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

Attorney Docket Number: V2071-3033PCT AAV CAPSID VARIANTS AND USES THEREOF RELATED APPLICATIONS

[0001] The application claims priority to U.S. Provisional Application No.63 / 533,054 filed on August 16, 2023; the entire contents 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 V2071-3033PCT_SL.xml, was created on July 10, 2024 and is 2,350,889 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 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 had 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 1 319351975.1Attorney Docket Number: V2071-3033PCT variant (e.g., an AAV5 capsid variant). In some embodiments, the AAV capsid variant has an enhanced tropism for a tissue or a cell, e.g., a CNS tissue, a CNS cell, a heart cell, a heart tissue, a muscle cell, a muscle tissue, a liver cell, or a liver tissue. 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, e.g., an AAV5 capsid variant, which comprises an amino acid other than T at position 577 (e.g., Y, N, G, or C), numbered relative to SEQ ID NO: 138. In some embodiments, the AAV capsid variant comprises a Y at position 577, numbered relative to SEQ ID NO: 138. In some embodiments, the AAV capsid variant comprises an N at position 577, numbered relative to SEQ ID NO: 138. In some embodiments, the AAV capsid variant comprises a C at position 577, numbered relative to SEQ ID NO: 138. In some embodiments, the AAV capsid variant comprises a G at position 577, numbered relative to SEQ ID NO: 138.

[0009] In another aspect, the present disclosure provides an AAV capsid variant, e.g., a variant of the wild-type AAV5 capsid, which comprises more than one amino acid that replaces the threonine (T) at position 577, numbered relative to SEQ ID NO: 138. In some embodiments, an insert of two, three, four, five, six, seven, eight, nine, or ten amino acids replaces the T at position 577, numbered relative to SEQ ID NO: 138. In some embodiments an insert of eight amino acids replaces the T at position 577, numbered relative to SEQ ID NO: 138.

[0010] In another aspect, the present disclosure provides an AAV capsid variant (e.g., an AAV5 capsid variant) comprising: (A) the formula [N2]-[N3], wherein: (i) [N2] comprises positions X1, X2, X3, X4, and X5, wherein: (a) position X1 is Y, N, C, G, or T; (b) position X2 is P, E, K, T, R, or Q; (c) position X3 is A, K, or P; (d) position X4 is E, S, D, T, G, or A; and (e) position X5 is V, L, I, R, or E; and (ii) the amino acid sequence of [N3] comprises the amino acid sequence of VQK, VQN, EQK, VKK, VHK, VQQ, IQK, or LQK; 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 (i) and / or (ii); optionally wherein [N2]-[N3] is present immediately subsequent to position 576, numbered relative to SEQ ID NO: 138 and replaces position 577, numbered relative to SEQ ID NO: 138; and (B) optionally one, two, three, or all of (1) the amino acid S, L, or G at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; (2) the amino acid F, M, or V at position 589 numbered according to SEQ ID NO: 982 or at position 582 numbered according to SEQ ID NO: 138; (3) the amino acid S at position 591 number according to SEQ ID NO: 982 or at position 584, numbered according to SEQ ID NO: 138; (4) the amino acid K at position 595 number according to SEQ ID NO: 982 or at position 588, numbered according to SEQ ID NO: 138. In some embodiments, [N2] comprises Y at position X1. In some embodiments, [N2] 2 319351975.1Attorney Docket Number: V2071-3033PCT comprises P at position X2. In some embodiments, [N2] comprises A at position X3. In some embodiments, [N2] comprises E at position X4. In some embodiments, [N2] comprises V at position X5. In some embodiments, the amino acid sequence of [N3] is VQK. In some embodiments, X1 of [N2] is present at position 577, X2 of [N2] is present at position 578, X3 of [N2] is present at position 579, X4 of [N2] is present at position 580, and of X5 of [N2] is present at position 581, numbered according to SEQ ID NO: 982. In some embodiments, [N2] is present at positions 577-581, numbered according to SEQ ID NO: 982. In some embodiments, [N3] is present at positions 582-584, numbered according to SEQ ID NO: 982. In some embodiments, [N2]-[N3] is present at positions 577-584, numbered according to SEQ ID NO: 982.

[0011] In some embodiments, the amino acid sequence of [N2] consists of YPAEV (SEQ ID NO: 1). In some embodiments, the amino acid sequence of [N3] consists of VQK. In some embodiments, [N2]-[N3] replaces the threonine (T) at position 577 of wild-type AAV5, e.g., SEQ ID NO: 138. In some embodiments, [N2]-[N3] replaces the threonine (T) at position 577 of wild-type AAV5, e.g., SEQ ID NO: 138, and the amino acid sequence of [N2] consists of YPAEV (SEQ ID NO: 1), and the amino acid sequence of [N3] consists of VQK. In some embodiments, [N2] is present at positions 577-581, numbered according to SEQ ID NO: 982. In some embodiments, [N3] is present at positions 582-584, numbered according to SEQ ID NO: 982. In some embodiments, [N2]-[N3] is present at positions 577-584, numbered according to SEQ ID NO: 982.

[0012] In another aspect, the present disclosure provides an AAV capsid variant (e.g., an AAV5 capsid variant) comprising: (A) one, two, three, or all of: (i) an [N0], wherein the amino acid sequence of [N0] comprises TNN, TNT, INN, TNS, NNN, or TNK; (ii) an [N1], wherein the amino acid sequence of [N1] comprises QSS, QSK, TSL, SSS, QSR, AGA, IGS, QAS, ASS, LGS, QST, HSS, LSS, VSS, or QRS; (iii) an [N2], wherein the amino acid sequence of [N2] comprises YPAEV (SEQ ID NO: 1), YPPSL (SEQ ID NO: 2), NKAEV (SEQ ID NO: 3), YTAEV (SEQ ID NO: 4), YPAEE (SEQ ID NO: 5), YQAEV (SEQ ID NO: 6), YTPSL (SEQ ID NO: 7), YPAAV (SEQ ID NO: 8), NPAEV (SEQ ID NO: 9), CPAEV (SEQ ID NO: 10), GPAEV (SEQ ID NO: 4722), YPKEV (SEQ ID NO: 4723), GRAEV (SEQ ID NO: 4724), YPASL (SEQ ID NO: 4725), YPATI (SEQ ID NO: 4726), YPAER (SEQ ID NO: 4727), YPASV (SEQ ID NO: 4728), YPAGV (SEQ ID NO: 4729), or YQAEE (SEQ ID NO: 11); (iv) an [N3], wherein the amino acid sequence of [N3] comprises VQK, EQK, VKK, VHK, VQQ, IQK, or LQK; and / or (v) an [N4], wherein the amino acid sequence of [N4] comprises TA, PA, RG, or NA; 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 (i)-(v); optionally wherein [N0] is present immediately subsequent to position 570, numbered relative to SEQ ID NO: 138; and (B) optionally one, two, three, or all of (1) the amino acid S, L, or G at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; (2) the amino acid F, M, or V at position 589 numbered according to SEQ ID NO: 982 or at position 582 numbered according to SEQ ID NO: 138; (3) the amino acid S at position 591 number according 3 319351975.1Attorney Docket Number: V2071-3033PCT to SEQ ID NO: 982 or at position 584, numbered according to SEQ ID NO: 138; and / or (4) the amino acid K at position 595 number according to SEQ ID NO: 982 or at position 588, numbered according to SEQ ID NO: 138. In some embodiments, the amino acid sequence of [N0] is TNN. In some embodiments, the amino acid sequence of [N1] is QSS. In some embodiments, the amino acid sequence of [N2] is YPAEV (SEQ ID NO: 1). In some embodiments, the amino acid sequence of [N3] is VQK. In some embodiments, the amino acid sequence of [N4] is TA. In some embodiments, the amino acid sequence of [N0] is TNN, the amino acid sequence of [N1] is QSS, the amino acid sequence of [N2] is YPAEV (SEQ ID NO: 1), the amino acid sequence of [N3] is VQK, and / or the amino acid sequence of [N4] is TA. In some embodiments, the amino acid sequence of [N0] is TNN, the amino acid sequence of [N1] is QSS, the amino acid sequence of [N2] is YPAEV (SEQ ID NO: 1), the amino acid sequence of [N3] is VQK, and the amino acid sequence of [N4] is TA. In any of these embodiments, [N0] is present immediately subsequent to position 570, numbered relative to SEQ ID NO: 138. In any of these embodiments, [N0] replaces positions 571-573 (e.g., T571, N572, and N573), numbered relative to SEQ ID NO: 138. In any of these embodiments, [N0] is present immediately subsequent to position 570, and [N0] positions 571-573 (e.g., T571, N572, and N573), numbered relative to SEQ ID NO: 138. In any of these embodiments, [N1] is present immediately subsequent to position 573, numbered relative to SEQ ID NO: 138. In any of these embodiments, [N1] replaces positions 574-576 (e.g., Q574, S575, and S576), numbered relative to SEQ ID NO: 138. In any of these embodiments, [N1] is present immediately subsequent to position 573, and [N1] replaces positions 574-576 (e.g., Q574, S575, and S576), numbered relative to SEQ ID NO: 138. In any of these embodiments, [N2] is present immediately subsequent to position 576, numbered relative to SEQ ID NO: 138. In any of these embodiments, [N2] replaces position 577 (e.g., T577), numbered relative to SEQ ID NO: 138. In any of these embodiments, [N2] is present immediately subsequent to position 576, and [N2] replaces position 577 (e.g., T577), numbered relative to SEQ ID NO: 138. In any of these embodiments, [N2]-[N3] is present immediately subsequent to position 576, numbered relative to SEQ ID NO: 138. In any of these embodiments, [N2]-[N3] replaces position 577 (e.g., T577), numbered relative to SEQ ID NO: 138. In any of these embodiments, [N2]-[N3] is present immediately subsequent to position 576, and [N2]-[N3] replaces position 577 (e.g., T577), numbered relative to SEQ ID NO: 138. In any of these embodiments, [N2]-[N3]-[N4] replaces positions 577- 579 (e.g., T577, T578, and A579), numbered relative to SEQ ID NO: 138. In any of these embodiments, [N2]-[N3]-[N4] is present immediately subsequent to position 576, and [N2]-[N3]-[N4] replaces positions 577-579 (e.g., T577, T578, and A579), numbered relative to SEQ ID NO: 138. In any of these embodiments, [N0]-[N1]-[N2]-[N3]-[N4] is present immediately subsequent to position 570, numbered relative to SEQ ID NO: 138. In some embodiments, [N0]-[N1]-[N2]-[N3]-[N4] replaces positions 571-579 (e.g., T571, N572, N573, Q574, S575, S576, T577, T578, and A579), numbered relative to SEQ ID NO: 138. In some embodiments, [N0]-[N1]-[N2]-[N3]-[N4] is present immediately subsequent to position 570, and [N0]-[N1]-[N2]-[N3]-[N4] replaces positions 571-579 4 319351975.1Attorney Docket Number: V2071-3033PCT (e.g., T571, N572, N573, Q574, S575, S576, T577, T578, and A579), numbered relative to SEQ ID NO: 138. For example, in some embodiments, [N0]-[N1]-[N2]-[N3]-[N4] is TNNQSSYPAEVVQKTA (SEQ ID NO: 1533) and is present immediately subsequent to position 570, numbered relative to SEQ ID NO: 138, wherein [N2]-[N3] (YPAEVVQK (SEQ ID NO: 943)) replaces position 577 (e.g., replaces T577), numbered relative to SEQ ID NO: 138. In some embodiments, [N0] is present at positions 571-573, numbered according to SEQ ID NO: 982. In some embodiments, [N1] is present at positions 574-576, numbered according to SEQ ID NO: 982. In some embodiments, [N2] is present at positions 577-581, numbered according to SEQ ID NO: 982. In some embodiments, [N3] is present at positions 582-584, numbered according to SEQ ID NO: 982. In some embodiments, [N4] is present at positions 585-586, numbered according to SEQ ID NO: 982. In some embodiments, [N2]-[N3] is present at positions 577-584, numbered according to SEQ ID NO: 982. In some embodiments, [N0]-[N1]-[N2]-[N3]-[N4] is present at positions 571-586, numbered according to SEQ ID NO: 982.

[0013] In yet another aspect, the present disclosure provides an AAV capsid variant (e.g., an AAV5 capsid variant) comprising: (A) the formula [B]-[C] (SEQ ID NO: 757), wherein: (i) [B] comprises positions X1, X2, and X3, wherein: (a) position X1 is Q, T, S, A, I, L, or H; (b) position X2 is S, G, or A; and (c) position X3 is S, K, L, R, or A; and (ii) [C] comprises the amino acid sequence of YPAEVVQK (SEQ ID NO: 943); 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 (i) and / or (ii); and further optionally wherein [B] is present immediately subsequent to position 573, numbered relative to SEQ ID NO: 138; and (B) optionally one or both of (1) the amino acid S or G at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; and / or (2) the amino acid S at position 591 number according to SEQ ID NO: 982 or at position 584, numbered according to SEQ ID NO: 138. In some embodiments, [B] comprises Q at position X1. In some embodiments, [B] comprises S at position X2. In some embodiments, [B] comprises S at position X3. In some embodiments, the amino acid sequence of [B] is QSS. In some embodiments, [B] is present immediately subsequent to position 573, relative to a reference sequence numbered according to SEQ ID NO: 138. In some embodiments, [B] replaces positions 574-576 (e.g., Q574, S575, and S576), relative to a reference sequence numbered according to SEQ ID NO: 138. In some embodiments, [B] is present immediately subsequent to position 573, and [B] replaces positions 574-576 (e.g., Q574, S575, and S576), relative to a reference sequence numbered according to SEQ ID NO: 138. In some embodiments, [C] is present immediately subsequent to position 576, relative to a reference sequence numbered according to SEQ ID NO: 138. In some embodiments, [C] replaces position 577 (e.g., T577), relative to a reference sequence numbered according to SEQ ID NO: 138. In some embodiments, [C] is present immediately subsequent to position 576, and [C] replaces position 577 (e.g., T577), relative to a reference sequence numbered according to SEQ ID NO: 138. In some embodiments, [B]-[C] is present immediately subsequent to position 573, relative 5 319351975.1Attorney Docket Number: V2071-3033PCT to a reference sequence numbered according to SEQ ID NO: 138. In some embodiments, [B]-[C] replaces positions 574-577 (e.g., Q574, S575, S576, and T577), relative to a reference sequence numbered according to SEQ ID NO: 138. In some embodiments, [B]-[C] is present immediately subsequent to position 573, and [B]-[C] replaces positions 574-577 (e.g., Q574, S575, S576, and T577), relative to a reference sequence numbered according to SEQ ID NO: 138. In some embodiments, X1 of [B] is present at position 574, X2 of [B] is present at position 575, and X3 of [B] is present at position 576, numbered according to SEQ ID NO: 982. In some embodiments, [B] is present at positions 574-576, numbered according to SEQ ID NO: 982. In some embodiments, [C] is present at positions 577-584, numbered according to SEQ ID NO: 982. In some embodiments, [B]- [C] is present at positions 574-584, numbered according to SEQ ID NO: 982.

[0014] In another aspect, the present disclosure provides an AAV capsid variant (e.g., an AAV5 capsid variant) comprising: (A) one, two, three, or all of (i) an [A], wherein the amino acid sequence of [A] comprises TNN, TNT, INN, NNN, TNS, or TNK; (ii) a [B], wherein the amino acid sequence of [B] comprises QSS, TSL, SSS, QSR, QSK, AGA, IGS, QAS, ASS, LGS, or HSS; (iii) a [C], wherein [C] comprises the amino acid sequence of YPAEVVQK (SEQ ID NO: 943); and (iv) a [D], wherein [D] comprises the amino acid sequence of TA or PA; 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 (i)-(v); optionally wherein [A] is present immediately subsequent to position 570, numbered relative to SEQ ID NO: 138 and [C] replaces position 577, numbered relative to SEQ ID NO: 138; and (B) optionally one or both of: (1) the amino acid S, L, or G at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; and / or (2) the amino acid S at position 591 number according to SEQ ID NO: 982 or at position 584, numbered according to SEQ ID NO: 138. In some embodiments, the amino acid sequence of [A] is TNN. In some embodiments, the amino acid sequence of [B] is QSS. In some embodiments, the amino acid sequence of [A] is TNN and the amino acid sequence of [B] is QSS. In some embodiments, the amino acid sequence of [A] is TNN, the amino acid sequence of [B] is QSS, and the amino acid sequence of [C] is YPAEVVQK (SEQ ID NO: 943). In some embodiments, the amino acid sequence of [A] is TNN, the amino acid sequence of [B] is QSS, the amino acid sequence of [C] is YPAEVVQK (SEQ ID NO: 943), and the amino acid sequence of [D] is TA. In any of these embodiments, [A] is present immediately subsequent to position 570, numbered relative to SEQ ID NO: 138. In any of these embodiments, [A] replaces positions 571-573 (e.g., T571, N572, and N573) numbered relative to SEQ ID NO: 138. In any of these embodiments, [A] is present immediately subsequent to position 570, and [A] replaces positions 571-573 (e.g., T571, N572, and N573) numbered relative to SEQ ID NO: 138. In any of these embodiments, [B] is present immediately subsequent to position 573, relative to a reference sequence numbered according to SEQ ID NO: 138. In any of these embodiments, [B] replaces positions 574-576 (e.g., Q574, S575, and S576), numbered relative to SEQ ID NO: 138. In any of these embodiments, [B] is present immediately subsequent to position 573, and [B] replaces 6 319351975.1Attorney Docket Number: V2071-3033PCT positions 574-576 (e.g., Q574, S575, and S576), numbered relative to SEQ ID NO: 138. In any of these embodiments, [C] is present immediately subsequent to position 576, numbered relative to SEQ ID NO: 138. In any of these embodiments, [C] replaces position 577 (e.g., T577), numbered relative to SEQ ID NO: 138. In any of these embodiments, [C] is present immediately subsequent to position 576, and [C] replaces position 577 (e.g., T577), numbered relative to SEQ ID NO: 138. In any of these embodiments, [B]-[C] is present immediately subsequent to position 573, numbered relative to SEQ ID NO: 138. In any of these embodiments, [B]-[C] replaces positions 574-577 (e.g., Q574, S575, S576, and T577), numbered relative to SEQ ID NO: 138. In any of these embodiments, [B]-[C] is present immediately subsequent to position 573, and [B]-[C] replaces positions 574-577 (e.g., Q574, S575, S576, and T577), numbered relative to SEQ ID NO: 138. In any of these embodiments, [C]-[D] is present immediately subsequent to position 576, numbered relative to SEQ ID NO: 138. In any of these embodiments, [C]-[D] replaces positions 577-579 (e.g., T577, T578, and A579), numbered relative to SEQ ID NO: 138. In any of these embodiments, [A]-[B]-[C]-[D] is present immediately subsequent to position 570, numbered relative to SEQ ID NO: 138. In any of these embodiments, [A]-[B]-[C]-[D] replaces positions 571-579 (e.g., T571, N572, N573, Q574, S575, S576, T577, T578, and A579), numbered relative to SEQ ID NO: 138. In any of these embodiments, [A]-[B]-[C]-[D] is present immediately subsequent to position 570, and [A]-[B]-[C]-[D] replaces positions 571-579 (e.g., T571, N572, N573, Q574, S575, S576, T577, T578, and A579), numbered relative to SEQ ID NO: 138. For example, in some embodiments, [A]-[B]-[C]-[D] is TNNQSSYPAEVVQKTA (SEQ ID NO: 1533) and is present immediately subsequent to position 570, numbered relative to SEQ ID NO: 138, wherein [C] (YPAEVVQK (SEQ ID NO: 943)) replaces position 577 (e.g., replaces T577) numbered relative to SEQ ID NO: 138. In some embodiments, [A] is present at positions 571-573, numbered according to SEQ ID NO: 982. In some embodiments, [B] is present at positions 574-576, numbered according to SEQ ID NO: 982. In some embodiments, [C] is present at positions 577-584, numbered according to SEQ ID NO: 982. In some embodiments, [D] is present at positions 585-586, numbered according to SEQ ID NO: 982. In some embodiments, [A]- [B]-[C]-[D] is present at positions 571-586, numbered according to SEQ ID NO: 982.

[0015] In yet another aspect, the present disclosure provides an AAV capsid variant (e.g., an AAV5 capsid variant) comprising: (A) the formula [N2]-[N3], wherein: (i) [N2] comprises positions X1, X2, X3, X4, and X5, wherein: (a) position X1 is Y or T; (b) position X2 is Q, T, P, or E; (c) position X3 is A; (d) position X4 is E or D; and (e) position X5 is V or E; and (ii) [N3] comprises the amino acid sequence of VQK or VQN; 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 (i) and / or (ii); and further optionally wherein [N2]-[N3] is present immediately subsequent to position 576, numbered relative to SEQ ID NO: 138 and replaces position 577, numbered relative to SEQ ID NO: 138; and (B) optionally one, two, or all of: (1) the amino acid S, L, or G at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; 7 319351975.1Attorney Docket Number: V2071-3033PCT (2) the amino acid F, M, or V at position 589 numbered according to SEQ ID NO: 982 or at position 582 numbered according to SEQ ID NO: 138; and / or (3) the amino acid K at position 595 number according to SEQ ID NO: 982 or at position 588, numbered according to SEQ ID NO: 138. In some embodiments, the amino acid sequence of [N2] consists of YPAEV (SEQ ID NO: 1). In some embodiments, the amino acid sequence of [N3] consists of VQK. In some embodiments, [N2]-[N3] replaces position 577 (e.g., T577) of wild-type AAV5, e.g., SEQ ID NO: 138. In some embodiments, [N2]-[N3] replaces the threonine (T) at position 577 of wild-type AAV5, e.g., SEQ ID NO: 138, and the amino acid sequence of [N2] consists of YPAEV (SEQ ID NO: 1), and the amino acid sequence of [N3] consists of VQK. In some embodiments, X1 of [N2] is present at position 577, X2 of [N2] is present at position 578, X3 of [N2] is present at position 579, X4 of [N2] is present at position 580, and of X5 of [N2] is present at position 581, numbered according to SEQ ID NO: 982. In some embodiments, [N2] is present at positions 577-581, numbered according to SEQ ID NO: 982. In some embodiments, [N3] is present at positions 582-584, numbered according to SEQ ID NO: 982. In some embodiments, [N2]-[N3] is present at positions 577-584, numbered according to SEQ ID NO: 982.

[0016] In another aspect, the present disclosure provides an AAV capsid variant (e.g., an AAV5 capsid variant) comprising: (A) one, two, three, four, or all of: (i) an [N0], wherein [N0] comprises the amino acid sequence of TNN, TNS, TNT, TNR, VNN, or TNK; (ii) an [N1], wherein [N1] comprises the amino acid of QSS, SLS, SLY, SAT, ASS, or QTS; (iii) an [N2] wherein [N2] comprises the amino acid sequence of YPAEV (SEQ ID NO: 1), YQAEV (SEQ ID NO: 6), YTAEV (SEQ ID NO: 4), YPAEE (SEQ ID NO: 5), TEAEV (SEQ ID NO: 12), or YPADV (SEQ ID NO: 13); (iv) an [N3] wherein [N3] comprises the amino acid sequence of VQK or VQN; and / or (v) an [N4] wherein [N4] comprises the amino acid sequence of TA, PA, TD, NA, or PA; and optionally wherein: (a) the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of the aforesaid amino acids in (i)-(v); and further optionally wherein [N0] is present immediately subsequent to position 570, numbered relative to SEQ ID NO: 138 and [N2]-[N3] replaces position 577, numbered relative to SEQ ID NO: 138; and (B) optionally one, two, or all of: (1) the amino acid S, L, or G at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; (2) the amino acid F, M, or V at position 589 numbered according to SEQ ID NO: 982 or at position 582 numbered according to SEQ ID NO: 138; and / or (3) the amino acid K at position 595 number according to SEQ ID NO: 982 or at position 588, numbered according to SEQ ID NO: 138. In any of these embodiments, [N0] is present immediately subsequent to position 570, numbered relative to SEQ ID NO: 138. In any of these embodiments, [N0] replaces positions 571-573 (e.g., T571, N572, and N573), numbered relative to SEQ ID NO: 138. In any of these embodiments, [N0] is present immediately subsequent to position 570, and [N0] replaces positions 571-573 (e.g., T571, N572, and N573), numbered relative to SEQ ID NO: 138. In any of these embodiments, [N1] is present immediately subsequent to position 573, numbered relative to SEQ ID 8 319351975.1Attorney Docket Number: V2071-3033PCT NO: 138. In any of these embodiments, [N1] replaces positions 574-576 (e.g., Q574, S575, and S576), numbered relative to SEQ ID NO: 138. In any of these embodiments, [N1] is present immediately subsequent to position 573, and [N1] replaces positions 574-576 (e.g., Q574, S575, and S576), numbered relative to SEQ ID NO: 138. In any of these embodiments, [N2] is present immediately subsequent to position 576, numbered relative to SEQ ID NO: 138. In any of these embodiments, [N2] replaces position 577 (e.g., T577), numbered relative to SEQ ID NO: 138. In any of these embodiments, [N2] is present immediately subsequent to position 576, and [N2] replaces position 577 (e.g., T577), numbered relative to SEQ ID NO: 138. In any of these embodiments, [N2]- [N3] is present immediately subsequent to position 576, numbered relative to SEQ ID NO: 138. In any of these embodiments, [N2]-[N3] replaces position 577 (e.g., T577), numbered relative to SEQ ID NO: 138. In any of these embodiments, [N2]-[N3] is present immediately subsequent to position 576, and [N2]-[N3] replaces position 577 (e.g., T577), numbered relative to SEQ ID NO: 138. In any of these embodiments, [N2]-[N3]-[N4] replaces positions 577-579 (e.g., T577, T578, and A579), numbered relative to SEQ ID NO: 138. In any of these embodiments, [N2]-[N3]-[N4] is present immediately subsequent to position 576, and [N2]-[N3]-[N4] replaces positions 577-579 (e.g., T577, T578, and A579), numbered relative to SEQ ID NO: 138. In any of these embodiments, [N0]-[N1]- [N2]-[N3]-[N4] is present immediately subsequent to position 570, numbered relative to SEQ ID NO: 138. In any of these embodiments, [N0]-[N1]-[N2]-[N3]-[N4] replaces positions 571-579 (e.g., T571, N572, N573, Q574, S575, S576, T577, T578, and A579), relative to a reference sequence numbered according to SEQ ID NO: 138. In any of these embodiments, [N0]-[N1]-[N2]-[N3]-[N4] is present immediately subsequent to position 570, and [N0]-[N1]-[N2]-[N3]-[N4] replaces positions 571-579 (e.g., T571, N572, N573, Q574, S575, S576, T577, T578, and A579), relative to a reference sequence numbered according to SEQ ID NO: 138. In some embodiments, [N0] is present at positions 571-573, numbered according to SEQ ID NO: 982. In some embodiments, [N1] is present at positions 574- 576, numbered according to SEQ ID NO: 982. In some embodiments, [N2] is present at positions 577-581, numbered according to SEQ ID NO: 982. In some embodiments, [N3] is present at positions 582-584, numbered according to SEQ ID NO: 982. In some embodiments, [N4] is present at positions 585-586, numbered according to SEQ ID NO: 982. In some embodiments, [N2]-[N3] is present at positions 577-584, numbered according to SEQ ID NO: 982. In some embodiments, [N0]- [N1]-[N2]-[N3]-[N4] is present at positions 571-586, numbered according to SEQ ID NO: 982.

[0017] In some embodiments, the amino acid sequence of [N0] is TNN, the amino acid sequence of [N1] is QSS, the amino acid sequence of [N2] is YPAEV (SEQ ID NO: 1), the amino acid sequence of [N3] is VQK, and / or the amino acid sequence of [N4] is TA. In some embodiments, the amino acid sequence of [N0] is TNN, the amino acid sequence of [N1] is QSS, the amino acid sequence of [N2] is YPAEV (SEQ ID NO: 1), the amino acid sequence of [N3] is VQK, and the amino acid sequence of [N4] is TA. In any of these embodiments, [N0]-[N1]-[N2]-[N3]-[N4] is present immediately subsequent to position 570, numbered relative to SEQ ID NO: 138. In any of 9 319351975.1Attorney Docket Number: V2071-3033PCT these embodiments, the amino acid sequence of [N2]-[N3] replaces position 577, numbered relative to SEQ ID NO: 138. For example, in some embodiments, [N0]-[N1]-[N2]-[N3]-[N4] is TNNQSSYPAEVVQKTA (SEQ ID NO: 1533) and is present immediately subsequent to position 570, numbered relative to SEQ ID NO: 138, wherein [N2]-[N3] (YPAEVVQK (SEQ ID NO: 943)) replaces position 577 (e.g., replaces T577) numbered relative to SEQ ID NO: 138. In some embodiments, [N0] is present at positions 571-573, numbered according to SEQ ID NO: 982. In some embodiments, [N1] is present at positions 574-576, numbered according to SEQ ID NO: 982. In some embodiments, [N2] is present at positions 577-581, numbered according to SEQ ID NO: 982. In some embodiments, [N3] is present at positions 582-584, numbered according to SEQ ID NO: 982. In some embodiments, [N4] is present at positions 585-586, numbered according to SEQ ID NO: 982. In some embodiments, [N2]-[N3] is present at positions 577-584, numbered according to SEQ ID NO: 982. In some embodiments, [N0]-[N1]-[N2]-[N3]-[N4] is present at positions 571-586, numbered according to SEQ ID NO: 982.

[0018] In another aspect, the present disclosure provides an AAV capsid variant (e.g., an AAV5 capsid variant) comprising: (A) [B]-[C] (SEQ ID NO: 759), wherein: (i) [B] comprises positions X1, X2, and X3, wherein (a) position X1 is Q, A, or S; (b) position X2 is S, L, or A; and (c) position X3 is S, Y, R, K or T; and (ii) [C] comprises the amino acid sequence of YPAEVVQK (SEQ ID NO: 943); 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 (i) and / or (ii); and further optionally wherein [B] is present immediately subsequent to position 573, numbered relative to SEQ ID NO: 138, and [C] replaces position 577, numbered relative to SEQ ID NO: 138; and (B) optionally one, two, three, or all of: (1) the amino acid S, L, or G at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; (2) the amino acid F, M, or V at position 589 numbered according to SEQ ID NO: 982 or at position 582 numbered according to SEQ ID NO: 138; (3) the amino acid S at position 591 number according to SEQ ID NO: 982 or at position 584, numbered according to SEQ ID NO: 138; and / or (4) the amino acid K at position 595 number according to SEQ ID NO: 982 or at position 588, numbered according to SEQ ID NO: 138. In some embodiments, [B] is QSS. In some embodiments, [C] consists of YPAEVVQK (SEQ ID NO: 943), is present immediately subsequent to position 576, numbered relative to SEQ ID NO: 138, and replaces position 577, numbered relative to SEQ ID NO: 138. In some embodiments, [B] is present immediately subsequent to position 573, relative to a reference sequence numbered according to SEQ ID NO: 138. In some embodiments, [B] replaces positions 574-576 (e.g., Q574, S575, and S576), relative to a reference sequence numbered according to SEQ ID NO: 138. In some embodiments, [B] is present immediately subsequent to position 573, and [B] replaces positions 574-576 (e.g., Q574, S575, and S576), relative to a reference sequence numbered according to SEQ ID NO: 138. In some embodiments, [C] is present immediately subsequent to position 576, relative to a reference sequence numbered according to SEQ ID NO: 138. In some embodiments, [C] replaces position 577 (e.g., 10 319351975.1Attorney Docket Number: V2071-3033PCT T577), relative to a reference sequence numbered according to SEQ ID NO: 138. In some embodiments, [C] is present immediately subsequent to position 576, and [C] replaces position 577 (e.g., T577), relative to a reference sequence numbered according to SEQ ID NO: 138. In some embodiments, [B]-[C] is present immediately subsequent to position 573, relative to a reference sequence numbered according to SEQ ID NO: 138. In some embodiments, [B]-[C] replaces positions 574-577 (e.g., Q574, S575, S576, and T577), relative to a reference sequence numbered according to SEQ ID NO: 138. In some embodiments, [B]-[C] is present immediately subsequent to position 573, and [B]-[C] replaces positions 574-577 (e.g., Q574, S575, S576, and T577), relative to a reference sequence numbered according to SEQ ID NO: 138. In some embodiments, X1 of [B] is present at position 574, X2 of [B] is present at position 575, and X3 of [B] is present at position 576, numbered according to SEQ ID NO: 982. In some embodiments, [B] is present at positions 574-576, numbered according to SEQ ID NO: 982. In some embodiments, [C] is present at positions 577-584, numbered according to SEQ ID NO: 982. In some embodiments, [B]-[C] is present at positions 574-584, numbered according to SEQ ID NO: 982.

[0019] In yet another aspect, the present disclosure provides an AAV capsid variant (e.g., an AAV5 capsid variant) comprising: (A) one, two, three, four, or all of: (i) an [A], wherein [A] comprises the amino acid sequence of TNN, TNS, TNT, TNR, VNN, or TNK; (ii) a [B], wherein [B] comprises the amino acid sequence of QSS, SLY, SAT, QSR, QSK, ASS, or SLS; (iii) a [C], wherein [C] comprises the amino acid sequence of YPAEVVQK (SEQ ID NO: 943); and (iv) a [D], wherein [D] comprises the amino acid sequence of TA, TD, NA, RG, or PA; 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 (i)-(v); and further optionally wherein [A] is present immediately subsequent to position 570, numbered relative to SEQ ID NO: 138, and [C] replaces position 577, numbered relative to SEQ ID NO: 138. In any of these embodiments, [A] is present immediately subsequent to position 570, numbered relative to SEQ ID NO: 138; and (B) optionally one, two, three, or all of: (1) the amino acid S, L, or G at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; (2) the amino acid F, M, or V at position 589 numbered according to SEQ ID NO: 982 or at position 582 numbered according to SEQ ID NO: 138; (3) the amino acid S at position 591 number according to SEQ ID NO: 982 or at position 584, numbered according to SEQ ID NO: 138; and / or (4) the amino acid K at position 595 number according to SEQ ID NO: 982 or at position 588, numbered according to SEQ ID NO: 138. In any of these embodiments, [A] replaces positions 571-573 (e.g., T571, N572, and N573) numbered relative to SEQ ID NO: 138. In any of these embodiments, [A] is present immediately subsequent to position 570, and [A] replaces positions 571-573 (e.g., T571, N572, and N573) numbered relative to SEQ ID NO: 138. In any of these embodiments, [B] is present immediately subsequent to position 573, relative to a reference sequence numbered according to SEQ ID NO: 138. In any of these embodiments, [B] replaces positions 574-576 (e.g., Q574, S575, and S576), relative to a reference sequence numbered 11 319351975.1Attorney Docket Number: V2071-3033PCT according to SEQ ID NO: 138. In any of these embodiments, [B] is present immediately subsequent to position 573, and [B] replaces positions 574-576 (e.g., Q574, S575, and S576), relative to a reference sequence numbered according to SEQ ID NO: 138. In any of these embodiments, [C] is present immediately subsequent to position 576, relative to a reference sequence numbered according to SEQ ID NO: 138. In any of these embodiments, [C] replaces position 577 (e.g., T577), relative to a reference sequence numbered according to SEQ ID NO: 138. In any of these embodiments, [C] is present immediately subsequent to position 576, and [C] replaces position 577 (e.g., T577), relative to a reference sequence numbered according to SEQ ID NO: 138. In any of these embodiments, [B]-[C] is present immediately subsequent to position 573, relative to a reference sequence numbered according to SEQ ID NO: 138. In any of these embodiments, [B]-[C] replaces positions 574-577 (e.g., Q574, S575, S576, and T577), relative to a reference sequence numbered according to SEQ ID NO: 138. In any of these embodiments, [B]-[C] is present immediately subsequent to position 573, and [B]-[C] replaces positions 574-577 (e.g., Q574, S575, S576, and T577), relative to a reference sequence numbered according to SEQ ID NO: 138. In any of these embodiments, [C]-[D] is present immediately subsequent to position 576, relative to a reference sequence numbered according to SEQ ID NO: 138. In any of these embodiments, [C]-[D] replaces positions 577-579 (e.g., T577, T578, and A579), relative to a reference sequence numbered according to SEQ ID NO: 138. In any of these embodiments, [C]-[D] is present immediately subsequent to position 576, and [C]-[D] replaces positions 577-579 (e.g., T577, T578, and A579), relative to a reference sequence numbered according to SEQ ID NO: 138. In some embodiments, [A] is present at positions 571-573, numbered according to SEQ ID NO: 982. In some embodiments, [B] is present at positions 574-576, numbered according to SEQ ID NO: 982. In some embodiments, [C] is present at positions 577-584, numbered according to SEQ ID NO: 982. In some embodiments, [D] is present at positions 585-586, numbered according to SEQ ID NO: 982. In some embodiments, [A]-[B]-[C]-[D] is present at positions 571-586, numbered according to SEQ ID NO: 982.

