Aav capsid variants and uses thereof

Abstract

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

Description

AAV CAPSID VARIANTS AND USES THEREOF RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Application No.63 / 464,034 filed on May 4, 2023, U.S. Provisional Application No.63 / 593,622 filed on October 27, 2023, and U.S. Provisional Application No.63 / 564,320 filed on March 12, 2024; the entire contents of each of which are hereby incorporated by reference in their entirety. SEQUENCE LISTING

[0002] The present application is being filed along with a Sequence Listing in electronic format. The Sequence Listing file, entitled V2071-3015PCT_SL.xml, was created on April 3, 2024, and is 5,493,507 bytes in size. The information in electronic format of the Sequence Listing is incorporated herein by reference in its entirety. FIELD OF THE DISCLOSURE

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

[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 because of their non- pathogenic nature, their low immunogenic profile, low rate of integration 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 applications, and capsid neutralization by pre- existing neutralizing antibodies may prevent treatment of a large proportion of patients. For these reasons, considerable efforts have been devoted to obtaining capsid variants with enhanced properties. Of many approaches tested so far, significant advances have resulted from directed evolution of AAV capsids using in vitro or in vivo selection of capsid variants created by capsid sequence randomization using either error-prone PCR, shuffling of various parent serotypes, or insertion of fully randomized short peptides at defined positions.

[0006] Attempts at providing AAV capsids with improved properties, e.g., improved tropism to a target cell or tissue upon systemic administration, have met with limited success. As such, there is a need for improved methods of producing AAV capsids and resulting AAV capsids for delivery of a payload of interest to a target cell or tissue, e.g., a CNS cell or tissue, or a muscle cell or tissue.SUMMARY OF THE DISCLOSURE

[0007] The present disclosure pertains at least in part, to compositions and methods for the production and use of an AAV particle comprising an AAV capsid polypeptide, e.g., an AAV capsid variant. In some embodiments, the AAV capsid variant has an enhanced tropism for a tissue or a cell, e.g., a CNS tissue or a CNS cell. Said tropism can be useful for delivery of a payload, e.g., a payload described herein to a cell or tissue, for the treatment of a disorder, e.g., a neurological or a neurodegenerative disorder, a muscular or a neuromuscular disorder, or a neuro-oncological disorder.

[0008] Accordingly, in one aspect, the present disclosure provides an AAV capsid variant, comprising: (A) a modification, e.g., a substitution (e.g., conservative substitution) in loop VIII; and / or (B) 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; (iii) [N3] comprises X4, X5, and X6, wherein at least one of X4, X5, or X6 is a basic amino acid, e.g., a K or R. In some embodiments, loop VIII comprises positions 587-599, numbered according to SEQ ID NO: 981, 982, 6411, or 6412; or positions 581- 593, numbered according to SEQ ID NO: 138 or 6414. In some embodiments, position X4 of [N3] is K. In some embodiments, position X5 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] is present immediately subsequent to position 455, numbered according to SEQ ID NO: 138, 981 or 982. In some embodiments, [N1] is present immediately subsequent to 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 H at position 454 and D at position 455, numbered according to SEQ ID NO: 138 or 982. In some embodiments, the AAV capsid variant comprises S at position 454 and G at position 455, numbered according to SEQ ID NO: 138 or 981. In some embodiments, an insert of 8 amino acids replaces the SG at positions 454-455, numbered according to SEQ ID NO: 138. In some embodiments, an insert of 6 amino acids is present immediately subsequent to position 455, numbered according to SEQ ID NO: 138, 981, or 982.

[0009] In another aspect, the present disclosure provides an AAV capsid variant comprising: (A) [A][B] (SEQ ID NO: 4694), wherein: (i) [A] comprises the amino acid sequence of GSGSPH (SEQ ID NO: 4695); and (ii) [B] comprises X1 X2 X3 X4 X5 X6 X7, wherein: (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; and (g) position X7 is Q, L, R, or V; and / or (B) a modification, e.g., a substitution (e.g., conservative substitution) in loop VIII. In some embodiments, loop VIII comprises positions 587-599, numbered according to SEQ ID NO: 981, 982, 6411, or 6412; or positions 581-593, numbered according to SEQ ID NO: 138 or 6414.

[0010] In yet another aspect, the present disclosure provides an AAV capsid variant comprising: (A) [ A] [B] (SEQ ID NO: 4699) wherein: (i) [A] comprises XI X2 X3 X4 X5 X6, wherein (a) position XI 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; and (ii) [B] comprises SPHKSG (SEQ ID NO: 946); and / or (B) a modification, e.g., a substitution (e.g., conservative substitution) in loop VIII, optionally wherein loop VIII comprises positions 587-599, numbered according to SEQ ID NO: 981, 982, 6411, or 6412; or positions 581-593, numbered according to SEQ ID NO: 138 or 6414.

[0011] In yet another aspect, the present disclosure provides an AAV capsid variant comprising: (A) an amino acid sequence having the following formula: [N1]-[N2]-[N3] (SEQ ID NO: 6407), wherein: (i) [Nl] comprises positions XI, X2, and X3, wherein 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, wherein position X5 is K; and / or (B) a modification, e.g., a substitution (e.g., conservative substitution) in loop VIII. In some embodiments, loop VIII comprises positions 587-599, numbered according to SEQ ID NO: 981, 982, 6411, or 6412; or positions 581-593, numbered according to SEQ ID NO: 138 or 6414. In some embodiments, [N1]-[N2]-[N3] is present immediately subsequent to position 452 and replaces positions 453-455, numbered according to SEQ ID NO: 138 or 982. In some embodiments, [N 1]-[N2J-[N3J is or comprises GSGSPHSKA (SEQ ID NO: 4697).

[0012] In another aspect, the present disclosure provides an AAV capsid variant comprising: (A) an amino acid sequence having the following formula: [N1]-[N2]-[N3] (SEQ ID NO: 6408), wherein: (i) [Nl] comprises positions XI, 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; and / or (B) a modification, e.g., a substitution (e.g., conservative substitution) in loop VIII. In some embodiments, loop VIII comprises positions 587-599, numbered according to SEQ ID NO: 981, 982, 6411, or 6412; or positions 581 - 593, numbered according to SEQ ID NO: 138 or 6414. In some embodiments, [N1]-[N2]-[N3] is present immediately subsequent to 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 present disclosure provides an AAV capsid variant comprising: (A) the formula [A]-[B] (SEQ ID NO: 4696), wherein: (i) [A] comprises GSGSPH (SEQ ID NO: 4695); and (ii) [B] comprises XI X2, X3, X4, and X5, wherein: (a) position XI 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; and (e) position X5 is A, N, Y, R, K. L, I, M. Q, S, C, W. F, T, G. V, or P; optionally wherein the AAV capsid variant comprises an amino acid modification, e.g.. a conservative substitution, of any of the aforesaid amino acids in (a)-(e); and / or(B) a modification, e.g., a substitution (e.g., conservative substitution) in loop VIII. In some embodiments, loop VIII comprises positions 587-599, numbered according to SEQ ID NO: 981, 982. 6411, or 6412; or positions 581-593, numbered according to SEQ ID NO: 138 or 6414. In some, embodiments, [A]-[B] is present immediately subsequent to position 452, and wherein [A]-[B] replaces positions 453-457 (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 a liver cell or tissue, relative to the tropism of a reference sequence comprising the amino acid sequence of SEQ ID NO: 138. In some embodiments, the AAV capsid shows preferential transduction in the liver relative to transduction in the brain and / or dorsal root ganglia (DRG), e.g., as compared to SEQ ID NO: 138.

[0014] In another aspect, the present disclosure provides an AAV capsid variant, comprising: (a) three, four, or all of the amino acid R at position 584, the amino acid T at position 586, the amino acid L at position 588, tire amino acid Q at position 589, and / or the amino acid L at position 590, numbered according to SEQ ID NO: 138; and (b) an amino acid sequence having the following formula: [N1]-[N2]-[N3], wherein [N1]-[N2]-[N3] is present in hypervariable loop IV, wherein: (i) [Nl] comprises XI, X2, and X3, wherein at least one of XI, X2, or X3 is G; (ii) [N2] comprises the amino acid sequence of SPH; and (iii) [N3] comprises X4, X5, and X6. wherein at least one of X4. X5. or X6 is a basic amino acid, e.g., a K or R; and wherein the AAV capsid variant comprises an amino acid sequence at least 95% identical to the amino acid sequence of positions 203-736 of SEQ ID NO: 138.

[0015] In another aspect, the present disclosure provides an AAV capsid variant, comprising three, four or all of the amino acid R at position 584. the amino acid T at position 586, the amino acid L at position 588, the amino acid Q at position 589, and / or the amino acid L at position 590, numbered according to SEQ ID NO: 138, wherein the AAV capsid variant comprises an amino acid sequence at least 95% identical to the amino acid sequence of positions 203-736 of SEQ ID NO: 138. In some embodiments, the AAV capsid variant comprises an amino acid sequence having the following formula: [N1]-[N2]-[N3]. wherein: (i) [Nl] comprises XI, X2, and X3, wherein at least one of XI. X2, or X3 is G; (ii) [N2] comprises the amino acid sequence of SPH; and (iii) [N3] comprises X4, X5, and X6, wherein at least one of X4, X5, or X6 is a basic amino acid, e.g., a K or R; wherein [N1]-[N2]-[N3] is present in hypervariable loop IV.

[0016] In another aspect, the present disclosure provides an AAV capsid variant, comprising: (a) three, four, or all of the amino acid R at position 584, the amino acid T at position 586, the amino acid L at position 588, tire amino acid Q at position 589, and / or the amino acid L at position 590, numbered according to SEQ ID NO: 138; and (b) the amino acid sequence of HDSPHK (SEQ ID NO: 2) in hypervariable loop IV; wherein the AAV capsid variant comprises an amino acid sequence at least 95% identical to the amino acid sequence of positions 203-736 of SEQ ID NO: 138. In someembodiments, the amino acid sequence of HDSPHK (SEQ ID NO: 2) is present immediately subsequent to amino acid 453, numbered according to SEQ ID NO: 982.

[0017] In yet another aspect, the present disclosure provides an AAV capsid variant, comprising: (a) three, four, or all of the amino acid R at position 584, the amino acid T at position 586, the amino acid L at position 588, the amino acid Q at position 589, and / or the amino acid L at position 590, numbered according to SEQ ID NO: 138; and (b) the amino acid sequence of SPHSKA (SEQ ID NO: 941) in hypervariable loop IV; wherein the AAV capsid variant comprises an amino acid sequence at least 95% identical to the amino acid sequence of positions 203-736 of SEQ ID NO: 138. In some embodiments, die ammo acid sequence of SPHSKA (SEQ ID NO: 941) is present immediately subsequent to amino acid 455, numbered according to SEQ ID NO: 981.

[0018] In another aspect, the present disclosure provides an AAV capsid variant comprising: (I) (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; (c) an amino acid sequence comprising at least one, two. or three, but no more than four different amino acids, relative to any one of the sequences provided in Tables 1, 2A, 2B, 13-19; or (d) an amino acid sequence comprising 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 the sequences provided in Tables 1, 2A, 2B, 13-19; and / or (II) (i) the amino acid sequence of SEQ ID NO: 6419; (ii) an amino acid sequence comprising at least one or two, but no more than three different amino acids, relative to the amino acid sequence of SEQ ID NO: 6419; (iii) an amino acid sequence comprising at least one or two modifications, e.g., substitutions (e.g., conservative substitutions), but no more than three modifications, e.g., substitutions (e g., conservative substitutions), relative to the amino acid sequence of SEQ ID NO: 6419; or (iv) at least 3. 4, 5, 6, or 7 consecutive amino acids from SEQ ID NO: 6419; optionally wherein the amino acid sequence of (i). (ii). (iii), and / or (iv) is present at positions 590-596, numbered according to the amino acid sequence of SEQ ID NO: 981. 982, 6411, or 6412. In some embodiments, the amino acid sequence is present in loop IV. In some embodiments, the amino acid sequence is present in loop VIII. In some embodiments, the amino acid sequence is present in loop IV and loop VIII. In some embodiments, the amino acid sequence is present immediately subsequent to position 448, 452, 453, 455, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 6414. In some embodiments, the amino acid sequence is present at positions 590, 592, 594, 595, and / or 596, numbered according to the amino acid sequence of SEQ ID NO: 981, 982, 6411, or 6412. In some embodiments, the amino acid sequence is present at positions 594, 597, 598, and / or 599, numbered according to die amino acid sequence of SEQ ID NO: 981, 982, 6411, or 6412.

[0019] In yet another aspect, the present disclosure provides an AAV capsid variant comprising: (I) (a) the amino acid sequence of any of SEQ ID NOs: 945-980 or 985-986; (b) an amino acidsequence 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 one. two. or three but no more than four different amino acids, relative to the amino acid sequence of any one of SEQ ID NOs: 945-980 or 985-986; (d) an amino acid sequence comprising 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: 945-980 or 985-986; and / or (II) (II) (i) the amino acid sequence of SEQ ID NO: 6419; (ii) an amino acid sequence comprising at least one or two. but no more than three different amino acids, relative to the amino acid sequence of SEQ ID NO: 6419; (iii) an amino acid sequence comprising at least one or two modifications, e.g., substitutions (e.g., conservative substitutions), but no more than three modifications, e.g., substitutions (e.g., conserv ative substitutions), relative to the amino acid sequence of SEQ ID NO: 6419; or (iv) at least 3, 4, 5, 6, or 7 consecutive amino acids from SEQ ID NO: 6419; optionally wherein the amino acid sequence of (i), (ii), (iii), and / or (iv) is present at positions 590-596, numbered according to the amino acid sequence of SEQ ID NO: 981, 982, 6411, or 6412. In some embodiments, the amino acid sequence is present in loop IV. In some embodiments, the amino acid sequence is present in loop VIII. In some embodiments, the amino acid sequence is present in loop IV and loop VIII. In some embodiments, the amino acid sequence is present immediately subsequent to position 448, 452, 453. 455, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 6414. In some embodiments, the amino acid sequence is present at positions 590, 592, 594, 595, and / or 596, numbered according to the amino acid sequence of SEQ ID NO: 981. 982, 6411, or 6412. In some embodiments, the amino acid sequence is present at positions 594, 597. 598, and / or 599. numbered according to the amino acid sequence of SEQ ID NO: 981. 982, 6411, or 6412.

[0020] In yet another aspect, the present disclosure provides an AAV capsid variant comprising: (I) (a) the amino acid sequence of any 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; (c) an amino acid sequence comprising at least one, two, or three, but no more than four 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; or (d) an amino acid sequence comprising 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; and / or (II) (i) the amino acid sequence of SEQ ID NO: 6419; (ii) an amino acid sequence comprising at least one or tw o, but no more than three different amino acids, relative to the amino acid sequence of SEQ ID NO: 6419; (iii) an amino acid sequence comprising at least one or two modifications, e.g., substitutions (e.g., conservative substitutions), but no more than three modifications, e.g., substitutions (e.g., conservative substitutions), relative to the amino acid sequence of SEQ ID NO: 6419; or (iv) at least 3. 4, 5, 6, or 7 consecutive amino acids from SEQ ID NO: 6419; optionally wherein the amino acidsequence of (i), (ii), (iii). and / or (iv) is present at positions 590-596, numbered according to the amino acid sequence of SEQ ID NO: 981, 982. 6411. or 6412. In some embodiments, the amino acid sequence is present in loop IV. In some embodiments, the amino acid sequence is present in loop VIII. In some embodiments, the amino acid sequence is present in loop IV and loop VIII. In some embodiments, the amino acid sequence is present immediately subsequent to position 448, 452. 453, 455. relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 6414. In some embodiments, the amino acid sequence is present at positions 590, 592, 594, 595. and / or 596, numbered according to the amino acid sequence of SEQ ID NO: 981, 982, 6411, or 6412. In some embodiments, the amino acid sequence is present at positions 594, 597, 598, and / or 599, numbered according to the amino acid sequence of SEQ ID NO: 981, 982, 6411, or 6412.

[0021] In yet another aspect, the present disclosure provides a polynucleotide encoding an AAV capsid variant described herein. In some embodiments, the polynucleotide comprises (i) a nucleotide sequence comprising at least one. two, three, four, five, six, or seven modifications, e.g., substitutions (e.g., conservative substitutions), but no more than ten modifications, e g., substitutions (e.g., conservative substitutions), relative to the nucleotide sequences of SEQ ID NO: 3 or 942; (ii) a nucleotide sequence comprising at least one, two, three, four, five, six, or seven, but no more than ten different nucleotides, relative to the nucleotide sequences of SEQ ID NO: 3 or 942; or (iii) the nucleotide sequence of SEQ ID NOs: 3 or 942, or nucleotide sequence substantially identical (e.g.. having at least 70%, 75%, 80%, 85%. 90%, 92%, 95%, 97%, 98%. or 99% sequence identity) thereto.

[0022] In yet another aspect, present 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) the 3 consecutive amino acids comprise SPH; (ii) the 4 consecutive amino acids comprise SPHS (SEQ ID NO: 4700); (iii) the 5 consecutive amino acids comprise SPHSK (SEQ ID NO: 4701); or (iv) the 6 consecutive amino acids comprise 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 with 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 ammo acid sequence is present immediately subsequent to positions 455, numbered according to SEQ ID NO: 138 or 981. In some embodiments, the AAV capsid variant comprises a modification, e.g., a substitution (e.g., conservative substitution) in loop VIII. In some embodiments, loop VIII comprises positions 587-599, numbered according to SEQ ID NO: 981, 982, 6411, or 6412; or positions 581-593, numbered according to SEQ ID NO: 138 or 6414.

[0023] In yet another aspect, the present disclosure provides an AAV capsid variant comprising one or two, but no 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 with 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 present immediately subsequent to positions 455. numbered according to SEQ ID NO: 138 or 981. In some embodiments, the AAV capsid variant comprises a modification, e.g., a substitution (e.g., conservative substitution) in loop VIII. In some embodiments, loop VIII comprises positions 587-599, numbered according to SEQ ID NO: 981, 982. 6411, or 6412; or positions 581-593, numbered according to SEQ ID NO: 138 or 6414.

[0024] In another aspect, the present 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) the 3 consecutive amino acids comprise HDS; (ii) tire 4 consecutive amino acids comprise HDSP (SEQ ID NO: 4702); (iii) the 5 consecutive amino acids comprise HDSPH (SEQ ID NO: 4703); and / or (iv) the 6 consecutive amino acids comprise 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 with 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 present immediately subsequent to positions 453, numbered according to SEQ ID NO: 138 or 982. In some embodiments, the AAV capsid variant comprises a modification, e.g., a substitution (e.g.. conservative substitution) in loop VIII. In some embodiments, loop VIII comprises positions 587-599, numbered according to SEQ ID NO: 981 , 982. 6411. or 6412; or positions 581- 593. numbered according to SEQ ID NO: 138 or 6414.

[0025] In another aspect, the present disclosure provides an AAV capsid variant comprising one or two, but no 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 with 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 AAV capsid variant comprises a modification, e.g., a substitution (e.g., conservative substitution) in loop VIII. In some embodiments, loop VIII comprises positions 587-599,numbered according to SEQ ID NO: 981, 982, 6411, or 6412; or positions 581-593, numbered according to SEQ ID NO: 138 or 6414.

[0026] In yet another aspect, the present disclosure provides a peptide comprising: (a) the amino acid sequence of any of the sequences provided in Tables 1, 2A, 2B, 13-19, or 33; (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 33; (c) an amino acid sequence comprising at least one, two, or three, but no more than four different amino acids relative to the amino acid sequence of any one of the sequences provided in Tables 1, 2A, 2B, 13-19, or 33; or (d) an amino acid sequence comprising at least one, two, or three but no more than four modifications, c.g., substitutions (c.g., conservative substitutions), relative to the amino acid sequence of any one of the sequences provided in Tables 1, 2A, 2B, 13-19, or 33.

[0027] In another aspect, the present disclosure provides a peptide comprising (a) the amino acid sequence of any 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 one, two, or three, but no more than four 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 comprising at least one, two, or three but no more than four 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.

[0028] In another aspect, the present disclosure provides a peptide comprising: (a) the amino acid sequence of any 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) an amino acid sequence comprising at least one, tw o, or three but no more than four 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; or (d) an amino acid sequence comprising at least one, two, or three but no more than four modifications, e.g., substitutions (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.

[0029] In yet another aspect, the present disclosure provides a peptide comprising: (i) the amino acid sequence of SPHSKA (SEQ ID NO: 941); (ii) an amino acid sequence comprising at least one, two, or three, but no more than four different amino acids relative to the amino acid sequence of SPHSKA (SEQ ID NO: 941); (iii) an amino acid sequence comprising 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) at least 3, 4, or 5 consecutive amino acids from the amino acid sequence of SPHSKA (SEQ ID NO: 941).

[0030] In yet another aspect, the present disclosure provides a peptide encoded by (i) the nucleotide sequence of SEQ ID NO: 942, or a nucleotide sequence substantially identical (e.g., having at least 70%. 75%, 80%, 85%, 90%. 92%, 95%, 97%, 98%. or 99% sequence identity) thereto; or (ii) a nucleotide sequence comprising at least one, two, three, four, five, six, or seven, but no more than ten different nucleotides relative to the nucleotide sequence of SEQ ID NO: 942; or (iii) a nucleotide sequence comprising at least one, two, three, four, five, six, or seven modifications, e.g., substitutions (e.g., conservative substitutions), but no more than ten modifications, e.g., substitutions (e.g., conservative substitutions), relative to the nucleotide sequence of SEQ ID NO: 942.

[0031] In yet another aspect, the present disclosure provides a peptide, wherein tire nucleotide sequence encoding the peptide comprises (i) the nucleotide sequence of SEQ ID NO: 942, or a nucleotide sequence substantially identical (e.g.. having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity) thereto; (ii) a nucleotide sequence comprising at least one, two, three, four, five, six, or seven, but not more than 10 different nucleotides, relative to the nucleotide sequence of SEQ ID NO: 942; or (iii) a nucleotide sequence comprising at least one, two, three, four, five, six, or seven modifications, e.g., substitutions (e.g., conservative substitutions), but no more than ten modifications, e.g., substitutions (e.g., conservative substitutions), relative to the nucleotide sequence of SEQ ID NO: 942.

[0032] In another aspect, the present disclosure provides a peptide comprising: (i) the amino acid sequence of HDSPHK (SEQ ID NO: 2); (ii) an amino acid sequence comprising at least one, two. or three, but no more than four different amino acids, relative to the amino acid sequence of HDSPHK (SEQ ID NO: 2); (iii) an amino acid sequence comprising at least one, tw o. or three modifications, e.g.. substitutions (e.g.. conserv ative substitutions), but no more than four modifications, e.g., substitutions (e.g., conserv ative substitutions), relative to the amino acid sequence of HDSPHK (SEQ ID NO: 2); or (iv) at least 3, 4, or 5 consecutive amino acids from the amino acid sequence of HDSPHK (SEQ ID NO: 2).

[0033] In yet another aspect, the present disclosure provides a peptide encoded by (i) the nucleotide sequence of SEQ ID NO: 3, or a nucleotide sequence substantially identical (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity ) thereto; (ii) a nucleotide sequence comprising at least one, two, three, four, five, six, or seven, but no more than ten different nucleotides, relative to the nucleotide sequence of SEQ ID NO: 3; (iii) a nucleotide sequence comprising at least one, two, three, four, five, six, or seven modifications, e.g., substitutions (e g., conservative substitutions), but no more than ten modifications, e.g., substitutions (e.g., conservative substitutions), relative to the nucleotide sequence of SEQ ID NO: 3.

[0034] In another aspect, the present 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 (e.g.. having at least 70%. 75%. 80%, 85%, 90%. 92%. 95%, 97%, 98%, or 99% sequence identity) thereto; (ii) a nucleotide sequence comprising at least one.two, three, four, five, six, or seven, but no more than ten different nucleotides relative to the nucleotide sequence of SEQ ID NO: 3; or (iii) a nucleotide sequence comprising at least one. two, three, four, five, six, or seven modifications, e.g., substitutions (e.g.. conservative substitutions), but no more than ten modifications, e.g., substitutions (e.g., conservative substitutions), relative to the nucleotide sequence of SEQ ID NO: 3.

[0035] In yet another aspect, the present disclosure provides a polynucleotide encoding an AAV capsid variant comprising: (I) (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; (c) an amino acid sequence comprising at least one, two, or three, but no more than four different amino acids, relative to any one of the sequences provided in Tables 1, 2A, 2B, 13-19; or (d) an amino acid sequence comprising 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 the sequences provided in Tables 1. 2A. 2B. 13-19; and / or (II) (i) the amino acid sequence of any of the sequences provided in Table 33; (ii) an amino acid sequence comprising at least one. two, or three, but no more than four different amino acids, relative to the amino acid sequence of any one of the amino acid sequences provided in Table 33; (iii) an amino acid sequence comprising 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 any one of the amino acid sequences provided in Table 33; or (iv) at least 3, 4, 5. 6. 7, 8, 9, 10, or 11 consecutive amino acids from any one of the amino acid sequences of Table 33. In some embodiments, the amino acid sequence of (a), (b). (c). and / or (d) is present immediately subsequent to 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. In some embodiments, the amino acid sequence of (i), (ii), (iii), and / or (iv) is present at positions 500-511. numbered according to the amino acid sequence of SEQ ID NO: 981 or 982.

[0036] In yet another aspect, the present disclosure provides a polynucleotide encoding an AAV capsid variant, wherein the AAV capsid variant comprises: (I) (a) the amino acid sequence of SPHSKA (SEQ ID NO: 941); (b) an amino acid sequence comprising at least one, two, or three, but no more than four different amino acids, relative to the amino acid sequence of SPHSKA (SEQ ID NO: 941); (c) an amino acid sequence comprising 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 (d) at least 3, 4, 5, 6, 7, 8, or 9 consecutive amino acids from the amino acid sequence of SPHSKA (SEQ ID NO: 941); and / or (II) (i) the amino acid sequence of any of die sequences provided in Table 33; (ii) an amino acid sequence comprising at least one, two, or three, but no more than four different amino acids, relative to the amino acid sequence of any one of the amino acid sequences provided inTable 33; (iii) an amino acid sequence comprising 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 any one of the amino acid sequences provided in Table 33; or (iv) at least 3, 4, 5, 6. 7. 8, 9, 10. or 11 consecutive amino acids from any one of the amino acid sequences of Table 33. In some embodiments, the amino acid sequence of (a), (b), (c), and / or (d) is present immediately subsequent to position 455, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. In some embodiments, the amino acid sequence of (i), (ii), (iii). and / or (iv) is present at positions 500-511, numbered according to the amino acid sequence of SEQ ID NO: 981 or 982.

