polypeptide has greater than 95%, greater than 96%, greater than 97%, greater than 98%, or greater than 99% sequence identity to the capsid polypeptide of SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, or SEQ ID NO:12, and wherein the sequence VGALQS (SEQ ID NO:268) is present at a position corresponding to amino acids 592-601 according to SEQ ID NO:1.

[0438] In some embodiments, the variant capsid polypeptide comprises the sequence VGALQS (SEQ ID NO:268), and optionally the variant capsid polypeptide has greater than 95%, greater than 96%, greater than 97%, greater than 98%, or greater than 99% sequence identity to the capsid polypeptide of SEQ ID NO: 1. In some embodiments, the variant capsid polypeptide comprises the sequence VGALQS (SEQ ID NO:268), and the variant capsid polypeptide has greater than 95%, greater than 96%, greater than 97%, greater than 98%, or greater than 99% sequence identity to the capsid polypeptide of SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, or SEQ ID NO:12. In some embodiments, the sequence VGALQS (SEQ ID NO:268) is present at a position corresponding to amino acids 593-598 according to SEQ ID NO:1.

[0439] In some embodiments, a variant capsid polypeptide is selected from the group consisting of SEQ ID NOs: 2, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82 , 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, or 139, optionally 15 or fewer edits relative to SEQ ID NO:2. and SEQ ID NOs: 2, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89 , 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, or 139.In such embodiments, the reference sequence used to calculate the edit distance is the same as the sequence from which the set of mutations present in the variant capsid polypeptide is derived. For example, in one embodiment, a variant capsid polypeptide is provided that comprises a sequence having an edit distance of 15 or less to SEQ ID NO:2, and further comprises the set of mutations of SEQ ID NO:2 (i.e., a valine at position 579, an isoleucine at position 592, a valine at position 593, an alanine at position 595, a leucine at position 596, a serine at position 598, and an alanine at position 601, all having numbering relative to SEQ ID NO:1).

