Compositions and methods for the treatment of TAU-related disorders

Abstract

The disclosure provides compositions and methods for the preparation, manufacture and use of an adeno-associated virus (AAV) particle for the vectorized delivery of an antibody molecule that binds to tau.

Description

COMPOSITIONS AND METHODS FOR THE TREATMENT OF TAU-RELATED DISORDERS RELATED APPLICATIONS

[0001] This application claims priority to U. S. Provisional Application No. 63 / 717,594 filed on November 7, 2024; the entire contents of which are hereby incorporated by reference in their entirety. FIELD OF THE DISCLOSURE

[0002] Described herein are compositions and methods relating to AAV particles for delivery of an anti-tau antibody molecule for use in the treatment of tau-related disorders (e.g., tauopathies).SEQUENCE LISTING

[0003] The present application is being filed along with a Sequence Listing in electronic format. The Sequence Listing file, entitled V2071-3058PCT_SL.xml, was created on August 29, 2025, and is 2,677,232 bytes in size. Tire information in electronic format of the Sequence Listing is incorporated herein by reference in its entirety.BACKGROUND

[0004] Tauopathies are a group of neurodegenerative diseases characterized by the dysfunction and / or aggregation of the microtubule associated protein tau. Tan is normally a very soluble protein known to associate with microtubules based on the extent of its phosphory lation. Tau is considered a critical component of intracellular trafficking processes, particularly in neuronal cells, given their unique and extended structure. Hyperphosphorylation of tau depresses its binding to microtubules and microtubule assembly activity. Further, hyperphosphorylation of tau renders it prone to misfolding and aggregation. In tauopathies, the tau becomes hyperphosphorylated, misfolds and aggregates as neurofibrillary tangles (NFT) of paired helical filaments (PHF), twisted ribbons or straight filaments. These NFT are largely considered indicative of impending neuronal cell death and thought to contribute to widespread neuronal cell loss, leading to a variety of behavioral and cognitive deficits.

[0005] Several approaches have been proposed for therapeutically interfering with progression of tau pathology and preventing the subsequent molecular and cellular consequences. Given that NFT are composed of hyperphosphorylated, misfolded and aggregated forms of tau, interference at each of these stages provides targets that can be pursued. Introducing agents that limit phosphorylation. block misfolding or prevent aggregation are promising strategies. It has also been suggested that introduction of anti-tau antibodies can prevent the trans-neuronal spread of tau pathology.

[0006] There remains a need for anti-tau antibodies for use in tauopathy treatment, diagnostics, and other applications. The present disclosure addresses this need with related compounds and methods described herein.SUMMARY

[0007] The present disclosure addresses the need in the art for improved methods for delivery of antibodies and antibody-based therapeutics targeting tau by providing novel AAV particles comprising an AAV capsid variant comprising viral genomes encoding an anti-tau antibody molecule and / or an antibody-based composition and methods of using the same for the treatment, prevention, diagnosis, and research of diseases, disorders and / or conditions associated with tau pathology.

[0008] Accordingly, in one aspect, the present disclosure provides an AAV particle comprising an AAV capsid variant and a nucleic acid encoding an antibody molecule which binds to tau (e.g., human tau), wherein the AAV capsid variant comprises: (a) one, two, three, four, or all of the amino acid R at position 584. the amino acid T at position 586, the amino acid L at position 588, the amino acid Q at position 589, and / or the amino acid L at position 590, numbered according to SEQ ID NO: 138; and (b) the amino acid sequence of HDSPHK (SEQ ID NO: 2) in hypervariable loop IV.

[0009] In another aspect, the present disclosure provides an AAV particle comprising an AAV capsid variant and a nucleic acid encoding an antibody molecule which binds to tau (e.g., human tau), wherein the AAV capsid variant comprises: (a) one, two. three, four, or all of the amino acid R at position 590, T at position 592, L at position 594, Q at position 595. and / or L at position 596, numbered according to SEQ ID NO: 981, 982, 6411, or 6412; and (b) the amino acid sequence of HDSPHK (SEQ ID NO: 2) in hypervariable loop IV.

[0010] In yet another aspect, the present disclosure provides an AAV particle comprising an AAV capsid variant and a nucleic acid encoding an antibody molecule which binds to tau (e.g., human tau), wherein the AAV capsid variant comprises: (a) the amino acid R at position 584, the amino acid T at position 586. the amino acid L at position 588, the amino acid Q at position 589, and the amino acid L at position 590, numbered according to SEQ ID NO: 138; and (b) the amino acid sequence of HDSPHK (SEQ ID NO: 2) in hypervariable loop IV.

[0011] In yet another aspect, the present disclosure provides an AAV particle comprising an AAV capsid variant and a nucleic acid encoding an antibody molecule which binds to tau (e.g., human tau), wherein the AAV capsid variant comprises: (a) the amino acid R at position 590, T at position 592, L at position 594, Q at position 595, and L at position 596, numbered according to SEQ ID NO: 981, 982, 6411, or 6412; and (b) the amino acid sequence of HDSPHK (SEQ ID NO: 2) in hypervariable loop IV.

[0012] In yet another aspect, the present disclosure provides an AAV particle comprising an AAV capsid variant and a nucleic acid encoding an antibody molecule which binds to tau (e.g., human tau), wherein the AAV capsid variant comprises: (a) one, two. three, four, or all of the amino acid R at position 584, the amino acid T at position 586, the amino acid L at position 588, the amino acid Q at position 589, and / orthe amino acid L at position 590, numbered according to SEQ ID NO: 138; and (b) the amino acid sequence of SPHSKA (SEQ ID NO: 941) in hypervariable loop IV.

[0013] In another aspect, the present disclosure provides an AAV particle comprising an AAV capsid variant and a nucleic acid encoding an antibody molecule which binds to tau (e.g., human tau), wherein the AAV capsid variant comprises: (a) one, two. three, four, or all of the amino acid R at position 590, T at position 592, L at position 594, Q at position 595, and / or L at position 596, numbered according to SEQ ID NO: 981, 982, 6411, or 6412; and (b) the amino acid sequence of SPHSKA (SEQ ID NO: 941) in hypervariable loop IV.

[0014] In yet another aspect, the present disclosure provides an AAV particle comprising an AAV capsid variant and a nucleic acid encoding an antibody molecule which binds to tau (e.g., human tau), wherein the AAV capsid variant comprises: (a) the amino acid R at position 584, the amino acid T at position 586, the amino acid L at position 588, the amino acid Q at position 589, and the amino acid L at position 590, numbered according to SEQ ID NO: 138; and (b) the amino acid sequence of SPHSKA (SEQ ID NO: 941) in hypervariable loop IV.

[0015] In yet another aspect, the present disclosure provides an AAV particle comprising an AAV capsid variant and a nucleic acid encoding an antibody molecule which binds to tau (e.g., human tau), wherein the AAV capsid variant comprises: (a) the amino acid R at position 590, T at position 592, L at position 594, Q at position 595, and L at position 596, numbered according to SEQ ID NO: 981, 982, 6411, or 6412; and (b) the amino acid sequence of SPHSKA (SEQ ID NO: 941) in hypervariable loop IV.

[0016] In yet another aspect, present disclosure provides an AAV particle comprising an AAV capsid variant and a nucleic acid encoding an antibody molecule which binds to tau (e.g., human tau), wherein the AAV capsid variant comprises: (a) one, two, three, four, or all of the amino acid R at position 584, the amino acid T at position 586, the amino acid L at position 588, the amino acid Q at position 589, and / or the amino acid L at position 590, numbered according to SEQ ID NO: 138; and (b) the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is present immediately subsequent to position 455, numbered according to the amino acid sequence of SEQ ID NO: 138.

[0017] In yet another aspect, present disclosure provides an AAV particle comprising an AAV capsid variant and a nucleic acid encoding an antibody molecule which binds to tau (e.g., human tau), wherein the AAV capsid variant comprises: (a) the amino acid R at position 584, the amino acid T at position 586, the amino acid L at position 588, the amino acid Q at position 589, and the amino acid L at position 590, numbered according to SEQ ID NO: 138; and (b) the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is present immediately subsequent to position 455, numbered according to the amino acid sequence of SEQ ID NO: 138.

[0018] In yet another aspect, present disclosure provides an AAV particle comprising an AAV capsid variant and a nucleic acid encoding an antibody molecule which binds to tau (e.g., human tau), wherein the AAV capsid variant comprises: (a) one, two, three, four or all of tire amino acid R at position 590, T at position 592, L at position 594, Q at position 595, and / or L at position 596, numbered according to SEQ ID NO: 981. 982, 6411, or 6412; and (b) tire amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is present immediately subsequent to position 455, numbered according to the amino acid sequence of SEQ ID NO: 981 or 6411.

[0019] In yet another aspect, present disclosure provides an AAV particle comprising an AAV capsid variant and a nucleic acid encoding an antibody molecule which binds to tau (e.g.. human tau), wherein the AAV capsid variant comprises: (a) the amino acid R at position 590, T at position 592, L at position 594, Q at position 595, and L at position 596, numbered according to SEQ ID NO: 981, 982, 6411, or 6412; and (b) 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 tire amino acid sequence of SEQ ID NO: 981 or 6411.

[0020] In yet another aspect, present disclosure provides an AAV particle comprising an AAV capsid variant and a nucleic acid encoding an antibody molecule which binds to tau (e.g., human tau), wherein the AAV capsid variant comprises: (a) one, two, three, four, or all of the amino acid R at position 584, the amino acid T at position 586, the amino acid L at position 588, the amino acid Q at position 589, and / or the amino acid L at position 590, numbered according to SEQ ID NO: 138; and (b) the amino acid sequence of HDSPHK (SEQ ID NO: 2), wherein the amino acid sequence is present immediately subsequent to position 453, numbered according to the amino acid sequence of SEQ ID NO: 138.

[0021] In yet another aspect, present disclosure provides an AAV particle comprising an AAV capsid variant and a nucleic acid encoding an antibody molecule which binds to tau (e.g., human tau), wherein the AAV capsid variant comprises: (a) the amino acid R at position 584, the amino acid T at position 586, the amino acid L at position 588, the amino acid Q at position 589, and the amino acid L at position 590, numbered according to SEQ ID NO: 138; and (b) the amino acid sequence of HDSPHK (SEQ ID NO: 2), wherein the amino acid sequence is present immediately subsequent to position 453, numbered according to the amino acid sequence of SEQ ID NO: 138.

[0022] In yet another aspect, present disclosure provides an AAV particle comprising an AAV capsid variant and a nucleic acid encoding an antibody molecule which binds to tau (e.g., human tau), wherein the AAV capsid variant comprises: (a) one, two. three, four or all of the amino acid R at position 590, T at position 592, L at position 594, Q at position 595, and / or L at position 596, numbered according to SEQ ID NO: 981, 982, 6411, or 6412; and (b) the amino acid sequence of HDSPHK (SEQ ID NO: 2), whereinthe amino acid sequence is present immediately subsequent to position 453, numbered according to the amino acid sequence of SEQ ID NO: 982 or 6412.

[0023] In yet another aspect, present disclosure provides an AAV particle comprising an AAV capsid variant and a nucleic acid encoding an antibody molecule which binds to tau (e.g., human tau), wherein the AAV capsid variant comprises: (a) the amino acid R at position 590, T at position 592, L at position 594, Q at position 595, and L at position 596, numbered according to SEQ ID NO: 981, 982, 6411, or 6412; and (b) 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 or 6412.

[0024] In yet another aspect, the present disclosure provides an AAV particle comprising an AAV capsid variant and a nucleic acid encoding an antibody molecule which binds to tau (e.g., human tau), wherein the AAV capsid variant comprises: (a) the amino acid R at position 584, the amino acid T at position 586, the amino acid L at position 588, the amino acid Q at position 589, and the amino acid L at position 590, numbered according to SEQ ID NO: 138; and (b) the amino acid sequence of SPHSKA (SEQ ID NO: 941) in hypervariable loop IV. In some embodiments, hypervariable loop IV comprises amino acids 449-460. numbered according to SEQ ID NO: 138. In some embodiments, tire amino acid sequence of SEQ ID NO: 941 is present immediately subsequent to position 455, numbered according to SEQ ID NO: 981. In some embodiments, the AAV capsid variant comprises the amino acid E at position 451, numbered according to SEQ ID NO: 981. In some embodiments, the AAV capsid variant comprises the amino acid V at position 453, numbered according to SEQ ID NO: 981. In some embodiments, the AAV capsid variant comprises the amino acid sequence of SPHSKA (SEQ ID NO: 941); the amino acid E at position 451. numbered according to SEQ ID NO: 981; the amino acid V at position 453, numbered according to SEQ ID NO: 3904 or 981; the amino acid R at position 590, numbered according to SEQ ID NO: 981; the amino acid T at position 592, numbered according to SEQ ID NO: 981; the amino acid L at position 594, numbered according to SEQ ID NO: 981; the amino acid Q at position 595, numbered according to SEQ ID NO: 981; and L at position 596, numbered according to SEQ ID NO: 981.

[0025] In yet another aspect, the present disclosure provides an AAV particle comprising an AAV capsid variant and a nucleic acid encoding an antibody molecule which binds to tau (e.g., human tau), wherein the AAV capsid variant comprises: (a) the amino acid R at position 584, the amino acid T at position 586, the amino acid L at position 588, the amino acid Q at position 589, and the amino acid L at position 590, numbered according to SEQ ID NO: 138; and (b) the amino acid sequence of SPHSKA (SEQ ID NO: 941) in hypervariable loop IV. In some embodiments, hypervariable loop IV comprises amino acids 449-460, numbered according to SEQ ID NO: 138. In some embodiments, the amino acid sequence of SEQ ID NO: 941 is present immediately subsequent to position 455, numbered according toSEQ ID NO: 981. In some embodiments, the AAV capsid variant comprises the amino acid E at position 451, numbered according to SEQ ID NO: 981. In some embodiments, the AAV capsid variant comprises the amino acid R at position 452, numbered according to SEQ ID NO: 981. In some embodiments, the AAV capsid variant comprises the amino acid V at position 453, numbered according to SEQ ID NO: 981. In some embodiments, the AAV capsid variant comprises the amino acid sequence of SPHSKA (SEQ ID NO: 941); the amino acid E at position 451, numbered according to SEQ ID NO: 981; the amino acid R at position 452, numbered according to SEQ ID NO: 981; the amino acid V at position 453, numbered according to SEQ ID NO: 36 or 981; the amino acid R at position 590, numbered according to SEQ ID NO: 981; the amino acid T at position 592, numbered according to SEQ ID NO: 981; the amino acid L at position 594, numbered according to SEQ ID NO: 981; the amino acid Q at position 595, numbered according to SEQ ID NO: 981; and L at position 596. numbered according to SEQ ID NO: 981.

[0026] In yet another aspect, the present disclosure provides an AAV particle comprising an AAV capsid variant and a nucleic acid encoding an antibody molecule which binds to tau (e.g., human tau), wherein the AAV capsid variant comprises (a) three, four, or all of the amino acid R at position 584, the amino acid T at position 586, the amino acid L at position 588, the amino acid Q at position 589, and / or the amino acid L at position 590, numbered according to SEQ ID NO: 138; and (b) the amino acid sequence of HDSPHK (SEQ ID NO: 2) in hypervariable loop IV; wherein the AAV capsid variant comprises an amino acid sequence at least 95% identical to the amino acid sequence of positions 203-736 of SEQ ID NO: 138. In some embodiments, hypervariable loop IV comprises amino acids 449-460, numbered according to SEQ ID NO: 138. In some embodiments, the AAV capsid variant 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. 6411. or 6412. In some embodiments, the AAV capsid variant comprises the amino acid R at position 584, T at position 586, L at position 588, Q at position 589, and L at position 590, numbered according to SEQ ID NO: 138 or 6414. In some embodiments, the amino acid sequence of HDSPHK (SEQ ID NO: 2) is present immediately subsequent to amino acid 453, numbered according to SEQ ID NO: 982. In some embodiments, the amino acid sequence of HDSPHK (SEQ ID NO: 2) is present at amino acids 454 to 459, numbered according to SEQ ID NO: 982 or 6412. In some embodiments, the AAV capsid variant comprises the amino acid sequence of amino acids 203-742 of SEQ ID NO: 6412, or an amino acid sequence at least 95% or at least 98% identical to amino acids 203-742 of SEQ ID NO: 6412. In some embodiments, the AAV capsid variant comprises the amino acid sequence of amino acids 138-742 of SEQ ID NO: 6412, or an amino acid sequence at least 95% or at least 98% identical to amino acids 138-742 of SEQ ID NO: 6412. In some embodiments, the AAV capsidvariant comprises the amino acid sequence of SEQ ID NO: 6412, or an amino acid sequence at least 95% or 98% identical thereto.

[0027] In yet another aspect, the present disclosure provides an AAV particle comprising an AAV capsid variant and a nucleic acid encoding an antibody molecule which binds to tau (e.g., human tau), wherein the AAV capsid variant comprises (a) three, four, or all of the amino acid R at position 584, the amino acid T at position 586, the amino acid L at position 588, the amino acid Q at position 589, and / or the amino acid L at position 590, numbered according to SEQ ID NO: 138; and (b) the amino acid sequence of SPHSKA (SEQ ID NO: 941) in hypervariable loop IV; wherein tire AAV capsid variant comprises an amino acid sequence at least 95% identical to the amino acid sequence of positions 203-736 of SEQ ID NO: 138. In some embodiments, hypervariable loop IV comprises amino acids 449-460, numbered according to SEQ ID NO: 138. In some embodiments, the AAV capsid variant 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, 6411, or 6412. In some embodiments, the AAV capsid variant comprises the amino acid R at position 584, T at position 586, L at position 588, Q at position 589, and L at position 590, numbered according to SEQ ID NO: 138 or 6414. In some embodiments, the amino acid sequence of SPHSKA (SEQ ID NO: 941) is present immediately subsequent to amino acid 455. numbered according to SEQ ID NO: 981. In some embodiments, the amino acid sequence of SPHSKA (SEQ ID NO: 941) is present at amino acids 456-461, numbered according to SEQ ID NO: 981 or 6411. In some embodiments, the AAV capsid variant comprises the amino acid sequence of amino acids 203-742 of SEQ ID NO: 6411, or an amino acid sequence at least 95% or at least 98% identical to amino acids 203-742 of SEQ ID NO: 6411. In some embodiments, the AAV capsid variant comprises the amino acid sequence of amino acids 138-742 of SEQ ID NO: 6411, or an amino acid sequence at least 95% or at least 98% identical to amino acids 138-742 of SEQ ID NO: 6411. In some embodiments, the AAV capsid variant comprises the amino acid sequence of SEQ ID NO: 6411, or an amino acid sequence at least 95% or 98% identical thereto.

[0028] In yet another aspect, the present disclosure provides an AAV particle comprising an AAV capsid variant described herein and a nucleic acid encoding an antibody molecule which binds to tau (e.g., human tau).

[0029] In some embodiments, the anti-tau antibody molecule binds to the N-terminal region, middomain region, C-terminal region, microtubule binding domain, or the proline-rich domain of a tau protein (e.g., a human tau protein comprising the amino acid sequence of SEQ ID NO: 9200). In some embodiments, the anti-tau antibody molecule binds to (a) all or a portion of (e.g., one or more residues within) amino acid residues (1) 9-18, (2) 15-25, (3) 25-30. and / or (4) 15-30. numbered according to SEQ ID NO: 9200; (b) all or a portion of (e.g., one or more residues within) amino acid residues (1) 125-131,(2) 204-222, (3) 234-246, (4) 234-259, and / or (5) 235-246, numbered according to SEQ ID NO: 9200; (c) an epitope which includes one or more of pT181, pS199, pS202, pT205, pT212, pS214, pT217, pT231, pS234, pS235, pS258, pS259, pS396, pS404, pS422, and / or pT217, numbered according to SEQ ID NO: 9200; (d) all or a portion of (one or more residues within) amino acid residues (1) 387-408 and / or (2) 409-436, numbered according to SEQ ID NO: 9200; (e) all or a portion of (e.g., one or more residues within) amino acid residues (1) 32-49. (2) 55-76, (3) 57-72, (4) 159-194, (5) 175-191. (6) 185-200, (7) 219-247, (8) 223-238, (9) 381-426, (10) 383-400, (11) 409-436, and / or (12) 413-430, numbered according to SEQ ID NO: 9200; (f) a conformational epitope which includes all or a portion of (e.g., one or more residues within) amino acid residues (1) 55-76, (2) 159-194, (3) 219-247, and / or (4) 381-426, numbered according to SEQ ID NO: 9200.

[0030] In some embodiments, the anti-tau antibody molecule comprises: (i) a heavy chain variable region comprising one, two, or three heavy chain complementary determining region (HCDR) sequences of any one of the anti-tau antibody molecules described herein (e.g., an antibody molecule listed in Tables 7-16, 13A, 13B, and 13C); and / or(ii) a light chain variable region comprising one, two, or three light chain complementary determining region (LCDR) sequences of any one of the anti-tau antibody molecules described herein (e.g., an antibody molecule listed in Tables 7-16. 13A, 13B, and 13C).

[0031] In some embodiments, the anti-tau antibody molecule comprises: (i) a heavy chain variable region (VH) comprising the amino acid sequence of the VH of any one of the anti-tau antibody molecules described herein (e.g., tire VH sequence of an antibody molecule listed in Tables 7-16, 13A, 13B, and 13C), or an amino acid sequence having at least 80% (e.g., 85, 90. 95, 96, 97, 98, or 99%) sequence identity to the VH sequence of any one of the anti-tau antibody molecules described herein (e.g., the VH sequence of an antibody molecule listed in Tables 7-16, 13A, 13B, and 13C), or an amino acid sequence having at least one, two or three modifications, but not more than 30, 20 or 10 modifications, to the amino acid sequence of the VH of any of the anti-tau antibody molecules described herein (e.g., the VH sequence of an antibody molecule listed in Tables 7-16, 13A, 13B, and 13C); and / or (ii) a light chain variable region (VL) comprising the amino acid sequence of the VL of any one of the anti-tau antibody molecules described herein (e.g., the VL sequence of an antibody molecule listed in Tables 7-16, 13A, 13B, and 13C), or an amino acid sequence having at least 80% (e.g., 85, 90, 95, 96, 97, 98, or 99%) sequence identity to the VL sequence of any one of the anti-tau antibody molecules described herein (e.g., the VL sequence of an antibody molecule listed in Tables 7-16, 13A, 13B, and 13C), or an amino acid sequence having at least one, two or three modifications, but not more than 30, 20 or 10 modifications, to the amino acid sequence of the VL of any of the anti-tau antibody molecules described herein (e.g., the VL sequence of an antibody molecule listed in Tables 7-16, 13A, 13B, and 13C).

[0032] In some embodiments, the anti-tau antibody molecule comprises (a) the HCDR1, HCDR2, and / or HCDR3 sequences, and / or LCDR1, LCDR2, and / or LCDR3 sequences, (b) the VH and / or VL sequences, or (c) the heavy chain and / or light chain sequences of IPN002, AT8, PT3, UCB, PT76, PHF1, C10.2. V0004, V0009, V0022, V0023, V0024, or V0052 (as described, e.g., in WO2020223276 and WO2021 / 211753, the entire of contents of which are hereby incorporated by reference in their entirety), or Abl, Ab2, Ab3, Ab4, or Ab5. In some embodiments, tire anti-tau antibody molecule has at most one, two, or three substitutions (e.g., conservative amino acid substitutions) in a CDR relative to the HCDR1-3 and LCDR1-3 sequences of IPN002, AT8, PT3, UCB, PT76, PHF1, C10.2, V0004, V0009, V0022, V0023, V0024, or V0052. In some embodiments, tire anti-tau antibody molecule comprises a VH sequence having at least 80% (e.g., 85, 90, 95. 96, 97, 98, or 99%) sequence identity to the VH sequence of any one of IPN002. AT8. PT3, UCB, PT76, PHF1, C10.2, V0004, V0009, V0022, V0023, V0024, V0052, Abl, Ab2, Ab3, Ab4, or Ab5, and / or a VL sequence having at least 80% (e.g., 85, 90, 95, 96, 97, 98, or 99%) sequence identity to the VL sequence of any one of IPN002, AT8, PT3, UCB, PT76, PHF1, C10.2, V0004, V0009, V0022, V0023, V0024, V0052, Abl, Ab2, Ab3, Ab4, or Ab5. In some embodiments, the anti-tau antibody molecule comprises a VH sequence having at least one, tw o. or three modifications, but not more than 30. 20, or 10 modifications, relative to the VH sequence of any one of IPN002. AT8. PT3, UCB. PT76, PHF1, C10.2, V0004, V0009, V0022, V0023, V0024, V0052, Abl, Ab2, Ab3, Ab4, or Ab5, and / or a VL sequence having at least one, two, or three modifications, but not more than 30, 20, or 10 modifications, relative to the VL sequence of any one of IPN002, AT8, PT3, UCB, PT76, PHF1, C10.2, V0004, V0009, V0022, V0023, V0024, V0052, Abl, Ab2, Ab3, Ab4, or Ab5.

[0033] In yet another aspect, the present disclosure provides an antibody molecule that binds to human tau, which comprises a heavy chain variable region (VH) comprising a heavy chain complementary determining region 1 (HCDR1), a heavy chain complementary determining region 2 (HCDR2), and a heavy chain complementary determining region 3 (HCDR3) and / or a light chain variable region (VL) comprising a light chain complementary determining region 1 (LCDR1), a light chain complementary determining region 2 (LCDR2), and a light chain complementary determining region 3 (LCDR3), wherein (a) the HCDR1, HCDR2, HCDR3. LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 64, 1554. 1557, 1567, 1565, and 1566, respectively; (b) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1553, 1554, 1552, 1567, 1565, and 1566, respectively; (c) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1555, SEQ ID NO: 1556, SEQ ID NO: 1557, SEQ ID NO: 1568, RVS, and SEQ ID NO: 1566, respectively; or (d) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1550, 1551, 1552, 1564, 1565, and 1566, respectively. In some embodiments, the antibody is a humanized antibody.

[0034] In yet another aspect, the present disclosure provides an antibody molecule that binds to human tau, which comprises a heavy chain variable region (VH) comprising a heavy chain complementary determining region 1 (HCDR1), a heavy chain complementary’ determining region 2 (HCDR2), and a heavy chain complementary determining region 3 (HCDR3) and / or a light chain variable region (VL) comprising a light chain complementary determining region 1 (LCDR1), a light chain complementary determining region 2 (LCDR2), and a light chain complementary determining region 3 (LCDR3), wherein: (a) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 64, 1554, 1557, 1567, 1565, and 1566, respectively; (b) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1553. 1554, 1552, 1567, 1565, and 1566, respectively; (c) the HCDR1, HCDR2, HCDR3, LCDR1. LCDR2. and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1555, SEQ ID NO: 1556, SEQ ID NO: 1557, SEQ ID NO: 1568, RVS, and SEQ ID NO: 1566, respectively; or (d) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1550, 1551, 1552, 1564, 1565, and 1566, respectively; and wherein: (i) the VH comprises an amino acid sequence comprising one, two, three, four, five, six, seven, eight, nine, or all of: an amino acid other than Q at position 5. P at position 7, T at position 9, L at position 11, V at position 12, N at position 19, L at position 20, K at position 67, A at position 68. and / or S at position 76. numbered according to SEQ ID NO: 1562; and / or (ii) the VL comprises and amino acid sequence comprising one, two, or all of: an amino acid other than D at position 17, Q at position 18, and / or G at position 68, numbered according to SEQ ID NO: 1573.

[0035] In yet another aspect, the present disclosure provides antibody molecule that binds to human tau, which comprises a heavy chain variable region (VH) comprising a heavy chain complementary determining region 1 (HCDR1), a heavy chain complementary' determining region 2 (HCDR2), and a heavy chain complementary determining region 3 (HCDR3) and / or a light chain variable region (VL) comprising a light chain complementary’ determining region 1 (LCDR1), a light chain complementary’ determining region 2 (LCDR2), and a light chain complementary’ determining region 3 (LCDR3), yvherein: (a) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 64, 1554, 1557, 1567, 1565. and 1566, respectively: (b) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1553, 1554, 1552, 1567, 1565, and 1566, respectively; (c) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1555, SEQ ID NO: 1556, SEQ ID NO: 1557, SEQ ID NO: 1568, RVS, and SEQ ID NO: 1566, respectively; or (d) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1550, 1551, 1552, 1564, 1565, and 1566. respectively; and wherein: (i) the VH comprises an amino acid sequencecomprising one, two, three, four, five, six, seven, eight, or all of: a V at position 5, an S at position 7, an A at position 9, a V at position 11, a K at position 12, a K at position 19, a V at position 20, an R at position 67, and / or a V at position 68, numbered according to SEQ ID NO: 1562; and / or (ii) the VL comprises and amino acid sequence comprising one, two, or all of: Q or E at position 17, P or R at position 18, and / or S at position 68, numbered according to SEQ ID NO: 1573.

[0036] In yet another aspect, the present disclosure provides antibody molecule that binds to human tau, which comprises a heavy chain variable region (VH) comprising a heavy chain complementary determining region 1 (HCDR1), a heavy chain complementary determining region 2 (HCDR2), and a heavy chain complementary determining region 3 (HCDR3) and / or a light chain variable region (VL) comprising a light chain complementary detennining region 1 (LCDR1), a light chain complementary determining region 2 (LCDR2), and a light chain complementary determining region 3 (LCDR3), wherein: (a) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 64, 1554, 1557, 1567, 1565, and 1566, respectively; (b) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1553, 1554, 1552, 1567, 1565, and 1566, respectively; (c) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1555, SEQ ID NO: 1556, SEQ ID NO: 1557, SEQ ID NO: 1568, RVS, and SEQ ID NO: 1566, respectively; or (d) the HCDR1. HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1550, 1551, 1552, 1564, 1565, and 1566, respectively; and wherein: (i) the VH comprises an amino acid sequence at least 86% (e.g., at least 90, 92, 95, 96, 97, 98, or 99%) identical to the amino acid sequence of any one of SEQ ID NOs: 67-71; and / or (ii) the VL comprises an amino acid sequence at least 91% (e.g., at least 92, 95, 96, 97, 98. or 99%) identical to the amino acid sequence of any one of SEQ ID NOs: 72-76.

[0037] In yet another aspect, the present disclosure provides an antibody molecule that binds to human tau, which comprises a heavy chain variable region (VH) comprising a heavy chain complementary determining region 1 (HCDR1), a heavy chain complementary determining region 2 (HCDR2), and a heavy chain complementary determining region 3 (HCDR3) and a light chain variable region (VL) comprising a light chain complementary determining region 1 (LCDR1), a light chain complementary determining region 2 (LCDR2), and a light chain complementary detennining region 3 (LCDR3), wherein: (a) the HCDRL HCDR2, HCDR3, LCDRL LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 64, 1554, 1557, 1567, 1565, and 1566, respectively; (b) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1553, 1554, 1552, 1567, 1565, and 1566, respectively; (c) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2. and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1555, SEQ ID NO: 1556, SEQ ID NO: 1557, SEQ ID NO: 1568, RVS, and SEQ ID NO: 1566, respectively; or (d) the HCDR1, HCDR2.HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1550, 1551, 1552, 1564, 1565, and 1566, respectively; and wherein: (i) the VH comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, or all of: V at position 5; S at position 7; A at position 9; V at position 11; K at position 12; S at position 14; A at position 16; K at position 19; V at position 20; R at position 38; Q at position 39; A at position 40; Q at position 43; R at position 67; V at position 68; I at position 71; R at position 72; D at position 73; T at position 74; T at position 76; T at position 84: and / or L at position 113, numbered according to SEQ ID NO: 1562; and (ii) the VL comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or all of: I at position 2; S at position 7; S at position 12; T at position 14; P at position 15; Q at position 17; P at position 18; Q at position 50; S at position 68; V at position 88; Y at position 92; Q at position 105; and / or V at position 109, numbered according to SEQ ID NO: 1573.

[0038] In yet another aspect, the present disclosure provides an antibody molecule that binds to human tau, which comprises a heavy chain variable region (VH) comprising a heavy chain complementary determining region 1 (HCDR1), a heavy chain complementary determining region 2 (HCDR2), and a heavy chain complementary determining region 3 (HCDR3) and / or a light chain variable region (VL) comprising a light chain complementary determining region 1 (LCDR1), a light chain complementary determining region 2 (LCDR2), and a light chain complementary determining region 3 (LCDR3). wherein: (a) the HCDR1. HCDR2, HCDR3, LCDR1. LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 64, 1554, 1557, 1567, 1565, and 1566, respectively; (b) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1553, 1554, 1552, 1567, 1565, and 1566, respectively; (c) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1555, SEQ ID NO: 1556, SEQ ID NO: 1557, SEQ ID NO: 1568, RVS, and SEQ ID NO: 1566, respectively; or (d) the HCDR1, HCDR2. HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1550, 1551.1552, 1564, 1565, and 1566, respectively; and wherein: (i) the VH comprises the amino acid sequence of SEQ ID NO: 69, or an amino acid sequence at least 86% (e.g., at least 90, 92, 95, 96, 97, 98, or 99%) identical to the amino acid sequence of SEQ ID NO: 69; and / or (ii) the VL comprises the amino acid sequence of SEQ ID NO: 73, or an amino acid sequence at least 91% (e g., at least 92, 95, 96, 97, 98, or 99%) identical to the amino acid sequence of SEQ ID NO: 73.

[0039] In yet another aspect, the present disclosure provides an antibody molecule that binds to human tau, which comprises a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 69, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 73.

[0040] In yet another aspect, the present disclosure provides an antibody molecule that binds to human tau, which comprises a heavy chain (HC) comprising the amino acid sequence of SEQ ID NO: 172, and a light chain (LC) comprising the amino acid sequence of SEQ ID NO: 176.

[0041] In some embodiments, the anti-tau antibody molecules have a heavy chain constant region and / or light chain constant region listed in Table 17, or a sequence having at least 80% (e.g., 85, 90, 95, 96, 97, 98, or 99%) sequence identity to the heavy chain and / or light chain constant region sequences in Table 17, or an amino acid sequence having at least one, two or three modifications, but not more than 30, 20 or 10 modifications, to the amino acid sequence of the heavy chain and / or light chain constant region sequences in Table 17.

[0042] In some embodiments, the anti-tau antibody molecule competes for binding to tau with an antibody described herein (e.g., an antibody molecule listed in Tables 7-16, 13A, 13B, and 13C). In some embodiments, the anti-tau antibody molecule binds to the same epitope, substantially the same epitope as, an epitope that overlaps with, or an epitope that substantially overlaps with an antibody described herein (e.g., an antibody molecule listed in Tables 7-16, 13A, 13B, and 13C).

[0043] In some embodiments, the anti-tau antibody molecule comprises one or more of (a) an Fc region or functional variant thereof, e.g., an Fc region with altered effector function (e.g., reduced affinity for Fc receptor, reduced ADCC, reduced CDC), (b) a signal sequence, (c) a linker (e.g., a linker listed in Table 19)

[0044] In some embodiments, the anti-tau antibody molecule is a multispecific antibody molecule comprising at least two antigen-binding domains (e.g., a bispecific antibody molecule).

[0045] In some embodiments, the AAV particle comprises a viral genome comprising one or more of the following: a promoter operably linked to the nucleic acid sequence encoding the antibody molecule, a poly A sequence, an inverted terminal repeat (ITR) sequence (positioned 5’ and / or 3’ relative to the encoded antibody molecule), an enhancer, a Kozak sequence (e.g., GCCGCCACCATG (SEQ ID NO: 9021) or GAGGAGCCACC (SEQ ID NO: 9022)), an intron region, and / or an exon region described herein. In some embodiments, the viral genome comprises a nucleotide sequence encoding a miR binding site described herein.

[0046] In some embodiments, the viral genome is single stranded or self-complementary. In some embodiments, the viral genome further comprises a nucleotide sequence encoding a Rep protein described herein.

[0047] Also provided herein are cells (e.g., a host cell) comprising an AAV particle described herein. In some embodiments, the cell is a mammalian cell (e.g., a cell of a brain region, such as a neuron, astrocyte, or glial cell) or an insect cell.

[0048] In yet another aspect, provided herein is a method of making an AAV particle described herein, comprising (a) providing a host cell comprising a viral genome; and (b) incubating the host cell under conditions suitable to enclose the viral genome in an AAV capsid variant, c.g., an AAV capsid variant described herein, thereby making the AAV particle.

[0049] In yet another aspect, provided herein is a pharmaceutical composition comprising an AAV particle described herein, and a carrier (e.g., a pharmaceutically acceptable excipient).

[0050] In yet another aspect, provided herein is a method of delivering a payload to a cell or tissue (e.g., CNS cell or CNS tissue) comprising administering an effective amount of a pharmaceutical composition described herein or an AAV particle described herein. In some embodiments, the cell or tissue is within a subject.

[0051] In yet another aspect, provided herein is a method of treating a subject having or diagnosed with having a neurological disorder (e.g., a neurodegenerative disorder), tau-related disease, or tauopathy, comprising administering to the subject an effective amount of the pharmaceutical composition described herein, or an AAV particle comprising an AAV capsid variant described herein described herein. In some embodiments, the AAV particles, compositions, and methods may, for example, be used for treating a tau-related disorder (e.g., disease associated with expression of tau, neurological (e.g., neurodegenerative) disorders, and / or tauopathies), such as Alzheimer’s disease (AD), frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), frontotemporal lobar degeneration (FTLD), frontotemporal dementia (FTD), chronic traumatic encephalopathy (CTE), progressive Supranuclear Palsy (PSP). Down's syndrome, Pick's disease, corticobasal degeneration (CBD), corticobasal syndrome, amyotrophic lateral sclerosis (ALS). prion diseases, Creutzfeldt-Jakob disease (CJD), multiple system atrophy, tangle-only dementia, and progressive subcortical gliosis.

[0052] In some embodiments, the AAV particle is administered to the subject intravenously, via intra-cistcma magna injection (ICM), intracerebrally, intrathccally, intraccrcbrovcntricularly, via intraparenchymal administration, or intramuscularly, or via focused ultrasound (FUS), e.g., coupled with the intravenous administration of microbubbles (FUS-MB), or MRI-guided FUS coupled with intravenous administration.

[0053] In some embodiments, administration of the AAV particle or pharmaceutical composition described herein results in a decreased presence, level, and / or activity of a tau mRNA, tau protein, or combination thereof. In other embodiments, administration of the AAV particle or pharmaceutical composition described herein results in a increased presence, level, and / or activity of a tau mRNA, tau protein, or combination thereof.

