AAV capsid variants and uses thereof
AAV capsid variants with specific amino acid modifications enhance tropism and transduction efficiency for CNS and muscle tissues, addressing low efficiency and antibody neutralization issues in gene therapy.
Patent Information
- Application Number
- PCT/US2025/028361
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2024-05-09
- Filing Date
- 2025-05-08
- Publication Date
- 2026-01-22
AI Technical Summary
Current AAV capsids have low transduction efficiency in certain organs and are neutralized by preexisting antibodies, limiting their effectiveness in gene therapy for the adult central nervous system and other tissues.
Development of AAV capsid variants with specific amino acid modifications at defined positions to enhance tropism for CNS and muscle tissues, including variants with sequences at least 95% identical to specified SEQ ID NOs, particularly in variable region IV, to improve delivery efficiency and evade neutralizing antibodies.
The modified AAV capsid variants demonstrate enhanced tropism and transduction efficiency for CNS and muscle tissues, overcoming the limitations of natural AAV variants and antibody neutralization, thereby improving gene therapy efficacy.
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Abstract
Description
Attorney Docket No.: V2071-3049PCTAAV CAPSID VARIANTS AND USES THEREOFRELATED APPLICATIONS
[0001] This application claims priority to U.S. Provisional Application No. 63 / 645,030 filed on May 9, 2024; 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 V2071-3049PCT_SL.xml, was created on May 2, 2025, and is 5,787,621 bytes in size. The information in electronic format of the Sequence Listing is incorporated herein by reference in its entirety.FIELD OF THE DISCLOSURE
[0003] The disclosure relates to compositions and methods for the preparation, use, and / or formulation of adeno-associated virus capsid proteins and variants thereof.BACKGROUND
[0004] Gene delivery to the adult central nervous system (CNS) remains a significant challenge in gene therapy. Engineered adeno-associated virus (AAV) capsids with improved brain tropism represent an attractive solution to the limitations of CNS delivery.
[0005] AAV-derived vectors are promising tools for clinical gene transfer because of their non- pathogenic nature, their low immunogenic profile, low rate of integration into the host genome and long-term transgene expression in non-dividing cells. However, the transduction efficiency of AAV natural variants in certain organs is too low for clinical applications, and capsid neutralization by preexisting 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, c.g., improved tropism to a target cell or tissue upon systemic administration, have met with limited success. As such, there is a need for improved methods of producing AAV capsids and resulting AAV capsids for delivery of a payload of interest to a target cell or tissue, e.g., a CNS cell or tissue, or a muscle cell or tissue.SUMMARY OF THE DISCLOSURE
[0007] The present disclosure pertains at least in part, to compositions and methods for the production and use of an AAV particle comprising an AAV capsid polypeptide, e g., an AAV capsid variant. In some embodiments, the AAV capsid variant has an enhanced tropism for a tissue or a cell,1323376583.1Attorney Docket No.: V2071-3049PCT e.g., a CNS tissue or a CNS cell. Said tropism can be useful for delivery of a pay load, e.g., a pay load described herein to a cell or tissue, for the treatment of a disorder, e.g., a neurological or a neurodegenerative disorder, a muscular or a neuromuscular disorder, or a neuro-oncological disorder.
[0008] Accordingly, in one aspect, the present disclosure provides an AAV capsid variant comprising: (i) two, three, or all of an amino acid other than D at position 657, P at position 659, T at position 660, and / or A at position 661, numbered according to SEQ ID NO: 138; (ii) two, three, four, five, six or all of an amino acid other than P at position 659, A at position 661, N at position 663. K at position 664, D at position 665, K at position 666, and / or N at position 668, numbered according to SEQ ID NO: 138; or (iii) two, three, four, five, six or all of an amino acid other than P at position 659, A at position 661, N at position 663, K at position 664, D at position 665, L at position 667, and / or N at position 668, numbered according to SEQ ID NO: 138.
[0009] In yet another aspect, the present disclosure provides an adeno-associated virus (AAV) capsid variant comprising an amino acid sequence at least 95% identical to amino acids 203-736 of SEQ ID NO: 138, wherein the amino acid sequence comprises: (i) A at position 659, E at position 661, L at position 663. S at position 664, V at position 665, P at position 666, and K at position 668, numbered according to SEQ ID NO: 138; (ii) the amino acid E at position 657, A at position 659, E at position 660, and L at position 661. numbered according to SEQ ID NO: 138; (iii) the amino acid E at position 657, S at position 659. D at position 660, and V at position 661, numbered according to SEQ ID NO: 138; (iv) the amino acid Q at position 657, S at position 659. E at position 660, and E at position 661, numbered according to SEQ ID NO: 138; (v) the amino acid E at position 657. F at position 659. S at position 660, and E at position 661, numbered according to SEQ ID NO: 138; (vi) the amino acid E at position 657, H at position 659, M at position 660, and E at position 661. numbered according to SEQ ID NO: 138; (vii) the amino acid E at position 657. S at position 659, D at position 660, and L at position 661. numbered according to SEQ ID NO: 138; (viii) the amino acid E at position 657, W at position 659, S at position 660. and E at position 661, numbered according to SEQ ID NO: 138; (ix) the amino acid T at position 657, W at position 659, E at position 660. and L at position 661, numbered according to SEQ ID NO: 138; (x) the amino acid A at position 659, E at position 661, L at position 663, Y at position 664, T at position 665, V at position 667. and R at position 668, numbered according to SEQ ID NO: 138; or (xi) the amino acid R at position 710, D at position 716, and D at position 717. numbered according to SEQ ID NO: 138.
[0010] In yet another aspect, die present disclosure provides an adeno-associated virus (AAV) capsid variant comprising an amino acid sequence at least 95% identical to amino acids 138-736 of SEQ ID NO: 138, wherein the amino acid sequence comprises: (i) A at position 659, E at position 661, L at position 663, S at position 664, V at position 665, P at position 666, and K at position 668, numbered according to SEQ ID NO: 138; (ii) the amino acid E at position 657, A at position 659, E at position 660, and L at position 661. numbered according to SEQ ID NO: 138; (iii) the amino acid E at position 657, S at position 659. D at position 660, and V at position 661, numbered according to SEQ2323376583.1Attorney Docket No.: V2071-3049PCTID NO: 138; (iv) the amino acid Q at position 657, S at position 659, E at position 660, and E at position 661. numbered according to SEQ ID NO: 138; (v) the amino acid E at position 657, F at position 659. S at position 660, and E at position 661, numbered according to SEQ ID NO: 138; (vi) the amino acid E at position 657, H at position 659, M at position 660, and E at position 661. numbered according to SEQ ID NO: 138; (vii) the amino acid E at position 657. S at position 659, D at position 660, and L at position 661. numbered according to SEQ ID NO: 138; (viii) the amino acid E at position 657, W at position 659, S at position 660. and E at position 661, numbered according to SEQ ID NO: 138; (ix) the amino acid T at position 657, W at position 659, E at position 660, and L at position 661, numbered according to SEQ ID NO: 138; (x) the amino acid A at position 659, E at position 661, L at position 663, Y at position 664, T at position 665, V at position 667, and R at position 668, numbered according to SEQ ID NO: 138; or (xi) the amino acid R at position 710, D at position 716, and D at position 717, numbered according to SEQ ID NO: 138.
[0011] In yet another aspect, the present disclosure provides an adeno-associated virus (AAV) capsid variant comprising an amino acid sequence at least 95% identical to SEQ ID NO: 138, wherein the amino acid sequence comprises: (i) A at position 659, E at position 661. L at position 663, S at position 664, V at position 665, P at position 666, and K at position 668, numbered according to SEQ ID NO: 138; (ii) the amino acid E at position 657, A at position 659, E at position 660, and L at position 661, numbered according to SEQ ID NO: 138; (iii) the amino acid E at position 657, S at position 659, D at position 660, and V at position 661. numbered according to SEQ ID NO: 138; (iv) the amino acid Q at position 657. S at position 659, E at position 660, and E at position 661. numbered according to SEQ ID NO: 138; (v) the amino acid E at position 657, F at position 659. S at position 660, and E at position 661. numbered according to SEQ ID NO: 138; (vi) the amino acid E at position 657, H at position 659. M at position 660, and E at position 661, numbered according to SEQ ID NO: 138; (vii) the amino acid E at position 657. S at position 659, D at position 660, and L at position 661. numbered according to SEQ ID NO: 138; (viii) the amino acid E at position 657, W at position 659. S at position 660, and E at position 661 , numbered according to SEQ ID NO: 138; (ix) the amino acid T at position 657, W at position 659, E at position 660, and L at position 661, numbered according to SEQ ID NO: 138; (x) the amino acid A at position 659, E at position 661. L at position 663, Y at position 664. T at position 665, V at position 667, and R at position 668. numbered according to SEQ ID NO: 138; or (xi) the amino acid R at position 710. D at position 716, and D at position 717, numbered according to SEQ ID NO: 138.
[0012] In yet another aspect, the present disclosure provides an adeno-associated virus (AAV) capsid variant comprising an amino acid sequence at least 95% identical to amino acids 203-742 of SEQ ID NO: 981, wherein the amino acid sequence comprises SPHSKA (SEQ ID NO: 941) in variable region IV (VR-IV) and comprises: (i) the amino acid A at position 665, the amino acid E at position 667, the amino acid L at position 669, the amino acid S at position 670, the amino acid V at position 671, the amino acid P at position 672, and the amino acid K at position 674, numbered3323376583.1Attorney Docket No.: V2071-3049PCT according to SEQ ID NO: 981; (ii) the amino acid E at position 663, the amino acid S at position 665, the amino acid D at position 666, and the amino acid V at position 667, numbered according to SEQ ID NO: 981 ; (iii) the amino acid E at position 663. the amino acid A at position 665. the amino acid E at position 666, and the amino acid L at position 667, numbered according to SEQ ID NO: 981; (iv) the amino acid Q at position 663, the amino acid S at position 665, the amino acid E at position 666, and the amino acid E at position 667, numbered according to SEQ ID NO: 981; (v) the amino acid E at position 663, the amino acid F at position 665, the amino acid S at position 666. and the amino acid E at position 667, numbered according to SEQ ID NO: 981; (vi) the amino acid E at position 663, the amino acid H at position 665. the amino acid M at position 666, and the amino acid E at position 667, numbered according to SEQ ID NO: 981; (vii) the amino acid E at position 663. the amino acid S at position 665, the amino acid D at position 666, and the amino acid L at position 667, numbered according to SEQ ID NO: 981; (viii) the amino acid E at position 663, the amino acid W at position 665, the amino acid S at position 666, and the amino acid E at position 667, numbered according to SEQ ID NO: 981; (ix) the amino acid A at position 665, the amino acid E at position 667, the amino acid L at position 669, the amino acid Y at position 670, the amino acid T at position 671, the amino acid V at position 673, and the amino acid R at position 674, numbered according to SEQ ID NO: 981; (x) the amino acid T at position 663, the amino acid W at position 665, die amino acid E at position 666, and the amino acid L at position 667, numbered according to SEQ ID NO: 981; or (xi) the amino acid R at position 716, the amino acid D at position 722, and the amino acid D at position 723, numbered according to SEQ ID NO: 981.
[0013] In yet another aspect, the present disclosure provides an adeno-associated virus (AAV) capsid variant comprising an amino acid sequence at least 95% identical to amino acids 203-742 of SEQ ID NO: 982, wherein the amino acid sequence comprises HDSPHK (SEQ ID NO: 2) in variable region IV (VR-IV) and comprises: (i) the amino acid A at position 665, the amino acid E at position 667. the amino acid L at position 669. the amino acid S at position 670, the amino acid V at position 671. the amino acid P at position 672, and the amino acid K at position 674. numbered according to SEQ ID NO: 982; (ii) the amino acid E at position 663. the amino acid S at position 665. the amino acid D at position 666, and the amino acid V at position 667, numbered according to SEQ ID NO: 982; (iii) the amino acid E at position 663. the amino acid A at position 665, the amino acid E at position 666, and the amino acid L at position 667, numbered according to SEQ ID NO: 982; (iv) the amino acid Q at position 663. the amino acid S at position 665, the amino acid E at position 666, and the amino acid E at position 667, numbered according to SEQ ID NO: 982; (v) the amino acid E at position 663, the amino acid F at position 665, the amino acid S at position 666, and the amino acid E at position 667, numbered according to SEQ ID NO: 982; (vi) the amino acid E at position 663, the amino acid H at position 665, the amino acid M at position 666, and the amino acid E at position 667, numbered according to SEQ ID NO: 982; (vii) the amino acid E at position 663, the amino acid S at position 665, the amino acid D at position 666, and the amino acid L at position 667, numbered4323376583.1Attorney Docket No.: V2071-3049PCT according to SEQ ID NO: 982; (viii) the amino acid E at position 663, the amino acid W at position 665. the amino acid S at position 666, and the amino acid E at position 667, numbered according to SEQ ID NO: 982; (ix) the amino acid A at position 665, the amino acid E at position 667, the amino acid L at position 669, the amino acid Y at position 670, the amino acid T at position 671, the amino acid V at position 673, and the amino acid R at position 674, numbered according to SEQ ID NO: 982; (x) the amino acid T at position 663, the amino acid W at position 665. the amino acid E at position 666, and the amino acid L at position 667. numbered according to SEQ ID NO: 982; or (xi) the amino acid R at position 716, the amino acid D at position 1 L, and the amino acid D at position 723, numbered according to SEQ ID NO: 982.
[0014] In yet another aspect, the present disclosure provides an adcno-associatcd virus (AAV) capsid variant comprising: (i) the amino acid A at position 665, the amino acid E at position 667, the amino acid L at position 669, the amino acid S at position 670, the amino acid V at position 671, the amino acid P at position 672, and the amino acid K at position 674, numbered according to SEQ ID NO: 981; (ii) tire amino acid E at position 663, the amino acid S at position 665, the amino acid D at position 666, and the amino acid V at position 667, numbered according to SEQ ID NO: 981; (iii) the amino acid E at position 663. the amino acid A at position 665. the amino acid E at position 666. and the amino acid L at position 667, numbered according to SEQ ID NO: 981; (iv) the amino acid Q at position 663, the amino acid S at position 665, the amino acid E at position 666, and the amino acid E at position 667, numbered according to SEQ ID NO: 981; (v) the amino acid E at position 663, the amino acid F at position 665. the amino acid S at position 666. and the amino acid E at position 667, numbered according to SEQ ID NO: 981; (vi) the amino acid E at position 663. the amino acid H at position 665, the amino acid M at position 666, and the amino acid E at position 667, numbered according to SEQ ID NO: 981; (vii) the amino acid E at position 663, the amino acid S at position 665. the amino acid D at position 666. and the amino acid L at position 667. numbered according to SEQ ID NO: 981; (viii) the amino acid E at position 663. the amino acid W at position 665, the amino acid S at position 666, and the amino acid E at position 667, numbered according to SEQ ID NO: 981 ; (ix) the amino acid A at position 665, the amino acid E at position 667, the amino acid L at position 669. the amino acid Y at position 670. the amino acid T at position 671. the amino acid V at position 673. and the amino acid R at position 674. numbered according to SEQ ID NO: 981; (x) the amino acid T at position 663, the amino acid W at position 665, the amino acid E at position 666, and the amino acid L at position 667, numbered according to SEQ ID NO: 981; or (xi) the amino acid R at position 716, the amino acid D at position 722, and the amino acid D at position 723, numbered according to SEQ ID NO: 981.
[0015] In yet another aspect, tire present disclosure provides an adeno-associated virus (AAV) capsid variant comprising the amino acid E at position 657, the amino acid S at position 659, the amino acid D at position 660, and the amino acid V at position 661, numbered according to SEQ ID NO: 138.5323376583.1Attorney Docket No.: V2071-3049PCT
[0016] In yet another aspect, the present disclosure provides an adeno-associated virus (AAV) capsid variant comprising an amino acid sequence at least 95% identical to amino acids 203-736 of SEQ ID NO: 138, wherein the amino acid sequence comprises the amino acid E at position 657, the amino acid S at position 659, the amino acid D at position 660, and the amino acid V at position 661, numbered according to SEQ ID NO: 138.
[0017] In yet another aspect, the present disclosure provides an adeno-associated virus (AAV) capsid variant comprising an amino acid sequence at least 95% identical to amino acids 138-736 of SEQ ID NO: 138, wherein the amino acid sequence comprises the amino acid E at position 657, the amino acid S at position 659, the amino acid D at position 660, and the amino acid V at position 661, numbered according to SEQ ID NO: 138.
[0018] In yet another aspect, the present disclosure provides an adeno-associated virus (AAV) capsid variant comprising an amino acid sequence at least 95% identical to SEQ ID NO: 138, wherein the amino acid sequence comprises the amino acid E at position 657, the amino acid S at position 659, the amino acid D at position 660. and the amino acid V at position 661. numbered according to SEQ ID NO: 138.
[0019] In yet another aspect, the present disclosure provides an adeno-associated virus (AAV) capsid variant comprising the amino acid E at position 663. the amino acid S at position 665. the amino acid D at position 666. and the amino acid V at position 667. numbered according to SEQ ID NO: 6437.
[0020] In yet another aspect, the present disclosure provides an adeno-associated virus (AAV) capsid variant comprising an amino acid sequence at least 95% identical to amino acids 203-742 of SEQ ID NO: 6437, wherein the amino acid sequence comprises SPHSKA (SEQ ID NO: 941) in variable region IV (VR-IV) and comprises the amino acid E at position 663, the amino acid S at position 665, the amino acid D at position 666, and the amino acid V at position 667, numbered according to SEQ ID NO: 6437.
[0021] In yet another aspect, the present disclosure provides an adeno-associated virus (AAV) capsid variant comprising an amino acid sequence at least 95% identical to amino acids 138-742 of SEQ ID NO: 6437, wherein the amino acid sequence comprises SPHSKA (SEQ ID NO: 941) in variable region IV (VR-IV) and comprises the amino acid E at position 663, the amino acid S at position 665, the amino acid D at position 666, and the amino acid V at position 667, numbered according to SEQ ID NO: 6437.
[0022] In yet another aspect, the present disclosure provides an adeno-associated virus (AAV) capsid variant comprising an amino acid sequence at least 95% identical to SEQ ID NO: 6437, wherein the amino acid sequence comprises SPHSKA (SEQ ID NO: 941) in variable region IV (VR- IV) and comprises the amino acid E at position 663, the amino acid S at position 665, the amino acid D at position 666, and the amino acid V at position 667, numbered according to SEQ ID NO: 6437.6323376583.1Attorney Docket No.: V2071-3049PCT
[0023] In yet another aspect, the present disclosure provides an adeno-associated virus (AAV) capsid variant comprising the amino acid A at position 659, the amino acid E at position 661. the amino acid L at position 663, the amino acid S at position 664, the amino acid V at position 665, the amino acid P at position 666, and the amino acid K at position 668, numbered according to SEQ ID NO: 138.
[0024] In yet another aspect, the present disclosure provides an adeno-associated virus (AAV) capsid variant an amino acid sequence at least 95% identical to amino acids 203-736 of SEQ ID NO: 138, wherein the amino acid sequence comprises the amino acid A at position 659, the amino acid E at position 661, the amino acid L at position 663, the amino acid S at position 664, the amino acid V at position 665, the amino acid P at position 666, and the amino acid K at position 668, numbered according to SEQ ID NO: 138.
[0025] In yet another aspect, the present disclosure provides an adeno-associated virus (AAV) capsid variant an amino acid sequence at least 95% identical to amino acids 138-736 of SEQ ID NO: 138, wherein the amino acid sequence comprises the amino acid A at position 659, the amino acid E at position 661, the amino acid L at position 663, the amino acid S at position 664, the amino acid V at position 665, the amino acid P at position 666, and the amino acid K at position 668, numbered according to SEQ ID NO: 138.
[0026] In yet another aspect, the present disclosure provides an adeno-associated virus (AAV) capsid variant an amino acid sequence at least 95% identical to SEQ ID NO: 138, wherein the amino acid sequence comprises the amino acid A at position 659, the amino acid E at position 661, the amino acid L at position 663, the amino acid S at position 664, the amino acid V at position 665, the amino acid P at position 666, and tire amino acid K at position 668, numbered according to SEQ ID NO: 138.
[0027] In yet another aspect, the present disclosure provides an adeno-associated virus (AAV) capsid variant comprising the amino acid A at position 665, the amino acid E at position 667, the amino acid L at position 669, the amino acid S at position 670, the amino acid V at position 671, the amino acid P at position 672, and die amino acid K at position 674, numbered according to SEQ ID NO: 6443.
[0028] In yet another aspect, the present disclosure provides an adeno-associated virus (AAV) capsid variant comprising an amino acid sequence at least 95% identical to amino acids 203-742 of SEQ ID NO: 6443, wherein the amino acid sequence comprises SPHSKA (SEQ ID NO: 941) in variable region IV (VR-1V) and comprises the amino acid A at position 665, the amino acid E at position 667, the amino acid L at position 669, the amino acid S at position 670, the amino acid V at position 671, the amino acid P at position 672, and the amino acid K at position 674, numbered according to SEQ ID NO: 6443.
[0029] In yet another aspect, the present disclosure provides an adeno-associated virus (AAV) capsid variant comprising an amino acid sequence at least 95% identical to amino acids 138-742 of7323376583.1Attorney Docket No.: V2071-3049PCTSEQ ID NO: 6443, wherein the amino acid sequence comprises SPHSKA (SEQ ID NO: 941) in variable region IV (VR-IV) and comprises the amino acid A at position 665. the amino acid E at position 667. the amino acid L at position 669. the amino acid S at position 670, the amino acid V at position 671. the amino acid P at position 672. and the amino acid K at position 674. numbered according to SEQ ID NO: 6443.
[0030] In yet another aspect, the present disclosure provides an adeno-associated virus (AAV) capsid variant comprising an amino acid sequence at least 95% identical to SEQ ID NO: 6443, wherein the amino acid sequence comprises SPHSKA (SEQ ID NO: 941) in variable region IV (VR- IV) and comprises the amino acid A at position 665, the amino acid E at position 667, the amino acid L at position 669, the amino acid S at position 670, the amino acid V at position 671, the amino acid P at position 672, and the amino acid K at position 674, numbered according to SEQ ID NO: 6443.
[0031] In yet another aspect, the present disclosure provides an adeno-associated virus (AAV) capsid variant comprising the amino acid E at position 657, the amino acid A at position 659, the amino acid E at position 660. and the amino acid L at position 661, numbered according to SEQ ID NO: 138.
[0032] In yet another aspect, the present disclosure provides an adeno-associated virus (AAV) capsid variant comprising an amino acid sequence at least 95% identical to amino acids 203-736 of SEQ ID NO: 138, wherein the amino acid sequence comprises the amino acid E at position 657, the amino acid A at position 659. the amino acid E at position 660, and the amino acid L at position 661, numbered according to SEQ ID NO: 138.
[0033] In yet another aspect, the present disclosure provides an adeno-associated virus (AAV) capsid variant comprising an amino acid sequence at least 95% identical to ammo acids 138-736 of SEQ ID NO: 138, wherein the amino acid sequence comprises the amino acid E at position 657, the amino acid A at position 659. the amino acid E at position 660, and the amino acid L at position 661, numbered according to SEQ ID NO: 138.
[0034] In yet another aspect, die present disclosure provides an adeno-associated virus (AAV) capsid variant comprising an amino acid sequence at least 95% identical to SEQ ID NO: 138, wherein the amino acid sequence comprises the amino acid E at position 657, the amino acid A at position 659, the amino acid E at position 660, and the amino acid L at position 661. numbered according to SEQ ID NO: 138.
[0035] In yet another aspect, the present disclosure provides an adeno-associated virus (AAV) capsid variant comprising the amino acid E at position 663, the amino acid A at position 665, the amino acid E at position 666. and the amino acid L at position 667. numbered according to SEQ ID NO: 6445.
[0036] In yet another aspect, the present disclosure provides an adeno-associated virus (AAV) capsid variant an adeno-associated virus (AAV) capsid variant comprising an amino acid sequence at least 95% identical to amino acids 203-742 of SEQ ID NO: 6445. wherein the amino acid sequence8323376583.1Attorney Docket No.: V2071-3049PCT comprises SPHSKA (SEQ ID NO: 941) in variable region IV (VR-IV) and comprises the amino acid E at position 663. the amino acid A at position 665, the amino acid E at position 666. and the amino acid L at position 667, numbered according to SEQ ID NO: 6445.
[0037] In yet another aspect, the present disclosure provides an adeno-associated virus (AAV) capsid variant an adeno-associated virus (AAV) capsid variant comprising an amino acid sequence at least 95% identical to amino acids 138-742 of SEQ ID NO: 6445, wherein the amino acid sequence comprises SPHSKA (SEQ ID NO: 941) in variable region IV (VR-IV) and comprises the amino acid E at position 663, the amino acid A at position 665, the amino acid E at position 666, and the amino acid L at position 667, numbered according to SEQ ID NO: 6445.
[0038] In yet another aspect, die present disclosure provides an adeno-associated virus (AAV) capsid variant an adeno-associated virus (AAV) capsid variant comprising an amino acid sequence at least 95% identical to SEQ ID NO: 6445, wherein the amino acid sequence comprises SPHSKA (SEQ ID NO: 941) in variable region IV (VR-IV) and comprises the amino acid E at position 663, the amino acid A at position 665, the amino acid E at position 666. and the amino acid L at position 667. numbered according to SEQ ID NO: 6445.
[0039] In another aspect, the present disclosure provides an adeno-associated virus (AAV) capsid variant comprising an amino acid sequence at least 95% identical to amino acids 203-742 of SEQ ID NO: 6437, wherein the amino acid sequence comprises SPHSKA (SEQ ID NO: 941) in variable region IV (VR-IV) and comprises the amino acid E at position 451, V at position 453, the amino acid E at position 663, the amino acid S at position 665. the amino acid D at position 666. and the amino acid V at position 667, numbered according to SEQ ID NO: 6437. In some embodiments, the AAV capsid variant comprises an amino acid sequence at least 98% identical to amino acids 203-742 of SEQ ID NO: 6437. In some embodiments, the AAV capsid variant comprises the amino acid sequence of amino acids 203-742 of SEQ ID NO: 6437. In some embodiments, the AAV capsid variant comprises an amino acid sequence at least 95% identical to amino acids 138-742 of SEQ ID NO: 6437. In some embodiments, the AAV capsid variant comprises an amino acid sequence at least 98% identical to amino acids 138-742 of SEQ ID NO: 6437. In some embodiments, the AAV capsid variant comprises the amino acid sequence of amino acids 138-742 of SEQ ID NO: 6437. In some embodiments, die AAV capsid variant comprises an amino acid sequence at least 95% identical to SEQ ID NO: 6437. In some embodiments, the AAV capsid variant comprises an amino acid sequence at least 98% identical to SEQ ID NO: 6437. In some embodiments, the AAV capsid variant comprises the amino acid sequence of SEQ ID NO: 6437.
[0040] In another aspect, the present disclosure provides an adeno-associated virus (AAV) capsid variant comprising an amino acid sequence at least 95% identical to amino acids 138-742 of SEQ ID NO: 6437, wherein the amino acid sequence comprises SPHSKA (SEQ ID NO: 941) in variable region IV (VR-IV) and comprises die amino acid E at position 451, V at position 453. the amino acid E at position 663, the amino acid S at position 665, the amino acid D at position 666, and the amino9323376583.1Attorney Docket No.: V2071-3049PCT acid V at position 667, numbered according to SEQ ID NO: 6437. In some embodiments, the AAV capsid variant comprises an amino acid sequence at least 98% identical to amino acids 138-742 of SEQ ID NO: 6437. In some embodiments, the AAV capsid variant comprises the amino acid sequence of amino acids 138-742 of SEQ ID NO: 6437. In some embodiments, the AAV capsid variant comprises an amino acid sequence at least 95% identical to SEQ ID NO: 6437. In some embodiments, the AAV capsid variant comprises an amino acid sequence at least 98% identical to SEQ ID NO: 6437. In some embodiments, the AAV capsid variant comprises the amino acid sequence of SEQ ID NO: 6437.
[0041] In another aspect, the present disclosure provides an adeno-associated virus (AAV) capsid variant comprising an amino acid sequence at least 95% identical to SEQ ID NO: 6437, wherein the amino acid sequence comprises SPHSKA (SEQ ID NO: 941) in variable region IV (VR-IV) and comprises the amino acid E at position 451, V at position 453, the amino acid E at position 663, the amino acid S at position 665, the amino acid D at position 666, and the amino acid V at position 667. numbered according to SEQ ID NO: 6437. In some embodiments, the AAV capsid variant comprises an amino acid sequence at least 98% identical to SEQ ID NO: 6437. In some embodiments, the AAV capsid variant comprises the amino acid sequence of SEQ ID NO: 6437.
[0042] In yet another aspect, the present disclosure provides adeno-associated virus (AAV) capsid variant comprising an amino acid sequence at least 95% identical to amino acids 203-742 of SEQ ID NO: 6443, wherein the amino acid sequence comprises SPHSKA (SEQ ID NO: 941) in variable region IV (VR-IV) and comprises the amino acid E at position 451, V at position 453. the amino acid A at position 665, the amino acid E at position 667, the amino acid L at position 669, the amino acid S at position 670. the amino acid V at position 671, the amino acid P at position 672. and the amino acid K at position 674, numbered according to SEQ ID NO: 6443. In some embodiments, the AAV capsid variant comprises an amino acid sequence at least 98% identical to amino acids 203-742 of SEQ ID NO: 6443. In some embodiments, the AAV capsid variant comprises the amino acid sequence of amino acids 203-742 of SEQ ID NO: 6443. In some embodiments, the AAV capsid variant comprises an amino acid sequence at least 95% identical to amino acids 138-742 of SEQ ID NO: 6443. In some embodiments, the AAV capsid variant comprises an amino acid sequence at least 98% identical to amino acids 138-742 of SEQ ID NO: 6443. In some embodiments, the AAV capsid variant comprises the amino acid sequence of amino acids 138-742 of SEQ ID NO: 6443. In some embodiments, the AAV capsid variant comprises an amino acid sequence at least 95% identical to SEQ ID NO: 6443. In some embodiments, the AAV capsid variant comprises an amino acid sequence at least 98% identical to SEQ ID NO: 6443. In some embodiments, the AAV capsid variant comprises the amino acid sequence of SEQ ID NO: 6443.
[0043] In yet another aspect, the present disclosure provides adeno-associated virus (AAV) capsid variant comprising an amino acid sequence at least 95% identical to amino acids 138-742 of SEQ ID NO: 6443, wherein the amino acid sequence comprises SPHSKA (SEQ ID NO: 941) in variable10323376583.1Attorney Docket No.: V2071-3049PCT region IV (VR-IV) and comprises the amino acid E at position 451, V at position 453, the amino acid A at position 665, the amino acid E at position 667, the amino acid L at position 669. the amino acid S at position 670, the amino acid V at position 671, the amino acid P at position 672. and the amino acid K at position 674, numbered according to SEQ ID NO: 6443. In some embodiments, the AAV capsid variant comprises an amino acid sequence at least 98% identical to amino acids 138-742 of SEQ ID NO: 6443. In some embodiments, the AAV capsid variant comprises the amino acid sequence of amino acids 138-742 of SEQ ID NO: 6443. In some embodiments, the AAV capsid variant comprises an amino acid sequence at least 95% identical to SEQ ID NO: 6443. In some embodiments, the AAV capsid variant comprises an amino acid sequence at least 98% identical to SEQ ID NO: 6443. In some embodiments, the AAV capsid variant comprises the amino acid sequence of SEQ ID NO: 6443.
[0044] In yet another aspect, die present disclosure provides adeno-associated virus (AAV) capsid variant comprising an amino acid sequence at least 95% identical to SEQ ID NO: 6443, wherein the amino acid sequence comprises SPHSKA (SEQ ID NO: 941) in variable region IV (VR-IV) and comprises the amino acid E at position 451, V at position 453, the amino acid A at position 665, the amino acid E at position 667. the amino acid L at position 669, the amino acid S at position 670, the amino acid V at position 671, the amino acid P at position 672. and the amino acid K at position 674. numbered according to SEQ ID NO: 6443. In some embodiments, the AAV capsid variant comprises an amino acid sequence at least 98% identical to SEQ ID NO: 6443. In some embodiments, the AAV capsid variant comprises the amino acid sequence of SEQ ID NO: 6443.
[0045] In yet another aspect, the present disclosure provides an adeno-associated virus (AAV) capsid variant comprising an amino acid sequence at least 95% identical to amino acids 203-742 of SEQ ID NO: 6445. wherein the amino acid sequence comprises SPHSKA (SEQ ID NO: 941) in variable region IV (VR-IV) and comprises the amino acid E at position 451. V at position 453, the amino acid E at position 663, the amino acid A at position 665, the amino acid E at position 666, and the amino acid L at position 667, numbered according to SEQ ID NO: 6445. In some embodiments, the AAV capsid variant comprises an amino acid sequence at least 98% identical to amino acids 203- 742 of SEQ ID NO: 6445. In some embodiments, the AAV capsid variant comprises the amino acid sequence of amino acids 203-742 of SEQ ID NO: 6445. In some embodiments, the AAV capsid variant comprises an amino acid sequence at least 95% identical to amino acids 138-742 of SEQ ID NO: 6445. In some embodiments, the AAV capsid variant comprises an amino acid sequence at least 98% identical to amino acids 138-742 of SEQ ID NO: 6445. In some embodiments, the AAV capsid variant comprises the amino acid sequence of amino acids 138-742 of SEQ ID NO: 6445. In some embodiments, die AAV capsid variant comprises an amino acid sequence at least 95% identical to SEQ ID NO: 6445. In some embodiments, the AAV capsid variant comprises an amino acid sequence at least 98% identical to SEQ ID NO: 6445. In some embodiments, the AAV capsid variant comprises the amino acid sequence of SEQ ID NO: 6445.11323376583.1Attorney Docket No.: V2071-3049PCT
[0046] In yet another aspect, the present disclosure provides an adeno-associated virus (AAV) capsid variant comprising an amino acid sequence at least 95% identical to amino acids 138-742 of SEQ ID NO: 6445. wherein the amino acid sequence comprises SPHSKA (SEQ ID NO: 941) in variable region IV (VR-IV) and comprises the amino acid E at position 451. V at position 453, the amino acid E at position 663, the amino acid A at position 665, the amino acid E at position 666, and the amino acid L at position 667, numbered according to SEQ ID NO: 6445. In some embodiments, the AAV capsid variant comprises an amino acid sequence at least 98% identical to amino acids 138- 742 of SEQ ID NO: 6445. In some embodiments, the AAV capsid variant comprises the amino acid sequence of amino acids 138-742 of SEQ ID NO: 6445. In some embodiments, the AAV capsid variant comprises an amino acid sequence at least 95% identical to SEQ ID NO: 6445. In some embodiments, die AAV capsid variant comprises an amino acid sequence at least 98% identical to SEQ ID NO: 6445. In some embodiments, the AAV capsid variant comprises the amino acid sequence of SEQ ID NO: 6445.
[0047] In yet another aspect, the present disclosure provides an adeno-associated virus (AAV) capsid variant comprising an amino acid sequence at least 95% identical to SEQ ID NO: 6445. wherein the amino acid sequence comprises SPHSKA (SEQ ID NO: 941) in variable region IV (VR- IV) and comprises the amino acid E at position 451. V at position 453, the amino acid E at position 663, the amino acid A at position 665, the amino acid E at position 666, and the amino acid L at position 667, numbered according to SEQ ID NO: 6445. In some embodiments, the AAV capsid variant comprises an amino acid sequence at least 98% identical to SEQ ID NO: 6445. In some embodiments, the AAV capsid variant comprises the amino acid sequence of SEQ ID NO: 6445.
[0048] In yet another aspect, the present disclosure provides an adeno-associated capsid variant comprising the amino acid sequence of SEQ ID NO: 6437. In some embodiments, the nucleotide sequence encoding the AAV capsid variant comprises the nucleotide sequence of SEQ ID NO: 6464, or a nucleotide sequence at least 95%. at least 96%, at least 97%, at least 98%, or at least 99% identical thereto.
[0049] In yet another aspect, the present disclosure provides an adeno-associated capsid variant comprising the amino acid sequence of SEQ ID NO: 6443. In some embodiments, the nucleotide sequence encoding the AAV capsid variant comprises die nucleotide sequence of SEQ ID NO: 6465, or a nucleotide sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical thereto.
[0050] In yet another aspect, the present disclosure provides an adeno-associated capsid variant comprising the amino acid sequence of SEQ ID NO: 6445. In some embodiments, the nucleotide sequence encoding die AAV capsid variant comprises the nucleotide sequence of SEQ ID NO: 6466. or a nucleotide sequence at least 95%, at least 96%, at least 97%. at least 98%, or at least 99% identical thereto.12323376583.1Attorney Docket No.: V2071-3049PCT
[0051] In yet another aspect, the present disclosure provides an AAV capsid variant, comprising: (A) a modification, e.g., a substitution (e.g., conservative substitution) in the HI loop, optionally wherein HI loop comprises positions 662-678. numbered according to SEQ ID NO: 981, 982, 5, 6411, or 6412; or positions 656-672, numbered according to SEQ ID NO: 138 or 6414; and / or (B) an amino acid sequence having the following formula: [N1]-[N2]-[N3], wherein: (i) optionally [Nl] comprises XI, X2, and X3, wherein at least one of XI, X2, or X3 is G; (ii) [N2] comprises the amino acid sequence of SPH; (iii) [N3] comprises X4, X5, and X6, wherein at least one of X4, X5, or X6 is a basic amino acid, e.g., a K or R. In some embodiments, loop VIII comprises positions 587-599, numbered according to SEQ ID NO: 981, 982, 6411, or 6412; or positions 581-593, numbered according to SEQ ID NO: 138 or 6414. In some embodiments, position X4 of [N3] is K. In some embodiments, position X5 of [N3] is K. In some embodiments, [N3] is or comprises SKA. In some embodiments [N3] is or comprises KSG. In some embodiments, [N2]-[N3] is present immediately subsequent to position 455, numbered according to SEQ ID NO: 138. 981 or 982. In some embodiments, [Nl] is present immediately subsequent to position 452, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138, 981. or 982. In some embodiments, [Nl] replaces positions 453-455 (e.g.. G453, S454, and G455), relative to a reference sequence numbered according to SEQ ID NO: 138. In some embodiments, the AAV capsid variant comprises H at position 454 and D at position 455, numbered according to SEQ ID NO: 138 or 982. In some embodiments, the AAV capsid variant comprises S at position 454 and G at position 455, numbered according to SEQ ID NO: 138 or 981. In some embodiments, an insert of 8 amino acids replaces the SG at positions 454-455. numbered according to SEQ ID NO: 138. In some embodiments, an insert of 6 amino acids is present immediately subsequent to position 455, numbered according to SEQ ID NO: 138, 981. or 982.
[0052] In yet another aspect, the present disclosure provides an AAV particle comprising an AAV capsid variant, described herein. In some embodiments, the AAV particle comprises a nucleic acid sequence encoding a payload. In some embodiments, the AAV particle further comprises a viral genome comprising a promoter operably linked to the nucleic acid encoding the payload.
[0053] In yet another aspect, the present disclosure provides a method of making an AAV particle comprising an AAV capsid variant described herein. The method comprises providing a host cell comprising a viral genome and incubating the host cell under conditions suitable to enclose the viral genome in the AAV capsid variant, e.g., an AAV capsid variant described herein, thereby making the AAV particle.
[0054] In yet another aspect, the present disclosure provides a method of delivering a payload to a cell or tissue (e.g., a CNS cell, a CNS tissue, a liver cell, or a liver tissue). The method comprising administering an effective amount of an AAV particle comprising an AAV capsid variant described herein.13323376583.1Attorney Docket No.: V2071-3049PCT
[0055] In yet another aspect, the present disclosure provides a method of treating a subject having or diagnosed with having a genetic disorder, e.g., a monogenic disorder or a polygenic disorder. The method comprising administering to the subject an effective amount an AAV particle comprising an AAV capsid variant described herein.
[0056] In yet another aspect, the present disclosure provides a method of treating a subject having or diagnosed with having neurological, e.g., a neurodegenerative. disorder. The method comprising administering an effective amount of an AAV particle comprising an AAV capsid variant described herein.
[0057] 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.