[0440] In some embodiments, the variant capsid polypeptide is selected from the group consisting of SEQ ID NOs: 2, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 1 for any one of 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, or 139 5 or less, and SEQ ID NOs: 2, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83 , 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, or 139.In some embodiments, the variant capsid polypeptide is selected from the group consisting of SEQ ID NOs: 2, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, any one of 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, or 139, optionally SEQ ID NO: 2, and SEQ ID NOs: 2, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82 , 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, or 139.In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO:2, and further comprises any one of the set of mutations in SEQ ID NO:2. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO:14, and further comprises any one of the set of mutations in SEQ ID NO:14. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO:15, and further comprises any one of the set of mutations in SEQ ID NO:15. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO:16, and further comprises any one of the set of mutations in SEQ ID NO:16. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO:17, and further comprises any one of the set of mutations in SEQ ID NO:17. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO:18, and further comprises any one of the set of mutations in SEQ ID NO:18. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 19, and further comprises any one of the set of mutations in SEQ ID NO: 19. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 20, and further comprises any one of the set of mutations in SEQ ID NO: 20. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 21, and further comprises any one of the set of mutations in SEQ ID NO: 21. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 22, and further comprises any one of the set of mutations in SEQ ID NO: 22. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 23, and further comprises any one of the set of mutations in SEQ ID NO: 23.In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO:24, and further comprises the set of mutations of any one of SEQ ID NO:24. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO:25, and further comprises the set of mutations of any one of SEQ ID NO:25. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO:26, and further comprises the set of mutations of any one of SEQ ID NO:26. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO:27, and further comprises the set of mutations of any one of SEQ ID NO:27. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO:28, and further comprises the set of mutations of any one of SEQ ID NO:28. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO:29, and further comprises the set of mutations of any one of SEQ ID NO:29. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 30, and further comprises any one of the set of mutations of SEQ ID NO: 30. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 31, and further comprises any one of the set of mutations of SEQ ID NO: 31. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 32, and further comprises any one of the set of mutations of SEQ ID NO: 32. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 33, and further comprises any one of the set of mutations of SEQ ID NO: 33. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 34, and further comprises any one of the set of mutations of SEQ ID NO: 34.In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 35, and further comprises any one of the set of mutations of SEQ ID NO: 35. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 36, and further comprises any one of the set of mutations of SEQ ID NO: 36. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 37, and further comprises any one of the set of mutations of SEQ ID NO: 37. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 38, and further comprises any one of the set of mutations of SEQ ID NO: 38. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 39, and further comprises any one of the set of mutations of SEQ ID NO: 39. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 40, and further comprises any one of the set of mutations of SEQ ID NO: 40. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 41, and further comprises any one of the set of mutations of SEQ ID NO: 41. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 42, and further comprises any one of the set of mutations of SEQ ID NO: 42. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 43, and further comprises any one of the set of mutations of SEQ ID NO: 43. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 44, and further comprises any one of the set of mutations of SEQ ID NO: 44. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 45, and further comprises any one of the set of mutations of SEQ ID NO: 45.In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 46, and further comprises the set of mutations of any one of SEQ ID NO: 46. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 47, and further comprises the set of mutations of any one of SEQ ID NO: 47. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 48, and further comprises the set of mutations of any one of SEQ ID NO: 48. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 49, and further comprises the set of mutations of any one of SEQ ID NO: 49. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO:50, and further comprises the set of mutations of any one of SEQ ID NO:50. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO:51, and further comprises the set of mutations of any one of SEQ ID NO:51. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO:52, and further comprises the set of mutations of any one of SEQ ID NO:52. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO:53, and further comprises the set of mutations of any one of SEQ ID NO:53. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO:54, and further comprises the set of mutations of any one of SEQ ID NO:54. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 55, and further comprises any one of the set of mutations of SEQ ID NO: 55. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 56, and further comprises any one of the set of mutations of SEQ ID NO: 56. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 57, and further comprises any one of the set of mutations of SEQ ID NO: 57. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 58, and further comprises any one of the set of mutations of SEQ ID NO: 58. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 59, and further comprises any one of the set of mutations of SEQ ID NO: 59. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 60, and further comprises any one of the set of mutations of SEQ ID NO: 60.In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 61, and further comprises any one of the set of mutations of SEQ ID NO: 61. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 62, and further comprises any one of the set of mutations of SEQ ID NO: 62. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 63, and further comprises any one of the set of mutations of SEQ ID NO: 63. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 64, and further comprises any one of the set of mutations of SEQ ID NO: 64. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 65, and further comprises any one of the set of mutations of SEQ ID NO: 65. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 66, and further comprises any one of the set of mutations of SEQ ID NO: 66. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 67, and further comprises any one of the set of mutations of SEQ ID NO: 67. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 68, and further comprises any one of the set of mutations of SEQ ID NO: 68. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 69, and further comprises any one of the set of mutations of SEQ ID NO: 69. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 70, and further comprises any one of the set of mutations of SEQ ID NO: 70. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 71, and further comprises any one of the set of mutations of SEQ ID NO: 71.In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 72, and further comprises any one of the set of mutations of SEQ ID NO: 72. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 73, and further comprises any one of the set of mutations of SEQ ID NO: 73. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 74, and further comprises any one of the set of mutations of SEQ ID NO: 74. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 75, and further comprises any one of the set of mutations of SEQ ID NO: 75. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 76, and further comprises any one of the set of mutations of SEQ ID NO: 76. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 77, and further comprises any one of the set of mutations of SEQ ID NO: 77. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 78, and further comprises any one of the set of mutations of SEQ ID NO: 78. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 79, and further comprises any one of the set of mutations of SEQ ID NO: 79. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 80, and further comprises any one of the set of mutations of SEQ ID NO: 80. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 81, and further comprises any one of the set of mutations of SEQ ID NO: 81. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 82, and further comprises any one of the set of mutations of SEQ ID NO: 82.In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 83, and further comprises the set of mutations of any one of SEQ ID NO: 83. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 84, and further comprises the set of mutations of any one of SEQ ID NO: 84. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 85, and further comprises the set of mutations of any one of SEQ ID NO: 85. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 86, and further comprises the set of mutations of any one of SEQ ID NO: 86. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 87, and further comprises the set of mutations of any one of SEQ ID NO: 87. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 88, and further comprises the set of mutations of any one of SEQ ID NO: 88. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 89, and further comprises the set of mutations of any one of SEQ ID NO: 89. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 90, and further comprises the set of mutations of any one of SEQ ID NO: 90. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 91, and further comprises the set of mutations of any one of SEQ ID NO: 91. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 92, and further comprises the set of mutations of any one of SEQ ID NO: 92. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 93, and further comprises the set of mutations of any one of SEQ ID NO: 93.In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 94, and further comprises the set of mutations of any one of SEQ ID NO: 94. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 95, and further comprises the set of mutations of any one of SEQ ID NO: 95. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 96, and further comprises the set of mutations of any one of SEQ ID NO: 96. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 97, and further comprises the set of mutations of any one of SEQ ID NO: 97. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 98, and further comprises the set of mutations of any one of SEQ ID NO: 98. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 99, and further comprises the set of mutations of any one of SEQ ID NO: 99. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 100, and further comprises any one of the set of mutations of SEQ ID NO: 100. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 101, and further comprises any one of the set of mutations of SEQ ID NO: 101. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 102, and further comprises any one of the set of mutations of SEQ ID NO: 102. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 103, and further comprises any one of the set of mutations of SEQ ID NO: 103. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 104, and further comprises any one of the set of mutations of SEQ ID NO: 104.In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 105, and further comprises a mutation set of any one of SEQ ID NO: 105. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 106, and further comprises a mutation set of any one of SEQ ID NO: 106. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 107, and further comprises a mutation set of any one of SEQ ID NO: 107. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 108, and further comprises said set of mutations of any one of SEQ ID NO: 108. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 109, and further comprises said set of mutations of any one of SEQ ID NO: 109. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 110, and further comprises said set of mutations of any one of SEQ ID NO: 110. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 111, and further comprises said set of mutations of any one of SEQ ID NO: 111. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 112, and further comprises said set of mutations of any one of SEQ ID NO: 112. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 113, and further comprises any one of the set of mutations of SEQ ID NO: 113. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 114, and further comprises any one of the set of mutations of SEQ ID NO: 114. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 115, and further comprises any one of the set of mutations of SEQ ID NO: 115. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 116, and further comprises any one of the set of mutations of SEQ ID NO: 116. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 117, and further comprises any one of the set of mutations of SEQ ID NO: 117. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO:118, and further comprises said set of mutations of any one of SEQ ID NO:118.In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 119, and further comprises said set of mutations of any one of SEQ ID NO: 119. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 120, and further comprises said set of mutations of any one of SEQ ID NO: 120. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 121, and further comprises said set of mutations of any one of SEQ ID NO: 121. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 122, and further comprises said set of mutations of any one of SEQ ID NO: 122. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 123, and further comprises said set of mutations of any one of SEQ ID NO: 123. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 124, and further comprises the set of mutations of any one of SEQ ID NO: 124. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 125, and further comprises the set of mutations of any one of SEQ ID NO: 125. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 126, and further comprises the set of mutations of any one of SEQ ID NO: 126. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 127, and further comprises the set of mutations of any one of SEQ ID NO: 127. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 128, and further comprises the set of mutations of any one of SEQ ID NO: 128. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 129, and further comprises a mutation set of any one of SEQ ID NO: 129.In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 130, and further comprises any one of the set of mutations of SEQ ID NO: 130. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 131, and further comprises any one of the set of mutations of SEQ ID NO: 131. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 132, and further comprises any one of the set of mutations of SEQ ID NO: 132. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 133, and further comprises any one of the set of mutations of SEQ ID NO: 133. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 134, and further comprises any one of the set of mutations of SEQ ID NO: 134. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 135, and further comprises any one of the set of mutations of SEQ ID NO: 135. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 136, and further comprises any one of the set of mutations of SEQ ID NO: 136. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 137, and further comprises any one of the set of mutations of SEQ ID NO: 137. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 138, and further comprises any one of the set of mutations of SEQ ID NO: 138. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 139, and further comprises any one of the set of mutations of SEQ ID NO: 139.