[0020] In yet another aspect, the present disclosure provides an AAV capsid variant comprising an amino sequence comprising the following formula: [N0]-[N1]-[N2]-[N3]-[N4], wherein [N2] comprises the amino acid sequence of GPAEV (SEQ ID NO: 4722), YPAEV (SEQ ID NO: 1), YPKEV (SEQ ID NO: 4723), GRAEV (SEQ ID NO: 4724), YPASL (SEQ ID NO: 4725), YPATI (SEQ ID NO: 4726), YPAER (SEQ ID NO: 4727), YPASV (SEQ ID NO: 4728), YPAGV (SEQ ID NO: 4729), and wherein one, two, three, or all of: (i) [N0] comprises TNR or VNN; (ii) [N1] comprises VSS; (iii) [N3] comprises IQK; and / or (iv) [N4] comprises RG. In some embodiments, [N0]-[N1]-[N2]-[N3]-[N4] is present in hypervariable loop VIII. In some embodiments, the AAV capsid variant comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 750 or 739

[0021] In yet another aspect, the present disclosure provides an AAV capsid variant (e.g., an AAV5 capsid variant) comprising: (A) [K1]-[K2], wherein: (i) [K1] comprises LSY or LYY, and (ii) 12 319351975.1Attorney Docket Number: V2071-3033PCT [K2] comprises positions X1, X2, X3, and X4, wherein (a) position X1 is Q, T, or P; (b) position X2 is A; (c) position X3 is E or D; and (d) position X4 is V or E; 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 (i) and / or (ii); and (B) optionally one, two, or all of: (1) the amino acid S, L, or G at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; (2) the amino acid F, M, or V at position 589 numbered according to SEQ ID NO: 982 or at position 582 numbered according to SEQ ID NO: 138; and / or (3) the amino acid K at position 595 number according to SEQ ID NO: 982 or at position 588, numbered according to SEQ ID NO: 138. In some embodiments, [K1]-[K2] is present immediately subsequent to position 574, relative to a reference sequence numbered according to SEQ ID NO: 138. In some embodiments, [K1]-[K2] replaces positions 575-577 (e.g., S575, S576, and T577), relative to a reference sequence numbered according to SEQ ID NO: 138. In some embodiments, [K1]-[K2] is present immediately subsequent to position 574, and [K1]-[K2] replaces positions 575-577 (e.g., S575, S576, and T577), relative to a reference sequence numbered according to SEQ ID NO: 138.

[0022] In yet another aspect, the present disclosure provides an AAV capsid variant (e.g., an AAV5 capsid variant) comprising: (A) one, two, three, four, or all of: (i) a [K0], which comprises TNNS (SEQ ID NO: 14); (ii) a [K1], which comprises LSY or LYY; (iii) a [K2], which comprises QAEV (SEQ ID NO: 15), TAEV (SEQ ID NO: 16), PAEV (SEQ ID NO: 17), PAEE (SEQ ID NO: 18), or PADV (SEQ ID NO: 19); (iv) a [K3], which comprise VQK or VQN; and (v) a [K4], which comprises TA, TD, NA, or PA; 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 (i)-(v); and (B) optionally one, two, or all of: (1) the amino acid S, L, or G at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; (2) the amino acid F, M, or V at position 589 numbered according to SEQ ID NO: 982 or at position 582 numbered according to SEQ ID NO: 138; and / or (3) the amino acid K at position 595 number according to SEQ ID NO: 982 or at position 588, numbered according to SEQ ID NO: 138. In some embodiments, [K0] is present immediately subsequent to position 570, relative to a reference sequence numbered according to SEQ ID NO: 138. In some embodiments, [K0] replaces positions 571-574 (e.g., T571, N572, N573, and Q574), relative to a reference sequence numbered according to SEQ ID NO: 138. In some embodiments, [K0] is present immediately subsequent to position 570, and [K0] replaces positions 571-574 (e.g., T571, N572, N573, and Q574), relative to a reference sequence numbered according to SEQ ID NO: 138. In some embodiments, [K1] is present immediately subsequent to position 574, relative to a reference sequence numbered according to SEQ ID NO: 138. In some embodiments, [K1] replaces positions 575-577 (e.g., S575, S576, and T577), relative to a reference sequence numbered according to SEQ ID NO: 138. In some embodiments, [K1] is present immediately subsequent to position 574, and [K1] replaces positions 575-577 (e.g., S575, S576, and T577), relative to a reference sequence numbered according to SEQ ID NO: 138. In some 13 319351975.1Attorney Docket Number: V2071-3033PCT embodiments, [K1]-[K2]-[K3] is present immediately subsequent to position 574, relative to a reference sequence numbered according to SEQ ID NO: 138. In some embodiments, [K1]-[K2]-[K3] replaces positions 575-577 (e.g., S575, S576, and T577), relative to a reference sequence numbered according to SEQ ID NO: 138. In some embodiments, [K1]-[K2]-[K3] is present immediately subsequent to position 574, and [K1]-[K2]-[K3] replaces positions 575-577 (e.g., S575, S576, and T577), relative to a reference sequence numbered according to SEQ ID NO: 138. In some embodiments, [K1]-[K2]-[K3]-[K4] is present immediately subsequent to position 574, relative to a reference sequence numbered according to SEQ ID NO: 138. In some embodiments, [K1]-[K2]- [K3]-[K4] replaces positions 575-579 (e.g., S575, S576, T577, T578, and A579), relative to a reference sequence numbered according to SEQ ID NO: 138. In some embodiments, [K1]-[K2]-[K3]- [K4] is present immediately subsequent to position 574, and [K1]-[K2]-[K3]-[K4] replaces positions 575-579 (e.g., S575, S576, T577, T578, and A579), relative to a reference sequence numbered according to SEQ ID NO: 138. In some embodiments, [K0]-[K1]-[K2]-[K3]-[K4] is present immediately subsequent to position 570, relative to a reference sequence numbered according to SEQ ID NO 138. In some embodiments, [K0]-[K1]-[K2]-[K3]-[K4] replaces positions 571-579 (e.g., T571, N572, N573, Q574, S575, S576, T577, T578, and T579), relative to a reference sequence numbered according to SEQ ID NO 138. In some embodiments, [K0]-[K1]-[K2]-[K3]-[K4] is present immediately subsequent to position 570, and [K0]-[K1]-[K2]-[K3]-[K4] replaces positions 571-579 (e.g., T571, N572, N573, Q574, S575, S576, T577, T578, and T579), relative to a reference sequence numbered according to SEQ ID NO 138.

[0023] In yet another aspect, the present disclosure provides an AAV capsid variant (e.g., an AAV5 capsid variant) comprising: (a) the amino acid sequence of any of the sequences provided in Tables 1, 2A, 2B, 9, or 15-20; (b) an amino acid sequence comprising at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 consecutive amino acids from any one of the sequences provided in Tables 1, 2A, 2B, 9, 15-20, or 26-30; (c) an amino acid sequence comprising 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 Tables 1, 2A, 2B, 9, 15-20, or 26-30; or (d) an amino sequence comprising one, two, or three but no more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to the amino acid sequence of any one of the amino acid sequences provided in Tables 1, 2A, 2B, 9, 15-20, or 26-30; optionally wherein the AAV capsid variant further comprises: (1) the amino acid S, L, or G at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; (2) the amino acid F, M, or V at position 589 numbered according to SEQ ID NO: 982 or at position 582 numbered according to SEQ ID NO: 138; (3) the amino acid S at position 591 number according to SEQ ID NO: 982 or at position 584, numbered according to SEQ ID NO: 138; and / or (4) the amino acid K at position 595 number according to SEQ ID NO: 982 or at position 588, numbered according to SEQ ID NO: 138. 14 319351975.1Attorney Docket Number: V2071-3033PCT

[0024] In yet another aspect, the present disclosure provides an AAV capsid variant (e.g., an AAV5 capsid variant) comprising: (a) the amino acid sequence of any of SEQ ID NOs: 943, 1021, 1024, 1027, 1112, 1142, 1214, 1232, 1254, 1300, 1310, 1327, 1331, 1342, 1419, 1453, 1533, 1538, 1539, 1575, 1578, 1583- 1587, 1590, 1591-1593, 1598-1608, or 1610-1624; (b) an amino acid sequence comprising at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 consecutive amino acids from any one of SEQ ID NOs: 943, 1021, 1024, 1027, 1112, 1142, 1214, 1232, 1254, 1300, 1310, 1327, 1331, 1342, 1419, 1453, 1533, 1538, 1539, 1575, 1578, 1583- 1587, 1590, 1591-1593, 1598-1608, 1610-1624, or 4681-4686, 4694, 4696, 4698, 4700-4705; (c) an amino acid sequence comprising 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: 943, 1021, 1024, 1027, 1112, 1142, 1214, 1232, 1254, 1300, 1310, 1327, 1331, 1342, 1419, 1453, 1533, 1538, 1539, 1575, 1578, 1583- 1587, 1590, 1591-1593, 1598-1608, 1610- 1624, or 4681-4686, 4694, 4696, 4698, 4700-4705; or (d) an amino sequence comprising one, two, or three but no more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to the amino acid sequence of any one of SEQ ID NOs: 943, 1021, 1024, 1027, 1112, 1142, 1214, 1232, 1254, 1300, 1310, 1327, 1331, 1342, 1419, 1453, 1533, 1538, 1539, 1575, 1578, 1583- 1587, 1590, 1591-1593, 1598-1608, 1610-1624, or 4681-4686, 4694, 4696, 4698, 4700-4705; optionally wherein the AAV capsid variant further comprises: (1) the amino acid S or G at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; and / or (2) the amino acid S at position 591 number according to SEQ ID NO: 982 or at position 584, numbered according to SEQ ID NO: 138.

[0025] In another aspect, the present disclosure provides an AAV capsid variant (e.g., an AAV5 capsid variant) comprising (a) the amino acid sequence of any of SEQ ID NOs: 943 or 2064-2080; (b) an amino acid sequence comprising at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 consecutive amino acids from any one of SEQ ID NOs: 943 or 2064-2080; (c) an amino acid sequence comprising 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: 943 or 2064-2080; or (d) an amino sequence comprising one, two, or three but no more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to the amino acid sequence of any one of SEQ ID NOs: 943 or 2064-2080; optionally wherein the AAV capsid variant further comprises: (1) the amino acid S, L, or G at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; (2) the amino acid F, M, or V at position 589 numbered according to SEQ ID NO: 982 or at position 582 numbered according to SEQ ID NO: 138; (3) the amino acid S at position 591 number according to SEQ ID NO: 982 or at position 584, numbered according to SEQ ID NO: 138; and / or (4) the amino acid K at position 595 number according to SEQ ID NO: 982 or at position 588, numbered according to SEQ ID NO: 138. 15 319351975.1Attorney Docket Number: V2071-3033PCT

[0026] In yet another aspect, present disclosure provides an AAV capsid variant (e.g., an AAV5 capsid variant) comprising the amino acid sequence of SEQ ID NO: 943; optionally wherein the AAV capsid variant further comprises: (1) the amino acid S, L, or G at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; (2) the amino acid F, M, or V at position 589 numbered according to SEQ ID NO: 982 or at position 582 numbered according to SEQ ID NO: 138; (3) the amino acid S at position 591 number according to SEQ ID NO: 982 or at position 584, numbered according to SEQ ID NO: 138; and / or (4) the amino acid K at position 595 number according to SEQ ID NO: 982 or at position 588, numbered according to SEQ ID NO: 138. In some embodiments, the amino acid sequence of SEQ ID NO: 943 is present immediately subsequent to position 576, relative to a reference sequence numbered according to SEQ ID NO: 138 or 982. In some embodiments, the amino acid sequence of SEQ ID NO: 943 replaces position 577 (e.g., replaces T577), relative to a reference sequence numbered according to SEQ ID NO: 138. In some embodiments, the amino acid sequence of SEQ ID NO: 943 is present immediately subsequent to position 576, wherein the amino acid sequence of SEQ ID NO: 943 replaces position 577 (e.g., replaces T577), relative to a reference sequence numbered according to SEQ ID NO: 138.

[0027] In yet another aspect, the present disclosure provides an AAV capsid variant (e.g., an AAV5 capsid variant) comprising YPAEVVQK (SEQ ID NO: 943), which is present immediately subsequent to position 576, numbered relative to SEQ ID NO: 138 or 982; optionally wherein the AAV capsid variant further comprises: (1) the amino acid S, L, or G at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; (2) the amino acid F, M, or V at position 589 numbered according to SEQ ID NO: 982 or at position 582 numbered according to SEQ ID NO: 138; (3) the amino acid S at position 591 number according to SEQ ID NO: 982 or at position 584, numbered according to SEQ ID NO: 138; and / or (4) the amino acid K at position 595 number according to SEQ ID NO: 982 or at position 588, numbered according to SEQ ID NO: 138. In some embodiments, the amino acid sequence of YPAEVVQK (SEQ ID NO: 943) replaces position 577 (e.g., replaces T577), numbered relative to SEQ ID NO: 138.

[0028] In yet another aspect, the present disclosure provides an AAV capsid variant (e.g., an AAV5 capsid variant) comprising YPAEVVQK (SEQ ID NO: 943), wherein YPAEVVQK (SEQ ID NO: 943) replaces position 577 (e.g., replaces T577), numbered relative to SEQ ID NO: 138; optionally wherein the AAV capsid variant further comprises: (1) the amino acid S, L, or G at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; (2) the amino acid F, M, or V at position 589 numbered according to SEQ ID NO: 982 or at position 582 numbered according to SEQ ID NO: 138; (3) the amino acid S at position 591 number according to SEQ ID NO: 982 or at position 584, numbered according to SEQ ID NO: 138; and / or (4) the amino acid K at position 595 number according to SEQ ID NO: 982 or at position 588, numbered according to SEQ ID NO: 138. 16 319351975.1Attorney Docket Number: V2071-3033PCT

[0029] In yet another aspect, the present disclosure provides an AAV capsid variant (e.g., an AAV5 capsid variant) comprising YPAEVVQK (SEQ ID NO: 943), which is present immediately subsequent to position 576, numbered relative to SEQ ID NO: 138, and wherein YPAEVVQK (SEQ ID NO: 943) replaces position 577 (e.g., replaces T577), numbered relative to SEQ ID NO: 138; optionally wherein the AAV capsid variant further comprises: (1) the amino acid S, L, or G at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; (2) the amino acid F, M, or V at position 589 numbered according to SEQ ID NO: 982 or at position 582 numbered according to SEQ ID NO: 138; (3) the amino acid S at position 591 number according to SEQ ID NO: 982 or at position 584, numbered according to SEQ ID NO: 138; and / or (4) the amino acid K at position 595 number according to SEQ ID NO: 982 or at position 588, numbered according to SEQ ID NO: 138.

[0030] In yet another aspect, the present disclosure provides an AAV capsid variant (e.g., an AAV5 capsid variant) which comprises the amino acid Y at position 577, and further comprises the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered relative to SEQ ID NO: 138; optionally wherein the AAV capsid variant further comprises: (1) the amino acid S, L, or G at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; (2) the amino acid F, M, or V at position 589 numbered according to SEQ ID NO: 982 or at position 582 numbered according to SEQ ID NO: 138; (3) the amino acid S at position 591 number according to SEQ ID NO: 982 or at position 584, numbered according to SEQ ID NO: 138; and / or (4) the amino acid K at position 595 number according to SEQ ID NO: 982 or at position 588, numbered according to SEQ ID NO: 138.

[0031] In yet another aspect, the present disclosure provides an AAV capsid variant (e.g., an AAV5 capsid variant) which comprises the amino acid Y at position 577, and comprises the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered relative to SEQ ID NO: 982; optionally wherein the AAV capsid variant further comprises: (1) the amino acid S, L, or G at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; (2) the amino acid F, M, or V at position 589 numbered according to SEQ ID NO: 982 or at position 582 numbered according to SEQ ID NO: 138; (3) the amino acid S at position 591 number according to SEQ ID NO: 982 or at position 584, numbered according to SEQ ID NO: 138; and / or (4) the amino acid K at position 595 number according to SEQ ID NO: 982 or at position 588, numbered according to SEQ ID NO: 138. In some embodiments, the AAV capsid variant further comprises the amino acid sequence of SEQ ID NO: 739, or an amino acid sequence at least 95% (e.g., at least 96, 97, 98, or 99%) identical thereto. In some embodiments, the AAV capsid variant further comprises the amino acid sequence of SEQ ID NO: 738, or an amino acid sequence at least 95% (e.g., at least 96, 97, 98, or 99%) identical thereto. 17 319351975.1Attorney Docket Number: V2071-3033PCT In some embodiments, the AAV capsid variant further comprises the amino acid sequence of SEQ ID NO: 982, or an amino acid sequence at least 95% (e.g., at least 96, 97, 98, or 99%) identical thereto.

[0032] In yet another aspect, the present disclosure provides an AAV capsid variant (e.g., an AAV5 capsid variant) comprising the amino acid Y at position 577 and the amino acid sequence of PAEVVQK (SEQ ID NO: 20) at positions 578-584, numbered relative to SEQ ID NO: 982; optionally wherein the AAV capsid variant further comprises: (1) the amino acid S, L, or G at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; (2) the amino acid F, M, or V at position 589 numbered according to SEQ ID NO: 982 or at position 582 numbered according to SEQ ID NO: 138; (3) the amino acid S at position 591 number according to SEQ ID NO: 982 or at position 584, numbered according to SEQ ID NO: 138; and / or (4) the amino acid K at position 595 number according to SEQ ID NO: 982 or at position 588, numbered according to SEQ ID NO: 138. In some embodiments, the AAV capsid variant further comprises the amino acid sequence of SEQ ID NO: 739, or an amino acid sequence at least 95% (e.g., at least 96, 97, 98, or 99%) identical thereto. In some embodiments, the AAV capsid variant further comprises the amino acid sequence of SEQ ID NO: 738, or an amino acid sequence at least 95% (e.g., at least 96, 97, 98, or 99%) identical thereto. In some embodiments, the AAV capsid variant further comprises the amino acid sequence of SEQ ID NO: 982, or an amino acid sequence at least 95% (e.g., at least 96, 97, 98, or 99%) identical thereto.

[0033] In yet another aspect, the present disclosure provides an AAV capsid variant (e.g., an AAV5 capsid variant) comprising TNNQSSYPAEVVQKTA (SEQ ID NO: 1533), which is present immediately subsequent to position 570, numbered relative to SEQ ID NO: 138 or 982; optionally wherein the AAV capsid variant further comprises: (1) the amino acid S, L, or G at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; (2) the amino acid F, M, or V at position 589 numbered according to SEQ ID NO: 982 or at position 582 numbered according to SEQ ID NO: 138; (3) the amino acid S at position 591 number according to SEQ ID NO: 982 or at position 584, numbered according to SEQ ID NO: 138; and / or (4) the amino acid K at position 595 number according to SEQ ID NO: 982 or at position 588, numbered according to SEQ ID NO: 138. In some embodiments, the amino acid sequence of YPAEVVQK (SEQ ID NO: 943), replaces position 577 (e.g., replaces T577) numbered relative to SEQ ID NO: 138.

[0034] In yet another aspect, the present disclosure provides an AAV capsid variant (e.g., an AAV5 capsid variant) comprising TNNQSSYPAEVVQKTA (SEQ ID NO: 1533), wherein YPAEVVQK (SEQ ID NO: 943) replaces position 577 (e.g., replaces T577), numbered relative to SEQ ID NO: 138; optionally wherein the AAV capsid variant further comprises: (1) the amino acid S, L, or G at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; (2) the amino acid F, M, or V at position 589 numbered according to SEQ ID NO: 982 or at position 582 numbered according to SEQ ID NO: 138; (3) the amino acid S at 18 319351975.1Attorney Docket Number: V2071-3033PCT position 591 number according to SEQ ID NO: 982 or at position 584, numbered according to SEQ ID NO: 138; and / or (4) the amino acid K at position 595 number according to SEQ ID NO: 982 or at position 588, numbered according to SEQ ID NO: 138.

[0035] In yet another aspect, the present disclosure provides an AAV capsid variant (e.g., an AAV5 capsid variant) comprising TNNQSSYPAEVVQKTA (SEQ ID NO: 1533), which is present immediately subsequent to position 570, numbered relative to SEQ ID NO: 138, wherein YPAEVVQK (SEQ ID NO: 943) replaces position 577 (e.g., replaces T577), numbered relative to SEQ ID NO: 138; optionally wherein the AAV capsid variant further comprises: (1) the amino acid S, L, or G at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; (2) the amino acid F, M, or V at position 589 numbered according to SEQ ID NO: 982 or at position 582 numbered according to SEQ ID NO: 138; (3) the amino acid S at position 591 number according to SEQ ID NO: 982 or at position 584, numbered according to SEQ ID NO: 138; and / or (4) the amino acid K at position 595 number according to SEQ ID NO: 982 or at position 588, numbered according to SEQ ID NO: 138.

[0036] In yet another aspect, the present disclosure provides an AAV capsid variant (e.g., an AAV5 capsid variant) comprising TNNQSSYPAEVVQKTA (SEQ ID NO: 1533), which is present at positions 571-586, numbered according to SEQ ID NO: 982.

[0037] In another aspect, the present disclosure provides an AAV capsid variant (e.g., an AAV5 capsid variant) comprising the amino acid sequence of SEQ ID NO: 982. In another aspect, the present disclosure provides an AAV capsid variant that consists of the amino acid sequence of SEQ ID NO: 982.

[0038] In another aspect, the present disclosure provides an AAV capsid variant (e.g., an AAV5 capsid variant) comprising the amino acid sequence of SEQ ID NO: 4680. In another aspect, the present disclosure provides an AAV capsid variant that consists of the amino acid sequence of SEQ ID NO: 4680.

[0039] In yet another aspect, the present disclosure provides an AAV capsid variant (e.g., an AAV5 capsid variant) comprising an amino acid sequence encoded by the nucleotide sequence of SEQ ID NO: 984; optionally wherein the AAV capsid variant further comprises: (1) the amino acid S, L, or G at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; (2) the amino acid F, M, or V at position 589 numbered according to SEQ ID NO: 982 or at position 582 numbered according to SEQ ID NO: 138; (3) the amino acid S at position 591 number according to SEQ ID NO: 982 or at position 584, numbered according to SEQ ID NO: 138; and / or (4) the amino acid K at position 595 number according to SEQ ID NO: 982 or at position 588, numbered according to SEQ ID NO: 138. In another aspect, the present disclosure provides an AAV capsid variant comprising an amino acid sequence encoded by a nucleotide sequence having at least 95% identity to SEQ ID NO: 984. 19 319351975.1Attorney Docket Number: V2071-3033PCT

[0040] In yet another aspect, the present disclosure provides an AAV capsid variant (e.g., an AAV5 capsid variant) comprising an amino acid sequence at least 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of positions 193-731 of SEQ ID NO: 982, wherein the AAV capsid variant comprises the amino acid sequence of YPAEVVQK (SEQ ID NO: 943); optionally wherein the AAV capsid variant further comprises: (1) the amino acid S, L, or G at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; (2) the amino acid F, M, or V at position 589 numbered according to SEQ ID NO: 982 or at position 582 numbered according to SEQ ID NO: 138; (3) the amino acid S at position 591 number according to SEQ ID NO: 982 or at position 584, numbered according to SEQ ID NO: 138; and / or (4) the amino acid K at position 595 number according to SEQ ID NO: 982 or at position 588, numbered according to SEQ ID NO: 138. In some embodiments, the AAV capsid variant comprises the amino acid sequence of positions 193-731 of SEQ ID NO: 982.

[0041] In yet another aspect, the present disclosure provides an AAV capsid variant (e.g., an AAV5 capsid variant) comprising an amino acid sequence at least 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 739, wherein the AAV capsid variant comprises the amino acid sequence of YPAEVVQK (SEQ ID NO: 943); optionally wherein the AAV capsid variant further comprises: (1) the amino acid S, L, or G at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; (2) the amino acid F, M, or V at position 589 numbered according to SEQ ID NO: 982 or at position 582 numbered according to SEQ ID NO: 138; (3) the amino acid S at position 591 number according to SEQ ID NO: 982 or at position 584, numbered according to SEQ ID NO: 138; and / or (4) the amino acid K at position 595 number according to SEQ ID NO: 982 or at position 588, numbered according to SEQ ID NO: 138. In some embodiments, the AAV capsid variant comprises the amino acid sequence of SEQ ID NO: 739.

[0042] In yet another aspect the present disclosure provides an AAV capsid variant (e.g., an AAV5 capsid variant) comprising: (i) R at position 576 and G at position 577, numbered according to SEQ ID NO: 138 or 982; and (ii) the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 138 or 982.

[0043] In yet another aspect, the present disclosure provides an AAV capsid variant (e.g., an AAV5 capsid variant) comprising: (i) Y at position 577, numbered according to SEQ ID NO: 982 or 138; (ii) the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138; and (iii) R at position 585 and G at position 586, numbered according to SEQ ID NO: 982; or an R at position 578 and G at position 579, numbered according to SEQ ID NO: 138.

[0044] In yet another aspect, the present disclosure provides an AAV capsid variant (e.g., an AAV5 capsid variant) comprising: (i) K at position 576 and G at position 577, numbered according to 20 319351975.1Attorney Docket Number: V2071-3033PCT SEQ ID NO: 138 or 982; and (ii) the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 138 or 982.

[0045] In yet another aspect, the present disclosure provides an AAV capsid variant (e.g., an AAV5 capsid variant) comprising: (i) Y at position 577, numbered according to SEQ ID NO: 982 or 138; and (ii) the amino acid sequence of PKEVVQK (SEQ ID NO: 4749), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138.

[0046] In another aspect, the present disclosure provides AAV capsid variant (e.g., an AAV5 capsid variant) comprising: (i) G at position 577, numbered according to SEQ ID NO: 982 or 138; and (ii) the amino acid sequence of RAEVVQK (SEQ ID NO: 4750), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138.

[0047] In yet another aspect, the present disclosure provides an AAV capsid variant (e.g., an AAV5 capsid variant) comprising: (i) Y at position 577, numbered according to SEQ ID NO: 982 or 138; and (ii) the amino acid sequence of PASLVQK (SEQ ID NO: 4751), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138.

[0048] In yet another aspect, the present disclosure provides an AAV capsid variant (e.g., an AAV5 capsid variant) comprising: (i) Y at position 577, numbered according to SEQ ID NO: 982 or 138; and (ii) the amino acid sequence of PATIVQK (SEQ ID NO: 4752), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138.

[0049] In yet another aspect, the present disclosure provides an AAV capsid variant (e.g., an AAV5 capsid variant) comprising: (i) Y at position 577, numbered according to SEQ ID NO: 982 or 138; and (ii) the amino acid sequence of PAERIQK (SEQ ID NO: 4753), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138.

[0050] In yet another aspect, the present disclosure provides an AAV capsid variant (e.g., an AAV5 capsid variant) comprising: (i) V at position 574 and Y at position 577, numbered relative to SEQ ID NO: 982 or 138; and (ii) the amino acid sequence of PASVVQK (SEQ ID NO: 4754), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138.

[0051] In yet another aspect, the present disclosure provides an AAV capsid variant (e.g., an AAV5 capsid variant) comprising: (i) R at position 576 and Y at position 577, numbered relative to SEQ ID NO: 982 or 138; (ii) the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138; and (iii) N at position 585, numbered according to SEQ ID NO: 982; or N at position 578, numbered according to SEQ ID NO: 138.

[0052] In yet another aspect, the present disclosure provides an AAV capsid variant (e.g., an AAV5 capsid variant) comprising: (i) V at position 574 and Y at position 577, numbered relative to SEQ ID NO: 982 or 138; and (ii) the amino acid sequence of PAGVVQK (SEQ ID NO: 4755), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138. 21 319351975.1Attorney Docket Number: V2071-3033PCT

[0053] In yet another aspect, the present disclosure provides an AAV capsid variant (e.g., an AAV5 capsid variant) comprising: (i) K at position 576 and Y at position 577, numbered relative to SEQ ID NO: 982 or 138; and (ii) the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138; (iii) N at position 585, numbered according to SEQ ID NO: 982; or N at position 578, numbered according to SEQ ID NO: 138.

[0054] In yet another aspect, the present disclosure provides an AAV capsid variant (e.g., an AAV5 capsid variant) comprising: (i) R at position 573, A at position 574 and Y at position 577, numbered relative to SEQ ID NO: 982 or 138; and (ii) the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138.

[0055] In yet another aspect, the present disclosure provides an AAV capsid variant (e.g., an AAV5 capsid variant) comprising: (i) V at position 571 and Y at position 577, numbered relative to SEQ ID NO: 982 or 138; and (ii) the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138.

[0056] In yet another aspect, the present disclosure provides an AAV capsid variant comprising: (i) Y at position 577, numbered relative to SEQ ID NO: 982 or 138; (ii) the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138; and (iii) S at position 591, numbered according to SEQ ID NO: 982; or S at position 584, numbered according to SEQ ID NO: 138.

[0057] In yet another aspect, the present disclosure provides an AAV capsid variant comprising: (i) Y at position 577, numbered relative to SEQ ID NO: 982 or 138; (ii) the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138; and (iii) S at position 588, numbered according to SEQ ID NO: 982; or S at position 581, numbered according to SEQ ID NO: 138.

[0058] In yet another aspect, the present disclosure provides an AAV capsid variant comprising: (i) Y at position 577, numbered relative to SEQ ID NO: 982 or 138; (ii) the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138; and (iii) G at position 588, numbered according to SEQ ID NO: 982; or G at position 581, numbered according to SEQ ID NO: 138.

[0059] In yet another aspect, the present disclosure provides an AAV capsid variant comprising: (i) Y at position 577, numbered relative to SEQ ID NO: 982 or 138; (ii) the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138; and (iii) S at position 588 and F at position 589, numbered according to SEQ ID NO: 982; or S at position 581 and F at position 582, numbered according to SEQ ID NO: 138. 22 319351975.1Attorney Docket Number: V2071-3033PCT

[0060] In yet another aspect, the present disclosure provides an AAV capsid variant comprising: (i) Y at position 577, numbered relative to SEQ ID NO: 982 or 138; (ii) the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138; and (iii) F at position 589, numbered according to SEQ ID NO: 982; or F at position 582, numbered according to SEQ ID NO: 138.

[0061] In yet another aspect, the present disclosure provides an AAV capsid variant comprising: (i) Y at position 577, numbered relative to SEQ ID NO: 982 or 138; (ii) the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138; and (iii) S at position 588 and M at position 589, numbered according to SEQ ID NO: 982; or S at position 581 and M at position 582, numbered according to SEQ ID NO: 138.

[0062] In yet another aspect, the present disclosure provides an AAV capsid variant comprising: (i) Y at position 577, numbered relative to SEQ ID NO: 982 or 138; (ii) the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138; and (iii) L at position 588 and F at position 589, numbered according to SEQ ID NO: 982; or L at position 581 and F at position 582, numbered according to SEQ ID NO: 138.

[0063] In yet another aspect, the present disclosure provides an AAV capsid variant comprising: (i) Y at position 577, numbered relative to SEQ ID NO: 982 or 138; (ii) the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138; and (iii) L at position 588, numbered according to SEQ ID NO: 982; or L at position 581, numbered according to SEQ ID NO: 138.

[0064] In yet another aspect, the present disclosure provides AAV capsid variant comprising: (i) Y at position 577, numbered relative to SEQ ID NO: 982 or 138; (ii) the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138; and (iii) G at position 588 and V at position 589, numbered according to SEQ ID NO: 982; or G at position 581 and V at position 582, numbered according to SEQ ID NO: 138.

[0065] In yet another aspect, the present disclosure provides an AAV capsid variant comprising: (i) Y at position 577, numbered relative to SEQ ID NO: 982 or 138; (ii) the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138; and (iii) K at position 595, numbered according to SEQ ID NO: 982; or K at position 588, numbered according to SEQ ID NO: 138.

[0066] 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, 9, or 15-20; (b) an amino acid sequence comprising at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 consecutive amino acids from 23 319351975.1Attorney Docket Number: V2071-3033PCT any one of the sequences provided in Tables 1, 2A, 2B, 9, 15-20, or 26-30; or (c) an amino acid sequence comprising 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 Tables 1, 2A, 2B, 9, 15-20, or 26-30; or (d) an amino sequence comprising one, two, or three but no more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to the amino acid sequence of any one of the amino acid sequences provided in Tables 1, 2A, 2B, 9, 15- 20, or 26-30.

[0067] In yet another aspect, the present disclosure provides a peptide comprising the amino acid sequence of YPAEVVQK (SEQ ID NO: 943). In yet another aspect, the present disclosure provides a peptide comprising (i) an amino acid sequence comprising one, two, or three, but no more than four different amino acids relative to the amino acid sequence of YPAEVVQK (SEQ ID NO: 943); (ii) an amino acid sequence comprising 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 YPAEVVQK (SEQ ID NO: 943); or (iii) at least 3, 4, 5, 6, or 7 consecutive amino acids from the amino acid sequence of YPAEVVQK (SEQ ID NO: 943).

[0068] In yet another aspect, the present disclosure provides a peptide encoded by the nucleotide sequence of SEQ ID NO: 944, 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. In yet another aspect, the present disclosure provides a peptide encoded by (i) a nucleotide sequence comprising one, two, three, four, five, six, or seven, but no more than ten different nucleotides, relative to the nucleotide sequence of SEQ ID NO: 944; or (ii) a nucleotide sequence comprising one, two, three, four, five, six, or seven modifications, e.g., substitutions, insertions or deletions, but no more than ten modifications, e.g., substitutions, insertions or deletions, relative to the nucleotide sequence of SEQ ID NO: 944.

[0069] In yet another aspect, the present disclosure provides a peptide, wherein the nucleotide sequence encoding the peptide comprises (i) the nucleotide sequence of SEQ ID NO: 944, 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 one, two, three, four, five, six, or seven, but no more than ten different nucleotides relative to the nucleotide sequence of SEQ ID NO: 944; or (iii) a nucleotide sequence comprising one, two, three, four, five, six, or seven modifications, e.g., substitutions, insertions or deletions, but no more than ten modifications, e.g., substitutions, insertions or deletions, relative to the nucleotide sequence of SEQ ID NO: 944.

[0070] In another aspect, the present disclosure provides a polynucleotide encoding an AAV capsid variant (e.g., an AAV5 capsid variant), wherein the encoded AAV capsid variant comprises: 24 319351975.1Attorney Docket Number: V2071-3033PCT (a) the amino acid sequence of any of the sequences provided in Tables 1, 2A, 2B, 9, or 15-20; (b) an amino acid sequence comprising at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 consecutive amino acids from any one of the sequences provided in Tables 1, 2A, 2B, 9, 15-20, or 26-30; or (c) an amino acid sequence comprising 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 Tables 1, 2A, 2B, 9, 15- 20, or 26-30; or (d) an amino sequence comprising one, two, or three but no more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to the amino acid sequence of any one of the amino acid sequences provided in Tables 1, 2A, 2B, 9, 15- 20, or 26-30; optionally wherein the encoded AAV capsid variant further comprises: (1) the amino acid S, L, or G at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; (2) the amino acid F, M, or V at position 589 numbered according to SEQ ID NO: 982 or at position 582 numbered according to SEQ ID NO: 138; (3) the amino acid S at position 591 number according to SEQ ID NO: 982 or at position 584, numbered according to SEQ ID NO: 138; and / or (4) the amino acid K at position 595 number according to SEQ ID NO: 982 or at position 588, numbered according to SEQ ID NO: 138.

[0071] In yet another aspect, the present disclosure provides a polynucleotide encoding an AAV capsid variant (e.g., an AAV5 capsid variant), wherein the encoded AAV capsid variant comprises the amino acid sequence of YPAEVVQK (SEQ ID NO: 943); optionally wherein the encoded AAV capsid variant further comprises: (1) the amino acid S, L, or G at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; (2) the amino acid F, M, or V at position 589 numbered according to SEQ ID NO: 982 or at position 582 numbered according to SEQ ID NO: 138; (3) the amino acid S at position 591 number according to SEQ ID NO: 982 or at position 584, numbered according to SEQ ID NO: 138; and / or (4) the amino acid K at position 595 number according to SEQ ID NO: 982 or at position 588, numbered according to SEQ ID NO: 138.

