AAV Capsid Variants and Uses Thereof

Abstract

The present disclosure relates to compositions and methods for the preparation, use and / or formulation of adeno-associated virus capsid protein variants.

Description

[Technical Field]

[0001] Related Applications This application claims priority to U.S. Provisional Application No. 63 / 274,806, filed November 2, 2021, and U.S. Provisional Application No. 63 / 339,711, filed May 9, 2022, the entire contents of each of which are incorporated herein by reference in their entirety.

[0002] Sequence Listing This application contains a Sequence Listing that has been submitted electronically in XML format and is incorporated herein by reference in its entirety. The XML copy, created on October 19, 2022, is named V2071-1125PCT_SL.xml and is 5,455,496 bytes in size.

[0003] The present disclosure relates to compositions and methods for the preparation, use, and / or formulation of adeno-associated virus capsid proteins and variants thereof. [Background technology]

[0004] Gene delivery to the adult central nervous system (CNS) remains a significant challenge in gene therapy. Engineered adeno-associated virus (AAV) capsids with improved brain tropism represent an attractive solution to the limitations of CNS delivery.

[0005] AAV-derived vectors are promising tools for clinical gene transfer due to their nonpathogenicity, low immunogenicity profile, low integration rate into the host genome, and long-term transgene expression in non-dividing cells. However, the transduction efficiency of AAV natural variants in certain organs is too low for clinical use, and capsid neutralization by pre-existing neutralizing antibodies may prevent treatment of a large proportion of patients. For these reasons, considerable efforts have been made to obtain capsid variants with improved characteristics. Of the many approaches tested to date, significant progress has come from directed evolution of AAV capsids using in vitro or in vivo selection of capsid variants generated by capsid sequence randomization using either error-prone PCR, shuffling of various parent serotypes, or insertion of completely randomized short peptides at defined positions.

[0006] Attempts to provide AAV capsids with improved properties, such as improved tropism for target cells or tissues upon systemic administration, have met with limited success. Thus, there is a need for improved methods of producing AAV capsids and resulting AAV capsids for delivery of a desired payload to target cells or tissues, such as CNS cells or tissues, or muscle cells or tissues. Summary of the Invention

[0007] The present disclosure relates, at least in part, to compositions and methods for the production and use of AAV particles comprising AAV capsid polypeptides, e.g., AAV capsid variants. In some embodiments, the AAV capsid variants have enhanced tropism for a tissue or cell, e.g., a CNS tissue or cell. Such tropism may be useful for delivering a payload, e.g., a payload described herein, to a cell or tissue for the treatment of a disorder, e.g., a neurological or neurodegenerative disorder, a muscular or neuromuscular disorder, or a neuro-oncological disorder.

[0008] Thus, in one aspect, the present disclosure provides an AAV capsid variant comprising an amino acid sequence having the following formula: [N1]-[N2]-[N3], wherein (i) optionally, [N1] comprises X1, X2, and X3, wherein at least one of X1, X2, or X3 is G; (ii) [N2] comprises the amino acid sequence of SPH; and (ii) [N3] comprises X4, X5, and X6, wherein at least one of X4, X5, or X6 is a basic amino acid, e.g., K or R. In some embodiments, the X4 position of [N3] is K. In some embodiments, the X5 position of [N3] is K. In some embodiments, [N3] is or comprises SKA. In some embodiments, [N3] is or comprises KSG. In some embodiments, [N2]-[N3] occur immediately after position 455, numbered according to SEQ ID NO: 138, 981, or 982. In some embodiments, [N1] occurs immediately after position 452 relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138, 981, or 982. In some embodiments, [N1] replaces positions 453-455 (e.g., G453, S454, and G455) relative to a reference sequence numbered according to SEQ ID NO: 138. In some embodiments, the AAV capsid variant comprises an H at position 454 and a D at position 455, numbered according to SEQ ID NO: 138 or 982. In some embodiments, the AAV capsid variant comprises an S at position 454 and a G at position 455, numbered according to SEQ ID NO: 138 or 981. In some embodiments, an insertion of eight amino acids replaces an SG at positions 454-455, numbered according to SEQ ID NO: 138. In some embodiments, the six amino acid insertion occurs immediately after position 455, numbered according to SEQ ID NO: 138, 981, or 982.

[0009] In another aspect, the disclosure provides an AAV capsid variant comprising [A][B] (SEQ ID NO: 4694), wherein (i) [A] comprises the amino acid sequence of GSGSPH (SEQ ID NO: 4695); and (ii) [B] comprises any of the amino acid sequences selected from the group consisting of X1, X2, X3, X4, X5, X6. (b) position X2 is K, L, R, I, E, Y, V, or S; (c) position X3 is A, R, L, G, I, Y, S, F, or W; (d) position X4 is W, Q, R, G, L, V, S, or F; (e) position X5 is N, Y, R, C, K, or L; (f) position X6 is Q, G, K, R, T, L, or Y; and (g) position X7 is Q, L, R, or V.

[0010] In yet another aspect, the disclosure provides an AAV capsid variant comprising [A][B] (SEQ ID NO: 4699), wherein (i) [A] comprises X1 X2 X3 X4 X5 X6; (a) position X1 is T, M, A, C, I, R, L, D, F, V, Q, N, or H; (b) position X2 is I, P, E, N, D, S, A, T, M, or Q; (c) position X3 is N, E, G, Y, W, M, T, I, K, Q, F, S, V, A, or L; (d) position X4 is G, D, R, or E; (e) position X5 is H, Q, N, or D; and (f) position X6 is D or R; and (ii) [B] comprises SPHKSG (SEQ ID NO: 946).

[0011] In yet another aspect, the disclosure provides an AAV capsid variant comprising an amino acid sequence having the following formula: [N1]-[N2]-[N3] (SEQ ID NO: 6407), wherein (i) [N1] comprises positions X1, X2, and X3, where position X2 is S and position X3 is G; (ii) [N2] comprises the amino acid sequence SPH; and (iii) [N3] comprises positions X4, X5, and X6, where position X5 is K. In some embodiments, [N1]-[N2]-[N3] occurs immediately after position 452 and replaces positions 453-455, numbered according to SEQ ID NO: 138 or 982. In some embodiments, [N1]-[N2]-[N3] is or comprises GSGSPHSKA (SEQ ID NO: 4697).

[0012] In another aspect, the disclosure provides an AAV capsid variant comprising an amino acid sequence having the following formula: [N1]-[N2]-[N3] (SEQ ID NO: 6408), wherein (i) [N1] comprises positions X1, X2, and X3, wherein position X2 is an amino acid other than S and position X3 is an amino acid other than G; (ii) [N2] comprises the amino acid sequence SPH; and (iii) [N3] comprises positions X4, X5, and X6, wherein position X4 is K. In some embodiments, [N1]-[N2]-[N3] occurs immediately after position 452 and replaces positions 453-455, numbered according to SEQ ID NO: 138 or 982. In some embodiments, [N1]-[N2]-[N3] is or comprises GHDSPHKSG (SEQ ID NO: 4698).

[0013] In yet another aspect, the disclosure provides an AAV capsid variant comprising the formula [A]-[B] (SEQ ID NO: 4696), wherein (i) [A] comprises GSGSPH (SEQ ID NO: 4695); (ii) [B] comprises X1 X2, X3, X4, and X5, wherein (a) position X1 is S, I, F, V, C, Y, W, R, P, L, Q, M, K, or G; (b) position X2 is K, M, R, F, V, C, P, Y, L, W, G, N, S, T, I, or A; (c) position X3 is A, Y, L, R, W, C, T, F, H, I, P, M, K, S, V, G, Q, or N; and (d) position X4 is Q, M, F, K, and (e) position X5 is A, N, Y, R, K, L, I, M, Q, S, C, W, F, T, G, V, or P, and optionally, the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of the amino acids described above in (a) through (e). In some embodiments, [A]-[B] is located immediately after position 452, and [A]-[B] replaces positions 453 through 457 (e.g., G453, S454, G455, Q456, N457) relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. In some embodiments, the AAV capsid variant has increased tropism for liver cells or tissues compared to the tropism of a reference sequence comprising the amino acid sequence of SEQ ID NO: 138. In some embodiments, the AAV capsid exhibits preferential transduction in the liver compared to transduction in the brain and / or dorsal root ganglia (DRG), for example, compared to SEQ ID NO: 138.

[0014] In another aspect, the disclosure provides AAV capsid variants comprising: (a) an amino acid sequence of any of the sequences provided in Tables 1, 2A, 2B, 13-19, (b) an amino acid sequence comprising at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 contiguous amino acids from any one of the sequences provided in Tables 1, 2A, 2B, 13-19, (c) an amino acid sequence that comprises at least 1, 2, or 3, but not more than 4, different amino acids from any one of the sequences provided in Tables 1, 2A, 2B, 13-19, or (d) an amino acid sequence that includes at least 1, 2, or 3, but not more than 4, modifications, e.g., substitutions (e.g., conservative substitutions), from the amino acid sequence of any one of the sequences provided in Tables 1, 2A, 2B, 13-19. In some embodiments, the amino acid sequence is present in loop IV. In some embodiments, the amino acid sequences are located immediately after positions 448, 452, 453, and 455 relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO:138.

[0015] In yet another aspect, the present disclosure provides an AAV capsid variant comprising: (a) an amino acid sequence of any one of SEQ ID NOs: 945-980 or 985-986; (b) an amino acid sequence comprising at least 3, 4, or 5 consecutive amino acids from any one of SEQ ID NOs: 945-980 or 985-986; (c) an amino acid sequence comprising at least 1, 2, or 3, but not more than 4, amino acids different from the amino acid sequence of any one of SEQ ID NOs: 945-980 or 985-986; or (d) an amino acid sequence comprising at least 1, 2, or 3, but not more than 4, modifications, e.g., substitutions (e.g., conservative substitutions), from the amino acid sequence of any one of SEQ ID NOs: 945-980 or 985-986. In some embodiments, the amino acid sequence is located in Loop IV. In some embodiments, the amino acid sequence is located immediately after positions 448, 452, 453, or 455 relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.

[0016] In yet another aspect, the disclosure provides a method for the preparation of a medicament ... or (d) an amino acid sequence that includes at least one, two, or three, but not more than four, amino acids that differ from the amino acid sequence of any one of SEQ ID NOs: 2, 200, 201, 941, 943, 204, 208, 404, or 903-909. In some embodiments, the amino acid sequence is located in Loop IV. In some embodiments, the amino acid sequence is located immediately after positions 448, 452, 453, or 455 relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.

[0017] In yet another aspect, the disclosure provides polynucleotides encoding the AAV capsid variants described herein. In some embodiments, the polynucleotides comprise: (i) a nucleotide sequence that contains at least 1, 2, 3, 4, 5, 6, or 7 modifications, e.g., substitutions (e.g., conservative substitutions), but no more than 10 modifications, e.g., substitutions (e.g., conservative substitutions), relative to the nucleotide sequence of SEQ ID NO: 3 or 942; (ii) a nucleotide sequence that contains at least 1, 2, 3, 4, 5, 6, or 7 but no more than 10 different nucleotides relative to the nucleotide sequence of SEQ ID NO: 3 or 942; or (iii) a nucleotide sequence of SEQ ID NO: 3 or 942, or a nucleotide sequence substantially identical thereto (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity).

[0018] In yet another aspect, the disclosure provides an AAV capsid variant comprising an amino acid sequence comprising at least 3, 4, 5, or 6 consecutive amino acids from the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein (i) 3 consecutive amino acids comprise SPH, (ii) 4 consecutive amino acids comprise SPHS (SEQ ID NO: 4700), (iii) 5 consecutive amino acids comprise SPHSSK (SEQ ID NO: 4701), or (iv) 6 consecutive amino acids comprise SPHSKA (SEQ ID NO: 941), wherein the AAV capsid variant also comprises (a) SEQ ID NO: 138. or 981, (b) a VP1 protein comprising the amino acid sequence of positions 138-736 of SEQ ID NO: 138 or positions 138-742 of SEQ ID NO: 981, (c) a VP3 protein comprising the amino acid sequence of positions 203-736 of SEQ ID NO: 138 or positions 203-742 of SEQ ID NO: 981, or (d) an amino acid sequence having at least 90% (e.g., at least about 95, 96, 97, 98, or 99%) sequence identity to any of the amino acid sequences in (a)-(c). In some embodiments, the amino acid sequence is located immediately after position 455, numbered according to SEQ ID NO: 138 or 981.

[0019] In yet another aspect, the disclosure provides an AAV capsid variant comprising one or two, but not more than three, substitutions relative to the amino acid sequence of SPHSKA (SEQ ID NO:941), wherein the AAV capsid variant comprises: (a) a VP1 protein comprising the amino acid sequence of SEQ ID NO:138 or SEQ ID NO:981; (b) a VP2 protein comprising the amino acid sequence of positions 138-736 of SEQ ID NO:138 or positions 138-742 of SEQ ID NO:981; (c) a VP3 protein comprising the amino acid sequence of positions 203-736 of SEQ ID NO:138 or positions 203-742 of SEQ ID NO:981; or (d) an amino acid sequence having at least 90% (e.g., at least about 95, 96, 97, 98, or 99%) sequence identity to any of the amino acid sequences in (a)-(c). In some embodiments, the amino acid sequence is located immediately after position 455, as numbered according to SEQ ID NO:138 or 981.

[0020] In another aspect, the disclosure provides an AAV capsid variant comprising at least 3, 4, 5, or 6 consecutive amino acids from the amino acid sequence of HDSPHK (SEQ ID NO:2), wherein (i) 3 consecutive amino acids comprise HDS; (ii) 4 consecutive amino acids comprise HDSP (SEQ ID NO:4702); (iii) 5 consecutive amino acids comprise HDSPH (SEQ ID NO:4703); and / or (iv) 6 consecutive amino acids comprise HDSPHK (SEQ ID NO:2), wherein the AAV capsid variant is selected from the group consisting of (a) SEQ ID NO:138 or SEQ ID NO:9. (b) a VP1 protein comprising the amino acid sequence of positions 138-736 of SEQ ID NO: 138 or positions 138-742 of SEQ ID NO: 982; (c) a VP3 protein comprising the amino acid sequence of positions 203-736 of SEQ ID NO: 138 or positions 203-742 of SEQ ID NO: 982; or (d) an amino acid sequence having at least 90% (e.g., at least about 95, 96, 97, 98, or 99%) sequence identity to any of the amino acid sequences in (a)-(c). In some embodiments, the amino acid sequence is located immediately after position 453, as numbered according to SEQ ID NO: 138 or 982.

[0021] In another aspect, the disclosure provides an AAV capsid variant comprising one or two, but not more than three, substitutions relative to the amino acid sequence of HDSPHK (SEQ ID NO: 2), wherein the AAV capsid variant comprises: (a) a VP1 protein comprising the amino acid sequence of SEQ ID NO: 138 or SEQ ID NO: 982; (b) a VP2 protein comprising the amino acid sequence of positions 138-736 of SEQ ID NO: 138 or positions 138-742 of SEQ ID NO: 982; (c) a VP3 protein comprising the amino acid sequence of positions 203-736 of SEQ ID NO: 138 or positions 203-742 of SEQ ID NO: 982; or (d) an amino acid sequence having at least 90% (e.g., at least about 95, 96, 97, 98, or 99%) sequence identity to any of the amino acid sequences in (a)-(c).

[0022] In yet another aspect, the disclosure provides a peptide comprising: (a) an amino acid sequence of any of the sequences provided in Tables 1, 2A, 2B, 13-19; (b) an amino acid sequence comprising at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 contiguous amino acids from any one of the sequences provided in Tables 1, 2A, 2B, 13-19; (c) an amino acid sequence that comprises at least 1, 2, or 3, but not more than 4, different amino acids relative to the amino acid sequence of any one of the sequences provided in Tables 1, 2A, 2B, 13-19; or (d) an amino acid sequence that includes at least 1, 2, or 3, but not more than 4, modifications, e.g., substitutions (e.g., conservative substitutions), relative to the amino acid sequence of any one of the sequences provided in Tables 1, 2A, 2B, 13-19.

[0023] In another aspect, the present disclosure provides a peptide comprising: (a) the amino acid sequence of any one of SEQ ID NOs: 945-980 or 985-986; (b) an amino acid sequence comprising at least 3, 4, or 5 contiguous amino acids from any one of SEQ ID NOs: 945-980 or 985-986; (c) an amino acid sequence that comprises at least 1, 2, or 3, but not more than 4, different amino acids relative to the amino acid sequence of any one of SEQ ID NOs: 945-980 or 985-986; or (d) an amino acid sequence that includes at least 1, 2, or 3, but not more than 4, modifications, e.g., substitutions (e.g., substitutions), relative to the amino acid sequence of any one of SEQ ID NOs: 945-980 or 985-986.

[0024] In another aspect, the disclosure provides a method for the preparation of a nucleotide sequence comprising: (a) any of the amino acid sequences of SEQ ID NOs: 2, 200, 201, 941, 943, 204, 208, 404, or 903-909; (b) an amino acid sequence comprising at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or 13 consecutive amino acids from any one of SEQ ID NOs: 2, 200, 201, 941, 943, 204, 208, 404, or 903-909; or (c) any of SEQ ID NOs: 2, 200, 201, 941, 943, 204, or (d) an amino acid sequence that includes at least one, two, or three, but not more than four, amino acids that differ from the amino acid sequence of any one of SEQ ID NOs: 2, 200, 201, 941, 943, 204, 208, 404, or 903-909; or (e) an amino acid sequence that includes at least one, two, or three, but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), from the amino acid sequence of any one of SEQ ID NOs: 2, 200, 201, 941, 943, 204, 208, 404, or 903-909.

[0025] In yet another aspect, the disclosure provides a peptide comprising: (i) the amino acid sequence of SPHSKA (SEQ ID NO:941); (ii) an amino acid sequence that includes at least one, two, or three, but not more than four, amino acids that differ from the amino acid sequence of SPHSKA (SEQ ID NO:941); (iii) an amino acid sequence that includes at least one, two, or three modifications, e.g., substitutions (e.g., conservative substitutions), but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), from the amino acid sequence of SPHSKA (SEQ ID NO:941); or (iv) at least 3, 4, or 5 consecutive amino acids from the amino acid sequence of SPHSKA (SEQ ID NO:941).

[0026] In yet another aspect, the disclosure provides a peptide encoded by (i) the nucleotide sequence of SEQ ID NO:942, or a nucleotide sequence substantially identical thereto (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity), or (ii) a nucleotide sequence that includes at least 1, 2, 3, 4, 5, 6, or 7 but not more than 10 different nucleotides relative to the nucleotide sequence of SEQ ID NO:942, or (iii) a nucleotide sequence that includes at least 1, 2, 3, 4, 5, 6, or 7 modifications, e.g., substitutions (e.g., conservative substitutions), but not more than 10 modifications, e.g., substitutions (e.g., conservative substitutions), relative to the nucleotide sequence of SEQ ID NO:942.

[0027] In yet another aspect, the disclosure provides a peptide, wherein the nucleotide sequence encoding the peptide comprises: (i) the nucleotide sequence of SEQ ID NO:942, or a nucleotide sequence substantially identical thereto (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity); (ii) a nucleotide sequence that includes at least 1, 2, 3, 4, 5, 6, or 7 but not more than 10 different nucleotides relative to the nucleotide sequence of SEQ ID NO:942; or (iii) a nucleotide sequence that includes at least 1, 2, 3, 4, 5, 6, or 7 modifications, e.g., substitutions (e.g., conservative substitutions), but not more than 10 modifications, e.g., substitutions (e.g., conservative substitutions), relative to the nucleotide sequence of SEQ ID NO:942.

[0028] In another aspect, the disclosure provides a peptide comprising: (i) the amino acid sequence of HDSPHK (SEQ ID NO:2); (ii) an amino acid sequence that contains at least one, two, or three, but not more than four, amino acids that differ from the amino acid sequence of HDSPHK (SEQ ID NO:2); (iii) an amino acid sequence that contains at least one, two, or three modifications, e.g., substitutions (e.g., conservative substitutions), but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), from the amino acid sequence of HDSPHK (SEQ ID NO:2); or (iv) at least three, four, or five consecutive amino acids from the amino acid sequence of HDSPHK (SEQ ID NO:2).

[0029] In yet another aspect, the disclosure provides peptides encoded by (i) the nucleotide sequence of SEQ ID NO:3, or a nucleotide sequence substantially identical thereto (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity); (ii) a nucleotide sequence that includes at least 1, 2, 3, 4, 5, 6, or 7 but not more than 10 different nucleotides relative to the nucleotide sequence of SEQ ID NO:3; or (iii) a nucleotide sequence that includes at least 1, 2, 3, 4, 5, 6, or 7 modifications, e.g., substitutions (e.g., conservative substitutions), but not more than 10 modifications, e.g., substitutions (e.g., conservative substitutions), relative to the nucleotide sequence of SEQ ID NO:3.

[0030] In another aspect, the disclosure provides a peptide, wherein the nucleotide sequence encoding the peptide comprises: (i) the nucleotide sequence of SEQ ID NO:3, or a nucleotide sequence substantially identical thereto (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity); (ii) a nucleotide sequence that includes at least 1, 2, 3, 4, 5, 6, or 7 but not more than 10 different nucleotides relative to the nucleotide sequence of SEQ ID NO:3; or (iii) a nucleotide sequence that includes at least 1, 2, 3, 4, 5, 6, or 7 modifications, e.g., substitutions (e.g., conservative substitutions), but not more than 10 modifications, e.g., substitutions (e.g., conservative substitutions), relative to the nucleotide sequence of SEQ ID NO:3.

[0031] In yet another aspect, the disclosure provides a polynucleotide encoding an AAV capsid variant, the polynucleotide comprising: (a) the amino acid sequence of any of the sequences provided in Tables 1, 2A, 2B, 13-19; (b) an amino acid sequence comprising at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 contiguous amino acids from any one of the sequences provided in Tables 1, 2A, 2B, 13-19; (c) an amino acid sequence that comprises at least 1, 2, or 3, but not more than 4, different amino acids from the amino acid sequence of any one of the sequences provided in Tables 1, 2A, 2B, 13-19; or (d) an amino acid sequence that includes at least 1, 2, or 3, but not more than 4, modifications, e.g., substitutions (conservative substitutions), from the amino acid sequence of any one of the sequences provided in Tables 1, 2A, 2B, 13-19. In some embodiments, the amino acid sequence of (a), (b), (c), and / or (d) is located immediately after position 448, 449, 450, 451, 452, 453, 454, or 455 relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.

[0032] In yet another aspect, the disclosure provides a polynucleotide encoding an AAV capsid variant, wherein the AAV capsid variant comprises: (i) the amino acid sequence of SPHSKA (SEQ ID NO:941); (ii) an amino acid sequence that includes at least one, two, or three, but not more than four, amino acids that differ from the amino acid sequence of SPHSKA (SEQ ID NO:941); (iii) an amino acid sequence that includes at least one, two, or three modifications, e.g., substitutions (e.g., conservative substitutions), but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), from the amino acid sequence of SPHSKA (SEQ ID NO:941); or (iv) at least 3, 4, 5, 6, 7, 8, or 9 contiguous amino acids from the amino acid sequence of SPHSKA (SEQ ID NO:941). In some embodiments, the amino acid sequences of (i), (ii), (iii), and / or (iv) occur immediately after position 455 relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO:138.

[0033] In another aspect, the disclosure provides a polynucleotide encoding an AAV capsid variant, wherein the AAV capsid variant comprises: (i) the amino acid sequence of HDSPHK (SEQ ID NO:2), (ii) an amino acid sequence that includes at least one, two, or three, but not more than four, amino acids that differ from the amino acid sequence of HDSPHK (SEQ ID NO:2), (iii) an amino acid sequence that includes at least one, two, or three modifications, e.g., substitutions (e.g., conservative substitutions), but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), from the amino acid sequence of HDSPHK (SEQ ID NO:2), or (iv) at least 3, 4, 5, or 6 contiguous amino acids from the amino acid sequence of HDSPHK (SEQ ID NO:2). In some embodiments, the amino acid sequences of (i), (ii), (iii), and / or (iv) are located immediately after position 453 relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO:138.

[0034] In yet another aspect, the present disclosure provides an AAV capsid variant comprising the amino acid sequence of SPH, wherein the amino acid sequence is located immediately after position 455, numbered according to the amino acid sequence of any one of SEQ ID NOs: 36-59, 138, 981, or 982.

[0035] In yet another aspect, the present disclosure provides an AAV capsid variant comprising the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is located immediately after position 455, numbered according to the amino acid sequence of SEQ ID NO: 138.

[0036] In yet another aspect, the present disclosure provides an AAV capsid variant comprising the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is located immediately after position 455, numbered according to the amino acid sequence of SEQ ID NO: 981.

[0037] In yet another aspect, the disclosure provides an AAV capsid variant comprising the amino acid sequence of HDSPHK (SEQ ID NO: 2), wherein the amino acid sequence is located immediately after position 453, numbered according to the amino acid sequence of SEQ ID NO: 138.

[0038] In yet another aspect, the present disclosure provides an AAV capsid variant comprising the amino acid sequence of HDSPHK (SEQ ID NO: 2), wherein the amino acid sequence is located immediately after position 453, numbered according to the amino acid sequence of SEQ ID NO: 982.

[0039] In yet another aspect, the disclosure provides an AAV capsid variant comprising the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is located in loop IV relative to the reference sequence of SEQ ID NO: 138. In some embodiments, loop IV comprises positions 449-460, numbered according to SEQ ID NO: 138.

[0040] In yet another aspect, the disclosure provides an AAV capsid variant comprising the amino acid sequence of HDSPHK (SEQ ID NO: 2), wherein the amino acid sequence is located in loop IV relative to the reference sequence of SEQ ID NO: 138. In some embodiments, loop IV comprises positions 449-460, numbered according to SEQ ID NO: 138.

[0041] In yet another aspect, the present disclosure provides an AAV particle comprising an AAV capsid variant described herein. In some embodiments, the AAV particle comprises a nucleic acid sequence encoding a payload. In some embodiments, the AAV particle further comprises a viral genome comprising a promoter operably linked to the nucleic acid encoding the payload.

[0042] In yet another aspect, the present disclosure provides a method of producing an AAV particle comprising an AAV capsid variant described herein, the method including providing a host cell comprising a viral genome and incubating the host cell under conditions suitable for encapsulating the viral genome into an AAV capsid variant, such as an AAV capsid variant described herein, thereby producing an AAV particle.

[0043] In yet another aspect, the present disclosure provides a method for delivering a payload to a cell or tissue (e.g., a CNS cell, CNS tissue, liver cell, or liver tissue), the method comprising administering an effective amount of AAV particles comprising an AAV capsid variant described herein.

[0044] In yet another aspect, the present disclosure provides a method of treating a subject having or diagnosed with a genetic disorder, e.g., a monogenic or polygenic disorder, comprising administering to the subject an effective amount of AAV particles comprising an AAV capsid variant described herein.

[0045] In yet another aspect, the present disclosure provides a method of treating a subject having or diagnosed with a neurological disorder, e.g., a neurodegenerative disorder, comprising administering an effective amount of AAV particles comprising an AAV capsid variant described herein.

[0046] In yet another aspect, the present disclosure provides a method of treating a subject having or diagnosed with a neuro-oncology disorder, the method comprising administering an effective amount of AAV particles comprising an AAV capsid variant described herein.

[0047] Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein which equivalents are intended to be encompassed by the embodiments recited below.

[0048] Enumeration of Embodiments 1. An AAV capsid variant comprising an amino acid sequence having the following formula: [N1]-[N2]-[N3], (i) optionally, [N1] includes X1, X2, and X3, and at least one of X1, X2, or X3 is G; (ii) [N2] comprises the amino acid sequence of SPH; (ii) An AAV capsid variant in which [N3] comprises X4, X5, and X6, and at least one of X4, X5, or X6 is a basic amino acid, e.g., K or R.

[0049] 2. The AAV capsid variant of embodiment 1, wherein X4, X5, or both of [N3] are K. 3. An AAV capsid variant described in embodiment 1 or 2, wherein X4, X5, or X6 of [N3] is R.

[0050] 4. (a) the X4 position of [N3] is K, S, A, V, T, G, F, W, V, N, or R; (b) the X5 position of [N3] is S, K, T, F, I, L, Y, H, M, or R; and / or (c) the X6 position of [N3] is G, A, R, M, I, N, T, Y, D, P, V, L, E, W, N, Q, K, or S; Optionally, the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of the above-mentioned amino acids in (a) to (c).

[0051] 5. The AAV capsid variant of any one of embodiments 1 to 4, wherein [N3] comprises SK, KA, KS, AR, RM, VK, AS, SR, VK, KR, KK, KN, VR, RS, RK, KT, TS, KF, FG, KI, IG, KL, LG, TT, TY, KY, YG, KD, KP, TR, RG, VR, GA, SL, SS, FL, WK, SA, RA, LR, KW, RR, GK, TK, NK, AK, KV, KG, KH, KM, TG, SE, SV, SW, SN, HG, SQ, LW, MG, MA, or SG.

[0052] 6. The AAV capsid variant of any one of embodiments 1 to 5, wherein [N3] is or comprises SKA, KSG, ARM, VKS, ASR, VKI, KKN, VRM, RKA, KTS, KFG, KIG, KLG, KTT, KTY, KYG, SKD, SKP, TRG, VRG, KRG, GAR, KSA, KSR, SKL, SRA, SKR, SLR, SRG, SSR, FLR, SKW, SKS, WKA, VRR, SKV, SKT, SKG, GKA, TKA, NKA, SKL, SKN, AKA, KTG, KSL, KSE, KSV, KSW, KSN, KHG, KSQ, KSK, KLW, WKG, KMG, KMA, or RSG.

[0053] 7. [N2]-[N3] are SPHSK (SEQ ID NO: 4701), SPHKS (SEQ ID NO: 4704), SPHAR (SEQ ID NO: 4705), SPHVK (SEQ ID NO: 4706), SPHAS (SEQ ID NO: 4707), SPHKK (SEQ ID NO: 4708), SPHVR (SEQ ID NO: 4709), SPHRK (SEQ ID NO: 4710), SPHKT (SEQ ID NO: 4711), SPHKF (SEQ ID NO: 4712), SPHKI (SEQ ID NO: 4713), SPHKL (SEQ ID NO: 4714), SPHKY (SEQ ID NO: 4715), SPHTR (SEQ ID NO: 4716), SPHKR (SEQ ID NO: 47 17), SPHGA (SEQ ID NO: 4718), SPHSR (SEQ ID NO: 4719), SPHSL (SEQ ID NO: 4720), SPHSS (SEQ ID NO: 4721), SPHFL (SEQ ID NO: 4722), SPHWK (SEQ ID NO: 4723), SPHGK (SEQ ID NO: 4724), SPHTK (SEQ ID NO: 4725), SPHNK (SEQ ID NO: 4726), SPHAK (SEQ ID NO: 4727), SPHKH (SEQ ID NO: 4728), SPHKM (SEQ ID NO: 4729), or SPHRS (SEQ ID NO: 4730).

[0054] 8.[N2]-[N3] (i) SPHSKA (SEQ ID NO: 941), SPHKSG (SEQ ID NO: 946), SPHARM (SEQ ID NO: 947), SPHVKS (SEQ ID NO: 948), SPHASR (SEQ ID NO: 949), SPHVKI (SEQ ID NO: 950), SPHKKN (SEQ ID NO: 954), SPHVRM (SEQ ID NO: 955), SPHRKA (SEQ ID NO: 956), SPHKFG (SEQ ID NO: 957), SPHKIG (SEQ ID NO: 958), SPHKLG (SEQ ID NO: 959), SPHKTS (SEQ ID NO: 963), SPHKTT (SEQ ID NO: 964), SPHKTY (SEQ ID NO: 965), Sequence number 965), SPHKYG (SEQ ID NO: 966), SPHSKD (SEQ ID NO: 967), SPHSKP (SEQ ID NO: 968), SPHTRG (SEQ ID NO: 972), SPHVRG (SEQ ID NO: 973), SPHKRG (SEQ ID NO: 974), SPHGAR (SEQ ID NO: 975), SPHKSA (SEQ ID NO: 977), SPHKSR (SEQ ID NO: 951), SPHSKL (SEQ ID NO: 960), SPHSRA (SEQ ID NO: 969), SPHSKR (SEQ ID NO: 978), SPHSLR (SEQ ID NO: 952), SPHSRG (SEQ ID NO: 961), SPH SSR (SEQ ID NO: 970), SPHFLR (SEQ ID NO: 979), SPHSKW (SEQ ID NO: 953), SPHSKS (SEQ ID NO: 962), SPHWKA (SEQ ID NO: 971), SPHVRR (SEQ ID NO: 980), SPHSKT (SEQ ID NO: 4731), SPHSKG (SEQ ID NO: 4732), SPHGKA (SEQ ID NO: 4733), SPHNKA (SEQ ID NO: 4734), SPHSKN (SEQ ID NO: 4735), SPHAKA (SEQ ID NO: 4736), SPHSKV (SEQ ID NO: 4737), SPHKTG (SEQ ID NO: 4738), SPHTKA (SEQ ID NO: 4739), SPHKSL (SEQ ID NO: 4740), SPHKSE (SEQ ID NO: 4741), SPHKSV (SEQ ID NO: 4742), SPHKSW (SEQ ID NO: 4743), SPHKSN (SEQ ID NO: 4744), SPHKHG (SEQ ID NO: 4745), SPHKSQ (SEQ ID NO: 4746), SPHKSK (SEQ ID NO: 4747), SPHKLW (SEQ ID NO: 4748), SPHWKG (SEQ ID NO: 4749), SPHKMG (SEQ ID NO: 4750), SPHKMA (SEQ ID NO: 4751), or SPHRSG (SEQ ID NO: 976), (ii) an amino acid sequence comprising a portion of any of the amino acid sequences in (i), e.g., 2, 3, 4, or 5 amino acids, e.g., consecutive amino acids, of any of them; (iii) an amino acid sequence that contains one, two, or three, but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to any of the amino acid sequences in (i); or (iv) An AAV capsid variant described in any one of embodiments 1 to 7, which is or comprises an amino acid sequence that contains 1, 2, or 3, but not more than 4, different amino acids from any one of the amino acid sequences in (i). 9. The AAV capsid variant of any one of embodiments 1 to 8, comprising an amino acid other than G at position 453 (e.g., V, R, D, E, M, T, I, S, A, N, L, K, H, P, W, or C), an amino acid other than S at position 454 (V, L, N, D, H, R, P, G, T, I, A, E, Y, M, or Q), and / or an amino acid other than G at position 455 (e.g., C, L, D, E, Y, H, V, A, N, P, or S), numbered according to any one of SEQ ID NOs: 36-59, 138, 981, 982.

[0055] 10. The AAV capsid variant of any one of embodiments 1 to 8, comprising an amino acid G at position 453, an amino acid S at position 454, and an amino acid G at position 455, numbered according to SEQ ID NO: 138 or 981.

[0056] 11. The AAV capsid variant of any one of embodiments 1 to 9, comprising an amino acid G at position 453, an amino acid H at position 454, and an amino acid D at position 455, numbered according to SEQ ID NO: 138 or 982.

[0057] 12. An AAV capsid variant described in any one of embodiments 1 to 11, wherein [N1] comprises X1, X2, and X3, and at least one of X1, X2, or X3 is G.

[0058] 13. (a) the X1 position of [N1] is G, V, R, D, E, M, T, I, S, A, N, L, K, H, P, W, or C; (b) position X2 of [N1] is S, V, L, N, D, H, R, P, G, T, I, A, E, Y, M, or Q; and / or (c) the X3 position of [N1] is G, C, L, D, E, Y, H, V, A, N, P, or S; 13. An AAV capsid variant according to any one of embodiments 1 to 12, optionally comprising an amino acid modification, e.g., a conservative substitution, of any of the above-mentioned amino acids in (a) to (c). 14. The AAV capsid variant of any one of embodiments 1 to 13, wherein [N1] comprises GS, SG, GH, HD, GQ, QD, VS, CS, GR, RG, QS, SH, MS, RN, TS, IS, GP, ES, SS, GN, AS, NS, LS, GG, KS, GT, PS, RS, GI, WS, DS, ID, GL, DA, DG, ME, EN, KN, KE, AI, NG, PG, TG, SV, IG, LG, AG, EG, SA, YD, HE, HG, RD, ND, PD, MG, QV, DD, HN, HP, GY, GM, GD, or HS.

[0059] 15. The AAV capsid variant of any one of embodiments 1 to 14, wherein [N1] is or comprises GSG, GHD, GQD, VSG, CSG, GRG, CSH, GQS, GSH, RVG, GSC, GLL, GDD, GHE, GNY, MSG, RNG, TSG, ISG, GPG, ESG, SSG, GNG, ASG, NSG, LSG, GGG, KSG, HSG, GTG, PSG, GSV, RSG, GIG, WSG, DSG, IDG, GLG, DAG, DGG, MEG, ENG, GSA, KNG, KEG, AIG, GYD, GHG, GRD, GND, GPD, GMG, GQV, GHN, GHP, or GHS.

[0060] 16.[N1]-[N2] (i) SGSPH (SEQ ID NO: 4752), HDSPH (SEQ ID NO: 4703), QDSPH (SEQ ID NO: 4753), RGSPH (SEQ ID NO: 4754), SHSPH (SEQ ID NO: 4755), QSSPH (SEQ ID NO: 4756), DDSPH (SEQ ID NO: 4757), HESPH (SEQ ID NO: 4758), NYSPH (SEQ ID NO: 4759), VGSPH (SEQ ID NO: 4760), SCSPH (SEQ ID NO: 4761), LLSPH (SEQ ID NO: 4762), NGSPH (SEQ ID NO: 4763), PGSPH (SEQ ID NO: 4764), GGSPH (SEQ ID NO: 4765), TGSPH (SEQ ID NO: 4766), SVSPH (SEQ ID NO: No. 4767), IGSPH (SEQ ID NO: 4768), DGSPH (SEQ ID NO: 4769), LGSPH (SEQ ID NO: 4770), AGSPH (SEQ ID NO: 4771), EGSPH (SEQ ID NO: 4772), SASPH (SEQ ID NO: 4773), YDSPH (SEQ ID NO: 4774), HGSPH (SEQ ID NO: 4775), RDSPH (SEQ ID NO: 4776), NDSPH (SEQ ID NO: 4777), PDSPH (SEQ ID NO: 4778), MGSPH (SEQ ID NO: 4779), QVSPH (SEQ ID NO: 4780), HNSPH (SEQ ID NO: 4781), HPSPH (SEQ ID NO: 4782), or HSSPH (SEQ ID NO: 4783), (ii) an amino acid sequence comprising a portion of any of the amino acid sequences in (i), e.g., 2, 3, or 4 amino acids, e.g., consecutive amino acids, of any of them; (iii) an amino acid sequence that contains one, two, or three, but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to any of the amino acid sequences in (i); or (iv) An AAV capsid variant described in any one of embodiments 1 to 15, comprising an amino acid sequence that contains 1, 2, or 3, but not more than 4, different amino acids from any one of the amino acid sequences in (i).

[0061] 17.[N1]-[N2] (i) GSGSPH (SEQ ID NO: 4695), GHDSPH (SEQ ID NO: 4784), GQDSPH (SEQ ID NO: 4785), VSGSPH (SEQ ID NO: 4786), CSGSPH (SEQ ID NO: 4787), GRGSPH (SEQ ID NO: 4788), CSHSPH (SEQ ID NO: 4789), GQSSPH (SEQ ID NO: 4790), GSHSPH (SEQ ID NO: 4791), GDDSPH (SEQ ID NO: 4792), GHESPH (SEQ ID NO: 4793), GNYSPH (SEQ ID NO: 4794), RVGSPH (SEQ ID NO: 4795), GSCSPH (SEQ ID NO: 4796) ), GLLSPH (SEQ ID NO: 4797), MSGSPH (SEQ ID NO: 4798), RNGSPH (SEQ ID NO: 4799), TSGSPH (SEQ ID NO: 4800), ISGSPH (SEQ ID NO: 4801), GPGSPH (SEQ ID NO: 4802), ESGSPH (SEQ ID NO: 4803), SSGSPH (SEQ ID NO: 4804), GNGSPH (SEQ ID NO: 4805), ASGSPH (SEQ ID NO: 4806), NSGSPH (SEQ ID NO: 4807), LSGSPH (SEQ ID NO: 4808), GGGSPH (SEQ ID NO: 4809), KSGSPH (SEQ ID NO: 4810), HSGSPH (SEQ ID NO: 4811), GTGSPH (SEQ ID NO: 4812), PSGSPH (SEQ ID NO: 4813), GSVSPH (SEQ ID NO: 4814), RSGSPH (SEQ ID NO: 4815), GIGSPH (SEQ ID NO: 4816), WSGSPH (SEQ ID NO: 4817), DSGSPH (SEQ ID NO: 4818), IDGSPH (SEQ ID NO: 4819), GLGSPH (SEQ ID NO: 4820), DAGSPH (SEQ ID NO: 4821), DGGSPH (SEQ ID NO: 4822), MEGSPH (SEQ ID NO: 4823), ENGSPH (SEQ ID NO: 4824), GS ASPH (SEQ ID NO: 4825), KNGSPH (SEQ ID NO: 4826), KEGSPH (SEQ ID NO: 4827), AIGSPH (SEQ ID NO: 4828), GYDSPH (SEQ ID NO: 4829), GHGSPH (SEQ ID NO: 4830), GRDSPH (SEQ ID NO: 4831), GNDSPH (SEQ ID NO: 4832), GPDSPH (SEQ ID NO: 4833), GMGSPH (SEQ ID NO: 4834), GQVSPH (SEQ ID NO: 4835), GHNSPH (SEQ ID NO: 4836), GHPSPH (SEQ ID NO: 4837), or GHSSPH (SEQ ID NO: 4838), (ii) an amino acid sequence comprising a portion of any of the amino acid sequences in (i), e.g., 2, 3, 4, or 5 amino acids, e.g., consecutive amino acids, of any of them; (iii) an amino acid sequence that contains one, two, or three, but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to any of the amino acid sequences in (i); or (iv) An AAV capsid variant described in any one of embodiments 1 to 16, which is or comprises an amino acid sequence that contains 1, 2, or 3, but not more than 4, different amino acids from any one of the amino acid sequences in (i).

[0062] 18.[N1]-[N2]-[N3] (i) SGSPHSK (SEQ ID NO: 4839), HDSPHKS (SEQ ID NO: 4840), SGSPHAR (SEQ ID NO: 4841), SGSPHVK (SEQ ID NO: 4842), QDSPHKS (SEQ ID NO: 4843), SGSPHKK (SEQ ID NO: 4844), SGSPHVR (SEQ ID NO: 4845), SGSPHAS (SEQ ID NO: 4846), SGSPHRK (SEQ ID NO: 4847), SGSPHKT (SEQ ID NO: 4848), SHSPHKS (SEQ ID NO: 4849), QSSPHRS (SEQ ID NO: 4850), RGSPHAS (SEQ ID NO: 4851), RGSPHSK (SEQ ID NO: No. 4852), SGSPHKF (SEQ ID NO: 4853), SGSPHKI (SEQ ID NO: 4854), SGSPHKL (SEQ ID NO: 4855), SGSPHKY (SEQ ID NO: 4856), SGSPHTR (SEQ ID NO: 4857), SHSPHKR (SEQ ID NO: 4858), SGSPHGA (SEQ ID NO: 4859), HDSPHKR (SEQ ID NO: 4860), DDSPHKS (SEQ ID NO: 4861), HESPHKS (SEQ ID NO: 4862), NYSPHKI (SEQ ID NO: 4863), SGSPHSR (SEQ ID NO: 4864), SGSPHSL (SEQ ID NO: 4865), SGSPHSS (SEQ ID NO: 4866), VGSPHSK (SEQ ID NO: 4867), SCSPHRK (SEQ ID NO: 4868), SGSPHFL (SEQ ID NO: 4869), LLSPHWK (SEQ ID NO: 4870), NGSPHSK (SEQ ID NO: 4871), PGSPHSK (SEQ ID NO: 4872), GGSPHSK (SEQ ID NO: 4873), TGSPHSK (SEQ ID NO: 4874), SVSPHGK (SEQ ID NO: 4875), SGSPHTK (SEQ ID NO: 4876), IGSPHSK (SEQ ID NO: 4877), DGSPHSK (SEQ ID NO: 4878), SGSPHNK (SEQ ID NO: 4879), LGS PHSK (SEQ ID NO: 4880), AGSPHSK (SEQ ID NO: 4881), EGSPHSK (SEQ ID NO: 4882), SASPHSK (SEQ ID NO: 4883), SGSPHAK (SEQ ID NO: 4884), HDSPHKI (SEQ ID NO: 4885), YDSPHKS (SEQ ID NO: 4886), HDSPHKT (SEQ ID NO: 4887), RGSPHKR (SEQ ID NO: 4888), HGSPHSK (SEQ ID NO: 4889), RDSPHKS (SEQ ID NO: 4890), NDSPHKS (SEQ ID NO: 4891), QDSPHKI (SEQ ID NO: 4892), PDSPHKI (SEQ ID NO: 4893),PDSPHKS (SEQ ID NO: 4894), MGSPHSK (SEQ ID NO: 4895), HDSPHKH (SEQ ID NO: 4896), QVSPHKS (SEQ ID NO: 4897), HNSPHKS (SEQ ID NO: 4898), NGSPHKR (SEQ ID NO: 4899), HDSPHKY (SEQ ID NO: 4900), NDSPHKI (SEQ ID NO: 4901), HDSPHKL (SEQ ID NO: 4902), HPSPHWK (SEQ ID NO: 4903), HDSPHKM (SEQ ID NO: 4904), or HSSPHRS (SEQ ID NO: 4905), (ii) an amino acid sequence comprising any part of the amino acid sequences in (i), e.g., 2, 3, 4, 5, or 6 amino acids, e.g., consecutive amino acids, of any of them; (iii) an amino acid sequence that contains one, two, or three, but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to any of the amino acid sequences in (i); or (iv) An AAV capsid variant described in any one of embodiments 1 to 17, comprising an amino acid sequence that contains 1, 2, or 3, but not more than 4, different amino acids from any one of the amino acid sequences in (i).

