A preparation for the treatment of disorders associated with glucosylceramides beta-1 deficiency.

Abstract

The invention relates to a preparation and method which, among other preparations and methods, alter, for example, the level of GBA1 protein through delivery using a variant of adeno-conjugated viral capsid (AAV). The preparation and method under the invention are useful, among other preparations and methods, in the treatment of subjects who have, are diagnosed with, or are at risk of having a GBA1-related disorder, for example, Parkinson's disease (PD), Gaucher disease (GD), Parkinsonian dementia (PDD), Lewy body dementia (DLB), or Lewy body dementia (LBD).

Description

COMPOSITIONS AND METHODS FOR THE TREATMENT OF DISORDERSRELATED TO GLUCOSYLCERAMIDASE BETA 1 DEFICIENCYRELATED APPLICATIONS

[0001] This application claims the benefit of and priority to US Provisional Application SerialNo. 63 / 463,836, filed May 3, 2023, US Provisional Application Serial No. 63 / 593,792, filed October 27, 2023, and US Provisional Application Serial No. 63 / 564,462, filed March 12, 2024, the contents of each of which are incorporated herein by reference in their entirety.SEQUENCE LISTING

[0002] The present application is being filed along with a Sequence Listing in electronic format.The Sequence Listing file, entitled 14640 0081-00304 SL.xml, was created on April 10, 2024, and is 5,682,716 bytes in size. The information in electronic format of the Sequence Listing is incorporated herein by reference in its entirety.FIELD

[0003] Described herein are compositions and methods relating to adeno-associated vims (AAV) viral particles for the delivery of polynucleotides, e.g., polynucleotides encoding glucosylceramidase beta 1 (GBA1) proteins (“GBA1 protein”) and peptides (“GBA1 peptide”) for use in the treatment of GBA1 -related disorders, which include Parkinson’s Disease (PD) and other GBA1-related disorders, including Gaucher Disease. Parkinson’s Disease Dementia (PDD), Dementia with Lewy Bodies (DLB), and Lewy Body Dementia (LBD). In some embodiments, compositions described herein may be used to treat a subject in need thereof, such as a human subject diagnosed with a GBA1-related disorder or other condition resulting from a deficiency in the quantity and / or function of GBA1 protein. BACKGROUND

[0004] Lysosomal acid glucosylceramidase, commonly called glucosylcerebrosidase or Gcase, a D-glucosyl-N-acylsphingosine glucohydrolase, is a lysosomal membrane protein important in glycolipid metabolism. The enzyme is encoded by the glucosylceramidase beta (GBA1) gene (Ensembl Gene ID No. ENSG00000177628). This enzyme, together with Saposin A and Saposin C, catalyzes the hydrolysis of glucosylceramide to ceramide and glucose. See Vaccaro, Anna Maria, et al. journal of Biological Chemistty 272.27 (1997): 16862-16867.

[0005] Mutations in GBA are known to cause disease in human subjects. Homozygous or compound heterozygous GBA1 mutations lead to Gaucher disease (“GD”). See Sardi, S, Pablo, Jesse M. Cedarbaum, and Patrik Brundin. Movement Disorders 33,5 (2018): 684-696. Gaucher disease is one of the most prevalent lysosomal storage disorders, with an estimated standardized birth incidencein the general population of 0.4 to 5.8 individuals per 100,000. Heterozy gous GBA1 mutations can lead to PD. Indeed, GBA1 mutations occur in 7-10% of total PD patients, making GBA1 mutations the most important genetic risk factor of PD. PD-GBA patients have reduced levels of the lysosomal enzy me beta-glucocerebrosidase (Gcase), which results in increased accumulations of glycosphingolipid glucosylceramide (GluCer), which in tarn is correlated with exacerbated α- Synuciein aggregation and concomitant neurological symptoms. GD and PD, as well as other lysosomal storage disorders or Lewy body diseases such as Lewy Body Dementia (LBD). See Sidransky. E. and Lopez, G. Lancet Neurol. 2012 November; 11(11): 986-998.

[0006] To date, there are limited available treatments for GBA1-related disorders such as PD, and dehveiy to the adult central nervous system (CNS) remains a significant challenge in the development of new and effective therapies. Thus, there remains a long-felt need to develop pharmaceutical compositions and methods that can be delivered to the CNS for the treatment of PD and other GBA1- related disorders and to ameliorate deficiencies of GBA1 protein in subjects, e.g., human subjects, afflicted with GBA1-related disorders.

[0007] Adeno-associated viruses (AAVs) have emerged as a widely studied and utilized viral particles for delivery of therapeutically effective polypeptides to mammalian cells. See, e.g., Tratschin et al., Mol. Cell Biol., 5(11):3251-3260 (1985) and Grimm et al., Hum. Gene Then, 10(15):2445-2450 (1999). The present disclosure provides improved pharmaceutical compositions and methods. In some embodiments, the disclosure provides methods of treatment using AAV capsid variants that are capable of delivering GBA1 to a target cell or tissue, e.g.. a CNS cell or tissue.SUMMARY

[0008] The present disclosure addresses these challenges by providing AAV-based compositions comprising AAV capsid variants and methods for treating Gcase deficiency in subjects. Disclosed herein are compositions and methods directed to AAV-based gene delivery of Gcase to ameliorate loss-of-function and to improve intracellular lipid trafficking. The compositions and methods are useful to improve lysosomal glycolipid metabolism, and to slow, halt, or reverse neurodegenerative and other symptoms of PD and other GBA1-related disorders (e.g., dementia with Lewy Bodies (DLB), Gaucher disease (GD)) in a subject (e.g., a subject having at least one mutation in a GBA1 gene). Unless otherwise specified, GBA protein, GBA1 protein, and Gcase protein are synonymous terms and used interchangeably to refer to the protein encoded by the GBA1 gene. Unless otherwise specified, a nucleotide sequence encoding a GBA1 protein (i.e., a GBA1-encoding sequence) refers to a nucleotide sequence that encodes the amino acids of a GBA1 protein, and may also be referred to as a GBA1 protein-encoding sequence.

[0009] In some embodiments, the present disclosure provides an AAV particle comprising a nucleotide sequence encoding a GBA1 protein, e.g., a wildtype GBA1 protein., and an AAV capsid, e.g., an AAV capsid variant. In some embodiments, the present disclosure provides an AAV particlecomprising a nucleotide sequence encoding a wildtype GBA1 protein and an AAV capsid variant. In some embodiments, the GBA1-encoding nucleotide sequence comprises an altered GC -content, and / or a reduced number of CpG motifs (e.g., lacking all CpG motifs) as compared to a wildtype GBA1-encoding sequence (e.g., comprising the nucleotide sequence of SEQ ID NO: 1776 or 1777), and wherein the AAW capsid variant is an AAV9 capsid variant.

[0010] In some embodiments, the AAV capsid variant is an AAV9 capsid variant comprising a peptide insert in the loop IV region. In some embodiments, the AAV capsid variant comprises the amino acid sequence of SPH in loop IV. In some embodiments, the AAV capsid variant comprises the amino acid sequence of SPH in loop IV wherein the amino acid sequence (SPH) is present immediately subsequent to position 455 as numbered according to SEQ ID NO: 138.

[0011] In some embodiments, the present disclosure provides an adeno-associated virus (AAV) particle comprising an AAV capsid variant comprising an amino acid sequence having the formula [N1]-[N2]-[N3], wherein: optionally [N1] comprises X1, X2, and X3, wherein at least one of X1, X2, or X3 is G; wherein [N2] comprises the amino acid sequence of SPH; and wherein [N3] comprises X4, X5, and X6, wherein at least one of X4, X5, or X6 is a basic amino acid; wherein the AAV particle further comprises a viral genome comprising a β -glucocerebrosidase 1 (GBA1)-encoding sequence. In some embodiments, the amino acid sequence [N1]-[N2]-[N3] is in hypervariable loop IV of the AAV capsid variant. In some embodiments, the AAV capsid variant is an AAV9 capsid variant. In some embodiments, [N1] comprises X1, X2, and X3, wherein at least one of X1, X2, or X3 is G, In some embodiments, [N2]-[N3] comprises the amino acid sequence of SPHSKA (SEQ ID NO: 941).

[0012] In some embodiments, the present disclosure provides an AAV particle comprising a viral genome comprising a GBA1-encoding sequence and an AAV9 capsid variant comprising the amino acid sequence of SPHSKA (SEQ ID NO: 941). In some embodiments, the amino acid sequence of SPHSKA (SEQ ID NO: 941) is in hypervariable loop IV of the AAV9 capsid variant. In some embodiments, the amino acid sequence of SPHSKA (SEQ ID NO: 941) is present immediately subsequent to an amino acid position corresponding to position 455 of SEQ ID NO: 4 or SEQ ID NO: 36.

[0013] In some embodiments, the A.AV9 capsid variant comprises one, two, or all of: an N at an amino acid position corresponding to position 452, an E at an amino acid position corresponding to position 451 , and / or a V at an amino acid position corresponding to position 453 of SEQ ID NO: 4. In some embodiments, the AAV9 capsid variant comprises the amino acid sequence of KTENVSGSPHSKAQNQQT (SEQ ID NO: 3272).

[0014] In some embodiments, the AAV9 capsid variant comprises a VP1 protein comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 4; a VP2 protein comprising an amino acid sequence having at least 90% identity to positions 138-742 of SEQ ID NO: 4; and / or a VP3 protein comprising an amino acid sequence having at least 90% identity to positions 203-742 of SEQ ID NO: 4. In some embodiments, the AAV9 capsid variant comprises a VP1 protein comprisingan amino acid sequence having at least 95% identity to SEQ ID NO: 4; a VP2 protein comprising an amino acid sequence having at least 95% identity to positions 138-742 of SEQ ID NO: 4; and / or a VP3 protein comprising an amino acid sequence having at least 95% identity to positions 203-742 of SEQ ID NO: 4, In some embodiments, the AAV9 capsid variant comprises a VP1 protein comprising an amino acid sequence having at least 99% identity to SEQ ID NO: 4; a VP2 protein comprising an amino acid sequence having at least 99% identity to positions 138-742 of SEQ ID NO: 4; and / or a VP3 protein comprising an amino acid sequence having at least 99% identity to positions 203-742 of SEQ ID NO: 4. In some embodiments, the AAV9 capsid variant comprises a VP1 protein comprising the amino acid seqUence of SEQ ID NO: 4; a VP2 protein comprising the amino acid sequence of positions 138-742 of SEQ ID NO: 4; and / or a VP3 protein comprising the amino acid sequence of positions 203-742 of SEQ ID NO: 4.