[0072] In yet another aspect, the present disclosure provides a polynucleotide encoding an AAV capsid variant, wherein the encoded AAV capsid variant comprises (i) an amino acid sequence comprising one, two, or three, but no more than four different amino acids relative to the amino acid sequence of YPAEVVQK (SEQ ID NO: 943); (ii) an amino acid sequence comprising 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 YPAEVVQK (SEQ ID NO: 943); or (iii) at least 3, 4, 5, 6, or 7 consecutive amino acids from the amino acid sequence of YPAEVVQK (SEQ ID NO: 943); optionally wherein the encoded AAV capsid variant further comprises: (1) the amino acid S, L, or G at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; (2) the amino acid F, M, or V at position 589 numbered according to SEQ ID NO: 982 or at position 582 numbered according to SEQ ID NO: 138; (3) the amino acid S at position 591 number according to SEQ ID NO: 25 319351975.1Attorney Docket Number: V2071-3033PCT 982 or at position 584, numbered according to SEQ ID NO: 138; and / or (4) the amino acid K at position 595 number according to SEQ ID NO: 982 or at position 588, numbered according to SEQ ID NO: 138.

[0073] In yet another aspect, the present disclosure provides an AAV particle comprising an AAV capsid polypeptide, e.g., an AAV capsid variant (e.g., an AAV5 capsid variant), described herein. In some embodiments, the AAV particle comprises a nucleic acid sequence encoding a payload. In some embodiments, the AAV particle further comprises a viral genome comprising a promoter operably linked to the nucleic acid sequence encoding the payload.

[0074] In yet another aspect, the present disclosure provides a method of making an AAV particle comprising an AAV capsid polypeptide, e.g., an AAV capsid variant (e.g., an AAV5 capsid variant), described herein. In some embodiments, 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.

[0075] 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 muscle cell, or a muscle tissue). The method comprising administering an effective amount of an AAV particle comprising an AAV capsid variant described herein (e.g., an AAV5 capsid variant).

[0076] 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 an effective amount of an AAV particle comprising an AAV capsid variant described herein (e.g., an AAV5 capsid variant).

[0077] In yet another aspect, the present disclosure provides a method of treating a subject having or diagnosed with having a neurological, e.g., a neurodegenerative, disorder. The method comprising administering an effective amount of an AAV particle comprising an AAV capsid variant described herein (e.g., an AAV5 capsid variant).

[0078] In yet another aspect, the present disclosure provides a method of treating a subject having or diagnosed with having a muscular disorder or a neuromuscular disorder. The method comprising administering an effective amount of an AAV particle comprising an AAV capsid variant described herein (e.g., an AAV5 capsid variant).

[0079] In yet another aspect, the present disclosure provides a method of treating a subject having or diagnosed with having a cardiac disorder, e.g., a cardiac disorder as described herein (e.g., a cardiomyopathy (e.g., arrhythmogenic right ventricular cardiomyopathy, dilated cardiomyopathy, or hypertrophic cardiomyopathy), congestive heart failure, tachycardia (e.g., catecholaminergic polymorphic ventricular tachycardia), ischemic heart disease, and / or myocardial infarction). The method comprising administering an effective amount of an AAV particle comprising an AAV capsid variant described herein (e.g., an AAV5 capsid variant). 26 319351975.1Attorney Docket Number: V2071-3033PCT

[0080] 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 (e.g., an AAV5 capsid variant).