[0037] In another aspect, the present disclosure provides a polynucleotide encoding an AAV capsid variant, wherein the AAV capsid variant comprises: (I) (a) the amino acid sequence of HDSPHK (SEQ ID NO: 2); (b) an amino acid sequence comprising at least one, two, or three, but no more than four different amino acids, relative to the amino acid sequence of HDSPHK (SEQ ID NO: 2); (c) an amino acid sequence comprising 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 (d) at least 3, 4, 5. or 6 consecutive amino acids from the amino acid sequence of HDSPHK (SEQ ID NO: 2); and / or (II) (i) the amino acid sequence of any of the sequences provided in Table 33; (ii) an amino acid sequence comprising at least one, two, or three, but no more than four different amino acids, relative to the amino acid sequence of any one of the amino acid sequences provided in Table 33; (iii) an amino acid sequence comprising 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 any one of the amino acid sequences provided in Table 33; or (iv) at least 3, 4, 5. 6. 7. 8, 9, 10, or 11 consecutive amino acids from any one of tire amino acid sequences of Table 33; optionally wherein the amino acid sequence of (i), (ii), (iii), and / or (iv) is present at positions 500-51 1 , numbered according to the amino acid sequence of SEQ ID NO: 981 or 982. In some embodiments, the amino acid sequence of (a), (b), (c), and / or (d) is present immediately subsequent to position 453, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. In some embodiments, the amino acid sequence of (i), (ii), (iii), and / or (iv) is present at positions 500-511, numbered according to the amino acid sequence of SEQ ID NO: 981 or 982.

[0038] In yet another aspect, the present disclosure provides an AAV capsid variant comprising: (i) the amino acid sequence of SPH, wherein the amino acid sequence is present immediately subsequent to position 455, numbered according to the amino acid sequence of any one of SEQ ID NOs: 5-10, 36-59, 138, 981, 982, or 6409-6413; and / or (ii) a modification, e.g., a substitution (e.g.. conservative substitution) in loop VIII. In some embodiments, loop VIII comprises positions 587-599,numbered according to SEQ ID NO: 981, 982, 6411, or 6412; or positions 581-593, numbered according to SEQ ID NO: 138 or 6414.

[0039] In yet another aspect, the present disclosure provides an AAV capsid variant comprising: (i) the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is present immediately subsequent to position 455, numbered according to the amino acid sequence of SEQ ID NO: 138; and / or (ii) a modification, e.g., a substitution (e.g., conservative substitution) in loop VIII. In some embodiments, loop VIII comprises positions 587-599, numbered according to SEQ ID NO: 981, 982, 6411, or 6412; or positions 581-593, numbered according to SEQ ID NO: 138 or 6414.

[0040] In yet another aspect, the present disclosure provides an AAV capsid variant comprising: (i) the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is present immediately subsequent to position 455. numbered according to the amino acid sequence of SEQ ID NO: 981 or 6411; and / or (ii) a modification, e.g., a substitution (e.g., conservative substitution) in loop VIII. In some embodiments, loop VIII comprises positions 587-599, numbered according to SEQ ID NO: 981, 982, 6411, or 6412; or positions 581-593, numbered according to SEQ ID NO: 138 or 6414.

[0041] In yet another aspect, the present disclosure provides an AAV capsid variant comprising: (i) the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is present immediately subsequent to position 455, numbered according to the amino acid sequence of SEQ ID NO: 138, 981, or 6411; and (ii) one. two, three, four, or all of an amino acid other than H at position 590. S at position 592, Q at position 594, A at position 595, and / or Q at position 596, numbered according to SEQ ID NO: 981 or 6411. In some embodiments, the amino acid sequence of SPHSKA (SEQ ID NO: 941) is present at amino acids 456-461, numbered according to SEQ ID NO: 981 or 6411.

[0042] In yet another aspect, the present disclosure provides an AAV capsid variant comprising: (i) the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is present immediately subsequent to position 455, numbered according to the amino acid sequence of SEQ ID NO: 138, 981, or 6411; and (ii) an amino acid other than H at position 590, S at position 592, Q at position 594, A at position 595, and Q at position 596, numbered according to SEQ ID NO: 981 or 6411. In some embodiments, the amino acid sequence of SPHSKA (SEQ ID NO: 941) is present at amino acids 456-461, numbered according to SEQ ID NO: 981 or 6411.

[0043] In yet another aspect, the present disclosure provides an AAV capsid variant comprising: (i) the amino acid sequence of SPHSKA (SEQ ID NO: 941). wherein the amino acid sequence is present immediately subsequent to position 455. numbered according to the amino acid sequence of SEQ ID NO: 138, 981. or 6411; and (ii) one, two, three, four, or all of the amino acid R at position 590, T at position 592. L at position 594, Q at position 595, and / or L at position 596, numbered according to SEQ ID NO: 981 or 6411, or a substitution, e.g., a conservative substitution thereof. Insome embodiments, the amino acid sequence of SPHSKA (SEQ ID NO: 941) is present at amino acids 456-461. numbered according to SEQ ID NO: 981 or 6411.

[0044] In yet another aspect, the present disclosure provides an AAV capsid variant comprising: (i) the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is present at amino acids 456-461. numbered according to SEQ ID NO: 981 or 6411; and (ii) one. two, three, four, or all of the amino acid R at position 590, T at position 592, L at position 594, Q at position 595, and / or L at position 596, numbered according to SEQ ID NO: 981 or 6411, or a substitution, e.g., a conservative substitution thereof.

[0045] In yet another aspect, the present disclosure provides an AAV capsid variant comprising: (i) the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is present immediately subsequent to position 455. numbered according to the amino acid sequence of SEQ ID NO: 138, 981. or 6411; and (ii) the amino acid R at position 590, T at position 592, L at position 594, Q at position 595, and L at position 596, numbered according to SEQ ID NO: 981 or 6411. In some embodiments, the amino acid sequence of SPHSKA (SEQ ID NO: 941) is present at amino acids 456-461, numbered according to SEQ ID NO: 981 or 6411.

[0046] In yet another aspect, the present disclosure provides an AAV capsid variant comprising: (i) the amino acid sequence of SPHSKA (SEQ ID NO: 941). wherein the amino acid sequence is present at amino acids 456-461, numbered according to SEQ ID NO: 981 or 6411; and (ii) the amino acid R at position 590, T at position 592. L at position 594. Q at position 595, and L at position 596, numbered according to SEQ ID NO: 981 or 6411.

[0047] In yet another aspect, the present disclosure provides an AAV capsid variant comprising: (i) the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is present immediately subsequent to position 455, numbered according to the amino acid sequence of SEQ ID NO: 138, 981, or 6411; and (ii) one, two, three, four, or all of an amino acid other than H at position 584, S at position 586, Q at position 588, A at position 589, and / or Q at position 590, numbered according to SEQ ID NO: 138 or 6414. In some embodiments, the amino acid sequence of SPHSKA (SEQ ID NO: 941) is present at amino acids 456-461, numbered according to SEQ ID NO: 981 or 6411.

[0048] In yet another aspect, the present disclosure provides an AAV capsid variant comprising: (i) the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is present immediately subsequent to position 455. numbered according to the amino acid sequence of SEQ ID NO: 138, 981. or 6411; and (ii) an amino acid other than H at position 584, S at position 586, Q at position 588, A at position 589, and Q at position 590, numbered according to SEQ ID NO: 138 or 6414. In some embodiments, the amino acid sequence of SPHSKA (SEQ ID NO: 941) is present at amino acids 456-461, numbered according to SEQ ID NO: 981 or 6411.

[0049] In yet another aspect, the present disclosure provides an AAV capsid variant comprising: (i) the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence ispresent immediately subsequent to position 455. numbered according to the amino acid sequence of SEQ ID NO: 138, 981, or 6411; and (ii) one. two, three, four, or all of the amino acid R at position 584. T at position 586, L at position 588, Q at position 589. and / or L at position 590. numbered according to SEQ ID NO: 138 or 6414, or a substitution, e.g.. a conservative substitution thereof. In some embodiments, the amino acid sequence of SPHSKA (SEQ ID NO: 941) is present at amino acids 456-461. numbered according to SEQ ID NO: 981 or 6411.

[0050] In yet another aspect, the present disclosure provides an AAV capsid variant comprising: (i) the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is present immediately subsequent to position 455, numbered according to the amino acid sequence of SEQ ID NO: 138, 981, or 6411; and (ii) the amino acid R at position 584, T at position 586, L at position 588, Q at position 589, and L at position 590, numbered according to SEQ ID NO: 138 or 6414. In some embodiments, the amino acid sequence of SPHSKA (SEQ ID NO: 941) is present at amino acids 456-461, numbered according to SEQ ID NO: 981 or 6411.

[0051] In yet another aspect, the present disclosure provides an AAV capsid variant comprising: (i) the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is present at amino acids 456-461, numbered according to SEQ ID NO: 981, or 6411; and (ii) the amino acid R at position 584. T at position 586, L at position 588, Q at position 589. and L at position 590, numbered according to SEQ ID NO: 138 or 6414.

[0052] In yet another aspect, the present disclosure provides an AAV capsid variant comprising: (i) the amino acid sequence of HDSPHK (SEQ ID NO: 2), wherein the amino acid sequence is present immediately subsequent to position 453. numbered according to the amino acid sequence of SEQ ID NO: 138, 982, or 6412; and / or (ii) a modification, e.g., a substitution (e.g.. conservative substitution) in loop VIII. In some embodiments, loop VIII comprises positions 587-599, numbered according to SEQ ID NO: 981, 982, 6411, or 6412; or positions 581-593, numbered according to SEQ ID NO: 138 or 6414. In some embodiments, the amino acid sequence of HDSPHK (SEQ ID NO: 2) is present at amino acids 454-459, numbered according to SEQ ID NO: 982 or 6412.

[0053] In yet another aspect, the present disclosure provides an AAV capsid variant comprising: (i) the amino acid sequence of HDSPHK (SEQ ID NO: 2), wherein the amino acid sequence is present immediately subsequent to position 453, numbered according to the amino acid sequence of SEQ ID NO: 138, 982, or 6412; and (ii) one, two, three, four, or all of an amino acid other than H at position 590, S at position 592, Q at position 594, A at position 595, and / or Q at position 596, numbered according to SEQ ID NO: 982 or 6412. In some embodiments, the amino acid sequence of HDSPHK (SEQ ID NO: 2) is present at amino acids 454-459, numbered according to SEQ ID NO: 982 or 6412.

[0054] In yet another aspect, the present disclosure provides an AAV capsid variant comprising: (i) the amino acid sequence of HDSPHK (SEQ ID NO: 2). wherein the amino acid sequence is present immediately subsequent to position 453, numbered according to the amino acid sequence of SEQ ID NO: 138, 982, or 6412; and (ii) an amino acid other than H at position 590, S at position 592, Q atposition 594, A at position 595, and Q at position 596, numbered according to SEQ ID NO: 982 or 6412. In some embodiments, the amino acid sequence of HDSPHK (SEQ ID NO: 2) is present at amino acids 454-459. numbered according to SEQ ID NO: 982 or 6412.

[0055] In yet another aspect, the present disclosure provides an AAV capsid variant comprising: (i) the amino acid sequence of HDSPHK (SEQ ID NO: 2), wherein the amino acid sequence is present immediately subsequent to position 453, numbered according to the amino acid sequence of SEQ ID NO: 138, 982, or 6412; and (ii) one, two, three, four, or all of the amino acid R at position 590. T at position 592, L at position 594, Q at position 595, and / or L at position 596, numbered according to SEQ ID NO: 982 or 6412, or a substitution, e.g.. a conservative substitution thereof. In some embodiments, die ammo acid sequence of HDSPHK (SEQ ID NO: 2) is present at amino acids 454- 459, numbered according to SEQ ID NO: 982 or 6412.

[0056] In yet another aspect, the present disclosure provides an AAV capsid variant comprising: (i) the amino acid sequence of HDSPHK (SEQ ID NO: 2), wherein the amino acid sequence is present at amino acids 454-459, numbered according to SEQ ID NO: 982 or 6412; and (ii) one, two, three, four, or all of the amino acid R at position 590, T at position 592, L at position 594, Q at position 595, and / or L at position 596, numbered according to SEQ ID NO: 982 or 6412, or a substitution, e.g., a conservative substitution thereof.

[0057] In yet another aspect, the present disclosure provides an AAV capsid variant comprising: (i) the amino acid sequence of HDSPHK (SEQ ID NO: 2), wherein the amino acid sequence is present immediately subsequent to position 453. numbered according to the amino acid sequence of SEQ ID NO: 138, 982, or 6412; and (ii) the amino acid R at position 590, T at position 592, L at position 594. Q at position 595, and L at position 596. numbered according to SEQ ID NO: 982 or 6412. In some embodiments, the amino acid sequence of HDSPHK (SEQ ID NO: 2) is present at amino acids 454- 459. numbered according to SEQ ID NO: 982 or 6412.

[0058] In yet another aspect, the present disclosure provides an AAV capsid variant comprising: (i) the amino acid sequence of HDSPHK (SEQ ID NO: 2), wherein the amino acid sequence is present at amino acids 454-459, numbered according to SEQ ID NO: 982 or 6412; and (ii) the amino acid R at position 590, T at position 592, L at position 594, Q at position 595, and L at position 596, numbered according to SEQ ID NO: 982 or 6412.

[0059] In yet another aspect, the present disclosure provides an AAV capsid variant comprising: (i) the amino acid sequence of HDSPHK (SEQ ID NO: 2), wherein the amino acid sequence is present immediately subsequent to position 453, numbered according to the amino acid sequence of SEQ ID NO: 138, 982. or 6412; and (ii) one, two, three, four, or all of an amino acid other than H at position 584, S at position 586. Q at position 588, A at position 589, and / or Q at position 590, numbered according to SEQ ID NO: 138 or 6414. In some embodiments, the amino acid sequence of HDSPHK (SEQ ID NO: 2) is present at amino acids 454-459, numbered according to SEQ ID NO: 982 or 6412.

[0060] In yet another aspect, the present disclosure provides an AAV capsid variant comprising: (i) the amino acid sequence of HDSPHK (SEQ ID NO: 2), wherein the amino acid sequence is present immediately subsequent to position 453. numbered according to the amino acid sequence of SEQ ID NO: 138, 982, or 6412; and (ii) an amino acid other than H at position 584, S at position 586. Q at position 588, A at position 589. and Q at position 590, numbered according to SEQ ID NO: 138 or 6414. In some embodiments, the amino acid sequence of HDSPHK (SEQ ID NO: 2) is present at amino acids 454-459, numbered according to SEQ ID NO: 982 or 6412.

[0061] In yet another aspect, the present disclosure provides an AAV capsid variant comprising: (i) the amino acid sequence of HDSPHK (SEQ ID NO: 2), wherein the amino acid sequence is present immediately subsequent to position 453, numbered according to the amino acid sequence of SEQ ID NO: 138, 982, or 6412; and (ii) one, two, three, four, or all of the amino acid R at position 584, T at position 586, L at position 588, Q at position 589, and / or L at position 590, numbered according to SEQ ID NO: 138 or 6414, or a substitution, e.g., a conservative substitution thereof. In some embodiments, the amino acid sequence of HDSPHK (SEQ ID NO: 2) is present at amino acids 454- 459, numbered according to SEQ ID NO: 982 or 6412.

[0062] In yet another aspect, the present disclosure provides an AAV capsid variant comprising: (i) the amino acid sequence of HDSPHK (SEQ ID NO: 2). wherein the amino acid sequence is present at amino acids 454-459, numbered according to SEQ ID NO: 982 or 6412; and (ii) one, two, three, four, or all of the amino acid R at position 584. T at position 586, L at position 588, Q at position 589, and / or L at position 590, numbered according to SEQ ID NO: 138 or 6414, or a substitution, e.g.. a conservative substitution thereof.

[0063] In yet another aspect, the present disclosure provides an AAV capsid variant comprising: (i) the amino acid sequence of HDSPHK (SEQ ID NO: 2), wherein the amino acid sequence is present immediately subsequent to position 453, numbered according to the amino acid sequence of SEQ ID NO: 138, 982, or 6412; and (ii) the amino acid R at position 584, T at position 586, L at position 588, Q at position 589, and L at position 590, numbered according to SEQ ID NO: 138 or 6414. In some embodiments, die ammo acid sequence of HDSPHK (SEQ ID NO: 2) is present at amino acids 454- 459, numbered according to SEQ ID NO: 982 or 6412.

[0064] In yet another aspect, the present disclosure provides an AAV capsid variant comprising: (i) the amino acid sequence of HDSPHK (SEQ ID NO: 2), wherein the amino acid sequence is present at amino acids 454-459, numbered according to SEQ ID NO: 982 or 6412; and (ii) the amino acid R at position 584, T at position 586, L at position 588, Q at position 589, and L at position 590, numbered according to SEQ ID NO: 138 or 6414.

[0065] In yet another aspect, the present disclosure provides an AAV capsid variant comprising: (i) the amino acid sequence of HDSPHK (SEQ ID NO: 2), wherein the amino acid sequence is present immediately subsequent to position 453. numbered according to the amino acid sequence of SEQ ID NO: 138 or 982; and (ii) one, two. three, or all of an amino acid other than Q at position 594. A atposition 597, Q at position 598, and / or T at position 599, numbered according to SEQ ID NO: 982 or6413. In some embodiments, the amino acid sequence of HDSPHK (SEQ ID NO: 2) is present at amino acids 454-459. numbered according to SEQ ID NO: 982 or 6412.

[0066] In yet another aspect, the present disclosure provides an AAV capsid variant comprising: (i) the amino acid sequence of HDSPHK (SEQ ID NO: 2), wherein the amino acid sequence is present immediately subsequent to position 453, numbered according to the amino acid sequence of SEQ ID NO: 138 or 982; and (ii) an amino acid other than Q at position 594, A at position 597, Q at position 598, and T at position 599, numbered according to SEQ ID NO: 982 or 6413. In some embodiments, die amino acid sequence of HDSPHK (SEQ ID NO: 2) is present at amino acids 454-459, numbered according to SEQ ID NO: 982 or 6412.

[0067] In yet another aspect, the present disclosure provides an AAV capsid variant comprising: (i) the amino acid sequence of HDSPHK (SEQ ID NO: 2), wherein the amino acid sequence is present immediately subsequent to position 453, numbered according to the amino acid sequence of SEQ ID NO: 138 or 982; and (ii) one. Evo, three, or all of the amino acid K at position 594, S at position 597. S at position 598, and / or A at position 599, numbered according to SEQ ID NO: 982 or 6413, or a substitution, e.g., a conservative substitution thereof. In some embodiments, the amino acid sequence of HDSPHK (SEQ ID NO: 2) is present at amino acids 454-459, numbered according to SEQ ID NO: 982 or 6412.

[0068] In yet another aspect, the present disclosure provides an AAV capsid variant comprising: (i) the amino acid sequence of HDSPHK (SEQ ID NO: 2), wherein the amino acid sequence is present immediately subsequent to position 453. numbered according to the amino acid sequence of SEQ ID NO: 138 or 982; and (ii) the amino acid K at position 594, S at position 597. S at position 598, and A at position 599, numbered according to SEQ ID NO: 982 or 6413. In some embodiments, the amino acid sequence of HDSPHK (SEQ ID NO: 2) is present at amino acids 454-459, numbered according to SEQ ID NO: 982 or 6412.

[0069] In yet another aspect, the present disclosure provides an AAV capsid variant comprising: (i) the amino acid sequence of HDSPHK (SEQ ID NO: 2), wherein the amino acid sequence is present immediately subsequent to position 453, numbered according to the amino acid sequence of SEQ ID NO: 138 or 982; and (ii) one, Evo, three, or all of an amino acid other than Q at position 588, A at position 591, Q at position 592, and / or T at position 593, numbered according to SEQ ID NO: 138 or6414. In some embodiments, the amino acid sequence of HDSPHK (SEQ ID NO: 2) is present at amino acids 454-459, numbered according to SEQ ID NO: 982 or 6412.

[0070] In yet another aspect, the present disclosure provides an AAV capsid variant comprising: (i) the amino acid sequence of HDSPHK (SEQ ID NO: 2). wherein the amino acid sequence is present immediately subsequent to position 453, numbered according to the amino acid sequence of SEQ ID NO: 138 or 982; and (ii) an amino acid other than Q at position 588, A at position 591, Q at position 592, and T at position 593, numbered according to SEQ ID NO: 138 or 6414. In some embodiments.the amino acid sequence of HDSPHK (SEQ ID NO: 2) is present at amino acids 454-459, numbered according to SEQ ID NO: 982 or 6412.

[0071] In yet another aspect, the present disclosure provides an AAV capsid variant comprising: (i) the amino acid sequence of HDSPHK (SEQ ID NO: 2), wherein the amino acid sequence is present immediately subsequent to position 453, numbered according to the amino acid sequence of SEQ ID NO: 138 or 982; and (ii) one, two, three, or all of the amino acid K at position 588, S at position 591, S at position 592, and / or A at position 593, numbered according to SEQ ID NO: 138 or 6414, or a substitution, e.g., a conservative substitution thereof. In some embodiments, the amino acid sequence of HDSPHK (SEQ ID NO: 2) is present at amino acids 454-459, numbered according to SEQ ID NO: 982 or 6412.

[0072] In yet another aspect, the present disclosure provides an AAV capsid variant comprising: (i) the amino acid sequence of HDSPHK (SEQ ID NO: 2), wherein the amino acid sequence is present immediately subsequent to position 453, numbered according to the amino acid sequence of SEQ ID NO: 138 or 982; and (ii) the amino acid K at position 588, S at position 591, S at position 592, and A at position 593, numbered according to SEQ ID NO: 138 or 6414. In some embodiments, the amino acid sequence of HDSPHK (SEQ ID NO: 2) is present at amino acids 454-459, numbered according to SEQ ID NO: 982 or 6412.

[0073] In yet another aspect, the present disclosure provides an AAV capsid variant comprising: (i) the amino acid sequence of HDSPHK (SEQ ID NO: 2), wherein the amino acid sequence is present immediately subsequent to position 453. numbered according to the amino acid sequence of SEQ ID NO: 982; and / or (ii) loop VIII comprises positions 587-599, numbered according to SEQ ID NO: 981, 982. 6411. or 6412; or positions 581-593, numbered according to SEQ ID NO: 138 or 6414. In some embodiments, the amino acid sequence of HDSPHK (SEQ ID NO: 2) is present at amino acids 454- 459. numbered according to SEQ ID NO: 982 or 6412.

[0074] In yet another aspect, the present disclosure provides an AAV capsid variant comprising: (i) the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is present in loop IV, relative to a reference sequence of SEQ ID NO: 138; and / or (ii) a modification, e.g., a substitution (e.g., conservative substitution) in loop VIII. In some embodiments, loop VIII comprises positions 587-599, numbered according to SEQ ID NO: 981, 982, 6411, or 6412; or positions 581-593, numbered according to SEQ ID NO: 138 or 6414. In some embodiments, loop IV comprises positions 449-460. numbered according to SEQ ID NO: 138.

[0075] In yet another aspect, the present disclosure provides an AAV capsid variant comprising: (i) the amino acid sequence of HDSPHK (SEQ ID NO: 2). wherein the amino acid sequence is present in loop IV, relative to a reference sequence of SEQ ID NO: 138; and / or (ii) a modification, e.g., a substitution (e.g., conservative substitution) in loop VIII. In some embodiments, loop VIII comprises positions 587-599. numbered according to SEQ ID NO: 981. 982, 6411, or 6412; or positions 581-593, numbered according to SEQ ID NO: 138 or 6414. In some embodiments, loop IV comprises positions 449-460, numbered according to SEQ ID NO: 138.

[0076] In yet another aspect the present disclosure provides an AAV capsid variant comprising the amino acid sequence of SEQ ID NO: 6411.

[0077] In yet another aspect the present disclosure provides an AAV capsid variant comprising the amino acid sequence of SEQ ID NO: 6412.

[0078] In yet another aspect the present disclosure provides an AAV capsid variant comprising the amino acid sequence of SEQ ID NO: 6413.

[0079] In yet another aspect the present disclosure provides an AAV capsid variant comprising the amino acid sequence of SEQ ID NO: 6414.

[0080] In yet another aspect, the present disclosure provides an AAV capsid variant comprising one, two, three, four, or all of the amino acid R at position 584, T at position 586. L at position 588, Q at position 589, and / or L at position 590, numbered according to SEQ ID NO: 138 or 6414, or a substitution, e.g.. a conservative substitution thereof.

[0081] In yet another aspect, the present disclosure provides an AAV capsid variant comprising the amino acid R at position 584, T at position 586, L at position 588. Q at position 589, and L at position 590, numbered according to SEQ ID NO: 138 or 6414.

[0082] 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 pay load. In some embodiments, the AAV particle further comprises a viral genome comprising a promoter operably linked to the nucleic acid encoding the payload.

[0083] In yet another aspect, the present disclosure provides a method of making an AAV particle comprising an AAV capsid variant described herein. The method comprises providing a host cell comprising a viral genome and incubating the host cell under conditions suitable to enclose the viral genome in the AAV capsid variant, e g., an AAV capsid variant described herein, thereby making the AAV particle.

[0084] In yet another aspect, the present disclosure provides a method of delivering a payload to a cell or tissue (e.g., a CNS cell, a CNS tissue, a liver cell, or a liver tissue). The method comprising administering an effective amount of an AAV particle comprising an AAV capsid variant described herein.

[0085] In yet another aspect, the present disclosure provides a method of treating a subject having or diagnosed with having a genetic disorder, e.g., a monogenic disorder or a polygenic disorder. The method comprising administering to the subject an effective amount an AAV particle comprising an AAV capsid variant described herein.

[0086] In yet another aspect, the present disclosure provides a method of treating a subject having or diagnosed with having neurological, e.g., a neurodegenerative, disorder. The method comprisingadministering an effective amount of an AAV particle comprising an AAV capsid variant described herein.

[0087] In yet another aspect, the present disclosure provides a method of treating a subject having or diagnosed with having a neuro-oncological disorder. The method comprising administering an effective amount of an AAV particle comprising an AAV capsid variant described herein.