[0015] In some embodiments, the AAV9 capsid variant comprises the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is present immediately subsequent to an amino acid position corresponding to position 455 of SEQ ID NO: 4; an E at an amino acid position corresponding to position 451 and a V at an amino acid position corresponding to position 453 of SEQ ID NO: 4; and no other modifications relative to wild type AAV9.

[0016] In some embodiments, the AAV9 capsid variant comprises one. two, or all of: an E at an amino acid position corresponding to position 451, an R at an amino acid position corresponding to position 452, and / or a V at an amino acid position corresponding to position 453 of SEQ ID NO: 36, In some embodiments, the AAV9 capsid variant comprises the amino acid sequence of KTERVSGSPHSKAQNQQT (SEQ ID NO: 3589).

[0017] In some embodiments, the AAV9 capsid variant comprises a VP1 protein comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 36; a VP2 protein comprising an amino acid sequence having at least 90% identity to positions 138-742 of SEQ ID NO: 36; and / or a VP3 protein comprising an amino acid sequence having at least 90% identity to positions 203-742 of SEQ ID NO: 36. In some embodiments, the AAV9 capsid variant comprises a VP1 protein comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 36; a VP2 protein comprising an amino acid sequence having at least 95% identity to positions 138-742 of SEQ ID NO: 36; and / or a VP3 protein comprising an amino acid sequence having at least 95% identity to positions 203-742 of SEQ ID NO: 36, In some embodiments, the AAV9 capsid variant comprises a VP1 protein comprising an amino acid sequence having at least 99% identity to SEQ ID NO: 36; a VP2 protein comprising an amino acid sequence having at least 99% identity to positions 138-742 of SEQ ID NO: 36; and / or a VP3 protein comprising an amino acid sequence having at least 99% identity to positions 203-742 of SEQ ID NO: 36. In some embodiments, the AAV9 capsid variant comprises a VP1 protein comprising the amino acid sequence of SEQ ID NO: 36; a VP2 protein comprising the amino acid sequence of positions 138-742 of SEQ ID NO: 36; and / or a VP3 protein comprising the amino acid sequence of positions 203-742 of SEQ ID NO: 36.

[0018] In some embodiments, the AAV9 capsid variant comprises the amino acid sequence SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is present immediately subsequent to an amino acid position corresponding to position 455 of SEQ ID NO: 36; an E at an amino acid position corresponding to position 451, an R at an amino acid position corresponding to position 452, and a V at an amino acid position corresponding to position 453 of SEQ ID NO: 36; and no other modifications relative to wild type AAV9.

[0019] In some embodiments, the AAV capsid variant (e.g., AAV9 capsid variant) comprises [N1]-[N2]-[N3] present immediately subsequent to a position corresponding to the amino acid position 452 of SEQ ID NO: 982, wherein the AAV capsid variant comprises an amino acid sequence at least 90% identical, e.g., at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical, to the amino acid sequence of SEQ ID NO: 982, e.g., to positions 203-742 of SEQ ID NO: 982. In some embodiments, [N1] comprises GHD. In some embodiments, [N 1] comprises the amino acid G at a position corresponding to position 453, the amino acid H at position 454, and the amino acid D at position 455 of SEQ ID NO: 138 or SEQ ID NO: 982. In some embodiments, [N3] comprises KSG.

[0020] In some embodiments, the AAV capsid variant comprises a VP1 protein comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 982; a VP2 protein comprising an amino acid sequence having at least 90% identity to positions 138-742. of SEQ ID NO: 982; and / or a VP3 protein comprising an amino acid sequence liaving at least 90% identity to positrons 203-742. of SEQ ID NO: 982. In some embodiments, the AAV capsid variant comprises a VP1 protein comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 982; a VP2 protein comprising an amino acid sequence having at least 95% identity to positions 138-742 of SEQ ID NO: 982; and / or a VP3 protein comprising an amino acid sequence having at least 95% identity to positions 203-742 of SEQ ID NO: 982. In some embodiments, the AAV capsid variant comprises a VP1 protein comprising an amino acid sequence having at least 99% identity to SEQ ID NO: 982; a VP2 protein comprising an amino acid sequence having at least 99% identity to positions 138-742 of SEQ ID NO: 982; and / or a VP3 protein comprising an amino acid sequence liaving at least 99% identity to positions 203-742 of SEQ ID NO: 982. In some embodiments, the AAV capsid variant comprises a VP1 protein comprising the amino acid sequence of SEQ ID NO: 982; a VP2 protein comprising the amino acid sequence of positions 138-742 of SEQ ID NO: 982; and / or a VP3 protein comprising the amino acid sequence of positions 2.03-742 of SEQ ID NO: 982.

[0021] In some embodiments, the viral genome of the AAV particle encodes a wildtype GBA1 protein. In some embodiments, the viral genome does not encode a hemagglutinin (HA) tag. In some embodiments, the viral genome encodes a human GBA1 protein, a dog GBA1 protein, or an equine GBA1 protein. In some embodiments, the viral genome encodes a human GBA1 protein. In some embodiments, the human GBA1 protein comprises the amino acid sequence of SEQ ID NO: 1775.

[0022] In some embodiments, the GBA1-encoding sequence of the viral genome comprises a nucleotide sequence that is at least 90% identical (e.g., at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%. at least 96%, at least 97%, at least 98%, at least 99%. or 100% identical) to SEQ ID NO: 2002. In some embodiments, the GBA1-encoding sequence comprises a nucleotide sequence that is at least 95% (e.g., at least 95%. at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 2002. In some embodiments, the GBA1 -encoding sequence comprises the nucleotide sequence of SEQ ID NO: 2002.

[0023] In some embodiments, the GBA1-encoding sequence encodes a signal sequence comprising an amino acid sequence that is at least 90% identical to SEQ ID: 2005. In some embodiments, the signal sequence comprises the amino acid sequence of SEQ ID NO: 2005.

[0024] In some embodiments, the GBA1-encoding sequence comprises a nucleotide sequence that is at least 90% identical (e.g., at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%. at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 2001. In some embodiments, the GBA1-encoding sequence comprises SEQ ID NO: 2001.

[0025] In some embodiments, the viral genome further comprises a miRNA (miR) binding site that modulates expression of the encoded GBA1 protein in a cell or tissue of the DRG, liver, heart, hematopoietic lineage, or a combination thereof,

[0026] In some embodiments, the viral genome further comprises a promoter operably linked to the GBA1-encoding sequence. In some embodiments, the promoter is at least 90% identical (e.g., at least 90%. at least 91%, at least 92%, at least 93%, at least 94%. at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the nucleotide sequence of SEQ ID NO: 1834. In some embodiments, the promoter comprises the nucleotide sequence of SEQ ID NO: 1834.

[0027] In some embodiments, the viral genome further comprises an enhancer. In some embodiments, the enhancer comprises a CMV immediate-early (CMVie) enhancer. In some embodiments, the CMVie enhancer is at least 90% identical (e.g., at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the nucleotide sequence of SEQ ID NO: 1831. In some embodiments, the CMVie enhancer comprises the nucleotide sequence of SEQ ID NO: 1831.

[0028] In some embodiments, the viral genome further comprises an intron. In some embodiments, the intron is at least 90% identical (e.g., at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%. at least 96%, at least 97%, at least 98%, at least 99%. or 100% identical) to the nucleotide sequence of SEQ ID NO: 1842. In some embodiments, the intron comprises the nucleotide sequence of SEQ ID NO: 1842.

[0029] In some embodiments, the viral genome further comprises a polyadenylation (poly A) region. In some embodiments, the poly A region is at least 90% identical (e.g., at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, atleast 99%, or 100% identical) to the nucleotide sequence of SEQ ID NO: 1846. In some embodiments, the poly A region comprises the nucleotide sequence of SEQ ID NO: 1846.

[0030] In some embodiments, the viral genome further comprises an inverted terminal repeat (ITR). In some embodiments, the ITR is at least 90% identical (e.g,, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%. at least 95%, at least 96%, at least 97%, at least 98%. at least 99%, or 100% identical) to the nucleotide sequence of SEQ ID NO: 182.9 or SEQ ID NO: 1830. In some embodiments, the ITR comprises the nucleotide sequence of SEQ ID NO: 1829 or SEQ ID NO: 1830. In some embodiments, the viral genome comprises a 5' ITR and a 3' ITR, wherein the 5' ITR comprises the nucleotide sequence of SEQ ID NO: 1829 and the 3' ITR comprises the nucleotide sequence of SEQ ID NO: 1830.

[0031] In some embodiments, the viral genome further comprises one or more miR183 binding sites. In some embodiments, the viral genome comprises four miR183 binding sites. In some embodiments, each of the four miR 183 binding sites comprises at least 70% identity to the nucleotide sequence of SEQ ID NO: 1847. In some embodiments, each of the four miR 183 binding sites comprises the nucleotide sequence of SEQ ID NO: 1847.

[0032] In some embodiments, the viral genome further comprises a miR 183 binding site series that comprises a sequence at least 95% (e.g., at least 95%, at least 96%. at least 97%, at least 98%, at least 99%, or 100%) identical to the nucleotide sequence of SEQ ID NO: 1849. In some embodiments, the miR183 binding site series comprises a nucleotide sequence of SEQ ID NO: 1849.