[0081] 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 Embodiments 1. An AAV capsid variant (e.g., an AAV5 capsid variant), comprising: (A) an amino sequence comprising the following formula: [N2]-[N3], wherein: (i) [N2] comprises positions X1, X2, X3, X4, and X5, wherein: (a) position X1 is Y, N, C, G, or T; (b) position X2 is P, E, K, T, R, or Q; (c) position X3 is A, K, or P; (d) position X4 is E, S, D, T, G, or A; and (e) position X5 is V, L, I, R, or E; and (ii) [N3] comprises the amino acid sequence of VQK, VQN, EQK, VKK, VHK, VQQ, IQK, or LQK; 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) and / or (ii); and (B) optionally one, two, three, or all of: (1) the amino acid S, L, or G at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; (2) the amino acid F, M, or V at position 589 numbered according to SEQ ID NO: 982 or at position 582 numbered according to SEQ ID NO: 138; (3) the amino acid S at position 591 number according to SEQ ID NO: 982 or at position 584, numbered according to SEQ ID NO: 138; and / or (4) the amino acid K at position 595 number according to SEQ ID NO: 982 or at position 588, numbered according to SEQ ID NO: 138. 2. An AAV capsid variant (e.g., an AAV5 capsid variant), comprising: (A) an amino sequence comprising the following formula: [N2]-[N3], wherein: (i) [N2] comprises positions X1, X2, X3, X4, and X5, wherein: (a) position X1 is Y, N, G, or C; (b) position X2 is P, K, T, R, or Q; (c) position X3 is A, K, or P; (d) position X4 is E, S, T, G, or A; and 27 319351975.1Attorney Docket Number: V2071-3033PCT (e) position X5 is V, L, I, R, or E; and (ii) [N3] comprises the amino acid sequence of VQK, EQK, VKK, VHK, VQQ, IQK, or LQK; 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) and / or (ii); and (B) optionally one, two, three, or all of: (1) the amino acid S, L, or G at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; (2) the amino acid F, M, or V at position 589 numbered according to SEQ ID NO: 982 or at position 582 numbered according to SEQ ID NO: 138; (3) the amino acid S at position 591 number according to SEQ ID NO: 982 or at position 584, numbered according to SEQ ID NO: 138; and / or (4) the amino acid K at position 595 number according to SEQ ID NO: 982 or at position 588, numbered according to SEQ ID NO: 138. 3. An AAV capsid variant (e.g., an AAV5 capsid variant) comprising: (A) one, two, three, four, or all of: (i) an [N0] comprising TNN, TNT, INN, TNS, NNN, or TNK; (ii) an [N1] comprising QSS, QSK, TSL, SSS, QSR, AGA, IGS, QAS, ASS, LGS, QST, HSS, LSS, VSS, or QRS; (iii) an [N2] comprising YPAEV (SEQ ID NO: 1), YPPSL (SEQ ID NO: 2), NKAEV (SEQ ID NO: 3), YTAEV (SEQ ID NO: 4), YPAEE (SEQ ID NO: 5), YQAEV (SEQ ID NO: 6), YTPSL (SEQ ID NO: 7), YPAAV (SEQ ID NO: 8), NPAEV (SEQ ID NO: 9), CPAEV (SEQ ID NO: 10), GPAEV (SEQ ID NO: 4722), YPKEV (SEQ ID NO: 4723), GRAEV (SEQ ID NO: 4724), YPASL (SEQ ID NO: 4725), YPATI (SEQ ID NO: 4726), YPAER (SEQ ID NO: 4727), YPASV (SEQ ID NO: 4728), YPAGV (SEQ ID NO: 4729), or YQAEE (SEQ ID NO: 11); (iv) an [N3] comprising VQK, EQK, VKK, VHK, VQQ, IQK, or LQK; and (v) an [N4] comprising TA, PA, RG, or NA; 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 (i)-(v); and (B) optionally one, two, three or all of: (1) the amino acid S, L, or G at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; (2) the amino acid F, M, or V at position 589 numbered according to SEQ ID NO: 982 or at position 582 numbered according to SEQ ID NO: 138; (3) the amino acid S at position 591 number according to SEQ ID NO: 982 or at position 584, numbered according to SEQ ID NO: 138; and / or 28 319351975.1Attorney Docket Number: V2071-3033PCT (4) the amino acid K at position 595 number according to SEQ ID NO: 982 or at position 588, numbered according to SEQ ID NO: 138. 4. The AAV capsid variant of embodiment 1 or 2, wherein: (a) position X1 is Y, N, or G; (b) position X2 is P, T, Q, or R; (c) position X3 is A or K; (d) position X4 is E, S, T or G; and / or (e) position X5 is V, L, I or R. 5. The AAV capsid variant of any one of embodiments 1, 2, or 4, wherein [N2] comprises YP, NK, YT, YQ, NP, CP, TH, AE, PS, AA, AS, PA, PP, KA, TA, QA, TP, HA, EV, SL, EE, AV, GP, GR, KE, AT, AG, PK, RA, TI, ER, SV, GV, or SH. 6. The AAV capsid variant of any one of embodiments 1, 2, 4, or 5, wherein [N2] comprises YPA, YPP, NKA, YTA, YQA, YTP, NPA, CPA, THA, PAE, PPS, KAE, TAE, QAE, TPS, PAA, HAS, AEV, PSL, AEE, GPA, YPK, GRA, PKE, RAE, PAS, PAT, PAG, KEV, ASL, ATI, AER, ASV, AGV, or AAV. 7. The AAV capsid variant of any one of embodiments 1-2 or 4-6, wherein [N2] comprises YPAE (SEQ ID NO: 21), YPPS (SEQ ID NO: 22), NKAE (SEQ ID NO: 23), YTAE (SEQ ID NO: 24), YQAE (SEQ ID NO: 25), YTPS (SEQ ID NO: 26), YPAA (SEQ ID NO: 27), NPAE (SEQ ID NO: 28), CPAE (SEQ ID NO: 29), THAS (SEQ ID NO: 30), PAEV (SEQ ID NO: 17), PPSL (SEQ ID NO: 31), KAEV (SEQ ID NO: 32), TAEV (SEQ ID NO: 16), PAEE (SEQ ID NO: 18), QAEV (SEQ ID NO: 15), TPSL (SEQ ID NO: 33), PAAV (SEQ ID NO: 34), GPAE (SEQ ID NO: 4730), YPKE (SEQ ID NO: 4731), GRAE (SEQ ID NO: 4732), YPAS (SEQ ID NO: 4733), YPAT (SEQ ID NO: 4734), YPAG (SEQ ID NO: 4735), PKEV (SEQ ID NO: 4736), RAEV (SEQ ID NO: 4737), PASL (SEQ ID NO: 4738), PATI (SEQ ID NO: 4739), PAER (SEQ ID NO: 4740), PASV (SEQ ID NO: 4741), PAGV (SEQ ID NO: 4742), or QAEE (SEQ ID NO: 35). 8. The AAV capsid variant of any one of embodiments 1-7, wherein [N2] is or comprises YPAEV (SEQ ID NO: 1), YPPSL (SEQ ID NO: 2), NKAEV (SEQ ID NO: 3), YTAEV (SEQ ID NO: 4), YPAEE (SEQ ID NO: 5), YQAEV (SEQ ID NO: 6), YTPSL (SEQ ID NO: 7), YPAAV (SEQ ID NO: 8), NPAEV (SEQ ID NO: 9), CPAEV (SEQ ID NO: 10), GPAEV (SEQ ID NO: 4722), YPKEV (SEQ ID NO: 4723), GRAEV (SEQ ID NO: 4724), YPASL (SEQ ID NO: 4725), YPATI (SEQ ID NO: 4726), YPAER (SEQ ID NO: 4727), YPASV (SEQ ID NO: 4728), YPAGV (SEQ ID NO: 4729), or YQAEE (SEQ ID NO: 11). 29 319351975.1Attorney Docket Number: V2071-3033PCT 9. The AAV capsid variant of any one of embodiments 1-2 or 4-8, wherein [N3] comprises the amino acid sequence of VQK, EQK, IQK, or VKK. 10. The AAV capsid variant of any one of embodiments 1-2 or 4-9, wherein [N3] comprises VQK. 11. The AAV capsid variant of any one of embodiments 1-2 or 4-9, wherein [N3] comprises EQK. 12. The AAV capsid variant of any one of embodiments 1-2 or 4-9, wherein [N3] comprises VKK 13. The AAV capsid variant of any one of embodiments 1-12, wherein [N2] is or comprises the amino acid sequence of YPAEV (SEQ ID NO: 1) and [N3] is or comprises the amino acid sequence of VQK. 14. The AAV capsid variant of any one of embodiments 1-12, wherein: (i) [N2] is or comprises the amino acid sequence of YTPSL (SEQ ID NO: 7) and [N3] is or comprises the amino acid sequence of VQK; (ii) [N2] is or comprises the amino acid sequence of YPPSL (SEQ ID NO: 2) and [N3] is or comprises the amino acid sequence of VQK; (iii) [N2] is or comprises the amino acid sequence of YPPS (SEQ ID NO: 22) and [N3] is or comprises the amino acid sequence of EQK; (iv) [N2] is or comprises the amino acid sequence of YPPSL (SEQ ID NO: 2) and [N3] is or comprises the amino acid sequence of VKK; (v) [N2] is or comprises the amino acid sequence of GPAEV (SEQ ID NO: 4722) and [N3] is or comprises the amino acid sequence of VQK; (vi) [N2] is or comprises the amino acid sequence of YPKEV (SEQ ID NO: 4723) and [N3] is or comprises the amino acid sequence of VQK; (vii) [N2] is or comprises the amino acid sequence of GRAEV (SEQ ID NO: 4724) and [N3] is or comprises the amino acid sequence of VQK; (viii) [N2] is or comprises the amino acid sequence of YPASL (SEQ ID NO: 4725) and [N3] is or comprises the amino acid sequence of VQK; (ix) [N2] is or comprises the amino acid sequence of YPATI (SEQ ID NO: 4726) and [N3] is or comprises the amino acid sequence of VQK; (x) [N2] is or comprises the amino acid sequence of YPAER (SEQ ID NO: 4727) and [N3] is or comprises the amino acid sequence of IQK; (xi) [N2] is or comprises the amino acid sequence of YPASV (SEQ ID NO: 4728) and [N3] is or comprises the amino acid sequence of VQK; 30 319351975.1Attorney Docket Number: V2071-3033PCT (xii) [N2] is or comprises the amino acid sequence of YPAGV (SEQ ID NO: 4729) and [N3] is or comprises the amino acid sequence of VQK. 15. The AAV capsid variant of any one of embodiments 1-2 or 4-14, wherein [N2]-[N3] comprises: (i) AEVVQK (SEQ ID NO: 36), PSLVQK (SEQ ID NO: 37), AEVEQK (SEQ ID NO: 38), AEEVQK (SEQ ID NO: 39), PSLEQK (SEQ ID NO: 40), PSLVKK (SEQ ID NO: 41), AEVVKK (SEQ ID NO: 42), AEVVHK (SEQ ID NO: 43), AAVVQK (SEQ ID NO: 44), AEVVQQ (SEQ ID NO: 45), KEVVQK (SEQ ID NO: 4743), ASLVQK (SEQ ID NO: 4744), ATIVQK (SEQ ID NO: 4745), AERIQK (SEQ ID NO: 4746), ASVVQK (SEQ ID NO: 4747), AGVVQK (SEQ ID NO: 4748), or AEVLQK (SEQ ID NO: 46); (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). 16. The AAV capsid variant of any one of embodiments 1-2 or 4-15, wherein [N2]-[N3] comprises: (i) PAEVVQK (SEQ ID NO: 20), PPSLVQK (SEQ ID NO: 47), KAEVVQK (SEQ ID NO: 48), TAEVVQK (SEQ ID NO: 49), PAEVEQK (SEQ ID NO: 50), PAEEVQK (SEQ ID NO: 51), QAEVVQK (SEQ ID NO: 52), TPSLVQK (SEQ ID NO: 53), PPSLEQK (SEQ ID NO: 54), PPSLVKK (SEQ ID NO: 55), PAEVVKK (SEQ ID NO: 56), PAEVVHK (SEQ ID NO: 57), PAAVVQK (SEQ ID NO: 58), PAEVVQQ (SEQ ID NO: 59), TAEVVKK (SEQ ID NO: 60), PAEVLQK (SEQ ID NO: 61), PKEVVQK (SEQ ID NO: 4749), RAEVVQK (SEQ ID NO: 4750), PASLVQK (SEQ ID NO: 4751), PATIVQK (SEQ ID NO: 4752), PAERIQK (SEQ ID NO: 4753), PASVVQK (SEQ ID NO: 4754), PAGVVQK (SEQ ID NO: 4755), or QAEEVQK (SEQ ID NO: 62); (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). 17. The AAV capsid variant of any one of embodiments 1-16, wherein [N2]-[N3] is or comprises: 31 319351975.1Attorney Docket Number: V2071-3033PCT (i) YPAEVVQK (SEQ ID NO: 943), YPPSLVQK (SEQ ID NO: 946), NKAEVVQK (SEQ ID NO: 947), YTAEVVQK (SEQ ID NO: 948), YPAEVEQK (SEQ ID NO: 949), YPAEEVQK (SEQ ID NO: 950), YQAEVVQK (SEQ ID NO: 951), YTPSLVQK (SEQ ID NO: 952), YPPSLEQK (SEQ ID NO: 953), YPPSLVKK (SEQ ID NO: 954), YPAEVVKK (SEQ ID NO: 955), YPAEVVHK (SEQ ID NO: 956), YPAAVVQK (SEQ ID NO: 957), NPAEVVQK (SEQ ID NO: 958), YPAEVVQQ (SEQ ID NO: 959), CPAEVVQK (SEQ ID NO: 960), YTAEVVKK (SEQ ID NO: 961), YPAEVLQK (SEQ ID NO: 962), GPAEVVQK (SEQ ID NO: 4714), YPKEVVQK (SEQ ID NO: 4715), GRAEVVQK (SEQ ID NO: 4716), YPASLVQK (SEQ ID NO: 4717), YPATIVQK (SEQ ID NO: 4718), YPAERIQK (SEQ ID NO: 4719), YPASVVQK (SEQ ID NO: 4720), YPAGVVQK (SEQ ID NO: 4721), or YQAEEVQK (SEQ ID NO: 963); (ii) an amino acid sequence comprising any portion of an amino acid sequence in (i), e.g., any 2, 3, 4, 5, 6, or 7 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, which further comprises one, two, three or all of an amino acid other than Q at position 574 (e.g., T, S, A, I, L, V, or H), an amino acid other than S at position 575 (e.g., G, A, or R), and / or an amino acid other than S at position 576 (e.g., K, L, R, A, or T), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 982. 19. The AAV capsid variant of any one of embodiments 1-17, which further comprises: (i) a Q at position 574, an S at position 575, and / or an S at position 576, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 982; (ii) a T at position 574, an S at position 575, and / or a L at position 576, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 982; (iii) an S at position 574, an S at position 575, and / or an S at position 576, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 982; (iv) a Q at position 574, an S at position 575, and / or an R at position 576, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 982; (v) a Q at position 574, an S at position 575, and / or a K at position 576, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 982; (vi) an A at position 574, a G at position 575, and / or an A at position 576, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 982; 32 319351975.1Attorney Docket Number: V2071-3033PCT (vii) an I at position 574, a G at position 575, and / or an S at position 576, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 982; (viii) a Q at position 574, an A at position 575, and / or an S at position 576, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 982; (ix) an A at position 574, an S at position 575, and / or an S at position 576, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 982; (x) an L at position 574, a G at position 575, and / or an S at position 576, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 982; (xi) a Q at position 574, an S at position 575, and / or a T at position 576, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 982; (xii) an H at position 574, an S at position 575, and / or an S at position 576, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 982; (xiii) an L at position 574, an S at position 575, and / or an S at position 576, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 982; (xiv) a Q at position 574, an R at position 575, and / or an S at position 576, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 982; (xv) a V at position 574, an S at position 575, and / or an S at position 576, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 982. 20. The AAV capsid variant of any one of embodiments 1-19, which further comprises [N1], wherein [N1] comprises positions XD, XE, and XF, wherein: (a) position XDis Q, T, S, A, I, L, V, or H; (b) position XEis S, G, A, or R; and (c) position XF is S, K, L, R, A, or T; 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). 21. The AAV capsid variant of embodiment 20, wherein [N1] comprises SK, SL, SS, SR, GA, GS, AS, ST, RS, QS, TS, AG, IG, QA, LG, HS, LS, VS, or QR. 22. The AAV capsid variant of any one of embodiments 3, 20, or 21, wherein [N1] is or comprises QSS, QSK, TSL, SSS, QSR, AGA, IGS, QAS, ASS, LGS, QST, HSS, LSS, VSS, or QRS. 23. The AAV capsid variant of any one of embodiments 20-22, wherein [N1]-[N2] comprises: (i) SSYPA (SEQ ID NO: 63), SKYPA (SEQ ID NO: 64), SLYPA (SEQ ID NO: 65), SRYPA (SEQ ID NO: 66), SSYPP (SEQ ID NO: 67), GAYPA (SEQ ID NO: 68), GSYPA (SEQ ID NO: 69), ASYPA (SEQ ID NO: 70), STNKA (SEQ ID NO: 71), SSYTA (SEQ ID NO: 72), SSYQA (SEQ ID 33 319351975.1Attorney Docket Number: V2071-3033PCT NO: 73), SSYTP (SEQ ID NO: 74), SSNPA (SEQ ID NO: 75), SLCPA (SEQ ID NO: 76), RSYTA (SEQ ID NO: 77), SRGPA (SEQ ID NO: 4756), SKGPA (SEQ ID NO: 4757), SSYPK (SEQ ID NO: 4758), SSGRA (SEQ ID NO: 4759), or SSTHA (SEQ ID NO: 78); (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). 24. The AAV capsid variant of any one of embodiments 20-23, wherein [N1]-[N2] comprises: (i) SSYPAE (SEQ ID NO: 79), SKYPAE (SEQ ID NO: 80), SLYPAE (SEQ ID NO: 81), SRYPAE (SEQ ID NO: 82), SSYPPS (SEQ ID NO: 83), GAYPAE (SEQ ID NO: 84), GSYPAE (SEQ ID NO: 85), ASYPAE (SEQ ID NO: 86), STNKAE (SEQ ID NO: 87), SSYTAE (SEQ ID NO: 88), SSYQAE (SEQ ID NO: 89), SSYTPS (SEQ ID NO: 90), SSYPAA (SEQ ID NO: 91), SSNPAE (SEQ ID NO: 92), SLCPAE (SEQ ID NO: 93), RSYTAE (SEQ ID NO: 94), SRGPAE (SEQ ID NO: 4760), SKGPAE (SEQ ID NO: 4761), SSYPKE (SEQ ID NO: 4762), SSGRAE (SEQ ID NO: 4763), SSYPAS (SEQ ID NO: 4764), SSYPAT (SEQ ID NO: 4765), SSYPAG (SEQ ID NO: 4766), or SSTHAS (SEQ ID NO: 95); (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). 25. The AAV capsid variant of any one of embodiments 3 or 20-24, wherein [N1]-[N2] is or comprises: (i) QSSYPAEV (SEQ ID NO: 96), QSKYPAEV (SEQ ID NO: 97), TSLYPAEV (SEQ ID NO: 98), SSSYPAEV (SEQ ID NO: 99), QSRYPAEV (SEQ ID NO: 100), QSSYPPSL (SEQ ID NO: 101), AGAYPAEV (SEQ ID NO: 102), IGSYPAEV (SEQ ID NO: 103), QASYPAEV (SEQ ID NO: 104), ASSYPAEV (SEQ ID NO: 105), LGSYPAEV (SEQ ID NO: 106), QSTNKAEV (SEQ ID NO: 107), HSSYPAEV (SEQ ID NO: 108), SSSYTAEV (SEQ ID NO: 109), TSLYPAEE (SEQ ID NO: 110), ASSYQAEV (SEQ ID NO: 111), QSSYTPSL (SEQ ID NO: 112), QSRYPAEE (SEQ ID NO: 113), LSSYQAEV (SEQ ID NO: 114), HSSYPAAV (SEQ ID NO: 115), QSSNPAEV (SEQ ID NO: 34 319351975.1Attorney Docket Number: V2071-3033PCT 116), QSSYTAEV (SEQ ID NO: 117), TSLCPAEV (SEQ ID NO: 118), QRSYTAEV (SEQ ID NO: 119), QSRGPAEV (SEQ ID NO: 4767), QSKGPAEV (SEQ ID NO: 4768), QSSYPKEV (SEQ ID NO: 4769), QSSGRAEV (SEQ ID NO: 4770), QSSYPASL (SEQ ID NO: 4771), QSSYPATI (SEQ ID NO: 4812), QSSYPAER (SEQ ID NO: 4772), VSSYPASV (SEQ ID NO: 4773), VSSYPAGV (SEQ ID NO: 4774), or QSSYQAEE (SEQ ID NO: 120); (ii) an amino acid sequence comprising any portion of an amino acid sequence in (i), e.g., any 2, 3, 4, 5, 6, or 7 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). 26. The AAV capsid variant of any one of embodiments 20-25, wherein [N1]-[N2]-[N3] comprises: (i) SSYPAEVVQ (SEQ ID NO: 121), SKYPAEVVQ (SEQ ID NO: 122), SLYPAEVVQ (SEQ ID NO: 123), SRYPAEVVQ (SEQ ID NO: 124), SSYPPSLVQ (SEQ ID NO: 125), GAYPAEVVQ (SEQ ID NO: 126), GSYPAEVVQ (SEQ ID NO: 127), ASYPAEVVQ (SEQ ID NO: 128), STNKAEVVQ (SEQ ID NO: 129), SSYTAEVVQ (SEQ ID NO: 130), SKYPAEVEQ (SEQ ID NO: 131), SLYPAEEVQ (SEQ ID NO: 132), SSYQAEVVQ (SEQ ID NO: 133), SSYTPSLVQ (SEQ ID NO: 134), SRYPAEEVQ (SEQ ID NO: 135), SSYPPSLEQ (SEQ ID NO: 136), SSYPPSLVK (SEQ ID NO: 140), SSYPAEVVK (SEQ ID NO: 141), SKYPAEVVH (SEQ ID NO: 142), SSYPAAVVQ (SEQ ID NO: 143), SSNPAEVVQ (SEQ ID NO: 144), SLCPAEVVQ (SEQ ID NO: 145), RSYTAEVVQ (SEQ ID NO: 146), SSYTAEVVK (SEQ ID NO: 147), SSYPAEVLQ (SEQ ID NO: 148), SRGPAEVVQ (SEQ ID NO: 4775), SKGPAEVVQ (SEQ ID NO: 4776), SSYPKEVVQ (SEQ ID NO: 4777), SSGRAEVVQ (SEQ ID NO: 4778), SSYPASLVQ (SEQ ID NO: 4779), SSYPATIVQ (SEQ ID NO: 4780), SSYPAERIQ (SEQ ID NO: 4781), SSYPASVVQ (SEQ ID NO: 4782), SSYPAGVVQ (SEQ ID NO: 4783), or SSYQAEEVQ (SEQ ID NO: 149); (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). 27. The AAV capsid variant of any one of embodiments 3 or 20-26, wherein [N1]-[N2]-[N3] is or comprises: 35 319351975.1Attorney Docket Number: V2071-3033PCT (i) QSSYPAEVVQK (SEQ ID NO: 150), QSKYPAEVVQK (SEQ ID NO: 151), TSLYPAEVVQK (SEQ ID NO: 152), SSSYPAEVVQK (SEQ ID NO: 153), QSRYPAEVVQK (SEQ ID NO: 154), QSSYPPSLVQK (SEQ ID NO: 155), AGAYPAEVVQK (SEQ ID NO: 156), IGSYPAEVVQK (SEQ ID NO: 157), QASYPAEVVQK (SEQ ID NO: 158), ASSYPAEVVQK (SEQ ID NO: 159), LGSYPAEVVQK (SEQ ID NO: 160), QSTNKAEVVQK (SEQ ID NO: 161), HSSYPAEVVQK (SEQ ID NO: 162), SSSYTAEVVQK (SEQ ID NO: 163), QSKYPAEVEQK (SEQ ID NO: 164), TSLYPAEEVQK (SEQ ID NO: 165), ASSYQAEVVQK (SEQ ID NO: 166), QSSYTPSLVQK (SEQ ID NO: 167), QSRYPAEEVQK (SEQ ID NO: 168), QSSYPPSLEQK (SEQ ID NO: 169), QSSYPPSLVKK (SEQ ID NO: 170), LSSYQAEVVQK (SEQ ID NO: 171), SSSYPAEVVKK (SEQ ID NO: 172), QSKYPAEVVHK (SEQ ID NO: 173), HSSYPAAVVQK (SEQ ID NO: 174), QSSNPAEVVQK (SEQ ID NO: 175), SSSYPAEVVQQ (SEQ ID NO: 176), QSSYTAEVVQK (SEQ ID NO: 177), TSLCPAEVVQK (SEQ ID NO: 178), QRSYTAEVVQK (SEQ ID NO: 179), QSSYTAEVVKK (SEQ ID NO: 180), HSSYPAEVLQK (SEQ ID NO: 181), QSRGPAEVVQK (SEQ ID NO: 4784), QSKGPAEVVQK (SEQ ID NO: 4785), QSSYPKEVVQK (SEQ ID NO: 4786), QSSGRAEVVQK (SEQ ID NO: 4787), QSSYPASLVQK (SEQ ID NO: 4788), QSSYPATIVQK (SEQ ID NO: 4789), QSSYPAERIQK (SEQ ID NO: 4790), VSSYPASVVQK (SEQ ID NO: 4791), VSSYPAGVVQK (SEQ ID NO: 4792), or QSSYQAEEVQK (SEQ ID NO: 182); (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). 28. The AAV capsid variant of any one of embodiments 1-27, which further comprises [N0], wherein [N0] comprises positions XA, XB, and XC, wherein: (a) position XAis T, I, V, or N; (b) position XB is N; (c) position XC is N, T, S, R, or K; 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). 29. The AAV capsid variant of embodiment 28, wherein [N0] comprises TN, IN, NN, NT, NS, NR, VN, or NK. 36 319351975.1Attorney Docket Number: V2071-3033PCT 30. The AAV capsid variant of embodiment 3, 28, or 29, wherein [N0] is or comprises TNN, TNT, INN, TNS, NNN, TNR, VNN, or TNK. 31. The AAV capsid variant of any one of embodiments 3 or 28-30, wherein [N0]-[N1] is or comprises: (i) TNNQSS (SEQ ID NO: 183), TNNQSK (SEQ ID NO: 184), TNNTSL (SEQ ID NO: 185), TNNSSS (SEQ ID NO: 186), TNNQSR (SEQ ID NO: 187), TNNAGA (SEQ ID NO: 188), TNNIGS (SEQ ID NO: 189), TNNQAS (SEQ ID NO: 190), TNTASS (SEQ ID NO: 191), TNNLGS (SEQ ID NO: 192), TNNQST (SEQ ID NO: 193), TNNHSS (SEQ ID NO: 194), TNNQSK (SEQ ID NO: 184), TNNLSS (SEQ ID NO: 195), INNQSS (SEQ ID NO: 196), TNSQSS (SEQ ID NO: 197), NNNQSR (SEQ ID NO: 198), TNSTSL (SEQ ID NO: 199), TNNQRS (SEQ ID NO: 200), TNNVSS (SEQ ID NO: 4793), TNRASS (SEQ ID NO: 4794), VNNQSS (SEQ ID NO: 4795), or TNKQAS (SEQ ID NO: 201); (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). 32. The AAV capsid variant of any one of embodiments 3 or 28-31, wherein [N0]-[N1]-[N2]-[N3] is or comprises: (i) TNNQSSYPAEVVQK (SEQ ID NO: 500), TNNQSKYPAEVVQK (SEQ ID NO: 503), TNNTSLYPAEVVQK (SEQ ID NO: 506), TNNSSSYPAEVVQK (SEQ ID NO: 508), TNNQSRYPAEVVQK (SEQ ID NO: 510), TNNQSSYPPSLVQK (SEQ ID NO: 512), TNNAGAYPAEVVQK (SEQ ID NO: 513), TNNIGSYPAEVVQK (SEQ ID NO: 514), TNNQASYPAEVVQK (SEQ ID NO: 517), TNTASSYPAEVVQK (SEQ ID NO: 520), TNNLGSYPAEVVQK (SEQ ID NO: 523), TNNQSTNKAEVVQK (SEQ ID NO: 524), TNNHSSYPAEVVQK (SEQ ID NO: 525), TNNSSSYTAEVVQK (SEQ ID NO: 526), TNNQSKYPAEVEQK (SEQ ID NO: 529), TNNTSLYPAEEVQK (SEQ ID NO: 530), TNTASSYQAEVVQK (SEQ ID NO: 531), TNNQSSYTPSLVQK (SEQ ID NO: 533), TNNQSRYPAEEVQK (SEQ ID NO: 534), TNNQSSYPPSLEQK (SEQ ID NO: 535), TNNQSSYPPSLVKK (SEQ ID NO: 536), TNNLSSYQAEVVQK (SEQ ID NO: 539), TNNSSSYPAEVVKK (SEQ ID NO: 540), TNNQSKYPAEVVHK (SEQ ID NO: 542), INNQSSYPAEVVQK (SEQ ID NO: 543), TNNHSSYPAAVVQK (SEQ ID NO: 545), TNSQSSNPAEVVQK (SEQ ID NO: 548), TNNSSSYPAEVVQQ (SEQ ID NO: 551), 37 319351975.1Attorney Docket Number: V2071-3033PCT NNNQSRYPAEVVQK (SEQ ID NO: 552), TNNQSSYTAEVVQK (SEQ ID NO: 553), TNNTSLCPAEVVQK (SEQ ID NO: 554), TNSTSLYPAEVVQK (SEQ ID NO: 556), TNNQRSYTAEVVQK (SEQ ID NO: 557), TNNQSSYTAEVVKK (SEQ ID NO: 558), TNNHSSYPAEVLQK (SEQ ID NO: 560), TNNQSSYQAEEVQK (SEQ ID NO: 562), TNNQSRGPAEVVQK (SEQ ID NO: 4796), TNNQSKGPAEVVQK (SEQ ID NO: 4797), TNNQSSYPKEVVQK (SEQ ID NO: 4798), TNNQSSGRAEVVQK (SEQ ID NO: 4799), TNNQSSYPASLVQK (SEQ ID NO: 4800), TNNQSSYPATIVQK (SEQ ID NO: 4801), TNNQSSYPAERIQK (SEQ ID NO: 4802), TNNVSSYPASVVQK (SEQ ID NO: 4803), TNNVSSYPAGVVQK (SEQ ID NO: 4804), TNRASSYPAEVVQK (SEQ ID NO: 4805), VNNQSSYPAEVVQK (SEQ ID NO: 4806), or TNKQASYPAEVVQK (SEQ ID NO: 563); (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). 33. The AAV capsid variant of embodiment 3 or 32, wherein [N0]-[N1]-[N2]-[N3] is or comprises TNNQSSYPAEVVQK (SEQ ID NO: 500). 34. The AAV capsid variant of embodiment 3 or 32, wherein [N0]-[N1]-[N2]-[N3] is or comprises TNNAGAYPAEVVQK (SEQ ID NO: 513), TNNTSLYPAEVVQK (SEQ ID NO: 506), TNNQSKYPAEVVQK (SEQ ID NO: 503), TNNQSSYTPSLVQK (SEQ ID NO: 533), TNNQSSYPPSLVQK (SEQ ID NO: 512), TNNQSRYPAEVVQK (SEQ ID NO: 510), TNNQSSYPPSLEQK (SEQ ID NO: 535), TNNQSSYPPSLVKK (SEQ ID NO: 536), or INNQSSYPAEVVQK (SEQ ID NO: 543). 35. The AAV capsid variant of any one of embodiments 1-34, which further comprises [N4], wherein [N4] comprises positions XG and XH, wherein: (a) position XG is T, P, R, or N; and (b) position XH is A or G; 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) or (b). 36. The AAV capsid variant of embodiment 35, wherein [N4] is or comprises TA, PA, RG, or NA. 38 319351975.1Attorney Docket Number: V2071-3033PCT 37. The AAV capsid variant of any one of embodiments 3, 35, or 36, wherein [N3]-[N4] is or comprises: (i) VQKTA (SEQ ID NO: 564), EQKTA (SEQ ID NO: 565), VKKTA (SEQ ID NO: 566), VQKPA (SEQ ID NO: 567), VHKTA (SEQ ID NO: 568), VQQTA (SEQ ID NO: 569), VQKNA (SEQ ID NO: 570), VQKRG (SEQ ID NO: 4807), IQKTA (SEQ ID NO: 4808), or LQKTA (SEQ ID NO: 571); (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). 38. The AAV capsid variant of any one of embodiments 3 or 35-37, wherein [N0]-[N1]-[N2]-[N3]- [N4] is or comprises: (i) TNNQSSYPAEVVQKTA (SEQ ID NO: 1533), TNNQSKYPAEVVQKTA (SEQ ID NO: 1538), TNNTSLYPAEVVQKTA (SEQ ID NO: 1232), TNNSSSYPAEVVQKTA (SEQ ID NO: 1539), TNNQSRYPAEVVQKTA (SEQ ID NO: 1327), TNNQSSYPPSLVQKTA (SEQ ID NO: 1300), TNNAGAYPAEVVQKTA (SEQ ID NO: 1021), TNNIGSYPAEVVQKTA (SEQ ID NO: 1112), TNNQASYPAEVVQKTA (SEQ ID NO: 1194), TNTASSYPAEVVQKTA (SEQ ID NO: 1575), TNNLGSYPAEVVQKTA (SEQ ID NO: 1027), TNNQSTNKAEVVQKTA (SEQ ID NO: 1578), TNNHSSYPAEVVQKTA (SEQ ID NO: 1310), TNNQSKYPAEVVQKTA (SEQ ID NO: 1538), TNNSSSYTAEVVQKTA (SEQ ID NO: 1214), TNNQSKYPAEVEQKTA (SEQ ID NO: 1254), TNNTSLYPAEEVQKTA (SEQ ID NO: 1583), TNTASSYQAEVVQKTA (SEQ ID NO: 1584), TNNQSSYTPSLVQKTA (SEQ ID NO: 1585), TNNQSRYPAEEVQKTA (SEQ ID NO: 1342), TNNQSSYPPSLEQKTA (SEQ ID NO: 1590), TNNQSSYPPSLVKKTA (SEQ ID NO: 1591), TNNLSSYQAEVVQKTA (SEQ ID NO: 1592), TNNQSSYPPSLVQKPA (SEQ ID NO: 1593), TNNSSSYPAEVVKKTA (SEQ ID NO: 1331), TNNQSKYPAEVVHKTA (SEQ ID NO: 1453), TNNSSSYPAEVVQKPA (SEQ ID NO: 1142), INNQSSYPAEVVQKTA (SEQ ID NO: 1024), TNNHSSYPAAVVQKTA (SEQ ID NO: 1598), TNSQSSNPAEVVQKTA (SEQ ID NO: 1599), TNNSSSYPAEVVQQTA (SEQ ID NO: 1419), NNNQSRYPAEVVQKTA (SEQ ID NO: 1601), TNNQSSYTAEVVQKNA (SEQ ID NO: 1602), TNNTSLCPAEVVQKTA (SEQ ID NO: 1603), TNSTSLYPAEVVQKTA (SEQ ID NO: 1605), TNNQRSYTAEVVQKTA (SEQ ID NO: 1604), TNNQSSYTAEVVKKTA (SEQ ID NO: 1606), TNNHSSYPAEVLQKTA (SEQ ID NO: 1607), TNNQSSYQAEEVQKTA (SEQ ID NO: 1608), TNNQSRGPAEVVQKTA (SEQ ID NO: 4684), TNNQSSYPAEVVQKRG (SEQ ID NO: 4685), TNNQSKGPAEVVQKTA (SEQ ID NO: 4686), 39 319351975.1Attorney Docket Number: V2071-3033PCT TNNQSSYPKEVVQKTA (SEQ ID NO: 4694), TNNQSSGRAEVVQKTA (SEQ ID NO: 4696), TNNQSSYPASLVQKTA (SEQ ID NO: 4698), TNNQSSYPATIVQKTA (SEQ ID NO: 4700), TNNQSSYPAERIQKTA (SEQ ID NO: 4701), TNNVSSYPASVVQKTA (SEQ ID NO: 4682), TNNQSRYPAEVVQKNA (SEQ ID NO: 4683), TNNVSSYPAGVVQKTA (SEQ ID NO: 4704), TNNQSKYPAEVVQKNA (SEQ ID NO: 4705), TNRASSYPAEVVQKTA (SEQ ID NO: 4708), VNNQSSYPAEVVQKTA (SEQ ID NO: 4710), or TNKQASYPAEVVQKTA (SEQ ID NO: 1587); (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). 39. The AAV capsid variant of embodiment 3 or 35-38, wherein [N0]-[N1]-[N2]-[N3]-[N4] is or comprises TNNQSSYPAEVVQKTA (SEQ ID NO: 1533). 40. The AAV capsid variant of embodiment 3 or 35-38, wherein [N0]-[N1]-[N2]-[N3]-[N4] is or comprises: (a) TNNAGAYPAEVVQKTA (SEQ ID NO: 1021), TNNTSLYPAEVVQKTA (SEQ ID NO: 1232), TNNQSKYPAEVVQKTA (SEQ ID NO: 1538), TNNQSSYTPSLVQKTA (SEQ ID NO: 1585), TNNQSSYPPSLVQKTA (SEQ ID NO: 1300), TNNQSRYPAEVVQKTA (SEQ ID NO: 1327), TNNQSSYPPSLEQKTA (SEQ ID NO: 1590), TNNQSSYPPSLVKKTA (SEQ ID NO: 1591), or INNQSSYPAEVVQKTA (SEQ ID NO: 1024); (b) TNNQSRGPAEVVQKTA (SEQ ID NO: 4684), TNNQSSYPAEVVQKRG (SEQ ID NO: 4685), TNNQSKGPAEVVQKTA (SEQ ID NO: 4686), TNNQSSYPKEVVQKTA (SEQ ID NO: 4694), TNNQSSGRAEVVQKTA (SEQ ID NO: 4696), TNNQSSYPASLVQKTA (SEQ ID NO: 4698), TNNQSSYPATIVQKTA (SEQ ID NO: 4700), TNNQSSYPAERIQKTA (SEQ ID NO: 4701), TNNVSSYPASVVQKTA (SEQ ID NO: 4682), TNNQSRYPAEVVQKNA (SEQ ID NO: 4683), TNNVSSYPAGVVQKTA (SEQ ID NO: 4704), TNNQSKYPAEVVQKNA (SEQ ID NO: 4705); or (c) TNRASSYPAEVVQKTA (SEQ ID NO: 4708) or VNNQSSYPAEVVQKTA (SEQ ID NO: 4710). 41. An AAV capsid variant (e.g., an AAV5 capsid variant) comprising: (A) an amino sequence comprising the following formula: [B]-[C] (SEQ ID NO: 757), wherein (i) [B] comprises positions X1, X2, and X3, wherein: (a) position X1 is Q, T, S, A, I, L, or H; 40 319351975.1Attorney Docket Number: V2071-3033PCT (b) position X2 is S, G, or A; and (c) position X3 is S, K, L, R, or A; and (ii) [C] comprises the amino acid sequence of YPAEVVQK (SEQ ID NO: 943); 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 (i) and / or (ii); and (B) optionally one or both of: (1) the amino acid S or G at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; and / or (2) the amino acid S at position 591 number according to SEQ ID NO: 982 or at position 584, numbered according to SEQ ID NO: 138. 42. An AAV capsid variant (e.g., an AAV5 capsid variant) comprising: (A) one, two, three, four, or all of: (i) an [A], wherein [A] comprises the amino acid sequence of TNN, TNT, INN, NNN, TNS, or TNK; (ii) a [B], wherein [B] comprises the amino acid sequence of QSS, TSL, SSS, QSR, QSK, AGA, IGS, QAS, ASS, LGS, or HSS; (iii) a [C], wherein [C] comprises the amino acid sequence of YPAEVVQK (SEQ ID NO: 943); and (iv) a [D], wherein [D] comprises the amino acid sequence of TA or PA; 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 (i)-(v); and / or [C] replaces position 577 relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138; and (B) optionally one or both of: (1) the amino acid S or G at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; and / or (2) the amino acid S at position 591 number according to SEQ ID NO: 982 or at position 584, numbered according to SEQ ID NO: 138. 43. The AAV capsid variant of embodiment 41, wherein: (a) position X1 is Q, T, S, A, or H; (b) position X2 is S or G; and (c) position X3 is S, K, L, or R. 44. The AAV capsid variant of embodiment 41 or 43, wherein [B] comprises QS, TS, SS, AG, IG, QA, AS, LG, HS, SK, SL, SR, GA, or GS. 41 319351975.1Attorney Docket Number: V2071-3033PCT 45. The AAV capsid variant of any one of embodiments 41-44, wherein [B] is or comprises QSS, TSL, SSS, QSR, QSK, AGA, IGS, QAS, ASS, LGS, or HSS. 46. The AAV capsid variant of any one of embodiments 41 or 43-45, wherein [B]-[C] comprises: (i) SSYPAEVVQK (SEQ ID NO: 572), SKYPAEVVQK (SEQ ID NO: 573), SLYPAEVVQK (SEQ ID NO: 574), SRYPAEVVQK (SEQ ID NO: 575), GAYPAEVVQK (SEQ ID NO: 576), GSYPAEVVQK (SEQ ID NO: 580), or ASYPAEVVQK (SEQ ID NO: 582); (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, 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). 47. The AAV capsid variant of any one of embodiments 41-46, wherein [B]-[C] is or comprises: (i) QSSYPAEVVQK (SEQ ID NO: 150), QSKYPAEVVQK (SEQ ID NO: 151), TSLYPAEVVQK (SEQ ID NO: 152), SSSYPAEVVQK (SEQ ID NO: 153), QSRYPAEVVQK (SEQ ID NO: 154), AGAYPAEVVQK (SEQ ID NO: 156), IGSYPAEVVQK (SEQ ID NO: 157), QASYPAEVVQK (SEQ ID NO: 158), ASSYPAEVVQK (SEQ ID NO: 159), LGSYPAEVVQK (SEQ ID NO: 160), or HSSYPAEVVQK (SEQ ID NO: 162); (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). 48. The AAV capsid variant of any one of embodiments 41-47, wherein [B]-[C] is or comprises QSSYPAEVVQK (SEQ ID NO: 150). 49. The AAV capsid variant of any one of embodiments embodiment 41-47, wherein [B]-[C] is or comprises AGAYPAEVVQK (SEQ ID NO: 156), TSLYPAEVVQK (SEQ ID NO: 152), QSKYPAEVVQK (SEQ ID NO: 151), or QSRYPAEVVQK (SEQ ID NO: 154). 42 319351975.1Attorney Docket Number: V2071-3033PCT 50. The AAV capsid variant of any one of embodiments 1-49, which further comprises one or both of an amino acid other than T at position 571 (e.g., I or N), and / or an amino acid other than N at position 573 (e.g., T, S, or K), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 982. 51. The AAV capsid variant of any one of embodiments 1-49, which further comprises: (i) a T at position 571, an N at position 572, and / or an N at position 573, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 982; (ii) a T at position 571, an N at position 572, and / or a T at position 573, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 982; (iii) an I at position 571, an N at position 572, and / or an N at position 573, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 982; (iv) a T at position 571, an N at position 572, and / or an S at position 573, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 982; (v) an N at position 571, an N at position 572, and / or an N at position 573, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 982; or (vi) a T at position 571, an N at position 572, and / or a K at position 573, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 982. 52. The AAV capsid variant of any one of embodiments 41-51, which further comprises [A], wherein [A] comprises positions XA, XB, and XC, wherein: (a) position XAis T, I, or N; (b) position XBis N; and (c) position XC is N, T, S, or K; 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). 53. The AAV capsid variant of embodiment 52, wherein [A] comprises TN, IN, NN, NT, NS, or NK. 54. The AAV capsid variant of any one of embodiments 42, 52, or 53, wherein [A] is or comprises TNN, TNT, INN, NNN, TNS, or TNK. 55. The AAV capsid variant of any one of embodiments 42 or 52-54, wherein [A]-[B] is or comprises: (i) TNNQSS (SEQ ID NO: 183), TNNQSK (SEQ ID NO: 184), TNNTSL (SEQ ID NO: 185), TNNSSS (SEQ ID NO: 186), TNNQSR (SEQ ID NO: 187), TNNAGA (SEQ ID NO: 188), TNNIGS (SEQ ID NO: 189), TNNQAS (SEQ ID NO: 190), TNTASS (SEQ ID NO: 191), TNNLGS (SEQ ID 43 319351975.1Attorney Docket Number: V2071-3033PCT NO: 192), TNNHSS (SEQ ID NO: 194), INNQSS (SEQ ID NO: 196), NNNQSR (SEQ ID NO: 198), TNSTSL (SEQ ID NO: 199), or TNKQAS (SEQ ID NO: 201); (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). 56. The AAV capsid variant of any one of embodiments 42 or 52-55, wherein [A]-[B]-[C] is or comprises: (i) TNNQSSYPAEVVQK (SEQ ID NO: 500), TNNQSKYPAEVVQK (SEQ ID NO: 503), TNNTSLYPAEVVQK (SEQ ID NO: 506), TNNSSSYPAEVVQK (SEQ ID NO: 508), TNNQSRYPAEVVQK (SEQ ID NO: 510), TNNAGAYPAEVVQK (SEQ ID NO: 513), TNNIGSYPAEVVQK (SEQ ID NO: 514), TNNQASYPAEVVQK (SEQ ID NO: 517), TNTASSYPAEVVQK (SEQ ID NO: 520), TNNLGSYPAEVVQK (SEQ ID NO: 523), TNNHSSYPAEVVQK (SEQ ID NO: 525), INNQSSYPAEVVQK (SEQ ID NO: 543), NNNQSRYPAEVVQK (SEQ ID NO: 552), TNSTSLYPAEVVQK (SEQ ID NO: 556), or TNKQASYPAEVVQK (SEQ ID NO: 563); (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). 57. The AAV capsid variant of any one of embodiments 42 or 52-54, wherein [A]-[B]-[C] is or comprises TNNQSSYPAEVVQK (SEQ ID NO: 500). 58. The AAV capsid variant of any one of embodiments 42 or 52-54, wherein [A]-[B]-[C] is or comprises TNNAGAYPAEVVQK (SEQ ID NO: 513), TNNTSLYPAEVVQK (SEQ ID NO: 506), TNNQSKYPAEVVQK (SEQ ID NO: 503), TNNQSRYPAEVVQK (SEQ ID NO: 510), or INNQSSYPAEVVQK (SEQ ID NO: 543). 59. The AAV capsid variant of any one of embodiments 1-58, which further comprises: 44 319351975.1Attorney Docket Number: V2071-3033PCT (i) an amino acid other than T at position 578 (e.g., P or N), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138; or an (ii) an amino acid other than T at position 585 (e.g., P or N), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 982. 60. The AAV capsid variant of any one of embodiments 1-58, which further comprises: (i) a T at position 578 and / or an A at position 579, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138; or a T at position 585 and / or an A at position 586 relative to a reference sequence numbered according to SEQ ID NO: 982; (ii) a P at position 578 and / or an A at position 579, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138; or a P at position 585 and / or an A at position 586 relative to a reference sequence numbered according to SEQ ID NO: 982; or (iii) an N at position 578 and / or an A at position 579, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138; or an N at position 585 and / or an A at position 586 relative to a reference sequence numbered according to SEQ ID NO: 982. 61. The AAV capsid variant of any one of embodiments 41-60, which further comprises [D], wherein [D] comprises positions X4 and X5, wherein: (a) position X4 is T or N; and (b) position X5 is A; 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) or (b). 62. The AAV capsid variant of embodiment 42 or 61, wherein [D] is or comprises TA or PA. 63. The AAV capsid variant of any one of embodiments 42, 61, or 62, wherein [C]-[D] is or comprises: (i) YPAEVVQKTA (SEQ ID NO: 584) or YPAEVVQKPA (SEQ ID NO: 586); (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, 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). 45 319351975.1Attorney Docket Number: V2071-3033PCT 64. The AAV capsid variant of any one of embodiments 42 or 61-63, wherein [A]-[B]-[C]-[D] is or comprises: (i) TNNQSSYPAEVVQKTA (SEQ ID NO: 1533), TNNQSKYPAEVVQKTA (SEQ ID NO: 1538), TNNTSLYPAEVVQKTA (SEQ ID NO: 1232), TNNSSSYPAEVVQKTA (SEQ ID NO: 1539), TNNQSRYPAEVVQKTA (SEQ ID NO: 1327), TNNAGAYPAEVVQKTA (SEQ ID NO: 1021), TNNIGSYPAEVVQKTA (SEQ ID NO: 1112), TNNQASYPAEVVQKTA (SEQ ID NO: 1194), TNTASSYPAEVVQKTA (SEQ ID NO: 1575), TNNLGSYPAEVVQKTA (SEQ ID NO: 1027), TNNHSSYPAEVVQKTA (SEQ ID NO: 1310), TNNSSSYPAEVVQKPA (SEQ ID NO: 1142), INNQSSYPAEVVQKTA (SEQ ID NO: 1024), NNNQSRYPAEVVQKTA (SEQ ID NO: 1601), TNSTSLYPAEVVQKTA (SEQ ID NO: 1605), or TNKQASYPAEVVQKTA (SEQ ID NO: 1587); (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). 65. The AAV capsid variant of any one of embodiments 42 or 61-64, wherein [A]-[B]-[C]-[D] is or comprises TNNQSSYPAEVVQKTA (SEQ ID NO: 1533). 66. The AAV capsid variant of any one of embodiments 42 or 61-64, wherein [A]-[B]-[C]-[D] is or comprises TNNAGAYPAEVVQKTA (SEQ ID NO: 1021), TNNTSLYPAEVVQKTA (SEQ ID NO: 1232), TNNQSKYPAEVVQKTA (SEQ ID NO: 1538), TNNQSRYPAEVVQKTA (SEQ ID NO: 1327), or INNQSSYPAEVVQKTA (SEQ ID NO: 1024). 67. An AAV capsid variant (e.g., an AAV5 capsid variant), comprising: (A) an amino sequence comprising the formula [N2]-[N3], wherein: (i) [N2] comprises positions X1, X2, X3, X4, and X5, wherein: (a) position X1 is Y or T; (b) position X2 is Q, T, P, or E; (c) position X3 is A; (d) position X4 is E or D; and (e) position X5 is V or E; and (ii) [N3] comprises the amino acid sequence of VQK or VQN; or 46 319351975.1Attorney Docket Number: V2071-3033PCT wherein the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of the aforesaid amino acids in (i) and / or (ii); and (B) optionally one, two, or all of: (1) the amino acid S, L, or G at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; (2) the amino acid F, M, or V at position 589 numbered according to SEQ ID NO: 982 or at position 582 numbered according to SEQ ID NO: 138; and / or (3) the amino acid K at position 595 number according to SEQ ID NO: 982 or at position 588, numbered according to SEQ ID NO: 138. 68. An AAV capsid variant (e.g., an AAV5 capsid variant) comprising: (A) one, two, three, four, or all of: (i) an [N0] comprising TNN, TNS, TNT, TNR, VNN, or TNK; (ii) an [N1] comprising QSS, SLS, SLY, SAT, ASS, or QTS; (iii) an [N2] comprising YPAEV (SEQ ID NO: 1), YQAEV (SEQ ID NO: 6), YTAEV (SEQ ID NO: 4), YPAEE (SEQ ID NO: 5), TEAEV (SEQ ID NO: 12), or YPADV (SEQ ID NO: 13); (iv) an [N3] comprising VQK or VQN; and (v) an [N4] comprising TA, PA, TD, NA, or PA; 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 (i)-(v); and (B) optionally one, two, or all of: (1) the amino acid S, L, or G at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; (2) the amino acid F, M, or V at position 589 numbered according to SEQ ID NO: 982 or at position 582 numbered according to SEQ ID NO: 138; and / or (3) the amino acid K at position 595 number according to SEQ ID NO: 982 or at position 588, numbered according to SEQ ID NO: 138. 69. The AAV capsid variant of embodiment 1 or 67, wherein [N2] comprises YP, YQ, YT, TE, QA, TA, PA, EA, EV, EE, DV, AE, or AD. 70. The AAV capsid variant of any one of embodiments 1, 67 or 69, wherein [N2] comprises YPA, YQA, YTA, TEA, QAE, TAE, PAE, EAE, PAD, AEV, AEE, or ADV. 71. The AAV capsid variant of any one of embodiments 1, 67, 69, or 70, wherein [N2] comprises YPAE (SEQ ID NO: 21), YQAE (SEQ ID NO: 25), YTAE (SEQ ID NO: 24), TEAE (SEQ ID NO: 47 319351975.1Attorney Docket Number: V2071-3033PCT 587), YPAD (SEQ ID NO: 588), QAEV (SEQ ID NO: 15), TAEV (SEQ ID NO: 16), PAEV (SEQ ID NO: 17), PAEE (SEQ ID NO: 18), EAEV (SEQ ID NO: 590), or PADV (SEQ ID NO: 19). 72. The AAV capsid variant of any one of embodiments 1 or 67-71, wherein [N2] is or comprises YPAEV (SEQ ID NO: 1), YQAEV (SEQ ID NO: 6), YTAEV (SEQ ID NO: 4), YPAEE (SEQ ID NO: 5), TEAEV (SEQ ID NO: 12), or YPADV (SEQ ID NO: 13). 73. The AAV capsid variant of any one of embodiments 1 or 67-72, wherein [N3] comprises the amino acid sequence of VQK. 74. The AAV capsid variant of any one of embodiments 1, 67, or 69-73, wherein [N2]-[N3] comprises: (i) AEVVQK (SEQ ID NO: 36), AEEVQK (SEQ ID NO: 39), AEVVQN (SEQ ID NO: 591), or ADVVQK (SEQ ID NO: 593); (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). 75. The AAV capsid variant of any one of embodiments 1, 67, or 69-74, wherein [N2]-[N3] comprises: (i) PAEVVQN (SEQ ID NO: 594), QAEVVQK (SEQ ID NO: 52), TAEVVQK (SEQ ID NO: 49), PAEVVQK (SEQ ID NO: 20), PAEEVQK (SEQ ID NO: 51), EAEVVQK (SEQ ID NO: 595), or PADVVQK (SEQ ID NO: 596); (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). 76. The AAV capsid variant of any one of embodiments 1 or 57-75, wherein [N2]-[N3] is or comprises: 48 319351975.1Attorney Docket Number: V2071-3033PCT (i) YPAEVVQK (SEQ ID NO: 943), YQAEVVQK (SEQ ID NO: 951), YTAEVVQK (SEQ ID NO: 948), YPAEEVQK (SEQ ID NO: 950), YPAEVVQN (SEQ ID NO: 964), TEAEVVQK (SEQ ID NO: 965), or YPADVVQK (SEQ ID NO: 966); (ii) an amino acid sequence comprising any portion of an amino acid sequence in (i), e.g., any 2, 3, 4, 5, 6, or 7 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). 77. The AAV capsid variant of any one of embodiments 1 or 67-76, wherein [N2]-[N3] is or comprises YPAEVVQK (SEQ ID NO: 943). 78. The AAV capsid variant of any one of embodiments 1-77, wherein [N2]-[N3] replaces position 577, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 79. The AAV capsid variant of any one of embodiments 1 or 67-78, which further comprises one, two, three or all of an amino acid other than Q at position 574 (e.g., A or S), an amino acid other than S at position 575 (e.g., L, A, or T), and / or an amino acid other than S at position 576 (e.g., Y or T), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 982. 