[0058] Those skilled in the art will recognize or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. Such equivalents are intended to be encompassed by the following enumerated embodiments.Enumerated Embodiments1. An adeno-associated (AAV) capsid variant comprising:(i) two, three, or all of an amino acid other than D at position 657, P at position 659, T at position 660, and / or A at position 661, numbered according to SEQ ID NO: 138;(ii) two, three, four, five, six or all of an amino acid other than P at position 659, A at position 661, N at position 663, K at position 664, D at position 665, K at position 666, and / or N at position 668, numbered according to SEQ ID NO: 138; or(iii) two, three, four, five, six or all of an amino acid other than P at position 659, A at position 661, N at position 663, K at position 664, D at position 665, L at position 667, and / or N at position 668, numbered according to SEQ ID NO: 138.2. An adeno-associated capsid variant (AAV) capsid variant, comprising:(A) a modification, e.g., a substitution (e.g., conservative substitution) in the HI loop, optionally wherein HI loop comprises positions 662-678, numbered according to SEQ ID NO: 981, 982, 5, 6411, or 6412; or positions 656-672. numbered according to SEQ ID NO: 138 or 6414; and(B) an amino acid sequence having the following formula: [N1]-[N2]-[N3]. wherein:(i) optionally [Nl] comprises XI, X2, and X3, wherein at least one of XI, X2, or X3 is G;(ii) [N2] comprises the amino acid sequence of SPH; and(iii) [N3] comprises X4. X5. and X6, wherein at least one of X4, X5, or X6 is a basic amino acid, e.g., a K or R.14323376583.1Attorney Docket No.: V2071-3049PCT3. The AAV capsid variant of embodiment 1 or 2. wherein comprising:(i) an amino acid other than D at position 657, P at position 659. T at position 660. and A at position 661. numbered according to SEQ ID NO: 138;(ii) an amino acid other than P at position 659, A at position 661, N at position 663, K at position 664. D at position 665. K at position 666, and N at position 668, numbered according to SEQ ID NO: 138; or(iii) an amino acid other than P at position 659, A at position 661. N at position 663, K at position 664, D at position 665. L at position 667, and N at position 668, numbered according to SEQ ID NO: 138.4. The AAV capsid variant of any one of embodiments 1-3, which comprises two, three, or all of:(i) the amino acid E, Q, or T at position 657. numbered according to SEQ ID NO: 138;(ii) the amino acid A, S, F, H, or W, at position 659, numbered according to SEQ ID NO: 138;(iii) the amino acid E, D, S, or M, at position 660, numbered according to SEQ ID NO: 138; and / or(iv) the amino acid L, V, or E, at position 661. numbered according to SEQ ID NO: 138.5. The AAV capsid variant of any one of embodiments 1-4, which comprises:(i) two, three, or all of: the amino acid E at position 657, A at position 659, E at position 660, and / or L at position 661, numbered according to SEQ ID NO: 138;(ii) two. three, or all of: the amino acid E at position 657. S at position 659, D at position 660, and / or V at position 661. numbered according to SEQ ID NO: 138;(iii) two, three, or all of: the amino acid Q at position 657, S at position 659, E at position 660, and / or E at position 661, numbered according to SEQ ID NO: 138;(iv) two, three, or all of: the amino acid E at position 657. F at position 659, S at position 660. and / or E at position 661, numbered according to SEQ ID NO: 138;(v) two, three, or all of: the amino acid E at position 657, H at position 659, M at position 660. and / or E at position 661. numbered according to SEQ ID NO: 138;(vi) two, three, or all of: the amino acid E at position 657, S at position 659, D at position 660, and / or L at position 661, numbered according to SEQ ID NO: 138;(vii) two, three, or all of: the amino acid E at position 657, W at position 659, S at position 660, and / or E at position 661. numbered according to SEQ ID NO: 138; or(viii) two, three, or all of: the amino acid T at position 657, W at position 659, E at position 660, and / or L at position 661, numbered according to SEQ ID NO: 138.6. The AAV capsid variant of any one of embodiments 1-5, which comprises:15323376583.1Attorney Docket No.: V2071-3049PCT(i) the amino acid E, Q, or T at position 657, numbered according to SEQ ID NO: 138;(ii) the amino acid A. S. F, H. or W. at position 659, numbered according to SEQ ID NO: 138;(iii) the amino acid E. D, S, or M, at position 660, numbered according to SEQ ID NO: 138; and(iv) the amino acid L, V, or E, at position 661, numbered according to SEQ ID NO: 138.7. The AAV capsid variant of any one of embodiments 1-6, which comprises:(i) the amino acid E at position 657, A at position 659, E at position 660, and L at position 661, numbered according to SEQ ID NO: 138;(ii) the amino acid E at position 657, S at position 659, D at position 660, and V at position 661, numbered according to SEQ ID NO: 138;(iii) the amino acid Q at position 657, S at position 659, E at position 660, and E at position 661, numbered according to SEQ ID NO: 138;(iv) the amino acid E at position 657, F at position 659, S at position 660, and E at position 661, numbered according to SEQ ID NO: 138;(v) the amino acid E at position 657, H at position 659, M at position 660, and E at position 661, numbered according to SEQ ID NO: 138;(vi) the amino acid E at position 657, S at position 659, D at position 660. and L at position 661, numbered according to SEQ ID NO: 138;(vii) the amino acid E at position 657. W at position 659. S at position 660, and E at position 661, numbered according to SEQ ID NO: 138; or(viii) the amino acid T at position 657, W at position 659, E at position 660. and L at position 661, numbered according to SEQ ID NO: 138.8. An adeno-associated (AAV) capsid variant comprising:(i) the amino acid E at position 657, S at position 659, D at position 660. and V at position 661. numbered according to SEQ ID NO: 138;(ii) the amino acid E at position 657, A at position 659. E at position 660, and L at position 661. numbered according to SEQ ID NO: 138;(iii) the amino acid Q at position 657, S at position 659, E at position 660, and E at position 661. numbered according to SEQ ID NO: 138;(iv) the amino acid E at position 657, F at position 659, S at position 660, and E at position 661, numbered according to SEQ ID NO: 138;(v) the amino acid E at position 657, H at position 659. M at position 660, and E at position 661, numbered according to SEQ ID NO: 138;16323376583.1Attorney Docket No.: V2071-3049PCT(vi) the amino acid E at position 657. S at position 659, D at position 660. and L at position661. numbered according to SEQ ID NO: 138;(vii) the amino acid E at position 657, W at position 659, S at position 660, and E at position661. numbered according to SEQ ID NO: 138; or(viii) the amino acid T at position 657. W at position 659. E at position 660, and L at position 661. numbered according to SEQ ID NO: 138.9. The AAV capsid variant of any one of 1-3, which comprises two, three, four, five, six, or all of the amino acid A at position 659. E at position 661, L at position 663, S at position 664, V at position 665, P at position 666, and / or K at position 668, numbered according to SEQ ID NO: 138.10. The AAV capsid variant of any one of 1-3 or 9, which comprises the amino acid A at position 659, E at position 661, L at position 663, S at position 664, V at position 665, P at position 666, and K at position 668, numbered according to SEQ ID NO: 138.11. An adeno-associated capsid variant comprising the ammo acid A at position 659, E at position 661, L at position 663, S at position 664, V at position 665, P at position 666, and K at position 668, numbered according to SEQ ID NO: 138.12. The AAV capsid variant of any one of 1-3, which comprises two. three, four, five, six, or all of the amino acid A at position 659, E at position 661, L at position 663, Y at position 664, T at position 665, V at position 667. and / or R at position 668. numbered according to SEQ ID NO: 138.13. The AAV capsid variant of any one of 1-3 or 12. which comprises the amino acid A at position 659, E at position 661, L at position 663, Y at position 664, T at position 665, V at position 667, and R at position 668, numbered according to SEQ ID NO: 138.14. An adeno-associated capsid variant comprising the amino acid A at position 659. E at position 661. L at position 663, Y at position 664, T at position 665. V at position 667, and R at position 668, numbered according to SEQ ID NO: 138.15. The AAV capsid variant of any one of embodiments 1-14, which comprises the amino acid sequence of any one of SEQ ID NOs: 78-136, 139-184, or 6463, optionally wherein the amino acid sequence is present at amino acids 656-672, numbered according to SEQ ID NO: 138.17323376583.1Attorney Docket No.: V2071-3049PCT16. The AAV capsid variant of any one of embodiments 1-15, which further comprises a modification, e.g., substitution, in hypervariable region X (VR-X), optionally wherein VR-X comprises amino acids 706-722, numbered according to SEQ ID NO: 138.17. An adeno-associated (AAV) capsid variant comprising two or all of an amino acid other than N at position 710, N at position 716. and / or T at position 717, numbered according to SEQ ID NO: 138.18. The AAV capsid variant of any one of embodiments 1-17, comprising two or all of an amino acid other than N at position 710, N at position 716, and / or T at position 717, numbered according to SEQ ID NO: 138.19. The AAV capsid variant of any one of embodiments 1-19, which comprises an amino acid other than N at position 710, N at position 716, and T at position 717, numbered according to SEQ ID NO: 138.20. The AAV capsid variant of any one of embodiments 1-19, which comprises two or all of the amino acid R at position 710, D at position 716, and / or D at position 717, numbered according to SEQ ID NO: 138.21. The AAV capsid variant of any one of embodiments 1-20, which comprises the amino acid R at position 710, D at position 716, and D at position 717. numbered according to SEQ ID NO: 138.22. An adeno-associated (AAV) capsid variant comprising the amino acid R at position 710. D at position 716, and D at position 717, numbered according to SEQ ID NO: 138.23. The AAV capsid variant of any one of embodiments 1-22, which comprises the amino acid sequence of any one of SEQ ID NOs: 4488-4584, optionally wherein the amino acid sequence is present at amino acids 706-722. numbered according to SEQ ID NO: 138.24. An adeno-associated (AAV) capsid variant comprising:(i) the amino acid A at position 659. E at position 661, L at position 663, S at position 664, V at position 665, P at position 666, and K at position 668, numbered according to SEQ ID NO: 138; and(ii) the amino acid R at position 710, D at position 716, and D at position 717, numbered according to SEQ ID NO: 138.25. An adeno-associated (AAV) capsid variant comprising:18323376583.1Attorney Docket No.: V2071-3049PCT(i) E at position 657, A at position 659, E at position 660, and L at position 661, numbered according to SEQ ID NO: 138; and(ii) the amino acid R at position 710. D at position 716. and D at position 717, numbered according to SEQ ID NO: 138.26. The AAV capsid variant of any one of the preceding embodiments, which further comprises a modification, e.g., substitution, in hypervariable region I (VR-I), optionally wherein VR-I comprises amino acids 254-272, numbered according to SEQ ID NO: 138. l ' l . The AAV capsid variant of any one of the preceding embodiments, which comprises the amino acid sequence of any one of SEQ ID NOs: 4584-4672, 185-199, or 6427-6436.28. The AAV capsid variant of any one of embodiments 1 or 3-27, which comprises an amino acid sequence having the following formula: [N1]-[N2]-[N3], wherein:(i) optionally [Nl] comprises XI, X2, and X3, wherein at least one of XI, X2, or X3 is G;(ii) [N2] comprises the amino acid sequence of SPH; and(iii) [N3] comprises X4, X5, and X6, wherein at least one of X4, X5, or X6 is a basic amino acid, e.g., a K or R29. The AAV capsid variant of any one of embodiments 2-7. 9, 10. 12, 13, 15, 16. 18-21, 23, 26-28, wherein X4. X5. or both of [N3] is a K.30. The AAV capsid variant of any one of embodiments 2-7. 9, 10. 12, 13, 15, 16. 18-21, 23, 26-29, wherein X4. X5. or X6 of [N3] is an R.31. The AAV capsid variant of any one of embodiments 2-7, 9. 10, 12, 13, 15, 16, 18-21, 23, 26-30, wherein:(a) position X4 of [N3] is: K, S, A, V, T. G, F, W, V. N, or R;(b) position X5 of [N3] is: S, K. T, F, I, L, Y, H, M, or R; and / or(c) position X6 of [N3] is: G, A, R, M, I, N, T, Y, D, P. V, L, E. W, N, Q, K, or S; optionally wherein the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of the aforesaid amino acids in (a)-(c).32. The AAV capsid variant of any one of embodiments 2-7, 9. 10, 12, 13, 15, 16, 18-21, 23. 26-31, wherein [N3] comprises SK, KA, KS, AR, RM, VK, AS, SR, VK, KR, KK, KN, VR, RS, RK, KT, TS, KF, FG, KI, IG, KL, LG, TT. TY, KY, YG, KD, KP, TR, RG, VR, GA, SL. SS, FL, WK, SA,19323376583.1Attorney Docket No.: V2071-3049PCTRA, LR, KW, RR, GK, TK, NK, AK, KV, KG, KH, KM, TG, SE, SV, SW. SN, HG, SQ, LW, MG, MA. or SG.33. The AAV capsid variant of any one of embodiments 2-7, 9. 10, 12, 13, 15. 16, 18-21. 23. 26-33, wherein [N3] is or comprises SKA, KSG, ARM. VKS. ASR, VKI, KKN, VRM. RKA. KTS, KFG, KIG, KLG, KTT, KTY, KYG, SKD, SKP, TRG, VRG, KRG, GAR, KSA, KSR, SKL. SRA. SKR, SLR, SRG, SSR. FLR, SKW. SKS, WKA, VRR, SKV, SKT. SKG. GKA. TKA, NKA, SKL, SKN. AKA, KTG, KSL, KSE, KSV, KSW, KSN, KHG, KSQ, KSK, KLW. WKG, KMG, KMA, or RSG.34. The AAV capsid variant of any one of embodiments 2-7, 9. 10, 12, 13, 15, 16, 18-21, 23. 26-33, wherein [N2]-[N3] comprises SPHSK (SEQ ID NO: 4701), SPHKS (SEQ ID NO: 4704), SPHAR (SEQ ID NO: 4705), SPHVK (SEQ ID NO: 4706), SPHAS (SEQ ID NO: 4707), SPHKK (SEQ ID NO: 4708), SPHVR (SEQ ID NO: 4709), SPHRK (SEQ ID NO: 4710), SPHKT (SEQ ID NO: 4711), SPHKF (SEQ ID NO: 4712), SPHKI (SEQ ID NO: 4713), SPHKL (SEQ ID NO: 4714). SPHKY (SEQ ID NO: 4715), SPHTR (SEQ ID NO: 4716), SPHKR (SEQ ID NO: 4717), SPHGA (SEQ ID NO: 4718), SPHSR (SEQ ID NO: 4719), SPHSL (SEQ ID NO: 4720), SPHSS (SEQ ID NO: 4721), SPHFL (SEQ ID NO: 4722), SPHWK (SEQ ID NO: 4723), SPHGK (SEQ ID NO: 4724), SPHTK (SEQ ID NO: 4725). SPHNK (SEQ ID NO: 4726), SPHAK (SEQ ID NO: 4727), SPHKH (SEQ ID NO: 4728), SPHKM (SEQ ID NO: 4729), or SPHRS (SEQ ID NO: 4730).35. The AAV capsid variant of any one of embodiments 2-7. 9, 10. 12, 13, 15, 16. 18-21, 23, 26-34, wherein [N2]-[N3] is or comprises:(i) SPHSKA (SEQ ID NO: 941), SPHKSG (SEQ ID NO: 946). SPHARM (SEQ ID NO: 947), SPHVKS (SEQ ID NO: 948), SPHASR (SEQ ID NO: 949), SPHVKI (SEQ ID NO: 950). SPHKKN (SEQ ID NO: 954), SPHVRM (SEQ ID NO: 955), SPHRKA (SEQ ID NO: 956), SPHKFG (SEQ ID NO: 957), SPHKIG (SEQ ID NO: 958), SPHKLG (SEQ ID NO: 959), SPHKTS (SEQ ID NO: 963), SPHKTT (SEQ ID NO: 964). SPHKTY (SEQ ID NO: 965), SPHKYG (SEQ ID NO: 966). SPHSKD (SEQ ID NO: 967), SPHSKP (SEQ ID NO: 968), SPHTRG (SEQ ID NO: 972), SPHVRG (SEQ ID NO: 973), SPHKRG (SEQ ID NO: 974), SPHGAR (SEQ ID NO: 975), SPHKSA (SEQ ID NO: 977), SPHKSR (SEQ ID NO: 951). SPHSKL (SEQ ID NO: 960), SPHSRA (SEQ ID NO: 969), SPHSKR (SEQ ID NO: 978), SPHSLR (SEQ ID NO: 952), SPHSRG (SEQ ID NO: 961), SPHSSR (SEQ ID NO: 970), SPHFLR (SEQ ID NO: 979). SPHSKW (SEQ ID NO: 953), SPHSKS (SEQ ID NO: 962), SPHWKA (SEQ ID NO: 971), SPHVRR (SEQ ID NO: 980). SPHSKT (SEQ ID NO: 4731), SPHSKG (SEQ ID NO: 4732), SPHGKA (SEQ ID NO: 4733), SPHNKA (SEQ ID NO: 4734), SPHSKN (SEQ ID NO: 4735), SPHAKA (SEQ ID NO: 4736), SPHSKV (SEQ ID NO: 4737), SPHKTG (SEQ ID NO: 4738), SPHTKA (SEQ ID NO: 4739), SPHKSL (SEQ ID NO: 4740), SPHKSE (SEQ ID NO: 4741), SPHKSV (SEQ ID NO: 4742), SPHKSW (SEQ ID NO: 4743),20323376583.1Attorney Docket No.: V2071-3049PCTSPHKSN (SEQ ID NO: 4744), SPHKHG (SEQ ID NO: 4745), SPHKSQ (SEQ ID NO: 4746). SPHKSK (SEQ ID NO: 4747), SPHKLW (SEQ ID NO: 4748). SPHWKG (SEQ ID NO: 4749), SPHKMG (SEQ ID NO: 4750). SPHKMA (SEQ ID NO: 4751), or SPHRSG (SEQ ID NO: 976);(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i). e.g., any 2, 3. 4, or 5 amino acids, e.g.. consecutive amino acids, thereof;(iii) an amino acid sequence comprising one. two, or three but no more than four modifications, e.g.. substitutions (e.g.. conservative substitutions), insertions, or deletions, relative to any of the amino acid sequences in (i); or(iv) an amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).36. The AAV capsid variant of any one of embodiments 2-7, 9, 10, 12, 13, 15, 16, 18-21, 23, 26-34, which comprises an amino acid other than G at position 453 (e g., V, R, D, E, M, T, I, S, A, N, L, K, H, P, W, or C), an amino acid other than S at position 454 (V, L, N, D, H, R, P, G, T, I, A, E, Y, M, or Q), and / or a G at position 455 (e.g., C, L, D, E, Y, H, V, A, N, P, or S), numbered according to any one of SEQ ID NOs: 5-10, 36-59, 138, 981, 982, or 6409-6414.37. The AAV capsid variant of any one of embodiments 2-7, 9, 10, 12, 13, 15, 16. 18-21, 23, 26-33, which comprises the amino acid G at position 453, the amino acid S at position 454. and the amino acid G at position 455. numbered according to SEQ ID NO: 138 or 981.38. The AAV capsid variant of any one of embodiments 2-7. 9, 10. 12, 13, 15, 16. 18-21, 23, 26-36, which comprises the amino acid G at position 453, tire amino acid H at position 454, and the amino acid D at position 455. numbered according to SEQ ID NO: 138 or 982.39. The AAV capsid variant of any one of embodiments 2-7, 9. 10, 12, 13, 15, 16, 18-21, 23, 26-38, wherein [Nl] comprises XI, X2, and X3, wherein at least one of XI, X2, or X3 is G.40. The AAV capsid variant of any one of embodiments 2-7, 9. 10, 12, 13, 15. 16, 18-21. 23. 26-39, wherein:(a) position XI of [Nl] is: G, V, R, D. E, M. T, I, S, A. N, L, K, H, P, W, or C;(b) position X2 of [Nl] is: S, V. L, N, D, H, R. P, G, T. I. A, E, Y, M, or Q; and / or(c) position X3 of [Nl] is: G, C, L, D, E, Y, H, V, A. N, P, or S; optionally wherein the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of die aforesaid amino acids in (a)-(c).21323376583.1Attorney Docket No.: V2071-3049PCT41. The AAV capsid variant of any one of embodiments 2-7, 9, 10, 12, 13, 15, 16, 18-21, 23, 26-40, wherein [Nl] comprises GS, SG, GH. HD. GQ, QD, VS. CS. GR. RG, QS, SH, MS. RN. TS. IS, GP, ES, SS, GN, AS. NS. LS. GG, KS, GT, PS, RS, GI, WS, DS, ID, GL, DA. DG, ME, EN. KN, KE, Al, NG. PG. TG, SV, IG. LG, AG, EG, SA, YD. HE, HG, RD, ND. PD, MG, QV. DD, HN, HP, GY. GM. GD, or HS.42. The AAV capsid variant of any one of embodiments 2-7, 9. 10, 12, 13, 15. 16, 18-21, 23. 26-41, wherein [Nl] is or comprises GSG, GHD, GQD. VSG. CSG, GRG. CSH, GQS, GSH, RVG, GSC, GLL, GDD, GHE, GNY, MSG, RNG, TSG. ISG, GPG, ESG, SSG. GNG, ASG, NSG, LSG, GGG, KSG, HSG, GTG, PSG, GSV, RSG, GIG. WSG, DSG, IDG, GLG, DAG. DGG, MEG, ENG, GSA, KNG, KEG, AIG, GYD, GHG, GRD, GND, GPD, GMG, GQV, GHN, GHP, or GHS.43. The AAV capsid variant of any one of embodiments 2-7, 9, 10, 12, 13, 15, 16, 18-21, 23, 26-42, wherein [N1]-[N2] comprises:(i) SGSPH (SEQ ID NO: 4752), HDSPH (SEQ ID NO: 4703), QDSPH (SEQ ID NO: 4753), RGSPH (SEQ ID NO: 4754), SHSPH (SEQ ID NO: 4755), QSSPH (SEQ ID NO: 4756), DDSPH (SEQ ID NO: 4757). HESPH (SEQ ID NO: 4758), NYSPH (SEQ ID NO: 4759), VGSPH (SEQ ID NO: 4760), SCSPH (SEQ ID NO: 4761), LLSPH (SEQ ID NO: 4762), NGSPH (SEQ ID NO: 4763). PGSPH (SEQ ID NO: 4764). GGSPH (SEQ ID NO: 4765), TGSPH (SEQ ID NO: 4766), SVSPH (SEQ ID NO: 4767). IGSPH (SEQ ID NO: 4768). DGSPH (SEQ ID NO: 4769), LGSPH (SEQ ID NO: 4770), AGSPH (SEQ ID NO: 4771). EGSPH (SEQ ID NO: 4772), SASPH (SEQ ID NO: 4773), YDSPH (SEQ ID NO: 4774), HGSPH (SEQ ID NO: 4775), RDSPH (SEQ ID NO: 4776), NDSPH (SEQ ID NO: 4777). PDSPH (SEQ ID NO: 4778), MGSPH (SEQ ID NO: 4779), QVSPH (SEQ ID NO: 4780), HNSPH (SEQ ID NO: 4781). HPSPH (SEQ ID NO: 4782). or HSSPH (SEQ ID NO: 4783);(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i). e.g.. any 2, 3. or 4 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one. two, or three but no more than four modifications, e.g.. substitutions (e.g.. conservative substitutions), insertions, or deletions, relative to any of 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).44. The AAV capsid variant of any one of embodiments 2-7, 9. 10, 12, 13, 15, 16, 18-21, 23. 26-43, wherein [N1]-[N2] is or comprises:(i) GSGSPH (SEQ ID NO: 4695), GHDSPH (SEQ ID NO: 4784), GQDSPH (SEQ ID NO: 4785), VSGSPH (SEQ ID NO: 4786), CSGSPH (SEQ ID NO: 4787), GRGSPH (SEQ ID NO: 4788),22323376583.1Attorney Docket No.: V2071-3049PCTCSHSPH (SEQ ID NO: 4789), GQSSPH (SEQ ID NO: 4790), GSHSPH (SEQ ID NO: 4791), GDDSPH (SEQ ID NO: 4792), GHESPH (SEQ ID NO: 4793). GNYSPH (SEQ ID NO: 4794). RVGSPH (SEQ ID NO: 4795), GSCSPH (SEQ ID NO: 4796), GLLSPH (SEQ ID NO: 4797), MSGSPH (SEQ ID NO: 4798), RNGSPH (SEQ ID NO: 4799). TSGSPH (SEQ ID NO: 4800), ISGSPH (SEQ ID NO: 4801), GPGSPH (SEQ ID NO: 4802), ESGSPH (SEQ ID NO: 4803). SSGSPH (SEQ ID NO: 4804), GNGSPH (SEQ ID NO: 4805), ASGSPH (SEQ ID NO: 4806), NSGSPH (SEQ ID NO: 4807), LSGSPH (SEQ ID NO: 4808), GGGSPH (SEQ ID NO: 4809), KSGSPH (SEQ ID NO: 4810), HSGSPH (SEQ ID NO: 4811), GTGSPH (SEQ ID NO: 4812), PSGSPH (SEQ ID NO: 4813), GSVSPH (SEQ ID NO: 4814), RSGSPH (SEQ ID NO: 4815), GIGSPH (SEQ ID NO: 4816), WSGSPH (SEQ ID NO: 4817), DSGSPH (SEQ ID NO: 4818), IDGSPH (SEQ ID NO: 4819), GLGSPH (SEQ ID NO: 4820), DAGSPH (SEQ ID NO: 4821), DGGSPH (SEQ ID NO: 4822), MEGSPH (SEQ ID NO: 4823), ENGSPH (SEQ ID NO: 4824), GSASPH (SEQ ID NO: 4825), KNGSPH (SEQ ID NO: 4826), KEGSPH (SEQ ID NO: 4827), AIGSPH (SEQ ID NO: 4828), GYDSPH (SEQ ID NO: 4829), GHGSPH (SEQ ID NO: 4830), GRDSPH (SEQ ID NO: 4831), GNDSPH (SEQ ID NO: 4832), GPDSPH (SEQ ID NO: 4833), GMGSPH (SEQ ID NO: 4834), GQVSPH (SEQ ID NO: 4835), GHNSPH (SEQ ID NO: 4836), GHPSPH (SEQ ID NO: 4837), or GHSSPH (SEQ ID NO: 4838);(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i), e.g., any 2. 3, 4, or 5 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to any of tire amino acid sequences in (i); or(iv) an amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).45. The AAV capsid variant of any one of embodiments 2-7, 9. 10, 12, 13, 15, 16, 18-21, 23, 26-44, wherein [N1]-[N2]-[N3] comprises:(i) SGSPHSK (SEQ ID NO: 4839), HDSPHKS (SEQ ID NO: 4840), SGSPHAR (SEQ ID NO: 4841), SGSPHVK (SEQ ID NO: 4842), QDSPHKS (SEQ ID NO: 4843). SGSPHKK (SEQ ID NO: 4844), SGSPHVR (SEQ ID NO: 4845), SGSPHAS (SEQ ID NO: 4846), SGSPHRK (SEQ ID NO: 4847), SGSPHKT (SEQ ID NO: 4848). SHSPHKS (SEQ ID NO: 4849), QSSPHRS (SEQ ID NO: 4850), RGSPHAS (SEQ ID NO: 48 1), RGSPHSK (SEQ ID NO: 4852), SGSPHKF (SEQ ID NO: 4853), SGSPHKI (SEQ ID NO: 4854), SGSPHKL (SEQ ID NO: 4855), SGSPHKY (SEQ ID NO: 4856), SGSPHTR (SEQ ID NO: 4857), SHSPHKR (SEQ ID NO: 4858), SGSPHGA (SEQ ID NO: 4859), HDSPHKR (SEQ ID NO: 4860), DDSPHKS (SEQ ID NO: 4861), HESPHKS (SEQ ID NO: 4862), NYSPHKI (SEQ ID NO: 4863). SGSPHSR (SEQ ID NO: 4864), SGSPHSL (SEQ ID NO: 4865), SGSPHSS (SEQ ID NO: 4866), VGSPHSK (SEQ ID NO: 4867), SCSPHRK (SEQ ID23323376583.1Attorney Docket No.: V2071-3049PCTNO: 4868), SGSPHFL (SEQ ID NO: 4869), LLSPHWK (SEQ ID NO: 4870), NGSPHSK (SEQ ID NO: 4871), PGSPHSK (SEQ ID NO: 4872). GGSPHSK (SEQ ID NO: 4873), TGSPHSK (SEQ ID NO: 4874), SVSPHGK (SEQ ID NO: 4875). SGSPHTK (SEQ ID NO: 4876), IGSPHSK (SEQ ID NO: 4877), DGSPHSK (SEQ ID NO: 4878). SGSPHNK (SEQ ID NO: 4879). LGSPHSK (SEQ ID NO: 4880), AGSPHSK (SEQ ID NO: 4881), EGSPHSK (SEQ ID NO: 4882), SASPHSK (SEQ ID NO: 4883), SGSPHAK (SEQ ID NO: 4884), HDSPHKI (SEQ ID NO: 4885), YDSPHKS (SEQ ID NO: 4886), HDSPHKT (SEQ ID NO: 4887), RGSPHKR (SEQ ID NO: 4888), HGSPHSK (SEQ ID NO: 4889), RDSPHKS (SEQ ID NO: 4890), NDSPHKS (SEQ ID NO: 4891). QDSPHKI (SEQ ID NO: 4892), PDSPHKI (SEQ ID NO: 4893), PDSPHKS (SEQ ID NO: 4894), MGSPHSK (SEQ ID NO: 4895), HDSPHKH (SEQ ID NO: 4896), QVSPHKS (SEQ ID NO: 4897), HNSPHKS (SEQ ID NO: 4898), NGSPHKR (SEQ ID NO: 4899), HDSPHKY (SEQ ID NO: 4900), NDSPHKI (SEQ ID NO: 4901), HDSPHKL (SEQ ID NO: 4902), HPSPHWK (SEQ ID NO: 4903), HDSPHKM (SEQ ID NO: 4904), or HSSPHRS (SEQ ID NO: 4905);(ii) an amino acid sequence comprising any 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).46. The AAV capsid variant of any one of embodiments 2-7. 9, 10. 12, 13, 15, 16. 18-21, 23, 26-45, wherein | N 1 J-[N2]-[N3] is or comprises:(i) GSGSPHSKA (SEQ ID NO: 4697), GHDSPHKSG (SEQ ID NO: 4698). GSGSPHARM (SEQ ID NO: 4906), GSGSPHVKS (SEQ ID NO: 4907), GQDSPHKSG (SEQ ID NO: 4908), GSGSPHASR (SEQ ID NO: 4909). GSGSPHVKI (SEQ ID NO: 4910). GSGSPHKKN (SEQ ID NO: 4911). GSGSPHVRM (SEQ ID NO: 4912), VSGSPHSKA (SEQ ID NO: 4913). CSGSPHSKA (SEQ ID NO: 4914), GSGSPHRKA (SEQ ID NO: 4915), CSGSPHKTS (SEQ ID NO: 4916), CSHSPHKSG (SEQ ID NO: 4917). GQSSPHRSG (SEQ ID NO: 4918), GRGSPHASR (SEQ ID NO: 4919). GRGSPHSKA (SEQ ID NO: 4920), GSGSPHKFG (SEQ ID NO: 4921), GSGSPHKIG (SEQ ID NO: 4922), GSGSPHKLG (SEQ ID NO: 4923), GSGSPHKTS (SEQ ID NO: 4924), GSGSPHKTT (SEQ ID NO: 4925). GSGSPHKTY (SEQ ID NO: 4926), GSGSPHKYG (SEQ ID NO: 4927), GSGSPHSKD (SEQ ID NO: 4928), GSGSPHSKP (SEQ ID NO: 4929), GSGSPHTRG (SEQ ID NO: 4930), GSGSPHVRG (SEQ ID NO: 4931), GSHSPHKRG (SEQ ID NO: 4932), GSHSPHKSG (SEQ ID NO: 4933), VSGSPHASR (SEQ ID NO: 4934), VSGSPHGAR (SEQ ID NO: 4935), VSGSPHKFG (SEQ ID NO: 4936), GHDSPHKRG (SEQ ID NO: 4937), GDDSPHKSG (SEQ ID NO: 4938), GHESPHKSA (SEQ ID NO: 4939), GHDSPHKSA (SEQ ID NO: 4940),24323376583.1Attorney Docket No.: V2071-3049PCTGNYSPHKIG (SEQ ID NO: 4941), GHDSPHKSR (SEQ ID NO: 4942), GSGSPHSKL (SEQ ID NO: 4943). GSGSPHSRA (SEQ ID NO: 4944). GSGSPHSKR (SEQ ID NO: 4945), GSGSPHSLR (SEQ ID NO: 4946), GSGSPHSRG (SEQ ID NO: 4947). GSGSPHSSR (SEQ ID NO: 4948), RVGSPHSKA (SEQ ID NO: 4949). GSCSPHRKA (SEQ ID NO: 4950), GSGSPHFLR (SEQ ID NO: 4951). GSGSPHSKW (SEQ ID NO: 4952), GSGSPHSKS (SEQ ID NO: 4953), GLLSPHWKA (SEQ ID NO: 4954), GSGSPHVRR (SEQ ID NO: 4955), GSGSPHSKV (SEQ ID NO: 4956), MSGSPHSKA (SEQ ID NO: 4957), RNGSPHSKA (SEQ ID NO: 4958), TSGSPHSKA (SEQ ID NO: 4959), ISGSPHSKA (SEQ ID NO: 4960), GPGSPHSKA (SEQ ID NO: 4961), GSGSPHSKT (SEQ ID NO: 4962), ESGSPHSKA (SEQ ID NO: 4963), SSGSPHSKA (SEQ ID NO: 4964), GNGSPHSKA (SEQ ID NO: 4965), ASGSPHSKA (SEQ ID NO: 4966), NSGSPHSKA (SEQ ID NO: 4967), LSGSPHSKA (SEQ ID NO: 4968), GGGSPHSKA (SEQ ID NO: 4969), KSGSPHSKA (SEQ ID NO: 4970), GGGSPHSKS (SEQ ID NO: 4971), GSGSPHSKG (SEQ ID NO: 4972), HSGSPHSKA (SEQ ID NO: 4973), GTGSPHSKA (SEQ ID NO: 4974), PSGSPHSKA (SEQ ID NO: 4975), GSVSPHGKA (SEQ ID NO: 4976), RSGSPHSKA (SEQ ID NO: 4977), GSGSPHTKA (SEQ ID NO: 4978), GIGSPHSKA (SEQ ID NO: 4979), WSGSPHSKA (SEQ ID NO: 4980), DSGSPHSKA (SEQ ID NO: 4981), IDGSPHSKA (SEQ ID NO: 4982), GSGSPHNKA (SEQ ID NO: 4983), GLGSPHSKS (SEQ ID NO: 4984), DAGSPHSKA (SEQ ID NO: 4985). DGGSPHSKA (SEQ ID NO: 4986), MEGSPHSKA (SEQ ID NO: 4987), ENGSPHSKA (SEQ ID NO: 4988), GSASPHSKA (SEQ ID NO: 4989), GNGSPHSKS (SEQ ID NO: 4990), KNGSPHSKA (SEQ ID NO: 4991), KEGSPHSKA (SEQ ID NO: 4992). AIGSPHSKA (SEQ ID NO: 4993). GSGSPHSKN (SEQ ID NO: 4994). GSGSPHAKA (SEQ ID NO: 4995), GHDSPHKIG (SEQ ID NO: 4996), GYDSPHKSG (SEQ ID NO: 4997), GHESPHKSG (SEQ ID NO: 4998). GHDSPHKTG (SEQ ID NO: 4999), GRGSPHKRG (SEQ ID NO: 5000), GQDSPHKSG (SEQ ID NO: 4908), GHDSPHKSL (SEQ ID NO: 5001). GHGSPHSKA (SEQ ID NO: 5002), GHDSPHKSE (SEQ ID NO: 5003). VSGSPHSKA (SEQ ID NO: 4913), GRDSPHKSG (SEQ ID NO: 5004), GNDSPHKSV (SEQ ID NO: 5005), GQDSPHKIG (SEQ ID NO: 5006), GHDSPHKSV (SEQ ID NO: 5007), GPDSPHKIG (SEQ ID NO: 5008), GPDSPHKSG (SEQ ID NO: 5009). GHDSPHKSW (SEQ ID NO: 5010). GHDSPHKSN (SEQ ID NO: 5011), GMGSPHSKT (SEQ ID NO: 5012), GHDSPHKHG (SEQ ID NO: 5013), GQVSPHKSG (SEQ ID NO: 5014). GDDSPHKSV (SEQ ID NO: 5015), GHNSPHKSG (SEQ ID NO: 5016), GNGSPHKRG (SEQ ID NO: 5017), GHDSPHKYG (SEQ ID NO: 5018), GHDSPHKSQ (SEQ ID NO: 5019), GNDSPHKIG (SEQ ID NO: 5020), GHDSPHKSK (SEQ ID NO: 5021), GHDSPHKLW (SEQ ID NO: 5022), GHPSPHWKG (SEQ ID NO: 5023), GHDSPHKMG (SEQ ID NO: 5024), GHDSPHKMA (SEQ ID NO: 5025), or GHSSPHRSG (SEQ ID NO: 5026);(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i), e.g., any 2, 3, 4, 5, 6, 7, or 8 amino acids, e.g., consecutive amino acids, thereof;25323376583.1Attorney Docket No.: V2071-3049PCT(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 2-7, 9. 10, 12, 13, 15. 16, 18-21, 23. 26-46, wherein [N3] comprises SK, KA, KS, or SG.48. The AAV capsid variant of any one of embodiments 2-7, 9. 10, 12, 13, 15, 16, 18-21, 23. 26-47, wherein [N3] is or comprises SKA, KSG, or KYG.49. The AAV capsid variant of any one of embodiments 2-7, 9, 10, 12, 13, 15, 16, 18-21, 23, 26-48, wherein [N2]-[N3] comprises SPHSK (SEQ ID NO: 4701), SPHKS (SEQ ID NO: 4704), or SPHKY (SEQ ID NO: 4715).50. The AAV capsid variant of any one of embodiments 2-7, 9, 10, 12, 13, 15, 16. 18-21, 23, 26-49, wherein [N2]-[N3] is or comprises SPHSKA (SEQ ID NO: 941).51. The AAV capsid variant of any one of embodiments 2-7. 9, 10. 12, 13, 15, 16. 18-21, 23, 26-50, wherein [N2]-[N3] is or comprises SPHKSG (SEQ ID NO: 946).52. The AAV capsid variant of any one of embodiments 2-7. 9, 10. 12, 13, 15, 16. 18-21, 23, 26-51, wherein [N2]-[N3] is or comprises SPHKYG (SEQ ID NO: 966).53. The AAV capsid variant of any one of embodiments 2-7, 9. 10, 12, 13, 15, 16, 18-21, 23, 26-52, wherein [Nl] comprises GS, SG, GH, or HD.54. The AAV capsid variant of any one of embodiments 2-7, 9. 10, 12, 13, 15. 16, 18-21. 23. 26-53, wherein [Nl] is or comprises GSG.55. The AAV capsid variant of any one of embodiments 2-7, 9. 10, 12, 13, 15, 16, 18-21, 23. 26-53, wherein [Nl] is or comprises GHD.56. The AAV capsid variant of any one of embodiments 2-7, 9. 10, 12, 13, 15, 16, 18-21, 23. 26-50, 53, or 54, wherein [N1]-[N2]-[N3] comprises SGSPHSK (SEQ ID NO: 4839).26323376583.1Attorney Docket No.: V2071-3049PCT57. The AAV capsid variant of any one of embodiments 2-7, 9, 10, 12, 13, 15, 16, 18-21, 23, 26-49, 51, 53. or 55. wherein [N1]-[N2]-[N3] comprises HDSPHKS (SEQ ID NO: 4840).58. The AAV capsid variant of any one of embodiments 2-7, 9. 10, 12, 13, 15. 16, 18-21. 23. 26-49 or 55-54. wherein [N1]-[N2]-[N3] comprises SGSPHKYG (SEQ ID NO: 5027).59. The AAV capsid variant of any one of embodiments 2-7, 9. 10, 12, 13, 15. 16, 18-21, 23. 26-35, 37, 39-50, 53-54, or 56, wherein [N1]-[N2]-[N3] is or comprises GSGSPHSKA (SEQ ID NO: 4697).60. The AAV capsid variant of any one of embodiments 2-7, 9. 10, 12, 13, 15, 16, 18-21, 23. 26-36, 38-49, 51, 53, 55, or 57, wherein [N1]-[N2]-[N3] is or comprises GHDSPHKSG (SEQ ID NO: 4698).61. The AAV capsid variant of any one of embodiments 2-7, 9, 10, 12, 13, 15, 16, 18-21, 23, 26-35, 37, 39-49, 52-54, or 58, wherein [N1]-[N2]-[N3] is or comprises GSGSPHKYG (SEQ ID NO: 4927).62. The AAV capsid variant of any one of embodiments 2-7, 9, 10, 12, 13, 15, 16, 18-21, 23, 26-61, wherein [N1]-[N2]-[N3] replaces positions 453-455. numbered according to the amino acid sequence of SEQ ID NO: 138.63. The AAV capsid variant of any one of embodiments 2-7. 9, 10. 12, 13, 15, 16. 18-21, 23, 26-62, which comprises an amino acid other than Q at position 456 (e.g., W. K, R, G, L, V. S, P, H. K, I, M, A, E, or F), an amino acid other than N at position 457 (e.g., Y, C, K. T, H, R, D, V. S, P, G. W, E. F, A, 1, M. Q, or L), an amino acid other than Q at position 458 (e.g., G. K, H. R, T, L. D, A. P. 1. F, V, M, W, Y, S. E, N. or Y). and / or an amino acid other than Q at position 459 (e.g., H. L. R, W, K, A. P, E, M, I, S, G, N, Y, C, V, T, D, or V), relative to a reference sequence numbered according to SEQ ID NO: 138.64. The AAV capsid variant of any one of embodiments 2-7. 9. 10. 12, 13, 15, 16. 18-21, 23, 26-63, which comprises an amino acid other than Q at position 462 (e.g.. W, K, R, G. L, V, S. P, H, K, I, M, A, E, or F), an amino acid other than N at position 463 (e.g., Y. C, K, T. H, R. D, V, S. P, G, W, E, F. A, I, M, Q, or L), an amino acid other than Q at position 464 (e.g., G, K, H, R. T, L, D, A, P, I, F. V, M, W. Y, S, E. N, or Y), and / or an amino acid other than Q at position 465 (e.g., H, L, R, W. K, A, P, E. M, I, S, G, N, Y, C, V, T, D, or V). relative to a reference sequence numbered according to SEQ ID NO: 981, 982, 36, 37, 39, 40, 42-46, 48. 49, 50, 52, 53, 56, or 57.65. The AAV capsid variant of any one of embodiments 2-7, 9, 10, 12, 13, 15, 16, 18-21, 23, 26-64, which comprises:27323376583.1Attorney Docket No.: V2071-3049PCT(a) the amino acid Q at position 456, the amino acid N at position 457, the amino acid Q at position 458. and / or the amino acid Q at position 459, relative to a reference sequence numbered according to SEQ ID NO: 138; or(b) the amino acid Q at position 462, the amino acid N at position 463, the amino acid Q at position 464. and / or the amino acid Q at position 465, relative to a reference sequence numbered according to SEQ ID NO: 981, 982. 36, 37, 39, 40. 42-46, 48, 49. 50, 52, 53, 56. or 57.66. The AAV capsid variant of any one of embodiments 2-7, 9. 10, 12, 13, 15. 16, 18-21, 23. 26-65, which further comprises [N4], wherein [N4] comprises X7 X8 X9 X10, and wherein:(a) position X7 is: Q, W, K, R, G, L, V, S, P, H, K, I. M, A, E, or F;(b) position X8 is: N. Y, C, K, T, H, R, D, V, S, P, G, W, E, F, A, I, M, Q, or L;(c) position X9 is: Q, G, K, H, R, T. L, D, A, P, I, F, V, M, W, Y, S, E, N, or Y; and(d) position X10 is: Q, H, L, R, W, K, A, P, E, M, I, S, G, N, Y, C, V, T, D, or V; optionally wherein the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of die aforesaid amino acids in (a)-(d).67. The AAV capsid variant of embodiment 66, wherein:(a) position X7 of [N4] is Q or R;(b) position X8 of [N4] is N or R;(c) position X9 of [N4] is Q or R; and(d) position X10 of [N4] is Q, L, or R.68. The AAV capsid variant of embodiment 66 or 67, wherein [N4] is or comprises:(i) QNQQ (SEQ ID NO: 5028). WNQQ (SEQ ID NO: 5029), QYYV (SEQ ID NO: 5030). RRQQ (SEQ ID NO: 5031), GCGQ (SEQ ID NO: 5032), LRQQ (SEQ ID NO: 5033), RNQQ (SEQ ID NO: 5034). VNQQ (SEQ ID NO: 5035), FRLQ (SEQ ID NO: 5036). FNQQ (SEQ ID NO: 5037). LLQQ (SEQ ID NO: 5038), SNQQ (SEQ ID NO: 5039). RLQQ (SEQ ID NO: 5040), LNQQ (SEQ ID NO: 5041), QRKL (SEQ ID NO: 5042), LRRQ (SEQ ID NO: 5043). QRLR (SEQ ID NO: 5044), QRRL (SEQ ID NO: 5045), RRLQ (SEQ ID NO: 5046), RLRQ (SEQ ID NO: 5047), SKRQ (SEQ ID NO: 5048), QLYR (SEQ ID NO: 5049). QLTV (SEQ ID NO: 5050), QNKQ (SEQ ID NO: 5051), KNQQ (SEQ ID NO: 5052), QKQQ (SEQ ID NO: 5053), QTQQ (SEQ ID NO: 5054), QNHQ (SEQ ID NO: 5055), QHQQ (SEQ ID NO: 5056), QNQH (SEQ ID NO: 5057), QHRQ (SEQ ID NO: 5058), LTQQ (SEQ ID NO: 5059), QNQW (SEQ ID NO: 5060), QNTH (SEQ ID NO: 5061), RRRQ (SEQ ID NO: 5062), QYQQ (SEQ ID NO: 5063), QNDQ (SEQ ID NO: 5064), QNRH (SEQ ID NO: 5065), RDQQ (SEQ ID NO: 5066), PNLQ (SEQ ID NO: 5067), HVRQ (SEQ ID NO: 5068), PNQH (SEQ ID NO: 5069), HNQQ (SEQ ID NO: 5070), QSQQ (SEQ ID NO: 5071), QPAK (SEQ ID NO: 5072), QNLA (SEQ ID NO: 5073), QNQL (SEQ ID NO: 5074), QGQQ (SEQ ID NO: 5075), LNRQ (SEQ28323376583.1Attorney Docket No.: V2071-3049PCTID NO: 5076), QNPP (SEQ ID NO: 5077), QNLQ (SEQ ID NO: 5078), QDQE (SEQ ID NO: 5079), QDQQ (SEQ ID NO: 5080), HWQQ (SEQ ID NO: 5081), PNQQ (SEQ ID NO: 5082), PEQQ (SEQ ID NO: 5083), QRTM (SEQ ID NO: 5084), LHQH (SEQ ID NO: 5085), QHRI (SEQ ID NO: 5086), QYIH (SEQ ID NO: 5087). QKFE (SEQ ID NO: 5088), QFPS (SEQ ID NO: 5089), QNPL (SEQ ID NO: 5090), QAIK (SEQ ID NO: 5091), QNRQ (SEQ ID NO: 5092), QYQH (SEQ ID NO: 5093), QNPQ (SEQ ID NO: 5094), QHQL (SEQ ID NO: 5095). QSPP (SEQ ID NO: 5096), QAKL (SEQ ID NO: 5097), KSQQ (SEQ ID NO: 5098). QDRP (SEQ ID NO: 5099), QNLG (SEQ ID NO: 5100), QAFH (SEQ ID NO: 5101), QNAQ (SEQ ID NO: 5102), HNQL (SEQ ID NO: 5103). QKLN (SEQ ID NO: 5104), QNVQ (SEQ ID NO: 5105), QAQQ (SEQ ID NO: 5106), QTPP (SEQ ID NO: 5107). QPPA (SEQ ID NO: 5108), QERP (SEQ ID NO: 5109), QDLQ (SEQ ID NO: 5110), QAMH (SEQ ID NO: 5111), QHPS (SEQ ID NO: 5112), PGLQ (SEQ ID NO: 5113). QGIR (SEQ ID NO: 5114), QAPA (SEQ ID NO: 5115), QIPP (SEQ ID NO: 5116), QTQL (SEQ ID NO: 5117), QAPS (SEQ ID NO: 5118), QNTY (SEQ ID NO: 5119), QDKQ (SEQ ID NO: 5120), QNHL (SEQ ID NO: 5121), QIGM (SEQ ID NO: 5122), LNKQ (SEQ ID NO: 5123), PNQL (SEQ ID NO: 5124), QLQQ (SEQ ID NO: 5125), QRMS (SEQ ID NO: 5126), QGIL (SEQ ID NO: 5127), QDRQ (SEQ ID NO: 5128), RDWQ (SEQ ID NO: 5129), QERS (SEQ ID NO: 5130), QNYQ (SEQ ID NO: 5131), QRTC (SEQ ID NO: 5132), QIGH (SEQ ID NO: 5133), QGAI (SEQ ID NO: 5134), QVPP (SEQ ID NO: 5135), QVQQ (SEQ ID NO: 5136), LMRQ (SEQ ID NO: 5137), QYSV (SEQ ID NO: 5138), QAIT (SEQ ID NO: 5139), QKTL (SEQ ID NO: 5140), QLHH (SEQ ID NO: 5141), QNII (SEQ ID NO: 5142), QGHH (SEQ ID NO: 5143), QSKV (SEQ ID NO: 5144), QLPS (SEQ ID NO: 5145), IGKQ (SEQ ID NO: 5146), QAIH (SEQ ID NO: 5147). QHGL (SEQ ID NO: 5148), QFMC (SEQ ID NO: 5149), QNQM (SEQ ID NO: 5150). QHLQ (SEQ ID NO: 5151), QPAR (SEQ ID NO: 5152), QSLQ (SEQ ID NO: 5153), QSQL (SEQ ID NO: 5154), HSQQ (SEQ ID NO: 5155), QMPS (SEQ ID NO: 5156). QGSL (SEQ ID NO: 5157), QVPA (SEQ ID NO: 5158), HYQQ (SEQ ID NO: 5159). QVPS (SEQ ID NO: 5160), RGEQ (SEQ ID NO: 5161), PGQQ (SEQ ID NO: 5162), LEQQ (SEQ ID NO: 5163). QNQS (SEQ ID NO: 5164), QKVI (SEQ ID NO: 5165), QNND (SEQ ID NO: 5166), QSVH (SEQ ID NO: 5167), QPLG (SEQ ID NO: 5168), HNQE (SEQ ID NO: 5169). QIQQ (SEQ ID NO: 5170), QVRN (SEQ ID NO: 5171), PSNQ (SEQ ID NO: 5172). QVGH (SEQ ID NO: 5173), QRDI (SEQ ID NO: 5174), QMPN (SEQ ID NO: 5175), RGLQ (SEQ ID NO: 5176), PSLQ (SEQ ID NO: 5177), QRDQ (SEQ ID NO: 5178), QAKG (SEQ ID NO: 5179), QSAH (SEQ ID NO: 5180). QSTM (SEQ ID NO: 5181), QREM (SEQ ID NO: 5182), QYRA (SEQ ID NO: 5183), QRQQ (SEQ ID NO: 5184), QWQQ (SEQ ID NO: 5185), QRMN (SEQ ID NO: 5186), GDSQ (SEQ ID NO: 5187), QKIS (SEQ ID NO: 5188), PSMQ (SEQ ID NO: 5189), SPRQ (SEQ ID NO: 5190). MEQQ (SEQ ID NO: 5191). QYQN (SEQ ID NO: 5192), QIRQ (SEQ ID NO: 5193), QSVQ (SEQ ID NO: 5194), RSQQ (SEQ ID NO: 5195), QNKL (SEQ ID NO: 5196), QIQH (SEQ ID NO: 197), PRQQ (SEQ ID NO: 5198), HTQQ (SEQ ID NO: 5199), QRQH (SEQ ID NO: 5200), RNQE (SEQ ID NO: 5201), QSKQ (SEQ ID NO: 5202), QNQP (SEQ ID NO: 5203), QSPQ (SEQ ID NO: 5204), QTRQ (SEQ ID NO: 5205),29323376583.1Attorney Docket No.: V2071-3049PCTQNLH (SEQ ID NO: 5206), QNQE (SEQ ID NO: 5207), LNQP (SEQ ID NO: 5208), QNQD (SEQ ID NO: 5209), QNLL (SEQ ID NO: 5210), QLVI (SEQ ID NO: 5211), RTQE (SEQ ID NO: 5212), QTHQ (SEQ ID NO: 5213), QDQH (SEQ ID NO: 5214), QSQH (SEQ ID NO: 5215). VRQQ (SEQ ID NO: 5216), AWQQ (SEQ ID NO: 5217). QSVP (SEQ ID NO: 5218), QNIQ (SEQ ID NO: 5219). LDQQ (SEQ ID NO: 5220), PDQQ (SEQ ID NO: 5221). ESQQ (SEQ ID NO: 5222), QRQL (SEQ ID NO: 5223), QIIV (SEQ ID NO: 5224), QKQS (SEQ ID NO: 5225), QSHQ (SEQ ID NO: 5226), QFVV (SEQ ID NO: 5227), QSQP (SEQ ID NO: 5228), QNEQ (SEQ ID NO: 5229), INQQ (SEQ ID NO: 5230), RNRQ (SEQ ID NO: 5231), RDQK (SEQ ID NO: 5232), QWKR (SEQ ID NO: 5233). ENRQ (SEQ ID NO: 5234), QTQP (SEQ ID NO: 5235), QKQL (SEQ ID NO: 5236), RNQL (SEQ ID NO: 5237), ISIQ (SEQ ID NO: 5238), QTVC (SEQ ID NO: 5239), QQIM (SEQ ID NO: 5240). LNHQ (SEQ ID NO: 5241), QNQA (SEQ ID NO: 5242), QMIH (SEQ ID NO: 5243), RNHQ (SEQ ID NO: 5244), or QKMN (SEQ ID NO: 5245);(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i), e.g., any 2, or 3 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no more than four modifications, e g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to any of tire amino acid sequences in (i); or(iv) an amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).69. The AAV capsid variant of any one of embodiments 66-68, wherein [N1]-[N2]-[N3]-[N4] is or comprises:(i) the amino acid sequence of any of SEQ ID NOs: 1800-2241;(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i), e.g., any 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one. two, or three but no more than four modifications, e.g.. substitutions (e.g.. conservative substitutions), insertions, or deletions, relative to any of the amino acid sequences in (i); or(iv) an amino acid sequence comprising one. two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).70. The AAV capsid variant of any one of embodiments 66-69. wherein [N1]-[N2]-[N3]-[N4] is or comprises GSGSPHSKAQNQQ (SEQ ID NO: 1801).71. The AAV capsid variant of any one of embodiments 66-70. wherein [N1]-[N2]-[N3]-[N4] is or comprises GHDSPHKSGQNQQ (SEQ ID NO: 1800).30323376583.1Attorney Docket No.: V2071-3049PCT72. The AAV capsid variant of any one of embodiments 66-71, wherein [N1]-[N2]-[N3]-[N4] is or comprises GSGSPHKYGQNQQT (SEQ ID NO: 910).73. The AAV capsid variant of any one of embodiments 2-7, 9. 