[0033] In some embodiments, the viral genome comprises, in 5' to 3' order: (i) a 5' ITR (ii) a promoter: (iii) the GBA1-encoding sequence, wherein the GBA1 -encoding sequence comprises the nucleotide sequence of SEQ ID NO: 2002 or a nucleotide sequence at least 90% identical (e.g., at least 93% identical) to SEQ ID NO: 2002; and (iv) a 3' ITR.

[0034] In some embodiments, the viral genome comprises, in 5' to 5' order: (i) a 5' ITR (ii) a promoter; (iii) the GBA1-encoding sequence, wherein the GBA1-encoding sequence comprises the nucleotide sequence of SEQ ID NO: 2001 or a nucleotide sequence at least 90% identical (e.g., at least 94% identical) to SEQ ID NO: 2001 ; and (iv) a 3' ITR.

[0035] Tn some embodiments, the viral genome comprises: (i) a 5' ITR, (ii) a CMVie enhancer comprising the nucleotide sequence SEQ ID NO: 1831 or a nucleotide sequence at least 95% identical (e.g,, at least 95%, at least 96%, at least 97%. at least 98%, or at least 99% identical) to SEQ ID NO: 18311 (iii) a a chicken beta actin (CBA) promoter comprising the nucleotide sequence of SEQ ID NO: 1834 or a nucleotide sequence at least 95% identical (e.g., al least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1834; (iv) an intron comprising the nucleotide sequence of SEQ ID NO: 1842 or a nucleotide sequence at least 95% identical (e.g.. at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1842; (v) the GBA1- encoding sequence, wherein the GBA1-encoding sequence comprises the nucleotide sequence of SEQID NO: 2002 or a nucleotide sequence at least 90% identical (e.g., at least 93% identical) to SEQ ID NO: 2002; and (vi) a 3’ ITR.

[0036] In some embodiments, the viral genome comprises: (i) a 5' TTR; (ii) a CMVie enhancer comprising the nucleotide sequence SEQ ID NO: 1831 or a nucleotide sequence at least 95% identical (e.g,, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1831; (iii) a CBA promoter comprising the nucleotide sequence of SEQ ID NO: 1834 or a nucleotide sequence at least 95% identical (e.g., at least 95%, al least 96%, at least 97%. at least 98%, or at least 99% identical) to SEQ ID NO: 1834; (iv) an intron comprising the nucleotide sequence of SEQ ID NO: 1842 or a nucleotide sequence at least 95% identical (e.g., at least 95%. at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1842; and (v) the GBA1-encoding sequence, wherein the GBA1-encoding sequence comprises the nucleotide sequence of SEQ ID NO: 2001 or a nucleotide sequence at least 90% identical (e.g., at least 94% identical) to SEQ ID NO: 2001 and (vi) a 3' ITR.

[0037] In some embodiments, the viral genome comprises: (i) a 5' ITR; (ii) a CMVie enhancer comprising the nucleotide sequence SEQ ID NO: 1831 or a nucleotide sequence at least 95% identical to SEQ ID NO: 1831; (iii) a CBA promoter comprising the nucleotide sequence of SEQ ID NO: 1834 or a nucleotide sequence at least 95% identical (e.g.. at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1834; (iv) an intron comprising the nucleotide sequence of SEQ ID NO: 1842 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%. at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1842; (v) the GBA1- encoding sequence, wherein the GBA1-encoding sequence comprises the nucleotide sequence of SEQ ID NO: 2002 or a nucleotide sequence at least 90% identical (e.g., at least 93% identical) to SEQ ID NO: 2002; (vi) a poly adenylation (poly A) region comprising the nucleotide sequence of SEQ ID NO: 1846 or a nucleotide sequence at least 95% identical to SEQ ID NO: 1846: and (vii) a 3' ITR.

[0038] In some embodiments, the viral genome comprises, in 5' to 3 ' order: (i) a 5' ITR: (ii) a CMVie enhancer comprising the nucleotide sequence SEQ ID NO: 1831 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1831; (iii) a CBA promoter comprising the nucleotide sequence of SEQ ID NO: 1834 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1834; (iv) an intron comprising the nucleotide sequence of SEQ ID NO: 1842 or a nucleotide sequence at least 95% identical (e.g.. at least 95%, at least 96%, at least 97%. at least 98%, or at least 99% identical) to SEQ ID NO: 1842; (v) the GBA1-encoding sequence, wherein the GBA1-encoding sequence comprises the nucleotide sequence of SEQ ID NO: 2001 or a nucleotide sequence at least 90% identical (e.g.. at least 94% identical) to SEQ ID NO: 2001; (vi) a poly A region comprising the nucleotide sequence of SEQ ID NO: 1846 or a nucleotide sequence at least 95% identical to SEQ ID NO: 1846; and (vii) a 3 ' ITR.

[0039] In some embodiments, the viral genome comprises, in 5' to 3' order: (i) a 5' ITR comprising the nucleotide sequence of SEQ ID NO: 1829 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1829: (ii) a CMVie enhancer comprising the nucleotide sequence SEQ ID NO: 1831 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1831 ; (iii) a CBA promoter comprising the nucleotide sequence of SEQ ID NO: 1834 or a nucleotide sequence at least 95% identical (e.g.. at least 95%, at least 96%, at least 97%, at least 98%. or at least 99% identical) to SEQ ID NO: 1834; (iv) an intron comprising the nucleotide sequence of SEQ ID NO: 1842 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1842; (v) the GBA1-encoding sequence, wherein the GBA1-encoding sequence comprises the nucleotide sequence of SEQ ID NO: 2002 or a nucleotide sequence at least 90% identical (e.g., at least 93% identical) to SEQ ID NO: 2002; (vi) a poly A region comprising the nucleotide sequence of SEQ ID NO: 1846 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1846; and (vii) a 3' ITR comprising the nucleotide sequence of SEQ ID NO: 1830 or a nucleotide sequence at least 95% identical to SEQ ID NO: 1830.

[0040] In some embodiments, the viral genome comprises: (i) a 5' ITR comprising the nucleotide sequence of SEQ ID NO: 1829 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%. at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1829; (ii) a CMVie enhancer comprising the nucleotide sequence SEQ ID NO: 1831 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1831; (iii) a CBA promoter comprising the nucleotide sequence of SEQ ID NO: 1834 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1834; (iv) an intron comprising the nucleotide sequence of SEQ ID NO: 1842 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1842; (v) the GBA1 - encoding sequence, wherein the GBA1-encoding sequence comprises the nucleotide sequence of SEQ ID NO: 2001 or a nucleotide sequence at least 90% identical (e.g., at least 94% identical) to SEQ ID NO: 2001; (vi) a poly A region comprising the nucleotide sequence of SEQ ID NO: 1846 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1846; and (vii) a 3 ' ITR comprising the nucleotide sequence of SEQ ID NO: 1830 or a nucleotide sequence at least 95% identical (e.g., al least 95%, at least 96%, al least 97?% at least 98% , or at least 99% identical) to SEQ ID NO: 1830.

[0041] In some embodiments, the viral genome comprises the nucleotide sequence of SEQ ID NO: 2006 or a nucleotide sequence at least 90% identical (e.g., at least 97% identical) to SEQ ID NO: 2006. In some embodiments, the viral genome comprises the nucleotide sequence of SEQ ID NO:2006. In some embodiments, the viral genome consists of the nucleotide sequence of SEQ ID NO: 2006.

[0042] In some embodiments, the viral genome comprises, in 5’ to 3' order: (i) a 5' ITR; (ii) a promoter; (iii) the GBA1-encoding sequence, wherein the GBA1 -encoding sequence comprises the nucleotide sequence of SEQ ID NO: 2002 or a nucleotide sequence at least 90% identical (e.g,, at least 93% identical) to SEQ ID NO: 2002; (iv) at least one miR183 binding site; and (v) a 3' ITR.

[0043] In some embodiments, the viral genome comprises, in 5' to 3' order: (i) a 5' ITR; (ii) a promoter; (iii) (lie GBA1-encoding sequence, wherein the GBA1-encoding sequence comprises the nucleotide sequence of SEQ ID NO: 2001 or a nucleotide sequence at least 90% identical (e.g., at least 94% identical) to SEQ ID NO: 2001; (iv) at least one miR183 binding site; and (v) a 3 ' ITR.

[0044] In some embodiments, the viral genome comprises, in 5’ to 3’ order: (i) a 5' ITR; (ii) a promoter; (iii) the GBA1-encoding sequence, wherein the GBA1-encoding sequence comprises the nucleotide sequence of SEQ ID NO: 2002 or a nucleotide sequence at least 90% identical (e.g., at least 93% identical) to SEQ ID NO: 2002; (iv) at least one miR183 binding site series comprising at least one miR183 binding site and at least one spacer sequence; and (v) a 3' ITR.

[0045] In some embodiments, the viral genome comprises, in 5' to 3' order: (i) a 5' ITR; (ii) a promoter; (iii) the GBA1 -encoding sequence, wherein the GBA1-encoding sequence comprises the nucleotide sequence of SEQ ID NO: 2001 or a nucleotide sequence at least 90% identical (e.g., at least 94% identical) to SEQ ID NO: 2001; (iv) at least one miR183 binding site series comprising at least one miR183 binding site and at least one spacer sequence; and (v) a 3' ITR.

[0046] In some embodiments, the viral genome comprises, in 5' to 3' order: (i) a 5' ITR; (ii) a CMVie enhancer comprising the nucleotide sequence SEQ ID NO: 1831 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1831; (iii) a CBA promoter comprising the nucleotide sequence of SEQ ID NO: 1834 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1834; (iv) an intron comprising the nucleotide sequence of SEQ ID NO: 1842 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1842; (v) the GBA1 -encoding sequence, wherein the GBA1-encoding sequence comprises the nucleotide sequence of SEQ ID NO: 2.002 or a nucleotide sequence at least 90% identical (e.g., at least 93% identical) to SEQ ID NO: 2002; (vi) at least one miR 183 binding site; and (vii) a 3 ' ITR.