[0088] 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. Such equivalents are intended to be encompassed by the following enumerated embodiments.Enumerated Embodiments1. An AAV capsid variant, comprising:(A) a modification, e.g., a substitution (e.g.. conservative substitution) in loop VIII, optionally wherein loop VIII comprises positions 587-599, numbered according to SEQ ID NO: 981, 982, 6411, or 6412; or positions 581-593, numbered according to SEQ ID NO: 138 or 6414; and / or(B) an amino acid sequence having the following formula: [N1]-[N2]-[N3], wherein:(i) optionally [Nl] comprises XI, X2, and X3, wherein at least one of XI, X2, or X3 is G;(ii) [N2] comprises the amino acid sequence of SPH; and(iii) [N3] comprises X4, X5, and X6, wherein at least one of X4, X5, or X6 is a basic amino acid, e.g., a K or R.2. The AAV capsid variant of embodiment 1, wherein X4, X5, or both of [N3] is a K.3. The AAV capsid variant of embodiment 1 or 2, wherein X4, X5, or X6 of [N3] is an R.4. The AAV capsid variant of any one of embodiments 1-3, wherein:(a) position X4 of [N3] is: K, S, A, V, T, G, F, W, V, N, or R;(b) position X5 of [N3] is: S, K, T, F, I, L. Y, H, M, or R; and / or(c) position X6 of [N3] is: G, A, R, M, I, N, T, Y, D. P, V, L. E, W. N, Q, K, or S; optionally wherein the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of the aforesaid amino acids in (a)-(c).5. The AAV capsid variant of any one of embodiments 1-4, wherein [N3] comprises SK, KA, KS, AR, RM, VK. AS. SR. VK, KR, KK. KN, VR, RS, RK, KT. TS. KF. FG. KI. 1G, 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.6. The AAV capsid variant of any one of embodiments 1-5, 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.7. The AAV capsid variant of any one of embodiments 1-6, wherein [N2]-[N3] comprises 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: 4717), 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).8. The AAV capsid variant of any one of embodiments 1-7, wherein [N2]-[N3] is or comprises:(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), 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), 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 any portion of an amino acid sequence in (i), e.g., any 2, 3. 4. or 5 amino acids, e.g.. consecutive amino acids, thereof(iii) an amino acid sequence comprising one. two, or three but no 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 amino acid sequence comprising one. two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).9. The AAV capsid variant of any one of embodiments 1-8, which comprises 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 a G at position 455 (e.g., C, L, D, E, Y, El, V, A, N, P. or S), numbered according to any one of SEQ ID NOs: 5-10, 36-59, 138, 981, 982, or 6409-6414.10. The AAV capsid variant of any one of embodiments 1-8, which comprises the amino acid G at position 453, tire amino acid S at position 454, and the amino acid G at position 455, numbered according to SEQ ID NO: 138 or 981.11. The AAV capsid variant of any one of embodiments 1-9. which comprises the amino acid G at position 453, the amino acid H at position 454, and the amino acid D at position 455, numbered according to SEQ ID NO: 138 or 982.12. The AAV capsid variant of any one of embodiments 1-11, wherein | N 1] comprises XI, X2, and X3. wherein at least one of XI. X2. or X3 is G.13. The AAV capsid variant of any one of embodiments 1-12, wherein:(a) position XI of [Nl] is: G, V. R, D. E, M. T, I, S, A. N, L, K. H, P, W, or C;(b) position X2 of [Nl] is: S, V. L, N, D. H, R. P, G, T. I. A, E, Y. M, or Q; and / or(c) position X3 of [Nl] is: G, C. L, D, E. Y, H. V, A. N, P, or S; optionally wherein the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of the aforesaid amino acids in (a)-(c).14. The AAV capsid variant of any one of embodiments 1-13, wherein [Nl] 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, Al, 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.15. The AAV capsid variant of any one of embodiments 1-14, wherein [Nl] 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.16. The AAV capsid variant of any one of embodiments 1-15, wherein [N1]-[N2] comprises:(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: 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 any portion of an amino acid sequence in (i), e.g., any 2. 3, or 4 amino acids, e.g.. consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to any of tire amino acid sequences in (i); or(iv) an amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).17. The AAV capsid variant of any one of embodiments 1-16, wherein [N1]-[N2] is or comprises:(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). 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);(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i). e.g., any 2, 3, 4, or 5 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no 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 amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).18. The AAV capsid variant of any one of embodiments 1-17, wherein [N1]-[N2]-[N3] comprises:(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: 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), SGSPHRK (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), LGSPHSK (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 IDNO: 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 portion of an amino acid sequence in (i). e.g., any 2, 3. 4, 5, or 6 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, tw o. or three but no 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 amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).19. The AAV capsid variant of any one of embodiments 1-18, wherein [N1]-[N2]-[N3] is or comprises:(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), 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), 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), 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 GHSSPHRSG (SEQ ID NO: 5026);(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i). e.g.. any 2, 3. 4. 5, 6, 7, or 8 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one. two, or three but no 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 amino acid sequence comprising one. two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).20. The AAV capsid variant of any one of embodiments 1-19, wherein [N3] comprises SK, KA, KS, or SG.21. The AAV capsid variant of any one of embodiments 1-20, wherein [N3] is or comprises SKA, KSG, or KYG.22. The AAV capsid variant of any one of embodiments 1-21, wherein [N2]-[N3] comprises SPHSK (SEQ ID NO: 4701), SPHKS (SEQ ID NO: 4704). or SPHKY (SEQ ID NO: 4715).23. The AAV capsid variant of any one of embodiments 1-22, wherein [N2]-[N3] is or comprises SPHSKA (SEQ ID NO: 941).24. The AAV capsid variant of any one of embodiments 1-22, wherein [N2]-[N3] is or comprises SPHKSG (SEQ ID NO: 946).25. The AAV capsid variant of any one of embodiments 1-22, wherein [N2]-[N3] is or comprises SPHKYG (SEQ ID NO: 966).26. The AAV capsid variant of any one of embodiments 1-25, wherein [Nl] comprises GS, SG, GH, or HD.27. The AAV capsid variant of any one of embodiments 1-26, wherein [Nl] is or comprises GSG.28. The AAV capsid variant of any one of embodiments 1-26, wherein [Nl] is or comprises GHD.29. The AAV capsid variant of any one of embodiments 1-23 or 26-27. wherein [N1]-[N2]-[N3] comprises SGSPHSK (SEQ ID NO: 4839).30. The AAV capsid variant of any one of embodiments 1-22, 24, 26, or 28, wherein [N1]-[N2]-[N3] comprises HDSPHKS (SEQ ID NO: 4840).31 . The AAV capsid variant of any one of embodiments 1 -22 or 25-27, wherein [N1]-[N2]-[N3] comprises SGSPHKYG (SEQ ID NO: 5027).32. The AAV capsid variant of any one of embodiments 1-8, 10, 12-23, 26-27, or 29, wherein [Nl]- [N2]-[N3] is or comprises GSGSPHSKA (SEQ ID NO: 4697).33. The AAV capsid variant of any one of embodiments 1-9, 11-22, 24, 26, 28, or 30, wherein [Nl]- [N2]-[N3] is or comprises GHDSPHKSG (SEQ ID NO: 4698).34. The AAV capsid variant of any one of embodiments 1-8, 10, 12-22, 25-27, or 31, wherein [Nl]- [N2]-[N3] is or comprises GSGSPHKYG (SEQ ID NO: 4927).35. The AAV capsid variant of any one of embodiments 1-34, wherein [N1]-[N2]-[N3] replaces positions 453-455, numbered according to the amino acid sequence of SEQ ID NO: 138.36. The AAV capsid variant of any one of embodiments 1-35, which comprises 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: 138.37. The AAV capsid variant of any one of embodiments 1-36, which comprises 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). 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 57.38. The AAV capsid variant of any one of embodiments 1-37, which comprises:(a) the amino acid Q at position 456, the amino acid N at position 457, the amino acid Q at position 458, and / or the amino acid Q at position 459. relative to a reference sequence numbered according to SEQ ID NO: 138; or(b) the amino acid Q at position 462. the amino acid N at position 463. the amino acid Q at position 464. and / or the 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 57.39. The AAV capsid variant of any one of embodiments 1 -38, which further comprises [N4], wherein[N4] comprises X7 X8 X9 X10, and wherein:(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; and(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 wherein the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of die aforesaid amino acids in (a)-(d).40. The AAV capsid variant of embodiment 39, wherein:(a) position X7 of [N4] is Q or R;(b) position X8 of [N4] is N or R;(c) position X9 of [N4] is Q or R; and(d) position XI 0 of [N4] is Q. L, or R.41. The AAV capsid variant of embodiment 39 or 40, wherein [N4] is or comprises:(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: 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), 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 (SEQID 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: 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), 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), QNLL (SEQ ID NO: 5210), QLV1 (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 comprising any portion of an amino acid sequence in (i). e.g., any 2, or 3 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no 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 amino acid sequence comprising one. two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).42. The AAV capsid variant of any one of embodiments 39-41. wherein [N1]-[N2]-[N3]-[N4] is or comprises:(i) the amino acid sequence of any of SEQ ID NOs: 1800-2241;(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i). e.g., any 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no 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 amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).43. The AAV capsid variant of any one of embodiments 39-42, wherein [N1]-[N2]-[N3]-[N4] is or comprises GSGSPHSKAQNQQ (SEQ ID NO: 1801).44. The AAV capsid variant of any one of embodiments 39-42, wherein [N1]-[N2]-[N3]-[N4] is or comprises GHDSPHKSGQNQQ (SEQ ID NO: 1800).45. The AAV capsid variant of any one of embodiments 39-42, wherein [N1]-[N2]-[N3]-[N4] is or comprises GSGSPHKYGQNQQT (SEQ ID NO: 910).46. The AAV capsid variant of any one of embodiments 1-45, which comprises 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: 5-10. 36-59, 138, 981. 982, or 6409-6414.47. The AAV capsid variant of any one of embodiments 1-46, which comprises the amino acid T at position 450, the amino acid I at position 451, and / or the amino acid N at position 452, relative to a reference sequence numbered according to any one of SEQ ID NOs: 138, 981, or 982.48. The AAV capsid variant of any one of embodiments 1-47, which further comprises [NO], wherein [NO] comprises XA XB and XC, and wherein:(a) position XA is: T. S. Y, M, A, C. I. R, L, D, F, V. Q, N, H, E, or G;(b) position XB is: I, M, P, E, N, D, S. A, T, G. Q, F, V, L, C. H, R, W, or L; and(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; and optionally wherein the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of the aforesaid amino acids in (a)-(c).49. The AAV capsid variant of embodiment 48, wherein [NO] is or comprises 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, UN, 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, NHL 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.50. The AAV capsid variant of embodiment 48 or 49, wherein [NO]-[N1]-[N2]-[N3]-[N4] is or comprises:(i) the amino acid sequence of any one of SEQ ID NOs: 2242-2886;(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i), e.g., any 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one. two, or three but no 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 amino acid sequence comprising one. two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).51. The AAV capsid variant of any one of embodiments 48-50. wherein [NO]-[N1]-[N2]-[N3]-[N4] is or comprises TINGSGSPHSKAQNQQ (SEQ ID NO: 2242).52. The AAV capsid variant of any one of embodiments 48-50. wherein [NO]-[N1]-[N2]-[N3]-[N4] is or comprises TINGHDSPHKSGQNQQ (SEQ ID NO: 2243).53. The AAV capsid variant of any one of embodiments 48-52, wherein [NO]-[N1]-[N2]-[N3]-[N4] is or comprises TINGSGSPHKYGQNQQT (SEQ ID NO: 5246).54. The AAV capsid variant of any one of embodiments 1-53, wherein [N1]-[N2]-[N3] is present in loop IV.55. The AAV capsid variant of any one of embodiments 48-54. wherein [NO] and [N4] are present in loop IV.56. The AAV capsid variant of any one of embodiments 48-55. wherein [NO] is present immediately subsequent to position 449, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.57. The AAV capsid variant of any one of embodiments 48-56, wherein [NO] is present immediately subsequent to position 449, relative to a reference sequence numbered according to the amino acid sequence of any one of SEQ ID NOs: 5-10, 36-59. 981, 982, or 6409-6413.58. The AAV capsid variant of any one of embodiments 48-57, wherein [NO] replaces positions 450, 451, and 452 (e.g.. T450, 1451, and N452), relative to a reference sequence numbered according to SEQ ID NO: 138.59. The AAV capsid variant of any one of embodiments 48-58, wherein [NO] replaces positions 450- 452 (e.g., T450, 1451, and N452), relative to a reference sequence numbered according to any one of SEQ ID NOs: 5-10, 36-59. 981, 982, or 6409-6413.60. The AAV capsid variant of any one of embodiments 48-59. wherein [NO] corresponds to positions 450-452 of any one of SEQ ID NOs: 5-10. 36-59, 138, 981 982. or 6409-6414.61 . The AAV capsid variant of any one of embodiments 48-60. wherein [NO] is present immediately subsequent to position 449 and wherein [NO] replaces positions 450-452 (e.g.. T450. 1451, and N452), relative to a reference sequence numbered according to SEQ ID NO: 138.62. The AAV capsid variant of any one of embodiments 48-61. wherein [NO] is present immediately subsequent to position 449 and wherein [NO] replaces positions 450-452 (e.g.. T450, 1451, and N452), relative to a reference sequence numbered according to any one of SEQ ID NOs: 5-10, 36-59, 981, 982, or 6409-6413.63. The AAV capsid variant of any one of embodiments 1-62, wherein [Nl] is present immediately subsequent to position 452, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.64. The AAV capsid variant of any one of embodiments 1 -63, wherein [Nl ] is present immediately subsequent to position 452, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 981 or 982.65. The AAV capsid variant of any one of embodiments 1-61, wherein [Nl] replaces positions 453- 455 (e.g., G453, S454, and G455), relative to a reference sequence numbered according to SEQ ID NO: 138.66. The AAV capsid variant of any one of embodiments 1-64, wherein [Nl] replaces positions 453 (e.g., G453), relative to a reference sequence numbered according to SEQ ID NO: 138.67. The AAV capsid variant of any one of embodiments 1-65, wherein [Nl] replaces positions 453- 455 (e.g., G453, S454, and G455), relative to a reference sequence numbered according to SEQ ID NO: 981.68. The AAV capsid variant of any one of embodiments 1-65 or 67, wherein [Nl] replaces positions 453-455, relative to a reference sequence numbered according to SEQ ID NO: 982.69. The AAV capsid variant of any one of embodiments 1-65, 67, or 68, wherein [N 1] is present immediately subsequent to position 452 and wherein [Nl] replaces positions 453-455 (e.g., G453, S454, and G455), relative to a reference sequence numbered according to SEQ ID NO: 138.70. The AAV capsid variant of any one of embodiments 1-64 or 66. wherein [Nl] is present immediately subsequent to position 452 and wherein [Nl] replaces positions 453 (e.g.. G453), relative to a reference sequence numbered according to SEQ ID NO: 138.71. The AAV capsid variant of any one of embodiments 1—64, 66 or 70, wherein [Nl] is present immediately subsequent to position 452 and wherein [Nl] replaces positions 453-455, relative to a reference sequence numbered according to SEQ ID NO: 981 or 982.72. The AAV capsid variant of any one of embodiments 1-71, wherein [Nl] corresponds to positions73. The AAV capsid variant of any one of embodiment 1-72, which comprises 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 982.74. The AAV capsid variant of any one of embodiments 1 -73, which comprises the amino acid H at position 454 and the amino acid D at position 455, numbered according to SEQ ID NO: 138 or 982.75. The AAV capsid variant of any one of embodiments 1-74, which comprises a substitution at position 454 (e.g., S454H) and / or a substitution at position 455 (e.g., G455D). numbered according to SEQ ID NO: 138.76. The AAV capsid variant of any one of embodiments 1-75, which comprises the amino acid H at position 454 and the amino acid D at position 455, and further comprises the amino acid sequence SPHSKA (SEQ ID NO: 941) immediately subsequent to position 455, relative to a reference sequence numbered according to SEQ ID NO: 138.77. The AAV capsid variant of any one of embodiments 1-76, which comprises the amino acid H at position 454 and the amino acid D at position 455, relative to a reference sequence numbered according to SEQ ID NO: 982.78. The AAV capsid variant of any one of embodiments 1-77, which comprises the amino acid H at position 454 and the amino acid D at position 455, and further comprises the amino acid sequence SPHSKA (SEQ ID NO: 941) immediately subsequent to position 455, relative to a reference sequence numbered according to SEQ ID NO: 982.79. The AAV capsid variant of any one of embodiments 1-72. which comprises the amino acid S at position 454 and the amino acid G at position 455, relative to a reference sequence numbered according to SEQ ID NO: 138.80. The AAV capsid variant of any one of embodiments 1-72 or 79. which comprises the amino acidS at position 454 and the amino acid G at position 455. and further comprises the amino acid sequence SPHSKA (SEQ ID NO: 941) immediately subsequent to position 455, relative to a reference sequence numbered according to SEQ ID NO: 138.81. The AAV capsid variant of any one of embodiments 1-72, 79, or 80, which comprises the amino acid S at position 454 and the amino acid G at position 455, relative to a reference sequence numbered according to SEQ ID NO: 981.82. The AAV capsid variant of any one of embodiments 1-72 or 79-81. which comprises the amino acid S at position 454 and the amino acid G at position 455. and further comprises the amino acid sequence SPHSKA (SEQ ID NO: 941) immediately subsequent to position 455, relative to a reference sequence numbered according to SEQ ID NO: 981.83. The AAV capsid variant of any one of embodiments 1-82, wherein [N2] is present immediately subsequent to position 455, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.84. The AAV capsid variant of any one of embodiments 1-83, wherein [N2] corresponds to positions 456-458 (e.g., S456, P457, H458) of SEQ ID NO: 981 or 982.85. The AAV capsid variant of any one of embodiments 1-83, wherein [N2] corresponds to positions 456-458 (e.g., S456, P457, H458) of any one of SEQ ID NOs: 5-10, 36-59, or 6409-6413.86. The AAV capsid variant of any one of embodiments 1-85, wherein [N2]-[N3] is present immediately subsequent to position 455, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.87. The AAV capsid variant of any one of embodiments 1-86, wherein [N2] is present immediately subsequent to position 455, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 981 or 982.88. The AAV capsid variant of any one of embodiments 1-87, wherein [N2]-[N3] is present immediately subsequent to position 455, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 981 or 982.89. The AAV capsid variant of any one of embodiments 1-88, wherein [N2]-[N3] corresponds to positions 456-461 (e.g.. S456, P457, H458, S459, K460, A461) of SEQ ID NO: 981.90. The AAV capsid variant of any one of embodiments 1-88, wherein [N2]-[N3] corresponds to positions 456-461 (e.g., S456, P457, H458, K459, S460, G461) of SEQ ID NO: 982.91. The AAV capsid variant of any one of embodiments 1-90, wherein [N2] is present immediately subsequent to [Nl],92. The AAV capsid variant of any one of embodiments 1-64, 66, 70, or 71, wherein [N3] is present immediately subsequent to [N2] and replaces positions 454 and 455 (e.g., S454 and G455). numbered according to SEQ ID NO: 138.93. The AAV capsid variant of any one of embodiments 1 -1 -64, 66. 70, 71 , or 92, wherein [N3] is present immediately subsequent to [N1]-[N2] and replaces positions 454 and 455 (e.g.. S454 and G455), numbered according to SEQ ID NO: 138.94. The AAV capsid variant of any one of embodiments 39-93. wherein [N4] is present immediately subsequent to position 455, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.95. The AAV capsid variant of any one of embodiments 39-94, wherein [N4] replaces positions 456- 459 (e.g., Q456, N457, Q458, and Q459), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.96. The AAV capsid variant of any one of embodiments 39-95, wherein [N4] corresponds to positions 462-465 (e.g., Q462. N463, Q464, Q465) of SEQ ID NO: 981 or 982.97. The AAV capsid variant of any one of embodiments 39-96, wherein [N2]-[N3]-[N4] replaces positions 456-459 (e.g., Q456, N457, Q458. and Q459), relative to a reference sequence numbered according to the ammo acid sequence of SEQ ID NO: 138.98. The AAV capsid variant of any one of embodiments 39-97, wherein [N2]-[N3]-[N4] is present immediately subsequent to position 455, and wherein [N2]-[N3]-[N4] replaces positions 456-459 (e.g., Q456, N457, Q458, and Q459), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.99. The AAV capsid variant of any one of embodiments 39-98. wherein [N2]-[N3]-[N4] corresponds to positions 456-465 (e.g., S456, P457, H458, S459, K460, A461. Q462, N463, Q464, Q465) of SEQ ID NO: 981.100. The AAV capsid variant of any one of embodiments 39-98, wherein [N2]-[N3]-[N4] corresponds to positions 456-465 (e.g., S456, P457, H458, K459, S460, G461, Q462, N463, Q464, Q465) of SEQ ID NO: 982.101. The AAV capsid variant of any one of embodiments 39-98, wherein [N2]-[N3]-[N4] corresponds to positions 456-465 of any one of SEQ ID NOs: 5-10, 36-59. 6409-6413.102. The AAV capsid variant of any one of embodiments 39-101. wherein [N1]-[N2]-[N3]-[N4] replaces positions 453-459 (e.g., G453, S454, G455, Q456. N457, Q458, and Q459). relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.103. The AAV capsid variant of any one of embodiments 39-102, wherein [N1]-[N2]-[N3]-[N4] is present immediately subsequent to position 452, and wherein [N1]-[N2]-[N3]-[N4] replaces positions 453-459 (e.g., G453, S454, G455, Q456, N457, Q458, and Q459), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.104. The AAV capsid variant of any one of embodiments 39-99, 102,103, wherein [N1]-[N2]-[N3]- [N4] corresponds to positions 453-465 (e.g., G453, S454, G455, S456, P457, H458, S459, K460, A461, Q462, N463, Q464, Q465) of SEQ ID NO: 981.105. The AAV capsid variant of any one of embodiments 39-98, 100, 102, orl03, wherein [N1]-[N2]- [N3]-[N4] corresponds to positions 453-465 (e.g., G453. H454, D455, S456, P457, H458, K459, S460, G461, Q462, N463, Q464, Q465) of SEQ ID NO: 982.106. The AAV capsid variant of any one of embodiments 39-98, 102. or 103, wherein [N1]-[N2]- [N3]-[N4] corresponds to positions 453-465 of any one of SEQ ID NOs: 5-10, 36-59, or 6409-6413.107. The AAV capsid variant of any one of embodiments 1-99 or 102-104, wherein [N1]-[N2]-[N3] corresponds to positions 453-461 (e.g., G453, S454, G455, S456, P457, H458, S459, K460, A461) of SEQ ID NO: 981.108. The AAV capsid variant of any one of embodiments 1-98. 100, 102, 103. or 105, wherein [Nl]- [N2]-[N3] corresponds to positions 453-461 (e.g, G453, H454. D455, S456, P457, H458, K459, S460, G461) of SEQ ID NO: 982.109. The AAV capsid variant of any one of embodiments 39-98, 102, 103, or 106. wherein [Nl]- [N2]-[N3] corresponds to positions 453-461 of any one of SEQ ID NOs: 5-10, 36-59, or 6409-6413.110. The AAV capsid variant of any one of embodiments 48-109, wherein [N0]-[Nl]-[N2]-[N3]-[N4] replaces positions 450-459 (e.g., T450, 1451, N452, G453, S454, G455, Q456, N457, Q458, andQ459), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.111. The AAV capsid variant of any one of embodiments 48-110. wherein [NO]-[N1]-[N2]-[N3]-[N4] is present immediately subsequent to position 449. and wherein [NO]-[N1 ]-[N2]-[N3]-[N4] replaces positions 450-459 (e.g., T450, 1451. 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: 138.112. The AAV capsid variant of any one of embodiments 48-99, 102-104, or 106, wherein [N0]-[Nl]- [N2]-[N3]-[N4] corresponds to positions 450-465 (e.g., T450, 1451, N452, G453, S454, G455, S456, P457, H458. S459, K460, A461, Q462, N463, Q464, Q465) of SEQ ID NO: 981.113. The AAV capsid variant of any one of embodiments 48-98, 100, 102, 103, 105, or 108, wherein [NO]-[N1]-[N2]-[N3]-[N4] corresponds to positions 450-465 (e.g., T450, 1451, N452, G453, H454, D455, S456, P457, H458, K459, S460, G461, Q462. N463, Q464, Q465) of SEQ ID NO: 982.114. The AAV capsid variant of any one of embodiments 48-98, 102, 103, 106, or 109, wherein [N0]- [N1]-[N2]-[N3]-[N4] corresponds to positions 450-465 of any one of SEQ ID NOs: 5-10, 36-59, or 6409-6413.115. The AAV capsid variant of any one of embodiments 39-114, wherein [N4] replaces positions 462-465 (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 982.116. The AAV capsid variant of any one of embodiments 39-115, wherein [N2]-[N3]-[N4] replaces positions 462-465 (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 982.1 17. The AAV capsid variant of any one of embodiments 39-1 16. wherein [N2]-[N3]-[N4] is present immediately subsequent to position 455, and wherein [N2]-[N3]-[N4] replaces positions 462-465 (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 982.118. The AAV capsid variant of any one of embodiments 1-117, wherein [N3] is present immediately subsequent to [N2] .119. The AAV capsid variant of any one of embodiments 1-118, which comprises from N-terminus to C-terminus, [N2]-[N3],120. The AAV capsid variant of any one of embodiments 1-119, which comprises from N-terminus to C-terminus, [N1]-[N2]-[N3],121. The AAV capsid variant of any one of embodiments 48-120, which comprises from N-terminus to C-terminus, [NO]-[N1]-[N2]-[N3],122. The AAV capsid variant of any one of embodiments 39-121, which comprises from N-terminus to C-terminus, [N1]-[N2]-[N3]-[N4],123. The AAV capsid variant of any one of embodiments 48-122, which comprises from N-terminus to C-terminus, [NO]-[N1]-[N2]-[N3]-[N4],124. The AAV capsid variant of any one of the preceding embodiments, which comprises an amino acid other T at position 460 (e.g., N, I, C, H, R, L, D, Y, A, M, Q, I, E, K. P, G or S), numbered according to the ammo acid sequence of SEQ ID NO: 138.125. The AAV capsid variant of any one of the preceding embodiments, which comprises 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: 138.126. The AAV capsid variant of any one of the preceding embodiments, which comprises an amino acid other T at position 466 (e.g., N, I, C, H, R, L, D, Y, A, M, Q, I, E, K, P, G or S), numbered according to the amino acid sequence of any one of SEQ ID NOs: 5-10, 36-59, 981, 982, or 6409- 6413.127. The AAV capsid variant of any one of the preceding embodiments, which comprises 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: 5-10. 36-59, 981 982, or 6409-6413.128. The AAV capsid variant of any one of the preceding embodiments, which comprises an amino acid other K at position 449 (e.g., an E, an N, or a T), numbered according to the amino acid sequence of any one of SEQ ID NOs: 36-59, 138, 981, or 982.129. The AAV capsid variant of any one of the preceding embodiments, which comprises the amino E. N, or T at position 449, numbered according to the amino acid sequence of any one of SEQ ID NOs: 5-10. 36-59, 138. 981 982, or 6409-6414.130. An AAV capsid variant, comprising:(A) a modification, e.g., a substitution (e.g., conservative substitution) in loop VIII, optionally wherein loop VIII comprises positions 587-599, numbered according to SEQ ID NO: 981, 982. 