80. The AAV capsid variant of any one of embodiments 1 or 67-78, which further comprises: (i) a Q at position 574, an S at position 575, and / or an S at position 576, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 982; (ii) an S at position 574, an L at position 575, and / or an S at position 576, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 982; (iii) an S at position 574, an L at position 575, and / or a Y at position 576, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 982; (iv) an S at position 574, an A at position 575, and / or a T at position 576, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 982; (v) a Q at position 574, a T at position 575, and / or an S at position 576, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 982; (vi) an A at position 574, an S at position 575, and / or an S at position 576, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 982. 49 319351975.1Attorney Docket Number: V2071-3033PCT 81. The AAV capsid variant of any one of embodiments 1 or 67-80, which further comprises [N1], wherein [N1] comprises positions XD, XE, and XF, wherein: (a) position XDis Q, A, or S; (b) position XEis S, L, A, or T; and (c) position XFis S, Y, or T; 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). 82. The AAV capsid variant of embodiment 81, wherein [N1] comprises QS, SL, SA, QT, LS, LY, AT, TS, AS, or SS. 83. The AAV capsid variant of any one of embodiment 68, 81, 82, wherein [N1] is or comprises QSS, SLS, SLY, SAT, ASS, or QTS. 84. The AAV capsid variant of any one of embodiments 81-83, wherein [N1]-[N2] comprises: (i) SSYPA (SEQ ID NO: 63), LSYQA (SEQ ID NO: 597), LSYTA (SEQ ID NO: 598), LYYPA (SEQ ID NO: 600), ATYPA (SEQ ID NO: 601), LSYPA (SEQ ID NO: 603), or TSTEA (SEQ ID NO: 605); (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). 85. The AAV capsid variant of any one of embodiments 81-84, wherein [N1]-[N2] comprises: (i) SSYPAE (SEQ ID NO: 79), LSYQAE (SEQ ID NO: 607), LSYTAE (SEQ ID NO: 610), LYYPAE (SEQ ID NO: 611), ATYPAE (SEQ ID NO: 613), LSYPAE (SEQ ID NO: 616), TSTEAE (SEQ ID NO: 619), or LSYPAD (SEQ ID NO: 621); (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). 50 319351975.1Attorney Docket Number: V2071-3033PCT 86. The AAV capsid variant of any one of embodiments 68 or 81-85, wherein [N1]-[N2] is or comprises: (i) QSSYPAEV (SEQ ID NO: 96), SLSYQAEV (SEQ ID NO: 622), SLSYTAEV (SEQ ID NO: 623), SLYYPAEV (SEQ ID NO: 624), SATYPAEV (SEQ ID NO: 625), SLSYPAEV (SEQ ID NO: 629), SLSYPAEE (SEQ ID NO: 632), QTSTEAEV (SEQ ID NO: 633), ASSYPAEV (SEQ ID NO: 4823), or SLSYPADV (SEQ ID NO: 634); (ii) an amino acid sequence comprising any portion of an amino acid sequence in (i), e.g., any 2, 3, 4, 5, 6, or 7 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). 87. The AAV capsid variant of any one of embodiments 68 or 81-86, wherein [N1]-[N2]-[N3] is or comprises: (i) QSSYPAEVVQK (SEQ ID NO: 150), SLSYQAEVVQK (SEQ ID NO: 635), SLSYTAEVVQK (SEQ ID NO: 637), SLYYPAEVVQK (SEQ ID NO: 639), SATYPAEVVQK (SEQ ID NO: 641), SLSYPAEVVQK (SEQ ID NO: 642), SLSYPAEEVQK (SEQ ID NO: 643), SLSYPAEVVQN (SEQ ID NO: 644), QTSTEAEVVQK (SEQ ID NO: 645), ASSYPAEVVQK (SEQ ID NO: 4824) or SLSYPADVVQK (SEQ ID NO: 646); (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). 88. The AAV capsid variant of any one of embodiments 68 or 81-87, wherein [N1]-[N2]-[N3] is or comprises QSSYPAEVVQK (SEQ ID NO: 150). 89. The AAV capsid variant of any one of embodiments 1 or 67-88, which further comprises [N0], wherein [N0] comprises positions XA, XB, and XC, wherein: (a) position XAis T or V; (b) position XBis N; and (c) position XC is N, T, S, R, or K; and 51 319351975.1Attorney Docket Number: V2071-3033PCT optionally wherein the AAV capsid comprises an amino acid modification, e.g., a conservative substitution, of any of the aforesaid amino acids in (a)-(c). 90. The AAV capsid variant of embodiment 89, wherein [N0]: (i) comprises TN, NS, NT, NN, NR, VN, or NK; and / or (ii) is or comprises TNS, TNT, TNN, TNR, VNN, or TNK. 91. The AAV capsid variant of any one of embodiments 68, 89, or 90, wherein [N0]-[N1] is or comprises: (i) TNNQSS (SEQ ID NO: 183), TNSSLS (SEQ ID NO: 647), TNSSLY (SEQ ID NO: 648), TNTSAT (SEQ ID NO: 649), TNNQTS (SEQ ID NO: 650), TNRASS (SEQ ID NO: 4825), VNNQSS (SEQ ID NO: 4826), or TNKSAT (SEQ ID NO: 651; (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). 92. The AAV capsid variant of any one of embodiments 68 or 89-91, wherein [N0]-[N1]-[N2]-[N3] is or comprises: (i) TNNQSSYPAEVVQK (SEQ ID NO: 500), TNSSLSYQAEVVQK (SEQ ID NO: 652), TNSSLSYTAEVVQK (SEQ ID NO: 654), TNSSLYYPAEVVQK (SEQ ID NO: 655), TNTSATYPAEVVQK (SEQ ID NO: 656), TNSSLSYPAEVVQK (SEQ ID NO: 657), TNSSLSYPAEEVQK (SEQ ID NO: 658), TNSSLSYPAEVVQN (SEQ ID NO: 660), TNNQTSTEAEVVQK (SEQ ID NO: 662), TNKSATYPAEVVQK (SEQ ID NO: 663), TNRASSYPAEVVQK (SEQ ID NO: 4805), VNNQSSYPAEVVQK (SEQ ID NO: 4806), or TNSSLSYPADVVQK (SEQ ID NO: 665); (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). 52 319351975.1Attorney Docket Number: V2071-3033PCT 93. The AAV capsid variant of any one of embodiments 68 or 89-92, wherein [N0]-[N1]-[N2]-[N3] is or comprises TNNQSSYPAEVVQK (SEQ ID NO: 500). 94. The AAV capsid variant of any one of embodiments 1 or 67-93, which further comprises [N4], wherein [N4] comprises positions XGand XH, wherein: (a) position XG is T, P, or N; and (b) position XH is A or D; and optionally wherein the AAV capsid variant comprise an amino acid modification, e.g., a conservative substitution, of any of the aforesaid amino acids in (a) or (b). 95. The AAV capsid variant of embodiment 94, wherein [N4] is or comprises TA, TD, PA, or NA. 96. The AAV capsid variant of embodiment 68, 94, or 95, wherein [N3]-[N4] is or comprises: (i) VQKTA (SEQ ID NO: 564), EQKTA (SEQ ID NO: 565), VKKTA (SEQ ID NO: 566), VQKPA (SEQ ID NO: 567), VHKTA (SEQ ID NO: 568), VQQTA (SEQ ID NO: 569), VQKNA (SEQ ID NO: 570), or LQKTA (SEQ ID NO: 571); (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). 97. The AAV capsid variant of any one of embodiments 68 or 94-96, wherein [N0]-[N1]-[N2]-[N3]- [N4] is or comprises: (i) TNNQSSYPAEVVQKTA (SEQ ID NO: 1533), TNSSLSYQAEVVQKTA (SEQ ID NO: 2064), TNSSLSYTAEVVQKTA (SEQ ID NO: 2065), TNSSLYYPAEVVQKTA (SEQ ID NO: 2066), TNTSATYPAEVVQKTA (SEQ ID NO: 2067), TNSSLSYPAEVVQKTA (SEQ ID NO: 2068), TNSSLSYPAEEVQKTA (SEQ ID NO: 2069), TNSSLSYPAEVVQKTD (SEQ ID NO: 2070), TNSSLSYPAEVVQNTA (SEQ ID NO: 2071), TNSSLSYPAEVVQKNA (SEQ ID NO: 2072), TNSSLSYPAEVVQKPA (SEQ ID NO: 2073), TNNQTSTEAEVVQKTA (SEQ ID NO: 2074), TNKSATYPAEVVQKTA (SEQ ID NO: 2075), TNRASSYPAEVVQKTA (SEQ ID NO: 4708), VNNQSSYPAEVVQKTA (SEQ ID NO: 4710), or TNSSLSYPADVVQKTA (SEQ ID NO: 2076); (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; 53 319351975.1Attorney Docket Number: V2071-3033PCT (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). 98. The AAV capsid variant of any one of embodiments 68 or 94-97, wherein [N0]-[N1]-[N2]-[N3]- [N4] is or comprises TNNQSSYPAEVVQKTA (SEQ ID NO: 1533). 99. An AAV capsid variant (e.g., an AAV5 capsid variant) comprises: (A) the formula [K1]-[K2], wherein: (i) [K1] comprises LSY or LYY; and (ii) [K2] comprises positions X1, X2, X3, and X4, wherein: (a) position X1 is Q, T, or P; (b) position X2 is A; (c) position X3 is E or D; and (d) position X4 is V or E; 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 (i) and / or (ii); and / or (B) optionally one, two, or all of: (1) the amino acid S, L, or G at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; (2) the amino acid F, M, or V at position 589 numbered according to SEQ ID NO: 982 or at position 582 numbered according to SEQ ID NO: 138; and / or (3) the amino acid K at position 595 number according to SEQ ID NO: 982 or at position 588, numbered according to SEQ ID NO: 138. 100. An AAV capsid variant (e.g., an AAV5 capsid variant) comprising: (A) one, two, three, four, or all of: (i) an [K0], which comprises TNNS (SEQ ID NO: 14); (ii) an [K1], which comprises LSY or LYY; (iii) an [K2], which comprises QAEV (SEQ ID NO: 15), TAEV (SEQ ID NO: 16), PAEV (SEQ ID NO: 17), PAEE (SEQ ID NO: 18), or PADV (SEQ ID NO: 19); (iv) an [K3], which comprise VQK or VQN; and (v) an [K4], which comprises TA, TD, NA, or PA; 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 (i)-(v); and 54 319351975.1Attorney Docket Number: V2071-3033PCT (B) optionally one, two, or all of: (1) the amino acid S, L, or G at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; (2) the amino acid F, M, or V at position 589 numbered according to SEQ ID NO: 982 or at position 582 numbered according to SEQ ID NO: 138; and / or (3) the amino acid K at position 595 number according to SEQ ID NO: 982 or at position 588, numbered according to SEQ ID NO: 138. 101. The AAV capsid variant of embodiment 99 or 100, wherein [K1] comprises LSY. 102. The AAV capsid variant of embodiment 99 or 101, wherein [K2] comprises QA, TA, PA, EV, EE, DV, AE, or AD. 103. The AAV capsid variant of any one of embodiments 99, 101, or 102, wherein [K2] comprises QAE, TAE, PAE, PAD, AEV, AEE, or ADV. 104. The AAV capsid variant of any one of embodiments 99-103, wherein [K2] is or comprises QAEV (SEQ ID NO: 15), TAEV (SEQ ID NO: 16), PAEV (SEQ ID NO: 17), PAEE (SEQ ID NO: 18), or PADV (SEQ ID NO: 19). 105. The AAV capsid variant of any one of embodiments 99 or 101-104, wherein [K1]-[K2] comprises LSYQA (SEQ ID NO: 597), LSYTA (SEQ ID NO: 598), LYYPA (SEQ ID NO: 600), or LSYPA (SEQ ID NO: 603). 106. The AAV capsid variant of any one of embodiments 99 or 101-105, wherein [K1]-[K2] comprises: (i) LSYQAE (SEQ ID NO: 607), LSYTAE (SEQ ID NO: 610), LYYPAE (SEQ ID NO: 611), LSYPAE (SEQ ID NO: 616), or LSYPAD (SEQ ID NO: 621); (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). 107. The AAV capsid variant of any one of embodiments 99-106, wherein [K1]-[K2] is or comprises: 55 319351975.1Attorney Docket Number: V2071-3033PCT (i) LSYQAEV (SEQ ID NO: 667), LSYTAEV (SEQ ID NO: 668), LYYPAEV (SEQ ID NO: 669), LSYPAEV (SEQ ID NO: 671), LSYPAEE (SEQ ID NO: 673), or LSYPADV (SEQ ID NO: 674); (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). 108. The AAV capsid variant of any one of embodiments 99-107, which further comprises an amino acid other than Q at position 574 (e.g., S), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 109. The AAV capsid variant of any one of embodiments 99-108, which further comprises S at position 574, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 110. The AAV capsid variant of any one of embodiments 99-109, which further comprises [K0], wherein [K0] is or comprises TNNS (SEQ ID NO: 14); an amino acid sequence comprising any portion of an amino acid sequence, e.g., any 2 or 3 amino acids, e.g., consecutive amino acids, thereof; 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 the amino acid sequence of TNNS (SEQ ID NO: 14); or an amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to the amino acid sequence of TNNS (SEQ ID NO: 14). 111. The AAV capsid variant of embodiment 110, wherein [K0]-[K1] comprises: (i) TNSSLS (SEQ ID NO: 647) or TNSSLY (SEQ ID NO: 648); (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). 56 319351975.1Attorney Docket Number: V2071-3033PCT 112. The AAV capsid variant of any one of embodiments 100, 110 or 111, wherein [K0]-[K1] is or comprises: (i) TNSSLSY (SEQ ID NO: 676) or TNSSLYY (SEQ ID NO: 678); (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). 113. The AAV capsid variant of any one of embodiments 110-112, wherein [K0]-[K1]-[K2] comprises: (i) TNSSLSYQA (SEQ ID NO: 679), TNSSLSYTA (SEQ ID NO: 681), TNSSLYYPA (SEQ ID NO: 682), or TNSSLSYPA (SEQ ID NO: 683); (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). 114. The AAV capsid variant of any one of embodiments 110-113, wherein [K0]-[K1]-[K2] comprises: (i) TNSSLSYQAE (SEQ ID NO: 684), TNSSLSYTAE (SEQ ID NO: 685), TNSSLYYPAE (SEQ ID NO: 686), TNSSLSYPAE (SEQ ID NO: 687), or TNSSLSYPAD (SEQ ID NO: 689); (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, 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). 115. The AAV capsid variant of any one of embodiments 100 or 110-114, wherein [K0]-[K1]-[K2] is or comprises: 57 319351975.1Attorney Docket Number: V2071-3033PCT (i) TNSSLSYQAEV (SEQ ID NO: 692), TNSSLSYTAEV (SEQ ID NO: 693), TNSSLYYPAEV (SEQ ID NO: 696), TNSSLSYPAEV (SEQ ID NO: 697), TNSSLSYPAEE (SEQ ID NO: 698), or TNSSLSYPADV (SEQ ID NO: 699); (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). 116. The AAV capsid variant of any one of embodiments 99-115, which further comprises [K3], wherein [K3] comprises positions XA, XB, and XC, wherein: (a) position XA is V; (b) position XB is Q; and (c) position XCis K or N; and optionally wherein the AAV capsid comprises an amino acid modification, e.g., a conservative substitution, of any of the aforesaid amino acids in (a)-(c). 117. The AAV capsid variant of embodiment 116, wherein [K3]: (i) comprises VQ, QK, or QN; (ii) is or comprises VQK or VQN. 118. The AAV capsid variant of embodiment 100, 116, or 117, wherein [K2]-[K3] is or comprises: (i) QAEVVQK (SEQ ID NO: 52), TAEVVQK (SEQ ID NO: 49), PAEVVQK (SEQ ID NO: 20), PAEEVQK (SEQ ID NO: 51), PAEVVQN (SEQ ID NO: 594), or PADVVQK (SEQ ID NO: 596); (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). 119. The AAV capsid variant of embodiment 100 or 116-118, wherein [K1]-[K2]-[K3] is or comprises: 58 319351975.1Attorney Docket Number: V2071-3033PCT (i) LSYQAEVVQK (SEQ ID NO: 700), LSYTAEVVQK (SEQ ID NO: 701), LYYPAEVVQK (SEQ ID NO: 702), LSYPAEVVQK (SEQ ID NO: 703), LSYPAEEVQK (SEQ ID NO: 704), LSYPAEVVQN (SEQ ID NO: 706), or LSYPADVVQK (SEQ ID NO: 708); (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, 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). 120. The AAV capsid variant of embodiment 100 or 116-119, wherein [K0]-[K1]-[K2]-[K3] is or comprises: (i) TNSSLSYQAEVVQK (SEQ ID NO: 652), TNSSLSYTAEVVQK (SEQ ID NO: 654), TNSSLYYPAEVVQK (SEQ ID NO: 655), TNSSLSYPAEVVQK (SEQ ID NO: 657), TNSSLSYPAEEVQK (SEQ ID NO: 658), TNSSLSYPAEVVQN (SEQ ID NO: 660), or TNSSLSYPADVVQK (SEQ ID NO: 665); (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). 121. The AAV capsid variant of any one of embodiments 99-120, which further comprises [K4], wherein [K4] comprises positions XD and XE, wherein: (a) position XDis T, P, or N; and (b) position XEis A or D; and optionally wherein the AAV capsid variant comprise an amino acid modification, e.g., a conservative substitution, of any of the aforesaid amino acids in (a) or (b). 122. The AAV capsid variant of embodiment 100 or 121, wherein [K4] is or comprises TA, TD, PA, or NA. 123. The AAV capsid variant of any one of embodiments 100, 121, or 122, wherein [K3]-[K4] is or comprises: 59 319351975.1Attorney Docket Number: V2071-3033PCT (i) VQKTA (SEQ ID NO: 564), VQKTD (SEQ ID NO: 714), VQNTA (SEQ ID NO: 715), VQKNA (SEQ ID NO: 570), or VQKPA (SEQ ID NO: 567); (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). 124. The AAV capsid variant of any one of embodiments 100 or 121-123, wherein [K0]-[K1]-[K2]- [K3]-[K4] is or comprises: (i) TNSSLSYQAEVVQKTA (SEQ ID NO: 2064), TNSSLSYTAEVVQKTA (SEQ ID NO: 2065), TNSSLYYPAEVVQKTA (SEQ ID NO: 2066), TNSSLSYPAEVVQKTA (SEQ ID NO: 2068), TNSSLSYPAEEVQKTA (SEQ ID NO: 2069), TNSSLSYPAEVVQKTD (SEQ ID NO: 2070), TNSSLSYPAEVVQNTA (SEQ ID NO: 2071), TNSSLSYPAEVVQKNA (SEQ ID NO: 2072), TNSSLSYPAEVVQKPA (SEQ ID NO: 2073), or TNSSLSYPADVVQKTA (SEQ ID NO: 2076); (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). 125. An AAV capsid variant (e.g., an AAV5 capsid variant) comprising: (A) [B]-[C] (SEQ ID NO: 759), wherein: (i) [B] comprises positions X1, X2, and X3, wherein: (a) position X1 is Q, A, or S; (b) position X2 is S, L, or A; and (c) position X3 is S, Y, R, K, or T; and (ii) [C] comprises the amino acid sequence of YPAEVVQK (SEQ ID NO: 943); and optionally wherein there AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of the aforesaid amino acids in (i) and / or (ii); and (B) optionally one, two, three or all of: 60 319351975.1Attorney Docket Number: V2071-3033PCT (1) the amino acid S, L, or G at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; (2) the amino acid F, M, or V at position 589 numbered according to SEQ ID NO: 982 or at position 582 numbered according to SEQ ID NO: 138; (3) the amino acid S at position 591 number according to SEQ ID NO: 982 or at position 584, numbered according to SEQ ID NO: 138; and / or (4) the amino acid K at position 595 number according to SEQ ID NO: 982 or at position 588, numbered according to SEQ ID NO: 138. 126. An AAV capsid variant (e.g., an AAV5 capsid variant) comprising: (A) one, two, three, four, or all of: (i) an [A] comprising TNN, TNS, TNT, TNR, VNN, or TNK; (ii) a [B] comprising QSS, SLY, SAT, QSR, QSK, ASS, or SLS; (iii) a [C] comprising YPAEVVQK (SEQ ID NO: 943); and (iv) a [D] comprising TA, TD, NA, RG, or PA; 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 (i)-(v), and further optionally wherein [C] replaces position 577 relative to reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138; and (B) optionally one, two, three or all of: (1) the amino acid S, L, or G at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; (2) the amino acid F, M, or V at position 589 numbered according to SEQ ID NO: 982 or at position 582 numbered according to SEQ ID NO: 138; (3) the amino acid S at position 591 number according to SEQ ID NO: 982 or at position 584, numbered according to SEQ ID NO: 138; and / or (4) the amino acid K at position 595 number according to SEQ ID NO: 982 or at position 588, numbered according to SEQ ID NO: 138. 127. The AAV capsid variant of embodiment 125, comprising wherein [B] comprises QS, SL, SA, LY, AT, LS, SR, SK, AS, or SS. 128. The AAV capsid variant of any one of embodiments 125-127, comprising wherein [B] is or comprises QSS, SLY, SAT, QSR QSK, ASS, or SLS. 129. The AAV capsid variant of any one of embodiments 125, 127, or 128, wherein [B]-[C] comprises: 61 319351975.1Attorney Docket Number: V2071-3033PCT (i) SSYPAEVVQK (SEQ ID NO: 572), LYYPAEVVQK (SEQ ID NO: 702), ATYPAEVVQK (SEQ ID NO: 718), SRYPAEVVQK (SEQ ID NO: 575), SKYPAEVVQK (SEQ ID NO: 573) or LSYPAEVVQK (SEQ ID NO: 703); (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, 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). 130. The AAV capsid variant of any one of embodiments 125-129, wherein [B]-[C] is or comprises: (i) QSSYPAEVVQK (SEQ ID NO: 150), SLYYPAEVVQK (SEQ ID NO: 639), SATYPAEVVQK (SEQ ID NO: 641), QSRYPAEVVQK (SEQ ID NO: 154), QSKYPAEVVQK (SEQ ID NO: 151), ASSYPAEVVQK (SEQ ID NO: 159) or SLSYPAEVVQK (SEQ ID NO: 642); (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). 131. The AAV capsid variant of embodiment 126 or 130, wherein [B]-[C] is or comprises QSSYPAEVVQK (SEQ ID NO: 150). 132. The AAV capsid variant of any one of embodiments 67-98 or 125-131, which further comprises an amino acid other than T at position 571 (e.g., V), numbered according to SEQ ID NO: 138 or 982, and / or an amino acid other than N at position 573 (e.g., T, S, R, or K), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 982. 133. The AAV capsid variant of any one of embodiments 67-98 or 125-131, which further comprises: (i) a T at position 571, an N at position 572, and / or an N at position 573, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 982; (ii) a T at position 571, an N at position 572, and / or a T at position 573, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 982; 62 319351975.1Attorney Docket Number: V2071-3033PCT (iii) a T at position 571, an N at position 572, and / or a S at position 573, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 982; (iv) a T at position 571, an N at position 572, and / or a K at position 573, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 982; (v) a T at position 571, an N at position 572, and / or an R at position 573, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 982; or (vi) a V at position 571, an N at position 572, and / or a N at position 573, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 982. 134. The AAV capsid variant of any one of embodiments 125-133, which further comprises [A], wherein [A] comprises positions XA, XB, and XC, wherein: (a) position XA is T or V; (b) position XB is N; and (c) position XC is N, T, S, R, or K; 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). 135. The AAV capsid variant of embodiment 126 or 134, wherein [A]: (i) comprises TN, NS, NT, NK, NR, VN, or NN; (ii) is or comprises TNN, TNS, TNT, VNN, TNR, or TNK. 136. The AAV capsid variant of any one of embodiments 126, 134, or 135, wherein [A]-[B] is or comprises: (i) TNNQSS (SEQ ID NO: 183), TNSSLY (SEQ ID NO: 648), TNTSAT (SEQ ID NO: 649), TNSSLS (SEQ ID NO: 647), TNRASS (SEQ ID NO: 4825), VNNQSS (SEQ ID NO: 4826), or TNKSAT (SEQ ID NO: 651); (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). 137. The AAV capsid variant of any one of embodiments 126 or 134-136, wherein [A]-[B]-[C] is or comprises: 63 319351975.1Attorney Docket Number: V2071-3033PCT (i) TNNQSSYPAEVVQK (SEQ ID NO: 500), TNSSLYYPAEVVQK (SEQ ID NO: 655), TNTSATYPAEVVQK (SEQ ID NO: 656), TNSSLSYPAEVVQK (SEQ ID NO: 657), TNNQSRYPAEVVQK (SEQ ID NO: 510), TNNQSKYPAEVVQK (SEQ ID NO: 503), TNRASSYPAEVVQK (SEQ ID NO: 4805), VNNQSSYPAEVVQK (SEQ ID NO: 4806), or TNKSATYPAEVVQK (SEQ ID NO: 663); (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). 138. The AAV capsid variant of any one of embodiments 126 or 134-137, wherein [A]-[B]-[C] is or comprises TNNQSSYPAEVVQK (SEQ ID NO: 500). 139. The AAV capsid variant of any one of embodiments 67-98 or 125-138, which further comprises one or both of an amino acid other than T at position 578 (e.g., P, R, or N) and / or an amino acid other than A at position 579 (e.g., G or D), 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 67-98 or 125-138, which further comprises: (i) a T at position 578 and / or an A at position 579, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138; (ii) a T at position 578 and / or a D at position 579, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138; (iii) a P at position 578 and / or an A at position 579, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138; (iv) an N at position 578 and / or an A at position 579, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138; or (v) a R at position 578 and / or an G at position 579, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 141. The AAV capsid variant of any one of embodiments 125-140, which further comprises [D], wherein [D] comprises positions X4 and X5, wherein: (a) position X4 is T, N, R, or P; and (b) position X5 is A, G, or D; and 64 319351975.1Attorney Docket Number: V2071-3033PCT 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) or (b). 142. The AAV capsid variant of embodiment 141, wherein [D] is or comprises TA, TD, NA, RG, or PA. 143. The AAV capsid variant of embodiment 126, 141, or 142, wherein [C]-[D] is or comprises: (i) YPAEVVQKTA (SEQ ID NO: 584), YPAEVVQKTD (SEQ ID NO: 719), YPAEVVQKNA (SEQ ID NO: 724), YPAEVVQKRG (SEQ ID NO: 4810), or YPAEVVQKPA (SEQ ID NO: 586); (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, 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). 144. The AAV capsid variant of any one of embodiments 126 or 141-143, wherein [A]-[B]-[C]-[D] is or comprises: (i) TNNQSSYPAEVVQKTA (SEQ ID NO: 1533), TNSSLYYPAEVVQKTA (SEQ ID NO: 2066), TNTSATYPAEVVQKTA (SEQ ID NO: 2067), TNSSLSYPAEVVQKTA (SEQ ID NO: 2068), TNSSLSYPAEVVQKTD (SEQ ID NO: 2070), TNSSLSYPAEVVQKNA (SEQ ID NO: 2072), TNSSLSYPAEVVQKPA (SEQ ID NO: 2073), TNNQSSYPAEVVQKRG (SEQ ID NO: 4685), TNNQSRYPAEVVQKNA (SEQ ID NO: 4683), TNNQSKYPAEVVQKNA (SEQ ID NO: 4705), TNRASSYPAEVVQKTA (SEQ ID NO: 4708), VNNQSSYPAEVVQKTA (SEQ ID NO: 4710), or TNKSATYPAEVVQKTA (SEQ ID NO: 2075); (ii) (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). 145. The AAV capsid variant of any one of embodiments 126 or 141-144, wherein [A]-[B]-[C]-[D] is or comprises TNNQSSYPAEVVQKTA (SEQ ID NO: 1533). 65 319351975.1Attorney Docket Number: V2071-3033PCT 146. An AAV capsid variant (e.g., an AAV5 capsid variant), comprising an amino sequence comprising the following formula: [N0]-[N1]-[N2]-[N3]-[N4], wherein [N2] comprises the amino acid sequence of GPAEV (SEQ ID NO: 4722), YPAEV (SEQ ID NO: 1), YPKEV (SEQ ID NO: 4723), GRAEV (SEQ ID NO: 4724), YPASL (SEQ ID NO: 4725), YPATI (SEQ ID NO: 4726), YPAER (SEQ ID NO: 4727), YPASV (SEQ ID NO: 4728), YPAGV (SEQ ID NO: 4729), wherein one, two, three, or all of: (i) [N0] comprises TNR or VNN; (ii) [N1] comprises VSS; (iii) [N3] comprises IQK; (iv) [N4] comprises RG. 147. The AAV capsid variant of embodiment 146, wherein [N3] comprises VQK or IQK. 148. The AAV capsid variant of embodiment 146 or 147, wherein [N2]-[N3] comprises GPAEVVQK (SEQ ID NO: 4714), YPAEVVQK (SEQ ID NO: 943), YPKEVVQK (SEQ ID NO: 4715), GRAEVVQK (SEQ ID NO: 4716), YPASLVQK (SEQ ID NO: 4717), YPATIVQK (SEQ ID NO: 4718), YPAERIQK (SEQ ID NO: 4719), YPASVVQK (SEQ ID NO: 4720), YPAGVVQK or (SEQ ID NO: 4721). 149. The AAV capsid variant of any one of embodiments 146-148, wherein [N1] comprises QSR, QSS, QSK, VSS, or ASS. 150. The AAV capsid variant of any one of embodiments 146-149, wherein [N1]-[N2] comprises QSRGPAEV (SEQ ID NO: 4767), QSSYPAEV (SEQ ID NO: 96), QSKGPAEV (SEQ ID NO: 4768), QSSYPKEV (SEQ ID NO: 4769), QSSGRAEV (SEQ ID NO: 4770), QSSYPASL (SEQ ID NO: 4771), QSSYPATI (SEQ ID NO: 4812), QSSYPAER (SEQ ID NO: 4772), VSSYPASV (SEQ ID NO: 4773), QSRYPAEV (SEQ ID NO: 100), VSSYPAGV (SEQ ID NO: 4774), QSKYPAEV (SEQ ID NO: 97), or ASSYPAEV (SEQ ID NO: 105). 151. The AAV capsid variant of any one of embodiments 146-150, wherein [N1]-[N2]-[N3] comprises: QSRGPAEVVQK (SEQ ID NO: 4784), QSSYPAEVVQK (SEQ ID NO: 150), QSKGPAEVVQK (SEQ ID NO: 4785), QSSYPKEVVQK (SEQ ID NO: 4786), QSSGRAEVVQK (SEQ ID NO: 4787), QSSYPASLVQK (SEQ ID NO: 4788), QSSYPATIVQK (SEQ ID NO: 4789), QSSYPAERIQK (SEQ ID NO: 4790), VSSYPASVVQK (SEQ ID NO: 4791), QSRYPAEVVQK (SEQ ID NO: 154), VSSYPAGVVQK (SEQ ID NO: 4792), QSKYPAEVVQK (SEQ ID NO: 151), or ASSYPAEVVQK (SEQ ID NO: 159). 66 319351975.1Attorney Docket Number: V2071-3033PCT 152. The AAV capsid variant of any one of embodiments 146-151, wherein [N0] comprises TNN, TNR, or VNN. 153. The AAV capsid variant of any one of embodiments 146-152, wherein [N0]-[N1] comprises TNNQSS (SEQ ID NO: 183), TNNQSK (SEQ ID NO: 184), TNNQSR (SEQ ID NO: 187), TNNVSS (SEQ ID NO: 4793), TNRASS (SEQ ID NO: 4794), or VNNQSS (SEQ ID NO: 4795). 154. The AAV capsid variant of any one of embodiments 146-153, wherein [N0]-[N1]-[N2]-[N3] comprises TNNQSRGPAEVVQK (SEQ ID NO: 4796), TNNQSSYPAEVVQK (SEQ ID NO: 500), TNNQSKGPAEVVQK (SEQ ID NO: 4797), TNNQSSYPKEVVQK (SEQ ID NO: 4798), TNNQSSGRAEVVQK (SEQ ID NO: 4799), TNNQSSYPASLVQK (SEQ ID NO: 4800), TNNQSSYPATIVQK (SEQ ID NO: 4801), TNNQSSYPAERIQK (SEQ ID NO: 4802), TNNVSSYPASVVQK (SEQ ID NO: 4803), TNNQSRYPAEVVQK (SEQ ID NO: 510), TNNVSSYPAGVVQK (SEQ ID NO: 4804), TNNQSKYPAEVVQK (SEQ ID NO: 503), TNRASSYPAEVVQK (SEQ ID NO: 4805), or VNNQSSYPAEVVQK (SEQ ID NO: 4806). 155. The AAV capsid variant of any one of embodiments 146-154, wherein [N4] comprises TA, RG, or NA. 156. The AAV capsid variant of any one of embodiments 146-155, wherein [N3]-[N4] comprises VQKTA (SEQ ID NO: 564), VQKRG (SEQ ID NO: 4807), IQKTA (SEQ ID NO: 4808), or VQKNA (SEQ ID NO: 570). 157. The AAV capsid variant of any one of embodiments 146-156, wherein [N0]-[N1]-[N2]-[N3]- [N4] comprises TNNQSRGPAEVVQKTA (SEQ ID NO: 4684), TNNQSSYPAEVVQKRG (SEQ ID NO: 4685), TNNQSKGPAEVVQKTA (SEQ ID NO: 4686), TNNQSSYPKEVVQKTA (SEQ ID NO: 4694), TNNQSSGRAEVVQKTA (SEQ ID NO: 4696), TNNQSSYPASLVQKTA (SEQ ID NO: 4698), TNNQSSYPATIVQKTA (SEQ ID NO: 4700), TNNQSSYPAERIQKTA (SEQ ID NO: 4701), TNNVSSYPASVVQKTA (SEQ ID NO: 4682), TNNQSRYPAEVVQKNA (SEQ ID NO: 4683), TNNVSSYPAGVVQKTA (SEQ ID NO: 4704), TNNQSKYPAEVVQKNA (SEQ ID NO: 4705), TNRASSYPAEVVQKTA (SEQ ID NO: 4708), or VNNQSSYPAEVVQKTA (SEQ ID NO: 4710). 158. The AAV capsid variant of any one of the embodiments 1-40, 59, 60, 67-98, 139, 140 or 146- 157, wherein [N2]-[N3] is present in loop VIII, optionally wherein loop VIII comprises positions 571- 592 (e.g., amino acids TNNQSSTTAPATGTYNLQEIVP (SEQ ID NO: 736)) numbered according to SEQ ID NO: 138, or positions 571-599, numbered according to SEQ ID NO: 982. 67 319351975.1Attorney Docket Number: V2071-3033PCT 159. The AAV capsid variant of any one of embodiments 2, 15-40, 59, 60, 68, 79-98, 139, 137, or 146-158 wherein [N0], [N1], and / or [N4] is present in loop VIII, optionally wherein loop VIII comprises positions 571-592 (e.g., amino acids TNNQSSTTAPATGTYNLQEIVP (SEQ ID NO: 736)) numbered according to SEQ ID NO: 138, or positions 571-599, numbered according to SEQ ID NO: 982. 160. The AAV capsid variant of any one of embodiments 2, 15-40, 59, 60, 68, 79-98, 139, 140, 145a-- 159, wherein [N0]-[N1]-[N2]-[N3]-[N4] is present in loop VIII, optionally wherein loop VIII comprises positions 571-592 (e.g., amino acids TNNQSSTTAPATGTYNLQEIVP (SEQ ID NO: 736)) numbered according to SEQ ID NO: 138, or positions 571-599, numbered according to SEQ ID NO: 982. 161. The AAV capsid variant of any one of embodiments 1-40, 59, 60, 67-98, 139, 140, or 146-148, wherein [N2] is present immediately subsequent to position 576, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 982. 162. The AAV capsid variant of any one of embodiments 1-40, 59, 60, 67-98, 139, 140, or 146-161, wherein [N2] replaces position 577 (e.g., T577), 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 1-40, 59, 60, 67-98, 139, 140, or 146-162, wherein [N2] is present immediately subsequent to position 576, and wherein [N2] replaces position 577 (e.g., T577), 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 1-40, 59, 60, 67-98, 139, 140, or 146-163, wherein [N2] corresponds to positions 577-581 (e.g., Y577, P578, A579, E580, V581) of SEQ ID NO: 982. 165. The AAV capsid variant of any one of embodiments 1-164, which comprises an amino acid other than T at position 577, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 166. The AAV capsid variant of any one of embodiments 1-165, which comprises a Y at position 577, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 982. 68 319351975.1Attorney Docket Number: V2071-3033PCT 167. The AAV capsid variant of any one of embodiments 1-40, 59, 60, 67-98, 139, 140, or 146-167, wherein X1 of [N2] is present at position 577 (e.g., T577), and positions X2-X5 of [N2] are present immediately subsequent to position 577, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 982. 168. The AAV capsid variant of any one of embodiments 1-40, 59, 60, 67-98, 139, 140, or 146-167, wherein X1 of [N2] corresponds to position 577 (e.g., Y577), X2 of [N2] corresponds to position 578 (e.g., P578), X3 of [N2] corresponds to position 579 (e.g., A579), X4 of [N2] corresponds to position 580 (e.g., E580), and X5 of [N2] corresponds to position 581 (e.g., V581) of SEQ ID NO: 982. 169. The AAV capsid variant of any one of embodiments 1-40, 59, 60, 67-98, 139, 140, or 146-168, wherein [N2]-[N3] is present immediately subsequent to position 576, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 982. 170. The AAV capsid variant of any one of embodiments 1-40, 59, 60, 67-98, 139, 140, or 146-169, wherein [N2]-[N3] replaces position 577 relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 171. The AAV capsid variant of any one of embodiments 1-40, 59, 60, 67-98, 139, 140, or 146-170, wherein [N2]-[N3] is present immediately subsequent to position 576, and wherein [N2]-[N3] replaces position 577 (e.g., T577), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 172. The AAV capsid variant of any one of embodiments 1-40, 59, 60, 67-98, 139, 140, or 146-171, wherein [N2]-[N3] corresponds to positions 577-584 (e.g., Y577, P578, A579, E580, V581, V582, Q583, K584) of SEQ ID NO: 982. 173. The AAV capsid variant of any one of embodiments 1-40, 59, 60, 67-98, 139, 140, or 146-172, wherein [N2]-[N3]-[N4] is present immediately subsequent to position 576, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 982. 174. The AAV capsid variant of any one of embodiments 1-40, 59, 60, 67-98, 139, 140, or 146-173, wherein [N2]-[N3]-[N4] replaces positions 577-579 (e.g., T577, T578, and A579), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 175. The AAV capsid variant of any one of embodiments 1-40, 59, 60, 67-98, 139, 140, or 146-174, wherein [N2]-[N3]-[N4] is present immediately subsequent to position 576, and wherein [N2]-[N3]- 69 319351975.1Attorney Docket Number: V2071-3033PCT [N4] replaces positions 577-579 (e.g., T577, T578, and A579), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 176. The AAV capsid variant of any one of embodiments 1-40, 59, 60, 67-98, 139, 140, or 146-175, wherein [N2]-[N3]-[N4] corresponds to positions 577-586 (e.g., Y577, P578, A579, E580, V581, V582, Q583, K584, T585, A586) of SEQ ID NO: 982. 177. The AAV capsid variant of any one of embodiments 3, 18-40, 59, 60, 68, 79-98, 139, 140, or 146-176, wherein [N1] is present immediately subsequent to position 573, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 982. 178. The AAV capsid variant of any one of embodiments 3, 18-40, 59, 60, 68, 79-98, 139, 140, or 146-177, wherein [N1] replaces positions 574-576 (e.g., Q574, S575, and S576), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 179. The AAV capsid variant of any one of embodiments 3, 18-40, 59, 60, 68, 79-98, 139, 140, or 146-178, wherein [N1] is present immediately subsequent to position 573, and wherein [N1] replaces positions 574-576 (e.g., Q574, S575, and S576), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 180. The AAV capsid variant of any one of embodiments 3, 18-40, 59, 60, 68, 79-98, 139, 140, or 146-179, wherein [N1] replaces positions 574-576 (e.g., Q574, S575, and S576), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 982. 181. The AAV capsid variant of any one of embodiments 3, 18-40, 59, 60, 68, 79-98, 139, 140, or 146-180, wherein [N1] is present immediately subsequent to position 573, and wherein [N1] replaces positions 574-576 (e.g., Q574, S575, and S576), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 982. 182. The AAV capsid variant of any one of embodiments 3, 18-40, 59, 60, 68, 79-98, 139, 140, or 146-181, wherein [N1] corresponds to positions 574-576 (e.g., Q574, S575, and S576) of SEQ ID NO: 982. 183. The AAV capsid variant of any one of embodiments 3, 18-40, 59, 60, 68, 79-98, 139, 140, or 146-182, wherein [N1]-[N2]-[N3]-[N4] is present immediately subsequent to position 573, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 982. 70 319351975.1Attorney Docket Number: V2071-3033PCT 184. The AAV capsid variant of any one of embodiments 3, 18-40, 59, 60, 68, 79-98, 139, 140, or 146-183, wherein [N1]-[N2]-[N3]-[N4] replaces positions 574-579 (e.g., Q574, S575, S576, T577, T578, and A579), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 185. The AAV capsid variant of any one of embodiments 3, 18-40, 59, 60, 68, 79-98, 139, 140, or 146-184, wherein [N1]-[N2]-[N3]-[N4] is present immediately subsequent to position 573, and wherein [N1]-[N2]-[N3]-[N4] replaces positions 574-579 (e.g., Q574, S575, S576, T577, T578, and A579), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 186. The AAV capsid variant of any one of embodiments 3, 18-40, 59, 60, 68, 79-98, 139, 140, or 146-185, wherein [N1]-[N2]-[N3]-[N4] corresponds to positions 574-586 (e.g., Q574, S575, S576, Y577, P578, A579, E580, V581, V582, Q583, K584, T585, A586) of SEQ ID NO: 982. 187. The AAV capsid variant of any one of embodiments 3, 18-40, 59, 60, 68, 79-98, 139, 140, or 146-186 wherein [N0] is present immediately subsequent to position 570, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 188. The AAV capsid variant of any one of embodiments 3, 18-40, 59, 60, 68, 79-98, 139, 140, or 146-187, wherein [N0] replaces positions 571-573 (e.g., T571, N572, and N573), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 189. The AAV capsid variant of any one of embodiments 3, 18-40, 59, 60, 68, 79-98, 139, 140, or 146-188, wherein [N0] is present immediately subsequent to position 570, and wherein [N0] replaces positions 571-573 (e.g., T571, N572, and N573), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 190. The AAV capsid variant of any one of embodiments 3, 18-40, 59, 60, 68, 79-98, 139, 140, or 146-189 wherein [N0] is present immediately subsequent to position 570, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 982. 191. The AAV capsid variant of any one of embodiments 3, 18-40, 59, 60, 68, 79-98, 139, 140, or 146-189, wherein [N0] replaces positions 571-573 (e.g., T571, N572, and N573), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 982. 71 319351975.1Attorney Docket Number: V2071-3033PCT 192. The AAV capsid variant of any one of embodiments 3, 18-40, 59, 60, 68, 79-98, 139, 140, or 146-191, wherein [N0] is present immediately subsequent to position 570, and wherein [N0] replaces positions 571-573 (e.g., T571, N572, and N573), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 982. 193. The AAV capsid variant of any one of embodiments 3, 18-40, 59, 60, 68, 79-98, 139, 140, or 146-192, wherein [N0] corresponds to positions 571-573 (e.g., T571, N572, and N573) of SEQ ID NO: 982. 194. The AAV capsid variant of any one of embodiments 3, 18-40, 59, 60, 68, 79-98, 139, 140, or 146-193, wherein [N0]-[N1]-[N2]-[N3]-[N4] is present immediately subsequent to position 570, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 982. 195. The AAV capsid variant of any one of embodiments 3, 18-40, 59, 60, 68, 79-98, 139, 140, or 146-194, wherein [N0]-[N1]-[N2]-[N3]-[N4] replaces positions 571-579 (e.g., T571, N572, N573, Q574, S575, S576, T577, T578, and A579), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 196. The AAV capsid variant of any one of embodiments 3, 18-40, 59, 60, 68, 79-98, 139, 140, or 146-195, wherein [N0]-[N1]-[N2]-[N3]-[N4] is present immediately subsequent to position 570, and wherein [N0]-[N1]-[N2]-[N3]-[N4] replaces positions 571-579 (e.g., T571, N572, N573, Q574, S575, S576, T577, T578, and A579), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 197. The AAV capsid variant of any one of embodiments 3, 18-40, 59, 60, 68, 79-98, 139, 140, or 146-196, wherein [N0]-[N1]-[N2]-[N3]-[N4] corresponds to positions 571-586 (e.g., T571, N572, N573, Q574, S575, S576, Y577, P578, A579, E580, V581, V582, Q583, K584, T585, A586), of SEQ ID NO: 982. 198. The AAV capsid variant of any one of embodiments 3, 31-40, 68, 94-98, 139, 140, or 146-197, wherein [N4] is present immediately subsequent to position 584, numbered according to SEQ ID NO: 982. 199. The AAV capsid variant of any one of embodiments 3, 31-40, 68, 94-98, 139, 140, or 146-198, wherein [N4] replaces position 578 and 579, numbered according to SEQ ID NO: 138; or positions 585 and 586 numbered according to SEQ ID NO: 982. 72 319351975.1Attorney Docket Number: V2071-3033PCT 200. The AAV capsid variant of any one of embodiments 3, 31-40, 68, 94-98, 139, 140, or 146-199, wherein [N4] is present immediately subsequent to position 584 and replaces positions 585 and 586 numbered according to SEQ ID NO: 982. 201. The AAV capsid variant of any one of embodiments 3, 31-40, 68, 94-98, 139, 140, or 146-200, wherein: (i) XA of [N0] is present at position 571, XB of [N0] is present at position 572, and XC of [N0] is present at position 573, numbered according to SEQ ID NO: 982; (ii) XD of [N1] is present at position 574, XE of [N1] is present at position 575, and XF of [N1] is present at position 576, numbered according to SEQ ID NO: 982; (iii) X1 of [N2] is present at position 577, X2 of [N2] is present at position 578, X3 of [N2] is present at position 579, X4 of [N2] is present at position 580, and X5 of [N2] is present at position 581, numbered according to SEQ ID NO: 982; (iv) [N3] is present at positions 582-584, numbered according to SEQ ID NO: 982; and / or (v) XG of [N4] is present at position 585 and XH of [N4] is present at position 586, numbered according to SEQ ID NO: 982. 202. The AAV capsid variant of any one of embodiments 3, 31-40, 68, 94-98, 139, 140, or 146-201, wherein: (i) [N0] is present at positions 571-573, numbered according to SEQ ID NO: 982; (ii) [N1] is present at positions 574-576, numbered according to SEQ ID NO: 982; (iii) [N2] is present at positions 577-581, numbered according to SEQ ID NO: 982; (iv) [N3] is present at positions 582-584, numbered according to SEQ ID NO: 982; (v) [N4] is present at positions 585-586, numbered according to SEQ ID NO: 982; (vi) [N2]-[N3] is present at positions 577-584, numbered according to SEQ ID NO: 982; and / or (vii) [N0]-[N1]-[N2]-[N3]-[N4] is present at positions 571-586, numbered according to SEQ ID NO: 982. 203. The AAV capsid variant of any one of embodiments 1-40, 59, 60, 67-98, 139, 140, or 146-202, wherein [N3] is present immediately subsequent to [N2]. 204. The AAV capsid variant of any one of embodiments 3, 31-40, 68, 94-98, 139, 140, or 146-203, wherein [N4] is present immediately subsequent to [N3]. 205. The AAV capsid variant of any one of embodiments 1-40, 59, 60, 67-98, 139, 140, or 146-204, which comprises from N-terminus to C-terminus [N2]-[N3]. 73 319351975.1Attorney Docket Number: V2071-3033PCT 206. The AAV capsid variant of any one of embodiments 1-40, 59, 60, 67-98, 139, 140, or 146-205, which comprises from N-terminus to C-terminus [N1]-[N2]-[N3]. 207. The AAV capsid variant of any one of embodiments 3, 18, 19, 28-40, 59, 60, 68, 89-98, 139, 140, or 146-206, which comprises from N-terminus to C-terminus [N0]-[N1]-[N2]-[N3]. 208. The AAV capsid variant of any one of embodiments 3, 18-40, 59, 60, 68, 79-98, 139, 140, or 146-207, which comprises from N-terminus to C-terminus [N1]-[N2]-[N3]-[N4]. 