[0047] In some embodiments, the viral genome comprises, in 5' to 3' order: (i) a 3' ITR; (ii) a CMVie enhancer comprising the nucleotide sequence SEQ ID NO: 1831 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98% , or at least 99% identical) to SEQ ID NO: 1831; (iii) a CBA promoter comprising the nucleotide sequence of SEQ ID NO: 1834 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1834; (iv) an intron comprising thenucleotide sequence of SEQ ID NO: 1842 or a nucleotide sequence at least 95% identical to SEQ ID NO: 1842; (v) the GBA1-encoding sequence, wherein the GBA1-encoding sequence comprises the nucleotide sequence of SEQ ID NO: 2001 or a nucleotide sequence at least 90% identical (e.g., at least 94% identical) to SEQ ID NO: 2001 ; (vi) at least one miR 183 binding site; and (vii) a 3 ’ ITR.

[0048] In some embodiments the viral genome comprises, in 5’ to 3’ order: (i) a 5’ ITR ; (ii) a CMVie enhancer comprising the nucleotide sequence SEQ ID NO: 1831 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98 % or at least 99% identical) to SEQ ID NO: 1831; (iii) a CBA promoter comprising the nucleotide sequence of SEQ ID NO: 1834 or a nucleotide sequence at least 95% identical (e.g., at least 95%. at least 96%, at least 97?% at least 98%, or at least 99% identical) to SEQ ID NO: 1834; (iv) an intron comprising the nucleotide sequence of SEQ ID NO: 1842 or a nucleotide sequence at least 95% identical (e.g., at least 95?% at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1842: (v) the GBA1-encoding sequence, wherein the GBA1-encoding sequence comprises the nucleotide sequence of SEQ ID NO: 2002 or a nucleotide sequence at least 90% identical (e.g., at least 93% identical) to SEQ ID NO: 2002; (vi) a miR183 binding site series comprising the nucleotide sequence of SEQ ID NO: 1849 or a nucleotide sequence at least 90% identical to SEQ ID NO: 1849; and (vii) a 3’ ITR.

[0049] In some embodiments the viral genome comprises, in 5’ to 3’ order: (i) a 5’ ITR; (ii) a CMVie enhancer comprising the nucleotide sequence SEQ ID NO: 1831 or a nucleotide sequence at least 95% identical (e.g.. at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1831; (iii) a CBA promoter comprising the nucleotide sequence of SEQ ID NO: 1834 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96?% at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1834; (iv) an intron comprising the nucleotide sequence of SEQ ID NO: 1842 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97?% at least 98%, or at least 99% identical) to SEQ ID NO: 1842; (v) the GBA1-encoding sequence, wherein the GBA1-encoding sequence comprises the nucleotide sequence of SEQ ID NO: 2001 or a nucleotide sequence at least 90% identical (e.g., at least 94% identical) to SEQ ID NO: 2001; (vi) a miR 183 binding site series comprising the nucleotide sequence of SEQ ID NO: 1849 or a nucleotide sequence at least 90% identical (e.g., at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1849; and (vii) a 3’ ITR ,

[0050] In some embodiments, the viral genome comprises, in 5’ to 3’ order: (i) a 5' ITR comprising the nucleotide sequence of SEQ ID NO: 1829 or a nucleotide sequence al least 95% identical (e.g., at least 95%. at least 96%, at least 97%, al least 98%, or at least 99% identical) to SEQ ID NO: 1829; (ii) a CMVie enhancer comprising the nucleotide sequence of SEQ ID NO: 1831 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96?% at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1831: (iii) a CBA promoter comprising the nucleotidesequence of SEQ ID NO: 1834 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1834; (iv) an intron comprising the nucleotide sequence of SEQ ID NO: 1842 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%. at least 97%, at least 98%, or at least 99% identical) to SEQID NO: 1842; (v) the GBA1 -encoding sequence, wherein the GBA1-encoding sequence comprises the nucleotide sequence of SEQ ID NO: 2002 or a nucleotide sequence at least 90% identical (e.g.. at least 93% identical) to SEQ ID NO: 2002; (vi) at least one rmR183 binding site comprising the nucleotide sequence of SEQ ID NO: 1847; (vii) a poly A region comprising the nucleotide sequence of SEQ ID NO: 1846 or a nucleotide sequence at least 95% identical (e.g., at least 95%. at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1846; and (viii) a 3’ ITR comprising the nucleotide sequence of SEQ ID NO: 1830 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1830.

[0051] In some embodiments, the viral genome comprises, in 5’ to 3’ order: (i) a 5’ ITR comprising the nucleotide sequence of SEQ ID NO: 1829 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1829; (ii) a CMVie enhancer comprising the nucleotide sequence of SEQ ID NO: 1831 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1831; (iii) a CEA promoter comprising the nucleotide sequence of SEQ ID NO: 1834 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%. at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1834; (iv) an intron comprising the nucleotide sequence of SEQ ID NO: 1842 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1842; (v) the GBA1-encoding sequence, wherein the GBA1-encoding sequence comprises the nucleotide sequence of SEQ ID NO: 2001 or a nucleotide sequence at least 90% identical (e.g., at least 94% identical) to SEQ ID NO: 2001 ; (vi) at least one miR 183 binding site comprising the nucleotide sequence of SEQ ID NO: 1847; (vii) a poly A region comprising the nucleotide sequence of SEQ ID NO: 1846 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1846; and (viii) a 3’ ITR comprising the nucleotide sequence of SEQ ID NO: 1830 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%. at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1830.

[0052] In some embodiments, the viral genome comprises, in 5’ to 3’ order: (i) a 5' ITR comprising the nucleotide sequence of SEQ ID NO: 1829 or a nucleotide sequence al least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1829; (ri) a CMVie enhancer comprising the nucleotide sequence of SEQ ID NO: 1831 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%,or at least 99% identical) to SEQ ID NO: 1831 ; (iii) a CBA promoter comprising the nucleotide sequence of SEQ ID NO: 1834 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1834; (iv) an intron comprising the nucleotide sequence of SEQ ID NO: 1842 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%. at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1842; (v) the GBA1 -encoding sequence, wherein the GBA1-encoding sequence comprises the nucleotide sequence of SEQ ID NO: 2002 or a nucleotide sequence at least 90% identical (e.g., at least 93% identical) to SEQ ID NO: 2002; (vi) a miR183 binding site senes comprising the nucleotide sequence of SEQ ID NO: 1849 or a nucleotide sequence at least 90% identical (e.g.. at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%„ at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1849; (vii) a poly A region comprising the nucleotide sequence of SEQ ID NO: 1846 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1846; and (viii) a 3’ ITR comprising the nucleotide sequence of SEQ ID NO: 1830 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1830.

[0053] In some embodiments, the viral genome comprises, in 5’ to 3’ order: (i) a 5’ ITR comprising the nucleotide sequence of SEQ ID NO: 1829 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%. or at least 99% identical) to SEQ ID NO: 1829; (ri) a CMVie enhancer comprising the nucleotide sequence of SEQ ID NO: 1831 or a nucleotide sequence at least 95% identical (e.g., at least 95%. at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1831; (iii) a CBA promoter comprising the nucleotide sequence of SEQ ID NO: 1834 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1834; (rv) an intron comprising the nucleotide sequence of SEQ ID NO: 1842 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1842; (v) the GBA1 -encoding sequence, wherein the GBA1-encoding sequence comprises the nucleotide sequence of SEQ ID NO: 2001 or a nucleotide sequence at least 90% identical (e.g., at least 94% identical) to SEQ ID NO: 2.001 ; (vi) a miRl 83 binding site series comprising the nucleotide sequence of SEQ ID NO: 1849 or a nucleotide sequence at least 90% identical (e.g., at least 90%. at least 91%, at least 92%, at least 93%. at least 94%, at least 95%, at least 96%, at least 97%. at least 98?A, or at least 99% identical) to SEQ ID NO: 1849; (vii) a poly A region comprising the nucleotide sequence of SEQ ID NO: 1846 or a nucleotide sequence at least 95% identical (e.g.. at least 95%, at least 96%, at least 97%, at least 98%. or at least 99% identical) to SEQ ID NO: 1846; and (viii) a 3’ ITR comprising the nucleotide sequence of SEQ ID NO: 1830 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1830.

[0054] In some embodiments, (i) the 5’ ITR comprises the nucleotide sequence of SEQ ID NO: 1829; (ii) the CMVie enhancer comprises the nucleotide sequence of SEQ ID NO: 1831; (iii) the CB A promoter comprises the nucleotide sequence of SEQ ID NO: 1834; (iv) the intron comprises the nucleotide sequence of SEQ ID NO: 1842; (v) the GBA1-encoding sequence comprises the nucleotide sequence of SEQ ID NO: 2.001 ; (vi) the miR183 binding site series comprises the nucleotide sequence of SEQ ID NO: 1849; (vii) the poly A region comprises the nucleotide sequence of SEQ ID NO: 1846; and (viii) the 3’ ITR comprises the nucleotide sequence of SEQ ID NO: 1830.

[0055] In some embodiments, the viral genome comprises the nucleotide sequence of SEQ ID NO: 2007 or a nucleotide sequence at least 90% identical (e.g., at least 97% identical) to SEQ ID NO: 2007. In some embodiments, the viral genome comprises the nucleotide sequence of SEQ ID NO: 2007. In some embodiments, the viral genome consists of the nucleotide sequence of SEQ ID NO: 2007.

[0056] In some embodiments, the present disclosure provides an AAV particle comprising a viral genome comprising the nucleotide sequence of SEQ ID NO: 2001 and an AAV capsid variant comprising a VP1 protein comprising the amino acid sequence of SEQ ID NO: 4; a VP2 protein comprising the amino acid sequence of positions 138-742 of SEQ ID NO: 4; and / or a VP3 protein comprising the amino acid sequence of positions 203-742 of SEQ ID NO: 4.