10, 12, 13, 15. 16, 18-21. 23. 26-72, which comprises an amino acid other than T at position 450 (e.g.. S, Y, M, A, C. I. R, L, D, F, V. Q, N, H, E, or G). an amino acid other than I at position 451 (e.g., M, P, E. N, D, S. A, T, G, Q, F. V, L, C. H, R, W, or L), and / or an amino acid other than N at position 452 (e.g.. M, E. G, Y. W, T. I. Q, F, V, A, L, I, P, K, R. H, S, D, or S). relative to a reference sequence numbered according to any one of SEQ ID NOs: 5-10, 36-59, 138, 981, 982, or 6409-6414.74. The AAV capsid variant of any one of embodiments 2-7, 9. 10, 12, 13, 15, 16, 18-21, 23. 26-73, which comprises the amino acid T at position 450, the amino acid I at position 451, and / or the amino acid N at position 452, relative to a reference sequence numbered according to any one of SEQ ID NOs: 138, 981, or 982.75. The AAV capsid variant of any one of embodiments 2-7, 9, 10, 12, 13, 15, 16, 18-21, 23, 26-74, which further comprises [NO], wherein [NO] comprises XA XB and XC, and wherein:(a) position XA is: T, S, Y, M, A. C, I, R, L. D, F, V, Q, N. H, E, or G;(b) position XB is: I, M, P, E. N, D. S, A, T. G, Q, F, V, L, C, H, R, W, or L; and(c) position XC is: N, M. E, G, Y, W, T, I, Q, F, V, A, L. I. P, K, R, H, S, D, or S; and optionally wherein the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of the aforesaid amino acids in (a)-(c).76. The AAV capsid variant of embodiment 75. wherein [NO] is or comprises TIN, SMN, TIM, YLS, GLS, MPE, MEG, MEY, AEW, CEW, ANN, IPE, ADM, IEY, ADY, IET, MEW, CEY, RIN, MEI, LEY, ADW. IEI. DIM. FEQ, MEF, CDQ. LPE, IEN. MES. AEI, VEY, UN, TSN, IEV, MEM, AEV, MDA. VEW, AEQ, LEW, MEL, MET, MEA, IES. MEV, CEL ATN. MDG, QEV, ADQ, NMN, IEM, ISN. TGN. QQQ. HDW, IEG. TIL TFP, TEK, EIN, TVN, TFN. SIN, TER, TSY, ELH. AIN, SVN, TDN, TFH, TVH, TEN, TSS. TID, TCN, NIN, TEH. AEM, AIK. TDK. TFK, SDQ, TEI, NTN, TET, SIK. TEL, TEA, TAN, TIY, TFS, TES, TTN, TED, TNN, EVH, TIS, TVR, TDR, TIK, NHL TIP. ESD, TDL, TVP, TVI, AEH, NCL, TVK, NAD, TIT, NCV, TIR, NAL, VIN. TIQ, TEF, TRE, QGE, SEK, NVN, GGE, EFV, SDK, TEQ, EVQ, TEY, NCW, TDV, SDI, NSI, NSL, EVV, TEP, SEL, TWQ, TEV, AVN, GVL, TLN, TEG, TRD, NAI, AEN, AET, ETA. NNL. or any dipeptide thereof.77. The AAV capsid variant of embodiment 75 or 76, wherein [NO]-[N1]-[N2]-[N3]-[N4] is or comprises:31323376583.1Attorney Docket No.: V2071-3049PCT(i) the amino acid sequence of any one of SEQ ID NOs: 2242-2886;(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i). e.g.. any 2, 3. 4. 5, 6, 7, 8. 9. 10, 11, 12, 13. 14. or 15 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one. two, or three but no more than four modifications, e.g.. substitutions (e.g.. conservative substitutions), insertions, or deletions, relative to any of the amino acid sequences in (i); or(iv) an amino acid sequence comprising one. two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).78. The AAV capsid variant of any one of embodiments 75-77. wherein [NO]-[N1]-[N2]-[N3]-[N4] is or comprises TINGSGSPHSKAQNQQ (SEQ ID NO: 2242).79. The AAV capsid variant of any one of embodiments 75-78, wherein [NO]-[N1]-[N2]-[N3]-[N4] is or comprises TINGHDSPHKSGQNQQ (SEQ ID NO; 2243).80. The AAV capsid variant of any one of embodiments 75-79, wherein [NO]-[N1]-[N2]-[N3]-[N4] is or comprises TINGSGSPHKYGQNQQT (SEQ ID NO: 5246).81. The AAV capsid variant of any one of embodiments 2-7. 9, 10. 12, 13, 15, 16. 18-21, 23, 26-80, wherein [N1]-[N2]-[N3] is present in loop IV.82. The AAV capsid variant of any one of embodiments 75-81, wherein [NO] and [N4] are present in loop IV.83. The AAV capsid variant of any one of embodiments 75-82, wherein [NO] is present immediately subsequent to position 449, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.84. The AAV capsid variant of any one of embodiments 75-83. wherein [NO] is present immediately subsequent to position 449, relative to a reference sequence numbered according to the amino acid sequence of any one of SEQ ID NOs: 5-10, 36-59, 981, 982, or 6409-6413.85. The AAV capsid variant of any one of embodiments 75-84. wherein [NO] replaces positions 450, 451, and 452 (e.g., T450, 1451, and N452), relative to a reference sequence numbered according to SEQ ID NO: 138.32323376583.1Attorney Docket No.: V2071-3049PCT86. The AAV capsid variant of any one of embodiments 75-85, wherein [NO] replaces positions 450- 452 (e.g., T450, 1451. and N452), relative to a reference sequence numbered according to any one of SEQ ID NOs: 5-10, 36-59, 981. 982, or 6409-6413.87. The AAV capsid variant of any one of embodiments 75-86. wherein [NO] corresponds to positions 450-452 of any one of SEQ ID NOs: 5-10. 36-59, 138, 981 982, or 6409-6414.88. The AAV capsid variant of any one of embodiments 75-87. wherein [NO] is present immediately subsequent to position 449 and wherein [NO] replaces positions 450-452 (e.g.. T450, 1451, and N452), relative to a reference sequence numbered according to SEQ ID NO: 138.89. The AAV capsid variant of any one of embodiments 75-88, wherein [NO] is present immediately subsequent to position 449 and wherein [NO] replaces positions 450-452 (e.g., T450, 1451, and N452), relative to a reference sequence numbered according to any one of SEQ ID NOs: 5-10, 36-59, 981, 982, or 6409-6413.90. The AAV capsid variant of any one of embodiments 2-7, 9, 10, 12, 13, 15, 16. 18-21, 23, 26-89, wherein [Nl] is present immediately subsequent to position 452, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.91. The AAV capsid variant of any one of embodiments 2-7. 9, 10. 12, 13, 15, 16. 18-21, 23, 26-63, wherein [Nl] is present immediately subsequent to position 452, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 981 or 982.92. The AAV capsid variant of any one of embodiments 2-7, 9, 10, 12, 13, 15, 16, 18-21, 23, 26-61, wherein [Nl] replaces positions 453-455 (e.g.. G453. S454. and G455), relative to a reference sequence numbered according to SEQ ID NO: 138.93. The AAV capsid variant of any one of embodiments 2-7, 9. 10, 12, 13, 15. 16, 18-21. 23. 26-64, wherein [Nl] replaces positions 453 (e.g., G453), relative to a reference sequence numbered according to SEQ ID NO: 138.94. The AAV capsid variant of any one of embodiments 2-7, 9. 10, 12, 13, 15, 16, 18-21, 23. 26-65, wherein [Nl] replaces positions 453-455 (e.g.. G453, S454, and G455), relative to a reference sequence numbered according to SEQ ID NO: 981.33323376583.1Attorney Docket No.: V2071-3049PCT95. The AAV capsid variant of any one of embodiments 2-7, 9, 10, 12, 13, 15, 16, 18-21, 23, 26-92 or 94, wherein [N 1 ] replaces positions 453-455, relative to a reference sequence numbered according to SEQ ID NO: 982.96. The AAV capsid variant of any one of embodiments 2-7, 9. 10, 12, 13, 15. 16, 18-21. 23. 26-92, 94, or 95, wherein [Nl] is present immediately subsequent to position 452 and wherein [Nl] replaces positions 453-455 (e.g., G453, S454, and G455). relative to a reference sequence numbered according to SEQ ID NO: 138.97. The AAV capsid variant of any one of embodiments 2-7, 9. 10, 12, 13, 15, 16, 18-21, 23. 26-64 or 66, wherein [Nl] is present immediately subsequent to position 452 and wherein [Nl] replaces positions 453 (e.g., G453), relative to a reference sequence numbered according to SEQ ID NO: 138.98. The AAV capsid variant of any one of embodiments 2-7, 9, 10, 12, 13, 15, 16, 18-21, 23, 26-91, 93 or 97, wherein [Nl] is present immediately subsequent to position 452 and wherein [Nl] replaces positions 453-455, relative to a reference sequence numbered according to SEQ ID NO: 981 or 982.99. The AAV capsid variant of any one of embodiments 2-7, 9, 10, 12, 13, 15, 16. 18-21, 23, 26-98, wherein [Nl] corresponds to positions 453-455 of any one of SEQ ID NOs: 5-10, 36-59, 981 982, or 6409-6413.100. The AAV capsid variant of any one of embodiment 2-7, 9, 10. 12. 13, 15, 16, 18-21, 23, 26-99, which comprises an amino acid other than S at position 454 and / or an amino acid other than G at position 455, numbered according to SEQ ID NO: 138, 981. or 982.101. The AAV capsid variant of any one of embodiments 2-7. 9, 10. 12, 13, 15, 16, 18-21, 23, 26-100, which comprises the amino acid H at position 454 and the amino acid D at position 455, numbered according to SEQ ID NO: 138 or 982.102. The AAV capsid variant of any one of embodiments 1-101, which comprises a substitution at position 454 (e.g., S454H) and / or a substitution at position 455 (e.g., G455D). numbered according to SEQ ID NO: 138.103. The AAV capsid variant of any one of embodiments 1-102, which comprises the amino acid H at position 454 and the amino acid D at position 455, and further comprises the amino acid sequence SPHSKA (SEQ ID NO: 941) immediately subsequent to position 455, relative to a reference sequence numbered according to SEQ ID NO: 138.34323376583.1Attorney Docket No.: V2071-3049PCT104. The AAV capsid variant of any one of embodiments 1-103, which comprises the amino acid H at position 454 and the amino acid D at position 455, relative to a reference sequence numbered according to SEQ ID NO: 982.105. The AAV capsid variant of any one of embodiments 1-104, which comprises the amino acid H at position 454 and the amino acid D at position 455, and further comprises the amino acid sequence SPHSKA (SEQ ID NO: 941) immediately subsequent to position 455, relative to a reference sequence numbered according to SEQ ID NO: 982.106. The AAV capsid variant of any one of embodiments 1-104, which comprises the amino acid S at position 454 and the amino acid G at position 455, relative to a reference sequence numbered according to SEQ ID NO: 138.107. The AAV capsid variant of any one of embodiments 1-99 or 106, which comprises the ammo acid S at position 454 and tire amino acid G at position 455, and further comprises the amino acid sequence SPHSKA (SEQ ID NO: 941) immediately subsequent to position 455. relative to a reference sequence numbered according to SEQ ID NO: 138.108. The AAV capsid variant of any one of embodiments 1-99, 106, or 107, which comprises the amino acid S at position 454 and the amino acid G at position 455, relative to a reference sequence numbered according to SEQ ID NO: 981.109. The AAV capsid variant of any one of embodiments 1-99 or 106-108, which comprises the amino acid S at position 454 and the amino acid G at position 455. and further comprises the amino acid sequence SPHSKA (SEQ ID NO: 941) immediately subsequent to position 455, relative to a reference sequence numbered according to SEQ ID NO: 981.110. The AAV capsid variant of any one of embodiments 2-7, 9, 10, 12. 13, 15, 16, 18-21, 23, 26-109, wherein [N2] is present immediately subsequent to position 455, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.111. The AAV capsid variant of any one of embodiments 2-7, 9, 10, 12, 13, 15, 16, 18-21, 23, 26-110, wherein [N2] corresponds to positions 456-458 (e.g., S456, P457, H458) of SEQ ID NO: 981 or 982.112. The AAV capsid variant of any one of embodiments 2-7, 9, 10, 12, 13, 15, 16, 18-21, 23, 26-110, wherein [N2] corresponds to positions 456-458 (e.g., S456, P457, H458) of any one of SEQ ID NOs: 5-10, 36-59, or 6409-6413.35323376583.1Attorney Docket No.: V2071-3049PCT113. The AAV capsid variant of any one of embodiments 2-7, 9, 10, 12, 13, 15, 16, 18-21, 23, 26-112, wherein [N2]-[N3] is present immediately subsequent to position 455. relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.1 14. The AAV capsid variant of any one of embodiments 2-7, 9, 10, 12. 13, 15, 16, 18-21 , 23, 26-113, wherein [N2] is present immediately subsequent to position 455, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 981 or 982.115. The AAV capsid variant of any one of embodiments 2-7, 9, 10, 12, 13, 15, 16, 18-21, 23, 26-114, wherein [N2]-[N3] is present immediately subsequent to position 455, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 981 or 982.116. The AAV capsid variant of any one of embodiments 2-7, 9, 10, 12, 13, 15, 16, 18-21, 23, 26-115, wherein [N2]-[N3] corresponds to positions 456-461 (e.g., S456, P457, H458, S459, K460, A461) of SEQ ID NO: 981.117. The AAV capsid variant of any one of embodiments 2-7, 9, 10, 12, 13. 15, 16, 18-21, 23, 26-115, wherein [N2]-[N3] corresponds to positions 456-461 (e.g., S456, P457, H458, K459, S460, G461) of SEQ ID NO: 982.118. The AAV capsid variant of any one of embodiments 2-7, 9, 10, 12, 13. 15, 16, 18-21. 23, 26-117, wherein [N2] is present immediately subsequent to [Nl],119. The AAV capsid variant of any one of embodiments 2-7, 9. 10, 12, 13. 15. 16, 18-21. 23. 26-91, 93, 97, or 98, wherein [N3] is present immediately subsequent to [N2] and replaces positions 454 and 455 (e.g., S454 and G455), numbered according to SEQ ID NO: 138.120. The AAV capsid variant of any one of embodiments 2-7, 9, 10, 12. 13, 15, 16, 18-21, 23, 26-91, 93, 97, 98. or 1 19, wherein [N3] is present immediately subsequent to [N 1]-[N2] and replaces positions 454 and 455 (e.g.. S454 and G455), numbered according to SEQ ID NO: 138.121. The AAV capsid variant of any one of embodiments 66-120, wherein [N4] is present immediately subsequent to position 455, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.36323376583.1Attorney Docket No.: V2071-3049PCT122. The AAV capsid variant of any one of embodiments 66-121, wherein [N4] replaces positions 456-459 (e.g., Q456, N457. Q458. and Q459), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.123. The AAV capsid variant of any one of embodiments 66-122. wherein [N4] corresponds to positions 462-465 (e.g., Q462, N463, Q464, Q465) of SEQ ID NO: 981 or 982.124. The AAV capsid variant of any one of embodiments 66-123, wherein [N2]-[N3]-[N4] replaces positions 456-459 (e.g., Q456, N457, Q458, and Q459), relative to a reference sequence numbered according to tire amino acid sequence of SEQ ID NO: 138.125. The AAV capsid variant of any one of embodiments 66-124, wherein [N2]-[N3]-[N4] is present immediately subsequent to position 455, and wherein [N2]-[N3]-[N4] replaces positions 456-459 (e.g., Q456, N457, Q458, and Q459), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.126. The AAV capsid variant of any one of embodiments 66-125, wherein [N2]-[N3]-[N4] corresponds to positions 456-465 (e.g., S456, P457, H458, S459, K460, A461, Q462, N463, Q464. Q465) of SEQ ID NO: 981.127. The AAV capsid variant of any one of embodiments 66-125, wherein [N2]-[N3]-[N4] corresponds to positions 456-465 (e.g., S456, P457, H458. K459, S460, G461, Q462, N463. Q464. Q465) of SEQ ID NO: 982.128. The AAV capsid variant of any one of embodiments 66-125, wherein [N2]-[N3]-[N4] corresponds to positions 456-465 of any one of SEQ ID NOs: 5-10, 36-59, 6409-6413.129. The AAV capsid variant of any one of embodiments 66-128. wherein [N1]-[N2]-[N3]-[N4] replaces positions 453-459 (e.g., G453, S454, G455, Q456. N457, Q458, and Q459). relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.130. The AAV capsid variant of any one of embodiments 66-129, wherein [N1]-[N2]-[N3]-[N4] is present immediately subsequent to position 452, and wherein [N1]-[N2]-[N3]-[N4] replaces positions 453-459 (e.g., G453, S454, G455, Q456, N457, Q458, and Q459), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.37323376583.1Attorney Docket No.: V2071-3049PCT131. The AAV capsid variant of any one of embodiments 66-126, 129,130, wherein [N1]-[N2]-[N3]- [N4] corresponds to positions 453-465 (e.g.. G453. S454. G455, S456, P457, H458, S459, K460. A461. Q462. N463, Q464, Q465) of SEQ ID NO: 981.132. The AAV capsid variant of any one of embodiments 66-125. 127, 129, or 130, wherein [Nl]- [N2]-[N3]-[N4] corresponds to positions 453-465 (e.g., G453, H454, D455, S456, P457, H458, K459, S460, G461. Q462, N463, Q464, Q465) of SEQ ID NO: 982.133. The AAV capsid variant of any one of embodiments 66-125, 129, or 130, wherein [N1]-[N2]- [N3]-[N4] corresponds to positions 453-465 of any one of SEQ ID NOs: 5-10, 36-59, or 6409-6413.134. The AAV capsid variant of any one of embodiments 2-7, 9, 10, 12, 13, 15, 16, 18-21, 23, 26-126 or 129-131, wherein [N1]-[N2]-[N3] corresponds to positions 453-461 (e.g., G453, S454, G455, S456, P457, H458, S459, K460, A461) of SEQ ID NO: 981.135. The AAV capsid variant of any one of embodiments 2-7, 9, 10, 12, 13. 15, 16, 18-21, 23, 26-125, 127, 129, 130, or 132, wherein [N1]-[N2]-[N3] corresponds to positions 453-461 (e.g., G453, H454, D455, S456, P457, H458, K459, S460, G461) of SEQ ID NO: 982.136. The AAV capsid variant of any one of embodiments 66-125, 129, 130. or 133, wherein [Nl]- [N2]-[N3] corresponds to positions 453-461 of any one of SEQ ID NOs: 5-10, 36-59, or 6409-6413.137. The AAV capsid variant of any one of embodiments 75-136, wherein [N0J N 1 J-[N2J -[N3J N4J replaces positions 450-459 (e.g., T450, 1451, N452, G453. S454. G455, Q456, N457, Q458. and Q459), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.138. The AAV capsid variant of any one of embodiments 75-136. wherein [NO]-[N1]-[N2]-[N3]-[N4] is present immediately subsequent to position 449. and wherein [NO]-[N1 ]-[N2]-[N3]-[N4] replaces positions 450-459 (e.g., T450, 1451. N452, G453, S454, G455, Q456. N457, Q458, and Q459). relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.139. The AAV capsid variant of any one of embodiments 75-126, 129-131, or 133, wherein [N0]- [N1]-[N2]-[N3]-[N4] corresponds to positions 450-465 (e.g., T450. 1451, N452, G453, S454, G455, S456, P457, H458, S459, K460, A461, Q462, N463, Q464, Q465) of SEQ ID NO: 981.38323376583.1Attorney Docket No.: V2071-3049PCT140. The AAV capsid variant of any one of embodiments 75-125, 127, 129, 130, 132, or 135, wherein [NO]-[N1]-[N2]-[N3]-[N4] corresponds to positions 450-465 (e.g., T450, 1451. N452, G453, H454. D455. S456. P457. H458. K459, S460, G461, Q462, N463. Q464, Q465) of SEQ ID NO: 982.141. The AAV capsid variant of any one of embodiments 75-125. 129, 130, 133, or 136, wherein [NO]-[N1]-[N2]-[N3]-[N4] corresponds to positions 450-465 of any one of SEQ ID NOs: 5-10. 36-59, or 6409-6413.142. The AAV capsid variant of any one of embodiments 66-141, wherein [N4] replaces positions 462-465 (e.g., Q462, N463, Q464, and Q465), relative to a reference sequence numbered according to die amino acid sequence of SEQ ID NO: 981 or 982.143. The AAV capsid variant of any one of embodiments 66-142, wherein [N2]-[N3]-[N4] replaces positions 462-465 (e.g., Q462, N463, Q464, and Q465), relative to a reference sequence numbered according to die amino acid sequence of SEQ ID NO: 981 or 982.144. The AAV capsid variant of any one of embodiments 66-143, wherein [N2]-[N3]-[N4] is present immediately subsequent to position 455, and wherein [N2]-[N3]-[N4] replaces positions 462-465 (e.g., Q462, N463. Q464, and Q465), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 981 or 982.145. The AAV capsid variant of any one of embodiments 2-7, 9, 10, 12, 13. 15. 16, 18-21. 23, 26-144, wherein LN3 J is present immediately subsequent to | N21146. The AAV capsid variant of any one of embodiments 2-7, 9, 10, 12, 13, 15, 16, 18-21, 23, 26-145, which comprises from N-terminus to C-terminus, [N2]-[N3],147. The AAV capsid variant of any one of embodiments 2-7, 9, 10, 12. 13, 15, 16, 18-21, 23, 26-146, which comprises from N-terminus to C-terminus, [N1]-[N2]-[N3],148. The AAV capsid variant of any one of embodiments 75-147, which comprises from N-terminus to C-terminus, [NO]-[N1]-[N2]-[N3],149. The AAV capsid variant of any one of embodiments 66-148, which comprises from N-terminus to C-terminus, [N1]-[N2]-[N3]-[N4],39323376583.1Attorney Docket No.: V2071-3049PCT150. The AAV capsid variant of any one of embodiments 75-149, which comprises from N-terminus to C -terminus, [NO]-[N1]-[N2]-[N3]-[N4],151. The AAV capsid variant of any one of the preceding embodiments, which comprises an amino acid other T at position 460 (e.g., N. I. C, H. R, L, D. Y, A. M, Q. I. E, K, P. G or S). numbered according to tire amino acid sequence of SEQ ID NO: 138.152. The AAV capsid variant of any one of the preceding embodiments, which comprises the amino acid N, I, C, H, R, L, D, Y, A, M, Q, I, E, K, P, G or S at position 460, numbered according to the amino acid sequence of SEQ ID NO: 138.153. The AAV capsid variant of any one of the preceding embodiments, which comprises an amino acid other T at position 466 (e.g., N, I, C, H, R, L, D, Y, A, M, Q, I, E, K, P, G or S), numbered according to the amino acid sequence of any one of SEQ ID NOs: 5-10, 36-59, 981, 982, or 6409- 6413.154. The AAV capsid variant of any one of the preceding embodiments, which comprises the amino acid N, I, C, H, R, L. D, Y. A, M. Q, I, E, K, P, G or S at position 466, numbered according to the amino acid sequence of any one of SEQ ID NOs: 5-10, 36-59, 981 982. or 6409-6413.155. The AAV capsid variant of any one of the preceding embodiments, which comprises an amino acid other K at position 449 (e.g.. an E, an N, or a T), numbered according to the amino acid sequence of any one of SEQ ID NOs: 36-59, 138. 981, or 982.156. The AAV capsid variant of any one of the preceding embodiments, which comprises the amino E, N, or T at position 449, numbered according to the amino acid sequence of any one of SEQ ID NOs: 5-10. 36-59, 138. 981 982, or 6409-6414.157. The AAV capsid variant of any one of embodiment 1 or 2-27 comprising [A][B] (SEQ ID NO: 4694). wherein:(i) [A] comprises the amino acid sequence of GSGSPH (SEQ ID NO: 4695); and(ii) [B] comprises XI X2 X3 X4 X5 X6 X7, wherein:(a) position XI is: S, C. F, or V;(b) position X2 is: K, L, R, I, E, Y, V, or S;(c) position X3 is: A, R, L, G, I, Y, S, F, or W;(d) position X4 is: W, Q, R, G, L, V, S, or F;(e) position X5 is: N, Y, R, C, K, or L;40323376583.1Attorney Docket No.: V2071-3049PCT(f) position X6 is: Q, G, K, R, T, L, or Y; and(g) position X7 is: Q, L. R, or V; optionally wherein the AAV capsid variant comprises an amino acid modification, e.g.. a conservative substitution, of any of the aforesaid amino acids in (a)-(g).158. The AAV capsid variant of embodiment 157, wherein(a) position XI is S;(b) position X2 is K or L;(c) position X3 is: A, R, or L;(d) position X4 is: Q or R;(e) position X5 is: N or R;(1) position X6 is: Q or R; and(g) position X7 is: Q, L, or R.159. The AAV capsid variant of embodiment 157 or 158, wherein [B] comprises:(i) SLLWNQQ (SEQ ID NO: 5247), SKAQYYV (SEQ ID NO: 5248), SKLRRQQ (SEQ ID NO: 5249), SIWQNQQ (SEQ ID NO: 5250), SKAGCGQ (SEQ ID NO: 5251), SRAQNQQ (SEQ ID NO: 5252), SKRLRQQ (SEQ ID NO: 5253), SLRRNQQ (SEQ ID NO: 5254), SRGRNQQ (SEQ ID NO: 5255), SEIVNQQ (SEQ ID NO: 5256), SSRRNQQ (SEQ ID NO: 5257). CLLQNQQ (SEQ ID NO: 5258), SKAFRLQ (SEQ ID NO: 5259), CLAQNQQ (SEQ ID NO: 5260), FLRQNQQ (SEQ ID NO: 5261), SLRFNQQ (SEQ ID NO: 5262), SYLRNQQ (SEQ ID NO: 5263), CSLQNQQ (SEQ ID NO: 5264), VLWQNQQ (SEQ ID NO: 5265), SKWLLQQ (SEQ ID NO: 5266), SLWSNQQ (SEQ ID NO: 5267), SKRRLQQ (SEQ ID NO: 5268). SVYLNQQ (SEQ ID NO: 5269), SLWLNQQ (SEQ ID NO: 5270), SKAQRKL (SEQ ID NO: 5271), SKALRRQ (SEQ ID NO: 5272), SKAQRLR (SEQ ID NO: 5273), SKAQNQQ (SEQ ID NO: 5274), SKAQRRL (SEQ ID NO: 5275), SKARRQQ (SEQ ID NO: 5276), SKARRLQ (SEQ ID NO: 5277), SKSRRQQ (SEQ ID NO: 5278), SKARLRQ (SEQ ID NO: 5279), SKASKRQ (SEQ ID NO: 5280), VRRQNQQ (SEQ ID NO: 5281). SKAQLYR (SEQ ID NO: 5282), SLFRNQQ (SEQ ID NO: 5283), SKAQLTV (SEQ ID NO: 5284);(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i). e.g., any 2, 3. 4, 5, or 6 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, tw o. or three but no more than four modifications, e.g., substitutions (e.g.. conservative substitutions), insertions, or deletions, relative to any of the amino acid sequences in (i); or(iv) an amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).160. The AAV capsid variant of any one of embodiments 157-159, wherein [A][B] comprises:41323376583.1Attorney Docket No.: V2071-3049PCT(i) GSGSPHSLLWNQQ (SEQ ID NO: 5285), GSGSPHSKAQYYV (SEQ ID NO: 2060), GSGSPHSKLRRQQ (SEQ ID NO: 2061). GSGSPHSIWQNQQ (SEQ ID NO: 5286), GSGSPHSKAGCGQ (SEQ ID NO: 2062), GSGSPHSRAQNQQ (SEQ ID NO: 2063). GSGSPHSKRLRQQ (SEQ ID NO: 2064). GSGSPHSLRRNQQ (SEQ ID NO: 2065), GSGSPHSRGRNQQ (SEQ ID NO: 2066), GSGSPHSEIVNQQ (SEQ ID NO: 5287), GSGSPHSSRRNQQ (SEQ ID NO: 2067). GSGSPHCLLQNQQ (SEQ ID NO: 5288), GSGSPHSKAFRLQ (SEQ ID NO: 2068). GSGSPHCLAQNQQ (SEQ ID NO: 5289), GSGSPHFLRQNQQ (SEQ ID NO: 2070), GSGSPHSLRFNQQ (SEQ ID NO: 2071), GSGSPHSYLRNQQ (SEQ ID NO: 5290), GSGSPHCSLQNQQ (SEQ ID NO: 5291), GSGSPHVLWQNQQ (SEQ ID NO: 5292), GSGSPHSKWLLQQ (SEQ ID NO: 2072), GSGSPHSLWSNQQ (SEQ ID NO: 5293), GSGSPHSKRRLQQ (SEQ ID NO: 2073), GSGSPHSVYLNQQ (SEQ ID NO: 5294), GSGSPHSLWLNQQ (SEQ ID NO: 5295), GSGSPHSKAQRKL (SEQ ID NO: 2074), GSGSPHSKALRRQ (SEQ ID NO: 2075), GSGSPHSKAQRLR (SEQ ID NO: 2076), GSGSPHSKAQNQQ (SEQ ID NO: 1801), GSGSPHSKAQRRL (SEQ ID NO: 2077), GSGSPHSKARRQQ (SEQ ID NO: 2078), GSGSPHSKARRLQ (SEQ ID NO: 2079), GSGSPHSKSRRQQ (SEQ ID NO: 2080), GSGSPHSKARLRQ (SEQ ID NO: 2082), GSGSPHSKASKRQ (SEQ ID NO: 2083), GSGSPHVRRQNQQ (SEQ ID NO: 2084), GSGSPHSKAQLYR (SEQ ID NO: 2085), GSGSPHSLFRNQQ (SEQ ID NO: 5296), GSGSPHSKAQLTV (SEQ ID NO: 2086);.(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i), e.g., any 2. 3, 4, 5, 6, 7. 8, 9, 10, 11. or 12 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to any of tire amino acid sequences in (i); or(iv) an amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i)161. The AAV capsid variant of any one of embodiments 157-160, which further comprises one, two. or all of an amino acid other than T at position 450 (e.g., S. Y, or G), an amino acid other than I at position 451 (e.g., M or L), and / or an amino acid other than N at position 452 (e.g., S). relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.162. The AAV capsid variant of any one of embodiments 157-161, which further comprises an S at position 450 and an M at position 451, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.42323376583.1Attorney Docket No.: V2071-3049PCT163. The AAV capsid variant of any one of embodiments 157-162, which further comprises a Y at position 450. an L at position 451. and an S at position 452. relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.164. The AAV capsid variant of any one of embodiments 157-162, which further comprises a G at position 450, an L at position 451, and an S at position 452, relative to a reference sequence numbered according to tire amino acid sequence of SEQ ID NO: 138.165. The AAV capsid variant of any one of embodiments 157-164, wherein [A][B] is present in loop IV.166. The AAV capsid variant of any one of embodiments 157-165, wherein [A] is present immediately subsequent to position 452, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.167. The AAV capsid variant of any one of embodiments 157-166, wherein [A] replaces positions 453-455 (e.g., G453. S454. G455), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.168. The AAV capsid variant of any one of embodiments 157-167. wherein [A] is present immediately subsequent to position 452, and wherein [A] replaces positions 453-455 (e.g.. G453, S454. G455), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.169. The AAV capsid variant of any one of embodiments 157-168, wherein [B] is present immediately subsequent to [A],170. The AAV capsid variant of any one of embodiments 157-169, wherein [B] replaces positions 456-459 (e.g., Q456, N457. Q458, Q459), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.171. The AAV capsid variant of any one of embodiments 157-170, wherein [A][B] replaces positions 453-459 (e.g., G453, S454, G455, Q456, N457, Q458, Q459), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.172. The AAV capsid variant of any one of embodiments 157-171, wherein [A][B] is present immediately subsequent to position 452, and wherein [A][B] replaces positions 453-459 (e.g., G453,43323376583.1Attorney Docket No.: V2071-3049PCTS454. G455, Q456, N457, Q458. Q459), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.173. The AAV capsid variant of any one of embodiments 157-172, which comprises from N-terminus to C-terminus, [A][B],174. The AAV capsid variant of any one of embodiments 1 or 2-27 comprising [A][B] (SEQ ID NO: 4699). wherein:(i) [A] comprises XI X2 X3 X4 X5 X6, wherein(a) position XI is T, M. A, C, I, R, L, D, F, V, Q, N, or H;(b) position X2 is I, P, E, N, D, S, A, T, M, or Q;(c) position X3 is N, E, G, Y, W, M, T, I, K, Q, F, S, V, A, or L;(d) position X4 is G, D, R, or E;(e) position X5 is H, Q, N, or D;(I) position X6 is D or R; optionally wherein the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of the aforesaid amino acids in (a)-(f); and(ii) [B] comprises SPHKSG (SEQ ID NO: 946).175. The AAV capsid of embodiment 174, wherein(a) position XI is: T. M, A. or I;(b) position X2 is: E. I or D;(c) position X3 is: N. Q, Y. 1. M, or V;(d) position X4 is G;(e) position X5 is H; and(f) position X6 is D.176. The AAV capsid variant of embodiment 174 or 175. wherein [A] comprises:(i) TINGHD (SEQ ID NO: 5297). MPEGHD (SEQ ID NO: 5298), MEGGHD (SEQ ID NO: 5299). MEYGHD (SEQ ID NO: 5300), AEWGHD (SEQ ID NO: 5301), CEWGHD (SEQ ID NO: 5302). ANNGQD (SEQ ID NO: 5303), IPEGHD (SEQ ID NO: 5304), ADMGHD (SEQ ID NO: 5305). IEYGHD (SEQ ID NO: 5306). ADYGHD (SEQ ID NO: 5307), IETGHD (SEQ ID NO: 5308), MEWGHD (SEQ ID NO: 5309), CEYGHD (SEQ ID NO: 5310). RINGED (SEQ ID NO: 5311), MEIGHD (SEQ ID NO: 5312), LEYGHD (SEQ ID NO: 5313), ADWGHD (SEQ ID NO: 5314), IEIGHD (SEQ ID NO: 5315), TIKDND (SEQ ID NO: 5316), DIMGHD (SEQ ID NO: 5317), FEQGHD (SEQ ID NO: 5318), MEFGHD (SEQ ID NO: 5319), CDQGHD (SEQ ID NO: 5320), LPEGHD (SEQ ID NO: 5321), IENGHD (SEQ ID NO: 5322), MESGHD (SEQ ID NO: 5323),44323376583.1Attorney Docket No.: V2071-3049PCTAEIGHD (SEQ ID NO: 5324), VEYGHD (SEQ ID NO: 5325), TSNGDD (SEQ ID NO: 5326), IEVGHD (SEQ ID NO: 5327), MEMGHD (SEQ ID NO: 5328), AEVGHD (SEQ ID NO: 5329). MDAGHD (SEQ ID NO: 5330), VEWGHD (SEQ ID NO: 5331). AEQGHD (SEQ ID NO: 5332), LEWGHD (SEQ ID NO: 5333), MELGHD (SEQ ID NO: 5334), METGHD (SEQ ID NO: 5335), MEAGHD (SEQ ID NO: 5336), TINRQR (SEQ ID NO: 5337), IESGHD (SEQ ID NO: 5338). TAKDHD (SEQ ID NO: 5339), MEVGHD (SEQ ID NO: 5340), CEIGHD (SEQ ID NO: 5341), ATNGHD (SEQ ID NO: 5342), MDGGHD (SEQ ID NO: 5343), QEVGHD (SEQ ID NO: 5344), ADQGHD (SEQ ID NO: 5345), NMNGHD (SEQ ID NO: 5346). TPWEHD (SEQ ID NO: 5347), IEMGHD (SEQ ID NO: 5348), TANEHD (SEQ ID NO: 5349), QQQGHD (SEQ ID NO: 5350), TPQDHD (SEQ ID NO: 5351). HDWGHD (SEQ ID NO: 5352), IEGGHD (SEQ ID NO: 5353)(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i), e.g., any 2, 3, 4, or 5 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no more than four modifications, e g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to any of tire amino acid sequences in (i); or(iv) an amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).177. The AAV capsid variant of any one of embodiments 174-176. wherein [A][B] comprises:(i) TINGHDSPHKR (SEQ ID NO: 5354). MPEGHDSPHKS (SEQ ID NO: 5355). MEGGHDSPHKS (SEQ ID NO: 5356), MEYGHDSPHKS (SEQ ID NO: 5357), AEWGHDSPHKS (SEQ ID NO: 5358). CEWGHDSPHKS (SEQ ID NO: 5359), ANNGQDSPHKS (SEQ ID NO: 5360), 1PEGHDSPHKS (SEQ ID NO: 5361), ADMGHDSPHKS (SEQ ID NO: 5362). IEYGHDSPHKS (SEQ ID NO: 5363). ADYGHDSPHKS (SEQ ID NO: 5364), IETGHDSPHKS (SEQ ID NO: 5365). MEWGHDSPHKS (SEQ ID NO: 5366), CEYGHDSPHKS (SEQ ID NO: 5367), RINGHDSPHKS (SEQ ID NO: 5368), MEIGHDSPHKS (SEQ ID NO: 5369), LEYGHDSPHKS (SEQ ID NO: 5370), ADWGHDSPHKS (SEQ ID NO: 5371). IEIGHDSPHKS (SEQ ID NO: 5372), TIKDNDSPHKS (SEQ ID NO: 5373), DIMGHDSPHKS (SEQ ID NO: 5374), FEQGHDSPHKS (SEQ ID NO: 5375), MEFGHDSPHKS (SEQ ID NO: 5376), CDQGHDSPHKS (SEQ ID NO: 5377). LPEGHDSPHKS (SEQ ID NO: 5378), IENGHDSPHKS (SEQ ID NO: 5379), MESGHDSPHKS (SEQ ID NO: 5380), AEIGHDSPHKS (SEQ ID NO: 5381), VEYGHDSPHKS (SEQ ID NO: 5382), TSNGDDSPHKS (SEQ ID NO: 5383), IEVGHDSPHKS (SEQ ID NO: 5384), MEMGHDSPHKS (SEQ ID NO: 5385). AEVGHDSPHKS (SEQ ID NO: 5386), MDAGHDSPHKS (SEQ ID NO: 5387), VEWGHDSPHKS (SEQ ID NO: 5388), AEQGHDSPHKS (SEQ ID NO: 5389). LEWGHDSPHKS (SEQ ID NO: 5390), MELGHDSPHKS (SEQ ID NO: 5391), METGHDSPHKS (SEQ ID NO: 5392), MEAGHDSPHKS (SEQ ID NO: 5393), TINRQRSPHKS (SEQ ID NO: 5394), IESGHDSPHKS (SEQ ID NO: 5395), TAKDHDSPHKS (SEQ ID NO: 5396), MEYGHDSPHKS (SEQ ID NO: 5397), CEIGHDSPHKS45323376583.1Attorney Docket No.: V2071-3049PCT(SEQ ID NO: 5398), ATNGHDSPHKS (SEQ ID NO: 5399), MDGGHDSPHKS (SEQ ID NO: 5400). QEVGHDSPHKS (SEQ ID NO: 5401), ADQGHDSPHKS (SEQ ID NO: 5402). NMNGHDSPHKS (SEQ ID NO: 5403), TPWEHDSPHKS (SEQ ID NO: 5404), IEMGHDSPHKS (SEQ ID NO: 5405), TANEHDSPHKS (SEQ ID NO: 5406), TINGHDSPHKS (SEQ ID NO: 5407), QQQGHDSPHKS (SEQ ID NO: 5408), TPQDHDSPHKS (SEQ ID NO: 5409), HDWGHDSPHKS (SEQ ID NO: 5410), IEGGHDSPHKS (SEQ ID NO: 5411)(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i). e.g., any 2, 3. 4, 5, 6, 7, 8. 