6411. or 6412; or positions 581-593, numbered according to SEQ ID NO: 138 or 6414; and / or(B) [A][B] (SEQ ID NO: 4694), wherein:(i) [A] comprises the amino acid sequence of GSGSPH (SEQ ID NO: 4695); and(ii) [B] comprises XI X2 X3 X4 X5 X6 X7, wherein:(a) position XI 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; and(g) position X7 is: Q. L, R, or V; optionally wherein the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of the aforesaid amino acids in (a)-(g).131. The AAV capsid variant of embodiment 130. wherein(a) position XI 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; and(g) position X7 is: Q. L, or R.132. The AAV capsid variant of embodiment 130 or 131, wherein [B] comprises:(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), SEIVNQQ (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 IDNO: 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), SKARLRQ (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 portion of an amino acid sequence in (i). e.g., any 2, 3, 4, 5, or 6 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no 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 amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).133. The AAV capsid variant of any one of embodiments 130-132, wherein [A][B] comprises:(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), GSGSPHSEIVNQQ (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). GSGSPHSKAQRRL (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 portion of an amino acid sequence in (i), e.g., any 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no 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 amino acid sequence comprising one. two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i)134. The AAV capsid variant of any one of embodiments 130-133, which further comprises one, two, or all of 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). relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.135. The AAV capsid variant of any one of embodiments 130-134, which further comprises an S at position 450 and an M at position 451, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.136. The AAV capsid variant of any one of embodiments 130-134, which further comprises a Y at position 450, an L at position 451, and an S at position 452, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.137. The AAV capsid variant of any one of embodiments 130-134. which further comprises a G at position 450, an L at position 451, and an S at position 452, relative to a reference sequence numbered according to the ammo acid sequence of SEQ ID NO: 138.138. The AAV capsid variant of any one of embodiments 130-137. wherein | A | | B| is present in loop IV.139. The AAV capsid variant of any one of embodiments 130-138, wherein [A] is present immediately subsequent to position 452. relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.140. The AAV capsid variant of any one of embodiments 130-139, wherein [A] replaces positions 453-455 (e.g., G453, S454, G455), relative to a reference sequence numbered according to tire amino acid sequence of SEQ ID NO: 138.141. The AAV capsid variant of any one of embodiments 130-140, wherein [A] is present immediately subsequent to position 452, and wherein [A] replaces positions 453-455 (e.g., G453, S454, G455), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.142. The AAV capsid variant of any one of embodiments 130-141 . wherein [B] is present immediately subsequent to [A],143. The AAV capsid variant of any one of embodiments 130-142, wherein [B] replaces positions 456-459 (e.g., Q456, N457. Q458, Q459), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.144. The AAV capsid variant of any one of embodiments 130-143, wherein [A][B] replaces positions 453-459 (e.g., G453, S454, G455, Q456, N457, Q458, Q459), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.145. The AAV capsid variant of any one of embodiments 130-144, wherein [A][B] is present immediately subsequent to position 452, and wherein [A][B] replaces positions 453-459 (e.g., G453, S454, G455, Q456, N457, Q458, Q459), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.146. The AAV capsid variant of any one of embodiments 130-145, which comprises from N-terminus to C-tenninus. [A][B] .147. An AAV capsid comprising:(A) a modification, e.g., a substitution (e.g.. conservative substitution) in loop VIII, optionally wherein loop VIII comprises positions 587-599. numbered according to SEQ ID NO: 981. 982, 6411, or 6412; or positions 581-593, numbered according to SEQ ID NO: 138 or 6414; and / or(B) [A] [B] (SEQ ID NO: 4699), wherein:(i) [A] comprises XI X2 X3 X4 X5 X6, wherein(a) position XI 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 wherein the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of the aforesaid amino acids in (a)-(f); and(it) [B] comprises SPHKSG (SEQ ID NO: 946).148. The AAV capsid of embodiment 147, wherein(a) position XI 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) position X5 is H; and(f) position X6 is D.149. The AAV capsid variant of embodiment 147or 148, wherein [A] comprises:(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), RINGED (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 any portion of an amino acid sequence in (i). e.g.. any 2, 3. 4. or 5 amino acids, e.g.. consecutive amino acids, thereof:(iii) an amino acid sequence comprising one. two, or three but no 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 amino acid sequence comprising one. two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).150. The AAV capsid variant of any one of embodiments 147-149, wherein [A][B] comprises:(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). IETGHDSPHKS (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), IEIGHDSPHKS (SEQ ID NO: 5372), TIKDNDSPHKS (SEQ ID NO: 5373), DIMGHDSPHKS (SEQ ID NO: 5374), FEQGHDSPHKS (SEQ ID NO: 5375), MEFGHDSPHKS (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: 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 portion of an amino acid sequence in (i), e.g., any 2. 3, 4, 5, 6. 7. 8, 9, or 10 amino acids, e.g.. consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no 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 amino acid sequence comprising one. two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).151. The AAV capsid variant of any one of embodiments 147-150, which further comprises one, two, three, four, or all of an amino acid other than Q at position 456 (e.g., R or L), N at position 457 (e.g., H, K, or R), Q at position 458 (e.g., R or T), Q at position 459 (H), and / or T at position 460 (N or S), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.152. The AAV capsid variant of any one of embodiments 147-151, which further comprises an R at position 456. relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.153. The AAV capsid variant of any one of embodiments 147-151, which further comprises an L at position 456, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.154. The AAV capsid variant of any one of embodiments 147-153, which further comprises an H at position 457 and an R at position 458. relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.155. The AAV capsid variant of any one of embodiments 147-153, which further comprises a K at position 457 and an N at position 460, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.156. The AAV capsid variant of any one of embodiments 147-153, which further comprises a T at position 458, an H at position 459, and an S at position 460, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.157. The AAV capsid variant of any one of embodiments 147-151. which further comprises an R at position 456, an R at position 457, and an R at position 458, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.158. The AAV capsid variant of any one of embodiments 147-157, wherein [A][B] is present in loop IV.159. The AAV capsid variant of any one of embodiments 147-158, wherein [A] is present immediately subsequent to position 449. relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.160. The AAV capsid variant of any one of embodiments 147-159, wherein [A] replaces positions 450-453 (e.g., T450, 1451, N452, G453), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.161. The AAV capsid variant of any one of embodiments 147-160, wherein [A] is present immediately subsequent to position 449, and wherein [A] replaces positions 450-453 (e.g., T450,I451, N452, G453), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 162. The AAV capsid variant of any one of embodiments 147-161, wherein [A][B] replaces positions 450-455 (e.g., T450, I451, N452, G453, S454, G455), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 163. The AAV capsid variant of any one of embodiments 147-162, wherein [A][B] is present immediately subsequent to position 449, and wherein [A][B] replaces positions 450-455 (e.g., T450, I451, N452, G453, S454, G455), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 164. The AAV capsid variant of any one of embodiments 147-163, wherein [B] is present immediately subsequent [A], and replaces positions 454 and 455 (e.g., S454 and G455), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 165. The AAV capsid variant of any one of embodiments 147-164, wherein [B] is present immediately subsequent to position 455, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 982. 166. The AAV capsid variant of any one of embodiments 147-165, wherein [B] is present immediately subsequent to [A]. 167. The AAV capsid variant of any one of embodiments 147-166, which comprises from N-terminus to C-terminus, [A][B]. 168. An AAV capsid variant comprising: (A) a modification, e.g., a substitution (e.g., conservative substitution) in loop VIII, optionally wherein loop VIII comprises positions 587-599, numbered according to SEQ ID NO: 981, 982, 6411, or 6412; or positions 581-593, numbered according to SEQ ID NO: 138 or 6414; and / or (B) an amino acid sequence having the following formula: [N1]-[N2]-[N3] (SEQ ID NO: 6407), wherein: (i) [N1] comprises positions X1, X2, and X3, wherein 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, wherein position X5 is K.169. The AAV capsid variant of embodiment 168, wherein:(i) X4 of [N3] is S, T. N, or A; and(ii) X5 of [N3] is A, V, T. S, G, R. L, or N; optionally wherein the AAV capsid variant comprises an amino acid modification, e.g.. a conservative substitution, of any of the aforesaid amino acids in (i) or (ii).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 168-170, wherein [N3] comprises SK, TK, NK. AK, KA, KV, KT, KS, KG, KR, KL, or KN.172. The AAV capsid variant of any one of embodiments 168-171, wherein [N3] is or comprises SKA, SKV, SKT, SKS, SKG, SKR, TKA, NKA, SKL, SKN, or AKA.173. The AAV capsid variant of any one of embodiments 168-172, wherein [N3] is or comprises SKA.174. The AAV capsid variant of any one of embodiments 168-173, wherein [N2]-[N3] comprises SPHSK (SEQ ID NO: 4701). SPHTK (SEQ ID NO: 4725), SPHNK (SEQ ID NO: 4726), or SPHAK (SEQ ID NO: 4727).175. The AAV capsid variant of any one of embodiments 168-174. wherein [N2]-[N3] is or comprises:(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 any portion of an amino acid sequence in (i). e.g., any 2, 3. 4, or 5 amino acids, e.g.. consecutive amino acids, thereof;(iii) an amino acid sequence comprising one. two, or three but no 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 amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).176. The AAV capsid variant of any one of embodiments 168-175, wherein [N2]-[N3] is or comprises SPHSKA (SEQ ID NO: 941).177. The AAV capsid variant of any one of embodiments 168-176, which comprises 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 981.178. The AAV capsid variant of any one of embodiments 168-177, which comprises the amino acid G at position 453, numbered according to SEQ ID NO: 138 or 981.179. The AAV capsid variant of any one of embodiments 168-178, wherein XI of [Nl] is chosen from: G, M, T. I. E, S, A. N, V, L, K, H, P, R, W, or D; optionally wherein the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of the aforesaid amino acids.180. The AAV capsid variant of any one of embodiments 168-179, wherein [Nl] comprises SG, GS, MS, TS, IS, ES, SS, AS, NS, VS, LS, KS, HS, PS, RS, WS, or DS.181. The AAV capsid variant of any one of embodiments 168-180, wherein [Nl] is or comprises: GSG, MSG, TSG, ISG, ESG, SSG, ASG, NSG, VSG, LSG, KSG, HSG, PSG, RSG, WSG, or DSG.182. The AAV capsid variant of any one of embodiments 168-181. wherein [Nl] is or comprises GSG.183. The AAV capsid variant of any one of embodiments 168-182. wherein [N 1 ]-[N2] comprises SGSPH (SEQ ID NO: 4752).184. The AAV capsid variant of any one of embodiments 168-183, wherein [N 1]-[N2] is or comprises:(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 any portion of an amino acid sequence in (i). e.g., any 2, 3, 4, or 5 amino acids, e.g.. consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no 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 amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).185. The AAV capsid variant of any one of embodiments 168-184, wherein [N1]-[N2]-[N3] is or comprises:(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 ammo acid sequence comprising any portion of an amino acid sequence in (i), e.g., any 2. 3, 4, 5, 6, 7, 8, or 9 amino acids, e.g., consecutive amino acids, thereof:(iii) an amino acid sequence comprising one, two, or three but no 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 amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).186. The AAV capsid variant of any one of embodiments 168-185. wherein [N1]-[N2]-[N3] is or comprises GSGSPHSKA (SEQ ID NO: 4697).187. The AAV capsid variant of any one of embodiments 168-186, which comprises 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), relative to a reference sequence numbered according to SEQ ID NO: 138.188. The AAV capsid variant of any one of embodiments 168-187, which comprises 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 atposition 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), relative to a reference sequence numbered according to SEQ ID NO: 981.189. The AAV capsid variant of any one of embodiments 168-188, which comprises the amino acid Q at position 456, the amino acid N at position 457, the amino acid Q at position 458, the amino acid Q at position 459, and / or the amino acid T at position 460, relative to a reference sequence numbered according to SEQ ID NO: 138.190. The AAV capsid variant of any one of embodiments 168-189, which comprises the amino acid Q at position 462, the amino acid N at position 463, the amino acid Q at position 464, the amino acid Q at position 465, and / or the amino acid T at position 466, numbered according to SEQ ID NO: 981191. The AAV capsid variant of any one of embodiments 168-190, further comprising [N4] wherein [N4] comprises X7, X8, X9, X10, and Xll, wherein:(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; and(e) XI 1 is T. I. N, S, H, R, L. D, Y, A, Q; optionally wherein the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of the aforesaid amino acids in (a)-(e).192. The AAV capsid variant of embodiment 191, wherein [N4] is or comprises:(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: 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), 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), 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 any portion of an amino acid sequence in (i), e.g., any 2, 3, or 4 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no 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 amino acid sequence comprising one. two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).193. The AAV capsid variant of embodiment 191or 192, wherein [N1]-[N2]-[N3]-[N4] is or comprises:(i) the amino acid sequence of any of SEQ ID NOs: 200 or 2887-3076;(ii) an amino acid sequence comprising any portion of an 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., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no 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 amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).194. The AAV capsid variant of any one of embodiments 191-193, wherein [N1]-[N2]-[N3]-[N4] is or comprises GSGSPHSKAQNQQT (SEQ ID NO: 200).195. The AAV capsid variant of any one of embodiments 191-193. wherein [N1]-[N2]-[N3]-[N4] is or comprises VSGSPHSKAQNQQT (SEQ ID NO: 903).196. The AAV capsid variant of any one of embodiments 168-195. which comprises an amino acid other than K at position 449 (e.g., T, E, or N), 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). relative to a reference sequence numbered according to SEQ ID NO: 138 or 981.197. The AAV capsid variant of any one of embodiments 168-196, which comprises the amino acid K at position 449, the amino acid T at position 450, the amino acid I at position 451, and / or the amino acid N at position 452, relative to a reference sequence numbered according to SEQ ID NO: 138 or 981.198. The AAV capsid variant of any one of embodiments 168-197, which further comprises [NO], wherein [NO] comprises XA, XB, Xc, and XD, wherein:(a) XAis K, T, E, or N;(b) Xbis T, S, E, A, N, V, Q, or G;(c) Xcis I, F. E, V, L. D, S, C. T, A. N, H. R. G, or W; and(d) XDis N, I, P, K. R, H. S. M, Q, D, T. L, A, Y, V, F. E, W. or G; optionally wherein the AAV capsid variant comprises an amino acid modification, e.g.. a conservative substitution, of any of the aforesaid amino acids in (a)-(d).199. The AAV capsid variant of embodiment 198, wherein [NO] is or comprises:(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), 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), KT1T (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 comprising any portion of an amino acid sequence in (i), e.g., any 2, or 3 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no 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 amino acid sequence comprising one. two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).200. The AAV capsid variant of embodiment 198 or 199, wherein [NO]-[N1]-[N2]-[N3]-[N4] is or comprises:(i) the amino acid sequence of any one of SEQ ID NOs: 3239-3526 or 3591-3605;(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i). e.g., any 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no more than four modifications, e g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to any of tire amino acid sequences in (i); or(iv) an amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).201. The AAV capsid variant of any one of embodiments 198-200. wherein [NO]-[N1]-[N2]-[N3]- [N4] is or comprises KTINGSGSPHSKAQNQQT (SEQ ID NO: 5660).202. The AAV capsid variant of any one of embodiments 198-200. wherein [NO]-[N1]-[N2]-[N3]- [N4J is or comprises KTERVSGSPHSKAQNQQT (SEQ ID NO: 3589).203. An AAV capsid variant comprising:(A) a modification, e.g., a substitution (e.g., conservative substitution) in loop VIII, optionally wherein loop VIII comprises positions 587-599, numbered according to SEQ ID NO: 981, 982, 6411, or 6412; or positions 581-593, numbered according to SEQ ID NO: 138 or 6414; and / or(B) an amino acid sequence having the following formula: [N1]-[N2]-[N3] (SEQ ID NO: 6408). wherein:(i) [Nl] comprises positions XI. 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.204. The AAV capsid variant of embodiment 203, wherein:(i) X5 of [N3] is S, I, T, R, H, Y, L, or M; and(ii) X6 of [N3] is G, A, L, E, V. R, W, N, Q, or K;optionally wherein the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of the aforesaid amino acids in (i) or (ii).205. The AAV capsid variant of embodiment 203or 204, wherein X5 is S and / or Xe is G.206. The AAV capsid variant of any one of embodiments 203-205, 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.207. The AAV capsid variant of any one of embodiments 203-206, 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.208. The AAV capsid variant of any one of embodiments 203-207, wherein [N3] is or comprises KSG.209. The AAV capsid variant of any one of embodiments 203-208, wherein [N2]-[N3] comprises 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).210. The AAV capsid variant of any one of embodiments 203-209. wherein [N2]-[N3] is or comprises:(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 any portion of an amino acid sequence in (i). e.g., any 2, 3. 4, or 5 amino acids, e.g.. consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no 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 amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).211. The AAV capsid variant of any one of embodiments 203-210, wherein [N2]-[N3] is or comprises SPHKSG (SEQ ID NO: 946).212. The AAV capsid variant of any one of embodiments 203-211, which comprises 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 981.213. The AAV capsid variant of any one of embodiments 203-212, which comprises the amino acid G at position 453, numbered according to SEQ ID NO: 138 or 981.214. The AAV capsid variant of any one of embodiments 203-214, wherein:(i) position XI of [Nl] is G, A, K, W, R, L, I, M, N, T, E, Q, Y, H, F, or V;(ii) position X2 of [Nl] is H, Y, R, Q, N, P, or D;(iii) position X3 of [Nl] is D, E, G, V, or N; optionally wherein the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of the aforesaid amino acids in (i), (ii), or (iii).215. The AAV capsid variant of any one of embodiments 203-214, wherein position X2 of [Nl] is H and position X3 of [Nl] is D.216. The AAV capsid variant of any one of embodiments 203-215. wherein position XI of [Nl] is G, position X2 of [Nl] is H and position X3 of [Nl] is D.217. The AAV capsid variant of any one of embodiments 203-216. wherein [Nl] 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 NG218. The AAV capsid variant of any one of embodiments 203-217, wherein [Nl] 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.219. The AAV capsid variant of any one of embodiments 203-218, wherein [Nl] is or comprises GHD.220. The AAV capsid variant of any one of embodiments 203-219, wherein [N1]-[N2] comprises HDSPH (SEQ ID NO: 4703).221. The AAV capsid variant of any one of embodiments 203-220, wherein [N1]-[N2] is or comprises:(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 any portion of an amino acid sequence in (i), e.g., any 2, 3, 4, or 5 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no more than four modifications, e g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to any of tire amino acid sequences in (i); or(iv) an amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).222. The AAV capsid variant of any one of embodiments 203-221. wherein [N1]-[N2]-[N3] is or comprises:(i) GHDSPHKSG (SEQ ID NO: 4698), GHDSPHK1G (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), AHDSPHKSG (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), RHDSPHKSG (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 IDNO: 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 portion of an amino acid sequence in (i). e.g., any 2, 3. 4, 5, 6, 7, 8. or 9 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, tw o. or three but no 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 amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).223. The AAV capsid variant of any one of embodiments 203-222, wherein [N1]-[N2]-[N3] is or comprises GHDSPHKSG (SEQ ID NO: 4698).224. The AAV capsid variant of any one of embodiments 203-223, which comprises 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), relative to a reference sequence numbered according to SEQ ID NO: 138.225. The AAV capsid variant of any one of embodiments 203-224. which comprises 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), relative to a reference sequence numbered according to SEQ ID NO: 982.226. The AAV capsid variant of any one of embodiments 203-225, which comprises the amino acid Q at position 456, the amino acid N at position 457, the amino acid Q at position 458, the amino acid Q at position 459, and / or the amino acid T at position 460, relative to a reference sequence numbered according to SEQ ID NO: 138.227. The AAV capsid variant of any one of embodiments 203-226, which comprises the amino acid Q at position 462, the amino acid N at position 463, the amino acid Q at position 464, the amino acid Qat position 465, and / or the amino acid T at position 466, relative to a reference sequence numbered according to SEQ ID NO: 138.228. The AAV capsid variant of any one of embodiments 203-227, further comprising [N4] wherein [N4] comprises X7, X8, X9, X10. and XI 1, wherein:(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; and(e) XI 1 is T, I, N, S, H, R, L, D, Y, A, Q; optionally wherein the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of die aforesaid amino acids in (a)-(e).229. The AAV capsid variant of embodiment 228, wherein [N4] is or comprises:(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: 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: 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 any portion of an amino acid sequence in (i). e.g., any 2, 3, or 4 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no 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 amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).230. The AAV capsid variant of embodiment 228or 229. wherein [N1]-[N2]-[N3]-[N4] is or comprises:(i) the amino acid sequence of any of SEQ ID NOs: 201 or 3160-3237;(ii) an amino acid sequence comprising any portion of an 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.. consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to any of tire amino acid sequences in (i); or(iv) an amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).231. The AAV capsid variant of any one of embodiments 228-230, wherein [N1]-[N2]-[N3]-[N4] is or comprises GHDSPHKSGQNQQT (SEQ ID NO: 201).232. The AAV capsid variant of any one of embodiments 203-231, which comprises an amino acid other than K at position 449 (e.g.. T), 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), relative to a reference sequence numbered according to SEQ ID NO: 138 or 982.233. The AAV capsid variant of any one of embodiments 203-232, which comprises the amino acid K at position 449. the amino acid T at position 450. the amino acid I at position 451, and / or the amino acid N at position 452, relative to a reference sequence numbered according to SEQ ID NO: 138 or 982.234. The AAV capsid variant of any one of embodiments 203-233, which further comprises [NO], wherein [NO] comprises XA, XB, Xc, and XD, wherein:(a) XAis K or T;(b) Xbis T, A, S, I, V, N, E, Y, C, G, W. or Q;(c) Xcis I, E, V, S, T, N, D, C, G. Q, L, P. A; and(d) XDis N, S, Y, I, K, F, T, D, E, G, V, L, A, M, Q, H, P, or R; optionally wherein the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of die aforesaid amino acids in (a)-(d).235. The AAV capsid variant of embodiment 234, wherein [NO] is or comprises:(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), 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), KGQN (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 comprising any portion of an amino acid sequence in (i). e.g., any 2, or 3 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, tw o. or three but no 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 amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).236. The AAV capsid variant of embodiment 234or 235, wherein [NO]-[N1]-[N2]-[N3]-[N4] is or comprises:(i) the amino acid sequence of any one of SEQ ID NOs: 3606-3836;(ii) an ammo acid sequence comprising any portion of an amino acid sequence in (i), e.g., any 2. 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 amino acids, e.g.. consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no 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 amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).237. The AAV capsid variant of any one of embodiments 234-236, wherein [NO]-[N1]-[N2]-[N3]- [N4] is or comprises KTINGHDSPHKSGQNQQT (SEQ ID NO: 5828).238. The AAV capsid variant of any one of embodiments 234-236, wherein [NO]-[N1]-[N2]-[N3]- [N4] is or comprises KAEIGHDSPHKSGQNQQT (SEQ ID NO: 1754).239. The AAV capsid variant of any one of embodiments 234-236, wherein [NO]-[N1]-[N2]-[N3]- [N4] is or comprises KTEKMSGSPHSKAQNQQT (SEQ ID NO: 3241).240. The AAV capsid variant of any one of embodiments 168-239, wherein [N1]-[N2]-[N3] is present in loop IV.241. The AAV capsid variant of any one of embodiments 198-202 or 234-240, wherein [NO] and [N4] are present in loop IV.242. The AAV capsid variant of any one of embodiments 198-202 or 234-241, wherein [NO] is present immediately subsequent to position 448, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138, 981, or 982.243. The AAV capsid variant of any one of embodiments 198-202 or 234-242, wherein [NO] replaces positions 449-452 (e.g., K449, T450, 1451, and N452), relative to a reference sequence numbered according to SEQ ID NO: 138, 981, or 982.244. The AAV capsid variant of any one of embodiments 198-202 or 234-243, wherein [NO] is present immediately subsequent to position 448 and wherein [NO] replaces positions 449-452 (e.g., K449, T450, 1451, and N452), relative to a reference sequence numbered according to SEQ ID NO: 138, 981, or 982.245. The AAV capsid variant of any one of embodiments 198-202 or 234-244, wherein [NO] corresponds to positions 449-452 (e.g., K449, T450, 1451, and N452) of any one of SEQ ID NOs: 138, 981, or 982.246. The AAV capsid variant of any one of embodiments 168-245. wherein [Nl] is present immediately subsequent to position 452, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138, 981, or 982.247. The AAV capsid variant of any one of embodiments 168-246, wherein [Nl] replaces positions 453-455 (e.g., G453, S454, and G455), relative to a reference sequence numbered according to SEQ ID NO: 138, 981, or 982.248. The AAV capsid variant of any one of embodiments 168-246, wherein [Nl] replaces position 453 (e.g., G453). relative to a reference sequence numbered according to SEQ ID NO: 138, 981, or 982.249. 