[0054] Those skilled in the art will recognize or be able to ascertain using no more than routineexperimentation, many equivalents to the specific embodiments of the invention described herein. Such equivalents are intended to be encompassed by the following enumerated embodiments.Enumerated Embodiments1. An AAV particle comprising an AAV capsid variant and a nucleic acid encoding an antibody molecule which binds to tau (e.g., human tau), wherein the AAV capsid variant comprises:(a) one, two, three, four, or all of an amino acid other than H at position 584, S at position 586, Q at position 588, A at position 589, and / or Q at position 590, numbered according to SEQ ID NO: 138 or 6414; and(b) the amino acid sequence of HDSPHK (SEQ ID NO: 2) in hypervariable loop IV.2. An AAV particle comprising an AAV capsid variant and a nucleic acid encoding an antibody molecule which binds to tau (e.g.. human tau), wherein the AAV capsid variant comprises:(a) one, two, three, four, or all of an amino acid other than H at position 584, S at position 586, Q at position 588, A at position 589, and / or Q at position 590, numbered according to SEQ ID NO: 138 or 6414; and(b) the amino acid sequence of SPHSKA (SEQ ID NO: 941) in hypervariable loop IV.3. The AAV particle of embodiment 1 or 2, wherein the AAV capsid variant comprises:(i) an amino acid other than H at position 590, S at position 592, Q at position 594, A at position 595, and Q at position 596, numbered according to SEQ ID NO: 981, 982, 6411, or 6412; or(ii) an amino acid other than H at position 584, S at position 586, Q at position 588, A at position 589, and Q at position 590, numbered according to SEQ ID NO: 138 or 6414.4. The AAV particle of any one of embodiments 1-3, wherein the AAV capsid variant comprises:(i) one, tw o, three, four, or all of the amino acid R at position 590, T at position 592, L at position 594, Q at position 595, and / or L at position 596, numbered according to SEQ ID NO: 981, 982, 6411, or 6412; or(ii) one, two, three, four, or all of the amino acid R at position 584, T at position 586, L at position 588. Q at position 589, and / or L at position 590. numbered according to SEQ ID NO: 138 or 6414.5. An AAV particle comprising an AAV capsid variant and a nucleic acid encoding an antibody molecule which binds to tau (e.g., human tau), wherein the AAV capsid variant comprises:(a) one, two, three, four, or all of the amino acid R at position 584, T at position 586, L at position 588, Q at position 589, and / or L at position 590, numbered according to SEQ ID NO: 138 or 6414; and(b) the amino acid sequence of HDSPHK (SEQ ID NO: 2) in hypervariable loop IV.6. An AAV particle comprising an AAV capsid variant and a nucleic acid encoding an antibody molecule which binds to tau (e.g., human tau), wherein the AAV capsid variant comprises:(a) one, two, three, four, or all of the amino acid R at position 584, T at position 586, L at position 588. Q at position 589, and / or L at position 590. numbered according to SEQ ID NO: 138 or 6414; and (b) the amino acid sequence of SPHSKA (SEQ ID NO: 941) in hypervariable loop IV.7. Tire AAV capsid variant of any one of embodiments 1-6, wherein the AAV capsid variant comprises:(i) the amino acid R at position 590, T at position 592, L at position 594, Q at position 595, and L at position 596, numbered according to SEQ ID NO: 981, 982, 6411, or 6412; or(ii) the amino acid R at position 584, T at position 586, L at position 588, Q at position 589. and L at position 590, numbered according to SEQ ID NO: 138 or 6414.8. An AAV particle comprising an AAV capsid variant and a nucleic acid encoding an antibody molecule which binds to tau (e.g., human tau), wherein tire AAV capsid variant comprises:(a) the amino acid R at position 584, T at position 586, L at position 588, Q at position 589, and L at position 590, numbered according to SEQ ID NO: 138 or 6414: and(b) the amino acid sequence of HDSPHK (SEQ ID NO: 2) in hypervariable loop IV.9. An AAV particle comprising an AAV capsid variant and a nucleic acid encoding an antibody molecule which binds to tau (e.g., human tau), wherein tire AAV capsid variant comprises:(a) the amino acid R at position 584, T at position 586, L at position 588, Q at position 589, and L at position 590, numbered according to SEQ ID NO: 138 or 6414: and(b) the amino acid sequence of SPHSKA (SEQ ID NO: 941) in hypervariable loop IV.10. The AAV particle of any one of embodiments 1-9, w herein hypervariablc loop IV comprises amino acids 449-460, numbered according to SEQ ID NO: 138.11. The AAV particle of any one of embodiments 1, 3-5, 7, 8, or 10, 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: 138.12. The AAV particle of any one of embodiments 1, 3-5, 7, 8, 10, or 11, wherein the amino acid sequence HDSPHK (SEQ ID NO: 2) is present at amino acids 454-459, numbered according to SEQ ID NO: 982 or 6412.13. The AAV particle of any one of embodiments 1. 3-5, 7, 8, or 10-12, wherein tire AAV capsid variant comprises an amino acid sequence at least 95% or at least 98% identical to amino acids 203-742 of SEQ ID NO: 6412.14. The AAV particle of any one of embodiments 1, 3-5, 7, 8, or 10-13, wherein the AAV capsid variant comprises an amino acid sequence at least 95% or at least 98% identical to amino acids 138-742 of SEQ ID NO: 6412.15. The AAV particle of any one of embodiments 1, 3-5, 7, 8, or 10-14, wherein tire AAV capsid variant comprises an amino acid sequence at least 95% or at least 98% identical to the amino acid sequence of SEQ ID NO: 6412.16. The AAV particle of any one of embodiments 1. 3-5, 7, 8, or 10-15, wherein tire AAV capsid variant comprises the amino acid sequence of amino acids 203-742 of SEQ ID NO: 6412.17. The AAV particle of any one of embodiments 1, 3-5, 7, 8, or 10-16, wherein the AAV capsid variant comprises the amino acid sequence of amino acids 138-742 of SEQ ID NO: 6412.18. The AAV particle of any one of embodiments 1. 3-5, 7, 8, or 10-16, wherein tire AAV capsid variant comprises the amino acid sequence of SEQ ID NO: 6412.19. The AAV particle of any one of any one of embodiments 2-4, 6, 7, 9, or 10, 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: 138.20. The AAV particle of any one of embodiments 2-4. 6, 7, 9, 10, or 19, wherein the amino acid sequence SPHSKA (SEQ ID NO: 941) is present at amino acids 456-461, numbered according to SEQ ID NO: 981 or 6411.21. The AAV particle of any one of embodiments 2-4, 6, 7, 9, 10, 19, or 20, wherein the AAV capsid variant comprises an amino acid sequence at least 95% or at least 98% identical to amino acids 203-742 of SEQ ID NO: 6411.22. The AAV particle of any one of embodiments 2-4. 6, 7, 9, 10, or 19-21, wherein the AAV capsid variant comprises an amino acid sequence at least 95% or at least 98% identical to amino acids 138-742 of SEQ ID NO: 6411.23. The AAV particle of any one of embodiments 2-4, 6, 7, 9, 10, or 19-22, wherein tire AAV capsid variant comprises an amino acid sequence at least 95% or at least 98% identical to the amino acid sequence of SEQ ID NO: 6411.24. The AAV particle of any one of embodiments 2-4, 6, 7, 9, 10, or 19-23, wherein the AAV capsid variant comprises the amino acid sequence of amino acids 203-742 of SEQ ID NO: 6411.25. The AAV particle of any one of embodiments 2-4, 6, 7, 9, 10, or 19-24, wherein the AAV capsid variant comprises the amino acid sequence of amino acids 138-742 of SEQ ID NO: 6411.26. The AAV particle of any one of embodiments 2-4, 6, 7, 9, 10, or 19-25, wherein the AAV capsid variant comprises the amino acid sequence of SEQ ID NO: 6411.27. The AAV particle of any one of embodiments 2-4. 6, 7, 9, 10, or 19-26, wherein the AAV capsid variant further comprises the amino acid E at position 451, numbered according to SEQ ID NO: 981.28. The AAV particle of any one of claims 2-4, 6, 7, 9, 10, or 19-27, wherein the AAV capsid variant comprises the amino acid V at position 453, numbered according to SEQ ID NO: 981.29. The AAV particle of any one of claims 2-4, 6, 7, 9, 10, or 19-28, wherein the AAV capsid variant comprises the amino acid R at position 452, numbered according to SEQ ID NO: 981.30. The AAV particle of any one of embodiments 1, 3-5, 7, 8, or 10-17, wherein the nucleotide sequence encoding the AAV capsid variant comprises the nucleotide sequence of SEQ ID NO: 6416, or a nucleotide sequence at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical thereto.31. The AAV particle of any one of embodiments 2-4, 6, 7, 9, 10, or 19-29, wherein the nucleotide sequence encoding the AAV capsid variant comprises the nucleotide sequence of SEQ ID NO: 6415, or a nucleotide sequence at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical thereto.32. The AAV particle of any one of embodiments 1-31, wherein the AAV capsid variant 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: 138.33. The AAV particle of any one of embodiments 1-32, wherein the AAV capsid variant transduces a brain region (e.g., a putamen, caudate or motor cortex), optionally wherein the level of transduction is at least 5, 10, 15, 20. 25, 30, 35, 40, 45, 50, 55, 60, 65. or 100-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 1.34. The AAV particle of any one of embodiments 1-33, wherein the AAV capsid variant delivers an increased level of a payload to a brain region, optionally wherein the level of the payload is increased by at least 5, 10, 15. 17. 18, 19, 20, 25, 30, 35, 40, 45. 50, 55, 60, 65, 70, 80, 90, 100, 200, 300, or 400-fold, as compared to a reference sequence of SEQ ID NO: 138, e.g., when measured by an assay, e.g., a qRT-PCR or a qPCR assay (e.g., as described in Example 1), optionally wherein the brain region is a caudate or motor cortex.35. The AAV particle of any one of embodiments 1-34, wherein the AAV capsid variant shows preferential transduction in a brain region relative to the transduction in the dorsal root ganglia (DRG) and / or the liver.36. The AAV particle of any one embodiments 1-35, wherein the AAV capsid variant is capable of transducing at least 10%, 15%, 20%, 25%, 30%, 40%, 50%, 55%, 60%, or 65% of neurons (e.g., NeuN+ neurons) in a brain region (e.g., a putamen, caudate, entorhinal cortex, hippocampus, thalamus, substantia nigra, motor cortex, frontal cortex, or temporal cortex).37. The AAV particle of any one of embodiments 1-36, wherein the AAV capsid variant is capable of transducing at least 70%, 75%, 80%, 85%, 90%, or 95% of astrocytes (e.g., Sox9+ astrocytes) in a brain region (e.g., a putamen, caudate, entorhinal cortex, hippocampus, thalamus, substantia nigra, motor cortex, frontal cortex, or temporal cortex), e.g., when measured by an assay as described in Example 1.38. The AAV particle of any one of embodiments 1-37, wherein the AAV capsid variant is capable of transducing at least 90% or 95% of neurons, e.g., motor neurons (e.g., ChAT+ neurons) in tire spinal cord (e.g., the cervical spinal cord, the thoracic spinal cord, or the lumbar spinal cord), e.g., when measured by an assay as described in Example 1.39. The AAV particle of any one of embodiments 1-38, wherein the AAV capsid variant is capable of transducing at least 90%, 95%, or 98% of astrocytes (e.g., Sox9+ astrocytes) in the spinal cord (e.g., the cervical spinal cord, the thoracic spinal cord, or the lumbar spinal cord), e.g., when measured by an assay as described in Example 1.40. The AAV particle of any one of embodiments 1-39, wherein the AAV capsid variant is capable of transducing at least 20%, 25%, 30%, 40%, 50%, 55%. 60%. 65%. 70%. 75%, 80%, or 85% of cells in a brain region (e.g., a putamen, caudate, entorhinal cortex, hippocampus, thalamus, substantia nigra, motor cortex, frontal cortex, temporal cortex, cerebral cortex, cerebellar cortex, cerebellum, dentate nucleus, and / or Lateral Geniculate Nucleus (LGN)), e.g., when measured by an assay as described in Example 1.41. The AAV particle of any one of the preceding embodiments, wherein the AAV capsid variant is capable of transducing neuronal cells, e.g., NeuN+ neurons or dopaminergic neurons (e.g., dopaminergic neurons in the substantia nigra), e.g., tyrosine hydroxylase (TH)+ neurons.42. The AAV particle of any one of the preceding embodiments, wherein the AAV capsid variant is capable of transducing NeuN+ cells (e.g., NeuN+ neurons) and / or TH+ cells (e.g., TH+ neurons, e.g., dopaminergic neurons).43. The AAV particle of any one of the preceding embodiments, wherein the AAV capsid variant is capable of transducing non-neuronal cells, e.g., glial cells (e.g., oligodendrocytes or astrocytes).44. The AAV particle of embodiment 416, wherein the non-neuronal cells comprise glial cells, oligodendrocytes (e.g., Olig2 positive oligodendrocytes), or astrocytes (e.g.. Olig2 positive astrocytes or Sox9+ astrocytes).45. The AAV particle of any one of the preceding embodiments, wherein the AAV capsid variant is capable of transducing Olig2 positive cells, e.g., Olig2 positive astrocytes or Olig2 positive oligodendrocytes.46. The AAV particle of any one of the preceding embodiments, wherein the AAV capsid variant is capable of transducing Sox9+ cells, e.g., Sox9+ astrocytes.47. Tire AAV particle of any one of embodiments 1-46, wherein the antibody molecule binds to the N-tenninal region or an epitope within the N-terminal region of a tau protein (e.g., human tau).48. The AAV particle of any one of embodiments 1-47, wherein the antibody molecule binds to all or a portion of (e.g., one or more residues within) amino acid residues (a) 9-18, (b) 15-25, (c) 25-30, and / or (d) 15-30 of a tau protein, numbered according to SEQ ID NO: 9200.49. The AAV particle of any one of embodiments 1-48. wherein the antibody molecule binds to the middomain region or an epitope within the mid-domain region of a tau protein (e.g., human tau).50. Tire AAV particle of any one of embodiments 1-49, wherein the antibody molecule binds to all or a portion of (e.g., one or more residues within) amino acid residues (a) 125-131, (b) 204-222, (c) 234-246, (d) 234-259, and / or (e) 235-246, numbered according to SEQ ID NO: 9200.51. The AAV particle of any one of embodiments 1-50, wherein the antibody molecule binds to an epitope comprises one or more of pS422, pT181, pS199, pS202, pT205, pT212, pS214, pT217, pT231, pS234, pS235, pS258, pS259, pS396, pS404, and pS409, numbered according to SEQ ID NO: 9200.52. The AAV particle of any one of embodiments 1-51, wherein the antibody molecule binds to an epitope comprises (a) pS202 and pT205, (b) pT212 and pS214, (c) pT212 and pT217, (c) pT217 and pT231, (d) pT231 and pT234 (orpT235), (e) pS234 and pS259: (f) pS258, and (g) pS396 and pS404, numbered according to SEQ ID NO: 9200.53. Tire AAV particle of any one of embodiments 1-46, wherein the antibody molecule binds to the C-tenninal region or an epitope within the C-terminal region of a tau protein (e.g., human tau).54. The AAV particle of any one of embodiments 1-53, wherein the antibody molecule binds to all or a portion of (e.g., one or more residues within) amino acid residues (a) 387-408 and / or (b) 409-436, numbered according to SEQ ID NO: 9200.55. The AAV particle of any one of embodiments 1-54, wherein the antibody molecule binds to anepitope comprises pS409, numbered according to SEQ ID NO: 9200.56. The AAV particle of embodiment 259, wherein the antibody molecule binds to an epitope comprising pS422, numbered according to SEQ ID NO: 9200.57. The AAV particle of any one of embodiments 1-46. wherein the antibody molecule binds to the microtubule -binding domain or an epitope within the microtubule -binding domain of a tau protein (e.g.. human tau).58. Tire AAV particle of any one of embodiments 1-46, wherein the antibody molecule binds to the proline rich domain or an epitope within the proline rich domain of a tau protein (e.g., human tau).59. The AAV particle of any one of embodiments 1-46. wherein the antibody molecule binds to a region that overlaps with the N-terminal domain and the mid-domain of a tau protein (e.g., human tau).60. Tire AAV particle of any one of embodiments 1-46, wherein the antibody molecule binds to a region that overlaps with the mid-domain and the microtubule-binding domain of a tau protein (e.g., human tau).61. The AAV particle of any one of embodiments 1-46, wherein the antibody molecule binds to a region that overlaps with the mid-domain and the C-terminal domain of a tau protein (e.g., human tau).62. Tire AAV particle of any one of embodiments 1-46, wherein the antibody molecule binds to all or a portion of (e.g., one or more residues within) amino acid residues (a) 32-49, (b) 55-76, (c) 57-72, (d) 159-194. (e) 175-191, (f) 185-200, (g) 219-247, (h) 223-238. (i) 381-426, (j) 383-400, (k) 409-436, and / or (1) 413-430, numbered according to SEQ ID NO: 9200.63. Tire AAV particle of any one of embodiments 1-62, wherein the antibody molecule binds to all or a portion of (e.g., one or more residues within) amino acid residues (a) 55-76, (b) 159-194, (c) 219-247, and / or (d) 381-426, numbered according to SEQ ID NO: 9200.64. The AAV particle of any one of embodiments 1-63, wherein the antibody molecule binds to all or a portion of (e.g., one or more residues within) amino acid residues (a) 57-72, (b) 175-191, (c) 223-238, and / or (d) 383-400, numbered according to SEQ ID NO: 9200.65. The AAV particle of embodiment 62 and 64, wherein the antibody molecule binds to all or a portion of (e.g., one or more residues within) amino acid residues 223-238, numbered according to SEQ ID NO: 9200.66. The AAV particle of embodiment 65, wherein tire antibody molecule binds a conformational epitope which includes all or a portion of (e.g., one or more residues within) amino acid residues (a) 55-76, (b) 159-194, (c) 219-247, and / or (d) 381-426, numbered according to SEQ ID NO: 9200.67. The AAV particle of any one of embodiments 1-66, wherein the antibody molecule comprises:(i) a heavy chain variable region comprising the HCDR1, HCDR2, and HCDR3 sequences of any one of the anti-tau antibody molecules in Tables 7-16, 13A, 13B, and 13C; and / or(ii) a light chain variable region comprising the LCDR1, LCDR2, and LCDR3 sequences of anyone ofthe anti-tau antibody molecules in Tables 7-16. 13A, 13B, and 13C.68. Tire AAV particle of any one of embodiments 1-66, wherein the antibody- molecule comprises a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, and a light chain variable region comprising LCDR1, LCDR2, and LCDR3, of any one of the anti-tau antibody molecules in Tables 7-16, 13A, 13B, and 13C;optionally wherein at least one, two, three, four, five or all of the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and / or LCDR3 comprises at most one, two, or three substitutions (e.g., conservative amino acid substitutions) in a CDR relative to the CDR sequences of any one of the anti-tau antibody molecules in Tables 7-16, 13 A, 13B, and 13C.69. The AAV particle of any one of embodiments 1-68. wherein the antibody molecule comprises:(i) a heavy chain variable region (VH) comprising the amino acid sequence of the VH of any one ofthe anti-tau antibody molecules of an antibody molecule in Tables 7-16, 13A, 13B, and 13C, or an amino acid sequence having at least 80% (e.g., 85, 90, 95, 96, 97, 98, or 99%) sequence identity to the VH sequence of any one of the anti-tau antibody molecules in Tables 7-16, 13A, 13B, and 13C, or an amino acid sequence having at least one, two or three modifications, but not more than 30, 20 or 10 modifications, to the amino acid sequence of the VH of any of the anti-tau antibody molecules of an antibody molecule in Tables 7-16, 13A, 13B, and 13C; and / or(ii) a light chain variable region (VL) comprising the amino acid sequence of the VL of any? one of the anti-tau antibody molecules in Tables 7-16, 13A, 13B, and 13C, or an amino acid sequence having at least 80% (e.g., 85, 90, 95, 96, 97, 98, or 99%) sequence identity- to the VL sequence of any one of the anti-tau antibody molecules in Tables 7-16, 13A, 13B, and 13C, or an amino acid sequence having at leastone, two or three modifications, but not more than 30, 20 or 10 modifications, to the amino acid sequence of the VL of any of the anti-tau antibody molecules Tables 7-16, 13A, 13B, and 13C.70. Tire AAV particle of any one of embodiments 1-69, wherein the antibody molecule comprises the VH region and the VL region of any one of the anti-tau antibody molecule in Tables 7-16, 13A, 13B, and 13C.71. The AAV particle of any one of embodiments 1-70, wherein the antibody molecule comprises the HCDR1, HCDR2, and / or HCDR3 sequences, and / or LCDR1, LCDR2, and / or LCDR3 sequences of Abl, Ab2, Ab3, Ab4, Ab5, V0022, V0004, V0009, V0023, V0024, V0052, IPN002, AT8, PT3, UCB, PT76, PHFL or C10.2.72. The AAV particle of any one of embodiments 1-71, wherein the antibody molecule comprises a VH region comprising an HCDR1, HCDR2, and HCDR3, and VL region comprising an LCDR1, LCDR2, and LCDR3, wherein:(a) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 64, 1554, 1557, 1567, 1565. and 1566, respectively:(b) the HCDRL HCDR2, HCDR3, LCDRL LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1553, 1554, 1552, 1567, 1565, and 1566, respectively:(c) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1555, SEQ ID NO: 1556, SEQ ID NO: 1557, SEQ ID NO: 1568, RVS, and SEQ ID NO: 1566, respectively; or(d) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1550, 1551, 1552, 1564, 1565, and 1566, respectively;optionally wherein, the antibody molecule is a humanized antibody.73. The AAV particle of any one of embodiments 1-72, wherein the antibody molecule comprises a VH region comprising an HCDR1, HCDR2, and HCDR3, and VL region comprising an LCDR1, LCDR2, and LCDR3, wherein:(a) the HCDRL HCDR2, HCDR3, LCDRL LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 64, 1554, 1557, 1567, 1565, and 1566, respectively;(b) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1553, 1554, 1552, 1567, 1565, and 1566, respectively;(c) the HCDRL HCDR2, HCDR3, LCDRL LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1555, SEQ ID NO: 1556, SEQ ID NO: 1557, SEQ ID NO: 1568, RVS, and SEQ ID NO: 1566, respectively; or(d) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1550, 1551, 1552, 1564, 1565, and 1566, respectively;optionally wherein:(i) the VH comprises an amino acid sequence comprising one, two, three, four, five, six, seven, eight, nine, or all of: an amino acid other than Q at position 5, P at position 7, T at position 9, L at position 11, V at position 12, N at position 19, L at position 20, K at position 67, A at position 68, and / or S at position 76, numbered according to SEQ ID NO: 1562; and / or(ii) the VL comprises and amino acid sequence comprising one. two, or all of: an amino acid other than D at position 17, Q at position 18, and / or G at position 68, numbered according to SEQ ID NO: 1573.74. The AAV particle of any one of embodiments 1-73, wherein the antibody molecule comprises a VH region comprising an HCDR1, HCDR2, and HCDR3, and VL region comprising an LCDR1, LCDR2, and LCDR3, wherein:(a) the HCDR1. HCDR2, HCDR3, LCDR1. LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 64, 1554, 1557, 1567, 1565, and 1566, respectively;(b) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1553, 1554, 1552, 1567, 1565, and 1566, respectively;(c) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1555, SEQ ID NO: 1556, SEQ ID NO: 1557, SEQ ID NO: 1568, RVS, and SEQ ID NO: 1566, respectively; or(d) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1550, 1551, 1552, 1564, 1565, and 1566, respectively;optionally wherein:(i) the VH comprises an amino acid sequence comprising one, two, three, four, five, six, seven, eight, or all of: a V at position 5, an S at position 7, an A at position 9. a V at position 11, a K at position 12, a K at position 19, a V at position 20, an R at position 67, and / or a V at position 68, numbered according to SEQ ID NO: 1562; and / or(ii) the VL comprises and amino acid sequence comprising one, two, or all of: Q or E at position 17, P or R at position 18, and / or S at position 68, numbered according to SEQ ID NO: 1573.75. The AAV particle of any one of embodiments 1-74, wherein the antibody molecule comprises a VH region comprising an HCDR1, HCDR2, and HCDR3, and VL region comprising an LCDR1, LCDR2, and LCDR3, wherein:(a) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 64, 1554, 1557, 1567, 1565. and 1566, respectively;(b) the HCDR1. HCDR2, HCDR3, LCDR1. LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1553, 1554, 1552, 1567, 1565, and 1566, respectively:(c) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1555, SEQ ID NO: 1556, SEQ ID NO: 1557, SEQ ID NO: 1568, RVS, and SEQ ID NO: 1566, respectively; or(d) the HCDR1, HCDR2, HCDR3, LCDR1. LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1550, 1551. 1552. 1564, 1565, and 1566, respectively; andoptionally wherein:(i) tire VH comprises an amino acid sequence at least 86% (e.g., at least 90, 92, 95, 96, 97, 98, or 99%) identical to the amino acid sequence of any one of SEQ ID NOs: 67-71; and / or(ii) the VL comprises an amino acid sequence at least 91% (e.g., at least 92, 95, 96, 97, 98, or 99%) identical to the amino acid sequence of any one of SEQ ID NOs: 72-76.76. The AAV particle of any one of embodiments 1-75, wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 64, 1554, 1557, 1567, 1565, and 1566, respectively.77. The AAV particle of any one of embodiments 1-76, wherein the HCDR1, HCDR2, HCDR3, LCDRl, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1553, 1554, 1552, 1567, 1565, and 1566, respectively.78. The AAV particle of any one of embodiments 1-77, wherein the HCDR1, HCDR2, HCDR3, LCDRl, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1555, SEQ ID NO: 1556, SEQ ID NO: 1557, SEQ ID NO: 1568, RVS, and SEQ ID NO: 1566, respectively.79. The AAV particle of any one of embodiments 1-78, wherein the HCDR1, HCDR2, HCDR3, LCDRl, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1550, 1551, 1552, 1564, 1565, and 1566, respectively.80. The AAV particle of any one of embodiments 1-79, wherein the VH comprises an amino acid sequence comprising one, two, three, four, five, six, seven, eight, nine, or all of: an amino acid other than Q at position 5, P at position 7, T at position 9, L at position 11, V at position 12, N at position 19, L at position 20, K at position 67, A at position 68, and / or S at position 76, numbered according to SEQ ID NO: 1562.81. The AAV particle of any one of embodiments 1-80, wherein the VH comprises:(a) 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, or all of: an amino acid other than Q at position 5; an amino acid other than Q at position 6; an amino acid other than P at position 7; an amino acid other than T at position 9; an amino acid other than L at position 11; an amino acid other than V at position 12; an amino acid other than S at position 16; an amino acid other than N at position 19; an amino acid other than L at position 20; an amino acid otherthan I at position 48; an amino acid other than K at position 67; an amino acid other than A at position 68; an amino acid other than L at position 70; an amino acid other than S at position 76; an amino acid other than T at position 77; an amino acid other than V at position 79; an amino acid other than F at position 80; an amino acid other than I at position 81; an amino acid other than Q at position 82; an amino acid other than T at position 87; an amino acid other than S at position 91; and / or an amino acid other than S at position 113. numbered according to SEQ ID NO: 1562:(b) 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or all of: an amino acid other than Q at position 5; an amino acid otherthan P at position 7; an amino acid otherthan T at position 9; an amino acid other than L at position 11; an amino acid other than V at position 12; an amino acid other than S at position 16; an amino acid other than N at position 19; an amino acid other than L at position 20; an amino acid other than K at position 38; an amino acid other than K at position 67; an amino acid other than A at position 68; an amino acid other than L at position 70: an amino acid other than S at position 76; an amino acid other than T at position 77; an amino acid other than V at position 79; an amino acid other than F at position 80; an amino acid other than I at position 81; an amino acid other than Q at position 82; an amino acid other than T at position 87; an amino acid other than E at position 89; and / or an amino acid other than S at position 113, numbered according to SEQ ID NO: 1562;(c) 1, 2, 3.4, 5, 6, 7. 8, 9, 10, 11, 12, 13, 14. 15, 16, 17, 18, 19, 20, 21, or all of: an amino acid other than Q at position 5: an amino acid other than P at position 7; an amino acid other than T at position 9; an amino acid other than L at position 11; an amino acid other than V at position 12; an amino acid other than P at position 14; an amino acid other than S at position 16; an amino acid other than N at position 19; an amino acid other than L at position 20; an amino acid other than K at position 38; an amino acid other than E at position 39; an amino acid other than R at position 40; an amino acid otherthan H at position 43; an amino acid other than K at position 67; an amino acid other than A at position 68; an amino acid other than T at position 71; an amino acid other than V at position 72; an amino acid other than H at position 73; an amino acid other than K at position 74; an amino acid other than S at position 76; an amino acid other than S at position 84; and / or an amino acid other than S at position 113, numbered according to SEQ ID NO: 1562;(d) 1, 2. 3, 4, 5, 6. 7, 8, 9, 10, 11, 12, 13, 14. 15. 16, 17, 18, 19, or all of: an amino acid other than Q at position 1: an amino acid other than Q at position 5; an amino acid other than P at position 7; an amino acid other than T at position 9; an amino acid other than L at position 11; an amino acid other than V at position 12; an amino acid other than N at position 19; an amino acid other than L at position 20; an amino acid other than K at position 67; an amino acid other than A at position 68; an amino acid other than L at position 70; an amino acid other than S at position 76; an amino acid other than V at position 79; an amino acid other than F at position 80; an amino acid other than I at position 81; an amino acid other than Q at position 82; an amino acid other than S at position 85; an amino acid other than E at position 89, an amino acid other than S at position 113; and / or an amino acid other than T at position 115, numbered according to SEQ ID NO: 1562; or(e) 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 or all of: an amino acid other than Q at position 5: an amino acid other than P at position 7; an amino acid other than T at position 9; an amino acid other than L at position 11; an amino acid other than V at position 12; an amino acid other than S at position 16; an amino acid other than N at position 19; an amino acid other than L at position 20; an amino acid other than H at position 43; an amino acid other than I at position 48; an amino acid other than K at position 67; an amino acid other than A at position 68; an amino acid other than L at position 70; an amino acid other than S at position 76; an amino acid other than T at position 77; an amino acid other than T at position 87; and / or an amino acid other than S at position 91, numbered according to SEQ ID NO: 1562.82. The AAV particle of any one of embodiments 1-81, wherein the VH comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, or all of: an amino acid other than Q at position 5; an amino acid other than P at position 7; an amino acid other than T at position 9; an amino acid other than L at position 11; an amino acid other than V at position 12; an amino acid other than P at position 14; an amino acid other than S at position 16; an amino acid other than N at position 19; an amino acid other than L at position 20; an amino acid other than K at position 38; an amino acid other than E at position 39; an amino acid other than R at position 40; an amino acid other than H at position 43; an amino acid other than K at position 67; an amino acid other than A at position 68; an amino acid other than T at position 71; an amino acid other than V at position 72; an amino acid other than H at position 73; anamino acid other than K at position 74; an amino acid other than S at position 76; an amino acid other than S at position 84; and / or an amino acid other than S at position 113, numbered according to SEQ ID NO: 1562.83. The AAV particle of any one of embodiments 181, wherein the VH comprises 1, 2, 3, 4. 5, 6, 7, 8, 9, 10, 11, 12. 13. 14. 15, 16, 17, 18, 19, 20, 21. or all of: an amino acid other than Q at position 5; an amino acid other than Q at position 6; an amino acid other than P at position 7; an amino acid other than T at position 9; an amino acid other than L at position 11; an amino acid other than V at position 12; an amino acid other than S at position 16; an amino acid other than N at position 19; an amino acid other than L at position 20; an amino acid other than I at position 48; an amino acid other than K at position 67; an amino acid other than A at position 68; an amino acid other than L at position 70; an amino acid other than S at position 76; an amino acid other than T at position 77: an amino acid other than V at position 79; an amino acid other than F at position 80; an amino acid other than I at position 81; an amino acid other than Q at position 82; an amino acid other than T at position 87; an amino acid other than S at position 91; and / or an amino acid other than S at position 113, numbered according to SEQ ID NO: 1562.84. The AAV particle of any one of embodiments 1-81, wherein the VH comprises 1, 2. 3, 4, 5, 6. 7, 8, 9, 10, 11, 12. 13, 14, 15, 16, 17, 18, 19, or all of: an amino acid other than Q at position 1; an amino acid other than Q at position 5; an amino acid other than P at position 7; an amino acid other than T at position 9; an amino acid other than L at position 11; an amino acid other than V at position 12; an amino acid other than N at position 19; an amino acid other than L at position 20; an amino acid other than K at position 67; an amino acid other than A at position 68; an amino acid other than L at position 70; an amino acid other than S at position 76; an amino acid other than V at position 79; an amino acid other than F at position 80; an amino acid other than I at position 81; an amino acid other than Q at position 82: an amino acid other than S at position 85; an amino acid other than E at position 89, an amino acid other than S at position 113; and / or an amino acid other than T at position 115, numbered according to SEQ ID NO: 1562.85. The AAV particle of any one of embodiments 1-81, wherein the VH comprises 1, 2. 3, 4, 5, 6. 7, 8, 9, 10, 11, 12. 13, 14, 15, 16 or all of: an amino acid other than Q at position 5: an amino acid other than P at position 7; an amino acid other than T at position 9; an amino acid other than L at position 11; an amino acid other than V at position 12; an amino acid other than S at position 16; an amino acid other than N at position 19; an amino acid other than L at position 20; an amino acid other than H at position 43; an amino acid other than I at position 48; an amino acid other than K at position 67; an amino acid other thanA at position 68; an amino acid other than L at position 70; an amino acid other than S at position 76; an amino acid other than T at position 77; an amino acid other than T at position 87; and / or an amino acid other than S at position 91, numbered according to SEQ ID NO: 1562.86. The AAV particle of any one of embodiments 1-85, wherein the VH comprises an amino acid sequence comprising one, two, three, four, five, six. seven, eight, or all of: a V at position 5. an S at position 7, an A at position 9, a V at position 11, a K at position 12, a K at position 19, a V at position 20, an R at position 67, and / or a V at position 68, numbered according to SEQ ID NO: 1562.87. The AAV particle of any one of embodiments 1-86, wherein tire VH comprises:(a) 1, 2, 3.4, 5, 6, 7. 8, 9, 10, 11, 12, 13, 14. 15, 16, 17, 18, 19, 20, 21, or all of: V at position 5; E at position 6; S at position 7; A at position 9; V at position 11; K at position 12; A at position 16; K at position 19; V at position 20; M at position 48; R at position 67; V at position 68; I at position 70; A at position 76; S at position 77; A at position 79; Y at position 80; M at position 81; E at position 82; R at position 87; T at position 91; and / or T at position 113, numbered according to SEQ ID NO: 1562;(b) 1, 2, 3. 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or all of: V at position 5; S at position 7: A at position 9; V at position 11; K at position 12; A at position 16; K at position 19: V at position 20; R at position 38; R at position 67; V at position 68; M at position 70; I at position 76; S at position 77; A at position 79; Y at position 80; M at position 81; E at position 82; R at position 87; D at position 89; and / or L at position 113, numbered according to SEQ ID NO: 1562;(c) 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, or all of: V at position 5; S at position 7; A at position 9; V at position 11; K at position 12; S at position 14; A at position 16; K at position 19; V at position 20; R at position 38; Q at position 39; A at position 40; Q at position 43; R at position 67; V at position 68; I at position 71; R at position 72; D at position 73; T at position 74; T at position 76; T at position 84; and / or L at position 113, numbered according to SEQ ID NO: 1562;(d) 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or all of: E at position 1; V at position 5; S at position 7; A at position 9; V at position 11; K at position 12; K at position 19; V at position 20; R at position 67; V at position 68; M at position 70; I at position 76; A at position 79; Y at position 80; M at position 81; E at position 82; Rat position 85; D at position 89, L at position 113; and / or S at position 115, numbered according to SEQ ID NO: 1562; or(e) I, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 or all of: V at position 5; S at position 7; A at position 9; V at position 11; K at position 12; A at position 16; K at position 19; V at position 20; Q at position 43; M at position 48; R at position 67; V at position 68; M at position 70; T at position 76; S at position 77; R at position 87; and / or T at position 91, numbered according to SEQ ID NO: 1562.88. The AAV particle of any one of embodiments 1-226 or 240-252, 278, 288, 292, or 293, wherein the VH comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, or all of: V at position 5; S at position 7; A at position 9; V at position 11; K at position 12; S at position 14; A at position 16; K at position 19; V at position 20; R at position 38; Q at position 39; A at position 40; Q at position 43; R at position 67; V at position 68; I at position 71; R at position 72; D at position 73: T at position 74; T at position 76; T at position 84; and / or L at position 113. numbered according to SEQ ID NO: 1562.89. The AAV particle of any one of embodiments 1-88, wherein the VH comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, or all of: V at position 5; E at position 6; S at position 7; A at position 9; V at position 11; K at position 12; A at position 16; K at position 19; V at position 20; M at position 48; R at position 67; V at position 68; I at position 70; A at position 76: S at position 77; A at position 79; Y at position 80; M at position 81; E at position 82: R at position 87; T at position 91; and / or T at position 113, numbered according to SEQ ID NO: 1562.90. The AAV particle of any one of embodiments 1-888, wherein the VH comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or all of: E at position 1; V at position 5; S at position 7; A at position 9: V at position 11; K at position 12; K at position 19; V at position 20: R at position 67; V at position 68; M at position 70; I at position 76: A at position 79; Y at position 80; M at position 81; E at position 82; R at position 85: D at position 89, L at position 113: and / or S at position 115, numbered according to SEQ ID NO: 1562.91. The AAV particle of any one of embodiments 1-88, wherein the VH comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12. 13. 14, 15, 16 or all of: V at position 5: S at position 7: A at position 9: V at position 11; K at position 12; A at position 16; K at position 19; V at position 20: Q at position 43; M at position 48; R at position 67; V at position 68: M at position 70: T at position 76; S at position 77; R at position 87; and / or T at position 91, numbered according to SEQ ID NO: 1562.92. The AAV particle of any one of embodiments 1-88, wherein the VL comprises and amino acid sequence comprising one, two, or all of: an amino acid other than D at position 17, Q at position 18. and / or G at position 68, numbered according to SEQ ID NO: 1573.93. The AAV particle of any one of embodiments 1-91, wherein the VL comprises:(a) 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or all of: an amino acid other than T at position 7; an amino acid other than S at position 14; an amino acid other than D at position 17; an amino acid other than Q atposition 18; an amino acid other than L at position 42; an amino acid other than K at position 44; an amino acid other than K at position 50; an amino acid other than G at position 68; an amino acid other than L at position 88; an amino acid other than F at position 92; and / or an amino acid other than G at position 105, numbered according to SEQ ID NO: 1573;(b) 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or all of: an amino acid other than V at position 2; an amino acid other than T at position 7; an amino acid other than P at position 12; an amino acid other than S at position 14; an amino acid other than L at position 15; an amino acid other than D at position 17: an amino acid other than Q at position 18; an amino acid other than K at position 50; an amino acid other than G at position 68; an amino acid other than L at position 88; an amino acid other than F at position 92; an amino acid other than G at position 105; and / or an amino acid other than L at position 109, numbered according to SEQ ID NO: 1573;(c) 1, 2, 3. 4, 5, 6, 7. 8, 9, 10, 11, 12, 13. or all of: an amino acid other than V at position 2; an amino acid other than L at position 11; an amino acid other than T at position 14; an amino acid other than D at position 17; an amino acid other than Q at position 18; an amino acid other than L at position 42; an amino acid other than K at position 44; an amino acid other than S at position 48; an amino acid other than K at position 50; an amino acid other than G at position 68; an amino acid other than S at position 72; an amino acid other than S at position 81; an amino acid other than L at position 88; and / or an amino acid other than G at position 105, numbered according to SEQ ID NO: 1573;(d) 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or all of: an amino acid other than V at position 2; an amino acid other than V at position 3; an amino acid other than T at position 7; an amino acid other than S at position 14; an amino acid other than D at position 17; an amino acid other than Q at position 18; an amino acid other than L at position 42; an amino acid other than K at position 44; an amino acid other than K at position 50; an amino acid other than L at position 51; an amino acid other than G at position 68; and / or an amino acid other than L at position 88, numbered according to SEQ ID NO: 1573; or (e) 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, or all of: an amino acid other than D at position 1; an amino acid other than V at position 2; an amino acid other than M at position 4; an amino acid other than T at position 7; an amino acid other than L at position 9; an amino acid other than S at position 10; an amino acid other than P at position 12; an amino acid other than V at position 13; an amino acid other than L at position 15; an amino acid other than D at position 17; an amino acid other than Q at position 18; an amino acid other than S at position 20; an amino acid other than I at position 21; an amino acid other than S at position 48; an amino acid other than V at position 63; an amino acid other than G at position 68; an amino acid other than S at position 72; an amino acid other than K at position 79; an amino acid other than R at position 82; an amino acid other than V at position83; an amino acid other than A at position 85; and / or an amino acid other than G at position 89, numbered according to SEQ ID NO: 1573.94. The AAV particle of any one of embodiments 1-93, wherein the VL comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12. or all of: an amino acid other than V at position 2; an amino acid other than T at position 7; an amino acid other than P at position 12; an amino acid other than S at position 14; an amino acid other than L at position 15; an amino acid other than D at position 17: an amino acid other than Q at position 18; an amino acid other than K at position 50; an amino acid other than G at position 68; an amino acid other than L at position 88; an amino acid other than F at position 92; an amino acid other than G at position 105; and / or an amino acid other than L at position 109, numbered according to SEQ ID NO: 1573.95. The AAV particle of any one of embodiments 1-93, wherein the VL comprises 1, 2. 3, 4, 5, 6. 7, 8, 9, 10, or all of: an amino acid other than T at position 7; an amino acid other than S at position 14; an amino acid other than D at position 17; an amino acid other than Q at position 18; an amino acid other than L at position 42; an amino acid other than K at position 44; an amino acid other than K at position 50; an amino acid other than G at position 68; an amino acid other than L at position 88; an amino acid other than F at position 92; and / or an amino acid other than G at position 105. numbered according to SEQ ID NO: 1573.96. The AAV particle of any one of embodiments 1-93, wherein the VL comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, or all of: an amino acid other than V at position 2; an amino acid other than L at position 11; an amino acid other than T at position 14; an amino acid other than D at position 17; an amino acid other than Q at position 18; an amino acid other than L at position 42; an amino acid other than K at position 44; an amino acid other than S at position 48: an amino acid other than K at position 50; an amino acid other than G at position 68: an amino acid other than S at position 72; an amino acid other than S at position 81; an amino acid other than L at position 88; and / or an amino acid other than G at position 105, numbered according to SEQ ID NO: 1573.97. The AAV particle of any one of embodiments 1-96, wherein the VL comprises and amino acid sequence comprising one, two, or all of: Q or E at position 17, P or R at position 18. and / or S at position 68, numbered according to SEQ ID NO: 157398. The AAV particle of any one of embodiments 1-97, wherein the VL comprises:(a) 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or all of: S at position 7; T at position 14; Q at position 17; P at position 18; Q at position 42; R at position 44; R at position 50; S at position 68; V at position 88; Y at position 92; and / or Q at position 105, numbered according to SEQ ID NO: 1573;(b) 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or all of: I at position 2; S at position 7; S at position 12; T at position 14; P at position 15; Q at position 17; P at position 18; Q at position 50; S at position 68; V at position 88; Y at position 92; Q at position 105; and / or V at position 109, numbered according to SEQ ID NO: 1573;(c) 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, or all of: I at position 2; S at position 11; T at position 14; Q at position 17; P at position 18; Q at position 42; R at position 44; P at position 48; R at position 50; S at position 68; A at position 72; N at position 81; V at position 88; and / or Q at position 105, numbered according to SEQ ID NO: 1573;(d) 1, 2. 3, 4, 5, 6. 7, 8, 9, 10, 11, or all of: I at position 2; E at position 3; S at position 7; T at position 14; Q at position 17; P at position 18; Q at position 42; R at position 44; R at position 50; R at position 51; S at position 68; and / or V at position 88, numbered according to SEQ ID NO: 1573; or (e) 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, or all of: E at position 1; I at position 2; L at position 4; S at position 7; A at position 9; T at position 10; S at position 12; L at position 13; P at position 15; E at position 17; R at position 18; T at position 20: L at position 21; A at position 48; I at position 63; S at position 68; P at position 72; T at position 79; S at position 82; L at position 83; P at position 85: and / or A at position 89, numbered according to SEQ ID NO: 1573.99. The AAV particle of any one of embodiments 1-98, wherein the VL comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12. or all of: I at position 2; S at position 7; S at position 12; T at position 14; P at position 15; Q at position 17; P at position 18; Q at position 50; S at position 68; V at position 88; Y at position 92; Q at position 105; and / or V at position 109, numbered according to SEQ ID NO: 1573.100. The AAV particle of any one of embodiments 1-99, wherein the VL comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or all of: S at position 7; T at position 14; Q at position 17; P at position 18; Q at position 42; R at position 44; R at position 50; S at position 68; V at position 88; Y at position 92; and / or Q at position 105, numbered according to SEQ ID NO: 1573.101. The AAV particle of any one of embodiments 1-99, wherein the VL comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, or all of: I at position 2; S at position 11; T at position 14; Q at position 17; P at position 18; Q at position 42; R at position 44; P at position 48; R at position 50; S at position 68; A at position 72; N at position 81; V at position 88; and / or Q at position 105, numbered according to SEQ ID NO: 1573.102. The AAV particle of any one of embodiments 1-101, wherein:(i) the VH comprises one, two, three, or four framework regions, e.g., one, two, three, or all of a FRH1, FRH2, FRH3, and / or FRH4; optionally wherein the VH comprises from N-terminus to C-terminus, FRH1-CDRH1-FRH2-CDRH2-FRH3-CDRH3-FRH4; and / or(ii) the VL comprises one. two, three, or four framework regions, e.g., one, two. three, or all of a FRL1. FRL2, FRL3, and / or FRL4; optionally wherein the VL comprises from N tenninus to C-terminus, FRL 1 -CDRL 1 -FRL2-CDRL2-FRL3-CDRL3-FRL4.103. The AAV particle of embodiment 102, wherein:(a) (i) the FRH1 corresponds to positions 1-25 of a heavy chain variable region, numbered according to any one of SEQ ID NOs: 1562 or 67-71; the FRH2 corresponds to positions 36-49, numbered according to any one of SEQ ID NOs: 1562 or 67-71; the FRH3 corresponds to positions 67-96. numbered according to any one of SEQ ID NOs: 1562 or 67-71; and / or the FRH4 corresponds to positions 108-118, numbered according to any one of SEQ ID NOs: 1562 or 67-71; or(ii) the FRH1 corresponds to positions 1-30 of a heavy chain variable region, numbered according to any one of SEQ ID NOs: 1562 or 67-71; the FRH2 corresponds to positions 36-49, numbered according to any one of SEQ ID NOs: 1562 or 67-71; the FRH3 corresponds to positions 67-98. numbered according to any one of SEQ ID NOs: 1562 or 67-71: and / or the FRH4 corresponds to positions 108-118, numbered according to any one of SEQ ID NOs: 1562 or 67-71; and / or(b) the FRL1 corresponds to positions 1-23 of a light chain variable region, numbered according to any one of SEQ ID NOs: 72-76 or 1573; the FRL2 corresponds to positions 40-54 of a light chain variable region, numbered according to any one of SEQ ID NOs: 72-76 or 1573; the FRL3 corresponds to positions 62-93 of a light chain variable region, numbered according to any one of SEQ ID NOs: 72-76 or 1573; and / or the FRL4 corresponds to positions 103-112, numbered according to any one of SEQ ID NOs: 72-76 or 1573.104. The AAV particle of any one of embodiments 72-103, wherein(a) the VH comprises one. two, three, or all of:(i) a FRH1 comprising amino acids 1-25 or 1-30 of any one of SEQ ID NOs: 67-71 (optionally any one of SEQ ID NOs: 67 or 69-71); an amino acid sequence comprising one, two, three but no more than four modifications (e.g., substitutions, e.g., conservative substitutions) relative to amino acids 1-25 or 1-30 of any one of SEQ ID NOs: 67-71 (optionally any one of SEQ ID NOs: 67 or 69-71); or an amino acid sequence comprising one, two, three, but no morethan four different amino acids relative to amino acids 1-25 or 1-30 of any one of SEQ ID NOs: 67-71 (optionally any one of SEQ ID NOs: 67 or 69-71);(ii) a FRH2 comprising amino acids 36-49 of any one of SEQ ID NOs: 67-71 (optionally any one of SEQ ID NOs: 67 or 69-71); an amino acid sequence comprising one, two, three but no more than four modifications (e g., substitutions, e.g., conservative substitutions) relative to amino acids 36-49 of any one of SEQ ID NOs: 67-71 (optionally any one of SEQ ID NOs: 67 or 69-71); or an amino acid sequence comprising one, two, three, but no more than four different amino acids relative to amino acids 36-49 of any one of SEQ ID NOs: 67-71 (optionally any one of SEQ ID NOs: 67 or 69-71);(iii) a FRH3 comprising amino acids 67-96 or 67-98 of any one of SEQ ID NOs: 67-71 (optionally any one of SEQ ID NOs: 67 or 69-71); an amino acid sequence comprising one, two, three but no more than four modifications (e.g., substitutions, e.g., conservative substitutions) relative to amino acids 67-96 or 67-98 of any one of SEQ ID NOs: 67-71 (optionally any one of SEQ ID NOs: 67 or 69-71); or an amino acid sequence comprising one, two, three, but no more than four different amino acids relative to amino acids 67-96 or 67-98 of any one of SEQ ID NOs: 67-71 (optionally any one of SEQ ID NOs: 67 or 69-71); and / or(iv) a FRH4 comprising amino acids 108-118 of any one of SEQ ID NOs: 67-71 (optionally any one of SEQ ID NOs: 67 or 69-71); an amino acid sequence comprising one, two, three but no more than four modifications (e.g., substitutions, e.g., conservative substitutions) relative to amino acids 108-118 of any one of SEQ ID NOs: 67-71 (optionally any one of SEQ ID NOs: 67 or 69-71); or an amino acid sequence comprising one, two, three, but no more than four different amino acids relative to amino acids 108-118 of any one of SEQ ID NOs: 67-71 (optionally any one of SEQ ID NOs: 67 or 69-71); and / or(b) the VL comprises one, two, three or all of:(i) a FRL1 comprising amino acids 1-23 of any one of SEQ ID NOs: 72-76 (optionally any one of SEQ ID NOs: 72-74); an amino acid sequence comprising one, two, three but no more than four modifications (e.g., substitutions, e.g., conservative substitutions) relative to amino acids 1-23 of any one of SEQ ID NOs: 72-76 (optionally any one of SEQ ID NOs: 72-74); or an amino acid sequence comprising one, two, three but no more than four different amino acids relative to amino acids 1-23 of any one of SEQ ID NOs: 72-76 (optionally any one of SEQ ID NOs: 72-74);(ii) a FRL2 comprising amino acids 40-54 of any one of SEQ ID NOs: 72-76 (optionally any one of SEQ ID NOs: 72-74); an amino acid sequence comprising one, two, three but no more than four modifications (e.g., substitutions, e.g., conservative substitutions) relative to aminoacids 40-54 of any one of SEQ ID NOs: 72-76 (optionally any one of SEQ ID NOs: 72-74); or an amino acid sequence comprising one, two, three but no more than four different amino acids relative to amino acids 40-54 of any one of SEQ ID NOs: 72-76 (optionally any one of SEQ ID NOs: 72-74);(iii) a FRL3 comprising amino acids 62-93 of any one of SEQ ID NOs: 72-76 (optionally any one of SEQ ID NOs: 72-74); an amino acid sequence comprising one, two, three but no more than four modifications (e.g., substitutions, e.g., conservative substitutions) relative to amino acids 62-93 of any one of SEQ ID NOs: 72-76 (optionally any one of SEQ ID NOs: 72-74); or an amino acid sequence comprising one, two, three but no more than four different amino acids relative to amino acids 62-93 of any one of SEQ ID NOs: 72-76 (optionally any one of SEQ ID NOs: 72-74); and / or(iv) a FRL4 comprising amino acids 103-112 of any one of SEQ ID NOs: 72-76 (optionally any one of SEQ ID NOs: 72-74); an amino acid sequence comprising one, two, three but no more than four modifications (e.g., substitutions, e.g., conservative substitutions) relative to amino acids 103-112 of any one of SEQ ID NOs: 72-76 (optionally any one of SEQ ID NOs: 72-74); or an amino acid sequence comprising one, two, three but no more than four different amino acids relative to amino acids 103-112 of any one of SEQ ID NOs: 72-76 (optionally any one of SEQ ID NOs: 72-74).105. The AAV particle of any one of embodiments 72-104, wherein the:(i) the VH does not comprise one, two, three, or all of a FRH1 comprising amino acids 1-25 or 1-30 of SEQ ID NO: 1562; a FRH2 comprising amino acids 36-49 of SEQ ID NO: 1562; an FRH3 comprising amino acids 67-96 or 67-98 of SEQ ID NO: 1562; and / or a FRH4 comprising amino acids 108-118 of SEQ ID NO: 1562; and / or(ii) the VL does not comprise one, two, three, or all of a FRL1 comprising amino acids 1-23 of SEQ ID NO: 1573; a FRL2 comprising amino acids 40-54 of SEQ ID NO: 1573; an FRL3 comprising amino acids 62-93 of SEQ ID NO: 1573; and / or a FRL4 comprising amino acids 103-112 of SEQ ID NO: 1573.106. The AAV particle of any one of embodiments 72-105, wherein the VH comprises the amino acid sequence of any one of SEQ ID NOs: 67-71; or an amino acid sequence at least 86% (e.g., at least 90, 92, 95, 96, 97, 98, or 99%) identical to the amino acid sequence of any one of SEQ ID NOs: 67-71.107. The AAV particle of any one of embodiments 72-106, wherein the VH comprises an amino acid sequence comprising at least one, two, three, four, or five but no more than 16 modifications, e.g., substitutions (e.g., conservative substitutions) relative to tire amino acid sequence of any one of SEQ ID NOs: 67-71.108. The AAV particle of any one of embodiments 72-106, wherein the VH comprises an amino acid sequence comprising at least one, tw o. three, four, or five but no more than 16 different amino acids relative to the amino acid sequence of any one of SEQ ID NOs: 67-71.109. The AAV particle of any one of embodiments 72-108, wherein VH comprises the amino acid sequence of SEQ ID NO: 69; or an amino acid sequence at least 86% (e g., at least 90, 92. 95, 96, 97, 98, or 99%) identical to the amino acid sequence of SEQ ID NO: 69.110. The AAV particle of any one of embodiments 72-108, wherein the VH comprises an amino acid sequence comprising at least one, two, three, four, or five but no more than 16 modifications, e.g., substitutions (e.g., conservative substitutions) relative to the amino acid sequence of SEQ ID NO: 69.111. The AAV particle of any one of embodiments 72-108, wherein the VH comprises an amino acid sequence comprising at least one, two, three, four, or five but no more than 16 different amino acids relative to the amino acid sequence of SEQ ID NO: 69.112. The AAV particle of any one of embodiments 72-108, wherein the VH comprises:(i) the amino acid sequence of SEQ ID NO: 67; or an amino acid sequence at least 86% (e.g., at least 90, 92, 95, 96, 97, 98, or 99%) identical to the amino acid sequence of SEQ ID NO: 67;(ii) an amino acid sequence comprising at least one, two, three, four, or five but no more than 16 modifications, e.g., substitutions (e.g., conservative substitutions) relative to the amino acid sequence of SEQ ID NO: 67; or(iii) an amino acid sequence comprising at least one, two, three, four, or five but no more than 16 different amino acids relative to the amino acid sequence of SEQ ID NO: 67.113. The AAV particle of any one of embodiments 72-108, wherein the VH comprises:(i) the amino acid sequence of SEQ ID NO: 70; or an amino acid sequence at least 86% (e.g., at least 90, 92, 95, 96, 97, 98, or 99%) identical to the amino acid sequence of SEQ ID NO: 70;(ii) an amino acid sequence comprising at least one, two, three, four, or five but no more than 16 modifications, e.g., substitutions (e.g., conservative substitutions) relative to the amino acid sequence of SEQ ID NO: 70; or(iii) an amino acid sequence comprising at least one, two, three, four, or five but no more than 16 different amino acids relative to the amino acid sequence of SEQ ID NO: 70.114. The AAV particle of any one of embodiments 72-108, wherein the VH comprises:(i) the amino acid sequence of SEQ ID NO: 71; or an amino acid sequence at least 86% (e.g., at least 90, 92, 95, 96, 97, 98, or 99%) identical to the amino acid sequence of SEQ ID NO: 71;(ii) an amino acid sequence comprising at least one, two, three, four, or five but no more than 16 modifications, e g., substitutions (e.g., conservative substitutions) relative to the amino acid sequence of SEQ ID NO: 71; or(iii) an amino acid sequence comprising at least one, two, three, four, or five but no more than 16 different amino acids relative to the amino acid sequence of SEQ ID NO: 71.115. The AAV particle of any one of embodiments 72-114, wherein VL comprises the amino acid sequence of any one of SEQ ID NOs: 72-76; or an amino acid sequence at least 91% (e.g., at least 92. 95, 96, 97, 98. or 99%) identical to the amino acid sequence of any one of SEQ ID NOs: 72-76.116. The AAV particle of any one of embodiments 72-115, wherein the VL comprises an amino acid sequence comprising at least one, two, three, four, or five but no more than 10 modifications, e.g., substitutions (e.g., conservative substitutions) relative to the amino acid sequence of any one of SEQ ID NOs: 72-76.117. The AAV particle of any one of embodiments 72-116, wherein the VL comprises an amino acid sequence comprising at least one, two, three, four, or five but no more than 10 different amino acids relative to the amino acid sequence of any one of SEQ ID NOs: 72-76.118. The AAV particle of any one of embodiments 72-117, wherein VL comprises the amino acid sequence of SEQ ID NO: 73; or an amino acid sequence at least 91% (e.g., at least 92, 95, 96, 97, 98, or 99%) identical to the amino acid sequence of SEQ ID NO: 73.119. The AAV particle of any one of embodiments 72-118, wherein the VL comprises an amino acid sequence comprising at least one, two, three, four, or five but no more than 10 modifications, e.g., substitutions (e.g., conservative substitutions) relative to the amino acid sequence of SEQ ID NO: 73.120. The AAV particle of any one of embodiments 72-119, wherein the VL comprises:(i) an amino acid sequence comprising at least one, two, three, four, or five but no more than 10 different amino acids relative to the amino acid sequence of SEQ ID NO: 73;(ii) the amino acid sequence of SEQ ID NO: 72; or an amino acid sequence at least 91% (e.g., at least 92, 95, 96, 97, 98, or 99%) identical to the amino acid sequence of SEQ ID NO: 72;(iii) an amino acid sequence comprising at least one, two, three, four, or five but no more than 10 modifications, e g., substitutions (e.g., conservative substitutions) relative to the amino acid sequence of SEQ ID NO: 72;(iv) an amino acid sequence comprising at least one, two, three, four, or five but no more than 10 different amino acids relative to the amino acid sequence of SEQ ID NO: 72.121. The AAV particle of any one of embodiments 72-117, wherein the VL comprises:(i) the amino acid sequence of SEQ ID NO: 74; or an amino acid sequence at least 91% (e.g., at least 92, 95, 96, 97, 98, or 99%) identical to the amino acid sequence of SEQ ID NO: 74;(ii) an amino acid sequence comprising at least one, two, three, four, or five but no more than 10 modifications, e.g., substitutions (e.g., conservative substitutions) relative to the amino acid sequence of SEQ ID NO: 74;(iii) an amino acid sequence comprising at least one, two, three, four, or five but no more than 10 different amino acids relative to the amino acid sequence of SEQ ID NO: 74.122. The AAV particle of any one of embodiments 72-121, wherein:(a) the VH comprises the amino acid sequence of any one of SEQ ID NOs: 67-71, or an amino acid sequence at least 86% (e.g., at least 90, 92, 95, 96, 97, 98, or 99%) identical to the amino acid sequence of any one of SEQ ID NOs: 67-71; an amino acid sequence comprising at least one, two, three, four, or five but no more than 10 modifications, e.g., substitutions (e.g., conservative substitutions) relative to the amino acid sequence of any one of SEQ ID NOs: 67-71; or an amino acid sequence comprising at least one, two, three, four, or five but no more than 16 different amino acids relative to the amino acid sequence of any one of SEQ ID NOs: 67-71; and(b) the VL comprises the amino acid sequence of any one of SEQ ID NOs: 72-76; or an amino acid sequence at least 91% (e.g., at least 92, 95, 96, 97, 98, or 99%) identical to the amino acid sequenceof any one of SEQ ID NOs: 72-76; an amino acid sequence comprising at least one, two, three, four, or five but no more than 10 modifications, e.g., substitutions (e.g., conservative substitutions) relative to the amino acid sequence of any one of SEQ ID NOs: 72-76; or an amino acid sequence comprising at least one, two, three, four, or five but no more than 10 different amino acids relative to the amino acid sequence of any one of SEQ ID NOs: 72-76.123. The AAV particle of any one of embodiments 72-122, wherein:(a) the VH comprises the amino acid sequence of any one of SEQ ID NOs: 67 or 69-71, or an amino acid sequence at least 86% (e.g., at least 90, 92, 95, 96, 97, 98, or 99%) identical to the amino acid sequence of any one of SEQ ID NOs: 67 or 69-71; an amino acid sequence comprising at least one, two, three, four, or five but no more than 10 modifications, e.g., substitutions (e.g., conservative substitutions) relative to the amino acid sequence of any one of SEQ ID NOs: 67 or 69-71; or an amino acid sequence comprising at least one, two, three, four, or five but no more than 16 different amino acids relative to the amino acid sequence of any one of SEQ ID NOs: 67 or 69-71; and(b) the VL comprises the amino acid sequence of any one of SEQ ID NOs: 72-74; or an amino acid sequence at least 91% (e.g.. at least 92, 95, 96, 97, 98, or 99%) identical to the amino acid sequence of any one of SEQ ID NOs: 72-74; an amino acid sequence comprising at least one, two, three, four, or five but no more than 10 modifications, e.g., substitutions (e.g., conservative substitutions) relative to the amino acid sequence of any one of SEQ ID NOs: 72-74; or an amino acid sequence comprising at least one, two, three, four, or five but no more than 10 different amino acids relative to the amino acid sequence of any one of SEQ ID NOs: 72-74.124. The AAV particle of any one of embodiments 72-123, wherein:(a) the VH comprises the amino acid sequence of any one of SEQ ID NOs: 67-71, or an amino acid sequence at least 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of any one of SEQ ID NOs: 67-71; and(b) the VL comprises the amino acid sequence of any one of SEQ ID NOs: 72-76; or an amino acid sequence at least 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of any one of SEQ ID NOs: 72-76.125. The AAV particle of any one of embodiments 72-124, wherein:(i) the VH comprises the amino acid sequence of any one of SEQ ID NOs: 67 or 69-71, or an amino acid sequence at least 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of anyone of SEQ ID NOs: 67 or 69-71; and the VL comprises the amino acid sequence of any one of SEQ IDNOs: 72-74; or an amino acid sequence at least 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of any one of SEQ ID NOs: 72-74;(ii) the VH comprises the amino acid sequence of SEQ ID NO: 67, or an amino acid sequence at least 86%, 87%, 88%, 90% 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 67; and the VL comprises the amino acid sequence of SEQ ID NO: 72, or an amino acid sequence at least 91%, 93%, 95%. 96%. 97%. 98%. or 99% identical to the amino acid sequence of SEQ ID NO: 72;(iii) the VH comprises the amino acid sequence of SEQ ID NO: 67, or an amino acid sequence at least 86%, 87%, 88%, 90% 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 67; and the VL comprises the amino acid sequence of SEQ ID NO: 73, or an amino acid sequence at least 91%, 93%, 95%. 96%. 