[0063] 19.[N1]-[N2]-[N3] (i) GSGSPHSKA (SEQ ID NO: 4697), GHDSPHKSG (SEQ ID NO: 4698), GSGSPHARM (SEQ ID NO: 4906), GSGSPHVKS (SEQ ID NO: 4907), GQDSPHKSG (SEQ ID NO: 4908), GSGSPHASR (SEQ ID NO: 4909), GSGSPHVKI (SEQ ID NO: 4910), GSGSPHKKN (SEQ ID NO: 4911), GSGSPHVRM (SEQ ID NO: 4912), VSGSPHSKA (SEQ ID NO: 4913), CSGSPHSKA (SEQ ID NO: 4914), GSGSPHRKA (SEQ ID NO: 4915), CS GSPHKTS (SEQ ID NO: 4916), CSHSPHKSG (SEQ ID NO: 4917), GQSSPHRSG (SEQ ID NO: 4918), GRGSPHASR (SEQ ID NO: 4919), GRGSPHSKA (SEQ ID NO: 4920), GSGSPHKFG (SEQ ID NO: 4921), GSGSPHKIG (SEQ ID NO: 4922), GSGSPHKLG (SEQ ID NO: 4923), GSGSPHKTS (SEQ ID NO: 4924), GSGSPHKTT (SEQ ID NO: 4925), GSGSPHKTY (SEQ ID NO: 4926), GSGSPHKYG (SEQ ID NO: 4927), GSGSPHSK D (SEQ ID NO: 4928), GSGSPHSKP (SEQ ID NO: 4929), GSGSPHTRG (SEQ ID NO: 4930), GSGSPHVRG (SEQ ID NO: 4931), GSHSPHKRG (SEQ ID NO: 4932), GSHSPHKSG (SEQ ID NO: 4933), VSGSPHASR (SEQ ID NO: 4934), VSGSPHGAR (SEQ ID NO: 4935), VSGSPHKFG (SEQ ID NO: 4936), GHDSPHKRG (SEQ ID NO: 4937), GDDSPHKSG (SEQ ID NO: 4938), GHESPHKSA (SEQ ID NO: 4939), GHDSPHKSA (SEQ ID NO: 4940), GNYSPHKIG (SEQ ID NO: 4941), GHDSPHKSR (SEQ ID NO: 4942), GSGSPHSKL (SEQ ID NO: 4943), GSGSPHSRA (SEQ ID NO: 4944), GSGSPHSKR (SEQ ID NO: 4945), GSGSPHSLR (SEQ ID NO: 4946), GSGSPHSRG (SEQ ID NO: 4947), GSGSPHSSR (SEQ ID NO: 4948), RVGSPHSKA (SEQ ID NO: 4949), GSCSPHRKA (SEQ ID NO: 4950), GSGSPHFLR (SEQ ID NO: 4951), GSGSPHSKW (SEQ ID NO: 4952),GSGSPHSKS (SEQ ID NO: 4953), GLLSPHWKA (SEQ ID NO: 4954), GSGSPHVRR (SEQ ID NO: 4955), GSGSPHSKV (SEQ ID NO: 4956), MSGSPHSKA (SEQ ID NO: 4957), RNGSPHSKA (SEQ ID NO: 4958), TSGSPHSKA (SEQ ID NO: 4959), ISGSPHSKA (SEQ ID NO: 4960), GPGSPHSKA (SEQ ID NO: 4961), GSGSPHSKT (SEQ ID NO: 4962), ESGSPHSKA (SEQ ID NO: 4963), SSGSPHSKA (SEQ ID NO: 4964), GNGSPHSKA ( SEQ ID NO: 4965), ASGSPHSKA (SEQ ID NO: 4966), NSGSPHSKA (SEQ ID NO: 4967), LSGSPHSKA (SEQ ID NO: 4968), GGGSPHSKA (SEQ ID NO: 4969), KSGSPHSKA (SEQ ID NO: 4970), GGGSPHSKS (SEQ ID NO: 4971), GSGSPHSKG (SEQ ID NO: 4972), HSGSPHSKA (SEQ ID NO: 4973), GTGSPHSKA (SEQ ID NO: 4974), PSGSPHSKA (SEQ ID NO: 4975), GSVSPHGKA (SEQ ID NO: 4976), RSGSPHSKA (SEQ ID NO: 4977), GSGSPHTKA (SEQ ID NO: 4978), GIGSPHSKA (SEQ ID NO: 4979), WSGSPHSKA (SEQ ID NO: 4980), DSGSPHSKA (SEQ ID NO: 4981), IDGSPHSKA (SEQ ID NO: 4982), GSGSPHNKA (SEQ ID NO: 4983), GLGSPHSKS (SEQ ID NO: 4984), DAGSPHSKA (SEQ ID NO: 4985), DGGSPHSKA (SEQ ID NO: 4986), MEGSPHSKA (SEQ ID NO: 4987), ENGSPHSKA (SEQ ID NO: 4988), GSASPHSKA (SEQ ID NO: 4989), GNGSPHSKS ( SEQ ID NO: 4990), KNGSPHSKA (SEQ ID NO: 4991), KEGSPHSKA (SEQ ID NO: 4992), AIGSPHSKA (SEQ ID NO: 4993), GSGSPHSKN (SEQ ID NO: 4994), GSGSPHAKA (SEQ ID NO: 4995), GHDSPHKIG (SEQ ID NO: 4996), GYDSPHKSG (SEQ ID NO: 4997), GHESPHKSG (SEQ ID NO: 4998), GHDSPHKTG (SEQ ID NO: 4999), GRGSPHKRG (SEQ ID NO: 5000), GQDSPHKSG (SEQ ID NO: 4908), GHDSPHKSL (SEQ ID NO: 5001),GHGSPHSKA (SEQ ID NO: 5002), GHDSPHKSE (SEQ ID NO: 5003), VSGSPHSKA (SEQ ID NO: 4913), GRDSPHKSG (SEQ ID NO: 5004), GNDSPHKSV (SEQ ID NO: 5005), GQDSPHKIG (SEQ ID NO: 5006), GHDSPHKSV (SEQ ID NO: 5007), GPDSPHKIG (SEQ ID NO: 5008), GPDSPHKSG (SEQ ID NO: 5009), GHDSPHKSW (SEQ ID NO: 5010), GHDSPHKSN (SEQ ID NO: 5011), GMGSPHSKT (SEQ ID NO: 5012), GHDSPHKHG (SEQ ID NO: 5013), GQ VSPHKSG (SEQ ID NO: 5014), GDDSPHKSV (SEQ ID NO: 5015), GHNSPHKSG (SEQ ID NO: 5016), GNGSPHKRG (SEQ ID NO: 5017), GHDSPHKYG (SEQ ID NO: 5018), GHDSPHKSQ (SEQ ID NO: 5019), GNDSPHKIG (SEQ ID NO: 5020), GHDSPHKSK (SEQ ID NO: 5021), GHDSPHKLW (SEQ ID NO: 5022), GHPSPHWKG (SEQ ID NO: 5023), GHDSPHKMG (SEQ ID NO: 5024), GHDSPHKMA (SEQ ID NO: 5025), or GHSSPHRSG (SEQ ID NO: 5026), (ii) an amino acid sequence comprising any part of the amino acid sequences in (i), e.g., 2, 3, 4, 5, 6, 7, or 8 amino acids, e.g., consecutive amino acids, of any of them; (iii) an amino acid sequence that contains one, two, or three, but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to any of the amino acid sequences in (i); or (iv) An AAV capsid variant described in any one of embodiments 1 to 18, which is or comprises an amino acid sequence that contains 1, 2, or 3, but not more than 4, different amino acids from any one of the amino acid sequences in (i).

[0064] 20. The AAV capsid variant of any one of embodiments 1 to 19, wherein [N3] comprises SK, KA, KS, or SG. 21. The AAV capsid variant of any one of embodiments 1 to 20, wherein [N3] is or comprises SKA, KSG, or KYG.

[0065] 22. An AAV capsid variant described in any one of embodiments 1 to 21, wherein [N2]-[N3] comprises SPHSK (sequence number 4701), SPHKS (sequence number 4704), or SPHKY (sequence number 4715).

[0066] 23. An AAV capsid variant described in any one of embodiments 1 to 22, wherein [N2]-[N3] is or comprises SPHSKA (sequence number 941). 24. An AAV capsid variant described in any one of embodiments 1 to 22, wherein [N2]-[N3] is or comprises SPHKSG (sequence number 946).

[0067] 25. An AAV capsid variant described in any one of embodiments 1 to 22, wherein [N2]-[N3] is or comprises SPHKYG (sequence number 966). 26. The AAV capsid variant of any one of embodiments 1 to 25, wherein [N1] comprises GS, SG, GH, or HD.

[0068] 27. The AAV capsid variant of any one of embodiments 1 to 26, wherein [N1] is or comprises GSG. 28. The AAV capsid variant according to any one of embodiments 1 to 26, wherein [N1] is or comprises GHD.

[0069] 29. An AAV capsid variant described in any one of embodiments 1 to 23 or 26 to 27, wherein [N1]-[N2]-[N3] comprises SGSPHSK (sequence number 4839).

[0070] 30. The AAV capsid variant of any one of embodiments 1 to 22, 24, 26, or 28, wherein [N1]-[N2]-[N3] comprises HDSPHKS (sequence number 4840).

[0071] 31. An AAV capsid variant described in any one of embodiments 1 to 22 or 25 to 27, wherein [N1]-[N2]-[N3] comprises SGSPHKYG (sequence number 5027).

[0072] 32. The AAV capsid variant of any one of embodiments 1 to 8, 10, 12 to 23, 26 to 27, or 29, wherein [N1]-[N2]-[N3] is or comprises GSGSPHSKA (sequence number 4697).

[0073] 33. The AAV capsid variant of any one of embodiments 1 to 9, 11 to 22, 24, 26, 28, or 30, wherein [N1]-[N2]-[N3] is or comprises GHDSPHKSG (sequence number 4698).

[0074] 34. The AAV capsid variant of any one of embodiments 1 to 8, 10, 12 to 22, 25 to 27, or 31, wherein [N1]-[N2]-[N3] is or comprises GSGSPHKYG (sequence number 4927).

[0075] 35. An AAV capsid variant described in any one of embodiments 1 to 34, wherein [N1]-[N2]-[N3] replaces positions 453 to 455, numbered according to the amino acid sequence of SEQ ID NO: 138.

[0076] 36. The AAV capsid variant of any one of embodiments 1 to 35, comprising an amino acid other than Q at position 456 (e.g., W, K, R, G, L, V, S, P, H, K, I, M, A, E, or F), an amino acid other than N at position 457 (e.g., Y, C, K, T, H, R, D, V, S, P, G, W, E, F, A, I, M, Q, or L), an amino acid other than Q at position 458 (e.g., G, K, H, R, T, L, D, A, P, I, F, V, M, W, Y, S, E, N, or Y), and / or an amino acid other than Q at position 459 (e.g., H, L, R, W, K, A, P, E, M, I, S, G, N, Y, C, V, T, D, or V), relative to a reference sequence numbered according to SEQ ID NO: 138.

[0077] 37. With respect to a reference sequence numbered according to SEQ ID NOs: 981, 982, 36, 37, 39, 40, 42-46, 48, 49, 50, 52, 53, 56, or 57, an amino acid other than Q at position 462 (e.g., W, K, R, G, L, V, S, P, H, K, I, M, A, E, or F), an amino acid other than N at position 463 (e.g., Y, C, K, T, H, R, D, V, S, P, G, W, E, F, A), , I, M, Q, or L), an amino acid other than Q at position 464 (e.g., G, K, H, R, T, L, D, A, P, I, F, V, M, W, Y, S, E, N, or Y), and / or an amino acid other than Q at position 465 (e.g., H, L, R, W, K, A, P, E, M, I, S, G, N, Y, C, V, T, D, or V).

[0078] 38. (a) an amino acid Q at position 456, an amino acid N at position 457, an amino acid Q at position 458, and / or an amino acid Q at position 459 relative to a reference sequence numbered according to SEQ ID NO: 138; or (b) An AAV capsid variant according to any one of embodiments 1 to 37, comprising an amino acid Q at position 462, an amino acid N at position 463, an amino acid Q at position 464, and / or an amino acid Q at position 465 relative to a reference sequence numbered according to SEQ ID NO: 981, 982, 36, 37, 39, 40, 42-46, 48, 49, 50, 52, 53, 56, or 57.

[0079] 39. [N4] further includes X7, X8, X9, and X10; (a) position X7 is Q, W, K, R, G, L, V, S, P, H, K, I, M, A, E, or F; (b) position X8 is N, Y, C, K, T, H, R, D, V, S, P, G, W, E, F, A, I, M, Q, or L; (c) position X9 is Q, G, K, H, R, T, L, D, A, P, I, F, V, M, W, Y, S, E, N, or Y; (d) position X10 is Q, H, L, R, W, K, A, P, E, M, I, S, G, N, Y, C, V, T, D, or V; Optionally, the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of the above-mentioned amino acids in (a) to (d).

[0080] 40. (a) The X7 position of [N4] is Q or R; (b) the X8 position of [N4] is N or R; (c) The X9 position of [N4] is Q or R; (d) The AAV capsid variant of embodiment 39, wherein the X10 position of [N4] is Q, L, or R.

[0081] 41. [N4] (i) QNQQ (SEQ ID NO: 5028), WNQQ (SEQ ID NO: 5029), QYYV (SEQ ID NO: 5030), RRQQ (SEQ ID NO: 5031), GCGQ (SEQ ID NO: 5032), LRQQ (SEQ ID NO: 5033), RNQQ (SEQ ID NO: 5034), VNQQ (SEQ ID NO: 5035), FRLQ (SEQ ID NO: 5036), FNQQ (SEQ ID NO: 5037), LLQQ (SEQ ID NO: 5038), SNQQ (SEQ ID NO: 5039), RLQQ (SEQ ID NO: 5040), LNQQ (SEQ ID NO: 5041), QRKL (SEQ ID NO: 5042), LRRQ (SEQ ID NO: 5043), QRLR ( SEQ ID NO: 5044), QRRL (SEQ ID NO: 5045), RRLQ (SEQ ID NO: 5046), RLRQ (SEQ ID NO: 5047), SKRQ (SEQ ID NO: 5048), QLYR (SEQ ID NO: 5049), QLTV (SEQ ID NO: 5050), QNKQ (SEQ ID NO: 5051), KNQQ (SEQ ID NO: 5052), QKQQ (SEQ ID NO: 5053), QTQQ (SEQ ID NO: 5054), QNHQ (SEQ ID NO: 5055), QHQQ (SEQ ID NO: 5056), QNQH (SEQ ID NO: 5057), QHRQ (SEQ ID NO: 5058), LTQQ (SEQ ID NO: 5059), QNQW (SEQ ID NO: 5060 ), QNTH (SEQ ID NO: 5061), RRRQ (SEQ ID NO: 5062), QYQQ (SEQ ID NO: 5063), QNDQ (SEQ ID NO: 5064), QNRH (SEQ ID NO: 5065), RDQQ (SEQ ID NO: 5066), PNLQ (SEQ ID NO: 5067), HVRQ (SEQ ID NO: 5068), PNQH (SEQ ID NO: 5069), HNQQ (SEQ ID NO: 5070), QSQQ (SEQ ID NO: 5071), QPAK (SEQ ID NO: 5072), QNLA (SEQ ID NO: 5073), QNQL (SEQ ID NO: 5074), QGQQ (SEQ ID NO: 5075), LNRQ (SEQ ID NO: 5076), QNPP (SEQ ID NO: Sequence number 5077), QNLQ (SEQ ID NO: 5078), QDQE (SEQ ID NO: 5079), QDQQ (SEQ ID NO: 5080), HWQQ (SEQ ID NO: 5081), PNQQ (SEQ ID NO: 5082), PEQQ (SEQ ID NO: 5083), QRTM (SEQ ID NO: 5084), LHQH (SEQ ID NO: 5085), QHRI (SEQ ID NO: 5086), QYIH (SEQ ID NO: 5087), QKFE (SEQ ID NO: 5088), QFPS (SEQ ID NO: 5089), QNPL (SEQ ID NO: 5090), QAIK (SEQ ID NO: 5091), QNRQ (SEQ ID NO: 5092), QYQH (SEQ ID NO: 5093),QNPQ (SEQ ID NO: 5094), QHQL (SEQ ID NO: 5095), QSPP (SEQ ID NO: 5096), QAKL (SEQ ID NO: 5097), KSQQ (SEQ ID NO: 5098), QDRP (SEQ ID NO: 5099), QNLG (SEQ ID NO: 5100), QAFH (SEQ ID NO: 5101), QNAQ (SEQ ID NO: 5102), HNQL (SEQ ID NO: 5103), QKLN (SEQ ID NO: 5104), QNVQ (SEQ ID NO: 5105), QAQQ (SEQ ID NO: 5106), QTPP (SEQ ID NO: 5107), QPPA (SEQ ID NO: 5108), QERP (SEQ ID NO: 5109), QDLQ (SEQ ID NO: 5110), No. 5110), QAMH (SEQ ID NO: 5111), QHPS (SEQ ID NO: 5112), PGLQ (SEQ ID NO: 5113), QGIR (SEQ ID NO: 5114), QAPA (SEQ ID NO: 5115), QIPP (SEQ ID NO: 5116), QTQL (SEQ ID NO: 5117), QAPS (SEQ ID NO: 5118), QNTY (SEQ ID NO: 5119), QDKQ (SEQ ID NO: 5120), QNHL (SEQ ID NO: 5121), QIGM (SEQ ID NO: 5122), LNKQ (SEQ ID NO: 5123), PNQL (SEQ ID NO: 5124), QLQQ (SEQ ID NO: 5125), QRMS (SEQ ID NO: 5126), QGIL (SEQ ID NO: 5127), QDRQ (SEQ ID NO: 5128), RDWQ (SEQ ID NO: 5129), QERS (SEQ ID NO: 5130), QNYQ (SEQ ID NO: 5131), QRTC (SEQ ID NO: 5132), QIGH (SEQ ID NO: 5133), QGAI (SEQ ID NO: 5134), QVPP (SEQ ID NO: 5135), QVQQ (SEQ ID NO: 5136), LMRQ (SEQ ID NO: 5137), QYSV (SEQ ID NO: 5138), QAIT (SEQ ID NO: 5139), QKTL (SEQ ID NO: 5140), QLHH (SEQ ID NO: 5141), QNII (SEQ ID NO: 5142), QGHH (SEQ ID NO: 514 ...GIL (SEQ ID NO: 5127), QDRQ (SEQ ID NO: 5128), RDWQ (SEQ ID NO: 5129), QERS (SEQ ID NO: 5130), QNYQ (SEQ ID NO: 5131), QRTC (SEQ ID NO: 5132), QIGH (SEQ ID NO: 51 No. 5143), QSKV (SEQ ID NO: 5144), QLPS (SEQ ID NO: 5145), IGKQ (SEQ ID NO: 5146), QAIH (SEQ ID NO: 5147), QHGL (SEQ ID NO: 5148), QFMC (SEQ ID NO: 5149), QNQM (SEQ ID NO: 5150), QHLQ (SEQ ID NO: 5151), QPAR (SEQ ID NO: 5152), QSLQ (SEQ ID NO: 5153), QSQL (SEQ ID NO: 5154), HSQQ (SEQ ID NO: 5155), QMPS (SEQ ID NO: 5156), QGSL (SEQ ID NO: 5157), QVPA (SEQ ID NO: 5158), HYQQ (SEQ ID NO: 5159),QVPS (SEQ ID NO: 5160), RGEQ (SEQ ID NO: 5161), PGQQ (SEQ ID NO: 5162), LEQQ (SEQ ID NO: 5163), QNQS (SEQ ID NO: 5164), QKVI (SEQ ID NO: 5165), QNND (SEQ ID NO: 5166), QSVH (SEQ ID NO: 5167), QPLG (SEQ ID NO: 5168), HNQE (SEQ ID NO: 5169), QIQQ (SEQ ID NO: 5170), QVRN (SEQ ID NO: 5171), PSNQ (SEQ ID NO: 5172), QVGH (SEQ ID NO: 5173), QRDI (SEQ ID NO: 5174), QMPN (SEQ ID NO: 5175), RGLQ (SEQ ID NO: 5176), No. 5176), PSLQ (SEQ ID NO: 5177), QRDQ (SEQ ID NO: 5178), QAKG (SEQ ID NO: 5179), QSAH (SEQ ID NO: 5180), QSTM (SEQ ID NO: 5181), QREM (SEQ ID NO: 5182), QYRA (SEQ ID NO: 5183), QRQQ (SEQ ID NO: 5184), QWQQ (SEQ ID NO: 5185), QRMN (SEQ ID NO: 5186), GDSQ (SEQ ID NO: 5187), QKIS (SEQ ID NO: 5188), PSMQ (SEQ ID NO: 5189), SPRQ (SEQ ID NO: 5190), MEQQ (SEQ ID NO: 5191), QYQN (SEQ ID NO: 5192), QIRQ (SEQ ID NO: 5193), QSVQ (SEQ ID NO: 5194), RSQQ (SEQ ID NO: 5195), QNKL (SEQ ID NO: 5196), QIQH (SEQ ID NO: 5197), PRQQ (SEQ ID NO: 5198), HTQQ (SEQ ID NO: 5199), QRQH (SEQ ID NO: 5200), RNQE (SEQ ID NO: 5201), QSKQ (SEQ ID NO: 5202), QNQP (SEQ ID NO: 5203), QSPQ (SEQ ID NO: 5204), QTRQ (SEQ ID NO: 5205), QNLH (SEQ ID NO: 5206), QNQE (SEQ ID NO: 5207), LNQP (SEQ ID NO: 5208), QNQD (SEQ ID NO: 5209), QNQH (SEQ ID NO: 5210), QNQH (SEQ ID NO: 5211), QNQH (SEQ ID NO: 5212), QNQH (SEQ ID NO: 5213), QNQH (SEQ ID NO: 5214), QNQH (SEQ ID NO: 5215), QNQH (SEQ ID NO: 5216), QNQH (SEQ ID NO: 5217), QNQH (SEQ ID NO: 5218), QNQH (SEQ ID NO: 5219), QNQH (SEQ ID NO: 5220), QNQH (SEQ ID NO: 5221), QNQH (SEQ ID NO: 5222), QNQH (SEQ ID NO: 5223), QNQH (SEQ ID NO: 5224), QNQH (SEQ ID No. 5209), QNLL (SEQ ID NO: 5210), QLVI (SEQ ID NO: 5211), RTQE (SEQ ID NO: 5212), QTHQ (SEQ ID NO: 5213), QDQH (SEQ ID NO: 5214), QSQH (SEQ ID NO: 5215), VRQQ (SEQ ID NO: 5216), AWQQ (SEQ ID NO: 5217), QSVP (SEQ ID NO: 5218), QNIQ (SEQ ID NO: 5219), LDQQ (SEQ ID NO: 5220), PDQQ (SEQ ID NO: 5221), ESQQ (SEQ ID NO: 5222), QRQL (SEQ ID NO: 5223), QIIV (SEQ ID NO: 5224), QKQS (SEQ ID NO: 5225),QSHQ (SEQ ID NO: 5226), QFVV (SEQ ID NO: 5227), QSQP (SEQ ID NO: 5228), QNEQ (SEQ ID NO: 5229), INQQ (SEQ ID NO: 5230), RNRQ (SEQ ID NO: 5231), RDQK (SEQ ID NO: 5232), QWKR (SEQ ID NO: 5233), ENRQ (SEQ ID NO: 5234), QTQP (SEQ ID NO: 5235), QKQL (SEQ ID NO: 5236), RNQL (SEQ ID NO: 5237), ISIQ (SEQ ID NO: 5238), QTVC (SEQ ID NO: 5239), QQIM (SEQ ID NO: 5240), LNHQ (SEQ ID NO: 5241), QNQA (SEQ ID NO: 5242), QMIH (SEQ ID NO: 5243), RNHQ (SEQ ID NO: 5244), or QKMN (SEQ ID NO: 5245), (ii) an amino acid sequence containing any part of the amino acid sequence in (i), for example, any two or three amino acids thereof, for example, consecutive amino acids; (iii) an amino acid sequence that contains one, two, or three, but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to any of the amino acid sequences in (i); or (iv) An AAV capsid variant described in embodiment 39 or 40, which is or comprises an amino acid sequence that contains 1, 2, or 3, but not more than 4, different amino acids from any one of the amino acid sequences in (i).

[0082] 42.[N1]-[N2]-[N3]-[N4] (i) any amino acid sequence of SEQ ID NOs: 1800 to 2241; (ii) an amino acid sequence comprising any part of the amino acid sequences in (i), e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 amino acids, e.g., consecutive amino acids, of any of them; (iii) an amino acid sequence that contains one, two, or three, but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to any of the amino acid sequences in (i); or (iv) An AAV capsid variant described in any one of embodiments 39 to 41, which is or comprises an amino acid sequence that contains 1, 2, or 3, but not more than 4, different amino acids from any one of the amino acid sequences in (i).

[0083] 43. An AAV capsid variant described in any one of embodiments 39 to 42, wherein [N1]-[N2]-[N3]-[N4] is or comprises GSGSPHSKAQNQQ (sequence number 1801).

[0084] 44. An AAV capsid variant described in any one of embodiments 39 to 42, wherein [N1]-[N2]-[N3]-[N4] is or comprises GHDSPHKSGQNQQ (sequence number 1800).

[0085] 45. An AAV capsid variant described in any one of embodiments 39 to 42, wherein [N1]-[N2]-[N3]-[N4] is or comprises GSGSPHKYGQNQQT (sequence number 910).

[0086] 46. ​​The AAV capsid variant of any one of embodiments 1 to 45, comprising an amino acid other than T at position 450 (e.g., S, Y, M, A, C, I, R, L, D, F, V, Q, N, H, E, or G), an amino acid other than I at position 451 (e.g., M, P, E, N, D, S, A, T, G, Q, F, V, L, C, H, R, W, or L), and / or an amino acid other than N at position 452 (e.g., M, E, G, Y, W, T, I, Q, F, V, A, L, I, P, K, R, H, S, D, or S), relative to a reference sequence numbered according to any one of SEQ ID NOs: 36-59, 138, 981, or 982.

[0087] 47. The AAV capsid variant of any one of embodiments 1 to 46, comprising an amino acid T at position 450, an amino acid I at position 451, and / or an amino acid N at position 452 relative to a reference sequence numbered according to any one of SEQ ID NOs: 138, 981, or 982.

[0088] 48. [N0] further includes XA, XB, and XC; (a) position XA is T, S, Y, M, A, C, I, R, L, D, F, V, Q, N, H, E, or G; (b) the XB position is I, M, P, E, N, D, S, A, T, G, Q, F, V, L, C, H, R, W, or L; (c) position XC is N, M, E, G, Y, W, T, I, Q, F, V, A, L, I, P, K, R, H, S, D, or S; Optionally, the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of the above-mentioned amino acids in (a) to (c).

[0089] 49.[N0] is TIN, SMN, TIM, YLS, GLS, MPE, MEG, MEY, AEW, CEW, ANN, IPE, ADM, IEY, ADY, IET, MEW, CEY, R IN, MEI, LEY, ADW, IEI, DIM, FEQ, MEF, CDQ, LPE, IEN, MES, AEI, VEY, IIN, TSN, IEV, MEM, AEV, MDA, VEW , AEQ, LEW, MEL, MET, MEA, IES, MEV, CEI, ATN, MDG, QEV, ADQ, NMN, IEM, ISN, TGN, QQQ, HDW, IEG, TII, T FP, TEK, EIN, TVN, TFN, SIN, TER, TSY, ELH, AIN, SVN, TDN, TFH, TVH, TEN, TSS, TID, TCN, NIN, TEH, AEM, 49. The AAV capsid variant of embodiment 48, which is or comprises AIK, TDK, TFK, SDQ, TEI, NTN, TET, SIK, TEL, TEA, TAN, TIY, TFS, TES, TTN, TED, TNN, EVH, TIS, TVR, TDR, TIK, NHI, TIP, ESD, TDL, TVP, TVI, AEH, NCL, TVK, NAD, TIT, NCV, TIR, NAL, VIN, TIQ, TEF, TRE, QGE, SEK, NVN, GGE, EFV, SDK, TEQ, EVQ, TEY, NCW, TDV, SDI, NSI, NSL, EVV, TEP, SEL, TWQ, TEV, AVN, GVL, TLN, TEG, TRD, NAI, AEN, AET, ETA, NNL, or any dipeptide thereof.

[0090] 50.[N0]-[N1]-[N2]-[N3]-[N4] (i) any one of the amino acid sequences of SEQ ID NOs: 2242 to 2886; (ii) an amino acid sequence comprising any portion of the amino acid sequences in (i), e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acids, e.g., consecutive amino acids, of any of them; (iii) an amino acid sequence that contains one, two, or three, but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to any of the amino acid sequences in (i); or (iv) An AAV capsid variant described in embodiment 48 or 49, which is or comprises an amino acid sequence that contains 1, 2, or 3, but not more than 4, different amino acids from any one of the amino acid sequences in (i).

[0091] 51. An AAV capsid variant described in any one of embodiments 48 to 50, wherein [N0]-[N1]-[N2]-[N3]-[N4] is or comprises TINGSGSPHSKAQNQQ (sequence number 2242).

[0092] 52. An AAV capsid variant described in any one of embodiments 48 to 50, wherein [N0]-[N1]-[N2]-[N3]-[N4] is or comprises TINGHDSPHKSGQNQQ (sequence number 2243).

[0093] 53. An AAV capsid variant described in any one of embodiments 48 to 52, wherein [N0]-[N1]-[N2]-[N3]-[N4] is or comprises TINGSGSPHKYGQNQQT (sequence number 5246).

[0094] 54. An AAV capsid variant according to any one of embodiments 1 to 53, wherein [N1]-[N2]-[N3] is present in loop IV. 55. An AAV capsid variant according to any one of embodiments 48 to 54, wherein [N0] and [N4] are present in loop IV.

[0095] 56. An AAV capsid variant described in any one of embodiments 48 to 55, wherein [N0] is located immediately after position 449 relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.

[0096] 57. An AAV capsid variant described in any one of embodiments 48 to 56, wherein [N0] is located immediately after position 449 relative to a reference sequence numbered according to the amino acid sequence of any one of SEQ ID NOs: 36 to 59, 981, or 982.

[0097] 58. An AAV capsid variant according to any one of embodiments 48 to 57, wherein [N0] replaces positions 450, 451, and 452 (e.g., T450, I451, and N452) relative to the reference sequence numbered according to SEQ ID NO: 138.

[0098] 59. An AAV capsid variant according to any one of embodiments 48 to 58, wherein [N0] replaces positions 450 to 452 (e.g., T450, I451, and N452) with respect to a reference sequence numbered according to any one of SEQ ID NOs: 36 to 59, 981, or 982.

[0099] 60. An AAV capsid variant described in any one of embodiments 48 to 59, wherein [N0] corresponds to positions 450 to 452 of any one of SEQ ID NOs: 36 to 59, 138, 981, or 982.

[0100] 61. An AAV capsid variant according to any one of embodiments 48 to 60, wherein [N0] is located immediately after position 449 and replaces positions 450 to 452 (e.g., T450, I451, and N452) relative to the reference sequence numbered according to SEQ ID NO: 138.

[0101] 62. The AAV capsid variant of any one of embodiments 48 to 61, wherein [N0] is located immediately after position 449 and replaces positions 450 to 452 (e.g., T450, I451, and N452) relative to a reference sequence numbered according to any one of SEQ ID NOs: 36 to 59, 981, or 982.

[0102] 63. An AAV capsid variant according to any one of embodiments 1 to 62, wherein [N1] is located immediately after position 452 relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.

[0103] 64. An AAV capsid variant according to any one of embodiments 1 to 63, wherein [N1] is located immediately after position 452 relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 981 or 982.

[0104] 65. An AAV capsid variant according to any one of embodiments 1 to 61, wherein [N1] replaces positions 453 to 455 (e.g., G453, S454, and G455) relative to the reference sequence numbered according to SEQ ID NO: 138.

[0105] 66. The AAV capsid variant of any one of embodiments 1 to 64, wherein [N1] replaces position 453 (e.g., G453) relative to the reference sequence numbered according to SEQ ID NO: 138.

[0106] 67. An AAV capsid variant according to any one of embodiments 1 to 65, wherein [N1] replaces positions 453 to 455 (e.g., G453, S454, and G455) relative to the reference sequence numbered according to SEQ ID NO: 981.

[0107] 68. The AAV capsid variant of any one of embodiments 1 to 65 or 67, wherein [N1] replaces positions 453 to 455 relative to the reference sequence numbered according to SEQ ID NO: 982.

[0108] 69. The AAV capsid variant of any one of embodiments 1 to 65, 67, or 68, wherein [N1] is located immediately after position 452 and [N1] replaces positions 453 to 455 (e.g., G453, S454, and G455) relative to the reference sequence numbered according to SEQ ID NO: 138.

[0109] 70. The AAV capsid variant of any one of embodiments 1 to 64 or 66, wherein [N1] is located immediately after position 452 and replaces position 453 (e.g., G453) relative to the reference sequence numbered according to SEQ ID NO: 138.

[0110] 71. The AAV capsid variant of any one of embodiments 1 to 64, 66 or 70, wherein [N1] is located immediately after position 452 and replaces positions 453 to 455 relative to the reference sequence numbered according to SEQ ID NO: 981 or 982.

[0111] 72. An AAV capsid variant according to any one of embodiments 1 to 71, wherein [N1] corresponds to positions 453 to 455 of any one of SEQ ID NOs: 36 to 59, 981 or 982.

[0112] 73. The AAV capsid variant of any one of embodiments 1 to 72, comprising an amino acid other than S at position 454 and / or an amino acid other than G at position 455, numbered according to SEQ ID NO: 138, 981, or 982.

[0113] 74. The AAV capsid variant of any one of embodiments 1 to 73, comprising an amino acid H at position 454 and an amino acid D at position 455, numbered according to SEQ ID NO: 138 or 982.

[0114] 75. An AAV capsid variant according to any one of embodiments 1 to 74, comprising a substitution at position 454 (e.g., S454H) and / or a substitution at position 455 (e.g., G455D), numbered according to SEQ ID NO: 138.

[0115] 76. An AAV capsid variant according to any one of embodiments 1 to 75, comprising an amino acid H at position 454 and an amino acid D at position 455, and further comprising the amino acid sequence SPHSKA (SEQ ID NO: 941) immediately after position 455, relative to the reference sequence numbered according to SEQ ID NO: 138.

[0116] 77. The AAV capsid variant of any one of embodiments 1 to 76, comprising an amino acid H at position 454 and an amino acid D at position 455 relative to the reference sequence numbered according to SEQ ID NO: 982.

[0117] 78. An AAV capsid variant according to any one of embodiments 1 to 77, comprising an amino acid H at position 454 and an amino acid D at position 455, and further comprising the amino acid sequence SPHSKA (SEQ ID NO: 941) immediately after position 455, relative to a reference sequence numbered according to SEQ ID NO: 982.

[0118] 79. The AAV capsid variant of any one of embodiments 1 to 72, comprising an amino acid S at position 454 and an amino acid G at position 455 relative to the reference sequence numbered according to SEQ ID NO: 138.

[0119] 80. An AAV capsid variant according to any one of embodiments 1 to 72 or 79, comprising an amino acid S at position 454 and an amino acid G at position 455, and further comprising the amino acid sequence SPHSKA (SEQ ID NO: 941) immediately after position 455, relative to the reference sequence numbered according to SEQ ID NO: 138.

[0120] 81. The AAV capsid variant of any one of embodiments 1 to 72, 79, or 80, comprising an amino acid S at position 454 and an amino acid G at position 455 relative to the reference sequence numbered according to SEQ ID NO: 981.

[0121] 82. An AAV capsid variant according to any one of embodiments 1 to 72 or 79 to 81, comprising an amino acid S at position 454 and an amino acid G at position 455, and further comprising the amino acid sequence SPHSKA (SEQ ID NO: 941) immediately after position 455, relative to a reference sequence numbered according to SEQ ID NO: 981.

[0122] 83. An AAV capsid variant according to any one of embodiments 1 to 82, wherein [N2] is located immediately after position 455 relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.

[0123] 84. An AAV capsid variant according to any one of embodiments 1 to 83, wherein [N2] corresponds to positions 456 to 458 (e.g., S456, P457, H458) of SEQ ID NO: 981 or 982.

[0124] 85. An AAV capsid variant described in any one of embodiments 1 to 83, wherein [N2] corresponds to positions 456 to 458 (e.g., S456, P457, H458) of any one of SEQ ID NOs: 36 to 59.

[0125] 86. An AAV capsid variant described in any one of embodiments 1 to 85, wherein [N2]-[N3] is located immediately after position 455 relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.

[0126] 87. An AAV capsid variant according to any one of embodiments 1 to 86, wherein [N2] is located immediately after position 455 relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 981 or 982.

[0127] 88. An AAV capsid variant described in any one of embodiments 1 to 87, wherein [N2]-[N3] is located immediately after position 455 relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 981 or 982.

[0128] 89. An AAV capsid variant described in any one of embodiments 1 to 88, wherein [N2]-[N3] correspond to positions 456 to 461 of SEQ ID NO: 981 (e.g., S456, P457, H458, S459, K460, A461).

[0129] 90. An AAV capsid variant described in any one of embodiments 1 to 88, wherein [N2]-[N3] correspond to positions 456 to 461 of SEQ ID NO: 982 (e.g., S456, P457, H458, K459, S460, G461).

[0130] 91. An AAV capsid variant according to any one of embodiments 1 to 90, wherein [N2] is located immediately after [N1]. 92. The AAV capsid variant of any one of embodiments 1 to 64, 66, 70, or 71, wherein [N3] replaces positions 454 and 455 (e.g., S454 and G455), located immediately after [N2] and numbered according to SEQ ID NO: 138.

[0131] 93. The AAV capsid variant of any one of embodiments 1-64, 66, 70, 71, or 92, wherein [N3] replaces positions 454 and 455 (e.g., S454 and G455), located immediately after [N1]-[N2] and numbered according to SEQ ID NO: 138.

[0132] 94. An AAV capsid variant described in any one of embodiments 39 to 93, wherein [N4] is located immediately after position 455 relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.

[0133] 95. An AAV capsid variant described in any one of embodiments 39 to 94, wherein [N4] replaces positions 456 to 459 (e.g., Q456, N457, Q458, and Q459) relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.

[0134] 96. An AAV capsid variant described in any one of embodiments 39 to 95, wherein [N4] corresponds to positions 462 to 465 (e.g., Q462, N463, Q464, Q465) of SEQ ID NO: 981 or 982.

[0135] 97. An AAV capsid variant described in any one of embodiments 39 to 96, wherein [N2]-[N3]-[N4] replace positions 456 to 459 (e.g., Q456, N457, Q458, and Q459) relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.

[0136] 98. An AAV capsid variant described in any one of embodiments 39 to 97, wherein [N2]-[N3]-[N4] is located immediately after position 455, and [N2]-[N3]-[N4] replaces positions 456 to 459 (e.g., Q456, N457, Q458, and Q459) relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.

[0137] 99. An AAV capsid variant described in any one of embodiments 39 to 98, wherein [N2]-[N3]-[N4] correspond to positions 456 to 465 of SEQ ID NO: 981 (e.g., S456, P457, H458, S459, K460, A461, Q462, N463, Q464, Q465).

[0138] 100. An AAV capsid variant described in any one of embodiments 39 to 98, wherein [N2]-[N3]-[N4] correspond to positions 456 to 465 of SEQ ID NO: 982 (e.g., S456, P457, H458, K459, S460, G461, Q462, N463, Q464, Q465).

[0139] 101. An AAV capsid variant described in any one of embodiments 39 to 98, wherein [N2]-[N3]-[N4] correspond to positions 456 to 465 of any one of SEQ ID NOs: 36 to 59.

[0140] 102. An AAV capsid variant described in any one of embodiments 39 to 101, wherein [N1]-[N2]-[N3]-[N4] replace positions 453 to 459 (e.g., G453, S454, G455, Q456, N457, Q458, and Q459) relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.

[0141] 103. An AAV capsid variant according to any one of embodiments 39 to 102, wherein [N1]-[N2]-[N3]-[N4] is located immediately after position 452, and [N1]-[N2]-[N3]-[N4] replaces positions 453 to 459 (e.g., G453, S454, G455, Q456, N457, Q458, and Q459) relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.

[0142] 104. An AAV capsid variant described in any one of embodiments 39 to 99, 102, and 103, wherein [N1]-[N2]-[N3]-[N4] correspond to positions 453 to 465 of SEQ ID NO: 981 (e.g., G453, S454, G455, S456, P457, H458, S459, K460, A461, Q462, N463, Q464, Q465).

[0143] 105. An AAV capsid variant described in any one of embodiments 39 to 98, 100, 102, or 103, wherein [N1]-[N2]-[N3]-[N4] correspond to positions 453 to 465 of SEQ ID NO: 982 (e.g., G453, H454, D455, S456, P457, H458, K459, S460, G461, Q462, N463, Q464, Q465).

[0144] 106. An AAV capsid variant described in any one of embodiments 39 to 98, 102, or 103, wherein [N1]-[N2]-[N3]-[N4] correspond to positions 453 to 465 of any one of SEQ ID NOs: 36 to 59.

[0145] 107. An AAV capsid variant described in any one of embodiments 1 to 99 or 102 to 104, wherein [N1]-[N2]-[N3] correspond to positions 453 to 461 of SEQ ID NO: 981 (e.g., G453, S454, G455, S456, P457, H458, S459, K460, A461).

[0146] 108. The AAV capsid variant of any one of embodiments 1 to 98, 100, 102, 103, or 105, wherein [N1]-[N2]-[N3] correspond to positions 453 to 461 of SEQ ID NO: 982 (e.g., G453, H454, D455, S456, P457, H458, K459, S460, G461).

[0147] 109. An AAV capsid variant described in any one of embodiments 39 to 98, 102, 103, or 106, wherein [N1]-[N2]-[N3] correspond to positions 453 to 461 of any one of SEQ ID NOs: 36 to 59.

[0148] 110. An AAV capsid variant according to any one of embodiments 48 to 109, wherein [N0]-[N1]-[N2]-[N3]-[N4] replace positions 450 to 459 (e.g., T450, I451, N452, G453, S454, G455, Q456, N457, Q458, and Q459) relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.

[0149] 111. An AAV capsid variant according to any one of embodiments 48 to 110, wherein [N0]-[N1]-[N2]-[N3]-[N4] is located immediately after position 449, and [N0]-[N1]-[N2]-[N3]-[N4] replaces positions 450 to 459 (e.g., T450, I451, N452, G453, S454, G455, Q456, N457, Q458, and Q459) relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.

[0150] 112. The AAV capsid variant of any one of embodiments 48 to 99, 102 to 104, or 106, wherein [N0]-[N1]-[N2]-[N3]-[N4] correspond to positions 450 to 465 of SEQ ID NO: 981 (e.g., T450, I451, N452, G453, S454, G455, S456, P457, H458, S459, K460, A461, Q462, N463, Q464, Q465).

[0151] 113. The AAV capsid variant of any one of embodiments 48 to 98, 100, 102, 103, 105, or 108, wherein [N0]-[N1]-[N2]-[N3]-[N4] correspond to positions 450 to 465 of SEQ ID NO: 982 (e.g., T450, I451, N452, G453, H454, D455, S456, P457, H458, K459, S460, G461, Q462, N463, Q464, Q465).

[0152] 114. An AAV capsid variant described in any one of embodiments 48 to 98, 102, 103, 106, or 109, wherein [N0]-[N1]-[N2]-[N3]-[N4] correspond to positions 450 to 465 of any one of SEQ ID NOs: 36 to 59.

[0153] 115. An AAV capsid variant according to any one of embodiments 39 to 114, wherein [N4] replaces positions 462 to 465 (e.g., Q462, N463, Q464, and Q465) relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 981 or 982.

[0154] 116. An AAV capsid variant described in any one of embodiments 39 to 115, wherein [N2]-[N3]-[N4] replace positions 462 to 465 (e.g., Q462, N463, Q464, and Q465) relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 981 or 982.

[0155] 117. An AAV capsid variant according to any one of embodiments 39 to 116, wherein [N2]-[N3]-[N4] is located immediately after position 455, and [N2]-[N3]-[N4] replaces positions 462 to 465 (e.g., Q462, N463, Q464, and Q465) relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 981 or 982.

[0156] 118. An AAV capsid variant according to any one of embodiments 1 to 117, wherein [N3] is located immediately after [N2]. 119. The AAV capsid variant of any one of embodiments 1 to 118, comprising, from N-terminus to C-terminus, [N2]-[N3].

[0157] 120. The AAV capsid variant of any one of embodiments 1 to 119, comprising, from N-terminus to C-terminus, [N1]-[N2]-[N3]. 121. The AAV capsid variant of any one of embodiments 48 to 120, comprising, from N-terminus to C-terminus, [N0]-[N1]-[N2]-[N3].

[0158] 122. The AAV capsid variant of any one of embodiments 39 to 121, comprising, from N-terminus to C-terminus, [N1]-[N2]-[N3]-[N4]. 123. The AAV capsid variant of any one of embodiments 48 to 122, comprising, from N-terminus to C-terminus, [N0]-[N1]-[N2]-[N3]-[N4].

[0159] 124. The AAV capsid variant of any one of the preceding embodiments, comprising another amino acid (e.g., N, I, C, H, R, L, D, Y, A, M, Q, I, E, K, P, G, or S) at T at position 460, numbered according to the amino acid sequence of SEQ ID NO: 138.

[0160] 125. The AAV capsid variant of any one of the preceding embodiments, comprising the amino acid N, I, C, H, R, L, D, Y, A, M, Q, I, E, K, P, G or S at position 460, numbered according to the amino acid sequence of SEQ ID NO: 138.

[0161] 126. The AAV capsid variant of any one of the preceding embodiments, comprising another amino acid (e.g., N, I, C, H, R, L, D, Y, A, M, Q, I, E, K, P, G, or S) at T at position 466, numbered according to the amino acid sequence of any one of SEQ ID NOs: 36-59, 981, or 982.

[0162] 127. The AAV capsid variant of any one of the preceding embodiments, comprising the amino acid N, I, C, H, R, L, D, Y, A, M, Q, I, E, K, P, G, or S at position 466, numbered according to the amino acid sequence of any one of SEQ ID NOs: 36-59, 981, or 982.

[0163] 128. The AAV capsid variant of any one of the preceding embodiments, comprising another amino acid (e.g., E, N, or T) at K position 449, numbered according to the amino acid sequence of any one of SEQ ID NOs: 36-59, 138, 981, or 982.

[0164] 129. The AAV capsid variant of any one of the preceding embodiments, comprising an amino acid E, N, or T at position 449, numbered according to the amino acid sequence of any one of SEQ ID NOs: 36-59, 138, 981, or 982.

[0165] 130. An AAV capsid variant comprising [A][B] (SEQ ID NO: 4694), (i) [A] comprises the amino acid sequence of GSGSPH (SEQ ID NO: 4695); (ii) [B] contains X1, X2, X3, X4, X5, X6, and X7; (a) position X1 is S, C, F, or V; (b) position X2 is K, L, R, I, E, Y, V, or S; (c) position X3 is A, R, L, G, I, Y, S, F, or W; (d) position X4 is W, Q, R, G, L, V, S, or F; (e) position X5 is N, Y, R, C, K, or L; (f) position X6 is Q, G, K, R, T, L, or Y; (g) position X7 is Q, L, R, or V; Optionally, the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of the amino acids listed above in (a) to (g).

[0166] 131. (a) X1 is S; (b) position X2 is K or L; (c) position X3 is A, R, or L; (d) position X4 is Q or R; (e) position X5 is N or R; (f) position X6 is Q or R; (g) The AAV capsid variant of embodiment 130, wherein position X7 is Q, L, or R.