[0857] In some embodiments, the present disclosure provides an partiAclAe V comprising a viral genome comprising the nucleotide sequence of SEQ ID NO: 2.001 and an AAV capsid variant comprising a VP1 protein comprising the amino acid sequence of SEQ ID NO: 36; a VP2 protein comprising the amino acid sequence of positions 138-742 of SEQ ID NO: 36; and / or a VP3 protein comprising the amino acid sequence of positions 203-742 of SEQ ID NO: 36.

[0058] In some embodiments, the present disclosure provides an AAV particle comprising a viral genome comprising the nucleotide sequence of SEQ ID NO: 2002 and an AAV capsid variant comprising a VP1 protein comprising the amino acid sequence of SEQ ID NO: 4; a VP2 protein comprising the amino acid sequence of positions 138-742 of SEQ ID NO: 4; and / or a VP3 protein comprising the amino acid sequence of positions 203-742 of SEQ ID NO: 4.

[0059] In some embodiments, the present disclosure provides an AAV particle comprising a viral genome comprising the nucleotide sequence of SEQ ID NO: 2002 and an AAV capsid variant comprising a VP1 protein comprising the amino acid sequence of SEQ ID NO: 36; a VP2 protein comprising the amino acid sequence of positions 138-742 of SEQ ID NO: 36; and / or a VP3 protein comprising the amino acid sequence of positions 2.03-742 of SEQ ID NO: 36.

[0060] In some embodiments, the present disclosure provides a ceil comprising an AAV particle described herein. In some embodiments, the cell is a mammalian cell (e.g., an IIEK293 cell), an insect cell (e.g., an SIP cell), or a bacterial cell.

[0861] In some embodiments, the present disclosure provides a method of making an AAV particle described herein, the method comprising: providing a cell comprising the viral genomecomprising a GBA1 -encoding sequence and a nucleic acid encoding the AAV capsid variant; and incubating the cell under conditions suitable to encapsulate the viral genome in the AAV capsid variant; thereby making the AAV particle.

[0062] In some embodiments, the present disclosure provides a method of making an AAV particle, wherein the viral genome of the AAV particle comprises (a) the nucleotide sequence of SEQ ID NO: 2006 or a nucleotide sequence at least 90% identical (e.g., at least 90%, at least 91%. at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) thereto; or (b) the nucleotide sequence of SEQ ID NO: 2007 or a nucleotide sequence at least 90% identical (e.g., at least 90%, at least 91%. at least 92%, at least 93% , at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) thereto; and the AAV capsid variant of the AAV particle comprises: (i) a VP1 protein comprising the amino acid sequence of SEQ ID NO: 4 or an amino acid sequence having at least 90% identity (e.g., at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity) to SEQ ID NO: 4; (ii) a VP2 protein comprising the amino acid sequence of positions 138-742 of SEQ ID NO: 4 or an amino acid sequence having at least 90% identity (e.g., at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%. or at least 99% identity) to positions 138-742 SEQ ID NO: 4; or (iii) a VP3 protein comprising the amino acid sequence of positions 203-742 of SEQ ID NO: 4 or an amino acid sequence having at least 90% identity (e.g., at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%. or at least 99% identity) to positions 203-742 of SEQ ID NO: 4.

[0063] In some embodiments, the present disclosure provides a method of making an AAV particle, wherein the viral genome of the AAV particle comprises (a) the nucleotide sequence of SEQ ID NO: 2006 or a nucleotide sequence at least 90% identical (e.g., at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) thereto; or (b) the nucleotide sequence of SEQ ID NO: 2007 or a nucleotide sequence at least 90% identical (e.g., at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) thereto; and the AAV capsid variant of the AAV particle comprises the amino acid sequence of SEQ ID NO: 4, the amino acid sequence of positions 138-742 of SEQ ID NO: 4, and / or the amino acid sequence of positions 203- 742 of SEQ ID NO: 4.

[0064] In some embodiments, the present disclosure provides a method of making an AAV particle, wherein the viral genome of the AAV particle comprises: (a) the nucleotide sequence of SEQ ID NO: 2006 or a nucleotide sequence at least 90% identical (e.g., at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) thereto; or (b) the nucleotide sequence of SEQ ID NO: 2007 or a nucleotide sequence at least 90% identical (e.g., at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) thereto; and the AAV capsid variant of the AAV particle comprises: (i) a VP1 protein comprising the amino acid sequence of SEQ ID NO: 36 or an amino acid sequence having at least 90% identity (e.g., at least 90%, at least 91%, at least 92%, at least 93%, at least 94%. at least 95%, at least 96%, at least 97%, at least 98%. or at least 99% identity) to SEQ ID NO: 36; (ii) a VP2 protein comprising the amino acid sequence of positions 138-742 of SEQ ID NO: 36 or an amino acid sequence having at least 90% identity (e.g., at least 90%, al least 91?% at least 92%, at least 93%, at least 94%, al least 95%, at least 96%, at least 97%, at least 98?% or at least 99% identity) to positions 138-742 SEQ ID NO: 36; and / or (iii) a VP3 protein comprising the amino acid sequence of positions 203-742 of SEQ ID NO: 36 or an amino acid sequence having at least 90% identity (e.g., at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity ) to positions 203-742 of SEQ ID NO: 36.[0651 In some embodiments, the present disclosure provides a method of making an AAV particle, wherein the viral genome of the AAV particle comprises: (a) the nucleotide sequence of SEQ ID NO: 2006 or a nucleotide sequence at least 90% identical (e.g. , at least 90%, at least 91 %, at least 92?% at least 93%, at least 94%, at least 95%, at least 96",,. at least 97%, at least 98%, or at least 99% identical) thereto; or (b) the nucleotide sequence of SEQ ID NO: 2.007 or a nucleotide sequence at least 90% identical (e.g., at least 90%, at least 91%, at least 92?% at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) thereto; and the AAV capsid variant of the AAV particle comprises the amino acid sequence of SEQ ID NO: 36. the amino acid sequence of positions 138-742 of SEQ ID NO: 36, and / or the amino acid sequence of positions 203- 742 of SEQ ID NO: 36.

[0066] In some embodiments, the present disclosure provides a method of making an AAV particle, wherein the viral genome of the AAV particle comprises: (a) the nucleotide sequence of SEQ ID NO: 2006 or a nucleotide sequence at least 90% identical (e.g., at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) thereto; or (b) the nucleotide sequence of SEQ ID NO: 2007 or a nucleotide sequence at least 90%, identical (e.g., at least 90%, at least 91%, at least 92% at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) thereto; and the AAV capsid variant of the AAV particle comprises: (i) a VP1 protein comprising the amino acid sequence of SEQ ID NO: 982. or an amino acid sequence having at least 90% identity (e.g., at least 90%, at least 91%, al least 92?% at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity) to SEQ ID NO: 982; (ii) a VP2 protein comprising the amino acid sequence of positions 138-742 of SEQ ID NO: 982 or an amino acid sequence having at least 90% identity (e.g., at least 90?% at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97?% at least 98%, or at least 99% identity) to positions 138-742 SEQ ID NO: 982; and / or (iii) a VP3 protein comprising the amino acid sequence of positions 203-742 of SEQ ID NO: 982 or an aminoacid sequence having at least 90% identity (e.g., at least 90% at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity) to positions 203-742 of SEQ ID NO: 982,

[0067] In some embodiments, the present disclosure provides a method of making an AAV particle, wherein the viral genome of the AAV particle comprises: (a) the nucleotide sequence of SEQ ID NO: 2006 or a nucleotide sequence at least 90% identical (e.g., at least 90%, at least 91%. at least 92%, at least 93%, at least 94%, at least 95%, al least 96%, at least 97%, at least 98%, or at least 99% identical) thereto; or (b) the nucleotide sequence of SEQ ID NO: 2007 or a nucleotide sequence at least 90% identical (e.g., at least 90%, at least 91%. at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) thereto; and the AAV capsid variant of the AAV particle comprises the amino acid sequence of SEQ ID NO: 982, the amino acid sequence of positions 138-742 of SEQ ID NO: 982, and / or the amino acid sequence of positions 203- 742 of SEQ ID NO: 982.

[0068] In some embodiments, the method of making an AAV particle further comprises, prior to step (i), introducing a first nucleic acid molecule comprising the viral genome into the cell. In some embodiments, the ceil comprises a second nucleic acid molecule encoding the AAV capsid variant. In some embodiments, the method of making an AAV particle further comprises, prior to step (i), introducing the second nucleic acid into the cell. In some embodiments, the cell comprises a mammalian cell (e.g., an I-IEK293 cell), an insect cell (e.g., an Sf9 cell), or a bacterial cell.

[0069] In some embodiments, the present disclosure provides a pharmaceutical composition comprising an AAV particle described herein and a pharmaceutically acceptable excipient.

[0070] In some embodiments, the present disclosure provides a method of delivering an AAV particle encoding a GBA1 protein to a subject, comprising administering to the subject an effective amount of a pharmaceutical composition or AAV particle described herein. In some embodiments, the subject has, has been diagnosed with having, or is at risk of having a GBA1-related disorder. In some embodiments, the GBA1-related disorder is a GBA1-related neurodegenerative or neuromuscular disorder. In some embodiments, the GBA1 -related disorder is Parkinson’s Disease (PD), Parkinson’s Disease Dementia (PDD), Gaucher Disease (GD) (e.g., GD type 1, 2, or 3), Dementia with Lewy Bodies (DLB), Lewy Body Dementia (LBD), Multiple System Atrophy (MSA), Alzheimer’s Disease (AD), Amyotrophic Lateral Sclerosis (ALS), Pure Autonomic Failure, Neurodegeneration with brain iron accumulation, type 1 (NBIA 1 ), or Hallervorden-Spatz Syndrome. In some embodiments, the subject lias, has been diagnosed with having, or is at risk of having PD.