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 73;(iv) the VH comprises the amino acid sequence of SEQ ID NO: 67, or an amino acid sequence at least 86%, 87%, 88%, 90% 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 67; and the VL comprises the amino acid sequence of SEQ ID NO: 74, or an amino acid sequence at least 91%, 93%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 74;(v) the VH comprises the amino acid sequence of SEQ ID NO: 67, or an amino acid sequence at least 86%, 87%, 88%, 90% 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 67; and the VL comprises the amino acid sequence of SEQ ID NO: 75, or an amino acid sequence at least 91%, 93%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 75;(vi) the VH comprises the amino acid sequence of SEQ ID NO: 67, or an amino acid sequence at least 86%, 87%, 88%, 90% 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 67; and the VL comprises the amino acid sequence of SEQ ID NO: 76, or an amino acid sequence at least 91%, 93%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 76;(vii) the VH comprises the amino acid sequence of SEQ ID NO: 68, or an amino acid sequence at least 86%. 87%, 88%, 90% 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 68; and the VL comprises the amino acid sequence of SEQ ID NO: 72, or an amino acid sequence at least 91%, 93%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 72;(viii) the VH comprises the amino acid sequence of SEQ ID NO: 68, or an amino acid sequence at least 86%, 87%, 88%. 90% 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQID NO: 68; and the VL comprises the amino acid sequence of SEQ ID NO: 73, or an amino acid sequence at least 91%, 93%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 73;(ix) the VH comprises the amino acid sequence of SEQ ID NO: 68, or an amino acid sequence at least 86%, 87%, 88%, 90% 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 68; and the VL comprises the amino acid sequence of SEQ ID NO: 74, or an amino acid sequence at least 91%, 93%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 74;(x) the VH comprises the amino acid sequence of SEQ ID NO: 68, or an amino acid sequence at least 86%, 87%, 88%, 90% 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 68; and the VL comprises the amino acid sequence of SEQ ID NO: 75, or an amino acid sequence at least 91%, 93%, 95%. 96%. 97%. 98%. or 99% identical to the amino acid sequence of SEQ ID NO: 75;(xi) the VH comprises the amino acid sequence of SEQ ID NO: 68, or an amino acid sequence at least 86%, 87%, 88%, 90% 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 68; and the VL comprises the amino acid sequence of SEQ ID NO: 76, or an amino acid sequence at least 91%, 93%, 95%. 96%. 97%. 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 76;(xii) the VH comprises the amino acid sequence of SEQ ID NO: 69, or an amino acid sequence at least 86%, 87%, 88%, 90% 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 69; and the VL comprises the amino acid sequence of SEQ ID NO: 72, or an amino acid sequence at least 91%, 93%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 72;(xiii) the VH comprises the amino acid sequence of SEQ ID NO: 69, or an amino acid sequence at least 86%, 87%, 88%, 90% 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 69; and the VL comprises the amino acid sequence of SEQ ID NO: 73, or an amino acid sequence at least 91%, 93%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 73;(xiv) the VH comprises the amino acid sequence of SEQ ID NO: 69, or an amino acid sequence at least 86%, 87%, 88%, 90% 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 69; and the VL comprises the amino acid sequence of SEQ ID NO: 74, or an amino acid sequence at least 91%, 93%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 74;(xv) the VH comprises the amino acid sequence of SEQ ID NO: 69, or an amino acid sequence at least 86%, 87%, 88%, 90% 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 69; and the VL comprises the amino acid sequence of SEQ ID NO: 75, or an amino acid sequence at least 91%, 93%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 75;(xvi) the VH comprises the amino acid sequence of SEQ ID NO: 69, or an amino acid sequence at least 86%, 87%, 88%, 90% 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 69; and the VL comprises the amino acid sequence of SEQ ID NO: 76, or an amino acid sequence at least 91%, 93%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 76;(xvii) the VH comprises the amino acid sequence of SEQ ID NO: 70, or an amino acid sequence at least 86%, 87%, 88%. 90% 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 70; and the VL comprises the amino acid sequence of SEQ ID NO: 72, or an amino acid sequence at least 91%, 93%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 72;(xviii) the VH comprises the amino acid sequence of SEQ ID NO: 70, or an amino acid sequence at least 86%, 87%, 88%. 90% 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 70; and the VL comprises the amino acid sequence of SEQ ID NO: 73, or an amino acid sequence at least 91%, 93%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 73;(xix) the VH comprises the amino acid sequence of SEQ ID NO: 70, or an amino acid sequence at least 86%, 87%, 88%, 90% 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 70; and the VL comprises the amino acid sequence of SEQ ID NO: 74, or an amino acid sequence at least 91%, 93%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 74;(xx) the VH comprises the amino acid sequence of SEQ ID NO: 70, or an amino acid sequence at least 86%, 87%, 88%, 90% 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 70; and the VL comprises the amino acid sequence of SEQ ID NO: 75, or an amino acid sequence at least 91%, 93%, 95%. 96%. 97%. 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 75;(xxi) the VH comprises the amino acid sequence of SEQ ID NO: 70, or an amino acid sequence at least 86%, 87%, 88%, 90% 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 70; and the VL comprises the amino acid sequence of SEQ ID NO: 76, or an amino acid sequenceat least 91%, 93%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 76;(xxii) the VH comprises the amino acid sequence of SEQ ID NO: 71, or an amino acid sequence at least 86%, 87%, 88%, 90% 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 71; and the VL comprises the amino acid sequence of SEQ ID NO: 72, or an amino acid sequence at least 91%, 93%, 95%. 96%. 97%. 98%. or 99% identical to the amino acid sequence of SEQ ID NO: 72;(xxiii) the VH comprises the amino acid sequence of SEQ ID NO: 71, or an amino acid sequence at least 86%, 87%, 88%, 90% 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 71; and the VL comprises the amino acid sequence of SEQ ID NO: 73, or an amino acid sequence at least 91%, 93%, 95%. 96%. 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 73;(xxiv) the VH comprises the amino acid sequence of SEQ ID NO: 71, or an amino acid sequence at least 86%, 87%, 88%, 90% 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 71; and the VL comprises the amino acid sequence of SEQ ID NO: 74, or an amino acid sequence at least 91%, 93%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 74;(xxv) the VH comprises the amino acid sequence of SEQ ID NO: 71, or an amino acid sequence at least 86%, 87%, 88%, 90% 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 71; and the VL comprises the amino acid sequence of SEQ ID NO: 75, or an amino acid sequence at least 91%, 93%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 75; or(xxvi) the VH comprises the amino acid sequence of SEQ ID NO: 71, or an amino acid sequence at least 86%, 87%, 88%, 90% 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 71; and the VL comprises the amino acid sequence of SEQ ID NO: 76, or an amino acid sequence at least 91%, 93%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 76.126. The AAV particle of any one of embodiments 72-125, wherein:(i) the VH comprises the amino acid sequence of SEQ ID NO: 69, or an amino acid sequence at least 86%, 87%, 88%, 90% 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 69; an amino acid sequence comprising at least one, two, three, four, or five but no more than 10 modifications, e.g., substitutions (e.g., conservative substitutions) relative to the amino acid sequence ofSEQ ID NO: 69; or an amino acid sequence comprising at least one, two, three, four, or five but no more than 16 different amino acids relative to the amino acid sequence of any one of SEQ ID NO: 69; and (ii) the VL comprises the amino acid sequence of SEQ ID NO: 73, or an amino acid sequence at least 91%, 93%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 73; an amino acid sequence comprising at least one, two, three, four, or five but no more than 10 modifications, e.g., substitutions (e.g.. conservative substitutions) relative to the amino acid sequence of SEQ ID NO: 73; or an amino acid sequence comprising at least one, two, three, four, or five but no more than 16 different amino acids relative to the amino acid sequence of any one of SEQ ID NO: 73.127. The AAV particle of any one of embodiments 72-126, wherein the VH comprises the amino acid sequence of SEQ ID NO: 69 and the VL comprises the amino acid sequence of SEQ ID NO: 73.128. The AAV particle of any one of embodiments 72-127, wherein:(i) the VH comprises the amino acid sequence of SEQ ID NO: 67, or an amino acid sequence at least 86%, 87%, 88%, 90% 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 67; an amino acid sequence comprising at least one, two, three, four, or five but no more than 10 modifications, e.g., substitutions (e.g., conservative substitutions) relative to the amino acid sequence of SEQ ID NO: 67; or an amino acid sequence comprising at least one. two, three, four, or five but no more than 16 different amino acids relative to the amino acid sequence of any one of SEQ ID NO: 67; and (ii) the VL comprises the amino acid sequence of SEQ ID NO: 72, or an amino acid sequence at least 91%, 93%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 72; an amino acid sequence comprising at least one, two, three, four, or five but no more than 10 modifications, e.g., substitutions (e.g.. conservative substitutions) relative to the amino acid sequence of SEQ ID NO: 72; or an amino acid sequence comprising at least one. two, three, four, or five but no more than 16 different amino acids relative to the amino acid sequence of any one of SEQ ID NO: 72.129. The AAV particle of any one of embodiments 72-125, wherein:(i) the VH comprises the amino acid sequence of SEQ ID NO: 70, or an amino acid sequence at least 86%. 87%, 88%, 90% 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 70; an amino acid sequence comprising at least one, two, three, four, or five but no more than 10 modifications, e g., substitutions (e g., conservative substitutions) relative to the amino acid sequence of SEQ ID NO: 70; or an amino acid sequence comprising at least one, two, three, four, or five but no more than 16 different amino acids relative to the amino acid sequence of any one of SEQ ID NO: 70; and(ii) the VL comprises the amino acid sequence of SEQ ID NO: 72, or an amino acid sequence at least 91%, 93%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 72; an amino acid sequence comprising at least one, two, three, four, or five but no more than 10 modifications, e.g., substitutions (e.g., conservative substitutions) relative to the amino acid sequence of SEQ ID NO: 72; or an amino acid sequence comprising at least one. two, three, four, or five but no more than 16 different amino acids relative to the amino acid sequence of any one of SEQ ID NO: 72.130. The AAV particle of any one of embodiments 72-125, wherein:(i) the VH comprises the amino acid sequence of SEQ ID NO: 71, or an amino acid sequence at least 86%, 87%, 88%, 90% 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 71; an amino acid sequence comprising at least one. two, three, four, or five but no more than 10 modifications, e.g., substitutions (e.g., conservative substitutions) relative to the amino acid sequence of SEQ ID NO: 71; or an amino acid sequence comprising at least one, two, three, four, or five but no more than 16 different amino acids relative to the amino acid sequence of any one of SEQ ID NO: 71; and (ii) the VL comprises the amino acid sequence of SEQ ID NO: 73, or an amino acid sequence at least 91%, 93%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 73; an amino acid sequence comprising at least one. two, three, four, or five but no more than 10 modifications, e.g., substitutions (e.g., conservative substitutions) relative to the amino acid sequence of SEQ ID NO: 73; or an amino acid sequence comprising at least one, two, three, four, or five but no more than 16 different amino acids relative to the amino acid sequence of any one of SEQ ID NO: 73.131. The AAV particle of any one of embodiments 72-125, wherein:(i) the VH comprises the amino acid sequence of SEQ ID NO: 71, or an amino acid sequence at least 86%, 87%, 88%, 90% 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 71; an amino acid sequence comprising at least one, two, three, four, or five but no more than 10 modifications, e.g., substitutions (e.g., conservative substitutions) relative to the amino acid sequence of SEQ ID NO: 71; or an amino acid sequence comprising at least one, two, three, four, or five but no more than 16 different amino acids relative to the amino acid sequence of any one of SEQ ID NO: 71; and (ii) the VL comprises the amino acid sequence of SEQ ID NO: 74, or an amino acid sequence at least 91%, 93%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 74; an amino acid sequence comprising at least one, two, three, four, or five but no more than 10 modifications, e.g., substitutions (e.g., conservative substitutions) relative to the amino acid sequence of SEQ ID NO: 74; or an amino acid sequence comprising at least one, two, three, four, or five but no more than 16 different amino acids relative to the amino acid sequence of any one of SEQ ID NO: 74.132. The AAV particle of any one of embodiments 72-131, wherein:(i) the nucleotide sequence encoding the VH comprises the nucleotide sequence of any one of SEQ ID NOs: 156-160, or a nucleotide sequence at least 80% (e.g., at least 85%, 87%, 90%, 91%, 95%, 96%, 97%, 98%, or 99%) identical thereto; and / or(ii) the nucleotide sequence encoding the VL comprises the nucleotide sequence of any one of SEQ ID NOs: 161-165; or a nucleotide sequence at least 80% (e.g., at least 85%, 87%, 90%, 91%, 95%, 96%, 97%, 98%, or 99%) identical thereto.133. The AAV particle of any one of embodiments 72-132, wherein:(i) the nucleotide sequence encoding the VH comprises the nucleotide sequence of any one of SEQ ID NOs: 156 or 158-160, or a nucleotide sequence at least 80% (e.g., at least 85%, 87%, 90%, 91%, 95%, 96%, 97%, 98%, or 99%) identical thereto; and / or(ii) the nucleotide sequence encoding the VL comprises the nucleotide sequence of any one of SEQ ID NOs: 161-163; or a nucleotide sequence at least 80% (e.g., at least 85%, 87%, 90%, 91%, 95%, 96%, 97%, 98%, or 99%) identical thereto.134. Tire AAV particle of any one of embodiments 278-288, 292-294. 298-300, 302-305, 308-315, 321-326. 329-335, 340, or 341, wherein:(i) the nucleotide sequence encoding the VH comprises the nucleotide sequence of SEQ ID NO: 158, or a nucleotide sequence at least 80% (e.g., at least 85%, 87%, 90%, 91%, 95%, 96%, 97%, 98%, or 99%) identical thereto; and / or(ii) the nucleotide sequence encoding the VL comprises the nucleotide sequence of any one of SEQ ID NO: 162; or a nucleotide sequence at least 80% (e.g., at least 85%, 87%, 90%, 91%, 95%, 96%, 97%, 98%, or 99%) identical thereto.135. The AAV particle of any one of embodiments 72-134, wherein:(i) the nucleotide sequence encoding the VH comprises the nucleotide sequence of SEQ ID NO: 156, or a nucleotide sequence at least 80% (e.g., at least 85%, 87%, 90%, 91%, 95%, 96%, 97%, 98%, or 99%) identical thereto; and / or(ii) the nucleotide sequence encoding the VL comprises the nucleotide sequence of any one of SEQ ID NO: 161; or a nucleotide sequence at least 80% (e.g., at least 85%, 87%, 90%, 91%, 95%, 96%, 97%, 98%, or 99%) identical thereto.136. The AAV particle of any one of embodiments 72-133, wherein:(i) the nucleotide sequence encoding the VH comprises the nucleotide sequence of SEQ ID NO: 159, or a nucleotide sequence at least 80% (e.g., at least 85%, 87%, 90%, 91%, 95%, 96%, 97%, 98%, or 99%) identical thereto; and / or(ii) the nucleotide sequence encoding the VL comprises the nucleotide sequence of any one of SEQ ID NO: 161; or a nucleotide sequence at least 80% (e.g., at least 85%, 87%, 90%, 91%, 95%, 96%, 97%, 98%, or 99%) identical thereto.137. The AAV particle of any one of embodiments 72-133, wherein:(i) the nucleotide sequence encoding the VH comprises the nucleotide sequence of SEQ ID NO: 160, or a nucleotide sequence at least 80% (e.g., at least 85%, 87%, 90%, 91%, 95%, 96%, 97%, 98%, or 99%) identical thereto; and / or(ii) the nucleotide sequence encoding the VL comprises the nucleotide sequence of any one of SEQ ID NO: 162 or 163; or a nucleotide sequence at least 80% (e.g., at least 85%, 87%, 90%, 91%, 95%, 96%, 97%, 98%, or 99%) identical thereto.138. The AAV particle of any one of embodiments 72-137, which does not comprise the amino acid sequence of SEQ ID NO: 1562 and / or the amino acid sequence of SEQ ID NO: 1573.139. The AAV particle of any one of embodiments 1-70, wherein the antibody molecule comprises a VH region comprising an HCDR1, HCDR2, and HCDR3, and VL region comprising an LCDR1, LCDR2, and LCDR3, wherein:(a) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 64, 1554, 1557, 1567, 1565. and 1566, respectively;(b) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1553, 1554, 1552, 1567, 1565, and 1566, respectively;(c) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1555, SEQ ID NO: 1556, SEQ ID NO: 1557, SEQ ID NO: 1568, RVS, and SEQ ID NO: 1566, respectively; or(d) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1550, 1551, 1552, 1564, 1565, and 1566, respectively; andoptionally wherein:(i) the VH comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, or all of: V at position 5; S at position 7; A at position 9; V at position 11; K at position 12; S at position 14; A at position 16; K at position 19; V at position 20; R at position 38; Q at position 39; A at position 40; Q atposition 43; R at position 67; V at position 68; I at position 71; R at position 72; D at position 73; T at position 74; T at position 76; T at position 84; and / or L at position 113, numbered according to SEQ ID NO: 1562; and(ii) the VL comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or all of: I at position 2; S at position 7; S at position 12; T at position 14; P at position 15; Q at position 17; P at position 18; Q at position 50; S at position 68; V at position 88; Y at position 92; Q at position 105; and / or V at position 109, numbered according to SEQ ID NO: 1573.140. The AAV particle of any one of embodiments 1-70, wherein the antibody molecule comprises a VH region comprising an HCDR1, HCDR2, and HCDR3, and VL region comprising an LCDR1, LCDR2, and LCDR3, wherein:(a) the HCDR1. HCDR2, HCDR3, LCDR1. LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 64, 1554, 1557, 1567, 1565, and 1566, respectively;(b) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1553, 1554, 1552, 1567, 1565, and 1566, respectively;(c) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1555, SEQ ID NO: 1556, SEQ ID NO: 1557, SEQ ID NO: 1568, RVS, and SEQ ID NO: 1566, respectively; or(d) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1550, 1551, 1552, 1564, 1565, and 1566, respectively; andoptionally wherein:(i) the VH comprises the amino acid sequence of SEQ ID NO: 69, or an amino acid sequence at least 86% (e.g., at least 90, 92, 95. 96, 97, 98, or 99%) identical to the amino acid sequence of SEQ ID NO: 69; and / or(ii) the VL comprises the amino acid sequence of SEQ ID NO: 73, or an amino acid sequence at least 91% (e.g., at least 92, 95, 96, 97, 98, or 99%) identical to the amino acid sequence of SEQ ID NO: 73.141. The AAV particle of any one of embodiments 1-70, 139, or 140, wherein the antibody molecule comprises a VH region comprising the amino acid sequence of SEQ ID NO: 69, and a VL region comprising the amino acid sequence of SEQ ID NO: 73.142. The AAV particle of any one of embodiments 1-70, wherein the antibody molecule comprises a VH region comprising an HCDR1, HCDR2, and HCDR3, and VL region comprising an LCDR1, LCDR2, and LCDR3, wherein:(a) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 64, 1554, 1557, 1567, 1565. and 1566, respectively;(b) the HCDR1. HCDR2, HCDR3, LCDR1. LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1553, 1554, 1552, 1567, 1565, and 1566, respectively:(c) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1555, SEQ ID NO: 1556, SEQ ID NO: 1557, SEQ ID NO: 1568, RVS, and SEQ ID NO: 1566, respectively; or(d) the HCDR1, HCDR2, HCDR3, LCDR1. LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1550, 1551. 1552. 1564, 1565, and 1566, respectively; andoptionally wherein:(i) the VH comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, or all of: V at position 5; E at position 6; S at position 7; A at position 9; V at position 11; K at position 12; A at position 16; K at position 19; V at position 20; M at position 48; R at position 67; V at position 68; I at position 70; A at position 76; S at position 77: A at position 79; Y at position 80; M at position 81; E at position 82; R at position 87; T at position 91: and / or T at position 113, numbered according to SEQ ID NO: 1562;(ii) the VL comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or all of: S at position 7; T at position 14; Q at position 17; P at position 18; Q at position 42; R at position 44; R at position 50; S at position 68; V at position 88; Y at position 92; and / or Q at position 105, numbered according to SEQ ID NO: 1573.143. The AAV particle of any one of embodiments 1-70, wherein the antibody molecule comprises a VH region comprising an HCDR1, HCDR2, and HCDR3, and VL region comprising an LCDR1, LCDR2, and LCDR3, wherein:(a) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 64, 1554, 1557, 1567, 1565, and 1566, respectively;(b) the HCDR1. HCDR2, HCDR3, LCDR1. LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1553, 1554, 1552, 1567, 1565, and 1566, respectively;(c) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1555, SEQ ID NO: 1556, SEQ ID NO: 1557, SEQ ID NO: 1568, RVS, and SEQ ID NO: 1566, respectively; or(d) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1550, 1551, 1552, 1564, 1565, and 1566, respectively;optionally wherein:(i) the VH comprises the amino acid sequence of SEQ ID NO: 67, or an amino acid sequence at least 86% (e.g., at least 90, 92, 95. 96, 97, 98, or 99%) identical to the amino acid sequence of SEQ ID NO: 67; and / or(ii) the VL comprises the amino acid sequence of SEQ ID NO: 72, or an amino acid sequence at least 91% (e.g., at least 92, 95, 96, 97, 98, or 99%) identical to the amino acid sequence of SEQ ID NO: 72.144. The AAV particle of any one of embodiments 1-70, 142, or 143, wherein the antibody molecule comprises a VH region comprising the amino acid sequence of SEQ ID NO: 67. and a VL region comprising the amino acid sequence of SEQ ID NO: 72.145. The AAV particle of any one of embodiments 1-70, wherein the antibody molecule comprises a VH region comprising an HCDR1, HCDR2, and HCDR3, and VL region comprising an LCDR1, LCDR2, and LCDR3, wherein:(a) the HCDR1. HCDR2, HCDR3, LCDR1. LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 64, 1554, 1557, 1567, 1565, and 1566, respectively;(b) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1553, 1554, 1552, 1567, 1565, and 1566, respectively;(c) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1555, SEQ ID NO: 1556, SEQ ID NO: 1557, SEQ ID NO: 1568, RVS, and SEQ ID NO: 1566, respectively; or(d) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1550, 1551, 1552, 1564, 1565, and 1566, respectively;optionally wherein:(i) the VH comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15. 16, 17, 18, 19, or all of: E at position 1; V at position 5; S at position 7; A at position 9; V at position 11; K at position 12; K at position 19; V at position 20; R at position 67; V at position 68; M at position 70; I at position 76; A at position 79; Y at position 80; M at position 81; E at position 82; R at position 85; D at position 89, L at position 113; and / or S at position 115, numbered according to SEQ ID NO: 1562; and(ii) the VL comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or all of: S at position 7; T at position 14; Q at position 17; P at position 18; Q at position 42; R at position 44; R at position 50; S at position 68; V at position 88; Y at position 92; and / or Q at position 105, numbered according to SEQ ID NO: 1573.146. Hie AAV particle of any one of embodiments 1-70, wherein the antibody molecule comprises a VH region comprising an HCDR1, HCDR2. and HCDR3, and VL region comprising an LCDR1, LCDR2, and LCDR3, wherein:(a) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 64, 1554, 1557, 1567, 1565, and 1566, respectively;(b) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1553, 1554, 1552, 1567, 1565, and 1566, respectively;(c) the HCDR1. HCDR2, HCDR3, LCDR1. LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1555, SEQ ID NO: 1556, SEQ ID NO: 1557, SEQ ID NO: 1568, RVS, and SEQ ID NO: 1566, respectively; or(d) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1550, 1551, 1552, 1564, 1565, and 1566, respectively;optionally wherein:(i) the VH comprises the amino acid sequence of SEQ ID NO: 70, or an amino acid sequence at least 86% (e.g., at least 90, 92, 95, 96, 97, 98, or 99%) identical to the amino acid sequence of SEQ ID NO: 70; and / or(ii) the VL comprises the amino acid sequence of SEQ ID NO: 72, or an amino acid sequence at least 91% (e.g., at least 92, 95, 96, 97, 98, or 99%) identical to the amino acid sequence of SEQ ID NO: 72.147. The AAV particle of any one of embodiments 1-70, 145, or 146, wherein the antibody molecule comprises a VH region comprising the amino acid sequence of SEQ ID NO: 70, and a VL region comprising the amino acid sequence of SEQ ID NO: 72.148. Hie AAV particle of any one of embodiments 1-70, wherein the antibody molecule comprises a VH region comprising an HCDR1, HCDR2, and HCDR3, and VL region comprising an LCDR1, LCDR2, and LCDR3, wherein:(a) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 64, 1554, 1557, 1567, 1565, and 1566, respectively;(b) the HCDRL HCDR2, HCDR3, LCDRL LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1553, 1554, 1552, 1567, 1565, and 1566, respectively;(c) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1555, SEQ ID NO: 1556, SEQ ID NO: 1557, SEQ ID NO: 1568, RVS, and SEQ ID NO: 1566, respectively; or(d) the HCDR1. HCDR2, HCDR3, LCDR1. LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1550, 1551, 1552, 1564, 1565, and 1566, respectively;optionally wherein:(i) tire VH comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 or all of: V at position 5; S at position 7; A at position 9; V at position 11; K at position 12; A at position 16; K at position 19; V at position 20; Q at position 43; M at position 48; R at position 67; V at position 68; M at position 70; T at position 76; S at position 77; R at position 87; and / or T at position 91. numbered according to SEQ ID NO: 1562; and(ii) the VL comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or all of: I at position 2; S at position 7; S at position 12; T at position 14; P at position 15; Q at position 17; P at position 18; Q at position 50; S at position 68; V at position 88; Y at position 92; Q at position 105; and / or V at position 109, numbered according to SEQ ID NO: 1573.149. The AAV particle of any one of embodiments 1-70, wherein the antibody molecule comprises a VH region comprising an HCDR1, HCDR2, and HCDR3, and VL region comprising an LCDR1, LCDR2, and LCDR3, wherein:(a) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 64, 1554, 1557, 1567, 1565. and 1566, respectively;(b) the HCDR1. HCDR2, HCDR3, LCDR1. LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1553, 1554, 1552, 1567, 1565, and 1566, respectively;(c) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1555, SEQ ID NO: 1556, SEQ ID NO: 1557, SEQ ID NO: 1568, RVS, and SEQ ID NO: 1566, respectively; or(d) the HCDR1. HCDR2, HCDR3, LCDR1. LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1550, 1551, 1552, 1564, 1565, and 1566, respectively;optionally wherein:(i) the VH comprises the amino acid sequence of SEQ ID NO: 71, or an amino acid sequence at least 86% (e.g., at least 90, 92, 95, 96, 97, 98, or 99%) identical to the amino acid sequence of SEQ ID NO: 71; and / or(ii) the VL comprises the amino acid sequence of SEQ ID NO: 73, or an amino acid sequence at least 91% (e.g., at least 92, 95, 96, 97, 98, or 99%) identical to the amino acid sequence of SEQ ID NO: 73.150. The AAV particle of any one of embodiments 1-70, 148, or 149, wherein the antibody molecule comprises a VH region comprising the amino acid sequence of SEQ ID NO: 71. and a VL region comprising the amino acid sequence of SEQ ID NO: 73.151. The AAV particle of any one of embodiments 1-70, wherein the antibody molecule comprises a VH region comprising an HCDR1, HCDR2, and HCDR3, and VL region comprising an LCDR1, LCDR2, and LCDR3, wherein:(a) the HCDRL HCDR2, HCDR3, LCDRL LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 64, 1554, 1557, 1567, 1565, and 1566, respectively;(b) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1553, 1554, 1552, 1567, 1565, and 1566, respectively;(c) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1555, SEQ ID NO: 1556, SEQ ID NO: 1557, SEQ ID NO: 1568, RVS, and SEQ ID NO: 1566, respectively; or(d) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1550, 1551, 1552, 1564, 1565, and 1566, respectively;optionally wherein:(i) the VH comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 or all of: V at position 5; S at position 7; A at position 9; V at position 11; K at position 12; A at position 16; K at position 19; V at position 20; Q at position 43; M at position 48; R at position 67; V at position 68; M at position 70; T at position 76; S at position 77; R at position 87; and / or T at position 91, numbered according to SEQ ID NO: 1562; and(ii) the VL comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, or all of: I at position 2; S at position 11; T at position 14; Q at position 17; P at position 18; Q at position 42; R at position 44; P at position 48; R at position 50: S at position 68; A at position 72; N at position 81; V at position 88; and / or Q at position 105, numbered according to SEQ ID NO: 1573.152. The AAV particle of any one of embodiments 1-70, wherein the antibody molecule comprises a VH region comprising an HCDR1, HCDR2, and HCDR3, and VL region comprising an LCDR1, LCDR2, and LCDR3, wherein:(a) the HCDRL HCDR2, HCDR3, LCDRL LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 64, 1554, 1557, 1567, 1565, and 1566, respectively;(b) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1553, 1554, 1552, 1567, 1565, and 1566, respectively;(c) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1555, SEQ ID NO: 1556, SEQ ID NO: 1557, SEQ ID NO: 1568, RVS, and SEQ ID NO: 1566, respectively; or(d) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequence of SEQ ID NO: 1550, 1551, 1552, 1564, 1565, and 1566, respectively;optionally wherein:(i) the VH comprises the amino acid sequence of SEQ ID NO: 71, or an amino acid sequence at least 86% (e.g., at least 90, 92, 95. 96. 97, 98, or 99%) identical to the amino acid sequence of SEQ ID NO: 71; and / or(ii) the VL comprises the amino acid sequence of SEQ ID NO: 74, or an amino acid sequence at least 91% (e.g., at least 92, 95, 96, 97, 98, or 99%) identical to the amino acid sequence of SEQ ID NO: 74.153. The AAV particle of any one of embodiments 1-70, 151, or 152, wherein the antibody molecule comprises a VH region comprising the amino acid sequence of SEQ ID NO: 71, and a VL region comprising the amino acid sequence of SEQ ID NO: 74.154. The AAV particle of any one of embodiments 1-153, wherein the antibody molecule is a humanized antibody molecule.155. The AAV particle of any one of embodiments 1-154, which is a full length antibody molecule, a bispecific antibody molecule, an Fab, an F(ab')2, an Fv, or a single chain Fv fragment (scFv).156. The AAV particle of any one of embodiments 1-155, which comprises a heavy chain constant region selected from IgGl, IgG2. IgG3, IgG4; and / or a light chain constant region of kappa or lambda.157. The AAV particle of any one of embodiments 1-156, which comprises a heavy chain constant region of IgG4 and a light chain constant region of kappa.158. The AAV particle of any one of embodiments 1-157, wherein:(i) the antibody molecule comprises a human IgG4 constant region, comprising an amino acid other than serine at position 228 according to EU numbering;(ii) the antibody molecule comprises a human IgG4 constant region, comprising a serine to proline mutation at position 228 according to EU numbering;(iii) the antibody molecule comprises a heavy chain constant region (e.g., a human IgG4 constant region) comprising the amino acid sequence of SEQ ID NO: 2503, or an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 2503; and / or(iv) the antibody molecule comprises a heavy chain constant region (e.g., a human IgG4 constant region), wherein the nucleotide sequence encoding the heavy chain constant region comprises the nucleotide sequence of any one of SEQ ID NOs: 2504, 2505, 2506, or 2507, or a nucleotide sequence at least 85%. 90%, 95%, 96%, 97%, 98%, or 99% identical any one of SEQ ID NOs: 2504, 2505, 2506, or 2507.159. The AAV particle of any one of embodiments 1-158, wherein the antibody molecule comprises a light chain constant region (e.g., a light chain constant region of kappa), wherein:(i) the light chain constant region comprises the amino acid sequence of SEQ ID NO: 2508, or an amino acid sequence at least 85%. 90%. 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 2508; and / or(ii) the nucleotide sequence encoding the light chain constant region comprises the nucleotide sequence of SEQ ID NO: 2509 or 2510, or a nucleotide sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 2509 or 2510.160. The AAV particle of any one of embodiments 1-159, wherein the antibody molecule comprises a heavy chain comprising the amino acid sequence of any one of SEQ ID NOs: 170-174, or an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 170-174.161. The AAV particle of any one of embodiments 1-160, wherein the antibody molecule comprises a light chain comprising the amino acid sequence of any one of SEQ ID NOs: 175-179, or an amino acid sequence at least 85%, 90%. 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 175-179.162. The AAV particle of any one of embodiments 1-161, wherein the antibody molecule comprises:(i) a heavy chain comprising the amino acid sequence of any one of SEQ ID NOs: 170-174, or an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 170-174; and(ii) a light chain comprising the amino acid sequence of any one of SEQ ID NOs: 175-179, or an amino acid sequence at least 85%. 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 175-179.163. The AAV particle of any one of embodiments 1-162, wherein the antibody molecule comprises:(i) a heavy chain comprising the amino acid sequence of any one of SEQ ID NOs: 170 or 172-174, or an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 170 or 172-174; and(ii) a light chain comprising the amino acid sequence of any one of SEQ ID NOs: 175-177, or an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 175-177.164. The AAV particle of any one of embodiments 1-163, which comprises:(i) a heavy chain comprising the amino acid sequence of SEQ ID NO: 170, or an amino acid sequence at least 85%, 90%. 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 170; and a light chain comprising the amino acid sequence of SEQ ID NO: 175, or an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 175;(ii) a heavy chain comprising the amino acid sequence of SEQ ID NO: 170, or an amino acid sequence at least 85%, 90%. 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 170: and a light chain comprising the amino acid sequence of SEQ ID NO: 176, or an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%. or 99% identical to SEQ ID NO: 176;(iii) a heavy chain comprising the amino acid sequence of SEQ ID NO: 170, or an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 170; and a light chain comprising the amino acid sequence of SEQ ID NO: 177, or an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%. or 99% identical to SEQ ID NO: 177;(iv) a heavy chain comprising the amino acid sequence of SEQ ID NO: 170, or an amino acid sequence at least 85%, 90%. 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 170: and a light chain comprising the amino acid sequence of SEQ ID NO: 178, or an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 178;(v) a heavy chain comprising the amino acid sequence of SEQ ID NO: 170, or an amino acid sequence at least 85%, 90%. 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 170: and a lightchain comprising the amino acid sequence of SEQ ID NO: 179, or an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 179;(vi) a heavy chain comprising the amino acid sequence of SEQ ID NO: 171, or an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 171; and a light chain comprising tire amino acid sequence of SEQ ID NO: 175, or an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%. or 99% identical to SEQ ID NO: 175;(vii) a heavy chain comprising the amino acid sequence of SEQ ID NO: 171, or an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 171; and a light chain comprising the amino acid sequence of SEQ ID NO: 176, or an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 176;(viii) a heavy chain comprising the amino acid sequence of SEQ ID NO: 171, or an amino acid sequence at least 85%, 90%. 95%. 96%. 97%. 98%, or 99% identical to SEQ ID NO: 171: and a light chain comprising the amino acid sequence of SEQ ID NO: 177, or an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 177;(ix) a heavy chain comprising the amino acid sequence of SEQ ID NO: 171, or an amino acid sequence at least 85%, 90%. 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 171: and a light chain comprising the amino acid sequence of SEQ ID NO: 178, or an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%. or 99% identical to SEQ ID NO: 178;(x) a heavy chain comprising the amino acid sequence of SEQ ID NO: 171, or an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 171; and a light chain comprising the amino acid sequence of SEQ ID NO: 179, or an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%. or 99% identical to SEQ ID NO: 179;(xi) a heavy chain comprising the amino acid sequence of SEQ ID NO: 172, or an amino acid sequence at least 85%, 90%. 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 172: and a light chain comprising the amino acid sequence of SEQ ID NO: 175, or an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 175;(xii) a heavy chain comprising the amino acid sequence of SEQ ID NO: 172, or an amino acid sequence at least 85%, 90%. 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 172: and a light chain comprising the amino acid sequence of SEQ ID NO: 176, or an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%. or 99% identical to SEQ ID NO: 176;(xiii) a heavy chain comprising the amino acid sequence of SEQ ID NO: 172, or an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 172; and a light chain comprising the amino acid sequence of SEQ ID NO: 177, or an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%. or 99% identical t(xiv) a heavy chain comprising the amino acid sequence of SEQ ID NO: 172, or an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 172; and a light chain comprising the amino acid sequence of SEQ ID NO: 178, or an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 178;(xv) a heavy chain comprising the amino acid sequence of SEQ ID NO: 172, or an amino acid sequence at least 85%, 90%. 95%. 96%. 97%. 98%, or 99% identical to SEQ ID NO: 172: and a light chain comprising the amino acid sequence of SEQ ID NO: 179, or an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 179;(xvi) a heavy chain comprising the amino acid sequence of SEQ ID NO: 173, or an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 173; and a light chain comprising tire amino acid sequence of SEQ ID NO: 175, or an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%. or 99% identical to SEQ ID NO: 175;(xvii) a heavy chain comprising the amino acid sequence of SEQ ID NO: 173, or an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 173; and a light chain comprising the amino acid sequence of SEQ ID NO: 176, or an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%. or 99% identical to SEQ ID NO: 176;(xviii) a heavy chain comprising the amino acid sequence of SEQ ID NO: 173, or an amino acid sequence at least 85%, 90%. 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 173: and a light chain comprising the amino acid sequence of SEQ ID NO: 177, or an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 177;(xix) a heavy chain comprising the amino acid sequence of SEQ ID NO: 173, or an amino acid sequence at least 85%, 90%. 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 173: and a light chain comprising the amino acid sequence of SEQ ID NO: 178, or an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%. or 99% identical to SEQ ID NO: 178;(xx) a heavy chain comprising the amino acid sequence of SEQ ID NO: 173, or an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 173; and a light chain comprising the amino acid sequence of SEQ ID NO: 179, or an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%. or 99% identical to SEQ ID NO: 179;(xxi) a heavy chain comprising the amino acid sequence of SEQ ID NO: 174, or an amino acid sequence at least 85%, 90%. 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 174: and a light chain comprising the amino acid sequence of SEQ ID NO: 175, or an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 175;(xxii) a heavy chain comprising the amino acid sequence of SEQ ID NO: 174, or an amino acid sequence at least 85%, 90%. 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 174: and a lightchain comprising the amino acid sequence of SEQ ID NO: 176, or an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 176;(xxiii) a heavy chain comprising the amino acid sequence of SEQ ID NO: 174, or an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 174; and a light chain comprising tire amino acid sequence of SEQ ID NO: 177, or an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%. or 99% identical to SEQ ID NO: 177;(xxiv) a heavy chain comprising the amino acid sequence of SEQ ID NO: 174, or an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 174; and a light chain comprising the amino acid sequence of SEQ ID NO: 178, or an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 178; or(xxv) a heavy chain comprising the amino acid sequence of SEQ ID NO: 174, or an amino acid sequence at least 85%, 90%. 95%. 96%. 97%. 98%, or 99% identical to SEQ ID NO: 174: and a light chain comprising the amino acid sequence of SEQ ID NO: 179, or an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 179.165. The AAV particle of any one of embodiments 1-70, wherein the antibody molecule comprises:(a) the VH and / or VL sequences of SEQ ID NOs: 1562 and 1573, respectively;(b) the VH and / or VL sequences of SEQ ID NOs: 1512 and 1523, respectively;(c) the VH and / or VL sequences of SEQ ID NOs: 1537 and 1548, respectively;(d) the VH and / or VL sequences of SEQ ID NOs: 1583 and 1591, respectively;(e) the VH and / or VL sequences of SEQ ID NOs: 1599 and 1606, respectively;(f) the VH and / or VL sequences of SEQ ID NOs: 1619 and 1629, respectively;(g) the VH and / or VL sequences of SEQ ID NOs: 1822 and 1941. respectively;(h) the VH and / or VL sequences of SEQ ID NOs: 1849 and 1970, respectively;(i) the VH and / or VL sequences of SEQ ID NOs: 1844 and 1964, respectively:(j) tire VH and / or VL sequences of SEQ ID NOs: 1803 and 1919, respectively;(k) a VH sequence having at least 80% (e.g., 85, 90, 95, 96, 97, 98, or 99%) sequence identity to the VH sequence of any one of (a)-(j), and / or a VL sequence having at least 80% (e.g., 85, 90, 95, 96, 97, 98, or 99%) sequence identity to the VL sequence of any one of (a)-(j ); or(l) a VH sequence having at least one, two, or three modifications, but not more than 30, 20, or 10 modifications, relative to the VH sequence of any one of (a)-(j), and / or a VL sequence having at least one, two, or three modifications, but not more than 30, 20, or 10 modifications, relative to the VL sequence of any one of (a)-(j).166. The AAV particle of embodiment 165, wherein tire antibody molecule comprises a VH sequence having at least 80% (e.g., 85, 90, 95, 96, 97, 98, or 99%) sequence identity to the VH sequence of SEQ ID NO: 1562, and / or a VL sequence having at least 80% (e.g., 85, 90, 95, 96, 97, 98, or 99%) sequence identity to the VL sequence of SEQ ID NO: 1573.167. The AAV particle of embodiment 165, wherein tire antibody molecule comprises a VH sequence having at least one, two, or three modifications, but not more than 30, 20, or 10 modifications, relative to the VH sequence of SEQ ID NO: 1562, and / or a VL sequence having at least one, two, or three modifications, but not more than 30, 20, or 10 modifications, relative to the VL sequence of SEQ ID NO: 1573.168. The AAV particle of embodiment 165, wherein tire antibody molecule comprises the VH and VL sequences of SEQ ID NOs: 1562 and 1573, respectively.169. The AAV particle of embodiment 168, wherein the antibody molecule comprises a VH sequence encoded by a nucleotide sequence having at least 80% (e.g., 85, 90, 95, 96, 97, 98, or 99%) sequence identity to any one of SEQ ID NOs: 158, 156, 157, 159, 160, 1563, 1513, 1538, 1584, 1600. or 1620 and / or a VL sequence encoded by a nucleotide sequence having at least 80% (e.g., 85, 90, 95, 96, 97, 98, or 99%) sequence identity to any one of SEQ ID NOs: 1574, 1524, 1549, 1592, 1607, or 1630.170. The AAV particle of embodiment 169, wherein the antibody molecule comprises VH and VL sequences encoded by nucleotide sequences set forth in (a) SEQ ID NOs: 1563 and 1574, respectively, (b) SEQ ID NOs: 1513 and 1524, respectively, (c) SEQ ID NOs: 1538 and 1549, respectively, (d) SEQ ID NOs: 1584 and 1592, respectively, (e) SEQ ID NOs: 1600 and 1607, respectively, (f) SEQ ID NOs: 1620 and 1630, respectively, or (g) a nucleotide sequence having at least 80% (e.g., 85, 90, 95, 96, 97, 98, or 99%) sequence identity to any one of (a)-(f).171. Hie AAV particle of embodiment 169 or 170, wherein the antibody molecule comprises a VH sequence encoded by the nucleotide sequence of SEQ ID NO: 1563 and a VL sequence encoded by the nucleotide sequence of SEQ ID NO: 1574.172. The AAV particle of any one of embodiments 1-70, wherein the antibody molecule comprises:(a) the HCDR1, HCDR2, and / or HCDR3 sequences of SEQ ID NOs: 1777, 1778, and 1779, respectively, and / or the LCDR1, LCDR2, and / or LCDR3 sequences of SEQ ID NOs: 1889, 1890, and 1891, respectively;(b) the HCDR1, HCDR2, and / or HCDR3 sequences of SEQ ID NOs: 1790, 1792, and 1794, respectively, and / or the LCDR1, LCDR2, and / or LCDR3 sequences of SEQ ID NOs: 1908, 1910, and 1912, respectively;(c) the HCDR1, HCDR2, and / or HCDR3 sequences of SEQ ID NOs: 1761, 1762, and 1763, respectively, and / or the LCDR1, LCDR2, and / or LCDR3 sequences of SEQ ID NOs: 1880, 1881, and 1882, respectively; or(d) the HCDRl, HCDR2, and / or HCDR3 sequences, and / or LCDR1, LCDR2, and / or LCDR3 sequences of any one of (a)-(c), with at most one, two, or three substitutions (e.g., conservative amino acid substitutions) in each CDR.173. The AAV particle of any one of embodiments 1-47, wherein the antibody molecule binds to all or a portion of amino acid residues oftau selected from: (a) 183-212, (b) 187-218, (c) 33-82, 159-182, 197-226, and 229-246; (d) 217-242, (e) 35-76 and 187-218, (f) 5-34, (g) 187-218, (h) 33-82, 159-188, and 191-230, (i) 35-62, 107-124, and 203-220. (j) 35-82, 159-188. and 197-224, and (k) 53-78, 329-348, or 381-408, wherein human tau is numbered according to SEQ ID NO: 9200.174. The AAV particle of embodiment 173, wherein one or more of the serines, threonines, and / or tyrosines in the stretch of amino acids selected from (a)-(k) are phosphory lated.175. Hie AAV particle of embodiment 173 or 174, wherein all of the serines, threonines, and / or tyrosines in the stretch of amino acids selected from (a)-(k) are phosphorylated.176. The AAV particle of any one of embodiments 1-175, wherein the antibody molecule binds to all or a portion of amino acids 195-215 oftau, e.g., with a dissociation constant (KD) of about 1 pM to about 50 pM, or about 1-25 pM, e.g., as assessed by bio-layer interferometry.177. The AAV particle of any one of embodiments 1-175, wherein the antibody molecule binds to all or a portion of amino acids 191-214 oftau phosphorylated at S199, e.g., with a dissociation constant (KD) of about 0.1 nM to about 10 nM, or about 0.5-5 nM, e.g., as assessed by bio-layer interferometry.178. The AAV particle of any one of embodiments 1-175, wherein the antibody molecule binds to all or a portion of amino acids 217-234 oftau phosphorylated at T217, T220, and T231, e.g., with a dissociation constant (KD) of about 0.1 nM to about 10 nM, or about 0.1-5 nM, e.g., as assessed by bio-layer interferometry.179. The AAV particle of any one of embodiments 1-175. wherein the antibody molecule binds to all or a portion of amino acids 225-240 oftau phosphorylated at T231, e.g., with a dissociation constant (KD) of about 0.1 nM to about 25 nM, or about 0.1-15 nM, e.g., as assessed by bio-layer interferometry.180. The AAV particle of any one of embodiments 1-175, wherein the antibody molecule binds to human tau phosphorylated at amino acid residue S404, or a peptide comprising or consisting of the amino acid sequence DHGAEIVYKSPVVSGDT(pS)PRHLSNVSSTG (SEQ ID NO: 2143), wherein p(S) corresponds to a phosphorylated serine residue, optionally wherein the antibody molecule comprises a heavy chain variable region (VEI) comprising HCDR1, HCDR2, and HCDR3 sequences comprising SEQ ID NOs: 2430, 2431, and 2432, respectively, and a light chain variable region (VL) comprising LCDR1, LCDR2, and LCDR3 sequences comprising SEQ ID NO: 2435, LGS, and SEQ ID NO: 2437, respectively.181. The AAV particle of any one of embodiments 1-175, wherein the antibody molecule binds to:(a) human tau phosphorylated at amino acid residue SI 99, but not at amino acid residues S202 and T205,(b) human tau phosphorylated at amino acid residue S202, but not at amino acid residues SI 99 and T205,(c) human tau phosphorylated at amino acid residue T205, but not at amino acid residues S199 and S202,(d) human tau phosphorylated at a combination of amino acid residues S199 and T205, but not at amino acid residue S202 (e.g., wherein binding tau phosphorylated at a combination of S199 and T205 is at least 3-times stronger (e.g., at least 4-time stronger) than background (e.g., non-specific) level of binding, e g., binding by hlgGl isotype control),(e) human tau phosphorylated at a combination of amino acid residues S202 and T205, but not at amino acid residue SI 99, but not human tau phosphorylated at a combination of residues SI 99 and S202, but not T205,(f) human tau phosphorylated at a combination of amino acid residues (i) S202 and T205, but not S 119, and (ii) S199 and T205, but not S202, e.g., at least 2 times (e.g., at least 3 times, at least 4 times, atleast 5 times, 2-6 times, 2-5 times, 2-4 times, 2-3 times, 3-5 times or 4-5 times) more strongly than background (e.g., non-specific) level of binding, e.g., binding by hlgGl isotype control).(g) human tau phosphorylated at a combination of amino acid residues (i) S199 and S202, but not T205, (ii) S202 and T205, but not S199, (iii) S199 and T205, but not S202, and (iv) S199, S202, and T205 (e.g., wherein binding to phosphorylated tau is at least 1.6-times stronger (e.g., at least 1.7 times, at least 1.8 times, at least 1.9 times, at least 2 times, at least 3 times, 1.6-3 times. 1.6-2 times stronger) than background (e.g., non-specific) level of binding, e.g., binding by hlgGl isotype control),(h) a peptide comprising or consisting of the amino acid sequence SGDRSGYS(pS)PGSPGTPGSRSRTPS (SEQ ID NO: 2146),(i) a peptide comprising or consisting of the amino acid sequence SGDRSGYSSPG(pS)PGTPGSRSRTPS (SEQ ID NO: 2147),i ) a peptide comprising or consisting of the amino acid sequence SGDRSGYSSPGSPG(pT)PGSRSRTPS (SEQ ID NO: 2148), or(k) a peptide comprising or consisting of the amino acid sequence SGDRSGYS(pS)PGSPG(pT)PGSRSRTPS (SEQ ID NO: 2152) (e.g., wherein binding to the peptide is at least 3 times stronger (e.g., at least 4 times stronger) than background (e.g., non-specific) level of binding, e.g., binding by hlgGl isotype control),(l) a peptide comprising or consisting of the amino acid sequence SGDRSGYSSPG(pS)PG(pT)PGSRSRTPS (SEQ ID NO: 2151), but not a peptide comprising or consisting of the amino acid sequence SGDRSGYS(pS)PG(pS)PGTPGSRSRTPS (SEQ ID NO: 2150), (m) peptides comprising or consisting of the amino acid sequences SGDRSGYSSPG(pS)PG(pT)PGSRSRTPS (SEQ ID NO: 2151) and SGDRSGYS(pS)PGSPG(pT)PGSRSRTPS (SEQ ID NO: 2152), wherein binding to the latter peptide is at least 2 times (e.g., at least 3 times, at least 4 times, at least 5 times, 2-6 times, 2-5 times, 2-4 times, 2-3 times, 3-5 times or 4-5 times) more stronger than background (e.g., non-specific) level of binding, e.g., binding by hlgGl isotype control), or(n) peptides comprising or consisting of the amino acid sequences SGDRSGYS(pS)PG(pS)PGTPGSRSRTPS (SEQ ID NO: 2150), SGDRSGYSSPG(pS)PG(pT)PGSRSRTPS (SEQ ID NO: 2151), SGDRSGYS(pS)PGSPG(pT)PGSRSRTPS (SEQ ID NO: 2152), and SGDRSGYS(pS)PG(pS)PG(pT)PGSRSRTPS (SEQ ID NO: 2149) (e.g., wherein binding to the peptides is at least 1.6 times stronger (e.g., at least 1.7 times, at least 1.8 times, at least 1.9 times, at least 2 times, at least 3 times, 1.6-4 times, 1.6-3 times stronger) than background (e.g., non-specific) level of binding, e.g., binding by hlgGl isotype control),wherein p(S) and p(T) correspond to a phosphorylated serine and phosphorylated threonine, respectively,optionally wherein binding is assessed, e.g., using ELISA, and optionally wherein human tau has the sequence set forth in SEQ ID NO: 9200, andoptionally wherein the antibody molecule comprises:(i) a heavy chain variable region (VH) comprising HCDR1. HCDR2, and HCDR3 sequences comprising SEQ ID NOs: 2200, 2201, and 2202, respectively, and a light chain variable region (VL) comprising LCDR1, LCDR2, and LCDR3 sequences comprising SEQ ID NO: 2207, KIS, and SEQ ID NO: 2209, respectively;(ii) a heavy chain variable region (VH) comprising HCDR1, HCDR2, and HCDR3 sequences comprising SEQ ID NOs: 2218, 2219. and 2220, respectively, and a light chain variable region (VL) comprising LCDRL LCDR2, and LCDR3 sequences comprising SEQ ID NO: 2207, KIS. and SEQ ID NO: 2224, respectively;(iii) a heavy chain variable region (VH) comprising HCDR1, HCDR2, and HCDR3 sequences comprising SEQ ID NOs: 2248, 2219, and 2249, respectively, and a light chain variable region (VL) comprising LCDR1, LCDR2, and LCDR3 sequences comprising SEQ ID NO: 2207, KIS, and SEQ ID NO: 2224. respectively;(iv) a heavy chain variable region (VH) comprising HCDR1, HCDR2, and HCDR3 sequences comprising SEQ ID NOs: 2273, 2274, and 2275, respectively, and a light chain variable region (VL) comprising LCDR1, LCDR2, and LCDR3 sequences comprising SEQ ID NOs: 2207, KIS, and SEQ ID NO: 2277, respectively; or(v) a heavy chain variable region (VH) comprising HCDR1, HCDR2, and HCDR3 sequences comprising SEQ ID NOs: 2371, 2372. and 2373, respectively, and a light chain variable region (VL) comprising LCDRL LCDR2, and LCDR3 sequences comprising SEQ ID NO: 2207, KIS, and SEQ ID NO: 2224, respectively.182. The AAV particle of any one of embodiments 1-46, wherein the antibody molecule binds to:(a) human tau phosphorylated at amino acid residue SI 99, but not at amino acid residues S202 and T205, optionally wherein the antibody molecule comprises a heavy chain variable region (VH) comprising HCDR1, HCDR2, and HCDR3 sequences comprising SEQ ID NOs: 2200, 2201, and 2202, respectively, and a light chain variable region (VL) comprising LCDR1, LCDR2, and LCDR3 sequences comprising SEQ ID NO: 2207, KIS, and SEQ ID NO: 2209, respectively;(b) human tau phosphory lated at amino acid residue S202, but not at amino acid residues SI 99 and T205, optionally wherein the antibody molecule comprises (i) a heavy chain variable region (VH)comprising HCDR1, HCDR2, and HCDR3 sequences comprising SEQ ID NOs: 2218, 2219, and 2220, respectively, and a light chain variable region (VL) comprising LCDR1, LCDR2, and LCDR3 sequences comprising SEQ ID NO: 2207, KIS, and SEQ ID NO: 2224, respectively; (ii) a heavy chain variable region (VH) comprising HCDR1, HCDR2, and HCDR3 sequences comprising SEQ ID NOs: 2248, 2219, and 2249, respectively, and a light chain variable region (VL) comprising LCDR1, LCDR2. and LCDR3 sequences comprising SEQ ID NO: 2207, KIS, and SEQ ID NO: 2224, respectively; or (iii) a heavy chain variable region (VH) comprising HCDR1, HCDR2, and HCDR3 sequences comprising SEQ ID NOs: 2371, 2372, and 2373, respectively, and a light chain variable region (VL) comprising LCDR1, LCDR2, and LCDR3 sequences comprising SEQ ID NO: 2207, KIS, and SEQ ID NO: 2224, respectively;(c) human tau phosphory lated at amino acid residue T205, but not at amino acid residues S199 and S202, optionally wherein the antibody molecule comprises (i) a heavy chain variable region (VH) comprising HCDR1, HCDR2. and HCDR3 sequences comprising SEQ ID NOs: 2218, 2219, and 2220, respectively, and a light chain variable region (VL) comprising LCDR1, LCDR2, and LCDR3 sequences comprising SEQ ID NO: 2207, KIS, and SEQ ID NO: 2224, respectively; (ii) a heavy chain variable region (VH) comprising HCDR1, HCDR2, and HCDR3 sequences comprising SEQ ID NOs: 2248, 2219, and 2249, respectively, and a light chain variable region (VL) comprising LCDR1, LCDR2, and LCDR3 sequences comprising SEQ ID NO: 2207, KIS, and SEQ ID NO: 2224, respectively; or (iii) a heavy chain variable region (VH) comprising HCDRL HCDR2, and HCDR3 sequences comprising SEQ ID NOs: 2371, 2372, and 2373, respectively, and a light chain variable region (VL) comprising LCDR1, LCDR2, and LCDR3 sequences comprising SEQ ID NO: 2207, KIS, and SEQ ID NO: 2224, respectively;(d) human tau phosphory lated at a combination of amino acid residues S199 and T205, but not at amino acid residue S202 (e.g., wherein binding tau phosphorylated at a combination of S199 and T205 is at least 3-times stronger (e.g., at least 4-time stronger) than background (e.g., non-specific) level of binding, e.g., binding by hlgGl isotype control), optionally wherein the antibody molecule comprises (i) a heavy chain variable region (VH) comprising HCDRL HCDR2, and HCDR3 sequences comprising SEQ ID NOs: 2218, 2219, and 2220, respectively, and a light chain variable region (VL) comprising LCDR1, LCDR2, and LCDR3 sequences comprising SEQ ID NO: 2207, KIS, and SEQ ID NO: 2224, respectively; (ii) a heavy chain variable region (VH) comprising HCDR1, HCDR2, and HCDR3 sequences comprising SEQ ID NOs: 2248, 2219, and 2249, respectively, and a light chain variable region (VL) comprising LCDRL LCDR2, and LCDR3 sequences comprising SEQ ID NO: 2207, KIS, and SEQ ID NO: 2224, respectively; (iii) a heavy chain variable region (VH) comprising HCDR1, HCDR2, and HCDR3 sequences comprising SEQ ID NOs: 2200, 2201, and 2202, respectively, and a light chain variable region (VL) comprising LCDR1, LCDR2, and LCDR3 sequences comprising SEQ ID NO: 2207, KIS. and SEQ ID NO: 2209, respectively; or (iv) a heavy chain variable region (VH) comprising HCDR1,HCDR2, and HCDR3 sequences comprising SEQ ID NOs: 2371, 2372, and 2373, respectively, and a light chain variable region (VL) comprising LCDR1, LCDR2, and LCDR3 sequences comprising SEQ ID NO: 2207, KIS, and SEQ ID NO: 2224, respectively;(e) human tau phosphorylated at a combination of amino acid residues S202 and T205, but not at amino acid residue SI 99, but not human tau phosphorylated at a combination of residues SI 99 and S202, but not T205, optionally wherein the antibody molecule comprises a heavy chain variable region (VH) comprising HCDR1, HCDR2, and HCDR3 sequences comprising SEQ ID NOs: 2273, 2274, and 2275, respectively, and a light chain variable region (VL) comprising LCDRL LCDR2, and LCDR3 sequences comprising SEQ ID NO: 2207, KIS, and SEQ ID NO: 2277, respectively;(f) human tau phosphorylated at a combination of amino acid residues (i) S202 and T205, but not S 119, and (ii) S199 and T205, but not S202. e.g., at least 2 times (e.g., at least 3 times, at least 4 times, at least 5 times, 2-6 times, 2-5 times. 2-4 times, 2-3 times, 3-5 times or 4-5 times) more strongly than background (non-specific) level of binding, e.g., binding by hlgGl isotype control), optionally wherein the antibody molecule comprises (i) a heavy chain variable region (VH) comprising HCDR1, HCDR2, and HCDR3 sequences comprising SEQ ID NOs: 2218, 2219, and 2220, respectively, and a light chain variable region (VL) comprising LCDR1, LCDR2, and LCDR3 sequences comprising SEQ ID NO: 2207, KIS. and SEQ ID NO: 2224, respectively; (ii) a heavy chain variable region (VH) comprising HCDR1, HCDR2, and HCDR3 sequences comprising SEQ ID NOs: 2248, 2219, and 2249, respectively, and a light chain variable region (VL) comprising LCDRL LCDR2, and LCDR3 sequences comprising SEQ ID NO: 2207, KIS, and SEQ ID NO: 2224, respectively; (iii) a heavy chain variable region (VH) comprising HCDR1, HCDR2, and HCDR3 sequences comprising SEQ ID NOs: 2200, 2201, and 2202, respectively, and a light chain variable region (VL) comprising LCDR1, LCDR2, and LCDR3 sequences comprising SEQ ID NO: 2207, KIS. and SEQ ID NO: 2209, respectively; or (iv) a heavy chain variable region (VH) comprising HCDR1, HCDR2, and HCDR3 sequences comprising SEQ ID NOs: 2371, 2372, and 2373, respectively, and a light chain variable region (VL) comprising LCDRL LCDR2, and LCDR3 sequences comprising SEQ ID NO: 2207, KIS, and SEQ ID NO: 2224, respectively;(g) human tau phosphor} dated at a combination of amino acid residues (i) S199 and S202, but not T205, (ii) S202 and T205, but not S199, (iii) S199 and T205, but not S202, and (iv) S199, S202, and T205 (e.g., wherein binding to phosphorylated tau is at least 1.6-times stronger (e.g., at least 1.7 times, at least 1.8 times, at least 1.9 times, at least 2 times, at least 3 times, 1.6-3 times, 1.6-2 times stronger) than background (non-specific) level of binding, e.g., binding by hlgGl isotype control), optionally wherein the antibody molecule comprises (i) a heavy chain variable region (VH) comprising HCDR1, HCDR2, and HCDR3 sequences comprising SEQ ID NOs: 2218, 2219, and 2220, respectively, and a light chain variable region (VL) comprising LCDR1, LCDR2, and LCDR3 sequences comprising SEQ ID NO: 2207,KIS, and SEQ ID NO: 2224, respectively; (ii) a heavy chain variable region (VH) comprising HCDR1, HCDR2, and HCDR3 sequences comprising SEQ ID NOs: 2248, 2219, and 2249, respectively, and a light chain variable region (VL) comprising LCDR1, LCDR2, and LCDR3 sequences comprising SEQ ID NO: 2207, KIS, and SEQ ID NO: 2224, respectively; (iii) a heavy chain variable region (VH) comprising HCDR1, HCDR2, and HCDR3 sequences comprising SEQ ID NOs: 2200, 2201, and 2202, respectively, and a light chain variable region (VL) comprising LCDR1, LCDR2. and LCDR3 sequences comprising SEQ ID NO: 2207, KIS, and SEQ ID NO: 2209, respectively; or (iv) a heavy chain variable region (VH) comprising HCDR1, HCDR2, and HCDR3 sequences comprising SEQ ID NOs: 2371, 2372, and 2373, respectively, and a light chain variable region (VL) comprising LCDR1, LCDR2, and LCDR3 sequences comprising SEQ ID NO: 2207, KIS, and SEQ ID NO: 2224, respectively;(h) a peptide comprising or consisting of the amino acid sequence SGDRSGYS(pS)PGSPGTPGSRSRTPS (SEQ ID NO: 2146), optionally wherein the antibody molecule comprises a heavy chain variable region (VH) comprising HCDR1, HCDR2, and HCDR3 sequences comprising SEQ ID NOs: 2200, 2201, and 2202, respectively, and a light chain variable region (VL) comprising LCDR1, LCDR2, and LCDR3 sequences comprising SEQ ID NO: 2207, KIS, and SEQ ID NO: 2209, respectively;(i) a peptide comprising or consisting of the amino acid sequence SGDRSGYSSPG(pS)PGTPGSRSRTPS (SEQ ID NO: 2147), optionally wherein the antibody molecule comprises (i) a heavy chain variable region (VH) comprising HCDR1, HCDR2, and HCDR3 sequences comprising SEQ ID NOs: 2218, 2219, and 2220, respectively, and a light chain variable region (VL) comprising LCDR1, LCDR2, and LCDR3 sequences comprising SEQ ID NO: 2207, KIS, and SEQ ID NO: 2224, respectively; (ii) a heavy chain variable region (VH) comprising HCDR1, HCDR2, and HCDR3 sequences comprising SEQ ID NOs: 2248, 2219, and 2249, respectively, and a light chain variable region (VL) comprising LCDR1, LCDR2, and LCDR3 sequences comprising SEQ ID NO: 2207, KIS, and SEQ ID NO: 2224, respectively; or (iii) a heavy chain variable region (VH) comprising HCDR1, HCDR2, and HCDR3 sequences comprising SEQ ID NOs: 2371, 2372, and 2373, respectively, and a light chain variable region (VL) comprising LCDR1, LCDR2, and LCDR3 sequences comprising SEQ ID NO: 2207, KIS, and SEQ ID NO: 2224, respectively;(j) a peptide comprising or consisting of the amino acid sequence SGDRSGYSSPGSPG(pT)PGSRSRTPS (SEQ ID NO: 2148), optionally wherein the antibody molecule comprises (i) a heavy chain variable region (VH) comprising HCDR1, HCDR2, and HCDR3 sequences comprising SEQ ID NOs: 2218, 2219, and 2220, respectively, and a light chain variable region (VL) comprising LCDR1, LCDR2, and LCDR3 sequences comprising SEQ ID NO: 2207, KIS, and SEQ ID NO: 2224, respectively; (ii) a heavy chain variable region (VH) comprising HCDR1, HCDR2, andHCDR3 sequences comprising SEQ ID NOs: 2248, 2219, and 2249, respectively, and a light chain variable region (VL) comprising LCDR1, LCDR2, and LCDR3 sequences comprising SEQ ID NO: 2207, KIS, and SEQ ID NO: 2224, respectively; or (iii) a heavy chain variable region (VH) comprising HCDR1, HCDR2, and HCDR3 sequences comprising SEQ ID NOs: 2371, 2372, and 2373, respectively, and a light chain variable region (VL) comprising LCDR1, LCDR2, and LCDR3 sequences comprising SEQ ID NO: 2207, KIS. and SEQ ID NO: 2224, respectively:(k) a peptide comprising or consisting of the amino acid sequence SGDRSGYS(pS)PGSPG(pT)PGSRSRTPS (SEQ ID NO: 2152) (e.g., wherein binding to the peptide is at least 3 times stronger (e.g., at least 4 times stronger) than background (non-specific) level of binding, e.g., binding by hlgGl isotype control), optionally wherein tire antibody molecule comprises (i) a heavy chain variable region (VH) comprising HCDR1. HCDR2, and HCDR3 sequences comprising SEQ ID NOs: 2218, 2219, and 2220. respectively, and a light chain variable region (VL) comprising LCDR1, LCDR2, and LCDR3 sequences comprising SEQ ID NO: 2207, KIS, and SEQ ID NO: 2224, respectively; (ii) a heavy chain variable region (VH) comprising HCDR1, HCDR2, and HCDR3 sequences comprising SEQ ID NOs: 2248, 2219, and 2249, respectively, and a light chain variable region (VL) comprising LCDR1, LCDR2, and LCDR3 sequences comprising SEQ ID NO: 2207, KIS, and SEQ ID NO: 2224, respectively; (iii) a heavy chain variable region (VH) comprising HCDR1, HCDR2, and HCDR3 sequences comprising SEQ ID NOs: 2200, 2201, and 2202, respectively, and a light chain variable region (VL) comprising LCDR1, LCDR2, and LCDR3 sequences comprising SEQ ID NO: 2207, KIS, and SEQ ID NO: 2209, respectively; or (iv) a heavy chain variable region (VH) comprising HCDR1, HCDR2, and HCDR3 sequences comprising SEQ ID NOs: 2371, 2372, and 2373, respectively, and a light chain variable region (VL) comprising LCDR1, LCDR2, and LCDR3 sequences comprising SEQ ID NO: 2207, KIS. and SEQ ID NO: 2224, respectively;(l) a peptide comprising or consisting of the amino acid sequence SGDRSGYSSPG(pS)PG(pT)PGSRSRTPS (SEQ ID NO: 2151), but not a peptide comprising or consisting of the amino acid sequence SGDRSGYS(pS)PG(pS)PGTPGSRSRTPS (SEQ ID NO: 2150), optionally wherein the antibody molecule comprises a heavy chain variable region (VH) comprising HCDR1, HCDR2, and HCDR3 sequences comprising SEQ ID NOs: 2273, 2274, and 2275, respectively, and a light chain variable region (VL) comprising LCDR1, LCDR2. and LCDR3 sequences comprising SEQ ID NO: 2207, KIS. and SEQ ID NO: 2277, respectively(m) peptides comprising or consisting of the amino acid sequences SGDRSGYSSPG(pS)PG(pT)PGSRSRTPS (SEQ ID NO: 2151) and SGDRSGYS(pS)PGSPG(pT)PGSRSRTPS (SEQ ID NO: 2152), e.g., wherein binding to the latter peptide is at least 2 times (e.g., at least 3 times, at least 4 times, at least 5 times, 2-6 times. 