9, or 10 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to any of the amino acid sequences in (i); or(iv) an amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).178. The AAV capsid variant of any one of embodiments 174-177, which further comprises one, two, three, four, or all of an amino acid other than Q at position 456 (e.g., R or L), N at position 457 (e.g., H, K, or R), Q at position 458 (e.g.. R or T), Q at position 459 (H), and / or T at position 460 (N or S), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.179. The AAV capsid variant of any one of embodiments 174-178. which further comprises an R at position 456, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.180. The AAV capsid variant of any one of embodiments 174-178. which further comprises an L at position 456, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.181. The AAV capsid variant of any one of embodiments 174-180, which further comprises an H at position 457 and an R at position 458. relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.182. The AAV capsid variant of any one of embodiments 174-181, which further comprises a K at position 457 and an N at position 460, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.46323376583.1Attorney Docket No.: V2071-3049PCT183. The AAV capsid variant of any one of embodiments 174-180, which further comprises a T at position 458. an H at position 459, and an S at position 460, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.184. The AAV capsid variant of any one of embodiments 174- 178, which further comprises an R at position 456, an R at position 457, and an R at position 458, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.185. The AAV capsid variant of any one of embodiments 174-184, wherein [A][B] is present in loop IV.186. The AAV capsid variant of any one of embodiments 174-185, wherein [A] is present immediately subsequent to position 449, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.187. The AAV capsid variant of any one of embodiments 174-186, wherein [A] replaces positions 450-453 (e.g., T450, 1451, N452, G453), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.188. The AAV capsid variant of any one of embodiments 174-187. wherein [A] is present immediately subsequent to position 449, and wherein [A] replaces positions 450-453 (e.g.. T450, 1451, N452. G453), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.189. The AAV capsid variant of any one of embodiments 174-188, wherein [A][B] replaces positions 450-455 (e.g., T450, 1451, N452, G453, S454, G455), 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 174- 189, wherein [A] [B] is present immediately subsequent to position 449, and wherein [A][B] replaces positions 450-455 (e.g., T450, 1451, N452, G453, S454. G455), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.191. The AAV capsid variant of any one of embodiments 174-190, wherein [B] is present immediately subsequent [A], and replaces positions 454 and 455 (e.g., S454 and G455), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.47323376583.1Attorney Docket No.: V2071-3049PCT192. The AAV capsid variant of any one of embodiments 174-191. wherein [B] is present immediately subsequent to position 455. relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 982.193. The AAV capsid variant of any one of embodiments 174-192, wherein [B] is present immediately subsequent to [A],194. The AAV capsid variant of any one of embodiments 174-193, which comprises from N-tenninus to C -terminus, [A][B],195. The AAV capsid variant of any one of embodiments 1 or 3-27, comprising an amino acid sequence having the following formula: [N1]-[N2]-[N3] (SEQ ID NO: 6407), wherein:(i) [Nl] comprises positions XI, X2, and X3, wherein position X2 is S and position X3 is G;(ii) [N2] comprises the amino acid sequence SPH; and(iii) [N3] comprises positions X4. X5, and X6, wherein position X5 is K.196. The AAV capsid variant of embodiment 195. wherein:(i) X4 of [N3] is S. T, N, or A; and(ii) X5 of [N3] is A, V. T, S, G. R, L, or N; optionally wherein the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of the aforesaid amino acids in (i) or (ii).197. The AAV capsid variant of embodiment 195 or 196, wherein X4 is S and / or X5 is A.198. The AAV capsid variant of any one of embodiments 195-197. wherein [N3] comprises SK. TK. NK, AK, KA, KV, KT, KS, KG, KR, KL. or KN.199. The AAV capsid variant of any one of embodiments 195-198, wherein [N3] is or comprises SKA, SKV, SKT, SKS. SKG. SKR. TKA. NKA. SKL. SKN. or AKA.200. The AAV capsid variant of any one of embodiments 195-199, wherein [N3] is or comprises SKA.201. The AAV capsid variant of any one of embodiments 195-200, wherein [N2]-[N3] comprises SPHSK (SEQ ID NO: 4701), SPHTK (SEQ ID NO: 4725), SPHNK (SEQ ID NO: 4726), or SPHAK (SEQ ID NO: 4727).48323376583.1Attorney Docket No.: V2071-3049PCT202. The AAV capsid variant of any one of embodiments 195-201, wherein [N2]-[N3] is or comprises:(i) SPHSKA (SEQ ID NO: 941), SPHSKV (SEQ ID NO: 4737), SPHSKT (SEQ ID NO: 4731). SPHSKS (SEQ ID NO: 962). SPHSKG (SEQ ID NO: 4732). SPHSKR (SEQ ID NO: 978), SPHTKA (SEQ ID NO: 4739), SPHNKA (SEQ ID NO: 4734). SPHSKL (SEQ ID NO: 960). SPHSKN (SEQ ID NO: 4735), or SPHAKA (SEQ ID NO: 4736);(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i). e.g., any 2, 3. 4, or 5 amino acids, e.g.. consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to any of the amino acid sequences in (i); or(iv) an amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).203. The AAV capsid variant of any one of embodiments 195-202, wherein [N2]-[N3] is or comprises SPHSKA (SEQ ID NO: 941).204. The AAV capsid variant of any one of embodiments 195-203, which comprises an amino acid other than G at position 453 (e.g., M, T. I. E, S, A. N, V. L, K, H, P, R, W, or D), numbered according to SEQ ID NO: 138 or 981.205. The AAV capsid variant of any one of embodiments 195-204. which comprises the amino acid G at position 453, numbered according to SEQ ID NO: 138 or 981.206. The AAV capsid variant of any one of embodiments 195-205, wherein XI of [Nl] is chosen from: G. M, T, I. E, S, A, N, V, L, K, H, P, R, W, or D; optionally wherein the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of the aforesaid amino acids.207. The AAV capsid variant of any one of embodiments 195-206, wherein [Nl] comprises SG, GS, MS. TS. IS, ES, SS, AS, NS, VS, LS, KS, HS. PS, RS, WS, or DS.208. The AAV capsid variant of any one of embodiments 195-207, wherein [Nl] is or comprises: GSG, MSG, TSG, ISG, ESG. SSG, ASG, NSG, VSG, LSG, KSG, HSG, PSG, RSG. WSG, or DSG.209. The AAV capsid variant of any one of embodiments 195-208, wherein [Nl] is or comprises GSG.49323376583.1Attorney Docket No.: V2071-3049PCT210. The AAV capsid variant of any one of embodiments 195-209, wherein [N1]-[N2] comprises SGSPH (SEQ ID NO: 4752).211. The AAV capsid variant of any one of embodiments 195-210. wherein [N 1]-[N2] is or comprises:(i) GSGSPH (SEQ ID NO: 4695). MSGSPH (SEQ ID NO: 4798), TSGSPH (SEQ ID NO: 4800). ISGSPH (SEQ ID NO: 4801), ESGSPH (SEQ ID NO: 4803), SSGSPH (SEQ ID NO: 4804), ASGSPH (SEQ ID NO: 4806), NSGSPH (SEQ ID NO: 4807), VSGSPH (SEQ ID NO: 4786), LSGSPH (SEQ ID NO: 4808), KSGSPH (SEQ ID NO: 4810), HSGSPH (SEQ ID NO: 4811), PSGSPH (SEQ ID NO: 4813), RSGSPH (SEQ ID NO: 4815), WSGSPH (SEQ ID NO: 4817), DSGSPH (SEQ ID NO: 4818);(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i), e.g., any 2, 3, 4, or 5 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no more than four modifications, e g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to any of tire ammo 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).212. The AAV capsid variant of any one of embodiments 195-211. wherein [N1]-[N2]-[N3] is or comprises:(i) GSGSPHSKA (SEQ ID NO: 4697), GSGSPHSKV (SEQ ID NO: 4956). MSGSPHSKA (SEQ ID NO: 4957). TSGSPHSKA (SEQ ID NO: 4959), 1SGSPHSKA (SEQ ID NO: 4960), GSGSPHSKT (SEQ ID NO: 4962). ESGSPHSKA (SEQ ID NO: 4963), SSGSPHSKA (SEQ ID NO: 4964), GSGSPHSKS (SEQ ID NO: 4953), ASGSPHSKA (SEQ ID NO: 4966), NSGSPHSKA (SEQ ID NO: 4967), VSGSPHSKA (SEQ ID NO: 4913). LSGSPHSKA (SEQ ID NO: 4968), KSGSPHSKA (SEQ ID NO: 4970). GSGSPHSKG (SEQ ID NO: 4972), GSGSPHSKR (SEQ ID NO: 4945). HSGSPHSKA (SEQ ID NO: 4973), PSGSPHSKA (SEQ ID NO: 4975), RSGSPHSKA (SEQ ID NO: 4977), GSGSPHTKA (SEQ ID NO: 4978), WSGSPHSKA (SEQ ID NO: 4980). DSGSPHSKA (SEQ ID NO: 4981). GSGSPHNKA (SEQ ID NO: 4983), GSGSPHSKL (SEQ ID NO: 4943). GSGSPHSKN (SEQ ID NO: 4994), or GSGSPHAKA (SEQ ID NO: 4995);(ii) an amino acid sequence comprising any 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); or50323376583.1Attorney Docket No.: V2071-3049PCT(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).213. The AAV capsid variant of any one of embodiments 195-212, wherein [N1]-[N2]-[N3] is or comprises GSGSPHSKA (SEQ ID NO: 4697).214. The AAV capsid variant of any one of embodiments 195-213, which comprises an amino acid other than Q at position 456 (e.g.. R, P, H. L, K, I, G, S, M, or E), an amino acid other than N at position 457 (e.g., D. V, S, P. T, G, Y, W, E, R, H. K, F, A, I, L, or M), an amino acid other than Q at position 458 (e.g., R, L, A, P. H, T, I, F. K, V, M, G. W, Y, S, E, N, or D), an amino acid other than Q at position 459 (e.g., H, K, A, L, P, E. M, I, S, N, R, Y, C, V, T, W. D, G), and / or an amino acid other than T at position 460 (e.g., I, N, S, H, R, L, D, Y, A, or Q), relative to a reference sequence numbered according to SEQ ID NO: 138.215. The AAV capsid variant of any one of embodiments 195-214, which comprises an amino acid other than Q at position 462 (e.g., R, P, H, L, K, I, G, S, M, or E), an amino acid other than N at position 463 (e.g., D, V, S, P, T, G, Y, W. E, R, H, K, F, A, I, L, or M), an amino acid other than Q at position 464 (e.g., R, L, A, P, H, T, I, F, K, V. M, G, W, Y, S, E, N, or D), an amino acid other than Q at position 465 (e.g., H, K, A, L, P, E, M, I, S. N, R, Y, C, V, T, W, D, G), and / or an amino acid other than T at position 466 (e g., I, N, S. H, R, L. D, Y. A, or Q), relative to a reference sequence numbered according to SEQ ID NO: 981.216. The AAV capsid variant of any one of embodiments 195-215. which comprises the amino acid Q at position 456, the amino acid N at position 457, the amino acid Q at position 458, the amino acid Q at position 459, and / or the amino acid T at position 460, relative to a reference sequence numbered according to SEQ ID NO: 138.217. The AAV capsid variant of any one of embodiments 195-216, which comprises the amino acid Q at position 462, the amino acid N at position 463, the amino acid Q at position 464, the amino acid Q at position 465, and / or the amino acid T at position 466, numbered according to SEQ ID NO: 981218. The AAV capsid variant of any one of embodiments 195-217, further comprising [N4] wherein [N4] comprises X7, X8, X9, X10, and XI 1, wherein:(a) X7 is Q, R, P, H, L, K, I, G, S. M, or E;(b) X8 is N, D. V, S, P, T, G, Y, W, E, R, H. K, F, A, I, L, or M;(c) X9 is Q, R, L, A, P, H, T, I, F, K, V, M, G, W, Y, S, E, N, D;(d) X10 is Q, H, K, A, L, P, E, M, I, S, N, R, Y, C, V, T, W, D, G; and51323376583.1Attorney Docket No.: V2071-3049PCT(e) XI 1 is T, I, N, S, H, R, L, D, Y, A, Q; optionally wherein the AAV capsid variant comprises an amino acid modification, e.g.. a conservative substitution, of any of the aforesaid amino acids in (a)-(e).219. The AAV capsid variant of embodiment 218, wherein [N4] is or comprises:(i) QNQQT (SEQ ID NO: 5412), QNRHT (SEQ ID NO: 5413). RDQQT (SEQ ID NO: 5414). PNLQT (SEQ ID NO: 5415), HVRQT (SEQ ID NO: 5416), PNQHT (SEQ ID NO: 5417), QSQQT (SEQ ID NO: 5418). QNQQI (SEQ ID NO: 5419), QPAKT (SEQ ID NO: 5420), QTQQN (SEQ ID NO: 5421), QNLAT (SEQ ID NO: 5422), QNQLT (SEQ ID NO: 5423), QGQQT (SEQ ID NO: 5424), LNRQS (SEQ ID NO: 5425), HNQQT (SEQ ID NO: 5426), QNPPT (SEQ ID NO: 5427), QNLQT (SEQ ID NO: 5428), QYQQT (SEQ ID NO: 5429), QDQET (SEQ ID NO: 5430), QNHQT (SEQ ID NO: 5431), QDQQT (SEQ ID NO: 5432), HWQQT (SEQ ID NO: 5433), PNQQT (SEQ ID NO: 5434), QNQLI (SEQ ID NO: 5435), PEQQT (SEQ ID NO: 5436), QRTMT (SEQ ID NO: 5437), QNQQH (SEQ ID NO: 5438), LHQHT (SEQ ID NO: 5439), QHRIT (SEQ ID NO: 5440), QYIHT (SEQ ID NO: 5441), QKFET (SEQ ID NO: 5442), QFPST (SEQ ID NO: 5443), HNQQR (SEQ ID NO: 5444), QAIKT (SEQ ID NO: 5445), QNRQT (SEQ ID NO: 5446), QYQHT (SEQ ID NO: 5447), QNPQS (SEQ ID NO: 5448), QHQLT (SEQ ID NO: 5449). QSPPT (SEQ ID NO: 5450). QAKLT (SEQ ID NO: 5451), KSQQT (SEQ ID NO: 5452), QDRPT (SEQ ID NO: 5453). QSQQL (SEQ ID NO: 5454). QAFHT (SEQ ID NO: 5455), QKQQD (SEQ ID NO: 5456), QNAQT (SEQ ID NO: 5457), HNQLT (SEQ ID NO: 5458). QNQQY (SEQ ID NO: 5459), QKLNT (SEQ ID NO: 5460), QNVQT (SEQ ID NO: 5461), QAQQT (SEQ ID NO: 5462), QNLQA (SEQ ID NO: 5463). QTPPT (SEQ ID NO: 5464). QYQHA (SEQ ID NO: 5465), QGQQA (SEQ ID NO: 5466), QPPAT (SEQ ID NO: 5467). QERPT (SEQ ID NO: 5468), QDLQT (SEQ ID NO: 5469), QAMHT (SEQ ID NO: 5470), LNQQT (SEQ ID NO: 5471). QHPST (SEQ ID NO: 5472), PGLQT (SEQ ID NO: 5473), QGIRT (SEQ ID NO: 5474), QAPAT (SEQ ID NO: 5475), QSQQI (SEQ ID NO: 5476), QIPPT (SEQ ID NO: 5477), QTQLT (SEQ ID NO: 5478), QAPST (SEQ ID NO: 5479), QNTYA (SEQ ID NO: 5480), QNQHI (SEQ ID NO: 5481), QNHLT (SEQ ID NO: 5482). QI GMT (SEQ ID NO: 5483), LNKQT (SEQ ID NO: 5484). QLQQT (SEQ ID NO: 5485), QRMST (SEQ ID NO: 5486). QGILT (SEQ ID NO: 5487), QDRQT (SEQ ID NO: 5488), RDWQT (SEQ ID NO: 5489). QNTHD (SEQ ID NO: 5490), PNLQI (SEQ ID NO: 5491), QERST (SEQ ID NO: 5492), QNYQT (SEQ ID NO: 5493). QRTCT (SEQ ID NO: 5494). QIGHT (SEQ ID NO: 5495), QGAIT (SEQ ID NO: 5496), QVPPT (SEQ ID NO: 5497), QVQQI (SEQ ID NO: 5498), LMRQT (SEQ ID NO: 5499), QYSVT (SEQ ID NO: 5500), QAITT (SEQ ID NO: 5501), QKTLT (SEQ ID NO: 5502), QNQWT (SEQ ID NO: 5503), QLHHT (SEQ ID NO: 5504), QNIII (SEQ ID NO: 5505), QGHHT (SEQ ID NO: 5506), QSKVT (SEQ ID NO: 5507), QLPST (SEQ ID NO: 5508), IGKQT (SEQ ID NO: 5509), QAIHT (SEQ ID NO: 5510), QHGLT (SEQ ID NO: 5511), QFMCT (SEQ ID NO: 5512), QHLQT (SEQ ID NO: 5513), QNHQN (SEQ ID NO: 5514), QPART (SEQ ID NO: 5515), QSLQT (SEQ ID NO:52323376583.1Attorney Docket No.: V2071-3049PCT5516), QSQLT (SEQ ID NO: 5517), QDRQS (SEQ ID NO: 5518), QMPST (SEQ ID NO: 5519), QGSLT (SEQ ID NO: 5520). QVPAT (SEQ ID NO: 5521), QDKQT (SEQ ID NO: 5522). HYQQT (SEQ ID NO: 5523), QVPST (SEQ ID NO: 5524). RGEQT (SEQ ID NO: 5525), PGQQT (SEQ ID NO: 5526), QSLQI (SEQ ID NO: 5527), LEQQT (SEQ ID NO: 5528), QNQST (SEQ ID NO: 5529). QKVIT (SEQ ID NO: 5530), QNNDQ (SEQ ID NO: 5531), QSVHT (SEQ ID NO: 5532). QPLGT (SEQ ID NO: 5533), HNQET (SEQ ID NO: 5534), QNLQI (SEQ ID NO: 5535), QIQQT (SEQ ID NO: 5536), QVRNT (SEQ ID NO: 5537), PSNQT (SEQ ID NO: 5538). QVGHT (SEQ ID NO: 5539). QRDIT (SEQ ID NO: 5540), QMPNT (SEQ ID NO: 5541), RGLQT (SEQ ID NO: 5542), QKQQT (SEQ ID NO: 5543), PSLQT (SEQ ID NO: 5544), QRDQT (SEQ ID NO: 5545), QAKGT (SEQ ID NO: 5546), QSAHT (SEQ ID NO: 5547), QSTMT (SEQ ID NO: 5548), QREMT (SEQ ID NO: 5549), QYRAT (SEQ ID NO: 5550), QWQQT (SEQ ID NO: 5551), QRMNT (SEQ ID NO: 5552), GDSQT (SEQ ID NO: 5553), QKIST (SEQ ID NO: 5554), PSMQT (SEQ ID NO: 5555), SPRQT (SEQ ID NO: 5556), MEQQT (SEQ ID NO: 5557), QYQNT (SEQ ID NO: 5558), QHQQT (SEQ ID NO: 5559), INQQT (SEQ ID NO: 5560), PNQQH (SEQ ID NO: 5561), ENRQT (SEQ ID NO: 5562), QTQQA (SEQ ID NO: 5563), or QNQAT (SEQ ID NO: 5564);(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i), e.g., any 2. 3, or 4 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no more than four modifications, e g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to any of the amino acid sequences in (i); or(iv) an amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).220. The AAV capsid variant of embodiment 218 or 219, wherein [N1]-[N2]-[N3]-[N4] is or comprises:(i) the amino acid sequence of any of SEQ ID NOs: 200 or 2887-3076;(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i). e.g.. any 2, 3. 4. 5, 6, 7, 8. 9. 10, 11, 12, or 13 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one. two, or three but no more than four modifications, e.g.. substitutions (e.g.. conservative substitutions), insertions, or deletions, relative to any of the amino acid sequences in (i); or(iv) an amino acid sequence comprising one. two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).221. The AAV capsid variant of any one of embodiments 218-220, wherein [N1]-[N2]-[N3]-[N4] is or comprises GSGSPHSKAQNQQT (SEQ ID NO: 200).53323376583.1Attorney Docket No.: V2071-3049PCT222. The AAV capsid variant of any one of embodiments 218-221. wherein [N1]-[N2]-[N3]-[N4] is or comprises VSGSPHSKAQNQQT (SEQ ID NO: 903).223. The AAV capsid variant of any one of embodiments 195-222, which comprises an amino acid other than K at position 449 (e.g.. T, E, or N), T at position 450 (e.g., S. E, A, N. V, Q. or G). an amino acid other than I at position 451 (e.g.. F, E, V. L, D, S. C, T, A, N, H. R, G, or W), and / or an amino acid other than N at position 452 (e.g., I, P, K, R, H. S, M, Q, D, T. L, A, Y, V, F. E, W. or G). relative to a reference sequence numbered according to SEQ ID NO: 138 or 981.224. The AAV capsid variant of any one of embodiments 195-223, which comprises the amino acid K at position 449, the amino acid T at position 450, the amino acid I at position 451, and / or the amino acid N at position 452, relative to a reference sequence numbered according to SEQ ID NO: 138 or 981.225. The AAV capsid variant of any one of embodiments 195-224, which further comprises [NO], wherein [NO] comprises XA, XB, XC, and XD, wherein:(a) XA is K, T, E, or N;(b) Xbis T, S, E, A, N, V, Q, or G;(c) Xcis I. F, E, V. L, D, S. C, T, A, N, H, R, G. or W: and(d) XDis N, I, P. K, R, H, S, M. Q, D. T, L, A. Y, V. F, E, W, or G: optionally wherein the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of the aforesaid amino acids in (a)-(d).226. The AAV capsid variant of embodiment 225. wherein [NO] is or comprises:(i) KTII (SEQ ID NO: 5565), KTFP (SEQ ID NO: 5566), KTEK (SEQ ID NO: 5567), KTVN (SEQ ID NO: 5568), KTFN (SEQ ID NO: 5569), KTIN (SEQ ID NO: 5570), TTIN (SEQ ID NO: 5571). KSIN (SEQ ID NO: 5572). KTER (SEQ ID NO: 5573), KELH (SEQ ID NO: 5574), KAIN (SEQ ID NO: 5575), KTDN (SEQ ID NO: 5576), KTFH (SEQ ID NO: 5577). KTSN (SEQ ID NO: 5578). ETIN (SEQ ID NO: 5579), NTIN (SEQ ID NO: 5580), KTEN (SEQ ID NO: 5581). KTSS (SEQ ID NO: 5582), KTCN (SEQ ID NO: 5583), KTEH (SEQ ID NO: 5584), KAEM (SEQ ID NO: 5585). KATN (SEQ ID NO: 5586), KAIK (SEQ ID NO: 5587), KTDK (SEQ ID NO: 5588), KTFK (SEQ ID NO: 5589), KSDQ (SEQ ID NO: 5590), KTEI (SEQ ID NO: 5591), KTID (SEQ ID NO: 5592), KNTN (SEQ ID NO: 5593), KTET (SEQ ID NO: 5594), KTEL (SEQ ID NO: 5595), KNIN (SEQ ID NO: 5596), KTEA (SEQ ID NO: 5597), KTAN (SEQ ID NO: 5598), NTIY (SEQ ID NO: 5599), KTFS (SEQ ID NO: 5600), KTES (SEQ ID NO: 5601), KTTN (SEQ ID NO: 5602), KTED (SEQ ID NO: 5603), KTNN (SEQ ID NO: 5604), KEVH (SEQ ID NO: 5605), KTIS (SEQ ID NO: 5606), KTVR (SEQ ID NO: 5607), KTDR (SEQ ID NO: 5608), ETIK (SEQ ID NO: 5609), KNHI54323376583.1Attorney Docket No.: V2071-3049PCT(SEQ ID NO: 5610), KESD (SEQ ID NO: 5611), KTIK (SEQ ID NO: 5612), KTDL (SEQ ID NO: 5613). KTVP (SEQ ID NO: 5614), KTVI (SEQ ID NO: 5615), KAEH (SEQ ID NO: 5616), KNCL (SEQ ID NO: 5617), KTVK (SEQ ID NO: 5618), KNAD (SEQ ID NO: 5619), KTIT (SEQ ID NO: 5620). KNCV (SEQ ID NO: 5621), KNAL (SEQ ID NO: 5622), KVIN (SEQ ID NO: 5623). KTEF (SEQ ID NO: 5624), KTRE (SEQ ID NO: 5625), KQGE (SEQ ID NO: 5626). KSEK (SEQ ID NO: 5627). KNVN (SEQ ID NO: 5628), KGGE (SEQ ID NO: 5629), KEFV (SEQ ID NO: 5630), KSDK (SEQ ID NO: 5631), KTEQ (SEQ ID NO: 5632), KEVQ (SEQ ID NO: 5633), KTEY (SEQ ID NO: 5634). KNCW (SEQ ID NO: 5635), KTDV (SEQ ID NO: 5636), KSDI (SEQ ID NO: 5637). KNSI (SEQ ID NO: 5638), KNSL (SEQ ID NO: 5639), KEVV (SEQ ID NO: 5640), KTEP (SEQ ID NO: 5641), KSEL (SEQ ID NO: 5642), KTWQ (SEQ ID NO: 5643), KTEV (SEQ ID NO: 5644), KAVN (SEQ ID NO: 5645), KGVL (SEQ ID NO: 5646), KTEG (SEQ ID NO: 5647), KTRD (SEQ ID NO: 5648), KTGN (SEQ ID NO: 5649), KNAI (SEQ ID NO: 5650), KAEN (SEQ ID NO: 5651), KAET (SEQ ID NO: 5652), KTVH (SEQ ID NO: 5653), KETA (SEQ ID NO: 5654), KNNL (SEQ ID NO: 5655), EAIN (SEQ ID NO: 5656), KSLN (SEQ ID NO: 5657), KTIP (SEQ ID NO: 5658), or KTIH (SEQ ID NO: 5659);(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i), e.g., any 2. or 3 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no more than four modifications, e g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to any of the amino acid sequences in (i); or(iv) an amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).227. The AAV capsid variant of embodiment 225 or 226, wherein [NO]-[N1]-[N2]-[N3]-[N4] is or comprises:(i) the amino acid sequence of any one of SEQ ID NOs: 3239-3526 or 3591-3605;(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i). e.g.. any 2, 3. 4. 5, 6, 7, 8. 9. 10, 11, 12, 13, 14. 15, 16, or 17 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one. two, or three but no more than four modifications, e.g.. substitutions (e.g.. conservative substitutions), insertions, or deletions, relative to any of 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).228. The AAV capsid variant of any one of embodiments 225-227, wherein [NO]-[N1]-[N2]-[N3]- [N4] is or comprises KTINGSGSPHSKAQNQQT (SEQ ID NO: 5660).55323376583.1Attorney Docket No.: V2071-3049PCT229. The AAV capsid variant of any one of embodiments 225-228. wherein [NO]-[N1]-[N2]-[N3]- [N4] is or comprises KTERVSGSPHSKAQNQQT (SEQ ID NO: 3589).230. The AAV capsid variant of any one of embodiments 1 or 3-27 comprising an amino acid sequence having the following formula: [N1]-[N2]-[N3] (SEQ ID NO: 6408), wherein:(i) [Nl] comprises positions XI, X2, and X3, wherein position X2 is an amino acid other than S and position X3 is an amino acid other than G;(ii) [N2] comprises the amino acid sequence SPH; and(iii) [N3] comprises positions X4, X5, and X6. wherein position X4 is K.231. The AAV capsid variant of embodiment 230, wherein:(i) X5 of [N3] is S, I, T, R, H, Y, L, or M; and(ii) X6 of [N3] is G, A, L, E, V, R, W, N, Q, or K; optionally wherein the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of the aforesaid amino acids in (i) or (ii).232. The AAV capsid variant of embodiment 230 or 231, wherein X5 is S and / or Xe is G.233. The AAV capsid variant of any one of embodiments 230-232. wherein [N3] comprises KS, KI, KT. KR, KH, KY, KL. KM, SG, IG, TG, RG, SA. SL. SE. SV. SR. SW, SN, HG, YG, SQ, IV, SK, LW, MG, or MA.234. The AAV capsid variant of any one of embodiments 230-233. wherein [N3J is or comprises KSG. KIG, KTG, KRG, KSA, KSL, KSE, KSV, KSR, KSW, KSN, KHG, KYG, KSQ, KIV, KSK, KLW, KMG, or KMA.235. The AAV capsid variant of any one of embodiments 230-234, wherein [N3] is or comprises KSG.236. The AAV capsid variant of any one of embodiments 230-235, wherein [N2]-[N3] comprises SPHKS (SEQ ID NO: 4704), SPHKI (SEQ ID NO: 4713), SPHKT (SEQ ID NO: 4711), SPHKR (SEQ ID NO: 4717), NPHKS (SEQ ID NO: 5661), SPHKH (SEQ ID NO: 4728), SPHKY (SEQ ID NO: 4715), SPHKL (SEQ ID NO: 4714), or SPHKM (SEQ ID NO: 4729).237. The AAV capsid variant of any one of embodiments 230-236, wherein [N2]-[N3] is or comprises:56323376583.1Attorney Docket No.: V2071-3049PCT(i) SPHKSG (SEQ ID NO: 946), SPHKIG (SEQ ID NO: 958), SPHKTG (SEQ ID NO: 4738). SPHKRG (SEQ ID NO: 974), NPHKSG (SEQ ID NO: 5662), SPHKSA (SEQ ID NO: 977). SPHKSL (SEQ ID NO: 4740), SPHKSE (SEQ ID NO: 4741), SPHKSV (SEQ ID NO: 4742), SPHKSR (SEQ ID NO: 951). SPHKSW (SEQ ID NO: 4743), SPHKSN (SEQ ID NO: 4744), SPHKHG (SEQ ID NO: 4745), SPHKYG (SEQ ID NO: 966), SPHKSQ (SEQ ID NO: 4746), SPHKIV (SEQ ID NO: 5663), SPHKSK (SEQ ID NO: 4747), SPHKLW (SEQ ID NO: 4748), SPHKMG (SEQ ID NO: 4750). or SPHKMA (SEQ ID NO: 4751);(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i). e.g., any 2, 3, 4, or 5 amino acids, e.g.. consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to any of the amino acid sequences in (i); or(iv) an amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).238. The AAV capsid variant of any one of embodiments 230-237, wherein [N2]-[N3] is or comprises SPHKSG (SEQ ID NO: 946).239. The AAV capsid variant of any one of embodiments 230-238. which comprises an amino acid other than G at position 453 (e.g., A, K. W, R, L, I, M. N, T, E, Q, Y. H, F, or V), numbered according to SEQ ID NO: 138 or 981.240. The AAV capsid variant of any one of embodiments 230-239. which comprises the amino acid G at position 453, numbered according to SEQ ID NO: 138 or 981.241. The AAV capsid variant of any one of embodiments 230-239, wherein:(i) position XI of [Nl] is G. A, K. W, R. L, I, M. N, T, E. Q, Y. H, F, or V;(ii) position X2 of [Nl] is H, Y. R, Q, N. P, or D;(iii) position X3 of [Nl] is D, E. G, V. or N; optionally wherein the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of the aforesaid amino acids in (i), (ii). or (iii).242. The AAV capsid variant of any one of embodiments 230-241, wherein position X2 of [Nl] is H and position X3 of [Nl] is D.243. The AAV capsid variant of any one of embodiments 230-242, wherein position XI of [Nl] is G, position X2 of [Nl] is H and position X3 of [Nl] is D.57323376583.1Attorney Docket No.: V2071-3049PCT244. The AAV capsid variant of any one of embodiments 230-243, wherein [Nl] comprises GH. HD, GY. GR. GQ, AH, GN. KH, GP, WH. RH. LH, IH. MH, GD. NH, TH, EH, QH. YH, HH, FH, VH. YD. HE. RG, QD, RD, ND. PD, QV, DD. HN. or NG245. The AAV capsid variant of any one of embodiments 230-244, wherein [Nl] is or comprises GHD, GYD. GHE. GRG. GQD, GRD, AHD, GND, KHD, GPD, WHD, RHD, LHD, GQV, IHD, MHD. GDD, GHN, NHD, THD, GNG, EHD, QHD, YHD. HHD, FHD, or VHD.246. The AAV capsid variant of any one of embodiments 230-245, wherein [Nl] is or comprises GHD.247. The AAV capsid variant of any one of embodiments 230-246, wherein [N1]-[N2] comprises HDSPH (SEQ ID NO: 4703).248. The AAV capsid variant of any one of embodiments 230-247, wherein [N1]-[N2] is or comprises:(i) GHDSPH (SEQ ID NO: 4784), GYDSPH (SEQ ID NO: 4829), GHESPH (SEQ ID NO: 4793), GRGSPH (SEQ ID NO: 4788), GHDNPH (SEQ ID NO: 5664), GQDSPH (SEQ ID NO: 4785), GRDSPH (SEQ ID NO: 4831), AHDSPH (SEQ ID NO: 5665), GNDSPH (SEQ ID NO: 4832), KHDSPH (SEQ ID NO: 5666), GPDSPH (SEQ ID NO: 4833), WHDSPH (SEQ ID NO: 5667), RHDSPH (SEQ ID NO: 5668), LHDSPH (SEQ ID NO: 5669), GQVSPH (SEQ ID NO: 4835), IHDSPH (SEQ ID NO: 5670), MHDSPH (SEQ ID NO: 5671). GDDSPH (SEQ ID NO: 4792), GHNSPH (SEQ ID NO: 4836). NHDSPH (SEQ ID NO: 5672), THDSPH (SEQ ID NO: 5673), GNGSPH (SEQ ID NO: 4805). EHDSPH (SEQ ID NO: 5674), QHDSPH (SEQ ID NO: 5675), YHDSPH (SEQ ID NO: 5676). HHDSPH (SEQ ID NO: 5677), FHDSPH (SEQ ID NO: 5678), or VHDSPH (SEQ ID NO: 5679);(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i). e.g.. any 2, 3. 4. or 5 amino acids, e.g.. consecutive amino acids, thereof;(iii) an amino acid sequence comprising one. two, or three but no more than four modifications, e.g.. substitutions (e.g.. conservative substitutions), insertions, or deletions, relative to any of 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).249. The AAV capsid variant of any one of embodiments 230-248, wherein [N1]-[N2]-[N3] is or comprises:58323376583.1Attorney Docket No.: V2071-3049PCT(i) GHDSPHKSG (SEQ ID NO: 4698), GHDSPHKIG (SEQ ID NO: 4996), GYDSPHKSG (SEQ ID NO: 4997), GHESPHKSG (SEQ ID NO: 4998). GHDSPHKTG (SEQ ID NO: 4999), GRGSPHKRG (SEQ ID NO: 5000), GHDNPHKSG (SEQ ID NO: 5680). GQDSPHKSG (SEQ ID NO: 4908), GHDSPHKSA (SEQ ID NO: 4940). GHDSPHKSL (SEQ ID NO: 5001), GHDSPHKSE (SEQ ID NO: 5003), GRDSPHKSG (SEQ ID NO: 5004), AHDSPHKSG (SEQ ID NO: 5681), GNDSPHKSV (SEQ ID NO: 5005), AHDSPHKIG (SEQ ID NO: 5682), GHESPHKSA (SEQ ID NO: 4939), GQDSPHKIG (SEQ ID NO: 5006), GHDSPHKSV (SEQ ID NO: 5007), GHDSPHKSR (SEQ ID NO: 4942), KHDSPHKSG (SEQ ID NO: 5683), GPDSPHKIG (SEQ ID NO: 5008), GPDSPHKSG (SEQ ID NO: 5009), GHDSPHKSW (SEQ ID NO: 5010), WHDSPHKSG (SEQ ID NO: 5684), RHDSPHKSG (SEQ ID NO: 5685), GHDSPHKSN (SEQ ID NO: 5011), GHDSPHKRG (SEQ ID NO: 4937), GHDSPHKHG (SEQ ID NO: 5013), LHDSPHKSG (SEQ ID NO: 5686), GQVSPHKSG (SEQ ID NO: 5014), IHDSPHKSG (SEQ ID NO: 5687), MHDSPHKSG (SEQ ID NO: 5688), GDDSPHKSV (SEQ ID NO: 5015), GHNSPHKSG (SEQ ID NO: 5016), NHDSPHKSG (SEQ ID NO: 5689), THDSPHKSG (SEQ ID NO: 5690), GNGSPHKRG (SEQ ID NO: 5017), EHDSPHKSG (SEQ ID NO: 5691), GHDSPHKYG (SEQ ID NO: 5018), GHDSPHKSQ (SEQ ID NO: 5019), QHDSPHKSG (SEQ ID NO: 5692), RHDSPHKIV (SEQ ID NO: 5693), YHDSPHKSG (SEQ ID NO: 5694). GNDSPHKIG (SEQ ID NO: 5020), HHDSPHKSG (SEQ ID NO: 5695), GHDSPHKSK (SEQ ID NO: 5021), FHDSPHKSG (SEQ ID NO: 5696), GHDSPHKLW (SEQ ID NO: 5022), VHDSPHKSG (SEQ ID NO: 5697), GHDSPHKMG (SEQ ID NO: 5024). GHDSPHKMA (SEQ ID NO: 5025), or GDDSPHKSG (SEQ ID NO: 4938);(ii) an amino acid sequence comprising any 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 tire amino acid sequences in (i); or(iv) an amino acid sequence comprising one. two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).250. The AAV capsid variant of any one of embodiments 230-249, wherein [N1]-[N2]-[N3] is or comprises GHDSPHKSG (SEQ ID NO: 4698).251. The AAV capsid variant of any one of embodiments 230-248, which comprises an amino acid other than Q at position 456 (e.g.. R, P, H. K, L, V, A, E. or I), an amino acid other than N at position 457 (e.g., I, K, S, H, R. T, D, Y, L, W, F, A, Q, or M), an amino acid other than Q at position 458 (e.g., R, V, K, P, Y, H, L, I, E, or M), an amino acid other than Q at position 459 (e.g., H, L, E, P, W. D, I, V, S, K, R, C, M, or N), and / or an amino acid other than T at position 460 (e.g., A, E, K, S, I, P, G, or N), relative to a reference sequence numbered according to SEQ ID NO: 138.59323376583.1Attorney Docket No.: V2071-3049PCT252. The AAV capsid variant of any one of embodiments 230-251, which comprises an amino acid other than Q at position 462 (e.g.. R. P, H. K, L, V. A, E. or I), an amino acid other than N at position 463 (e.g., I, K, S. H, R. T, D, Y. L, W. F, A, Q, or M), an amino acid other than Q at position 464 (e.g., R, V. K, P, Y, H, L. I. E, or M), an amino acid other than Q at position 465 (e.g., H, L, E. P. W. D. I, V, S, K, R, C. M, or N), and / or an amino acid other than T at position 466 (e.g.. A, E, K, S, I, P, G, or N), relative to a reference sequence numbered according to SEQ ID NO: 982.253. The AAV capsid variant of any one of embodiments 230-252, which comprises the amino acid Q at position 456, the amino acid N at position 457, the amino acid Q at position 458, the amino acid Q at position 459, and / or the amino acid T at position 460, relative to a reference sequence numbered according to SEQ ID NO: 138.254. The AAV capsid variant of any one of embodiments 230-253, which comprises the amino acid Q at position 462, the amino acid N at position 463, the amino acid Q at position 464, the amino acid Q at position 465, and / or the amino acid T at position 466, relative to a reference sequence numbered according to SEQ ID NO: 138.255. The AAV capsid variant of any one of embodiments 230-254, further comprising [N4] wherein [N4] comprises X7, X8, X9, X10, and Xll, wherein:(a) X7 is Q, R. P, H, L. K, I, G. S, M, or E;(b) X8 is N, D, V, S, P. T, G, Y, W. E, R, H, K, F, A, I, L, or M;(c) X9 is Q, R. L, A, P. H, T, I, F. K, V. M, G. W, Y, S, E, N, D;(d) X10 is Q, H, K, A, L. P, E, M, 1, S, N. R, Y, C. V, T. W, D. G; and(e) XI 1 is T, I, N, S. H, R, L. D, Y. A, Q; optionally wherein the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of the aforesaid amino acids in (a)-(e).256. The AAV capsid variant of embodiment 255, wherein [N4] is or comprises:(i) QNQQT (SEQ ID NO: 5412), QIRQT (SEQ ID NO: 5698), QNQHA (SEQ ID NO: 5699), QKQQT (SEQ ID NO: 5543), QSVQT (SEQ ID NO: 5700), RSQQT (SEQ ID NO: 5701). QNKLE (SEQ ID NO: 5702), QNQQK (SEQ ID NO: 5703), QHQQA (SEQ ID NO: 5704), QIQHT (SEQ ID NO: 5705), PRQQT (SEQ ID NO: 5706), HTQQT (SEQ ID NO: 5707), QRQHT (SEQ ID NO: 5708), QSQQT (SEQ ID NO: 5418), QNQQS (SEQ ID NO: 5709). RNQET (SEQ ID NO: 5710), QTQLT (SEQ ID NO: 5478), KNQQT (SEQ ID NO: 5711), QDQQT (SEQ ID NO: 5432), HNQQT (SEQ ID NO: 5426), QNQLT (SEQ ID NO: 5423), QTQQT (SEQ ID NO: 5712), QTQQI (SEQ ID NO: 5713), QSKQA (SEQ ID NO: 5714), QNQPP (SEQ ID NO: 5715), QSPQT (SEQ ID NO: 5716), QNYQT (SEQ ID NO: 5493), QNHQT (SEQ ID NO: 5431), QNRQT (SEQ ID NO: 5446), QNQQG60323376583.1Attorney Docket No.: V2071-3049PCT(SEQ ID NO: 5717), QNHLT (SEQ ID NO: 5482), QYQHT (SEQ ID NO: 5447), QNQWT (SEQ ID NO: 5503), QNQHT (SEQ ID NO: 5718). QTRQT (SEQ ID NO: 5719), QNLHT (SEQ ID NO: 5720). LNQQT (SEQ ID NO: 5471), QNQET (SEQ ID NO: 5721). QHLQT (SEQ ID NO: 5513), LNQPT (SEQ ID NO: 5722). QNQDT (SEQ ID NO: 5723), RNQQT (SEQ ID NO: 5724). QNLLT (SEQ ID NO: 5725), QLVIT (SEQ ID NO: 5726), RTQET (SEQ ID NO: 5727). QTHQT (SEQ ID NO: 5728), QNQPA (SEQ ID NO: 5729), QDQHT (SEQ ID NO: 5730), QSQHT (SEQ ID NO: 5731). RNQQI (SEQ ID NO: 5732), VRQQT (SEQ ID NO: 5733), QNQHS (SEQ ID NO: 5734), AWQQT (SEQ ID NO: 5735), QSVPT (SEQ ID NO: 5736), QNIQP (SEQ ID NO: 5737), QNHLN (SEQ ID NO: 5738), LDQQT (SEQ ID NO: 5739), PDQQS (SEQ ID NO: 5740), ESQQT (SEQ ID NO: 5741), QNKQT (SEQ ID NO: 5742). QRQLT (SEQ ID NO: 5743), QIIVT (SEQ ID NO: 5744), QKQST (SEQ ID NO: 5745), QSHQT (SEQ ID NO: 5746), QFVVT (SEQ ID NO: 5747), QNLQT (SEQ ID NO: 5428), QNQQI (SEQ ID NO: 5419), QSQPT (SEQ ID NO: 5748), QNEQT (SEQ ID NO: 5749), QSLQT (SEQ ID NO: 5516), RNRQT (SEQ ID NO: 5750), QSKQT (SEQ ID NO: 5751), QNPLT (SEQ ID NO: 5752), RDQKT (SEQ ID NO: 5753), HNQQN (SEQ ID NO: 5754), QWKRT (SEQ ID NO: 5755), QSQQI (SEQ ID NO: 5476), QAQQT (SEQ ID NO: 5462), QNHQI (SEQ ID NO: 5756), QNQQA (SEQ ID NO: 5757), QNQLN (SEQ ID NO: 5758), QTQPT (SEQ ID NO: 5759), INQQT (SEQ ID NO: 5560), QKQLT (SEQ ID NO: 5760), RNQLA (SEQ ID NO: 5761), RNQQS (SEQ ID NO: 5762), ISIQT (SEQ ID NO: 5763), QNQQN (SEQ ID NO: 5764), QSQQS (SEQ ID NO: 5765). QTVCT (SEQ ID NO: 5766), QYQQI (SEQ ID NO: 5767), QQIMT (SEQ ID NO: 5768), QNEQS (SEQ ID NO: 5769). LNHQT (SEQ ID NO: 5770), QMIHT (SEQ ID NO: 5771), RNHQS (SEQ ID NO: 5772), QKMNT (SEQ ID NO: 5773), QSQQN (SEQ ID NO: 5774). QYQHA (SEQ ID NO: 5465);(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i), e.g., any 2. 3, or 4 amino acids, e.g.. consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no more than four modifications, e.g.. substitutions (e.g.. conservative substitutions), insertions, or deletions, relative to any of the amino acid sequences in (i); or(iv) an amino acid sequence comprising one. two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).257. The AAV capsid variant of embodiment 255 or 256, wherein [N1]-[N2]-[N3]-[N4] is or comprises:(i) the amino acid sequence of any of SEQ ID NOs: 201 or 3160-3237;(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i). e.g., any 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or 13 amino acids, e.g., consecutive amino acids, thereof;61323376583.1Attorney Docket No.: V2071-3049PCT(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).258. The AAV capsid variant of any one of embodiments 255-257, wherein [N1]-[N2]-[N3]-[N4] is or comprises GHDSPHKSGQNQQT (SEQ ID NO: 201).259. The AAV capsid variant of any one of embodiments 230-258, which comprises an amino acid other than K at position 449 (e.g.. T), T at position 450 (e.g., A, S, I, V, N, E, Y, C, G, W, or Q), an amino acid other than I at position 451 (e.g., E, V, S, T, N, D, C, G, Q, L, P, A), and / or an amino acid other than N at position 452 (e.g., S, Y, I, K, F, T, D, E, G, V, L, A, M, Q, H, P, or R), relative to a reference sequence numbered according to SEQ ID NO: 138 or 982.260. The AAV capsid variant of any one of embodiments 230-259, which comprises the amino acid K at position 449, the amino acid T at position 450, tire amino acid I at position 451, and / or the amino acid N at position 452, relative to a reference sequence numbered according to SEQ ID NO: 138 or 982.261. The AAV capsid variant of any one of embodiments 230-260. which further comprises [NO], wherein [NO] comprises XA, XB, Xc, and XD, wherein:(a) XAis K or T;(b) Xbis T, A. S. I. V, N. E, Y. C. G, W, or Q;(c) Xcis I, E, V, S, T, N, D, C, G, Q, L, P, A; and(d) XDis N, S, Y. I. K, F, T. D, E, G, V, L. A, M. Q, H. P. or R; optionally wherein the AAV capsid variant comprises an amino acid modification, e.g.. a conservative substitution, of any of the aforesaid amino acids in (a)-(d).262. The AAV capsid variant of embodiment 261, wherein [NO] is or comprises:(i) KAIN (SEQ ID NO: 5575), KTIN (SEQ ID NO: 5570), KTES (SEQ ID NO: 5601). TTIN (SEQ ID NO: 5571), KSIN (SEQ ID NO: 5572), KTVN (SEQ ID NO: 5568), KSIY (SEQ ID NO: 5775), KTSN (SEQ ID NO: 5578), KTTN (SEQ ID NO: 5602), KIIN (SEQ ID NO: 5776), KTIS (SEQ ID NO: 5606), KAII (SEQ ID NO: 5777), KTIK (SEQ ID NO: 5612), KTEF (SEQ ID NO: 5624), KTIT (SEQ ID NO: 5620), KTNN (SEQ ID NO: 5604). KTID (SEQ ID NO: 5592), KAIS (SEQ ID NO: 5778), KTVD (SEQ ID NO: 5779), KTIE (SEQ ID NO: 5780), KTEG (SEQ ID NO: 5647), KVIN (SEQ ID NO: 5623), KAVN (SEQ ID NO: 5645), KTIY (SEQ ID NO: 5781), KTDN62323376583.1Attorney Docket No.: V2071-3049PCT(SEQ ID NO: 5576), KTCN (SEQ ID NO: 5583), KNVV (SEQ ID NO: 5782), KTEL (SEQ ID NO: 5595). KTDA (SEQ ID NO: 5783), KTEV (SEQ ID NO: 5644), KSEL (SEQ ID NO: 5642), KTEM (SEQ ID NO: 5784), KTEQ (SEQ ID NO: 5632), KTII (SEQ ID NO: 5565). KIVN (SEQ ID NO: 5785). KTEK (SEQ ID NO: 5567), KTEN (SEQ ID NO: 5581), KIGN (SEQ ID NO: 5786), KEVM (SEQ ID NO: 5787), KYQV (SEQ ID NO: 5788), KTEA (SEQ ID NO: 5597), KATN (SEQ ID NO: 5586). KTEH (SEQ ID NO: 5584), KTVE (SEQ ID NO: 5789), KAID (SEQ ID NO: 5790), KTIM (SEQ ID NO: 5791), KEVG (SEQ ID NO: 5792), KSEM (SEQ ID NO: 5793), KAQQ (SEQ ID NO: 5794). KCGE (SEQ ID NO: 5795), KASN (SEQ ID NO: 5796), KTET (SEQ ID NO: 5594), KTIG (SEQ ID NO: 5797), KTDP (SEQ ID NO: 5798), KELV (SEQ ID NO: 5799). KELM (SEQ ID NO: 5800), KNEI (SEQ ID NO: 5801), KTPN (SEQ ID NO: 5802), KITN (SEQ ID NO: 5803), KTDI (SEQ ID NO: 5804), KTDQ (SEQ ID NO: 5805), KGIN (SEQ ID NO: 5806), KSEI (SEQ ID NO: 5807), KSEK (SEQ ID NO: 5627), KWSA (SEQ ID NO: 5808), KELA (SEQ ID NO: 5809), KQTQ (SEQ ID NO: 5810), KGAD (SEQ ID NO: 5811), KVGE (SEQ ID NO: 5812), KANE (SEQ ID NO: 5813), KTDT (SEQ ID NO: 5814), KTCI (SEQ ID NO: 5815), KELR (SEQ ID NO: 5816), KCQI (SEQ ID NO: 5817), KGVM (SEQ ID NO: 5818). KACD (SEQ ID NO: 5819), KNEL (SEQ ID NO: 5820), KAAE (SEQ ID NO: 5821), KGQN (SEQ ID NO: 5822), KNEF (SEQ ID NO: 5823), KTSI (SEQ ID NO: 5824). KAEH (SEQ ID NO: 5616), KCDQ (SEQ ID NO: 5825), KEIL (SEQ ID NO: 5826), KTER (SEQ ID NO: 5573), KNAI (SEQ ID NO: 5650), KTDK (SEQ ID NO: 5588), KTPD (SEQ ID NO: 5827). KTIH (SEQ ID NO: 5659), or KTEI (SEQ ID NO: 5591);(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i), e.g., any 2. or 3 amino acids, e.g., consecutive amino acids, thereof:(iii) an amino acid sequence comprising one, two, or three but no more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to any of tire amino acid sequences in (i); or(iv) an amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).263. The AAV capsid variant of embodiment 261 or 262. wherein [NO]-[N1]-[N2]-[N3]-[N4] is or comprises:(i) the amino acid sequence of any one of SEQ ID NOs: 3606-3836;(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i). e.g., any 2, 3. 