[0167] 132. [B] is (i) SLLWNQQ (SEQ ID NO: 5247), SKAQYYV (SEQ ID NO: 5248), SKLRRQQ (SEQ ID NO: 5249), SIWQNQQ (SEQ ID NO: 5250), SKAGCGQ (SEQ ID NO: 5251), SRAQNQQ (SEQ ID NO: 5252), SKRLRQQ (SEQ ID NO: 5253), SLRRNQQ (SEQ ID NO: 5254), SRGRNQQ (SEQ ID NO: 5255), SEIVNQ Q (SEQ ID NO: 5256), SSRRNQQ (SEQ ID NO: 5257), CLLQNQQ (SEQ ID NO: 5258), SKAFRLQ (SEQ ID NO: 5259), CLAQNQQ (SEQ ID NO: 5260), FLRQNQQ (SEQ ID NO: 5261), SLRFNQQ (SEQ ID NO: 5262), SYLRNQQ (SEQ ID NO: 5263), CSLQNQQ (SEQ ID NO: 5264), VLWQNQQ (SEQ ID NO: 5265 ), SKWLLQQ (SEQ ID NO: 5266), SLWSNQQ (SEQ ID NO: 5267), SKRRLQQ (SEQ ID NO: 5268), SVYLNQQ (SEQ ID NO: 5269), SLWLNQQ (SEQ ID NO: 5270), SKAQRKL (SEQ ID NO: 5271), SKALRRQ (SEQ ID NO: 5272), SKAQRLR (SEQ ID NO: 5273), SKAQNQQ (SEQ ID NO: 5274), SKAQRRL ( SEQ ID NO: 5275), SKARRQQ (SEQ ID NO: 5276), SKARRLQ (SEQ ID NO: 5277), SKSRRQQ (SEQ ID NO: 5278), SKALRQ (SEQ ID NO: 5279), SKASKRQ (SEQ ID NO: 5280), VRRQNQQ (SEQ ID NO: 5281), SKAQLYR (SEQ ID NO: 5282), SLFRNQQ (SEQ ID NO: 5283), SKAQLTV (SEQ ID NO: 5284), (ii) an amino acid sequence comprising any part of the amino acid sequences in (i), e.g., 2, 3, 4, 5, or 6 amino acids, e.g., consecutive amino acids, of any of them; (iii) an amino acid sequence that contains one, two, or three, but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to any of the amino acid sequences in (i); or (iv) An AAV capsid variant described in embodiment 130 or 131, comprising an amino acid sequence that contains 1, 2, or 3, but not more than 4, different amino acids from any one of the amino acid sequences in (i).

[0168] 133. [A] [B] (i) GSGSPHSLLWNQQ (SEQ ID NO: 5285), GSGSPHSKAQYYV (SEQ ID NO: 2060), GSGSPHSKLRRQQ (SEQ ID NO: 2061), GSGSPHSIWQNQQ (SEQ ID NO: 5286), GSGSPHSKAGCGQ (SEQ ID NO: 2062), GSGSPHSRAQNQQ (SEQ ID NO: 2063), GSGSPHSKRLRQQ (SEQ ID NO: 2064), GSGSPHSLRRNQQ (SEQ ID NO: 2065), GSGSPHSRGRNQQ (SEQ ID NO: 2066), GSGSPHSEI VNQQ (SEQ ID NO: 5287), GSGSPHSSRRNQQ (SEQ ID NO: 2067), GSGSPHCLLQNQQ (SEQ ID NO: 5288), GSGSPHSKAFRLQ (SEQ ID NO: 2068), GSGSPHCLAQNQQ (SEQ ID NO: 5289), GSGSPHFLRQNQQ (SEQ ID NO: 2070), GSGSPHSLRFNQQ (SEQ ID NO: 2071), GSGSPHSYLRNQQ (SEQ ID NO: 5290), GSGSPHCSLQNQQ (SEQ ID NO: 5291), GSGSPHVLWQNQQ (SEQ ID NO: 5292 ), GSGSPHSKWLLQQ (SEQ ID NO: 2072), GSGSPHSLWSNQQ (SEQ ID NO: 5293), GSGSPHSKRRLQQ (SEQ ID NO: 2073), GSGSPHSVYLNQQ (SEQ ID NO: 5294), GSGSPHSLWLNQQ (SEQ ID NO: 5295), GSGSPHSKAQRKL (SEQ ID NO: 2074), GSGSPHSKALRRQ (SEQ ID NO: 2075), GSGSPHSKAQRLR (SEQ ID NO: 2076), GSGSPHSKAQNQQ (SEQ ID NO: 1801), GSGSPHSKAQR RL (SEQ ID NO: 2077), GSGSPHSKARRQQ (SEQ ID NO: 2078), GSGSPHSKARRLQ (SEQ ID NO: 2079), GSGSPHSKSRRQQ (SEQ ID NO: 2080), GSGSPHSKARLRQ (SEQ ID NO: 2082), GSGSPHSKASKRQ (SEQ ID NO: 2083), GSGSPHVRRQNQQ (SEQ ID NO: 2084), GSGSPHSKAQLYR (SEQ ID NO: 2085), GSGSPHSLFRNQQ (SEQ ID NO: 5296), GSGSPHSKAQLTV (SEQ ID NO: 2086), (ii) an amino acid sequence comprising any part of the amino acid sequences in (i), e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 amino acids, e.g., consecutive amino acids, of any of them; (iii) an amino acid sequence that contains one, two, or three, but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to any of the amino acid sequences in (i); or (iv) The AAV capsid variant of any one of embodiments 130 to 132, comprising an amino acid sequence that contains 1, 2, or 3, but not more than 4, different amino acids from any one of the amino acid sequences in (i). 134. The AAV capsid variant of any one of embodiments 130 to 133, further comprising one, two, or all of the following, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138: an amino acid other than T at position 450 (e.g., S, Y, or G), an amino acid other than I at position 451 (e.g., M or L), and / or an amino acid other than N at position 452 (e.g., S).

[0169] 135. The AAV capsid variant of any one of embodiments 130 to 134, further comprising an S at position 450 and an M at position 451 relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.

[0170] 136. The AAV capsid variant of any one of embodiments 130 to 134, further comprising a Y at position 450, an L at position 451, and an S at position 452 relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.

[0171] 137. The AAV capsid variant of any one of embodiments 130 to 134, further comprising a G at position 450, an L at position 451, and an S at position 452 relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.

[0172] 138. An AAV capsid variant according to any one of embodiments 130 to 137, wherein [A][B] is present in loop IV. 139. An AAV capsid variant according to any one of embodiments 130 to 138, wherein [A] is located immediately after position 452 relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.

[0173] 140. An AAV capsid variant according to any one of embodiments 130 to 139, wherein [A] replaces positions 453 to 455 (e.g., G453, S454, G455) relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.

[0174] 141. An AAV capsid variant according to any one of embodiments 130 to 140, wherein [A] is present immediately after position 452 and [A] replaces positions 453 to 455 (e.g., G453, S454, G455) relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.

[0175] 142. An AAV capsid variant according to any one of embodiments 130 to 141, wherein [B] is located immediately after [A]. 143. An AAV capsid variant according to any one of embodiments 130 to 142, wherein [B] replaces positions 456 to 459 (e.g., Q456, N457, Q458, Q459) relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.

[0176] 144. An AAV capsid variant according to any one of embodiments 130 to 143, wherein [A][B] replaces positions 453 to 459 (e.g., G453, S454, G455, Q456, N457, Q458, Q459) relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.

[0177] 145. An AAV capsid variant according to any one of embodiments 130 to 144, wherein [A][B] is present immediately after position 452 and [A][B] replaces positions 453 to 459 (e.g., G453, S454, G455, Q456, N457, Q458, Q459) relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.

[0178] 146. The AAV capsid variant of any one of embodiments 130-145, comprising, from N-terminus to C-terminus, [A][B]. 147. An AAV capsid comprising [A][B] (SEQ ID NO: 4699), (i) [A] contains X1, X2, X3, X4, X5, and X6; (a) position X1 is T, M, A, C, I, R, L, D, F, V, Q, N, or H; (b) position X2 is I, P, E, N, D, S, A, T, M, or Q; (c) position X3 is N, E, G, Y, W, M, T, I, K, Q, F, S, V, A, or L; (d) position X4 is G, D, R, or E; (e) position X5 is H, Q, N, or D; (f) position X6 is D or R; Optionally, the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of the above-mentioned amino acids in (a)-(f); (ii) [B] an AAV capsid comprising SPHKSG (sequence number 946).

[0179] 148. (a) position X1 is T, M, A, or I; (b) position X2 is E, I or D; (c) position X3 is N, Q, Y, I, M, or V; (d) position X4 is G; (e) X5 is H; (f) An AAV capsid described in embodiment 147, wherein position X6 is D.

[0180] 149. [A] (i) TINGHD (SEQ ID NO: 5297), MPEGHD (SEQ ID NO: 5298), MEGGHD (SEQ ID NO: 5299), MEYGHD (SEQ ID NO: 5300), AEWGHD (SEQ ID NO: 5301), CEWGHD (SEQ ID NO: 5302), ANNGQD (SEQ ID NO: 5303), IPEGHD (SEQ ID NO: 5304), ADMGHD (SEQ ID NO: 5305), IEYGHD (SEQ ID NO: 5306), ADYGHD (SEQ ID NO: 5307), IETGHD (SEQ ID NO: 5308), MEWGHD (SEQ ID NO: 5309), CEYGHD (SEQ ID NO: 5310), R INGHD (SEQ ID NO: 5311), MEIGHD (SEQ ID NO: 5312), LEYGHD (SEQ ID NO: 5313), ADWGHD (SEQ ID NO: 5314), IEIGHD (SEQ ID NO: 5315), TIKDND (SEQ ID NO: 5316), DIMGHD (SEQ ID NO: 5317), FEQGHD (SEQ ID NO: 5318), MEFGHD (SEQ ID NO: 5319), CDQGHD (SEQ ID NO: 5320), LPEGHD (SEQ ID NO: 5321), IENGHD (SEQ ID NO: 5322), MESGHD (SEQ ID NO: 5323), AEIGHD (SEQ ID NO: 5324), VEYGHD (SEQ ID NO: 5325), TSNGDD (SEQ ID NO: 5326), IEVGHD (SEQ ID NO: 5327), MEMGHD (SEQ ID NO: 5328), AEVGHD (SEQ ID NO: 5329), MDAGHD (SEQ ID NO: 5330), VEWGHD (SEQ ID NO: 5331), AEQGHD (SEQ ID NO: 5332), LEWGHD (SEQ ID NO: 5333), MELGHD (SEQ ID NO: 5334), METGHD (SEQ ID NO: 5335), MEAGHD (SEQ ID NO: 5336), TINRQR (SEQ ID NO: 5337), IESGHD (SEQ ID NO: 5338), TAKDHD (SEQ ID NO: 5339), MEVGHD (SEQ ID NO: 5340), CEIGHD (SEQ ID NO: 5341), ATNGHD (SEQ ID NO: 5342), MDGGHD (SEQ ID NO: 5343), QEVGHD (SEQ ID NO: 5344), ADQGHD (SEQ ID NO: 5345), NMNGHD (SEQ ID NO: 5346), TPWEHD (SEQ ID NO: 5347), IEMGHD (SEQ ID NO: 5348), TANEHD (SEQ ID NO: 5349), QQQGHD (SEQ ID NO: 5350), TPQDHD (SEQ ID NO: 5351), HDWGHD (SEQ ID NO: 5352), IEGGHD (SEQ ID NO: 5353) (ii) an amino acid sequence comprising a portion of any of the amino acid sequences in (i), e.g., 2, 3, 4, or 5 amino acids, e.g., consecutive amino acids, of any of them; (iii) an amino acid sequence that contains one, two, or three, but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to any of the amino acid sequences in (i); or (iv) An AAV capsid variant described in embodiment 147 or 148, comprising an amino acid sequence that contains 1, 2, or 3, but not more than 4, different amino acids from any one of the amino acid sequences in (i).

[0181] 150. [A] [B] (i) TINGHDSPHKR (SEQ ID NO: 5354), MPEGHDSPHKS (SEQ ID NO: 5355), MEGGHDSPHKS (SEQ ID NO: 5356), MEYGHDSPHKS (SEQ ID NO: 5357), AEWGHDSPHKS (SEQ ID NO: 5358), CEWGHDSPHKS (SEQ ID NO: 5359), ANNGQDSPHKS (SEQ ID NO: 5360), IPEGHDSPHKS (SEQ ID NO: 5361), ADMGHDSPHKS (SEQ ID NO: 5362), IEYGHDSPHKS (SEQ ID NO: 5363), ADYGHDSPHKS (SEQ ID NO: 5364), IET GHDSPHKS (SEQ ID NO: 5365), MEWGHDSPHKS (SEQ ID NO: 5366), CEYGHDSPHKS (SEQ ID NO: 5367), RINGHDSPHKS (SEQ ID NO: 5368), MEIGHDSPHKS (SEQ ID NO: 5369), LEYGHDSPHKS (SEQ ID NO: 5370), ADWGHDSPHKS (SEQ ID NO: 5371), IEIGHSDPHKS (SEQ ID NO: 5372), TIKDNDSPHKS (SEQ ID NO: 5373), DIMGHDSPHKS (SEQ ID NO: 5374), FEQGHDSPHKS (SEQ ID NO: 5375), MEFGHDSPH KS (SEQ ID NO: 5376), CDQGHDSPHKS (SEQ ID NO: 5377), LPEGHDSPHKS (SEQ ID NO: 5378), IENGHDSPHKS (SEQ ID NO: 5379), MESGHDSPHKS (SEQ ID NO: 5380), AEIGHDSPHKS (SEQ ID NO: 5381), VEYGHDSPHKS (SEQ ID NO: 5382), TSNGDDSPHKS (SEQ ID NO: 5383), IEVGHDSPHKS (SEQ ID NO: 5384), MEMGHDSPHKS (SEQ ID NO: 5385), AEVGHDSPHKS (SEQ ID NO: 5386), MDAGHDSPHKS (SEQ ID NO: No. 5387), VEWGHDSPHKS (SEQ ID NO: 5388), AEQGHDSPHKS (SEQ ID NO: 5389), LEWGHDSPHKS (SEQ ID NO: 5390), MELGHDSPHKS (SEQ ID NO: 5391), METGHDSPHKS (SEQ ID NO: 5392), MEAGHDSPHKS (SEQ ID NO: 5393), TINRQRSPHKS (SEQ ID NO: 5394), IESGHDSPHKS (SEQ ID NO: 5395), TAKDHDSPHKS (SEQ ID NO: 5396), MEVGHDSPHKS (SEQ ID NO: 5397), CEIGHDSPHKS (SEQ ID NO: 5398),ATNGHDSPHKS (SEQ ID NO: 5399), MDGGHDSPHKS (SEQ ID NO: 5400), QEVGHDSPHKS (SEQ ID NO: 5401), ADQGHDSPHKS (SEQ ID NO: 5402), NMNGHDSPHKS (SEQ ID NO: 5403), TPWEHDSPHKS (SEQ ID NO: 5404), IEMGHDSPHKS (SEQ ID NO: 5405), TANEHDSPHKS (SEQ ID NO: 5406), TINGHDSPHKS (SEQ ID NO: 5407), QQQGHDSPHKS (SEQ ID NO: 5408), TPQDHDSPHKS (SEQ ID NO: 5409), HDWGHDSPHKS (SEQ ID NO: 5410), IEGGHDSPHKS (SEQ ID NO: 5411), (ii) an amino acid sequence comprising any part of the amino acid sequences in (i), e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids, e.g., consecutive amino acids, of any of them; (iii) an amino acid sequence that contains one, two, or three, but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to any of the amino acid sequences in (i); or (iv) An AAV capsid variant described in any one of embodiments 147 to 149, comprising an amino acid sequence that contains 1, 2, or 3, but not more than 4, different amino acids from any one of the amino acid sequences in (i).

[0182] 151. The AAV capsid variant of any one of embodiments 147-150, further comprising one, two, three, four, or all of the following, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138: an amino acid other than Q (e.g., R or L) at position 456, an amino acid other than N (e.g., H, K, or R) at position 457, an amino acid other than Q (e.g., R or T) at position 458, an amino acid other than Q (H) at position 459, and / or an amino acid other than T (N or S) at position 460.

[0183] 152. The AAV capsid variant of any one of embodiments 147 to 151, further comprising an R at position 456 relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.

[0184] 153. The AAV capsid variant of any one of embodiments 147 to 151, further comprising an L at position 456 relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.

[0185] 154. The AAV capsid variant of any one of embodiments 147 to 153, further comprising an H at position 457 and an R at position 458 relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.

[0186] 155. The AAV capsid variant of any one of embodiments 147 to 153, further comprising a K at position 457 and an N at position 460 relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.

[0187] 156. The AAV capsid variant of any one of embodiments 147 to 153, further comprising a T at position 458, an H at position 459, and an S at position 460 relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.

[0188] 157. The AAV capsid variant of any one of embodiments 147 to 151, further comprising an R at position 456, an R at position 457, and an R at position 458 relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.

[0189] 158. An AAV capsid variant according to any one of embodiments 147 to 157, wherein [A][B] is present in loop IV. 159. An AAV capsid variant according to any one of embodiments 147 to 158, wherein [A] is located immediately after position 449 relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.

[0190] 160. An AAV capsid variant according to any one of embodiments 147 to 159, wherein [A] replaces positions 450 to 453 (e.g., T450, I451, N452, G453) relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.

[0191] 161. An AAV capsid variant according to any one of embodiments 147 to 160, wherein [A] is present immediately after position 449 and [A] replaces positions 450 to 453 (e.g., T450, I451, N452, G453) relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.

[0192] 162. An AAV capsid variant according to any one of embodiments 147 to 161, wherein [A][B] replaces positions 450 to 455 (e.g., T450, I451, N452, G453, S454, G455) relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.

[0193] 163. An AAV capsid variant according to any one of embodiments 147 to 162, wherein [A][B] is present immediately after position 449 and [A][B] replaces positions 450 to 455 (e.g., T450, I451, N452, G453, S454, G455) relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.

[0194] 164. An AAV capsid variant according to any one of embodiments 147 to 163, wherein [B] is located immediately after [A] and replaces positions 454 and 455 (e.g., S454 and G455) relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.

[0195] 165. An AAV capsid variant described in any one of embodiments 147 to 164, wherein [B] is located immediately after position 455 relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 982.

[0196] 166. An AAV capsid variant according to any one of embodiments 147 to 165, wherein [B] is located immediately after [A]. 167. The AAV capsid variant of any one of embodiments 147 to 166, comprising, from N-terminus to C-terminus, [A][B].

[0197] 168. An AAV capsid variant comprising an amino acid sequence having the following formula: [N1]-[N2]-[N3] (SEQ ID NO: 6407), (i) [N1] comprises positions X1, X2, and X3, where position X2 is S and position X3 is G; (ii) [N2] comprises the amino acid sequence SPH; (iii) An AAV capsid variant in which [N3] comprises positions X4, X5, and X6, and position X5 is K.

[0198] 169. (i) X4 in [N3] is S, T, N, or A; (ii) X5 of [N3] is A, V, T, S, G, R, L, or N; Optionally, the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of the above-mentioned amino acids in (i) or (ii).

[0199] 170. The AAV capsid variant of embodiment 168 or 169, wherein X4 is S and / or X5 is A. 171. The AAV capsid variant of any one of embodiments 168 to 170, wherein [N3] comprises SK, TK, NK, AK, KA, KV, KT, KS, KG, KR, KL, or KN.

[0200] 172. The AAV capsid variant of any one of embodiments 168 to 171, wherein [N3] is or comprises SKA, SKV, SKT, SKS, SKG, SKR, TKA, NKA, SKL, SKN, or AKA.

[0201] 173. The AAV capsid variant according to any one of embodiments 168 to 172, wherein [N3] is or comprises SKA. 174. An AAV capsid variant described in any one of embodiments 168 to 173, wherein [N2]-[N3] comprises SPHSK (sequence number 4701), SPHTK (sequence number 4725), SPHNK (sequence number 4726), or SPHAK (sequence number 4727).

[0202] 175.[N2]-[N3] (i) SPHSKA (SEQ ID NO: 941), SPHSKV (SEQ ID NO: 4737), SPHSKT (SEQ ID NO: 4731), SPHSKS (SEQ ID NO: 962), SPHSKG (SEQ ID NO: 4732), SPHSKR (SEQ ID NO: 978), SPHTKA (SEQ ID NO: 4739), SPHNKA (SEQ ID NO: 4734), SPHSKL (SEQ ID NO: 960), SPHSKN (SEQ ID NO: 4735), or SPHAKA (SEQ ID NO: 4736); (ii) an amino acid sequence comprising a portion of any of the amino acid sequences in (i), e.g., 2, 3, 4, or 5 amino acids, e.g., consecutive amino acids, of any of them; (iii) an amino acid sequence that contains one, two, or three, but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to any of the amino acid sequences in (i); or (iv) An AAV capsid variant described in any one of embodiments 168 to 174, which is or comprises an amino acid sequence that contains 1, 2, or 3, but not more than 4, different amino acids from any one of the amino acid sequences in (i).

[0203] 176. An AAV capsid variant according to any one of embodiments 168 to 175, wherein [N2]-[N3] is or comprises SPHSKA (sequence number 941). 177. The AAV capsid variant of any one of embodiments 168 to 176, comprising an amino acid other than G at position 453 (e.g., M, T, I, E, S, A, N, V, L, K, H, P, R, W, or D), numbered according to SEQ ID NO: 138 or 981.

[0204] 178. The AAV capsid variant of any one of embodiments 168 to 177, comprising an amino acid G at position 453, numbered according to SEQ ID NO: 138 or 981. 179. An AAV capsid variant according to any one of embodiments 168 to 178, wherein X1 in [N1] is selected from G, M, T, I, E, S, A, N, V, L, K, H, P, R, W, or D, and optionally the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of the above-mentioned amino acids.

[0205] 180. The AAV capsid variant of any one of embodiments 168 to 179, wherein [N1] comprises SG, GS, MS, TS, IS, ES, SS, AS, NS, VS, LS, KS, HS, PS, RS, WS, or DS.

[0206] 181. The AAV capsid variant of any one of embodiments 168 to 180, wherein [N1] is or comprises GSG, MSG, TSG, ISG, ESG, SSG, ASG, NSG, VSG, LSG, KSG, HSG, PSG, RSG, WSG, or DSG.

[0207] 182. The AAV capsid variant of any one of embodiments 168 to 181, wherein [N1] is or comprises GSG. 183. An AAV capsid variant according to any one of embodiments 168 to 182, wherein [N1]-[N2] comprises SGSPH (sequence number 4752).

[0208] 184.[N1]-[N2] (i) GSGSPH (SEQ ID NO: 4695), MSGSPH (SEQ ID NO: 4798), TSGSPH (SEQ ID NO: 4800), ISGSPH (SEQ ID NO: 4801), ESGSPH (SEQ ID NO: 4803), SSGSPH (SEQ ID NO: 4804), ASGSPH (SEQ ID NO: 4806), NSGSPH (SEQ ID NO: 4807), VSGSPH (SEQ ID NO: 4786), LSGSPH (SEQ ID NO: 4808), KSGSPH (SEQ ID NO: 4810), HSGSPH (SEQ ID NO: 4811), PSGSPH (SEQ ID NO: 4813), RSGSPH (SEQ ID NO: 4815), WSGSPH (SEQ ID NO: 4817), DSGSPH (SEQ ID NO: 4818), (ii) an amino acid sequence comprising a portion of any of the amino acid sequences in (i), e.g., 2, 3, 4, or 5 amino acids, e.g., consecutive amino acids, of any of them; (iii) an amino acid sequence that contains one, two, or three, but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to any of the amino acid sequences in (i); or (iv) An AAV capsid variant described in any one of embodiments 168 to 183, which is or comprises an amino acid sequence that contains 1, 2, or 3, but not more than 4, different amino acids from any one of the amino acid sequences in (i).

[0209] 185.[N1]-[N2]-[N3] (i) GSGSPHSKA (SEQ ID NO: 4697), GSGSPHSKV (SEQ ID NO: 4956), MSGSPHSKA (SEQ ID NO: 4957), TSGSPHSKA (SEQ ID NO: 4959), ISGSPHSKA (SEQ ID NO: 4960), GSGSPHSKT (SEQ ID NO: 4962), ESGSPHSKA (SEQ ID NO: 4963), SSGSPHSKA (SEQ ID NO: 4964), GSGSPHSKS (SEQ ID NO: 4953), ASGSPHSKA (SEQ ID NO: 4966), NSGSPHSKA (SEQ ID NO: 4967), VSGSPHSKA (SEQ ID NO: 4913), LSGSPHSKA (SEQ ID NO: 4968), KSGSPHSKA (SEQ ID NO: 4970), GSGSPHSKG (SEQ ID NO: 4972), GSGSPHSKR (SEQ ID NO: 4945), HSGSPHSKA (SEQ ID NO: 4973), PSGSPHSKA (SEQ ID NO: 4975), RSGSPHSKA (SEQ ID NO: 4977), GSGSPHTKA (SEQ ID NO: 4978), WSGSPHSKA (SEQ ID NO: 4980), DSGSPHSKA (SEQ ID NO: 4981), GSGSPHNKA (SEQ ID NO: 4983), GSGSPHSKL (SEQ ID NO: 4943), GSGSPHSKN (SEQ ID NO: 4994), or GSGSPHAKA (SEQ ID NO: 4995), (ii) an amino acid sequence comprising any part of the amino acid sequences in (i), e.g., 2, 3, 4, 5, 6, 7, 8, or 9 amino acids, e.g., consecutive amino acids, of any of them; (iii) an amino acid sequence that contains one, two, or three, but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to any of the amino acid sequences in (i); or (iv) An AAV capsid variant described in any one of embodiments 168 to 184, which is or comprises an amino acid sequence that contains 1, 2, or 3, but not more than 4, different amino acids from any one of the amino acid sequences in (i).

[0210] 186. An AAV capsid variant according to any one of embodiments 168 to 185, wherein [N1]-[N2]-[N3] is or comprises GSGSPHSKA (sequence number 4697).

[0211] 187. With respect to a reference sequence numbered according to SEQ ID NO: 138, an amino acid other than Q at position 456 (e.g., R, P, H, L, K, I, G, S, M, or E), an amino acid other than N at position 457 (e.g., D, V, S, P, T, G, Y, W, E, R, H, K, F, A, I, L, or M), an amino acid other than Q at position 458 (e.g., R, L, A, P, H, T, I, F, K), , V, M, G, W, Y, S, E, N, or D), an amino acid other than Q at position 459 (e.g., H, K, A, L, P, E, M, I, S, N, R, Y, C, V, T, W, D, G), and / or an amino acid other than T at position 460 (e.g., I, N, S, H, R, L, D, Y, A, or Q).

[0212] 188. With respect to a reference sequence numbered according to SEQ ID NO: 981, an amino acid other than Q at position 462 (e.g., R, P, H, L, K, I, G, S, M, or E), an amino acid other than N at position 463 (e.g., D, V, S, P, T, G, Y, W, E, R, H, K, F, A, I, L, or M), an amino acid other than Q at position 464 (e.g., R, L, A, P, H, T, I, F, K), , V, M, G, W, Y, S, E, N, or D), an amino acid other than Q at position 465 (e.g., H, K, A, L, P, E, M, I, S, N, R, Y, C, V, T, W, D, G), and / or an amino acid other than T at position 466 (e.g., I, N, S, H, R, L, D, Y, A, or Q).

[0213] 189. The AAV capsid variant of any one of embodiments 168 to 188, comprising an amino acid Q at position 456, an amino acid N at position 457, an amino acid Q at position 458, an amino acid Q at position 459, and / or an amino acid T at position 460, relative to the reference sequence numbered according to SEQ ID NO: 138.

[0214] 190. The AAV capsid variant of any one of embodiments 168 to 189, comprising an amino acid Q at position 462, an amino acid N at position 463, an amino acid Q at position 464, an amino acid Q at position 465, and / or an amino acid T at position 466, numbered according to SEQ ID NO: 981.

[0215] 191. [N4] further includes X7, X8, X9, X10, and X11; (a) X7 is Q, R, P, H, L, K, I, G, S, M, or E; (b) X8 is N, D, V, S, P, T, G, Y, W, E, R, H, K, F, A, I, L, or M; (c) X9 is Q, R, L, A, P, H, T, I, F, K, V, M, G, W, Y, S, E, N, D; (d) X10 is Q, H, K, A, L, P, E, M, I, S, N, R, Y, C, V, T, W, D, G; (e) X11 is T, I, N, S, H, R, L, D, Y, A, or Q; Optionally, the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of the above-mentioned amino acids in (a) to (e).

[0216] 192.[N4] (i) QNQQT (SEQ ID NO: 5412), QNRHT (SEQ ID NO: 5413), RDQQT (SEQ ID NO: 5414), PNLQT (SEQ ID NO: 5415), HVRQT (SEQ ID NO: 5416), PNQHT (SEQ ID NO: 5417), QSQQT (SEQ ID NO: 5418), QNQQI (SEQ ID NO: 5419), QPAKT (SEQ ID NO: 5420), QTQQN (SEQ ID NO: 5421), QNLAT (SEQ ID NO: 5422), QNQLT (SEQ ID NO: 5423), QGQQT (SEQ ID NO: 5424), LNRQS (SEQ ID NO: 5425), HNQQT (SEQ ID NO: 5426), QNPPT (SEQ ID NO: 5427), QNLQT (SEQ ID NO: 5428), QYQQT (SEQ ID NO: 5429), QDQET (SEQ ID NO: 5430), QNHQT (SEQ ID NO: 5431), QDQQT (SEQ ID NO: 5432), HWQQT (SEQ ID NO: 5433), PNQQT (SEQ ID NO: 5434), QNQLI (SEQ ID NO: 5435), PEQQT (SEQ ID NO: 5436), QRTMT (SEQ ID NO: 5437), QNQQH (SEQ ID NO: 5438), LHQHT (SEQ ID NO: 5439), QHRIT (SEQ ID NO: 5440), QYIHT (SEQ ID NO: 5441), QKFET (SEQ ID NO: 5442) ), QFPST (SEQ ID NO: 5443), HNQQR (SEQ ID NO: 5444), QAIKT (SEQ ID NO: 5445), QNRQT (SEQ ID NO: 5446), QYQHT (SEQ ID NO: 5447), QNPQS (SEQ ID NO: 5448), QHQLT (SEQ ID NO: 5449), QSPPT (SEQ ID NO: 5450), QAKLT (SEQ ID NO: 5451), KSQQT (SEQ ID NO: 5452), QDRPT (SEQ ID NO: 5453), QSQQL (SEQ ID NO: 5454), QAFHT (SEQ ID NO: 5455), QKQQD (SEQ ID NO: 5456), QNAQT (SEQ ID NO: 5457), HNQLT (SEQ ID NO: Sequence number 5458), QNQQY (SEQ ID NO: 5459), QKLNT (SEQ ID NO: 5460), QNVQT (SEQ ID NO: 5461), QAQQT (SEQ ID NO: 5462), QNLQA (SEQ ID NO: 5463), QTPPT (SEQ ID NO: 5464), QYQHA (SEQ ID NO: 5465), QGQQA (SEQ ID NO: 5466), QPPAT (SEQ ID NO: 5467), QERPT (SEQ ID NO: 5468), QDLQT (SEQ ID NO: 5469), QAMHT (SEQ ID NO: 5470), LNQQT (SEQ ID NO: 5471), QHPST (SEQ ID NO: 5472), PGLQT (SEQ ID NO: 5473),QGIRT (SEQ ID NO: 5474), QAPAT (SEQ ID NO: 5475), QSQQI (SEQ ID NO: 5476), QIPPT (SEQ ID NO: 5477), QTQLT (SEQ ID NO: 5478), QAPST (SEQ ID NO: 5479), QNTYA (SEQ ID NO: 5480), QNQHI (SEQ ID NO: 5481), QNHLT (SEQ ID NO: 5482), QIGMT (SEQ ID NO: 5483), LNKQT (SEQ ID NO: 5484), QLQQT (SEQ ID NO: 5485), QRMST (SEQ ID NO: 5486), QGILT (SEQ ID NO: 5487), QDRQT (SEQ ID NO: 5488), RDWQT (SEQ ID NO: 5489), No. 5489), QNTHD (SEQ ID NO: 5490), PNLQI (SEQ ID NO: 5491), QERST (SEQ ID NO: 5492), QNYQT (SEQ ID NO: 5493), QRTCT (SEQ ID NO: 5494), QIGHT (SEQ ID NO: 5495), QGAIT (SEQ ID NO: 5496), QVPPT (SEQ ID NO: 5497), QVQQI (SEQ ID NO: 5498), LMRQT (SEQ ID NO: 5499), QYSVT (SEQ ID NO: 5500), QAITT (SEQ ID NO: 5501), QKTLT (SEQ ID NO: 5502), QNQWT (SEQ ID NO: 5503), QLHHT (SEQ ID NO: 5504), QNIII (SEQ ID NO: 5505), QGHHT (SEQ ID NO: 5506), QSKVT (SEQ ID NO: 5507), QLPST (SEQ ID NO: 5508), IGKQT (SEQ ID NO: 5509), QAIHT (SEQ ID NO: 5510), QHGLT (SEQ ID NO: 5511), QFMCT (SEQ ID NO: 5512), QHLQT (SEQ ID NO: 5513), QNHQN (SEQ ID NO: 5514), QPART (SEQ ID NO: 5515), QSLQT (SEQ ID NO: 5516), QSQLT (SEQ ID NO: 5517), QDRQS (SEQ ID NO: 5518), QMPST (SEQ ID NO: 5519), QGSLT (SEQ ID NO: 5520), QGSLT (SEQ ID NO: 5521), QGSLT (SEQ ID NO: 5522), QGSLT (SEQ ID NO: 5523), QGSLT (SEQ ID NO: 5524), QGSLT (SEQ ID NO: 5525), QGSLT (SEQ ID NO: 5526), ​​QGSLT (SEQ ID NO: 5527), QGSLT (SEQ ID NO: 5528), QGSLT (SEQ ID NO: 5529), QGSLT (SEQ ID NO: 5530), QGSLT (SEQ ID NO: 5531), QGSLT (SEQ ID NO: 5532), QGSLT (SEQ ID NO: 5533), QGSLT (SEQ ID NO: 5534), QGSLT (SEQ ID NO: 5535), QGSLT (SEQ ID NO: 5536), QGSLT (SEQ ID NO: 5537), QGSLT (SEQ ID NO: 5 No. 5520), QVPAT (SEQ ID NO: 5521), QDKQT (SEQ ID NO: 5522), HYQQT (SEQ ID NO: 5523), QVPST (SEQ ID NO: 5524), RGEQT (SEQ ID NO: 5525), PGQQT (SEQ ID NO: 5526), ​​QSLQI (SEQ ID NO: 5527), LEQQT (SEQ ID NO: 5528), QNQST (SEQ ID NO: 5529), QKVIT (SEQ ID NO: 5530), QNNDQ (SEQ ID NO: 5531), QSVHT (SEQ ID NO: 5532), QPLGT (SEQ ID NO: 5533), HNQET (SEQ ID NO: 5534), QNLQI (SEQ ID NO: 5535),QIQQT (SEQ ID NO: 5536), QVRNT (SEQ ID NO: 5537), PSNQT (SEQ ID NO: 5538), QVGHT (SEQ ID NO: 5539), QRDIT (SEQ ID NO: 5540), QMPNT (SEQ ID NO: 5541), RGLQT ​​(SEQ ID NO: 5542), QKQQT (SEQ ID NO: 5543), PSLQT (SEQ ID NO: 5544), QRDQT (SEQ ID NO: 5545), QAKGT (SEQ ID NO: 5546), QSAHT (SEQ ID NO: 5547), QSTMT (SEQ ID NO: 5548), QREMT (SEQ ID NO: 5549), QYRAT (SEQ ID NO: 5550), QWQQT (SEQ ID NO: 5551), QRMNT (SEQ ID NO: 5552), GDSQT (SEQ ID NO: 5553), QKIST (SEQ ID NO: 5554), PSMQT (SEQ ID NO: 5555), SPRQT (SEQ ID NO: 5556), MEQQT (SEQ ID NO: 5557), QYQNT (SEQ ID NO: 5558), QHQQT (SEQ ID NO: 5559), INQQT (SEQ ID NO: 5560), PNQQH (SEQ ID NO: 5561), ENRQT (SEQ ID NO: 5562), QTQQA (SEQ ID NO: 5563), or QNQAT (SEQ ID NO: 5564), (ii) an amino acid sequence comprising a portion of any of the amino acid sequences in (i), e.g., 2, 3, or 4 amino acids, e.g., consecutive amino acids, of any of them; (iii) an amino acid sequence that contains one, two, or three, but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to any of the amino acid sequences in (i); or (iv) An AAV capsid variant described in embodiment 191, which is or comprises an amino acid sequence that contains 1, 2, or 3, but not more than 4, different amino acids from any one of the amino acid sequences in (i).

[0217] 193.[N1]-[N2]-[N3]-[N4] (i) an amino acid sequence of any one of SEQ ID NOs: 200 and 2887 to 3076; (ii) any part of the amino acid sequence in (i), e.g., any 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or 13 amino acids, e.g., an amino acid sequence comprising those consecutive amino acids; (iii) an amino acid sequence that contains one, two, or three, but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to any of the amino acid sequences in (i); or (iv) An AAV capsid variant described in embodiment 191 or 192, which is or comprises an amino acid sequence that contains 1, 2, or 3, but not more than 4, different amino acids from any one of the amino acid sequences in (i).

[0218] 194. An AAV capsid variant according to any one of embodiments 191 to 193, wherein [N1]-[N2]-[N3]-[N4] is or comprises GSGSPHSKAQNQQT (SEQ ID NO: 200).

[0219] 195. An AAV capsid variant according to any one of embodiments 191 to 193, wherein [N1]-[N2]-[N3]-[N4] is or comprises VSGSPHSKAQNQQT (sequence number 903).

[0220] 196. The AAV capsid variant of any one of embodiments 168 to 195, comprising, relative to a reference sequence numbered according to SEQ ID NO: 138 or 981, an amino acid other than K at position 449 (e.g., T, E, or N), an amino acid other than T at position 450 (e.g., S, E, A, N, V, Q, or G), an amino acid other than I at position 451 (e.g., F, E, V, L, D, S, C, T, A, N, H, R, G, or W), and / or an amino acid other than N at position 452 (e.g., I, P, K, R, H, S, M, Q, D, T, L, A, Y, V, F, E, W, or G).

[0221] 197. The AAV capsid variant of any one of embodiments 168 to 196, comprising an amino acid K at position 449, an amino acid T at position 450, an amino acid I at position 451, and / or an amino acid N at position 452 relative to a reference sequence numbered according to SEQ ID NO: 138 or 981.

[0222] 198. [N0] is further included, and [N0] is X A , X B , X C , and X D Including, (a)X A is K, T, E, or N, (b)X b is T, S, E, A, N, V, Q, or G, (c)X C is I, F, E, V, L, D, S, C, T, A, N, H, R, G, or W, (d)X D is N, I, P, K, R, H, S, M, Q, D, T, L, A, Y, V, F, E, W, or G, Optionally, the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of the above-mentioned amino acids in (a) to (d).

[0223] 199.[N0] (i) KTII (SEQ ID NO: 5565), KTFP (SEQ ID NO: 5566), KTEK (SEQ ID NO: 5567), KTVN (SEQ ID NO: 5568), KTFN (SEQ ID NO: 5569), KTIN (SEQ ID NO: 5570), TTIN (SEQ ID NO: 5571), KSIN (SEQ ID NO: 5572), KTER (SEQ ID NO: 5573), KELH (SEQ ID NO: 5574), KAIN (SEQ ID NO: 5575), KTDN (SEQ ID NO: 5576), KTFH (SEQ ID NO: 5577), KTSN (SEQ ID NO: 5578), ETIN (SEQ ID NO: 5579), NTIN (SEQ ID NO: 5580), KTEN ( SEQ ID NO: 5581), KTSS (SEQ ID NO: 5582), KTCN (SEQ ID NO: 5583), KTEH (SEQ ID NO: 5584), KAEM (SEQ ID NO: 5585), KATN (SEQ ID NO: 5586), KAIK (SEQ ID NO: 5587), KTDK (SEQ ID NO: 5588), KTFK (SEQ ID NO: 5589), KSDQ (SEQ ID NO: 5590), KTEI (SEQ ID NO: 5591), KTID (SEQ ID NO: 5592), KNTN (SEQ ID NO: 5593), KTET (SEQ ID NO: 5594), KTEL (SEQ ID NO: 5595), KNIN (SEQ ID NO: 5596), KTEA (SEQ ID NO: 5597) ), KTAN (SEQ ID NO: 5598), NTIY (SEQ ID NO: 5599), KTFS (SEQ ID NO: 5600), KTES (SEQ ID NO: 5601), KTTN (SEQ ID NO: 5602), KTED (SEQ ID NO: 5603), KTNN (SEQ ID NO: 5604), KEVH (SEQ ID NO: 5605), KTIS (SEQ ID NO: 5606), KTVR (SEQ ID NO: 5607), KTDR (SEQ ID NO: 5608), ETIK (SEQ ID NO: 5609), KNHI (SEQ ID NO: 5610), KESD (SEQ ID NO: 5611), KTIK (SEQ ID NO: 5612), KTDL (SEQ ID NO: 5613), KTVP (SEQ ID NO: 5614), Sequence number 5614), KTVI (SEQ ID NO: 5615), KAEH (SEQ ID NO: 5616), KNCL (SEQ ID NO: 5617), KTVK (SEQ ID NO: 5618), KNAD (SEQ ID NO: 5619), KTIT (SEQ ID NO: 5620), KNCV (SEQ ID NO: 5621), KNAL (SEQ ID NO: 5622), KVIN (SEQ ID NO: 5623), KTEF (SEQ ID NO: 5624), KTRE (SEQ ID NO: 5625), KQGE (SEQ ID NO: 5626), KSEK (SEQ ID NO: 5627), KNVN (SEQ ID NO: 5628), KGGE (SEQ ID NO: 5629), KEFV (SEQ ID NO: 5630),KSDK (SEQ ID NO: 5631), KTEQ (SEQ ID NO: 5632), KEVQ (SEQ ID NO: 5633), KTEY (SEQ ID NO: 5634), KNCW (SEQ ID NO: 5635), KTDV (SEQ ID NO: 5636), KSDI (SEQ ID NO: 5637), KNSI (SEQ ID NO: 5638), KNSL (SEQ ID NO: 5639), KEVV (SEQ ID NO: 5640), KTEP (SEQ ID NO: 5641), KSEL (SEQ ID NO: 5642), KTWQ (SEQ ID NO: 5643), KTEV (SEQ ID NO: 5644), KAVN (SEQ ID NO: 5645), KGVL (SEQ ID NO: 5646), KTEG (SEQ ID NO: 5647), KTRD (SEQ ID NO: 5648), KTGN (SEQ ID NO: 5649), KNAI (SEQ ID NO: 5650), KAEN (SEQ ID NO: 5651), KAET (SEQ ID NO: 5652), KTVH (SEQ ID NO: 5653), KETA (SEQ ID NO: 5654), KNNL (SEQ ID NO: 5655), EAIN (SEQ ID NO: 5656), KSLN (SEQ ID NO: 5657), KTIP (SEQ ID NO: 5658), or KTIH (SEQ ID NO: 5659), (ii) an amino acid sequence containing any part of the amino acid sequence in (i), for example, any two or three amino acids thereof, for example, consecutive amino acids; (iii) an amino acid sequence that contains one, two, or three, but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to any of the amino acid sequences in (i); or (iv) An AAV capsid variant described in embodiment 198, which is or comprises an amino acid sequence that contains 1, 2, or 3, but not more than 4, different amino acids from any one of the amino acid sequences in (i).

[0224] 200.[N0]-[N1]-[N2]-[N3]-[N4] (i) any one of the amino acid sequences of SEQ ID NOs: 3239 to 3526 or 3591 to 3605; (ii) an amino acid sequence comprising any portion of the amino acid sequences in (i), e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 amino acids, e.g., consecutive amino acids, of any of them; (iii) an amino acid sequence that contains one, two, or three, but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to any of the amino acid sequences in (i); or (iv) An AAV capsid variant described in embodiment 198 or 199, which is or comprises an amino acid sequence that contains 1, 2, or 3, but not more than 4, different amino acids from any one of the amino acid sequences in (i).

[0225] 201. An AAV capsid variant described in any one of embodiments 198 to 200, wherein [N0]-[N1]-[N2]-[N3]-[N4] is or comprises KTINGSGSPHSKAQNQQT (sequence number 5660).

[0226] 202. An AAV capsid variant described in any one of embodiments 198 to 200, wherein [N0]-[N1]-[N2]-[N3]-[N4] is or comprises KTERVSGSPHSKAQNQQT (sequence number 3589).

[0227] 203. An AAV capsid variant comprising an amino acid sequence having the following formula: [N1]-[N2]-[N3] (SEQ ID NO: 6408), (i) [N1] comprises positions X1, X2, and X3, where position X2 is an amino acid other than S and position X3 is an amino acid other than G; (ii) [N2] comprises the amino acid sequence SPH; (iii) An AAV capsid variant in which [N3] comprises positions X4, X5, and X6, and position X4 is K.

[0228] 204. (i) X5 in [N3] is S, I, T, R, H, Y, L, or M; (ii) X6 in [N3] is G, A, L, E, V, R, W, N, Q, or K; Optionally, the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of the above-mentioned amino acids in (i) or (ii).

[0229] 205. The AAV capsid variant of embodiment 203 or 204, wherein X5 is S and / or X6 is G. 206. The AAV capsid variant of any one of embodiments 203 to 205, wherein [N3] comprises KS, KI, KT, KR, KH, KY, KL, KM, SG, IG, TG, RG, SA, SL, SE, SV, SR, SW, SN, HG, YG, SQ, IV, SK, LW, MG, or MA.

[0230] 207. The AAV capsid variant of any one of embodiments 203 to 206, wherein [N3] is or comprises KSG, KIG, KTG, KRG, KSA, KSL, KSE, KSV, KSR, KSW, KSN, KHG, KYG, KSQ, KIV, KSK, KLW, KMG, or KMA.

[0231] 208. The AAV capsid variant according to any one of embodiments 203 to 207, wherein [N3] is or comprises KSG. 209. An AAV capsid variant described in any one of embodiments 203 to 208, wherein [N2]-[N3] comprise SPHKS (SEQ ID NO: 4704), SPHKI (SEQ ID NO: 4713), SPHKT (SEQ ID NO: 4711), SPHKR (SEQ ID NO: 4717), NPHKS (SEQ ID NO: 5661), SPHKH (SEQ ID NO: 4728), SPHKY (SEQ ID NO: 4715), SPHKL (SEQ ID NO: 4714), or SPHKM (SEQ ID NO: 4729).