2-5 times, 2-4times, 2-3 times, 3-5 times or 4-5 times) more stronger than background (non-specific) level of binding, e.g., binding by hlgGl isotype control), optionally wherein the antibody molecule comprises (i) a heavy chain variable region (VH) comprising HCDR1, HCDR2, and HCDR3 sequences comprising SEQ ID NOs: 2218, 2219, and 2220, respectively, and a light chain variable region (VL) comprising LCDR1, LCDR2. and LCDR3 sequences comprising SEQ ID NO: 2207, KIS, and SEQ ID NO: 2224, respectively; (ii) a heavy chain variable region (VH) comprising HCDR1, HCDR2, and HCDR3 sequences comprising SEQ ID NOs: 2248, 2219, and 2249, respectively, and a light chain variable region (VL) comprising LCDR1, LCDR2, and LCDR3 sequences comprising SEQ ID NO: 2207, KIS, and SEQ ID NO: 2224, respectively; (iii) a heavy chain variable region (VH) comprising HCDR1, HCDR2, and HCDR3 sequences comprising SEQ ID NOs: 2200, 2201, and 2202, respectively, and a light chain variable region (VL) comprising LCDR1, LCDR2, and LCDR3 sequences comprising SEQ ID NO: 2207, KIS. and SEQ ID NO: 2209, respectively; or (iv) a heavy chain variable region (VH) comprising HCDR1, HCDR2, and HCDR3 sequences comprising SEQ ID NOs: 2371, 2372, and 2373, respectively, and a light chain variable region (VL) comprising LCDR1, LCDR2, and LCDR3 sequences comprising SEQ ID NO: 2207, KIS, and SEQ ID NO: 2224, respectively; or(n) peptides comprising or consisting of the amino acid sequences SGDRSGYS(pS)PG(pS)PGTPGSRSRTPS (SEQ ID NO: 2150), SGDRSGYSSPG(pS)PG(pT)PGSRSRTPS (SEQ ID NO: 2151), SGDRSGYS(pS)PGSPG(pT)PGSRSRTPS (SEQ ID NO: 2152), and SGDRSGYS(pS)PG(pS)PG(pT)PGSRSRTPS (SEQ ID NO: 2149) (e.g., wherein binding to the peptides is at least 1.6 times stronger (e.g., at least 1.7 times, at least 1.8 times, at least 1.9 times, at least 2 times, at least 3 times, 1.6-4 times, 1.6-3 times stronger) than background (non-specific) level of binding, e.g., binding by hlgGl isotype control), optionally wherein the antibody molecule comprises (i) a heavy chain variable region (VH) comprising HCDR1, HCDR2, and HCDR3 sequences comprising SEQ ID NOs: 2218, 2219, and 2220, respectively, and a light chain variable region (VL) comprising LCDR1, LCDR2, and LCDR3 sequences comprising SEQ ID NO: 2207, KIS, and SEQ ID NO: 2224, respectively; (ii) a heavy chain variable region (VH) comprising HCDR1, HCDR2, and HCDR3 sequences comprising SEQ ID NOs: 2248, 2219, and 2249, respectively, and a light chain variable region (VL) comprising LCDR1, LCDR2. and LCDR3 sequences comprising SEQ ID NO: 2207, KIS, and SEQ ID NO: 2224, respectively; (iii) a heavy chain variable region (VH) comprising HCDR1, HCDR2, and HCDR3 sequences comprising SEQ ID NOs: 2200, 2201, and 2202, respectively, and a light chain variable region (VL) comprising LCDR1, LCDR2, and LCDR3 sequences comprising SEQ ID NO: 2207, KIS, and SEQ ID NO: 2209, respectively; or (iv) a heavy chain variable region (VH) comprising HCDR1, HCDR2, and HCDR3 sequences comprising SEQ ID NOs: 2371, 2372, and 2373, respectively, and a light chainvariable region (VL) comprising LCDR1, LCDR2, and LCDR3 sequences comprising SEQ ID NO: 2207, KIS, and SEQ ID NO: 2224, respectively;wherein p(S) and p(T) correspond to a phosphorylated serine and phosphorylated threonine, respectively,optionally wherein binding is assessed, e.g., using ELISA, and optionally wherein human tau has the sequence set forth in SEQ ID NO: 9200.183. The AAV particle of any one of embodiments 1-46, wherein the antibody molecule binds to:(a) tau phosphorylated at T217, but not at T212 or T214, or(b) peptides comprising or consisting of tire sequences GTPGSRSRTPSLP(pT)PPTRE (SEQ ID NO: 2155) and GTPGSRSRTP(pS)LP(pT)PPTRE (SEQ ID NO: 2158), but not peptides comprising or consisting of the sequences GTPGSRSR(pT)PSLPTPPTRE (SEQ ID NO: 2153), GTPGSRSRTP(pS)LPTPPTRE (SEQ ID NO: 2154), and GTPGSRSR(pT)P(pS)LPTPPTRE (SEQ ID NO: 2156),wherein p(S) and p(T) correspond to a phosphorylated serine and phosphorylated threonine, respectively,optionally wherein binding of the antibody molecule to tau or the peptide is at least 1.5 times stronger (e.g., at least 1.6 times, at least 1.7 times, at least 1.8 times, at least 1.9 times, at least 2 times, at least 3 times, at least 4 times, at least 5 times, at least 6 times, 1.5-4 times, 1.5-3, 4-6 times stronger) than background (non-specific) level of binding, e.g., binding by hlgGl isotype control),optionally wherein binding of the antibody molecule to tau or the peptide is assessed, e.g., using one point ELISA as described, and optionally wherein human tau has the sequence set forth in SEQ ID NO: 9200. andoptionally wherein the antibody molecule comprises:(i) a heavy chain variable region (VH) comprising HCDR1, HCDR2, and HCDR3 sequences comprising SEQ ID NOs: 2232, 2233, and 2234, respectively, and a light chain variable region (VL) comprising LCDR1, LCDR2, and LCDR3 sequences comprising SEQ ID NO: 2238, DVS, and SEQ ID NO: 2240, respectively;(ii) a heavy chain variable region (VH) comprising HCDR1, HCDR2. and HCDR3 sequences comprising SEQ ID NOs: 2284, 2392, and 2393, respectively, and a light chain variable region (VL) comprising LCDR1, LCDR2, and LCDR3 sequences comprising SEQ ID NO: 2404, AAS, and SEQ ID NO: 2406, respectively; or(iii) a heavy chain variable region (VH) comprising HCDR1, HCDR2, and HCDR3 sequences comprising SEQ ID NOs: 2445, 2446, and 2447, respectively, and a light chain variable region (VL)comprising LCDR1, LCDR2, and LCDR3 sequences comprising SEQ ID NO: 2452, WAS, and SEQ ID NO: 2453, respectively.184. The AAV particle of any one of embodiments 1-46, wherein tire antibody molecule comprises a heavy chain variable region (VH) comprising one. two, or three of a heavy chain complementary determining region 1 (HCDR1). a heavy chain complementary determining region 2 (HCDR2), and a heavy chain complementary determining region 3 (HCDR3), and / or a light chain variable region (VL) comprising one, two, or three of a light chain complementary determining region 1 (LCDR1), a light chain complementary determining region 2 (LCDR2), and a light chain complementary determining region 3 (LCDR3), wherein:(i) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NO: 2200, SEQ ID NO: 2201, SEQ ID NO: 2202. SEQ ID NO: 2207. KIS, and SEQ ID NO: 2209, respectively;(ii) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NO: 2232, SEQ ID NO: 2233, SEQ ID NO: 2234, SEQ ID NO: 2238, DVS, and SEQ ID NO: 2240, respectively;(iii) the HCDR1, HCDR2. HCDR3, LCDR1, LCDR2. and LCDR3 comprise the amino acid sequences of SEQ ID NO: 2248, SEQ ID NO: 2219, SEQ ID NO: 2249. SEQ ID NO: 2207. KIS, and SEQ ID NO: 2224, respectively;(iv) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 compnse the amino acid sequences of SEQ ID NO: 2218, SEQ ID NO: 2219, SEQ ID NO: 2220, SEQ ID NO: 2207, KIS, and SEQ ID NO: 2224, respectively;(v) the HCDR1. HCDR2, HCDR3, LCDR1. LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NO: 2200, SEQ ID NO: 2257, SEQ ID NO: 2258. SEQ ID NO: 2262. KDS, and SEQ ID NO: 2264, respectively;(vi) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 compnse the amino acid sequences of SEQ ID NO: 2415, SEQ ID NO: 2416, SEQ ID NO: 2417, SEQ ID NO: 2420, WAS, and SEQ ID NO: 2422, respectively;(vii) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NO: 2273, SEQ ID NO: 2274, SEQ ID NO: 2275. SEQ ID NO: 2207. KIS, and 2277, respectively:(viii) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NO: 2284, SEQ ID NO: 2285, SEQ ID NO: 2286, SEQ ID NO: 2289, GNS, and SEQ ID NO: 2291, respectively;(ix) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NO: 2284, SEQ ID NO: 2299, SEQ ID NO: 2300, SEQ ID NO: 2302, DAS, and SEQ ID NO: 2304, respectively;(x) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NO: 2313, SEQ ID NO: 2314, SEQ ID NO: 2315. SEQ ID NO: 2319. DDS, and SEQ ID NO: 2321, respectively;(xi) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NO: 2330, SEQ ID NO: 2331, SEQ ID NO: 2332, SEQ ID NO: 2262, KDT, and SEQ ID NO: 2337, respectively;(xii) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise tire amino acid sequences of SEQ ID NO: 2345, SEQ ID NO: 2346, SEQ ID NO: 2347. SEQ ID NO: 2351. KVS, and SEQ ID NO: 2353, respectively;(xiii) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 2345, 2346, 2347, 2361, 2362, and 2363, respectively;(xiv) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NO: 2371, SEQ ID NO: 2372, SEQ ID NO: 2373, SEQ ID NO: 2207, KIS, and SEQ ID NO: 2224, respectively;(xv) the HCDR1, HCDR2, HCDR3. LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NO: 2381, SEQ ID NO: 2382, SEQ ID NO: 2383, SEQ ID NO: 2262, KDS, and SEQ ID NO: 2385, respectively;(xvi) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NO: 2284, SEQ ID NO: 2392, SEQ ID NO: 2393. SEQ ID NO: 2396, DVS, and SEQ ID NO: 2397, respectively;(xvii) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NO: 2284, SEQ ID NO: 2392, SEQ ID NO: 2393, SEQ ID NO: 2404, AAS, and SEQ ID NO: 2406, respectively;(xviii) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NO: 2430, SEQ ID NO: 2431, SEQ ID NO: 2432. SEQ ID NO: 2435, LGS, and SEQ ID NO: 2437, respectively;(xix) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NO: 2445, SEQ ID NO: 2446, SEQ ID NO: 2447, SEQ ID NO: 2452, WAS, and SEQ ID NO: 2453, respectively;(xx) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NO: 2459, SEQ ID NO: 2460, SEQ ID NO: 2461, SEQ ID NO: 2465, VGS, and SEQ ID NO: 2467, respectively;(xxi) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of any of the HCDR and LCDR sequences provided in Tables 14-16; or(xxii) a variant, e.g., functional variant, of the antibody molecules of any one of (i)-(xxi), wherein any one, two, three, four, five or all of the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and / or LCDR3 comprises one, two, or at most three substitutions (e.g., conservative substitutions); or wherein any one, two, three, four, five or all of the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and / or LCDR3 comprises one, two, or at most three different amino acids relative to any of the sequences in (i)-(xxi).185. The AAV particle of embodiment 1-46, or 173-184, wherein the antibody molecule comprises:(a) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NO: 2248, SEQ ID NO: 2219, SEQ ID NO: 2249, SEQ ID NO: 2207, KIS, and SEQ ID NO: 2224, respectively;(b) the HCDRl, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NO: 2200, SEQ ID NO: 2201, SEQ ID NO: 2202. SEQ ID NO: 2207. KIS, and SEQ ID NO: 2209, respectively;(c) the HCDRl, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NO: SEQ ID NO: 2232, SEQ ID NO: 2233, SEQ ID NO: 2234, SEQ ID NO: 2238, DVS, and SEQ ID NO: 2240, respectively;(d) the HCDRl, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NO: 2218, SEQ ID NO: 2219, SEQ ID NO: 2220. SEQ ID NO: 2207. KIS, and SEQ ID NO: 2224, respectively;(e) the HCDRl, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NO: 2415, SEQ ID NO: 2416, SEQ ID NO: 2417, SEQ ID NO: 2420, WAS, and SEQ ID NO: 2422, respectively; or(f) the HCDRl, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NO: 2200, SEQ ID NO: 2257, SEQ ID NO: 2258. SEQ ID NO: 2262. KDS, and SEQ ID NO: 2264, respectively.186. The AAV particle of any one of embodiments 1-46, or 173-185, wherein the antibody molecule comprises a heavy chain CDR1, CDR2, and CDR3, and / or a light chain CDR1, CDR2, and CDR3 of an antibody molecule comprising a heavy chain variable region (VH) and light chain variable region (VL)comprising: (i) SEQ ID NOs: 2214 and 2215, respectively; (ii) SEQ ID NOs: 2244 and 2245, respectively; (iii) SEQ ID NOs: 2253 and 2254, respectively; (iv) SEQ ID NOs: 2228 and 2229, respectively; (v) SEQ ID NOs: 2269 and 2270, respectively; (vi) SEQ ID NOs: 2426 and 2427, respectively; (vii) SEQ ID NOs: 2280 and 2281, respectively; (viii) SEQ ID NOs: 2295 and 2296, respectively; (ix) SEQ ID NOs: 2309 and 2310, respectively; (x) SEQ ID NOs: 2326 and 2327, respectively; (xi) SEQ ID NOs: 2341 and 2342, respectively; (xii) SEQ ID NOs: 2357 and 2358, respectively; (xiii) SEQ ID NOs: 2367 and 2368, respectively; (xiv) SEQ ID NOs: 2377 and 2378, respectively; (xv) SEQ ID NOs: 2388 and 2389, respectively; (xvi) SEQ ID NOs: 2400 and 2401, respectively; (xvii) SEQ ID NOs: 2411 and 2412, respectively; (xviii) SEQ ID NOs: 2441 and 2442, respectively; (xix) SEQ ID NOs: 2455 and 2456, respectively; or (xx) SEQ ID NOs: 2470 and 2471, respectively.187. The AAV particle of any one of embodiments 1-46, or 173-168, wherein the antibody molecule comprises a VH comprising:(i) the amino acid sequence of any VEI provided in Table 14 or 15, or an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;(ii) an amino acid sequence comprising at least one, two or three modifications, but not more than 30, 20 or 10 modifications relative to the amino acid sequence of any VH provided in Table 14 or 15;(iii) an amino acid sequence comprising at least one, two or three, but not more than 30, 20 or 10 different amino acids relative to any one of the amino acid sequences of any VH sequences provided in Table 14 or 15; or(iv) an amino acid sequence encoded by a nucleotide sequence of any VH provided in Table 14 or 15, or a nucleotide sequence having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 96%. 97%, 98%, or 99% sequence identity thereto.188. The AAV particle of any one of embodiments 1-46, or 173-187, wherein tire antibody molecule comprises a VH comprising:(i) the amino acid sequence of any of SEQ ID NOs: 2253. 2214, 2244, 2228, 2426, and 2269, or an amino acid sequence having at least 70%, 75%, 80%. 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;(ii) an amino acid sequence comprising at least one, two or three modifications, but not more than 30, 20 or 10 modifications of the amino acid sequence of any of SEQ ID NOs: 2253, 2214, 2244, 2228, 2426, and 2269;(iii) an amino acid sequence comprising at least one, two or three, but not more than 30, 20 or 10 different amino acids relative to any one of the amino acid sequences of any of SEQ ID NOs: 2253, 2214, 2244, 2228, 2426, and 2269; or(iv) an amino acid sequence encoded by a nucleotide sequence of any of SEQ ID NOs: 2255, 2216, 2246, 2230, 2428, and 2271, or a nucleotide sequence having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 96%, 97%, 98%. or 99% sequence identity thereto.189. The AAV particle of any one of embodiments 1-46, or 173-188, wherein the antibody molecule comprises a VL comprising:(i) the amino acid sequence of any VL provided in Table 14 or 15, or an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;(ii) an amino acid sequence comprising at least one, two or three modifications, but not more than 30, 20 or 10 modifications relative to the amino acid sequence of any VL provided in Table 14 or 15;(iii) an amino acid sequence comprising at least one, two or three, but not more than 30, 20 or 10 different amino acids relative to any one of the amino acid sequences of any VL sequences provided in Table 14 or 15; or(iv) an amino acid sequence encoded by a nucleotide sequence of any VL provided in Table 14 or 15, or a nucleotide sequence having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto.190. Hie AAV particle of any one of embodiments 1-46, or 173-189, wherein the antibody molecule comprises a VL comprising:(i) the amino acid sequence of any of SEQ ID NOs: 2254, 2215, 2245, 2229, 2427, and 2270, or an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;(ii) an amino acid sequence comprising at least one, two or three modifications, but not more than 30, 20 or 10 modifications of the amino acid sequence of any of SEQ ID NOs: 2254, 2215, 2245, 2229, 2427, and 2270;(iii) an amino acid sequence comprising at least one, two or three, but not more than 30, 20 or 10 different amino acids relative to any one of the amino acid sequences of any of SEQ ID NOs: 2254, 2215, 2245, 2229, 2427, and 2270; or(iv) an amino acid sequence encoded by a nucleotide sequence of any of SEQ ID NOs: 2256, 2217, 2247, 2231, 2429, and 2272, or a nucleotide sequence having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto.191. Hie AAV particle of any one of embodiments 1-46, or 173-190, wherein the antibody molecule comprises:(i) a VH comprising:(a) the amino acid sequence of any VH provided in Table 14 or 15, or an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;(b) an amino acid sequence comprising at least one, two or three modifications, but not more than 30, 20 or 10 modifications relative to the amino acid sequence of any VH provided in Table 14 or 15;(c) an amino acid sequence comprising at least one, two or three, but not more than 30, 20 or 10 different amino acids relative to any one of the amino acid sequences of any VH sequences provided in Table 14 or 15; or(d) an amino acid sequence encoded by a nucleotide sequence of any VH provided in Table 14 or 15, or a nucleotide sequence having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 96%. 97%. 98%. or 99% sequence identity thereto; and(ii) a VL comprising:(a) the amino acid sequence of any VL provided in Table 14 or 15, or an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;(b) an amino acid sequence comprising at least one, two or three modifications, but not more than 30, 20 or 10 modifications relative to the amino acid sequence of any VL provided in Table 14 or 15;(c) an amino acid sequence comprising at least one, two or three, but not more than 30, 20 or 10 different amino acids relative to any one of the amino acid sequences of any VL sequences provided in Table 14 or 15; or(d) an amino acid sequence encoded by a nucleotide sequence of any VL provided in Table 14 or 15, or a nucleotide sequence having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 96%. 97%. 98%. or 99% sequence identity thereto.192. The AAV particle of any one of embodiments 1-46, or 173-191, wherein the antibody molecule comprises the amino acid sequence of any VH of an antibody molecule provided in Table 14 or 15, and the amino acid sequence of tire VL of the antibody molecule provided in Table 14 or 15.193. The AAV particle of any one of embodiments 1-46, or 173-192, wherein the antibody molecule comprises:(i) a VH comprising the amino acid sequence of SEQ ID NO: 2253; an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; an amino acid sequence comprising at least one, two or three, but not more than 30, 20 or 10 different amino acids relative to SEQ ID NO: 2253; or an amino acid sequence comprising at least one, two or three, but not more than 30, 20 or 10 modifications, e.g., substitutions (e.g., conservative substitutions) relative to SEQ ID NO: 2253; and(ii) a VL comprising the amino acid sequence of SEQ ID NO: 2254, or an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; an amino acid sequence comprising at least one, two or three, but not more than 30, 20 or 10 different amino acids relative to SEQ ID NO: 2254; or an amino acid sequence comprising at least one, two or three, but not more than 30, 20 or 10 modifications, e.g., substitutions (e.g., conservative substitutions) relative to SEQ ID NO: 2254.194. Hie AAV particle of any one of embodiments 1-46, or 173-193, wherein the antibody molecule comprises:(i) a VH comprising the amino acid sequence of SEQ ID NO: 2214: an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; an amino acid sequence comprising at least one, two or three, but not more than 30, 20 or 10 different amino acids relative to SEQ ID NO: 2214; or an amino acid sequence comprising at least one, two or three, but not more than 30, 20 or 10 modifications, e.g., substitutions (e.g., conservative substitutions) relative to SEQ ID NO: 2214; and(ii) a VL comprising the amino acid sequence of SEQ ID NO: 2215, or an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; an amino acid sequence comprising at least one, two or three, but not more than 30, 20 or 10 different amino acids relative to SEQ ID NO: 2215; or an amino acid sequence comprising at least one, two or three, but not more than 30, 20 or 10 modifications, e.g., substitutions (e.g., conservative substitutions) relative to SEQ ID NO: 2215.195. The AAV particle of any one of embodiments 1-46, or 173-192, wherein the antibody molecule comprises:(i) a VH comprising the amino acid sequence of SEQ ID NO: 2244; an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% sequence identitythereto; an amino acid sequence comprising at least one, two or three, but not more than 30, 20 or 10 different amino acids relative to SEQ ID NO: 2244; or an amino acid sequence comprising at least one, two or three, but not more than 30, 20 or 10 modifications, e.g., substitutions (e.g., conservative substitutions) relative to SEQ ID NO: 2244; and(ii) a VL comprising tire amino acid sequence of SEQ ID NO: 2245, or an amino acid sequence having at least 70%. 75%. 80%, 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; an amino acid sequence comprising at least one, two or three, but not more than 30, 20 or 10 different amino acids relative to SEQ ID NO: 2245; or an amino acid sequence comprising at least one, two or three, but not more than 30, 20 or 10 modifications, e.g., substitutions (e.g., conservative substitutions) relative to SEQ ID NO: 2245.196. The AAV particle of any one of embodiments 1-46, or 173-192, wherein the antibody molecule comprises:(i) a VH comprising the amino acid sequence of SEQ ID NO: 2228; an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% sequence identity' thereto; an amino acid sequence comprising at least one, two or three, but not more than 30, 20 or 10 different amino acids relative to SEQ ID NO: 2228; or an amino acid sequence comprising at least one, two or three, but not more than 30, 20 or 10 modifications, e.g., substitutions (e.g., conservative substitutions) relative to SEQ ID NO: 2228; and(ii) a VL comprising the amino acid sequence of SEQ ID NO: 2229, or an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% sequence identity' thereto; an amino acid sequence comprising at least one, two or three, but not more than 30, 20 or 10 different amino acids relative to SEQ ID NO: 2229; or an amino acid sequence comprising at least one, two or three, but not more than 30, 20 or 10 modifications, e.g., substitutions (e.g., conservative substitutions) relative to SEQ ID NO: 2229.197. The AAV particle of any one of embodiments 1-46, or 173-192, wherein tire antibody' molecule comprises:(i) a VH comprising the amino acid sequence of SEQ ID NO: 2269: an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; an amino acid sequence comprising at least one, two or three, but not more than 30, 20 or 10 different amino acids relative to SEQ ID NO: 2269; or an amino acid sequence comprising at least one, two or three, but not more than 30, 20 or 10 modifications, e.g., substitutions (e.g., conservative substitutions) relative to SEQ ID NO: 2269; and(ii) a VL comprising the amino acid sequence of SEQ ID NO: 2270, or an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; an amino acid sequence comprising at least one, two or three, but not more than 30, 20 or 10 different amino acids relative to SEQ ID NO: 2270; or an amino acid sequence comprising at least one, two or three, but not more than 30, 20 or 10 modifications, e.g., substitutions (e.g., conservative substitutions) relative to SEQ ID NO: 2270.198. The AAV particle of any one of embodiments 1-46, or 173-192, wherein the antibody molecule comprises:(i) a VH comprising the amino acid sequence of SEQ ID NO: 2426; an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; an amino acid sequence comprising at least one, two or three, but not more than 30. 20 or 10 different amino acids relative to SEQ ID NO: 2426; or an amino acid sequence comprising at least one, two or three, but not more than 30, 20 or 10 modifications, e.g., substitutions (e.g., conservative substitutions) relative to SEQ ID NO: 2426; and(ii) a VL comprising tire amino acid sequence of SEQ ID NO: 2427, or an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; an amino acid sequence comprising at least one, two or three, but not more than 30, 20 or 10 different amino acids relative to SEQ ID NO: 2427; or an amino acid sequence comprising at least one, two or three, but not more than 30, 20 or 10 modifications, e.g., substitutions (e.g., conservative substitutions) relative to SEQ ID NO: 2427.199. Hie AAV particle of any one of embodiments 1-46, or 173-198, wherein the antibody molecule comprises a heavy chain variable region (VH) and / or a light chain variable region (VL) comprising:: (i) SEQ ID NOs: 2214 and 2215, respectively; (ii) SEQ ID NOs: 2244 and 2245, respectively; (iii) SEQ ID NOs: 2253 and 2254, respectively; (iv) SEQ ID NOs: 2228 and 2229, respectively; (v) SEQ ID NOs: 2269 and 2270, respectively; (vi) SEQ ID NOs: 2426 and 2427, respectively; (vii) SEQ ID NOs: 2280 and 2281, respectively; (viii) SEQ ID NOs: 2295 and 2296, respectively; (ix) SEQ ID NOs: 2309 and 2310, respectively; (x) SEQ ID NOs: 2326 and 2327, respectively; (xi) SEQ ID NOs: 2341 and 2342, respectively; (xii) SEQ ID NOs: 2357 and 2358, respectively; (xiii) SEQ ID NOs: 2367 and 2368, respectively; (xiv) SEQ ID NOs: 2377 and 2378, respectively; (xv) SEQ ID NOs: 2388 and 2389, respectively; (xvi) SEQ ID NOs: 2400 and 2401, respectively; (xvii) SEQ ID NOs: 2411 and 2412, respectively; (xviii) SEQ ID NOs: 2441 and 2442, respectively; (xix) SEQ ID NOs: 2455 and 2456, respectively; (xx) SEQ ID NOs: 2470 and 2471, respectively, (xxi) a variant, e.g., functional variant, ofthe antibody molecules of any one of (i)-(xx), wherein the VH and / or VL has an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; or (xxii) a variant, e.g., functional variant, of the antibody molecules of any one of (i)-(xx), wherein the VH and / or VL comprises at least one, two, or three modifications, but not more than 30, 20, or 10 modifications (e g., amino acid substitutions, e.g., conservative substitutions) or wherein the VH and / or VL comprises at least one, two, or three, but not more than 30, 20, or 10 different amino acids.200. The AAV particle of any one of embodiments 1-46, or 173-199, wherein the antibody molecule comprises VH and VL sequences comprising the amino acid sequences of:(a) SEQ ID NOs: 2253 and 2254, respectively,(b) SEQ ID NOs: 2214 and 2215, respectively,(c) SEQ ID NOs: 2244 and 2245, respectively,(d) SEQ ID NOs: 2228 and 2229, respectively,(e) SEQ ID NOs: 2426 and 2427, respectively, or(f) SEQ ID NOs: 2269 and 2270, respectively.201. Hie AAV particle of embodiment 1-46, or 173-200, wherein the antibody molecule comprises a VH sequence encoded by a nucleotide sequence having at least 80% (e.g., 85, 90, 95, 96, 97, 98, or 99%) sequence identity to any one of SEQ ID NOs: 2255, 2216, 2246, 2230, 2428, 2271, 2282, 2297, 2311, 2328, 2343, 2359, 2369, 2379, 2390, 2402, 2413, 2443, 2457, or 2472 and / or a VL sequence encoded by a nucleotide sequence having at least 80% (e.g., 85, 90, 95, 96, 97, 98, or 99%) sequence identity to anyone of SEQ ID NOs: 2256, 2217, 2247, 2231, 2429, 2272, 2283, 2298, 2312, 2329, 2344, 2360, 2370. 2380, 2391, 2403, 2414. 2444, 2458, or 2473.202. The AAV particle of embodiment 201, wherein the antibody molecule comprises VH and VL sequences encoded by nucleotide sequences set forth in (a) SEQ ID NOs: 2255 and 2256, respectively, (b) SEQ ID NOs: 2216 and 2217, respectively, (c) SEQ ID NOs: 2246 and 2247, respectively, (d) SEQ ID NOs: 2230 and 2231, respectively, (e) SEQ ID NOs: 2428 and 2429, respectively, (f) SEQ ID NOs: 2271 and 2272, respectively, (g) SEQ ID NOs: 2282 and 2283, respectively, (h) SEQ ID NOs: 2297 and 2298, respectively, (i) SEQ ID NOs: 2311 and 2312, respectively, (j) SEQ ID NOs: 2328 and 2329, respectively, (k) SEQ ID NOs: 2343 and 2344, respectively, (1) SEQ ID NOs: 2359 and 2360, respectively, (m) SEQ ID NOs: 2369 and 2370, respectively, (n) SEQ ID NOs: 2379 and 2380, respectively, (o) SEQ ID NOs: 2390 and 2391, respectively, (p) SEQ ID NOs: 2402 and 2403, respectively, (q) SEQ ID NOs: 2413 and 2414, respectively, (r) SEQ ID NOs: 2443 and 2444,respectively, (s) SEQ ID NOs: 2457 and 2458, respectively, (t) SEQ ID NOs: 2472 and 2473, respectively, or (u) a nucleotide sequence having at least 80% (e.g., 85, 90, 95, 96, 97, 98, or 99%) sequence identity to any one of (a)-(t).203. The AAV particle of any one of embodiments 1-46, or 173-202, wherein the antibody molecule comprises:(i) a heavy chain constant region comprising an amino acid sequence of any of the heavy chain constant region sequences in Table 17, or a sequence having at least 80% (e.g., 85, 90, 95, 96, 97, 98, or 99%) sequence identity to the heavy chain constant region sequences in Table 17, or an amino acid sequence having at least one, two or three modifications, but not more than 30, 20 or 10 modifications, to the amino acid sequence of tire heavy chain constant region sequences in Table 17; and / or(ii) a light chain constant region (CL) comprising an amino acid sequence of any of the CL sequences in Table 17, or a sequence having at least 80% (e.g., 85, 90, 95, 96, 97, 98, or 99%) sequence identity to any of the CL sequences in Table 17, or an amino acid sequence having at least one, two or three modifications, but not more than 30, 20 or 10 modifications, to the amino acid sequence of the light chain constant region sequences in Table 17.204. The AAV particle of any one of embodiments 1-46, or 173-203, wherein the antibody molecule comprises:(i) a heavy chain (HC) comprising the amino acid sequence of the HC of any one of the anti-tau antibody molecules described herein (e.g., the HC of any one of the anti-tau antibody molecules listed in Tables 7-16, 13A, 13B, and 13C), or a sequence having at least 80% (e.g., 85, 90, 95, 96, 97, 98, or 99%) sequence identity to the HC sequence of any of the anti-tau antibody molecules described herein (e.g.. the HC of any one of the anti-tau antibody molecules listed in Tables 7-16, 13A, 13B, and 13C), or an amino acid sequence having at least one, two or three modifications, but not more than 30, 20 or 10 modifications, to the amino acid sequence of the HC sequence of any of the anti-tau antibody molecules described herein (e.g., tire HC of any one of the anti-tau antibody molecules listed in Tables 7-16, 13 A, 13B, and 13C); and / or(ii) a light chain (LC) comprising the amino acid sequence of the LC of any of any one of the anti-tau antibody molecules described herein (e.g., the LC of any one of the anti-tau antibody molecules listed in Tables 7-16, 13A, 13B, and 13C), or a sequence having at least 80% (e.g., 85, 90, 95, 96, 97, 98, or 99%) sequence identity to the LC sequence of any of the anti-tau antibody molecules described herein (e.g., the LC of any one of the anti-tau antibody molecules listed in Tables 7-16, 13A, 13B, and 13C), or an amino acid sequence having at least one, two or three modifications, but not more than 30, 20 or 10modifications, to the amino acid sequence of the LC sequence of any of the anti-tau antibody molecules described herein (e.g., the LC of any one of the anti-tau antibody molecules listed in Tables 7-16, 13A, 13B, and 13C).205. The isolated AAV particle of any one of embodiments 1-204, wherein the antibody molecule is a full length antibody, a bispecific antibody, a Fab, a F(ab')2, a Fv, a single chain Fv fragment (scFv). single domain antibody, or a camelid antibody.206. The AAV particle of any one of embodiments 1-205, wherein the antibody molecule comprises a heavy chain constant region selected from human IgGl, human IgG2, human IgG3, human IgG4, murine IgGl, murine IgG2a, murine IgG2b. murine IgG2c, and murine IgG3; and / or a light chain constant region selected from the light chain constant regions of kappa or lambda.207. The AAV particle of any one of embodiments 1-206, wherein the antibody molecule comprises an Fc region or functional variant thereof.208. The AAV particle of any one of embodiments 1-207, wherein the antibody molecule comprises an Fc region which has reduced affinity, e.g., ablated, affinity for an Fc receptor, e.g., as compared to a reference, wherein the reference is a wild-type Fc receptor.209. The AAV particle of any one of embodiments 1-208, wherein the antibody molecule comprises an Fc region which comprises a mutation at one, two, or all of positions 1253 (e.g., I235A), H310 (e.g., H310A or H310Q), and / or H435 (e.g.. H435A or H435Q), numbered according to the EU index as in Kabat.210. The AAV particle of any one of embodiments 1-226 or 240-420, wherein the antibody molecule comprises an Fc region which has reduced effector function (e.g., reduced ADCC), compared to a reference wherein the reference is a wild-type Fc receptor.211. The AAV particle of any one of embodiments 1-209, wherein the antibody molecule comprises an Fc region which comprises a mutation at one, two, three, four, or all of positions L235 (e g., L235V), F243 (e.g., F243L), R292 (e.g., R292P), Y300 (e.g., Y300L), and P396 (e.g., P396L), numbered according to the EU index as in Kabat.212. The AAV particle of any one of embodiments 1-211, wherein the antibody molecule comprises a signal sequence.213. The AAV particle of embodiment 212, wherein the signal sequence is encoded by a nucleotide sequence comprising of any of the signal sequences listed in Table 20, or a nucleotide sequence with at least 95% sequence identity thereto.214. The AAV particle of embodiment 212 or 213, wherein the antibody molecule further comprises a second signal sequence, wherein the second signal sequence is encoded by a nucleotide sequence comprising any of the signal sequences listed in Table 20, or a nucleotide sequence with at least 95% sequence identity thereto.215. The AAV particle of embodiment 212, wherein the signal sequence comprises the amino acid sequence comprising any one of the signal sequences listed in Table 20, or an amino acid sequence with at least 95% sequence identity thereto.216. Hie AAV particle of embodiment 212 or 215, wherein the antibody molecule further comprises a second signal sequence, wherein the second signal sequence comprises the amino acid sequence of any one of the signal sequences listed in Table 20, or an amino acid sequence with at least 95% sequence identity thereto.217. The AAV particle of any one of embodiments 212-216, wherein:(i) the signal sequence is located 5’ relative to the VH and / or the heavy chain; and / or(ii) the signal sequence is located 5’ relative to the VL and / or the light chain.218. The AAV particle of any one of embodiments 1-46, wherein the antibody molecule is selected from E2814, semorinemab (RG6100, R07105705, MTAU9937A), gosuranemab (BIIB092, BMS-986168, IPN007 / IPN002), tilavonemab (ABBV-8E12, C2N-8E12, HJ8.5), zagotenemab (LY3303560, MC-1 IgGl). posdinemab (JNJ-63733657, B296, PT3), bepranemab (UCB0107), BIIB076 (NI-105.6C5 huIgGIX), RG7345 (RO6926496), UCB0107 (D IgG4), NPT088, PNT001, Lu AF87908, PRX005, or APNmAbOO5.219. The AAV particle of any one of embodiments 72-218, wherein:(i) the VH and VL are connected directly, e.g., without a linker;(ii) the VH and VL are connected via a linker (e.g., a linker provided in Table 19);(iii) the heavy chain and light chain are connected directly, e.g., without a linker; or(iv) the heavy chain and light chain are connected via a linker (e.g., a linker provided in Table 19).220. The AAV particle of embodiment 219, wherein:(i) the linker comprises an encoded furin cleavage site;(ii) the linker comprises an encoded T2A linker; and / or(iii) the linker comprises a glycine -serine linker, e.g., a G4S linker (SEQ ID NO: 4535) or a (G4S)3 linker (SEQ ID NO: 3734).221. The AAV particle of any one of embodiments 1-220, wherein the antibody molecule comprises a second antigen-binding region having a different binding specificity than the antigen-binding region that binds to tau.222. Tire AAV particle of any one of embodiments 1-221. wherein tire antibody molecule is a multispecific antibody molecule comprising at least a first antigen-binding domain and a second antigenbinding domain, e g., a bispecific antibody molecule.223. The AAV particle of embodiment 222, wherein the first and / or second antigen binding domain of the antibody molecule comprise an IgG antibody, single-chain Fv (scFv), a scFv fragment, a Fab, an F(ab’)2, a single-chain Fab (scFabs), a single-chain antibody, a diabody, a bispecific antibody, an antibody variable domain, a VHH, a single domain antibody, a camelid antibody, an intrabody, and / or a nanobody.224. The AAV particle of any one of embodiments 1-223, which comprises a viral genome comprising a promoter operably linked to the nucleic acid sequence encoding the antibody molecule, wherein the promoter comprises a tissue specific promoter or a ubiquitous promoter.225. The AAV particle of embodiment 224, wherein the promoter is chosen from human elongation factor la-subunit (EFla), cytomegalovirus (CMV) immediate-early enhancer and / or promoter, chicken |3-actin (CBA) and its derivative CAG, glucuronidase (GUSB), or ubiquitin C (UBC), neuron-specific enolase (NSE), platclct-dcrivcd growth factor (PDGF), platclct-dcrivcd growth factor B-chain (PDGF- ), intercellular adhesion molecule 2 (ICAM-2), synapsin (Syn), methyl-CpG binding protein 2 (MeCP2),Ca2+ / calmodulin-dependent protein kinase II (CaMKII), metabotropic glutamate receptor 2 (mGluR2), neurofilament light (NFL) or heavy (NFH), P-globin minigene np2, preproenkephalin (PPE), enkephalin (Enk) and excitatory amino acid transporter 2 (EAAT2), glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), a cardiovascular promoter (e.g., aMHC, cTnT, and CMV-MLC2k), a liver promoter (e.g., hAAT, TBG), a skeletal muscle promoter (e g., desmin, MCK, C512) or a fragment, e g., a truncation, or a functional variant thereof.226. The AAV particle of embodiment 225, wherein the promoter is an EF-la promoter variant, e.g., a truncated EF-la promoter.227. Hie AAV particle of any one of embodiments 224-226, wherein the promoter comprises the nucleotide sequence of any one of SEQ ID NOs: 9000, 9001, 9003, 9004, 9008. 9009. 9011-9020, GCATG, CGTGAG, GT, GCTCCGGT, or GTAAG, a nucleotide sequence comprising at least one, two, or three but no more than four modifications, e.g., substitutions (e.g., conservative substitutions), insertions, or deletions, relative to the nucleotide sequence of SEQ ID NOs: 9000, 9001, 9003, 9004, 9008, 9009, 9011-9020, GCATG, CGTGAG, GT, GCTCCGGT, or GTAAG, or a nucleotide sequence with at least 80% (e.g., 85%, 90%, 95%, 96%. 97%. 98%, or 99%) sequence identity to any one of SEQ ID NOs: 9000, 9001, 9003, 9004, 9008, 9009. 9011-9020. GCATG, CGTGAG, GT, GCTCCGGT, or GTAAG.228. The AAV particle of any one of embodiments 224-227, wherein the viral genome further comprises a polyA signal sequence.229. The AAV particle of any one of embodiments 224-228, wherein the viral genome further comprises an inverted terminal repeat (ITR) sequence.230. The AAV particle of any one of embodiments 224-229, wherein the viral genome comprises an ITR sequence positioned 5’ relative to the encoded antibody molecule.231. The AAV particle of any one of embodiments 224-230, wherein the viral genome comprises an ITR sequence positioned 3’ relative to the encoded antibody molecule.232. The AAV particle of any one of embodiments 224-441, wherein the viral genome comprises an ITR sequence positioned 5’ relative to the encoded antibody molecule and an ITR sequence positioned 3’ relative to the encoded antibody molecule.233. Tire AAV particle of any one of embodiments 224-232, wherein the viral genome further comprises an enhancer, a Kozak sequence (e.g., GCCGCCACCATG (SEQ ID NO: 9021) or GAGGAGCCACC (SEQ ID NO: 9022), an intron region, and / or an exon region.234. The AAV particle of any one of embodiments 224-233, wherein the viral genome comprises:(a) one or more inverted terminal repeat (ITR) sequences, optionally wherein the ITR sequence is positioned 5’ relative to the nucleic acid encoding the antibody molecule and / or the ITR sequence is positioned 3’ relative to the nucleic acid encoding the antibody molecule, optionally wherein the ITR comprises the nucleotide sequence of SEQ ID NO: 2026 and / or 2039,(b) an enhancer, optionally wherein the enhancer comprises the nucleotide sequence of SEQ ID NO: 2027,(d) an intron region, optionally wherein the intron region comprises the nucleotide sequence of SEQ ID NO: 2029,(e) a nucleotide sequence encoding one or more signal sequences, optionally wherein the signal sequence comprises the nucleotide sequence of SEQ ID NO: 2030 and / or 2035,(f) a nucleotide sequence encoding a heavy chain variable region (VH) of the antibody molecule, optionally wherein the VH is encoded by the nucleotide sequence of SEQ ID NO: 2031,(g) a nucleotide sequence encoding an IgGl heavy chain constant region, optionally wherein tire IgGl heavy chain constant region is encoded by the nucleotide sequence of SEQ ID NO: 2032,(h) a furin cleavage site, optionally wherein the furin cleavage site comprises the nucleotide sequence of SEQ ID NO: 2033,(i) a linker, optionally wherein the linker is a T2A linker, optionally wherein the T2A linker comprises the nucleotide sequence of SEQ ID NO: 2034;(j) a nucleotide sequence encoding a light chain variable region (VL), optionally wherein the VL is encoded by the nucleotide sequence of SEQ ID NO: 2036;(k) a nucleotide sequence encoding a IgG kappa light chain constant region, optionally wherein the IgG kappa light chain constant region is encoded by the nucleotide sequence of SEQ ID NO: 2037; and / or(l) a polyadcnylation (poly A) signal region, optionally wherein the T2A linker comprises the nucleotide sequence of SEQ ID NO: 2038.235. The AAV particle of any one of embodiments 224-234, wherein the viral genome comprises in 5’ to 3’ order:(i) a 5' ITR, optionally wherein the 5’ AAV ITR comprises the nucleotide sequence of SEQ ID NO: 2026, or a nucleotide sequence at least 95% identical thereto;(ii) a CMVie enhancer, optionally wherein the CMVie enhancer comprises the nucleotide sequence of SEQ ID NO: 2027, or a nucleotide sequence at least 95% identical thereto;(iii) a CBA promoter or functional variant thereof, optionally wherein the CBA promoter or functional variant thereof comprises the nucleotide sequence of SEQ ID NO: 2028, or a nucleotide sequence at least 95% identical thereto;(iv) an intron, optionally wherein the intron comprises the nucleotide sequence of SEQ ID NO: 2029, or a nucleotide sequence at least 95% identical thereto;(v) a nucleotide sequence encoding a signal sequence, optionally wherein the nucleotide sequence encoding the signal sequence comprises the nucleotide sequence of SEQ ID NO: 2030, or a nucleotide sequence at least 95% identical thereto;(vi) a nucleic acid encoding a heavy chain variable region (VH) of the antibody molecule, wherein the nucleotide sequence encoding the VH comprises the nucleotide sequence of SEQ ID NO: 2031 or a nucleotide sequence at least 80% (e.g., at least 85. 90, 95, 96, 97, 98, or 99%) identical thereto;(vii) a nucleotide sequence encoding an IgGI heavy chain constant region, optionally wherein the nucleotide sequence encoding the IgGI heavy chain constant region comprises the nucleotide sequence of SEQ ID NO: 2032, or a nucleotide sequence at least 80% (e.g., at least 85, 90, 95, 96, 97, 98, or 99%) identical thereto;(viii) a furin cleavage site, optionally wherein the furin cleavage site comprises the nucleotide sequence of SEQ ID NO: 2033, or a nucleotide sequence at least 95% identical thereto;(ix) a T2A linker, optionally wherein the T2A linker comprises the nucleotide sequence of SEQ ID NO: 2034, or a nucleotide sequence at least 95% identical thereto;(x) a nucleotide sequence encoding a signal sequence, optionally wherein the nucleotide sequence encoding the signal sequence comprises the nucleotide sequence of SEQ ID NO: 2035, or a nucleotide sequence at least 95% identical thereto;(xi) a nucleic acid encoding a light chain variable region (VL) of the antibody molecule, wherein the nucleotide sequence encoding the VL comprises the nucleotide sequence of SEQ ID NO: 2036 or a nucleotide sequence at least 80% (e.g., at least 85, 90, 95, 96, 97, 98, or 99%) identical thereto;(xii) a nucleotide sequence encoding an IgG kappa light chain constant region, optionally wherein the nucleotide sequence encoding the IgG kappa light chain constant region comprises the nucleotidesequence of SEQ ID NO: 2037, or a nucleotide sequence at least 80% (e.g., at least 85, 90, 95, 96, 97, 98, or 99%) identical thereto;(xiii) a polyA signal region, optionally wherein the polyA signal region comprises the nucleotide sequence of SEQ ID NO: 2038, or a nucleotide sequence at least 95% identical thereto; and(xiv) an ITR, optionally wherein the 3’ AAV ITR comprises the nucleotide sequence of SEQ ID NO: 2039. or a nucleotide sequence at least 95% identical thereto.236. The AAV particle of any one of embodiments 224-235, wherein the viral genome comprises the nucleotide sequence of SEQ ID NO: 2025, or a nucleotide sequence at least 80% (e.g., at least 85, 90, 95, 96, 97, 98, or 99%) identical thereto.237. The AAV particle of any one of embodiments 224-236, wherein the viral genome further comprises a nucleotide sequence encoding a miR binding site, e.g., a miR binding site that modulates, e.g., reduces, expression of the antibody molecule encoded by tire viral genome in a cell or tissue where the corresponding miRNA is expressed.238. Hie AAV particle of embodiment 237, wherein the encoded miRNA binding site is complementary, e.g., fully complementary or partially complementary, to a miRNA expressed in a cell or tissue of the DRG. liver, heart, hematopoietic, or a combination thereof.239. The AAV particle of embodiment 237 or 238, wherein the encoded miR binding site modulates, e.g., reduces, expression of the encoded antibody molecule in a cell or tissue of the DRG, liver, heart, hematopoietic lineage, or a combination thereof.240. The AAV particle of any one of embodiments 224-239, wherein the viral genome comprises at least 1-5 copies of the encoded miR binding site, e.g., at least 1, 2, 3, 4, or 5 copies.241. The AAV particle of any one of embodiments 224-240, wherein the viral genome comprises at least 3 copies of an encoded miR binding sites, optionally wherein all three copies comprise the same miR binding site, or at least one, two, three, or all of the copies comprise a different miR binding site.242. The AAV particle of embodiment 241, wherein the at least 3 copies of the encoded miR binding sites are continuous (e.g., not separated by a spacer), or are separated by a spacer, optionally wherein tire spacer comprises the nucleotide sequence GATAGTTA, or a nucleotide sequence having at least one, two, or three modifications, e.g., substitutions (e.g., conservative substitutions), but no more than fourmodifications, e.g., substitutions (e.g., conservative substitutions), relative to the nucleotide sequence GATAGTTA.243. The AAV particle of any one of embodiments 224-242, wherein the viral genome comprises at least 4 copies of an encoded miR binding site, optionally wherein all four copies comprise the same miR binding site, or at least one, two, three, or all of the copies comprise a different miR binding site.244. The AAV particle of embodiment 244, wherein the at least 4 copies of the encoded miR binding sites are continuous (e.g., not separated by a spacer), or are separated by a spacer, optionally wherein tire spacer comprises the nucleotide sequence GATAGTTA, or a nucleotide sequence having at least one, two, or three modifications, e.g., substitutions (e.g., conservative substitutions), but no more than four modifications, e.g., substitutions (e.g.. conservative substitutions), relative to the nucleotide sequence GATAGTTA.245. The AAV particle of any one of embodiments 237-244, wherein the encoded miR binding site comprises a miR122 binding site, a miR183 binding site, a miR-1 binding site, a miR-142-3p, or a combination thereof, optionally wherein:(i) the encoded miR122 binding site comprises the nucleotide sequence of SEQ ID NO: 3672, or a nucleotide sequence substantially identical (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity) thereto; or a nucleotide sequence having at least one, two, three, four, five, six, or seven modifications, e.g., substitutions (e.g., conservative substitutions), but no more than ten modifications, e.g., substitutions (e.g., conservative substitutions), relative to SEQ ID NO: 3672;(ii) the encoded miR183 binding site comprises the nucleotide sequence of SEQ ID NO: 3675, or a nucleotide sequence substantially identical (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity) thereto; or a nucleotide sequence having at least one, two, three, four, five, six, or seven modifications, e.g., substitutions (e.g., conservative substitutions), but no more than ten modifications, e.g., substitutions (e.g., conservative substitutions), relative to SEQ ID NO: 3675;(iii) the encoded miR-1 binding site comprises the nucleotide sequence of SEQ ID NO: 4679, or a nucleotide sequence substantially identical (e.g.. having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity) thereto: or a nucleotide sequence having at least one, two, three, four, five, six, or seven modifications, e.g., substitutions (e g., conservative substitutions), but no more than ten modifications, e.g., substitutions (e.g., conservative substitutions), relative to SEQ ID NO: 4679; and / or(iv) the encoded miR-142-3p binding site comprises the nucleotide sequence of SEQ ID NO: 3674, or a nucleotide sequence substantially identical (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity) thereto; or a nucleotide sequence having at least one, two, three, four, five, six, or seven modifications, e.g., substitutions (e.g., conservative substitutions), but no more than ten modifications, e.g., substitutions (e.g., conservative substitutions), relative to SEQ ID NO: 3674.246. The AAV particle of any one of embodiments 224-245, wherein the viral genome comprises an encoded miR122 binding site.247. The AAV particle of any one of embodiments 224-246, wherein the viral genome comprises at least 1-5 copies, e.g., 1. 2, or 3 copies of amiR122 binding site, optionally wherein each copy is continuous (e.g., not separated by a spacer), or each copy is separated by a spacer, optionally wherein the spacer comprises the nucleotide sequence GATAGTTA, or a nucleotide sequence having at least one, two, or three modifications, e.g., substitutions (e.g., conservative substitutions), but no more than four modifications, e g., substitutions (e.g., conservative substitutions), relative to the nucleotide sequence GATAGTTA.248. The AAV particle of any one of embodiments 245-247, wherein the encoded miR122 binding site comprises the nucleotide sequence of SEQ ID NO: 3672, or a nucleotide sequence substantially identical (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity) thereto; or a nucleotide sequence having at least one, two, three, four, five, six, or seven modifications, e.g., substitutions (e.g., conservative substitutions), but no more than ten modifications, e.g., substitutions (e.g., conservative substitutions), relative to SEQ ID NO: 3672.249. The AAV particle of any one of embodiments 224-248, wherein the viral genome comprises:(A) (i) a first encoded miR122 binding site comprising the nucleotide sequence of SEQ ID NO: 3672, or a nucleotide sequence substantially identical (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity) thereto; or a nucleotide sequence having at least one, two, three, four, five, six, or seven modifications, e.g., substitutions (e.g., conservative substitutions), but no more than ten modifications, e.g., substitutions (e.g., conservative substitutions), relative to SEQ ID NO: 3672;(ii) a first spacer comprising the nucleotide sequence GATAGTTA, or a nucleotide sequence having at least one, two, or three modifications, e.g., substitutions (e.g., conservative substitutions), butno more than four modifications, e.g., substitutions (e.g., conservative substitutions), relative to the nucleotide sequence GATAGTTA; and(iii) a second encoded miR122 binding site comprising the nucleotide sequence of SEQ ID NO: 3672, or a nucleotide sequence substantially identical (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity) thereto; or a nucleotide sequence having at least one, two. three, four, five, six, or seven modifications, e.g.. substitutions (e.g., conservative substitutions), but no more than ten modifications, e.g., substitutions (e.g., conservative substitutions), relative to SEQ ID NO: 3672; or(B) (i) a first encoded miR122 binding site comprising the nucleotide sequence of SEQ ID NO: 3672, or a nucleotide sequence substantially identical (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity) thereto; or a nucleotide sequence having at least one, two, three, four, five. six. or seven modifications, e.g., substitutions (e.g.. conservative substitutions), but no more than ten modifications, e.g., substitutions (e.g., conservative substitutions), relative to SEQ ID NO: 3672;(ii) a first spacer comprising the nucleotide sequence GATAGTTA, or a nucleotide sequence having at least one, two, or three modifications, e.g., substitutions (e.g., conservative substitutions), but no more than four modifications, e.g., substitutions (e.g., conservative substitutions), relative to the nucleotide sequence GATAGTTA;(iii) a second encoded miR122 binding site comprising the nucleotide sequence of SEQ ID NO: 3672, or a nucleotide sequence substantially identical (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity) thereto; or a nucleotide sequence having at least one, two, three, four, five, six, or seven modifications, e.g., substitutions (e.g., conservative substitutions), but no more than ten modifications, e.g., substitutions (e.g., conservative substitutions), relative to SEQ ID NO: 3672:(iv) a second spacer comprising the nucleotide sequence GATAGTTA, or a nucleotide sequence having at least one, two, or three modifications, e.g., substitutions (e.g., conservative substitutions), but no more than four modifications, e.g., substitutions (e.g., conservative substitutions), relative to the nucleotide sequence GATAGTTA; and(v) a third encoded miR122 binding site comprising the nucleotide sequence of SEQ ID NO: 3672, or a nucleotide sequence substantially identical (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity) thereto; or a nucleotide sequence having at least one, two, three, four, five, six, or seven modifications, e.g., substitutions (e.g., conservative substitutions), but no more than ten modifications, e.g., substitutions (e.g., conservative substitutions), relative to SEQ ID NO: 3672.250. The AAV particle of any one of embodiments 224-249, wherein the viral genome comprises an encoded miR183 binding site.251. The AAV particle of any one of embodiments 224-250, wherein the viral genome comprises at least 1-5 copies, e.g., 1, 2, or 3 copies of amiR183 binding site, optionally wherein each copy is continuous (e.g., not separated by a spacer), or each copy is separated by a spacer, optionally wherein the spacer comprises the nucleotide sequence GATAGTTA, or a nucleotide sequence having at least one, two, or three modifications, e.g., substitutions (e.g., conservative substitutions), but no more than four modifications, e.g., substitutions (e.g., conservative substitutions), relative to the nucleotide sequence GATAGTTA.252. The AAV particle of embodiment 251, wherein the encoded miR183 binding site comprises the nucleotide sequence of SEQ ID NO: 3675, or a nucleotide sequence substantially identical (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity) thereto; or a nucleotide sequence having at least one, two, three, four, five, six, or seven modifications, e.g., substitutions (e.g., conservative substitutions), but no more than ten modifications, e.g., substitutions (e.g., conservative substitutions), relative to SEQ ID NO: 3675.253. The AAV particle of any one of embodiments 224-252, wherein the viral genome comprises:(A) (i) a first encoded miR183 binding site comprising the nucleotide sequence of SEQ ID NO: 3675, or a nucleotide sequence substantially identical (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity) thereto; or a nucleotide sequence having at least one, two, three, four, five, six. or seven modifications, e.g., substitutions (e.g.. conservative substitutions), but no more than ten modifications, e.g., substitutions (e.g., conservative substitutions), relative to SEQ ID NO: 3675;(ii) a first spacer comprising the nucleotide sequence GATAGTTA, or a nucleotide sequence having at least one, two, or three modifications, e.g., substitutions (e.g., conservative substitutions), but no more than four modifications, e.g., substitutions (e.g., conservative substitutions), relative to the nucleotide sequence GATAGTTA; and(iii) a second encoded miR183 binding site comprising the nucleotide sequence of SEQ ID NO: 3675, or a nucleotide sequence substantially identical (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity) thereto; or a nucleotide sequence having at least one, two, three, four, five, six, or seven modifications, e.g., substitutions (e.g., conservative substitutions), butno more than ten modifications, e.g., substitutions (e.g., conservative substitutions), relative to SEQ ID NO: 3675; or(B) (i) a first encoded miR183 binding site comprising the nucleotide sequence of SEQ ID NO: 3675, or a nucleotide sequence substantially identical (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity) thereto; or a nucleotide sequence having at least one, two, three, four, five. six. or seven modifications, e.g., substitutions (e.g.. conservative substitutions), but no more than ten modifications, e.g., substitutions (e.g., conservative substitutions), relative to SEQ ID NO: 3675;(ii) a first spacer comprising the nucleotide sequence GATAGTTA, or a nucleotide sequence having at least one, two, or three modifications, e.g., substitutions (e.g., conservative substitutions), but no more than four modifications, e.g., substitutions (e.g., conservative substitutions), relative to the nucleotide sequence GATAGTTA;(iii) a second encoded miR183 binding site comprising the nucleotide sequence of SEQ ID NO: 3675, or a nucleotide sequence substantially identical (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity) thereto; or a nucleotide sequence having at least one, two, three, four, five, six, or seven modifications, e.g., substitutions (e.g., conservative substitutions), but no more than ten modifications, e.g., substitutions (e.g., conservative substitutions), relative to SEQ ID NO: 3675:(iv) a second spacer comprising the nucleotide sequence GATAGTTA, or a nucleotide sequence having at least one, two, or three modifications, e.g., substitutions (e.g., conservative substitutions), but no more than four modifications, e.g., substitutions (e.g., conservative substitutions), relative to the nucleotide sequence GATAGTTA; and(v) a third encoded miR183 binding site comprising the nucleotide sequence of SEQ ID NO: 3675, or a nucleotide sequence substantially identical (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity) thereto; or a nucleotide sequence having at least one, two, three, four, five, six, or seven modifications, e.g., substitutions (e.g., conservative substitutions), but no more than ten modifications, e.g., substitutions (e.g., conservative substitutions), relative to SEQ ID NO: 3675.254. The AAV particle of any one of embodiments 224-253, wherein the viral genome comprises an encoded miR122 binding site and a miR-1 binding site.255. The AAV particle of any one of embodiments 224-254, wherein the viral genome is single stranded or self-complementary.256. The AAV particle of any one of embodiments 224-255, wherein the viral genome further comprises a nucleotide sequence encoding a Rep protein, e.g., a non-structural protein, wherein the Rep protein comprises a Rep78 protein, a Rep68, Rep52 protein, and / or a Rep40 protein.257. The AAV particle of embodiment 256, wherein the Rep78 protein, the Rep68 protein, tire Rep52 protein, and / or the Rep40 protein are encoded by at least one Rep gene.258. A cell, e.g., a host cell, comprising the AAV particle of any one of embodiments 1-257.259. The cell of embodiment 258, wherein the cell is a mammalian cell or an insect cell.260. The cell of embodiment 258 or 259, wherein the cell is a cell of a brain region or a spinal cord region, optionally a cell of the frontal cortex, sensory cortex, motor cortex, caudate, dentate nucleus, cerebellar cortex, cerebral cortex, brain stem, hippocampus, thalamus, putamen, cervical spinal cord region, thoracic spinal cord region, and / or lumbar spinal cord region.261. The cell of any one of embodiments 258-260, wherein the cell is a neuron, a sensory neuron, a motor neuron, an astrocyte, or a glial cell.262. A method of making the AAV particle of any one of embodiments 1-257, comprising(i) providing a host cell comprising a viral genome; and(ii) incubating the host cell under conditions suitable to enclose the viral genome in an AAV capsid variant, e.g., an AAV capsid variant described herein;thereby making the AAV particle.263. The method of embodiment 262, further comprising, prior to step (i), introducing a first nucleic acid molecule comprising the viral genome into the host cell.264. The method of embodiment 262 or 263, wherein the host cell comprises a second nucleic acid encoding the capsid variant.265. The method of embodiment 264, wherein the second nucleic acid molecule is introduced into the host cell prior to, concurrently with, or after the first nucleic acid molecule.266. A pharmaceutical composition comprising the AAV particle of any one of embodiments 1-257, and a pharmaceutically acceptable excipient.267. 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 embodiment 266 or the AAV particle of any one of embodiments 1-257.268. The method of embodiment 267, wherein the cell is a cell a cell of a brain region or a spinal cord region, optionally a cell of the frontal cortex, sensory cortex, motor cortex, caudate, dentate nucleus, cerebellar cortex, cerebral cortex, brain stem, hippocampus, thalamus, putamen, cervical spinal cord region, thoracic spinal cord region, and / or lumbar spinal cord region.269. The method of embodiment 267 or 268, wherein the cell is a neuron, a sensory neuron, a motor neuron, glial cell, oligodendrocyte, or an astrocyte.270. The method of any one of embodiments 267-269, wherein the cell or tissue is within a subject.271. The method of embodiment 270, wherein the subject has or has been diagnosed with having a genetic disorder (e.g., a monogenic disorder or a polygenic disorder).272. The method of embodiment 270 or 270, wherein the subject has, has been diagnosed with having, or is at risk of having a neurological, e.g., a neurodegenerative disorder.273. The method of any one of embodiments 270-272, wherein the subject has, has been diagnosed with having, or is at risk of having a disease associated with tau expression or activity, e.g., aberrant tau expression.274. The method of any one of embodiments 270-273, wherein the subject has, has been diagnosed with having, or is at risk of having a tau-related disease (e.g., a tauopathy).275. The method of any one of embodiments 270-274, wherein the subject has, has been diagnosed with having, or is at risk of having Alzheimer’s disease (AD), frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), frontotemporal lobar degeneration (FTLD), frontotemporal dementia (FTD), chronic traumatic encephalopathy (CTE), progressive Supranuclear Palsy (PSP).Down’s syndrome, Pick’s disease, corticobasal degeneration (CBD), corticobasal syndrome, amyotrophic lateral sclerosis (ALS), prion diseases, Creutzfeldt-Jakob disease (CJD), multiple system atrophy, tangle-only dementia, or progressive subcortical gliosis.276. A method of treating a subject having or diagnosed with having a genetic disorder, e.g., a monogenic disorder or a polygenic disorder, comprising administering to the subject an effective amount of the pharmaceutical composition of embodiment 266 or the AAV particle of any one of embodiments 1-257.277. A method of treating a subject having or diagnosed with having a neurological disorder, e.g., a neurodegenerative disorder, comprising administering to the subject an effective amount of the pharmacal composition of embodiment 266 or the AAV particle of any one of embodiments 1-257.278. A method of treating a subject having or diagnosed with having a disease related to expression of tan expression, e.g., aberrant tau expression, comprising administering to the subject an effective amount of the pharmaceutical composition of embodiment 266 or the AAV particle of any one of embodiments 1-257.279. A method of treating a subject having or diagnosed with a tauopathy, comprising administering to the subject an effective amount of the pharmaceutical composition of embodiment 266 or the AAV particle of any one of embodiments 1-257.280. The method of any one of embodiments 272-279, wherein the neurological disorder, neurodegenerative disorder, disease associated with tau. or tauopathy is Alzheimer's Disease, frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), frontotemporal lobar degeneration (FTLD), frontotemporal dementia (FTD), chronic traumatic encephalopathy (CTE), progressive Supranuclear Palsy (PSP), Down’s syndrome, Pick’s disease, corticobasal degeneration (CBD), corticobasal syndrome, amyotrophic lateral sclerosis (ALS), prion diseases, Creutzfeldt- Jakob disease (CJD). multiple system atrophy, tangle-only dementia, or progressive subcortical gliosis.281. The method of any one of embodiments 277-280, where treating comprises prevention of progression of the disease or disorder in the subject.282. The method of any one of embodiments 270-281, wherein the subject is a human.283. The method of any one of embodiments 270-282, wherein the pharmaceutical composition or the AAV particle is administered to the subject intravenously, via intra-cistema magna injection (ICM), intracerebrally, intrathecally, intracerebroventricularly, via intraparenchymal administration, or intramuscularly.284. The method of any one of embodiments 270-283, wherein the pharmaceutical composition or the AAV particle is administered to the subject via focused ultrasound (FUS), e.g., coupled with the intravenous administration of microbubbles (FUS-MB), or MRI -guided FUS coupled with intravenous administration.285. The method of any one of embodiments 270-284, wherein the pharmaceutical composition or the AAV particle is administered to the subject intravenously.286. The method of any one of embodiments 270-285, wherein administration of the pharmaceutical composition or the AAV particle results in a decreased presence, level, and / or activity of tau mRNA, tau protein, or combination thereof.287. The method of any one of embodiments 270-286, wherein administration of the pharmaceutical composition or the AAV particle results in an increased presence, level, and / or activity of tau mRNA, tau protein, or a combination thereof.288. The pharmaceutical composition of embodiment 266 or the AAV particle of any one of embodiments 1-257. for use in a method of delivering a pay load to a cell or tissue.289. The pharmaceutical composition of embodiment 266 or the AAV particle of any one of embodiments 1-257, for use in a method of treating a neurological disorder, a neurodegenerative disorder, a disease associated with tau expression or activity, or a tauopathy.290. The pharmaceutical composition of embodiment 266 or the AAV particle of any one of embodiments 1-257, for use in the manufacture of a medicament.291. Use of the pharmaceutical composition of embodiment 266 or the AAV particle of any one of embodiments 1-257, in the manufacture of a medicament.292. Use of the pharmaceutical composition of embodiment 266 or the AAV particle of any one of embodiments 1-257, in the manufacture of a medicament for treating a neurological disorder, a neurodegenerative disorder, a disease associated with tau expression or activity (e.g., aberrant tau expression), or a tauopathy.BRIEF DESCRIPTION OF THE DRAWINGS