4, 5, 6, 7, 8. 9, 10, 11, 12, 13, 14. 15, 16, or 17 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to any of the amino acid sequences in (i); or63323376583.1Attorney Docket No.: V2071-3049PCT(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).264. The AAV capsid variant of any one of embodiments 261-263, wherein [NO]-[N1]-[N2]-[N3]- [N4] is or comprises KTINGHDSPHKSGQNQQT (SEQ ID NO: 5828).265. The AAV capsid variant of any one of embodiments 261-264, wherein [NO]-[N1]-[N2]-[N3]- [N4] is or comprises KAEIGHDSPHKSGQNQQT (SEQ ID NO: 1754).266. The AAV capsid variant of any one of embodiments 261-265, wherein [NO]-[N1]-[N2]-[N3]- [N4] is or comprises KTEKMSGSPHSKAQNQQT (SEQ ID NO: 3241).267. The AAV capsid variant of any one of embodiments 195-266, wherein [N1]-[N2]-[N3] is present in loop IV.268. The AAV capsid variant of any one of embodiments 225-229 or 261-267, wherein [NO] and [N4] are present in loop IV.269. The AAV capsid variant of any one of embodiments 225-229 or 261-268, wherein [NO] is present immediately subsequent to position 448. relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. 981, or 982.270. The AAV capsid variant of any one of embodiments 225-229 or 261-269, wherein [NO] replaces positions 449-452 (e.g., K449, T450. 1451, and N452). relative to a reference sequence numbered according to SEQ ID NO: 138, 981, or 982.271. The AAV capsid variant of any one of embodiments 225-229 or 261-270. wherein [NO] is present immediately subsequent to position 448 and wherein [NO] replaces positions 449-452 (e.g., K449, T450. 1451, and N452), relative to a reference sequence numbered according to SEQ ID NO: 138. 981, or 982.272. The AAV capsid variant of any one of embodiments 225-229 or 261-271, wherein [NO] corresponds to positions 449-452 (e.g., K449, T450, 1451, and N452) of any one of SEQ ID NOs: 138, 981, or 982.64323376583.1Attorney Docket No.: V2071-3049PCT273. The AAV capsid variant of any one of embodiments 195-272. wherein [Nl] is present immediately subsequent to position 452. relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138, 981. or 982.274. The AAV capsid variant of any one of embodiments 195-273, wherein [Nl] replaces positions 453-455 (e.g., G453, S454, and G455), relative to a reference sequence numbered according to SEQ ID NO: 138, 981, or 982.275. The AAV capsid variant of any one of embodiments 195-274, wherein [Nl] replaces position 453 (e.g., G453), relative to a reference sequence numbered according to SEQ ID NO: 138, 981, or 982.276. The AAV capsid variant of any one of embodiments 195-204, 206-208, 210-212, 214-220, 222- 227, 229, or 267-273, wherein:(i) position XI of [Nl] replaces position 453 (e.g., G453);(ii) position X2 of [Nl] corresponds to position 454 (e.g., S454); and(iii) position X3 of [Nl] corresponds to position 455 (e.g., G455), wherein (i), (ii), and (iii) are numbered according to SEQ ID NO: 138 or SEQ ID NO: 981.277. The AAV capsid variant of any one of embodiments 195-203. 205-228, or 267-273, wherein:(i) position XI of [Nl] corresponds to position 453 (e.g.. G453);(ii) position X2 of [Nl] corresponds to position 454 (e.g., S454); and(iii) position X3 of [Nl] corresponds to position 455 (e.g., G455); wherein (i), (ii), and (iii) are numbered according to SEQ ID NO: 138 or SEQ ID NO: 981.278. The AAV capsid variant of any one of embodiments 230-275, wherein:(i) position XI of [Nl] corresponds to position 453 (e.g., G453);(ii) position X2 of [Nl] replaces position 454 (e.g.. S454); and(iii) position X3 of [Nl] replaces position 455 (e.g., G455). wherein (i), (ii), and (iii) are numbered according to SEQ ID NO: 138 or SEQ ID NO: 982.279. The AAV capsid variant of any one of embodiments 230-275 or 278, wherein [Nl] corresponds to positions 453-455 (e.g., G453, H454, D455) of SEQ ID NO 982.280. The AAV capsid variant of any one of embodiments 195-203, 205-228, 267-274, or 277, wherein [Nl] corresponds to positions 453-455 (e.g., G453, S454, G455) of SEQ ID NO: 138, or 981.65323376583.1Attorney Docket No.: V2071-3049PCT281. The AAV capsid variant of any one of embodiments 195-280, wherein [N2] is present immediately subsequent to position 455. relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138, 981. or 982.282. The AAV capsid variant of any one of embodiments 195-280, wherein [N2] corresponds to positions 456-458 (e.g., S456, P457, and H458) of SEQ ID NO: 981 or 982.283. The AAV capsid variant of any one of embodiments 195-281, wherein [N2] corresponds to positions 456-458 (e.g., S456, P457, and H458) of any one of SEQ ID NOs: 5-10, 36-59, or 6409- 6413.284. The AAV capsid variant of any one of embodiments 195-283, wherein [N2] is present immediately subsequent to [Nl],285. The AAV capsid variant of any one of embodiments 195-229, 267-274, 276-284, wherein [N3] corresponds to positions 459-460 (e.g., S459, K460, A461) of SEQ ID NO: 981.286. The AAV capsid variant of any one of embodiments 195-229, 267-274, 276-284. wherein [N3] corresponds to positions 459-460 (e.g., S459, K460, A461) of SEQ ID NO: 36, 38, 39, 40. 41, 42, 43, 44, 45, 46, 47. 48, 49, 50, 51. 52, 53, 54, 55, 57. or 59.287. The AAV capsid variant of any one of embodiments 195-286. wherein [N2]-[N3] is present immediately subsequent to position 455, relative to a reference sequence numbered according to the amino acid sequence of any one of SEQ ID NOs: 138. 981, or 982.288. The AAV capsid variant of any one of embodiments 195-286, wherein [N2]-[N3] is present immediately subsequent to position 455. relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 981.289. The AAV capsid variant of any one of embodiments 195-288, wherein [N2]-[N3] corresponds to positions 456-461 (e.g., S456, P457, H458, S459, K460, A461) of SEQ ID NO: 981.290. The AAV capsid variant of any one of embodiments 195-289, wherein [N2]-[N3] corresponds to positions 456-461 (e.g., S456, P457, H458, S459, K460, A461) of any one of SEQ ID NOs: 36, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 57, or 59.66323376583.1Attorney Docket No.: V2071-3049PCT291. The AAV capsid variant of any one of embodiments 230-284 or 286-288, wherein [N3] corresponds to positions 459-460 (e.g., K459, S460, G461) of SEQ ID NO: 982.292. The AAV capsid variant of any one of embodiments 230-284 or 286-288, wherein [N3] corresponds to positions 459-460 (e.g., K459, S460, G461) of SEQ ID NO: 37.293. The AAV capsid variant of any one of embodiments 230-292, wherein [N2]-[N3] is present immediately subsequent to position 455, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 982.294. The AAV capsid variant of any one of embodiments 230-273, 275, 279, 282, 284, 287, 290-293, wherein [N3] replaces positions 454 and 455 (e.g., S454 and G455), numbered according to SEQ ID NO: 138.295. The AAV capsid variant of any one of embodiments 230-273, 275, 279, 282, 284, 287, 290-293, wherein [N3] is present immediately subsequent to [N2] and replaces positions 454 and 455 (e.g., S454 and G455), numbered according to SEQ ID NO: 138.296. The AAV capsid variant of any one of embodiments 230-273. 275, 279, 282. 284, 287, 290-294, wherein [N3] is present immediately subsequent to [N1]-[N2] and replaces positions 454 and 455 (e.g., S454 and G455). numbered according to SEQ ID NO: 138.297. The AAV capsid variant of any one of embodiments 230-286. 287, 291-296. wherein IN2J-[N3] corresponds to positions 456-461 (e.g., S456, P457, H458. K459, S460, G461) of SEQ ID NO: 982.298. The AAV capsid variant of any one of embodiments 230-284, 287, 291-297, wherein [N2]-[N3] corresponds to positions 456-461 (e.g., S456, P457, H458, K459, S460. G461) of SEQ ID NO: 37.299. The AAV capsid variant of any one of embodiments 218-229 or 255-298, wherein [N4] is present immediately subsequent to position 455, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.300. The AAV capsid variant of any one of embodiments 218-229 or 255-299, wherein [N4] replaces positions 456-460 (e.g., Q456, N457, Q458, Q459, and T460), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.67323376583.1Attorney Docket No.: V2071-3049PCT301. The AAV capsid variant of any one of embodiments 218-229 or 255-300, wherein [N4] corresponds to positions 462-466 (e.g., Q462, N463, Q464. Q465. and T466) of SEQ ID NO: 981 or 982.302. The AAV capsid variant of any one of embodiments 218-229 or 255-300, wherein [N4] corresponds to positions 462-466 of any one of SEQ ID NOs: 5-10. 36-59, or 6409-6413.303. The AAV capsid variant of any one of embodiments 218-229 or 255-301, wherein [N4] corresponds to positions 456-460 (e.g., Q456, N457, Q458, Q459, and T460) of SEQ ID NO: 138.304. The AAV capsid variant of any one of embodiments 218-229 or 255-303, wherein [N2]-[N3]- [N4] replaces positions 456-460 (e.g., Q456, N457, Q458, Q459, and T460), relative to a reference sequence numbered according to the ammo acid sequence of SEQ ID NO: 138.305. The AAV capsid variant of any one of embodiments 218-229 or 255-304, wherein [N2]-[N3]- [N4] is present immediately subsequent to position 455, and wherein [N2]-[N3]-[N4] replaces positions 456-460 (e.g., Q456, N457, Q458. Q459, and T460), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.306. The AAV capsid variant of any one of embodiments 218-229 or 255-305, wherein [N1]-[N2]- [N3]-[N4] replaces positions 453-460 (e.g., G453. S454. G455, Q456, N457, Q458, Q459. and T460), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.307. The AAV capsid variant of any one of embodiments 218-229 or 255-306, wherein [N1]-[N2]- [N3]-[N4] is present immediately subsequent to position 452, and wherein [N1]-[N2]-[N3]-[N4] replaces positions 453-460 (e.g.. G453, S454, G455, Q456, N457, Q458, Q459, and T460), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.308. The AAV capsid variant of any one of embodiments 218-229, 267-274, 276, il. 280-290, 293, or 299-307, wherein [N1]-[N2]-[N3]-[N4] corresponds to positions 453-466 (e.g., G453. S454. G455, S456, P457, H458. S459. K460, A461, Q462, N463, Q464. Q465, and T466) of SEQ ID NO: 981.309. The AAV capsid variant of any one of embodiments 195-229, 267-274, 276, 277 280-290, 293, or 299-307, wherein [N1]-[N2]-[N3] corresponds to positions 453-461 (e.g., G453, S454, G455, S456, P457, H458, S459, K460, A461) of SEQ ID NO: 981.68323376583.1Attorney Docket No.: V2071-3049PCT310. The AAV capsid variant of any one of embodiments 255-284, 287, 288, 291-309, wherein [Nl]- [N2]-[N3]-[N4] corresponds to positions 453-466 (e.g.. G453, H454, D455, S456, P457, H458. K459, S460, G461. Q462. N463, Q464, Q465, T466) of SEQ ID NO: 982.311. The AAV capsid variant of any one of embodiments 230-284, 287. 288, 291 -310. wherein [N 1]- [N2]-[N3] corresponds to positions 453-461 (e.g., G453, H454. D455, S456, P457, H458, K459, S460, G461) of SEQ ID NO: 982.312. The AAV capsid variant of any one of embodiments 255-284, 287, 288, 291-309. wherein [Nl]- [N2]-[N3]-[N4] corresponds to positions 453-466 of any one of SEQ ID NOs: 5-10, 36-59, or 6409- 6413.313. The AAV capsid variant of any one of embodiments 225-229 or 261-312, wherein [N0]-[Nl]- [N2]-[N3]-[N4] replaces positions 449-460 (e.g, K449, T450, 1451, N452, G453, S454, G455, Q456, N457, Q458, Q459, and T460), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.314. The AAV capsid variant of any one of embodiments 225-229 or 261-313, wherein [N0]-[Nl]- [N2]-[N3]-[N4] is present immediately subsequent to position 448. and wherein [NO]-[N1]-[N2]- [N3]-[N4] replaces positions 449-460 (e.g., K449. T450. 1451, N452. G453, S454, G455, Q456, N457, Q458, Q459, and T460). relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.315. The AAV capsid variant of any one of embodiments 225-229. 267-274, 276. 277, 280-290. 293, 299-308, 313, or 314 , wherein [NO]-[N1]-[N2]-[N3]-[N4] corresponds to positions 449-466 (e.g., K449, T450. 1451, N452. G453, S454, G455, S456, P457, H458, S459, K460. A461, Q462, N463, Q464. Q465. T466) of SEQ ID NO: 981.316. The AAV capsid variant of any one of embodiments 261-284, 287. 288, 291-311. 313, or 314. wherein [NO]-[N1]-[N2]-[N3]-[N4] corresponds to positions 449-466 (e.g., K449, T450, 1451, N452, G453. H454, D455, S456, P457, H458, K459, S460, G461. Q462, N463, Q464, Q465. T466) of SEQ ID NO: 982.317. The AAV capsid variant of any one of embodiments 261-284, 287, 288, 291-311, 313, or 314, wherein [N0]-[N 1]-[N2]-[N3]-[N4] corresponds to positions 449-466 of any one of SEQ ID NOs: 5- 10, 36-59, or 6409-6413.69323376583.1Attorney Docket No.: V2071-3049PCT318. The AAV capsid variant of any one of embodiments 218-229 or 255-317, wherein [N4] is present immediately subsequent to position 461, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 981 or 982.319. The AAV capsid variant of any one of embodiments 218-229 or 255-318, wherein [N4] replaces positions 462-466 (e.g., Q462, N463, Q464, Q465. and T466), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 981 or 982.320. The AAV capsid variant of any one of embodiments 218-229 or 255-318, wherein [N2]-[N3]- [N4] replaces positions 462-466 (e.g., Q462, N463, Q464, Q465, and T466), relative to a reference sequence numbered according to the ammo acid sequence of SEQ ID NO: 981 or 982.321. The AAV capsid variant of any one of embodiments 218-229 or 255-318, wherein [N2]-[N3]- [N4] is present immediately subsequent to position 455, and wherein [N2]-[N3]-[N4] replaces positions 462-466 (e.g., Q462, N463, Q464, Q465, and T466), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 981 or 982.322. The AAV capsid variant of any one of embodiments 195-321, which comprises from N-terminus to C-tenninus. [N2]-[N3],323. The AAV capsid variant of any one of embodiments 195-322. which comprises from N-terminus to C-tenninus. [N1]-[N2]-[N3],324. The AAV capsid variant of any one of embodiments 195-323. which comprises from N-terminus to C -terminus, [NO]-[N1]-[N2]-[N3],325. The AAV capsid variant of any one of embodiments 195-324, which comprises from N-terminus to C -terminus, [N1]-[N2]-[N3]-[N4],326. The AAV capsid variant of any one of embodiments 195-325, which comprises from N-terminus to C -terminus, [NO]-[N1]-[N2]-[N3]-[N4],327. The AAV capsid variant of any one of embodiments 1 or 3-27, comprising the formula [A]-[B] (SEQ ID NO: 4696), wherein:(i) [A] comprises GSGSPH (SEQ ID NO: 4695); and(ii) [B] comprises XI X2, X3, X4, and X5, wherein:(a) position XI is S, I, F, V, C, Y, W, R, P, L, Q, M, K, or G;70323376583.1Attorney Docket No.: V2071-3049PCT(b) position X2 is K, M, R, F, V, C, P, Y, L, W, G, N, S, T, I, or A;(c) position X3 is A, Y, L. R, W. C, T. F. H, I, P, M, K. S. V, G. Q, or N;(d) position X4 is Q, M. F, K, H, R, C. W, P. V, L, G. S, Y, I, A, T, D. N, or E: and(e) position X5 is A, N, Y, R, K. L, I, M. Q, S, C. W, F. T, G, V, or P; optionally wherein the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of the aforesaid amino acids in (a)-(e).328. The AAV capsid variant of embodiment 327, wherein:(a) position XI is S, L, R, V, or P;(b) position X2 is K, C. F, L, P, R, S, or V;(c) position X3 is A, C. F, I, K, L. M, P, R, T, W, or Y;(d) position X4 is Q, R, S, T, C, F, K, L, P or Y; and(e) position X5 is N, R, S, T, K, M, Q or Y; optionally wherein the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of die aforesaid amino acids in (a)-(e).329. The AAV capsid variant of embodiment 327 or 328, wherein [B] comprises SKA, SMY, SKL, SKR, SKW. SRC, SFT, SKF, IVW, SKY, SCH. FPW. SKI, VYY, SLY, SKP, SRF. SRM. SVK. SWA. SLW, SFR, SKK, SY A, SCS, SGA, SFP. SFF, SMC, SKT, SGK, FYR, CRV, YGI. VNC, SLA, WSY. RWL, PSC, SSW, SKG, VPW. SGC. STT, PKR, SKC, WVP, SFW, RIK, SKM, LRW, LPT, SYM, LLC, RCC, LCV, SYL, QGC, MAF, SFQ, SLC. RPW, RPR. SCP, SVR, SLP, VYH, SYT, LVY, YRY. SWL. CPA, SPP, RWT, PRK, PFV, SKS. WVA, SKV, CAL, SSC. SKN. LCT. STC, SKQ, KSG, SYY, SLT, SCQ. FPF, SVF, GRY, AQA, AQN. YMN, AFY, LKR, RHR, AQK, WRL, CRN, TCN. FFI, AQY, WQN. YFM, ARQ, HQN, IRR. YQN. YWN, AFS, FWN, AQC, MRN, KKN, APN, WKN, ARW. RPN, KVF, AFN, ACS, RLW, SRN, CPN, ACN, FRQ, PFN, FGN. CQN, LFW, TRK, KRN, RQN. VQN. IQN, AQR. PFR, AWN. RSY. LQN. WLN. RRA. AQT. GCT. RYT, TPN, ARM, CFL, PQN, WSN, FKN, KQN, APR, RYN, MIC, TQN, WKS, AAR, LTR, IRG, LVN, FQN, ACQ, WGL. ILR, QIN. ACI, ALR, AHA. CLN. AFV, AQF, RCN, MPC. KTS, PYN, AQS, TRN, LKN, AQM. CTN. PDN, RNY. ACR. CSV, ARI, LPK, SEQ. VRM, NSR, RKR, ARN, QRP, RVV, GQN, YSN, QSN, AKG, CTS, FEN, AKK, KAQ, MYM, KAF, KLK, KRH, KWR, RCR, FTC, KFF, VWQ, KYF, KAR, CHQ, PWQ, KIR, YYQ, LYW. KPK. RFW, RMR, VKK, WAP, LWK, FRP, KKV. YAF. KAC, KRL. CSR, RCP, GAC, KFR, FFG, MCQ, KLF, KTR, GKR, YRQ, RVQ, GIQ, NCQ, KPF, LAW, KRS, SYQ, WLQ, KRR, KGC. KRY. GCQ, FTP, TTC, KRQ, KCF, VPQ, FWS, KFK, IKQ, KAP, FRY, KMI. RWQ, PTQ, KWK, YMR, KAA. LCQ. CCQ. CVQ, KLT, KLC, YLV, AFQ, KWG, KIL, FQI, KAL, KAH, LCL, PRQ, CPQ, VRY, VRC, KMP, KKT, LPY, YHQ, YTR, VYQ, RYQ, WLK, PAQ, MCT, PPD, WTQ, RKQ, KCS, FVQ, KLP, KSE, VAQ,71323376583.1Attorney Docket No.: V2071-3049PCTLYQ, KVR, ALQ, SCT, KNS, KRK, CTQ, TCL, YAR, KQR, KRV, SGQ, YYS, LTC, CQS, KAK, KPQ, PFQ, KCT, or VFE.330. The AAV capsid variant of any one of embodiments 327-329, wherein [B] comprises SKAQ (SEQ ID NO: 5829), SMYM (SEQ ID NO: 5830), SKAF (SEQ ID NO: 5831), SKLK (SEQ ID NO: 5832). SKRH (SEQ ID NO: 5833), SKWR (SEQ ID NO: 5834), SRCR (SEQ ID NO: 5835). SFTC (SEQ ID NO: 5836), SKFF (SEQ ID NO: 5837), IVWQ (SEQ ID NO: 5838), SKYF (SEQ ID NO: 5839). SKAR (SEQ ID NO: 5840), SCHQ (SEQ ID NO: 5841), FPWQ (SEQ ID NO: 5842). SKIR (SEQ ID NO: 5843), VYYQ (SEQ ID NO: 5844), SLYW (SEQ ID NO: 5845), SKPK (SEQ ID NO: 5846), SRFW (SEQ ID NO: 5847), SRMR (SEQ ID NO: 5848), SVKK (SEQ ID NO: 5849), SWAP (SEQ ID NO: 5850), SLWK (SEQ ID NO: 5851), SFRP (SEQ ID NO: 5852), SKKV (SEQ ID NO: 5853), SYAF (SEQ ID NO: 5854), SKAC (SEQ ID NO: 5855), SKRL (SEQ ID NO: 5856), SCSR (SEQ ID NO: 5857), SRCP (SEQ ID NO: 5858), SGAC (SEQ ID NO: 5859), SKFR (SEQ ID NO: 5860), SFPF (SEQ ID NO: 5861), SFFG (SEQ ID NO: 5862), SMCQ (SEQ ID NO: 5863), SKLF (SEQ ID NO: 5864), SKTR (SEQ ID NO: 5865), SGKR (SEQ ID NO: 5866), FYRQ (SEQ ID NO: 5867), CRVQ (SEQ ID NO: 5868), YGIQ (SEQ ID NO: 5869), VNCQ (SEQ ID NO: 5870), SKPF (SEQ ID NO: 5871). SLAW (SEQ ID NO: 5872), SKRS (SEQ ID NO: 5873), WSYQ (SEQ ID NO: 5874), RWLQ (SEQ ID NO: 5875), PSCQ (SEQ ID NO: 5876), SSWL (SEQ ID NO: 5877), SKRR (SEQ ID NO: 5878). SKGC (SEQ ID NO: 5879), VPWQ (SEQ ID NO: 5880), SKRY (SEQ ID NO: 5881), SGCQ (SEQ ID NO: 5882), SFTP (SEQ ID NO: 5883). STTC (SEQ ID NO: 5884), PKRQ (SEQ ID NO: 5885). SKCF (SEQ ID NO: 5886), WVPQ (SEQ ID NO: 5887), SFWS (SEQ ID NO: 5888), SKFK (SEQ ID NO: 5889), RIKQ (SEQ ID NO: 5890). SKAP (SEQ ID NO: 5891), SFRY (SEQ ID NO: 5892). SKMI (SEQ ID NO: 5893), LRWQ (SEQ ID NO: 5894), LPTQ (SEQ ID NO: 5895), SKWK (SEQ ID NO: 5896), SYMR (SEQ ID NO: 5897). SKAA (SEQ ID NO: 5898), LLCQ (SEQ ID NO: 5899), RCCQ (SEQ ID NO: 5900), LCVQ (SEQ ID NO: 5901), SKLT (SEQ ID NO: 5902). SKLC (SEQ ID NO: 5903), SYLV (SEQ ID NO: 5904). QGCQ (SEQ ID NO: 5905), MAFQ (SEQ ID NO: 5906), SKWG (SEQ ID NO: 5907), SKIL (SEQ ID NO: 5908), SFQI (SEQ ID NO: 5909). SKAL (SEQ ID NO: 5910), SKAH (SEQ ID NO: 5911). SLCL (SEQ ID NO: 5912), RPWQ (SEQ ID NO: 5913), RPRQ (SEQ ID NO: 5914), SCPQ (SEQ ID NO: 5915), SVRY (SEQ ID NO: 5916). SVRC (SEQ ID NO: 5917), SKMP (SEQ ID NO: 5918), SKKT (SEQ ID NO: 5919), SLPY (SEQ ID NO: 5920), VYHQ (SEQ ID NO: 5921), SYTR (SEQ ID NO: 5922), LVYQ (SEQ ID NO: 5923). YRYQ (SEQ ID NO: 5924), SWLK (SEQ ID NO: 5925), CPAQ (SEQ ID NO: 5926), SMCT (SEQ ID NO: 5927), SPPD (SEQ ID NO: 5928), SKRN (SEQ ID NO: 5929), RWTQ (SEQ ID NO: 5930), PRKQ (SEQ ID NO: 5931), SKCS (SEQ ID NO: 5932), PFVQ (SEQ ID NO: 5933), SKLP (SEQ ID NO: 5934), SKSE (SEQ ID NO: 5935), WVAQ (SEQ ID NO: 5936), SLYQ (SEQ ID NO: 5937), SKVR (SEQ ID NO: 5938), CALQ (SEQ ID NO: 5939), SSCT (SEQ ID NO: 5940), SKNS (SEQ ID NO: 5941), SKRK (SEQ ID NO: 5942), LCTQ (SEQ ID NO: 5943), STCL (SEQ ID NO:72323376583.1Attorney Docket No.: V2071-3049PCT5944), SY AR (SEQ ID NO: 5945), SKQR (SEQ ID NO: 5946), SKRV (SEQ ID NO: 5947), KSGQ (SEQ ID NO: 5948), SYYS (SEQ ID NO: 5949). SLTC (SEQ ID NO: 5950), SCQS (SEQ ID NO: 5951). SKAK (SEQ ID NO: 5952), SKPQ (SEQ ID NO: 5953). FPFQ (SEQ ID NO: 5954), SKCT (SEQ ID NO: 5955), SVFE (SEQ ID NO: 5956). GRYQ (SEQ ID NO: 5957). KAQA (SEQ ID NO: 5958). KAQN (SEQ ID NO: 5959), MYMN (SEQ ID NO: 5960). KAFY (SEQ ID NO: 5961), KLKR (SEQ ID NO: 5962), KRHR (SEQ ID NO: 5963), KAQK (SEQ ID NO: 5964), KWRL (SEQ ID NO: 5965). RCRN (SEQ ID NO: 5966), FTCN (SEQ ID NO: 5967), KFFI (SEQ ID NO: 5968), KAQY (SEQ ID NO: 5969), VWQN (SEQ ID NO: 5970). KYFM (SEQ ID NO: 5971), KARQ (SEQ ID NO: 5972), CHQN (SEQ ID NO: 5973), PWQN (SEQ ID NO: 5974), KIRR (SEQ ID NO: 5975), YYQN (SEQ ID NO: 5976), LYWN (SEQ ID NO: 5977), KPKR (SEQ ID NO: 5978), KAFS (SEQ ID NO: 5979), RFWN (SEQ ID NO: 5980), KAQC (SEQ ID NO: 5981), RMRN (SEQ ID NO: 5982), VKKN (SEQ ID NO: 5983), WAPN (SEQ ID NO: 5984), LWKN (SEQ ID NO: 5985), KARW (SEQ ID NO: 5986), FRPN (SEQ ID NO: 5987), KKVF (SEQ ID NO: 5988), YAFN (SEQ ID NO: 5989), KACS (SEQ ID NO: 5990), KRLW (SEQ ID NO: 5991), CSRN (SEQ ID NO: 5992), RCPN (SEQ ID NO: 5993), GACN (SEQ ID NO: 5994), KFRQ (SEQ ID NO: 5995), FPFN (SEQ ID NO: 5996), FFGN (SEQ ID NO: 5997). MCQN (SEQ ID NO: 5998). KLFW (SEQ ID NO: 5999), KTRK (SEQ ID NO: 6000), GKRN (SEQ ID NO: 6001). YRQN (SEQ ID NO: 6002), RVQN (SEQ ID NO: 6003), GIQN (SEQ ID NO: 6004). KAQR (SEQ ID NO: 6005), NCQN (SEQ ID NO: 6006), KPFR (SEQ ID NO: 6007), LAWN (SEQ ID NO: 6008), KRSY (SEQ ID NO: 6009), SYQN (SEQ ID NO: 6010), WLQN (SEQ ID NO: 6011). SCQN (SEQ ID NO: 6012), SWLN (SEQ ID NO: 6013), KRRA (SEQ ID NO: 6014), KAQT (SEQ ID NO: 6015). KGCT (SEQ ID NO: 6016), KRYT (SEQ ID NO: 6017), GCQN (SEQ ID NO: 6018). FTPN (SEQ ID NO: 6019), TTCN (SEQ ID NO: 6020). KARM (SEQ ID NO: 6021), KRQN (SEQ ID NO: 6022). KCFL (SEQ ID NO: 6023), VPQN (SEQ ID NO: 6024), FWSN (SEQ ID NO: 6025). KFKN (SEQ ID NO: 6026). IKQN (SEQ ID NO: 6027), KAPR (SEQ ID NO: 6028), FRYN (SEQ ID NO: 6029), KMIC (SEQ ID NO: 6030), RWQN (SEQ ID NO: 6031), PTQN (SEQ ID NO: 6032), KWKS (SEQ ID NO: 6033), YMRN (SEQ ID NO: 6034), KAAR (SEQ ID NO: 6035). LCQN (SEQ ID NO: 6036), CCQN (SEQ ID NO: 6037), CVQN (SEQ ID NO: 6038). KLTR (SEQ ID NO: 6039), KLCT (SEQ ID NO: 6040), KIRG (SEQ ID NO: 6041), YLVN (SEQ ID NO: 6042). AFQN (SEQ ID NO: 6043), KACQ (SEQ ID NO: 6044), KWGL (SEQ ID NO: 6045), KILR (SEQ ID NO: 6046), FQIN (SEQ ID NO: 6047). KACI (SEQ ID NO: 6048), KALR (SEQ ID NO: 6049). KAHA (SEQ ID NO: 6050), LCLN (SEQ ID NO: 6051), KAFV (SEQ ID NO: 6052), PRQN (SEQ ID NO: 6053), CPQN (SEQ ID NO: 6054), KAQF (SEQ ID NO: 6055), VRYN (SEQ ID NO: 6056), VRCN (SEQ ID NO: 6057), KMPC (SEQ ID NO: 6058), KKTS (SEQ ID NO: 6059), LPYN (SEQ ID NO: 6060), YHQN (SEQ ID NO: 6061), KAQS (SEQ ID NO: 6062), YTRN (SEQ ID NO: 6063), VYQN (SEQ ID NO: 6064), RYQN (SEQ ID NO: 6065), WLKN (SEQ ID NO: 6066), KAQM (SEQ ID NO: 6067), PAQN (SEQ ID NO: 6068), MCTN (SEQ ID NO: 6069), PPDN (SEQ ID NO: 6070), KRNY (SEQ ID NO: 6071), WTQN (SEQ ID NO: 6072), KACR (SEQ ID NO: 6073),73323376583.1Attorney Docket No.: V2071-3049PCTRKQN (SEQ ID NO: 6074), KCSV (SEQ ID NO: 6075), KARI (SEQ ID NO: 6076), FVQN (SEQ ID NO: 6077), KLPK (SEQ ID NO: 6078), KSEQ (SEQ ID NO: 6079), VAQN (SEQ ID NO: 6080). LYQN (SEQ ID NO: 6081), KVRM (SEQ ID NO: 6082), ALQN (SEQ ID NO: 6083). SCTN (SEQ ID NO: 6084), KNSR (SEQ ID NO: 6085), KRKR (SEQ ID NO: 6086), CTQN (SEQ ID NO: 6087). TCLN (SEQ ID NO: 6088), YARN (SEQ ID NO: 6089). KQRP (SEQ ID NO: 6090), KRVV (SEQ ID NO: 6091), SGQN (SEQ ID NO: 6092), YYSN (SEQ ID NO: 6093), LTCN (SEQ ID NO: 6094), CQSN (SEQ ID NO: 6095), KAKG (SEQ ID NO: 6096), KPQN (SEQ ID NO: 6097), PFQN (SEQ ID NO: 6098), KCTS (SEQ ID NO: 6099), VFEN (SEQ ID NO: 6100). or KAKK (SEQ ID NO: 6101).331. The AAV capsid variant of any one of embodiments 327-330, wherein [B] is or comprises:(i) SKAQA (SEQ ID NO: 6102), SKAQN (SEQ ID NO: 6103), SMYMN (SEQ ID NO: 6104), SKAFY (SEQ ID NO: 6105), SKLKR (SEQ ID NO: 6106), SKRHR (SEQ ID NO: 6107), SKAQK (SEQ ID NO: 6108), SKWRL (SEQ ID NO: 6109), SRCRN (SEQ ID NO: 6110), SFTCN (SEQ ID NO: 6111), SKFFI (SEQ ID NO: 6112), SKAQY (SEQ ID NO: 6113), IVWQN (SEQ ID NO: 6114), SKYFM (SEQ ID NO: 6115). SKARQ (SEQ ID NO: 6116), SCHQN (SEQ ID NO: 6117), FPWQN (SEQ ID NO: 6118), SKIRR (SEQ ID NO: 6119), VYYQN (SEQ ID NO: 6120), SLYWN (SEQ ID NO: 6121), SKPKR (SEQ ID NO: 6122), SKAFS (SEQ ID NO: 6123), SRFWN (SEQ ID NO: 6124). SKAQC (SEQ ID NO: 6125), SRMRN (SEQ ID NO: 6126), SVKKN (SEQ ID NO: 6127), SWAPN (SEQ ID NO: 6128), SLWKN (SEQ ID NO: 6129), SKARW (SEQ ID NO: 6130), SFRPN (SEQ ID NO: 6131), SKKVF (SEQ ID NO: 6132), SYAFN (SEQ ID NO: 6133). SKACS (SEQ ID NO: 6134), SKRLW (SEQ ID NO: 6135), SCSRN (SEQ ID NO: 6136). SRCPN (SEQ ID NO: 6137). SGACN (SEQ ID NO: 6138), SKFRQ (SEQ ID NO: 6139). SFPFN (SEQ ID NO: 6140), SFFGN (SEQ ID NO: 6141). SMCQN (SEQ ID NO: 6142), SKLFW (SEQ ID NO: 6143), SKTRK (SEQ ID NO: 6144), SGKRN (SEQ ID NO: 6145), FYRQN (SEQ ID NO: 6146), CRVQN (SEQ ID NO: 6147), YGIQN (SEQ ID NO: 6148), SKAQR (SEQ ID NO: 6149). VNCQN (SEQ ID NO: 6150), SKPFR (SEQ ID NO: 6151), SLAWN (SEQ ID NO: 6152), SKRSY (SEQ ID NO: 6153), WSYQN (SEQ ID NO: 6154). RWLQN (SEQ ID NO: 6155). PSCQN (SEQ ID NO: 6156). SSWLN (SEQ ID NO: 6157), SKRRA (SEQ ID NO: 6158), SKAQT (SEQ ID NO: 6159), SKGCT (SEQ ID NO: 6160). VPWQN (SEQ ID NO: 6161), SKRYT (SEQ ID NO: 6162). SGCQN (SEQ ID NO: 6163), SFTPN (SEQ ID NO: 6164), STTCN (SEQ ID NO: 6165). SKARM (SEQ ID NO: 6166), PKRQN (SEQ ID NO: 6167), SKCFL (SEQ ID NO: 6168). WVPQN (SEQ ID NO: 6169), SFWSN (SEQ ID NO: 6170), SKFKN (SEQ ID NO: 6171), RIKQN (SEQ ID NO: 6172). SKAPR (SEQ ID NO: 6173). SFRYN (SEQ ID NO: 6174), SKMIC (SEQ ID NO: 6175), LRWQN (SEQ ID NO: 6176), LPTQN (SEQ ID NO: 6177), SKWKS (SEQ ID NO: 6178), SYMRN (SEQ ID NO: 6179), SKAAR (SEQ ID NO: 6180), LLCQN (SEQ ID NO: 6181), RCCQN (SEQ ID NO: 6182), LCVQN (SEQ ID NO: 6183), SKLTR (SEQ ID NO: 6184), SKLCT (SEQ ID NO: 6185),74323376583.1Attorney Docket No.: V2071-3049PCTSKIRG (SEQ ID NO: 6186), SYLVN (SEQ ID NO: 6187), QGCQN (SEQ ID NO: 6188), MAFQN (SEQ ID NO: 6189), SKACQ (SEQ ID NO: 6190). SKWGL (SEQ ID NO: 6191). SKILR (SEQ ID NO: 6192), SFQIN (SEQ ID NO: 6193). SKACI (SEQ ID NO: 6194). SKALR (SEQ ID NO: 6195), SKAHA (SEQ ID NO: 6196). SLCLN (SEQ ID NO: 6197), SKAFV (SEQ ID NO: 6198), RPWQN (SEQ ID NO: 6199), RPRQN (SEQ ID NO: 6200), SCPQN (SEQ ID NO: 6201), SKAQF (SEQ ID NO: 6202), SVRYN (SEQ ID NO: 6203), SVRCN (SEQ ID NO: 6204), SKMPC (SEQ ID NO: 6205). SKKTS (SEQ ID NO: 6206), SLPYN (SEQ ID NO: 6207), VYHQN (SEQ ID NO: 6208), SKAQS (SEQ ID NO: 6209). SYTRN (SEQ ID NO: 6210), LVYQN (SEQ ID NO: 6211). YRYQN (SEQ ID NO: 6212), SWLKN (SEQ ID NO: 6213), SKAQM (SEQ ID NO: 6214), CPAQN (SEQ ID NO: 6215), SMCTN (SEQ ID NO: 6216), SPPDN (SEQ ID NO: 6217), SKRNY (SEQ ID NO: 6218), RWTQN (SEQ ID NO: 6219), SKACR (SEQ ID NO: 6220), PRKQN (SEQ ID NO: 6221), SKCSV (SEQ ID NO: 6222), SKARI (SEQ ID NO: 6223), PFVQN (SEQ ID NO: 6224), SKLPK (SEQ ID NO: 6225), SKSEQ (SEQ ID NO: 6226), WVAQN (SEQ ID NO: 6227), SLYQN (SEQ ID NO: 6228), SKVRM (SEQ ID NO: 6229), CALQN (SEQ ID NO: 6230), SSCTN (SEQ ID NO: 6231), SKNSR (SEQ ID NO: 6232), SKRKR (SEQ ID NO: 6233), LCTQN (SEQ ID NO: 6234), STCLN (SEQ ID NO: 6235). SYARN (SEQ ID NO: 6236), SKQRP (SEQ ID NO: 6237), SKRVV (SEQ ID NO: 6238), KSGQN (SEQ ID NO: 6239). SYYSN (SEQ ID NO: 6240), SLTCN (SEQ ID NO: 6241), SCQSN (SEQ ID NO: 6242), SKAKG (SEQ ID NO: 6243), SKPQN (SEQ ID NO: 6244). FPFQN (SEQ ID NO: 6245). SKCTS (SEQ ID NO: 6246), SVFEN (SEQ ID NO: 6247), SKAKK (SEQ ID NO: 6248), or GRYQN (SEQ ID NO: 6249);(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i), e.g., any 2. 3, or 4 amino acids, e.g.. consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to any of tire amino acid sequences in (i); or(iv) an amino acid sequence comprising one. two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).332. The AAV capsid variant of any one of embodiments 327-331, wherein [A]-[B] is or comprises: (i) GSGSPHSKAQA (SEQ ID NO: 6250). GSGSPHSKAQN (SEQ ID NO: 6251).GSGSPHSMYMN (SEQ ID NO: 6252), GSGSPHSKAFY (SEQ ID NO: 6253). GSGSPHSKLKR (SEQ ID NO: 6254), GSGSPHSKRHR (SEQ ID NO: 6255), GSGSPHSKAQK (SEQ ID NO: 6256), GSGSPHSKWRL (SEQ ID NO: 6257), GSGSPHSRCRN (SEQ ID NO: 6258), GSGSPHSFTCN (SEQ ID NO: 6259), GSGSPHSKFFI (SEQ ID NO: 6260), GSGSPHSKAQY (SEQ ID NO: 6261), GSGSPHIVWQN (SEQ ID NO: 6262), GSGSPHSKYFM (SEQ ID NO: 6263), GSGSPHSKARQ (SEQ ID NO: 6264), GSGSPHSCHQN (SEQ ID NO: 6265), GSGSPHFPWQN (SEQ ID NO: 6266), GSGSPHSKIRR (SEQ ID NO: 6267), GSGSPHVYYQN (SEQ ID NO: 6268), GSGSPHSLYWN75323376583.1Attorney Docket No.: V2071-3049PCT(SEQ ID NO: 6269), GSGSPHSKPKR (SEQ ID NO: 6270), GSGSPHSKAFS (SEQ ID NO: 6271), GSGSPHSRFWN (SEQ ID NO: 6272), GSGSPHSKAQC (SEQ ID NO: 6273), GSGSPHSRMRN (SEQ ID NO: 6274), GSGSPHSVKKN (SEQ ID NO: 6275), GSGSPHSWAPN (SEQ ID NO: 6276). GSGSPHSLWKN (SEQ ID NO: 6277), GSGSPHSKARW (SEQ ID NO: 6278). GSGSPHSFRPN (SEQ ID NO: 6279), GSGSPHSKKVF (SEQ ID NO: 6280), GSGSPHSYAFN (SEQ ID NO: 6281), GSGSPHSKACS (SEQ ID NO: 6282), GSGSPHSKRLW (SEQ ID NO: 6283), GSGSPHSCSRN (SEQ ID NO: 6284), GSGSPHSRCPN (SEQ ID NO: 6285), GSGSPHSGACN (SEQ ID NO: 6286), GSGSPHSKFRQ (SEQ ID NO: 6287), GSGSPHSFPFN (SEQ ID NO: 6288). GSGSPHSFFGN (SEQ ID NO: 6289), GSGSPHSMCQN (SEQ ID NO: 6290), GSGSPHSKLFW (SEQ ID NO: 6291), GSGSPHSKTRK (SEQ ID NO: 6292), GSGSPHSGKRN (SEQ ID NO: 6293), GSGSPHFYRQN (SEQ ID NO: 6294), GSGSPHCRVQN (SEQ ID NO: 6295), GSGSPHYGIQN (SEQ ID NO: 6296), GSGSPHSKAQR (SEQ ID NO: 6297), GSGSPHVNCQN (SEQ ID NO: 6298), GSGSPHSKPFR (SEQ ID NO: 6299), GSGSPHSLAWN (SEQ ID NO: 6300), GSGSPHSKRSY (SEQ ID NO: 6301), GSGSPHWSYQN (SEQ ID NO: 6302), GSGSPHRWLQN (SEQ ID NO: 6303), GSGSPHPSCQN (SEQ ID NO: 6304), GSGSPHSSWLN (SEQ ID NO: 6305), GSGSPHSKRRA (SEQ ID NO: 6306), GSGSPHSKAQT (SEQ ID NO: 6307), GSGSPHSKGCT (SEQ ID NO: 6308), GSGSPHVPWQN (SEQ ID NO: 6309). GSGSPHSKRYT (SEQ ID NO: 6310), GSGSPHSGCQN (SEQ ID NO: 6311), GSGSPHSFTPN (SEQ ID NO: 6312), GSGSPHSTTCN (SEQ ID NO: 6313), GSGSPHSKARM (SEQ ID NO: 6314). GSGSPHPKRQN (SEQ ID NO: 6315). GSGSPHSKCFL (SEQ ID NO: 6316), GSGSPHWVPQN (SEQ ID NO: 6317), GSGSPHSFWSN (SEQ ID NO: 6318), GSGSPHSKFKN (SEQ ID NO: 6319). GSGSPHRIKQN (SEQ ID NO: 6320), GSGSPHSKAPR (SEQ ID NO: 6321), GSGSPHSFRYN (SEQ ID NO: 6322), GSGSPHSKMIC (SEQ ID NO: 6323), GSGSPHLRWQN (SEQ ID NO: 6324). GSGSPHLPTQN (SEQ ID NO: 6325). GSGSPHSKWKS (SEQ ID NO: 6326). GSGSPHSYMRN (SEQ ID NO: 6327). GSGSPHSKAAR (SEQ ID NO: 6328). GSGSPHLLCQN (SEQ ID NO: 6329), GSGSPHRCCQN (SEQ ID NO: 6330), GSGSPHLCVQN (SEQ ID NO: 6331), GSGSPHSKLTR (SEQ ID NO: 6332), GSGSPHSKLCT (SEQ ID NO: 6333). GSGSPHSKIRG (SEQ ID NO: 6334), GSGSPHSYLVN (SEQ ID NO: 6335), GSGSPHQGCQN (SEQ ID NO: 6336). GSGSPHMAFQN (SEQ ID NO: 6337). GSGSPHSKACQ (SEQ ID NO: 6338). GSGSPHSKWGL (SEQ ID NO: 6339), GSGSPHSKILR (SEQ ID NO: 6340), GSGSPHSFQIN (SEQ ID NO: 6341), GSGSPHSKACI (SEQ ID NO: 6342), GSGSPHSKALR (SEQ ID NO: 6343). GSGSPHSKAHA (SEQ ID NO: 6344), GSGSPHSLCLN (SEQ ID NO: 6345), GSGSPHSKAFV (SEQ ID NO: 6346), GSGSPHRPWQN (SEQ ID NO: 6347). GSGSPHRPRQN (SEQ ID NO: 6348), GSGSPHSCPQN (SEQ ID NO: 6349), GSGSPHSKAQF (SEQ ID NO: 6350), GSGSPHSVRYN (SEQ ID NO: 6351), GSGSPHSVRCN (SEQ ID NO: 6352), GSGSPHSKMPC (SEQ ID NO: 6353), GSGSPHSKKTS (SEQ ID NO: 6354), GSGSPHSLPYN (SEQ ID NO: 6355), GSGSPHVYHQN (SEQ ID NO: 6356), GSGSPHSKAQS (SEQ ID NO: 6357), GSGSPHSYTRN (SEQ ID NO: 6358), GSGSPHLVYQN (SEQ ID NO: 6359), GSGSPHYRYQN (SEQ ID NO: 6360), GSGSPHSWLKN (SEQ ID NO: 6361),76323376583.1Attorney Docket No.: V2071-3049PCTGSGSPHSKAQM (SEQ ID NO: 6362), GSGSPHCPAQN (SEQ ID NO: 6363), GSGSPHSMCTN (SEQ ID NO: 6364), GSGSPHSPPDN (SEQ ID NO: 6365), GSGSPHSKRNY (SEQ ID NO: 6366), GSGSPHRWTQN (SEQ ID NO: 6367). GSGSPHSKACR (SEQ ID NO: 6368). GSGSPHPRKQN (SEQ ID NO: 6369), GSGSPHSKCSV (SEQ ID NO: 6370), GSGSPHSKARI (SEQ ID NO: 6371). GSGSPHPFVQN (SEQ ID NO: 6372), GSGSPHSKLPK (SEQ ID NO: 6373), GSGSPHSKSEQ (SEQ ID NO: 6374), GSGSPHWVAQN (SEQ ID NO: 6375), GSGSPHSLYQN (SEQ ID NO: 6376), GSGSPHSKVRM (SEQ ID NO: 6377), GSGSPHCALQN (SEQ ID NO: 6378). GSGSPHSSCTN (SEQ ID NO: 6379), GSGSPHSKNSR (SEQ ID NO: 6380), GSGSPHSKRKR (SEQ ID NO: 6381), GSGSPHLCTQN (SEQ ID NO: 6382), GSGSPHSTCLN (SEQ ID NO: 6383), GSGSPHSYARN (SEQ ID NO: 6384), GSGSPHSKQRP (SEQ ID NO: 6385), GSGSPHSKRVV (SEQ ID NO: 6386), GSGSPHKSGQN (SEQ ID NO: 6387), GSGSPHSYYSN (SEQ ID NO: 6388), GSGSPHSLTCN (SEQ ID NO: 6389), GSGSPHSCQSN (SEQ ID NO: 6390), GSGSPHSKAKG (SEQ ID NO: 6391), GSGSPHSKPQN (SEQ ID NO: 6392), GSGSPHFPFQN (SEQ ID NO: 6393), GSGSPHSKCTS (SEQ ID NO: 6394), GSGSPHSVFEN (SEQ ID NO: 6395), GSGSPHSKAKK (SEQ ID NO: 6396), or GSGSPHGRYQN (SEQ ID NO: 6397);(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i), e.g., any 2. 3, 4, 5, 6, 7, 8, 9, or 10 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no more than four modifications, e g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to any of the amino acid sequences in (i); or(iv) an amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i)333. The AAV capsid of any one of embodiments 327-332, wherein [A]-[B] does not comprise the amino acid sequence of GSGSPHSKAQN (SEQ ID NO: 6251).334. The AAV capsid variant of any one of embodiments 327-333, which comprises one, tw o. or all of an amino acid other than Q at position 458 (e g.. R, C, S. W, L. F, Y, H, I, V, A. or P). an amino acid other than Q at position 459 (e.g., K, I, R. L or S). and / or an amino acid other than T at position 460 (e.g., R), numbered relative to SEQ ID NO: 138.335. The AAV capsid variant of any one of embodiments 327-334, which comprises:(i) the amino acid R at position 458;(ii) the amino acid W at position 458;(iii) the amino acid Y at position 458;(iv) the amino acid F at position 458;(v) the amino acid S at position 458;77323376583.1Attorney Docket No.: V2071-3049PCT(vi) the amino acid C at position 458;(vii) the amino acid I at position 458;(viii) the amino acid L at position 458;(ix) the amino acid P at position 458;(x) the amino acid I at position 459;(xi) the amino acid H at position 458; or(xii) the amino acid V at position 458; wherein (i)-(xii) are numbered according to SEQ ID NO: 138.336. The AAV capsid variant of any one of embodiments 327-333, which comprises:(i) the amino acid R at position 458 and tire amino acid K at position 459;(ii) the amino acid C at position 458 and the amino acid I at position 459;(iii) the amino acid S at position 458 and the amino acid R at position 459’(iv) the amino acid L at position 458 and the amino acid K at position 459;(v) the amino acid F at position 458 and the amino acid K at position 459;(vi) the amino acid C at position 458 and the amino acid R at position 459;(vii) the amino acid H at position 458 and the amino acid R at position 459;(viii) the amino acid I at position 458 and the amino acid L at position 459;(ix) the amino acid V at position 458 and the amino acid R at position 459;(x) the amino acid A at position 458 and the amino acid K at position 459;(xi) the amino acid I at position 458 and the amino acid K at position 459;(xii) the amino acid C at position 458 and the amino acid S at position 459; or(xiii) the amino acid C at position 458 and the amino acid L at position 459 wherein (i)-(xiii) are numbered according to SEQ ID NO: 138.337. The AAV capsid variant of any one of embodiments 327-333, which comprises the amino acid F at position 458, the amino acid K at position 459, and the amino acid R at position 460, numbered relative to SEQ ID NO: 138.338. The AAV capsid variant of any one of embodiments 327-337, which comprises one, two, or all of an amino acid other than T at position 450 (e.g.. Y, P, W, R, K, S, or F), an amino acid other than I at position 451 (e.g., R, S, Y, L, V, H. P, A, or F), and / or an amino acid other than N at position 452 (e.g., V, W, A. T, F, Y. L, R, H, S, or M), numbered relative to SEQ ID NO: 138.339. The AAV capsid variant of any one of embodiments 327-338, which comprises the amino acid V at position 452, numbered according to SEQ ID NO: 138.78323376583.1Attorney Docket No.: V2071-3049PCT340. The AAV capsid variant of any one of embodiments 327-339, which comprises the amino acid Y at position 450 and the amino acid V at position 452. numbered according to SEQ ID NO: 138.341. The AAV capsid variant of any one of embodiments 327-339, which comprises the amino acid R at position 450 and the amino acid Y at position 451. numbered according to SEQ ID NO: 138.342. The AAV capsid variant of any one of embodiments 327-338, which comprises:(i) the amino acid P at position 450, the amino acid R at position 451, and the amino acid W at position 452;(ii) the amino acid Y at position 450, the amino acid S at position 451, and the amino acid A at position 452;(iii) the amino acid Y at position 450, die amino acid Y at position 451, and the amino acid T at position 452;(iv) the amino acid P at position 450, the amino acid R at position 451, and the amino acid F at position 452;(v) the amino acid W at position 450, the amino acid L at position 451, and the amino acid T at position 452;(vi) the amino acid R at position 450, the amino acid S at position 451, and the amino acid Y at position 452;(vii) the amino acid Y at position 450, the amino acid V at position 451, and the amino acid F at position 452;(viii) the amino acid K at position 450, the amino acid H at position 451, and the amino acidL at position 452;(ix) the amino acid P at position 450, the amino acid P at position 451, and the amino acid L at position 452;(x) the amino acid P at position 450, the amino acid A at position 451, and the amino acid R at position 452;(xi) the amino acid S at position 450, the amino acid R at position 451, and the amino acid R at position 452;(xii) the amino acid F at position 450, the amino acid F at position 451, and the amino acid H at position 452;(xiii) the amino acid R at position 450, the amino acid F at position 451, and the amino acid S at position 452;(xiv) the amino acid Y at position 450, the amino acid S at position 451, and the amino acidM at position 452; or(xv) the amino acid P at position 450, the amino acid F at position 451, and the amino acid L at position 452;79323376583.1Attorney Docket No.: V2071-3049PCT wherein (i)-(xv) is numbered according to SEQ ID NO: 138.343. The AAV capsid variant of any one of embodiments 327-342, which comprises:(i) the amino acid sequence of any one of SEQ ID NOs: 3849-3982. 