[0232] 210.[N2]-[N3] (i) SPHKSG (SEQ ID NO: 946), SPHKIG (SEQ ID NO: 958), SPHKTG (SEQ ID NO: 4738), SPHKRG (SEQ ID NO: 974), NPHKSG (SEQ ID NO: 5662), SPHKSA (SEQ ID NO: 977), SPHKSL (SEQ ID NO: 4740), SPHKSE (SEQ ID NO: 4741), SPHKSV (SEQ ID NO: 4742), SPHKSR (SEQ ID NO: 951), SPHKSW (SEQ ID NO: 4743), SPHKSN (SEQ ID NO: 4744), SPHKHG (SEQ ID NO: 4745), SPHKYG (SEQ ID NO: 966), SPHKSQ (SEQ ID NO: 4746), SPHKIV (SEQ ID NO: 5663), SPHKSK (SEQ ID NO: 4747), SPHKLW (SEQ ID NO: 4748), SPHKMG (SEQ ID NO: 4750), or SPHKMA (SEQ ID NO: 4751), (ii) an amino acid sequence comprising a portion of any of the amino acid sequences in (i), e.g., 2, 3, 4, or 5 amino acids, e.g., consecutive amino acids, of any of them; (iii) an amino acid sequence that contains one, two, or three, but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to any of the amino acid sequences in (i); or (iv) An AAV capsid variant described in any one of embodiments 203 to 209, which is or comprises an amino acid sequence that contains 1, 2, or 3, but not more than 4, different amino acids from any one of the amino acid sequences in (i).

[0233] 211. An AAV capsid variant according to any one of embodiments 203 to 210, wherein [N2]-[N3] is or comprises SPHKSG (sequence number 946). 212. The AAV capsid variant of any one of embodiments 203 to 211, comprising an amino acid other than G at position 453 (e.g., A, K, W, R, L, I, M, N, T, E, Q, Y, H, F, or V), numbered according to SEQ ID NO: 138 or 981.

[0234] 213. The AAV capsid variant of any one of embodiments 203 to 212, comprising an amino acid G at position 453, numbered according to SEQ ID NO: 138 or 981. 214. (i) the X1 position of [N1] is G, A, K, W, R, L, I, M, N, T, E, Q, Y, H, F, or V; (ii) Position X2 of [N1] is H, Y, R, Q, N, P, or D; (iii) the X3 position of [N1] is D, E, G, V, or N; Optionally, the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of the above-mentioned amino acids in (i), (ii), or (iii), of any one of embodiments 203 to 214.

[0235] 215. The AAV capsid variant according to any one of embodiments 203 to 214, wherein position X2 of [N1] is H and position X3 of [N1] is D. 216. An AAV capsid variant according to any one of embodiments 203 to 215, wherein position X1 of [N1] is G, position X2 of [N1] is H, and position X3 of [N1] is D.

[0236] 217. The AAV capsid variant of any one of embodiments 203 to 216, wherein [N1] comprises GH, HD, GY, GR, GQ, AH, GN, KH, GP, WH, RH, LH, IH, MH, GD, NH, TH, EH, QH, YH, HH, FH, VH, YD, HE, RG, QD, RD, ND, PD, QV, DD, HN, or NG.

[0237] 218. The AAV capsid variant of any one of embodiments 203 to 217, wherein [N1] is or comprises GHD, GYD, GHE, GRG, GQD, GRD, AHD, GND, KHD, GPD, WHD, RHD, LHD, GQV, IHD, MHD, GDD, GHN, NHD, THD, GNG, EHD, QHD, YHD, HHD, FHD, or VHD.

[0238] 219. The AAV capsid variant according to any one of embodiments 203 to 218, wherein [N1] is or comprises GHD. 220. An AAV capsid variant according to any one of embodiments 203 to 219, wherein [N1]-[N2] comprises HDSPH (sequence number 4703).

[0239] 221.[N1]-[N2] (i) GHDSPH (SEQ ID NO: 4784), GYDSPH (SEQ ID NO: 4829), GHESPH (SEQ ID NO: 4793), GRGSPH (SEQ ID NO: 4788), GHDNPH (SEQ ID NO: 5664), GQDSPH (SEQ ID NO: 4785), GRDSPH (SEQ ID NO: 4831), AHDSPH (SEQ ID NO: 5665), GNDSPH (SEQ ID NO: 4832), KHDSPH (SEQ ID NO: 5666), GPDSPH (SEQ ID NO: 4833), WHDSPH (SEQ ID NO: 5667), RHDSPH (SEQ ID NO: 5668), LHDSPH (SEQ ID NO: 5669), GQVSPH (SEQ ID NO: 4835), IHDSPH (SEQ ID NO: 5670), MHDSPH (SEQ ID NO: 5671), GDDSPH (SEQ ID NO: 4792), GHNSPH (SEQ ID NO: 4836), NHDSPH (SEQ ID NO: 5672), THDSPH (SEQ ID NO: 5673), GNGSPH (SEQ ID NO: 4805), EHDSPH (SEQ ID NO: 5674), QHDSPH (SEQ ID NO: 5675), YHDSPH (SEQ ID NO: 5676), HHDSPH (SEQ ID NO: 5677), FHDSPH (SEQ ID NO: 5678), or VHDSPH (SEQ ID NO: 5679), (ii) an amino acid sequence comprising a portion of any of the amino acid sequences in (i), e.g., 2, 3, 4, or 5 amino acids, e.g., consecutive amino acids, of any of them; (iii) an amino acid sequence that contains one, two, or three, but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to any of the amino acid sequences in (i); or (iv) An AAV capsid variant described in any one of embodiments 203 to 220, which is or comprises an amino acid sequence that contains 1, 2, or 3, but not more than 4, different amino acids from any one of the amino acid sequences in (i).

[0240] 222.[N1]-[N2]-[N3] (i) GHDSPHKSG (SEQ ID NO: 4698), GHDSPHKIG (SEQ ID NO: 4996), GYDSPHKSG (SEQ ID NO: 4997), GHESPHKSG (SEQ ID NO: 4998), GHDSPHKTG (SEQ ID NO: 4999), GRGSPHKRG (SEQ ID NO: 5000), GHDNPHKSG (SEQ ID NO: 5680), GQDSPHKSG (SEQ ID NO: 4908), GHDSPHKSA (SEQ ID NO: 4940), GHDSPHKSL (SEQ ID NO: 5001), GHDSPHKSE (SEQ ID NO: 5003), GRDSPHKSG (SEQ ID NO: 5004), AH DSPHKSG (SEQ ID NO: 5681), GNDSPHKSV (SEQ ID NO: 5005), AHDSPHKIG (SEQ ID NO: 5682), GHESPHKSA (SEQ ID NO: 4939), GQDSPHKIG (SEQ ID NO: 5006), GHDSPHKSV (SEQ ID NO: 5007), GHDSPHKSR (SEQ ID NO: 4942), KHDSPHKSG (SEQ ID NO: 5683), GPDSPHKIG (SEQ ID NO: 5008), GPDSPHKSG (SEQ ID NO: 5009), GHDSPHKSW (SEQ ID NO: 5010), WHDSPHKSG (SEQ ID NO: 5684), RHDSPHKS G (SEQ ID NO: 5685), GHDSPHKSN (SEQ ID NO: 5011), GHDSPHKRG (SEQ ID NO: 4937), GHDSPHKHG (SEQ ID NO: 5013), LHDSPHKSG (SEQ ID NO: 5686), GQVSPHKSG (SEQ ID NO: 5014), IHDSPHKSG (SEQ ID NO: 5687), MHDSPHKSG (SEQ ID NO: 5688), GDDSPHKSV (SEQ ID NO: 5015), GHNSPHKSG (SEQ ID NO: 5016), NHDSPHKSG (SEQ ID NO: 5689), THDSPHKSG (SEQ ID NO: 5690), GNGSPHKRG (SEQ ID NO: 5017), EHDSPHKSG (SEQ ID NO: 5691), GHDSPHKYG (SEQ ID NO: 5018), GHDSPHKSQ (SEQ ID NO: 5019), QHDSPHKSG (SEQ ID NO: 5692), RHDSPHKIV (SEQ ID NO: 5693), YHDSPHKSG (SEQ ID NO: 5694), GNDSPHKIG (SEQ ID NO: 5020), HHDSPHKSG (SEQ ID NO: 5695), GHDSPHKSK (SEQ ID NO: 5021), FHDSPHKSG (SEQ ID NO: 5696), GHDSPHKLW (SEQ ID NO: 5022), VHDSPHKSG (SEQ ID NO: 5697),GHDSPHKMG (SEQ ID NO: 5024), GHDSPHKMA (SEQ ID NO: 5025), or GDDSPHKSG (SEQ ID NO: 4938), (ii) an amino acid sequence comprising any part of the amino acid sequences in (i), e.g., 2, 3, 4, 5, 6, 7, 8, or 9 amino acids, e.g., consecutive amino acids, of any of them; (iii) an amino acid sequence that contains one, two, or three, but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to any of the amino acid sequences in (i); or (iv) An AAV capsid variant described in any one of embodiments 203 to 221, which is or comprises an amino acid sequence that contains 1, 2, or 3, but not more than 4, different amino acids from any one of the amino acid sequences in (i).

[0241] 223. The AAV capsid variant of any one of embodiments 203 to 222, wherein [N1]-[N2]-[N3] is or comprises GHDSPHKSG (sequence number 4698).

[0242] 224. The AAV capsid variant of any one of embodiments 203 to 223, comprising, relative to a reference sequence numbered according to SEQ ID NO: 138, an amino acid other than Q at position 456 (e.g., R, P, H, K, L, V, A, E, or I), an amino acid other than N at position 457 (e.g., I, K, S, H, R, T, D, Y, L, W, F, A, Q, or M), an amino acid other than Q at position 458 (e.g., R, V, K, P, Y, H, L, I, E, or M), an amino acid other than Q at position 459 (e.g., H, L, E, P, W, D, I, V, S, K, R, C, M, or N), and / or an amino acid other than T at position 460 (e.g., A, E, K, S, I, P, G, or N).

[0243] 225. The AAV capsid variant of any one of embodiments 203 to 224, comprising, relative to a reference sequence numbered according to SEQ ID NO: 982, an amino acid other than Q at position 462 (e.g., R, P, H, K, L, V, A, E, or I), an amino acid other than N at position 463 (e.g., I, K, S, H, R, T, D, Y, L, W, F, A, Q, or M), an amino acid other than Q at position 464 (e.g., R, V, K, P, Y, H, L, I, E, or M), an amino acid other than Q at position 465 (e.g., H, L, E, P, W, D, I, V, S, K, R, C, M, or N), and / or an amino acid other than T at position 466 (e.g., A, E, K, S, I, P, G, or N).

[0244] 226. The AAV capsid variant of any one of embodiments 203 to 225, comprising an amino acid Q at position 456, an amino acid N at position 457, an amino acid Q at position 458, an amino acid Q at position 459, and / or an amino acid T at position 460 relative to the reference sequence numbered according to SEQ ID NO: 138.

[0245] 227. The AAV capsid variant of any one of embodiments 203 to 226, comprising an amino acid Q at position 462, an amino acid N at position 463, an amino acid Q at position 464, an amino acid Q at position 465, and / or an amino acid T at position 466, relative to the reference sequence numbered according to SEQ ID NO: 138.

[0246] 228. [N4] further includes X7, X8, X9, X10, and X11; (a) X7 is Q, R, P, H, L, K, I, G, S, M, or E; (b) X8 is N, D, V, S, P, T, G, Y, W, E, R, H, K, F, A, I, L, or M; (c) X9 is Q, R, L, A, P, H, T, I, F, K, V, M, G, W, Y, S, E, N, D; (d) X10 is Q, H, K, A, L, P, E, M, I, S, N, R, Y, C, V, T, W, D, G; (e) X11 is T, I, N, S, H, R, L, D, Y, A, or Q; Optionally, the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of the above-mentioned amino acids in (a) to (e).

[0247] 229.[N4] (i) QNQQT (SEQ ID NO: 5412), QIRQT (SEQ ID NO: 5698), QNQHA (SEQ ID NO: 5699), QKQQT (SEQ ID NO: 5543), QSVQT (SEQ ID NO: 5700), RSQQT (SEQ ID NO: 5701), QNKLE (SEQ ID NO: 5702), QNQQK (SEQ ID NO: 5703), QHQQA (SEQ ID NO: 5704), QIQHT (SEQ ID NO: 5705), PRQQT (SEQ ID NO: 5706), HTQQT (SEQ ID NO: 5707), QRQHT (SEQ ID NO: 5708), QSQQT (SEQ ID NO: 5418), QNQQS (SEQ ID NO: 5709), RNQET (SEQ ID NO: 5710), QTQLT (SEQ ID NO: 5478), KNQQT (SEQ ID NO: 5711), QDQQT (SEQ ID NO: 5432), HNQQT (SEQ ID NO: 5426), QNQLT (SEQ ID NO: 5423), QTQQT (SEQ ID NO: 5712), QTQQI (SEQ ID NO: 5713), QSKQA (SEQ ID NO: 5714), QNQPP (SEQ ID NO: 5715), QSPQT (SEQ ID NO: 5716), QNYQT (SEQ ID NO: 5493), QNHQT (SEQ ID NO: 5431), QNRQT (SEQ ID NO: 5446), QNQQG (SEQ ID NO: 5717), QNHLT (SEQ ID NO: 5482 ), QYQHT (SEQ ID NO: 5447), QNQWT (SEQ ID NO: 5503), QNQHT (SEQ ID NO: 5718), QTRQT (SEQ ID NO: 5719), QNLHT (SEQ ID NO: 5720), LNQQT (SEQ ID NO: 5471), QNQET (SEQ ID NO: 5721), QHLQT (SEQ ID NO: 5513), LNQPT (SEQ ID NO: 5722), QNQDT (SEQ ID NO: 5723), RNQQT (SEQ ID NO: 5724), QNLLT (SEQ ID NO: 5725), QLVIT (SEQ ID NO: 5726), RTQET (SEQ ID NO: 5727), QTHQT (SEQ ID NO: 5728), QNQPA (SEQ ID NO: Sequence number 5729), QDQHT ​​(SEQ ID NO: 5730), QSQHT (SEQ ID NO: 5731), RNQQI (SEQ ID NO: 5732), VRQQT (SEQ ID NO: 5733), QNQHS (SEQ ID NO: 5734), AWQQT (SEQ ID NO: 5735), QSVPT (SEQ ID NO: 5736), QNIQP (SEQ ID NO: 5737), QNHLN (SEQ ID NO: 5738), LDQQT (SEQ ID NO: 5739), PDQQS (SEQ ID NO: 5740), ESQQT (SEQ ID NO: 5741), QNKQT (SEQ ID NO: 5742), QRQLT (SEQ ID NO: 5743), QIIVT (SEQ ID NO: 5744),QKQST (SEQ ID NO: 5745), QSHQT (SEQ ID NO: 5746), QFVVT (SEQ ID NO: 5747), QNLQT (SEQ ID NO: 5428), QNQQI (SEQ ID NO: 5419), QSQPT (SEQ ID NO: 5748), QNEQT (SEQ ID NO: 5749), QSLQT (SEQ ID NO: 5516), RNRQT (SEQ ID NO: 5750), QSKQT (SEQ ID NO: 5751), QNPLT (SEQ ID NO: 5752), RDQKT (SEQ ID NO: 5753), HNQQN (SEQ ID NO: 5754), QWKRT (SEQ ID NO: 5755), QSQQI (SEQ ID NO: 5476), QAQQT (SEQ ID NO: 5462), QNHQI (SEQ ID NO: 5756), QNQQA (SEQ ID NO: 5757), QNQLN (SEQ ID NO: 5519), QSQPT (SEQ ID NO: 5748), QNEQT (SEQ ID NO: 5749), QSLQT (SEQ ID NO: 5516), RNRQT (SEQ ID NO: 5750), QSKQT (SEQ ID NO: 5751), QNPLT (SEQ ID NO: 5752), RDQKT (SEQ ID NO: 5753), HNQQN (SEQ ID NO: 5754), QWKRT (SEQ ID NO: 5755), QSQQI (SEQ ID NO: 5476), QAQQT (SEQ ID NO: 5462), QNHQI (SEQ ID NO: 5756), QNQQA ( No. 5758), QTQPT (SEQ ID NO: 5759), INQQT (SEQ ID NO: 5560), QKQLT (SEQ ID NO: 5760), RNQLA (SEQ ID NO: 5761), RNQQS (SEQ ID NO: 5762), ISIQT (SEQ ID NO: 5763), QNQQN (SEQ ID NO: 5764), QSQQS (SEQ ID NO: 5765), QTVCT (SEQ ID NO: 5766), QYQQI (SEQ ID NO: 5767), QQIMT (SEQ ID NO: 5768), QNEQS (SEQ ID NO: 5769), LNHQT (SEQ ID NO: 5770), QMIHT (SEQ ID NO: 5771), RNHQS (SEQ ID NO: 5772), QKMNT (SEQ ID NO: 5773), QSQQN (SEQ ID NO: 5774), QYQHA (SEQ ID NO: 5465), (ii) an amino acid sequence comprising a portion of any of the amino acid sequences in (i), e.g., 2, 3, or 4 amino acids, e.g., consecutive amino acids, of any of them; (iii) an amino acid sequence that contains one, two, or three, but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to any of the amino acid sequences in (i); or (iv) An AAV capsid variant described in embodiment 228, which is or comprises an amino acid sequence that contains 1, 2, or 3, but not more than 4, different amino acids from any one of the amino acid sequences in (i).

[0248] 230.[N1]-[N2]-[N3]-[N4] (i) an amino acid sequence of any one of SEQ ID NOs: 201 and 3160 to 3237; (ii) any part of the amino acid sequence in (i), e.g., any 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or 13 amino acids, e.g., an amino acid sequence comprising those consecutive amino acids; (iii) an amino acid sequence that contains one, two, or three, but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to any of the amino acid sequences in (i); or (iv) An AAV capsid variant described in embodiment 228 or 229, which is or comprises an amino acid sequence that contains 1, 2, or 3, but not more than 4, different amino acids from any one of the amino acid sequences in (i).

[0249] 231. The AAV capsid variant of any one of embodiments 228 to 230, wherein [N1]-[N2]-[N3]-[N4] is or comprises GHDSPHKSGQNQQT (SEQ ID NO: 201).

[0250] 232. The AAV capsid variant of any one of embodiments 203 to 231, comprising, relative to a reference sequence numbered according to SEQ ID NO: 138 or 982, an amino acid other than K at position 449 (e.g., T), an amino acid other than T at position 450 (e.g., A, S, I, V, N, E, Y, C, G, W, or Q), an amino acid other than I at position 451 (e.g., E, V, S, T, N, D, C, G, Q, L, P, A), and / or an amino acid other than N at position 452 (e.g., S, Y, I, K, F, T, D, E, G, V, L, A, M, Q, H, P, or R).

[0251] 233. The AAV capsid variant of any one of embodiments 203 to 232, comprising an amino acid K at position 449, an amino acid T at position 450, an amino acid I at position 451, and / or an amino acid N at position 452 relative to a reference sequence numbered according to SEQ ID NO: 138 or 982.

[0252] 234. [N0] is further included, and [N0] is X A , X B , X C , and X D Including, (a)X A is K or T, (b)X b is T, A, S, I, V, N, E, Y, C, G, W, or Q, (c)X C are I, E, V, S, T, N, D, C, G, Q, L, P, A, and (d)X D is N, S, Y, I, K, F, T, D, E, G, V, L, A, M, Q, H, P, or R, Optionally, the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of the above-mentioned amino acids in (a) to (d).

[0253] 235. [N0] (i) KAIN (SEQ ID NO: 5575), KTIN (SEQ ID NO: 5570), KTES (SEQ ID NO: 5601), TTIN (SEQ ID NO: 5571), KSIN (SEQ ID NO: 5572), KTVN (SEQ ID NO: 5568), KSIY (SEQ ID NO: 5775), KTSN (SEQ ID NO: 5578), KTTN (SEQ ID NO: 5602), KIIN (SEQ ID NO: 5776), KTIS (SEQ ID NO: 5606), KAII (SEQ ID NO: 5777), KTIK (SEQ ID NO: 5612), KTEF (SEQ ID NO: 5624), KTIT (SEQ ID NO: 5620), KTNN (SEQ ID NO: 5604), KTID ( SEQ ID NO: 5592), KAIS (SEQ ID NO: 5778), KTVD (SEQ ID NO: 5779), KTIE (SEQ ID NO: 5780), KTEG (SEQ ID NO: 5647), KVIN (SEQ ID NO: 5623), KAVN (SEQ ID NO: 5645), KTIY (SEQ ID NO: 5781), KTDN (SEQ ID NO: 5576), KTCN (SEQ ID NO: 5583), KNVV (SEQ ID NO: 5782), KTEL (SEQ ID NO: 5595), KTDA (SEQ ID NO: 5783), KTEV (SEQ ID NO: 5644), KSEL (SEQ ID NO: 5642), KTEM (SEQ ID NO: 5784), KTEQ (SEQ ID NO: 5632) ), KTII (SEQ ID NO: 5565), KIVN (SEQ ID NO: 5785), KTEK (SEQ ID NO: 5567), KTEN (SEQ ID NO: 5581), KIGN (SEQ ID NO: 5786), KEVM (SEQ ID NO: 5787), KYQV (SEQ ID NO: 5788), KTEA (SEQ ID NO: 5597), KATN (SEQ ID NO: 5586), KTEH (SEQ ID NO: 5584), KTVE (SEQ ID NO: 5789), KAID (SEQ ID NO: 5790), KTIM (SEQ ID NO: 5791), KEVG (SEQ ID NO: 5792), KSEM (SEQ ID NO: 5793), KAQQ (SEQ ID NO: 5794), KCGE (SEQ ID NO: 5795), Sequence number 5795), KASN (SEQ ID NO: 5796), KTET (SEQ ID NO: 5594), KTIG (SEQ ID NO: 5797), KTDP (SEQ ID NO: 5798), KELV (SEQ ID NO: 5799), KELM (SEQ ID NO: 5800), KNEI (SEQ ID NO: 5801), KTPN (SEQ ID NO: 5802), KITN (SEQ ID NO: 5803), KTDI (SEQ ID NO: 5804), KTDQ (SEQ ID NO: 5805), KGIN (SEQ ID NO: 5806), KSEI (SEQ ID NO: 5807), KSEK (SEQ ID NO: 5627), KWSA (SEQ ID NO: 5808), KELA (SEQ ID NO: 5809),KQTQ (SEQ ID NO: 5810), KGAD (SEQ ID NO: 5811), KVGE (SEQ ID NO: 5812), KANE (SEQ ID NO: 5813), KTDT (SEQ ID NO: 5814), KTCI (SEQ ID NO: 5815), KELR (SEQ ID NO: 5816), KCQI (SEQ ID NO: 5817), KGVM (SEQ ID NO: 5818), KACD (SEQ ID NO: 5819), KNEL (SEQ ID NO: 5820), KAAE (SEQ ID NO: 5821), KG QN (SEQ ID NO: 5822), KNEF (SEQ ID NO: 5823), KTSI (SEQ ID NO: 5824), KAEH (SEQ ID NO: 5616), KCDQ (SEQ ID NO: 5825), KEIL (SEQ ID NO: 5826), KTER (SEQ ID NO: 5573), KNAI (SEQ ID NO: 5650), KTDK (SEQ ID NO: 5588), KTPD (SEQ ID NO: 5827), KTIH (SEQ ID NO: 5659), or KTEI (SEQ ID NO: 5591), (ii) an amino acid sequence containing any part of the amino acid sequence in (i), for example, any two or three amino acids thereof, for example, consecutive amino acids; (iii) an amino acid sequence that contains one, two, or three, but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to any of the amino acid sequences in (i); or (iv) An AAV capsid variant described in embodiment 234, which is or comprises an amino acid sequence that contains 1, 2, or 3, but not more than 4, different amino acids from any one of the amino acid sequences in (i).

[0254] 236.[N0]-[N1]-[N2]-[N3]-[N4] (i) any one of the amino acid sequences of SEQ ID NOs: 3606 to 3836; (ii) an amino acid sequence comprising any portion of the amino acid sequences in (i), e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 amino acids, e.g., consecutive amino acids, of any of them; (iii) an amino acid sequence that contains one, two, or three, but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to any of the amino acid sequences in (i); or (iv) An AAV capsid variant described in embodiment 234 or 235, which is or comprises an amino acid sequence that contains 1, 2, or 3, but not more than 4, different amino acids from any one of the amino acid sequences in (i).

[0255] 237. An AAV capsid variant according to any one of embodiments 234 to 236, wherein [N0]-[N1]-[N2]-[N3]-[N4] is or comprises KTINGHDSPHKSGQNQQT (sequence number 5828).

[0256] 238. An AAV capsid variant according to any one of embodiments 234 to 236, wherein [N0]-[N1]-[N2]-[N3]-[N4] is or comprises KAEIGHDSPHKSGQNQQT (sequence number 1754).

[0257] 239. An AAV capsid variant according to any one of embodiments 234 to 236, wherein [N0]-[N1]-[N2]-[N3]-[N4] is or comprises KTEKMSGSPHSKAQNQQT (sequence number 3241).

[0258] 240. The AAV capsid variant according to any one of embodiments 168 to 239, wherein [N1]-[N2]-[N3] is present in loop IV. 241. The AAV capsid variant according to any one of embodiments 198 to 202 or 234 to 240, wherein [N0] and [N4] are present in loop IV.

[0259] 242. An AAV capsid variant according to any one of embodiments 198 to 202 or 234 to 241, wherein [N0] is located immediately after position 448 relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138, 981, or 982.

[0260] 243. An AAV capsid variant according to any one of embodiments 198 to 202 or 234 to 242, wherein [N0] replaces positions 449 to 452 (e.g., K449, T450, I451, and N452) relative to a reference sequence numbered according to SEQ ID NO: 138, 981, or 982.

[0261] 244. An AAV capsid variant according to any one of embodiments 198 to 202 or 234 to 243, wherein [N0] is located immediately after position 448 and [N0] replaces positions 449 to 452 (e.g., K449, T450, I451, and N452) relative to a reference sequence numbered according to SEQ ID NO: 138, 981, or 982.

[0262] 245. An AAV capsid variant according to any one of embodiments 198 to 202 or 234 to 244, wherein [N0] corresponds to positions 449 to 452 (e.g., K449, T450, I451, and N452) of any one of SEQ ID NOs: 138, 981, or 982.

[0263] 246. An AAV capsid variant according to any one of embodiments 168 to 245, wherein [N1] is located immediately after position 452 relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138, 981 or 982.

[0264] 247. An AAV capsid variant according to any one of embodiments 168 to 246, wherein [N1] replaces positions 453 to 455 (e.g., G453, S454, and G455) relative to a reference sequence numbered according to SEQ ID NO: 138, 981, or 982.

[0265] 248. An AAV capsid variant according to any one of embodiments 168 to 246, wherein [N1] replaces position 453 (e.g., G453) relative to a reference sequence numbered according to SEQ ID NO: 138, 981, or 982.

[0266] 249. (i) position X1 of [N1] replaces position 453 (e.g., G453); (ii) position X2 of [N1] corresponds to position 454 (e.g., S454); (iii) position X3 of [N1] corresponds to position 455 (e.g., G455); The AAV capsid variant of any one of embodiments 168-177, 179-181, 183-185, 187-193, 195-200, 202, or 240-246, wherein (i), (ii), and (iii) are numbered according to SEQ ID NO: 138 or SEQ ID NO: 981.

[0267] 250. (i) position X1 of [N1] corresponds to position 453 (e.g., G453); (ii) position X2 of [N1] corresponds to position 454 (e.g., S454); (iii) position X3 of [N1] corresponds to position 455 (e.g., G455); An AAV capsid variant described in any one of embodiments 168 to 176, 178 to 201, or 240 to 246, wherein (i), (ii), and (iii) are numbered according to SEQ ID NO: 138 or SEQ ID NO: 981.

[0268] 251. (i) position X1 of [N1] corresponds to position 453 (e.g., G453); (ii) position X2 of [N1] replaces position 454 (e.g., S454); (iii) position X3 of [N1] replaces position 455 (e.g., G455); An AAV capsid variant described in any one of embodiments 203 to 248, wherein (i), (ii), and (iii) are numbered according to SEQ ID NO: 138 or SEQ ID NO: 982.

[0269] 252. The AAV capsid variant of any one of embodiments 203 to 248 or 251, wherein [N1] corresponds to positions 453 to 455 (e.g., G453, H454, D455) of SEQ ID NO: 982.

[0270] 253. The AAV capsid variant of any one of embodiments 168-176, 178-201, 240-247, or 250, wherein [N1] corresponds to positions 453-455 (e.g., G453, S454, G455) of SEQ ID NO: 138 or 981.

[0271] 254. An AAV capsid variant according to any one of embodiments 168 to 253, wherein [N2] is located immediately after position 455 relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138, 981 or 982.

[0272] 255. An AAV capsid variant according to any one of embodiments 168 to 254, wherein [N2] corresponds to positions 456 to 458 (e.g., S456, P457, and H458) of SEQ ID NO: 981 or 982.

[0273] 256. An AAV capsid variant according to any one of embodiments 168 to 254, wherein [N2] corresponds to positions 456 to 458 (e.g., S456, P457, and H458) of any one of SEQ ID NOs: 36 to 59.

[0274] 257. An AAV capsid variant according to any one of embodiments 168 to 256, wherein [N2] is located immediately after [N1]. 258. The AAV capsid variant according to any one of embodiments 168 to 202, 240 to 247, 249 to 257, wherein [N3] corresponds to positions 459 to 460 (e.g., S459, K460, A461) of SEQ ID NO: 981.

[0275] 259. The AAV capsid variant of any one of embodiments 168 to 202, 240 to 247, 249 to 257, wherein [N3] corresponds to positions 459 to 460 (e.g., S459, K460, A461) of SEQ ID NO: 36, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 57, or 59.

[0276] 260. An AAV capsid variant described in any one of embodiments 168 to 259, wherein [N2]-[N3] is located immediately after position 455 relative to a reference sequence numbered according to the amino acid sequence of any one of SEQ ID NOs: 138, 981, or 982.

[0277] 261. An AAV capsid variant according to any one of embodiments 168 to 259, wherein [N2]-[N3] is located immediately after position 455 relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 981.

[0278] 262. An AAV capsid variant according to any one of embodiments 168 to 261, wherein [N2]-[N3] correspond to positions 456 to 461 of SEQ ID NO: 981 (e.g., S456, P457, H458, S459, K460, A461).

[0279] 263. An AAV capsid variant according to any one of embodiments 168 to 262, wherein [N2]-[N3] correspond to positions 456 to 461 (e.g., S456, P457, H458, S459, K460, A461) of any one of SEQ ID NOs: 36, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 57, or 59.

[0280] 264. The AAV capsid variant of any one of embodiments 203 to 257 or 259 to 261, wherein [N3] corresponds to positions 459 to 460 (e.g., K459, S460, G461) of SEQ ID NO: 982.

[0281] 265. The AAV capsid variant according to any one of embodiments 203 to 257 or 259 to 261, wherein [N3] corresponds to positions 459 to 460 of SEQ ID NO: 37 (e.g., K459, S460, G461).

[0282] 266. An AAV capsid variant according to any one of embodiments 203 to 265, wherein [N2]-[N3] is located immediately after position 455 relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 982.

[0283] 267. The AAV capsid variant according to any one of embodiments 203 to 246, 248, 252, 255, 257, 260, 263 to 266, wherein [N3] replaces positions 454 and 455 (e.g., S454 and G455), numbered according to SEQ ID NO: 138.

[0284] 268. The AAV capsid variant according to any one of embodiments 203 to 246, 248, 252, 255, 257, 260, 263 to 267, wherein [N3] replaces positions 454 and 455 (e.g., S454 and G455), which are located immediately after [N2] and numbered according to SEQ ID NO: 138.

[0285] 269. An AAV capsid variant according to any one of embodiments 203 to 246, 248, 252, 255, 257, 260, 263 to 268, wherein [N3] replaces positions 454 and 455 (e.g., S454 and G455), located immediately after [N1]-[N2] and numbered according to SEQ ID NO: 138.

[0286] 270. An AAV capsid variant according to any one of embodiments 203 to 257, 260, 264 to 269, wherein [N2]-[N3] correspond to positions 456 to 461 of SEQ ID NO: 982 (e.g., S456, P457, H458, K459, S460, G461).

[0287] 271. An AAV capsid variant according to any one of embodiments 203 to 257, 260, 264 to 270, wherein [N2]-[N3] correspond to positions 456 to 461 of SEQ ID NO: 37 (e.g., S456, P457, H458, K459, S460, G461).

[0288] 272. The AAV capsid variant of any one of embodiments 191 to 202 or 228 to 271, wherein [N4] is located immediately after position 455 relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.

[0289] 273. The AAV capsid variant of any one of embodiments 191 to 202 or 228 to 272, wherein [N4] replaces positions 456 to 460 (e.g., Q456, N457, Q458, Q459, and T460) relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.

[0290] 274. The AAV capsid variant of any one of embodiments 191 to 202 or 228 to 273, wherein [N4] corresponds to positions 462 to 466 (e.g., Q462, N463, Q464, Q465, and T466) of SEQ ID NO: 981 or 982.

[0291] 275. The AAV capsid variant of any one of embodiments 191 to 202 or 228 to 273, wherein [N4] corresponds to positions 462 to 466 of any one of SEQ ID NOs: 36 to 59.

[0292] 276. The AAV capsid variant of any one of embodiments 191 to 202 or 228 to 274, wherein [N4] corresponds to positions 456 to 460 (e.g., Q456, N457, Q458, Q459, and T460) of SEQ ID NO: 138.

[0293] 277. The AAV capsid variant of any one of embodiments 191 to 202 or 228 to 276, wherein [N2]-[N3]-[N4] replace positions 456 to 460 (e.g., Q456, N457, Q458, Q459, and T460) relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.

[0294] 278. The AAV capsid variant of any one of embodiments 191 to 202 or 228 to 277, wherein [N2]-[N3]-[N4] is located immediately after position 455, and [N2]-[N3]-[N4] replaces positions 456 to 460 (e.g., Q456, N457, Q458, Q459, and T460) relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.

[0295] 279. The AAV capsid variant of any one of embodiments 191 to 202 or 228 to 278, wherein [N1]-[N2]-[N3]-[N4] replace positions 453 to 460 (e.g., G453, S454, G455, Q456, N457, Q458, Q459, and T460) relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.

[0296] 280. The AAV capsid variant of any one of embodiments 191 to 202 or 228 to 279, wherein [N1]-[N2]-[N3]-[N4] is located immediately after position 452, and [N1]-[N2]-[N3]-[N4] replaces positions 453 to 460 (e.g., G453, S454, G455, Q456, N457, Q458, Q459, and T460) relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.

[0297] 281. The AAV capsid variant of any one of embodiments 191-202, 240-247, 249, 250, 253-263, 266, or 272-280, wherein [N1]-[N2]-[N3]-[N4] correspond to positions 453 to 466 of SEQ ID NO: 981 (e.g., G453, S454, G455, S456, P457, H458, S459, K460, A461, Q462, N463, Q464, Q465, and T466).

[0298] 282. The AAV capsid variant of any one of embodiments 168-202, 240-247, 249, 250, 253-263, 266, or 272-280, wherein [N1]-[N2]-[N3] correspond to positions 453-461 of SEQ ID NO: 981 (e.g., G453, S454, G455, S456, P457, H458, S459, K460, A461).

[0299] 283. An AAV capsid variant according to any one of embodiments 228 to 257, 260, 261, 264 to 282, wherein [N1]-[N2]-[N3]-[N4] correspond to positions 453 to 466 of SEQ ID NO: 982 (e.g., G453, H454, D455, S456, P457, H458, K459, S460, G461, Q462, N463, Q464, Q465, T466).

[0300] 284. An AAV capsid variant according to any one of embodiments 203 to 257, 260, 261, 264 to 283, wherein [N1]-[N2]-[N3] correspond to positions 453 to 461 of SEQ ID NO: 982 (e.g., G453, H454, D455, S456, P457, H458, K459, S460, G461).

[0301] 285. An AAV capsid variant according to any one of embodiments 228 to 257, 260, 261, 264 to 282, wherein [N1]-[N2]-[N3]-[N4] correspond to positions 453 to 466 of any one of SEQ ID NOs: 36 to 59.

[0302] 286. The AAV capsid variant of any one of embodiments 198 to 202 or 234 to 286, wherein [N0]-[N1]-[N2]-[N3]-[N4] replace positions 449 to 460 (e.g., K449, T450, I451, N452, G453, S454, G455, Q456, N457, Q458, Q459, and T460) relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.

[0303] 287. The AAV capsid variant of any one of embodiments 198 to 202 or 234 to 286, wherein [N0]-[N1]-[N2]-[N3]-[N4] is located immediately after position 449, and [N0]-[N1]-[N2]-[N3]-[N4] replaces positions 449 to 460 (e.g., K449, T450, I451, N452, G453, S454, G455, Q456, N457, Q458, Q459, and T460) relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.

[0304] 288. The AAV capsid variant of any one of embodiments 198-202, 240-247, 249, 250, 253-263, 266, 272-281, 286, or 287, wherein [N0]-[N1]-[N2]-[N3]-[N4] correspond to positions 449-466 of SEQ ID NO: 981 (e.g., K449, T450, I451, N452, G453, S454, G455, S456, P457, H458, S459, K460, A461, Q462, N463, Q464, Q465, T466).

[0305] 289. The AAV capsid variant of any one of embodiments 234-257, 260, 261, 264-284, 286, or 287, wherein [N0]-[N1]-[N2]-[N3]-[N4] correspond to positions 449-466 of SEQ ID NO: 982 (e.g., K449, T450, I451, N452, G453, H454, D455, S456, P457, H458, K459, S460, G461, Q462, N463, Q464, Q465, T466).

[0306] 290. The AAV capsid variant of any one of embodiments 234-257, 260, 261, 264-284, 286, or 287, wherein [N0]-[N1]-[N2]-[N3]-[N4] correspond to positions 449-466 of any one of SEQ ID NOs: 36-59.

[0307] 291. An AAV capsid variant according to any one of embodiments 191 to 202 or 228 to 290, wherein [N4] is located immediately after position 461 relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 981 or 982.

[0308] 292. The AAV capsid variant of any one of embodiments 191 to 202 or 228 to 291, wherein [N4] replaces positions 462 to 466 (e.g., Q462, N463, Q464, Q465, and T466) relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 981 or 982.

[0309] 293. The AAV capsid variant of any one of embodiments 191 to 202 or 228 to 292, wherein [N2]-[N3]-[N4] replace positions 462 to 466 (e.g., Q462, N463, Q464, Q465, and T466) relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 981 or 982.

[0310] 294. The AAV capsid variant of any one of embodiments 191 to 202 or 228 to 293, wherein [N2]-[N3]-[N4] is located immediately after position 455, and [N2]-[N3]-[N4] replaces positions 462 to 466 (e.g., Q462, N463, Q464, Q465, and T466) relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 981 or 982.

[0311] 295. The AAV capsid variant of any one of embodiments 168 to 294, comprising, from N-terminus to C-terminus, [N2]-[N3]. 296. The AAV capsid variant of any one of embodiments 168-295, comprising, from N-terminus to C-terminus, [N1]-[N2]-[N3].

[0312] 297. The AAV capsid variant of any one of embodiments 168-296, comprising, from N-terminus to C-terminus, [N0]-[N1]-[N2]-[N3]. 298. The AAV capsid variant of any one of embodiments 168-297, comprising, from N-terminus to C-terminus, [N1]-[N2]-[N3]-[N4].

[0313] 299. The AAV capsid variant of any one of embodiments 168-298, comprising, from N-terminus to C-terminus, [N0]-[N1]-[N2]-[N3]-[N4]. 300. An AAV capsid variant comprising the formula [A]-[B] (SEQ ID NO: 4696), (i) [A] comprises GSGSPH (SEQ ID NO: 4695); (ii) [B] includes X1, X2, X3, X4, and X5; (a) position X1 is S, I, F, V, C, Y, W, R, P, L, Q, M, K, or G; (b) position X2 is K, M, R, F, V, C, P, Y, L, W, G, N, S, T, I, or A; (c) position X3 is A, Y, L, R, W, C, T, F, H, I, P, M, K, S, V, G, Q, or N; (d) position X4 is Q, M, F, K, H, R, C, W, P, V, L, G, S, Y, I, A, T, D, N, or E; (e) position X5 is A, N, Y, R, K, L, I, M, Q, S, C, W, F, T, G, V, or P; Optionally, the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of the above-mentioned amino acids in (a) to (e).

[0314] 301. (a) position X1 is S, L, R, V, or P; (b) position X2 is K, C, F, L, P, R, S, or V; (c) position X3 is A, C, F, I, K, L, M, P, R, T, W, or Y; (d) position X4 is Q, R, S, T, C, F, K, L, P, or Y; (e) position X5 is N, R, S, T, K, M, Q, or Y; Optionally, the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of the above-mentioned amino acids in (a) to (e).