209. The AAV capsid variant of any one of embodiments 3, 18, 19, 28-40, 59, 60, 68, 89-98, 139, 140, or 146-208, which comprises from N-terminus to C-terminus [N0]-[N1]-[N2]-[N3]-[N4]. 210. The AAV capsid variant of any one of embodiments 41-66 or 125-145, wherein [B]-[C] is present in loop VIII, optionally wherein loop VIII comprises positions 571-592 (e.g., amino acids TNNQSSTTAPATGTYNLQEIVP (SEQ ID NO: 736)) numbered according to SEQ ID NO: 138, or positions 571-599, numbered according to SEQ ID NO: 982. 211. The AAV capsid variant of any one of embodiments 42, 52-66, 126, 134-145, or 210, wherein [A] and / or [D] is present in loop VIII, optionally wherein loop VIII comprises positions 571-592 (e.g., amino acids TNNQSSTTAPATGTYNLQEIVP (SEQ ID NO: 736)) numbered according to SEQ ID NO: 138, or positions 571-599, numbered according to SEQ ID NO: 982. 212. The AAV capsid variant of any one of embodiments 42, 52-66, 126, 134-145, 210, or 211, wherein [A]-[B]-[C]-[D] is present in loop VIII, optionally wherein loop VIII comprises positions 571-592 (e.g., amino acids TNNQSSTTAPATGTYNLQEIVP (SEQ ID NO: 736)) numbered according to SEQ ID NO: 138, or positions 571-599, numbered according to SEQ ID NO: 982. 213. The AAV capsid variant of any one of embodiments 41-66, 125-145, or 210-212, wherein [B] is present immediately subsequent to position 573, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 214. The AAV capsid variant of any one of embodiments 41-66, 125-145, or 210-213, wherein [B] replaces positions 574-576 (e.g., Q574, S575, and S576), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 215. The AAV capsid variant of any one of embodiments 41-66, 125-145, or 210-214, wherein [B] is present immediately subsequent to position 573, and wherein [B] replaces positions 574-576 (e.g., 74 319351975.1Attorney Docket Number: V2071-3033PCT Q574, S575, and S576), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 216. The AAV capsid variant of any one of embodiments 41-66, 125-145, or 210-215, wherein [B] is present immediately subsequent to position 573, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 982. 217. The AAV capsid variant of any one of embodiments 41-66, 125-145, or 210-216, wherein [B] replaces positions 574-576 (e.g., Q574, S575, and S576), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 982. 218. The AAV capsid variant of any one of embodiments 41-66, 125-145, or 210-217, wherein [B] is present immediately subsequent to position 573, and wherein [B] replaces positions 574-576 (e.g., Q574, S575, and S576), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 982. 219. The AAV capsid variant of any one of embodiments 41-66, 125-145, or 210-218, wherein [B] corresponds to positions 574-576 (e.g., Q574, S575, and S576) of SEQ ID NO: 982. 220. The AAV capsid variant of any one of embodiments 41-66, 125-145, or 210-219, wherein [B]- [C] is present immediately subsequent to position 573, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 982. 221. The AAV capsid variant of any one of embodiments 41-66, 125-145, or 210-220, wherein [B]- [C] replaces positions 574-577 (e.g., Q574, S575, S576, and T577), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 222. The AAV capsid variant of any one of embodiments 41-66, 125-145, or 210-221, wherein [B]- [C] is present immediately subsequent to position 573, and wherein [B]-[C] replaces positions 574- 577 (e.g., Q574, S575, S576, and T577), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 223. The AAV capsid variant of any one of embodiments 41-66, 125-145, or 210-222, wherein [B]- [C] corresponds to positions 574-584 (e.g., Q574, S575, S576, Y577, P578, A579, E580, V581, V582, Q583, K584) of SEQ ID NO: 982. 75 319351975.1Attorney Docket Number: V2071-3033PCT 224. The AAV capsid variant of any one of embodiments 41-66, 125-145, or 210-223, wherein [B]- [C]-[D] is present immediately subsequent to position 573, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 982. 225. The AAV capsid variant of any one of embodiments 41-66, 125-145, or 210-224, wherein [B]- [C]-[D] replaces positions 574-579 (e.g., Q574, S575, S576, T577, T578, and A579), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 226. The AAV capsid variant of any one of embodiments 41-66, 125-145, or 210-225, wherein [B]- [C]-[D] is present immediately subsequent to position 573, and wherein [B]-[C]-[D] replaces positions 574-579 (e.g., Q574, S575, S576, T577, T578, and A579), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 227. The AAV capsid variant of any one of embodiments 41-66, 125-145, or 210-226, wherein [B]- [C]-[D] corresponds to positions 574-586 (e.g., Q574, S575, S576, Y577, P578, A579, E580, V581, V582, Q583, K584, T585, A586) of SEQ ID NO: 982. 228. The AAV capsid variant of any one of embodiments 41-66, 125-145, or 210-227, wherein [C] is present immediately subsequent to position 576, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 229. The AAV capsid variant of any one of embodiments 41-66, 125-145, or 210-228, wherein [C] replaces position 577 (e.g., T577), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 230. The AAV capsid variant of any one of embodiments 41-66, 125-145, or 210-229, wherein [C] is present immediately subsequent to position 576, and wherein [C] replaces 577 (e.g., T577), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 231. The AAV capsid variant of any one of embodiments 41-66, 125-145, or 210-230, wherein [C] corresponds to positions 577-584 (e.g., Y577, P578, A579, E580, V581, V582, Q583, K584) of SEQ ID NO: 982. 232. The AAV capsid variant of any one of embodiments 42, 52-66, 126, 134-145, or 210-231, wherein [A] is present immediately subsequent to position 570, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 76 319351975.1Attorney Docket Number: V2071-3033PCT 233. The AAV capsid variant of any one of embodiments 42, 52-66, 126, 134-145, or 210-232, wherein [A] replaces positions 571-573 (e.g., T571, N572, and N573), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 234. The AAV capsid variant of any one of embodiments 42, 52-66, 126, 134-145, or 210-233, wherein [A] is present immediately subsequent to position 570, and wherein [A] replaces positions 571-573 (e.g., T571, N572, and N573), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 235. The AAV capsid variant of any one of embodiments 42, 52-66, 126, 134-145, or 210-234, wherein [A] is present immediately subsequent to position 570, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 982. 236. The AAV capsid variant of any one of embodiments 42, 52-66, 126, 134-145, or 210-235, wherein [A] replaces positions 571-573 (e.g., T571, N572, and N573), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 982. 237. The AAV capsid variant of any one of embodiments 42, 52-66, 126, 134-145, or 210-236, wherein [A] is present immediately subsequent to position 570, and wherein [A] replaces positions 571-573 (e.g., T571, N572, and N573), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 982. 238. The AAV capsid variant of any one of embodiments 42, 52-66, 126, 134-145, or 210-237, wherein [A] corresponds to positions 571-573 (e.g., T571, N572, and N573) of SEQ ID NO: 982. 239. The AAV capsid variant of any one of embodiments 42, 52-66, 126, 134-145, or 210-238, wherein [D] is present immediately subsequent to position 584, numbered according to SEQ ID NO: 982. 240. The AAV capsid variant of any one of embodiments 42, 52-66, 126, 134-145, or 210-239, wherein [D] replaces positions 578 and 579 numbered according to SEQ ID NO: 138; or positions 585 and 586, numbered according to SEQ ID NO: 982. 241. The AAV capsid variant of any one of embodiments 42, 52-66, 126, 134-145, or 210-240, wherein [D] is present immediately subsequent to position 584 and replaces positions 585 and 586, numbered according to SEQ ID NO: 982. 77 319351975.1Attorney Docket Number: V2071-3033PCT 242. The AAV capsid variant of any one of embodiments 42, 52-66, 126, 134-145, or 210-241, wherein [A]-[B]-[C]-[D] is present immediately subsequent to position 570, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 982. 243. The AAV capsid variant of any one of embodiments 42, 52-66, 126, 134-145, or 210-242, wherein [A]-[B]-[C]-[D] replaces positions 571-579 (e.g., T571, N572, N573, Q574, S575, S576, T577, T578, and A579), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 244. The AAV capsid variant of any one of embodiments 42, 52-66, 126, 134-145, or 210-243, wherein [A]-[B]-[C]-[D] is present immediately subsequent to position 570, and wherein [A]-[B]-[C]- [D] replaces positions 571-579 (e.g., T571, N572, N573, Q574, S575, S576, T577, T578, and A579), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 245. The AAV capsid variant of any one of embodiments 42, 52-66, 126, 134-145, or 210-244, wherein [A]-[B]-[C]-[D] corresponds to positions 571-586 (e.g., T571, N572, N573, Q574, S575, S576, Y577, P578, A579, E580, V581, V582, Q583, K584, T585, A586) of SEQ ID NO: 982. 246. The AAV capsid variant of any one of embodiments 42, 52-66, 126, 134-145, or 210-245, wherein: (i) XAof [A] is present at position 571, XBof [A] is present at position 572, and XCof [A] is present at position 573, numbered according to SEQ ID NO: 982; (ii) X1 of [B] is present at position 574, X2 of [B] is present at position 575, and X3 of [B] is present at position 576, numbered according to SEQ ID NO: 982; (iii) [C] is present at positions 577-584, numbered according to SEQ ID NO: 982; and / or (iv) X4 of [D] is present at position 585 and position X5 of [D] is present at position 586, numbered according to SEQ ID NO: 982. 247. The AAV capsid variant of any one of embodiments 42, 52-66, 126, 134-145, or 210-246, wherein: (i) [A] is present at positions 571-573, numbered according to SEQ ID NO: 982; (ii) [B] is present at positions 574-576, numbered according to SEQ ID NO: 982; (iii) [C] is present at positions 577-584, numbered according to SEQ ID NO: 982; (iv) [D] is present at positions 585-586, numbered according to SEQ ID NO: 982; and / or (v) [A]-[B]-[C]-[D] is present at positions 571-586, numbered according to SEQ ID NO: 982. 78 319351975.1Attorney Docket Number: V2071-3033PCT 248. The AAV capsid variant of any one of embodiments 41-66, 125-145, or 210-247, wherein [C] is present immediately subsequent to [B]. 249. The AAV capsid variant of any one of embodiments 42, 61-66, 126, 141-145, or 210-248 wherein [D] is present immediately subsequent to [C]. 250. The AAV capsid variant of any one of embodiments 41-66, 125-145, or 210-249, which comprises from N-terminus to C-terminus [B]-[C]. 251. The AAV capsid variant of any one of embodiments 42, 52-66, 126, 134-145, or 210-250, which comprises from N-terminus to C-terminus [A]-[B]-[C]. 252. The AAV capsid variant of any one of embodiments 42, 61-66, 126, 141-145, or 210-241, which comprises from N-terminus to C-terminus [B]-[C]-[D]. 253. The AAV capsid variant of any one of embodiments 42, 61-66, 126, 141-145, or 210-252, which comprises from N-terminus to C-terminus [A]-[B]-[C]-[D]. 254. The AAV capsid variant of any one of the embodiments 99-124, wherein [K1]-[K2] is present in loop VIII. 255. The AAV capsid variant of any one of embodiments 100, 92-124, or 254, wherein [K0], [K3], and / or [K4] is present in loop VIII, optionally wherein loop VIII comprises positions 571-592 (e.g., amino acids TNNQSSTTAPATGTYNLQEIVP (SEQ ID NO: 736)) numbered according to SEQ ID NO: 138, or positions 571-599, numbered according to SEQ ID NO: 982. 256. The AAV capsid variant of any one of embodiments 100, 92-124, 254, or 255, wherein [K0]- [K1]-[K2]-[K3]-[K4] is present in loop VIII, optionally wherein loop VIII comprises positions 571- 592 (e.g., amino acids TNNQSSTTAPATGTYNLQEIVP (SEQ ID NO: 736)) numbered according to SEQ ID NO: 138, or positions 571-599, numbered according to SEQ ID NO: 982. 257. The AAV capsid variant of any one of embodiments 99-124 or 254-256, wherein [K1] is present immediately subsequent to position 574, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 79 319351975.1Attorney Docket Number: V2071-3033PCT 258. The AAV capsid variant of any one of embodiments 99-124 or 254-257, wherein [K1] replaces positions 575-577 (e.g., S575, S576, and T577), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 259. The AAV capsid variant of any one of embodiments 99-124 or 254-258, wherein [K1] is present immediately subsequent to position 574, and wherein [K1] replaces positions 575-577 (e.g., S575, S576, and T577), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 260. The AAV capsid variant of any one of embodiments 100, 116-124, or 254-259, wherein [K1]- [K2]-[K3] is present immediately subsequent to position 574, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 261. The AAV capsid variant of any one of embodiments 100, 116-124, or 254-260, wherein [K1]- [K2]-[K3] replaces positions 575-577 (e.g., S575, S576, and T577), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 262. The AAV capsid variant of any one of embodiments 100, 116-124, or 254-261, wherein [K1]- [K2]-[K3] is present immediately subsequent to position 574, and wherein [K1]-[K2]-[K3] replaces positions 575-577 (e.g., S575, S576, and T577), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 263. The AAV capsid variant of any one of embodiments 100, 121-124, or 254-262, wherein [K1]- [K2]-[K3]-[K4] is present immediately subsequent to position 574, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 264. The AAV capsid variant of any one of embodiments 100, 121-124, or 254-263, wherein [K1]- [K2]-[K3]-[K4] replaces positions 575-579 (e.g., S575, S576, T577, T578, and A579), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 265. The AAV capsid variant of any one of embodiments 100, 121-124, or 254-264, wherein [K1]- [K2]-[K3]-[K4] is present immediately subsequent to position 574, and wherein [K1]-[K2]-[K3]-[K4] replaces positions 575-579 (e.g., S575, S576, T577, T578, and A579), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 80 319351975.1Attorney Docket Number: V2071-3033PCT 266. The AAV capsid variant of any one of embodiments 100, 110-124, or 254-265, wherein [K0] is present immediately subsequent to position 570, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 267. The AAV capsid variant of any one of embodiments 100, 110-124, or 254-266, wherein [K0] replaces positions 571 to 574 (e.g., T571, N572, N573, and Q574), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 268. The AAV capsid variant of any one of embodiments 100, 110-124, or 254-267, wherein [K0] is present immediately subsequent to position 570, and wherein [K0] replaces positions 571 to 574 (e.g., T571, N572, N573, and Q574), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 269. The AAV capsid variant of any one of embodiments 100, 121-124, or 254-268, wherein [K0]- [K1]-[K2]-[K3]-[K4] is present immediately subsequent to position 570, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 270. The AAV capsid variant of any one of embodiments 100, 121-124, or 254-269, wherein [K0]- [K1]-[K2]-[K3]-[K4] replaces positions 571-579 (e.g., T571, N572, N573, Q574, S575, S576, T577, T578, and A579), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 271. The AAV capsid variant of any one of embodiments 100, 121-124, or 254-270, wherein [K0]- [K1]-[K2]-[K3]-[K4] is present immediately subsequent to position 570, and wherein [K0]-[K1]- [K2]-[K3]-[K4] replaces positions 571-579 (e.g., T571, N572, N573, Q574, S575, S576, T577, T578, and A579), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 272. The AAV capsid variant of any one of embodiments 100, 116-124, or 254-271, wherein [K3] is present immediately subsequent [K2]. 273. The AAV capsid variant of any one of embodiments 100, 121-124, or 254-272, wherein [K4] is present immediately subsequent [K3]. 274. The AAV capsid variant of any one of embodiments 100, 121-124, or 254-273, which comprises from N-terminus to C-terminus [K1]-[K2]. 81 319351975.1Attorney Docket Number: V2071-3033PCT 275. The AAV capsid variant of any one of embodiments 100, 116-124, or 254-274, which comprises from N-terminus to C-terminus [K1]-[K2]-[K3]. 276. The AAV capsid variant of any one of embodiments 100, 116-124, or 254-275, which comprises from N-terminus to C-terminus [K0]-[K1]-[K2]-[K3]. 277. The AAV capsid variant of any one of embodiments 100, 121-124, or 254-276, which comprises from N-terminus to C-terminus [K1]-[K2]-[K3]-[K4]. 278. The AAV capsid variant of any one of embodiments 100, 121-124, or 254-277, which comprises from N-terminus to C-terminus [K0]-[K1]-[K2]-[K3]-[K4]. 279. An AAV capsid variant (e.g., an AAV5 capsid variant) comprising: (a) the amino acid sequence of any of the sequences provided in Tables 1, 2A, 2B, 9, 15-20, or 26-30; (b) an amino acid sequence comprising at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 consecutive amino acids from any one of the sequences provided in Tables 1, 2A, 2B, 9, 15-20, or 26- 30; (c) an amino acid sequence comprising 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 Tables 1, 2A, 2B, 9, 15-20, or 26-30; or (d) an amino sequence comprising one, two, or three but no more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to the amino acid sequence of any one of the amino acid sequences provided in Tables 1, 2A, 2B, 9, 15-20, or 26-30; optionally wherein the AAV capsid variant further comprises: (1) the amino acid S, L, or G at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; (2) the amino acid F, M, or V at position 589 numbered according to SEQ ID NO: 982 or at position 582 numbered according to SEQ ID NO: 138; (3) the amino acid S at position 591 number according to SEQ ID NO: 982 or at position 584, numbered according to SEQ ID NO: 138; and / or (4) the amino acid K at position 595 number according to SEQ ID NO: 982 or at position 588, numbered according to SEQ ID NO: 138. 280. An AAV capsid variant (e.g., an AAV5 capsid variant) comprising: 82 319351975.1Attorney Docket Number: V2071-3033PCT (a) the amino acid sequence of any of SEQ ID NOs: 943, 1021, 1024, 1027, 1112, 1142, 1214, 1232, 1254, 1300, 1310, 1327, 1331, 1342, 1419, 1453, 1533, 1538, 1539, 1575, 1578, 1583- 1587, 1590, 1591-1593, 1598-1608, 1610-1624, or 4681-4686, 4694, 4696, 4698, 4700-4705; (b) an amino acid sequence comprising at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 consecutive amino acids from any one of SEQ ID NOs: 943, 1021, 1024, 1027, 1112, 1142, 1214, 1232, 1254, 1300, 1310, 1327, 1331, 1342, 1419, 1453, 1533, 1538, 1539, 1575, 1578, 1583-1587, 1590, 1591-1593, 1598-1608, 1610-1624, or 4682-4686, 4694, 4696, 4698, 4700, 4701, 4704, or 4705; or an amino acid sequence comprising at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 consecutive amino acids from any one of SEQ ID NOs: 4681, 4702, or 4703; (c) an amino acid sequence comprising 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: 943, 1021, 1024, 1027, 1112, 1142, 1214, 1232, 1254, 1300, 1310, 1327, 1331, 1342, 1419, 1453, 1533, 1538, 1539, 1575, 1578, 1583-1587, 1590, 1591-1593, 1598-1608, 1610-1624, or 4681-4686, 4694, 4696, 4698, or 4700-4705; or (d) an amino sequence comprising one, two, or three but no more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to the amino acid sequence of any one of SEQ ID NOs: 943, 1021, 1024, 1027, 1112, 1142, 1214, 1232, 1254, 1300, 1310, 1327, 1331, 1342, 1419, 1453, 1533, 1538, 1539, 1575, 1578, 1583-1587, 1590, 1591-1593, 1598-1608, 1610-1624, or 4681-4686, 4694, 4696, 4698, or 4700-4705 optionally wherein the AAV capsid variant further comprises: (1) the amino acid S or G at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; and / or (2) the amino acid S at position 591 number according to SEQ ID NO: 982 or at position 584, numbered according to SEQ ID NO: 138. 281. An AAV capsid variant (e.g., an AAV5 capsid variant) comprising: (a) the amino acid sequence of any of SEQ ID NOs: 943 or 2064-2080; (b) an amino acid sequence comprising at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 consecutive amino acids from any one of SEQ ID NOs: 943 or 2064-2080; (c) an amino acid sequence comprising 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: 943 or 2064-2080; or (d) an amino sequence comprising one, two, or three but no more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to the amino acid sequence of any one of SEQ ID NOs: 943 or 2064-2080; optionally wherein the AAV capsid variant further comprises: 83 319351975.1Attorney Docket Number: V2071-3033PCT (1) the amino acid S, L, or G at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; (2) the amino acid F, M, or V at position 589 numbered according to SEQ ID NO: 982 or at position 582 numbered according to SEQ ID NO: 138; (3) the amino acid S at position 591 number according to SEQ ID NO: 982 or at position 584, numbered according to SEQ ID NO: 138; and / or (4) the amino acid K at position 595 number according to SEQ ID NO: 982 or at position 588, numbered according to SEQ ID NO: 138. 282. An AAV capsid variant (e.g., an AAV5 capsid variant) comprising: (a) the amino acid sequence of any of SEQ ID NOs: 1021, 1024, 1232, 1300, 1327, 1533, 1538, 1585, 1590, or 1591; (b) an amino acid sequence comprising at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 consecutive amino acids from any one of SEQ ID NOs: 1021, 1024, 1232, 1300, 1327, 1533, 1538, 1585, 1590, or 1591; (c) an amino acid sequence comprising 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: 1021, 1024, 1232, 1300, 1327, 1533, 1538, 1585, 1590, or 1591; or (d) an amino sequence comprising one, two, or three but no more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to the amino acid sequence of any one of SEQ ID NOs: 1021, 1024, 1232, 1300, 1327, 1533, 1538, 1585, 1590, or 1591; optionally wherein the AAV capsid variant further comprises: (1) the amino acid S, L, or G at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; (2) the amino acid F, M, or V at position 589 numbered according to SEQ ID NO: 982 or at position 582 numbered according to SEQ ID NO: 138; (3) the amino acid S at position 591 number according to SEQ ID NO: 982 or at position 584, numbered according to SEQ ID NO: 138; and / or (4) the amino acid K at position 595 number according to SEQ ID NO: 982 or at position 588, numbered according to SEQ ID NO: 138. 283. The AAV capsid variant of any one of embodiments 279-282, which comprises at least 3, 4, 5, 6, or 7 consecutive amino acids from of any one of SEQ ID NOs: 943 or 946-966. 284. The AAV capsid variant of embodiment 279-283, wherein the 3 consecutive amino acids comprise YPA. 84 319351975.1Attorney Docket Number: V2071-3033PCT 285. The AAV capsid variant of embodiment 279-284, wherein the 4 consecutive amino acids comprise YPAE (SEQ ID NO: 21). 286. The AAV capsid variant of embodiment 279-285, wherein the 5 consecutive amino acids comprise YPAEV (SEQ ID NO: 1). 287. The AAV capsid variant of embodiment 279-286, wherein the 6 consecutive amino acids comprise YPAEVV (SEQ ID NO: 725). 288. The AAV capsid variant of embodiment 279-287, wherein the 7 consecutive amino acids comprise YPAEVVQ (SEQ ID NO: 726). 289. The AAV capsid variant of embodiment 279-288, wherein the amino acid sequence comprises YPAEVVQK (SEQ ID NO: 943). 290. The AAV capsid variant of any one of embodiments 279, 280, or 282, wherein: (i) the 3 consecutive amino acids comprise YTP; (ii) the 4 consecutive amino acids comprise YTPS (SEQ ID NO: 26); (iii) the 5 consecutive amino acids comprise YTPSL (SEQ ID NO: 7); (iv) the 6 consecutive amino acids comprise YTPSLV (SEQ ID NO: 727); (v) the 7 consecutive amino acids comprise YTPSLVQ (SEQ ID NO: 728); and / or (vi) the amino acid sequence comprises YTPSLVQK (SEQ ID NO: 952). 291. The AAV capsid variant of any one of embodiments 279, 280, or 282, wherein: (i) the 3 consecutive amino acids comprise YPP; (ii) the 4 consecutive amino acids comprise YPPS (SEQ ID NO: 22); (iii) the 5 consecutive amino acids comprise YPPSL (SEQ ID NO: 2); (iv) the 6 consecutive amino acids comprise YPPSLV (SEQ ID NO: 729); (v) the 7 consecutive amino acids comprise YPPSLVQ (SEQ ID NO: 732); and / or (vi) the amino acid sequence comprises YPPSLVQK (SEQ ID NO: 946). 292. The AAV capsid variant of any one of embodiments 279, 280, or 291, wherein: (i) the 3 consecutive amino acids comprise YPP; (ii) the 4 consecutive amino acids comprise YPPS (SEQ ID NO: 22); (iii) the 5 consecutive amino acids comprise YPPSL (SEQ ID NO: 2); (iv) the 6 consecutive amino acids comprise YPPSLE (SEQ ID NO: 733); (v) the 7 consecutive amino acids comprise YPPSLEQ (SEQ ID NO: 734); and / or 85 319351975.1Attorney Docket Number: V2071-3033PCT (vi) the amino acid sequence comprises YPPSLEQK (SEQ ID NO: 953). 293. The AAV capsid variant of any one of embodiments 279, 280, or 292, wherein: (i) the 3 consecutive amino acids comprise YPP; (ii) the 4 consecutive amino acids comprise YPPS (SEQ ID NO: 22); (iii) the 5 consecutive amino acids comprise YPPSL (SEQ ID NO: 2); (iv) the 6 consecutive amino acids comprise YPPSLV (SEQ ID NO: 729); (v) the 7 consecutive amino acids comprise YPPSLVK (SEQ ID NO: 735); and / or (vi) the amino acid sequence comprises YPPSLVKK (SEQ ID NO: 954). 294. The AAV capsid variant of any one of embodiments 279-289, which comprises an amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to the amino acid sequence of YPAEVVQK (SEQ ID NO: 943). 295. The AAV capsid variant of any one of embodiments 279, 280, 282, or 290-293, which comprises an amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to the amino acid sequence of any of SEQ ID NOs: 1021, 1024, 1232, 1300, 1327, 1533, 1538, 1585, 1590, or 1591. 296. The AAV capsid variant of any one of embodiments 279, 280, 282, or 290-293, which comprises an amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to the amino acid sequence of any of SEQ ID NOs: 946, 952, 953, or 954. 297. The AAV capsid variant of any one of embodiments 279-289 or 296, which comprises 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 the amino acid sequence of YPAEVVQK (SEQ ID NO: 943). 298. The AAV capsid variant of any one of embodiments 279, 280, 282, 290-293, or 295, which comprises 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 the amino acid sequence of any one of SEQ ID NOs: 1021, 1024, 1232, 1300, 1327, 1533, 1538, 1585, 1590, or 1591. 299. The AAV capsid variant of any one of embodiments 279, 280, 282, 290-293, or 296, which comprises an amino acid sequence comprising one, two, or three but no more than four modifications, 86 319351975.1Attorney Docket Number: V2071-3033PCT e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to the amino acid sequence of any one of SEQ ID NOs: 946, 952, 953, or 954. 300. The AAV capsid variant of any one of embodiments 279-289, 294, or 297, which comprises an amino acid sequence encoded by: (i) 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: 944; 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: 944. 301. The AAV capsid variant of any one of embodiments 279-289, 294, 297, or 300, wherein the nucleotide sequence encoding the amino acid sequence comprises: (i) 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: 944; 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: 944. 302. The AAV capsid variant of embodiment 279, which comprises: (a) the amino acid sequence of any of SEQ ID NOs: 2024-2063 or 4706-4713; (b) an amino acid sequence comprising at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 consecutive amino acids from any one of SEQ ID NOs: 2024-2063, 4708, or 4710; or an amino acid sequence comprising at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 consecutive amino acids from any one of SEQ ID NOs: 4706, 4607, 4709, or 4711-4713; (c) an amino acid sequence comprising 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: 2024-2063 or 4706- 4713; or (d) an amino sequence comprising one, two, or three but no more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to the amino acid sequence of any one of SEQ ID NOs: 2024-2063 or 4706-4713. 303. The AAV capsid variant of embodiment 279 or 302, wherein the different amino acids of the amino acid sequence comprising 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: 2024-2063, are present at one or more of the following positions: (i) position 1, wherein the different amino acid is T or L; 87 319351975.1Attorney Docket Number: V2071-3033PCT (ii) position 2, wherein the different amino acid is N, L, K, A, T, or P; (iii) position 3, wherein the different amino acid is N, K, L, A, Y, or S; (iv) position 4, wherein the different amino acid is Q, L, T, S, F, Y, K, or A; (v) position 5, wherein the different amino acid is S, H, A, M, Q, T, V, or F; (vi) position 6, wherein the different amino acid is S, P, V, A, Q, L, T, N, or M; (vii) position 7, wherein the different amino acid is Y, H, S, V, A, L, or T; (viii) position 8, wherein the different amino acid is D, P, A, Q, F, L, S, H, or M; (ix) position 9, wherein the different amino acid is F, A, L, D, or Q; (x) position 10, wherein the different amino acid is T, E, I, or S; (xi) position 11, wherein the different amino acid is V, A, N, or S; (xii) position 12, wherein the different amino acid is V, L, or P; (xiii) position 13, wherein the different amino acid is Q, E, or P; (xiv) position 14, wherein the different amino acid is K, N, S, or L; (xv) position 15, wherein the different amino acid is T, V, M, or L; and / or (xvi) position 16, wherein the different amino acid is A, G, or R. 304. The AAV capsid variant of embodiment 279, which comprises: (a) the amino acid sequence of any one of SEQ ID NOs: 1632-2023; (b) an amino acid sequence comprising at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 consecutive amino acids from any one of SEQ ID NOs: 1632-2023; (c) an amino acid sequence comprising 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: 1632-2023; or (d) an amino sequence comprising one, two, or three but no more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to the amino acid sequence of any one of SEQ ID NOs: 1632-2023. 305. The AAV capsid variant of embodiment 279 or 304, wherein the different amino acids of the amino acid sequence comprising 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: 1632-2023, are present at one or more of the following positions: (i) position 1, wherein the different amino acid is T, G, N, S, E, L, Y, V, or I; (ii) position 2, wherein the different amino acid is D, N, K, E, V, G, R, L, H, F, P, T, A, S, I, or Y; (iii) position 3, wherein the different amino acid is Y, N, K, T, W, Q, M, V, C, A, L, F, H, G, R, S, or P; (iv) position 4, wherein the different amino acid is H, Q, P, E, R, K, A, S, V, L, T, D, I, G, M, or N; 88 319351975.1Attorney Docket Number: V2071-3033PCT (v) position 5, wherein the different amino acid is R, S, K, N, H, G, W, A, P, V, Q, Y, L, or F; (vi) position 6, wherein the different amino acid is G, S, F, R, W, H, I, C, M, A, Y, K, N, Q, V, P, E, D, T, or L; (vii) position 7, wherein the different amino acid is D, Y, S, I, H, F, P, K, R, G, L, Q, A, M, T, N, V, W, C, or E; (viii) position 8, wherein the different amino acid is P, L, Q, T, W, V, G, K, I, Y, N, H, R, D, S, M, A, F, or E; (ix) position 9, wherein the different amino acid is A, R, T, Q, S, M, L, E, K, V, G, D, N, H, F, P, or I; (x) position 10, wherein the different amino acid is K, E, Q, H, V, G, R, S, P, I, N, M, A, L, D, or T; (xi) position 11, wherein the different amino acid is V, A, E, N, R, L, M, T, Q, S, K, C, G, D, Y, P, H, F, or I; (xii) position 12, wherein the different amino acid is V, P, L, S, T, N, A, G, K, R, I, H, E, Q, or M; (xiii) position 13, wherein the different amino acid is Q, K, N, A, H, R, T, V, E, I, P, G, S, or L; (xiv) position 14, wherein the different amino acid is K, E, I, Y, Q, R, G, D, L, N, or S; (xv) position 15, wherein the different amino acid is S, T, N, Q, I, P, E, G, K, M, or H; and / or (xvi) position 16, wherein the different amino acid is A, D, L, Y, Q, or T. 306. The AAV capsid variant of embodiment 279, wherein: (a) the amino acid sequence of any one of SEQ ID NOs: 4681-4686, 4694, 4696, 4698, or 4700-4713; (b) an amino acid sequence comprising at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 consecutive amino acids from any one of SEQ ID NOs: 4681-4686, 4694, 4696, 4698, or 4700-4713; (c) an amino acid sequence comprising 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: 4681-4686, 4694, 4696, 4698, or 4700-4713; or (d) an amino sequence comprising one, two, or three but no more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to the amino acid sequence of any one of SEQ ID NOs: 4681-4686, 4694, 4696, 4698, or 4700-4713. 307. The AAV capsid variant of any one of embodiments 279-306, wherein the amino acid sequence is present in loop VIII. 89 319351975.1Attorney Docket Number: V2071-3033PCT 308. The AAV capsid variant of any one of embodiments 279-307, wherein the amino acid sequence is present immediately subsequent to position 570, 571, 572, 573, 574, 575, or 576, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 982. 309. The AAV capsid variant of any one of embodiments 279-308, wherein the amino acid sequence replaces one, two, three, four, five or all of positions 571, 572, 573, 574, 575, and / or 576 (e.g., positions T571, N572, N573, Q574, S575, S576, T577, T578, and / or A579), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 310. The AAV capsid variant of any one of embodiments 279-309, wherein the amino acid sequence is present immediately subsequent to position 576, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 982. 311. The AAV capsid variant of any one of embodiments 279-310, which comprises an amino acid residue other than T at position 577, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 312. The AAV capsid variant of any one of embodiments 279-311, which comprises the amino acid Y at position 577, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 982. 313. The AAV capsid variant of any one of embodiments 279-312, which comprises the substitution T577Y, numbered according to SEQ ID NO: 138. 314. The AAV capsid variant of any one of embodiments 311-313, wherein the amino acid sequence is or comprises YPAEVVQK (SEQ ID NO: 943), and starts at position 577, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 982. 315. The AAV capsid variant of any one of embodiments 279-289, 294, 297, 300, 301, or 307-314, which comprises an amino acid other than T at position 577, and further comprises the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered relative to SEQ ID NO: 138. 316. The AAV capsid variant of any one of embodiments 279-289, 294, 297, 300, 301, or 307-315, which comprises the amino acid Y at position 577, and further comprises the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered relative to SEQ ID NO: 138. 90 319351975.1Attorney Docket Number: V2071-3033PCT 317. The AAV capsid variant of any one of embodiments 279-289, 294, 297, 300, 301, or 307-316, which comprises the amino acid Y at position 577, and further comprises the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577 (e.g., at positions 578-584), numbered relative to SEQ ID NO: 982. 318. The AAV capsid variant of any one of embodiments 279-289, 294, 297, 300, 301, or 307-317, which comprises the amino acid sequence of YPAEVVQK (SEQ ID NO: 943), wherein the amino acid sequence replaces position 577 (e.g., T577), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 319. The AAV capsid variant of any one of embodiments 279-289, 294, 297, 300, 301, or 307-318, which comprises the amino acid sequence of YPAEVVQK (SEQ ID NO: 943), wherein the amino acid sequence: (i) is present immediately subsequent to position 576; and (ii) replaces position 577 (e.g., T577), wherein in (i) and (ii) are numbered relative to SEQ ID NO: 138. 320. The AAV capsid variant of any one of embodiments 279-289, 294, 297, 300, 301, or 307-319, which further comprises an amino acid other than T at position 571 (e.g., I or V), numbered relative to SEQ ID NO: 138 or SEQ ID NO: 982. 321. The AAV capsid variant of any one of embodiments 279-289, 294, 297, 300, 301, or 307-320, which further comprises I or V at position 571, numbered relative to SEQ ID NO: 138 or SEQ ID NO: 982. 322. The AAV capsid variant of any one of embodiments 279-289, 294, 297, 300, 301, or 307-321, which further comprises one, two, or all of an amino acid other than Q at position 574 (e.g., A, V, or T), S at position 575 (e.g., G), and / or S (e.g., A, L, K, or R) at position 576, numbered relative to SEQ ID NO: 138 or SEQ ID NO: 982. 323. The AAV capsid variant of any one of embodiments 279-289, 294, 297, 300, 301, or 307-322, which further comprises: (i) A at position 574, G at position 575, and A at position 576, numbered relative to SEQ ID NO: 138 or 982; (ii) T at position 574 and L at position 576, numbered relative to SEQ ID NO: 138 or 982; (iii) A at position 574, S at position 575, and S at position 576, numbered relative to SEQ ID NO: 138 or 982; 91 319351975.1Attorney Docket Number: V2071-3033PCT (iv) V at position 574, S at position 575, and S at position 576, numbered relative to SEQ ID NO: 138 or 982. 324. The AAV capsid variant of any one of embodiments 279-289, 294, 297, 300, 301, or 307-322, which further comprises: (i) K at position 576, numbered relative to SEQ ID NO: 138 or 982; or (ii) R at position 576, numbered relative to SEQ ID NO: 138 or 982. 325. The AAV capsid variant of any one of embodiments 279-289, 294, 297, 300, 301, or 307-323, which comprises: (i) A at position 574, G at position 575, A at position 576, and Y at position 577, numbered relative to SEQ ID NO: 138 or 982; and (ii) the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 138 or 982. 326. The AAV capsid variant of any one of embodiments 279-289, 294, 297, 300, 301, or 307-323, which comprises: (i) T at position 574, L at position 576, and Y at position 577, numbered relative to SEQ ID NO: 138 or 982; and (ii) the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 138 or 982. 327. The AAV capsid variant of any one of embodiments 279-289, 294, 297, 300, 301, 306-322, or 324, which comprises: (i) K at position 576 and Y at position 577, numbered relative to SEQ ID NO: 138 or 982; and (ii) the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 138 or 982. 328. The AAV capsid variant of any one of embodiments 279-289, 294, 297, 300, 301, 308-322, or 324, which comprises: (i) R at position 576 and Y at position 577, numbered relative to SEQ ID NO: 138 or 982; and (ii) the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 138 or 982. 329. The AAV capsid variant of any one of embodiments 279-289, 294, 297, 300, 301, 307-321, which comprises: (i) I at position 571 and Y at position 577, numbered relative to SEQ ID NO: 138 or 982; and 92 319351975.1Attorney Docket Number: V2071-3033PCT (ii) the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 138 or 982. 330. The AAV capsid variant of any one of embodiments 279, 280, 282, 293, 295, 296, 297, or 299, which comprises Y at position 577 and the amino acid sequence TPSLVQK (SEQ ID NO: 53), which is present immediately subsequent to position 577, all numbered according to SEQ ID NO: 138 or 982. 331. The AAV capsid variant of any one of embodiments 279, 280, 282, 293, 295, 296, 297, or 299, which comprises Y at position 577 and the amino acid sequence PPSLVQK (SEQ ID NO: 47), which is present immediately subsequent to position 577, all numbered according to SEQ ID NO: 138 or 982. 332. The AAV capsid variant of any one of embodiments 279, 280, 282, 293, 295, 296, 297, or 299, which comprises Y at position 577 and the amino acid sequence PPSLEQK (SEQ ID NO: 54), which is present immediately subsequent to position 577, all numbered according to SEQ ID NO: 138 or 982. 333. The AAV capsid variant of any one of embodiments 279, 280, 282, 293, 295, 296, 297, or 299, which comprises Y at position 577 and the amino acid sequence PPSLVKK (SEQ ID NO: 55), which is present immediately subsequent to position 577, all numbered according to SEQ ID NO: 138 or 982. 334. An AAV capsid variant (e.g., an AAV5 capsid variant) comprising: (i) R at position 576 and G at position 577, numbered according to SEQ ID NO: 138 or 982; and (ii) the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 138 or 982. 335. An AAV capsid variant (e.g., an AAV5 capsid variant) comprising: (i) Y at position 577, numbered according to SEQ ID NO: 982 or 138; (ii) the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138; and (iii) R at position 585 and G at position 586, numbered according to SEQ ID NO: 982; or an R at position 578 and G at position 579, numbered according to SEQ ID NO: 138. 336. An AAV capsid variant (e.g., an AAV5 capsid variant) comprising: 93 319351975.1Attorney Docket Number: V2071-3033PCT (i) K at position 576 and G at position 577, numbered according to SEQ ID NO: 138 or 982; and (ii) the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 138 or 982. 337. An AAV capsid variant (e.g., an AAV5 capsid variant) comprising: (i) Y at position 577, numbered according to SEQ ID NO: 982 or 138; and (ii) the amino acid sequence of PKEVVQK (SEQ ID NO: 4749), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138. 338. An AAV capsid variant (e.g., an AAV5 capsid variant) comprising: (i) G at position 577, numbered according to SEQ ID NO: 982 or 138; and (ii) the amino acid sequence of RAEVVQK (SEQ ID NO: 4750), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138. 