[0055] FIG. 1 A is a graph showing virus detected in the bottom chamber as a percentage to the load in a transcytosis assay in a transwell model, where AAV particles comprising the indicated capsid (from left to right on the X-axis: AAV9, TTM-002, or TTM-001) were added to the top of either a pool of MDCK cells expressing ALPL (left-half of graph labeled “MDCK”) or MDCK cells that expressed ALPL from a single clone (right-half of tire graph labeled “MDCK C21”), and the ability of these particles to move from the top to the bottom chamber was measured (virus detected in the bottom chamber (% to the load)); data represent averages of n=2 or n=3 measurements. FIG. 1B is a graph showing virus detected in the bottom chamber as a percentage to the load in a transcytosis assay in a transwell model, where AAV particles comprising the indicated capsid (from left to right on the X-axis: AAV9, TTM-003, TTM-043, TTM-027, or TTM-002) were added to the top of MDCK cells that expressed ALPL from a single clone, and the ability of these particles to move from the top to the bottom chamber was measured (virus detected in the bottom chamber (% to the load)); data represents an average of n=2 measurements.DETAILED DESCRIPTIONOverview

[0056] Described herein, inter alia, are compositions comprising isolated, e.g., recombinant, viral particles, e.g., AAV particles, for delivering functional anti-tau antibody molecules, and methods of making and using the same. Adeno-associated viruses (AAV) are small non-enveloped icosahedral capsid viruses of the Parvoviridae family characterized by a single stranded DNA viral genome.Parvoviridae family viruses consist of two subfamilies: Parvovirinae, which infect vertebrates, and Densovirinae, which infect invertebrates. The Parvoviridae family includes the Dependovirus genus which includes AAV, capable of replication in vertebrate hosts including, but not limited to, human, primate, bovine, canine, equine, and ovine species.