2984-4010, 4681-4693;(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i). e.g., any 2, 3. 4, 5, 6, 7, 8. 9, 10, 11, 12, 13, 14. 15, 16, or 17 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, tw o. or three but no more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to any of the amino acid sequences in (i); or(iv) an amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).344. The AAV capsid variant of any one of embodiments 327-343, which does not comprise die amino acid sequence of GSGSPHSKAQNQQ (SEQ ID NO: 1801) or GSGSPHSKAQNQQT (SEQ ID NO: 200).345. The AAV capsid variant of any one of embodiments 327-344, wherein [A]-[B] is present in loop IV.346. The AAV capsid variant of any one of embodiments 327-345. wherein [A] is present immediately subsequent to position 452, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 981.347. The AAV capsid variant of any one of embodiments 327-346, wherein [A] replaces positions 453-455 (e.g., G453, S454, G455), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 981.348. The AAV capsid variant of any one of embodiments 327-347, w herein [A] is present immediately subsequent to position 452, and wherein [A] replaces positions 453-455 (e.g., G453. S454, G455), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138 or 981.349. The AAV capsid variant of any one of embodiments 327-348, wherein [B] is present immediately subsequent to [A],80323376583.1Attorney Docket No.: V2071-3049PCT350. The AAV capsid variant of any one of embodiments 327-349, wherein [B] replaces positions 456 and 457 (e.g., Q456, N457). numbered relative to SEQ ID NO: 138.351. The AAV capsid variant of any one of embodiments 327-350, wherein [A]-[B] replaces positions 453-457 (e g., G453, S454, G455. Q456, N457). relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.352. The AAV capsid variant of any one of embodiments 327-351, wherein [A]-[B] is present immediately subsequent to position 452, and wherein [A]-[B] replaces positions 453-457 (e.g., G453, S454, G455. Q456, N457), relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.353. The AAV capsid variant of any one of embodiments 327-352, which comprises from N-tenninus to C -terminus, [A][B],354. The AAV capsid variant of any one of the preceding embodiments, which comprises at least one, two, three or four (e.g., from 1-4 to 1-5) charged amino acid residues (e.g., acidic and / or basic amino acid residues) relative to SEQ ID NO: 138, which is present N-terminal to the amino acid sequence of SPH (e.g.. within 1, 2, 3, 4, 5, or 6 amino acids from the start of the SPH amino acid sequence (e.g., within positions 450-455 numbered according to SEQ ID NO: 138)), optionally wherein the ammo acid sequence of SPH is present at positions 456-458 numbered according to any one of SEQ ID NOs: 5-10, 36-59. 981, 982, or 6409-6413.355. The AAV capsid variant of embodiment 354. wherein the amino acid sequence of SPH is present at positions 456-458 numbered according to any one of SEQ ID NOs: 5-10, 36-59, 981, 982, or 6409- 6413.356. The AAV capsid variant of embodiment 354 or 355. which comprises less than four, less than three, less than two (e.g., two or one) charged amino acid residues (e.g.. acidic and / or basic amino acid residues) relative to SEQ ID NO: 138.357. The AAV capsid variant of any one of embodiments 354-356, which comprises one charged amino acid residues (e.g., an acidic or basic amino acid residue) relative to SEQ ID NO: 138, optionally at any one of positions 450-455 numbered relative to SEQ ID NO: 138.358. The AAV capsid variant of any one of embodiments 327-330, wherein the charged amino acid residue is an acidic amino acid (e.g., D or E).81323376583.1Attorney Docket No.: V2071-3049PCT359. The AAV capsid variant of any one of embodiments 354-358, wherein the charged amino acid residue is a negatively charged amino acid (e.g., D or E).360. The AAV capsid variant of any one of embodiments 354-359, wherein the charged amino acid residue is D.361. The AAV capsid variant of any one of embodiments 354-360, wherein the charged amino acid residue is E.362. The AAV capsid variant of any one of embodiments 354-361, wherein the charged amino acid residue is a basic amino acid (e.g., K, R, or H).363. The AAV capsid variant of any one of embodiments 354-362, wherein the charged amino acid residue is a positively charged amino acid (e.g., K, R, or H).364. The AAV capsid variant of any one of embodiments 354-363, wherein the charged amino acid residue is H.365. The AAV capsid variant of any one of embodiments 354-364. wherein the charged amino acid residue is R.366. The AAV capsid variant of any one of embodiments 354-365. wherein the charged amino acid residue is K.367. The AAV capsid variant of any one of embodiments 354-366, wherein the AAV capsid variant comprises an acidic amino acid (e.g., E or D) and a basic amino acid (e.g.. R, K, or H).368. The AAV capsid variant of any one of embodiments 354-367, at least one, two. three or four charged amino acid residues is present within 1, 2, 3. 4, 5, or 6 (e.g., 1-6) amino acids from the start of the SPH amino acid sequence.369. The AAV capsid variant of any one of embodiments 354-368, which comprises two charged amino acid residue immediately preceding the amino acid sequence of SPH (e.g., at positions 454 and 455, numbered according to SEQ ID NO: 138 or SEQ ID NO: 982).82323376583.1Attorney Docket No.: V2071-3049PCT370. The AAV capsid variant of any one of embodiments 354-369. which comprises a charged amino acid residue (e.g., E) within 1. 2, 3, 4, 5 (e.g., 5) amino acids from the start of the SPH amino acid sequence.371. The AAV capsid variant of any one of embodiments 354-370, which comprises a charged amino acid residue (e.g., E) at position 451, numbered according to any one of SEQ ID NO: 138, 981. or 982.372. The AAV capsid variant of any one of embodiments 354-371, which comprises E at position451, numbered according to any one of SEQ ID NOs: 138, 981, or 982.373. The AAV capsid variant of any one of embodiments 354-372, which comprises a charged amino acid residue (e.g., R or K) at position 452, numbered according to any one of SEQ ID NOs: 138, 981, or 982.374. The AAV capsid variant of any one of embodiments 354-373, which comprises R at position452, numbered according to SEQ ID NO: 138 or SEQ ID NO: 982.375. The AAV capsid variant of any one of embodiments 354-374. which comprises E at position 451 and R at position 452, numbered according to SEQ ID NO: 138 or SEQ ID NO: 982.376. The AAV capsid variant of any one of embodiments 354-375. which has decreased tropism for a liver cell or tissue, relative to the tropism of a reference sequence comprising the amino acid sequence of SEQ ID NO: 138 or SEQ ID NO: 981.377. The AAV capsid variant of any one of the preceding embodiments, which comprises at least one, two. three or four (e.g.. from 1-4 to 1-5) charged amino acid residues (e.g., basic amino acid residues) relative to SEQ ID NO: 138, which is present C-terminal to the amino acid sequence of SPH (e.g., within 1. 2, 3, 4, 5. 6. or 7 amino acids from the end of the SPH amino acid sequence (e.g.. within positions 459-465 numbered according to any one of SEQ ID NOs: 5-10, 36-59. 981, or 6409-6413)). optionally wherein the amino acid sequence of SPH is present at positions 456-458 numbered according to any one of SEQ ID NOs: 36-59, 981, or 982.378. The AAV capsid variant of embodiment 377, wherein the amino acid sequence of SPH is present at positions 456-458 numbered according to any one of SEQ ID NOs: 5-10, 36-59, 981, 982, or 6409- 6413.83323376583.1Attorney Docket No.: V2071-3049PCT379. The AAV capsid variant of embodiment 377 or 378, which comprises less than four, less than three, less than two (e.g., two or one) charged amino acid residues (e.g.. basic amino acid residues) relative to SEQ ID NO: 138.380. The AAV capsid variant of any one of embodiments 377-379, which comprises one charged amino acid residues (e.g.. an basic amino acid residue) relative to SEQ ID NO: 138, optionally at any one of positions 456-460 numbered relative to SEQ ID NO: 138 or at positions 462-466 numbered according to any one of SEQ ID NOs: 5-10, 36-59, 981, 982, or 6409-6413.381. The AAV capsid variant of any one of embodiments 377-380, wherein the charged amino acid residue is a basic amino acid (e.g., R or K).382. The AAV capsid variant of any one of embodiments 377-381, wherein the charged amino acid residue is a positively charged amino acid (e.g., R or K).383. The AAV capsid variant of any one of embodiments 377-382, wherein the charged amino acid residue is R.384. The AAV capsid variant of any one of embodiments 377-382. wherein the charged amino acid residue is K.385. The AAV capsid variant of any one of embodiments 377-384. at least one. two, three or four charged amino acid residues is present within 1. 2, 3, 4, 5, 6. 7 (e.g., 1-7) amino acids from the end of the SPH amino acid sequence.386. The AAV capsid variant of any one of embodiments 377-385, which comprises a charged amino acid residue (e.g., K or R) immediately after the SPH sequence (e.g., at position 459 numbered according to SEQ ID NO: 981).387. The AAV capsid variant of any one of embodiments 377-386, which comprises a charged amino acid residue (e.g., K or R) at position 459, numbered according to SEQ ID NO: 138 or SEQ ID NO: 982.388. The AAV capsid variant of any one of embodiments 377-387, which comprises K at position 459, numbered according to SEQ ID NO: 981.84323376583.1Attorney Docket No.: V2071-3049PCT389. The AAV capsid variant of any one of embodiments 377-387, which comprises R at position 459. numbered according to SEQ ID NO: 981.390. The AAV capsid variant of any one of embodiments 377-389, which comprises a charged amino acid residue (e.g., R or K) at one, two three, four, five, or all of positions 460, 461. 462, 463, 464. and / or 465, numbered according to SEQ ID NO: 138 or 981.391. The AAV capsid variant of any one of embodiments 327-353 or 377-390, which has increased tropism for a liver cell or tissue, relative to the tropism of a reference sequence comprising the amino acid sequence of SEQ ID NO: 138.392. The AAV capsid variant of any one of embodiments 327-353 or 377-391, which is enriched at least about 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 150, 160, 170, 180, 190, or 200-fold, in die liver compared to a reference sequence of SEQ ID NO: 138, e.g., when measured by an assay as described in Example 4.393. The AAV capsid variant of any one of embodiments 327-353, 391, or 392, which has reduced tropism for a CNS cell or tissue, e.g., a brain cell, brain tissue, spinal cord cell, or spinal cord tissue, relative to the tropism of a reference sequence comprising the amino acid sequence of SEQ ID NO: 138.394. The AAV capsid variant of any one of embodiments 327-353 or 391-393, which shows preferential transduction in a liver region relative to the transduction in the brain and / or dorsal root ganglia (DRG).395. The AAV capsid variant of any one of embodiments 327-353 or 391-394. which shows preferential transduction in a liver region relative to the transduction in the heart and / or muscle (e.g., quadriceps).396. The AAV capsid variant of any one of embodiments 1-395, which is capable of evading antibody neutralization.397. An AAV capsid variant comprising:(I) (a) the amino acid sequence of any of the sequences provided in Tables 1, 2A, 2B, 13-19;(b) an amino acid sequence comprising at least 3, 4, 5, 6, 7. 8, 9, 10, 11, 12, 13, 14, 15, 16, or17 consecutive amino acids from any one of the sequences provided in Tables 1, 2A, 2B, 13-19; or85323376583.1Attorney Docket No.: V2071-3049PCT(c) an amino acid sequence comprising at least one, two, or three but no more than four different amino acids, relative to any one of the sequences provided in Tables 1, 2A, 2B, 13-19; or(d) an amino acid sequence comprising at least one, tw o. or three but no more than four modifications, e.g.. substitutions (e.g.. conservative substitutions), relative to the amino acid sequence of any one of the sequences provided in Tables 1 , 2A, 2B, 13-19;(II) (i) the amino acid sequence of SEQ ID NO: 6419;(ii) an amino acid sequence comprising at least one or two, but no more than three different amino acids, relative to the amino acid sequence of SEQ ID NO: 6419;(iii) an amino acid sequence comprising at least one or two modifications, e.g., substitutions (e.g., conservative substitutions), but no more than three modifications, e.g., substitutions (e.g.. conservative substitutions), relative to the amino acid sequence of SEQ ID NO: 6419; or(iv) at least 3, 4, 5, 6. or 7 consecutive amino acids from SEQ ID NO: 6419; optionally wherein the amino acid sequence of (i), (ii), (iii), and / or (iv) is present at positions 590-596, numbered according to the amino acid sequence of SEQ ID NO: 981, 982, 6411, or 6412; and / or(III) (i) the ammo acid sequence of any one of the amino acid sequences of Tables 54-56;(ii) an amino acid sequence comprising at least one or two, but no more than three different amino acids, relative to any one of the amino acid sequences of Tables 54-56;(iii) an amino acid sequence comprising at least one or two modifications, e.g., substitutions (e.g., conservative substitutions), but no more than three modifications, e.g., substitutions (e.g., conservative substitutions), relative to any one of the amino acid sequences of Tables 54-56; or(iv) at least 3, 4, 5. 6, or 7 consecutive amino acids from any one of the amino acid sequences of Tables 54-56; optionally wherein the amino acid sequence of (i). (ii). (iii), and / or (iv) is present at positions 242-272, 656-672, and / or 706-722, numbered according to the amino acid sequence of SEQ ID NO: 138.398. An adeno-associated (AAV) capsid variant comprising:(I) (a) the amino acid sequence of any of SEQ ID NOs: 945-980 or 985-986;(b) an amino acid sequence comprising at least 3, 4, or 5 consecutive amino acids from any one of SEQ ID NOs: 945-980 or 985-986; or(c) an amino acid sequence comprising at least one, two, or three but no more than four different amino acids, relative to the amino acid sequence of any one of SEQ ID NOs: 945-980 or 985-986;(d) an amino sequence comprising at least one, two, or three but no more than four modifications, e.g., substitutions (e.g., conserv ative substitutions), relative to the amino acid sequence of any one of SEQ ID NOs: 945-980 or 985-986;86323376583.1Attorney Docket No.: V2071-3049PCT(II) (i) the amino acid sequence of SEQ ID NO: 6419;(ii) an amino acid sequence comprising at least one or tw o. but no more than three different amino acids, relative to the amino acid sequence of SEQ ID NO: 6419;(iii) an amino acid sequence comprising at least one or two modifications, e.g.. substitutions (e.g., conservative substitutions), but no more than three modifications, e.g.. substitutions (e.g.. conservative substitutions), relative to the amino acid sequence of SEQ ID NO: 6419; or(iv) at least 3, 4, 5, 6. or 7 consecutive amino acids from SEQ ID NO: 6419; optionally wherein the amino acid sequence of (i), (ii), (iii). and / or (iv) is present at positions 590-596, numbered according to the amino acid sequence of SEQ ID NO: 981, 982, 6411, or 6412; and / or(III) (i) the amino acid sequence of any one of the amino acid sequences of Tables 54-56;(ii) an amino acid sequence comprising at least one or two, but no more than three different amino acids, relative to any one of the amino acid sequences of Tables 54-56;(iii) an ammo acid sequence comprising at least one or two modifications, e.g., substitutions (e.g., conservative substitutions), but no more than three modifications, e.g., substitutions (e.g., conservative substitutions), relative to any one of the amino acid sequences of Tables 54-56; or(iv) at least 3, 4, 5, 6, or 7 consecutive amino acids from any one of the amino acid sequences of Tables 54-56; optionally wherein the amino acid sequence of (i), (ii), (iii), and / or (iv) is present at positions 242-272, 656-672. and / or 706-722, numbered according to the amino acid sequence of SEQ ID NO: 138.399. An adeno-associated (AAV) capsid variant comprising:(I) (a) the amino acid sequence of any of SEQ ID NOs: 2. 200, 201, 941. 943, 204. 208. 404, or 903-909;(b) an amino acid sequence comprising at least 3, 4, 5, 6, 7. 8, 9, 10, 11, 12, or 13 consecutive amino acids from any one of SEQ ID NOs: 2, 200. 201, 941, 943. 204, 208, 404. or 903-909;(c) an amino acid sequence comprising at least one, two. or three but no more than four different amino acids, relative to the amino acid sequence of any one of SEQ ID NOs: 2, 200, 201 , 941. 943, 204, 208, 404, or 903-909; or(d) an amino acid sequence comprising at least one, tw o, or three but no more than four modifications, e.g., substitutions (e.g.. conservative substitutions), relative to the amino acid sequence of any one of SEQ ID NOs: 2, 200, 201, 941, 943, 204, 208, 404, or 903-909;(II) (i) the amino acid sequence of SEQ ID NO: 6419;(ii) an amino acid sequence comprising at least one or two, but no more than three different amino acids, relative to the amino acid sequence of SEQ ID NO: 6419;87323376583.1Attorney Docket No.: V2071-3049PCT(iii) an amino acid sequence comprising at least one or two modifications, e.g., substitutions (e.g., conservative substitutions), but no more than three modifications, e.g.. substitutions (e.g.. conservative substitutions), relative to the amino acid sequence of SEQ ID NO: 6419; or(iv) at least 3, 4, 5, 6. or 7 consecutive amino acids from SEQ ID NO: 6419; optionally wherein the amino acid sequence of (i), (ii), (iii). and / or (iv) is present at positions 590-596, numbered according to the amino acid sequence of SEQ ID NO: 981, 982, 6411, or 6412; and / or(III) (i) the amino acid sequence of any one of the amino acid sequences of Tables 54-56;(ii) an amino acid sequence comprising at least one or two, but no more than three different amino acids, relative to any one of the amino acid sequences of Tables 54-56;(iii) an amino acid sequence comprising at least one or two modifications, e.g., substitutions (e.g., conservative substitutions), but no more than three modifications, e.g., substitutions (e.g., conservative substitutions), relative to any one of the amino acid sequences of Tables 54-56; or(iv) at least 3, 4, 5, 6, or 7 consecutive amino acids from any one of the amino acid sequences of Tables 54-56; optionally wherein the amino acid sequence of (i), (ii), (iii), and / or (iv) is present at positions 242-272, 656-672, and / or 706-722, numbered according to the amino acid sequence of SEQ ID NO: 138.400. An adeno-associated (AAV) capsid variant comprising:(a) the amino acid sequence of any of SEQ ID NOs: 3849-4051 or 4681-4693;(b) an amino acid sequence comprising at least 3, 4, 5, 6. 7, 8, 9, 10, 11. 12. 13, 14, 15, 16 or 17 consecutive amino acids from any one of SEQ ID NOs: 3849-4051 or 4681-4693;(c) an amino acid sequence comprising at least one, two. or three but no more than four different amino acids, relative to the amino acid sequence of any one of SEQ ID NOs: 3849-4051 or 4681-4693; or(d) an amino acid sequence comprising at least one, tw o. or three but no more than four modifications, e.g.. substitutions (e.g.. conservative substitutions), relative to the amino acid sequence of any one of SEQ ID NOs: 3849-4051 or 4681 -4693.401. An adeno-associated (AAV) capsid variant comprising:(a) the amino acid sequence of any of SEQ ID NOs: 4052-4092;(b) an amino acid sequence comprising at least 3, 4, 5, 6, 7. 8, 9, 10, 11, 12, 13, 14, 15. 16 or 17 consecutive amino acids from any one of SEQ ID NOs: 4052-4092;(c) an amino acid sequence comprising at least one, two. or three but no more than four different amino acids, relative to the amino acid sequence of any one of SEQ ID NOs: 4052-4092; or88323376583.1Attorney Docket No.: V2071-3049PCT(d) an amino acid sequence comprising at least one, two, or three but no more than four modifications, e.g.. substitutions (e.g.. conservative substitutions), relative to the amino acid sequence of any one of SEQ ID NOs: 4052-4092.402. An adeno-associated (AAV) capsid variant comprising:(a) the amino acid sequence of any of SEQ ID NOs: 4056, 4058, 4059, 4062-4064. 4066. 4067, 4080, 4084, 4090, or 4095-4097;(b) an amino acid sequence comprising at least 3, 4, 5, 6, 7. 8, 9, 10, 11, 12, 13, 14, 15. 16 or 17 consecutive amino acids from any one of SEQ ID NOs: 4056, 4058, 4059, 4062-4064, 4066, 4067, 4080, 4084, 4090, or 4095-4097;(c) an amino acid sequence comprising at least one, two. or three but no more than four different amino acids, relative to the amino acid sequence of any one of SEQ ID NOs: 4056, 4058, 4059, 4062-4064, 4066, 4067, 4080, 4084, 4090, or 4095-4097; or(d) an amino acid sequence comprising at least one, two, or three but no more than four modifications, e g., substitutions (e.g., conservative substitutions), relative to the amino acid sequence of any one of SEQ ID NOs: 4056, 4058, 4059, 4062-4064, 4066, 4067, 4080, 4084, 4090, or 4095- 4097.403. The AAV capsid variant of embodiment 397 or 401, comprising an amino acid sequence comprising at least 4, 5, 6, 7, 8. 9, 10. 11, 12, or 13 consecutive amino acids from any one of SEQ ID NOs: 2. 200, 201, 941. 943, 204, 208. 404, or 903-909.404. The AAV capsid variant of any one of embodiments 397-403. wherein the at least 3 consecutive amino acids comprise SPH.405. The AAV capsid variant of any one of embodiments 397-399 or 404, wherein the at least 4 consecutive amino acids comprise SPHS (SEQ ID NO: 4700).406. The AAV capsid variant of any one of embodiments 397-399, 404. or 405, wherein the at least 5 consecutive amino acids comprise SPHSK (SEQ ID NO: 4701).407. The AAV capsid variant of any one of embodiments 397-399 or 404-406, wherein the at least 6 consecutive amino acids comprise SPHSKA (SEQ ID NO: 941).408. The AAV capsid variant of embodiment 397-399, wherein the at least 3 consecutive amino acids comprise HDS.89323376583.1Attorney Docket No.: V2071-3049PCT409. The AAV capsid variant of any one of embodiments 397-399 or 408, wherein the at least 4 consecutive amino acids comprise HDSP (SEQ ID NO: 4702).410. The AAV capsid variant of any one of embodiments 397-399, 408. or 409, wherein the at least 5 consecutive amino acids comprise HDSPH (SEQ ID NO: 4703).411. The AAV capsid variant of any one of embodiments 397-399 or 408-410, wherein the at least 6 consecutive amino acids comprise HDSPHK (SEQ ID NO: 2).412. The AAV capsid variant of any one of embodiments 397-399, wherein:(i) the at least 3 consecutive amino acids comprise SPH;(ii) the at least 4 consecutive amino acids comprise SPHK (SEQ ID NO: 6398);(iii) the at least 5 consecutive amino acids comprise SPHKY (SEQ ID NO: 4715); and / or(iv) the at least 6 consecutive amino acids comprise SPHKYG (SEQ ID NO: 966).413. The AAV capsid variant of embodiment 397 or 399, which comprises an amino acid sequence comprising at least one, two, or three but no more than four modifications, e.g., substitutions (e.g., conservative substitutions), relative to the amino acid sequence of any one of SEQ ID NOs: 2, 200. 201, 941, 943. 204, 208, 404. or 903-909.414. The AAV capsid variant of any one of embodiments 397, 399, or 413, which comprises an amino acid sequence comprising at least one, two, or three but no more than four modifications, e.g., substitutions (e.g.. conservative substitutions), relative to the amino acid sequence of SPHSKA (SEQ ID NO: 941).415. The AAV capsid variant of any one of embodiments 397, 399, or 413, which comprises an amino acid sequence comprising at least one. two, or three but no more than four modifications, e.g., substitutions (e g., conservative substitutions), relative to the amino acid sequence of HDSPHK (SEQ ID NO: 2).416. The AAV capsid variant of any one of embodiments 397-399, 412. or 413, which comprises an amino acid sequence comprising at least one, two, or three but no more than four modifications, e.g., substitutions (e.g., conservative substitutions), relative to the amino acid sequence of SPHKYG (SEQ ID NO: 966).417. The AAV capsid variant of embodiment 398, which comprises:90323376583.1Attorney Docket No.: V2071-3049PCT(i) an amino acid sequence comprising at least one, two, or three but no more than four modifications, e.g.. substitutions (e.g.. conservative substitutions), relative to the amino acid sequence of KTENVSGSPHSKAQNQQT (SEQ ID NO: 3272);(ii) an amino acid sequence comprising at least one, tw o. or three but no more than four modifications, e.g.. substitutions (e.g.. conservative substitutions), relative to the amino acid sequence of KTERVSGSPHSKAQNQQT (SEQ ID NO: 3589);(iii) an amino acid sequence comprising at least one, two. or three but no more than four modifications, e.g., substitutions (e.g.. conservative substitutions), relative to the amino acid sequence of KAEIGHDSPHKSGQNQQT (SEQ ID NO: 1754)(iv) an amino acid sequence comprising at least one, two, or three but no more than four modifications, e.g., substitutions (e.g., conservative substitutions), relative to the amino acid sequence of KTEKMSGSPHSKAQNQQT (SEQ ID NO: 3241);(v) an amino acid sequence comprising at least one, two, or three but no more than four modifications, e g., substitutions (e.g., conservative substitutions), relative to the amino acid sequence of KTINGHDSPHSKAQNLQT (SEQ ID NO: 4100); or(vi) an amino acid sequence comprising at least one, two, or three but no more than four modifications, e g., substitutions (e.g., conservative substitutions), relative to the amino acid sequence of KTVNGHDSPHSKAQNQQT (SEQ ID NO: 4062).418. The AAV capsid variant of embodiment 397 or 399, which comprises an amino acid sequence comprising at least one, two, or three but no more than four different amino acids relative to the amino acid sequence of any one of SEQ ID NOs: 2, 200. 201, 941, 943, 204, 208. 404, or 903-909.419. The AAV capsid variant of any one of embodiments 397. 399, or 418. which comprises an amino acid sequence comprising at least one, two, or three but no more than four different amino acids relative to the amino acid sequence of SPHSKA (SEQ ID NO: 941).420. The AAV capsid variant of any one of embodiments 397, 399. or 418, which comprises an amino acid sequence comprising at least one. two, or three but no more than four different amino acids relative to the amino acid sequence of HDSPHK (SEQ ID NO: 2).421. The AAV capsid variant of any one of embodiments 397, 399. 412, or 418. which comprises an amino acid sequence comprising at least one, two, or three but no more than four different amino acids relative to the amino acid sequence of SPHKYG (SEQ ID NO: 966).422. The AAV capsid variant of embodiment 397, which comprises:91323376583.1Attorney Docket No.: V2071-3049PCT(i) an amino acid sequence comprising at least one, two. or three but no more than four different amino acids relative to the amino acid sequence of KTERVSGSPHSKAQNQQT (SEQ ID NO: 3589);(ii) an amino acid sequence comprising at least one, tw o. or three but no more than four different amino acids relative to the amino acid sequence of KAETGHDSPHKSGQNQQT (SEQ ID NO: 1754);(iii) an amino acid sequence comprising at least one, two. or three but no more than four different amino acids relative to the amino acid sequence of KTEKMSGSPHSKAQNQQT (SEQ ID NO: 3241);(iv) an amino acid sequence comprising at least one, two, or three but no more than four different amino acids relative to the amino acid sequence of KTINGHDSPHSKAQNLQT (SEQ ID NO: 4100);(v) an amino acid sequence comprising at least one, two, or three but no more than four different amino acids relative to the amino acid sequence of KTVNGHDSPHSKAQNQQT (SEQ ID NO: 4062);(vi) an amino acid sequence comprising at least one, two, or three but no more than four different amino acids relative to the amino acid sequence of KTENVSGSPHSKAQNQQT (SEQ ID NO: 3272);(vii) an amino acid sequence comprising at least one, two, or three but no more than four different amino acids relative to the amino acid sequence of KTEKVSGSPHSKAQNQQT (SEQ ID NO: 3274);(viii) an amino acid sequence comprising at least one, two, or three but no more than four different amino acids relative to the amino acid sequence of KTINGSGSPHKSGQNKTS (SEQ ID NO: 4406);(ix) an amino acid sequence comprising at least one. two, or three but no more than four different amino acids relative to the amino acid sequence of KTSNASGSPHSKAHNQQT (SEQ ID NO: 3382);(x) an amino acid sequence comprising at least one, two, or three but no more than four different amino acids relative to the amino acid sequence of KNSIGSGSPHSKAQNQQT (SEQ ID NO: 3421);(xi) an amino acid sequence comprising at least one, two. or three but no more than four different amino acids relative to the amino acid sequence of KTVNGHDSPHKSGQRPST (SEQ ID NO: 4478);(xii) an amino acid sequence comprising at least one. two, or three but no more than four different amino acids relative to the amino acid sequence of KAENGSGSPHSKAQNQQT (SEQ ID NO: 3487); or(xiii) an amino acid sequence comprising at least one, two, or three but no more than four different amino acids relative to the amino acid sequence of KTINGSGSPHKSGQNQQP (SEQ ID NO: 4081).423. The AAV capsid variant of any one of embodiments 1-156, 296, 298, 403-416, or 418-422, which comprises the amino acid sequence of any of SEQ ID NOs: 2, 200, 201, 941, 943, 204, 208, 404, or 903-909.92323376583.1Attorney Docket No.: V2071-3049PCT424. The AAV capsid variant of any one of embodiments 322-324, 328-332, 340, 340, 345, 346, or 350. which comprises the amino acid sequence of ERVSGSPHSKA (SEQ ID NO: 6399), optionally wherein the amino acid sequence is present immediately subsequent to position 450 and replaces positions 451-455 (e.g.. 1451. N542. G453, S454, G455). numbered according to SEQ ID NO: 138.425. The AAV capsid variant of any one of embodiments 397-399, 403-407, 413, 414. 417-419, or 422-424, which comprises the amino acid sequence of KTERVSGSPHSKAQNQQT (SEQ ID NO: 3589). optionally wherein the amino acid sequence is present immediately subsequent to position 448 and replaces positions 449-460 (e.g., K449, T450, 1451, N452, G453, S454, G455, Q456, N457, Q458. Q459, T460), numbered according to SEQ ID NO: 138.426. The AAV capsid variant of any one of embodiments 296-399, 403, 408-411, 413, 415, 417, 418, 421, or 422, which comprises the amino acid sequence of AEIGHDSPHKSG (SEQ ID NO: 6400), optionally wherein the amino acid sequence is present immediately subsequent to position 449 and replaces positions 450-455 (e.g., T450, 1451, N452, G453, S454, G455), numbered according to SEQ ID NO: 138.427. The AAV capsid variant of any one of embodiments 397-399, 403, 408-411, 413, 415, 417, 418, 421, 422, or 426, which comprises the amino acid sequence of KAEIGHDSPHKSGQNQQT (SEQ ID NO: 1754), optionally wherein the amino acid sequence is present immediately subsequent to position 448 and replaces positions 449-460 (e.g., K449. T450. 1451, N452. G453, S454, G455, Q456, N457, Q458, Q459, T460). numbered according to SEQ ID NO: 138.428. The AAV capsid variant of any one of embodiments 397-399. 403-407, 418. 419, or 423. which comprises the amino acid sequence of EKMSGSPHSKA (SEQ ID NO: 6401), optionally wherein the amino acid sequence is present immediately subsequent to position 450 and replaces positions 451- 455 (e.g., 1451. N452, G453, S454, G455), numbered according to SEQ ID NO: 138.429. The AAV capsid variant of any one of embodiments 397-399, 403-407, 418, 419. or 423, which comprises the amino acid sequence of KTEKMSGSPHSKAQNQQT (SEQ ID NO: 3241), optionally wherein the amino acid sequence is present immediately subsequent to position 448 and replaces positions 449-460 (e.g., K449, T450, 1451, N452, G453, S454, G455. Q456, N457, Q458, Q459, T460), numbered according to SEQ ID NO: 138.430. The AAV capsid variant of any one of embodiments 397-399, 403-407, 418, 419, or 423, which comprises the amino acid sequence of HDSPHSKAQNL (SEQ ID NO: 6402), optionally wherein the93323376583.1Attorney Docket No.: V2071-3049PCT amino acid sequence is present immediately subsequent to position 453 and replaces positions 456- 458 (e.g., Q456, N457, Q458), numbered according to SEQ ID NO: 138.431. The AAV capsid variant of any one of embodiments 397-399, 403-407, 418, 419. or 423, which comprises the amino acid sequence of KTINGHDSPHSKAQNLQT (SEQ ID NO: 4100), optionally wherein the amino acid sequence is present immediately subsequent to position 448 and replaces positions 449-460 (e.g., K449, T450, 1451, N452, G453, S454, G455. Q456, N457, Q458, Q459, T460), numbered according to SEQ ID NO: 138.432. The AAV capsid variant of any one of embodiments 397-399, 403-407, 418, 419. or 423, which comprises the amino acid sequence of VNGHDSPHSKA (SEQ ID NO: 6403), optionally wherein the amino acid sequence is present immediately subsequent to position 450 and replaces positions 451- 455 (e.g., 1451, N452, G453, S454, G455), numbered according to SEQ ID NO: 138.433. The AAV capsid variant of any one of embodiments 397-399, 403-407, 418, 419, or 423, which comprises:(i) the amino acid sequence of KTVNGHDSPHSKAQNQQT (SEQ ID NO: 4062), optionally wherein the amino acid sequence is present immediately subsequent to position 448 and replaces positions 449-460 (e.g., K449, T450, 1451, N452, G453, S454, G455, Q456, N457, Q458, Q459. T460), numbered according to SEQ ID NO: 138; or(ii) the AAV capsid variant comprises the amino acid sequence of ENVSGSPHSKA (SEQ ID NO: 60), optionally wherein the amino acid sequence is present immediately subsequent to position 450 and replaces positions 451-455 (e.g., 1451, N452, G453. S454. G455), numbered according to SEQ ID NO: 138; corresponds to positions 451 to 461 of SEQ ID NO: 5; or is present at positions 451 to 461 numbered according to SEQ ID NO: 5 or 981.434. The AAV capsid variant of any one of embodiments 1-50. 53-56, 59. 62-70, 73-73, 81-99. 106- 116. 118, 121-126. 129-131, 134, 137-139, 142-156. 195-229, 267-274. 276, 277, 280-290, 293, 299- 308. 313, 315, 318-326, 354-390, 397-399, 403-407. 413, 414, 418. 419, or 423. comprising an amino acid sequence encoded by: the nucleotide sequence of SEQ ID NO: 942; a nucleotide sequence comprising at least one, tw o, three, four, five, six, or seven modifications, e.g., substitutions, but no more than ten modifications, e.g., substitutions, relative to the nucleotide sequence of SEQ ID NO: 942; or a nucleotide sequence comprising at least one, two. three, four, five, six, or seven, but no more than ten different nucleotides relative to the nucleotide sequence of SEQ ID NO: 942.435. The AAV capsid variant of any one of embodiments 1-36, 38-49, 51, 53, 55, 57, 60, 65-69, 71, 73-77, 79, 81-104, 110-115, 117-124, 127-130, 132, 137, 138, 140-156, 230-275, 278, 279, 281-284,94323376583.1Attorney Docket No.: V2071-3049PCT287, 288, 291-307, 310-314, 316-326, 354-390, 397, 397, 399, 408-411, 413, 414, 418, 420, or 423, comprising an amino acid sequence encoded by: the nucleotide sequence of SEQ ID NO: 3; a nucleotide sequence comprising at least one. two, three, four, five, six, or seven modifications, e.g.. substitutions, but no more than ten modifications, e.g., substitutions, relative to the nucleotide sequence of SEQ ID NO: 3; or a nucleotide sequence comprising at least one, two. three, four, five, six, or seven, but no more than ten different nucleotides relative to the nucleotide sequence of SEQ ID NO: 3.436. The AAV capsid variant of any one of embodiments 1-50. 53-56, 59, 62-70, 73-73, 81-99, 106- 116, 118, 121-126. 129-131, 134, 137-139, 142-156. 195-229, 267-274, 276, 277, 280-290, 293, 299- 308, 313, 315, 318-326, 354-390, 397-399, 403-407. 413, 414, 418, 419, 423, or 434, wherein the nucleotide sequence encoding the capsid variant comprises the nucleotide sequence of SEQ ID NO: 942; a nucleotide sequence comprising at least one, two, three, four, five, six, or seven modifications, e.g., substitutions, but no more than ten modifications, e g., substitutions, relative to the nucleotide sequence of SEQ ID NO: 942; or a nucleotide sequence comprising at least one, two, three, four, five, six, or seven, but no more than ten different nucleotides relative to the nucleotide sequence of SEQ ID NO: 942.437. The AAV capsid variant of any one of embodiments 1-36, 38-49, 51, 53. 55, 57, 60, 65-69, 71, 73-77, 79. 81-104. 110-115, 117-124. 127-130, 132. 