339. An AAV capsid variant (e.g., an AAV5 capsid variant) comprising: (i) Y at position 577, numbered according to SEQ ID NO: 982 or 138; and (ii) the amino acid sequence of PASLVQK (SEQ ID NO: 4751), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138. 340. An AAV capsid variant (e.g., an AAV5 capsid variant) comprising: (i) Y at position 577, numbered according to SEQ ID NO: 982 or 138; and (ii) the amino acid sequence of PATIVQK (SEQ ID NO: 4752), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138. 341. An AAV capsid variant (e.g., an AAV5 capsid variant) comprising: (i) Y at position 577, numbered according to SEQ ID NO: 982 or 138; and (ii) the amino acid sequence of PAERIQK (SEQ ID NO: 4753), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138. 342. An AAV capsid variant (e.g., an AAV5 capsid variant) comprising: (i) V at position 574 and Y at position 577, numbered relative to SEQ ID NO: 982 or 138; and (ii) the amino acid sequence of PASVVQK (SEQ ID NO: 4754), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138. 343. An AAV capsid variant (e.g., an AAV5 capsid variant) comprising: (i) R at position 576 and Y at position 577, numbered relative to SEQ ID NO: 982 or 138; 94 319351975.1Attorney Docket Number: V2071-3033PCT (ii) the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138; and (iii) N at position 585, numbered according to SEQ ID NO: 982; or N at position 578, numbered according to SEQ ID NO: 138. 344. An AAV capsid variant (e.g., an AAV5 capsid variant) comprising: (i) V at position 574 and Y at position 577, numbered relative to SEQ ID NO: 982 or 138; and (ii) the amino acid sequence of PAGVVQK (SEQ ID NO: 4755), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138. 345. An AAV capsid variant (e.g., an AAV5 capsid variant) comprising: (i) K at position 576 and Y at position 577, numbered relative to SEQ ID NO: 982 or 138; and (ii) the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138; and (iii) N at position 585, numbered according to SEQ ID NO: 982; or N at position 578, numbered according to SEQ ID NO: 138. 346. An AAV capsid variant (e.g., an AAV5 capsid variant) comprising: (i) R at position 573, A at position 574 and Y at position 577, numbered relative to SEQ ID NO: 982 or 138; and (ii) the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138. 347. An AAV capsid variant (e.g., an AAV5 capsid variant) comprising: (i) V at position 571 and Y at position 577, numbered relative to SEQ ID NO: 982 or 138; and (ii) the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138. 348. The AAV capsid variant of any one of the preceding embodiments, which comprises the amino acid S, L, or G at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138. 349. The AAV capsid variant of any one of the preceding embodiments, which comprises the amino acid F, M, or V at position 589 numbered according to SEQ ID NO: 982 or at position 582 numbered according to SEQ ID NO: 138. 350. The AAV capsid variant of any one of the preceding embodiments, which comprises: 95 319351975.1Attorney Docket Number: V2071-3033PCT (i) the amino acid S, L, or G at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; and (ii) the amino acid F, M, or V at position 589 numbered according to SEQ ID NO: 982 or at position 582 numbered according to SEQ ID NO: 138. 351. The AAV capsid variant of any one of embodiments 1-350, which comprises: (i) the amino acid S at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; and (ii) the amino acid F at position 589 numbered according to SEQ ID NO: 982 or at position 582 numbered according to SEQ ID NO: 138. 352. The AAV capsid variant of any one of embodiments 1-350, which comprises: (i) the amino acid S at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; and (ii) the amino acid M at position 589 numbered according to SEQ ID NO: 982 or at position 582 numbered according to SEQ ID NO: 138. 353. The AAV capsid variant of any one of embodiments 1-350, which comprises: (i) the amino acid L at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; and (ii) the amino acid F at position 589 numbered according to SEQ ID NO: 982 or at position 582 numbered according to SEQ ID NO: 138. 354. The AAV capsid variant of any one of embodiments 1-350, which comprises: (i) the amino acid G at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; and (ii) the amino acid V at position 589 numbered according to SEQ ID NO: 982 or at position 582 numbered according to SEQ ID NO: 138. 355. The AAV capsid variant of any one of the preceding embodiments, which comprises the amino acid S at position 591 number according to SEQ ID NO: 982 or at position 584, numbered according to SEQ ID NO: 138. 356. The AAV capsid variant of any one of the preceding embodiments, which comprises the amino acid K at position 595 number according to SEQ ID NO: 982 or at position 588, numbered according to SEQ ID NO: 138. 96 319351975.1Attorney Docket Number: V2071-3033PCT 357. An AAV capsid variant comprising: (i) Y at position 577, numbered relative to SEQ ID NO: 982 or 138; (ii) the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138; and (iii) S at position 591, numbered according to SEQ ID NO: 982; or S at position 584, numbered according to SEQ ID NO: 138. 358. An AAV capsid variant comprising: (i) Y at position 577, numbered relative to SEQ ID NO: 982 or 138; (ii) the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138; and (iii) S at position 588, numbered according to SEQ ID NO: 982; or S at position 581, numbered according to SEQ ID NO: 138. 359. An AAV capsid variant comprising: (i) Y at position 577, numbered relative to SEQ ID NO: 982 or 138; (ii) the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138; and (iii) G at position 588, numbered according to SEQ ID NO: 982; or G at position 581, numbered according to SEQ ID NO: 138. 360. An AAV capsid variant comprising: (i) Y at position 577, numbered relative to SEQ ID NO: 982 or 138; (ii) the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138; and (iii) S at position 588 and F at position 589, numbered according to SEQ ID NO: 982; or S at position 581 and F at position 582, numbered according to SEQ ID NO: 138. 361. An AAV capsid variant comprising: (i) Y at position 577, numbered relative to SEQ ID NO: 982 or 138; (ii) the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138; and (iii) F at position 589, numbered according to SEQ ID NO: 982; or F at position 582, numbered according to SEQ ID NO: 138. 362. An AAV capsid variant comprising: (i) Y at position 577, numbered relative to SEQ ID NO: 982 or 138; 97 319351975.1Attorney Docket Number: V2071-3033PCT (ii) the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138; and (iii) S at position 588 and M at position 589, numbered according to SEQ ID NO: 982; or S at position 581 and M at position 582, numbered according to SEQ ID NO: 138. 363. An AAV capsid variant comprising: (i) Y at position 577, numbered relative to SEQ ID NO: 982 or 138; (ii) the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138; and (iii) L at position 588 and F at position 589, numbered according to SEQ ID NO: 982; or L at position 581 and F at position 582, numbered according to SEQ ID NO: 138. 364. An AAV capsid variant comprising: (i) Y at position 577, numbered relative to SEQ ID NO: 982 or 138; (ii) the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138; and (iii) L at position 588, numbered according to SEQ ID NO: 982; or L at position 581, numbered according to SEQ ID NO: 138. 365. An AAV capsid variant comprising: (i) Y at position 577, numbered relative to SEQ ID NO: 982 or 138; (ii) the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138; and (iii) G at position 588 and V at position 589, numbered according to SEQ ID NO: 982; or G at position 581 and V at position 582, numbered according to SEQ ID NO: 138. 366. An AAV capsid variant comprising: (i) Y at position 577, numbered relative to SEQ ID NO: 982 or 138; (ii) the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138; and (iii) K at position 595, numbered according to SEQ ID NO: 982; or K at position 588, numbered according to SEQ ID NO: 138. 367. The AAV capsid variant, of any one of the preceding embodiments, which further comprises a modification, e.g., an insertion, substitution (e.g., conservative substitution), and / or deletion, in loop I, II, IV, and / or VI. 98 319351975.1Attorney Docket Number: V2071-3033PCT 368. 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), insertions, or deletions, but not more than 30, 20 or 10 modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to the amino acid sequence of SEQ ID NO: 138. 369. 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. 370. 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. 371. The AAV capsid variant, of any one of the preceding embodiments, which comprises the amino acid sequence of SEQ ID NO: 138. 372. The AAV capsid variant, of any one of the preceding embodiments, which comprises an amino acid sequence encoded by 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. 373. 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. 374. 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. 375. The AAV capsid variant, of any one of embodiments 1-98, 125-254, 279-289, 294, 297, 300, 301, 307-319, or 367-374, which comprises the amino acid sequence corresponding to positions 137- 731, e.g., a VP2, of SEQ ID NO: 982, or a sequence with at least 80% (e.g., at least about 85, 90, 95, 96, 97, 98, or 99%) sequence identity thereto. 376. The AAV capsid variant, of any one of embodiments 1-98, 125-254, 279-289, 294, 297, 300, 301, 307-319, or 367-375, which comprises the amino acid sequence corresponding to positions 193- 99 319351975.1Attorney Docket Number: V2071-3033PCT 731, e.g., a VP3, of SEQ ID NO: 982, or a sequence with at least 80% (e.g., at least about 85, 90, 95, 96, 97, 98, or 99%) sequence identity thereto. 377. The AAV capsid variant, of any one of embodiments 1-376, which comprises the amino acid sequence corresponding to positions 137-724, 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. 378. The AAV capsid variant, of any one of embodiments 1-377, which comprises the amino acid sequence corresponding to positions 193-724, 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. 379. The AAV capsid variant, of any one of embodiments 279-289, 294, 297, 300, 301, 306-319, or 367-374, comprising an amino acid sequence comprising at least 3, 4, 5, or 6 consecutive amino acids from the amino acid sequence of YPAEVVQK (SEQ ID NO: 943), wherein: (i) the 3 consecutive amino acids comprise YPA; (ii) the 4 consecutive amino acids comprise YPAE (SEQ ID NO: 21); (iii) the 5 consecutive amino acids comprise YPAEV (SEQ ID NO: 1); (iv) the 6 consecutive amino acids comprise YPAEVV (SEQ ID NO: 725); (v) the 7 consecutive amino acids comprise YPAEVVQ (SEQ ID NO: 726); wherein the AAV capsid variant comprises the amino acid sequence of SEQ ID NO: 739, or an amino acid sequence at least 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 739. 380. The AAV capsid variant, of any one of embodiments 279-289, 294, 297, 300, 301, 306-319, 367-374, or 379, comprising an amino acid sequence comprising at least 3, 4, 5, or 6 consecutive amino acids from the amino acid sequence of YPAEVVQK (SEQ ID NO: 943), wherein: (i) the 3 consecutive amino acids comprise YPA; (ii) the 4 consecutive amino acids comprise YPAE (SEQ ID NO: 21); (iii) the 5 consecutive amino acids comprise YPAEV (SEQ ID NO: 1); (iv) the 6 consecutive amino acids comprise YPAEVV (SEQ ID NO: 725); (v) the 7 consecutive amino acids comprise YPAEVVQ (SEQ ID NO: 726); 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 137-724 of SEQ ID NO: 138 or positions 137-731 of SEQ ID NO: 982; (c) a VP3 protein comprising the amino acid sequence of positions 193-724 of SEQ ID NO: 138 or positions 193-731 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). 100 319351975.1Attorney Docket Number: V2071-3033PCT 381. The AAV capsid variant, of any one of embodiments 279-289, 294, 297, 300, 301, 306-319, 367-374, or 380, comprising one, two, or three but no more than four different amino acids, relative to the amino acid sequence of YPAEVVQK (SEQ ID NO: 943), 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 137-724 of SEQ ID NO: 138 or positions 137-731 of SEQ ID NO: 982; (c) a VP3 protein comprising the amino acid sequence of positions 193-724 of SEQ ID NO: 138 or positions 193-731 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). 382. The AAV capsid variant, of any one of embodiments 279-289, 294, 297, 300, 301, 306-319, 367-374, or 379-381, comprising one, two, or three but no more than four different amino acids, relative to the amino acid sequence of YPAEVVQK (SEQ ID NO: 943), wherein the AAV capsid variant comprises the amino acid sequence of SEQ ID NO: 739; or an amino acid sequence at least 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 739. 383. The AAV capsid variant, of any one of embodiments 279-289, 294, 297, 300, 301, 306-319, 367-374, or 379-381, comprising one or two, but no more than three substitutions relative to the amino acid sequence of YPAEVVQK (SEQ ID NO: 943), 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. 384. The AAV capsid variant, of any one of embodiments 1-98, 125-241, 279-289, 294, 297, 300, 301, 306-319, or 367-374, or 379-383, 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. 385. The AAV capsid variant, of any one of embodiments 1-98, 125-241, 279-289, 294, 297, 300, 301, 306-319, 367-374, or 379-384, which comprises the amino acid sequence of SEQ ID NO: 982 or an amino acid sequence with at least 95% identity thereto. 101 319351975.1Attorney Docket Number: V2071-3033PCT 386. The AAV capsid variant, of any one of embodiments 1-98, 125-241, 279-289, 294, 297, 300, 301, 306-319, 367-374, or 379-385, which comprises the amino acid sequence of SEQ ID NO: 982 or an amino acid sequence with at least 98% identity thereto. 387. The AAV capsid variant of any one of embodiments 1-98, 125-241, 279-289, 294, 297, 300, 301, 306-319, 367-374, or 379-386, which comprises an amino acid sequence comprising at least one, two or three modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, but not more than 30, 20 or 10 modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to the amino acid sequence of SEQ ID NO: 982. 388. The AAV capsid variant, of any one of embodiments 1-98, 125-241, 279-289, 294, 297, 300, 301, 306-319, 367-374, or 379-387, 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. 389. The AAV capsid variant, of any one of the preceding embodiments 1-98, 125-241, 279-289, 294, 297, 300, 301, 306-319, 367-374, or 379-388, 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. 390. The AAV capsid variant, of any one of the preceding embodiments, wherein the nucleotide sequence encoding the capsid variant is codon optimized. 391. An AAV capsid variant (e.g., an AAV5 capsid variant) comprising the amino acid sequence of any one of embodiments 279-289, 294, 297, 300, 301, 306-319, 367-374, or 379-388, and further comprising an amino acid sequence at least 80% (e.g., at least about 85, 90, 95, 96, 97, 98, or 99%) identical to SEQ ID NO: 982. 392. An AAV capsid variant (e.g., an AAV5 capsid variant) comprising an amino acid sequence at least 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 739, wherein the AAV capsid variant comprises the amino acid sequence of YPAEVVQK (SEQ ID NO: 943). 393. The AAV capsid variant of embodiment 392, wherein the AAV capsid variant comprises the amino acid sequence of SEQ ID NO: 739. 102 319351975.1Attorney Docket Number: V2071-3033PCT 394. An AAV capsid variant (e.g., an AAV5 capsid variant) comprising the amino acid sequence of SEQ ID NO: 982. 395. An AAV capsid variant (e.g., an AAV5 capsid variant) comprising an amino acid sequence encoded by the nucleotide sequence of SEQ ID NO: 984, or a nucleotide sequence at least 95% identical thereto. 396. The AAV capsid variant of any one embodiments 1-66, 139, 140, 146-241, 279, 280, 292-301, or 306-345, 348-350, 355-359, or 367-395, 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. 397. The AAV capsid variant of any one embodiments 1-66, 139, 140, 146-241, 279, 280, 292-301, or 306-345, 348-350, 355-359, or 367-350, 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: 982. 398. The AAV capsid variant of any one embodiments 1-66, 139, 140, 146-241, 279, 280, 292-301, 306-345, 348-350, 355-359, or 367-397, 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: 139. 399. The AAV capsid variant of any one of embodiments 1-66, 139, 140, 146-241, 267, 268, 270-289, 294-345, 348-350, 355-359, or 367-352, which transduces a brain region, e.g., a temporal cortex, perirhinal cortex, globus pallidus, putamen, caudate, thalamus, hippocampus, geniculate nucleus, Purkinje Layer, deep cerebellar nuclei, and / or cerebellum, optionally wherein the level of transduction is at least 1.5, 2.2, 2.4, 2.5, 2.6, 2.7, 3.0, 3.2, 3.5, 3.7, 4.0, 4.2, 4.5, 4.7, 4.9, 5, 10, 15, 20, 25, 30, 35- fold greater as compared to a reference sequence of SEQ ID NO: 139, e.g., when measured by an assay, e.g., an immunohistochemistry assay or a qPCR assay, e.g., as described in Example 2. 400. The AAV capsid variant of any one of embodiments 1-66, 139, 140, 146-241, 279, 280, 292-301, 306-345, 348-350, 355-359, or 367-399, which is enriched at least about 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 15, 17, 20, 25, 30, 35, 40, 45, 50, 55, 60, or 65-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. 401. The AAV capsid variant of any one of embodiments 1-66, 139, 140, 146-241, 279, 280, 292-301, 306-345, 348-350, 355-359, or 367-400, which is enriched at least about 10, 12, 15, 17, 20, 25, 30, 35, 103 319351975.1Attorney Docket Number: V2071-3033PCT 40, 45, 50, 55, 60, 61, 62, 63, 64, or 65-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. 402. The AAV capsid variant of any one of embodiments 1-66, 139, 140, 146-241, 279, 280, 292-301, 306-345, 348-350, 355-359, or 367-401, which is enriched in the brain of at least two to three species, e.g., a non-human primate and rodent (e.g., rat and / or mouse), e.g., as compared to a reference sequence of SEQ ID NO: 138. 403. The AAV capsid variant, of any one of embodiments 1-66, 139, 140, 146-241, 279, 280, 292- 301, 306-345, 348-350, 355-359, or 367-402, which is enriched at least about 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 15, 17, 20, 25, 30, 35, 40, 45-fold, in the brain of at least two to three species, e.g., a non-human primate and rodent (e.g., rat and / or mouse), compared to a reference sequence of SEQ ID NO: 138, e.g., when measured by an assay as described in Examples 1, 2, 4, and 5. 404. The AAV capsid variant of embodiment 402 or 403, wherein the at least two to three species are Macaca fascicularis, Chlorocebus sabaeus, Callithrix jacchus, rat, and / or mouse (e.g., BALB / c mice). 405. The AAV capsid variant, of any one of embodiments 1-66, 139, 140, 146-241, 279, 280, 292- 301, 306-345, 348-350, 355-359, or 367-404, which is enriched at least about 1.5, 2, 2.5, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 100, 125, 150, 175, 200, or 225-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 4. 406. The AAV capsid variant of any one of embodiments 1-66, 139, 140, 146-241, 279, 280, 292-301, 306-345, 348-350, 355-359, or 367-405, which delivers an increased level of a payload to a brain region, optionally wherein the level of the payload is increased by at least 20, 25, 30, 35-fold, as compared to a reference sequence of SEQ ID NO: 139, e.g., when measured by an assay, e.g., a qRT- PCR or a qPCR assay (e.g., as described in Example 2). 407. The AAV capsid variant of any one of embodiments 1-66, 139, 140, 146-241, 279, 280, 292-301, 306-345, 348-350, 355-359, or 367-406, which delivers an increased level of viral genomes to a brain region, optionally wherein the level of viral genomes is increased by at least 1.5, 2.2, 2.4, 2.5, 2.6, 2.7, 3.0, 3.2, 3.5, 3.7, 4.0, 4.2, 4.5, 4.7, 4.9, or 5-fold, as compared to a reference sequence of SEQ ID NO: 139, e.g., when measured by an assay, e.g., a qRT-PCR or a qPCR assay (e.g., as described in Example 2). 104 319351975.1Attorney Docket Number: V2071-3033PCT 408. The AAV capsid variant of any one of embodiments 396-407, wherein the brain region is a temporal cortex, perirhinal cortex, globus pallidus, putamen, caudate, thalamus, hippocampus, geniculate nucleus, Purkinje Layer, deep cerebellar nuclei, cerebellum, or a combination thereof. 409. The AAV capsid variant of any one of embodiments 1-66, 139, 140, 146-241, 279, 280, 282-301, 307-333 or 367-408, which is enriched at least about 3, 3.5, 4.0, 4.5, 5, 5.0, 6.0, or 6.5-fold, in a spinal cord region compared to a reference sequence of SEQ ID NO: 139, e.g., when measured by an assay as described in Example 2. 410. The AAV capsid variant of any one of embodiments 409, wherein the spinal cord region is a cervical region, a lumbar region, a thoracic region, or a combination thereof. 411. The AAV capsid variant of any one of the preceding embodiments, which shows preferential transduction in a brain region relative to the transduction in the dorsal root ganglia (DRG). 412. The AAV capsid variant of any one of embodiments 1-66, 139, 140, 146-241, 279, 280, 292-301, 306-345, 348-350, 355-359, or 367-411, which is capable of transducing neuronal cells. 413. The AAV capsid variant of any one of embodiments 1-66, 139, 140, 146-241, 279, 280, 292-301, 306-345, 348-350, 355-359, or 367-412, which is capable of transducing non-neuronal cells, e.g., glial cells (e.g., oligodendrocytes). 414. The AAV capsid variant of any one of embodiments 1-66, 139, 140, 146-241, 279, 280, 292-301, 306-345, 348-350, 355-359, or 367-413, which shows preferential transduction in a brain region relative to the transduction in the liver. 415. The AAV capsid variant of any one embodiments 67-279, 281, 283-289, 294, 297, 300, 301, 306-319, 346-354, or 360--395, which has an increased tropism for a heart cell or heart tissue, e.g., a heart ventricle or heart atrium, relative to the tropism of a reference sequence comprising the amino acid sequence of SEQ ID NO: 138. 416. The AAV capsid variant of any one embodiments 67-279, 281, 283-289, 294, 297, 300, 301, 306-319, 346-354, 360--395, or 415, which has an increased tropism for a heart cell or tissue, e.g., a heart ventricle or heart atrium, relative to the tropism of a reference sequence comprising the amino acid sequence of SEQ ID NO: 139. 105 319351975.1Attorney Docket Number: V2071-3033PCT 417. The AAV capsid variant of any one of embodiments 67-279, 281, 283-289, 294, 297, 300, 301, 306-319, 346-354, 360--395, 415, or 416, which delivers an increased level of a payload to a heart region, optionally wherein the level of the payload is increased by at least 1.5, 2, or 2.5-fold, as compared to a reference sequence of SEQ ID NO: 139, e.g., when measured by an assay, e.g., an IHC assay or a RT-ddPCR assay (e.g., as described in Example 2). 418. The AAV capsid variant of any one embodiments 67-279, 281, 283-289, 294, 297, 300, 301, 306-319, 346-354, 360--395, or 415-417, which has an increased tropism for a heart cell or tissue, e.g., a heart ventricle or heart atrium, relative to the tropism of a reference sequence comprising the amino acid sequence of SEQ ID NO: 982. 419. The AAV capsid variant, of any one of embodiments 67, 279, 281, 283-289, 294, 297, 300, 301, 306-319, 346-354, 360--395, or 415-418, which is enriched at least about 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, or 50-fold, in the heart compared to a reference sequence of SEQ ID NO: 982, e.g., when measured by an assay as described in Example 4. 420. The AAV capsid variant of any one embodiments 1, 4-38, 40, 67-98, 125-137, 139-144, 146- 253, 279, 302, 303, 306, 346-354, 360-374, 377, 378, or 390, which has an increased tropism for a muscle cell or tissue, relative to the tropism of a reference sequence comprising the amino acid sequence of SEQ ID NO: 982. 421. The AAV capsid variant, of any one of embodiments 1, 4-38, 40, 67-98, 125-137, 139-144, 146- 253, 279, 302, 303, 306, 346-354, 360-374, 377, 378, 390, or 420, which is enriched at least about 1.5, 1.8, 2, 3, 4, 5, 10, 15, 20, 25, 30, or 35-fold, in the muscle compared to a reference sequence of SEQ ID NO: 982, e.g., when measured by an assay as described in Example 4 or 6. 422. The AAV capsid variant of any one embodiments 1, 4-38, 40, 67-98, 125-137, 139-144, 146- 253, 279, 302, 303, 306, 346-354, 360-374, 377, 378, 420, or 421, which has an increased tropism for a muscle cell or tissue, relative to the tropism of a reference sequence comprising the amino acid sequence of SEQ ID NO: 138. 423. The AAV capsid variant of any one embodiments 1, 4-38, 40, 67-98, 125-137, 139-144, 146- 253, 279, 302, 303, 306, 346-354, 360-374, 377, 378, or 420-422, which is enriched at least about 5, 6, 7, 8, 9, 10, 12, 14, 15, 18, 19, 20, 21, 23, 24, 25, 27, 30, 32, 34, 35, 37, 40, or 45-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 6. 106 319351975.1Attorney Docket Number: V2071-3033PCT 424. The AAV capsid variant of any one of embodiments 420-423, wherein the muscle cell or tissue is a heart muscle (e.g., a heart ventricle or a heart atrium, or both), a quadriceps muscle, a diaphragm muscle, an intercostal muscle, or a combination thereof. 425. The AAV capsid variant of any one embodiments 279, 304, 305, 367-374, 377, 378, or 390, which has an 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: 982. 426. The AAV capsid variant, of any one of embodiments 279, 304, 305, 367-374, 377, 378, 390 or 425, 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, 110, 115, 120, 130, 140, 150, 160, 170, 180, 185, or 190-fold, in the liver compared to a reference sequence of SEQ ID NO: 982, e.g., when measured by an assay as described in Example 4. 427. A polynucleotide encoding the AAV capsid variant of any one of embodiments 1-426. 428. The polynucleotide of embodiment 427, which comprises: (i) 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 sequences of SEQ ID NO: 944; (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: 944; or (iii) the nucleotide sequence of SEQ ID NO: 944, or nucleotide sequence substantially identical (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity) thereto. 429. The polynucleotide of embodiment 427 or 428, which 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. 430. A polynucleotide encoding an AAV capsid variant (e.g., an AAV5 capsid variant), wherein the polynucleotide comprises the nucleotide sequence of SEQ ID NO: 984. 431. A polynucleotide encoding an AAV capsid variant (e.g., an AAV5 capsid variant), wherein the encoded AAV capsid variant comprises the amino acid sequence of SEQ ID NO: 982. 432. A polynucleotide encoding an AAV capsid variant (e.g., an AAV5 capsid variant), wherein the encoded AAV capsid variant comprises: 107 319351975.1Attorney Docket Number: V2071-3033PCT (a) the amino acid sequence of any one of the sequences provided in Tables 1, 2A, 2B, 9, 15- 20, or 26-30; (b) an amino acid sequence comprising at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 consecutive amino acids from any one of the sequences provided in Tables 1, 2A, 2B, 9, 15-20, or 26- 30; or (c) an amino acid sequence comprising 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 Tables 1, 2A, 2B, 9, 15-20, or 26-30; or (d) an amino sequence comprising one, two, or three but no more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to the amino acid sequence of any one of the amino acid sequences provided in Tables 1, 2A, 2B, 9, 15-20, or 26-30; optionally wherein the encoded AAV capsid variant further comprises: (1) the amino acid S, L, or G at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; (2) the amino acid F, M, or V at position 589 numbered according to SEQ ID NO: 982 or at position 582 numbered according to SEQ ID NO: 138; (3) the amino acid S at position 591 number according to SEQ ID NO: 982 or at position 584, numbered according to SEQ ID NO: 138; and / or (4) the amino acid K at position 595 number according to SEQ ID NO: 982 or at position 588, numbered according to SEQ ID NO: 138. 433. A polynucleotide encoding an AAV capsid variant (e.g., an AAV5 capsid variant), wherein the encoded AAV capsid variant comprises: (i) the amino acid sequence of YPAEVVQK (SEQ ID NO: 943); (ii) an amino acid sequence comprising one, two, or three, but no more than four different amino acids relative to the amino acid sequence of YPAEVVQK (SEQ ID NO: 943); (iii) an amino acid sequence comprising 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 YPAEVVQK (SEQ ID NO: 943); or (iv) at least 3, 4, 5, 6, or 7 consecutive amino acids from the amino acid sequence of YPAEVVQK (SEQ ID NO: 943); optionally wherein the encoded AAV capsid variant further comprises: (1) the amino acid S, L, or G at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; (2) the amino acid F, M, or V at position 589 numbered according to SEQ ID NO: 982 or at position 582 numbered according to SEQ ID NO: 138; 108 319351975.1Attorney Docket Number: V2071-3033PCT (3) the amino acid S at position 591 number according to SEQ ID NO: 982 or at position 584, numbered according to SEQ ID NO: 138; and / or (4) the amino acid K at position 595 number according to SEQ ID NO: 982 or at position 588, numbered according to SEQ ID NO: 138. 434. The polynucleotide of any one of embodiments 432 or 433, which comprises: (i) the nucleotide sequence of SEQ ID NO: 944, 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: 944; or (iii) a nucleotide sequence comprising at least one, two, three, four, five, six, or seven modifications, e.g., substitutions, insertions, or deletions, but no more than ten modifications, e.g., substitutions, insertions, or deletions, relative to the nucleotide sequence of SEQ ID NO: 944. 435. The polynucleotide of any one of embodiments 432-434, wherein the AAV capsid variant comprises: (i) 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; (ii) an amino acid sequence comprising one, two or three, but no more than four different amino acids, relative to the amino acid sequence of SEQ ID NO: 982; or (iii) an amino acid sequence comprising one, two or three modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, but not more than 30, 20 or 10 modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to the amino acid sequence of SEQ ID NO: 982. 436. The polynucleotide of any one of embodiments 432-435, comprising 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. 437. The polynucleotide of any one of embodiments 432-436, which comprises a nucleotide sequence that is codon optimized. 438. A peptide comprising: (a) the amino acid sequence of any one of the sequences provided in Tables 1, 2A, 2B, 9, 15- 20, or 26-30; 109 319351975.1Attorney Docket Number: V2071-3033PCT (b) an amino acid sequence comprising at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 consecutive amino acids from any one of the sequences provided in Tables 1, 2A, 2B, 9, 15-20, or 26- 30; or (c) an amino acid sequence comprising 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 Tables 1, 2A, 2B, 9, 15-20, or 26-30; or (d) an amino sequence comprising one, two, or three but no more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to the amino acid sequence of any one of the amino acid sequences provided in Tables 1, 2A, 2B, 9, 15-20, or 26-30. 439. A peptide comprising: (a) the amino acid sequence of any one of SEQ ID NOs: 4681-4686, 4694, 4696, 4698, 4700- 4713; (b) an amino acid sequence comprising at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 consecutive amino acids from any one of SEQ ID NOs: 4681-4686, 4694, 4696, 4698, 4700-4713; (c) an amino acid sequence comprising 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: 1632-2023; or (d) an amino sequence comprising one, two, or three but no more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to the amino acid sequence of any one of SEQ ID NOs: 4681-4686, 4694, 4696, 4698, 4700-4713. 440. The peptide of embodiment 438 or 439, which comprises the amino acid sequence of any one of SEQ ID NOs: 4681-4686, 4694, 4696, 4698, 4700-4713. 441. A peptide comprising: (i) the amino acid sequence of YPAEVVQK (SEQ ID NO: 943); (ii) an amino acid sequence comprising one, two, or three, but no more than four different amino acids relative to the amino acid sequence of YPAEVVQK (SEQ ID NO: 943); (iii) an amino acid sequence comprising 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 YPAEVVQK (SEQ ID NO: 943); or (iv) at least 3, 4, 5, 6, or 7 consecutive amino acids from the amino acid sequence of YPAEVVQK (SEQ ID NO: 943). 442. A peptide comprising the amino acid sequence of YPAEVVQK (SEQ ID NO: 943). 110 319351975.1Attorney Docket Number: V2071-3033PCT 443. A peptide encoded by: (i) the nucleotide sequence of SEQ ID NO: 944, 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: 944; (iii) a nucleotide sequence comprising at least one, two, three, four, five, six, or seven modifications, e.g., substitutions, insertions, or deletions, but no more than ten modifications, e.g., substitutions, insertions, or deletions, relative to the nucleotide sequence of SEQ ID NO: 944. 444. A peptide wherein the nucleotide sequence encoding the peptide comprises: (i) the nucleotide sequence of SEQ ID NO: 944, 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: 944; or (iii) a nucleotide sequence comprising at least one, two, three, four, five, six, or seven modifications, e.g., substitutions, insertions, or deletions, but no more than ten modifications, e.g., substitutions, insertions, or deletions, relative to the nucleotide sequence of SEQ ID NO: 944. 445. An AAV capsid variant (e.g., an AAV5 capsid variant) comprising the peptide of any one of embodiments 390-394. 446. An AAV capsid variant (e.g., an AAV5 capsid variant) encoded by the polynucleotide of any one of embodiments 382-389. 447. An AAV particle comprising the AAV capsid variant of any one of embodiments 1-426, 445, or 446. 448. The AAV particle of embodiment 447, which comprises a nucleotide sequence encoding a payload. 449. The AAV particle of embodiment 448, 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. 111 319351975.1Attorney Docket Number: V2071-3033PCT 450. The AAV particle of embodiment 449, wherein 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. 451. The AAV particle of embodiment 449 or 450, 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. 452. The AAV particle of embodiment 449, wherein the antibody or antibody binding fragment binds to: (i) a CNS related target, e.g., an antigen associated with a neurological or neurodegenerative disorder, e.g., β-amyloid, APOE, tau, superoxide dismutase 1 (SOD1), TAR DNA binding protein 43 (TDP-43), huntingtin (HTT), and / or synuclein; (ii) a muscular or neuromuscular related target, e.g., an antigen associated with a muscular or neuromuscular disorder; or (iii) a neuro-oncology related target, e.g., an antigen associated with a neuro-oncological disorder, e.g., human epidermal growth factor receptor 2 (HER2), or epidermal growth factor receptor (EGFR) (e.g., EGFRvIII). 453. The AAV particle of embodiment 449, wherein the enzyme comprises a meganuclease, a zinc finger nuclease, a TALEN, a recombinase, integrase, a base editor, a Cas9, or a fragment thereof. 454. The AAV particle of embodiment 449, wherein the component of a gene editing system comprises one or more components of a CRISPR-Cas system. 455. The AAV particle of embodiment 454, 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), optionally wherein: (i) the sgRNA is located upstream (5’) of the Cas9 enzyme; or (ii) the sgRNA is located downstream (3’) of the Cas9 enzyme. 112 319351975.1Attorney Docket Number: V2071-3033PCT 456. The AAV particle of embodiment 449, wherein 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. 457. The AAV particle of embodiment 456, wherein the CNS related gene is chosen from SOD1, microtubule-associated protein tau (MAPT), APOE, HTT, TDP-43, amyloid precursor protein (APP), beta secretase (BACE), alpha-synuclein (SNCA), ataxin 1 (ATXN1), ataxin 3 (ATXN3), ataxin 7 (ATXN7), sodium voltage-gated channel alpha subunit 1A (SCN1A)-SCN5A, SCN8A-SCN11A, or a combination thereof. 458. The AAV particle of any one of embodiments 447-457, which comprises a viral genome comprising a promoter operably linked to the nucleic acid sequence encoding the payload. 459. The AAV particle of embodiment 458, 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 chain (NFL) or neurofilament heavy chain (NFH), β-globin minigene nβ2, preproenkephalin (PPE), enkephalin (Enk) and excitatory amino acid transporter 2 (EAAT2), glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), 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 functional fragment, e.g., a truncation, or a functional variant thereof. 460. The AAV particle of embodiment 458 or 459, wherein the promoter is an EF-1a promoter variant, e.g., a truncated EF-1a promoter. 461. The AAV particle of any one of embodiments 458-460, wherein the promoter comprises the nucleotide sequence of any one of SEQ ID NOs: 2100, 2101, 2103, 2104, 2108, 2109, 2111-2120, or any one of the nucleotide sequences provided in Table 8, a nucleotide sequence comprising at least one, two, three, four, five, six, or seven but no more than ten modifications, e.g., substitutions, insertions, or deletions, relative to the nucleotide sequence of SEQ ID NOs: 2100, 2101, 2103, 2104, 2108, 2109, 2111-2120, or any one of the nucleotide sequences provided in Table 8, or a nucleotide sequence with at least 80% (e.g., 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to any 113 319351975.1Attorney Docket Number: V2071-3033PCT one of SEQ ID NOs: 2100, 2101, 2103, 2104, 2108, 2109, 2111-2120, or any one of the nucleotide sequences provided in Table 8. 462. The AAV particle of any one of embodiments 458-461 wherein the viral genome further comprises a polyA signal sequence. 463. The AAV particle of any one of embodiments 458-462, wherein the viral genome further comprises an inverted terminal repeat (ITR) sequence. 464. The AAV particle of any one of embodiments 458-463, wherein the viral genome comprises an ITR sequence positioned 5’ relative to the nucleic acid sequence encoding the payload. 465. The AAV particle of any one of embodiments 458-464, wherein the viral genome comprises an ITR sequence positioned 3’ relative to the nucleic acid sequence encoding the payload. 466. The AAV particle of any one of embodiments 458-465, wherein the viral genome comprises an ITR sequence positioned 5’ relative to the payload and an ITR sequence positioned 3’ relative to the nucleic acid sequence encoding the payload. 467. The AAV particle of any one of embodiments 458-466, wherein the viral genome further comprises an enhancer, a Kozak sequence, an intron region, and / or an exon region. 468. The AAV particle of any one of embodiments 458-467, wherein the viral genome further comprises a nucleotide sequence encoding a miR binding site, e.g., a miR binding site that modulates, e.g., reduces, expression of payload encoded by the viral genome in a cell or tissue where the corresponding miRNA is expressed. 469. The AAV particle of embodiment 468, wherein the encoded miRNA binding site is complementary, e.g., fully complementary or partially complementary, to a miRNA expressed in a cell or tissue of the DRG, liver, heart, hematopoietic, or a combination thereof. 470. The AAV particle of embodiment 468 or 469, 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. 471. The AAV particle of any one of embodiments 458-470, wherein the viral genome comprises at least 1-5 copies of the encoded miR binding site, e.g., at least 1, 2, 3, 4, or 5 copies. 114 319351975.1Attorney Docket Number: V2071-3033PCT 472. The AAV particle of any one of embodiments 458-471, wherein the viral genome comprises at least 3 copies of an encoded miR binding sites, optionally wherein 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. 473. The AAV particle of embodiment 472, wherein the 3 copies of the encoded miR binding sites are continuous (e.g., not separated by a spacer). 474. The AAV particle of embodiment 472, wherein the 3 copies of the encoded miR binding sites are separated by a spacer, optionally wherein the spacer comprises the nucleotide sequence of GATAGTTA, or a nucleotide sequence comprising one, two, or three modifications, e.g., substitutions, insertions, or deletions, but no more than four modifications, e.g., substitutions, insertions, or deletions, relative to GATAGTTA. 475. The AAV particle of any one of embodiments 458-474, wherein the viral genome comprises at least 4 copies of an encoded miR binding site, optionally wherein 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. 476. The AAV particle of embodiment 475, wherein the 4 copies of the encoded miR binding sites are continuous (e.g., not separated by a spacer). 477. The AAV particle of embodiment 475, wherein the 4 copies of the encoded miR binding sites are separated by a spacer, optionally wherein the spacer comprises the nucleotide sequence of GATAGTTA, or a nucleotide sequence comprising at one, two, or three modifications, e.g., substitutions, insertions, or deletions, but no more than four modifications, e.g., substitutions, insertions, or deletions, relative to GATAGTTA. 478. The AAV particle of any one of embodiments 458-478, wherein the encoded miR binding site comprises a miR122 binding site, a miR183 binding ...