[0315] 302. YY、SLY、SKP、SRF、SRM、SVK、SWA、SLW、SFR、SKK、SYA、SCS、SGA、SFP、SFF、SMC、 SKT、SGK、FYR、CRV、YGI、VNC、SLA、WSY、RWL、PSC、SSW、SKG、VPW、SGC、STT、PKR、SKC、WVP、SFW、RIK、SKM、LRW、LPT、SYM、LLC、RCC、LCV、SYL、QGC、MAF、SFQ、S LC、RPW、RPR、SCP、SVR、SLP、VYH、SYT、LVY、YRY、SWL、CPA、SPP、RWT、PRK、PFV 、SKS、WVA、SKV、CAL、SSC、SKN、LCT、STC、SKQ、KSG、SYY、SLT、SCQ、FPF、SVF、GR Y、AQA、AQN、YMN、AFY、LKR、RHR、AQK、WRL、CRN、TCN、FFI、AQY、WQN、YFM、ARQ、 HQN、IRR、YQN、YWN、AFS、FWN、AQC、MRN、KKN、APN、WKN、ARW、RPN、KVF、AFN、ACS 、RLW、SRN、CPN、ACN、FRQ、PFN、FGN、CQN、LFW、TRK、KRN、RQN、VQN、IQN、AQR、P FR、AWN、RSY、LQN、WLN、RRA、AQT、GCT、RYT、TPN、ARM、CFL、PQN、WSN、FKN、KQN、 APR、RYN、MIC、TQN、WKS、AAR、LTR、IRG、LVN、FQN、ACQ、WGL、ILR、QIN、ACI、AL R、AHA、CLN、AFV、AQF、RCN、MPC、KTS、PYN、AQS、TRN、LKN、AQM、CTN、PDN、RNY、A CR、CSV、ARI、LPK、SEQ、VRM、NSR、RKR、ARN、QRP、RVV、GQN、YSN、QSN、AKG、CTS、FEN、AKK、KAQ、MYM、KAF、KLK、KRH、KWR、RCR、FTC、KFF、VWQ、KYF、KAR、CHQ、PW Q、KIR、YYQ、LYW、KPK、RFW、RMR、VKK、WAP、LWK、FRP、KKV、YAF、KAC、KRL、CSR、R CP、GAC、KFR、FFG、MCQ、KLF、KTR、GKR、YRQ、RVQ、GIQ、NCQ、KPF、LAW、KRS、SYQ、An AAV capsid variant according to embodiment 300 or 301, comprising WLQ, KRR, KGC, KRY, GCQ, FTP, TTC, KRQ, KCF, VPQ, FWS, KFK, IKQ, KAP, FRY, KMI, RWQ, PTQ, KWK, YMR, KAA, LCQ, CCQ, CVQ, KLT, KLC, YLV, AFQ, KWG, KIL, FQI, KAL, KAH, LCL, PRQ, CPQ, VRY, VRC, KMP, KKT, LPY, YHQ, YTR, VYQ, RYQ, WLK, PAQ, MCT, PPD, WTQ, RKQ, KCS, FVQ, KLP, KSE, VAQ, LYQ, KVR, ALQ, SCT, KNS, KRK, CTQ, TCL, YAR, KQR, KRV, SGQ, YYS, LTC, CQS, KAK, KPQ, PFQ, KCT, or VFE.,

[0316] 303. [B] is SKAQ (SEQ ID NO: 5829), SMYM (SEQ ID NO: 5830), SKAF (SEQ ID NO: 5831), SKLK (SEQ ID NO: 5832), SKRH (SEQ ID NO: 5833), SKWR (SEQ ID NO: 5834), SRCR (SEQ ID NO: 5835), SFTC (SEQ ID NO: 5836), SKFF (SEQ ID NO: 5837), IVWQ (SEQ ID NO: 5838), SKYF (SEQ ID NO: 5839), SKAR (SEQ ID NO: 5840), SCHQ (SEQ ID NO: 5841), FPWQ (SEQ ID NO: 5842), SKIR (SEQ ID NO: 5843), VYYQ (SEQ ID NO: 5844), SLYW (SEQ ID NO: 5845), SKPK (SEQ ID NO: 5846), SRFW (SEQ ID NO: 5847), SRMR (SEQ ID NO: 5848), SVKK (SEQ ID NO: 5849), SWAP (SEQ ID NO: 5850), SLWK (SEQ ID NO: 5851), SFRP (SEQ ID NO: 5852), SKKV (SEQ ID NO: 5853), SYAF (SEQ ID NO: 5854), SKAC (SEQ ID NO: 5855), SKRL (SEQ ID NO: 5856), SCSR (SEQ ID NO: 5857), SRCP (SEQ ID NO: 5858), SGAC (SEQ ID NO: 5859), SKFR (SEQ ID NO: 5860), SFPF (SEQ ID NO: 5861). 861), SFFG (SEQ ID NO: 5862), SMCQ (SEQ ID NO: 5863), SKLF (SEQ ID NO: 5864), SKTR (SEQ ID NO: 5865), SGKR (SEQ ID NO: 5866), FYRQ (SEQ ID NO: 5867), CRVQ (SEQ ID NO: 5868), YGIQ (SEQ ID NO: 5869), VNCQ (SEQ ID NO: 5870), SKPF (SEQ ID NO: 5871), SLAW (SEQ ID NO: 5872), SKRS (SEQ ID NO: 5873), WSYQ (SEQ ID NO: 5874), RWLQ (SEQ ID NO: 5875), PSCQ (SEQ ID NO: 5876), SSWL (SEQ ID NO: 5877), SKRR ( SEQ ID NO: 5878), SKGC (SEQ ID NO: 5879), VPWQ (SEQ ID NO: 5880), SKRY (SEQ ID NO: 5881), SGCQ (SEQ ID NO: 5882), SFTP (SEQ ID NO: 5883), STTC (SEQ ID NO: 5884), PKRQ (SEQ ID NO: 5885), SKCF (SEQ ID NO: 5886), WVPQ (SEQ ID NO: 5887), SFWS (SEQ ID NO: 5888), SKFK (SEQ ID NO: 5889), RIKQ (SEQ ID NO: 5890), SKAP (SEQ ID NO: 5891), SFRY (SEQ ID NO: 5892), SKMI (SEQ ID NO: 5893), LRWQ (SEQ ID NO: 5894),LPTQ (SEQ ID NO: 5895), SKWK (SEQ ID NO: 5896), SYMR (SEQ ID NO: 5897), SKAA (SEQ ID NO: 5898), LLCQ (SEQ ID NO: 5899), RCCQ (SEQ ID NO: 5900), LCVQ (SEQ ID NO: 5901), SKLT (SEQ ID NO: 5902), SKLC (SEQ ID NO: 5903), SYLV (SEQ ID NO: 5904), QGCQ (SEQ ID NO: 5905), MAFQ (SEQ ID NO: 5906), SKWG (SEQ ID NO: 5907), SKIL (SEQ ID NO: 5908), SFQI (SEQ ID NO: 5909), SKAL (SEQ ID NO: 5910), SKAH (SEQ ID NO: 5911), No. 5911), SLCL (SEQ ID NO: 5912), RPWQ (SEQ ID NO: 5913), RPRQ (SEQ ID NO: 5914), SCPQ (SEQ ID NO: 5915), SVRY (SEQ ID NO: 5916), SVRC (SEQ ID NO: 5917), SKMP (SEQ ID NO: 5918), SKKT (SEQ ID NO: 5919), SLPY (SEQ ID NO: 5920), VYHQ (SEQ ID NO: 5921), SYTR (SEQ ID NO: 5922), LVYQ (SEQ ID NO: 5923), YRYQ (SEQ ID NO: 5924), SWLK (SEQ ID NO: 5925), CPAQ (SEQ ID NO: 5926), SMCT (SEQ ID NO: 5927), SPPD (SEQ ID NO: 5928), SKRN (SEQ ID NO: 5929), RWTQ (SEQ ID NO: 5930), PRKQ (SEQ ID NO: 5931), SKCS (SEQ ID NO: 5932), PFVQ (SEQ ID NO: 5933), SKLP (SEQ ID NO: 5934), SKSE (SEQ ID NO: 5935), WVAQ (SEQ ID NO: 5936), SLYQ (SEQ ID NO: 5937), SKVR (SEQ ID NO: 5938), CALQ (SEQ ID NO: 5939), SSCT (SEQ ID NO: 5940), SKNS (SEQ ID NO: 5941), SKRK (SEQ ID NO: 5942), LCTQ (SEQ ID NO: 5943), STCL (SEQ ID NO: 5944), No. 5944), SYAR (SEQ ID NO: 5945), SKQR (SEQ ID NO: 5946), SKRV (SEQ ID NO: 5947), KSGQ (SEQ ID NO: 5948), SYYS (SEQ ID NO: 5949), SLTC (SEQ ID NO: 5950), SCQS (SEQ ID NO: 5951), SKAK (SEQ ID NO: 5952), SKPQ (SEQ ID NO: 5953), FPFQ (SEQ ID NO: 5954), SKCT (SEQ ID NO: 5955), SVFE (SEQ ID NO: 5956), GRYQ (SEQ ID NO: 5957), KAQA (SEQ ID NO: 5958), KAQN (SEQ ID NO: 5959), MYMN (SEQ ID NO: 5960),KAFY (SEQ ID NO: 5961), KLKR (SEQ ID NO: 5962), KRHR (SEQ ID NO: 5963), KAQK (SEQ ID NO: 5964), KWRL (SEQ ID NO: 5965), RCRN (SEQ ID NO: 5966), FTCN (SEQ ID NO: 5967), KFFI (SEQ ID NO: 5968), KAQY (SEQ ID NO: 5969), VWQN (SEQ ID NO: 5970), KYFM (SEQ ID NO: 5971), KARQ (SEQ ID NO: 5972), CHQN (SEQ ID NO: 5973), PWQN (SEQ ID NO: 5974), KIRR (SEQ ID NO: 5975), YYQN (SEQ ID NO: 5976), LYWN (SEQ ID NO: 5977), No. 5977), KPKR (SEQ ID NO: 5978), KAFS (SEQ ID NO: 5979), RFWN (SEQ ID NO: 5980), KAQC (SEQ ID NO: 5981), RMRN (SEQ ID NO: 5982), VKKN (SEQ ID NO: 5983), WAPN (SEQ ID NO: 5984), LWKN (SEQ ID NO: 5985), KARW (SEQ ID NO: 5986), FRPN (SEQ ID NO: 5987), KKVF (SEQ ID NO: 5988), YAFN (SEQ ID NO: 5989), KACS (SEQ ID NO: 5990), KRLW (SEQ ID NO: 5991), CSRN (SEQ ID NO: 5992), RCPN (SEQ ID NO: 5993), GACN (SEQ ID NO: 5994), KFRQ (SEQ ID NO: 5995), FPFN (SEQ ID NO: 5996), FFGN (SEQ ID NO: 5997), MCQN (SEQ ID NO: 5998), KLFW (SEQ ID NO: 5999), KTRK (SEQ ID NO: 6000), GKRN (SEQ ID NO: 6001), YRQN (SEQ ID NO: 6002), RVQN (SEQ ID NO: 6003), GIQN (SEQ ID NO: 6004), KAQR (SEQ ID NO: 6005), NCQN (SEQ ID NO: 6006), KPFR (SEQ ID NO: 6007), LAWN (SEQ ID NO: 6008), KRSY (SEQ ID NO: 6009), SYQN (SEQ ID NO: 6010), No. 6010), WLQN (SEQ ID NO: 6011), SCQN (SEQ ID NO: 6012), SWLN (SEQ ID NO: 6013), KRRA (SEQ ID NO: 6014), KAQT (SEQ ID NO: 6015), KGCT (SEQ ID NO: 6016), KRYT (SEQ ID NO: 6017), GCQN (SEQ ID NO: 6018), FTPN (SEQ ID NO: 6019), TTCN (SEQ ID NO: 6020), KARM (SEQ ID NO: 6021), KRQN (SEQ ID NO: 6022), KCFL (SEQ ID NO: 6023), VPQN (SEQ ID NO: 6024), FWSN (SEQ ID NO: 6025), KFKN (SEQ ID NO: 6026),IKQN (SEQ ID NO: 6027), KAPR (SEQ ID NO: 6028), FRYN (SEQ ID NO: 6029), KMIC (SEQ ID NO: 6030), RWQN (SEQ ID NO: 6031), PTQN (SEQ ID NO: 6032), KWKS (SEQ ID NO: 6033), YMRN (SEQ ID NO: 6034), KAAR (SEQ ID NO: 6035), LCQN (SEQ ID NO: 6036), CCQN (SEQ ID NO: 6037), CVQN (SEQ ID NO: 6038), KLTR (SEQ ID NO: 6039), KLCT (SEQ ID NO: 6040), KIRG (SEQ ID NO: 6041), YLVN (SEQ ID NO: 6042), AFQN (SEQ ID NO: 6043), No. 6043), KACQ (SEQ ID NO: 6044), KWGL (SEQ ID NO: 6045), KILR (SEQ ID NO: 6046), FQIN (SEQ ID NO: 6047), KACI (SEQ ID NO: 6048), KALR (SEQ ID NO: 6049), KAHA (SEQ ID NO: 6050), LCLN (SEQ ID NO: 6051), KAFV (SEQ ID NO: 6052), PRQN (SEQ ID NO: 6053), CPQN (SEQ ID NO: 6054), KAQF (SEQ ID NO: 6055), VRYN (SEQ ID NO: 6056), VRCN (SEQ ID NO: 6057), KMPC (SEQ ID NO: 6058), KKTS (SEQ ID NO: 6059), LPYN (SEQ ID NO: 6060), YHQN (SEQ ID NO: 6061), KAQS (SEQ ID NO: 6062), YTRN (SEQ ID NO: 6063), VYQN (SEQ ID NO: 6064), RYQN (SEQ ID NO: 6065), WLKN (SEQ ID NO: 6066), KAQM (SEQ ID NO: 6067), PAQN (SEQ ID NO: 6068), MCTN (SEQ ID NO: 6069), PPDN (SEQ ID NO: 6070), KRNY (SEQ ID NO: 6071), WTQN (SEQ ID NO: 6072), KACR (SEQ ID NO: 6073), RKQN (SEQ ID NO: 6074), KCSV (SEQ ID NO: 6075), KARI (SEQ ID NO: 6076), KACR (SEQ ID NO: 6077), RKQN (SEQ ID NO: 6078), KCSV (SEQ ID NO: 6079), KARI (SEQ ID NO: 6080), KACR (SEQ ID NO: 6081), RKQN (SEQ ID NO: 6082), RKCR (SEQ ID NO: 6083), RKCR (SEQ ID NO: 6084), RKCR (SEQ ID NO: 6085), RKCR (SEQ ID NO: 6086), RKCR (SEQ ID NO: 6087), RKCR (SEQ ID NO: 6088), RKCR (SEQ ID NO: 6089), RKCR (SEQ ID NO: 6090), RKCR (SEQ ID NO: 6091), RKCR (SEQ ID NO: 6092), RKCR (SEQ ID No. 6076), FVQN (SEQ ID NO: 6077), KLPK (SEQ ID NO: 6078), KSEQ (SEQ ID NO: 6079), VAQN (SEQ ID NO: 6080), LYQN (SEQ ID NO: 6081), KVRM (SEQ ID NO: 6082), ALQN (SEQ ID NO: 6083), SCTN (SEQ ID NO: 6084), KNSR (SEQ ID NO: 6085), KRKR (SEQ ID NO: 6086), CTQN (SEQ ID NO: 6087), TCLN (SEQ ID NO: 6088), YARN (SEQ ID NO: 6089), KQRP (SEQ ID NO: 6090), KRVV (SEQ ID NO: 6091), SGQN (SEQ ID NO: 6092),The AAV capsid variant of any one of embodiments 300 to 302, comprising YYSN (SEQ ID NO: 6093), LTCN (SEQ ID NO: 6094), CQSN (SEQ ID NO: 6095), KAKG (SEQ ID NO: 6096), KPQN (SEQ ID NO: 6097), PFQN (SEQ ID NO: 6098), KCTS (SEQ ID NO: 6099), VFEN (SEQ ID NO: 6100), or KAKK (SEQ ID NO: 6101).

[0317] 304. [B] is (i) SKAQA (SEQ ID NO: 6102), SKAQN (SEQ ID NO: 6103), SMYMN (SEQ ID NO: 6104), SKAFY (SEQ ID NO: 6105), SKLKR (SEQ ID NO: 6106), SKRHR (SEQ ID NO: 6107), SKAQK (SEQ ID NO: 6108), SKWRL (SEQ ID NO: 6109), SRCRN (SEQ ID NO: 6110), SFTCN (SEQ ID NO: 6111), SKFFI (SEQ ID NO: 6112), SKAQY (SEQ ID NO: 6113), IVWQN (SEQ ID NO: 6114), SKYFM (SEQ ID NO: 6115), SKARQ (SEQ ID NO: 6116), SCHQN (SEQ ID NO: 6117), FPWQN (SEQ ID NO: 6118), SKIRR (SEQ ID NO: 6119), VYYQN (SEQ ID NO: 6120), SLYWN (SEQ ID NO: 6121), SKPKR (SEQ ID NO: 6122), SKAFS (SEQ ID NO: 6123), SRFWN (SEQ ID NO: 6124), SKAQC (SEQ ID NO: 6125), SRMRN (SEQ ID NO: 6126), SVKKN (SEQ ID NO: 6127), SWAPN (SEQ ID NO: 6128), SLWKN (SEQ ID NO: 6129), SKARW (SEQ ID NO: 6130), SFRPN (SEQ ID NO: 6131), SKKVF (SEQ ID NO: 6132) ), SYAFN (SEQ ID NO: 6133), SKACS (SEQ ID NO: 6134), SKRLW (SEQ ID NO: 6135), SCSRN (SEQ ID NO: 6136), SRCPN (SEQ ID NO: 6137), SGACN (SEQ ID NO: 6138), SKFRQ (SEQ ID NO: 6139), SFPFN (SEQ ID NO: 6140), SFFGN (SEQ ID NO: 6141), SMCQN (SEQ ID NO: 6142), SKLFW (SEQ ID NO: 6143), SKTRK (SEQ ID NO: 6144), SGKRN (SEQ ID NO: 6145), FYRQN (SEQ ID NO: 6146), CRVQN (SEQ ID NO: 6147), YGIQN (SEQ ID NO: 6148), Sequence number 6148), SKAQR (SEQ ID NO: 6149), VNCQN (SEQ ID NO: 6150), SKPFR (SEQ ID NO: 6151), SLAWN (SEQ ID NO: 6152), SKRSY (SEQ ID NO: 6153), WSYQN (SEQ ID NO: 6154), RWLQN (SEQ ID NO: 6155), PSCQN (SEQ ID NO: 6156), SSWLN (SEQ ID NO: 6157), SKRRA (SEQ ID NO: 6158), SKAQT (SEQ ID NO: 6159), SKGCT (SEQ ID NO: 6160), VPWQN (SEQ ID NO: 6161), SKRYT (SEQ ID NO: 6162), SGCQN (SEQ ID NO: 6163),SFTPN (SEQ ID NO: 6164), STTCN (SEQ ID NO: 6165), SKARM (SEQ ID NO: 6166), PKRQN (SEQ ID NO: 6167), SKCFL (SEQ ID NO: 6168), WVPQN (SEQ ID NO: 6169), SFWSN (SEQ ID NO: 6170), SKFKN (SEQ ID NO: 6171), RIKQN (SEQ ID NO: 6172), SKAPR (SEQ ID NO: 6173), SFRYN (SEQ ID NO: 6174), SKMIC (SEQ ID NO: 6175), LRWQN (SEQ ID NO: 6176), LPTQN (SEQ ID NO: 6177), SKWKS (SEQ ID NO: 6178), SYMRN (SEQ ID NO: 6179), No. 6179), SKAAR (SEQ ID NO: 6180), LLCQN (SEQ ID NO: 6181), RCCQN (SEQ ID NO: 6182), LCVQN (SEQ ID NO: 6183), SKLTR (SEQ ID NO: 6184), SKLCT (SEQ ID NO: 6185), SKIRG (SEQ ID NO: 6186), SYLVN (SEQ ID NO: 6187), QGCQN (SEQ ID NO: 6188), MAFQN (SEQ ID NO: 6189), SKACQ (SEQ ID NO: 6190), SKWGL (SEQ ID NO: 6191), SKILR (SEQ ID NO: 6192), SFQIN (SEQ ID NO: 6193), SKACI (SEQ ID NO: 6194), SKALR (SEQ ID NO: 6195), SKAHA (SEQ ID NO: 6196), SLCLN (SEQ ID NO: 6197), SKAFV (SEQ ID NO: 6198), RPWQN (SEQ ID NO: 6199), RPRQN (SEQ ID NO: 6200), SCPQN (SEQ ID NO: 6201), SKAQF (SEQ ID NO: 6202), SVRYN (SEQ ID NO: 6203), SVRCN (SEQ ID NO: 6204), SKMPC (SEQ ID NO: 6205), SKKTS (SEQ ID NO: 6206), SLPYN (SEQ ID NO: 6207), VYHQN (SEQ ID NO: 6208), SKAQS (SEQ ID NO: 6209), SYTRN (SEQ ID NO: 6210), No. 6210), LVYQN (SEQ ID NO: 6211), YRYQN (SEQ ID NO: 6212), SWLKN (SEQ ID NO: 6213), SKAQM (SEQ ID NO: 6214), CPAQN (SEQ ID NO: 6215), SMCTN (SEQ ID NO: 6216), SPPDN (SEQ ID NO: 6217), SKRNY (SEQ ID NO: 6218), RWTQN (SEQ ID NO: 6219), SKACR (SEQ ID NO: 6220), PRKQN (SEQ ID NO: 6221), SKCSV (SEQ ID NO: 6222), SKARI (SEQ ID NO: 6223), PFVQN (SEQ ID NO: 6224), SKLPK (SEQ ID NO: 6225),SKSEQ (SEQ ID NO: 6226), WVAQN (SEQ ID NO: 6227), SLYQN (SEQ ID NO: 6228), SKVRM (SEQ ID NO: 6229), CALQN (SEQ ID NO: 6230), SSCTN (SEQ ID NO: 6231), SKNSR (SEQ ID NO: 6232), SKRKR (SEQ ID NO: 6233), LCTQN (SEQ ID NO: 6234), STCLN (SEQ ID NO: 6235), SYARN (SEQ ID NO: 6236), SKQRP (SEQ ID NO: 6237), SK RVV (SEQ ID NO: 6238), KSGQN (SEQ ID NO: 6239), SYYSN (SEQ ID NO: 6240), SLTCN (SEQ ID NO: 6241), SCQSN (SEQ ID NO: 6242), SKAKG (SEQ ID NO: 6243), SKPQN (SEQ ID NO: 6244), FPFQN (SEQ ID NO: 6245), SKCTS (SEQ ID NO: 6246), SVFEN (SEQ ID NO: 6247), SKAKK (SEQ ID NO: 6248), or GRYQN (SEQ ID NO: 6249), (ii) an amino acid sequence comprising a portion of any of the amino acid sequences in (i), e.g., 2, 3, or 4 amino acids, e.g., consecutive amino acids, of any of them; (iii) an amino acid sequence that contains one, two, or three, but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to any of the amino acid sequences in (i); or (iv) An AAV capsid variant described in any one of embodiments 300 to 303, which is or comprises an amino acid sequence that contains 1, 2, or 3, but not more than 4, different amino acids from any one of the amino acid sequences in (i).

[0318] 305. [A]-[B] (i) GSGSPHSKAQA (SEQ ID NO: 6250), GSGSPHSKAQN (SEQ ID NO: 6251), GSGSPHSMYMN (SEQ ID NO: 6252), GSGSPHSKAFY (SEQ ID NO: 6253), GSGSPHSKLKR (SEQ ID NO: 6254), GSGSPHSKRHR (SEQ ID NO: 6255), GSGSPHSKAQK (SEQ ID NO: 6256), GSGSPHSKWRL (SEQ ID NO: 6257), GSGSPHSRCRN (SEQ ID NO: 6258), GSGSPHSFTCN (SEQ ID NO: 6259), GSGSPHSKFFI (SEQ ID NO: 6260), GSG SPHSKAQY (SEQ ID NO: 6261), GSGSPHIVWQN (SEQ ID NO: 6262), GSGSPHSKYFM (SEQ ID NO: 6263), GSGSPHSKARQ (SEQ ID NO: 6264), GSGSPHSCHQN (SEQ ID NO: 6265), GSGSPHFPWQN (SEQ ID NO: 6266), GSGSPHSKIRR (SEQ ID NO: 6267), GSGSPHVYYQN (SEQ ID NO: 6268), GSGSPHSLYWN (SEQ ID NO: 6269), GSGSPHSKPKR (SEQ ID NO: 6270), GSGSPHSKAFS (SEQ ID NO: 6271), GSGSPHSRF WN (SEQ ID NO: 6272), GSGSPHSKAQC (SEQ ID NO: 6273), GSGSPHSRMRN (SEQ ID NO: 6274), GSGSPHSVKKN (SEQ ID NO: 6275), GSGSPHSWAPN (SEQ ID NO: 6276), GSGSPHSLWKN (SEQ ID NO: 6277), GSGSPHSKARW (SEQ ID NO: 6278), GSGSPHSFRPN (SEQ ID NO: 6279), GSGSPHSKKVF (SEQ ID NO: 6280), GSGSPHSYAFN (SEQ ID NO: 6281), GSGSPHSKACS (SEQ ID NO: 6282), GSGSPHSKRLW (SEQ ID NO: No. 6283), GSGSPHSCSRN (SEQ ID NO: 6284), GSGSPHSRCPN (SEQ ID NO: 6285), GSGSPHSGACN (SEQ ID NO: 6286), GSGSPHSKFRQ (SEQ ID NO: 6287), GSGSPHSFPFN (SEQ ID NO: 6288), GSGSPHSFFGN (SEQ ID NO: 6289), GSGSPHSMCQN (SEQ ID NO: 6290), GSGSPHSKLFW (SEQ ID NO: 6291), GSGSPHSKTRK (SEQ ID NO: 6292), GSGSPHSGKRN (SEQ ID NO: 6293), GSGSPHFYRQN (SEQ ID NO: 6294),GSGSPHCRVQN (SEQ ID NO: 6295), GSGSPHYGIQN (SEQ ID NO: 6296), GSGSPHSKAQR (SEQ ID NO: 6297), GSGSPHVNCQN (SEQ ID NO: 6298), GSGSPHSKPFR (SEQ ID NO: 6299), GSGSPHSLAWN (SEQ ID NO: 6300), GSGSPHSKRSY (SEQ ID NO: 6301), GSGSPHWSYQN (SEQ ID NO: 6302), GSGSPHRWLQN (SEQ ID NO: 6303), GSGSPHPSCQN (SEQ ID NO: 6304), GSGSPHSSWLN (SEQ ID NO: 6305), GSGSP HSKRRA (SEQ ID NO: 6306), GSGSPHSKAQT (SEQ ID NO: 6307), GSGSPHSKGCT (SEQ ID NO: 6308), GSGSPHVPWQN (SEQ ID NO: 6309), GSGSPHSKRYT (SEQ ID NO: 6310), GSGSPHSGCQN (SEQ ID NO: 6311), GSGSPHSFTPN (SEQ ID NO: 6312), GSGSPHSTTCN (SEQ ID NO: 6313), GSGSPHSKARM (SEQ ID NO: 6314), GSGSPHPKRQN (SEQ ID NO: 6315), GSGSPHSKCFL (SEQ ID NO: 6316), GSGSPHWVPQN (SEQ ID NO: 6317), GSGSPHSFWSN (SEQ ID NO: 6318), GSGSPHSKFKN (SEQ ID NO: 6319), GSGSPHRIKQN (SEQ ID NO: 6320), GSGSPHSKAPR (SEQ ID NO: 6321), GSGSPHSFRYN (SEQ ID NO: 6322), GSGSPHSKMIC (SEQ ID NO: 6323), GSGSPHLRWQN (SEQ ID NO: 6324), GSGSPHLPTQN (SEQ ID NO: 6325), GSGSPHSKWKS (SEQ ID NO: 6326), GSGSPHSYMRN (SEQ ID NO: 6327), GSGSPHSKAAR (SEQ ID NO: 6328), GSGSPHLLCQN (SEQ ID NO: 6329), GSGSPHRCCQN (SEQ ID NO: 6330), GSGSPHLCVQN (SEQ ID NO: 6331), GSGSPHSKLTR (SEQ ID NO: 6332), GSGSPHSKLCT (SEQ ID NO: 6333), GSGSPHSKIRG (SEQ ID NO: 6334), GSGSPHSYLVN (SEQ ID NO: 6335), GSGSPHQGCQN (SEQ ID NO: 6336), GSGSPHMAFQN (SEQ ID NO: 6337), GSGSPHSKACQ (SEQ ID NO: 6338), GSGSPHSKWGL (SEQ ID NO: 6339),GSGSPHSKILR (SEQ ID NO: 6340), GSGSPHSFQIN (SEQ ID NO: 6341), GSGSPHSKACI (SEQ ID NO: 6342), GSGSPHSKALR (SEQ ID NO: 6343), GSGSPHSKAHA (SEQ ID NO: 6344), GSGSPHSLCLN (SEQ ID NO: 6345), GSGSPHSKAFV (SEQ ID NO: 6346), GSGSPHRPWQN (SEQ ID NO: 6347), GSGSPHRPRQN (SEQ ID NO: 6348), GSGSPHSCPQN (SEQ ID NO: 6349), GSGSPHSKAQF (SEQ ID NO: 6350), GSGSP HSVRYN (SEQ ID NO: 6351), GSGSPHSVRCN (SEQ ID NO: 6352), GSGSPHSKMPC (SEQ ID NO: 6353), GSGSPHSKKTS (SEQ ID NO: 6354), GSGSPHSLPYN (SEQ ID NO: 6355), GSGSPHVYHQN (SEQ ID NO: 6356), GSGSPHSKAQS (SEQ ID NO: 6357), GSGSPHSYTRN (SEQ ID NO: 6358), GSGSPHLVYQN (SEQ ID NO: 6359), GSGSPHYRYQN (SEQ ID NO: 6360), GSGSPHSWLKN (SEQ ID NO: 6361), GSGSPHSKAQM (SEQ ID NO: 6362), GSGSPHCPAQN (SEQ ID NO: 6363), GSGSPHSMCTN (SEQ ID NO: 6364), GSGSPHSPPDN (SEQ ID NO: 6365), GSGSPHSKRNY (SEQ ID NO: 6366), GSGSPHRWTQN (SEQ ID NO: 6367), GSGSPHSKACR (SEQ ID NO: 6368), GSGSPHPRKQN (SEQ ID NO: 6369), GSGSPHSKCSV (SEQ ID NO: 6370), GSGSPHSKARI (SEQ ID NO: 6371), GSGSPHPFVQN (SEQ ID NO: 6372), GSGSPHSKLPK (SEQ ID NO: 6373), GSGSPHSKSEQ (SEQ ID NO: 6374), GSGSPHWVAQN (SEQ ID NO: 6375), GSGSPHSLYQN (SEQ ID NO: 6376), GSGSPHSKVRM (SEQ ID NO: 6377), GSGSPHCALQN (SEQ ID NO: 6378), GSGSPHSSCTN (SEQ ID NO: 6379), GSGSPHSKNSR (SEQ ID NO: 6380), GSGSPHSKRKR (SEQ ID NO: 6381), GSGSPHLCTQN (SEQ ID NO: 6382), GSGSPHSTCLN (SEQ ID NO: 6383), GSGSPHSYARN (SEQ ID NO: 6384),GSGSPHSKQRP (SEQ ID NO: 6385), GSGSPHSKRVV (SEQ ID NO: 6386), GSGSPHKSGQN (SEQ ID NO: 6387), GSGSPHSYYSN (SEQ ID NO: 6388), GSGSPHSLTCN (SEQ ID NO: 6389), GSGSPHSCQSN (SEQ ID NO: 6390), GSGSPHSKAKG (SEQ ID NO: 6391), GSGSPHSKPQN (SEQ ID NO: 6392), GSGSPHFPFQN (SEQ ID NO: 6393), GSGSPHSKCTS (SEQ ID NO: 6394), GSGSPHSVFEN (SEQ ID NO: 6395), GSGSPHSKAKK (SEQ ID NO: 6396), or GSGSPHGRYQN (SEQ ID NO: 6397), (ii) an amino acid sequence comprising any part of the amino acid sequences in (i), e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids, e.g., consecutive amino acids, of any of them; (iii) an amino acid sequence that contains one, two, or three, but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to any of the amino acid sequences in (i); or (iv) An AAV capsid variant described in any one of embodiments 300 to 304, which is or comprises an amino acid sequence that contains 1, 2, or 3, but not more than 4, different amino acids from any one of the amino acid sequences in (i).

[0319] 306. An AAV capsid according to any one of embodiments 300 to 305, wherein [A]-[B] does not comprise the amino acid sequence GSGSPHSKAQN (SEQ ID NO: 6251). 307. The AAV capsid variant of any one of embodiments 300 to 306, comprising one, two, or all of the following: an amino acid other than Q at position 458 (e.g., R, C, S, W, L, F, Y, H, I, V, A, or P), an amino acid other than Q at position 459 (e.g., K, I, R, L, or S), and / or an amino acid other than T at position 460 (e.g., R), numbered relative to SEQ ID NO: 138.

[0320] 308. (i) amino acid R at position 458; (ii) amino acid W at position 458; (iii) amino acid Y at position 458; (iv) amino acid F at position 458; (v) amino acid S at position 458; (vi) amino acid C at position 458; (vii) amino acid I at position 458; (viii) amino acid L at position 458; (ix) amino acid P at position 458; (x) amino acid I at position 459; (xi) amino acid H at position 458, or (xii) containing the amino acid V at position 458; An AAV capsid variant described in any one of embodiments 300 to 307, wherein (i) to (xii) are numbered according to SEQ ID NO: 138.

[0321] 309. (i) the amino acid R at position 458 and the amino acid K at position 459; (ii) amino acid C at position 458 and amino acid I at position 459; (iii) the amino acid S at position 458 and the amino acid R at position 459′; (iv) amino acid L at position 458 and amino acid K at position 459; (v) amino acid F at position 458 and amino acid K at position 459; (vi) amino acid C at position 458 and amino acid R at position 459; (vii) amino acid H at position 458 and amino acid R at position 459; (viii) amino acid I at position 458 and amino acid L at position 459; (ix) amino acid V at position 458 and amino acid R at position 459; (x) amino acid A at position 458 and amino acid K at position 459; (xi) amino acid I at position 458 and amino acid K at position 459; (xii) the amino acid C at position 458 and the amino acid S at position 459, or (xiii) containing an amino acid C at position 458 and an amino acid L at position 459; An AAV capsid variant described in any one of embodiments 300 to 307, wherein (i) to (xiii) are numbered according to SEQ ID NO: 138.

[0322] 310. The AAV capsid variant of any one of embodiments 300 to 307, comprising an amino acid F at position 458, an amino acid K at position 459, and an amino acid R at position 460, numbered relative to SEQ ID NO: 138.

[0323] 311. The AAV capsid variant of any one of embodiments 300 to 310, comprising one, two, or all of the following: an amino acid other than T at position 450 (e.g., Y, P, W, R, K, S, or F); an amino acid other than I at position 451 (e.g., R, S, Y, L, V, H, P, A, or F); and / or an amino acid other than N at position 452 (e.g., V, W, A, T, F, Y, L, R, H, S, or M), numbered relative to SEQ ID NO: 138.

[0324] 312. The AAV capsid variant of any one of embodiments 300 to 311, comprising an amino acid V at position 452, numbered according to SEQ ID NO: 138. 313. The AAV capsid variant of any one of embodiments 300 to 312, comprising an amino acid Y at position 450 and an amino acid V at position 452, numbered according to SEQ ID NO: 138.

[0325] 314. The AAV capsid variant of any one of embodiments 300 to 312, comprising an amino acid R at position 450 and an amino acid Y at position 451, numbered according to SEQ ID NO: 138.

[0326] 315. (i) the amino acid P at position 450, the amino acid R at position 451, and the amino acid W at position 452; (ii) amino acid Y at position 450, amino acid S at position 451, and amino acid A at position 452; (iii) amino acid Y at position 450, amino acid Y at position 451, and amino acid T at position 452; (iv) the amino acid P at position 450, the amino acid R at position 451, and the amino acid F at position 452; (v) amino acid W at position 450, amino acid L at position 451, and amino acid T at position 452; (vi) amino acid R at position 450, amino acid S at position 451, and amino acid Y at position 452; (vii) amino acid Y at position 450, amino acid V at position 451, and amino acid F at position 452; (viii) an amino acid K at position 450, an amino acid H at position 451, and an amino acid L at position 452; (ix) the amino acid P at position 450, the amino acid P at position 451, and the amino acid L at position 452; (x) amino acid P at position 450, amino acid A at position 451, and amino acid R at position 452; (xi) an amino acid S at position 450, an amino acid R at position 451, and an amino acid R at position 452; (xii) amino acid F at position 450, amino acid F at position 451, and amino acid H at position 452; (xiii) an amino acid R at position 450, an amino acid F at position 451, and an amino acid S at position 452; (xiv) amino acid Y at position 450, amino acid S at position 451, and amino acid M at position 452, or (xv) containing the amino acid P at position 450, the amino acid F at position 451, and the amino acid L at position 452; An AAV capsid variant described in any one of embodiments 300 to 311, wherein (i) to (xv) are numbered according to SEQ ID NO: 138.

[0327] 316. (i) an amino acid sequence set forth in any one of SEQ ID NOs: 3849 to 3982, 2984 to 4010, and 4681 to 4693; (ii) an amino acid sequence comprising any portion of the amino acid sequences in (i), e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 amino acids, e.g., consecutive amino acids, of any of them; (iii) an amino acid sequence that contains one, two, or three, but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to any of the amino acid sequences in (i); or (iv) An AAV capsid variant described in any one of embodiments 300 to 315, comprising an amino acid sequence that contains 1, 2, or 3, but not more than 4, different amino acids from any one of the amino acid sequences in (i).

[0328] 317. The AAV capsid variant of any one of embodiments 300 to 316, which does not comprise the amino acid sequence GSGSPHSKAQNQQ (SEQ ID NO: 1801) or GSGSPHSKAQNQQT (SEQ ID NO: 200).

[0329] 318. The AAV capsid variant according to any one of embodiments 300 to 317, wherein [A]-[B] is present in loop IV. 319. An AAV capsid variant according to any one of embodiments 300 to 318, wherein [A] is located immediately after position 452 relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 981.

[0330] 320. An AAV capsid variant according to any one of embodiments 300 to 319, wherein [A] replaces positions 453 to 455 (e.g., G453, S454, G455) relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 981.

[0331] 321. An AAV capsid variant according to any one of embodiments 300 to 320, wherein [A] is present immediately after position 452 and [A] replaces positions 453 to 455 (e.g., G453, S454, G455) relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 981.

[0332] 322. An AAV capsid variant according to any one of embodiments 300 to 321, wherein [B] is located immediately after [A]. 323. An AAV capsid variant according to any one of embodiments 300 to 322, wherein [B] replaces positions 456 and 457 (e.g., Q456, N457) numbered relative to SEQ ID NO: 138.

[0333] 324. An AAV capsid variant according to any one of embodiments 300 to 323, wherein [A]-[B] replaces positions 453 to 457 (e.g., G453, S454, G455, Q456, N457) relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.

[0334] 325. An AAV capsid variant according to any one of embodiments 300 to 324, wherein [A]-[B] is located immediately after position 452 and replaces positions 453 to 457 (e.g., G453, S454, G455, Q456, N457) relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.

[0335] 326. The AAV capsid variant of any one of embodiments 300 to 325, comprising, from N-terminus to C-terminus, [A][B]. 327. The AAV capsid variant of any one of the preceding embodiments, comprising at least 1, 2, 3, or 4 (e.g., 1-4 to 1-5) charged amino acid residues (e.g., acidic and / or basic amino acid residues) relative to SEQ ID NO: 138, and present N-terminally to the amino acid sequence of SPH (e.g., within 1, 2, 3, 4, 5, or 6 amino acids (e.g., within positions 450-455 numbered according to SEQ ID NO: 138) of the start of the SPH amino acid sequence), and optionally the amino acid sequence of SPH is present at positions 456-458 numbered according to any one of SEQ ID NOs: 36-59, 981, or 982.

[0336] 328. The AAV capsid variant of embodiment 327, wherein the amino acid sequence of SPH is located at positions 456 to 458 numbered according to any one of SEQ ID NOs: 36 to 59, 981, or 982.

[0337] 329. The AAV capsid variant of embodiment 327 or 328, comprising fewer than 4, fewer than 3, fewer than 2 (e.g., 2 or 1) charged amino acid residues (e.g., acidic and / or basic amino acid residues) relative to SEQ ID NO: 138.

[0338] 330. The AAV capsid variant of any one of embodiments 327 to 329, comprising one charged amino acid residue (e.g., an acidic or basic amino acid residue) relative to SEQ ID NO: 138, optionally at any one of positions 450 to 455 numbered relative to SEQ ID NO: 138.

[0339] 331. The AAV capsid variant of any one of embodiments 327-330, wherein the charged amino acid residue is an acidic amino acid (e.g., D or E). 332. The AAV capsid variant of any one of embodiments 327-331, wherein the charged amino acid residue is a negatively charged amino acid (e.g., D or E).

[0340] 333. The AAV capsid variant of any one of embodiments 327-332, wherein the charged amino acid residue is D. 334. The AAV capsid variant of any one of embodiments 327 to 333, wherein the charged amino acid residue is E.

[0341] 335. The AAV capsid variant of any one of embodiments 327-334, wherein the charged amino acid residue is a basic amino acid (e.g., K, R, or H). 336. The AAV capsid variant of any one of embodiments 327-335, wherein the charged amino acid residue is a positively charged amino acid (e.g., K, R, or H).

[0342] 337. The AAV capsid variant of any one of embodiments 327 to 336, wherein the charged amino acid residue is H. 338. The AAV capsid variant of any one of embodiments 327 to 337, wherein the charged amino acid residue is R.

[0343] 339. The AAV capsid variant of any one of embodiments 327-338, wherein the charged amino acid residue is K. 340. The AAV capsid variant of any one of embodiments 327 to 339, wherein the AAV capsid variant comprises an acidic amino acid (e.g., E or D) and a basic amino acid (e.g., R, K, or H).

[0344] 341. The AAV capsid variant of any one of embodiments 327-340, wherein at least 1, 2, 3, or 4 charged amino acid residues are present within 1, 2, 3, 4, 5, or 6 (e.g., 1-6) amino acids from the start of the SPH amino acid sequence.

[0345] 342. An AAV capsid variant according to any one of embodiments 327 to 341, comprising two charged amino acid residues immediately preceding the amino acid sequence of SPH (e.g., at positions 454 and 455 numbered according to SEQ ID NO: 138 or SEQ ID NO: 982).

[0346] 343. The AAV capsid variant of any one of embodiments 327-342, comprising a charged amino acid residue (e.g., E) within 1, 2, 3, 4, 5 (e.g., 5) amino acids from the start of the SPH amino acid sequence.

[0347] 344. The AAV capsid variant of any one of embodiments 327 to 343, comprising a charged amino acid residue (e.g., E) at position 451, numbered according to any one of SEQ ID NOs: 138, 981, or 982.

[0348] 345. The AAV capsid variant of any one of embodiments 327 to 344, comprising an E at position 451, numbered according to any one of SEQ ID NOs: 138, 981, or 982.

[0349] 346. The AAV capsid variant of any one of embodiments 327 to 345, comprising a charged amino acid residue (e.g., R or K) at position 452, numbered according to any one of SEQ ID NOs: 138, 981, or 982.

[0350] 347. The AAV capsid variant of any one of embodiments 327 to 346, comprising an R at position 452, numbered according to SEQ ID NO: 138 or SEQ ID NO: 982. 348. The AAV capsid variant of any one of embodiments 327 to 347, comprising an E at position 451 and an R at position 452, numbered according to SEQ ID NO: 138 or SEQ ID NO: 982.

[0351] 349. An AAV capsid variant according to any one of embodiments 327 to 348, having a reduced tropism for liver cells or tissues compared to the tropism of a reference sequence comprising the amino acid sequence of SEQ ID NO: 138 or SEQ ID NO: 981.

[0352] 350. The AAV capsid variant of any one of the preceding embodiments, comprising at least 1, 2, 3, or 4 (e.g., 1-4 to 1, 1-5) charged amino acid residues (e.g., basic amino acid residues) relative to SEQ ID NO: 138, and located C-terminally to the amino acid sequence of SPH (e.g., within 1, 2, 3, 4, 5, 6, or 7 amino acids (e.g., within positions 459-465 numbered according to any one of SEQ ID NOs: 36-59, 981, or 982) of the end of the amino acid sequence of SPH), and optionally, the amino acid sequence of SPH is located at positions 456-458 numbered according to any one of SEQ ID NOs: 36-59, 981, or 982.

[0353] 351. The AAV capsid variant of embodiment 350, wherein the amino acid sequence of SPH is located at positions 456 to 458 numbered according to any one of SEQ ID NOs: 36 to 59, 981, or 982.

[0354] 352. The AAV capsid variant of embodiment 350 or 351, which comprises fewer than 4, fewer than 3, fewer than 2 (e.g., 2 or 1) charged amino acid residues (e.g., basic amino acid residues) relative to SEQ ID NO: 138.

[0355] 353. The AAV capsid variant of any one of embodiments 350-352, comprising one charged amino acid residue (e.g., a basic amino acid residue) at any one of positions 456-460 numbered relative to SEQ ID NO: 138, or at positions 462-466 ​​numbered according to any one of SEQ ID NOs: 36-59, 981, or 982.

[0356] 354. The AAV capsid variant of any one of embodiments 350 to 353, wherein the charged amino acid residue is a basic amino acid (e.g., R or K). 355. The AAV capsid variant of any one of embodiments 350 to 354, wherein the charged amino acid residue is a positively charged amino acid (e.g., R or K).

[0357] 356. The AAV capsid variant of any one of embodiments 350 to 355, wherein the charged amino acid residue is R. 357. The AAV capsid variant of any one of embodiments 350 to 355, wherein the charged amino acid residue is K.

[0358] 358. The AAV capsid variant of any one of embodiments 350 to 357, wherein at least 1, 2, 3, or 4 charged amino acid residues are present within 1, 2, 3, 4, 5, 6, 7 (e.g., 1 to 7) amino acids from the end of the SPH amino acid sequence.

[0359] 359. An AAV capsid variant according to any one of embodiments 350 to 358, comprising a charged amino acid residue (e.g., K or R) immediately following the SPH sequence (e.g., at position 459 numbered according to SEQ ID NO: 981).

[0360] 360. The AAV capsid variant of any one of embodiments 350 to 359, comprising a charged amino acid residue (e.g., K or R) at position 459, numbered according to SEQ ID NO: 138 or SEQ ID NO: 982.

[0361] 361. The AAV capsid variant of any one of embodiments 350 to 360, comprising a K at position 459, numbered according to SEQ ID NO: 981. 362. The AAV capsid variant of any one of embodiments 350 to 360, comprising an R at position 459, numbered according to SEQ ID NO: 981.

[0362] 363. The AAV capsid variant of any one of embodiments 350 to 362, comprising a charged amino acid residue (e.g., R or K) at one, two, three, four, five, or all of positions 460, 461, 462, 463, 464, and / or 465, numbered according to SEQ ID NO: 138 or 981.

[0363] 364. An AAV capsid variant according to any one of embodiments 300 to 326 or 350 to 363, having increased tropism for liver cells or tissues compared to the tropism of a reference sequence comprising the amino acid sequence of SEQ ID NO: 138.

[0364] 365. The AAV capsid variant of any one of embodiments 300-326 or 350-364, which is enriched in the liver by at least about 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 150, 160, 170, 180, 190, or 200-fold compared to the reference sequence of SEQ ID NO: 138, e.g., as measured by the assay described in Example 4.

[0365] 366. The AAV capsid variant of any one of embodiments 300 to 326, 364, or 365, having reduced tropism for CNS cells or tissues, e.g., brain cells, brain tissue, spinal cord cells, or spinal cord tissue, compared to the tropism of a reference sequence comprising the amino acid sequence of SEQ ID NO: 138.

[0366] 367. An AAV capsid variant according to any one of embodiments 300-326 or 364-366, which exhibits preferential transduction in the liver region compared to transduction in the brain and / or dorsal root ganglia (DRG).

[0367] 368. An AAV capsid variant according to any one of embodiments 300-326 or 364-367, which exhibits preferential transduction in the liver region compared to transduction in the heart and / or muscle (e.g., quadriceps).

[0368] 369. An AAV capsid variant, (a) the amino acid sequence of any of the sequences provided in Tables 1, 2A, 2B, 13-19; (b) an amino acid sequence comprising at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 consecutive amino acids from any one of the sequences provided in Tables 1, 2A, 2B, 13-19; or (c) an amino acid sequence that contains at least 1, 2, or 3, but not more than 4, different amino acids from any one of the sequences provided in Tables 1, 2A, 2B, 13-19; or (d) An AAV capsid variant comprising an amino acid sequence containing at least one, two, or three, but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), relative to the amino acid sequence of any one of the sequences provided in Tables 1, 2A, 2B, 13-19.

[0369] 370. An AAV capsid variant, (a) an amino acid sequence of any one of SEQ ID NOs: 945 to 980 or 985 to 986; (b) an amino acid sequence comprising at least 3, 4, or 5 consecutive amino acids from any one of SEQ ID NOs: 945-980 or 985-986; or (c) an amino acid sequence containing at least 1, 2, or 3, but not more than 4, different amino acids from any one of the amino acid sequences of SEQ ID NOs: 945 to 980 or 985 to 986; (d) An AAV capsid variant comprising an amino acid sequence containing at least one, two, or three, but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), relative to the amino acid sequence of any one of SEQ ID NOs: 945-980 or 985-986.

[0370] 371. An AAV capsid variant, (a) any one of the amino acid sequences of SEQ ID NOs: 2, 200, 201, 941, 943, 204, 208, 404, and 903 to 909; (b) an amino acid sequence comprising at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or 13 consecutive amino acids from any one of SEQ ID NOs: 2, 200, 201, 941, 943, 204, 208, 404, or 903-909; (c) an amino acid sequence containing at least one, two, or three, but not more than four, different amino acids from any one of the amino acid sequences of SEQ ID NOs: 2, 200, 201, 941, 943, 204, 208, 404, or 903 to 909; or (d) An AAV capsid variant comprising an amino acid sequence containing at least one, two, or three, but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), relative to any one of the amino acid sequences of SEQ ID NOs: 2, 200, 201, 941, 943, 204, 208, 404, or 903-909.

[0371] 372. An AAV capsid variant, (a) an amino acid sequence of any one of SEQ ID NOs: 3849 to 4051 or 4681 to 4693; (b) an amino acid sequence comprising at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 consecutive amino acids from any one of SEQ ID NOs: 3849-4051 or 4681-4693; (c) an amino acid sequence containing at least one, two, or three, but not more than four, different amino acids from any one of the amino acid sequences of SEQ ID NOs: 3849 to 4051 or 4681 to 4693; or (d) An AAV capsid variant comprising an amino acid sequence containing at least one, two, or three, but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), relative to the amino acid sequence of any one of SEQ ID NOs: 3849-4051 or 4681-4693.

[0372] 373. An AAV capsid variant, (a) any one of the amino acid sequences of SEQ ID NOs: 4052 to 4092; (b) an amino acid sequence comprising at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 consecutive amino acids from any one of SEQ ID NOs: 4052-4092; (c) an amino acid sequence containing at least one, two, or three, but not more than four, different amino acids from any one of the amino acid sequences of SEQ ID NOs: 4052 to 4092; or (d) An AAV capsid variant comprising an amino acid sequence containing at least one, two, or three, but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), relative to the amino acid sequence of any one of SEQ ID NOs: 4052 to 4092.

[0373] 374. An AAV capsid variant, (a) any amino acid sequence selected from SEQ ID NOs: 4056, 4058, 4059, 4062 to 4064, 4066, 4067, 4080, 4084, 4090, and 4095 to 4097; (b) an amino acid sequence comprising at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 consecutive amino acids from any one of SEQ ID NOs: 4056, 4058, 4059, 4062-4064, 4066, 4067, 4080, 4084, 4090, or 4095-4097; (c) an amino acid sequence containing at least one, two, or three, but not more than four, different amino acids from any one of the amino acid sequences of SEQ ID NOs: 4056, 4058, 4059, 4062 to 4064, 4066, 4067, 4080, 4084, 4090, or 4095 to 4097; or (d) An AAV capsid variant comprising an amino acid sequence containing at least one, two, or three, but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), relative to the amino acid sequence of any one of SEQ ID NOs: 4056, 4058, 4059, 4062-4064, 4066, 4067, 4080, 4084, 4090, or 4095-4097.

[0374] 375. The AAV capsid variant of embodiment 369 or 371, comprising an amino acid sequence comprising at least 4, 5, 6, 7, 8, 9, 10, 11, 12, or 13 consecutive amino acids from any one of SEQ ID NOs: 2, 200, 201, 941, 943, 204, 208, 404, or 903-909.

[0375] 376. The AAV capsid variant of any one of embodiments 369-375, wherein three consecutive amino acids comprise SPH. 377. The AAV capsid variant of any one of embodiments 369-371 or 376, wherein 4 contiguous amino acids comprise SPHS (SEQ ID NO: 4700).