[0071] In some embodiments, the present disclosure provides a method of treating a subject having or diagnosed with having a GBA1-related disorder, comprising administering to the subject an effective amount of a pharmaceutical composition or AAV particle described herein. In some embodiments, the GBA1-related disorder is a GBA1-related neurodegenerative or neuromuscular disorder. In some embodiments, the GBA1-related disorder is PD, PDD, GD (e.g., GD type 1, 2, or 3),DLB, LBD, MSA, AD, ALS, Pure Autonomic Failure, NBIA 1, or Hallervorden-Spatz Syndrome. In some embodiments, the GBA1-related neurodegenerative or neuromuscular disorder is PD. In some embodiments, the GBA1 -related neurodegenerative or neuromuscular disorder is GD (e.g., GD type 1, 2, or 3). In some embodiments, the GBA1 -related neurodegenerative or neuromuscular disorder is GD type 1 , In some embodiments, the GBA1-related neurodegenerative or neuromuscular disorder is GD type 2, In some embodiments, the GBA1-related neurodegenerative or neuromuscular disorder is GD type 3. In some embodiments, the GBA1-related neurodegenerative or neuromuscular disorder is DLB. In some embodiments, the GBA1-related neurodegenerative or neuromuscular disorder is LBD.

[0072] In some embodiments, the present disclosure provides a method of treating a subject having PD or diagnosed with having PD, comprising administering to the subject an effective amount of a pharmaceutical composition or AAV particle described herein.

[0073] In some embodiments, the present disclosure provides a method of treating a subject having GD (e.g., GD type I, 2, or 3) or diagnosed with having GD (e.g., GD type 1, 2, or 3), comprising administering to the subject an effective amount of a pharmaceutical composition or AAV particle described herein. In some embodiments, the GD is GD type I. In some embodiments, the GD is GD type 2. In some embodiments, the GD is GD type 3.

[0074] In some embodiments, the present disclosure provides a method of treating a subject having LBD, comprising administering to the subject an effective amount of a pharmaceutical composition or AAV particle described herein. In some embodiments, the present disclosure provides a method of treating a subject having DLB, comprising administering to the subject an effective amount of a pharmaceutical composition or AAV particle described herein.

[0075] In some embodiments, the present disclosure provides a method of heating a subject, wherein the subject has one or more mutations in the GBA1 gene. In some embodiments, the subject has lower GCase activity as compared to GCase activity in an individual who does not have a GBA1- related disorder. In some embodiments, the level of GCase activity is measured by a 4-MIJG assay or a SensoLyte Blue Glucocerebrosidase assay.

[0076] In some embodiments, treating results in prevention of progression of the disorder in the subject. In some embodiments, treating results in amelioration of the disorder. In some embodiments, treating results in a change in one or more biomarkers of the disorder. In some embodiments, the one or more biomarkers comprises a GCase activity, a level of glucocerebroside and other glycolipids, (e.g., within immune cells such as macrophages), a level of synuclein aggregates (e.g.. Lewy bothes), a level of neurofilament light chain, or a combination thereof. In some embodiments, treating results in amelioration of at least one symptom of the disorder. In some embodiments, the at least one symptom comprises developmental delay, progressive encephalopathy, progressive dementia, ataxia, myoclonus, oculomotor dysfunction, bulbar palsy, generalized weakness, trembling of a limb, depression, visual hallucinations, cognitive decline, or a combination thereof.

[0077] In some embodiments, the subject is a human.

[0078] In some embodiments, the AAV particle is delivered to a cell, tissue, or region of the CNS, e.g., a region of the brain or spinal cord, e.g., the parenchyma, the cortex, substantia nigra, caudate cerebellum, striatum, corpus callosum, cerebellum, brain stem caudate-putamen, thalamus, superior colliculus, the spinal cord, or a combination thereof, wherein the AAV particle or a plrarmaceutical composition comprising the AAV particle is delivered via intravenous administration,

[0079] In some embodiments, the present disclosure provides a method of treating a subject, further comprising evaluating, e.g., measuring, the level of GBA1 expression, e.g., GBA1 gene expression, GBA1 mRNA expression, and / or GBA1 protein expression, in the subject, e.g., in a cell, tissue, or fluid of the subject. In some embodiments, the level of GBA1 protein expression is measured by an ELISA, a Western blot, or an immunohistochemistry assay. In some embodiments, evaluating the level of GBA1 expression is performed prior to and subsequent to administration of the AAV. In some embodiments, the level of GBA1 expression prior to administration is compared to the level of GBA1 expression subsequent to administration.

[0080] In some embodiments, the method of delivering or treating comprises evaluating the level of GBA1 expression in a cell or tissue of the central nervous system (e.g., parenchyma). In some embodiments, the subject’s level of GBA1 protein expression subsequent to administration is increased relative to the subject’s level of GBA1 protein expression prior to administration.

[0881] In some embodiments, the method further comprises evaluating, e.g., measuring, the level of GCase activity in the subject.

[0082] In some embodiments, administration of an AAV particle or pharmaceutical composition described herein results in an increase in: (i) GCase activity in a cell, tissue, (e.g., a cell or tissue of the CNS, e.g., the cortex, striatum, thalamus, cerebellum, and / or brainstem), and / or fluid (e.g., CSF andtor serum) of the subject, optionally wherein GCase activity in the subject subsequent to the administration is increased by at least 2-fold, at least 3-fold, at least 4-fold, or at least 5-fold relative to GCase activity in the subject prior to the administration; (ii) viral genomes (VG) per cell level in a CNS tissue (e.g., the cortex, striatum, thalamus, cerebellum, brainstem, and / or spinal cord) of the subject, optionally wherein the subject’s VG per cell level in the CNS tissue is increased by greater than 50 VG per cell relative to the subject’s VG per cell level in a peripheral tissue; and / or (iii) GBA1 mRNA expression in a cell or tissue (e.g,, a cell or tissue of the CNS, e.g.. the cortex, thalamus, and / or brainstem) of the subject, optionally wherein GBA1 mRNA expression in the subject subsequent to the administration is increased by at least 100-1300-fold as compared to GBA1 mRNA expression in the subject prior to the administration.

[0083] In some embodiments, the present disclosure provides a method of treating a subject, further comprising administering to the subject an additional agent suitable for treatment or prevention of the GBA1 -related disorder. In some embodiments, the additional agent comprises enzyme replacement therapy (ERT) (e.g., imiglucerase, velaglucerase alfa, or taliglucerase alfa);substrate reduction therapy (SRT) (e.g., eliglustat or miglustat), levodopa, carbidopa. Safinamide, a dopamine agonist (e.g., quetiapine, clozapine, pramipexole, rotigotine, or ropinirole), an anticholinergic (e.g., benztropine or trihexyphenidyl), a cholinesterase inhibitor (e.g., rivastigmine, donepezil, or galantamine), an N-methyl-d-aspartate (NMDA) receptor antagonist (e.g., memantine), or a combination thereof. In some embodiments, the method further comprises administering a blood transfusion to the subject. In some embodiments, the method further comprises administering an immunosuppressant to the subject. In some embodiments, the immunosuppressant comprises a corticosteroid (e.g., prednisone, prednisolone, methylprednisolone, and / or dexamethasone), rapamycin, mycophenolate mofetil, tacrolimus, rituximab, and / or eculizumab hydroxychloroquine.

[0084] In some embodiments, the present disclosure provides a pharmaceutical composition or AAV particle described herein for use in the treatment of a GBA1-related disorder. In some embodiments, the GBA1-related disorder is PD, PDD, GD (e.g., GD type 1, 2, or 3), DLB, LBD, MSA, AD, ALS, Pure Autonomic Failure, NBIA 1, or Hallervorden-Spatz Syndrome. In some embodiments, the GBA1-related disorder is PD. In some embodiments, the GBA1-related disorder is GD (e.g., GD type 1 , 2, or 3). In some embodiments, the GD is GD type 1. In some embodiments, the GD is GD type 2. In some embodiments, the GD is GD type 3. In some embodiments, the GBA1- related disorder is DLB. In some embodiments, the GBA1 -related disorder is LBD.