Claims

Attorney Docket Number: V2071-3033PCT We claim:

1. An AAV capsid variant (e.g., an AAV5 capsid variant), comprising an amino sequence comprising the following formula: [N0]-[N1]-[N2]-[N3]-[N4], wherein [N2] comprises the amino acid sequence of GPAEV (SEQ ID NO: 4722), YPAEV (SEQ ID NO: 1), YPKEV (SEQ ID NO: 4723), GRAEV (SEQ ID NO: 4724), YPASL (SEQ ID NO: 4725), YPATI (SEQ ID NO: 4726), YPAER (SEQ ID NO: 4727), YPASV (SEQ ID NO: 4728), YPAGV (SEQ ID NO: 4729), wherein one, two, three, or all of: (i) [N0] comprises TNR or VNN; (ii) [N1] comprises VSS; (iii) [N3] comprises IQK; or (iv) [N4] comprises RG; wherein [N0]-[N1]-[N2]-[N3]-[N4] is present in hypervariable loop VIII and the AAV capsid variant comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 750 or 739.

2. The AAV capsid variant of claim 3, wherein: (a) [N3] comprises VQK or IQK; (b) [N1] comprises QSR, QSS, QSK, VSS, or ASS; (c) [N0] comprises TNN, TNR, or VNN; and / or (d) [N4] comprises TA, RG, or NA.

3. The AAV capsid variant of claim 2 or 3, wherein: (a) [N2]-[N3] comprises GPAEVVQK (SEQ ID NO: 4714), YPAEVVQK (SEQ ID NO: 943), YPKEVVQK (SEQ ID NO: 4715), GRAEVVQK (SEQ ID NO: 4716), YPASLVQK (SEQ ID NO: 4717), YPATIVQK (SEQ ID NO: 4718), YPAERIQK (SEQ ID NO: 4719), YPASVVQK (SEQ ID NO: 4720), YPAGVVQK or (SEQ ID NO: 4721); (b) [N1]-[N2] comprises QSRGPAEV (SEQ ID NO: 4767), QSSYPAEV (SEQ ID NO: 96), QSKGPAEV (SEQ ID NO: 4768), QSSYPKEV (SEQ ID NO: 4769), QSSGRAEV (SEQ ID NO: 4770), QSSYPASL (SEQ ID NO: 4771), QSSYPATI (SEQ ID NO: 4812), QSSYPAER (SEQ ID NO: 4772), VSSYPASV (SEQ ID NO: 4773), QSRYPAEV (SEQ ID NO: 100), VSSYPAGV (SEQ ID NO: 4774), QSKYPAEV (SEQ ID NO: 97), or ASSYPAEV (SEQ ID NO: 105); (c) [N1]-[N2]-[N3] comprises: QSRGPAEVVQK (SEQ ID NO: 4784), QSSYPAEVVQK (SEQ ID NO: 150), QSKGPAEVVQK (SEQ ID NO: 4785), QSSYPKEVVQK (SEQ ID NO: 4786), QSSGRAEVVQK (SEQ ID NO: 4787), QSSYPASLVQK (SEQ ID NO: 4788), QSSYPATIVQK (SEQ ID NO: 4789), QSSYPAERIQK (SEQ ID NO: 4790), VSSYPASVVQK (SEQ ID NO: 4791), QSRYPAEVVQK (SEQ ID NO: 154), VSSYPAGVVQK (SEQ ID NO: 4792), QSKYPAEVVQK (SEQ ID NO: 151), or ASSYPAEVVQK (SEQ ID NO: 159); 302 319351975.1Attorney Docket Number: V2071-3033PCT (d) [N0]-[N1] comprises TNNQSS (SEQ ID NO: 183), TNNQSK (SEQ ID NO: 184), TNNQSR (SEQ ID NO: 187), TNNVSS (SEQ ID NO: 4793), TNRASS (SEQ ID NO: 4794), or VNNQSS (SEQ ID NO: 4795); and / or (e) [N3]-[N4] comprises VQKTA (SEQ ID NO: 564), VQKRG (SEQ ID NO: 4807), IQKTA (SEQ ID NO: 4808), or VQKNA (SEQ ID NO: 570).

4. The AAV capsid variant of any one of claims 2-3, wherein: (a) [N0]-[N1]-[N2]-[N3] comprises TNNQSRGPAEVVQK (SEQ ID NO: 4796), TNNQSSYPAEVVQK (SEQ ID NO: 500), TNNQSKGPAEVVQK (SEQ ID NO: 4797), TNNQSSYPKEVVQK (SEQ ID NO: 4798), TNNQSSGRAEVVQK (SEQ ID NO: 4799), TNNQSSYPASLVQK (SEQ ID NO: 4800), TNNQSSYPATIVQK (SEQ ID NO: 4801), TNNQSSYPAERIQK (SEQ ID NO: 4802), TNNVSSYPASVVQK (SEQ ID NO: 4803), TNNQSRYPAEVVQK (SEQ ID NO: 510), TNNVSSYPAGVVQK (SEQ ID NO: 4804), TNNQSKYPAEVVQK (SEQ ID NO: 503), TNRASSYPAEVVQK (SEQ ID NO: 4805), or VNNQSSYPAEVVQK (SEQ ID NO: 4806); and / or (d) [N0]-[N1]-[N2]-[N3]-[N4] comprises TNNQSRGPAEVVQKTA (SEQ ID NO: 4684), TNNQSSYPAEVVQKRG (SEQ ID NO: 4685), TNNQSKGPAEVVQKTA (SEQ ID NO: 4686), TNNQSSYPKEVVQKTA (SEQ ID NO: 4694), TNNQSSGRAEVVQKTA (SEQ ID NO: 4696), TNNQSSYPASLVQKTA (SEQ ID NO: 4698), TNNQSSYPATIVQKTA (SEQ ID NO: 4700), TNNQSSYPAERIQKTA (SEQ ID NO: 4701), TNNVSSYPASVVQKTA (SEQ ID NO: 4682), TNNQSRYPAEVVQKNA (SEQ ID NO: 4683), TNNVSSYPAGVVQKTA (SEQ ID NO: 4704), TNNQSKYPAEVVQKNA (SEQ ID NO: 4705), TNRASSYPAEVVQKTA (SEQ ID NO: 4708), or VNNQSSYPAEVVQKTA (SEQ ID NO: 4710).

5. The AAV capsid variant of any one of claims 1-4, wherein hypervariable loop VIII comprises positions 571-599 of SEQ ID NO: 982 or positions 571-592 numbered according to SEQ ID NO:

138.

6. The AAV capsid variant of any one of claims 1-6, wherein: (i) XA of [N0] is present at position 571, XB of [N0] is present at position 572, and XC of [N0] is present at position 573, numbered according to SEQ ID NO: 982; and / or [N0] is present at positions 571-573, numbered according to SEQ ID NO: 982; (ii) XDof [N1] is present at position 574, XEof [N1] is present at position 575, and XFof [N1] is present at position 576, numbered according to SEQ ID NO: 982; and / or [N1] is present at position 574-576, numbered according to SEQ ID NO: 982; (iii) X1 of [N2] is present at position 577, X2 of [N2] is present at position 578, X3 of [N2] is present at position 579, X4 of [N2] is present at position 580, and X5 of [N2] is present at position 303 319351975.1Attorney Docket Number: V2071-3033PCT 581, numbered according to SEQ ID NO: 982; and / or [N2] is present at position 577-581, numbered according to SEQ ID NO: 982; (iv) [N3] is present at positions 582-584, numbered according to SEQ ID NO: 982; and / or (v) XGof [N4] is present at position 585 and XHof [N4] is present at position 586, numbered according to SEQ ID NO: 982; and / or [N4] is present at position 585-586, numbered according to SEQ ID NO:

982.

7. The AAV capsid variant of any one of claims 1-6, wherein the amino acid Y is present at position 577, and the amino acid sequence of PAEVVQK (SEQ ID NO: 20) is present at positions 578-584, numbered relative to SEQ ID NO:

982.

8. An adeno-associated virus (AAV) capsid variant (e.g., an AAV5 capsid variant) comprising: (i) R at position 576 and G at position 577, numbered according to SEQ ID NO: 138 or 982; and the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 138 or 982; (ii) Y at position 577, numbered according to SEQ ID NO: 982 or 138; the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138; and R at position 585 and G at position 586, numbered according to SEQ ID NO: 982; or an R at position 578 and G at position 579, numbered according to SEQ ID NO: 138; (iii) K at position 576 and G at position 577, numbered according to SEQ ID NO: 138 or 982; and the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 138 or 982; (iv) Y at position 577, numbered according to SEQ ID NO: 982 or 138; and the amino acid sequence of PKEVVQK (SEQ ID NO: 4749), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138; (v) G at position 577, numbered according to SEQ ID NO: 982 or 138; and the amino acid sequence of RAEVVQK (SEQ ID NO: 4750), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138; (vi) Y at position 577, numbered according to SEQ ID NO: 982 or 138; and the amino acid sequence of PASLVQK (SEQ ID NO: 4751), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138; (vii) Y at position 577, numbered according to SEQ ID NO: 982 or 138; and the amino acid sequence of PATIVQK (SEQ ID NO: 4752), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138; 304 319351975.1Attorney Docket Number: V2071-3033PCT (viii) Y at position 577, numbered according to SEQ ID NO: 982 or 138; and the amino acid sequence of PAERIQK (SEQ ID NO: 4753), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138; (ix) V at position 574 and Y at position 577, numbered relative to SEQ ID NO: 982 or 138; and the amino acid sequence of PASVVQK (SEQ ID NO: 4754), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138; (x) R at position 576 and Y at position 577, numbered relative to SEQ ID NO: 982 or 138; the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138; and N at position 585, numbered according to SEQ ID NO: 982; or N at position 578, numbered according to SEQ ID NO: 138; (xi) V at position 574 and Y at position 577, numbered relative to SEQ ID NO: 982 or 138; and the amino acid sequence of PAGVVQK (SEQ ID NO: 4755), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138 (xii) K at position 576 and Y at position 577, numbered relative to SEQ ID NO: 982 or 138; and the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138; and N at position 585, numbered according to SEQ ID NO: 982; or N at position 578, numbered according to SEQ ID NO: 138; (xiii) R at position 573, A at position 574 and Y at position 577, numbered relative to SEQ ID NO: 982 or 138; and the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138; or (xiv) V at position 571 and Y at position 577, numbered relative to SEQ ID NO: 982 or 138; and the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138; and wherein the AAV capsid variant comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 750 or 739.

9. The AAV capsid variant of any one of claims 1-10, which comprises: (a) the amino acid S, L, or G at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; (b) the amino acid F, M, or V at position 589 numbered according to SEQ ID NO: 982 or at position 582 numbered according to SEQ ID NO: 138; (c) the amino acid S, L, or G at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; and the amino acid F, M, or V at position 589 numbered according to SEQ ID NO: 982 or at position 582 numbered according to SEQ ID NO: 138; 305 319351975.1Attorney Docket Number: V2071-3033PCT (d) the amino acid S at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; and the amino acid F at position 589 numbered according to SEQ ID NO: 982 or at position 582 numbered according to SEQ ID NO: 138; (e) the amino acid S at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; and the amino acid M at position 589 numbered according to SEQ ID NO: 982 or at position 582 numbered according to SEQ ID NO: 138; (f) the amino acid L at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; and the amino acid F at position 589 numbered according to SEQ ID NO: 982 or at position 582 numbered according to SEQ ID NO: 138; (g) the amino acid G at position 588 numbered according to SEQ ID NO: 982 or at position 581 numbered according to SEQ ID NO: 138; and the amino acid V at position 589 numbered according to SEQ ID NO: 982 or at position 582 numbered according to SEQ ID NO: 138; (h) the amino acid S at position 591 number according to SEQ ID NO: 982 or at position 584, numbered according to SEQ ID NO: 138; or (i) the amino acid K at position 595 number according to SEQ ID NO: 982 or at position 588, numbered according to SEQ ID NO:

138.

10. An adeno-associated virus (AAV) capsid variant (e.g., an AAV5 capsid variant) comprising: (i) Y at position 577, numbered relative to SEQ ID NO: 982 or 138; the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138; and S at position 591, numbered according to SEQ ID NO: 982; or S at position 584, numbered according to SEQ ID NO: 138; (ii) Y at position 577, numbered relative to SEQ ID NO: 982 or 138; the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138; and S at position 588, numbered according to SEQ ID NO: 982; or S at position 581, numbered according to SEQ ID NO: 138; (iii) Y at position 577, numbered relative to SEQ ID NO: 982 or 138; the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138; and G at position 588, numbered according to SEQ ID NO: 982; or G at position 581, numbered according to SEQ ID NO: 138; (iv) Y at position 577, numbered relative to SEQ ID NO: 982 or 138; the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138; and S at position 588 and F at position 589, numbered according to SEQ ID NO: 982; or S at position 581 and F at position 582, numbered according to SEQ ID NO: 138; (v) Y at position 577, numbered relative to SEQ ID NO: 982 or 138; the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered 306 319351975.1Attorney Docket Number: V2071-3033PCT according to SEQ ID NO: 982 or 138; and F at position 589, numbered according to SEQ ID NO: 982; or F at position 582, numbered according to SEQ ID NO: 138; (vi) Y at position 577, numbered relative to SEQ ID NO: 982 or 138; the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138; and S at position 588 and M at position 589, numbered according to SEQ ID NO: 982; or S at position 581 and M at position 582, numbered according to SEQ ID NO: 138; (vii) Y at position 577, numbered relative to SEQ ID NO: 982 or 138; the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138; and L at position 588 and F at position 589, numbered according to SEQ ID NO: 982; or L at position 581 and F at position 582, numbered according to SEQ ID NO: 138; (viii) Y at position 577, numbered relative to SEQ ID NO: 982 or 138; the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138; and L at position 588, numbered according to SEQ ID NO: 982; or L at position 581, numbered according to SEQ ID NO: 138; (ix) Y at position 577, numbered relative to SEQ ID NO: 982 or 138; the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138; and G at position 588 and V at position 589, numbered according to SEQ ID NO: 982; or G at position 581 and V at position 582, numbered according to SEQ ID NO: 138; (x) Y at position 577, numbered relative to SEQ ID NO: 982 or 138; the amino acid sequence of PAEVVQK (SEQ ID NO: 20), which is present immediately subsequent to position 577, numbered according to SEQ ID NO: 982 or 138; and K at position 595, numbered according to SEQ ID NO: 982; or K at position 588, numbered according to SEQ ID NO: 138; and wherein the AAV capsid variant comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 750 or 739.

11. The AAV capsid variant of any one of claims 1-10, which comprises the amino acid sequence of any one of SEQ ID NOs: 4681-4686, 4694, 4696, 4698, or 4701-4713.

12. The AAV capsid variant of any one of claims 1-11, which comprises: (i) the amino acid sequence of any one of SEQ ID NOs: 4681, 4702, or 4703 at amino acids 571-594, numbered according to SEQ ID NO: 982; (ii) the amino acid sequence of any one of SEQ ID NOs: 4682-4686, 4694, 4696, 4698, 4700, 4701, 4704, 4705, 4708, or 4710 at amino acids 571-586, numbered according to SEQ ID NO: 982; or 307 319351975.1Attorney Docket Number: V2071-3033PCT (iii) the amino acid sequence of any one of SEQ ID NOs: 4706, 4707, 4709, or 4711-4713 at amino acids 571-594, numbered according to SEQ ID NO:

982.

13. The AAV capsid variant of any one of claims 1-12, which comprises: (i) an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 750; (ii) an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 744; and / or (iii) an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:

138.

14. The AAV capsid variant of any one of the preceding claims, which comprises: (i) an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 739; (ii) an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 738; and / or (iii) an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:

982.

15. The AAV capsid variant of any one of claims 1-7 or 9-14, which comprises: (i) the amino acid sequence of amino acids 193-731 of SEQ ID NO: 4680, or an amino acid sequence at least 95% identical thereto; (ii) the amino acid sequence of amino acids 137-731 of SEQ ID NO: 4860, or an amino acid sequence at least 95% sequence identical thereto; (iii) the amino acid sequence of SEQ ID NO: 4680, or an amino acid sequence at least 95% sequence identical thereto.

16. The AAV capsid variant, of any one of claims 1-13, 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, 139, or 982; (ii) transduces a brain region, e.g., a temporal cortex, perirhinal cortex, globus pallidus, putamen, caudate, thalamus, hippocampus, geniculate nucleus, Purkinje Layer, deep cerebellar nuclei, and / or cerebellum, optionally wherein the level of transduction is at least 1.5, 2.2, 2.4, 2.5, 2.6, 2.7, 3.0, 3.2, 3.5, 3.7, 4.0, 4.2, 4.5, 4.7, 4.9, 5, 10, 15, 20, 25, 30, 35-fold greater as compared to a reference sequence of SEQ ID NO: 139 , e.g., when measured by an assay, e.g., an immunohistochemistry assay or a qPCR assay, e.g., as described in Example 2; 308 319351975.1Attorney Docket Number: V2071-3033PCT (iii) is enriched at least about 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 15, 17, 20, 25, 30, 35, 40, 45, 50, 55, 60, or 65-fold, in the brain compared to a reference sequence of SEQ ID N O: 138, e.g., when measured by an assay as described in Example 1; (iv) is enriched at least about 10, 12, 15, 17, 20, 25, 30, 35, 40, 45, 50, 55, 60, 61, 62, 63, 64, or 65-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; (v) is enriched at least about 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 15, 17, 20, 25, 30, 35, 40, 45-fold, in the brain of at least two to three species, e.g., a non-human primate and rodent (e.g., rat or mouse), compared to a reference sequence of SEQ ID NO: 138, e.g., when measured by an assay as described in Examples 1, 2, and 4; (vi) is enriched at least about 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 100, 125, 150, 175, 200, or 225-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 4; (vii) delivers an increased level of a payload to a brain region, optionally wherein the level of the payload is increased by at least 20, 25, 30, 35-fold, as compared to a reference sequence of SEQ ID NO: 139, e.g., when measured by an assay, e.g., a qRT-PCR or a qPCR assay (e.g., as described in Example 2), optionally wherein the brain region is a temporal cortex, perirhinal cortex, globus pallidus, putamen, caudate, thalamus, hippocampus, geniculate nucleus, Purkinje Layer, deep cerebellar nuclei, and / or cerebellum; (viii) delivers an increased level of viral genomes to a brain region, optionally wherein the level of viral genomes is increased by at least 1.5, 2.2, 2.4, 2.5, 2.6, 2.7, 3.0, 3.2, 3.5, 3.7, 4.0, 4.2, 4.5, 4.7, 4.9, or 5-fold, as compared to a reference sequence of SEQ ID NO: 139, e.g., when measured by an assay, e.g., a qRT-PCR or a qPCR assay (e.g., as described in Example 2), optionally wherein the brain region is a temporal cortex, perirhinal cortex, globus pallidus, putamen, caudate, thalamus, hippocampus, geniculate nucleus, Purkinje Layer, deep cerebellar nuclei, and / or cerebellum; (ix) enriched at least about 3, 3.5, 4.0, 4.5, 5, 5.0, 6.0, or 6.5-fold, in a spinal cord region compared to a reference sequence of SEQ ID NO: 139, e.g., when measured by an assay as described in Example 2, optionally wherein the spinal cord region is a cervical region, a lumbar region, a thoracic region, or a combination thereof; (x) shows preferential transduction in a brain region relative to the transduction in the dorsal root ganglia (DRG); (xi) shows preferential transduction in a brain region relative to the transduction in the liver; and / or (xii) is capable of transducing neuronal cell and non-neuronal cells, e.g., glial cells (e.g., oligodendrocytes or astrocytes).

17. The AAV capsid variant, of any one of claims 1-16, wherein the AAV capsid variant: 309 319351975.1Attorney Docket Number: V2071-3033PCT (i) has an increased tropism for a muscle cell or tissue, relative to the tropism of a reference sequence comprising the amino acid sequence of SEQ ID NO: 982 or 138, optionally wherein the muscle cell or tissue is a quadriceps muscle cell or tissue, a diaphragm muscle cell or tissue, an intercostal muscle cell or tissue, or a combination thereof; (ii) is enriched at least about 1.5, 1.8, 2, 3, 4, 5, 10, 15, 20, 25, 30, or 35-fold, in the muscle compared to a reference sequence of SEQ ID NO: 982, e.g., when measured by an assay as described in Example 4 or 6, optionally wherein the muscle is a quadriceps muscle, a diaphragm muscle, an intercostal muscle, or a combination thereof; (iii) is enriched at least about 5, 6, 7, 8, 9, 10, 12, 14, 15, 18, 19, 20, 21, 23, 24, 25, 27, 30, 32, 34, 35, 37, 40, or 45-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 6, optionally wherein the muscle is a quadriceps muscle, a diaphragm muscle, an intercostal muscle, or a combination thereof; and / or (iv) has an increased tropism for a heart cell or heart tissue, e.g., a heart ventricle or heart atrium, relative to the tropism of a reference sequence comprising the amino acid sequence of SEQ ID NO: 138, 139, or 982.

18. A polynucleotide encoding the AAV capsid variant of any one of claims 1-17.

19. A peptide comprising the amino acid sequence of any one of SEQ ID NOs: 4681-4686, 4694, 4696, 4698, or 4700-4713.

20. An AAV capsid variant comprising the peptide of claim 19.

21. An adeno-associated virus (AAV) particle comprising the AAV capsid variant of any one of claims 1-17, an AAV capsid variant encoded by the polynucleotide of claim 18, or an AAV capsid variant comprising the peptide of claim 19.

22. The AAV particle of claim 21, 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.

23. The AAV particle of claim 22, wherein 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 310 319351975.1Attorney Docket Number: V2071-3033PCT 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.

24. The AAV particle of claim 22 or 23, wherein the antibody or antibody binding fragment binds to (a) a central nervous system (CNS) related target, e.g. an antigen associated with a neurological or neurodegenerative disorder, e.g., β-amyloid, APOE, tau, superoxide dismutase 1 (SOD1), TAR DNA binding protein 43 (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., human epidermal growth factor receptor 2 (HER2), or pidermal growth factor receptor (EGFR) (e.g., EGFRvIII).

25. The AAV particle of any one of claims 22-24, wherein the enzyme comprises a meganuclease, a zinc finger nuclease, a TALEN, a recombinase, integrase, a base editor, a Cas9, or a fragment thereof.

26. The AAV particle of any one of claims 22-25, wherein 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.

27. The AAV particle of any one of claims 22-26, wherein 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, microtubule-associated protein tau (MAPT), APOE, HTT, TDP- 43, amyloid precursor protein (APP), beta secretase (BACE), alpha-synuclein (SNCA), ataxin 1 (ATXN1), ataxin 3 (ATXN3), ataxin 7 (ATXN7), sodium voltage-gated channel alpha subunit 1A (SCN1A)-SCN5A, SCN8A-SCN11A, or a combination thereof.

28. The AAV particle of any one of claims 21-27, which comprises a viral genome comprising a promoter operably linked to the nucleic acid sequence encoding the payload. 311 319351975.1Attorney Docket Number: V2071-3033PCT 29. The AAV particle of claim 28, wherein: (i) 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 chain (NFL) or heavy chain (NFH), β-globin minigene nβ2, preproenkephalin (PPE), enkephalin (Enk) and excitatory amino acid transporter 2 (EAAT2), glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), 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; (ii) the promoter is an EF-1a promoter variant, e.g., a truncated EF-1a promoter; or (iii) the promoter comprises the nucleotide sequence of any one of SEQ ID NOs: 2100, 2101, 2103, 2104, 2108, 2109, 2111-2120, or any one of the nucleotide sequences provided in Table 8, a nucleotide sequence comprising at least one, two, three, four, five, six, or seven but no more than four modifications, e.g., substitutions, relative to the nucleotide sequence of SEQ ID NOs: 2100, 2101, 2103, 2104, 2108, 2109, 2111-2120, or any one of the nucleotide sequences provided in Table 8, or a nucleotide sequence with at least 80% (e.g., 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to any one of SEQ ID NOs: 2100, 2101, 2103, 2104, 2108, 2109, 2111-2120, or any one of the nucleotide sequences provided in Table 8.

30. The AAV particle of claim 28 or 29, wherein the viral genome further comprises: (i) a polyadenylation (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; and / or (iv) a nucleotide sequence encoding a microRNA (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.

31. The AAV particle of claim 30, 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: 312 319351975.1Attorney Docket Number: V2071-3033PCT (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 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 GATAGTTA.

32. The AAV particle of claim 31 or 32, 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 substantially identical (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity) thereto; or a nucleotide sequence comprising at least one, two, three, four, five, six, or seven modifications, e.g., substitutions, insertions, or deletions, but no more than ten modifications, e.g., substitutions, insertions, or deletions, relative to SEQ ID NO: 4673; (ii) the encoded miR183 binding site comprises the nucleotide sequence of SEQ ID NO: 4676, or a nucleotide sequence substantially identical (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity) thereto; or a nucleotide sequence comprising at least one, two, three, four, five, six, or seven modifications, e.g., substitutions, insertions, or deletions, but no more than ten modifications, e.g., substitutions, insertions, or deletions, relative to SEQ ID NO: 4676; (iii) the encoded miR-1 binding site comprises the nucleotide sequence of SEQ ID NO: 4679, or a nucleotide sequence substantially identical (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity) thereto; or a nucleotide sequence comprising at least one, two, three, four, five, six, or seven modifications, e.g., substitutions, insertions, or deletions, but 313 319351975.1Attorney Docket Number: V2071-3033PCT no more than ten modifications, e.g., substitutions, insertions, or deletions, 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 substantially identical (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity) thereto; or a nucleotide sequence comprising at least one, two, three, four, five, six, or seven modifications, e.g., substitutions, insertions, or deletions, but no more than ten modifications, e.g., substitutions, insertions, or deletions, relative to SEQ ID NO: 4675.

33. The AAV particle of any one of claims 28-32, wherein the viral genome is single stranded.

34. The AAV particle of any one of claims 28-32, wherein the viral genome is self-complementary.

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

36. A vector comprising a polynucleotide encoding the AAV capsid variant of any one of claims 1-17, 20, or 35, the polynucleotide of claim 18 or 35, or a polynucleotide encoding the peptide of claim 19 or 35.

37. A cell, e.g., a host cell, comprising the AAV capsid variant of any one of claims 1-17, 20, or 35, the polynucleotide of claim 18 or 35, the peptide of claim 19 or 35, the AAV particle of any one of claims 21-35, or the vector of claim 36, 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 brain stem, hippocampus, or thalamus; and / or (iii) the cell is a neuron, a sensory neuron, a motor neuron, an astrocyte, a glial cell, oligodendrocyte, or a muscle cell (e.g., a cell of the heart, diaphragm, intercostal muscle, or quadriceps).

38. 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 1-17, 20, or 35, or an AAV capsid variant encoded by the polynucleotide of claim 18 or 35; thereby making the AAV particle. 314 319351975.1Attorney Docket Number: V2071-3033PCT 39. A pharmaceutical composition comprising the AAV particle of any one of claims 21-35, an AAV particle comprising the AAV capsid variant of any one of claims 1-17, 20, or 35, an AAV particle comprising the peptide of claim 18 or 35, and a pharmaceutically acceptable excipient.

40. A method of delivering a payload to a cell or tissue (e.g., a CNS cell or a CNS tissue or a muscle cell or tissue), comprising administering an effective amount of the pharmaceutical composition of claim 39, the AAV particle of any one of claims 21-35, an AAV particle comprising the AAV capsid variant of any one of claims 1-17, 20, or 35, or an AAV particle comprising the peptide of claim 19 or 35.

41. The method of claim 40, wherein the cell is: (i) a cell of a brain region or a or a spinal cord region, optionally a cell of the temporal cortex, perirhinal cortex, globus pallidus, putamen, caudate, thalamus, hippocampus, geniculate nucleus, Purkinje Layer, deep cerebellar nuclei, cerebellum, cervical spinal cord region, thoracic spinal cord region, lumbar spinal cord region, or a combination thereof; (ii) a cell of the heart, e.g., a heart atrium or a heart ventricle; (iii) a cell of the muscle (e.g., a cell of the quadriceps, diaphragm, or intercostal muscle); (iv) a cell of the liver; (v) a neuron, a sensory neuron, a motor neuron, an astrocyte, a glial cell, or an oligodendrocyte; (vi) within a subject, optionally wherein the subject has, has been diagnosed with having, or is at risk of having a genetic disorder (e.g., a monogenic disorder or a polygenic disorder), a neurological disorder (e.g., a neurodegenerative disorder), a neuro-oncological disorder, a muscular disorder, a muscular dystrophy, or a neuromuscular disorder.

42. A method of treating a subject having or diagnosed with having a genetic disorder, e.g., a monogenic disorder or a polygenic disorder, comprising administering to the subject an effective amount of the pharmaceutical composition of claim 39, the AAV particle of any one of claims 21-35, an AAV particle comprising the AAV capsid variant of any one of claims 1-17, 20, or 35, or an AAV particle comprising the peptide of claim 19 or 35.

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 39, the AAV particle of any one of claims 21-35, an AAV particle comprising the AAV capsid variant of any one of claims 1-17, 20, or 35, or an AAV particle comprising the peptide of claim 19 or 35. 315 319351975.1Attorney Docket Number: V2071-3033PCT 44. A method of treating a subject having or diagnosed with having a muscular disorder, a muscular dystrophy, or a neuromuscular disorder, comprising administering to the subject an effective amount of the pharmaceutical composition of claim 39, the AAV particle of any one of claims 21-35, an AAV particle comprising the AAV capsid variant of any one of claims 1-17, 20, or 35, or an AAV particle comprising the peptide of claim 19 or 35.

45. A method of treating a subject having or diagnosed with having a neuro-oncological disorder, comprising administering to the subject an effective amount of the pharmaceutical composition of claim 39, the AAV particle of any one of claims 21-35, an AAV particle comprising the AAV capsid variant of any one of claims 1-17, 20, or 35, or an AAV particle comprising the peptide of claim 19 or 35.

46. The method of any one of claims 41-45, wherein the genetic disorder, neurological disorder, neurodegenerative disorder, muscular disorder, muscular dystrophy, 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), Duchenne muscular dystrophy (DMD), Limb-Girdle Muscular Dystrophy (LGMD2A), Becker muscular dystrophy (BMD), congenital muscular dystrophy, Facioscapulohumeral muscular dystrophy, titinopathy, Emery Dreifuss muscular dystrophy, X-linked myotubular myopathy, or a cancer (e.g., a HER2 / neu positive cancer or a glioblastoma).

47. The method of any one of claims 41-46, wherein treating comprises prevention of progression of the disease or disorder in the subject.

48. The method of any one of claims 41-47, wherein the subject is a human.

49. The method of any one of claims 41-48, wherein the AAV particle 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; (iii) intramuscularly; or (iv) intravenously. 316 319351975.1Attorney Docket Number: V2071-3033PCT 50. The pharmaceutical composition of claim 39, the AAV particle of any one of claims 21-35, an AAV particle comprising the AAV capsid variant of any one of claims 1-17, 20, or 35, or an AAV particle comprising the peptide of claim 19 or 35, for use in a method of delivering a payload to a cell or tissue.

51. The pharmaceutical composition of claim 39, the AAV particle of any one of claims 21-35, an AAV particle comprising the AAV capsid variant of any one of claims 1-17, 20, or 35, or an AAV particle comprising the peptide of claim 19 or 35, for use in a method of treating a genetic disorder, a neurological disorder, a neurodegenerative disorder, a muscular disorder, a neuromuscular disorder, or a neuro-oncological disorder.

52. The pharmaceutical composition of claim 39, the AAV particle of any one of claims 21-35, an AAV particle comprising the AAV capsid variant of any one of claims 1-17, 20, or 35, or an AAV particle comprising the peptide of claim 19 or 35, for use in the manufacture of a medicament.

53. Use of the pharmaceutical composition of claim 39, the AAV particle of any one of claims 21-35, an AAV particle comprising the AAV capsid variant of any one of claims 1-17, 20, or 35, or an AAV particle comprising the peptide of claim 19 or 35, in the manufacture of a medicament.

54. Use of the pharmaceutical composition of claim 39, the AAV particle of any one of claims 21-35, an AAV particle comprising the AAV capsid variant of any one of claims 1-17, 20, or 35, or an AAV particle comprising the peptide of claim 19 or 35, in the manufacture of a medicament for treating a genetic disorder, a neurological disorder, a neurodegenerative disorder, a muscular disorder, a neuromuscular disorder, or a neuro-oncological disorder. 317 319351975.1

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