[0441] In some embodiments, a variant capsid polypeptide is selected from the group consisting of SEQ ID NOs: 2, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, or 139, optionally having an edit distance of 15 or less to SEQ ID NO:2. SEQ ID NOs: 2, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 70% or more of single amino acid mutations in any one of the mutation sets 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, or 139;(b) When the mutation set contains 10 to 19 single amino acid mutations, SEQ ID NOs: 2, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 1 80% or more of single amino acid mutations in any one of the mutation sets of 4, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, or 139, or c) if the mutation set contains 20 or more single amino acid mutations, SEQ ID NOs: 2, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84; 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, or 139, further comprising 90% or more single amino acid mutations in said set of mutations.Variant capsid polypeptides are described herein. In such embodiments, the reference sequence (e.g., SEQ ID NO: 2) used to calculate the edit distance is the same as the sequence from which the set of mutations present in the variant capsid polypeptide is derived. For example, in one embodiment, a variant capsid polypeptide is provided, comprising a sequence having an edit distance of 15 or less to SEQ ID NO: 2, and further comprising at least five of the seven single amino acid mutations of the set of mutations of SEQ ID NO: 2 (i.e., at least five of: a valine at position 579, an isoleucine at position 592, a valine at position 593, an alanine at position 595, a leucine at position 596, a serine at position 598, and an alanine at position 601, all having numbering relative to SEQ ID NO: 1).

[0442] In some embodiments, a variant capsid polypeptide is selected from the group consisting of SEQ ID NOs: 2, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84 , 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, or 139, optionally comprising a sequence with an edit distance of 15 or less to SEQ ID NO:2; (a) if the mutation set contains fewer than 10 single amino acid mutations, SEQ ID NOs: 2, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83; 70% or more of single amino acid mutations in any one of the mutation sets 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, or 139; (b) When the mutation set contains 10 to 19 single amino acid mutations, SEQ ID NOs: 2, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 80% or more of single amino acid mutations in any one of the sets of mutations 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, or 139; or (c) If the mutation set includes 20 or more single amino acid mutations, SEQ ID NOs: 2, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87 , 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, or 139.