137, 138, 140-156, 230-275, 278, 279, 281-284. 287, 288, 291-307, 310-314, 316-326, 354-390, 397, 397, 399, 408-411, 413, 414, 418, 420. 423, or 434, wherein the nucleotide sequence encoding the capsid variant comprises the nucleotide sequence of SEQ ID NO: 3; a nucleotide sequence comprising at least one. two, three, four, five, six, or seven modifications, e.g., substitutions, but no more than ten modifications, e.g., substitutions, relative to the nucleotide sequence of SEQ ID NO: 3; or a nucleotide sequence comprising at least one, two, three, four, five, six, or seven, but no more than ten different nucleotides relative to the nucleotide sequence of SEQ ID NO: 3.438. The AAV capsid variant of any one of embodiments 397-437, wherein the amino acid sequence is present in loop IV.439. The AAV capsid variant of any one of embodiments 397-438, wherein the amino acid sequence is present immediately subsequent to position 448. 449, 450, 451, 452, 453, 454, or 455, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.440. The AAV capsid variant of any one of embodiments 397-439, wherein the amino acid sequence replaces amino acids 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, and / or 460 (e.g., K449,95323376583.1Attorney Docket No.: V2071-3049PCTT450, 1451, N452, G453, S454, G455, Q456, N457, Q458, Q459, and / or T460), numbered according to the amino acid sequence of SEQ ID NO: 138.441. The AAV capsid variant of any one of embodiments 397-440, wherein the amino acid sequence is present immediately subsequent to position 455. relative to a reference sequence numbered according to tire amino acid sequence of SEQ ID NO: 138.442. The AAV capsid variant of any one of embodiments 397-441, wherein the amino acid sequence is present immediately subsequent to position 453. relative to a reference sequence numbered according to tire amino acid sequence of SEQ ID NO: 138.443. The AAV capsid variant of any one of embodiments 1-50, 53-56, 59, 62-70, 73-73, 81-99, 106- 116, 118, 121-126, 129-131, 134, 137-139, 142-156, 195-229, 267-274, 276, 277, 280-290, 293, 299- 308, 313, 315, 318-326, 354-390, 397-399, 403-407, 413, 414, 418, 419, 423, 434, 436, or 438-441, comprising the amino acid sequence of SPHSKA (SEQ ID NO: 941). wherein the amino acid sequence is present immediately subsequent to position 455, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.444. The AAV capsid variant of any one of embodiments 1-50, 53-56, 59, 62-70, 73-73. 81-99, 106- 116, 118, 121-126, 129-131, 134. 137-139, 142-156, 195-229, 267-274, 276, 277. 280-290, 293, 299- 308, 313, 315. 318-326, 354-390. 397-399, 403-407, 413, 414. 418, 419, 423. 434, 436, 438-441, or 443, comprising the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is present immediately subsequent to position 455. relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 981.445. The AAV capsid variant of embodiment 443 or 444. which further comprises:(i) an amino acid other than I at position 451, an amino acid other than N at position 452. and an amino acid other than G at position 453, numbered according to any one of SEQ ID NOs: 36, 138. or 981 ; or(ii) an amino acid other than I at position 451 and / or G at position 453, numbered according to SEQ ID NO: 5, 138, or 981.446. The AAV capsid variant of any one of embodiments 443-445, which further comprises:(i) E at position 451, R at position 452, and V at position 453, numbered according to any one of SEQ ID NOs: 36, 138, or 981; or(ii) E at position 451 and / or V at position 453, numbered according to SEQ ID NO: 138, 981, or 5.96323376583.1Attorney Docket No.: V2071-3049PCT447. The AAV capsid variant of any one of embodiments 443-446, which further comprises:(i) the substitutions 145 IE, N452R, and G453V, numbered according to any one of SEQ ID NOs: 36. 138, or 981; or(ii) the substitutions I451E or G453V, numbered according to SEQ ID NO: 138, 981. or 5.448. The AAV capsid variant of any one of embodiments 443-447, which comprises:(A) (i) E at position 451, R at position 452, and V at position 453, numbered according to any one of SEQ ID NOs: 36, 138. or 981; and(ii) the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is present immediately subsequent to position 455, numbered according to any one of SEQ ID NOs: 36, 138, or 981; or(B) (i) E at position 451 and V at position 453, numbered according to SEQ ID NO: 5 or 138; and (ii) the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is present immediately subsequent to position 455, at positions 456-461, numbered according to SEQ ID NO: 5 or 138.449. The AAV capsid variant of embodiment 443 or 444, which further comprises an amino acid other than I at position 451, an amino acid other than N at position 452. and / or G at position 453, numbered according to SEQ ID NO: 39 or 138.450. The AAV capsid variant of any one of embodiments 443, 444, or 449, which further comprises E at position 451, K at position 452, and / or M at position 453, numbered according to SEQ ID NO: 138 or 39.451. The AAV capsid variant of any one of embodiments 443, 444, 449, or 450, which further comprises the substitutions 145 IE. N452K. and G453M, numbered according to SEQ ID NO: 39 or 138.452. The AAV capsid variant of any one of embodiments 443, 444. or 450-451, which comprises:(i) E at position 451, K at position 452, and M at position 453, numbered according to SEQ ID NO: 39 or 138; and(ii) the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is present immediately subsequent to position 455, numbered according to SEQ ID NO: 39 or 138.97323376583.1Attorney Docket No.: V2071-3049PCT453. The AAV capsid variant of embodiment 443 or 444, which further comprises an amino acid other than S at position 454. an amino acid other than G at position 455. and / or Q at position 458. numbered according to SEQ ID NO: 138.454. The AAV capsid variant of any one of embodiments 443, 444. or 453, which further comprises H at position 454, D at position 455. and / or L at position 458. numbered according to SEQ ID NO: 138.455. The AAV capsid variant of any one of embodiments 443, 444, 453, or 454. which further comprises the substitutions S454H, G455D, and Q458L, numbered according to SEQ ID NO: 138.456. The AAV capsid variant of any one of embodiments 443, 444. or 453-455, which comprises:(i) H at position 454, D at position 455, and / or L at position 458, numbered according to SEQ ID NO: 138; and(ii) the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is present immediately subsequent to position 455, numbered according to SEQ ID NO: 138.457. The AAV capsid variant of embodiment 443 or 444, which further comprises an amino acid other than I at position 451, an amino acid other than S at position 454, and / or an amino acid other than G at position 455. numbered according to SEQ ID NO: 52 or 138.458. The AAV capsid variant of any one of embodiments 443, 444, or 457, which further comprises V at position 451, H at position 454, and / or D at position 455, numbered according to SEQ ID NO: 52 or 138.459. The AAV capsid variant of any one of embodiments 443, 444, 457, or 458, which further comprises the substitutions 145 IV, S454H, and / or G455D, numbered according to SEQ ID NO: 52 or 138.460. The AAV capsid variant of any one of embodiments 443, 444. or 457-459, which comprises:(i) V at position 451, H at position 454, and / or D at position 455, numbered according to SEQ ID NO: 52 or 138; and(ii) the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is present immediately subsequent to position 455, numbered according to SEQ ID NO: 52 or 138.98323376583.1Attorney Docket No.: V2071-3049PCT461. The AAV capsid variant of any one of embodiments 1-36, 38-49, 51, 53, 55, 57, 60, 65-69, 71, 73-77. 79, 81-104, 110-115. 117-124, 127-130, 132, 137. 138, 140-156. 230-275, 278, 279. 281-284, 287. 288, 291-307. 310-314, 316-326. 354-390, 397. 397, 399, 408-411. 413, 414. 418, 420, 423. 434, 437-440. or 442, comprising the amino acid sequence of HDSPHK (SEQ ID NO: 2). wherein the amino acid sequence is present immediately subsequent to position 453. numbered according to the amino acid sequence of SEQ ID NO: 138.462. The AAV capsid variant of any one of embodiments 1-36. 38-49, 51, 53, 55, 57, 60, 65-69, 71, 73-77, 79, 81-104, 110-115, 117-124, 127-130, 132, 137, 138, 140-156. 230-275, 278, 279, 281-284, 287, 288, 291-307. 310-314, 316-326, 354-390, 397. 397, 399, 408-411, 413, 414. 418, 420, 423, 434, 437-440, 442, or 461, comprising the amino acid sequence of HDSPHK (SEQ ID NO: 2), wherein the amino acid sequence is present immediately subsequent to position 453, numbered according to the amino acid sequence of SEQ ID NO: 982.463. The AAV capsid variant of any one of embodiments 1-36, 38-49, 51, 53, 55, 57, 60, 65-69, 71, 73-77, 79, 81-104, 110-115, 117-124. 127-130, 132, 137, 138, 140-156, 230-275, 278, 279, 281-284, 287, 288, 291-307, 310-314, 316-326, 354-390, 397, 397, 399, 408-411, 413, 414, 418, 420, 423, 434, 437-440, 442, 461, or 462, comprising the amino acid sequence of SPHKSG (SEQ ID NO: 946). wherein the amino acid sequence is present immediately subsequent to position 455, numbered relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 982.464. The AAV capsid variant of any one of embodiments 397-463. which comprises:(i) the amino acid sequence of HDSPHSKA (SEQ ID NO: 4486). which is present immediately subsequent to position 453; and(ii) a deletion of amino acids SG at position 454 and 455; wherein (i) and (ii) are numbered according to SEQ ID NO: 138.465. The AAV capsid variant of any one of embodiments 397-464, which comprises the amino acids HD at position 454 and 455, and further comprises the amino acid sequence of SPHSKA (SEQ ID NO: 941), which is present immediately subsequent to position 455, numbered relative to SEQ ID NO: 138.466. The AAV capsid variant of any one of embodiments 461-463, which further comprises an amino acid other than T at position 450, an amino acid other than I at position 4 1. and an amino acid other than N at position 452, numbered according to SEQ ID NO: 138 or 982.99323376583.1Attorney Docket No.: V2071-3049PCT467. The AAV capsid variant of any one of embodiments 489-493 or 465, which further comprises A at position 450. E at position 451. and I at position 452. numbered according to SEQ ID NO: 138 or 982.468. The AAV capsid variant of any one of embodiments 489-493, 465. or 467, which further comprises the substitutions T450A, 145 IE, and N452I, numbered according to SEQ ID NO: 138 or 982.469. The AAV capsid variant of any one of embodiments 489, 493. or 465-467, which comprises:(i) A at position 450, E at position 451, and I at position 452, numbered according to SEQ ID NO: 138 or 982; and(ii) the amino acid sequence of HDSPHK (SEQ ID NO: 2), which is present immediately subsequent to positions 453, numbered according to SEQ ID NO: 138 or 982.470. The AAV capsid variant of any one of embodiments 1-49, 52-54, 58, 61-69, 72-77, 80-90, 96, 106, 110-113, 118-125, 129, 130. 137, 138, 145-156, 397-399, 412, 413, 418, 421, 423, 438-441, comprising the amino acid sequence of SPHKYG (SEQ ID NO: 966), wherein the amino acid sequence is present immediately subsequent to position 455, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138.471. An adeno-associated (AAV) capsid variant comprising:(i) the amino acid sequence of HDSPHK (SEQ ID NO: 2), wherein the amino acid sequence is present immediately subsequent to position 453, numbered according to the amino acid sequence of SEQ ID NO: 982;(ii) a modification, e.g., a substitution (e.g., conservative substitution) in loop VIII, optionally wherein loop VIII comprises positions 587-599, numbered according to SEQ ID NO: 981, 982, 6411, or 6412; or positions 581-593, numbered according to SEQ ID NO: 138 or 6414;(iii) a modification, e.g., a substitution, in the HI loop, optionally wherein the HI loop comprises positions 656-672, numbered according to SEQ ID NO: 138; and / or(iv) a modification, e.g., a substitution, in VR-X. optionally wherein VR-X comprises positions 706-722, numbered according to SEQ ID NO: 138.472. An adeno-associated (AAV) capsid variant comprising:(i) the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is present immediately subsequent to position 455, numbered according to the amino acid sequence of SEQ ID NO: 981;100323376583.1Attorney Docket No.: V2071-3049PCT(ii) a modification, e.g., a substitution (e.g., conservative substitution) in loop VIII, optionally wherein loop VIII comprises positions 587-599, numbered according to SEQ ID NO: 981, 982. 6411. or 6412; or positions 581-593, numbered according to SEQ ID NO: 138 or 6414;(iii) a modification, e.g., a substitution, in the HI loop, optionally wherein the HI loop comprises positions 656-672, numbered according to SEQ ID NO: 138; and / or(iv) a modification, e.g., a substitution, in VR-X. optionally wherein VR-X comprises positions 706-722, numbered according to SEQ ID NO: 138.473. An adeno-associated (AAV) capsid variant comprising:(A) the amino acid sequence of HDSPHK (SEQ ID NO: 2), wherein the amino acid sequence is present immediately subsequent to position 453, numbered according to the amino acid sequence of SEQ ID NO: 37, and optionally further comprising:(i) one, two, or all of an amino acid other than T at position 450, an amino acid other than I at position 541, and / or an amino acid other than N at position 452, numbered according to SEQ ID NO: 138 or 37:(ii) one, two, or all of A at position 4 0, E at position 451, and / or I at position 452, numbered according to SEQ ID NO: 138 or 37; and / or(B) a modification, e.g., a substitution (e.g., conservative substitution) in loop VIII, optionally wherein loop VIII comprises positions 587-599, numbered according to SEQ ID NO: 981, 982, 6411, or 6412; or positions 581-593, numbered according to SEQ ID NO: 138 or 6414.474. An adeno-associated (AAV) capsid variant comprising:(i) the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is present immediately subsequent to position 455. numbered according to the amino acid sequence of any one of SEQ ID NO: 36, 38-55, 57, or 59;(ii) a modification, e.g.. a substitution (e.g., conservative substitution) in loop VIII. optionally wherein loop VIII comprises positions 587-599, numbered according to SEQ ID NO: 981, 982. 6411, or 6412; or positions 581-593. numbered according to SEQ ID NO: 138 or 6414;(iii) a modification, e.g., a substitution, in the HI loop, optionally wherein the HI loop comprises positions 656-672, numbered according to SEQ ID NO: 138; and / or(iv) a modification, e.g., a substitution, in VR-X. optionally wherein VR-X comprises positions 706-722, numbered according to SEQ ID NO: 138.475. The AAV capsid variant of any one of the preceding embodiments, which further comprises:(i) a modification, e.g., an insertion, substitution (e.g., conservative substitution), and / or deletion, in loop I, II, V, VI and / or VIII; and / or101323376583.1Attorney Docket No.: V2071-3049PCT(ii) a substitution at position K449, e.g., a K449R substitution, numbered according to SEQ ID NO: 138.476. The AAV capsid variant of any one of the preceding embodiments, which comprises an amino acid sequence comprising at least one. two or three modifications, e.g., substitutions (e.g., conservative substitutions), but not more than 30, 20 or 10 modifications, e.g.. substitutions (e.g.. conservative substitutions), relative to the amino acid sequence of SEQ ID NO: 138.477. 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: 138.478. 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.479. The AAV capsid variant of any one of the preceding embodiments, which comprises the amino acid sequence of SEQ ID NO: 138.480. 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.481. 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.482. 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.483. The AAV capsid variant of any one of embodiments 1-482, which comprises the amino acid sequence corresponding to positions 138-742, e.g.. a VP2, of SEQ ID NO: 981 or 982. or a sequence with at least 80% (e.g., at least about 85, 90. 95, 96, 97, 98, or 99%) sequence identity thereto.102323376583.1Attorney Docket No.: V2071-3049PCT484. The AAV capsid variant of any one of embodiments 1-483, which comprises the amino acid sequence corresponding to positions 203-742, e.g.. a VP3, of SEQ ID NO: 981 or 982. or a sequence with at least 80% (e.g., at least about 85. 90. 95, 96, 97. 98. or 99%) sequence identity thereto.485. The AAV capsid variant of any one of embodiments 1 -484, which comprises the amino acid sequence corresponding to positions 138-736, e.g.. a VP2, of SEQ ID NO: 138, or a sequence with at least 80% (e.g., at least about 85, 90, 95, 96. 97, 98, or 99%) sequence identity thereto.486. The AAV capsid variant of any one of embodiments 1-485, which comprises the amino acid sequence corresponding to positions 203-736, e.g.. a VP3, of SEQ ID NO: 138, or a sequence with at least 80% (e.g., at least about 85, 90, 95, 96. 97, 98, or 99%) sequence identity thereto.487. The AAV capsid variant of any one of embodiments 1-50, 53-56, 59, 62-70, 73-73, 81-99, 106- 116, 118, 121-126, 129-131, 134, 137-139, 142-156, 195-229, 267-274, 276, 277, 280-290, 293, 299- 308, 313, 315, 318-326, 354-390. 397-399, 403-407, 413, 414, 418, 419, 423, 434, 436, 438-441, 443- 460, 472, or 474-486, comprising an amino acid sequence comprising at least 3, 4, 5, or 6 consecutive amino acids from the amino acid sequence of SPHSKA (SEQ ID NO: 941). wherein:(i) the at least 3 consecutive amino acids comprise SPH;(ii) the at least 4 consecutive amino acids comprise SPHS (SEQ ID NO: 4700);(iii) the at least 5 consecutive amino acids comprise SPHSK (SEQ ID NO: 4701); or(iv) the at least 6 consecutive amino acids comprise SPHSKA (SEQ ID NO: 941): wherein the AAV capsid variant comprises: (a) a VP1 protein comprising the amino acid sequence of SEQ ID NO: 138 or SEQ ID NO: 981; (b) a VP2 protein comprising the amino acid sequence of positions 138-736 of SEQ ID NO: 138 or positions 138-742 of SEQ ID NO: 981; (c) a VP3 protein comprising the amino acid sequence of positions 203-736 of SEQ ID NO: 138 or positions 203-742 of SEQ ID NO: 981; or (d) an amino acid sequence with at least 90% (e.g.. at least about 95, 96. 97, 98, or 99%) sequence identity to any of the amino acid sequences in (a)-(c).488. The AAV capsid variant of any one of embodiments 1 -50. 53-56, 59. 62-70, 73-73, 81-99. 106- 116. 118, 121-126. 129-131, 134, 137-139, 142-156. 195-229, 267-274. 276, Til, 280-290, 293, 299- 308. 313, 315, 318-326, 354-390, 397-399, 403-407. 413, 414, 418. 419, 423, 434, 436, 438-441. 443- 460. 472, or 474-487, comprising an amino acid sequence comprising at least 3, 4. 5, or 6 consecutive amino acids from the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein:(i) the at least 3 consecutive amino acids comprise SPH;(ii) the at least 4 consecutive ammo acids comprise SPHS (SEQ ID NO: 4700);(iii) the at least 5 consecutive amino acids comprise SPHSK (SEQ ID NO: 4701); or(iv) the at least 6 consecutive amino acids comprise SPHSKA (SEQ ID NO: 941);103323376583.1Attorney Docket No.: V2071-3049PCT wherein the AAV capsid variant comprises an amino acid sequence at least 90% (e.g.. at least about 95, 96. 97. 98, or 99%) identical to the amino acid sequence of SEQ ID NO: 981.489. The AAV capsid variant of any one of embodiments 1-50. 53-56, 59. 62-70, 73-73, 81-99. 106- 1 16. 118, 121 -126. 129-131 , 134, 137-139, 142-156. 195-229, 267-274. 276, 277, 280-290, 293, 299- 308. 313, 315, 318-326, 354-390, 397-399, 403-407. 413, 414, 418. 419, 423, 434. 436, 438-441. 443- 460. 472, or 474-488, comprising one or tw o. but no more than three substitutions relative to the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the AAV capsid variant comprises:(a) a VP1 protein comprising the ammo acid sequence of SEQ ID NO: 138 or SEQ ID NO: 981;(b) a VP2 protein comprising the amino acid sequence of positions 138-736 of SEQ ID NO: 138 or positions 138-742 of SEQ ID NO: 981;(c) a VP3 protein comprising the amino acid sequence of positions 203-736 of SEQ ID NO: 138 or positions 203-742 of SEQ ID NO: 981; or(d) an amino acid sequence with at least 90% (e.g., at least about 95, 96, 97, 98, or 99%) sequence identity to any of the amino acid sequences in (a)-(c).490. The AAV capsid variant of any one of embodiments 1-50, 53-56, 59, 62-70, 73-73, 81-99, 106- 116, 118, 121-126, 129-131, 134. 137-139, 142-156, 195-229, 267-274, 276, 277. 280-290, 293, 299- 308, 313, 315. 318-326, 354-390. 397-399, 403-407, 413, 414, 418, 419, 423. 434, 436, 438-441, 443- 460, 472, or 474-489, comprising one or two, but no more than three substitutions relative to the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the AAV capsid variant comprises an amino acid sequence at least 90% (e.g.. at least about 95, 96. 97, 98, or 99%) identical to the amino acid sequence of SEQ ID NO: 138 or SEQ ID NO: 981.491. The AAV capsid variant of any one of embodiments 487-490, w herein the amino acid sequence is present immediately subsequent to position 455. numbered according to SEQ ID NO: 138 or 981.492. The AAV capsid variant of any one of embodiments 1 -36. 38-49, 51. 53, 55, 57, 60. 65-69, 71, 73-77. 79, 81-104, 110-115, 117-124, 127-130, 132, 137. 138, 140-156. 230-275, 278, 279, 281-284, 287. 288, 291-307. 310-314, 316-326. 354-390, 397. 397, 399, 408-411, 413, 414. 418, 420, 423. 434, 437-440, 442, 461. 461-463, 466-469. 471, 473, or 475-486, comprising an amino acid sequence comprising at least 3, 4, 5, or 6 consecutive amino acids from the amino acid sequence of HDSPHK (SEQ ID NO: 2), wherein:(i) the at least 3 consecutive amino acids comprise HDS;(ii) the at least 4 consecutive amino acids comprise HDSP (SEQ ID NO: 4702);(iii) the at least 5 consecutive amino acids comprise HDSPH (SEQ ID NO: 4703); or104323376583.1Attorney Docket No.: V2071-3049PCT(iv) the at least 6 consecutive amino acids comprise HDSPHK (SEQ ID NO: 2); wherein the AAV capsid variant comprises: (a) a VP1 protein comprising the amino acid sequence of SEQ ID NO: 138 or SEQ ID NO: 982; (b) a VP2 protein comprising the amino acid sequence of positions 138-736 of SEQ ID NO: 138 or positions 138-742 of SEQ ID NO: 982; (c) a VP3 protein comprising the amino acid sequence of positions 203-736 of SEQ ID NO: 138 or positions 203-742 of SEQ ID NO: 982; or (d) an amino acid sequence with at least 90% (e.g., at least about 95, 96, 97, 98, or 99%) sequence identity to any of the amino acid sequences in (a)-(c).493. The AAV capsid variant of any one of embodiments 1-36. 38-49, 51, 53, 55, 57, 60, 65-69, 71, 73-77, 79, 81-104, 110-115, 117-124, 127-130, 132, 137, 138, 140-156. 230-275, 278, 279, 281-284, 287, 288, 291-307, 310-314, 316-326, 354-390, 397. 397, 399, 408-411, 413, 414. 418, 420, 423, 434, 437-440, 442, 461, 461-463, 466-469, 471, 473, 475-486, or 492, comprising an amino acid sequence comprising at least 3, 4, 5, or 6 consecutive amino acids from the amino acid sequence of HDSPHK (SEQ ID NO: 2), wherein:(i) the at least 3 consecutive amino acids comprise HDS;(ii) the at least 4 consecutive amino acids comprise HDSP (SEQ ID NO: 4702);(iii) the at least 5 consecutive amino acids comprise HDSPH (SEQ ID NO: 4703); or(iv) the at least 6 consecutive amino acids comprise HDSPHK (SEQ ID NO: 2); wherein the AAV capsid variant comprises an amino acid sequence at least 90% (e.g., at least about 95, 96, 97, 98. or 99%) identical to the amino acid sequence of SEQ ID NO: 982.494. The AAV capsid variant of any one of embodiments 1-36, 38-49, 51, 53. 55. 57, 60, 65-69, 71, 73-77, 79. 81-104. 110-115, 117-124. 127-130, 132. 137, 138, 140-156, 230-275, 278, 279, 281-284. 287, 288, 291-307, 310-314, 316-326, 354-390. 397, 397, 399. 408-411, 413. 414, 418, 420. 423, 434, 437-440, 442, 461, 461-463, 466-469, 471, 473, 475-486, 492, or 493, comprising one or two, but no more than three substitutions relative to the amino acid sequence of HDSPHK (SEQ ID NO: 2), wherein the AAV capsid variant comprises:(a) a VP1 protein comprising the amino acid sequence of SEQ ID NO: 138 or SEQ ID NO: 982;(b) a VP2 protein comprising the amino acid sequence of positions 138-736 of SEQ ID NO: 138 or positions 138-742 of SEQ ID NO: 982;(c) a VP3 protein comprising the amino acid sequence of positions 203-736 of SEQ ID NO: 138 or positions 203-742 of SEQ ID NO: 982; or(d) an amino acid sequence with at least 90% (e.g.. at least about 95, 96, 97, 98, or 99%) sequence identity to any of the amino acid sequences in (a)-(c).105323376583.1Attorney Docket No.: V2071-3049PCT495. The AAV capsid variant of any one of embodiments 1-36, 38-49, 51, 53, 55, 57, 60, 65-69, 71, 73-77. 79, 81-104, 110-115. 117-124, 127-130, 132, 137. 138, 140-156. 230-275, 278, 279. 281-284, 287. 288, 291-307. 310-314, 316-326. 354-390, 397. 397, 399, 408-411. 413, 414. 418, 420, 423. 434, 437-440, 442, 461. 461-463, 466-469. 471, 473, 475-486, or 492-494. comprising one or two, but no more than three substitutions relative to the amino acid sequence of HDSPHK (SEQ ID NO: 2), wherein the AAV capsid variant comprises an amino acid sequence at least 90% (e.g., at least about 95, 96, 97. 98, or 99%) identical to the amino acid sequence of SEQ ID NO: 982.496. The AAV capsid variant of any one of embodiments 492-495, wherein the amino acid sequence is present immediately subsequent to position 453. numbered according to SEQ ID NO: 138 or 982.497. The AAV capsid variant of any one of embodiments 1-496, which comprises the amino acid sequence of any one of SEQ ID NO: 981 or 982, or an amino acid sequence with at least 80% (e.g., at least about 85, 90, 95, 96, 97, 98, or 99%) sequence identity thereto.498. The AAV capsid variant of any one of embodiments 1-497, which comprises an amino acid sequence comprising at least one. Ivo or three modifications, e.g., substitutions (e.g., conservative substitutions), but not more than 30, 20 or 10 modifications, e.g., substitutions (e.g., conservative substitutions), relative to the amino acid sequence of SEQ ID NO: 981 or 982.499. The AAV capsid variant of any one of embodiments, 1-498. which comprises an amino acid sequence comprising at least one. two or three, but not more than 30. 20 or 10 different amino acids, relative to the amino acid sequence of SEQ ID NO: 981 or 982.500. The AAV capsid variant of any one of embodiments 1-50, 53-56, 59, 62-70, 73-73, 81-99, 106- 116. 118, 121-126. 129-131, 134, 137-139, 142-156. 195-229, 267-274. 276, 277, 280-290, 293, 299- 308. 313, 315, 318-326, 354-390, 397-399, 403-407. 413, 414, 418. 419, 423, 434. 436, 438-441. 443- 460. 472, 474-490. or 497-499, which comprises the amino acid sequence of SEQ ID NO: 981. or an amino acid sequence with at least 80% (e.g.. at least about 85, 90. 95, 96, 97, 98. or 99%) sequence identity thereto.501. The AAV capsid variant of any one of embodiments 1-50. 53-56, 59, 62-70, 73-73, 81-99, 106- 116, 118, 121-126. 129-131, 134, 137-139, 142-156. 195-229, 267-274. 276, 277, 280-290, 293, 299- 308, 313, 315, 318-326, 354-390, 397-399, 403-407. 413, 414, 418, 419, 423, 434, 436, 438-441, 443- 460, 472, 474-490, or 497-500, which comprises an amino acid sequence comprising at least one, two or three modifications, e.g., substitutions (e.g., conservative substitutions), but not more than 30, 20 or106323376583.1Attorney Docket No.: V2071-3049PCT10 modifications, e.g., substitutions (e.g., conservative substitutions), relative to the amino acid sequence of SEQ ID NO: 981.502. The AAV capsid variant of any one of embodiments 1-50. 53-56, 59. 62-70, 73-73, 81-99. 106- 1 16. 118, 121 -126. 129-131 , 134, 137-139, 142-156. 195-229, 267-274. 276, 277, 280-290, 293, 299- 308. 313, 315, 318-326, 354-390, 397-399, 403-407. 413, 414, 418. 419, 423, 434. 436, 438-441. 443- 460. 472, 474-490. or 497-501, which comprises an amino acid sequence comprising at least one, two or three, but not more than 30, 20 or 10 different amino acids, relative to the amino acid sequence of SEQ ID NO: 981.503. The AAV capsid variant of any one of embodiments 1-36. 38-49, 51, 53, 55, 57, 60, 65-69, 71, 73-77, 79, 81-104, 110-115, 117-124, 127-130, 132, 137, 138, 140-156, 230-275, 278, 279, 281-284, 287, 288, 291-307, 310-314, 316-326, 354-390, 397, 397, 399, 408-411, 413, 414, 418, 420, 423, 434, 437-440, 442, 461, 461-463, 466-469, 471, 473, 475-486, or 492-499, 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.504. The AAV capsid variant of any one of embodiments 1-36, 38-49, 51, 53. 55, 57, 60, 65-69, 71, 73-77, 79. 81-104. 110-115, 117-124. 127-130, 132. 137, 138, 140-156, 230-275, 278, 279, 281-284. 287, 288, 291-307, 310-314, 316-326, 354-390, 397, 397, 399, 408-411, 413, 414, 418, 420, 423, 434, 437-440, 442, 461, 461-463, 466-469, 471, 473. 475-486, 492-499. or 503, which comprises an amino acid sequence comprising at least one, two or three modifications, e.g., substitutions (e.g., conservative substitutions), but not more than 30, 20 or 10 modifications, e.g., substitutions (e.g., conservative substitutions), relative to the amino acid sequence of SEQ ID NO: 982.505. The AAV capsid variant of any one of embodiments 1-36. 38-49, 51, 53, 55, 57, 60, 65-69, 71, 73-77. 79, 81-104, 110-115, 117-124, 127-130, 132, 137. 138, 140-156. 230-275, 278, 279. 281-284, 287. 288, 291-307. 310-314, 316-326. 354-390, 397. 397, 399, 408-411. 413, 414. 418, 420, 423. 434, 437-440, 442, 461. 461 -463, 466-469. 471 , 473, 475-486, 492-499, 503, or 504, 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: 982.506. The AAV capsid variant of any one of embodiments 1-505, which comprises an amino acid sequence encoded by the nucleotide sequence of SEQ ID NO: 983 or 984, or a nucleotide sequence with at least 80% (e.g., at least about 85, 90. 95, 96, 97, 98, or 99%) sequence identity thereto.107323376583.1Attorney Docket No.: V2071-3049PCT507. The AAV capsid variant of any one of the preceding embodiments 1-506, wherein the nucleotide sequence encoding the capsid variant comprises the nucleotide sequence of SEQ ID NOs: 983 or 984. or a nucleotide sequence with at least 80% (e.g., at least about 85. 90, 95, 96, 97. 98. or 99%) sequence identity thereto.508. The AAV capsid variant of any one of the preceding embodiments 1-50, 53-56. 59, 62-70. 73-73, 81-99. 106-116, 118. 121-126, 129-131. 134, 137-139, 142-156, 195-229. 267-274, 276, 277, 280- 290, 293, 299-308. 313, 315, 318-326, 354-390, 397-399, 403-407, 413, 414, 418. 419, 423, 434. 436, 438-441, 443-460, 472, 474-490, 497-502, 506, or 507, wherein the nucleotide sequence encoding the capsid variant comprises the nucleotide sequence of SEQ ID NO: 983, or a nucleotide sequence with at least 80% (e.g., at least about 85, 90, 95, 96, 97, 98, or 99%) sequence identity thereto.509. The AAV capsid variant of any one of the preceding embodiments 1-36, 38-49, 51, 53, 55, 57, 60, 65-69, 71, 73-77, 79, 81-104, 110-115, 117-124, 127-130, 132, 137, 138, 140-156, 230-275, 278, 279, 281-284, 287, 288, 291-307, 310-314, 316-326, 354-390, 397, 397, 399, 408-411, 413, 414, 418, 420, 423, 434, 437-440, 442, 461, 461-463, 466-469, 471, 473. 475-486, 492-499, or 503-507, 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.510. The AAV capsid variant of any one of the preceding embodiments, wherein the nucleotide sequence encoding the capsid variant is codon optimized.511. An AAV capsid variant, comprising the amino acid sequence of any one of embodiments 1-50, 53-56. 59, 62-70, 73-73, 81-99, 106-116, 118, 121-126, 129-131, 134, 137-139, 142-156, 195-229, 267-274, 276, Til. 280-290, 293, 299-308, 313, 315, 318-326, 354-390, 397-399, 403-407, 413, 414, 418, 419, 423, 434, 436, 438-441, 443-460, 472. 474-490, 497-502, 506-508, or 510, and further comprising an amino acid sequence at least 95% identical to SEQ ID NO: 981.512. An AAV capsid variant comprising the amino acid sequence of SEQ ID NO: 981, which further comprises a modification, e.g., a substitution (e.g., conservative substitution) in loop VIII, optionally wherein loop VIII comprises positions 587-599, numbered according to SEQ ID NO: 981, 982, 6411, or 6412; or positions 581-593, numbered according to SEQ ID NO: 138 or 6414.513. The AAV capsid variant of embodiment 511 or 512, wherein the nucleotide sequence encoding the AAV capsid variant comprises the nucleotide sequence of SEQ ID NO: 983, or a nucleotide sequence at least 90%. 95%, or 99% identical thereto.108323376583.1Attorney Docket No.: V2071-3049PCT514. An AAV capsid variant, comprising the amino acid sequence of any one of embodiments 1-36, 38-49. 51, 53, 55, 57. 60. 65-69. 71. 73-77, 79. 81-104. 110-115, 117-124. 127-130, 132. 137, 138, 140-156, 230-275, 278. 279, 281-284. 287, 288, 291-307, 310-314, 316-326, 354-390, 397, 397, 399. 408-411, 413, 414. 418, 420, 423. 434, 437-440. 442, 461, 461-463, 466-469, 471. 473, 475-486. 492- 499. 503-507, 509. or 510, and further comprising an amino acid sequence at least 95% identical to SEQ ID NO: 982.515. An AAV capsid variant comprising the amino acid sequence of SEQ ID NO: 982, which further comprises:(i) a modification, e.g., a substitution (e.g., conservative substitution) in loop VIII, optionally wherein loop VIII comprises positions 587-599, numbered according to SEQ ID NO: 981, 982, 6411, or 6412; or positions 581-593, numbered according to SEQ ID NO: 138 or 6414;(ii) a modification, e g., a substitution, in the HI loop, optionally wherein the HI loop comprises positions 656-672. numbered according to SEQ ID NO: 138; and / or(iii) a modification, e.g., a substitution, in VR-X, optionally wherein VR-X comprises positions 706-722, numbered according to SEQ ID NO: 138.516. The AAV capsid variant of embodiment 514 or 515, wherein the nucleotide sequence encoding the AAV capsid variant comprises the nucleotide sequence of SEQ ID NO: 984, or a nucleotide sequence at least 90%. 95%, or 99% identical thereto.517. An adeno-associated (AAV) capsid variant comprising an amino acid sequence encoded by the nucleotide sequence of SEQ ID NOs: 983 or 984, or a nucleotide sequence at least 95% identical thereto; which further comprises a modification, e.g., a substitution (e.g., conservative substitution) in loop VIII, optionally loop VIII comprises positions 587-599, numbered according to SEQ ID NO: 981. 