[0885] In some embodiments, the present disclosure provides a use of a pliarmaceutical composition or AAV particle described herein in the manufacture of a medicament for the treatment of a GBA1-related disorder. In some embodiments, the GBA1-related disorder is PD, PDD, GD (e.g., GD type 1, 2, or 3), DLB, LBD, MSA, AD, ALS, Pure Autonomic Failure, NBIA 1, or Hallervorden- Spatz Syndrome. In some embodiments, the GBA1-related disorder is PD. In some embodiments, the GBA1-related disorder is GD (e.g., GD type 1, 2, or 3). In some embodiments, the GD is GD type 1. In some embodiments, the GD is GD type 2. In some embodiments, the GD is GD type 3. In some embodiments, the GBA1-related disorder is DLB. In some embodiments, the GBA1-related disorder is LBD.Enumerated Embodiments1. An adeno-associated virus (AAV) particle comprising an AAV capsid variant (e.g., an AAV9 capsid variant) and a viral genome comprising a p-glucocerebrosidase 1 (GBA1)-encoding sequence (e.g., encoding a human GBA1 protein), wherein the AAV capsid variant comprises an amino acid sequence having the following formula: [N1]-[N2]-[N3], wherein:(i) optionally [N1] comprises X1, X2, and X3, wherein at least one of X1, X2, or X3 is G;(ii) [N2] comprises the amino acid sequence of SPH; and(iii) [N3] comprises X4, X5, and X6, wherein at least one of X4, X5, or X6 is a basic amino acid, e.g., aK or R.2. The AAV particle of embodiment 1, wherein X4, X5, or both of [N3 ] is a K.3. The AAV particle of embodiment 1 or 2, wherein X4, X5, or X6 of [N3] is an R.4. The AAV particle of any one of embodiments 1-3, wherein:(a) X4 of [N3] is: K, S, A, V, T. G, F, W, V, N, or R;(b) X5 of [N3] is: S, K, T, F, I, L, Y, H, M, or R; and / or(c) X6 of [N3] is: G, A, R, M, I, N, T, Y, D, P, V, L, E, W, N, Q, K, or S; optionally wherein the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of the aforesaid amino acids in (a)-(c).5. The AAV particle of any one of embodiments 1-4, wherein [N3] comprises SK, KA, KS, AR, RM, VK, AS, SR, VK, KR, KK, KN, VR, RS, RK, KT, TS, KF, FG, KI, IG, KL, LG, TT, TY, KY, YG, KD, KP, TR, RG, VR, GA, SL, SS, FL, WK, SA, RA, LR, KW, RR, GK, TK, NK, AK, KV, KG, KH, KM, TG, SE, SV, SW, SN, HG, SQ, LW, MG, MA, or SG,6. The AAV particle of any one of embodiments 1-5, wherein [N3] is or comprises SKA, KSG, ARM, VKS ASR, VKI KKN, VRM, RKA, KTS, KFG, KIG, KLG, KTT, KTY, KYG, SKD, SKP, TRG, VRG, KRG, GAR, KSA, KSR, SKI.,, SRA, SKR, SLR, SRG. SSR, FLR, SKW, SKS, WKA, VRR, SKV, SKT, SKG, GKA, TKA. NKA. SKL, SKN, AKA, KTG, KSL, KSE, KSV, KSW, KSN, KHG, KSQ. KSK, KLW, WKG, KMG, KMA, or RSG.7. The AAV particle of any one of embodiments 1-6, wherein [N2]-[N3] comprises SPHSK (SEQ ID NO: 4701), SPHKS (SEQ ID NO: 4704), SPHAR (SEQ ID NO: 4705), SPHVK (SEQ ID NO: 4706), SPHAS (SEQ ID NO: 4707), SPHKK (SEQ ID NO: 4708), SPH VR (SEQ ID NO: 4709), SPHRK (SEQ ID NO: 4710), SPHKT (SEQ ID NO: 4711), SPHKF (SEQ ID NO: 4712), SPHKI (SEQ ID NO: 4713), SPHKL (SEQ ID NO: 4714), SPHKY (SEQ ID NO: 4715), SPHTR (SEQ ID NO: 4716), SPHKR (SEQ ID NO: 4717), SPHGA (SEQ ID NO: 4718), SPHSR (SEQ ID NO: 4719), SPHSL (SEQ ID NO: 4720), SPHSS (SEQ ID NO: 4721), SPHFL (SEQ ID NO: 4722), SPHWK (SEQ ID NO: 472.3), SPHGK (SEQ ID NO: 4724), SPHTK (SEQ ID NO: 4725), SPUNK (SEQ ID NO: 4726), SPHAK (SEQ ID NO: 4727), SPHKH (SEQ ID NO: 4728), SPHKM (SEQ ID NO: 472.9), or SPURS (SEQ ID NO: 4730).8. The AAV particle of any one of embodiments 1-7. wherein [N2]-[N3] is or comprises:(i) SPHSKA (SEQ ID NO: 941), SPHKSG (SEQ ID NO: 946), SPHARM (SEQ ID NO: 947), SPHVKS (SEQ ID NO: 948), SPHASR (SEQ ID NO: 949), SPHVKI (SEQ ID NO: 950), SPHKKN (SEQ ID NO: 954), SPHVRM (SEQ ID NO: 955), SPHRKA (SEQ ID NO: 956), SPHKFG (SEQ IDNO: 957), SPHKIG (SEQ ID NO: 958), SPHKLG (SEQ ID NO: 959), SPHKTS (SEQ ID NO: 963), SPHKTT (SEQ ID NO: 964), SPHKTY (SEQ ID NO: 965), SPHKYG (SEQ ID NO: 966), SPHSKD (SEQ ID NO: 967), SPHSKP (SEQ ID NO: 968), SPHTRG (SEQ ID NO: 972), SPHVRG (SEQ ID NO: 973), SPHKRG (SEQ ID NO: 974), SPHGAR (SEQ ID NO: 975), SPHKSA (SEQ ID NO: 977), SPHKSR (SEQ ID NO: 951), SPHSKL (SEQ ID NO: 960), SPHSRA (SEQ ID NO: 969), SPHSKR (SEQ ID NO: 978), SPHSLR (SEQ ID NO: 952), SPHSRG (SEQ ID NO: 961). SPHSSR (SEQ ID NO: 970). SPHFLR (SEQ ID NO: 979), SPHSKW (SEQ ID NO: 953), SPHSKS (SEQ ID NO: 962), SPHWKA (SEQ ID NO: 971), SPHVRR (SEQ ID NO: 980), SPHSKT (SEQ ID NO: 4731). SPHSKG (SEQ ID NO: 4732), SPIIGKA (SEQ ID NO: 4733). SPIENKA (SEQ ID NO: 4734), SPHSKN (SEQ ID NO: 4735), SPHAKA (SEQ ID NO: 4736), SPHSKV (SEQ ID NO: 4737), SPHKTG (SEQ ID NO: 4738), SPHTKA (SEQ ID NO: 4739), SPHKSL (SEQ ID NO: 4740), SPHKSE (SEQ ID NO: 4741), SPHKSV (SEQ ID NO: 4742), SPHKSW (SEQ ID NO: 4743), SPHKSN (SEQ ID NO: 4744), SPHKHG (SEQ ID NO: 4745), SPHKSQ (SEQ ID NO: 4746), SPHKSK (SEQ ID NO: 4747), SPHKLW (SEQ ID NO: 4748), SPHWKG (SEQ ID NO: 4749), SPHKMG (SEQ ID NO: 4750). SPHKMA (SEQ ID NO: 4751), or SPHRSG (SEQ ID NO: 976);(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i). e.g., any 2. 3, 4, or 5 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no more than four modifications relative to any of the amino acid sequences in (i); or(iv) an amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).9. The AAV particle of any one of embodiments 1-8, wherein the AAV capsid variant comprises an amino acid other than G at position 453 (e.g., V, R, D, E, M, T, I, S, A, N, L, K, H, P, W, or C), an amino acid other than S at position 454 (e.g., V, L, N, D, H, R, P, G, T, I, A, E, Y, M, or Q), and / or an amino acid other than G at position 455 (e.g., C, L, D, E. Y, H, V, A, N. P, or S), numbered according to any one of SEQ ID NOs: 36-59, 138, 981, or 982.10. The AAV particle of any one of embodiments 1-8, wherein the AAV capsid variant comprises the amino acid G at position 453, the amino acid S at position 454, and the amino acid G at position 455, numbered according to SEQ ID NO: 138 or 981.11. The AAV particle of any one of embodiments 1-9, wherein the AAV capsid variant comprises the amino acid G at position 453, the amino acid H at position 454, and the amino acid D at position 455, numbered according to SEQ ID NO: 138 or 982.12. The AAV particle of any one of embodiments 1-11, wherein [N1 ] comprises X1, X2, and X3, wherein at least one of X1 , X2, or X3 is G.13. The AAV particle of any one of embodiments 1-12, wherein:(a) X1 of [N1] is: G, V, R, D, E, M, T, I. S, A. N, L, K, H. P, W, or C;(b) X2 of [N1 ] is: S, V, L, N, D, H, R, P, G, T, I, A, E, Y, M, or Q; and / or(c) X3 of [N1] is: G, C. L, D, E, Y, H, V, A, N, P, or S: optionally wherein the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of the aforesaid amino acids in (a)-(c).14. The AAV particle of any one of embodiments 1-13, wherein [N1] comprises GS, SG, GH, HD, GQ, QD, VS, CS, GR, RG, QS, SH, MS, RN, TS, IS, GP, ES, SS, GN, AS, NS, LS, GG, KS, GT, PS, RS, GI, WS, DS, ID, GL, DA, DG, ME, EN, KN, KE, Al, NG, PG, TG, SV, IG, LG, AG, EG, SA, YD, HE, HG, RD, ND, PD, MG, QV, DD, HN, HP, GY, GM, GD, or