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) position XI of [Nl] replaces position 453 (e.g., G453);(ii) position X2 of [Nl] corresponds to position 454 (e.g., S454); and(iii) position X3 of [Nl] corresponds to position 455 (e.g., G455),wherein (i), (ii), and (iii) are numbered according to SEQ ID NO: 138 or SEQ ID NO: 981.250. The AAV capsid variant of any one of embodiments 168-176, 178-201. or 240-246. wherein:(i) position XI of [Nl] corresponds to position 453 (e.g., G453);(ii) position X2 of [Nl] corresponds to position 454 (e.g.. S454); and(iii) position X3 of [Nl] corresponds to position 455 (e.g., G455); wherein (i), (ii), and (iii) are numbered according to SEQ ID NO: 138 or SEQ ID NO: 981.251. The AAV capsid variant of any one of embodiments 203-248, wherein:(i) position XI of [Nl] corresponds to position 453 (e.g., G453);(ii) position X2 of [Nl] replaces position 454 (e.g., S454); and(iii) position X3 of [Nl] replaces position 455 (e.g., G455), wherein (i), (ii), and (iii) are numbered according to SEQ ID NO: 138 or SEQ ID NO: 982.252. The AAV capsid variant of any one of embodiments 203-248 or 251, wherein [Nl] corresponds to positions 453-455 (e.g., G453, H454. D455) of SEQ ID NO 982.253. The AAV capsid variant of any one of embodiments 168-176, 178-201, 240-247. or 250, wherein [Nl] corresponds to positions 453-455 (e.g., G453, S454, G455) of SEQ ID NO: 138, or 981.254. The AAV capsid variant of any one of embodiments 168-253. wherein [N2] is present immediately subsequent to position 455, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138, 981, or 982.255. The AAV capsid variant of any one of embodiments 168-254, wherein [N2] corresponds to positions 456-458 (e.g.. S456. P457. and H458) of SEQ ID NO: 981 or 982.256. The AAV capsid variant of any one of embodiments 168-254, wherein [N2] corresponds to positions 456-458 (e.g., S456, P457, and H458) of any one of SEQ ID NOs: 5-10, 36-59. or 6409- 6413.257. The AAV capsid variant of any one of embodiments 168-256, wherein [N2] is present immediately subsequent to [Nl],258. The AAV capsid variant of any one of embodiments 168-202, 240-247, 249-257, wherein [N3] corresponds to positions 459-460 (e.g., S459, K460, A461) of SEQ ID NO: 981.259. The AAV capsid variant of any one of embodiments 168-202, 240-247, 249-257, wherein [N3] corresponds to positions 459-460 (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 59.260. The AAV capsid variant of any one of embodiments 168-259, wherein [N2]-[N3] is present immediately subsequent to position 455, relative to a reference sequence numbered according to the amino acid sequence of any one of SEQ ID NOs: 138, 981. or 982.261. The AAV capsid variant of any one of embodiments 168-259, wherein [N2]-[N3] is present immediately subsequent to position 455, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 981.262. The AAV capsid variant of any one of embodiments 168-261, wherein [N2]-[N3] corresponds to positions 456-461 (e.g, S456, P457, H458, S459, K460, A461) of SEQ ID NO: 981.263. The AAV capsid variant of any one of embodiments 168-262, wherein [N2]-[N3] corresponds to positions 456-461 (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 59.264. The AAV capsid variant of any one of embodiments 203-257 or 259-261, wherein [N3] corresponds to positions 459-460 (e.g, K.459, S460, G461) of SEQ ID NO: 982.265. The AAV capsid variant of any one of embodiments 203-257 or 259-261, wherein [N3J corresponds to positions 459-460 (e.g, K459. S460. G461) of SEQ ID NO: 37.266. The AAV capsid variant of any one of embodiments 203-265, wherein [N2]-[N3] is present immediately subsequent to position 455. relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 982.267. The AAV capsid variant of any one of embodiments 203-246, 248. 252, 255, 257, 260, 263-266. wherein [N3] replaces positions 454 and 455 (e.g, S454 and G455), numbered according to SEQ ID NO: 138.268. The AAV capsid variant of any one of embodiments 203-246, 248, 252, 255, 257, 260, 263-267, wherein [N3] is present immediately subsequent to [N2] and replaces positions 454 and 455 (e.g, S454 and G455), numbered according to SEQ ID NO: 138.269. The AAV capsid variant of any one of embodiments 203-246, 248, 252, 255, 257, 260, 263-268, wherein [N3] is present immediately subsequent to [N1]-[N2] and replaces positions 454 and 455 (e.g., S454 and G455), numbered according to SEQ ID NO: 138.270. The AAV capsid variant of any one of embodiments 203-257, 260. 264-269, wherein [N2]-[N3] corresponds to positions 456-461 (e.g., S456, P457, H458, K459, S460. G461) of SEQ ID NO: 982.271. The AAV capsid variant of any one of embodiments 203-257, 260, 264-270, wherein [N2]-[N3] corresponds to positions 456-461 (e.g., S456, P457, H458, K459, S460. G461) of SEQ ID NO: 37.272. The AAV capsid variant of any one of embodiments 191-202 or 228-271, wherein [N4] is present immediately subsequent to position 455, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.273. The AAV capsid variant of any one of embodiments 191-202 or 228-272, wherein [N4] replaces positions 456-460 (e.g., Q456, N457, Q458. Q459, and T460), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.274. The AAV capsid variant of any one of embodiments 191-202 or 228-273, wherein [N4] corresponds to positions 462-466 (e.g., Q462, N463. Q464, Q465, and T466) of SEQ ID NO: 981 or 982.275. The AAV capsid variant of any one of embodiments 191-202 or 228-273, wherein [N4J corresponds to positions 462-466 of any one of SEQ ID NOs: 5-10, 36-59, or 6409-6413.276. The AAV capsid variant of any one of embodiments 191-202 or 228-274, wherein [N4] corresponds to positions 456-460 (e.g., Q456, N457, Q458. Q459, and T460) of SEQ ID NO: 138.277. The AAV capsid variant of any one of embodiments 191-202 or 228-276, wherein [N2]-[N3]- [N4] replaces positions 456-460 (e.g., Q456. N457, Q458, Q459, and T460), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.278. The AAV capsid variant of any one of embodiments 191-202 or 228-277, wherein [N2]-[N3]- [N4] is present immediately subsequent to position 455, and wherein [N2]-[N3]-[N4] replaces positions 456-460 (e.g., Q456, N457, Q458, Q459, and T460), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.279. The AAV capsid variant of any one of embodiments 191-202 or 228-278, wherein [N1]-[N2]- [N3]-[N4] replaces positions 453-460 (e.g., G453, S454, G455. Q456. N457, Q458, Q459, and T460), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.280. The AAV capsid variant of any one of embodiments 191 -202 or 228-279, wherein [N1 ]-[N2]- [N3]-[N4] is present immediately subsequent to position 452. and wherein [N1]-[N2]-[N3]-[N4] replaces positions 453-460 (e.g., G453, S454, G455, Q456. N457, Q458, Q459, and T460), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.281. 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] corresponds to positions 453-466 (e.g., G453, S454, G455, S456, P457, H458, S459, K460, A461, Q462, N463, Q464, Q465, and T466) of SEQ ID NO: 981.282. 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] corresponds to positions 453-461 (e g., G453, S454, G455, S456, P457, H458, S459, K460, A461) of SEQ ID NO: 981.283. The AAV capsid variant of any one of embodiments 228-257, 260, 261, 264-282, wherein [Nl]- [N2]-[N3]-[N4] corresponds to positions 453-466 (e.g., G453, H454, D455, S456, P457, H458, K459, S460. G461, Q462, N463, Q464, Q465. T466) of SEQ ID NO: 982.284. The AAV capsid variant of any one of embodiments 203-257. 260, 261, 264-283, wherein [Nl]- [N2J-IN3J corresponds to positions 453-461 (e.g.. G453. H454, D455, S456, P457, H458, K459. S460. G461) of SEQ ID NO: 982.285. The AAV capsid variant of any one of embodiments 228-257, 260, 261, 264-282. wherein [Nl]- [N2]-[N3]-[N4] corresponds to positions 453-466 of any one of SEQ ID NOs: 5-10, 36-59. or 6409- 6413.286. The AAV capsid variant of any one of embodiments 198-202 or 234-286, wherein [N0]-[Nl]- [N2]-[N3]-[N4] replaces positions 449-460 (e.g., K449, T450, 1451, N452, G453, S454, G455, Q456, N457. Q458, Q459, and T460), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.287. The AAV capsid variant of any one of embodiments 198-202 or 234-286, wherein [N0]-[Nl]- [N2]-[N3]-[N4] is present immediately subsequent to position 448, and wherein [NO]-[N1]-[N2]- [N3]-[N4] replaces positions 449-460 (e.g., K449, T450, 1451, N452, G453, S454, G455, Q456,N457, Q458, Q459, and T460), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.288. The AAV capsid variant of any one of embodiments 198-202, 240-247, 249, 250. 253-263, 266, 272-281, 286, or 287 , wherein [NO]-[N1]-[N2]-[N3]-[N4] corresponds to positions 449-466 (e.g., K449, T450. 1451, N452. G453, S454, G455, S456, P457, H458, S459, K460. A461, Q462, N463, Q464. Q465, T466) of SEQ ID NO: 981.289. The AAV capsid variant of any one of embodiments 234-257, 260, 261, 264-284. 286, or 287. wherein [NO]-[N1]-[N2]-[N3]-[N4] corresponds to positions 449-466 (e.g., K449, T450, 1451, N452, G453. H454, D455, S456, P457, H458, K459, S460, G461, Q462, N463, Q464, Q465. T466) of SEQ ID NO: 982.290. The AAV capsid variant of any one of embodiments 234-257, 260, 261, 264-284, 286, or 287, wherein [NO]-[N1]-[N2]-[N3]-[N4] corresponds to positions 449-466 of any one of SEQ ID NOs: 5- 10, 36-59, or 6409-6413.291. The AAV capsid variant of any one of embodiments 191-202 or 228-290, wherein [N4] is present immediately subsequent to position 461. relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 981 or 982.292. The AAV capsid variant of any one of embodiments 191-202 or 228-291, wherein [N4] replaces positions 462-466 (e.g., Q462, N463. Q464. Q465, and T466). relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 981 or 982.293. The AAV capsid variant of any one of embodiments 191-202 or 228-292. wherein [N2]-[N3]- [N4] replaces positions 462-466 (e.g., Q462. N463, Q464, Q465, and T466). relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 981 or 982.294. The AAV capsid variant of any one of embodiments 191-202 or 228-293, wherein [N2]-[N3]- [N4] is present immediately subsequent to position 455, and wherein [N2]-[N3]-[N4] replaces positions 462-466 (e.g., Q462, N463, Q464, Q465, and T466), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 981 or 982.295. The AAV capsid variant of any one of embodiments 168-294, which comprises from N-tenninus to C-terminus, [N2]-[N3],296. The AAV capsid variant of any one of embodiments 168-295, which comprises from N-terminus to C -terminus, [N1]-[N2]-[N3],297. The AAV capsid variant of any one of embodiments 168-296, which comprises from N-terminus to C-terminus, [NO]-[N1]-[N2]-[N3],298. The AAV capsid variant of any one of embodiments 168-297, which comprises from N-terminus to C-terminus, [N1]-[N2]-[N3]-[N4],299. The AAV capsid variant of any one of embodiments 168-298, which comprises from N-tenninus to C-terminus, [NO]-[N1]-[N2]-[N3]-[N4],300. An AAV capsid variant comprising:(A) a modification, e.g., a substitution (e.g., conservative substitution) in loop VIII, optionally wherein loop VIII comprises positions 587-599, numbered according to SEQ ID NO: 981, 982, 6411, or 6412; or positions 581-593, numbered according to SEQ ID NO: 138 or 6414; and / or(B) the formula [A]-[B] (SEQ ID NO: 4696), wherein:(i) [A] comprises GSGSPH (SEQ ID NO: 4695); and(ii) [B] comprises XI X2, X3, X4, and X5, wherein:(a) position XI 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. 1. A, T, D, N, orE; and(e) position X5 is A, N, Y, R, K, L, I, M, Q, S, C, W, F, T, G, V, or P; optionally wherein the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of the aforesaid amino acids in (a)-(e).301. The AAV capsid variant of embodiment 300, wherein:(a) position XI 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; and(e) position X5 is N, R, S, T, K, M, Q or Y; optionally wherein the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of die aforesaid amino acids in (a)-(e).302. The AAV capsid variant of embodiment 300 or 301, wherein [B] comprises SKA, SMY, SKL, SKR, SKW, SRC, SFT. SKF. IVW. SKY. SCH, FPW, SKI, VYY, SLY. SKP. SRF, SRM, SVK, SWA, SLW. SFR, SKK, SY A, 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. SLC, 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, GRY, 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. PFR, 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, ALR, AHA, CLN. AFV, AQF, RCN, MPC, KTS, PYN, AQS, TRN, LKN, AQM, CTN, PDN, RNY, ACR, 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, PWQ, KIR, YYQ, LYW, KPK, RFW, RMR, VKK, WAP, LWK, FRP. KKV, YAF, KAC, KRL, CSR. RCP, GAC, KFR, FFG, MCQ, KLF, KTR, GKR, YRQ, RVQ. GIQ, NCQ, KPF, LAW, KRS, SYQ, 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.303. The AAV capsid variant of any one of embodiments 300-302. wherein [B] comprises 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), 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), 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), 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), 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). 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), 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), 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), K.VRM (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), 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).304. The AAV capsid variant of any one of embodiments 300-303, wherein [B] is or comprises:(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), 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), 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), 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), SKRVV (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 any portion of an amino acid sequence in (i). e.g., any 2, 3. or 4 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one. two, or three but no 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 amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).305. The AAV capsid variant of any one of embodiments 300-304, wherein [A]-[B] is or comprises:(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), GSGSPHSKAQY (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), GSGSPHSRFWN (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: 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), GSGSPHSKRRA (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), GSGSPHSVRYN (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 portion of an amino acid sequence in (i), e.g., any 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no 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 amino acid sequence comprising one. two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i)306. The AAV capsid of any one of embodiments 300-305, wherein [A]-[B] does not comprise the amino acid sequence of GSGSPHSKAQN (SEQ ID NO: 6251).307. The AAV capsid variant of any one of embodiments 300-306, which comprises one, two, or all of 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: 138.308. The AAV capsid variant of any one of embodiments 300-307, which comprises:(i) the ammo acid R at position 458;(ii) the amino acid W at position 458;(iii) the amino acid Y at position 458;(iv) the amino acid F at position 458;(v) the amino acid S at position 458;(vi) the amino acid C at position 458;(vii) the amino acid I at position 458;(viii) the amino acid L at position 458;(ix) the amino acid P at position 458;(x) the amino acid I at position 459;(xi) the amino acid H at position 458; or(xii) the amino acid V at position 458; wherein (i)-(xii) are numbered according to SEQ ID NO: 138.309. The AAV capsid variant of any one of embodiments 300-307, which comprises:(i) the amino acid R at position 458 and the amino acid K at position 459;(ii) the amino acid C at position 458 and the amino acid I at position 459;(iii) the amino acid S at position 458 and the amino acid R at position 459’(iv) the amino acid L at position 458 and the amino acid K at position 459;(v) the amino acid F at position 458 and the amino acid K at position 459;(vi) the amino acid C at position 458 and the amino acid R at position 459;(vii) the amino acid H at position 458 and the amino acid R at position 459;(viii) the amino acid I at position 458 and the amino acid L at position 459;(ix) the amino acid V at position 458 and the amino acid R at position 459;(x) the amino acid A at position 458 and the amino acid K at position 459;(xi) the amino acid I at position 458 and the amino acid K at position 459;(xii) the amino acid C at position 458 and the amino acid S at position 459; or(xiii) the amino acid C at position 458 and the amino acid L at position 459 wherein (i)-(xiii) are numbered according to SEQ ID NO: 138.310. The AAV capsid variant of any one of embodiments 300-307, which comprises the amino acid F at position 458, the amino acid K at position 459, and the amino acid R at position 460, numbered relative to SEQ ID NO: 138.311. The AAV capsid variant of any one of embodiments 300-310, which comprises one, two, or all of 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: 138.312. The AAV capsid variant of any one of embodiments 300-311, which comprises the amino acid V at position 452, numbered according to SEQ ID NO: 138.313. The AAV capsid variant of any one of embodiments 300-312. which comprises the amino acid Y at position 450 and the amino acid V at position 452, numbered according to SEQ ID NO: 138.314. The AAV capsid variant of any one of embodiments 300-312. which comprises the amino acid R at position 450 and the amino acid Y at position 451, numbered according to SEQ ID NO: 138.315. The AAV capsid variant of any one of embodiments 300-311, which comprises:(i) the amino acid P at position 450, the amino acid R at position 451, and the amino acid W at position 452;(ii) the amino acid Y at position 450, the amino acid S at position 451, and the amino acid A at position 452;(iii) the amino acid Y at position 450, the amino acid Y at position 451, and the 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) the amino acid W at position 450, the amino acid L at position 451, and the amino acid T at position 452;(vi) the amino acid R at position 450. the amino acid S at position 451, and the amino acid Y at position 452;(vii) the amino acid Y at position 450. the amino acid V at position 451. and the amino acid F at position 452;(viii) the amino acid K at position 450, the amino acid H at position 451, and the 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) the amino acid P at position 450, the amino acid A at position 451, and the amino acid R at position 452;(xi) the amino acid S at position 450, the amino acid R at position 451, and the amino acid R at position 452;(xii) the amino acid F at position 450, the amino acid F at position 451, and the amino acid H at position 452;(xiii) the amino acid R at position 450, the amino acid F at position 451, and the amino acid S at position 452;(xiv) the amino acid Y at position 450, the amino acid S at position 451, and the amino acid M at position 452; or(xv) the amino acid P at position 450, the amino acid F at position 451, and the amino acid L at position 452; wherein (i)-(xv) is numbered according to SEQ ID NO: 138.316. The AAV capsid variant of any one of embodiments 300-315. which comprises:(i) the amino acid sequence of any one of SEQ ID NOs: 3849-3982, 2984-4010. 4681-4693;(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i), e.g., any 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one. two, or three but no 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 amino acid sequence comprising one. two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).317. The AAV capsid variant of any one of embodiments 300-316, which does not comprise tire amino acid sequence of GSGSPHSKAQNQQ (SEQ ID NO: 1801) or GSGSPHSKAQNQQT (SEQ ID NO: 200).318. The AAV capsid variant of any one of embodiments 300-317, wherein [A]-[B] is present in loop IV.319. The AAV capsid variant of any one of embodiments 300-318, wherein [A] is present immediately subsequent to position 452. relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 981.320. The AAV capsid variant of any one of embodiments 300-319, wherein [A] replaces positions 453-455 (e.g., G453, S454, G455), relative to a reference sequence numbered according to tire amino acid sequence of SEQ ID NO: 138 or 981.321. The AAV capsid variant of any one of embodiments 300-320, wherein [A] is present immediately subsequent to position 452, and wherein [A] replaces positions 453-455 (e.g., G453, S454, G455), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 981.322. The AAV capsid variant of any one of embodiments 300-321, wherein [B] is present immediately subsequent to [A],323. The AAV capsid variant of any one of embodiments 300-322. wherein [B] replaces positions 456 and 457 (e.g., Q456. N457), numbered relative to SEQ ID NO: 138.324. The AAV capsid variant of any one of embodiments 300-323. wherein (AJ-(BJ replaces positions 453-457 (e.g.. G453. S454. G455, Q456, N457), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.325. The AAV capsid variant of any one of embodiments 300-324, wherein [A]-[B] is present immediately subsequent to position 452. and wherein [A]-[B] replaces positions 453-457 (e.g., G453. S454, G455. Q456. N457), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.326. The AAV capsid variant of any one of embodiments 300-325, which comprises from N-tenninus to C -terminus, [A][B],327. The AAV capsid variant of any one of the preceding embodiments, which comprises at least one, two. three or four (e.g., from 1-4 to 1-5) charged amino acid residues (e.g., acidic and / or basic amino acid residues) relative to SEQ ID NO: 138, which is present N-terminal to the amino acid sequence ofSPH (e.g.. within 1, 2. 3. 4, 5, or 6 amino acids from the start of the SPH amino acid sequence (e.g., within positions 450-455 numbered according to SEQ ID NO: 138)), optionally wherein the amino acid sequence of SPH is present at positions 456-458 numbered according to any one of SEQ ID NOs: 5-10, 36-59, 981. 982, or 6409-6413.328. The AAV capsid variant of embodiment 327, wherein the amino acid sequence of SPH is present at positions 456-458 numbered according to any one of SEQ ID NOs: 5-10, 36-59, 981, 982, or 6409- 6413.329. The AAV capsid variant of embodiment 327 or 328, which comprises less than four, less than three, less than two (e.g., Evo or one) charged amino acid residues (e.g., acidic and / or basic amino acid residues) relative to SEQ ID NO: 138.330. The AAV capsid variant of any one of embodiments 327-329, which comprises one charged amino acid residues (e.g., an acidic or basic amino acid residue) relative to SEQ ID NO: 138, optionally at any one of positions 450-455 numbered relative to SEQ ID NO: 138.331. 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 ammo acid (e.g.. D or E).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 327-333, wherein the charged amino acid residue is E.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).337. The AAV capsid variant of any one of embodiments 327-336, wherein the charged amino acid residue is H.338. The AAV capsid variant of any one of embodiments 327-337, wherein the charged amino acid residue is R.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 327-339, 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).341. The AAV capsid variant of any one of embodiments 327-340, at least one, tw o. three or four charged amino acid residues is present within 1, 2, 3, 4, 5, or 6 (e.g., 1-6) amino acids from the start of die SPH amino acid sequence.342. The AAV capsid variant of any one of embodiments 327-341, which comprises two charged amino acid residue 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).343. The AAV capsid variant of any one of embodiments 327-342. which comprises 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.344. The AAV capsid variant of any one of embodiments 327-343. which comprises a charged amino acid residue (e.g., E) at position 451, numbered according to any one of SEQ ID NO: 138. 981, or 982.345. The AAV capsid variant of any one of embodiments 327-344, which comprises E at position451. numbered according to any one of SEQ ID NOs: 138, 981. or 982.346. The AAV capsid variant of any one of embodiments 327-345, which comprises 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 982.347. The AAV capsid variant of any one of embodiments 327-346, which comprises R at position452, numbered according to SEQ ID NO: 138 or SEQ ID NO: 982.348. The AAV capsid variant of any one of embodiments 327-347, which comprises E at position 451 and R at position 452, numbered according to SEQ ID NO: 138 or SEQ ID NO: 982.349. The AAV capsid variant of any one of embodiments 327-348, which has decreased tropism for a liver cell or tissue, relative to the tropism of a reference sequence comprising the amino acid sequence of SEQ ID NO: 138 or SEQ ID NO: 981.350. The AAV capsid variant of any one of the preceding embodiments, which comprises at least one, two, three or four (e.g.. from 1-4 to 1-5) charged amino acid residues (e.g., basic amino acid residues) relative to SEQ ID NO: 138, which is present C -terminal to the amino acid sequence of SPH (e.g., within 1, 2, 3, 4, 5. 6, or 7 amino acids from the end of the SPH amino acid sequence (e.g.. within positions 459-465 numbered according to any one of SEQ ID NOs: 5-10, 36-59, 981, or 6409-6413)), optionally wherein 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 982.351. The AAV capsid variant of embodiment 350, wherein the amino acid sequence of SPH is present at positions 456-458 numbered according to any one of SEQ ID NOs: 5-10, 36-59, 981, 982. or 6409- 6413.352. The AAV capsid variant of embodiment 350or 351. which comprises less than four, less than three, less than two (e.g.. two or one) charged amino acid residues (e.g., basic amino acid residues) relative to SEQ ID NO: 138.353. The AAV capsid variant of any one of embodiments 350-352. which comprises one charged amino acid residues (e.g., an basic amino acid residue) relative to SEQ ID NO: 138, optionally 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: 5-10, 36-59. 981, 982, or 6409-6413.354. The AAV capsid variant of any one of embodiments 350-353, 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 350-354, wherein the charged amino acid residue is a positively charged amino acid (e.g., R or K).356. The AAV capsid variant of any one of embodiments 350-355, wherein the charged amino acid residue is R.357. The AAV capsid variant of any one of embodiments 350-355, wherein the charged amino acid residue is K.358. The AAV capsid variant of any one of embodiments 350-357, at least one, two. three or four charged amino acid residues is present within 1, 2, 3. 4, 5, 6, 7 (e.g., 1-7) amino acids from the end of the SPH amino acid sequence.359. The AAV capsid variant of any one of embodiments 350-358, which comprises a charged amino acid residue (e.g., K or R) immediately after the SPH sequence (e.g., at position 459 numbered according to SEQ ID NO: 981).360. The AAV capsid variant of any one of embodiments 350-359, which comprises a charged amino acid residue (e.g., K or R) at position 459, numbered according to SEQ ID NO: 138 or SEQ ID NO: 982.361. The AAV capsid variant of any one of embodiments 350-360, which comprises K at position 459, numbered according to SEQ ID NO: 981.362. The AAV capsid variant of any one of embodiments 350-360. which comprises R at position 459, numbered according to SEQ ID NO: 981.363. The AAV capsid variant of any one of embodiments 350-362. which comprises 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 981.364. The AAV capsid variant of any one of embodiments 300-326 or 350-363, which has increased tropism for a liver cell or tissue, relative to the tropism of a reference sequence comprising the amino acid sequence of SEQ ID NO: 138.365. The AAV capsid variant of any one of embodiments 300-326 or 350-364, which is enriched 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, in the liver compared to a reference sequence of SEQ ID NO: 138, e.g., when measured by an assay as described in Example 4.366. The AAV capsid variant of any one of embodiments 300-326, 364, or 365, which has reduced tropism for a CNS cell or tissue, e.g., a brain cell, brain tissue, spinal cord cell, or spinal cord tissue,relative to the tropism of a reference sequence comprising the amino acid sequence of SEQ ID NO: 138.367. The AAV capsid variant of any one of embodiments 300-326 or 364-366. which shows preferential transduction in a liver region relative to the transduction in the brain and / or dorsal root ganglia (DRG).368. The AAV capsid variant of any one of embodiments 300-326 or 364-367, which shows preferential transduction in a liver region relative to the transduction in the heart and / or muscle (e.g., quadriceps).369. An AAV capsid variant comprising:(I) (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, or17 consecutive amino acids from any one of the sequences provided in Tables 1, 2A, 2B, 13-19; or(c) an amino acid sequence comprising at least one, two, or three but no more than four different amino acids, relative to any one of the sequences provided in Tables 1. 