[0376] 378. The AAV capsid variant of any one of embodiments 369-371, 376, or 377, wherein 5 consecutive amino acids comprise SPHSK (SEQ ID NO: 4701).

[0377] 379. The AAV capsid variant of any one of embodiments 369-371, or 376-378, wherein 6 contiguous amino acids comprise SPHSKA (SEQ ID NO: 941).

[0378] 380. The AAV capsid variant of embodiments 369-371, wherein 3 consecutive amino acids comprise an HDS. 381. The AAV capsid variant of any one of embodiments 369-371 or 380, wherein 4 consecutive amino acids comprise HDSP (SEQ ID NO: 4702).

[0379] The AAV capsid variant of any one of embodiments 369-371, 380, or 381, wherein 382.5 contiguous amino acids comprise HDSPH (sequence number 4703).

[0380] 383. The AAV capsid variant of any one of embodiments 369-371 or 380-382, wherein 6 contiguous amino acids comprise HDSPHK (SEQ ID NO: 2).

[0381] 384. (i) three consecutive amino acids comprise SPH; and (ii) four consecutive amino acids comprise SPHK (SEQ ID NO: 6398); (iii) five consecutive amino acids comprise SPHKY (SEQ ID NO: 4715); and / or (iv) An AAV capsid variant described in any one of embodiments 369 to 371, wherein six consecutive amino acids comprise SPHKYG (sequence number 966).

[0382] 385. The AAV capsid variant of embodiment 369 or 371, comprising an amino acid sequence containing at least one, two, or three, but no more than four modifications, e.g., substitutions (e.g., conservative substitutions), relative to the amino acid sequence of any one of SEQ ID NOs: 2, 200, 201, 941, 943, 204, 208, 404, or 903-909.

[0383] 386. The AAV capsid variant of any one of embodiments 369, 371, or 385, comprising an amino acid sequence that includes at least one, two, or three, but not more than four, modifications, e.g., substitutions (e.g., conservative substitutions), relative to the amino acid sequence of SPHSKA (SEQ ID NO: 941).

[0384] 387. The AAV capsid variant of any one of embodiments 369, 371, or 385, comprising an amino acid sequence that includes at least one, two, or three, but not more than four, modifications, e.g., substitutions (e.g., conservative substitutions), relative to the amino acid sequence of HDSPHK (SEQ ID NO: 2).

[0385] 388. The AAV capsid variant of any one of embodiments 369-371, 384, or 385, comprising an amino acid sequence that includes at least one, two, or three, but not more than four, modifications, e.g., substitutions (e.g., conservative substitutions), relative to the amino acid sequence of SPHKYG (SEQ ID NO: 966).

[0386] 389. (i) an amino acid sequence containing at least one, two, or three, but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), relative to the amino acid sequence of KTERVSGSPHSKAQNQQT (SEQ ID NO: 3589); (ii) an amino acid sequence containing at least one, two, or three, but not more than four, modifications, e.g., substitutions (e.g., conservative substitutions), relative to the amino acid sequence of KAEIGHDSPHKSGQNQQT (SEQ ID NO: 1754); (iii) an amino acid sequence containing at least one, two, or three, but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), relative to the amino acid sequence of KTEKMSGSPHSKAQNQQT (SEQ ID NO: 3241); (iv) an amino acid sequence that contains at least one, two, or three, but not more than four, modifications, e.g., substitutions (e.g., conservative substitutions), relative to the amino acid sequence of KTINGHDSPHSKAQNLQT (SEQ ID NO: 4100); or (v) An AAV capsid variant described in embodiment 370, comprising an amino acid sequence containing at least one, two, or three, but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), relative to the amino acid sequence of KTVNGHDSPHSKAQNQQT (sequence number 4062).

[0387] 390. The AAV capsid variant of embodiment 369 or 371, comprising an amino acid sequence that contains at least 1, 2, or 3, but no more than 4, different amino acids relative to the amino acid sequence of any one of SEQ ID NOs: 2, 200, 201, 941, 943, 204, 208, 404, or 903-909.

[0388] 391. The AAV capsid variant of any one of embodiments 369, 371, or 390, comprising an amino acid sequence that includes at least 1, 2, or 3, but not more than 4, different amino acids relative to the amino acid sequence of SPHSKA (SEQ ID NO: 941).

[0389] 392. The AAV capsid variant of any one of embodiments 369, 371, or 390, comprising an amino acid sequence that includes at least 1, 2, or 3, but not more than 4, different amino acids relative to the amino acid sequence of HDSPHK (SEQ ID NO: 2).

[0390] 393. The AAV capsid variant of any one of embodiments 369-371, 384, or 390, comprising an amino acid sequence that includes at least 1, 2, or 3, but not more than 4, different amino acids relative to the amino acid sequence of SPHKYG (SEQ ID NO: 966).

[0391] 394. (i) an amino acid sequence that contains at least one, two, or three, but not more than four, amino acids that differ from the amino acid sequence of KTERVSGSPHSKAQNQQT (SEQ ID NO: 3589); (ii) an amino acid sequence that contains at least one, two, or three, but not more than four, amino acids that differ from the amino acid sequence of KAEIGHDSPHKSGQNQQT (SEQ ID NO: 1754); (iii) an amino acid sequence that contains at least one, two, or three, but not more than four, amino acids that differ from the amino acid sequence of KTEKMSGSPHSKAQNQQT (SEQ ID NO: 3241); (iv) an amino acid sequence that contains at least one, two, or three, but not more than four, amino acids that differ from the amino acid sequence of KTINGHDSPHSKAQNLQT (SEQ ID NO: 4100); or (v) An AAV capsid variant described in embodiment 369, comprising an amino acid sequence that contains at least 1, 2, or 3, but not more than 4, different amino acids from the amino acid sequence of KTVNGHDSPHSKAQNQQT (sequence number 4062).

[0392] 395. The AAV capsid variant of any one of embodiments 1-129, 269, 271, 375-388, or 390-394, comprising the amino acid sequence of any of SEQ ID NOs: 2, 200, 201, 941, 943, 204, 208, 404, or 903-909.

[0393] 396. The AAV capsid variant of any one of embodiments 295-297, 301-305, 313, 314, 318, 319, or 323, comprising the amino acid sequence ERVSGSPHSKA (SEQ ID NO: 6399), optionally replacing positions 451-455 (e.g., I451, N542, G453, S454, G455) located immediately after position 450 and numbered according to SEQ ID NO: 138.

[0394] 397. The AAV capsid variant of any one of embodiments 369-371, 375-379, 385, 386, 389-391, or 394-396, comprising the amino acid sequence KTERVSGSPHSKAQNQQT (SEQ ID NO: 3589), optionally wherein the amino acid sequence is located immediately after position 448 and replaces positions 449-460 (e.g., K449, T450, I451, N452, G453, S454, G455, Q456, N457, Q458, Q459, T460), numbered according to SEQ ID NO: 138.

[0395] 398. The AAV capsid variant of any one of embodiments 269-371, 375, 380-383, 385, 387, 389, 390, 393, or 394, comprising the amino acid sequence AEIGHDSPHKSG (SEQ ID NO: 6400), optionally wherein the amino acid sequence is located immediately after position 449 and replaces positions 450-455 (e.g., T450, I451, N452, G453, S454, G455), numbered according to SEQ ID NO: 138.

[0396] 399. The AAV capsid variant of any one of embodiments 369-371, 375, 380-383, 385, 387, 389, 390, 393, 394, or 398, comprising the amino acid sequence KAEIGHDSPHKSGQNQQT (SEQ ID NO: 1754), optionally wherein the amino acid sequence is located immediately after position 448 and replaces positions 449-460 (e.g., K449, T450, I451, N452, G453, S454, G455, Q456, N457, Q458, Q459, T460), numbered according to SEQ ID NO: 138.

[0397] 400. The AAV capsid variant of any one of embodiments 369-371, 375-379, 390, 391, or 395, comprising the amino acid sequence of EKMSGSPHSKA (SEQ ID NO: 6401), optionally replacing positions 451-455 (e.g., I451, N452, G453, S454, G455) immediately following position 450 and numbered according to SEQ ID NO: 138.

[0398] 401. The AAV capsid variant of any one of embodiments 369-371, 375-379, 390, 391, or 395, comprising the amino acid sequence KTEKMSGSPHSKAQNQQT (SEQ ID NO: 3241), optionally wherein the amino acid sequence is located immediately after position 448 and replaces positions 449-460 (e.g., K449, T450, I451, N452, G453, S454, G455, Q456, N457, Q458, Q459, T460), numbered according to SEQ ID NO: 138.

[0399] 402. The AAV capsid variant of any one of embodiments 369-371, 375-379, 390, 391, or 395, comprising the amino acid sequence HDSPHSKAQNL (SEQ ID NO: 6402), optionally replacing positions 456-458 (e.g., Q456, N457, Q458) immediately following position 453, numbered according to SEQ ID NO: 138.

[0400] 403. The AAV capsid variant of any one of embodiments 369-371, 375-379, 390, 391, or 395, comprising the amino acid sequence KTINGHDSPHSKAQNLQT (SEQ ID NO: 4100), optionally wherein the amino acid sequence is located immediately after position 448 and replaces positions 449-460 (e.g., K449, T450, I451, N452, G453, S454, G455, Q456, N457, Q458, Q459, T460), numbered according to SEQ ID NO: 138.

[0401] 404. The AAV capsid variant of any one of embodiments 369-371, 375-379, 390, 391, or 395, comprising the amino acid sequence of VNGHDSPHSKA (SEQ ID NO: 6403), optionally replacing positions 451-455 (e.g., I451, N452, G453, S454, G455) located immediately after position 450 and numbered according to SEQ ID NO: 138.

[0402] 405. The AAV capsid variant of any one of embodiments 369-371, 375-379, 390, 391, or 395, comprising the amino acid sequence KTVNGHDSPHSKAQNQQT (SEQ ID NO: 4062), optionally wherein the amino acid sequence is located immediately after position 448 and replaces positions 449-460 (e.g., K449, T450, I451, N452, G453, S454, G455, Q456, N457, Q458, Q459, T460), numbered according to SEQ ID NO: 138.

[0403] 406. An amino acid sequence encoded by a nucleotide sequence of SEQ ID NO: 942, a nucleotide sequence containing at least 1, 2, 3, 4, 5, 6, or 7 modifications, e.g., substitutions (e.g., conservative substitutions), but not more than 10 modifications, e.g., substitutions (e.g., conservative substitutions), relative to the nucleotide sequence of SEQ ID NO: 942, or a nucleotide sequence containing at least 1, 2, 3, 4, 5, 6, or 7 but not more than 10 different nucleotides relative to the nucleotide sequence of SEQ ID NO: 942. 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 486, 490, 491, 500, 501, 502, 503, 504,

[0404] 407. An amino acid sequence encoded by a nucleotide sequence containing at least 1, 2, 3, 4, 5, 6, or 7 modifications, e.g., substitutions (e.g., conservative substitutions), but not more than 10 modifications, e.g., substitutions (e.g., conservative substitutions), relative to the nucleotide sequence of SEQ ID NO: 3, or at least 1, 2, 3, 4, 5, 6, or 7 but not more than 10 different nucleotides relative to the nucleotide sequence of SEQ ID NO: 3, 260, 261, 264-280, 283-287, 289-299, 327-363, 369, 369, 371, 380-383, 385, 386, 390, 392, or 395.

[0405] 408. The nucleotide sequence encoding the capsid variant is a nucleotide sequence of SEQ ID NO: 942, a nucleotide sequence containing at least 1, 2, 3, 4, 5, 6, or 7 modifications, e.g., substitutions (e.g., conservative substitutions), but not more than 10 modifications, e.g., substitutions (e.g., conservative substitutions), relative to the nucleotide sequence of SEQ ID NO: 942, or a nucleotide sequence containing at least 1, 2, 3, 4, 5, 6, or 7 but not more than 10 different nucleotides relative to the nucleotide sequence of SEQ ID NO: 942. 26. The AAV capsid variant of any one of embodiments 1-23, 26-29, 32, 35-43, 46-51, 54-72, 69-89, 91, 94-99, 102-104, 107, 110-112, 115-129, 168-202, 02, 240-247, 249, 250, 253-263, 266, 272-281, 286, 288, 291-299, 327-363, 369-371, 375-379, 385, 386, 390, 391, 395, or 406, comprising a nucleotide sequence.

[0406] 409. The nucleotide sequence encoding the capsid variant comprises the nucleotide sequence of SEQ ID NO: 3, a nucleotide sequence containing at least 1, 2, 3, 4, 5, 6, or 7 modifications, e.g., substitutions (e.g., conservative substitutions), but not more than 10 modifications, e.g., substitutions (e.g., conservative substitutions), relative to the nucleotide sequence of SEQ ID NO: 3, or a nucleotide sequence containing at least 1, 2, 3, 4, 5, 6, or 7 but not more than 10 different nucleotides relative to the nucleotide sequence of SEQ ID NO: 3; 203-248, 251, 252, 254-257, 260, 261, 264-280, 283-287, 289-299, 327-363, 369, 369, 371, 380-383, 385, 386, 390, 392, 395, or 407.

[0407] 410. The AAV capsid variant of any one of embodiments 369-409, wherein the amino acid sequence is present in loop IV. 411. The AAV capsid variant of any one of embodiments 369 to 410, wherein the amino acid sequence is located immediately after position 448, 449, 450, 451, 452, 453, 454, or 455 relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.

[0408] 412. The AAV capsid variant of any one of embodiments 369-411, wherein the amino acid sequence replaces amino acids 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, and / or 460 (e.g., K449, T450, I451, N452, G453, S454, G455, Q456, N457, Q458, Q459, and / or T460), numbered according to the amino acid sequence of SEQ ID NO: 138.

[0409] 413. The AAV capsid variant of any one of embodiments 369 to 412, wherein the amino acid sequence is located immediately after position 455 relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.

[0410] 414. The AAV capsid variant of any one of embodiments 369 to 413, wherein the amino acid sequence is located immediately after position 453 relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.

[0411] 415. The amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is located immediately after position 455 relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138, in embodiments 1 to 23, 26 to 29, 32, 35 to 43, 46 to 51, 54 to 72, 69 to 89, 91, 94 to 99, 102 to 104, 107, 110 to 112; 115-129, 168-202, 02, 240-247, 249, 250, 253-263, 266, 272-281, 286, 288, 291-299, 327-363, 369-371, 375-379, 385, 386, 390, 391, 395, 406, 408, or 410-413.

[0412] 416. The amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is located immediately after position 455 relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 981, in embodiments 1 to 23, 26 to 29, 32, 35 to 43, 46 to 51, 54 to 72, 69 to 89, 91, 94 to 99, 102 to 104, 107, 110 to 112, 11 5-129, 168-202, 02, 240-247, 249, 250, 253-263, 266, 272-281, 286, 288, 291-299, 327-363, 369-371, 375-379, 385, 386, 390, 391, 395, 406, 408, 410-413, or 415.

[0413] 417. The AAV capsid variant of embodiment 415 or 416, further comprising an amino acid other than I at position 451, an amino acid other than N at position 452, and an amino acid other than G at position 453, numbered according to any one of SEQ ID NOs: 36, 138, or 981.

[0414] 418. The AAV capsid variant of any one of embodiments 415 to 417, further comprising an E at position 451, an R at position 452, and a V at position 453, numbered according to any one of SEQ ID NOs: 36, 138, or 981.

[0415] 419. The AAV capsid variant of any one of embodiments 415 to 418, further comprising the substitutions I451E, N452R, and G453V, numbered according to any one of SEQ ID NOs: 36, 138, or 981.

[0416] 420. (i) an E at position 451, an R at position 452, and a V at position 453, numbered according to any one of SEQ ID NOs: 36, 138, or 981; and (ii) An AAV capsid variant described in any one of embodiments 415 to 419, comprising the amino acid sequence of SPHSKA (sequence number 941), wherein the amino acid sequence is located immediately after position 455, numbered according to any one of sequence numbers 36, 138, or 981.

[0417] 421. The AAV capsid variant of embodiment 415 or 416, further comprising an amino acid other than I at position 451, an amino acid other than N at position 452, and / or an amino acid other than G at position 453, numbered according to SEQ ID NO: 39 or 138.

[0418] 422. The AAV capsid variant of any one of embodiments 415, 416, or 421, further comprising an E at position 451, a K at position 452, and / or an M at position 453, numbered according to SEQ ID NO: 138 or 39.

[0419] 423. The AAV capsid variant of any one of embodiments 415, 416, 421, or 422, further comprising the substitutions I451E, N452K, and G453M, numbered according to SEQ ID NO: 39 or 138.

[0420] 424. (i) an E at position 451, a K at position 452, and an M at position 453, numbered according to SEQ ID NO: 39 or 138; and (ii) An AAV capsid variant described in any one of embodiments 415, 416, or 421 to 423, wherein the amino acid sequence is the amino acid sequence of SPHSKA (SEQ ID NO: 941), and the amino acid sequence is located immediately after position 455, numbered according to SEQ ID NO: 39 or 138.

[0421] 425. The AAV capsid variant of embodiment 415 or 416, further comprising an amino acid other than S at position 454, an amino acid other than G at position 455, and / or an amino acid other than Q at position 458, numbered according to SEQ ID NO: 138.

[0422] 426. The AAV capsid variant of any one of embodiments 415, 416, or 425, further comprising an H at position 454, a D at position 455, and / or an L at position 458, numbered according to SEQ ID NO: 138.

[0423] 427. The AAV capsid variant of any one of embodiments 415, 416, 425, or 426, further comprising the substitutions S454H, G455D, and Q458L, numbered according to SEQ ID NO: 138.

[0424] 428. (i) H at position 454, D at position 455, and / or L at position 458, numbered according to SEQ ID NO: 138; and (ii) An AAV capsid variant described in any one of embodiments 415, 416, or 425 to 427, comprising the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is located immediately after position 455, numbered according to SEQ ID NO: 138.

[0425] 429. The AAV capsid variant of embodiment 415 or 416, further comprising an amino acid other than I at position 451, an amino acid other than S at position 454, and / or an amino acid other than G at position 455, numbered according to SEQ ID NO: 52 or 138.

[0426] 430. The AAV capsid variant of any one of embodiments 415, 416, or 429, further comprising a V at position 451, an H at position 454, and / or a D at position 455, numbered according to SEQ ID NO: 52 or 138.

[0427] 431. The AAV capsid variant of any one of embodiments 415, 416, 429, or 430, further comprising the substitutions I451V, S454H, and / or G455D, numbered according to SEQ ID NO: 52 or 138.

[0428] 432. (i) a V at position 451, an H at position 454, and / or a D at position 455, numbered according to SEQ ID NO: 52 or 138, and (ii) An AAV capsid variant described in any one of embodiments 415, 416, or 429 to 431, comprising the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is located immediately after position 455, as numbered according to SEQ ID NO: 52 or 138.

[0429] 433. The amino acid sequence of HDSPHK (SEQ ID NO: 2), wherein the amino acid sequence is located immediately after position 453, numbered according to the amino acid sequence of SEQ ID NO: 138, in embodiments 1 to 9, 11, 12 to 22, 24, 26, 28, 30, 33, 35 to 42, 44, 46 to 50, 52, 54 to 77, 83 to 88, 90 to 97, 100 to 103, 105, 110 , 111, 113-129, 203-248, 251, 252, 254-257, 260, 261, 264-280, 283-287, 289-299, 327-363, 369, 369, 371, 380-383, 385, 386, 390, 392, 395, 407, 409-412, or 414.

[0430] 434. The amino acid sequence of HDSPHK (SEQ ID NO: 2), wherein the amino acid sequence is located immediately after position 453, numbered according to the amino acid sequence of SEQ ID NO: 982, in embodiments 1 to 9, 11, 12 to 22, 24, 26, 28, 30, 33, 35 to 42, 44, 46 to 50, 52, 54 to 77, 83 to 88, 90 to 97, 100 to 103, 105, 110, 1 11, 113-129, 203-248, 251, 252, 254-257, 260, 261, 264-280, 283-287, 289-299, 327-363, 369, 369, 371, 380-383, 385, 386, 390, 392, 395, 407, 409-412, 414, or 433.

[0431] 435. The amino acid sequence of SPHKSG (SEQ ID NO: 946), wherein the amino acid sequence is located immediately after position 455, numbered relative to the reference sequence numbered according to the amino acid sequence of SEQ ID NO: 982, in embodiments 1 to 9, 11, 12 to 22, 24, 26, 28, 30, 33, 35 to 42, 44, 46 to 50, 52, 54 to 77, 83 to 88, 90 to 97, 100 to 103, 105 , 110, 111, 113-129, 203-248, 251, 252, 254-257, 260, 261, 264-280, 283-287, 289-299, 327-363, 369, 369, 371, 380-383, 385, 386, 390, 392, 395, 407, 409-412, 414, 433, or 434.

[0432] 436. (i) the amino acid sequence of HDSPHSKA (SEQ ID NO: 4486) located immediately after position 453; and (ii) a deletion of amino acids SG at positions 454 and 455; An AAV capsid variant described in any one of embodiments 369 to 435, wherein (i) and (ii) are numbered according to SEQ ID NO: 138.

[0433] 437. An AAV capsid variant described in any one of embodiments 369 to 436, comprising the amino acids HD at positions 454 and 455, and further comprising the amino acid sequence of SPHSKA (SEQ ID NO: 941), located immediately after position 455, numbered relative to SEQ ID NO: 138.

[0434] 438. The AAV capsid variant of any one of embodiments 433 to 435, further comprising an amino acid other than T at position 450, an amino acid other than I at position 451, and an amino acid other than N at position 452, numbered according to SEQ ID NO: 138 or 982.

[0435] 439. The AAV capsid variant of any one of embodiments 433 to 435 or 438, further comprising an A at position 450, an E at position 451, and an I at position 452, numbered according to SEQ ID NO: 138 or 982.

[0436] 440. The AAV capsid variant of any one of embodiments 433-435, 438, or 439, further comprising the substitutions T450A, I451E, and N452I, numbered according to SEQ ID NO: 138 or 982.

[0437] 441. (i) an A at position 450, an E at position 451, and an I at position 452, numbered according to SEQ ID NO: 138 or 982; and (ii) An AAV capsid variant described in any one of embodiments 433, 434, or 438 to 440, comprising the amino acid sequence of HDSPHK (SEQ ID NO: 2), located immediately after position 453, numbered according to SEQ ID NO: 138 or 982.

[0438] 442. The AAV capsid variant of any one of embodiments 1-22, 25-27, 31, 34-42, 45-50, 53-63, 69, 79, 83-86, 91-98, 102, 103, 110, 111, 118-129, 369-371, 384, 385, 390, 393, 395, 410-413, comprising the amino acid sequence of SPHKYG (SEQ ID NO: 966), wherein the amino acid sequence is located immediately after position 455 relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.

[0439] 443. An AAV capsid variant comprising the amino acid sequence of HDSPHK (SEQ ID NO: 2), wherein the amino acid sequence is located immediately after position 453, numbered according to the amino acid sequence of SEQ ID NO: 982.

[0440] 444. An AAV capsid variant comprising the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is located immediately after position 455, numbered according to the amino acid sequence of SEQ ID NO: 981.

[0441] 445. An AAV capsid variant comprising the amino acid sequence of HDSPHK (SEQ ID NO: 2), wherein the amino acid sequence is located immediately after position 453, numbered according to the amino acid sequence of SEQ ID NO: 37, and optionally (i) one, two, or all of an amino acid other than T at position 450, an amino acid other than I at position 541, and / or an amino acid other than N at position 452, numbered according to SEQ ID NO: 138 or 37; (ii) An AAV capsid variant further comprising one, two, or all of A at position 450, E at position 451, and / or I at position 452, numbered according to SEQ ID NO: 138 or 37.

[0442] 446. An AAV capsid variant comprising the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is located immediately after position 455, numbered according to the amino acid sequence of any one of SEQ ID NOs: 36, 38-55, 57, or 59.

[0443] 447. (i) modifications, such as insertions, substitutions (e.g., conservative substitutions), and / or deletions, in loops I, II, VI, and / or VIII; and / or (ii) The AAV capsid variant of any one of the preceding embodiments, further comprising a substitution at position K449, e.g., a K449R substitution, numbered according to SEQ ID NO: 138.

[0444] 448. The AAV capsid variant of any one of the preceding embodiments, comprising an amino acid sequence comprising at least one, two, or three modifications, e.g., substitutions (e.g., conservative substitutions), but no more than 30, 20, or 10 modifications, e.g., substitutions (e.g., conservative substitutions), relative to the amino acid sequence of SEQ ID NO: 138.

[0445] 449. The AAV capsid variant of any one of the preceding embodiments, comprising an amino acid sequence that includes at least 1, 2, or 3, but no more than 30, 20, or 10, different amino acids relative to the amino acid sequence of SEQ ID NO: 138.

[0446] 450. The AAV capsid variant of any one of the preceding embodiments, comprising the amino acid sequence of SEQ ID NO: 138, or an amino acid sequence having at least 80% (e.g., at least about 85, 90, 95, 96, 97, 98, or 99%) sequence identity thereto.

[0447] 451. The AAV capsid variant of any one of the preceding embodiments, comprising the amino acid sequence of SEQ ID NO: 138. 452. The AAV capsid variant of any one of the preceding embodiments, comprising an amino acid sequence encoded by the nucleotide sequence of SEQ ID NO: 137, or a sequence having at least 80% (e.g., at least about 85, 90, 95, 96, 97, 98, or 99%) sequence identity thereto.

[0448] 453. The AAV capsid variant of any one of the preceding embodiments, wherein the nucleotide sequence encoding the capsid variant comprises the nucleotide sequence of SEQ ID NO: 137, or a sequence having at least 80% (e.g., at least about 85, 90, 95, 96, 97, 98, or 99%) sequence identity thereto.

[0449] 454. The AAV capsid variant of any one of the preceding embodiments, comprising a VP1 protein, a VP2 protein, a VP3 protein, or a combination thereof. 455. The AAV capsid variant of any one of embodiments 1 to 454, comprising an amino acid sequence corresponding to positions 138 to 742 of SEQ ID NO: 981 or 982, e.g., VP2, or a sequence having at least 80% (e.g., at least about 85, 90, 95, 96, 97, 98, or 99%) sequence identity thereto.

[0450] 456. The AAV capsid variant of any one of embodiments 1 to 455, comprising an amino acid sequence corresponding to positions 203 to 742 of SEQ ID NO: 981 or 982, e.g., VP3, or a sequence having at least 80% (e.g., at least about 85, 90, 95, 96, 97, 98, or 99%) sequence identity thereto.

[0451] 457. The AAV capsid variant of any one of embodiments 1 to 456, comprising an amino acid sequence corresponding to positions 138 to 736 of SEQ ID NO: 138, e.g., VP2, or a sequence having at least 80% (e.g., at least about 85, 90, 95, 96, 97, 98, or 99%) sequence identity thereto.

[0452] 458. The AAV capsid variant of any one of embodiments 1 to 457, comprising an amino acid sequence corresponding to positions 203 to 736 of SEQ ID NO: 138, e.g., VP3, or a sequence having at least 80% (e.g., at least about 85, 90, 95, 96, 97, 98, or 99%) sequence identity thereto.

[0453] 459. An amino acid sequence comprising at least 3, 4, 5, or 6 consecutive amino acids from the amino acid sequence of SPHSKA (SEQ ID NO: 941), (i) three consecutive amino acids contain SPH, (ii) four consecutive amino acids comprise SPHS (SEQ ID NO: 4700); (iii) 5 consecutive amino acids comprise SPHSK (SEQ ID NO: 4701); or (iv) 6 consecutive amino acids comprise SPHSKA (SEQ ID NO: 941); The AAV capsid variant is (a) a VP1 protein comprising the amino acid sequence of SEQ ID NO: 138 or SEQ ID NO: 981; (b) a VP2 protein comprising the amino acid sequence of positions 138 to 736 of SEQ ID NO: 138 or positions 138 to 742 of SEQ ID NO: 981; (c) a VP3 protein comprising the amino acid sequence of positions 203 to 736 of SEQ ID NO: 138 or positions 203 to 742 of SEQ ID NO: 981; or (d) an amino acid sequence having at least 90% (e.g., at least about 95, 96, 97, 98, or 99%) sequence identity to any of the amino acid sequences in (a) to (c). 272-281, 286, 288, 291-299, 327-363, 369-371, 375-379, 385, 386, 390, 391, 395, 406, 408, 410-413, 415-432, 444, or 446-458, comprising the amino acid sequence:

[0454] 460. An amino acid sequence comprising at least 3, 4, 5, or 6 consecutive amino acids from the amino acid sequence of SPHSKA (SEQ ID NO: 941), (i) three consecutive amino acids contain SPH, (ii) four consecutive amino acids comprise SPHS (SEQ ID NO: 4700); (iii) 5 consecutive amino acids comprise SPHSK (SEQ ID NO: 4701); or (iv) 6 consecutive amino acids comprise SPHSKA (SEQ ID NO: 941); 981. The AAV capsid variant of any of embodiments 1-23, 26-29, 32, 35-43, 46-51, 54-72, 69-89, 91, 94-99, 102-104, 107, 110-112, 115-129, 168-202, wherein the AAV capsid variant comprises an amino acid sequence at least 90% (e.g., at least about 95, 96, 97, 98, or 99%) identical to the amino acid sequence of SEQ ID NO: 981. 02, 02, 240-247, 249, 250, 253-263, 266, 272-281, 286, 288, 291-299, 327-363, 369-371, 375-379, 385, 386, 390, 391, 395, 406, 408, 410-413, 415-432, 444, or 446-459.

[0455] 461. The AAV capsid variant comprises one or two, but not more than three, substitutions relative to the amino acid sequence of SPHSKA (SEQ ID NO: 941), (a) a VP1 protein comprising the amino acid sequence of SEQ ID NO: 138 or SEQ ID NO: 981; (b) a VP2 protein comprising the amino acid sequence of positions 138 to 736 of SEQ ID NO: 138 or positions 138 to 742 of SEQ ID NO: 981; (c) a VP3 protein comprising the amino acid sequence of positions 203 to 736 of SEQ ID NO: 138 or positions 203 to 742 of SEQ ID NO: 981, or (d) any of the amino acid sequences in (a)-(c) comprising an amino acid sequence having at least 90% (e.g., at least about 95, 96, 97, 98, or 99%) sequence identity to any of the amino acid sequences in (a)-(c), 168-202, 02, 240-247, 249, 250, 253-263, 266, 272-281, 286, 288, 291-299, 327-363, 369-371, 375-379, 385, 386, 390, 391, 395, 406, 408, 410-413, 415-432, 444, or 446-460.

[0456] 462. Embodiments 1-23, 26-29, 32, 35-43, 46-51, 54-72, 69-89, 91, 94-99, which comprise one or two, but not more than three, substitutions relative to the amino acid sequence of SPHSKA (SEQ ID NO: 941), and wherein the AAV capsid variant comprises an amino acid sequence that is at least 90% (e.g., at least about 95, 96, 97, 98, or 99%) identical to the amino acid sequence of SEQ ID NO: 138 or SEQ ID NO: 981; 102-104, 107, 110-112, 115-129, 168-202, 02, 240-247, 249, 250, 253-263, 266, 272-281, 286, 288, 291-299, 327-363, 369-371, 375-379, 385, 386, 390, 391, 395, 406, 408, 410-413, 415-432, 444, or 446-461.

[0457] 463. The AAV capsid variant of any one of embodiments 459 to 462, wherein the amino acid sequence occurs immediately after position 455, numbered according to SEQ ID NO: 138 or 981.

[0458] 464. An amino acid sequence comprising at least 3, 4, 5, or 6 consecutive amino acids from the amino acid sequence of HDSPHK (SEQ ID NO: 2), (i) 3 consecutive amino acids contain an HDS; (ii) 4 consecutive amino acids include HDSP (SEQ ID NO: 4702); (iii) 5 consecutive amino acids comprise HDSPH (SEQ ID NO: 4703); or (iv) 6 consecutive amino acids comprise HDSPHK (SEQ ID NO: 2);

[0023] Embodiment 1, wherein the AAV capsid variant comprises: (a) a VP1 protein comprising the amino acid sequence of SEQ ID NO: 138 or SEQ ID NO: 982; (b) a VP2 protein comprising the amino acid sequence of positions 138 to 736 of SEQ ID NO: 138 or positions 138 to 742 of SEQ ID NO: 982; (c) a VP3 protein comprising the amino acid sequence of positions 203 to 736 of SEQ ID NO: 138 or positions 203 to 742 of SEQ ID NO: 982; or (d) an amino acid sequence having at least 90% (e.g., at least about 95, 96, 97, 98, or 99%) sequence identity to any of the amino acid sequences in (a) to (c). ~9, 11, 12~22, 24, 26, 28, 30, 33, 35~42, 44, 46~50, 52, 54~77, 83~88, 90~97, 100~103, 105, 110, 111, 113~129, 203~248, 251, 252, 254~257, 260, 261, 264~280, 283 287, 289-299, 327-363, 369, 369, 371, 380-383, 385, 386, 390, 392, 395, 407, 409-412, 414, 433-435, 438-441, 443, 445, or 447-458.

[0459] 465. An amino acid sequence comprising at least 3, 4, 5, or 6 consecutive amino acids from the amino acid sequence of HDSPHK (SEQ ID NO: 2), (i) 3 consecutive amino acids contain an HDS; (ii) 4 consecutive amino acids include HDSP (SEQ ID NO: 4702); (iii) 5 consecutive amino acids comprise HDSPH (SEQ ID NO: 4703); or (iv) 6 consecutive amino acids comprise HDSPHK (SEQ ID NO: 2); 100-103, 105, 110, 111, 113-129, 203, wherein the AAV capsid variant comprises an amino acid sequence at least 90% (e.g., at least about 95, 96, 97, 98, or 99%) identical to the amino acid sequence of SEQ ID NO: 982. 248, 251, 252, 254-257, 260, 261, 264-280, 283-287, 289-299, 327-363, 369, 369, 371, 380-383, 385, 386, 390, 392, 395, 407, 409-412, 414, 433-435, 438-441, 443, 445, 447-458, or 464.

[0460] 466. The AAV capsid variant comprises one or two, but not more than three, substitutions relative to the amino acid sequence of HDSPHK (SEQ ID NO: 2), (a) a VP1 protein comprising the amino acid sequence of SEQ ID NO: 138 or SEQ ID NO: 982; (b) a VP2 protein comprising the amino acid sequence of positions 138 to 736 of SEQ ID NO: 138 or positions 138 to 742 of SEQ ID NO: 982; (c) a VP3 protein comprising the amino acid sequence of positions 203 to 736 of SEQ ID NO: 138 or positions 203 to 742 of SEQ ID NO: 982, or (d) any of the amino acid sequences in (a)-(c) comprising an amino acid sequence having at least 90% (e.g., at least about 95, 96, 97, 98, or 99%) sequence identity to any of the amino acid sequences in (a)-(c), 203-248, 251, 252, 254-257, 260, 261, 264-280, 283-287, 289-299, 327-363, 369, 369, 371, 380-383, 385, 386, 390, 392, 395, 407, 409-412, 414, 433-435, 438-441, 443, 445, 447-458, 464, or 465.

[0461] 467. The AAV capsid variant of any of embodiments 1-9, 11, 12-22, 24, 26, 28, 30, 33, 35-42, 44, 46-50, 52, 54-77, 83-88, 90-97, 100-100, which comprises one or two, but not more than three, substitutions relative to the amino acid sequence of HDSPHK (SEQ ID NO: 2), and wherein the AAV capsid variant comprises an amino acid sequence that is at least 90% (e.g., at least about 95, 96, 97, 98, or 99%) identical to the amino acid sequence of SEQ ID NO: 982. 3. The AAV capsid variant of any one of 3, 105, 110, 111, 113-129, 203-248, 251, 252, 254-257, 260, 261, 264-280, 283-287, 289-299, 327-363, 369, 369, 371, 380-383, 385, 386, 390, 392, 395, 407, 409-412, 414, 433-435, 438-441, 443, 445, 447-458, or 464-466.

[0462] 468. The AAV capsid variant of any one of embodiments 464 to 468, wherein the amino acid sequence is located immediately after position 453, numbered according to SEQ ID NO: 138 or 982.

[0463] 469. The AAV capsid variant of any one of embodiments 1 to 468, comprising the amino acid sequence of any one of SEQ ID NOs: 981 or 982, or an amino acid sequence having at least 80% (e.g., at least about 85, 90, 95, 96, 97, 98, or 99%) sequence identity thereto.

[0464] 470. The AAV capsid variant of any one of embodiments 1 to 469, comprising an amino acid sequence containing at least one, two, or three modifications, e.g., substitutions (e.g., conservative substitutions), but no more than 30, 20, or 10 modifications, e.g., substitutions (e.g., conservative substitutions), relative to the amino acid sequence of SEQ ID NO: 981 or 982.

[0465] 471. The AAV capsid variant of any one of embodiments 1 to 470, comprising an amino acid sequence that contains at least 1, 2, or 3, but no more than 30, 20, or 10, different amino acids relative to the amino acid sequence of SEQ ID NO: 981 or 982.

[0466] 472. The amino acid sequence of SEQ ID NO: 981, or an amino acid sequence having at least 80% (e.g., at least about 85, 90, 95, 96, 97, 98, or 99%) sequence identity thereto, of embodiments 1-23, 26-29, 32, 35-43, 46-51, 54-72, 69-89, 91, 94-99, 102-104, 107, 110-112, 115-129, 168- 202, 02, 240-247, 249, 250, 253-263, 266, 272-281, 286, 288, 291-299, 327-363, 369-371, 375-379, 385, 386, 390, 391, 395, 406, 408, 410-413, 415-432, 444, 446-463, or 469-471.

[0467] 473. The amino acid sequence of any of embodiments 1 to 23, 26 to 29, 32, 35 to 43, 46 to 51, 54 to 72, 69 to 89, 91, 94 to 99, 102 to 104, 107, 110 to 112, 1 ... 15-129, 168-202, 02, 240-247, 249, 250, 253-263, 266, 272-281, 286, 288, 291-299, 327-363, 369-371, 375-379, 385, 386, 390, 391, 395, 406, 408, 410-413, 415-432, 444, 446-463, or 469-472.

[0468] 474. Embodiments 1-23, 26-29, 32, 35-43, 46-51, 54-72, 69-89, 91, 94-99, 102-104, 107, 110-112, 115-129, 168-202, 02, including amino acid sequences containing at least 1, 2, or 3, but not more than 30, 20, or 10, different amino acids relative to the amino acid sequence of SEQ ID NO: 981. , 240-247, 249, 250, 253-263, 266, 272-281, 286, 288, 291-299, 327-363, 369-371, 375-379, 385, 386, 390, 391, 395, 406, 408, 410-413, 415-432, 444, 446-463, or 469-473.

[0469] 475. Embodiments 1-9, 11, 12-22, 24, 26, 28, 30, 33, 35-42, 44, 46-50, 52, 54-77, 83-88, 90-97, 100-103, 105, 110, 111, 113-129, comprising the amino acid sequence of SEQ ID NO: 982, or an amino acid sequence having at least 80% (e.g., at least about 85, 90, 95, 96, 97, 98, or 99%) sequence identity thereto; 203-248, 251, 252, 254-257, 260, 261, 264-280, 283-287, 289-299, 327-363, 369, 369, 371, 380-383, 385, 386, 390, 392, 395, 407, 409-412, 414, 433-435, 438-441, 443, 445, 447-458, or 464-471.

[0470] 476. Embodiments 1 to 9, 11, 12 to 22, 24, 26, 28, 30, 33, 35 to 42, 44, 46 to 50, 52, 54 to 77, 83 to 88, 90 to 97, 100 to 103, 105, 110, 111, including amino acid sequences containing at least 1, 2, or 3 modifications, e.g., substitutions (e.g., conservative substitutions), but no more than 30, 20, or 10 modifications, e.g., substitutions (e.g., conservative substitutions), relative to the amino acid sequence of SEQ ID NO: 982. , 113-129, 203-248, 251, 252, 254-257, 260, 261, 264-280, 283-287, 289-299, 327-363, 369, 369, 371, 380-383, 385, 386, 390, 392, 395, 407, 409-412, 414, 433-435, 438-441, 443, 445, 447-458, 464-471, or 475.

[0471] 477. Embodiments 1-9, 11, 12-22, 24, 26, 28, 30, 33, 35-42, 44, 46-50, 52, 54-77, 83-88, 90-97, 100-103, 105, 110, 111, 113-129, 203-248, 25 ...29, 30, 31, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 1, 252, 254-257, 260, 261, 264-280, 283-287, 289-299, 327-363, 369, 369, 371, 380-383, 385, 386, 390, 392, 395, 407, 409-412, 414, 433-435, 438-441, 443, 445, 447-458, 464-471, 475, or 476.

[0472] 478. The AAV capsid variant of any one of embodiments 1 to 477, comprising an amino acid sequence encoded by the nucleotide sequence of SEQ ID NO: 983 or 984, or a nucleotide sequence having at least 80% (e.g., at least about 85, 90, 95, 96, 97, 98, or 99%) sequence identity thereto.

[0473] 479. The AAV capsid variant of any one of the preceding embodiments 1 to 478, wherein the nucleotide sequence encoding the capsid variant comprises the nucleotide sequence of SEQ ID NO: 983 or 984, or a nucleotide sequence having at least 80% (e.g., at least about 85, 90, 95, 96, 97, 98, or 99%) sequence identity thereto.

[0474] 480. The preceding embodiments 1-23, 26-29, 32, 35-43, 46-51, 54-72, 69-89, 91, 94-99, 102-104, 107, 110-112, wherein the nucleotide sequence encoding the capsid variant comprises the nucleotide sequence of SEQ ID NO: 983, or a nucleotide sequence having at least 80% (e.g., at least about 85, 90, 95, 96, 97, 98, or 99%) sequence identity thereto. 115-129, 168-202, 02, 240-247, 249, 250, 253-263, 266, 272-281, 286, 288, 291-299, 327-363, 369-371, 375-379, 385, 386, 390, 391, 395, 406, 408, 410-413, 415-432, 444, 446-463, 469-474, 478, or 479.

[0475] 481. The preceding embodiments 1-9, 11, 12-22, 24, 26, 28, 30, 33, 35-42, 44, 46-50, 52, 54-77, 83-88, 90-97, 100-103, 105, 110, wherein the nucleotide sequence encoding the capsid variant comprises the nucleotide sequence of SEQ ID NO: 984, or a nucleotide sequence having at least 80% (e.g., at least about 85, 90, 95, 96, 97, 98, or 99%) sequence identity thereto. 111, 113-129, 203-248, 251, 252, 254-257, 260, 261, 264-280, 283-287, 289-299, 327-363, 369, 369, 371, 380-383, 385, 386, 390, 392, 395, 407, 409-412, 414, 433-435, 438-441, 443, 445, 447-458, 464-471, or 475-479.

[0476] 482. The AAV capsid variant of any one of the preceding embodiments, wherein the nucleotide sequence encoding the capsid variant is codon-optimized. 483. Embodiments 1-23, 26-29, 32, 35-43, 46-51, 54-72, 69-89, 91, 94-99, 102-104, 107, 110-112, 115-129, 168-202, 02, 240-247, 249, 250, 253-263, 266, 272-281, 286, 288, 291-299, 327-363, 36 An AAV capsid variant comprising an amino acid sequence set forth in any one of SEQ ID NO: 9-371, 375-379, 385, 386, 390, 391, 395, 406, 408, 410-413, 415-432, 444, 446-463, 469-474, 478-480, or 482, and further comprising an amino acid sequence at least 95% identical to SEQ ID NO: 981.

[0477] 484. An AAV capsid variant comprising the amino acid sequence of SEQ ID NO: 981. 485. The AAV capsid variant of embodiment 483 or 484, wherein the nucleotide sequence encoding the AAV capsid variant comprises the nucleotide sequence of SEQ ID NO: 983, or a nucleotide sequence at least 90%, 95%, or 99% identical thereto.

[0478] 486. Embodiments 1-9, 11, 12-22, 24, 26, 28, 30, 33, 35-42, 44, 46-50, 52, 54-77, 83-88, 90-97, 100-103, 105, 110, 111, 113-129, 203-248, 251, 252, 254-257, 260, 261, 264-280, 283-287, 289-299, 327-363, 369, 369 , 371, 380-383, 385, 386, 390, 392, 395, 407, 409-412, 414, 433-435, 438-441, 443, 445, 447-458, 464-471, 475-479, 481, or 482, and further comprising an amino acid sequence at least 95% identical to SEQ ID NO: 982.

[0479] 487. An AAV capsid variant comprising the amino acid sequence of SEQ ID NO: 982. 488. The AAV capsid variant of embodiment 486 or 487, wherein the nucleotide sequence encoding the AAV capsid variant comprises the nucleotide sequence of SEQ ID NO: 984, or a nucleotide sequence at least 90%, 95%, or 99% identical thereto.

[0480] 489. An AAV capsid variant comprising an amino acid sequence encoded by the nucleotide sequence of SEQ ID NO: 983 or 984, or a nucleotide sequence at least 95% identical thereto.

[0481] 490. An AAV capsid variant comprising the amino acid sequence of any one of SEQ ID NOs: 36 to 59. 491. An AAV capsid variant comprising an amino acid sequence encoded by the nucleotide sequence of any one of SEQ ID NOs: 12-35, or a nucleotide sequence at least 95% identical thereto.

[0482] 492. The AAV capsid variant of 490 or 491, wherein the nucleotide sequence encoding the AAV capsid variant comprises the nucleotide sequence of any one of SEQ ID NOs: 12-35, or a nucleotide sequence at least 95% identical thereto.

[0483] 493. The AAV capsid variant of any one of embodiments 1 to 299, 369 to 371, or 375 to 492, having increased tropism for CNS cells or tissue, e.g., brain cells, brain tissue, spinal cord cells, or spinal cord tissue, compared to the tropism of a reference sequence comprising the amino acid sequence of SEQ ID NO: 138.

[0484] 494. The AAV capsid variant of any one of embodiments 1-129, 168-299, 369-371, or 375-493, which transduces a brain region, e.g., a midbrain region (e.g., the hippocampus, or the thalamus), or the brainstem, and optionally, the level of transduction is at least 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, or 65 times greater compared to the reference sequence of SEQ ID NO: 138, for example, as measured by an assay, e.g., an immunohistochemistry assay, or a qPCR assay, e.g., as described in Example 2.

[0485] 495. The AAV capsid variant of any one of embodiments 1-129, 168-299, 369-371, or 375-494, which transduces a brain region, e.g., a midbrain region (e.g., the hippocampus, or the thalamus), or the brainstem, and optionally, the level of transduction is at least 30, 35, 40, 45, 50, 55, 60, or 65 times greater compared to the reference sequence of SEQ ID NO: 138, e.g., as measured, e.g., by an assay, e.g., an immunohistochemistry assay, or a qPCR assay, e.g., as described in Example 2.

[0486] 496. The AAV capsid variant of any one of embodiments 1-129, 168-299, 369-371, or 375-495, which is enriched in the brain by at least about 3, 4, 5, 6, 7, 8, 9, or 10-fold compared to the reference sequence of SEQ ID NO: 138, e.g., as measured by the assay described in Example 1.