982, 6411, or 6412; or positions 581-593. numbered according to SEQ ID NO: 138 or 6414.518. An adeno-associated (AAV) capsid variant comprising the amino acid sequence of any one of SEQ ID NOs: 5-10, 36-59, or 6409-6413, which optionally further comprises:(i) a modification, e.g., a substitution (e.g.. conservative substitution) in loop VIII, optionally wherein loop VIII comprises positions 587-599, numbered according to SEQ ID NO: 981, 982, 6411. or 6412; or positions 581-593, numbered according to SEQ ID NO: 138 or 6414;(ii) a modification, e.g., a substitution, in the HI loop, optionally wherein the HI loop comprises positions 656-672, numbered according to SEQ ID NO: 138; and / or(iii) a modification, e.g., a substitution, in VR-X, optionally wherein VR-X comprises positions 706-722, numbered according to SEQ ID NO: 138.109323376583.1Attorney Docket No.: V2071-3049PCT519. An AAV capsid variant comprising an amino acid sequence encoded by the nucleotide sequence of any one of SEQ ID NOs: 4 or 12-35, or a nucleotide sequence at least 95% identical thereto, which optionally further comprises a modification, e g., a substitution (e g., conservative substitution) in loop VIII, optionally wherein loop VIII comprises positions 587-599, numbered according to SEQ ID NO: 981, 982, 6411, or 6412; or positions 581-593, numbered according to SEQ ID NO: 138 or 6414.520. The AAV capsid variant of 518 or 519. wherein the nucleotide sequence encoding the AAV capsid variant comprises the nucleotide sequence of any one of SEQ ID NOs: 4 or 12-35, or a nucleotide sequence at least 95% identical thereto.521. An adeno-associated virus (AAV) capsid variant comprising an amino acid sequence at least 95% identical to amino acids 203-742 of SEQ ID NO: 981, wherein the amino acid sequence comprises SPHSKA (SEQ ID NO: 941) in variable region IV (VR-IV) and comprises:(i) two, three, or all of an amino acid other than D at position 663, P at position 665, T at position 666, and / or A at position 667, numbered according to SEQ ID NO: 981;(ii) two, three, four, five, six or all of an amino acid other than P at position 665, A at position 667, N at position 669. K at position 670, D at position 671, K at position 672, and / or N at position 674, numbered according to SEQ ID NO: 981; or(iii) two, three, four, five, six or all of an amino acid other than P at position 659, A at position 661, N at position 663, K at position 664. D at position 665, L at position 667, and / or N at position 668, numbered according to SEQ ID NO: 981.522. An adeno-associated virus (AAV) capsid variant comprising an amino acid sequence at least 95% identical to amino acids 203-742 of SEQ ID NO: 982, wherein the amino acid sequence comprises HDSPHK (SEQ ID NO: 2) in variable region IV (VR-IV) and comprises:(i) two, three, or all of an amino acid other than D at position 663. P at position 665, T at position 666. and / or A at position 667, numbered according to SEQ ID NO: 982;(ii) tw o. three, four, five, six or all of an amino acid other than P at position 665, A at position 667. N at position 669, K at position 670, D at position 671, K at position 672, and / or N at position 674. numbered according to SEQ ID NO: 982; or(iii) two. three, four, five, six or all of an amino acid other than P at position 659, A at position 661, N at position 663. K at position 664, D at position 665, L at position 667, and / or N at position 668, numbered according to SEQ ID NO: 982.523. The AAV capsid variant of embodiment 521 or 522, comprising:110323376583.1Attorney Docket No.: V2071-3049PCT(i) an amino acid other than D at position 663. P at position 665, T at position 666, and A at position 667. numbered according to SEQ ID NO: 981 or 982;(ii) an amino acid other than P at position 665, A at position 667, N at position 669, K at position 670. D at position 671. K at position 672, and N at position 674, numbered according to SEQ ID NO: 981 or 982; or(iii) an amino acid other than P at position 659, A at position 661. N at position 663, K at position 664, D at position 665. L at position 667, and N at position 668, numbered according to SEQ ID NO: 981 or 982.524. The AAV capsid variant of any one of embodiments 521-523, comprising:(i) the amino acid E at position 663, tire amino acid S at position 665, the amino acid D at position 666, and the amino acid V at position 667, numbered according to SEQ ID NO: 981;(ii) the amino acid A at position 665, the amino acid E at position 667, the amino acid L at position 669, the amino acid S at position 670, the amino acid V at position 671, the amino acid P at position 672, and the amino acid K at position 674, numbered according to SEQ ID NO: 981;(iii) the amino acid E at position 663, the amino acid A at position 665, the amino acid E at position 666, and the amino acid L at position 667, nmnbered according to SEQ ID NO: 981;(iv) the amino acid Q at position 663, the amino acid S at position 665, the amino acid E at position 666, and the amino acid E at position 667, nmnbered according to SEQ ID NO: 981;(v) the amino acid E at position 663, the amino acid F at position 665, the amino acid S at position 666, and the amino acid E at position 667, nmnbered according to SEQ ID NO: 981;(vi) the amino acid E at position 663, the amino acid H at position 665, the amino acid M at position 666, and the amino acid E at position 667, nmnbered according to SEQ ID NO: 981;(vii) the amino acid E at position 663. the amino acid S at position 665. the amino acid D at position 666, and the amino acid L at position 667, nmnbered according to SEQ ID NO: 981;(viii) the amino acid E at position 663, the amino acid W at position 665, the amino acid S at position 666. and the amino acid E at position 667. nmnbered according to SEQ ID NO: 981;(ix) the amino acid A at position 665, the amino acid E at position 667, the amino acid L at position 669. the amino acid Y at position 670, the amino acid T at position 671. the amino acid V at position 673, and the amino acid R at position 674, numbered according to SEQ ID NO: 981;(x) the amino acid T at position 663, the amino acid W at position 665, the amino acid E at position 666, and the amino acid L at position 667, numbered according to SEQ ID NO: 981; or(xi) the amino acid R at position 716, the amino acid D at position 722, and the amino acid D at position 723, numbered according to SEQ ID NO: 981.111323376583.1Attorney Docket No.: V2071-3049PCT525. The AAV capsid variant of any one of embodiments 521-524, which comprises the amino acid E at position 663. the amino acid S at position 665. the amino acid D at position 666. and the amino acid V at position 667, numbered according to SEQ ID NO: 981.526. The AAV capsid variant of any one of embodiments 521-524, which comprises the amino acid A at position 665, the amino acid E at position 667, the amino acid L at position 669. the amino acid S at position 670, the amino acid V at position 671, the amino acid P at position 672. and the amino acid K at position 674, numbered according to SEQ ID NO: 981.527. The AAV capsid variant of any one of embodiments 521-526, which comprises the amino acid E at position 663, the amino acid A at position 665, the amino acid E at position 666, and the amino acid L at position 667, numbered according to SEQ ID NO: 981.528. The AAV capsid variant of embodiment 526 or 527, which further comprises the amino acid R at position 716, the amino acid D at position 722, and tire amino acid D at position 723, numbered according to SEQ ID NO: 981, 982, or 6411.529. The AAV capsid variant of any one of embodiments 526-528, which comprises:(i) the amino acid A at position 665, the amino acid E at position 667, the amino acid L at position 669, the amino acid S at position 670, the amino acid V at position 671, the amino acid P at position 672, the amino acid K at position 674, the amino acid R at position 716, the amino acid D at position 722, and the amino acid D at position 723, numbered according to SEQ ID NO: 981; or(ii) the amino acid E at position 663, the amino acid A at position 665, the amino acid E at position 666, and the amino acid L at position 667, the amino acid R at position 716, the amino acid D at position 722, and the amino acid D at position 723, numbered according to SEQ ID NO: 981.530. The AAV capsid variant of any one of embodiments 521-529, which further comprises the amino acid R at position 590, T at position 592, L at position 594. Q at position 595, and L at position 596, numbered according to SEQ ID NO: 981 , 982. or 6411 .531. The AAV capsid variant of any one of embodiments 521 or 523-530. which further comprises the amino acid E at position 451 and V at position 453, numbered according to SEQ ID NO: 981.532. The AAV capsid variant of any one of embodiments 521 or 523-531, wherein the amino acid sequence of SPHSKA (SEQ ID NO: 941) is present immediately subsequent to amino acid 455, numbered according to SEQ ID NO: 981.112323376583.1Attorney Docket No.: V2071-3049PCT533. The AAV capsid variant of any one of embodiments 522-532, wherein the amino acid sequence of HDSPHK (SEQ ID NO: 2) is present immediately subsequent to amino acid 453, numbered according to SEQ ID NO: 982.534. The AAV capsid variant of any one of embodiments 521 or 523-532. which comprises an amino acid sequence at least 95% or at least 98% identical to amino acids 203-742 of any one of SEQ ID NOs: 6437- 6449.535. The AAV capsid variant of any one of embodiments 521, 523-532, or 534, which comprises an amino acid sequence at least 95% or at least 98% identical to amino acids 138-742 of any one of SEQ ID NOs: 6437- 6449.536. The AAV capsid variant of any one of embodiments 521, 523-532, 534, or 535, which comprises an amino acid sequence at least 95% or at least 98% identical to any one of SEQ ID NOs: 6437-6449.537. The AAV capsid variant of any one of embodiments 521, 523-532, or 534-536, which comprises the amino acid sequence of amino acids 203-742 of any one of SEQ ID NOs: 6437- 6449.538. The AAV capsid variant of any one of embodiments 521, 523-532, or 534-537, which comprises the amino acid sequence of amino acids 138-742 of any one of SEQ ID NOs: 6437-6449.539. The AAV capsid variant of any one of embodiments 521, 523-532, or 534-538, which comprises the amino acid sequence of any one of SEQ ID NOs: 6437-6449.540. The AAV capsid variant of any one of embodiments 522-530 or 533, which comprises:(i) an amino acid sequence at least 95% or at least 98% identical to amino acids 203-742 of any one of SEQ ID NOs: 6450-6462;(ii) an amino acid sequence at least 95% or at least 98% identical to amino acids 138-742 of any one of SEQ ID NOs: 6450-6462; and / or(iii) an amino acid sequence at least 95% or at least 98% identical to any one of SEQ ID NOs: 6450-6462.541. The AAV capsid variant of any one of embodiments 522-530, 533, or 540, which comprises:(i) the amino acid sequence of amino acids 203-742 of any one of SEQ ID NOs: 6450-6462;(ii) the amino acid sequence of amino acids 138-742 of any one of SEQ ID NOs: 6450-6462; and / or(iii) the amino acid sequence of any one of SEQ ID NOs: 6450-6462.113323376583.1Attorney Docket No.: V2071-3049PCT542. An adeno-associated virus (AAV) capsid variant comprising an amino acid sequence at least 95% identical to amino acids 203-742 of SEQ ID NO: 6437, wherein the amino acid sequence comprises SPHSKA (SEQ ID NO: 941) in variable region IV (VR-IV) and comprises the amino acid E at position 451 , V at position 453. the amino acid E at position 663. the amino acid S at position 665. the amino acid D at position 666. and the amino acid V at position 667. numbered according to SEQ ID NO: 6437.543. The AAV capsid variant of any one of embodiments 521, 523-525, 531, 532, or 542, which comprises the amino acid sequence of amino acids 203-742 of SEQ ID NO: 6437, or an amino acid sequence at least 95% or at least 98% identical to amino acids 203-742 of SEQ ID NO: 6437.544. The AAV capsid variant of any one of embodiments 521, 523-525, 531, 532, 542, or 543, which comprises the amino acid sequence of amino acids 138-742 of SEQ ID NO: 6437, or an amino acid sequence at least 95% or at least 98% identical to amino acids 138-742 of SEQ ID NO: 6437.545. The AAV capsid variant of any one of embodiments 521, 523-525, 531, 532. or 542-544, which comprises the amino acid sequence of SEQ ID NO: 6437, or an amino acid sequence at least 95% or at least 98% identical to SEQ ID NO: 6437.546. An adeno-associated virus (AAV) capsid variant comprising an amino acid sequence at least 95% identical to amino acids 203-742 of SEQ ID NO: 6443. wherein the amino acid sequence comprises SPHSKA (SEQ ID NO: 941) in variable region IV (VR-IV) and comprises the amino acid E at position 451, V at position 453, the amino acid A at position 665, the amino acid E at position 667, the amino acid L at position 669, the amino acid S at position 670, the amino acid V at position 671, the amino acid P at position 672, and the amino acid K at position 674. numbered according to SEQ ID NO: 6443.547. The AAV capsid variant of any one of embodiments 521, 523, 524, 526, 531. 532, 542, or 546, which comprises the amino acid sequence of amino acids 203-742 of SEQ ID NO: 6443. or an amino acid sequence at least 95% or at least 98% identical to amino acids 203-742 of SEQ ID NO: 6443.548. The AAV capsid variant of any one of embodiments 521, 523, 524, 526, 531. 532, 542, 546, or 547, which comprises the amino acid sequence of amino acids 138-742 of SEQ ID NO: 6443, or an amino acid sequence at least 95% or at least 98% identical to amino acids 138-742 of SEQ ID NO: 6443.114323376583.1Attorney Docket No.: V2071-3049PCT549. The AAV capsid variant of any one of embodiments 521, 523, 524, 526, 531, 532, 542, or 546- 548. which comprises the amino acid sequence of SEQ ID NO: 6443, or an amino acid sequence at least 95% or at least 98% identical to SEQ ID NO: 6443.550. An adeno-associated virus (AAV) capsid variant comprising an amino acid sequence at least 95% identical to amino acids 203-742 of SEQ ID NO: 6445, wherein the amino acid sequence comprises SPHSKA (SEQ ID NO: 941) in variable region IV (VR-IV) and comprises the amino acid E at position 451, V at position 453, the amino acid E at position 663. the amino acid A at position 665, the amino acid E at position 666. and the amino acid L at position 667, numbered according to SEQ ID NO: 6445.551. The AAV capsid variant of any one of embodiments 521, 523, 524, 527, 531, 532, 542, or 550, which comprises the amino acid sequence of amino acids 203-742 of SEQ ID NO: 6445, or an amino acid sequence at least 95% or at least 98% identical to amino acids 203-742 of SEQ ID NO: 6445.552. The AAV capsid variant of any one of embodiments 521, 523, 524, 527, 531, 532, 542, 550, or551, which comprises the amino acid sequence of amino acids 138-742 of SEQ ID NO: 6445, or an amino acid sequence at least 95% or at least 98% identical to amino acids 138-742 of SEQ ID NO: 6445.553. The AAV capsid variant of any one of embodiments 521, 523, 524, 527, 531, 532, 542. or 550-552, which comprises the amino acid sequence of SEQ ID NO: 6445. or an amino acid sequence at least 95% or at least 98% identical to SEQ ID NO: 6445.554. The AAV capsid variant of any one of embodiments 542-553, wherein VR-IV comprises amino acids 449-460, numbered according to SEQ ID NO: 138.555. The AAV capsid variant of any one of embodiments 542-554, wherein the amino acid sequence of SPHSKA (SEQ ID NO: 941) is present immediately subsequent to amino acid 455, numbered according to SEQ ID NO: 6437, 6443, or 6445.556. An adeno-associated virus (AAV) capsid variant comprising an amino acid sequence at least 95% identical to amino acids 203-742 of SEQ ID NO: 6450, wherein the amino acid sequence comprises HDSPHK (SEQ ID NO: 2) in variable region IV (VR-IV) and comprises the amino acid R at position 590, T at position 592, L at position 594, Q at position 595, and L at position 596, the amino acid A at position 665, the amino acid E at position 667, the amino acid L at position 669, the115323376583.1Attorney Docket No.: V2071-3049PCT amino acid S at position 670. the amino acid V at position 671, the amino acid P at position 672. and the amino acid K at position 674, numbered according to SEQ ID NO: 6450.557. The AAV capsid variant of embodiment 556, which comprises the amino acid sequence of amino acids 203-742 of SEQ ID NO: 6450, or an amino acid sequence at least 95% or at least 98% identical thereto.558. The AAV capsid variant of embodiment 556 or 557, which comprises the amino acid sequence of amino acids 138-742 of SEQ ID NO: 6450, or an amino acid sequence at least 95% or at least 98% identical thereto.559. The AAV capsid variant of any one of embodiments 556-558, which comprises the amino acid sequence of SEQ ID NO: 6450, or an amino acid sequence at least 95% or at least 98% identical thereto.560. An adeno-associated virus (AAV) capsid variant comprising an amino acid sequence at least 95% identical to ammo acids 203-742 of SEQ ID NO: 6456, wherein the amino acid sequence comprises HDSPHK (SEQ ID NO: 2) in variable region IV (VR-IV) and comprises the amino acid R at position 590, T at position 592, L at position 594, Q at position 595, and L at position 596, the amino acid A at position 665, the amino acid E at position 667. the amino acid L at position 669. the amino acid S at position 670. the amino acid V at position 671. the amino acid P at position 672, and the amino acid K at position 674. numbered according to SEQ ID NO: 6456.561. The AAV capsid variant of embodiment 560. which comprises the amino acid sequence of amino acids 203-742 of SEQ ID NO: 6456, or an amino acid sequence at least 95% or at least 98% identical thereto.562. The AAV capsid variant of embodiment 560 or 561. which comprises the amino acid sequence of amino acids 138-742 of SEQ ID NO: 6456, or an amino acid sequence at least 95% or at least 98% identical thereto.563. The AAV capsid variant of any one of embodiments 560-562, which comprises the amino acid sequence of SEQ ID NO: 6456. or an amino acid sequence at least 95% or at least 98% identical thereto.564. An adeno-associated virus (AAV) capsid variant comprising an amino acid sequence at least 95% identical to amino acids 203-742 of SEQ ID NO: 6458, wherein the amino acid sequence116323376583.1Attorney Docket No.: V2071-3049PCT comprises HDSPHK (SEQ ID NO: 2) in variable region IV (VR-IV) and comprises the amino acid R at position 590. T at position 592. L at position 594, Q at position 595, and L at position 596. the amino acid E at position 663, the amino acid A at position 665, the amino acid E at position 666, and the amino acid L at position 667, numbered according to SEQ ID NO: 6458.565. The AAV capsid variant of embodiment 564, which comprises the amino acid sequence of amino acids 203-742 of SEQ ID NO: 6458, or an amino acid sequence at least 95% or at least 98% identical thereto.566. The AAV capsid variant of embodiment 564 or 565, which comprises the amino acid sequence of amino acids 138-742 of SEQ ID NO: 6458, or an amino acid sequence at least 95% or at least 98% identical thereto.567. The AAV capsid variant of any one of embodiments 564-566, which comprises the amino acid sequence of SEQ ID NO: 6458, or an amino acid sequence at least 95% or at least 98% identical thereto.568. The AAV capsid variant of any one of embodiments 1-326, 397-399, or 403-567. 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: 138.569. The AAV capsid variant of any one of embodiments 1-156, 195-326, 397-399. or 403-568, which transduces a brain region, e.g.. a midbrain region (e.g., the hippocampus, or thalamus) or the brain stem, optionally wherein the level of transduction is at least 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, or 65-fold greater as compared to a reference sequence of SEQ ID NO: 138, e.g., when measured by an assay, e.g., an immunohistochemistry assay or a qPCR assay, e.g.. as described in Example 2.570. The AAV capsid variant of any one of embodiments 1-156, 195-326. 397-399, or 103-568, which transduces a brain region, e.g., a midbrain region (e.g.. the hippocampus, or thalamus) or the brain stem, optionally wherein the level of transduction is at least 30, 35, 40, 45. 50, 55, 60, or 65-fold greater as compared to a reference sequence of SEQ ID NO: 138, e.g., when measured by an assay, e.g.. an immunohistochemistry’ assay or a qPCR assay, e.g., as described in Example 2.117323376583.1Attorney Docket No.: V2071-3049PCT571. The AAV capsid variant of any one of embodiments 1-156, 195-326, 397-399, or 103-570, which is enriched at least about 3. 4. 5, 6, 7, 8. 9. or 10-fold, in the brain compared to a reference sequence of SEQ ID NO: 138, e.g., when measured by an assay as described in Example 1.572. The AAV capsid variant of any one of embodiments 1-156, 195-326. 397-399, or 103-571 , which is enriched at least about 20, 25, 30, 35. 40, 45, 50, 55. 60, 65, 70, 75, 80 or 85-fold, in the brain compared to a refere...
Claims
Attorney Docket No.: V2071-3049PCTWe claim:
1. An adeno-associated virus (AAV) capsid variant comprising an amino acid sequence at least 95% identical to amino acids 203-742 of SEQ ID NO: 981, wherein the amino acid sequence comprises SPHSKA (SEQ ID NO: 941) in variable region IV (VR-IV) and comprises:(i) the amino acid A at position 665. the amino acid E at position 667, the amino acid L at position 669, the amino acid S at position 670. the amino acid V at position 671. the amino acid P at position 672, and the amino acid K at position 674, numbered according to SEQ ID NO: 981;(ii) the amino acid E at position 663, the amino acid S at position 665. the amino acid D at position 666, and the amino acid V at position 667, numbered according to SEQ ID NO: 981;(iii) the amino acid E at position 663, the amino acid A at position 665, the amino acid E at position 666, and the amino acid L at position 667, numbered according to SEQ ID NO: 981;(iv) the amino acid Q at position 663, die amino acid S at position 665, the amino acid E at position 666, and the amino acid E at position 667, numbered according to SEQ ID NO: 981;(v) the amino acid E at position 663, the amino acid F at position 665, the amino acid S at position 666, and die amino acid E at position 667, numbered according to SEQ ID NO: 981;(vi) the amino acid E at position 663, the amino acid H at position 665, the amino acid M at position 666, and the amino acid E at position 667, numbered according to SEQ ID NO: 981;(vii) the amino acid E at position 663. the amino acid S at position 665, the amino acid D at position 666, and the amino acid L at position 667, numbered according to SEQ ID NO: 981;(viii) the amino acid E at position 663, the amino acid W at position 665, the amino acid S at position 666, and the amino acid E at position 667, numbered according to SEQ ID NO: 981;(ix) the amino acid A at position 665. the amino acid E at position 667, the amino acid L at position 669, the amino acid Y at position 670, the amino acid T at position 671, the amino acid V at position 673, and the amino acid R at position 674, numbered according to SEQ ID NO: 981;(x) the amino acid T at position 663, the amino acid W at position 665, the amino acid E at position 666, and the amino acid L at position 667, numbered according to SEQ ID NO: 981; or(xi) the amino acid R at position 716, the amino acid D at position 722, and the amino acid D at position 723, numbered according to SEQ ID NO: 981.
2. The AAV capsid variant of claim 1, which comprises:(i) the amino acid E at position 4 1 and V at position 453, numbered according to SEQ ID NO: 981; or(ii) the amino acid E at position 451, R at position 452. and V at position 453, numbered according to SEQ ID NO: 981.
3. The AAV capsid variant of claim 1 or 2, wherein the amino acid sequence of SPHSKA (SEQ ID NO: 941) is present immediately subsequent to amino acid 455, numbered according to SEQ ID NO:443323376583.1Attorney Docket No.: V2071-3049PCT981.
4. An adeno-associated virus (AAV) capsid variant comprising an amino acid sequence at least 95% identical to amino acids 203-742 of SEQ ID NO: 982, wherein the amino acid sequence comprises HDSPHK (SEQ ID NO: 2) in variable region IV (VR-IV) and comprises:(i) the amino acid A at position 665. the amino acid E at position 667, the amino acid L at position 669, the amino acid S at position 670. the amino acid V at position 671. the amino acid P at position 672, and the amino acid K at position 674, numbered according to SEQ ID NO: 982;(ii) the amino acid E at position 663, the amino acid S at position 665, the amino acid D at position 666, and the amino acid V at position 667, numbered according to SEQ ID NO: 982;(iii) the amino acid E at position 663, the amino acid A at position 665, the amino acid E at position 666, and the amino acid L at position 667, numbered according to SEQ ID NO: 982;(iv) the amino acid Q at position 663, die amino acid S at position 665, the amino acid E at position 666, and the amino acid E at position 667, numbered according to SEQ ID NO: 982;(v) the amino acid E at position 663, the amino acid F at position 665, the amino acid S at position 666, and die amino acid E at position 667, numbered according to SEQ ID NO: 982;(vi) the amino acid E at position 663, the amino acid H at position 665, the amino acid M at position 666, and the amino acid E at position 667, numbered according to SEQ ID NO: 982;(vii) the amino acid E at position 663. the amino acid S at position 665, the amino acid D at position 666, and the amino acid L at position 667, numbered according to SEQ ID NO: 982;(viii) the amino acid E at position 663, the amino acid W at position 665, the amino acid S at position 666, and the amino acid E at position 667, numbered according to SEQ ID NO: 982;(ix) the amino acid A at position 665. the amino acid E at position 667, the amino acid L at position 669, the amino acid Y at position 670, the amino acid T at position 671, the amino acid V at position 673, and the amino acid R at position 674, numbered according to SEQ ID NO: 982;(x) the amino acid T at position 663, the amino acid W at position 665, the amino acid E at position 666. and the amino acid L at position 667. numbered according to SEQ ID NO: 982; or(xi) the amino acid R at position 716, the amino acid D at position 722, and the amino acid D at position 723, numbered according to SEQ ID NO: 982.
5. The AAV capsid variant of claim 4, wherein the amino acid sequence of HDSPHK (SEQ ID NO: 2) is present immediately subsequent to amino acid 453, numbered according to SEQ ID NO: 982.
6. The AAV capsid variant of any one of claims 1-5, which further comprises the amino acid R at position 590, T at position 592, L at position 594, Q at position 595, and L at position 596, numbered according to SEQ ID NO: 981, 982, or 6411.444323376583.1Attorney Docket No.: V2071-3049PCT7. The AAV capsid variant of any one of claims 1 -6. which comprises the amino acid A at position 665. the amino acid E at position 667. the amino acid L at position 669, the amino acid S at position 670. the amino acid V at position 671. the amino acid P at position 672. and the amino acid K at position 674. numbered according to SEQ ID NO: 981.
8. The AAV capsid variant of any one of claims 1 -6, which comprises the amino acid E at position 663. the amino acid A at position 665. the amino acid E at position 666. and the amino acid L at position 667, numbered according to SEQ ID NO: 981.
9. The AAV capsid variant of claim 7 or 8, further comprising the amino acid R at position 71 , the amino acid D at position 722, and the amino acid D at position 723, numbered according to SEQ ID NO: 981, 982, or 6411.
10. The AAV capsid variant of any one of claims 1-9, which comprises:(i) the amino acid A at position 665, the amino acid E at position 667, the amino acid L at position 669, tire amino acid S at position 670, the amino acid V at position 671, the amino acid P at position 672, the amino acid K at position 674, the amino acid R at position 716, tire amino acid D at position 722, and the amino acid D at position 723, numbered according to SEQ ID NO: 981; or(ii) the amino acid E at position 663, the amino acid A at position 665, the amino acid E at position 666, and the amino acid L at position 667, the amino acid R at position 716, the amino acid D at position 722, and the amino acid D at position 723, numbered according to SEQ ID NO: 981.
11. The AAV capsid variant of any one of claims 1-6, which comprises the amino acid E at position 663, the amino acid S at position 665. the amino acid D at position 666, and the amino acid V at position 667, numbered according to SEQ ID NO: 981.
12. The AAV capsid variant of any one of claims 1-3 or 6-11. which comprises:(i) an amino acid sequence at least 95% or at least 98% identical to amino acids 203-742 of any one of SEQ ID NOs: 6437-6449;(ii) an amino acid sequence at least 95% or at least 98% identical to amino acids 138-742 of any one of SEQ ID NOs: 6437-6449; and / or(iii) an amino acid sequence at least 95% or at least 98% identical to any one of SEQ ID NOs: 6437-6449.
13. The AAV capsid variant of any one of claims 1-3 or 6-12, which comprises:(i) the amino acid sequence of amino acids 203-742 of any one of SEQ ID NOs: 6437-6449;(ii) the amino acid sequence of amino acids 138-742 of any one of SEQ ID NOs: 6437-6449;445323376583.1Attorney Docket No.: V2071-3049PCT and / or(iii) the amino acid sequence of any one of SEQ ID NOs: 6437-6449.
14. The AAV capsid variant of any one of claims 4-11. which comprises:(i) an amino acid sequence at least 95% or at least 98% identical to amino acids 203-742 of any one of SEQ ID NOs: 6450-6462;(ii) an amino acid sequence at least 95% or at least 98% identical to amino acids 138-742 of any one of SEQ ID NOs: 6450-6462; and / or(iii) an amino acid sequence at least 95% or at least 98% identical to any one of SEQ ID NOs: 6450-6462.
15. The AAV capsid variant of any one of claims 4-11 or 14, which comprises:(i) the amino acid sequence of amino acids 203-742 of any one of SEQ ID NOs: 6450-6462;(ii) the amino acid sequence of amino acids 138-742 of any one of SEQ ID NOs: 6450-6462; and / or(iii) the amino acid sequence of any one of SEQ ID NOs: 6450-6462.
16. An adeno-associated virus (AAV) capsid variant comprising:(i) an amino acid sequence at least 95% identical to amino acids 203-742 of SEQ ID NO: 6443, wherein the amino acid sequence comprises SPHSKA (SEQ ID NO: 941) in variable region IV (VR-IV) and comprises the amino acid E at position 451, V at position 453. the amino acid A at position 665, the amino acid E at position 667, the amino acid L at position 669, the amino acid S at position 670, the amino acid V at position 671, the amino acid P at position 672, and the amino acid K at position 674, numbered according to SEQ ID NO: 6443;(ii) an amino acid sequence at least 95% identical to amino acids 203-742 of SEQ ID NO: 6437, wherein the amino acid sequence comprises SPHSKA (SEQ ID NO: 941) in variable region IV (VR-IV) and comprises the amino acid E at position 451. V at position 453, the amino acid E at position 663. the amino acid S at position 665. the amino acid D at position 666. and the amino acid V at position 667, numbered according to SEQ ID NO: 6437; or(iii) an amino acid sequence at least 95% identical to amino acids 203-742 of SEQ ID NO: 6445, wherein the amino acid sequence comprises SPHSKA (SEQ ID NO: 941) in variable region IV (VR-IV) and comprises the amino acid E at position 451. V at position 453, the amino acid E at position 663, the amino acid A at position 665, the amino acid E at position 666, and the amino acid L at position 667, numbered according to SEQ ID NO: 6445.
17. The AAV capsid variant of claim 16, wherein the amino acid sequence of SPHSKA (SEQ ID NO: 941) is present immediately subsequent to amino acid 455, numbered according to SEQ ID NO: 6437,446323376583.1Attorney Docket No.: V2071-3049PCT6443, or 6445.
18. The AAV capsid variant of claim 16 or 17. which comprises:(i) an amino acid sequence at least 95% or at least 98% identical to amino acids 203-742 of any one of SEQ ID NOs: 6437, 6443, or 6445;(ii) an amino acid sequence at least 95% or at least 98% identical to amino acids 138-742 of any one of SEQ ID NOs: 6437, 6443, or 6445; and / or(iii) an amino acid sequence at least 95% or at least 98% identical to any one of SEQ ID NOs: 6437, 6443, or 6445.
19. The AAV capsid variant of any one of claims 16-18, which comprises:(i) the amino acid sequence of amino acids 203-742 of any one of SEQ ID NOs: 6437, 6443, or 6445;(ii) the amino acid sequence of amino acids 138-742 of any one of SEQ ID NOs: 6437, 6443, or 6445; and / or(iii) the amino acid sequence of any one of SEQ ID NOs: 6437, 6443. or 6445.
20. The AAV capsid variant of any one of claims 1-19, wherein VR-IV comprises amino acids 449- 460, numbered according to SEQ ID NO: 138.
21. The AAV capsid variant of any one of claims 1-20, which is capable of evading antibody neutralization.
22. The AAV capsid variant of any one of claims 1-21, which has an increased tropism for a brain cell or a brain tissue, relative to the tropism of a wild-type AAV9 capsid protein comprising the amino acid sequence of SEQ ID NO: 138.
23. A polynucleotide encoding the AAV capsid variant of any one of claims 1-24, optionally wherein the polynucleotide comprises the nucleotide sequence of any one of SEQ ID NOs: 6464-6466, or a nucleotide sequence at least 90%. at least 95%, or at least 98% identical thereto.
24. A peptide comprising the amino acid sequence of any one of SEQ ID NOs: 78-199, 989, 4488- 4672, or 6427-6436, or a peptide comprising no more than one or two different amino acids relative to any one of SEQ ID NOs: 78-199, 989, 4488-4672, or 6427-6436.
25. An AAV particle comprising the AAV capsid variant of any one of claims 1-22, an AAV capsid variant encoded by the polynucleotide of claim 23, or an AAV capsid variant comprising the peptide447323376583.1Attorney Docket No.: V2071-3049PCT of claim 24.
26. The AAV particle of claim 32. which comprises a nucleotide sequence encoding a payload comprising a protein or functional variant thereof, an antibody or antibody fragment, an enzyme, a component of a gene editing system, or an inhibitory' RNAi (e.g., a dsRNA, siRNA, shRNA, pre- miRNA. pri-miRNA. miRNA, stRNA, IncRNA, piRNA, or snoRNA).
27. The AAV particle of claim 35, which further comprises:(i) a promoter operably linked to the nucleotide sequence encoding the payload;(ii) a 5 ’ inverted terminal repeat (ITR) and / or a 3 ’ ITR;(iii) an enhancer;(iv) a Kozak sequence;(v) an intron;(vi) an exon;(vii) a nucleotide sequence encoding a miR binding site; and / or(viii) a polyadenylation (poly A) sequence.
28. A vector comprising a polynucleotide encoding the AAV capsid variant of any one of claims 1-22, the polynucleotide of claim 23, or a polynucleotide encoding the peptide of claim 24.
29. A cell, e.g., a host cell, comprising the AAV capsid variant of any one of claims 1-22, the polynucleotide of claim 23, the peptide of claim 24, the AAV particle of any one of claims 25-27, or the vector of claim 28.
30. The cell of claim 29, which is a mammalian cell or an insect cell.
31. The cell of claim 29 or 30, which is a cell of a brain region or a spinal cord region.
32. The cell of any one of claims 29-31 , which is a cell of the a putamen, caudate, entorhinal cortex, hippocampus, thalamus, substantia nigra, motor cortex, frontal cortex, temporal cortex, cerebral cortex, dentate nucleus, Lateral Geniculate Nucleus (LGN), thoracic spinal cord, cervical spinal cord, and / or lumbar spinal cord.
33. The cell of any one of claims 30-32, which is a neuron or an astrocyte.
34. A method of making an AAV particle, comprising448323376583.1Attorney Docket No.: V2071-3049PCT(i) providing a host cell comprising a viral genome and a polynucleotide encoding the AAV capsid variant of any one of claims 1-22; and(ii) incubating the host cell under conditions suitable to enclose the viral genome in the AAV capsid variant; thereby making the AAV particle.
35. A pharmaceutical composition comprising the AAV particle of any one of claims 25-28, an AAV particle comprising the AAV capsid variant of any one of claims 1-22, an AAV particle comprising the peptide of claim 24, and a pharmaceutically acceptable excipient.
36. A method of delivering a payload to a cell or tissue (e.g., a CNS cell or a CNS tissue), comprising administering an effective amount of the pharmaceutical composition of claim 35, the AAV particle of any one of claims 25-28, an AAV particle comprising the AAV capsid variant of any one of claims 1-22, or an AAV particle comprising the peptide of claim 24.
37. The method of claim 36, wherein the cell is a cell of a brain region or a spinal cord region.
38. The method of claim 36 or 37, wherein the cell is a cell of the a putamen, caudate, entorhinal cortex, hippocampus, thalamus, substantia nigra, motor cortex, frontal cortex, temporal cortex, cerebral cortex, dentate nucleus, Lateral Geniculate Nucleus (LGN), thoracic spinal cord, cervical spinal cord, and / or lumbar spinal cord.
39. The method of any one of claims 36-38. wherein the cells is a neuron or an astrocyte.
40. The method of any one of claims 36-39, wherein the cell is within a subject.
41. The method of claim 40, wherein the subject has. has been diagnosed with having, or is at risk of having a neurological disorder, a neurodegenerative disorder, a neuro-oncological disorder, a muscular disorder, or a neuromuscular disorder.
42. A method of treating a subject having or diagnosed with having a neurological disorder, 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 35, the AAV particle of any one of claims 25-28, an AAV particle comprising the AAV capsid variant of any one of claims 1-22, or an AAV particle comprising the peptide of claim 24.449323376583.1Attorney Docket No.: V2071-3049PCT43. The method of claim 41 or 42, wherein the neurological disorder, neurodegenerative disorder, muscular disorder, neuromuscular disorder, or neuro-oncological disorder is Huntington’s Disease, Amyotrophic Lateral Sclerosis (ALS). Gaucher Disease, Dementia with Lewy’ Bodies, Parkinson’s disease, Spinal Muscular Atrophy, Alzheimer's Disease, a leukodystrophy (e g., Alexander disease, autosomal dominant leukodystrophy with autonomic diseases (ADLD), Canavan disease, cerebrotendinous xanthomatosis (CTX). metachromatic leukodystrophy (MLD). Pelizaeus- Merzbacher disease, or Refsum disease), or a cancer (e.g., a HER2 / neu positive cancer or a glioblastoma).
44. The method of any one of claims 40-43, wherein the AAV particle or pharmaceutical composition is administered to the subject intravenously, via intra-cistema inagna injection (ICM), intracerebrally, intrathecally, intracerebroventricularly, via intraparenchymal administration, or intramuscularly.
45. The pharmaceutical composition of claim 35, the AAV particle of any one of claims 25-28, an AAV particle comprising the AAV capsid variant of any one of claims 1-22, or an AAV particle comprising the peptide of claim 24, for use in a method of delivering a pay load to a cell or tissue.
46. The pharmaceutical composition of claim 35, the AAV particle of any one of claims 25-28, an AAV particle comprising the AAV capsid variant of any one of claims 1-22, or an AAV particle comprising the peptide of claim 24. for use in a method of treating a neurological disorder, a neurodegenerative disorder, a muscular disorder, a neuromuscular disorder, or a neuro-oncological disorder.
47. The pharmaceutical composition of claim 35, the AAV particle of any one of claims 25-28, an AAV particle comprising the AAV capsid variant of any one of claims 1-22, an AAV particle comprising the peptide of claim 24, for use in the manufacture of a medicament.
48. Use of the pharmaceutical composition of claim 35, the AAV particle of any one of claims 25-28. an AAV particle comprising the AAV capsid variant of any one of claims 1-22, or an AAV particle comprising the peptide of claim 24, in the manufacture of a medicament for treating a neurological disorder, a neurodegenerative disorder, a muscular disorder, a neuromuscular disorder, or a neuro- oncological disorder.
49. Use of the pharmaceutical composition of claim 35, the AAV particle of any one of claims 25-28, an AAV particle comprising the AAV capsid variant of any one of claims 1-22, or an AAV particle comprising the peptide of claim 24, in the manufacture of a medicament.450323376583.1