2A, 2B. 13-19; or(d) an amino acid sequence comprising 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 the sequences provided in Tables 1, 2 A, 2B, 13-19; and / or(II) (i) the amino acid sequence of SEQ ID NO: 6419;(ii) an amino acid sequence comprising at least one or two. but no more than three different amino acids, relative to the amino acid sequence of SEQ ID NO: 6419;(iii) an amino acid sequence comprising at least one or two modifications, e.g., substitutions (e.g., conservative substitutions), but no more than three modifications, e.g., substitutions (e.g., conservative substitutions), relative to the amino acid sequence of SEQ ID NO: 6419; or(iv) at least 3, 4, 5, 6. or 7 consecutive amino acids from SEQ ID NO: 6419; optionally wherein the amino acid sequence of (i), (ii), (iii). and / or (iv) is present at positions 590-596, numbered according to the amino acid sequence of SEQ ID NO: 981 , 982, 641 1, or 6412.370. An AAV capsid variant comprising:(I) (a) the amino acid sequence of any 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; or(c) an amino acid sequence comprising at least one, two. or three but no more than four different amino acids, relative to the amino acid sequence of any one of SEQ ID NOs: 945-980 or 985-986;(d) an amino sequence comprising 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: 945-980 or 985-986; and / or(II) (i) the amino acid sequence of SEQ ID NO: 6419;(ii) an amino acid sequence comprising at least one or two. but no more than three different amino acids, relative to the amino acid sequence of SEQ ID NO: 6419;(iii) an amino acid sequence comprising at least one or two modifications, e.g., substitutions (e.g., conservative substitutions), but no more than three modifications, e.g.. substitutions (e.g.. conservative substitutions), relative to the amino acid sequence of SEQ ID NO: 6419; or(iv) at least 3, 4, 5, 6. or 7 consecutive amino acids from SEQ ID NO: 6419; optionally wherein the amino acid sequence of (i), (ii), (iii), and / or (iv) is present at positions 590-596, numbered according to the amino acid sequence of SEQ ID NO: 981, 982, 6411, or 6412.371. An AAV capsid variant comprising:(I) (a) the amino acid sequence of any 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;(c) an amino acid sequence comprising at least one, two, or three but no more than four 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; or(d) an amino acid sequence comprising 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; and / or(II) (i) the amino acid sequence of SEQ ID NO: 6419;(ii) an amino acid sequence comprising at least one or tw o. but no more than three different amino acids, relative to the amino acid sequence of SEQ ID NO: 6419;(iii) an amino acid sequence comprising at least one or two modifications, e.g.. substitutions (e.g., conservative substitutions), but no more than three modifications, e.g.. substitutions (e.g.. conservative substitutions), relative to the amino acid sequence of SEQ ID NO: 6419; or(iv) at least 3, 4, 5, 6. or 7 consecutive amino acids from SEQ ID NO: 6419; optionally wherein the amino acid sequence of (i), (ii), (iii), and / or (iv) is present at positions 590-596, numbered according to the amino acid sequence of SEQ ID NO: 981, 982, 6411, or 6412.372. An AAV capsid variant comprising:(a) the amino acid sequence of any of SEQ ID NOs: 3849-4051 or 4681-4693;(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 comprising at least one. two, or three but no more than four different amino acids, relative to the amino acid sequence of any one of SEQ ID NOs: 3849-4051 or 4681-4693; or(d) an amino acid sequence comprising 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: 3849-4051 or 4681-4693.373. An AAV capsid variant comprising:(a) the amino acid sequence of any of SEQ ID NOs: 4052-4092;(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 comprising at least one, two, or three but no more than four different amino acids, relative to the amino acid sequence of any one of SEQ ID NOs: 4052-4092; or(d) an amino acid sequence comprising 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: 4052-4092.374. An AAV capsid variant comprising:(a) the amino acid sequence of any of SEQ ID NOs: 4056, 4058, 4059, 4062-4064, 4066, 4067. 4080. 4084, 4090, or 4095-4097;(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 comprising at least one. two, or three but no more than four different amino acids, 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; or(d) an amino acid sequence comprising 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: 4056. 4058. 4059. 4062-4064, 4066, 4067, 4080, 4084, 4090, or 4095- 4097.375. 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 903-909.376. The AAV capsid variant of any one of embodiments 369-375, wherein the at least 3 consecutive amino acids comprise SPH.377. The AAV capsid variant of any one of embodiments 369-371 or 376. wherein the at least 4 consecutive amino acids comprise SPHS (SEQ ID NO: 4700).378. The AAV capsid variant of any one of embodiments 369-371, 376. or 377, wherein the at least 5 consecutive amino acids comprise SPHSK (SEQ ID NO: 4701).379. The AAV capsid variant of any one of embodiments 369-371 or 376-378, wherein the at least 6 consecutive amino acids comprise SPHSKA (SEQ ID NO: 941).380. The AAV capsid variant of embodiment 369-371, wherein the at least 3 consecutive amino acids comprise HDS.381. The AAV capsid variant of any one of embodiments 369-371 or 380, wherein tire at least 4 consecutive amino acids comprise HDSP (SEQ ID NO: 4702).382. The AAV capsid variant of any one of embodiments 369-371. 380, or 381. wherein the at least 5 consecutive amino acids comprise HDSPH (SEQ ID NO: 4703).383. The AAV capsid variant of any one of embodiments 369-371 or 380-382, wherein the at least 6 consecutive amino acids comprise HDSPHK (SEQ ID NO: 2).384. The AAV capsid variant of any one of embodiments 369-371, wherein:(i) the at least 3 consecutive amino acids comprise SPH;(ii) the at least 4 consecutive amino acids comprise SPHK (SEQ ID NO: 6398);(iii) the at least 5 consecutive amino acids comprise SPHKY (SEQ ID NO: 4715); and / or(iv) the at least 6 consecutive amino acids comprise SPHKYG (SEQ ID NO: 966).385. The AAV capsid variant of embodiment 369 or 371, which comprises an amino acid sequence comprising 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 903-909.386. The AAV capsid variant of any one of embodiments 369,371, or 385, which comprises an amino acid sequence comprising 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 SPHSKA (SEQ ID NO: 941).387. The AAV capsid variant of any one of embodiments 369, 371. or 385, which comprises an amino acid sequence comprising 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 HDSPHK (SEQ ID NO: 2).388. The AAV capsid variant of any one of embodiments 369-371, 384, or 385, which comprises an amino acid sequence comprising 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 SPHKYG (SEQ ID NO: 966).389. The AAV capsid variant of embodiment 370, which comprises:(i) an amino acid sequence comprising 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 KTENVSGSPHSKAQNQQT (SEQ ID NO: 3272);(ii) an amino acid sequence comprising 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 KTERVSGSPHSKAQNQQT (SEQ ID NO: 3589);(iii) an amino acid sequence comprising 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 KAEIGHDSPHKSGQNQQT (SEQ ID NO: 1754)(iv) an amino acid sequence comprising 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 KTEKMSGSPHSKAQNQQT (SEQ ID NO: 3241);(v) an amino acid sequence comprising at least one, tw o. or three but no more than four modifications, e.g.. substitutions (e.g.. conservative substitutions), relative to the amino acid sequence of KTINGHDSPHSKAQNLQT (SEQ ID NO: 4100); or(vi) an amino acid sequence comprising 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 KTVNGHDSPHSKAQNQQT (SEQ ID NO: 4062).390. The AAV capsid variant of embodiment 369 or 371, which comprises an amino acid sequence comprising at least one, two, or three but no more than four 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 903-909.391. The AAV capsid variant of any one of embodiments 369,371, or 390, which comprises an amino acid sequence comprising at least one. two, or three but no more than four different amino acids relative to the amino acid sequence of SPHSKA (SEQ ID NO: 941).392. The AAV capsid variant of any one of embodiments 369, 371. or 390, which comprises an amino acid sequence comprising at least one. two, or three but no more than four different amino acids relative to the amino acid sequence of HDSPHK (SEQ ID NO: 2).393. The AAV capsid variant of any one of embodiments 369, 371. 384, or 390. which comprises an amino acid sequence comprising at least one, two, or three but no more than four different amino acids relative to the amino acid sequence of SPHKYG (SEQ ID NO: 966).394. The AAV capsid variant of embodiment 369, which comprises:(i) an amino acid sequence comprising at least one, two, or three but no more than four different amino acids relative to the amino acid sequence of KTERVSGSPHSKAQNQQT (SEQ ID NO: 3589);(ii) an ammo acid sequence comprising at least one, two, or three but no more than four different amino acids relative to the amino acid sequence of KAEIGHDSPHKSGQNQQT (SEQ ID NO: 1754);(iii) an amino acid sequence comprising at least one, two, or three but no more than four different amino acids relative to the amino acid sequence of KTEKMSGSPHSKAQNQQT (SEQ ID NO: 3241);(iv) an amino acid sequence comprising at least one. two, or three but no more than four different amino acids relative to the amino acid sequence of KT1NGHDSPHSKAQNLQT (SEQ ID NO: 4100);(v) an amino acid sequence comprising at least one, two, or three but no more than four different amino acids relative to the amino acid sequence of KTVNGHDSPHSKAQNQQT (SEQ ID NO: 4062);(vi) an amino acid sequence comprising at least one, two. or three but no more than four different amino acids relative to the amino acid sequence of KTENVSGSPHSKAQNQQT (SEQ ID NO: 3272);(vii) an amino acid sequence comprising at least one. two, or three but no more than four different amino acids relative to the amino acid sequence of KTEKVSGSPHSKAQNQQT (SEQ ID NO: 3274);(viii) an amino acid sequence comprising at least one, tw o, or three but no more than four different amino acids relative to the amino acid sequence of KTINGSGSPHKSGQNKTS (SEQ ID NO: 4406);(ix) an amino acid sequence comprising at least one, tw o. or three but no more than four different amino acids relative to the amino acid sequence of KTSNASGSPHSKAHNQQT (SEQ ID NO: 3382);(x) an amino acid sequence comprising at least one, two, or three but no more than four different amino acids relative to the amino acid sequence of KNSIGSGSPHSKAQNQQT (SEQ ID NO: 3421);(xi) an amino acid sequence comprising at least one, two. or three but no more than four different amino acids relative to the amino acid sequence of KTVNGHDSPHKSGQRPST (SEQ ID NO: 4478);(xii) an amino acid sequence comprising at least one. two, or three but no more than four different amino acids relative to the amino acid sequence of KAENGSGSPHSKAQNQQT (SEQ ID NO: 3487); or(xiii) an amino acid sequence comprising at least one, two, or three but no more than four different amino acids relative to the amino acid sequence of KTINGSGSPHKSGQNQQP (SEQ ID NO: 4081).395. The AAV capsid variant of any one of embodiments 1-129, 269, 271, 375-388, or 390-394, which comprises the amino acid sequence of any of SEQ ID NOs: 2, 200, 201, 941, 943, 204, 208, 404, or 903-909.396. The AAV capsid variant of any one of embodiments 295-297, 301-305, 313, 314, 318, 319, or 323, which comprises the amino acid sequence of ERVSGSPHSKA (SEQ ID NO: 6399), optionally wherein the amino acid sequence is present immediately subsequent to position 450 and replaces positions 451-455 (e.g., 1451, N542, G453, S454, G455), numbered according to SEQ ID NO: 138.397. The AAV capsid variant of any one of embodiments 369-371. 375-379, 385, 386, 389-391, or 394-396, which comprises the amino acid sequence of KTERVSGSPHSKAQNQQT (SEQ ID NO: 3589), optionally wherein the amino acid sequence is present immediately subsequent to position 448 and replaces positions 449-460 (e.g., K449. T450. 1451, N452. G453. S454, G455, Q456, N457.Q458, Q459, T460). numbered according to SEQ ID NO: 138.398. The AAV capsid variant of any one of embodiments 269-371, 375, 380-383, 385. 387, 389, 390, 393. or 394, which comprises the amino acid sequence of AEIGHDSPHKSG (SEQ ID NO: 6400), optionally wherein the amino acid sequence is present immediately subsequent to position 449 and replaces positions 450-455 (e.g., T450, 1451, N452, G453, S454, G455), numbered according to SEQ ID NO: 138.399. The AAV capsid variant of any one of embodiments 369-371, 375, 380-383, 385. 387, 389, 390, 393, 394, or 398, which comprises the amino acid sequence of KAEIGHDSPHKSGQNQQT (SEQ ID NO: 1754), optionally wherein the amino acid sequence is present immediately subsequent to position 448 and replaces positions 449-460 (e.g., K449, T450, 1451, N452, G453. S454, G455, Q456, N457, Q458. Q459, T460), numbered according to SEQ ID NO: 138.400. The AAV capsid variant of any one of embodiments 369-371, 375-379, 390, 391, or 395, which comprises the amino acid sequence of EKMSGSPHSKA (SEQ ID NO: 6401). optionally wherein the amino acid sequence is present immediately subsequent to position 450 and replaces positions 451- 455 (e.g., 1451. N452, G453, S454, G455), numbered according to SEQ ID NO: 138.401. The AAV capsid variant of any one of embodiments 369-371 , 375-379, 390, 391. or 395, which comprises the amino acid sequence of KTEKMSGSPHSKAQNQQT (SEQ ID NO: 3241), optionally wherein the amino acid sequence is present immediately subsequent to position 448 and replaces positions 449-460 (e.g., K449, T450, 1451, N452, G453, S454, G455. Q456, N457, Q458, Q459, T460), numbered according to SEQ ID NO: 138.402. The AAV capsid variant of any one of embodiments 369-371, 375-379, 390, 391, or 395, which comprises the amino acid sequence of HDSPHSKAQNL (SEQ ID NO: 6402), optionally wherein the amino acid sequence is present immediately subsequent to position 453 and replaces positions 456- 458 (e.g., Q456, N457, Q458), numbered according to SEQ ID NO: 138.403. The AAV capsid variant of any one of embodiments 369-371, 375-379, 390, 391, or 395, which comprises the amino acid sequence of KTINGHDSPHSKAQNLQT (SEQ ID NO: 4100), optionally wherein the amino acid sequence is present immediately subsequent to position 448 and replaces positions 449-460 (e.g., K449, T450, 1451, N452, G453, S454, G455, Q456, N457, Q458, Q459. T460), numbered according to SEQ ID NO: 138.404. The AAV capsid variant of any one of embodiments 369-371. 375-379, 390. 391, or 395. which comprises the amino acid sequence of VNGHDSPHSKA (SEQ ID NO: 6403), optionally wherein the amino acid sequence is present immediately subsequent to position 450 and replaces positions 451- 455 (e.g., 1451, N452, G453, S454, G455), numbered according to SEQ ID NO: 138.405. The AAV capsid variant of any one of embodiments 369-371, 375-379. 390, 391. or 395, which comprises:(i) the amino acid sequence of KTVNGHDSPHSKAQNQQT (SEQ ID NO: 4062). optionally wherein the amino acid sequence is present immediately subsequent to position 448 and replaces positions 449-460 (e.g., K449, T450, 1451, N452, G453, S454, G455. Q456, N457, Q458, Q459, T460), numbered according to SEQ ID NO: 138; or(ii) the AAV capsid variant comprises tire amino acid sequence of ENVSGSPHSKA (SEQ ID NO: 60), optionally wherein the amino acid sequence is present immediately subsequent to position 450 and replaces positions 451-455 (e.g., 1451, N452, G453, S454, G455), numbered according to SEQ ID NO: 138; corresponds to positions 451 to 461 of SEQ ID NO: 5; or is present at positions 451 to 461 numbered according to SEQ ID NO: 5 or 981.406. 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. or 395, comprising an amino acid sequence encoded by: the nucleotide sequence of SEQ ID NO: 942: a nucleotide sequence comprising at least one, two. three, four, five, six, or seven modifications, e.g., substitutions, but no more than ten modifications, e.g.. substitutions, relative to the nucleotide sequence of SEQ ID NO: 942; or a nucleotide sequence comprising at least one, two, three, four, five, six, or seven, but no more than ten different nucleotides relative to the nucleotide sequence of SEQ ID NO: 942.407. The AAV capsid variant of any one of embodiments 1-9, 11, 12-22, 24, 26, 28, 30, 33, 35-42, 44, 46-50, 52, 54-77, 83-88, 90-97, 100-103, 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, or 395, comprising an amino acid sequence encoded by: the nucleotide sequence of SEQ ID NO: 3; a nucleotide sequence comprising at least one, two, three, four, five, six, or seven modifications, e.g., substitutions, but no more than ten modifications, e.g., substitutions, relative to the nucleotide sequence of SEQ ID NO: 3; or a nucleotide sequence comprising at least one, two, three, four, five, six, or seven, but no more than ten different nucleotides relative to the nucleotide sequence of SEQ ID NO: 3.408. 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, wherein the nucleotide sequence encoding the capsid variant comprises the nucleotide sequence of SEQ ID NO: 942; a nucleotide sequence comprising at least one, two, three, four, five, six, or seven modifications, e.g.. substitutions, but no more than ten modifications, e.g.. substitutions, relative to the nucleotide sequence of SEQ ID NO: 942; or a nucleotide sequence comprising at least one, two. three, four, five, six, or seven, but no more than ten different nucleotides relative to the nucleotide sequence of SEQ ID NO: 942.409. The AAV capsid variant of any one of embodiments 1-9, 11, 12-22, 24, 26. 28, 30, 33, 35-42, 44, 46-50. 52, 54-77, 83-88, 90-97, 100-103, 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, or 407, wherein the nucleotide sequence encoding the capsid variant comprises the nucleotide sequence of SEQ ID NO: 3; a nucleotide sequence comprising at least one, two. three, four, five, six, or seven modifications, e.g., substitutions, but no more than ten modifications, e.g., substitutions, relative to the nucleotide sequence of SEQ ID NO: 3; or a nucleotide sequence comprising at least one, two, three,four, five, six, or seven, but no more than ten different nucleotides relative to the nucleotide sequence of SEQ ID NO: 3.410. 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 369-410, wherein the amino acid sequence is present immediately subsequent to 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: 138.412. The AAV capsid variant of any one of embodiments 369-411, wherein the amino acid sequence replaces ammo acids 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, and / or 460 (e.g., K449, T450, 1451, N452, G453, S454, G455, Q456, N457, Q458, Q459, and / or T460), numbered according to the amino acid sequence of SEQ ID NO: 138.413. The AAV capsid variant of any one of embodiments 369-412, wherein the amino acid sequence is present immediately subsequent to position 455, relative to a reference sequence numbered according to the ammo acid sequence of SEQ ID NO: 138.414. The AAV capsid variant of any one of embodiments 369-413. wherein the amino acid sequence is present immediately subsequent to position 453, relative to a reference sequence numbered according to the ammo acid sequence of SEQ ID NO: 138.415. 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, 406, 408. or 410-413. comprising the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is present immediately subsequent to position 455, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.416. 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, 406, 408, 410-413, or 415, comprising the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is present immediately subsequent to position 455, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 981.417. The AAV capsid variant of embodiment 415 or 416, which further comprises:(i) 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; or(ii) an amino acid other than I at position 451 and / or G at position 453, numbered according to SEQ ID NO: 5, 138, or 981.418. The AAV capsid variant of any one of embodiments 415-417, which further comprises:(i) E at position 451, R at position 452, and V at position 453, numbered according to any one of SEQ ID NOs: 36, 138. or 981; or(ii) E at position 451 and / or V at position 453, numbered according to SEQ ID NO: 138, 981, or 5.419. The AAV capsid variant of any one of embodiments 415-418, which further comprises:(i) the substitutions 145 IE, N452R, and G453V, numbered according to any one of SEQ ID NOs: 36, 138, or 981; or(ii) the substitutions I451E or G453V. numbered according to SEQ ID NO: 138. 981, or 5.420. The AAV capsid variant of any one of embodiments 415-419. which comprises:(A) (i) E at position 451, R at position 452, and V at position 453, numbered according to any one of SEQ ID NOs: 36, 138, or 981; and(ii) the amino acid sequence of SPHSKA (SEQ ID NO: 941). wherein the amino acid sequence is present immediately subsequent to position 455. numbered according to any one of SEQ ID NOs: 36. 138, or 981: or(B) (i) E at position 451 and V at position 453, numbered according to SEQ ID NO: 5 or 138; and (ii) the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is present immediately subsequent to position 455, at positions 456-461, numbered according to SEQ ID NO: 5 or 138.421. The AAV capsid variant of embodiment 415 or 416, which further comprises an amino acid other than I at position 451. an amino acid other than N at position 452, and / or G at position 453, numbered according to SEQ ID NO: 39 or 138.422. The AAV capsid variant of any one of embodiments 415, 416. or 421, which further comprises E at position 451, K at position 452, and / or M at position 453, numbered according to SEQ ID NO: 138 or 39.423. The AAV capsid variant of any one of embodiments 415, 416, 421, or 422, which further comprises the substitutions 145 IE. N452K, and G453M, numbered according to SEQ ID NO: 39 or 138.424. The AAV capsid variant of any one of embodiments 415, 416. or 421-423, which comprises:(i) E at position 451, K at position 452, and M at position 453, numbered according to SEQ ID NO: 39 or 138; and(ii) the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is present immediately subsequent to position 455, numbered according to SEQ ID NO: 39 or 138.425. The AAV capsid variant of embodiment 415 or 416, which further comprises an ammo acid other than S at position 454, an amino acid other than G at position 455, and / or Q at position 458, numbered according to SEQ ID NO: 138.426. The AAV capsid variant of any one of embodiments 415, 416, or 425, which further comprises H at position 454, D at position 455, and / or L at position 458, numbered according to SEQ ID NO: 138.427. The AAV capsid variant of any one of embodiments 415, 416, 425, or 426, which further comprises the substitutions S454H. G455D. and Q458L, numbered according to SEQ ID NO: 138.428. The AAV capsid variant of any one of embodiments 415, 416, or 425-427. which comprises:(i) H at position 454. D at position 455, and / or L at position 458, numbered according to SEQ ID NO: 138; and(ii) the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is present immediately subsequent to position 455, numbered according to SEQ ID NO: 138.429. The AAV capsid variant of embodiment 415 or 416. which further comprises 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 138.430. The AAV capsid variant of any one of embodiments 415, 416. or 429, which further comprises V at position 451, H at position 454, and / or D at position 455, numbered according to SEQ ID NO: 52 or 138.431. The AAV capsid variant of any one of embodiments 415, 416, 429, or 430, which further comprises the substitutions 145 IV, S454H. and / or G455D, numbered according to SEQ ID NO: 52 or 138.432. The AAV capsid variant of any one of embodiments 415, 416. or 429-431 , which comprises:(i) V at position 451, H at position 454, and / or D at position 455, numbered according to SEQ ID NO: 52 or 138; and(ii) the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is present immediately subsequent to position 455, numbered according to SEQ ID NO: 52 or 138.433. The AAV capsid variant of any one of embodiments 1-9, 11, 12-22, 24, 26, 28, 30, 33, 35-42, 44, 46-50, 52, 54-77, 83-88, 90-97, 100-103, 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, comprising the amino acid sequence of HDSPHK (SEQ ID NO: 2). wherein the amino acid sequence is present immediately subsequent to position 453. numbered according to the amino acid sequence of SEQ ID NO: 138.434. The AAV capsid variant of any one of embodiments 1-9, 11, 12-22, 24, 26, 28. 30, 33, 35-42, 44, 46-50, 52. 54-77, 83-88, 90-97. 100-103, 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, or 433, comprising the amino acid sequence of HDSPHK (SEQ ID NO: 2), wherein the amino acid sequence is present immediately subsequent to position 453, numbered according to the amino acid sequence of SEQ ID NO: 982.435. The AAV capsid variant of any one of embodiments 1-9, 11, 12-22, 24. 26, 28, 30, 33, 35-42, 44, 46-50. 52, 54-77. 83-88, 90-97, 100-103, 105, 110. I l l, 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, comprising the amino acid sequence of SPHKSG (SEQ ID NO: 946), wherein the ammo acid sequence is present immediately subsequent to position 455, numbered relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 982.436. The AAV capsid variant of any one of embodiments 369-435, which comprises:(i) the amino acid sequence of HDSPHSKA (SEQ ID NO: 4486), which is present immediately subsequent to position 453; and(ii) a deletion of amino acids SG at position 454 and 455; wherein (i) and (ii) are numbered according to SEQ ID NO: 138.437. The AAV capsid variant of any one of embodiments 369-436, which comprises the amino acids HD at position 454 and 455, and further comprises the amino acid sequence of SPHSKA (SEQ ID NO: 941), which is present immediately subsequent to position 455. numbered relative to SEQ ID NO: 138.438. The AAV capsid variant of any one of embodiments 433-435, which further comprises 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 982.439. The AAV capsid variant of any one of embodiments 433-435 or 438, which further comprises A at position 450, E at position 451, and I at position 452, numbered according to SEQ ID NO: 138 or 982.440. The AAV capsid variant of any one of embodiments 433-435, 438, or 439, which further comprises the substitutions T450A, 145 IE, and N452I, numbered according to SEQ ID NO: 138 or 982.441. The AAV capsid variant of any one of embodiments 433, 434, or 438-440, which comprises:(i) A at position 450. E at position 451, and I at position 452, numbered according to SEQ ID NO: 138 or 982: and(ii) the amino acid sequence of HDSPHK (SEQ ID NO: 2). which is present immediately subsequent to positions 453, numbered according to SEQ ID NO: 138 or 982.442. 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 present immediately subsequent to position 455, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.443. An AAV capsid variant comprising:(i) the amino acid sequence of HDSPHK (SEQ ID NO: 2), wherein the amino acid sequence is present immediately subsequent to position 453. numbered according to the amino acid sequence of SEQ ID NO: 982; and / or(ii) a modification, e.g., a substitution (e.g., conservative substitution) in loop VIII, optionally wherein loop VIII comprises positions 587-599, numbered according to SEQ ID NO: 981, 982, 6411, or 6412; or positions 581-593, numbered according to SEQ ID NO: 138 or 6414.444. An AAV capsid variant comprising:(i) the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is present immediately subsequent to position 455, numbered according to the amino acid sequence of SEQ ID NO: 981; and / or(ii) a modification, e.g.. a substitution (e.g., conservative substitution) in loop VIII. optionally wherein loop VIII comprises positions 587-599, numbered according to SEQ ID NO: 981, 982. 6411. or 6412; or positions 581-593, numbered according to SEQ ID NO: 138 or 6414.445. An AAV capsid variant comprising:(A) the amino acid sequence of HDSPHK (SEQ ID NO: 2), wherein the amino acid sequence is present immediately subsequent to position 453, numbered according to the amino acid sequence of SEQ ID NO: 37, and optionally further comprising:(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) 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; and / or(B) a modification, e.g., a substitution (e.g., conservative substitution) in loop VIII, optionally wherein loop VIII comprises positions 587-599, numbered according to SEQ ID NO: 981, 982, 6411, or 6412; or positions 581-593, numbered according to SEQ ID NO: 138 or 6414.446. An AAV capsid variant comprising:(i) the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is present immediately subsequent to position 455. numbered according to the amino acid sequence of any one of SEQ ID NO: 36, 38-55, 57, or 59; and / or(ii) a modification, e.g.. a substitution (e.g., conservative substitution) in loop VIII, optionally wherein loop VIII comprises positions 587-599, numbered according to SEQ ID NO: 981, 982. 6411. or 6412; or positions 581-593, numbered according to SEQ ID NO: 138 or 6414.447. The AAV capsid variant of any one of the preceding embodiments, which further comprises:(i) a modification, e.g., an insertion, substitution (e.g., conservative substitution), and / or deletion, in loop I, II, V, VI and / or VIII; and / or(ii) a substitution at position K449, e.g., a K449R substitution, numbered according to SEQ ID NO: 138.448. The AAV capsid variant of any one of the preceding embodiments, which comprises an amino acid sequence comprising 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: 138.449. The AAV capsid variant of any one of the preceding embodiments, which comprises an amino acid sequence comprising at least one. two or three, but no more than 30, 20 or 10 different amino acids relative to the amino acid sequence of SEQ ID NO: 138.450. The AAV capsid variant of any one of the preceding embodiments, which comprises the amino acid sequence of SEQ ID NO: 138, or an amino acid sequence with at least 80% (e.g., at least about 85, 90, 95, 96, 97, 98, or 99%) sequence identity thereto.451. The AAV capsid variant of any one of the preceding embodiments, which comprises the amino acid sequence of SEQ ID NO: 138.452. The AAV capsid variant of any one of the preceding embodiments, which comprises an amino acid sequence encoded by tire nucleotide sequence of SEQ ID NO: 137, or a sequence with at least 80% (e.g.. at least about 85, 90, 95, 96, 97, 98, or 99%) sequence identity thereto.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 with at least 80% (e.g., at least about 85. 90, 95, 96, 97. 