[0487] 497. The AAV capsid variant of any one of embodiments 1-129, 168-299, 369-371, or 375-496, which is enriched in the brain by at least about 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, or 85-fold compared to the reference sequence of SEQ ID NO: 138, e.g., as measured by the assay described in Example 1.

[0488] 498. The AAV capsid variant of any one of embodiments 1-129, 168-299, 369-371, or 375-497, which is enriched in the brain of at least two to three species, e.g., a non-human primate and a rodent (e.g., a mouse), for example, compared to the reference sequence of SEQ ID NO: 138.

[0489] 499. The AAV capsid variant of any one of embodiments 1-129, 168-299, 369-371, or 375-498, which is enriched in the brain of at least two to three species, e.g., non-human primates and rodents (e.g., mice), by at least about 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180, 190, 200, 205, or 210-fold compared to the reference sequence of SEQ ID NO: 138, e.g., as measured by an assay described in Example 1 or 5.

[0490] 500. The AAV capsid variant of embodiment 498 or 499, wherein at least two to three species are Macaca fascicularis, Chlorocebus sabaeus, Callithrix jacchus, and / or mouse (e.g., BALB / c mouse, C57Bl / 6 mouse, and / or CD-1 outbred mouse).

[0491] 501. The AAV capsid variant of any one of embodiments 130-146, 369, 410-414, 447-454, 457, 458, 482, or 493, which is enriched in the brain by at least about 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, or 8-fold compared to the reference sequence of SEQ ID NO: 981, e.g., as measured by the assay described in Example 3.

[0492] 502. The AAV capsid variant of any one of embodiments 147-167, 369, 410-414, 447-454, 457, 458, 482, or 493, which is enriched in the brain by at least about 2, 2.5, 3, 3.5, 4, 4.5, 5, or 5.5-fold compared to the reference sequence of SEQ ID NO: 982, e.g., as measured by the assay described in Example 3.

[0493] 503. The AAV capsid variant of any one of embodiments 1-129, 168-299, 369-371, or 375-500, which delivers increased levels of payload to a brain region, and optionally, the level of payload is increased by at least 10, 12, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, or 70 fold compared to the reference sequence of SEQ ID NO: 138, e.g., as measured by an assay, e.g., a qRT-PCR or qPCR assay (e.g., as described in Example 2 or 8).

[0494] 504. The AAV capsid variant of any one of embodiments 1-129, 168-299, 369-371, 375-500, or 503, which delivers increased levels of viral genomes to brain regions, and optionally, the level of viral genomes is increased by at least 5, 10, 15, 17, 18, 19, 20, 25, 30, 35, 40, 45, or 50 fold compared to the reference sequence of SEQ ID NO: 138, e.g., as measured by an assay, e.g., a qRT-PCR or qPCR assay (e.g., as described in Example 2 or 8).

[0495] 505. The AAV capsid variant of embodiment 504 or 504, wherein the brain region is the midbrain region (e.g., the hippocampus or thalamus), the frontal cortex, the temporal cortex, the motor cortex, the cerebral cortex, the caudate cortex, the nucleus palpebrae, the dentate nucleus, the substantia nigra, or the brainstem.

[0496] 506. The AAV capsid variant of any one of embodiments 1-129, 168-299, 369-371, 375-500, or 503-505, which is enriched in the spinal cord by at least about 4, 5, 10, 15, 20, 25, 30, or 35-fold compared to the reference sequence of SEQ ID NO: 138, e.g., as measured by an assay such as that described in Example 1 or 8, and optionally the region of the spinal cord is the thoracic spinal cord region, the cervical spinal cord region, the C5 anterior horn region, the lumbar spinal cord region, or the L5 anterior horn region.

[0497] 507. An AAV capsid variant according to any one of embodiments 1-129, 168-299, 369-371, 375-500, or 503-506, which exhibits preferential transduction in brain regions compared to transduction in dorsal root ganglia (DRG).

[0498] 508. An AAV capsid variant according to any one of embodiments 1-129, 168-299, 369-371, 375-500, or 503-507, which exhibits preferential transduction in brain regions compared to the liver.

[0499] 509. An AAV capsid variant according to any one of embodiments 1-129, 168-299, 369-371, 375-500, or 503-508, which exhibits preferential transduction in brain regions compared to transduction in the heart.

[0500] 510. An AAV capsid variant according to any one of embodiments 1-129, 168-299, 369-371, 375-500, or 503-509, which exhibits preferential transduction in brain regions compared to transduction in the dorsal root ganglia (DRG) and heart.

[0501] 511. The AAV capsid variant of any one of the preceding embodiments, which is capable of transducing a non-neuronal cell, e.g., a glial cell (e.g., an oligodendrocyte or an astrocyte).

[0502] 512. The AAV capsid variant of embodiment 511, wherein the non-neuronal cells comprise glial cells, oligodendrocytes (e.g., Olig2-positive oligodendrocytes), or astrocytes (e.g., Olig2-positive astrocytes).

[0503] 513. The AAV capsid variant of any one of the preceding embodiments, which is capable of transducing Olig2-positive cells, such as Olig2-positive astrocytes or Olig2-positive oligodendrocytes.

[0504] 514. The AAV capsid variant of any one of embodiments 369, 373, 447-454, 457, 458, or 482, having increased tropism for cardiac cells or tissues, e.g., the ventricles or atria, compared to the tropism of the reference sequence of SEQ ID NO: 138.

[0505] 515. The AAV capsid variant of any one of embodiments 369, 373, 447-454, 457, 458, 482, or 514, which is enriched in the heart by at least about 4, 5, 8, 10, 11, 12, 13, 14, 18, 19, 20, 21, 22, 24, 25, 27, 31, 33, or 34-fold compared to the reference sequence of SEQ ID NO: 138, e.g., as measured by the assay described in Example 4.

[0506] 516. An AAV capsid variant according to any one of embodiments 369, 374, 447-454, 457, 458, 482, having increased tropism for muscle cells or tissue (e.g., quadriceps cells or quadriceps tissue) compared to the tropism of a reference sequence comprising the amino acid sequence of SEQ ID NO: 138.

[0507] 517. The AAV capsid variant of any one of embodiments 369, 374, 447-454, 457, 458, 482, which is enriched in muscle by at least about 4, 5, 8, 12, 17, 18, 20, 26, 27, 28, 30, or 36-fold compared to the reference sequence of SEQ ID NO: 138, e.g., as measured by the assay described in Example 4.

[0508] 518. The AAV capsid variant of embodiment 516 or 517, wherein the muscle cell or tissue is myocardium (e.g., ventricle or atrium, or both), quadriceps, or both.

[0509] 519. The AAV capsid variant of any one of the preceding embodiments, which is isolated, e.g., recombinant. 520. A polynucleotide encoding the AAV capsid variant of any one of embodiments 1 to 519.

[0510] 521. (i) a nucleotide sequence that contains at least 1, 2, 3, 4, 5, 6, or 7 modifications, e.g., substitutions (e.g., conservative substitutions), but not more than 10 modifications, e.g., substitutions (e.g., conservative substitutions), relative to the nucleotide sequence of SEQ ID NO: 3 or 942; (ii) a nucleotide sequence that contains at least 1, 2, 3, 4, 5, 6, or 7, but not more than 10, different nucleotides relative to the nucleotide sequence of SEQ ID NO: 3 or 942; or (iii) The polynucleotide of embodiment 520, comprising the nucleotide sequence of SEQ ID NO: 3 or 942, or a nucleotide sequence substantially identical thereto (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity).

[0511] 522. The polynucleotide of embodiment 520 or 521, comprising the nucleotide sequence of SEQ ID NO: 983 or 984, or a nucleotide sequence having at least 80% (e.g., at least about 85, 90, 95, 96, 97, 98, or 99%) sequence identity thereto.

[0512] 523. The polynucleotide of any one of embodiments 520-522, comprising a nucleotide sequence that is codon-optimized. 524. A peptide comprising an amino acid sequence having the following formula: [N1]-[N2]-[N3] according to any one of embodiments 1-8, 12-35, 39-45, 48-53, 91, or 118-123.

[0513] 525. A peptide comprising an amino acid sequence having the following formula: [A][B] according to any one of embodiments 130-133, 142, or 146. 526. A peptide comprising an amino acid sequence having the following formula: [A][B] according to any one of embodiments 147-150, 166 or 167.

[0514] 527. A peptide comprising an amino acid sequence having the following formula: [N1]-[N2]-[N3] according to any one of embodiments 168-176, 179-186, 191-195, 198-202, or 295-299.

[0515] 528. A peptide comprising an amino acid sequence having the following formula: [N1]-[N2]-[N3] according to any one of embodiments 203-211, 214-223, 228-231, 234-239, or 295-299.

[0516] 529. A peptide comprising an amino acid sequence having the following formula: [A]-[B] according to any one of embodiments 300-306, 316, 317, 322, or 326. 530. A peptide, (a) the amino acid sequence of any of the sequences provided in Tables 1, 2A, 2B, 13-19; (b) an amino acid sequence comprising at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 consecutive amino acids from any one of the sequences provided in Tables 1, 2A, 2B, and 13-19; (c) an amino acid sequence that contains at least 1, 2, or 3, but not more than 4, different amino acids from any one of the amino acid sequences provided in Tables 1, 2A, 2B, 13-19; or (d) A peptide comprising an amino acid sequence containing at least one, two, or three, but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), relative to any one of the amino acid sequences provided in Tables 1, 2A, 2B, 13-19.

[0517] 531. A peptide, (a) an amino acid sequence of any one of SEQ ID NOs: 3849 to 4051 or 4681 to 4693; (b) an amino acid sequence comprising at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 consecutive amino acids from any one of SEQ ID NOs: 3849-4051 or 4681-4693; (c) an amino acid sequence containing at least one, two, or three, but not more than four, different amino acids from any one of the amino acid sequences of SEQ ID NOs: 3849 to 4051 or 4681 to 4693; or (d) A peptide comprising an amino acid sequence containing at least one, two, or three, but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), relative to the amino acid sequence of any one of SEQ ID NOs: 3849-4051 or 4681-4693.

[0518] 532. A peptide, (a) any one of the amino acid sequences of SEQ ID NOs: 4052 to 4092; (b) an amino acid sequence comprising at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 consecutive amino acids from any one of SEQ ID NOs: 4052-4092; (c) an amino acid sequence containing at least one, two, or three, but not more than four, different amino acids from any one of the amino acid sequences of SEQ ID NOs: 4052 to 4092; or (d) A peptide comprising an amino acid sequence containing at least one, two, or three, but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), relative to the amino acid sequence of any one of SEQ ID NOs: 4052 to 4092.

[0519] 533. A peptide, (a) any amino acid sequence selected from SEQ ID NOs: 4056, 4058, 4059, 4062 to 4064, 4066, 4067, 4080, 4084, 4090, and 4095 to 4097; (b) an amino acid sequence comprising at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 consecutive amino acids from any one of SEQ ID NOs: 4056, 4058, 4059, 4062-4064, 4066, 4067, 4080, 4084, 4090, or 4095-4097; (c) an amino acid sequence containing at least one, two, or three, but not more than four, different amino acids from any one of the amino acid sequences of SEQ ID NOs: 4056, 4058, 4059, 4062 to 4064, 4066, 4067, 4080, 4084, 4090, or 4095 to 4097; or (d) A peptide comprising an amino acid sequence containing at least one, two, or three, but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), relative to the amino acid sequence of any one of SEQ ID NOs: 4056, 4058, 4059, 4062-4064, 4066, 4067, 4080, 4084, 4090, or 4095-4097.

[0520] 534. A peptide, (a) an amino acid sequence of any one of SEQ ID NOs: 945 to 980 or 985 to 986; (b) an amino acid sequence comprising at least 3, 4, or 5 consecutive amino acids from any one of SEQ ID NOs: 945-980 or 985-986; (c) an amino acid sequence containing at least one, two, or three, but not more than four, different amino acids from any one of the amino acid sequences of SEQ ID NOs: 945 to 980 or 985 to 986; or (d) A peptide comprising an amino acid sequence containing at least one, two, or three, but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), relative to the amino acid sequence of any one of SEQ ID NOs: 945-980 or 985-986.

[0521] 535. A peptide, (a) any one of the amino acid sequences of SEQ ID NOs: 2, 200, 201, 941, 943, 204, 208, 404, and 903 to 909; (b) an amino acid sequence comprising at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or 13 consecutive amino acids from any one of SEQ ID NOs: 2, 200, 201, 941, 943, 204, 208, 404, or 903-909; (c) an amino acid sequence containing at least one, two, or three, but not more than four, different amino acids from any one of the amino acid sequences of SEQ ID NOs: 2, 200, 201, 941, 943, 204, 208, 404, or 903 to 909; or (d) A peptide comprising an amino acid sequence containing at least one, two, or three, but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), relative to the amino acid sequence of any one of SEQ ID NOs: 2, 200, 201, 941, 943, 204, 208, 404, or 903-909.

[0522] 536. A peptide, (i) the amino acid sequence of SPHSKA (SEQ ID NO: 941); (ii) an amino acid sequence that contains at least one, two, or three, but not more than four, amino acids that differ from the amino acid sequence of SPHSKA (SEQ ID NO: 941); (iii) an amino acid sequence that contains at least one, two, or three modifications, e.g., substitutions (e.g., conservative substitutions), but no more than four modifications, e.g., substitutions (e.g., conservative substitutions), relative to the amino acid sequence of SPHSKA (SEQ ID NO: 941); or (iv) A peptide comprising at least 3, 4, or 5 consecutive amino acids from the amino acid sequence of SPHSKA (SEQ ID NO: 941).

[0523] 537. A peptide, (i) the nucleotide sequence of SEQ ID NO: 942, or a nucleotide sequence substantially identical thereto (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity); (ii) a nucleotide sequence that contains at least 1, 2, 3, 4, 5, 6, or 7, but not more than 10, different nucleotides relative to the nucleotide sequence of SEQ ID NO: 942; or (iii) A peptide encoded by a nucleotide sequence containing at least 1, 2, 3, 4, 5, 6, or 7 modifications, e.g., substitutions (e.g., conservative substitutions), but not more than 10 modifications, e.g., substitutions (e.g., conservative substitutions), relative to the nucleotide sequence of SEQ ID NO: 942.

[0524] 538. The nucleotide sequence encoding the peptide is (i) the nucleotide sequence of SEQ ID NO: 942, or a nucleotide sequence substantially identical thereto (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity); (ii) a nucleotide sequence that contains at least 1, 2, 3, 4, 5, 6, or 7, but not more than 10, different nucleotides relative to the nucleotide sequence of SEQ ID NO: 942; or (iii) A peptide comprising a nucleotide sequence containing at least 1, 2, 3, 4, 5, 6, or 7 modifications, e.g., substitutions (e.g., conservative substitutions), but not more than 10 modifications, e.g., substitutions (e.g., conservative substitutions), relative to the nucleotide sequence of SEQ ID NO: 942.

[0525] 539. A peptide, (i) the amino acid sequence of HDSPHK (SEQ ID NO: 2); (ii) an amino acid sequence that contains at least one, two, or three, but not more than four, amino acids that differ from the amino acid sequence of HDSPHK (SEQ ID NO: 2); (iii) an amino acid sequence that contains at least one, two, or three modifications, e.g., substitutions (e.g., conservative substitutions), but no more than four modifications, e.g., substitutions (e.g., conservative substitutions), relative to the amino acid sequence of HDSPHK (SEQ ID NO: 2); or (iv) A peptide comprising at least 3, 4, or 5 consecutive amino acids from the amino acid sequence of HDSPHK (SEQ ID NO: 2).

[0526] 540. A peptide, (i) the nucleotide sequence of SEQ ID NO: 3, or a nucleotide sequence substantially identical thereto (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity); or (ii) a nucleotide sequence that contains at least 1, 2, 3, 4, 5, 6, or 7, but not more than 10, different nucleotides relative to the nucleotide sequence of SEQ ID NO:3; (iii) A peptide encoded by a nucleotide sequence containing at least 1, 2, 3, 4, 5, 6, or 7 modifications, e.g., substitutions (e.g., conservative substitutions), but not more than 10 modifications, e.g., substitutions (e.g., conservative substitutions), relative to the nucleotide sequence of SEQ ID NO:3.

[0527] 541. The nucleotide sequence encoding the peptide is (i) the nucleotide sequence of SEQ ID NO: 3, or a nucleotide sequence substantially identical thereto (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity); (ii) a nucleotide sequence that contains at least 1, 2, 3, 4, 5, 6, or 7, but not more than 10, different nucleotides relative to the nucleotide sequence of SEQ ID NO: 3; or (iii) A peptide comprising a nucleotide sequence containing at least 1, 2, 3, 4, 5, 6, or 7 modifications, e.g., substitutions (e.g., conservative substitutions), but not more than 10 modifications, e.g., substitutions (e.g., conservative substitutions), relative to the nucleotide sequence of SEQ ID NO: 3.

[0528] 542. A peptide, (i) the amino acid sequence of KTERVSGSPHSKAQNQQT (SEQ ID NO: 3589); (ii) an amino acid sequence that contains at least one, two, or three, but not more than four, amino acids that differ from the amino acid sequence of KTERVSGSPHSKAQNQQT (SEQ ID NO: 3589); (iii) an amino acid sequence that contains at least one, two, or three modifications, e.g., substitutions (e.g., conservative substitutions), but no more than four modifications, e.g., substitutions (e.g., conservative substitutions), relative to the amino acid sequence of KTERVSGSPHSKAQNQQT (SEQ ID NO: 3589); or (iv) A peptide comprising at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 consecutive amino acids from the amino acid sequence of KTERVSGSPHSKAQNQQT (SEQ ID NO: 3589).

[0529] 543. A peptide, (i) the amino acid sequence of KAEIGHDSPHKSGQNQQT (SEQ ID NO: 1754); (ii) an amino acid sequence that contains at least one, two, or three, but not more than four, amino acids that differ from the amino acid sequence of KAEIGHDSPHKSGQNQQT (SEQ ID NO: 1754); (iii) an amino acid sequence that contains at least one, two, or three modifications, e.g., substitutions (e.g., conservative substitutions), but no more than four modifications, e.g., substitutions (e.g., conservative substitutions), relative to the amino acid sequence of KAEIGHDSPHKSGQNQQT (SEQ ID NO: 1754); or (iv) A peptide comprising at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 consecutive amino acids from the amino acid sequence of KAEIGHDSPHKSGQNQQT (SEQ ID NO: 1754).

[0530] 544. The peptide according to any one of embodiments 524-543, which is fused or attached, e.g., conjugated, to an active agent, e.g., a therapeutic or diagnostic agent.

[0531] 545. The peptide according to any one of embodiments 524 to 544, wherein at least 1 to 5, e.g., at least 1, 2, 3, 4, or 5, peptides are fused or linked, e.g., conjugated, to an active agent, e.g., a therapeutic or diagnostic agent.

[0532] 546. The peptide according to embodiment 545, wherein at least 1 to 5, for example at least 1, 2, 3, 4, or 5, peptides comprise the same amino acid sequence. 547. The peptide according to embodiment 454, wherein at least 1 to 5, for example at least 1, 2, 3, 4, or 5, peptides comprise different amino acid sequences.

[0533] 548. The peptide according to any one of embodiments 545-547, wherein at least 1-5, e.g., at least 1, 2, 3, 4, or 5, peptides are present in tandem (e.g., connected directly or indirectly via a linker) or in a multimeric configuration.

[0534] 549. The peptide according to any one of embodiments 524-548, wherein the peptide comprises an amino acid sequence of at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 20, 25, 30, or 35 amino acids in length.

[0535] 550. The peptide of any one of embodiments 544-549, wherein the active agent is or comprises a therapeutic agent selected from a protein (e.g., an enzyme), an antibody molecule, a nucleic acid molecule (e.g., an RNAi agent), or a small molecule.

[0536] 551. The peptide of any one of embodiments 544 to 549, wherein the active agent is or comprises a ribonucleic acid complex (e.g., a Cas9 / gRNA complex), a plasmid, a closed-end DNA, a circ-RNA, or an mRNA.

[0537] 552. The peptide of any one of embodiments 544-549, wherein the active agent is an RNAi agent. 553. The peptide of embodiment 552, wherein the RNAi agent is a dsRNA, siRNA, shRNA, pre-miRNA, pri-miRNA, miRNA, stRNA, lncRNA, piRNA, antisense oligonucleotide agent (ASO), or snoRNA, optionally wherein the RNAi agent is an siRNA or ASO, and further optionally comprises at least one modified nucleotide.

[0538] 554. The peptide of any one of embodiments 544-553, wherein the active agent modulates, e.g., inhibits, decreases, or increases, the expression of a CNS-related gene, mRNA, and / or protein.

[0539] 555. The peptide of any one of embodiments 544-449, wherein the active agent is or comprises a diagnostic and imaging agent (e.g., a protein or small molecule compound bound to a detectable moiety).

[0540] 556. The peptide according to any one of embodiments 544-555, wherein the peptide is covalently attached to the active agent directly or indirectly, for example via a linker. 557. The peptide according to any one of embodiments 544-556, wherein the peptide is conjugated to the active agent via a linker.

[0541] 558. The peptide according to embodiment 557, wherein the linker is a cleavable linker or a non-cleavable linker. 559. The peptide according to embodiment 558, wherein the cleavable linker is a pH-sensitive linker or an enzyme-sensitive linker.

[0542] 560. (i) the pH-sensitive linker comprises a hydrazine / hydrazone linker or a disulfide linker; (ii) the enzyme-sensitive linker comprises a peptide-based linker, e.g., a peptide linker that is sensitive to a protease (e.g., a lysosomal protease), or a beta-glucuronide linker; or (iii) The peptide of embodiment 558 or 559, wherein the non-cleavable linker is a linker comprising a thioether group or a maleimidocaproyl group.

[0543] 561. (i) the peptide and active agent are post-translationally fused or conjugated, for example, using click chemistry; or (ii) The peptide of any one of embodiments 544 to 560, wherein the peptide and the active agent are fused or conjugated via chemically induced dimerization.

[0544] 562. The peptide of any one of embodiments 544-561, wherein the peptide is N-terminal to the active agent. 563. The peptide of any one of embodiments 544-561, wherein the peptide is C-terminal to the active agent.

[0545] 564. The peptide of any one of embodiments 544-549, 554, or 556-56, wherein the peptide is present in or bound to a carrier, e.g., an exosome, microvesicle, or lipid nanoparticle (LNP), and optionally the carrier comprises a therapeutic agent (e.g., an RNAi agent (e.g., dsRNA, siRNA, shRNA, pre-miRNA, pri-miRNA, miRNA, stRNA, lncRNA, piRNA, antisense oligonucleotide agent (ASO), or snoRNA), mRNA, a ribonucleoprotein complex (e.g., Cas9 / gRNA complex), or a circular RNA).

[0546] 565. The peptide according to embodiment 564, wherein the peptides are present on the surface of the carrier, and optionally at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, or 80% of the surface of the carrier comprises at least 1 to 5, for example at least 1, 2, 3, 4, or 5, peptides according to any one of embodiments 422 to 436.

[0547] 566. An AAV capsid variant comprising a peptide according to any one of embodiments 524 to 543. 567. A polynucleotide encoding an AAV capsid variant, (a) the amino acid sequence of any of the sequences provided in Tables 1, 2A, 2B, 13-19; (b) an amino acid sequence comprising at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 consecutive amino acids from any one of the sequences provided in Tables 1, 2A, 2B, and 13-19; (c) an amino acid sequence that contains at least 1, 2, or 3, but not more than 4, different amino acids from any one of the amino acid sequences provided in Tables 1, 2A, 2B, 13-19; or (d) an amino acid sequence containing at least one, two, or three, but no more than four modifications, e.g., substitutions (e.g., conservative substitutions), relative to any one of the amino acid sequences provided in Tables 1, 2A, 2B, 13-19; Optionally, the amino acid sequence of (a), (b), (c), and / or (d) is located immediately after position 448, 449, 450, 451, 452, 453, 454, or 455 relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138, 981, or 982.

[0548] 568. A polynucleotide encoding an AAV capsid variant, wherein the AAV capsid variant is (i) the amino acid sequence of SPHSKA (SEQ ID NO: 941); (ii) an amino acid sequence that contains at least one, two, or three, but not more than four, amino acids that differ from the amino acid sequence of SPHSKA (SEQ ID NO: 941); (iii) an amino acid sequence that contains at least one, two, or three modifications, e.g., substitutions (e.g., conservative substitutions), but no more than four modifications, e.g., substitutions (e.g., conservative substitutions), relative to the amino acid sequence of SPHSKA (SEQ ID NO: 941); or (iv) comprises at least 3, 4, 5, 6, 7, 8, or 9 consecutive amino acids from the amino acid sequence of SPHSKA (SEQ ID NO: 941); Optionally, the amino acid sequence of (i), (ii), (iii), and / or (iv) is located immediately after position 455 relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.

[0549] 569. (i) the nucleotide sequence of SEQ ID NO: 942, or a nucleotide sequence substantially identical thereto (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity); (ii) a nucleotide sequence that contains at least 1, 2, 3, 4, 5, 6, or 7 modifications, e.g., substitutions (e.g., conservative substitutions), but not more than 10 modifications, e.g., substitutions (e.g., conservative substitutions), relative to the nucleotide sequence of SEQ ID NO: 942; (iii) The polynucleotide of embodiment 567 or 568, comprising a nucleotide sequence containing at least 1, 2, 3, 4, 5, 6, or 7 modifications, e.g., substitutions (e.g., conservative substitutions), but not more than 10 modifications, e.g., substitutions (e.g., conservative substitutions), relative to the nucleotide sequence of SEQ ID NO: 942.

[0550] 570. A polynucleotide encoding an AAV capsid variant, wherein the AAV capsid variant is (i) the amino acid sequence of HDSPHK (SEQ ID NO: 2); (ii) an amino acid sequence that contains at least one, two, or three, but not more than four, amino acids that differ from the amino acid sequence of HDSPHK (SEQ ID NO: 2); (iii) an amino acid sequence that contains at least one, two, or three modifications, e.g., substitutions (e.g., conservative substitutions), but no more than four modifications, e.g., substitutions (e.g., conservative substitutions), relative to the amino acid sequence of HDSPHK (SEQ ID NO: 2); or (iv) comprises at least 3, 4, or 5 consecutive amino acids from the amino acid sequence of HDSPHK (SEQ ID NO: 2); Optionally, the amino acid sequence of (i), (ii), (iii), and / or (iv) is located immediately after position 453 relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.

[0551] 571. (i) the nucleotide sequence of SEQ ID NO: 3, or a nucleotide sequence substantially identical thereto (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity); (ii) a nucleotide sequence that contains at least 1, 2, 3, 4, 5, 6, or 7, but not more than 10, different nucleotides relative to the nucleotide sequence of SEQ ID NO:3; (iii) The polynucleotide of any one of embodiments 567 or 570, comprising a nucleotide sequence containing at least 1, 2, 3, 4, 5, 6, or 7 modifications, e.g., substitutions (e.g., conservative substitutions), but not more than 10 modifications, e.g., substitutions (e.g., conservative substitutions), relative to the nucleotide sequence of SEQ ID NO: 3.

[0552] 572.AAV capsid variant, (i) the amino acid sequence of SEQ ID NO: 981 or 982, or an amino acid sequence having at least 80% (e.g., at least about 85, 90, 95, 96, 97, 98, or 99%) sequence identity thereto; (ii) an amino acid sequence that has at least one, two, or three, but not more than four, amino acids that differ from the amino acid sequence of SEQ ID NO: 981 or 982; or (iii) The polynucleotide of any one of embodiments 567 to 571, comprising an amino acid sequence having at least one, two, or three modifications, e.g., substitutions (e.g., conservative substitutions), but not more than 30, 20, or 10 modifications, e.g., substitutions (e.g., conservative substitutions), relative to the amino acid sequence of SEQ ID NO: 981 or 982.

[0553] 573. The polynucleotide of any one of embodiments 567-572, comprising the nucleotide sequence of SEQ ID NO: 983 or 984, or a nucleotide sequence having at least 80% (e.g., at least about 85, 90, 95, 96, 97, 98, or 99%) sequence identity thereto.

[0554] 574. The polynucleotide, peptide, or AAV capsid variant of any one of embodiments 1 to 573, which is isolated, e.g., recombinant. 575. An AAV particle comprising an AAV capsid variant described in any one of embodiments 1 to 519, 566, or 574.

[0555] 576. The AAV particle of embodiment 575, comprising a nucleotide sequence encoding a payload. 577. The AAV particle of embodiment 576, wherein the encoded payload comprises a therapeutic protein or a functional variant thereof, an antibody or antibody fragment, an enzyme, a component of a gene editing system, an RNAi agent (e.g., dsRNA, siRNA, shRNA, pre-miRNA, pri-miRNA, miRNA, stRNA, lncRNA, piRNA, or snoRNA), or a combination thereof.

[0556] 578. The AAV particle of embodiment 577, wherein the therapeutic protein or functional variant thereof, e.g., recombinant protein, is associated with (e.g., is aberrantly expressed by) a neurological or neurodegenerative disorder, a muscular or neuromuscular disorder, or a neuro-oncological disorder.

[0557] 579. The AAV particle of embodiment 577 or 578, wherein the therapeutic protein or functional variant thereof is selected from apolipoprotein E (APOE) (e.g., ApoE2, ApoE3, and / or ApoE4), survival of human motor neuron (SMN) 1 or SMN2, glucocerebrosidase (GBA1), aromatic L-amino acid decarboxylase (AADC), aspartoacylase (ASPA), tripeptidyl peptidase I (CLN2), beta-galactosidase (GLB1), N-sulfoglucosamine sulfohydrolase (SGSH), N-acetyl-alpha-glucosaminidase (NAGLU), iduronate 2-sulfatase (IDS), intracellular cholesterol transporter (NPC1), gigaxonin (GAN), or a combination thereof.

[0558] 580.An antibody or antibody-binding fragment is (i) CNS-related targets, e.g., antigens associated with neurological or neurodegenerative disorders, e.g., β-amyloid, APOE, tau, SOD1, TDP-43, huntingtin (HTT), and / or synuclein; (ii) a muscle- or neuromuscular-related target, e.g., an antigen associated with a muscle disorder or a neuromuscular disorder; or (iii) An AAV particle described in embodiment 577, which binds to a neuro-oncology-associated target, e.g., an antigen associated with a neuro-oncology disorder, e.g., HER2, or EGFR (e.g., EGFRvIII).

[0559] 581. The AAV particle of embodiment 577, wherein the enzyme comprises a meganuclease, zinc finger nuclease, TALEN, recombinase, integrase, base editor, Cas9, or a fragment thereof.

[0560] 582. The AAV particle of embodiment 577, wherein the components of the gene editing system include one or more components of a CRISPR-Cas system. 583. One or more components of the CRISPR-Cas system include Cas9, e.g., a Cas9 ortholog or Cpf1, and a single guide RNA (sgRNA), and optionally: (i) the sgRNA is located upstream (5') of the cas9 enzyme, or (ii) An AAV particle described in embodiment 582, wherein the sgRNA is located downstream (3') of the cas9 enzyme.

[0561] 584. The AAV particle of embodiment 577, wherein the RNAi agent (e.g., dsRNA, siRNA, shRNA, pre-miRNA, pri-miRNA, miRNA, stRNA, lncRNA, piRNA, or snoRNA) regulates, e.g., inhibits, the expression of, a CNS-related gene, mRNA, and / or protein.

[0562] 585. The AAV particle of embodiment 584, wherein the CNS-related gene is selected from SOD1, MAPT, APOE, HTT, C9ORF72, TDP-43, APP, BACE, SNCA, ATXN1, ATXN3, ATXN7, SCN1A-SCN5A, SCN8A-SCN11A, or a combination thereof.

[0563] 586. An AAV particle described in any one of embodiments 575 to 585, comprising a viral genome comprising a promoter operably linked to a nucleic acid sequence encoding a payload. 587. The promoter is selected from the group consisting of human elongation factor 1 α-subunit (EF1α), cytomegalovirus (CMV) immediate early enhancer and / or promoter, chicken β-actin (CBA) and its derivatives CAG, β-glucuronidase (GUSB), or ubiquitin C (UBC), neuron-specific enolase (NSE), platelet-derived growth factor (PDGF), platelet-derived growth factor B chain (PDGF-β), intercellular adhesion molecule 2 (ICAM-2), synapsin (Syn), methyl-CpG-binding protein 2 (MeCP2), Ca2+ / calmodulin-dependent protein kinase II (CaMKII), metabotropic glutamate receptor 2 (mG luR2), neurofilament light chain (NFL) or heavy chain (NFH), β-globin minigene nβ2, preproenkephalin (PPE), enkephalin (Enk) and excitatory amino acid transporter 2 (EAAT2), glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), cardiovascular promoters (e.g., αMHC, cTnT, and CMV-MLC2k), liver promoters (e.g., hAAT, TBG), skeletal muscle promoters (e.g., desmin, MCK, C512) or fragments thereof, e.g., truncated forms, or functional variants thereof.

[0564] 588. The AAV particle of embodiment 586 or 587, wherein the promoter is an EF-1a promoter variant, such as a truncated EF-1a promoter. 589. The promoter comprises the nucleotide sequence of any one of SEQ ID NOs: 987, 988, 990, 991, 995, 996, 998-1007, or any one of the sequences provided in Table 8; the nucleotide sequence of any one of SEQ ID NOs: 987, 988, 990, 991, 995, 996, 998-1007, or any one of the sequences provided in Table 8; For example, the AAV particle of any one of embodiments 586 to 588, comprising a nucleotide sequence that includes a substitution (e.g., a conservative substitution) or has at least 80% (e.g., 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to any one of SEQ ID NOs: 987, 988, 990, 991, 995, 996, 998-1007, or any one of the sequences provided in Table 8.

[0565] 590. The AAV particle of any one of embodiments 586 to 589, wherein the viral genome further comprises a polyA signal sequence. 591. The AAV particle of any one of embodiments 586 to 590, wherein the viral genome further comprises an inverted terminal repeat (ITR) sequence.

[0566] 592. An AAV particle described in any one of embodiments 586 to 591, wherein the viral genome comprises an ITR sequence located 5' to the encoded payload. 593. An AAV particle according to any one of embodiments 586 to 592, wherein the viral genome comprises an ITR sequence located 3' to the encoded payload.

[0567] 594. An AAV particle described in any one of embodiments 586 to 593, wherein the viral genome comprises an ITR sequence located 5' to the encoded payload and an ITR sequence located 3' to the encoded payload.

[0568] 595. An AAV particle described in any one of embodiments 586 to 594, wherein the viral genome further comprises an enhancer, a Kozak sequence, an intron region, and / or an exon region.

[0569] 596. An AAV particle described in any one of embodiments 586 to 594, wherein the viral genome further comprises a nucleotide sequence encoding an miR binding site, e.g., an miR binding site that regulates, e.g., reduces, the expression of an antibody molecule encoded by the viral genome in cells or tissues in which the corresponding miRNA is expressed.

[0570] 597. The AAV particle of embodiment 596, wherein the encoded miRNA binding site is complementary, e.g., fully complementary or partially complementary, to an miRNA expressed in cells or tissues of DRG, liver, heart, hematopoietic, or a combination thereof.

[0571] 598. The AAV particle of embodiment 596 or 597, wherein the encoded miR binding site regulates, e.g., reduces, expression of the encoded antibody molecule in cells or tissues of, for example, the DRG, liver, heart, hematopoietic system, or a combination thereof.

[0572] 599. An AAV particle described in any one of embodiments 586 to 598, wherein the viral genome comprises at least 1 to 5 copies of the encoded miR binding site, for example at least 1, 2, 3, 4, or 5 copies.

[0573] 600. An AAV particle described in any one of embodiments 586 to 599, wherein the viral genome comprises at least three copies of the encoded miR binding site, and optionally, all three copies comprise the same miR binding site, or at least one, two, three, or all of the copies comprise different miR binding sites.

[0574] 601. The AAV particle of embodiment 600, wherein the three copies of the encoded miR binding site are contiguous (e.g., not separated by a spacer) or separated by a spacer, and optionally the spacer comprises a nucleotide sequence of GATAGTTA or a nucleotide sequence having at least one, two, or three modifications, e.g., substitutions (e.g., conservative substitutions), but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), relative to the nucleotide sequence of GATAGTTA.

[0575] 602. An AAV particle described in any one of embodiments 586 to 601, wherein the viral genome comprises at least four copies of the encoded miR binding site, and optionally, all four copies comprise the same miR binding site, or at least one, two, three, or all of the copies comprise different miR binding sites.

[0576] 603. The AAV particle of embodiment 602, wherein the four copies of the encoded miR binding site are contiguous (e.g., not separated by a spacer) or separated by a spacer, and optionally the spacer comprises a nucleotide sequence of GATAGTTA or a nucleotide sequence having at least one, two, or three modifications, e.g., substitutions (e.g., conservative substitutions), but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), relative to the nucleotide sequence of GATAGTTA.

[0577] 604. The encoded miR binding site comprises a miR122 binding site, a miR183 binding site, a miR-1 binding site, a miR-142-3p, or a combination thereof, and optionally (i) the encoded miR122 binding site comprises the nucleotide sequence of SEQ ID NO: 4673, or a nucleotide sequence substantially identical thereto (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity), or a nucleotide sequence having at least 1, 2, 3, 4, 5, 6, or 7 modifications, e.g., substitutions (e.g., conservative substitutions), but not more than 10 modifications, e.g., substitutions (e.g., conservative substitutions), relative to SEQ ID NO: 4673; (ii) the encoded miR183 binding site comprises the nucleotide sequence of SEQ ID NO: 4676, or a nucleotide sequence substantially identical thereto (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity), or a nucleotide sequence having at least 1, 2, 3, 4, 5, 6, or 7 modifications, e.g., substitutions (e.g., conservative substitutions), but not more than 10 modifications, e.g., substitutions (e.g., conservative substitutions), relative to SEQ ID NO: 4676; (iii) the encoded miR-1 binding site comprises the nucleotide sequence of SEQ ID NO: 4679, or a nucleotide sequence substantially identical thereto (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity), or a nucleotide sequence having at least 1, 2, 3, 4, 5, 6, or 7 modifications, e.g., substitutions (e.g., conservative substitutions), but not more than 10 modifications, e.g., substitutions (e.g., conservative substitutions), relative to SEQ ID NO: 4679; and / or (iv) The AAV particle of any one of embodiments 596 to 603, wherein the encoded miR-142-3p binding site comprises the nucleotide sequence of SEQ ID NO: 4675, or a nucleotide sequence substantially identical thereto (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity), or a nucleotide sequence having at least 1, 2, 3, 4, 5, 6, or 7 modifications, e.g., substitutions (e.g., conservative substitutions), but not more than 10 modifications, e.g., substitutions (e.g., conservative substitutions), relative to SEQ ID NO: 4675.

[0578] 605. An AAV particle described in any one of embodiments 586 to 604, wherein the viral genome comprises an encoded miR122 binding site. 606. An AAV particle according to any one of embodiments 586 to 605, wherein the viral genome comprises at least 1 to 5 copies, e.g., 1, 2, or 3 copies, of the miR122 binding site, optionally wherein each copy is contiguous (e.g., not separated by a spacer) or each copy is separated by a spacer, and optionally wherein the spacer comprises a nucleotide sequence of GATAGTTA, or a nucleotide sequence having at least 1, 2, or 3 modifications, e.g., substitutions (e.g., conservative substitutions), but not more than 4 modifications, e.g., substitutions (e.g., conservative substitutions), relative to the nucleotide sequence of GATAGTTA.

[0579] 607. The AAV particle of embodiment 605 or 606, wherein the encoded miR122 binding site comprises the nucleotide sequence of SEQ ID NO: 4673, or a nucleotide sequence substantially identical thereto (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity), or a nucleotide sequence having at least 1, 2, 3, 4, 5, 6, or 7 modifications, e.g., substitutions (e.g., conservative substitutions), but not more than 10 modifications, e.g., substitutions (e.g., conservative substitutions), relative to SEQ ID NO: 4673.

[0580] 608. The viral genome is (A)(i) the first encoded miR122 binding site comprises the nucleotide sequence of SEQ ID NO: 4673, or a nucleotide sequence substantially identical thereto (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity), or a nucleotide sequence having at least 1, 2, 3, 4, 5, 6, or 7 modifications, e.g., substitutions (e.g., conservative substitutions), but not more than 10 modifications, e.g., substitutions (e.g., conservative substitutions), relative to SEQ ID NO: 4673; (ii) the first spacer comprises a nucleotide sequence of GATAGTTA or a nucleotide sequence having at least one, two, or three modifications, e.g., substitutions (e.g., conservative substitutions), but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), relative to the nucleotide sequence of GATAGTTA; (iii) the second encoded miR122 binding site comprises the nucleotide sequence of SEQ ID NO: 4673, or a nucleotide sequence substantially identical thereto (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity), or a nucleotide sequence having at least 1, 2, 3, 4, 5, 6, or 7 modifications, e.g., substitutions (e.g., conservative substitutions), but not more than 10 modifications, e.g., substitutions (e.g., conservative substitutions), relative to SEQ ID NO: 4673; or (B)(i) the first encoded miR122 binding site comprises the nucleotide sequence of SEQ ID NO: 4673, or a nucleotide sequence substantially identical thereto (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity), or a nucleotide sequence having at least 1, 2, 3, 4, 5, 6, or 7 modifications, e.g., substitutions (e.g., conservative substitutions), but not more than 10 modifications, e.g., substitutions (e.g., conservative substitutions), relative to SEQ ID NO: 4673; (ii) the first spacer comprises a nucleotide sequence of GATAGTTA or a nucleotide sequence having at least one, two, or three modifications, e.g., substitutions (e.g., conservative substitutions), but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), relative to the nucleotide sequence of GATAGTTA; (iii) the second encoded miR122 binding site comprises the nucleotide sequence of SEQ ID NO: 4673, or a nucleotide sequence substantially identical thereto (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity), or a nucleotide sequence having at least 1, 2, 3, 4, 5, 6, or 7 modifications, e.g., substitutions (e.g., conservative substitutions), but not more than 10 modifications, e.g., substitutions (e.g., conservative substitutions), relative to SEQ ID NO: 4673; (iv) the second spacer comprises a nucleotide sequence of GATAGTTA or a nucleotide sequence having at least one, two, or three modifications, e.g., substitutions (e.g., conservative substitutions), but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), relative to the nucleotide sequence of GATAGTTA; (v) The AAV particle of any one of embodiments 586 to 607, wherein the third encoded miR122 binding site comprises the nucleotide sequence of SEQ ID NO: 4673, or a nucleotide sequence substantially identical thereto (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity), or a nucleotide sequence having at least 1, 2, 3, 4, 5, 6, or 7 modifications, e.g., substitutions (e.g., conservative substitutions), but not more than 10 modifications, e.g., substitutions (e.g., conservative substitutions), relative to SEQ ID NO: 4673.

[0581] 609. An AAV particle described in any one of embodiments 586 to 608, wherein the viral genome comprises an encoded miR183 binding site. 610. The AAV particle of any one of embodiments 586 to 609, wherein the viral genome comprises at least 1 to 5 copies, e.g., 1, 2, or 3 copies, of the miR183 binding site, optionally wherein each copy is contiguous (e.g., not separated by a spacer) or each copy is separated by a spacer, and optionally wherein the spacer comprises the nucleotide sequence GATAGTTA, or a nucleotide sequence having at least 1, 2, or 3 modifications, e.g., substitutions (e.g., conservative substitutions), but not more than 4 modifications, e.g., substitutions (e.g., conservative substitutions), relative to the nucleotide sequence GATAGTTA.

[0582] 611. The AAV particle of embodiment 609 or 610, wherein the encoded miR183 binding site comprises the nucleotide sequence of SEQ ID NO: 4673, or a nucleotide sequence substantially identical thereto (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity), or a nucleotide sequence having at least 1, 2, 3, 4, 5, 6, or 7 modifications, e.g., substitutions (e.g., conservative substitutions), but not more than 10 modifications, e.g., substitutions (e.g., conservative substitutions), relative to SEQ ID NO: 4673.

[0583] 612. The viral genome is (A)(i) the first encoded miR183 binding site comprises the nucleotide sequence of SEQ ID NO: 4676, or a nucleotide sequence substantially identical thereto (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity), or a nucleotide sequence having at least 1, 2, 3, 4, 5, 6, or 7 modifications, e.g., substitutions (e.g., conservative substitutions), but not more than 10 modifications, e.g., substitutions (e.g., conservative substitutions), relative to SEQ ID NO: 4676; (ii) the first spacer comprises a nucleotide sequence of GATAGTTA or a nucleotide sequence having at least one, two, or three modifications, e.g., substitutions (e.g., conservative substitutions), but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), relative to the nucleotide sequence of GATAGTTA; (iii) the second encoded miR183 binding site comprises the nucleotide sequence of SEQ ID NO: 4676, or a nucleotide sequence substantially identical thereto (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity), or a nucleotide sequence having at least 1, 2, 3, 4, 5, 6, or 7 modifications, e.g., substitutions (e.g., conservative substitutions), but not more than 10 modifications, e.g., substitutions (e.g., conservative substitutions), relative to SEQ ID NO: 4676; or (B)(i) the first encoded miR183 binding site comprises the nucleotide sequence of SEQ ID NO: 4676, or a nucleotide sequence substantially identical thereto (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity), or a nucleotide sequence having at least 1, 2, 3, 4, 5, 6, or 7 modifications, e.g., substitutions (e.g., conservative substitutions), but not more than 10 modifications, e.g., substitutions (e.g., conservative substitutions), relative to SEQ ID NO: 4676; (ii) the first spacer comprises a nucleotide sequence of GATAGTTA or a nucleotide sequence having at least one, two, or three modifications, e.g., substitutions (e.g., conservative substitutions), but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), relative to GATAGTTA; (iii) the second encoded miR183 binding site comprises the nucleotide sequence of SEQ ID NO: 4676, or a nucleotide sequence substantially identical thereto (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity), or a nucleotide sequence having at least 1, 2, 3, 4, 5, 6, or 7 modifications, e.g., substitutions (e.g., conservative substitutions), but not more than 10 modifications, e.g., substitutions (e.g., conservative substitutions), relative to SEQ ID NO: 4676; (iv) the second spacer comprises a nucleotide sequence of GATAGTTA or a nucleotide sequence having at least one, two, or three modifications, e.g., substitutions (e.g., conservative substitutions), but not more than four modifications, e.g., substitutions (e.g., conservative substitutions), relative to the nucleotide sequence of GATAGTTA; (v) The AAV particle of any one of embodiments 586 to 611, wherein the third encoded miR183 binding site comprises the nucleotide sequence of SEQ ID NO: 4676, or a nucleotide sequence substantially identical thereto (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity), or a nucleotide sequence having at least 1, 2, 3, 4, 5, 6, or 7 modifications, e.g., substitutions (e.g., conservative substitutions), but not more than 10 modifications, e.g., substitutions (e.g., conservative substitutions), relative to SEQ ID NO: 4676.