[0057] Without wishing to be bound by theory, it is believed in some embodiments, that the use of an AAV particle or plurality of AAV particles for the vectorized delivery of an antibody molecule, e.g., antibody molecule that binds to tau described herein, would lead to increased exposure in the central nervous system (CNS), and robust expression of the antibody molecule that binds to tau in a subject, e.g., a subject having or diagnosed with having a disease associated with expression of tau or a neurological disorder described herein (e.g., a tauopathy).

[0058] Also contemplated herein, inter alia, are compositions comprising an AAV capsid variant, e.g., an AAV capsid variant described herein for delivery, e.g., vectorized delivery, of an antibody molecule which binds to tau (e.g., human tau) described herein, and methods of making and using the same. Generally, the AAV capsid variant has enhanced tropism for a cell or tissue, e.g., for the delivery of a payload to said cell or tissue, for example a CNS tissue or a CNS cell.

[0059] As demonstrated in the Examples herein below, certain AAV capsid variants described herein show multiple advantages over wild-type AAV9, including (i) increased penetrance through the blood brain barrier following intravenous administration, (ii) wider distribution throughout the multiple brain regions, e.g., the frontal cortex, sensory cortex, motor cortex, putamen, thalamus, cerebellar cortex, dentate nucleus, caudate, hippocampus, globus pallidus. substantia nigra, oculomotor nucleus, geniculate nucleus, central grey, inferior colliculus, external cunate nucleus, gracile nucleus, nucleus ambiguous, vestibular nucleus, inferior olivary7complex, deep cerebellar nuclei, ventral pallidum, amygdala, temporal cortex, auditory cortex, and / or somatosensory cortex, and / or (iii) elevated payload expression in multiple brain regions. Without wishing to be being bound by theory, it is believed that these advantages may be due, in part, to the dissemination of the AAV capsid variants through the brain vasculature. In some embodiments, the AAV capsids described herein enhance the delivery of a payload, e.g., an anti-tau antibody molecule described herein, to multiple regions of the brain including for example, the frontal cortex, sensory cortex, motor cortex, putamen, thalamus, cerebellar cortex, dentate nucleus, caudate, hippocampus, globus pallidus, substantia nigra, oculomotor nucleus, geniculate nucleus, central grey, inferior colliculus, external cunate nucleus, gracile nucleus, nucleus ambiguous, vestibular nucleus, inferior olivary complex, deep cerebellar nuclei, ventral pallidum, amygdala, temporal cortex, auditory cortex, and / or somatosensory cortex.

[0060] In some embodiments, an AAV capsid variant disclosed herein comprises a modification in loop IV of AAV9, e.g., at positions between 449-460, e.g., at position 454 and / or 455, numbered relative to SEQ ID NO: 138, 981, or 982. In some embodiments, loop (e.g., loop IV) is used interchangeably herein with the term variable region (e.g., variable region IV), or VR (e.g., VR-IV). In some embodiments loop IV comprises positions 449-475 (e.g., amino acids KT1NGSGQNQQTLKFSVAGPSNMAVQG (SEQ ID NO: 6404)), numbered according to SEQ ID NO: 138. In some embodiments loop IV comprises positions 449-460 (e.g., amino acids KTINGSGQNQQT (SEQ ID NO: 6405)), numbered according to SEQ ID NO: 138. In some embodiments, loop IV or variable region IV (VR-IV) is as described in DiMattia et al. “Structural Insights into the Unique Properties of the Adeno-Associated Virus Serotype 9,” Journal of Virology, 12(86):6947-6958 (the contents of which are hereby incorporated by reference in their entirety), e.g., comprising positions 452-460 (e.g., NGSGQNQQT (SEQ ID NO: 4487)). numbered according to SEQ ID NO: 138.

[0061] In some embodiments, an AAV capsid variant disclosed herein comprises a modification in loop VIII of AAV9, e.g., at positions between 580-599 (e.g., at one, two, three, four, or all of positions 584, 586, 588, 589, and / or 590; or at one, two, three, or all of positions 588, 591, 592, and / or 593) numbered relative to SEQ ID NO: 138 or 6414, or at positions 586 to 605 (e.g., at one, two, three, four, or all of positions 590, 592, 594, 595, and / or 596; or at one, two. three, or all of positions 594, 597, 598, and / or 599), numbered relative to SEQ ID NO: 981, 982, 6411, or 6412. In some embodiments, loop (e.g., loop VIII) is used interchangeably herein with the term variable region (e.g., variable region VIII), or VR (e.g., VR-VIII). In some embodiments loop VIII comprises positions 580-599 (e.g., amino acids VATNHQSAQAQAQTGWVQNQ (SEQ ID NO: 6425)), numbered according to SEQ ID NO: 138 or 6414. In some embodiments loop VIII comprises positions 586-605 (e.g., amino acids VATNHQSAQAQAQTGWVQNQ (SEQ ID NO: 6425)). numbered according to SEQ ID NO: 981, 982, 6411, or 6412. In some embodiments loop VIII comprises positions 582-593 (e.g., amino acids TNHQSAQAQAQT (SEQ ID NO: 6426)), numbered according to SEQ ID NO: 138 or 6414. In some embodiments loop VIII comprises positions 588-599 (e.g., amino acids TNHQSAQAQAQT (SEQ ID NO: 6426)), numbered according to SEQ ID NO: 981, 982, 6411, or 6412. In some embodiments loop VIII comprises positions 587-593 (e.g., amino acids AQAQAQT (SEQ ID NO: 6423)), numbered according to SEQ ID NO: 138 or 6414. In some embodiments loop VIII comprises positions 593-599 (e.g., amino acids AQAQAQT (SEQ ID NO: 6423)), numbered according to SEQ ID NO: 981, 982, 6411, or 6412. In some embodiments loop VIII comprises positions 587-590 (e.g., amino acids AQAQ (SEQ ID NO: 6424)), numbered according to SEQ ID NO: 138 or 6414. In some embodiments loop VIII comprises positions 593-596 (e.g., amino acids AQAQ (SEQ ID NO: 6424)), numbered according to SEQ ID NO: 981. 982, 6411, or 6412. In some embodiments, loop VIII or variable region VIII (VR-VIII) is as described in DiMattia et al. "‘Structural Insights into the Unique Properties of the Adeno-Associated Virus Serotype 9, ” Journal of Virology, 12(86): 6947-6958 (the contents of which are hereby incorporated by reference in their entirety), e.g., comprising positions 581-593, numbered according to SEQ ID NO: 138 or 6414 or positions 587-599, numbered according to SEQ ID NO: 981, 982, 6411, or 6412.