98. or 99%) sequence identity thereto.454. The AAV capsid variant of any one of the preceding embodiments, which comprises a VP1 protein, a VP2 protein, a VP3 protein, or a combination thereof.455. The AAV capsid variant of any one of embodiments 1-454, which comprises the amino acid sequence corresponding to positions 138-742, e.g.. a VP2, of SEQ ID NO: 981 or 982. or a sequence with at least 80% (e.g., at least about 85, 90. 95, 96, 97, 98. or 99%) sequence identity thereto.456. The AAV capsid variant of any one of embodiments 1-455, which comprises the amino acid sequence corresponding to positions 203-742, e.g.. a VP3, of SEQ ID NO: 981 or 982. or a sequence with at least 80% (e.g., at least about 85, 90. 95, 96, 97, 98, or 99%) sequence identity thereto.457. The AAV capsid variant of any one of embodiments 1-456, which comprises the amino acid sequence corresponding to positions 138-736, e.g., a VP2, of SEQ ID NO: 138, or a sequence with at least 80% (e.g., at least about 85, 90, 95, 96, 97, 98, or 99%) sequence identity thereto.458. The AAV capsid variant of any one of embodiments 1-457, which comprises the amino acid sequence corresponding to positions 203-736, e.g.. a VP3, of SEQ ID NO: 138, or a sequence with at least 80% (e.g., at least about 85, 90, 95. 96. 97, 98, or 99%) sequence identity thereto.459. 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, 406, 408, 410-413, 415-432, 444, or 446-458, , 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) the at least 3 consecutive amino acids comprise SPH;(ii) the at least 4 consecutive ammo acids comprise SPHS (SEQ ID NO: 4700);(iii) the at least 5 consecutive amino acids comprise SPHSK (SEQ ID NO: 4701); or(iv) the at least 6 consecutive amino acids comprise 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 with 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).460. 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, 406. 408, 410-413. 415-432, 444, or 446-459. 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) the at least 3 consecutive amino acids comprise SPH;(ii) the at least 4 consecutive amino acids comprise SPHS (SEQ ID NO: 4700);(iii) the at least 5 consecutive amino acids comprise SPHSK (SEQ ID NO: 4701); or(iv) the at least 6 consecutive amino acids comprise SPHSKA (SEQ ID NO: 941); 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: 981.461. 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, 406, 408, 410-413, 415-432, 444, or 446-460, comprising one or two, but no 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 with 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).462. 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, 406, 408, 410-413, 415-432, 444, or 446-461, comprising one or two, but no more than three substitutions relative to the amino acid sequence of SPHSKA (SEQ ID NO: 941), 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: 138 or SEQ ID NO: 981.463. The AAV capsid variant of any one of embodiments 459-462, wherein the amino acid sequence is present immediately subsequent to position 455, numbered according to SEQ ID NO: 138 or 981.464. The AAV capsid variant of any one of embodiments 1-9, 11, 12-22, 24, 26, 28. 30, 33, 35-42. 44, 46-50, 52. 54-77, 83-88, 90-97. 100-103, 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, comprising 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), wherein:(i) the at least 3 consecutive amino acids comprise HDS;(ii) the at least 4 consecutive amino acids comprise HDSP (SEQ ID NO: 4702);(iii) the at least 5 consecutive amino acids comprise HDSPH (SEQ ID NO: 4703); or(iv) the at least 6 consecutive amino acids comprise HDSPHK (SEQ ID NO: 2); wherein the AAV capsid variant comprises: (a) a VP1 protein comprising the ammo 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 with 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).465. The AAV capsid variant of any one of embodiments 1-9, 11, 12-22, 24, 26, 28, 30, 33, 35-42, 44, 46-50. 52, 54-77. 83-88, 90-97, 100-103, 105, 110. I l l, 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, comprising 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). wherein:(i) the at least 3 consecutive amino acids comprise HDS;(ii) the at least 4 consecutive amino acids comprise HDSP (SEQ ID NO: 4702);(iii) the at least 5 consecutive amino acids comprise HDSPH (SEQ ID NO: 4703); or(iv) the at least 6 consecutive amino acids comprise HDSPHK (SEQ ID NO: 2); 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: 982.466. The AAV capsid variant of any one of embodiments 1-9, 11, 12-22, 24, 26, 28, 30, 33, 35-42, 44, 46-50, 52, 54-77, 83-88, 90-97. 100-103, 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, or 465, comprising one or two, but no 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 with 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).467. The AAV capsid variant of any one of embodiments 1 -9, 1 1. 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, or 464-466, comprising one or two, but no more than three substitutions relative to the amino acid sequence of HDSPHK (SEQ ID NO: 2), 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: 982.468. The AAV capsid variant of any one of embodiments 464-468, wherein the amino acid sequence is present immediately subsequent to position 453. numbered according to SEQ ID NO: 138 or 982.469. The AAV capsid variant of any one of embodiments 1-468, which comprises the amino acid sequence of any one of SEQ ID NO: 981 or 982. or an amino acid sequence with at least 80% (e.g.. at least about 85, 90, 95, 96, 97. 98, or 99%) sequence identity thereto.470. The AAV capsid variant of any one of embodiments 1-469, which comprises an amino acid sequence comprising 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 982.471. The AAV capsid variant of any one of embodiments, 1-470, which comprises an amino acid sequence comprising at least one, two or three, but not more than 30, 20 or 10 different amino acids, relative to the amino acid sequence of SEQ ID NO: 981 or 982.472. 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, 406. 408, 410-413, 415-432, 444, 446-463, or 469-471, which comprises the amino acid sequence of SEQ ID NO: 981, or an amino acid sequence with at least 80% (e.g., at least about 85, 90, 95. 96, 97, 98, or 99%) sequence identity thereto.473. 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, 406, 408. 410-413, 415-432. 444. 446-463, or 469-472, which comprises an amino acid sequence comprising 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: 981.474. 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, 406, 408, 410-413, 415-432, 444, 446-463, or 469-473, which comprises an amino acid sequence comprising at least one, two or three, but not more than 30, 20 or 10 different amino acids, relative to the amino acid sequence of SEQ ID NO: 981.475. The AAV capsid variant of any one of embodiments 1-9, 11, 12-22, 24, 26, 28, 30, 33, 35-42, 44, 46-50. 52, 54-77. 83-88, 90-97, 100-103, 105, 110. I l l, 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 464-471, which comprises the amino acid sequence of SEQ ID NO: 982, or an amino acid sequence with at least 80% (e.g., at least about 85, 90, 95, 96, 97. 98, or 99%) sequence identity thereto.476. The AAV capsid variant of any one of embodiments 1-9, 11, 12-22, 24, 26. 28, 30, 33, 35-42, 44, 46-50, 52, 54-77, 83-88, 90-97, 100-103, 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, or 475. which comprises an amino acid sequence comprising 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: 982.477. The AAV capsid variant of any one of embodiments 1-9, 11, 12-22, 24, 26, 28, 30, 33, 35-42, 44, 46-50, 52. 54-77, 83-88, 90-97. 100-103, 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, or 476, which comprises an amino acid sequence comprising at least one. two or three, but not more than 30, 20 or 10 different amino acids, relative to the amino acid sequence of SEQ ID NO: 982.478. The AAV capsid variant of any one of embodiments 1-477, which comprises an amino acid sequence encoded by the nucleotide sequence of SEQ ID NO: 983 or 984, or a nucleotide sequence with at least 80% (e.g.. at least about 85, 90, 95, 96, 97, 98, or 99%) sequence identity thereto.479. The AAV capsid variant of any one of the preceding embodiments 1-478. wherein the nucleotide sequence encoding the capsid variant comprises the nucleotide sequence of SEQ ID NOs: 983 or 984. or a nucleotide sequence with at least 80% (e.g., at least about 85. 90, 95, 96, 97, 98. or 99%) sequence identity thereto.480. The AAV capsid variant of any one of the preceding 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, 469-474, 478, or 479, wherein the nucleotide sequence encoding the capsid variant comprises the nucleotide sequence of SEQ ID NO: 983, or a nucleotide sequence with at least 80% (e.g., at least about 85, 90, 95, 96, 97, 98, or 99%) sequence identity thereto.481. The AAV capsid variant of any one of 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. I l l, 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. wherein the nucleotide sequence encoding the capsid variant comprises the nucleotide sequence of SEQ ID NO: 984. or a nucleotide sequence with at least 80% (e.g., at least about 85, 90, 95. 96, 97, 98, or 99%) sequence identity thereto.482. The AAV capsid variant of any one of the preceding embodiments, wherein the nucleotide sequence encoding the capsid variant is codon optimized.483. An AAV capsid variant, comprising the amino acid sequence 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, 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: 981.484. An AAV capsid variant comprising the amino acid sequence of SEQ ID NO: 981, which further comprises a modification, e.g., a substitution (e.g., conservative substitution) in loop VIII, optionally wherein loop VIII comprises positions 587-599, numbered according to SEQ ID NO: 981, 982. 6411. or 6412: or positions 581-593, numbered according to SEQ ID NO: 138 or 6414.485. 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.486. An AAV capsid variant, comprising the amino acid sequence of any one of embodiments 1-9, 11, 12-22, 24, 26, 28, 30. 33, 35-42, 44, 46-50, 52. 54-77, 83-88, 90-97, 100-103, 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: 982.487. An AAV capsid variant comprising the amino acid sequence of SEQ ID NO: 982, which further comprises a modification, e.g., a substitution (e.g.. conservative substitution) in loop VIII, optionally wherein loop VIII comprises positions 587-599, numbered according to SEQ ID NO: 981, 982, 6411, or 6412; or positions 581-593, numbered according to SEQ ID NO: 138 or 6414.488. 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.489. An AAV capsid variant comprising an amino acid sequence encoded by the nucleotide sequence of SEQ ID NOs: 983 or 984, or a nucleotide sequence at least 95% identical thereto; which further comprises a modification, e.g., a substitution (e.g., conservative substitution) in loop VIII, optionally loop VIII comprises positions 587-599, numbered according to SEQ ID NO: 981, 982. 6411, or 6412; or positions 581-593, numbered according to SEQ ID NO: 138 or 6414.490. An AAV capsid variant comprising the amino acid sequence of any one of SEQ ID NOs: 5-10, 36-59, or 6409-6413, which optionally further comprises a modification, e.g., a substitution (e.g., conservative substitution) in loop VIII, optionally wherein loop VIII comprises positions 587-599, numbered according to SEQ ID NO: 981, 982, 6411, or 6412; or positions 581-593, numbered according to SEQ ID NO: 138 or 6414.491. An AAV capsid variant comprising an amino acid sequence encoded by the nucleotide sequence of any one of SEQ ID NOs: 4 or 12-35, or a nucleotide sequence at least 95% identical thereto, which optionally further comprises a modification, e g., a substitution (e.g., conservative substitution) in loop VIII. optionally wherein loop VIII comprises positions 587-599. numbered according to SEQ ID NO: 981, 982. 6411. or 6412; or positions 581-593, numbered according to SEQ ID NO: 138 or 6414.492. 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: 4 or 12-35, or a nucleotide sequence at least 95% identical thereto.493. The AAV capsid variant of any one of embodiments 1-299, 369-371. or 375-492, which has an increased tropism for a CNS cell or tissue, e.g., a brain cell, brain tissue, spinal cord cell, or spinal cord tissue, relative to the tropism of a reference sequence comprising the amino acid sequence of SEQ ID NO: 138.494. 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 thalamus) or the brain stem, optionally wherein the level of transduction is at least 5, 10, 15, 20, 25, 30. 35, 40, 45, 50, 55, 60, or 65-fold greater as compared to a reference sequence of SEQ ID NO: 138, e.g., when measured by an assay, e.g., an immunohistochemistry assay or a qPCR assay, e.g., as described in Example 2.495. 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 thalamus) or the brain stem, optionally wherein the level of transduction is at least 30, 35, 40. 45. 50, 55, 60, or 65-fold greater as compared to a reference sequence of SEQ ID NO: 138, e.g.. when measured by an assay, e.g.. an immunohistochemistry assay or a qPCR assay, e.g.. as described in Example 2.496. The AAV capsid variant of any one of embodiments 1-129, 168-299. 369-371, or 375-495, which is enriched at least about 3. 4, 5, 6, 7, 8. 9, or 10-fold, in the brain compared to a reference sequence of SEQ ID NO: 138, e.g., when measured by an assay as described in Example 1.497. The AAV capsid variant of any one of embodiments 1-129, 168-299, 369-371, or 375-496, which is enriched at least about 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80 or 85-fold, in the brain compared to a reference sequence of SEQ ID NO: 138, e.g., when measured by an assay as described in Example 1.498. 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 rodent (e.g., mouse), e.g., as compared to a reference sequence of SEQ ID NO: 138.499. The AAV capsid variant of any one of embodiments 1-129, 168-299, 369-371, or 375-498, which is enriched 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, in the brain of at least two to three species, e.g., a non-human primate and rodent (e.g., mouse), compared to a reference sequence of SEQ ID NO: 138, e.g., when measured by an assay as described in Example 1 or 5.500. The AAV capsid variant of embodiment 498 or 499. wherein the at least two to three species are Macaca fascicularis, Chlorocebus sabaeus, Callithrix jacchns, and / or mouse (e.g.. BALB / c mice, C57B1 / 6 mice, and / or CD-I outbred mice).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 at least about 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, or 8-fold, in the brain compared to a reference sequence of SEQ ID NO: 981, e.g., when measured by an assay as described in Example 3.502. The AAV capsid variant of any one of embodiments 147-167, 369, 410-414, 447-454, 457, 458, 482, or 493, which:(i) is enriched at least about 2, 2.5, 3, 3.5, 4, 4.5, 5, or 5.5-fold, in the brain compared to a reference sequence of SEQ ID NO: 982. e.g., when measured by an assay as described in Example 3;(ii) is capable of transducing at least 20%, 25%, 30%, 40%. 50%, 55%, 60%, 65%. 70%, 75%, 80%. or 85% of cells in a brain region (e g., a putamen. caudate, entorhinal cortex, hippocampus, thalamus, substantia nigra, motor cortex, frontal cortex, temporal cortex, cerebral cortex, cerebellar cortex, cerebellum, dentate nucleus, and / or Lateral Geniculate Nucleus (LGN)) , e.g.. when measured by an assay as described in Example 8;(iii) is capable of transducing at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45% 50%, 55%, 60%, or 65% of neurons (e.g.. NeuN+ neurons) in a brain region (e.g.. a putamen, caudate, entorhinal cortex, hippocampus, thalamus, substantia nigra, motor cortex, frontal cortex, or temporal cortex)and / or(iv) is capable of transducing at least 70%, 75%, 80%, 85%, 90%, or 95% of astrocytes (e.g., Sox9+ astrocytes) in a brain region (e.g., a putamen, caudate, entorhinal cortex, hippocampus, thalamus, substantia nigra, motor cortex, frontal cortex, or temporal cortex), e.g., when measured by an assay as described in Example 8.503. The AAV capsid variant of any one of embodiments 1-129, 168-299, 369-371, or 375-500, which delivers an increased level of a pay load to a brain region, optionally wherein the level of the payload is increased by at least 10, 12, 15, 20. 25, 30, 35, 40. 45, 50, 55, 60, 65. or 70-fold, as compared to a reference sequence of SEQ ID NO: 138, e.g., when measured by an assay, e.g., a qRT- PCR or a qPCR assay (e.g., as described in Example 2 or 8).504. The AAV capsid variant of any one of embodiments 1-129, 168-299, 369-371. 375-500, or 503. which delivers an increased level of viral genomes to a brain region, optionally wherein 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, as compared to a reference sequence of SEQ ID NO: 138, e.g.. when measured by an assay, e.g., a qRT- PCR or a qPCR assay (e.g.. as described in Example 2 or 8).505. The AAV capsid variant of embodiment 504 or 504. wherein the brain region is a midbrain region (e.g., the hippocampus or thalamus), frontal cortex, temporal cortex, motor cortex, cerebral cortex, cerebellum, cerebellar cortex, caudate, putamen, dentate nucleus, substantia nigra, entorhinal cortex, Lateral Geniculate Nucleus (LGN), or the brainstem.506. The AAV capsid variant of any one of embodiments 1-129, 168-299, 369-371, 375-500, or 503- 505, which:(i) is enriched at least about 4, 5, 10, 15, 20, 25, 30, or 35-fold, in the spinal cord compared to a reference sequence of SEQ ID NO: 138, e.g., when measured by an assay as described in Example 1I l lor 8, optionally wherein the region of the spinal cord is a thoracic spinal cord region, cervical spinal cord region, C5 ventral horn region, lumbar spinal cord region, or L5 ventral horn region;(ii) is capable of transducing at least 90% or 95% of neurons, e.g.. motor neurons (e.g.. ChAT+ neurons) in the spinal cord (e.g.. the cervical spinal cord, the thoracic spinal cord, or the lumbar spinal cord), e.g., when measured by an assay as described in Example 8; and / or(iii) is capable of transducing at least 90%. 95%, or 98% of astrocytes (e.g., Sox9+ astrocytes) in the spinal cord (e.g., the cervical spinal cord, the thoracic spinal cord, or the lumbar spinal cord), e.g.. when measured by an assay as described in Example 8.507. The AAV capsid variant of any one of embodiments 1-129, 168-299, 369-371, 375-500, or 503-506, which shows preferential transduction in a brain region relative to the transduction in the dorsal root ganglia (DRG).508. The AAV capsid variant of any one of embodiments 1-129, 168-299, 369-371, 375-500, or 503-507, which shows preferential transduction in a brain region relative to the liver.509. The AAV capsid variant of any one of embodiments 1-129, 168-299, 369-371, 375-500, or 503-508, which shows preferential transduction in a brain region relative to the transduction in the heart.510. The AAV capsid variant of any one of embodiments 1-129, 168-299, 369-371, 375-500, or 503-509, which shows preferential transduction in a brain region relative to the transduction in the dorsal root ganglia (DRG) and the heart.511. The AAV capsid variant of any one of the preceding embodiments, which is capable of transducing neuronal cells, e.g., NeuN+ neurons, ChAT+ neurons, or dopaminergic neurons (e.g., dopaminergic neurons in the substantia nigra), e.g., tyrosine hydroxylase (TH)+ neurons.512. The AAV capsid variant of any one of the preceding embodiments, which is capable of transducing NeuN+ cells (e.g., NeuN+ neurons). ChAT + cells (e.g., ChAT + neurons) and / or TH+ cells (e.g., TH+ neurons. e.g., dopaminergic neurons).513. The AAV capsid variant of any one of the preceding embodiments, which is capable of transducing non-neuronal cells, e.g., glial cells (e.g., oligodendrocytes or astrocytes).514. The AAV capsid variant of embodiment 513, wherein the non-neuronal cells comprise glial cells, oligodendrocytes (e.g., Olig2 positive oligodendrocytes), or astrocytes (e.g., Olig2 positive astrocytes or Sox9+ astrocytes).515. The AAV capsid variant of any one of the preceding embodiments, which is capable of transducing Olig2 positive cells, e.g., Olig2 positive astrocytes or Olig2 positive oligodendrocytes.516. The AAV capsid variant of any one of the preceding embodiments, which is capable of transducing Sox9+ cells, e.g.. Sox9+ astrocytes.517. The AAV capsid variant of any one of embodiments 369, 373. 447-454, 457, 458, or 482, which has increased tropism for a heart cell or tissue, e.g., a heart ventricle or heart atrium, relative to the tropism of a reference sequence of SEQ ID NO: 138.518. The AAV capsid variant of any one of embodiments 369, 373, 447-454, 457, 458, 482, or 517, which is enriched at least about 4, 5, 8, 10, 11, 12, 13, 14, 18, 19, 20, 21, 22, 24. 25, 27, 31, 33, or 34- fold, in the heart compared to a reference sequence of SEQ ID NO: 138, e.g., when measured by an assay as described in Example 4.519. The AAV capsid variant of any one of embodiments 369, 374, 447-454, 457, 458, 482, which has an increased tropism for a muscle cell or tissue (e.g., a quadriceps cell or a quadriceps tissue), relative to the tropism of a reference sequence comprising the amino acid sequence of SEQ ID NO: 138.520. The AAV capsid variant of any one of embodiments 369, 374, 447-454, 457. 458, 482, which is enriched at least about 4. 5, 8, 12, 17. 18, 20, 26, l ' l. 28, 30, or 36-fold, in the muscle compared to a reference sequence of SEQ ID NO: 138, e.g., when measured by an assay as described in Example 4.521. The AAV capsid variant of embodiment 519 or 520, wherein the muscle cell or tissue is a heart muscle (e.g.. a heart ventricle or a heart atrium, or both), a quadriceps muscle, or both.522. An AAV capsid variant comprising:(i) the amino acid sequence HDSPHK (SEQ ID NO: 2), wherein the amino acid sequence is present at positions 454-459 (e.g.. immediately subsequent to position 453), numbered according to SEQ ID NO: 982; and(ii) a modification, e.g., a substitution (e.g., conservative substitution) in loop VIII, optionally wherein loop VIII comprises positions 587-599, numbered according to SEQ ID NO: 981, 982, 6411, or 6412; or positions 581-593, numbered according to SEQ ID NO: 138 or 6414.523. An AAV capsid variant comprising:(i) the amino acid sequence SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is present at positions 456-461 (e.g.. immediately subsequent to position 455), numbered according to SEQ ID NO: 981; and(ii) a modification, e.g.. a substitution (e.g., conservative substitution) in loop VIII. optionally wherein loop VIII comprises positions 587-599, numbered according to SEQ ID NO: 981 , 982. 6411. or 6412; or positions 581-593, numbered according to SEQ ID NO: 138 or 6414.524. The AAV capsid variant of any one of the preceding embodiments, which comprises a modification, e.g., a substitution (e.g.. conservative substitution) in loop VIII, optionally wherein loop VIII comprises positions 587-599, numbered according to SEQ ID NO: 981, 982, 6411, or 6412; or positions 581-593, numbered according to SEQ ID NO: 138 or 6414.525. The AAV capsid variant of any one of the preceding embodiments, which comprises:(i) one, two, three, four, or all of an amino acid other than H at position 590, S at position 592, Q at position 594, A at position 595, and / or Q at position 596, numbered according to SEQ ID NO: 981, 982, 6411, or 6412; or(ii) one, two, three, four, or all of an amino acid other than H at position 584, S at position 586, Q at position 588. A at position 589, and / or Q at position 590, numbered according to SEQ ID NO: 138 or 6414.526. The AAV capsid variant of any one of the preceding embodiments, which comprises:(i) an amino acid other than H at position 590. S at position 592, Q at position 594, A at position 595, and Q at position 596, numbered according to SEQ ID NO: 981, 982, 6411, or 6412; or(ii) an amino acid other than H at position 584, S at position 586. Q at position 588, A at position 589, and Q at position 590, numbered according to SEQ ID NO: 138 or 6414.527. The AAV capsid variant of any one of the preceding embodiments, which comprises:(i) one, two. three, four, or all of the amino acid R at position 590. T at position 592, L at position 594. Q at position 595. and / or L at position 596, numbered according to SEQ ID NO: 981 , 982. 6411. or 6412, or a substitution, e.g., a conservative substitution thereof; or(ii) one, two. three, four, or all of the amino acid R at position 584, T at position 586, L at position 588, Q at position 589. and / or L at position 590, numbered according to SEQ ID NO: 138 or 6414, or a substitution, e.g., a conservative substitution thereof.528. The AAV capsid variant of any one of the preceding embodiments, which comprises:(i) the amino acid R at position 590, T at position 592, L at position 594, Q at position 595, and L at position 596, numbered according to SEQ ID NO: 981, 982, 6411, or 6412;(ii) the amino acid R at position 584, T at position 586, L at position 588, Q at position 589, and L at position 590, numbered according to SEQ ID NO: 138 or 6414.529. The AAV capsid variant of any one of embodiments 1-527, which comprises:(i) one, two, three, or all of an amino acid other than Q at position 594, A at position 597. Q at position 598, and / or T at position 599. numbered according to SEQ ID NO: 981. 982, 6411, or 6412;(ii) one, two. three, or all of an amino acid other than Q at position 588, A at position 591, Q at position 592, and / or T at position 593, numbered according to SEQ ID NO: 138 or 6414;(iii) an amino acid other than Q at position 594, A at position 597, Q at position 598. and T at position 599, numbered according to SEQ ID NO: 981, 982, 6411, or 6412; or(iv) an amino acid other than Q at position 588, A at position 591, Q at position 592, and T at position 593, numbered according to SEQ ID NO: 138 or 6414.530. The AAV capsid variant of any one of embodiments 1-527 or 529, which comprises:(i) one, two, three, or all of the amino acid K at position 594, S at position 597, S at position598, and / or A at position 599, numbered according to SEQ ID NO: 981, 982, 6411, or 6412, or a substitution, e g., a conservative substitution thereof;(ii) one, two, three, or all of the amino acid K at position 588, S at position 591, S at position592, and / or A at position 593, numbered according to SEQ ID NO: 138 or 6414, or a substitution, e.g., a conservative substitution thereof:(iii) the amino acid K at position 594. S at position 597, S at position 598. and A at position599, numbered according to SEQ ID NO: 981, 982, 6411, or 6412; or(iv) the amino acid K at position 588. S at position 591, S at position 592. and A at position593, numbered according to SEQ ID NO: 138 or 6414.531. An AAV capsid variant comprising:(i) one, two, three, four, or all of an amino acid other than H at position 584. S at position 586. Q at position 588, A at position 589, and / or Q at position 590, numbered according to SEQ ID NO: 138 or 6414; or(ii) an amino acid other than H at position 584. S at position 586, Q at position 588, A at position 589, and / or Q at position 590, numbered according to SEQ ID NO: 138 or 6414.532. An AAV capsid variant comprising:(i) one, two. three, four, or all of the amino acid R at position 584, T at position 586, L at position 588, Q at position 589. and / or L at position 590, numbered according to SEQ ID NO: 138 or 6414, or a substitution, e.g., a conservative substitution thereof; or(ii) the amino acid R at position 584, T at position 586, L at position 588, Q at position 589, and / or L at position 590, numbered according to SEQ ID NO: 138 or 6414.533. An AAV capsid variant comprising:(i) the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is present immediately subsequent to position 455, numbered according to the amino acid sequence of SEQ ID NO: 138 or 981; and(ii) one, two. three, four, or all of an amino acid other than H at position 590, S at position 592, Q at position 594, A at position 595, and / or Q at position 596, numbered according to SEQ ID NO: 981 or 6411.534. An AAV capsid variant comprising:(i) the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is present immediately subsequent to position 455, numbered according to the amino acid sequence of SEQ ID NO: 138 or 981 (e.g., at positions 456-461 numbered according to the amino acid sequence of SEQ ID NO: 981); and(ii) an amino acid other than H at position 590, S at position 592, Q at position 594, A at position 595, and Q at position 596, numbered according to SEQ ID NO: 981 or 6411.535. An AAV capsid variant comprising:(i) the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is present immediately subsequent to position 455, numbered according to the amino acid sequence of SEQ ID NO: 138 or 981 (e.g., at positions 456-461 numbered according to the amino acid sequence of SEQ ID NO: 981); and(ii) one, two, three, four, or all of the amino acid R at position 590, T at position 592, L at position 594, Q at position 595, and / or L at position 596, numbered according to SEQ ID NO: 981 or 6411, or a substitution, e.g.. a conservative substitution thereof.536. An AAV capsid variant comprising:(i) the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is present immediately subsequent to position 455, numbered according to the amino acid sequence of SEQ ID NO: 138 or 981 (e.g., at positions 456-461 numbered according to the amino acid sequence of SEQ ID NO: 981); and(ii) the amino acid R at position 590, T at position 592, L at position 594, Q at position 595, and L at position 596, numbered according to SEQ ID NO: 981 or 6411.537. An AAV capsid variant comprising:(A) the amino acid sequence of HDSPHK (SEQ ID NO: 2), wherein the amino acid sequence is present immediately subsequent to position 453, numbe...