[0584] 613. An AAV particle described in any one of embodiments 586 to 612, wherein the viral genome comprises an encoded miR122 binding site and a miR-1 binding site. 614. An AAV particle according to any one of embodiments 586 to 613, wherein the viral genome is single-stranded.

[0585] 615. An AAV particle described in any one of embodiments 586 to 613, wherein the viral genome is self-complementary. 616. An AAV particle described in any one of embodiments 586 to 615, wherein the viral genome further comprises a nucleotide sequence encoding a Rep protein, e.g., a nonstructural protein, and the Rep protein comprises a Rep78 protein, a Rep68 protein, a Rep52 protein, and / or a Rep40 protein (e.g., a Rep78 protein and a Rep52 protein).

[0586] 617. An AAV particle described in any one of embodiments 586 to 615, wherein the AAV particle further comprises a nucleotide sequence encoding a Rep protein, e.g., a nonstructural protein, and the Rep protein comprises a Rep78 protein, a Rep68 protein, a Rep52 protein, and / or a Rep40 protein (e.g., a Rep78 protein and a Rep52 protein).

[0587] 618. The AAV particle of embodiment 616 or 617, wherein the Rep78 protein, the Rep68 protein, the Rep52 protein, and / or the Rep40 protein are encoded by at least one Rep gene.

[0588] 619. An AAV particle described in any one of embodiments 586 to 618, wherein the viral genome further comprises a nucleic acid sequence encoding an AAV capsid variant described in any one of embodiments 1 to 519, 566, or 574.

[0589] 620. The AAV particle of any one of embodiments 575 to 519, which is isolated, e.g., recombinant. 621. A vector comprising a polynucleotide encoding an AAV capsid variant according to any one of embodiments 1 to 519, 566, or 574, a polynucleotide according to any one of embodiments 520 to 523 or 567 to 574, or a polynucleotide encoding a peptide according to any one of embodiments 524 to 543 or 574.

[0590] 622. A cell, e.g., a host cell, comprising an AAV capsid variant according to any one of embodiments 1 to 519, 566, or 574, a polynucleotide according to any one of embodiments 520 to 523, or 567 to 574, a peptide according to any one of embodiments 524 to 565, or 574, an AAV particle according to any one of embodiments 575 to 620, or a vector according to embodiment 621.

[0591] 623. The cell according to embodiment 622, wherein the cell is a mammalian cell or an insect cell. 624. The cell according to embodiment 622 or 623, wherein the cell is a cell of the brain or spinal cord region, optionally a cell of the brainstem, hippocampus, or thalamus.

[0592] 625. The cell of any one of embodiments 622-624, wherein the cell is a neuron, sensory neuron, motor neuron, astrocyte, glial cell, oligodendrocyte, or muscle cell (e.g., a cardiac, diaphragm, or quadriceps cell).

[0593] 626. The method of embodiment 622 or 623, wherein the cells are liver cells. 627. A method for producing AAV particles, comprising: (i) providing a host cell containing a viral genome; (ii) incubating the host cell under conditions suitable for encapsulation of the viral genome into an AAV capsid variant of any one of embodiments 1 to 519, 566, or 574, or an AAV capsid variant encoded by a polynucleotide of any one of embodiments 520 to 523, or 567 to 574; This method produces AAV particles.

[0594] 628. The method of embodiment 627, further comprising, prior to step (i), introducing into the host cell a first nucleic acid molecule comprising a viral genome. 629. The method of embodiment 628, wherein the host cell comprises a second nucleic acid encoding a capsid variant.

[0595] 630. The method of embodiment 629, wherein the second nucleic acid molecule is introduced into the host cell before, simultaneously with, or after the first nucleic acid molecule. 631. A pharmaceutical composition comprising an AAV particle according to any one of embodiments 575 to 620, an AAV particle comprising a capsid variant according to any one of embodiments 1 to 519, 566, or 574, an AAV particle comprising a peptide according to any one of embodiments 524 to 543, or 574, and a pharmaceutically acceptable excipient.

[0596] 632. A method for delivering a payload to a cell or tissue (e.g., a CNS cell, a CNS tissue, a liver cell, or a liver tissue), comprising administering an effective amount of a pharmaceutical composition described in embodiment 631, an AAV particle described in any one of embodiments 575-620, an AAV particle comprising a capsid variant described in any one of embodiments 1-519, 566, or 574, or an AAV particle comprising a peptide described in a...

Claims

1. An adeno-associated virus (AAV) capsid variant comprising an amino acid sequence at least 95% identical to amino acids 203 to 742 of SEQ ID NO: 981, wherein the amino acid sequence comprises SPHSKA (SEQ ID NO: 941) in variable region IV (VR-IV).

2. An AAV capsid variant as described in claim 1, wherein the amino acid sequence of SPHSKA (sequence number 941) is located immediately after amino acid 455 numbered according to sequence number 981.

3. An adeno-associated virus (AAV) capsid variant comprising an amino acid sequence at least 95% identical to amino acids 203 to 742 of SEQ ID NO: 982, wherein the amino acid sequence comprises HDSPHK (SEQ ID NO: 2) in variable region IV (VR-IV).

4. An AAV capsid variant as described in claim 3, wherein the amino acid sequence of HDSPHK (sequence number 2) is located immediately after amino acid 453, numbered according to sequence number 982.

5. The following formula: An adeno-associated virus (AAV) capsid variant comprising an amino acid sequence having [N1]-[N2]-[N3], (i) [N1] comprises X1, X2, and X3, and at least one of X1, X2, or X3 is G; (ii) [N2] comprises the amino acid sequence of SPH; and (iii) [N3] comprises X4, X5, and X6, and at least one of X4, X5, or X6 is K or R; [N1]-[N2]-[N3] are located N-terminally to C-terminally immediately after position 452, numbered according to any one of SEQ ID NOs: 138; The AAV capsid variant, wherein the AAV capsid variant comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of positions 203 to 736 of SEQ ID NO:

138.

6. (a) the X4 position of [N3] is K, S, A, V, T, G, F, W, V, N, or R; (b) the X5 position of [N3] is S, K, T, F, I, L, Y, H, M, or R; and / or (c) The AAV capsid variant of claim 5, wherein the X6 position of [N3] is G, A, R, M, I, N, T, Y, D, P, V, L, E, W, N, Q, K, or S. (a) The X1 position of [N1] is G, V, R, D, E, M, T, I, S, A, N, L, K, H, P, W, or C; (b) the X2 position of [N1] is H, S, V, L, N, D, R, P, G, T, I, A, E, Y, M, or Q; and / or (c) The AAV capsid variant of claim 5, wherein the X3 position of [N1] is D, G, C, L, E, Y, H, V, A, N, P, or S.

8. (i) [N3] is KSG, SKA, ARM, VKS, ASR, VKI, KKN, VRM, RKA, KTS, KFG, KIG, KLG, KT T, KTY, KYG, SKD, SKP, TRG, VRG, KRG, GAR, KSA, KSR, SKL, SRA, SKR, SLR, SRG, SS R, FLR, SKW, SKS, WKA, VRR, SKV, SKT, SKG, GKA, TKA, NKA, SKL, SKN, AKA, KTG, KSL, KSE, KSV, KSW, KSN, KHG, KSQ, KSK, KLW, WKG, KMG, KMA, or RSG; and / or (ii) The AAV capsid variant of claim 5, wherein [N1] comprises GHD, GSG, GQD, VSG, CSG, GRG, CSH, GQS, GSH, RVG, GSC, GLL, GDD, GHE, GNY, MSG, RNG, TSG, ISG, GPG, ESG, SSG, GNG, ASG, NSG, LSG, GGG, KSG, HSG, GTG, PSG, GSV, RSG, GIG, WSG, DSG, IDG, GLG, DAG, DGG, MEG, ENG, GSA, KNG, KEG, AIG, GYD, GHG, GRD, GND, GPD, GMG, GQV, GHN, GHP, or GHS.

9. (i) [N2] to [N3] are selected from the group consisting of SPHKSG (SEQ ID NO: 946), SPHSKA (SEQ ID NO: 941), SPHARM (SEQ ID NO: 947), SPHVKS (SEQ ID NO: 948), SPHASR (SEQ ID NO: 949), SPHVKI (SEQ ID NO: 950), SPHKKN (SEQ ID NO: 954), SPHVRM (SEQ ID NO: 955), SPHRKA (SEQ ID NO: 956), SPHKFG (SEQ ID NO: 957), SPHKIG (SEQ ID NO: 958), SPHKLG (SEQ ID NO: 959), SPHKTS (SEQ ID NO: 963), SPHKTT (SEQ ID NO: 964), SPHKTY (SEQ ID NO: 965), SPHKYG (SEQ ID NO: 966), SPHSKD (SEQ ID NO: 967), SPHSKP (SEQ ID NO: 968), SPHTRG (SEQ ID NO: 972), SPHVRG (SEQ ID NO: 973), SPHKRG (SEQ ID NO: 974), SPHGAR (SEQ ID NO: 975), SPHKSA (SEQ ID NO: 977), SPHKSR (SEQ ID NO: 951), SPHSKL (SEQ ID NO: 960), SPHSRA (SEQ ID NO: 969), SPHSKR (SEQ ID NO: 978), SPHSLR (SEQ ID NO: 952), SPHSRG (SEQ ID NO: 961) , SPHSSR (SEQ ID NO: 970), SPHFLR (SEQ ID NO: 979), SPHSKW (SEQ ID NO: 953), SPHSKS (SEQ ID NO: 962), SPHWKA (SEQ ID NO: 971), SPHVRR (SEQ ID NO: 980), SPHSKT (SEQ ID NO: 4731), SPHSKG (SEQ ID NO: 4732), SPHGKA (SEQ ID NO: 4733), SPHNKA (SEQ ID NO: 4734), SPHSKN (SEQ ID NO: 4735), SPHAKA (SEQ ID NO: 4736), SPHSKV (SEQ ID NO: 4737), SPHKTG (SEQ ID NO: 4738), SPHTK A (SEQ ID NO:4739), SPHKSL (SEQ ID NO:4740), SPHKSE (SEQ ID NO:4741), SPHKSV (SEQ ID NO:4742), SPHKSW (SEQ ID NO:4743), SPHKSN (SEQ ID NO:4744), SPHKHG (SEQ ID NO:4745), SPHKSQ (SEQ ID NO:4746), SPHKSK (SEQ ID NO:4747), SPHKLW (SEQ ID NO:4748), SPHWKG (SEQ ID NO:4749), SPHKMG (SEQ ID NO:4750), SPHKMA (SEQ ID NO:4751), or SPHRSG (SEQ ID NO:976), (ii) [N2] to [N3] are GHDSPH (SEQ ID NO: 4784), GSGSPH (SEQ ID NO: 4695), GQDSPH (SEQ ID NO: 4785), VSGSPH (SEQ ID NO: 4786), CSGSPH (SEQ ID NO: 4787), GRGSPH (SEQ ID NO: 4788), CSHSPH (SEQ ID NO: 4789), GQSSPH (SEQ ID NO: 4790), GSHSPH (SEQ ID NO: 4791), GDDSPH (SEQ ID NO: 4792), GHESPH (SEQ ID NO: 4793), GNYSPH (SEQ ID NO: 4794), RVGSPH (SEQ ID NO: 4795), GSCSPH (sequence No. 4796), GLLSPH (SEQ ID NO: 4797), MSGSPH (SEQ ID NO: 4798), RNGSPH (SEQ ID NO: 4799), TSGSPH (SEQ ID NO: 4800), ISGSPH (SEQ ID NO: 4801), GPGSPH (SEQ ID NO: 4802), ESGSPH (SEQ ID NO: 4803), SSGSPH (SEQ ID NO: 4804), GNGSPH (SEQ ID NO: 4805), ASGSPH (SEQ ID NO: 4806), NSGSPH (SEQ ID NO: 4807), LSGSPH (SEQ ID NO: 4808), GGGSPH (SEQ ID NO: 4809), KSGSPH (SEQ ID NO: 4810) , HSGSPH (SEQ ID NO: 4811), GTGSPH (SEQ ID NO: 4812), PSGSPH (SEQ ID NO: 4813), GSVSPH (SEQ ID NO: 4814), RSGSPH (SEQ ID NO: 4815), GIGSPH (SEQ ID NO: 4816), WSGSPH (SEQ ID NO: 4817), DSGSPH (SEQ ID NO: 4818), IDGSPH (SEQ ID NO: 4819), GLGSPH (SEQ ID NO: 4820), DAGSPH (SEQ ID NO: 4821), DGGSPH (SEQ ID NO: 4822), MEGSPH (SEQ ID NO: 4823), ENGSPH (SEQ ID NO: 4824), GSASPH (SEQ ID NO:4825), KNGSPH (SEQ ID NO:4826), KEGSPH (SEQ ID NO:4827), AIGSPH (SEQ ID NO:4828), GYDSPH (SEQ ID NO:4829), GHGSPH (SEQ ID NO:4830), GRDSPH (SEQ ID NO:4831), GNDSPH (SEQ ID NO:4832), GPDSPH (SEQ ID NO:4833), GMGSPH (SEQ ID NO:4834), GQVSPH (SEQ ID NO:4835), GHNSPH (SEQ ID NO:4836), GHPSPH (SEQ ID NO:4837), or GHSSPH (SEQ ID NO:4838), and / or (iii) [N1] -[N2] -[N3] is GHDSPHKSG (SEQ ID NO: 4698), GSGSPHSKA (SEQ ID NO: 4697), GSGSPHARM (SEQ ID NO: 4906), GSGSPHVKS (SEQ ID NO: 4907), GQDSPHKSG (SEQ ID NO: 4908), GSGSPHASR (SEQ ID NO: 4909), GSGSPHVKI (SEQ ID NO: 4910), GSGSPHKKN (SEQ ID NO: 4911), GSGSPHVRM (SEQ ID NO: 4912), VSGSPHSKA (SEQ ID NO: 4913), CSGSPHSKA (SEQ ID NO: 4914), GSGSPHRKA (SEQ ID NO: 4915), CSGSPHKTS (SEQ ID NO: 4916), CSHSPHKSG (SEQ ID NO: 4917), GQSSPHRSG (SEQ ID NO: 4918), GRGSPHASR (SEQ ID NO: 4919), GRGSPHSKA (SEQ ID NO: 4920), GSGSPHKFG (SEQ ID NO: 4921), GSGSPHKIG (SEQ ID NO: 4922), GSGSPHKLG (SEQ ID NO: 4923), GSGSPHKTS (SEQ ID NO: 4924), GSGSPHKTT (SEQ ID NO: 4925), GSGSPHKTY (SEQ ID NO: 4926), GSGSPHKYG (SEQ ID NO: 4927) , GSGSPHSKD (SEQ ID NO: 4928), GSGSPHSKP (SEQ ID NO: 4929), GSGSPHTRG (SEQ ID NO: 4930), GSGSPHVRG (SEQ ID NO: 4931), GSHSPHKRG (SEQ ID NO: 4932), GSHSPHKSG (SEQ ID NO: 4933), VSGSPHASR (SEQ ID NO: 4934), VSGSPHGAR (SEQ ID NO: 4935), VSGSPHKFG (SEQ ID NO: 4936), GHDSPHKRG (SEQ ID NO: 4937), GDDSPHKSG (SEQ ID NO: 4938), GHESPHKSA (SEQ ID NO: 4939), GHDSPHKSA (SEQ ID NO: 4940), GNYSPHKIG (SEQ ID NO: 4941), GHDSPHKSR (SEQ ID NO: 4942), GSGSPHSKL (SEQ ID NO: 4943), GSGSPHSRA (SEQ ID NO: 4944), GSGSPHSKR (SEQ ID NO: 4945), GSGSPHSLR (SEQ ID NO: 4946), GSGSPHSRG (SEQ ID NO: 4947), GSGSPHSSR (SEQ ID NO: 4948), RVGSPHSKA (SEQ ID NO: 4949), GSCSSPHRKA (SEQ ID NO: 4950), GSGSPHLR (SEQ ID NO: 4951), GSGSPHSKW (SEQ ID NO: 4952),GSGSPHSKS (SEQ ID NO: 4953), GLLSPHWKA (SEQ ID NO: 4954), GSGSPHVRR (SEQ ID NO: 4955), GSGSPHSKV (SEQ ID NO: 4956), MSGSPHSKA (SEQ ID NO: 4957), RNGSPHSKA (SEQ ID NO: 4958), TSGSPHHSKA (SEQ ID NO: 4959), ISGSPHSKA (SEQ ID NO: 4960), GPGSPHSKA (SEQ ID NO: 4961), GSGSPHSKT (SEQ ID NO: 4962), ESGSPHSKA (SEQ ID NO: 4963), SSGSPHHSKA (SEQ ID NO: 4964), GNGSPHSKA ( SEQ ID NO: 4965), ASGSPHSKA (SEQ ID NO: 4966), NSGSPHHSKA (SEQ ID NO: 4967), LSGSPHHSKA (SEQ ID NO: 4968), GGGSPHSKA (SEQ ID NO: 4969), KSGSPHHSKA (SEQ ID NO: 4970), GGGSPHSKS (SEQ ID NO: 4971), GSGSPHSKG (SEQ ID NO: 4972), HSGSPHHSKA (SEQ ID NO: 4973), GTGSPHSKA (SEQ ID NO: 4974), PSGSPHHSKA (SEQ ID NO: 4975), GSVSPHGKA (SEQ ID NO: 4976), RSGSPHSKA (SEQ ID NO: 4977), GSGSPHTKA (SEQ ID NO: 4978), GIGSPHSKA (SEQ ID NO: 4979), WSGSPHHSKA (SEQ ID NO: 4980), DSGSPHHSKA (SEQ ID NO: 4981), IDGSPHSKA (SEQ ID NO: 4982), GSGSPHNKA (SEQ ID NO: 4983), GLGSPHSKS (SEQ ID NO: 4984), DAGSPHHSKA (SEQ ID NO: 4985), DGGSPHSKA (SEQ ID NO: 4986), MEGSPHSKA (SEQ ID NO: 4987), ENGSPHSKA (SEQ ID NO: 4988), GSASPHSKA (SEQ ID NO: 4989), GNGSPHSKS ( SEQ ID NO: 4990), KNGSPHSKA (SEQ ID NO: 4991), KEGSPHSKA (SEQ ID NO: 4992), AIGSPHSKA (SEQ ID NO: 4993), GSGSPHSKN (SEQ ID NO: 4994), GSGSPHAK (SEQ ID NO: 4995), GHDSPHKIG (SEQ ID NO: 4996), GYDSPHKSG (SEQ ID NO: 4997), GHESPHKSG (SEQ ID NO: 4998), GHDSPHKTG (SEQ ID NO: 4999), GRGSPHKRG (SEQ ID NO: 5000), GQDSPHKSG (SEQ ID NO: 4908), GHDSPHKSL (SEQ ID NO: 5001),GHGSPHSKA (SEQ ID NO: 5002), GHDSPHKSE (SEQ ID NO: 5003), VSGSPHHSKA (SEQ ID NO: 4913), GRDSPHKSG (SEQ ID NO: 5004), GNDSPHKSV (SEQ ID NO: 5005), GQDSPHKIG (SEQ ID NO: 5006), GHDSPHKSV (SEQ ID NO: 5007), GPDSPHKIG (SEQ ID NO: 5008), GPDSPHKSG (SEQ ID NO: 5009), GHDSPHKSW (SEQ ID NO: 5010), GHDSPHKSN (SEQ ID NO: 5011), GMGSPHSKT (SEQ ID NO: 5012), GHDSPHKHG (SEQ ID NO: 5013), GQVSPHKSG (SEQ ID NO: 5014), GDDSPHKSV (SEQ ID NO: 5015), GHNSPHKSG (SEQ ID NO: 5016), GNGSPHKRG (SEQ ID NO: 5017), GHDSPHKYG (SEQ ID NO: 5018), GHDSPHKSQ (SEQ ID NO: 5019), GNDSPHKIG (SEQ ID NO: 5020), GHDSPHKSK (SEQ ID NO: 5021), GHDSPHKLW (SEQ ID NO: 5022), GHPSPHWKG (SEQ ID NO: 5023), GHDSPHKMG (SEQ ID NO: 5024), GHDSPHKMA (SEQ ID NO: 5025), or GHSSPHHRSG (SEQ ID NO: 5026).

10. (i) Further comprising [N4], wherein [N4] is selected from the group consisting of QNQQ (SEQ ID NO: 5028), WNQQ (SEQ ID NO: 5029), QYYV (SEQ ID NO: 5030), RRQQ (SEQ ID NO: 5031), GCGQ (SEQ ID NO: 5032), LRQQ (SEQ ID NO: 5033), RNQQ (SEQ ID NO: 5034), VNQQ (SEQ ID NO: 5035), FRLQ (SEQ ID NO: 5036), FNQQ (SEQ ID NO: 5037), LLQQ (SEQ ID NO: 5038), SNQQ (SEQ ID NO: 5039), RLQQ (SEQ ID NO: 5040), LNQQ (SEQ ID NO: 5041), QRKL (SEQ ID NO: 5042), LRRQ (SEQ ID NO: 5043), QRLR (SEQ ID NO: 5044), QRRL (SEQ ID NO: 5045), RRLQ (SEQ ID NO: 5046), RLRQ (SEQ ID NO: 5047), SKRQ (SEQ ID NO: 5048), QLYR (SEQ ID NO: 5049), QLTV (SEQ ID NO: 5050), QNKQ (SEQ ID NO: 5051), KNQQ (SEQ ID NO: 5052), QKQQ (SEQ ID NO: 5053), QTQQ (SEQ ID NO: 5054), QNHQ (SEQ ID NO: 5055), QHQQ (SEQ ID NO: 5056), QNQH (SEQ ID NO: 5057), QHRQ (SEQ ID NO: 5058), LTQQ ( SEQ ID NO: 5059), QNQW (SEQ ID NO: 5060), QNTH (SEQ ID NO: 5061), RRRQ (SEQ ID NO: 5062), QYQQ (SEQ ID NO: 5063), QNDQ (SEQ ID NO: 5064), QNRH (SEQ ID NO: 5065), RDQQ (SEQ ID NO: 5066), PNLQ (SEQ ID NO: 5067), HVRQ (SEQ ID NO: 5068), PNQH (SEQ ID NO: 5069), HNQQ (SEQ ID NO: 5070), QSQQ (SEQ ID NO: 5071), QPAK (SEQ ID NO: 5072), QNLA (SEQ ID NO: 5073), QNQL (SEQ ID NO: 5074), QGQQ (SEQ ID NO: 5075), 075), LNRQ (SEQ ID NO: 5076), QNPP (SEQ ID NO: 5077), QNLQ (SEQ ID NO: 5078), QDQE (SEQ ID NO: 5079), QDQQ (SEQ ID NO: 5080), HWQQ (SEQ ID NO: 5081), PNQQ (SEQ ID NO: 5082), PEQQ (SEQ ID NO: 5083), QRTM (SEQ ID NO: 5084), LHQH (SEQ ID NO: 5085), QHRI (SEQ ID NO: 5086), QYIH (SEQ ID NO: 5087), QKFE (SEQ ID NO: 5088), QFPS (SEQ ID NO: 5089), QNPL (SEQ ID NO: 5090), QAIK (SEQ ID NO: 5091),QNRQ (SEQ ID NO: 5092), QYQH (SEQ ID NO: 5093), QNPQ (SEQ ID NO: 5094), QHQL (SEQ ID NO: 5095), QSPP (SEQ ID NO: 5096), QAKL (SEQ ID NO: 5097), KSQQ (SEQ ID NO: 5098), QDRP (SEQ ID NO: 5099), QNLG (SEQ ID NO: 5100), QAFH (SEQ ID NO: 5101), QNAQ (SEQ ID NO: 5102), HNQL (SEQ ID NO: 5103), QKLN (SEQ ID NO: 5104), QNVQ (SEQ ID NO: 5105), QAQQ (SEQ ID NO: 5106), QTPP (SEQ ID NO: 5107), QPPA (SEQ ID NO: 5108), No. 5108), QERP (SEQ ID NO: 5109), QDLQ (SEQ ID NO: 5110), QAMH (SEQ ID NO: 5111), QHPS (SEQ ID NO: 5112), PGLQ (SEQ ID NO: 5113), QGIR (SEQ ID NO: 5114), QAPA (SEQ ID NO: 5115), QIPP (SEQ ID NO: 5116), QTQL (SEQ ID NO: 5117), QAPS (SEQ ID NO: 5118), QNTY (SEQ ID NO: 5119), QDKQ (SEQ ID NO: 5120), QNHL (SEQ ID NO: 5121), QIGM (SEQ ID NO: 5122), LNKQ (SEQ ID NO: 5123), PNQL (SEQ ID NO: 5124), QLQQ (SEQ ID NO: 5125), QRMS (SEQ ID NO: 5126), QGIL (SEQ ID NO: 5127), QDRQ (SEQ ID NO: 5128), RDWQ (SEQ ID NO: 5129), QERS (SEQ ID NO: 5130), QNYQ (SEQ ID NO: 5131), QRTC (SEQ ID NO: 5132), QIGH (SEQ ID NO: 5133), QGAI (SEQ ID NO: 5134), QVPP (SEQ ID NO: 5135), QVQQ (SEQ ID NO: 5136), LMRQ (SEQ ID NO: 5137), QYSV (SEQ ID NO: 5138), QAIT (SEQ ID NO: 5139), QKTL (SEQ ID NO: 5140), QLHH (SEQ ID NO: 5141), No. 5141), QNII (SEQ ID NO: 5142), QGHH (SEQ ID NO: 5143), QSKV (SEQ ID NO: 5144), QLPS (SEQ ID NO: 5145), IGKQ (SEQ ID NO: 5146), QAIH (SEQ ID NO: 5147), QHGL (SEQ ID NO: 5148), QFMC (SEQ ID NO: 5149), QNQM (SEQ ID NO: 5150), QHLQ (SEQ ID NO: 5151), QPAR (SEQ ID NO: 5152), QSLQ (SEQ ID NO: 5153), QSQL (SEQ ID NO: 5154), HSQQ (SEQ ID NO: 5155), QMPS (SEQ ID NO: 5156), QGSL (SEQ ID NO: 5157),QVPA (SEQ ID NO: 5158), HYQQ (SEQ ID NO: 5159), QVPS (SEQ ID NO: 5160), RGEQ (SEQ ID NO: 5161), PGQQ (SEQ ID NO: 5162), LEQQ (SEQ ID NO: 5163), QNQS (SEQ ID NO: 5164), QKVI (SEQ ID NO: 5165), QNND (SEQ ID NO: 5166), QSVH (SEQ ID NO: 5167), QPLG (SEQ ID NO: 5168), HNQE (SEQ ID NO: 5169), QIQQ (SEQ ID NO: 5170), QVRN (SEQ ID NO: 5171), PSNQ (SEQ ID NO: 5172), QVGH (SEQ ID NO: 5173), QRDI ...VIII (SEQ ID NO: 5164), QVIII (SEQ ID NO: 5165), QVIII (SEQ ID NO: 5166), QVIII (SEQ ID NO: 5167), QVIII (SEQ ID NO: 5168), QVIII (SEQ ID NO: 5169), QVIII (SEQ ID NO: No. 5174), QMPN (SEQ ID NO: 5175), RGLQ (SEQ ID NO: 5176), PSLQ (SEQ ID NO: 5177), QRDQ (SEQ ID NO: 5178), QAKG (SEQ ID NO: 5179), QSAH (SEQ ID NO: 5180), QSTM (SEQ ID NO: 5181), QREM (SEQ ID NO: 5182), QYRA (SEQ ID NO: 5183), QRQQ (SEQ ID NO: 5184), QWQQ (SEQ ID NO: 5185), QRMN (SEQ ID NO: 5186), GDSQ (SEQ ID NO: 5187), QKIS (SEQ ID NO: 5188), PSMQ (SEQ ID NO: 5189), SPRQ (SEQ ID NO: 5190), MEQQ (SEQ ID NO: 5191), QYQN (SEQ ID NO: 5192), QIRQ (SEQ ID NO: 5193), QSVQ (SEQ ID NO: 5194), RSQQ (SEQ ID NO: 5195), QNKL (SEQ ID NO: 5196), QIQH (SEQ ID NO: 5197), PRQQ (SEQ ID NO: 5198), HTQQ (SEQ ID NO: 5199), QRQH (SEQ ID NO: 5200), RNQE (SEQ ID NO: 5201), QSKQ (SEQ ID NO: 5202), QNQP (SEQ ID NO: 5203), QSPQ (SEQ ID NO: 5204), QTRQ (SEQ ID NO: 5205), QNLH (SEQ ID NO: 5206), QNQE (SEQ ID NO: 5207), No. 5207), LNQP (SEQ ID NO: 5208), QNQD (SEQ ID NO: 5209), QNLL (SEQ ID NO: 5210), QLVI (SEQ ID NO: 5211), RTQE (SEQ ID NO: 5212), QTHQ (SEQ ID NO: 5213), QDQH (SEQ ID NO: 5214), QSQH (SEQ ID NO: 5215), VRQQ (SEQ ID NO: 5216), AWQQ (SEQ ID NO: 5217), QSVP (SEQ ID NO: 5218), QNIQ (SEQ ID NO: 5219), LDQQ (SEQ ID NO: 5220), PDQQ (SEQ ID NO: 5221), ESQQ (SEQ ID NO: 5222), QRQL (SEQ ID NO: 5223),QIIV (SEQ ID NO: 5224), QKQS (SEQ ID NO: 5225), QSHQ (SEQ ID NO: 5226), QFVV (SEQ ID NO: 5227), QSQP (SEQ ID NO: 5228), QNEQ (SEQ ID NO: 5229), INQQ (SEQ ID NO: 5230), RNRQ (SEQ ID NO: 5231), RDQK (SEQ ID NO: 5232), QWKR (SEQ ID NO: 5233), ENRQ (SEQ ID NO: 5234), QTQP (SEQ ID NO: 5235), and / or comprising QKQL (SEQ ID NO: 5236), RNQL (SEQ ID NO: 5237), ISIQ (SEQ ID NO: 5238), QTVC (SEQ ID NO: 5239), QQIM (SEQ ID NO: 5240), LNHQ (SEQ ID NO: 5241), QNQA (SEQ ID NO: 5242), QMIH (SEQ ID NO: 5243), RNHQ (SEQ ID NO: 5244), or QKMN (SEQ ID NO: 5245), and / or (ii) further includes [N0], where [N0] is TIN, SMN, TIM, YLS, GLS, MPE, MEG, MEY, AEW, CEW, ANN, IPE, ADM, IEY, ADY, IET, MEW, CEY, RIN, MEI, LEY, ADW, IEI, DIM, FEQ, MEF, CDQ, LPE, IEN, MES, AEI, VEY, IIN, TSN, IEV, MEM, AEV, MDA, VEW, AEQ, LEW, MEL, MET, MEA, IES, MEV, CEI, ATN, MDG, QEV, ADQ, NMN, IEM, ISN, TGN, QQQ, HDW, IEG, TII, TFP, TEK, EIN, TVN, TFN, SIN, TER, TSY, ELH, AIN, SVN, TDN, TFH, TVH, TEN, TSS, TID, TCN, NIN, TEH, AEM, AIK, TDK, TFK, SDQ, TEI, NTN, TET, SIK, TEL, TEA, TAN, TIY, TFS, TES, TTN, TED, TNN, EVH, TIS, TVR, TDR, TIK, NHI, TIP, ESD, TDL, TVP, TVI, AEH, NCL, TVK, NAD, TIT, NCV, TIR, NAL, VIN, TIQ, TEF, TRE, QGE, SEK, NVN, GGE, EFV, SDK, TEQ, EVQ, TEY, NCW, TDV, SDI, NSI, NSL, EVV, 6. The AAV capsid variant of claim 5, comprising TEP, SEL, TWQ, TEV, AVN, GVL, TLN, TEG, TRD, NAI, AEN, AET, ETA, NNL.

11. The AAV capsid variant of claim 10, wherein [N0]-[N1]-[N2]-[N3]-[N4] comprises any one of the amino acid sequences of SEQ ID NOs: 2243, 2242, 2242-2886.

12. comprising, from the N-terminus to the C-terminus, [N0]-[N1]-[N2]-[N3]-[N4]; (i) [NO] is located immediately after position 449 and replaces positions 450-452, numbered according to the amino acid sequence of any one of SEQ ID NOs: 982, 981, or 138; (ii) [N1] occurs immediately after position 452 and replaces positions 453-455, numbered according to the amino acid sequence of SEQ ID NO: 138; (iii) [N2] is located immediately after position 455, numbered according to the amino acid sequence of SEQ ID NO: 138; (iv) [N3] is present immediately after [N2]; (v) [N4] occurs immediately after position 455 and replaces positions 456 to 459, numbered according to the amino acid sequence of SEQ ID NO: 138; (vi) [N2]-[N3]-[N4] corresponds to positions 456 to 465 of SEQ ID NO: 982 or 981; (vii) [N1]-[N2]-[N3] corresponds to positions 453 to 461 of SEQ ID NO: 982 or 981; and / or (viii) The AAV capsid variant of claim 10, wherein [N0]-[N1]-[N2]-[N3]-[N4] corresponds to positions 450 to 465 of SEQ ID NO: 982 or 981.

13. 1. An adeno-associated virus (AAV) capsid variant comprising an amino acid sequence having the following formula: [N1]-[N2]-[N3] (SEQ ID NO: 6408), (i) [N1] comprises positions X1, X2, and X3, where position X2 is an amino acid other than S and position X3 is an amino acid other than G; (ii) [N2] comprises the amino acid sequence SPH; (iii) [N3] comprises positions X4, X5, and X6, and position X4 is K; [N1]-[N2]-[N3] are located N-terminally to C-terminally immediately after position 452, numbered according to any one of SEQ ID NOs: 982; The AAV capsid variant, wherein the AAV capsid variant comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of positions 203 to 742 of SEQ ID NO:

982.

14. 1. An adeno-associated virus (AAV) capsid variant comprising an amino acid sequence having the following formula: [N1]-[N2]-[N3] (SEQ ID NO: 6407), (i) [N1] comprises positions X1, X2, and X3, where position X2 is S and position X3 is G; (ii) [N2] comprises the amino acid sequence SPH; (iii) [N3] comprises positions X4, X5, and X6, and position X5 is K; [N1]-[N2]-[N3] are located N-terminally to C-terminally immediately after position 452, numbered according to any one of SEQ ID NOs: 981; The AAV capsid variant, wherein the AAV capsid variant comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of positions 203 to 742 of SEQ ID NO:

981.

15. (a) the amino acid sequence of any of the sequences provided in Tables 1, 2A, 2B, 9-11, 13-19; (b) an amino acid sequence comprising at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 consecutive amino acids from any one of the sequences provided in Tables 1, 2A, 2B, 9-11, 13-19, or (c) An adeno-associated virus (AAV) capsid variant comprising an amino acid sequence containing at least one, two, or three, but no more than four modifications, to the amino acid sequence of any one of the sequences provided in Tables 1, 2A, 2B, 9-11, 13-19.

16. (A) (i) at least three consecutive amino acids comprise an HDS; (ii) at least four consecutive amino acids comprise HDSP (SEQ ID NO: 4702); (iii) at least five consecutive amino acids comprise HDSPH (SEQ ID NO: 4703); and / or (iv) at least 6 consecutive amino acids comprise HDSPHK (SEQ ID NO: 2); or (B) (i) at least three consecutive amino acids comprise an SPH; (ii) at least four consecutive amino acids comprise SPHS (SEQ ID NO: 4700); (iii) at least five consecutive amino acids comprise SPHSK (SEQ ID NO: 4701); and / or (iv) The AAV capsid variant of claim 15, wherein at least six consecutive amino acids comprise SPHSKA (SEQ ID NO: 941).

17. (i) the AAV capsid variant comprises the amino acid sequence of HDSPHK (SEQ ID NO: 2) or an amino acid sequence that includes at least one, two, or three, but not more than four, amino acids that differ from the amino acid sequence of HDSPHK (SEQ ID NO: 2); (ii) the AAV capsid variant comprises an amino acid sequence encoded by the nucleotide sequence of SEQ ID NO:3, or a nucleotide sequence that contains at least 1, 2, 3, 4, 5, 6, or 7, but not more than 10, nucleotide differences relative to the nucleotide sequence of SEQ ID NO:3; and / or (iii) The AAV capsid variant of claim 15, wherein the nucleotide sequence encoding the AAV capsid variant comprises the nucleotide sequence of SEQ ID NO: 3 or a nucleotide sequence that contains at least 1, 2, 3, 4, 5, 6, or 7, but not more than 10, different nucleotides relative to the nucleotide sequence of SEQ ID NO:

3.

18. (i) the AAV capsid variant comprises the amino acid sequence of SPHSKA (SEQ ID NO:941) or an amino acid sequence that includes at least one, two, or three, but no more than four, amino acids that differ from the amino acid sequence of SPHSKA (SEQ ID NO:941); (ii) the AAV capsid variant comprises an amino acid sequence encoded by the nucleotide sequence of SEQ ID NO:942, or a nucleotide sequence that contains at least 1, 2, 3, 4, 5, 6, or 7, but not more than 10, nucleotides that differ from the nucleotide sequence of SEQ ID NO:942; and / or (ii) The AAV capsid variant of claim 15, wherein the nucleotide sequence encoding the AAV capsid variant comprises the nucleotide sequence of SEQ ID NO:942 or a nucleotide sequence that contains at least 1, 2, 3, 4, 5, 6, or 7, but not more than 10, different nucleotides relative to the nucleotide sequence of SEQ ID NO:

942.

19. The amino acid sequence (i) is present in variable region IV (VR-IV), wherein VR-IV comprises positions 449 to 460, numbered according to SEQ ID NO: 138; (ii) immediately following position 448, 449, 450, 451, 452, 453, 454, or 455, as numbered according to the amino acid sequence of SEQ ID NO: 138; (iii) located immediately after position 453 numbered according to the amino acid sequence of SEQ ID NO: 138 or 982; and / or (iv) The AAV capsid variant of claim 15, which is located immediately after position 455 numbered according to the amino acid sequence of SEQ ID NO: 138 or 981.

20. (i) the amino acid sequence of HDSPHK (SEQ ID NO: 2), wherein the amino acid sequence is located immediately after position 453 numbered according to the amino acid sequence of SEQ ID NO: 138 or 982; or (ii) The AAV capsid variant of claim 15, comprising the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is located immediately after position 455 numbered according to the amino acid sequence of SEQ ID NO: 138 or 981. (i) an amino acid sequence that is at least 98% identical to amino acid sequence 203-742 of SEQ ID NO:981 or SEQ ID NO:982; (ii) an amino acid sequence that is at least 95%, or at least 98%, identical to amino acid sequence 138-742 of SEQ ID NO: 981 or SEQ ID NO: 982; and / or (iii) An AAV capsid variant according to any one of claims 1 to 20, comprising an amino acid sequence that is at least 95%, or at least 98%, identical to SEQ ID NO: 981 or SEQ ID NO:

982.

22. (i) an amino acid sequence of amino acid sequence 203 to 742 of SEQ ID NO: 981 or SEQ ID NO: 982; (ii) the amino acid sequence of amino acids 138 to 742 of SEQ ID NO: 981 or SEQ ID NO: 982, and / or (iii) An AAV capsid variant according to any one of claims 1 to 20, comprising the amino acid sequence of SEQ ID NO: 981 or SEQ ID NO:

982.

23. 21. The AAV capsid variant of any one of claims 1 to 20, wherein the AAV capsid variant has an increased tropism for brain cells or brain tissue compared to an AAV capsid protein comprising the amino acid sequence of SEQ ID NO:

138.

24. A polynucleotide encoding the AAV capsid variant of any one of claims 1 to 20, optionally comprising: A polynucleotide comprising SEQ ID NO:934 or the nucleotide sequence of SEQ ID NO:934, or a nucleotide sequence at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:934 or the nucleotide sequence of SEQ ID NO:

934.

25. A peptide, (a) the amino acid sequence of any of the sequences provided in Tables 1, 2A, 2B, 9-11, 13-19; (b) an amino acid sequence comprising at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 consecutive amino acids from any one of the sequences provided in Tables 1, 2A, 2B, 9-11, 13-19, or (c) an amino acid sequence that contains at least one, two, or three, but no more than four, different amino acids to any one of the sequences provided in Tables 1, 2A, 2B, 9-11, 13-19; or (d) The peptide comprises an amino acid sequence containing at least one, two, or three, but no more than four modifications, relative to the amino acid sequence of any one of the sequences provided in Tables 1, 2A, 2B, 9-11, 13-19.

26. An AAV particle comprising the AAV capsid variant of any one of claims 1 to 20.

27. 27. The AAV particle of claim 26, comprising a nucleotide sequence encoding a payload, wherein the encoded payload comprises a protein, an antibody, an enzyme, or an inhibitory RNA agent.

28. (i) a 5′ inverted terminal repeat (ITR) and / or a 3′ ITR; (ii) a promoter operably linked to a nucleotide sequence encoding the payload; (iii) an enhancer, (iv) Kozak sequence, (v) introns, (vi) exons, (vii) a nucleotide sequence encoding a miR binding site, and / or (v) polyadenylation (poly A) sequence 28. The AAV particle of claim 27, further comprising:

29. A vector comprising a polynucleotide encoding the AAV capsid variant of any one of claims 1 to 20.

30. A cell comprising the AAV capsid variant of any one of claims 1 to 20, optionally comprising: (i) a mammalian cell or an insect cell; (ii) cells of the brain or spinal cord region, optionally cells of the brainstem, hippocampus, or thalamus; and / or (iii) The cell is a neuron, a sensory neuron, a motor neuron, an astrocyte, a glial cell, an oligodendrocyte, or a muscle cell.

31. 1. A method of producing AAV particles, comprising: (i) providing a host cell comprising a viral genome and a polynucleotide encoding the AAV capsid variant of any one of claims 1 to 20; (ii) incubating the host cells under conditions suitable for packaging the viral genome into the AAV capsid variant; This method thereby produces the AAV particles.

32. 27. A pharmaceutical composition comprising the AAV particles of claim 26 and a pharmaceutically acceptable excipient.

33. A pharmaceutical composition for delivery of a payload to a cell or tissue, comprising: Optionally, the pharmaceutical composition is formulated for intravenous, intramuscular, intracerebral, intrathecal, intraventricular, intraparenchymal, or intracisternal injection (ICM), and / or the cells are (i) a cell of a brain or spinal cord region, optionally a cell of the frontal cortex, sensory cortex, motor cortex, caudate nucleus, cerebellar cortex, cerebral cortex, brainstem, hippocampus, or thalamus; (ii) a neuron, sensory neuron, motor neuron, astrocyte, glial cell, or oligodendrocyte; and / or 33. The pharmaceutical composition of claim 32, wherein (iii) the pharmaceutical composition is in a subject, optionally wherein the subject has, has been diagnosed with, or is at risk of having a neurological, neurodegenerative, neuro-oncological, myopathic, or neuromuscular disorder, and optionally wherein the neurological, neurodegenerative, myopathic, neuromuscular, or neuro-oncological disorder is Huntington's disease, amyotrophic lateral sclerosis (ALS), Gaucher's disease, dementia with Lewy bodies, Parkinson's disease, spinal muscular atrophy, Alzheimer's disease, leukodystrophy (e.g., Alexander disease, autosomal dominant leukodystrophy with autonomic dysfunction (ADLD), Canavan disease, cerebrotendinous xanthomatosis (CTX), metachromatic leukodystrophy (MLD), Pelizaeus-Merzbacher disease, or Refsum's disease), or cancer (e.g., HER2 / neu positive cancer or glioblastoma).

34. 33. The pharmaceutical composition of claim 32 for the treatment of a subject having or diagnosed as having a neurological, neurodegenerative, neuro-oncological, myopathic, or neuromuscular disorder.

35. 35. The pharmaceutical composition of claim 34, wherein the neurological, neurodegenerative, myopathic, neuromuscular, or neuro-oncological disorder is Huntington's disease, amyotrophic lateral sclerosis (ALS), Gaucher disease, dementia with Lewy bodies, Parkinson's disease, spinal muscular atrophy, Alzheimer's disease, leukodystrophy (e.g., Alexander disease, autosomal dominant leukodystrophy with autonomic dysfunction (ADLD), Canavan disease, cerebrotendinous xanthomatosis (CTX), metachromatic leukodystrophy (MLD), Pelizaeus-Merzbacher disease, or Refsum disease), or cancer (e.g., HER2 / neu-positive cancer or glioblastoma).

36. The pharmaceutical composition of claim 34, formulated for intravenous administration, intramuscular administration, intracerebral administration, intrathecal administration, intraventricular administration, intraparenchymal administration, or intracisternal injection (ICM).

37. Use of the AAV particles of claim 26 in the manufacture of a medicament for delivery of a payload to a cell or tissue, comprising: Optionally, the AAV particles are formulated for intravenous, intramuscular, intracerebral, intrathecal, intraventricular, intraparenchymal, or intracisternal injection (ICM), and / or the cells are (i) a cell of a brain or spinal cord region, optionally a cell of the frontal cortex, sensory cortex, motor cortex, caudate nucleus, cerebellar cortex, cerebral cortex, brainstem, hippocampus, or thalamus; (ii) a neuron, sensory neuron, motor neuron, astrocyte, glial cell, or oligodendrocyte; and / or (iii) In a subject, optionally wherein the subject has, has been diagnosed with, or is at risk of having a neurological, neurodegenerative, neuro-oncological, myopathic, or neuromuscular disorder, and optionally wherein the neurological, neurodegenerative, myopathic, neuromuscular, or neuro-oncological disorder is Huntington's disease, amyotrophic lateral sclerosis (ALS), Gaucher's disease, dementia with Lewy bodies, Parkinson's disease, spinal muscular atrophy, Alzheimer's disease, leukodystrophy (e.g., Alexander disease, autosomal dominant leukodystrophy with autonomic dysfunction (ADLD), Canavan disease, cerebrotendinous xanthomatosis (CTX), metachromatic leukodystrophy (MLD), Pelizaeus-Merzbacher disease, or Refsum's disease), or cancer (e.g., HER2 / neu positive cancer or glioblastoma).

38. Use of the AAV particles described in claim 26 in the manufacture of a medicament for the treatment of a subject having or diagnosed as having a neurological disorder, a neurodegenerative disorder, a neuro-oncological disorder, a muscle disorder, or a neuromuscular disorder.

39. The use of claim 38, wherein the neurological, neurodegenerative, myopathic, neuromuscular, or neuro-oncological disorder is Huntington's disease, amyotrophic lateral sclerosis (ALS), Gaucher disease, dementia with Lewy bodies, Parkinson's disease, spinal muscular atrophy, Alzheimer's disease, leukodystrophy (e.g., Alexander disease, autosomal dominant leukodystrophy with autonomic dysfunction (ADLD), Canavan disease, cerebrotendinous xanthomatosis (CTX), metachromatic leukodystrophy (MLD), Pelizaeus-Merzbacher disease, or Refsum disease), or cancer (e.g., HER2 / neu-positive cancer or glioblastoma).

40. The use of claim 39, wherein the AAV particles are formulated for intravenous administration, intramuscular administration, intracerebral administration, intrathecal administration, intraventricular administration, intraparenchymal administration, or intracisternal injection (ICM).