[0443] In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO:2 (optionally SEQ ID NO:2), and further comprises 70% or more of the single amino acid mutations in the mutation set of SEQ ID NO:2. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO:14 (optionally SEQ ID NO:2), and further comprises 70% or more of the single amino acid mutations in the mutation set of SEQ ID NO:14. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO:15 (optionally SEQ ID NO:2), and further comprises 70% or more of the single amino acid mutations in the mutation set of SEQ ID NO:15. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO:16 (optionally SEQ ID NO:2), and further comprises 70% or more of the single amino acid mutations in the mutation set of SEQ ID NO:16. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 17 (optionally SEQ ID NO: 2), and further comprises 70% or more of the single amino acid mutations in the mutation set of SEQ ID NO: 17. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 18 (optionally SEQ ID NO: 2), and further comprises 70% or more of the single amino acid mutations in the mutation set of SEQ ID NO: 18. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 19 (optionally SEQ ID NO: 2), and further comprises 70% or more of the single amino acid mutations in the mutation set of SEQ ID NO: 19. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 20 (optionally SEQ ID NO: 2), and further comprises 70% or more of the single amino acid mutations in the mutation set of SEQ ID NO: 20. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO:21 (optionally SEQ ID NO:2), and further comprises 70% or more of the single amino acid mutations in the mutation set of SEQ ID NO:21.In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO:22 (optionally SEQ ID NO:2), and further comprises 70% or more of the single amino acid mutations in the mutation set of SEQ ID NO:22. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO:23 (optionally SEQ ID NO:2), and further comprises 70% or more of the single amino acid mutations in the mutation set of SEQ ID NO:23. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO:24 (optionally SEQ ID NO:2), and further comprises 70% or more of the single amino acid mutations in the mutation set of SEQ ID NO:24. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO:25 (optionally SEQ ID NO:2), and further comprises 70% or more of the single amino acid mutations in the mutation set of SEQ ID NO:25. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO:26 (optionally SEQ ID NO:2), and further comprises 70% or more of the single amino acid mutations in the mutation set of SEQ ID NO:26. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO:27 (optionally SEQ ID NO:2), and further comprises 70% or more of the single amino acid mutations in the mutation set of SEQ ID NO:27. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO:28 (optionally SEQ ID NO:2), and further comprises 70% or more of the single amino acid mutations in the mutation set of SEQ ID NO:28. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO:29 (optionally SEQ ID NO:2), and further comprises 70% or more of the single amino acid mutations in the mutation set of SEQ ID NO:29. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO: 30 (optionally SEQ ID NO: 2), and further comprises 70% or more of the single amino acid mutations in the mutation set of SEQ ID NO: 30.In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO:31 (optionally SEQ ID NO:2), and further comprises 70% or more of the single amino acid mutations in the mutation set of SEQ ID NO:31. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO:32 (optionally SEQ ID NO:2), and further comprises 70% or more of the single amino acid mutations in the mutation set of SEQ ID NO:32. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO:33 (optionally SEQ ID NO:2), and further comprises 70% or more of the single amino acid mutations in the mutation set of SEQ ID NO:33. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO:34 (optionally SEQ ID NO:2), and further comprises 70% or more of the single amino acid mutations in the mutation set of SEQ ID NO:34. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO:35 (optionally SEQ ID NO:2), and further comprises 70% or more of the single amino acid mutations in the mutation set of SEQ ID NO:35. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO:36 (optionally SEQ ID NO:2), and further comprises 70% or more of the single amino acid mutations in the mutation set of SEQ ID NO:36. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO:37 (optionally SEQ ID NO:2), and further comprises 70% or more of the single amino acid mutations in the mutation set of SEQ ID NO:37. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO:38 (optionally SEQ ID NO:2), and further comprises 70% or more of the single amino acid mutations in the mutation set of SEQ ID NO:38. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO:39 (optionally SEQ ID NO:2), and further comprises 70% or more of the single amino acid mutations in the mutation set of SEQ ID NO:39.In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO:40 (optionally SEQ ID NO:2), and further comprises 70% or more of the single amino acid mutations in the mutation set of SEQ ID NO:40. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO:41 (optionally SEQ ID NO:2), and further comprises 70% or more of the single amino acid mutations in the mutation set of SEQ ID NO:41. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO:42 (optionally SEQ ID NO:2), and further comprises 70% or more of the single amino acid mutations in the mutation set of SEQ ID NO:42. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO:43 (optionally SEQ ID NO:2), and further comprises 70% or more of the single amino acid mutations in the mutation set of SEQ ID NO:43. In some embodiments, the variant capsid polypeptide comprises a sequence having an edit distance of 15 or less to SEQ ID NO:44 (optionally SEQ ID NO:2), and further comprises 70% or...

Claims

[Claim 1] The invention described in the specification.

Images