Claims

We claim:

1. An AAV capsid variant, comprising: (a) three, four, or all of the amino acid R at position 584, the amino acid T at position 586, the amino acid L at position 588, the amino acid Q at position 589, and / or the amino acid L at position 590, numbered according to SEQ ID NO: 138; and (b) an amino acid sequence having the following formula: [N1]-[N2]-[N3], wherein [N1]-[N2]- [N3] is present in hypervariable loop IV, wherein: (i) [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 (iii) [N3] comprises X4, X5, and X6, wherein at least one of X4, X5, or X6 is a basic amino acid, e.g., a K or R; and wherein the AAV capsid variant comprises an amino acid sequence at least 95% identical to the amino acid sequence of positions 203-736 of SEQ ID NO:

138.

2. An AAV capsid variant, comprising three, four or all of the amino acid R at position 584, the amino acid T at position 586, the amino acid L at position 588, the amino acid Q at position 589, and / or the amino acid L at position 590, numbered according to SEQ ID NO: 138, wherein the AAV capsid variant comprises an amino acid sequence at least 95% identical to the amino acid sequence of positions 203-736 of SEQ ID NO:

138.

3. The AAV capsid variant of claim 2, which comprises an amino acid sequence having the following formula: [N1]-[N2]-[N3], wherein: (i) [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 (iii) [N3] comprises X4, X5, and X6, wherein at least one of X4, X5, or X6 is a basic amino acid, e.g., a K or R; wherein [N1]-[N2]-[N3] is present in hypervariable loop IV.

4. The AAV capsid variant of claim 1 or 3, wherein [N3] 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.

5. The AAV capsid variant of any one of claims 1, 3, or 4, wherein [N2]-[N3] comprises 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), 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), 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).

6. The AAV capsid variant of any one of claims 1 or 3-5, wherein [N1] comprises GSG, GHD, VSG, GQD, 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.

7. The AAV capsid variant of any one of claims 1 or 3-6, wherein [N1]-[N2]-[N3] comprises: (i) GSGSPHSKA (SEQ ID NO: 4697), GHDSPHKSG (SEQ ID NO: 4698), VSGSPHSKA (SEQ ID NO: 4913), 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), 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 (SEQID 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), 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 GHSSPHRSG (SEQ ID NO: 5026); or (ii) GSGSPHSKA (SEQ ID NO: 4697), GHDSPHKSG (SEQ ID NO: 4698), or VSGSPHSKA (SEQ ID NO: 4913).

8. The AAV particle of any one of claims 1 or 3-7, which further comprises: (i) [N0], wherein [N0] comprises TIN, TEN, TER, 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, TSY, ELH, AIN, SVN, TDN, TFH, TVH, 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, TEP, SEL, TWQ, TEV, AVN, GVL, TLN, TEG, TRD, NAI, AEN, AET, ETA, or NNL; and / or (ii) [N4], wherein [N4] comprises 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: 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), 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 IDNO: 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: 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), 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), 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).

9. The AAV capsid variant of claim 8, wherein [N0]-[N1]-[N2]-[N3]-[N4] comprises: (i) the amino acid sequence of any one of SEQ ID NOs: 2242-2886; or (ii) TENVSGSPHSKAQNQQ (SEQ ID NO: 2283), TERVSGSPHSKAQNQQ (SEQ ID NO: 2272), TINGSGSPHSKAQNQQ (SEQ ID NO: 2242), or TINGHDSPHKSGQNQQ (SEQ ID NO: 2243).

10. The AAV capsid variant of claim 8 or 9, wherein: (i) [N0] is present at amino acids 450-452, numbered according to SEQ ID NO: 981, 982, or 138; (ii) [N1] is present at amino acids 453-455, numbered according to SEQ ID NO: 981, 982, or 138; (iii) [N2] is present at amino acids 456-458, numbered according to SEQ ID NO: 981 or 982; (iv) [N3] is present at amino acids 459-461, numbered according to SEQ ID NO: 981 or 982; (v) [N4] is present at amino acids 462-465, numbered according to SEQ ID NO: 981 or 982; and / or (vi) [N0]-[N1]-[N2]-[N3]-[N4] is present at amino acids 450-465, numbered according to SEQ ID NO: 981 or 982.

11. An AAV capsid variant, comprising: (a) three, four, or all of the amino acid R at position 584, the amino acid T at position 586, the amino acid L at position 588, the amino acid Q at position 589, and / or the amino acid L at position 590, numbered according to SEQ ID NO: 138; and (b) the amino acid sequence of HDSPHK (SEQ ID NO: 2) in hypervariable loop IV; wherein the AAV capsid variant comprises an amino acid sequence at least 95% identical to the amino acid sequence of positions 203-736 of SEQ ID NO:

138.

12. The AAV capsid variant of claim 11, wherein the amino acid sequence of HDSPHK (SEQ ID NO: 2) is present immediately subsequent to amino acid 453, numbered according to SEQ ID NO:

982.

13. An AAV capsid variant, comprising: (a) three, four, or all of the amino acid R at position 584, the amino acid T at position 586, the amino acid L at position 588, the amino acid Q at position 589, and / or the amino acid L at position 590, numbered according to SEQ ID NO: 138; and (b) the amino acid sequence of SPHSKA (SEQ ID NO: 941) in hypervariable loop IV; wherein the AAV capsid variant comprises an amino acid sequence at least 95% identical to the amino acid sequence of positions 203-736 of SEQ ID NO: 138.

14. The AAV capsid variant of claim 13, wherein the amino acid sequence of SPHSKA (SEQ ID NO: 941) is present immediately subsequent to amino acid 455, numbered according to SEQ ID NO:

981.

15. The AAV capsid variant of claim 13 or 14, wherein the AAV capsid variant further comprises the amino acid E at position 451, numbered according to SEQ ID NO:

981.

16. The AAV capsid variant of any one of claims 13-15, which comprises the amino acid V at position 453, numbered according to SEQ ID NO:

981.

17. The AAV capsid variant of any one of claims 13-16, which comprises the amino acid R at position 452, numbered according to SEQ ID NO:

981.

18. The AAV capsid variant of any one of claims 1-17, which comprises: (i) the amino acid R at position 590, T at position 592, L at position 594, Q at position 595, and L at position 596, numbered according to SEQ ID NO: 981, 982, 6411, or 6412; or (ii) the amino acid R at position 584, T at position 586, L at position 588, Q at position 589, and L at position 590, numbered according to SEQ ID NO: 138 or 6414.

19. The AAV capsid variant of any one of claims 1-12 or 18, which comprises: comprises: (i) an amino acid sequence at least 95% or at least 98% identical to amino acids 203-742 of SEQ ID NO: 6412; (ii) an amino acid sequence at least 95% or at least 98% identical to amino acids 138-742 of SEQ ID NO: 6412; and / or (iii) an amino acid sequence at least 95% or at least 98% identical to the amino acid sequence of SEQ ID NO: 6412.

20. The AAV capsid variant of any one of claims 1-12, 18, or 19, which comprises: comprises: (i) the amino acid sequence of amino acids 203-742 of SEQ ID NO: 6412; (ii) the amino acid sequence of amino acids 138-742 of SEQ ID NO: 6412; and / or (iii) the amino acid sequence of SEQ ID NO: 6412.

21. The AAV capsid variant of any one of claims 1-10 or 13-18, which comprises: comprises: (i) an amino acid sequence at least 95% or at least 98% identical to amino acids 203-742 of SEQ ID NO: 6411;(ii) an amino acid sequence at least 95% or at least 98% identical to amino acids 138-742 of SEQ ID NO: 6411; and / or (iii) an amino acid sequence at least 95% or at least 98% identical to the amino acid sequence of SEQ ID NO: 6411.

22. The AAV capsid variant of any one of claims 1-10, 13, 14, 18, or 21, which comprises: comprises: (i) the amino acid sequence of amino acids 203-742 of SEQ ID NO: 6411; (ii) the amino acid sequence of amino acids 138-742 of SEQ ID NO: 6411; and / or (iii) the amino acid sequence of SEQ ID NO: 6411.

23. The AAV capsid variant of any one of claims 1 or 3-22, wherein hypervariable loop IV comprises amino acids 449-460, numbered according to SEQ ID NO:

138.

24. The AAV capsid variant of any one of claims 1-23, wherein the AAV capsid variant (i) has an increased tropism for a CNS cell or tissue, e.g., a brain cell, brain tissue, spinal cord cell, or spinal cord tissue, relative to the tropism of a reference sequence comprising the amino acid sequence of SEQ ID NO: 138 (ii) transduces a brain region (e.g., a putamen, caudate, entorhinal cortex, hippocampus, thalamus, substantia nigra, motor cortex, frontal cortex, temporal cortex, cerebral cortex, dentate nucleus, and / or Lateral Geniculate Nucleus (LGN)), optionally wherein the level of transduction is at least 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, or 65-fold greater as compared to a reference sequence of SEQ ID NO: 138, e.g., when measured by an assay, e.g., an immunohistochemistry assay or a qPCR assay, e.g., as described in Example 2; (iii) is enriched at least about 3, 4, 5, 6, 7, 8, 9, or 10-fold, in the brain compared to a reference sequence of SEQ ID NO: 138, e.g., when measured by an assay as described in Example 1; (iv) is capable of transducing the brain of at least two to three species, e.g., a non-human primate and / or rodent (e.g., Macaca fascicularis, Chlorocebus sabaeus, Callithrix jacchus, and / or mouse (e.g., BALB / c mice, C57Bl / 6 mice, and / or CD-1 outbred mice), when measured by an assay as described in Example 1 or 5; (v) delivers an increased level of a payload to a brain region, optionally wherein the level of the payload is increased by at least 5, 10, 15, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, or 70- fold, as compared to a reference sequence of SEQ ID NO: 138, e.g., when measured by an assay, e.g., a qRT-PCR or a qPCR assay (e.g., as described in Example 2 or 8), optionally wherein the brain region is a putamen, caudate, entorhinal cortex, hippocampus, thalamus, substantia nigra, motor cortex, frontal cortex, temporal cortex, cerebral cortex, dentate nucleus, and / or Lateral Geniculate Nucleus (LGN);(vi) delivers an increased level of viral genomes to a brain region, optionally wherein 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, as compared to a reference sequence of SEQ ID NO: 138, e.g., when measured by an assay, e.g., a qRT-PCR or a qPCR assay (e.g., as described in Example 2 or 8), optionally wherein the a putamen, caudate, entorhinal cortex, hippocampus, thalamus, substantia nigra, motor cortex, frontal cortex, temporal cortex, cerebral cortex, dentate nucleus, and / or Lateral Geniculate Nucleus (LGN); (vii) is enriched at least about 5, 10, 15, 20, 25, 30, or 35-fold, in the spinal cord compared to a reference sequence of SEQ ID NO: 138, e.g., when measured by an assay as described in Example 1 or 8, optionally wherein the region of the spinal cord is a thoracic spinal cord region, cervical spinal cord region, lumbar spinal cord region; (viii) shows preferential transduction in a brain region relative to the transduction in the dorsal root ganglia (DRG) and / or the liver; (xi) is capable of transducing neuronal cells and non-neuronal cells, e.g., glial cells (e.g., astrocytes); (ix) is capable of transducing at least 20%, 25%, 30%, 40%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, or 85% of cells in a brain region (e.g., a putamen, caudate, entorhinal cortex, hippocampus, thalamus, substantia nigra, motor cortex, frontal cortex, temporal cortex, cerebral cortex, cerebellar cortex, cerebellum, dentate nucleus, and / or Lateral Geniculate Nucleus (LGN)), e.g., when measured by an assay as described in Example 8; (x) is capable of transducing at least 10%, 15%, 20%, 25%, 30%, 40%, 50%, 55%, 60%, or 65% of neurons (e.g., NeuN+ neurons) in a brain region (e.g., a putamen, caudate, entorhinal cortex, hippocampus, thalamus, substantia nigra, motor cortex, frontal cortex, or temporal cortex); (xi) is capable of transducing at least 70%, 75%, 80%, 85%, 90%, or 95% of astrocytes (e.g., Sox9+ astrocytes) in a brain region (e.g., a putamen, caudate, entorhinal cortex, hippocampus, thalamus, substantia nigra, motor cortex, frontal cortex, or temporal cortex), e.g., when measured by an assay as described in Example 8; (xii) is capable of transducing at least 90% or 95% of neurons, e.g., motor neurons (e.g., ChAT+ neurons) in the spinal cord (e.g., the cervical spinal cord, the thoracic spinal cord, or the lumbar spinal cord), e.g., when measured by an assay as described in Example 8; and / or (xiii) is capable of transducing at least 90%, 95%, or 98% of astrocytes (e.g., Sox9+ astrocytes) in the spinal cord (e.g., the cervical spinal cord, the thoracic spinal cord, or the lumbar spinal cord), e.g., when measured by an assay as described in Example 8.

25. A polynucleotide encoding the AAV capsid variant of any one of claims 1-24.

26. The polynucleotide of claim 25, which comprises:(i) a nucleotide sequence comprising at least one, two, three, four, five, six, or seven, but no more than ten different nucleotides, relative to the nucleotide sequences of SEQ ID NO: 6415 or 6416; and / or (ii) the nucleotide sequence of SEQ ID NO: 6415 or 6416, or nucleotide at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% identical thereto; optionally wherein the polynucleotide comprises a nucleotide sequence that is codon optimized.

27. A peptide comprising: (a) the amino acid sequence of SEQ ID NO: 6419; (b) an amino acid sequence comprising at least 3 or 4 consecutive amino acids of SEQ ID NO: 6419; or (c) an amino acid sequence comprising no more than one or two different amino acids, relative to the amino acid sequence of SEQ ID NO: 6419.

28. An AAV particle comprising the AAV capsid variant of any one of claims 1-24, an AAV capsid variant encoded by the polynucleotide of claim 25 or 26, or an AAV capsid variant comprising the peptide of claim 27.

29. The AAV particle of claim 28, which comprises a nucleotide sequence encoding a payload, optionally wherein the encoded payload comprises a therapeutic protein or functional variant thereof; an antibody or antibody fragment; an enzyme; a component of a gene editing system; an RNAi agent (e.g., a dsRNA, siRNA, shRNA, pre-miRNA, pri-miRNA, miRNA, stRNA, lncRNA, piRNA, or snoRNA); or a combination thereof.

30. The AAV particle of claim 29, wherein: (i) the therapeutic protein or functional variant thereof, e.g., a recombinant protein, is associated with (e.g., aberrantly expressed in) a neurological or neurodegenerative disorder, a muscular or neuromuscular disorder, or a neuro-oncological disorder, optionally wherein the therapeutic protein or functional variant thereof is chosen from apolipoprotein E (APOE) (e.g., ApoE2, ApoE3 and / or ApoE4); human survival of motor neuron (SMN) 1 or SMN2; aromatic L- amino acid decarboxylase (AADC); aspartoacylase (ASPA); tripeptidyl peptidase I (CLN2); beta- galactosidase (GLB1); N-sulphoglucosamine sulphohydrolase (SGSH); N-acetyl-alpha- glucosaminidase (NAGLU); iduronate 2-sulfatase (IDS); intracellular cholesterol transporter (NPC1); gigaxonin (GAN); or a combination thereof; (ii) the antibody or antibody binding fragment binds to(a) a CNS related target, e.g. an antigen associated with a neurological or neurodegenerative disorder, e.g., β-amyloid, APOE, tau, SOD1, TDP-43, huntingtin (HTT), and / or synuclein; (b) a muscular or neuromuscular related target, e.g., an antigen associated with a muscular or neuromuscular disorder; or (c) a neuro-oncology related target, e.g., an antigen associated with a neuro- oncological disorder, e.g., HER2, or EGFR (e.g., EGFRvIII); (iii) the enzyme comprises a meganuclease, a zinc finger nuclease, a TALEN, a recombinase, integrase, a base editor, a Cas9, or a fragment thereof; (iv) the component of a gene editing system comprises one or more components of a CRISPR-Cas system, optionally wherein the one or more components of the CRISPR-Cas system comprises a Cas9, e.g., a Cas9 ortholog or a Cpf1, and a single guide RNA (sgRNA), wherein: (a) the sgRNA is located upstream (5’) of the cas9 enzyme; and / or (b) the sgRNA is located downstream (3’) of the cas9 enzyme; and / or (v) the RNAi agent (e.g., a dsRNA, siRNA, shRNA, pre-miRNA, pri-miRNA, miRNA, stRNA, lncRNA, piRNA, or snoRNA), modulates, e.g., inhibits, expression of, a CNS related gene, mRNA, and / or protein, optionally wherein the CNS related gene is chosen from SOD1, MAPT, APOE, HTT, TDP-43, APP, BACE, SNCA, ATXN1, ATXN3, ATXN7, SCN1A-SCN5A, SCN8A- SCN11A, or a combination thereof.

31. The AAV particle of any one of claims 28-30, which comprises a viral genome comprising a promoter operably linked to the nucleic acid sequence encoding the payload, optionally wherein the promoter is chosen from human elongation factor 1α-subunit (EF1α), cytomegalovirus (CMV) immediate-early enhancer and / or promoter, chicken β-actin (CBA) and its derivative 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 (mGluR2), neurofilament light (NFL) or heavy (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), a cardiovascular promoter (e.g., αMHC, cTnT, and CMV-MLC2k), a liver promoter (e.g., hAAT, TBG), a skeletal muscle promoter (e.g., desmin, MCK, C512) or a fragment, e.g., a truncation, or a functional variant thereof.

32. The AAV particle of claim 31, wherein the viral genome further comprises: (i) a polyA signal sequence;(ii) an inverted terminal repeat (ITR) sequence, optionally wherein the ITR sequence is positioned 5’ relative to the encoded payload and / or the ITR sequence is positioned 3’ relative to the encoded payload; (iii) an enhancer, a Kozak sequence, an intron region, and / or an exon region; (iv) a nucleotide sequence encoding a miR binding site, e.g., a miR binding site that modulates, e.g., reduces, expression of the antibody molecule encoded by the viral genome in a cell or tissue where the corresponding miRNA is expressed, optionally wherein the encoded miR binding site modulates, e.g., reduces, expression of the encoded antibody molecule in a cell or tissue of the DRG, liver, heart, hematopoietic lineage, or a combination thereof; and / or (v) a nucleotide sequence encoding a Rep protein, e.g., a non-structural protein, wherein the Rep protein comprises a Rep78 protein, a Rep68, Rep52 protein, and / or a Rep40 protein, optionally wherein the Rep78 protein, the Rep68 protein, the Rep52 protein, and / or the Rep40 protein are encoded by at least one Rep gene.

33. The AAV particle of claim 31 or 32, wherein the viral genome comprises: (i) at least 1-5 copies of the encoded miR binding site, e.g., at least 1, 2, 3, 4, or 5 copies; (ii) at least 3 copies of an encoded miR binding sites, optionally wherein: (a) all three copies comprise the same miR binding site, or at least one, two, three, or all of the copies comprise a different miR binding site; and / or (b) the 3 copies of the encoded miR binding sites are continuous (e.g., not separated by a spacer), or are separated by a spacer, optionally wherein the spacer comprises the nucleotide sequence of GATAGTTA, or a nucleotide sequence having 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 nucleotide sequence of GATAGTTA; or (iii) at least 4 copies of an encoded miR binding site, optionally wherein (a) all four copies comprise the same miR binding site, or at least one, two, three, or all of the copies comprise a different miR binding site; and / or (b) the 4 copies of the encoded miR binding sites are continuous (e.g., not separated by a spacer), or are separated by a spacer, optionally wherein the spacer comprises the nucleotide sequence of GATAGTTA, or a nucleotide sequence having 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 nucleotide sequence of GATAGTTA.

34. The AAV particle of claim 32 or 33, wherein 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, optionally wherein: (i) the encoded miR122 binding site comprises the nucleotide sequence of SEQ ID NO: 4673, or a nucleotide sequence at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% identical thereto; or a nucleotide sequence having at least one, two, three, four, five, six, or seven modifications, e.g., substitutions, but no more than ten modifications, e.g., 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 at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% identical thereto; or a nucleotide sequence having at least one, two, three, four, five, six, or seven modifications, e.g., substitutions, but no more than ten modifications, e.g., 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 at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% identical thereto; or a nucleotide sequence having at least one, two, three, four, five, six, or seven modifications, e.g., substitutions, but no more than ten modifications, e.g., substitutions, relative to SEQ ID NO: 4679; and / or (iv) the encoded miR-142-3p binding site comprises the nucleotide sequence of SEQ ID NO: 4675, or a nucleotide sequence at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% identical thereto; or a nucleotide sequence having at least one, two, three, four, five, six, or seven modifications, e.g., substitutions, but no more than ten modifications, e.g., substitutions, relative to SEQ ID NO: 4675.

35. The AAV particle of any one of claims 32-34, wherein the viral genome: (i) is single stranded; (ii) is self-complementary; and / or (ii) further comprises a nucleic acid encoding the AAV capsid variant of any one of claims 1- 24.

36. The AAV capsid variant, polynucleotide, peptide, or AAV particle of any one of the preceding claims which is isolated, e.g., recombinant.

37. A vector comprising a polynucleotide encoding the AAV capsid variant of any one of claims 1-24 or 36, the polynucleotide of any one of claims 25, 26, or 36, or a polynucleotide encoding the peptide of claim 27 or 36.

38. A cell, e.g., a host cell, comprising the AAV capsid variant of any one of claims 1-24 or 36, the polynucleotide of any one of claims 25, 26, or 36, the peptide of claim 49 or 60, the AAV particle of any one of claims 28-36, or the vector of claim 37, optionally wherein: (i) the cell is a mammalian cell or an insect cell; (ii) the cell is a cell of a brain region or a spinal cord region, optionally a cell of the a putamen, caudate, entorhinal cortex, hippocampus, thalamus, substantia nigra, motor cortex, frontal cortex, temporal cortex, cerebral cortex, dentate nucleus, Lateral Geniculate Nucleus (LGN), thoracic spinal cord, cervical spinal cord, and / or lumbar spinal cord; and / or (iii) the cell is a neuron or an astrocyte.

39. A method of making an AAV particle, comprising (i) providing a host cell comprising a viral genome; and (ii) incubating the host cell under conditions suitable to enclose the viral genome in the AAV capsid variant of any one of claims 1-24 or 36, or an AAV capsid variant encoded by the polynucleotide of any one of claims 25, 26, or 36; thereby making the AAV particle.

40. A pharmaceutical composition comprising the AAV particle of any one of claims 28-36, an AAV particle comprising the AAV capsid variant of any one of claims 1-24 or 36, an AAV particle comprising the peptide of claim 27 or 36, and a pharmaceutically acceptable excipient.

41. A method of delivering a payload to a cell or tissue (e.g., a CNS cell or a CNS tissue), comprising administering an effective amount of the pharmaceutical composition of claim 40, the AAV particle of any one of claims 28-36, an AAV particle comprising the AAV capsid variant of any one of claims 1-24 or 36, or an AAV particle comprising the peptide of claim 27 or 36.

42. The method of claim 41, wherein the cell is: (i) a cell of a brain region or a spinal cord region, optionally a cell of the a cell of the a putamen, caudate, entorhinal cortex, hippocampus, thalamus, substantia nigra, motor cortex, frontal cortex, temporal cortex, cerebral cortex, dentate nucleus, Lateral Geniculate Nucleus (LGN), thoracic spinal cord, cervical spinal cord, and / or lumbar spinal cord; (ii) a neuron, a motor neuron, or an astrocyte; and / or (iii) within a subject, optionally wherein the subject has, has been diagnosed with having, or is at risk of having a neurological disorder, e.g., a neurodegenerative disorder, a neuro-oncological disorder, a muscular disorder, or a neuromuscular disorder.

43. A method of treating a subject having or diagnosed with having a neurological disorder, e.g., a neurodegenerative disorder, a neuro-oncological disorder, a muscular disorder, or a neuromuscular disorder, comprising administering to the subject an effective amount of the pharmaceutical composition of claim 40, the AAV particle of any one of claims 28-36, an AAV particle comprising the AAV capsid variant of any one of claims 1-24 or 36, or an AAV particle comprising the peptide of claim 27 or 36.

44. The method of claim 42 or 43, wherein the neurological disorder, neurodegenerative disorder, muscular disorder, neuromuscular disorder, 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, a leukodystrophy (e.g., Alexander disease, autosomal dominant leukodystrophy with autonomic diseases (ADLD), Canavan disease, cerebrotendinous xanthomatosis (CTX), metachromatic leukodystrophy (MLD), Pelizaeus- Merzbacher disease, or Refsum disease), or a cancer (e.g., a HER2 / neu positive cancer or a glioblastoma).

45. The method of claim 43 or 44, where treating comprises prevention of progression of the disease or disorder in the subject, optionally wherein the subject is a human.

46. The method of any one of claims 41-45, wherein the AAV particle or pharmaceutical composition is administered to the subject: (i) intravenously, via intra-cisterna magna injection (ICM), intracerebrally, intrathecally, intracerebroventricularly, via intraparenchymal administration, or intramuscularly; (ii) via focused ultrasound (FUS), e.g., coupled with the intravenous administration of microbubbles (FUS-MB), or MRI-guided FUS coupled with intravenous administration; or (iii) intravenously.

47. The pharmaceutical composition of claim 40, the AAV particle of any one of claims 28-36, an AAV particle comprising the AAV capsid variant of any one of claims 1-24 or 36, or an AAV particle comprising the peptide of claim 27 or 36, for use in a method of delivering a payload to a cell or tissue.

48. The pharmaceutical composition of claim 40, the AAV particle of any one of claims 28-36, an AAV particle comprising the AAV capsid variant of any one of claims 1-24 or 36, or an AAV particle comprising the peptide of claim 27 or 36, for use in a method of treating a neurological disorder, a neurodegenerative disorder, a muscular disorder, a neuromuscular disorder, or a neuro-oncological disorder.

49. The pharmaceutical composition of claim 40, the AAV particle of any one of claims 28-36, an AAV particle comprising the AAV capsid variant of any one of claims 1-24 or 36, or an AAV particle comprising the peptide of claim 27 or 36, for use in the manufacture of a medicament.

50. Use of the pharmaceutical composition of claim 40, the AAV particle of any one of claims 28-36, an AAV particle comprising the AAV capsid variant of any one of claims 1-24 or 36, or an AAV particle comprising the peptide of claim 27 or 36, in the manufacture of a medicament for treating a neurological disorder, a neurodegenerative disorder, a muscular disorder, a neuromuscular disorder, or a neuro-oncological disorder.

51. Use of the pharmaceutical composition of claim 40, the AAV particle of any one of claims 28-36, an AAV particle comprising the AAV capsid variant of any one of claims 1-24 or 36, or an AAV particle comprising the peptide of claim 27 or 36, in the manufacture of a medicament.

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