[0062] In some embodiments, an AAV capsid variant described herein comprises (i) a modification in loop IV of AAV9. e.g., at positions between 449-460, e.g., at position 454 and / or 455. numbered relative to SEQ ID NO: 138, 981, or 982; and (ii) a modification in loop VIII, e.g., at positions between 587-599 (e.g., at positions 590, 592, 594, 595, 596, 597, 598, and / or 599), numbered according to SEQ ID NO: 982. In some embodiments, loop IV comprises positions 449-460 (e.g., amino acids KTINGSGQNQQT (SEQ ID NO: 6405)), numbered according to SEQ ID NO: 138. In some embodiments loop IV comprises positions 449-466 (e.g., amino acids KTINGHDSPHKSGQNQQT (SEQ ID NO: 5828)), numbered according to SEQ ID NO: 982. In some embodiments, loop VIII comprises positions 587-599, numberedaccording to SEQ ID NO: 981, 982, 6411, or 6412. In some embodiments, loop VIII comprises positions 581-593, numbered according to SEQ ID NO: 138 or 6414.I. Compositions

[0063] According to the present disclosure, compositions for delivering functional anti-tau antibody molecules by adeno-associated virus particles (AAVs) are provided. In some embodiments, an AAV particle, e.g., an AAV particle as described herein, or plurality of particles, may be provided, e.g., delivered, via any of several routes of administration, to a cell, tissue, organ, or organism, in vivo, ex vivo, or in vitro.

[0064] In some embodiments, AAV particles, nucleic acids, e.g., nucleic acid molecules encoding an antibody molecule, and / or payloads, e g., an antibody molecule, and methods of using and making the same are described in WO2017189963, the contents of which are herein incorporated by reference in their entirety.

[0065] In some embodiments, the nucleic acid sequences, genetic elements, AAV vectors, and polypeptides disclosed herein may be engineered to contain modular elements and / or sequence motifs assembled to enable expression of an antibody molecule, e.g., an antibody molecule described herein. In some embodiments, the genetic element comprises a nucleotide sequence encoding an antibody molecule (e.g., an antibody molecule described herein). In some embodiments, the nucleic acid sequence encodes an antibody molecule comprising one or more of the CDRs (e.g., heavy chain and / or light chain CDRs) of an antibody molecule, a variable heavy (VH) chain region and / or variable light (VL) chain region, a heavy and / or light chain constant region, a heavy and / or light chain, or a combination thereof. In some embodiments, the nucleic acid sequence encoding the antibody molecule may also encode a linker, e.g.. such that the VH / heavy chain and the VL / light chain of the encoded antibody molecule are connected via a linker. In some embodiments, the order of expression, structural position, or concatemer count (e.g., the VH, VL, heavy chain, light chain, and / or linker) may be different within or among genetic element sequences. In some embodiments, the identity, position, and number of linkers expressed by a genetic element described herein may vary. In some embodiments, the genetic element may further comprise an internal repeat (ITR) sequence, promoter region, an intron region, an exon region, a Kozak sequence, an enhancer, a polyadenylation sequence, or combination thereof.

[0066] In some embodiments, the present disclosure provides methods for delivering an antibody molecule (e.g., an anti-tau antibody described herein) and / or a nucleic acid sequence encoding an antibody molecule (e.g., an anti-tau antibody molecule described herein) comprised within the genetic element comprised within a recombinant, AAV particle (e.g., an AAV particle described herein) to a cell, tissue, organ, or subject.Adeno-associated viral (AA V) particles

[0067] Described herein, inter alia, are compositions comprising isolated, e.g., recombinant, viral particles, e.g., AAV particles, for delivery, e.g., vectorized delivery’, of an antibody molecule, e.g., an antibody molecule that binds to tau, and methods of making and using the same.

[0068] In some embodiments, an adeno-associated virus (AAV) comprises a small non-enveloped icosahedral capsid virus of the Parvoviridae family and is characterized by a single stranded DNA viral genome. The parvoviruses and other members of the Parvoviridae family are generally described in Kenneth I. Bems, “Parvoviridae: The Viruses and Their Replication,” Chapter 69 in FIELDS VIROLOGY (3d Ed. 1996), the contents of which are incorporated by reference in their entirety. In some embodiments, AAV is capable of replication in vertebrate hosts including, but not limited to, human, primate, bovine, canine, equine, and ovine species

[0069] In some embodiments, an AAV particle is used as a biological tool due to a relatively simple structure, their ability to infect a wide range of cells (including quiescent and dividing cells) without integration into the host genome and without replicating, and their relatively benign immunogenic profile. The genome of the virus may be manipulated to contain a minimum of components for the assembly of a functional recombinant virus, or viral particle, which is loaded with or engineered to target a particular tissue and express or deliver a desired payload, e.g., an antibody molecule which binds to tau.

[0070] In some embodiments, the AAV particle is a naturally occurring (e.g., wild-type) AAV or a recombinant AAV. In some embodiments, the wild-type AAV viral genome is a linear, single -stranded DNA (ssDNA) molecule approximately 5.000 nucleotides (nt) in length. In some embodiments, inverted terminal repeats (ITRs) cap the viral genome at both the 5' and the 3’ end. providing origins of replication for the viral genome. In some embodiments, an AAV viral genome typically comprises two ITR sequences. These ITRs have a characteristic T-shaped hairpin structure defined by a self-complementary region (145nt in wild-type AAV) at the 5’ and 3’ ends of the ssDNA which form an energetically stable double stranded region. Tire double stranded hairpin structures comprise multiple functions including, but not limited to, acting as an origin for DNA replication by functioning as primers for the endogenous DNA polymerase complex of the host viral replication cell.

[0071] In some embodiments, the AAV particle, e.g., an AAV particle (e.g., ssAAVs) described herein comprises a viral genome that is self-complementary (scAAV). In some embodiments, the ssAAV comprises nucleic acid molecules, e.g., DNA strands, that anneal together to form double stranded DNA. In some embodiments, a scAAV allows for rapid expression in a transduced cell as it bypasses second strand synthesis.

[0072] In some embodiments, the wild-type AAV viral genome further comprises nucleotide sequences for two open reading frames, one for the four non-structural Rep proteins (Rep78, Rep68, Rcp52, Rcp40, encoded by Rep genes) and one for the three capsid, or structural, proteins (VP1, VP2, VP3, encoded by capsid genes or Cap genes). The Rep proteins are used for replication and packaging, while the capsid proteins are assembled to create the protein shell of the AAV, or AAV capsid polypeptide, e.g., an AAV capsid variant. Alternative splicing and alternate initiation codons and promoters result in the generation of four different Rep proteins from a single open reading frame and the generation of three capsid proteins from a single open reading frame. Though it varies by AAV serotype, as a non-limiting example, for AAV9 (SEQ ID NO: 138) VP1 refers to amino acids 1-736, VP2 refers to amino acids 138-736, and VP3 refers to amino acids 203-736. In other words, VP1 is the full-length capsid sequence, while VP2 and VP3 are shorter components of the whole. As a result, changes in the sequence in the VP3 region, are also changes to VP1 and VP2, however, the percent difference as compared to the parent sequence will be greatest for VP3 since it is the shortest sequence of the three. Though described here in relation to the amino acid sequence, the nucleic acid sequence encoding these proteins can be similarly described. Together, the three capsid proteins assemble to create the “AAV capsid” protein. While not wishing to be bound by theory, the AAV capsid protein typically comprises a molar ratio of 1:1:10 of VP1: VP2: VP3. In some embodiments, a viral genome of a wild-type, e.g., naturally occurring, AAV can be modified to replace the rep / cap sequences with a nucleic acid encoding a payload, e.g., an antibody molecule, wherein the viral genome comprises at least one ITR region. In some embodiments, the viral genome of a recombinant AAV comprises two ITR regions, e.g., a 5’ITR or a 3 TR. In some embodiments, tire rep / cap sequences can be provided in trans during production to generate AAV particles. In some embodiments, the viral genome of an AAV is comprised in an AAV vector, which further encodes a capsid protein e.g., a structural protein, wherein the capsid protein comprises a VP1 polypeptide, a VP2 polypeptide, and / or a VP3 polypeptide: and / or a Rep protein, e.g., a non-structural protein, wherein the Rep protein comprises a Rep78 protein, a Rep68, Rep52 protein, and / or a Rep40 protein.

[0073] In some embodiments, AAV particles of the present disclosure are recombinant AAV particles which are replication defective and lacking the nucleotide sequences encoding functional Rep and Cap proteins. In some embodiments, these defective AAV particles may lack most or all parental coding sequences and carry only one or two AAV ITR sequences and the nucleic acid of interest for delivery to a cell, a tissue, an organ, or an organism.

[0074] Methods for producing and / or modifying AAV particles are disclosed in the art such as pseudotyped AAV particles (PCT Patent Publication Nos. W0200028004; WO200123001;W02004112727; W02005005610; and W02005072364, the content of each of which is incorporated herein by reference in its entirety).

[0075] As described herein, the AAV particles of the disclosure comprising an AAV capsid polypeptide, and a viral genome are capable of providing, e.g., delivering, a payload to a cell, e.g., a mammalian cell, and / or a subject. In some embodiments, the recombinant AAV particles of the present disclosure are capable of vectorized delivery of an antibody molecule (e.g., an antibody molecule which binds to tau (e.g., human tau)).AAV Capsids an Variants thereof

[0076] In some embodiments, an AAV particle, e.g., an AAV particle for the vectorized delivery of protein described herein (e.g., an anti-tau antibody molecule), may comprise an AAV capsid polypeptide, e.g., an AAV capsid variant. In some embodiments, an AAV capsid variant described herein comprises one or more modifications, e g., relative to a wild-type AAV capsid. In some embodiments, an AAV capsid variant described herein comprises one or more modifications, e.g., relative to a wild-type AAV capsid, for enhanced or improved transduction of a target cell or tissue (e.g., a cell, region, and / or tissue of the CNS and / or PNS). In some embodiments, the one or more modifications are present in VP1, VP2, and / or VP3 of the AAV capsid variant.

[0077] In some embodiments, the AAV capsid variant allows for blood brain barrier penetration following intravenous administration. In some embodiments, the AAV capsid, e.g., AAV capsid variant, allows for blood brain barrier penetration following focused ultrasound (FUS), e.g., coupled with the intravenous administration of microbubbles (FUS-MB), or MRI-guided FUS coupled with intravenous administration. In some embodiments the AAV capsid, e.g., AAV capsid variant allows for increased distribution to a brain region. In some embodiments, the brain region comprises a frontal cortex, sensory cortex, motor cortex, caudate, dentate nucleus, cerebellar cortex, cerebral cortex, brain stem, hippocampus, thalamus, putamen, or a combination thereof. In some embodiments, the AAV capsid, e.g., AAV capsid variant allows for preferential transduction in a brain region relative to the transduction in the dorsal root ganglia (DRG).

[0078] In some embodiments the AAV capsid variant allows for increased distribution to a spinal cord region. In some embodiments, the spinal region comprises a cervical spinal cord region, thoracic spinal cord region, and / or lumbar spinal cord region.

[0079] In some embodiments, the AAV capsid polypeptide, e.g., an AAV capsid variant comprises a VOY101 capsid polypeptide, an AAVPHP. B (PHP. B) capsid polypeptide, a AAVPHP. N (PHP. N) capsid polypeptide, an AAV1 capsid polypeptide, an AAV2 capsid polypeptide, an AAV5 capsid polypeptide, an AAV9 capsid polypeptide, an AAV9 K449R capsid polypeptide, an AAVrhlO capsid polypeptide, or a functional variant thereof. In some embodiments, the AAV capsid polypeptide, e.g., AAV capsid variant,comprises an amino acid sequence of any of the AAV capsid polypeptides in Table 1A, or an amino acid sequence substantially identical (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity) thereto. In some embodiments, the nucleotide sequence encoding the AAV capsid polypeptide comprises any one of the nucleotide sequences in Table 1A, or a nucleotide sequence substantially identical (e.g., having at least 70%, 75%. 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity) thereto.

[0080] In any of the embodiments described herein, the indicated position or amino acid numbered relative to SEQ ID NO: 138 or 981 can be identified by providing an alignment of a reference sequence and a query sequence, wherein the reference sequence is SEQ ID NO: 138 or 981, and identifying tire residues corresponding to the positions in the query sequence that correspond to the positions or amino acids indicated in the reference sequence.Table 1A: Exemplary full length capsid sequences

[0081] In some embodiments, the AAV capsid polypeptide, e.g., the AAV capsid variant, comprises the amino acid sequence of SEQ ID NO: 138 or an amino acid sequence substantially identical (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity) thereto. In some embodiments the AAV capsid polypeptide, e.g., the AAV capsid variant, comprises an amino acid sequence comprising at least one, two, or three modifications, e.g., substitutions (e.g., conservative substitutions), but no more than 30, 20, or 10 modifications, e g., substitutions (e.g., conservative substitutions), relative to the amino acid sequence of SEQ ID NO: 138. In some embodiments, the AAV capsid polypeptide, e.g., the AAV capsid variant, comprises an amino acid sequence encoded by the nucleotide sequence of SEQ ID NO: 137 or a nucleotide sequence substantially identical (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity) thereto. In some embodiments, the nucleotide sequence encoding tire AAV capsid polypeptide, e.g., the AAV capsid variant, comprises the nucleotide sequence of SEQ ID NO: 137 or a nucleotide sequence substantially identical (e.g.. having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%. 97%. 98%. or 99% sequence identity) thereto. In some embodiments, the AAV capsid polypeptide, e.g., the AAV capsid variant,comprises substitution at position K449, e.g., a K449R substitution, numbered according to SEQ ID NO: 138.

[0082] In some embodiments, the capsid polypeptide, comprises the amino acid sequence of SEQ ID NO: 1 or an amino acid sequence substantially identical (e.g., having at least 70%, 75%, 80%. 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity) thereto. In some embodiments the AAV capsid polypeptide, e.g., the AAV capsid variant, comprises an amino acid sequence comprising at least one, two, or three modifications, e.g., substitutions (e.g., conservative substitutions), but no more than 30, 20, or 10 modifications, e.g., substitutions (e.g., conservative substitutions), relative to the amino acid sequence of SEQ ID NO: 1.

[0083] In some embodiments, an AAV capsid variant described herein comprises a modification or a peptide that increases distribution of an AAV particle to a cell, region, or tissue of the CNS. The cell of the CNS may be, but is not limited to, neurons (e.g., excitatory, inhibitory, motor, sensory, autonomic, sympathetic, parasympathetic, Purkinje, Betz, etc.), glial cells (e.g., microglia, astrocytes, oligodendrocytes) and / or supporting cells of tire brain such as immune cells (e.g., T cells). Tire tissue of the CNS may be, but is not limited to, the cortex (e.g., frontal, parietal, occipital, temporal), thalamus, hypothalamus, striatum, putamen, caudate nucleus, hippocampus, entorhinal cortex, basal ganglia, or deep cerebellar nuclei. In some embodiments, the tissue of the CNS is a sensory cortex, motor cortex, putamen, thalamus, caudate, hippocampus, cerebellum, or a combination thereof.

[0084] In some embodiments, an AAV capsid variant described herein comprises a modification or a peptide that increase distribution of an AAV particle to a cell, region, or tissue of the PNS. The cell or tissue of the PNS may be, but is not limited to, a dorsal root ganglion (DRG).

[0085] In some embodiments, the peptide may increase distribution of an AAV particle to a cell, region, or tissue of the PNS. The cell or tissue of the PNS may be, but is not limited to, a dorsal root ganglion (DRG).

[0086] In some embodiments, the modification or peptide may increase distribution of an AAV particle to the CNS (e.g., sensory cortex, motor cortex, putamen, thalamus, caudate, hippocampus, and / or cerebellum) after intravenous administration. In some embodiments, the modification or peptide may increase distribution of an AAV particle to the CNS (e.g., the sensory cortex, motor cortex, putamen, thalamus, caudate, hippocampus, and / or cerebellum) following focused ultrasound (FUS), e.g., coupled with the intravenous administration of microbubblcs (FUS-MB), or MRI-guidcd FUS coupled with intravenous administration.

[0087] In some embodiments, the modification or peptide may increase distribution of an AAV particle to the PNS (e.g., DRG) after intravenous administration. In some embodiments, the modificationor peptide may increase distribution of an AAV particle to the PNS (e.g., DRG) following focused ultrasound (FUS), e.g., coupled with the intravenous administration of microbubbles (FUS-MB), or MRI-guided FUS coupled with intravenous administration.

[0088] In some embodiments, an AAV capsid variant described herein comprises an amino acid sequence as set forth in Table 1. In some embodiments, an AAV capsid variant described herein may comprise a sequence as set forth in Table 2A. In some embodiments, an AAV capsid variant described herein comprises a sequence as set forth in Table 2B (e.g., a sequence of any of SEQ ID NOs: 201, 205-209, 211-214, 216, 219, 220, 230, 232, 237, 238, 255, 262-265, 274, 283, 286, 290, 291, 293, 301, 306, 307, 308, 309, 314, or 336). In some embodiments, an AAV capsid variant described herein comprises a sequence set forth in Table 9A. In some embodiments, an AAV capsid variant described herein comprises a sequence as set forth in Table 14A. In some embodiments, an AAV capsid variant described herein comprises a sequence as set forth in Table 15 A. In some embodiments, an AAV capsid variant described herein comprises a sequence as set forth in Table 16A. In some embodiments, an AAV capsid variant described herein comprises a sequence as set forth in any one of Tables 26-31.Table 2A. Exemplary Peptide Sequences

[0089] In some embodiments, an AAV capsid variant described herein comprises at least 3, 4, 5, or 6 consecutive amino acids of SPHSKA (SEQ ID NO: 941). In some embodiments, the at least 3 consecutive amino acids comprise SPH. In some embodiments, the at least 4 consecutive amino acids comprise SPHS (SEQ ID NO: 63). In some embodiments, the at least 5 consecutive amino acids comprise SPHSK (SEQ ID NO: 12). In some embodiments, the at least 6 consecutive amino acids comprise SPHSKA (SEQ ID NO: 941).

[0090] In some embodiments, the amino acid sequence of SPHSKA (SEQ ID NO: 941) is present at amino acids 456-461, numbered according to SEQ ID NO: 981. In some embodiments, the amino acid sequence of SPHSKA (SEQ ID NO: 941) is present at amino acids 456-461, numbered according to SEQ ID NO: 3904. In some embodiments, the amino acid sequence of SPHSKA (SEQ ID NO: 941) is present at amino acids 456-461, numbered according to SEQ ID NO: 36. In some embodiments, the amino acid sequence of SPHSKA (SEQ ID NO: 941) is present at amino acids 456-461, numbered according to SEQ ID NO: 6411.

[0091] In some embodiments, an AAV capsid variant described herein comprises at least 3, 4, 5, or 6 consecutive amino acids of HDSPHK (SEQ ID NO: 2). In some embodiments, the at least 3 consecutive amino acids comprise HDS. In some embodiments, the at least 4 consecutive amino acids comprise HDSP (SEQ ID NO: 13). In some embodiments, the at least 5 consecutive amino acids comprise HDSPH (SEQ ID NO: 14). In some embodiments, the at least 6 consecutive amino acids comprise HDSPHK (SEQ ID NO: 2).

[0092] In some embodiments, the amino acid sequence of HDSPHK (SEQ ID NO: 2) is present at amino acids 454-459, numbered according to SEQ ID NO: 982. In some embodiments, the amino acid sequence of HDSPHK (SEQ ID NO: 2) is present at amino acids 454-459, numbered according to SEQ ID NO: 6412.

[0093] In some embodiments, the AAV capsid variant comprises the amino acid sequence of SEQ ID NO: 2. In some embodiments, the AAV capsid variant comprises the amino acid sequence of SEQ ID NO: 941. In some embodiments, the AAV capsid variant comprises the amino acid sequence of SEQ ID NO: 3589. In some embodiments, the AAV capsid variant comprises the amino acid sequence of SEQ ID NO: 3272. In some embodiments, the amino acid sequence is present in loop IV. In some embodiments, the amino acid sequence is present immediately subsequent to position 448. relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. In some embodiments, the amino acid sequence replaces positions 449-460 (e.g., K449, T450, 1451, N452, G453, S454, G455, Q456, N457, Q458, Q459, and T460), numbered relative to SEQ ID NO: 138. In some embodiments, tire 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. and T460), numbered relative to SEQ ID NO: 138. In some embodiments, the amino acid sequence is present immediately subsequent to position 453, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. In some embodiments, the amino acid sequence replaces positions 454-460 (e.g., S454, G455, Q456, N457, Q458, Q459, and T460), numbered relative to SEQ ID NO: 138. In some embodiments, the amino acid sequence is present immediately subsequent to position 453, and replaces positions 454-460 (e.g., S454, G455, Q456, N457, Q458. Q459, and T460), numbered relative to SEQ ID NO: 138. In some embodiments, 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. In some embodiments, 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: 982. In some embodiments, the amino acid sequence replaces positions 456-460 (e.g., Q456, N457, Q458, Q459, and T460). numbered relative to SEQ ID NO: 138. In some embodiments, the amino acidIllsequence is present immediately subsequent to position 455, and replaces positions 456-460 (e.g., Q456, N457, Q458, Q459, and T460), numbered relative to SEQ ID NO: 138.

[0094] In some embodiments, the AAV capsid variant (e.g., an AAV capsid variant described herein), comprises an amino acid sequence encoded by the nucleotide sequence of SEQ ID NO: 3 or 942, or a nucleotide sequence substantially identical (e.g.. having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity) thereto. In some embodiments, the AAV capsid variant described herein, comprises an amino acid sequence encoded by the nucleotide sequence of SEQ ID NO: 3 or 942, or a nucleotide sequence comprising at least one, two, three, four, five, six, or seven modifications, e.g., substitutions, insertions, or deletions, but no more than ten modifications, e.g., substitutions, insertions, or deletions, relative to the nucleotide sequence of SEQ ID NO: 3 or 942. In some embodiments, the AAV capsid variant comprises an amino acid sequence encoded by a nucleotide sequence comprising at least one, two, three, four, five, six, or seven, but no more than ten different nucleotides relative to the nucleotide sequence of SEQ ID NO: 3 or 942.

[0095] In some embodiments, the nucleotide sequence encoding the AAV capsid variant (e.g., an AAV capsid variant described herein), comprises the nucleotide sequence of SEQ ID NO: 942, or a nucleotide sequence substantially identical (e.g.. having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity) thereto. In some embodiments, the nucleic acid sequence encoding the AAV capsid variant comprises a nucleotide sequence comprising at least one, two, three, four, five, six, or seven modifications, e.g., substitutions, insertions, or deletions, but no more than ten modifications, e.g., substitutions, insertions, or deletions, relative to the nucleotide sequences of SEQ ID NO: 942. In some embodiments, the nucleotide sequence encoding an AAV capsid variant described herein comprises 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.

[0096] In some embodiments, the nucleotide sequence encoding the AAV capsid variant (e.g., an AAV capsid variant described herein), comprises the nucleotide sequence of SEQ ID NO: 3, or a nucleotide sequence substantially identical (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity) thereto. In some embodiments, the nucleic acid sequence encoding the AAV capsid variant comprises a nucleotide sequence comprising at least one, two, three, four, five, six, or seven modifications, e g., substitutions, insertions, or deletions, but no more than ten modifications, e.g., substitutions, insertions, or deletions, relative to the nucleotide sequences of SEQ ID NO: 3. In some embodiments, the nucleotide sequence encoding an AAV capsid variant described herein comprises 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.

[0097] In some embodiments, the nucleotide sequence encoding the AAV capsid variant (e.g., an AAV capsid variant described herein), comprises the nucleotide sequence of SEQ ID NO: 6420 or 6422, or a nucleotide sequence substantially identical (e.g., having at least 70%, 75%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% sequence identity) thereto. In some embodiments, the nucleic acid sequence encoding the AAV capsid variant comprises a nucleotide sequence comprising at least one, two, three, four, five, six, or seven modifications, e.g., substitutions, insertions, or deletions, but no more than ten modifications, e g., substitutions, insertions, or deletions, relative to the nucleotide sequences of SEQ ID NO: 6420 or 6422. In some embodiments, the nucleotide sequence encoding an AAV capsid variant described herein comprises 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: 6420 or 6422.

[0098] In some embodiments, an AAV capsid variant described herein comprises 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. In some embodiments, an AAV capsid variant described herein comprises 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 tire amino acid sequence of SEQ ID NO: 981 or 6411.

[0099] In some embodiments, an AAV capsid variant described herein comprises the amino acid sequence of HDSPHK (SEQ ID NO: 2), wherein the amino acid sequence is present immediately subsequent to position 453, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. In some embodiments, an AAV capsid variant described herein comprises the amino acid sequence of HDSPHK (SEQ ID NO: 2), wherein the amino acid sequence is present immediately subsequent to position 453, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 982 or 6412.

[0100] In some embodiments, the AAV capsid variant 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. In some embodiments, the AAV capsid variant 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. In some embodiments, the AAV capsid variant 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. In some embodiments, the AAV capsid variant further comprises a G at position 450, an L at position 451,and an S at position 452, relative to a reference sequence numbered according to the amino acid sequence ofSEQ ID NO: 138.

[0101] In some embodiments, the AAV capsid variant 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. In some embodiments, the AAV capsid variant further comprises an R at position 456, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. In some embodiments, the AAV capsid variant further comprises an L at position 456, relative to a reference sequence numbered according to the amino acid sequence of SEQ ID NO: 138. In some embodiments, the AAV capsid variant 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. In some embodiments, the AAV capsid variant 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. In some embodiments, the AAV capsid variant 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. In some embodiments, the AAV capsid variant 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 ofSEQ ID NO: 138.

[0102] In some embodiments, an AAV capsid variant described herein comprises 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 SEQ ID NO: 138 or 981. In some embodiments, the AAV capsid variant comprises E at position 451, R at position 452, and V at position 453, numbered according to SEQ ID NO: 138 or 981. In some embodiments, the AAV capsid variant comprises the substitutions 145 IE, N452R, and G453V, numbered according to SEQ ID NO: 138 or 981.

[0103] In some embodiments, the AAV capsid variant comprises the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is present immediately subsequent to position 455 and wherein the AAV capsid variant comprises the E at position 451, R at position 452, and V at position 453, numbered according to the amino acid sequence ofSEQ ID NO: 138 or 981. In some embodiments, the AAV capsid variant comprises the substitutions 145 IE, N452R, and G453V, and further comprises the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is present immediately subsequent to position 455, all numbered according to SEQ ID NO: 138 or 981. In some embodiments, the AAV capsid variant comprises the amino acid sequence of ERVSGSPHSKA (SEQ ID NO: 3877), and wherein the amino acid sequence is present immediatelysubsequent to position 449 and replaces positions 450-45, numbered according to SEQ ID NO: 138. In some embodiments, the AAV capsid variant comprises the amino acid sequence of KTERVSGS...

Claims

1. We claim:

1. An AAV particle comprising an AAV capsid variant and a nucleic acid encoding an antibody molecule which binds to human tau, wherein the AAV capsid variant comprises:3.(i) three, four, or all of the amino acid R at position 584, the amino acid T at position 586, the amino acid L at position 588, the amino acid Q at position 589, and / or the amino acid L at position 590, numbered according to SEQ ID NO: 138; and4.(ii) the amino acid sequence of HDSPHK (SEQ ID NO: 2) in hypervariable loop IV: wherein the AAV capsid variant comprises an amino acid sequence at least 95% identical to the amino acid sequence of positions 203-736 of SEQ ID NO: 138.

2. The AAV particle of claim 1, 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 or 6412.

3. Tire AAV particle of claim 1 or 2, wherein the amino acid sequence of HDSPHK (SEQ ID NO: 2) is present at amino acids 454-459, numbered according to SEQ ID NO: 982 or 6412.

4. An AAV particle comprising an AAV capsid variant and a nucleic acid encoding an antibody molecule which binds to human tau, wherein the AAV capsid variant comprises:8.(i) three, four, or all of the amino acid R at position 584, the amino acid T at position 586, the amino acid L at position 588, the amino acid Q at position 589, and / or the amino acid L at position 590, numbered according to SEQ ID NO: 138; and9.(ii) tire amino acid sequence of SPHSKA (SEQ ID NO: 941) in hypervariable loop IV; wherein the AAV capsid variant comprises an amino acid sequence at least 95% identical to tire amino acid sequence of positions 203-736 of SEQ ID NO: 138.

5. Tire AAV particle of claim 4, 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.

6. The AAV particle of claim 4 or 5, wherein the amino acid sequence SPHSKA (SEQ ID NO: 941) is present at amino acids 456-461, numbered according to SEQ ID NO: 981 or 6411.

7. Tire AAV particle of any one of claims 4-6, wherein the AAV capsid variant further comprises:13.(a) the amino acid E at position 451, numbered according to SEQ ID NO: 981;14.(b) the amino acid V at position 453, numbered according to SEQ ID NO: 981; and / or (c) the amino acid R at position 452, numbered according to SEQ ID NO: 981.

8. The AAV particle of any one of claims 1-7, wherein the AAV capsid variant comprises:16.(i) the amino acid R at position 590, T at position 592, L at position 594, Q at position 595, and L at position 596, numbered according to SEQ ID NO: 981, 982, 6411, or 6412; or17.(ii) the amino acid R at position 584, T at position 586, L at position 588, Q at position 589. and L at position 590, numbered according to SEQ ID NO: 138 or 6414.

9. Tire AAV particle of any one of claims 1-3 or 8, wherein the AAV capsid variant comprises:19.(i) an amino acid sequence at least 95% or at least 98% identical to amino acids 203-742 of SEQ ID NO: 6412;20.(ii) an amino acid sequence at least 95% or at least 98% identical to amino acids 138-742 of SEQ ID NO: 6412; and / or21.(iii) an amino acid sequence at least 95% or at least 98% identical to the amino acid sequence of SEQ ID NO: 6412.

10. The AAV particle of any one of claims 1-3, 8, or 9, wherein the AAV capsid variant comprises:23.(i) the amino acid sequence of amino acids 203-742 of SEQ ID NO: 6412;24.(ii) the amino acid sequence of amino acids 138-742 of SEQ ID NO: 6412; and / or25.(iii) the amino acid sequence of SEQ ID NO: 6412.

11. The AAV particle of any one of claims 1-3, or 8-10, wherein the nucleotide sequence encoding the AAV capsid variant comprises the nucleotide sequence of SEQ ID NO: 6416, or nucleotide sequence at least 90%, 92%, 95%, 97%, 98%, or 99% identical thereto.

12. The AAV particle of any one of claims 4-8, wherein the AAV capsid variant comprises:28.(i) an amino acid sequence at least 95% or at least 98% identical to amino acids 203-742 of SEQ ID NO: 6411;29.(ii) an amino acid sequence at least 95% or at least 98% identical to amino acids 138-742 of SEQ ID NO: 6411; and / or30.(iii) an amino acid sequence at least 95% or at least 98% identical to the amino acid sequence of SEQ ID NO: 6411.

13. The AAV particle of any one of claims 4-8 or 12, wherein the AAV capsid variant comprises:(i) the amino acid sequence of amino acids 203-742 of SEQ ID NO: 6411;32.(ii) the amino acid sequence of amino acids 138-742 of SEQ ID NO: 6411; and / or33.(iii) the amino acid sequence of SEQ ID NO: 6411.

14. The AAV particle of any one of claims 4-8, 12, or 13, wherein the nucleotide sequence encoding the AAV capsid variant comprises the nucleotide sequence of SEQ ID NO: 6415. or nucleotide at least 90%, 92%, 95%, 97%, 98%, or 99% identical thereto.

15. The AAV particle of any one of claims 1-14, wherein hypervariable loop IV comprises amino acids 449-460, numbered according to SEQ ID NO: 138.

16. The AAV particle of any one of claims 1-15, wherein the AAV capsid variant:37.(i) has an increased tropism for a CNS cell or tissue, e.g., a brain cell, brain tissue, spinal cord cell, or spinal cord tissue, relative to the tropism of a reference sequence comprising the amino acid sequence of SEQ ID NO: 13838.(ii) transduces a brain region (e.g., a putamen, caudate, entorhinal cortex, hippocampus, thalamus, substantia nigra, motor cortex, frontal cortex, temporal cortex, cerebral cortex, dentate nucleus, and / or Lateral Geniculate Nucleus (LGN)), optionally wherein the level of transduction is at least 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, or 65-fold greater as compared to a reference sequence of SEQ ID NO: 138, e.g., when measured by an assay, e.g., an immunohistochemistry assay or a qPCR assay, e.g., as described in Example 2;39.(iii) is enriched at least about 3, 4, 5, 6, 7, 8, 9, or 10-fold, in the brain compared to a reference sequence of SEQ ID NO:

138. e.g., when measured by an assay as described in Example 1;40.(iv) is capable of transducing the brain of at least two to three species, e.g., a non-human primate and / or rodent (e.g., Macaca fascicularis, Chlorocebus sabaeus, Callithrix jacchus, and / or mouse (e.g., BALB / c mice, C57B1 / 6 mice, and / or CD-I outbred mice), when measured by an assay as described in Example 2;41.(v) delivers an increased level of a payload to a brain region, optionally wherein the level of the payload is increased by at least 5, 10, 15, 17, 18, 19.

20. 25, 30, 35, 40, 45, 50, 55, 60. 65, or 70-fold, as compared to a reference sequence of SEQ ID NO: 138, e.g., when measured by an assay, e.g., a qRT-PCR or a qPCR assay (e.g., as described in Example 2), optionally wherein the brain region is a putamen, caudate, entorhinal cortex, hippocampus, thalamus, substantia nigra, motor cortex, frontal cortex, temporal cortex, cerebral cortex, dentate nucleus, and / or Lateral Geniculate Nucleus (LGN); (vi) delivers an increased level of viral genomes to a brain region, optionally wherein the level of viral genomes is increased by at least 5, 10, 15, 17, 18, 19, 20, 25, 30, 35, 40, 45, or 50-fold, as compared to a reference sequence of SEQ ID NO: 138, e.g., when measured by an assay, e.g., a qRT-PCR or a qPCR assay (e.g., as described in Example 2), optionally wherein the a putamen, caudate, entorhinal cortex, hippocampus, thalamus, substantia nigra, motor cortex, frontal cortex, temporal cortex, cerebral cortex, dentate nucleus, and / or Lateral Geniculate Nucleus (LGN);42.(vii) is enriched at least about 5, 10, 15, 20, 25, 30, or 35 -fold, in the spinal cord compared to a reference sequence of SEQ ID NO: 138, e.g., when measured by an assay as described in Example 2, optionally wherein the region of tire spinal cord is a thoracic spinal cord region, cervical spinal cord region, lumbar spinal cord region;43.(viii) shows preferential transduction in a brain region relative to the transduction in the dorsal root ganglia (DRG) and / or the liver:44.(xi) is capable of transducing neuronal cells and non-neuronal cells, e.g., glial cells (e.g., astrocytes);45.(ix) is capable of transducing at least 20%, 25%, 30%, 40%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, or 85% of cells in a brain region (e.g., a putamen, caudate, entorhinal cortex, hippocampus, thalamus, substantia nigra, motor cortex, frontal cortex, temporal cortex, cerebral cortex, cerebellar cortex, cerebellum, dentate nucleus, and / or Lateral Geniculate Nucleus (LGN)), e.g., when measured by an assay as described in Example 1;46.(x) is capable of transducing at least 10%, 15%, 20%, 25%, 30%, 40%, 50%, 55%, 60%, or 65% of neurons (e.g., NeuN+ neurons) in a brain region (e.g., a putamen, caudate, entorhinal cortex, hippocampus, thalamus, substantia nigra, motor cortex, frontal cortex, or temporal cortex);47.(xi) is capable of transducing at least 70%, 75%, 80%, 85%, 90%. or 95% of astrocytes (e.g., Sox9+ astrocytes) in a brain region (e.g., a putamen, caudate, entorhinal cortex, hippocampus, thalamus, substantia nigra, motor cortex, frontal cortex, or temporal cortex), e.g., when measured by an assay as described in Example 1;48.(xii) is capable of transducing at least 90% or 95% of neurons, e.g., motor neurons (e.g., ChAT+ neurons) in the spinal cord (e.g., the cervical spinal cord, the thoracic spinal cord, or the lumbar spinal cord), e.g., when measured by an assay as described in Example 2; and / or49.(xiii) is capable of transducing at least 90%, 95%, or 98% of astrocytes (e.g., Sox9+ astrocytes) in the spinal cord (e.g., the cervical spinal cord, the thoracic spinal cord, or tire lumbar spinal cord), e g., when measured by an assay as described in Example 1.

17. The AAV particle of any one of claims 1-16, wherein the encoded antibody molecule:(i) binds to the N-terminal region of a human tau protein;51.(ii) binds to the mid-domain region of a human tau protein;52.(iii) binds to the C-terminal region of a human tau protein, e.g., residues 409-436 numbered according to SEQ ID NO: 9200;53.(iv) binds a phosphorylated residue of a tau protein;54.(iii) preferentially binds pathological tau (e.g., PHF-tau or ePHF). compared to wild-type tau. e.g., as measured by an assay, e.g., an ELISA assay, an SPR assay or a Biacore assay, e.g., an assay as described in Example 8 or 10;55.(iv) reduces, e.g., inhibits, aggregation of tau; and / or56.(v) binds an epitope comprising a region formed by a complex of at least two tau proteins, e.g., a tau dimer.

18. The AAV particle of any one of claims 1-17, wherein the encoded antibody molecule comprises a heavy chain variable region (VH) comprising heavy chain complementarity determining region 1 (HC CDR1), a HC CDR2, and a HC CDR3; and a light chain variable region (VL) comprising light chain complementarity detennining region 1 (LC CDR1), a LC CDR2, and a LC CDR3, wherein:58.(i) the HC CDR1, HC CDR 2. and HC CDR 3 comprise the amino acid sequences of SEQ ID NOs: 1631, 1551, and 1552, respectively; and the LC CDR1, LC CDR2, and LC CDR3 comprise the amino acid sequences of SEQ ID NOs: 1632, 1633, and 1566, respectively;59.(ii) the HC CDR 1 comprises the amino acid sequence of XIX2WMH, wherein Xi is R or I and X2is Y or F; HC CDR2 comprises the amino acid sequence of SEQ ID NO: 1635; and HC CDR3 comprises the amino acid sequence of SEQ ID NO: 1552; and tire LC CDR1, LC CDR2, and LC CDR3 comprise the amino acid sequences of SEQ ID NOs: 1636, 1633, and 1566, respectively; or60.(iii) the HC CDR1, HC CDR 2, and HC CDR 3 comprise the amino acid sequences of SEQ ID NOs: 1637, 1638, and 1557, respectively; and the LC CDR1 comprises the amino acid sequence of SEQ ID NO: 1639, the LC CDR2 comprises the amino acid sequence of RVS, and the LC CDR3 comprises the amino acid sequence of SEQ ID NO: 1566, respectively.

19. The AAV particle of claim 18. wherein:62.(i) the HCDR1, HCDR2, and HCDR3 comprise the amino acid sequences of SEQ ID NOs: 1553, 1554, and 1552, respectively; and the LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 1567, 1565, and 1566, respectively; (ii) the HCDR1, HCDR2, and HCDR3 comprise the amino acid sequences of SEQ ID NOs: 1550, 1551, and 1552, respectively; and the LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 1564, 1565, and 1566, respectively;63.(iii) the HCDR1, HCDR2, and HCDR3 comprise the amino acid sequences of SEQ ID NOs: 1555, 1556, and 1557, respectively; and the LCDR1 comprises the amino acid sequence of SEQ ID NO: 1568, the LC CDR2 comprises the amino acid sequence of RVS, and the LC CDR3 comprises the amino acid sequence of SEQ ID NO: 1566;64.(iv) the HCDR1, HCDR2, and HCDR3 comprise the amino acid sequences of SEQ ID NOs: 64, 1554, and 1557, respectively; and the LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 1567, 1565, and 1566, respectively;65.(v) the HCDR1, HCDR2, and HCDR3 comprise the amino acid sequences of SEQ ID NOs: 1576.66.1577, and 1552. respectively; and the LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 1585, 1565, and 1566, respectively:67.(vi) the HCDR1, HCDR2, and HCDR3 comprise the amino acid sequences of SEQ ID NOs: 1575, 1551, and 1552, respectively; and the LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 1585, 1565, and 1566, respectively;68.(vii) the HCDR1, HCDR2, and HCDR3 comprise the amino acid sequences of SEQ ID NOs: 1578, 1579, and 1557, respectively; and the LCDR1 comprises the amino acid sequence of SEQ ID NO: 1586, the LC CDR2 comprises the amino acid sequence of RVS, and the LC CDR3 comprises the amino acid sequence of SEQ ID NO: 1566;69.(viii) the HCDR1, HCDR2, and HCDR3 comprise the amino acid sequences of SEQ ID NOs: 1594, 1595, and 1552, respectively; and the LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 1601, 1602, and 1566. respectively;70.(ix) the HCDR1, HCDR2, and HCDR3 comprise the amino acid sequences of SEQ ID NOs: 1593, 1551, and 1552, respectively; and the LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 1601, 1602, and 1566, respectively; or71.(x) the HCDR1, HCDR2, and HCDR3 comprise the amino acid sequences of SEQ ID NOs: 1596, 1556, and 1557, respectively; and the LCDR1 comprises the amino acid sequence of SEQ ID NO: 1603, the LC CDR2 comprises the amino acid sequence of RVS, and the LC CDR3 comprises the amino acid sequence of SEQ ID NO: 1566.

20. The AAV particle of claim 18 or 19, wherein:73.(i) tire VH comprises the amino acid sequence of any one of SEQ ID NOs: 69, 67, 68, 70, 71, 1562, 1583, or 1599; an amino acid sequence at least 85%, 90%, 92%, 95%, 96%. 97%, 98%, or 99% identical to any one of SEQ ID NOs: 69, 67, 68, 70, 71, 1562, 1583, or 1599; or an amino acid sequence comprising at least one, tw o. or three modifications but no more than 30, 20 or 10 modifications relative to tire amino acid sequence of any one of SEQ ID NOs: 69, 67, 70, 71, 1562, 1583, or 1599; and / or the VL comprises he amino acid sequence of any one of SEQ ID NOs: 73, 72, 74, 1573, 1591, or 1606; an amino acid sequence at least 85%, 90%, 92%. 95%. 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 73, 72, 74, 1573, 1591. or 1606; or an amino acid sequence comprising at least one, two, or three modifications but no more than 30, 20 or 10 modifications relative to the amino acid sequence of any one of SEQ ID NOs: 73, 72, 74, 1573, 1591, or 1606;74.(ii) the VH comprises the amino acid sequence of SEQ ID NO: 69; an amino acid sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 69, or an amino acid sequence comprising at least one, tw o, or three modifications but no more than 30, 20 or 10 modifications relative to the amino acid sequence of SEQ ID NO: 69; and the VL comprises tire amino acid sequence of SEQ ID NO: 73; an amino acid sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 73, or an amino acid sequence comprising at least one, two, or three modifications but no more than 30, 20 or 10 modifications relative to the amino acid sequence of SEQ ID NO: 73;75.(iii) the VH comprises tire amino acid sequence of SEQ ID NO: 67; an amino acid sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 67, or an amino acid sequence comprising at least one, tw o, or three modifications but no more than 30, 20 or 10 modifications relative to tire amino acid sequence of SEQ ID NO: 67; and the VL comprises the amino acid sequence of SEQ ID NO: 72; an amino acid sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 72, or an amino acid sequence comprising at least one, two. or three modifications but no more than 30, 20 or 10 modifications relative to the amino acid sequence of SEQ ID NO: 72;76.(iv) the VH comprises the amino acid sequence of SEQ ID NO: 70; an amino acid sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 70, or an amino acid sequence comprising at least one, tw o, or three modifications but no more than 30, 20 or 10 modifications relative to the amino acid sequence of SEQ ID NO: 70; and the VL comprises the amino acid sequence of SEQ ID NO: 72; an amino acid sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 72, or an amino acid sequence comprising at least one, two. or three modifications but no more than 30, 20 or 10 modifications relative to the amino acid sequence of SEQ ID NO: 72;77.(v) the VH comprises the amino acid sequence of SEQ ID NO: 71; an amino acid sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 71, or an ammo acid sequence comprising at least one, tw o. or three modifications but no more than 30, 20 or 10 modifications relative to the amino acid sequence of SEQ ID NO: 71; and the VL comprises the amino acid sequence of SEQ ID NO: 73; an amino acid sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 73, or an amino acid sequence comprising at least one, two, or three modifications but no more than 30, 20 or 10 modifications relative to the amino acid sequence of SEQ ID NO: 73;78.(vi) the VH comprises the amino acid sequence of SEQ ID NO: 71; an amino acid sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 71, or an amino acid sequence comprising at least one, two, or three modifications but no more than 30, 20 or 10 modifications relative to tire amino acid sequence of SEQ ID NO: 71; and tire VL comprises the amino acid sequence of SEQ ID NO: 74; an amino acid sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:

74. or an amino acid sequence comprising at least one. two, or three modifications but no more than 30, 20 or 10 modifications relative to the amino acid sequence of SEQ ID NO: 74;79.(v) the VH comprises the amino acid sequence of SEQ ID NO: 1562; an amino acid sequence at least 85% 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 1562; or an amino acid sequence comprising at least one. two or three modifications, but no more than 30, 20, or 10 modifications relative to the amino acid sequence of SEQ ID NO: 1562: and the VL comprises the amino acid sequence of SEQ ID NO: 1573, an amino acid sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 1573; or amino acid sequence comprising at least one, tw o or three modifications, but no more than 30, 20, or 10 modifications relative to the amino acid sequence of SEQ ID NO: 1573;80.(vi) the VH comprises the amino acid sequence of SEQ ID NO: 1583; an amino acid sequence at least 85% 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 1583; or an amino acid sequence comprising at least one, two or three modifications, but no more than 30, 20, or 10 modifications relative to the amino acid sequence of SEQ ID NO: 1583; and the VL comprises the amino acid sequence of SEQ ID NO: 1591, an amino acid sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 1591; or amino acid sequence comprising at least one, two or three modifications, but no more than 30, 20, or 10 modifications relative to the amino acid sequence of SEQ ID NO: 1591; or81.(vii) the VH comprises the amino acid sequence of SEQ ID NO: 1599; an amino acid sequence at least 85% 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 1583; or an amino acid sequence comprising at least one, two or three modifications, but no more than 30, 20, or 10 modifications relative to the amino acid sequence of SEQ ID NO: 1599; and the VL comprises the amino acid sequence of SEQ ID NO: 1606, an amino acid sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 1606; or amino acid sequence comprising at least one, two or three modifications, but no more than 30, 20, or 10 modifications relative to the amino acid sequence of SEQ ID NO: 1606.

21. The AAV particle of any one of claims 18-20. wherein:83.(i) the nucleotide sequence encoding the VH comprises the nucleotide sequence of any one of SEQ ID NOs: 158, 156, 157, 159, 160, 1563, 7, 190, 1584, or 1600, a nucleotide sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 158, 156, 157, 159, 160, 1563, 7, 190, 1584, or 1600; or a nucleotide sequence having at least one, two, or three, but no more than 30, 20, or 10 different nucleotides relative to any one of SEQ ID NOs: 158, 156, 157, 159. 160, 1563, 7. 190, 1584, or 1600: an / or the nucleotide sequence encoding tire VL comprises the nucleotide sequence of any one of SEQ ID NOs: 162, 161, 163, 164, 165, 1574, 22, 192, 1592, or 1607, a nucleotide sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 162, 161, 163, 164, 165, 1574, 22, 192, 1592, or 1607; or a nucleotide sequence having at least one, two, or three, but no more than 30, 20. or 10 different nucleotides relative to anyone of SEQ ID NOs: 162, 161, 163, 164, 165, 1574.22, 192, 1592, or 1607:84.(ii) the nucleotide sequence encoding the VH comprises the nucleotide sequence of SEQ ID NO: 158, or a nucleotide sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto; and the nucleotide sequence encoding the VL comprises the nucleotide sequence of SEQ ID NO: 162, or a nucleotide sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto;85.(iii) the nucleotide sequence encoding the VH comprises the nucleotide sequence of SEQ ID NO: 159, or a nucleotide sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto; and the nucleotide sequence encoding the VL comprises the nucleotide sequence of SEQ ID NO: 161, or a nucleotide sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto;86.(iv) the nucleotide sequence encoding the VH comprises tire nucleotide sequence of SEQ ID NO: 156, or a nucleotide sequence at least 85%. 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto; and the nucleotide sequence encoding the VL comprises tire nucleotide sequence of SEQ ID NO: 161, or a nucleotide sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto;87.(v) the nucleotide sequence encoding the VH comprises the nucleotide sequence of SEQ ID NO: 160, or a nucleotide sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto; and the nucleotide sequence encoding the VL comprises the nucleotide sequence of SEQ ID NO: 162, or a nucleotide sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto;88.(vi) the nucleotide sequence encoding the VH comprises the nucleotide sequence of SEQ ID NO: 1563. or a nucleotide sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto; and the nucleotide sequence encoding the VL comprises tire nucleotide sequence of SEQ ID NO: 1574, or a nucleotide sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto;89.(vii) the nucleotide sequence encoding the VH comprises the nucleotide sequence of SEQ ID NO: 1584, or a nucleotide sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto; and the nucleotide sequence encoding the VL comprises tire nucleotide sequence of SEQ ID NO: 1592. or a nucleotide sequence at least 95% identical thereto:90.(viii) the nucleotide sequence encoding the VH comprises the nucleotide sequence of SEQ ID NO: 1600, or a nucleotide sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto; and the nucleotide sequence encoding the VL comprises the nucleotide sequence of SEQ ID NO: 1607, or a nucleotide sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto; or91.(ix) the nucleotide sequence encoding the VH comprises the nucleotide sequence of SEQ ID NO: 160, or a nucleotide sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto; and the nucleotide sequence encoding the VL comprises the nucleotide sequence of SEQ ID NO: 163, or a nucleotide sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto.

22. Hie AAV particle of any one of claims 1-17, wherein the encoded antibody molecule comprises a heavy chain variable region (VH) comprising heavy chain complementarity determining region 1 (HC CDR1), a HC CDR2, and a HC CDR3; and a light chain variable region (VL) comprising light chain complementarity determining region 1 (LC CDR1). A LC CDR2, and a LC CDR3, wherein:93.(i) the HC CDR1, HC CDR2, and HC CDR3 comprise tire amino acid sequences of SEQ ID NOs: 1503, 1504, and 1502. respectively; and the LC CDR1, LC CDR2, and LC CDR3 comprise the amino acid sequences of SEQ ID NOs: 1514, 1515, and 1516, respectively;94.(ii) the HC CDR1, HC CDR2, and HC CDR3 comprise the amino acid sequences of SEQ ID NOs: 1528, 1529, and 1527, respectively; and the LC CDR1, LC CDR2, and LC CDR3 comprise the amino acid sequences of SEQ ID NOs: 1539, 1540, and 1541, respectively; (iii) the HC CDR1, HC CDR2, and HC CDR3 comprise the amino acid sequences of SEQ ID NOs: 1611, 1612, and 1610, respectively; and the LC CDR1, LC CDR2, and LC CDR3 comprise the amino acid sequences of SEQ ID NOs: 1621, 1622, and 1623, respectively95.(iv) the HC CDR1, HC CDR2, and HC CDR3 comprise tire amino acid sequences of SEQ ID NOs: 2200, 2257, and 2258, respectively; and the LC CDR1 comprises the amino acid sequence of SEQ ID NO: 2262, the LC CDR2 comprises the amino acid sequence of KDS, and the LC CDR3 comprises the amino acid sequence of SEQ ID NO: 2264;96.(v) the HC CDR1, HC CDR2, and HC CDR3 comprise the amino acid sequences of SEQ ID NOs: 2371, 2372, and 2373, respectively; and the LC CDR1 comprises the amino acid sequence of SEQ ID NO: 2207, the LC CDR2 comprises the amino acid sequence of KIS, and the LC CDR3 comprises the amino acid sequence of SEQ ID NO: 2224;97.(vi) the HC CDR1, HC CDR2, and HC CDR3 comprise the amino acid sequences of SEQ ID NOs: 2200, 2201, and 2202, respectively; and the LC CDR1 comprises the amino acid sequence of SEQ ID NO: 2207, the LC CDR2 comprises the amino acid sequence of KIS, and the LC CDR3 comprises the amino acid sequence of SEQ ID NO: 2209;98.(vii) the HC CDR1, HC CDR2, and HC CDR3 comprise the amino acid sequences of SEQ ID NOs: 2232, 2233, and 2234. respectively; and the LC CDR1 comprises the amino acid sequence of SEQ ID NO: 2238, the LC CDR2 comprises the amino acid sequence of DVS, and the LC CDR3 comprises the amino acid sequence of SEQ ID NO: 2240;99.(viii) the HC CDR1, HC CDR2, and HC CDR3 comprise the amino acid sequences of SEQ ID NOs: 2248, 2219, and 2249, respectively; and the LC CDR1 comprises the amino acid sequence of SEQ ID NO: 2207, the LC CDR2 comprises the amino acid sequence of KIS, and the LC CDR3 comprises the amino acid sequence of SEQ ID NO: 2224;100.(ix) the HC CDR1, HC CDR2, and HC CDR3 comprise the amino acid sequences of SEQ ID NOs: 2415, 2416, and 2417, respectively; and the LC CDR1 comprises the amino acid sequence of SEQ ID NO: 2420, the LC CDR2 comprises the amino acid sequence of WAS, and the LC CDR3 comprises the amino acid sequence of SEQ ID NO: 2422;101.(x) the HC CDRL HC CDR2, and HC CDR3 comprise the amino acid sequences of SEQ ID NOs: 2218, 2219, and 2220. respectively; and the LC CDR1 comprises the amino acid sequence of SEQ ID NO: 2207, the LC CDR2 comprises the amino acid sequence of KIS, and the LC CDR3 comprises the amino acid sequence of SEQ ID NO: 2224; or102.(xi) the HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and LC CDR3 comprise the amino acid sequences of any of the HC CDR and LC CDR sequences provided in any one of Tables 7-16.

23. The AAV particle of claim 22, wherein:103.(i) the VH comprises the amino acid sequence of any one of SEQ ID NOs: 1512, 1537, 1619, 2214, 2228, 2244, 2253, 2269, 2280, 2295, 2309, 2326, 2341, 2357, 2367, 2377, 2388, 2400, 2411, 2426, 2441, 2455, or 2470, an amino acid sequence at least 85% 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 1512. 1537, 1619, 2214, 2228, 2244, 2253, 2269. 2280, 2295, 2309, 2326. 2341. 2357, 2367, 2377, 2388, 2400, 2411. 2426. 2441, 2455, or 2470, or an amino acid sequence comprising at least one, two, or three but no more than 30, 20, or 10 modifications relative to any one of SEQ ID NOs: 1512, 1537, 1619, 2214, 2228, 2244, 2253, 2269, 2280, 2295, 2309, 2326, 2341, 2357, 2367, 2377, 2388, 2400, 2411, 2426, 2441, 2455, or 2470; and / orthe VL comprises the amino acid sequence of any one of SEQ ID NOs: 1523, 1548, 1629, 2215, 2229, 2245, 2254, 2270, 2281, 2296. 2310, 2327, 2342, 2358, 2368, 2378, 2389. 2401, 2412, 2427, 2442, 2456, or 2471, an amino acid sequence at least 85% 90%, 92%, 95%, 96%. 97%. 98%. or 99% identical to any one of SEQ ID NOs: 1523, 1548, 1629, 2215, 2229, 2245, 2254, 2270, 2281, 2296, 2310, 2327, 2342, 2358, 2368, 2378, 2389, 2401, 2412, 2427, 2442, 2456, or 2471, or an amino acid sequence comprising at least one, two, or three but no more than 30, 20, or 10 modifications relative to any one of SEQ ID NOs: 1523, 1548, 1629, 2215, 2229, 2245, 2254, 2270, 2281, 2296, 2310, 2327, 2342, 2358, 2368, 2378, 2389. 2401, 2412, 2427, 2442, 2456, or 2471;104.(ii) the VH comprises the amino acid sequence of SEQ ID NO: 1512: an amino acid sequence at least 85% 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 1512: or an amino acid sequence comprising at least one, two or three modifications, but no more than 30, 20, or 10 modifications relative to the amino acid sequence of SEQ ID NO: 1512; and the VL comprises the amino acid sequence of SEQ ID NO: 1523, an amino acid sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 1523; or amino acid sequence comprising at least one, two or three modifications, but no more than 30, 20, or 10 modifications relative to the amino acid sequence of SEQ ID NO: 1523;105.(iii) the VH comprises the amino acid sequence of SEQ ID NO: 1537; an amino acid sequence at least 85% 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 1537; or an amino acid sequence comprising at least one, two or three modifications, but no more than 30, 20, or 10 modifications relative to the amino acid sequence of SEQ ID NO: 1537; and the VL comprises the amino acid sequence of SEQ ID NO: 1548, an amino acid sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 1548; or amino acid sequence comprising at least one, two or three modifications, but no more than 30, 20, or 10 modifications relative to the amino acid sequence of SEQ ID NO: 1548; (iv) the VH comprises the amino acid sequence of SEQ ID NO: 1619; an amino acid sequence at least 85% 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 1619; or an amino acid sequence comprising at least one, two or three modifications, but no more than 30, 20, or 10 modifications relative to the amino acid sequence of SEQ ID NO: 1619; and the VL comprises the amino acid sequence of SEQ ID NO: 1629, an amino acid sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 1629; or amino acid sequence comprising at least one, two or three modifications, but no more than 30, 20, or 10 modifications relative to the amino acid sequence of SEQ ID NO: 1629;106.(v) the VH comprises the amino acid sequence of SEQ ID NO: 2269; an amino acid sequence at least 85% 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 2269; or an amino acid sequence comprising at least one. two or three modifications, but no more than 30, 20, or 10 modifications relative to the amino acid sequence of SEQ ID NO: 2269; and the VL comprises the amino acid sequence of SEQ ID NO: 2270, an amino acid sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 2270; or amino acid sequence comprising at least one, two or three modifications, but no more than 30, 20, or 10 modifications relative to the amino acid sequence of SEQ ID NO: 2270;107.(vi) the VH comprises the amino acid sequence of SEQ ID NO: 2377; an amino acid sequence at least 85% 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 2377; or an amino acid sequence comprising at least one, two or three modifications, but no more than 30, 20, or 10 modifications relative to the amino acid sequence of SEQ ID NO: 2377; and the VL comprises the amino acid sequence of SEQ ID NO: 2378, an amino acid sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 2378; or amino acid sequence comprising at least one, two or three modifications, but no more than 30, 20, or 10 modifications relative to the amino acid sequence of SEQ ID NO: 2378;108.(vii) the VH comprises the amino acid sequence of SEQ ID NO: 2214; an amino acid sequence at least 85% 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 2214; or an amino acid sequence comprising at least one, two or three modifications, but no more than 30, 20, or 10 modifications relative to the amino acid sequence of SEQ ID NO: 2214; and the VL comprises the amino acid sequence of SEQ ID NO: 2215, an amino acid sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 2215; or amino acid sequence comprising at least one, two or three modifications, but no more than 30, 20, or 10 modifications relative to the amino acid sequence of SEQ ID NO: 2215;109.(viii) the VH comprises the amino acid sequence of SEQ ID NO: 2228; an amino acid sequence at least 85% 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 2228; or an amino acid sequence comprising at least one, two or three modifications, but no more than 30, 20, or 10 modifications relative to the amino acid sequence of SEQ ID NO: 2228; and the VL comprises the amino acid sequence of SEQ ID NO: 2229, an amino acid sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 2229; or amino acid sequence comprising at least one, two or three modifications, but no more than 30, 20, or 10 modifications relative to the amino acid sequence of SEQ ID NO: 2229;110.(ix) the VH comprises the amino acid sequence of SEQ ID NO: 2244; an amino acid sequence at least 85% 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 2244; or an amino acid sequence comprising at least one, two or three modifications, but no more than 30, 20, or 10 modifications relative to the amino acid sequence of SEQ ID NO: 2244; and the VL comprises the amino acid sequence of SEQ ID NO: 2245, an amino acid sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 2245; or amino acid sequence comprising at least one, two or three modifications, but no more than 30, 20, or 10 modifications relative to the amino acid sequence of SEQ ID NO: 2245;111.(x) the VH comprises the amino acid sequence of SEQ ID NO: 2253; an amino acid sequence at least 85% 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 2253; or an amino acid sequence comprising at least one. two or three modifications, but no more than 30, 20, or 10 modifications relative to the amino acid sequence of SEQ ID NO: 2253; and the VL comprises the amino acid sequence of SEQ ID NO: 2254, an amino acid sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 2254; or amino acid sequence comprising at least one, two or three modifications, but no more than 30, 20, or 10 modifications relative to the amino acid sequence of SEQ ID NO: 2254;112.(xi) the VH comprises the amino acid sequence of SEQ ID NO: 2426; an amino acid sequence at least 85% 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 2426; or an amino acid sequence comprising at least one, two or three modifications, but no more than 30, 20, or 10 modifications relative to the amino acid sequence of SEQ ID NO: 2426; and the VL comprises the amino acid sequence of SEQ ID NO: 2427, an amino acid sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 2427; or amino acid sequence comprising at least one, two or three modifications, but no more than 30, 20, or 10 modifications relative to the amino acid sequence of SEQ ID NO: 2427; or113.(xii) the VH comprises the amino acid sequence of any one of the VH sequences provided in any one of Tables 7, 8, 13, 13A, 13B, 13C, or 14, an amino acid sequence at least 85% 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical to any one of the VH sequences provided in any one of Tables 7, 8, 13, 13A, 13B, 13C, or 14, or amino acid sequence comprising at least one, two or three modifications, but no more than 30, 20, or 10 modifications relative to any one of the VH sequences provided in any one of Tables 7, 8, 13, 13A, 13B, 13C, or 14; and the VL comprises the amino acid sequence of any one of the VL sequences provided in any one of Tables 7, 8, 13, 13A, 13B, 13C, or 14, an amino acid sequence at least 85% 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical to any one of the VL sequences provided in any one of Tables 7, 8. 13, 13A, 13B, 13C, or 14, or amino acid sequence comprising at least one, two or three modifications, but no more than 30, 20, or 10 modifications relative to any one of the VL sequences provided in any one of Tables 7, 8, 13, 13A, 13B, 13C, or 14.

24. The AAV particle of claim 22 or 23, wherein:115.(i) the nucleotide sequence encoding the VH comprises the nucleotide sequence of any one of SEQ ID NOs: 1513. 1538. 1620, 2216, 2230, 2246, 2255, 2271. 2282. 2297, 2311, 2328, 2343, 2359, 2369, 2379, 2390, 2402, 2413, 2428, 2443, 2457, or 2472, a nucleotide sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 1513, 1538, 1620, 2216, 2230, 2246, 2255, 2271, 2282, 2297, 2311, 2328, 2343, 2359, 2369, 2379, 2390, 2402, 2413, 2428, 2443, 2457, or 2472; or a nucleotide sequence having at least one, two, or three, but no more than 30, 20, or 10 different nucleotides relative to any one of SEQ ID NOs: 1513, 1538, 1620, 2216, 2230. 2246, 2255, 2271. 2282. 2297, 2311, 2328, 2343, 2359. 2369. 2379. 2390, 2402, 2413, 2428, 2443.116.2457, or 2472; an / or the nucleotide sequence encoding the VL comprises the nucleotide sequence of any one of SEQ ID NOs: 1524, 1549, 1630, 2217, 2231, 2247, 2256, 2272, 2283, 2298, 2312, 2329, 2344, 2360, 2370, 2380, 2391, 2403, 2414, 2429, 2444, 2458, or 2473, a nucleotide sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 1524, 1549, 1630, 2217, 2231, 2247. 2256, 2272, 2283, 2298, 2312, 2329, 2344. 2360, 2370, 2380, 2391, 2403, 2414, 2429, 2444, 2458, or 2473; or a nucleotide sequence having at least one, two, or three, but no more than 30, 20, or 10 different nucleotides relative to any one of SEQ ID NOs: 1524, 1549, 1630, 2217, 2231, 2247, 2256, 2272, 2283, 2298, 2312, 2329, 2344, 2360, 2370, 2380, 2391, 2403, 2414, 2429, 2444, 2458, or 2473;117.(ii) the nucleotide sequence encoding the VH comprises the nucleotide sequence of SEQ ID NO: 1513. or a nucleotide sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto; and the nucleotide sequence encoding the VL comprises tire nucleotide sequence of SEQ ID NO: 1524, or a nucleotide sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto;118.(iii) the nucleotide sequence encoding the VH comprises the nucleotide sequence of SEQ ID NO: 1538, or a nucleotide sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto; and the nucleotide sequence encoding the VL comprises the nucleotide sequence of SEQ ID NO: 1549, or a nucleotide sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto;119.(iv) the nucleotide sequence encoding the VH comprises the nucleotide sequence of SEQ ID NO: 1620. or a nucleotide sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto; and the nucleotide sequence encoding the VL comprises tire nucleotide sequence of SEQ ID NO: 1630, or a nucleotide sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto;120.(v) the nucleotide sequence encoding the VH comprises the nucleotide sequence of SEQ ID NO: 2271, or a nucleotide sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto; and the nucleotide sequence encoding the VL comprises tire nucleotide sequence of SEQ ID NO: 2272. or a nucleotide sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto;121.(vi) the nucleotide sequence encoding the VH comprises the nucleotide sequence of SEQ ID NO: 2379, or a nucleotide sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto; and the nucleotide sequence encoding the VL comprises the nucleotide sequence of SEQ ID NO: 2380. or a nucleotide sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto;122.(vii) the nucleotide sequence encoding the VH comprises the nucleotide sequence of SEQ ID NO: 2216, or a nucleotide sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto; and the nucleotide sequence encoding the VL comprises the nucleotide sequence of SEQ ID NO: 2217, or a nucleotide sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto;123.(viii) the nucleotide sequence encoding the VH comprises the nucleotide sequence of SEQ ID NO: 2230, or a nucleotide sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto; and the nucleotide sequence encoding the VL comprises the nucleotide sequence of SEQ ID NO: 2231, or a nucleotide sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto;124.(ix) the nucleotide sequence encoding the VH comprises tire nucleotide sequence of SEQ ID NO: 2246, or a nucleotide sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto; and the nucleotide sequence encoding the VL comprises the nucleotide sequence of SEQ ID NO: 2247, or a nucleotide sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto; (x) the nucleotide sequence encoding the VH comprises the nucleotide sequence of SEQ ID NO: 2255, or a nucleotide sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto; and the nucleotide sequence encoding the VL comprises the nucleotide sequence of SEQ ID NO: 2256, or a nucleotide sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto;125.(xi) the nucleotide sequence encoding the VH comprises the nucleotide sequence of SEQ ID NO: 2248, or a nucleotide sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto; and the nucleotide sequence encoding the VL comprises the nucleotide sequence of SEQ ID NO: 2249, or a nucleotide sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto; or126.(xii) the nucleotide sequence encoding the VH comprises any one of the nucleotide sequence encoding a VH as provided in any one of Tables 7, 8, 13, 13A, 13B. 13C, or 14. or a nucleotide sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto; and the nucleotide sequence encoding the VL comprises any one of the nucleotide sequence encoding a VL as provided in any one of Tables 7, 8, 13, 13A, 13B, 13C, or 14, or a nucleotide sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%. or 99% identical thereto.

25. The AAV particle of any one of claims 1-24, wherein the encoded antibody molecule is:128.(i) a full length antibody, a bispecific antibody, an Fab, an F(ab')2, an Fv, or a single chain Fv fragment (scFv); and / or129.(ii) a human antibody, a humanized antibody, or a murine antibody.

26. The AAV particle of any one of claims 1-25, wherein the encoded antibody molecule comprises:131.(i) a heavy chain constant region selected from IgGl, IgG2, IgG3, IgG4; and / or a light chain constant region of kappa or lambda; or132.(ii) a heavy chain constant region of IgG4 and a light chain constant region of kappa.

27. The AAV particle of any one of claims 1-26, wherein the encoded antibody molecule comprises:134.(i) a human IgG4 constant region, comprising an amino acid other than serine at position 228 according to EU numbering:135.(ii) a human IgG4 constant region, comprising a serine to proline substitution at position 228 according to EU numbering; (iii) a heavy chain constant region (e.g., a human IgG4 constant region) comprising the amino acid sequence of SEQ ID NO: 2503, or an amino acid sequence at least 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 2503; and / or136.(iv) a heavy chain constant region (e.g., a human IgG4 constant region), wherein the nucleotide sequence encoding the heavy chain constant region comprises the nucleotide sequence of any one of SEQ ID NOs: 2504, 2505, 2506, or 2507, or a nucleotide sequence at least 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical any one of SEQ ID NOs: 2504, 2505, 2506, or 2507.

28. The AAV particle of any one of claims 1-27, wherein the encoded antibody comprises a light chain constant region (e.g., a light chain constant region of kappa), wherein:138.(i) the light chain constant region comprises the amino acid sequence of SEQ ID NO: 2508, or an amino acid sequence at least 90%. 92%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 2508; and / or139.(ii) the nucleotide sequence encoding the light chain constant region comprises the nucleotide sequence of SEQ ID NO: 2509 or 2510, or a nucleotide sequence at least 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 2509 or 2510.

29. The AAV particle of any one of claims 1-28, wherein the encoded antibody molecules comprises:141.(i) a heavy chain comprising the amino acid sequence of any one of SEQ ID NOs: 170-174, 8, or 65, or an amino acid sequence at least 85%, 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 170-174, 8, or 65; and / or a light chain comprising the amino acid sequence of any one of SEQ ID NOs: 175-179, 23, or 66, or an amino acid sequence at least 90%, 92%, 95%, 96%, 97%, 98%. or 99% identical to any one of SEQ ID NOs: 175-179, 23, or 66;142.(ii) a heavy chain comprising the amino acid sequence of SEQ ID NO: 172, or an amino acid sequence at least 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto; and a light chain comprising the amino acid sequence of SEQ ID NO: 176, or an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical thereto;143.(iii) a heavy chain comprising the amino acid sequence of SEQ ID NO: 173, or an amino acid sequence at least 90%, 92%. 95%. 96%, 97%, 98%, or 99% identical thereto; and a light chain comprising the amino acid sequence of SEQ ID NO: 175, or an amino acid sequence at least 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto;144.(iv) a heavy chain comprising the amino acid sequence of SEQ ID NO: 170, or an amino acid sequence at least 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto; and a light chain comprising the amino acid sequence of SEQ ID NO: 175, or an amino acid sequence at least 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto;145.(v) a heavy chain comprising the amino acid sequence of SEQ ID NO: 174, or an amino acid sequence at least 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto; and a light chain comprising tire amino acid sequence of SEQ ID NO: 176, or an amino acid sequence at least 90%, 92%, 95%, 96%, 97%, 98%. or 99% identical thereto:146.(vi) a heavy chain comprising the amino acid sequence of SEQ ID NO: 174, or an amino acid sequence at least 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto; and a light chain comprising the amino acid sequence of SEQ ID NO: 177, or an amino acid sequence at least 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto;147.(vii) a heavy chain comprising tire amino acid sequence of SEQ ID NO: 65, or an amino acid sequence at least 90%, 92%. 95%. 96%. 97%. 98%, or 99% identical thereto; and a light chain comprising the amino acid sequence of SEQ ID NO: 66, or an amino acid sequence at least 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto; or148.(viii) a heavy chain comprising the amino acid sequence of SEQ ID NO: 8, or an amino acid sequence at least 90%, 92%. 95%, 96%, 97%, 98%, or 99% identical thereto; and a light chain comprising the amino acid sequence of SEQ ID NO:

23. or an amino acid sequence at least 90%, 92%, 95%, 96%, 97%, 98%. or 99% identical thereto.

30. The AAV particle of claim 29, wherein:150.(i) tire nucleotide sequence encoding the heavy chain comprises tire nucleotide sequence of any one of SEQ ID NOs: 180-184, 10, or 191, or an nucleotide acid sequence at least 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 180-184, 10, or 191; and / or the nucleotide sequence encoding the light chain comprises the nucleotide sequence of any one of SEQ ID NOs: 185-189, 24, or 193, or an nucleotide acid sequence at least 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 185-189, 24, or 193;151.(ii) the nucleotide sequence encoding the heavy chain comprises the nucleotide sequence of SEQ ID NO: 182, or a nucleotide sequence at least 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto; and the nucleotide sequence encoding the light chain comprises the nucleotide sequence of SEQ ID NO: 186, or a nucleotide sequence at least 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto;152.(iii) the nucleotide sequence encoding the heavy chain comprises the nucleotide sequence of SEQ ID NO: 183, or a nucleotide sequence at least 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto; and the nucleotide sequence encoding the light chain comprises tire nucleotide sequence of SEQ ID NO: 185, or a nucleotide sequence at least 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto;153.(iv) the nucleotide sequence encoding the heavy chain comprises the nucleotide sequence of SEQ ID NO: 180, or a nucleotide sequence at least 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto; and the nucleotide sequence encoding the light chain comprises the nucleotide sequence of SEQ ID NO:

185. or a nucleotide sequence at least 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto;154.(iv) the nucleotide sequence encoding the heavy chain comprises the nucleotide sequence of SEQ ID NO: 184, or a nucleotide sequence at least 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto; and the nucleotide sequence encoding the light chain comprises the nucleotide sequence of SEQ ID NO:

186. or a nucleotide sequence at least 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto: or155.(vi) the nucleotide sequence encoding the heavy chain comprises the nucleotide sequence of SEQ ID NO: 184, or a nucleotide sequence at least 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto; and the nucleotide sequence encoding the light chain comprises the nucleotide sequence of SEQ ID NO: 187, or a nucleotide sequence at least 90%, 92%, 95%, 96%, 97%, 98%, or 99% identical thereto.

31. The AAV particle of claim 29 or 30, wherein:157.(i) the nucleotide sequence encoding the heavy chain and the nucleotide sequence encoding the light chain are connected directly; or158.(ii) tire nucleotide sequence encoding the heavy chain and the nucleotide sequence encoding the light chain are connected via a linker, optionally wherein the linker comprises the nucleotide sequence of any of the linker sequences provided in Table 19, or a nucleotide sequence at least 95% identical thereto.

32. The AAV particle of any one of claims 18-31, where the nucleic acid encoding the antibody molecule comprises:160.(i) a signal sequence present 5' relative to the nucleotide sequence encoding the VH; and / or (ii) a signal sequence present 5’ relative to the nucleotide sequence encoding the VL; optionally wherein the signal sequence comprises the nucleotide sequence of any of the signal sequences provided in Table 20, or a nucleotide sequence at least 95% identical thereto.

33. The AAV particle of any one of claims 1-32, which comprises a viral genome comprising a promoter operably linked to the nucleic acid encoding the antibody molecule which binds to human tau.

34. The AAV particle of claim 33. wherein tire promoter is a ubiquitous promoter.

35. The AAV particle of claim 33, wherein the promoter is a cell-type specific promoter or a tissuespecific promoter.

36. The AAV particle of any one of claims 33-35, wherein the promoter is chosen from human elongation factor la-subunit (EFla), cytomegalovirus (CMV) immediate-early enhancer and / or promoter, chicken P-actin (CBA) and its derivative CAG, glucuronidase (GUSB). or ubiquitin C (UBC), neuron-specific enolase (NSE), platelet-derived growth factor (PDGF), platelet-derived growth factor B-chain (PDGF-P), intercellular adhesion molecule 2 (ICAM-2), synapsin (Syn), methyl-CpG binding protein 2 (MeCP2), Ca2+ / calmodulin-dependent protein kinase II (CaMKII), metabotropic glutamate receptor 2 (mGluR2), neurofilament light (NFL) or heavy (NFH), p-globin minigene np2, preproenkephalin (PPE), enkephalin (Enk) and excitatory amino acid transporter 2 (EAAT2), glial fibrillary acidic protein (GFAP), myelin basic protein (MBP). or a fragment, e.g., a truncation, or a functional variant thereof.

37. The AAV particle of any one of claims 33-36, wherein the viral genome further comprises:165.(i) an enhancer;166.(ii) a polyadenylation (polyA) signal region;167.(ii) a 5’ inverted terminal repeat (ITR) and a 3’ ITR;168.(iii) at least 1, 2, or 3 intron regions;169.(iv) at least 1, 2, or 3 exon regions; and / or170.(v) a nucleotide sequence encoding a microRNA (miR) binding site, e.g., a miR binding site that modulates, e.g., reduces expression of payload encoded by the viral genome in a cell or tissue where the corresponding miRNA is expressed; optionally wherein the encoded miR binding site modulates, e.g., reduces expression of the payload encoded by the viral genome in a cell or tissue of the DRG, liver, heart, hematopoietic lineage, or a combination thereof.

38. The AAV particle of any one of claims 33-37, wherein the viral genome is self-complementary or single stranded.

39. A cell comprising the AAV particle of any one of claims 1-38, optionally wherein, the cell is: (a) a mammalian cell or an insect cell;172.(b) a cell of a brain region or a spinal cord region (e.g., a CNS cell);173.(c) a cell of the brain or the spinal cord (e.g., a cell of a putamen, caudate, hippocampus, thalamus, substantia nigra, motor cortex, frontal cortex, temporal cortex, cerebral cortex, dentate nucleus. Lateral Geniculate Nucleus (LGN). cervical spinal cord, lumbar spinal cord, and / or thoracic spinal cord); or174.(d) a neuron or an astrocyte.

40. A method of making the AAV particle of any one of claims 1-38, comprising:176.(i) providing a host cell comprising a AAV viral genome;177.(ii) incubating the host cell under conditions suitable to enclose the viral genome in an AAV capsid protein;178.thereby making the AAV particle.

41. A pharmaceutical composition comprising the AAV particle of any one of claims 1-38, and a pharmacally acceptable excipient.

42. A method of delivering an antibody molecule that binds to human tau to a subject, comprising administering to the cell an effective amount of the pharmaceutical composition of claim 41 or the AAV particle of any one of claims 1-38, thereby delivering the antibody molecule that binds to human tau to tire subject.

43. The method of claim 42, wherein the subject has or has been diagnosed with having a genetic disorder (e.g., a monogenic disorder or a polygenic disorder); a neurological disorder (e.g., a neurodegenerative disorder); a disorder associated with tau expression, e.g., aberrant tau expression; and / or a tauopathy.

44. A method of treating a subject having or diagnosed with having a genetic disorder (e.g., a monogenic disorder or a polygenic disorder); a neurological disorder (e.g., a neurodegenerative disorder); a disorder associated with tau expression, e.g., aberrant tau expression; and / or a tauopathy, the method comprising administering to the subject an effective amount of the pharmaceutical composition of claim 41 or the AAV particle of any one of claims 1-38, thereby treating the subject.

45. The method of claim 44, wherein the genetic disorder, neurological disorder (e.g., neurodegenerative disorder), disorder associated with tau expression (e.g., aberrant tan expression), and / or tauopathy is Alzheimer’s disease (AD), Frontotemporal dementia (FTD), frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), frontotemporal lobar degeneration (FTLD). Dravet syndrome (DS), neurodegenerative disease, traumatic brain injury (TBI), chronic traumatic encephalopathy (CTE), progressive supranuclear palsy (PSP). Down’s syndrome. Pick’s disease, corticobasal degeneration (CBD), corticobasal syndrome, amyotrophic lateral sclerosis (ALS), Prion diseases, CJD, Multiple system atrophy, mild cognitive impairment, Tangle-only dementia, or Progressive subcortical gliosis.

46. The method of claim 44 or 45, wherein treating comprises prevention of progression of the genetic disorder, neurological disorder (e.g.. neurodegenerative disorder), disorder associated with tau expression (e.g., aberrant tau expression), and / or tauopathy in the subject in the subject.

47. The method of any one of claims 42-46, further comprising performing a blood test, an imaging test (e.g., a PET scan or a PET scan in combination with biomarker, e.g., serum biomarker staining), a CNS biopsy sample, or an aqueous cerebral spinal fluid biopsy, optionally wherein the blood test, imaging test, biopsy sample, or aqueous cerebral spinal fluid biopsy is performed prior to, during, or after treatment with the AAV particle, modulatory' polynucleotide, siRNA, or pharmaceutical composition.

48. The method of any one of claims 42-47, wherein the pharmaceutical composition or AAV particle are administered to the subject:186.(i) intravenously, via intra-cistema magna injection (ICM), intracerebrally, intrathecally, intracerebroventricularly, via intraparenchymal administration, or intramuscularly:187.(ii) via focused ultrasound (FUS), e.g., coupled with the intravenous administration of microbubbles (FUS-MB), or MRI-guided FUS coupled with intravenous administration;188.(iii) intravenously.

49. The pharmaceutical composition of claim 41 or the AAV particle of any one of claims 1-38, for use in a method of delivering an antibody molecule that binds to human tau to a subject.

50. The pharmaceutical composition of claim 41 or the AAV particle of any one of claims 1-38, for use in the treatment of a genetic disorder, neurological disorder (e.g., neurodegenerative disorder), disorder associated with tau expression (e.g., aberrant tau expression), and / or tauopathy.

51. Use of the pharmaceutical composition of claim 41 or the AAV particle of any one of claims 1-38, in the manufacture of a medicament for delivering an antibody molecule that binds to human tau to a subject.

52. Use of the pharmaceutical composition of claim 41 or the AAV particle of any one of claims 1-38, in the manufacture of a medicament for treating a genetic disorder, neurological disorder (e.g., neurodegenerative disorder), disorder associated with tau expression (e.g.. aberrant tau expression), and / or tauopathy.

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