HS.15. The AAV particle of any one of embodiments 1-14, wherein [N1] is or comprises GSG, GHD, GQD, VSG, CSG, GRG, CSH, GQS, GSH, RVG, GSC, GLL, GDD, GHE, GNY, MSG, RNG, TSG. ISG, GPG, ESG, SSG, GNG, ASG, NSG, LSG, GGG, KSG, HSG, GTG, PSG, GSV, RSG. GIG, WSG, DSG, IDG. GLG, DAG, DGG, MEG, ENG. GSA, KNG, KEG, AIG, GYD, GHG, GRD. GND. GPD. GMG, GQV, GHN, GHP. or GHS.16. The AAV particle of any one of embodiments 1-15, wherein [N1]-[N2] comprises:(i) SGSPH (SEQ ID NO: 4752), HDSPH (SEQ ID NO: 4703), QDSPH (SEQ ID NO: 4753), RGSPH (SEQ ID NO: 4754), SHSPH (SEQ ID NO: 4755), QSSPH (SEQ ID NO: 4756), DDSPH (SEQ ID NO: 4757), HESPH (SEQ ID NO: 4758), NYSPH (SEQ ID NO: 4759), VGSPH (SEQ ID NO: 4760), SCSPH (SEQ ID NO: 4761), LLSPH (SEQ ID NO: 4762), NGSPH (SEQ ID NO: 4763), PGSPH (SEQ ID NO: 4764), GGSPH (SEQ ID NO: 4765), TGSPH (SEQ ID NO: 4766), SVSPH (SEQ ID NO: 4767), IGSPH (SEQ ID NO: 4768), DGSPH (SEQ ID NO: 4769), LGSPH (SEQ ID NO: 4770), AGSPH (SEQ ID NO: 4771), EGSPH (SEQ ID NO: 4772), SASPH (SEQ ID NO: 4773), YDSPH (SEQ ID NO: 4774), HGSPH (SEQ ID NO: 4775), RDSPH (SEQ ID NO: 4776), NDSPH (SEQ ID NO: 4777), PDSPH (SEQ ID NO: 4778), MGSPH (SEQ ID NO: 4779), QVSPH (SEQ ID NO: 4780), HNSPH (SEQ ID NO: 4781), HPSPII (SEQ ID NO: 4782), or HSSPH (SEQ ID NO: 4783);(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i), e.g., any 2, 3, or 4 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no more than four modifications relative to any of the amino acid sequences in (i); or(iv) an amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).17. The A.AV particle of any one of embodiments 1-16, wherein [N1]-[N2] is or comprises:(i) GSGSPH (SEQ ID NO: 4695). GHDSPH (SEQ ID NO: 4784), GQDSPH (SEQ ID NO: 4785), VSGSPH (SEQ ID NO: 4786), CSGSPH (SEQ ID NO: 4787), GRGSPH (SEQ ID NO: 4788), CSHSPH (SEQ ID NO: 4789), GQSSPH (SEQ ID NO: 4790), GSHSPH (SEQ ID NO: 4791), GDDSPH (SEQ ID NO: 4792), GHESPH (SEQ ID NO: 4793), GNYSPH (SEQ ID NO: 4794), RVGSPH (SEQ ID NO: 4795), GSCSPH (SEQ ID NO: 4796), GLLSPH (SEQ ID NO: 4797), MSGSPH (SEQ ID NO: 4798), RNGSPH (SEQ ID NO: 4799), TSGSPH (SEQ ID NO: 4800), 1SGSPH (SEQ ID NO: 4801), GPGSPH (SEQ ID NO: 4802), ESGSPH (SEQ ID NO: 4803), SSGSPH (SEQ ID NO: 4804), GNGSPH (SEQ ID NO: 4805), ASGSPH (SEQ ID NO: 4806), NSGSPH (SEQ ID NO: 4807), LSGSPH (SEQ ID NO: 4808), GGGSPH (SEQ ID NO: 4809), KSGSPH (SEQ ID NO: 4810), HSGSPH (SEQ ID NO: 4811), GTGSPH (SEQ ID NO: 4812), PSGSPH (SEQ ID NO: 4813), GSVSPH (SEQ ID NO: 4814), RSGSPH (SEQ ID NO: 4815), GIGSPH (SEQ ID NO: 4816). WSGSPH (SEQ ID NO: 4817), DSGSPH (SEQ ID NO: 4818), IDGSPH (SEQ ID NO: 4819). GLGSPH (SEQ ID NO: 4820), DAGSPH (SEQ ID NO: 4821), DGGSPH (SEQ ID NO: 4822). MEGSPH (SEQ ID NO: 482.3 ), ENGSPH (SEQ ID NO: 4824), GSASPH (SEQ ID NO: 4825), KNGSPH (SEQ ID NO: 4826), KEGSPH (SEQ ID NO: 4827), AIGSPH (SEQ ID NO: 4828). GYDSPH (SEQ ID NO: 4829), GHGSPH (SEQ ID NO: 4830), GRDSPH (SEQ ID NO: 4831). GNDSI-TI (SEQ ID NO: 4832), GPDSPH (SEQ ID NO: 4833), GMGSPH (SEQ ID NO: 4834), GQVSPH (SEQ ID NO: 4835), GHNSPH (SEQ ID NO: 4836), GHPSPH (SEQ ID NO: 4837), or GHSSPH (SEQ ID NO: 4838);(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i), e.g., any 2, 3, 4, or 5 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no more than four modifications relative to any of the amino acid sequences in (i); or(iv) an amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).18. The AAV particle of any one of embodiments 1-17, wherein [N1]-[N2]-[N3] comprises:(i) SGSPHSK (SEQ ID NO: 4839). HDSPHKS (SEQ ID NO: 4840), SGSPHAR (SEQ ID NO: 4841), SGSI-TIVK (SEQ ID NO: 4842), QDSPHKS (SEQ ID NO: 4843), SGSPHKK (SEQ ID NO: 4844), SGSI-TIVR (SEQ ID NO: 4845), SGSPHAS (SEQ ID NO: 4846), SGSPHRK (SEQ ID NO: 4847), SGSPHKT (SEQ ID NO: 4848), SHSPHKS (SEQ ID NO: 4849), QSSPHRS (SEQ ID NO: 4850), RGSPHAS (SEQ ID NO: 4851), RGSPHSK (SEQ ID NO: 4852), SGSPHKF (SEQ ID NO: 4853), SGSPHKI (SEQ ID NO: 4854), SGSPHKL (SEQ ID NO: 4855), SGSPHKY (SEQ IDNO: 4856), SGSPHTR (SEQ ID NO: 4857). SHSPHKR (SEQ ID NO: 4858), SGSPHGA (SEQ ID NO: 4859), HDSPHKR (SEQ ID NO: 4860), DDSPHKS (SEQ ID NO: 4861), HESPHKS (SEQ ID NO: 4862), NYSPHKI (SEQ ID NO: 4863), SGSPHSR (SEQ ID NO: 4864), SGSPHSL (SEQ ID NO: 4865), SGSPHSS (SEQ ID NO: 4866), VGSPHSK (SEQ ID NO: 4867). SCSPHRK (SEQ ID NO: 4868), SGSPHFL (SEQ ID NO: 4869), LLSPHWK (SEQ ID NO: 4870), NGSPHSK (SEQ ID NO: 4871), PGSPHSK (SEQ ID NO: 4872), GGSPHSK (SEQ ID NO: 4873), TGSPHSK (SEQ ID NO: 4874), SVSPHGK (SEQ ID NO: 4875), SGSPHTK (SEQ ID NO: 4876), IGSPHSK (SEQ ID NO: 4877), DGSPHSK (SEQ ID NO: 4878), SGSPHNK (SEQ ID NO: 4879), LGSPHSK (SEQ ID NO: 4880), AGSPHSK (SEQ ID NO: 4881), EGSPIISK (SEQ ID NO: 4882), SASPHSK (SEQ ID NO: 4883), SGSPHAK (SEQ ID NO: 4884), HDSPHKI (SEQ ID NO: 4885), YDSPHKS (SEQ ID NO: 4886), HDSPHKT (SEQ ID NO: 4887), RGSPHKR (SEQ ID NO: 4888), HGSPHSK (SEQ ID NO: 4889), RDSPHKS (SEQ ID NO: 4890), NDSPHKS (SEQ ID NO: 4891), QDSPHKI (SEQ ID NO: 4892), PDSPHKI (SEQ ID NO: 4893), PDSPHKS (SEQ ID NO: 4894), MGSPHSK (SEQ ID NO: 4895), HDSPHKH (SEQ ID NO: 4896), QVSPHKS (SEQ ID NO: 4897), HNSPHKS (SEQ ID NO: 4898), NGSPHKR (SEQ ID NO: 4899), HDSPHKY (SEQ ID NO: 4900), NDSPHKI (SEQ ID NO: 4901), HDSPHKL (SEQ ID NO: 4902), HPSPHWK (SEQ ID NO: 4903), HDSPHKM (SEQ ID NO: 4904). or HSSPHRS (SEQ ID NO: 4905);(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i), e.g., any 2. 3, 4, 5, or 6 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no more than four modifications relative to any of the amino acid sequences in (i); or(iv) an amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).19. The AAV particle of any one of embodiments 1-18, wherein [N1]-[N2]-[N3] is or comprises:(i) GSGSPHSKA (SEQ ID NO: 4697), GHDSPHKSG (SEQ ID NO: 4698), GSGSPHARM (SEQ ID NO: 4906), GSGSPHVKS (SEQ ID NO: 4907), GQDSPHKSG (SEQ ID NO: 4908), GSGSPHASR (SEQ ID NO: 4909). GSGSPHVKI (SEQ ID NO: 4910), GSGSPHKKN (SEQ ID NO: 4911), GSGSPHVRM (SEQ ID NO: 4912), VSGSPHSKA (SEQ ID NO: 4913), GSGSPHSKA (SEQ ID NO: 4914), GSGSPHRKA (SEQ ID NO: 4915), CSGSPHK.TS (SEQ ID NO: 4916), CSHSPHKSG (SEQ ID NO: 4917), GQSSPHRSG (SEQ ID NO: 4918), GRGSPHASR (SEQ ID NO: 4919), GRGSPHSKA (SEQ ID NO: 4920), GSGSPHKFG (SEQ ID NO: 4921), GSGSPHKIG (SEQ ID NO: 4922), GSGSPHKLG (SEQ ID NO: 4923), GSGSPHKTS (SEQ ID NO: 4924), GSGSPIIKTT (SEQ ID NO: 4925). GSGSPHKTY (SEQ ID NO: 4926), GSGSPHKYG (SEQ ID NO: 4927), GSGSPHSKD (SEQ ID NO: 4928), GSGSPHSKP (SEQ ID NO: 4929), GSGSPHTRG (SEQ ID NO: 4930), GSGSPHVRG (SEQ ID NO: 4931), GSHSPHKRG (SEQ ID NO: 4932), GSHSPHKSG (SEQ ID NO: 4933), VSGSPHASR (SEQ ID NO: 4934), VSGSPHGAR (SEQ ID NO:4935), VSGSPHKFG (SEQ ID NO: 4936). GHDSPHKRG (SEQ ID NO: 4937), GDDSPHKSG (SEQ ID NO: 4938), GHESPHKSA (SEQ ID NO: 4939), GHDSPHKSA (SEQ ID NO: 4940), GNYSPHKIG (SEQ ID NO: 4941), GHDSPHKSR (SEQ ID NO: 4942), GSGSPHSKL (SEQ ID NO: 4943), GSGSPHSRA (SEQ ID NO: 4944), GSGSPHSKR (SEQ ID NO: 4945), GSGSPHSLR (SEQ ID NO: 4946), GSGSPHSRG (SEQ ID NO: 4947), GSGSPHSSR (SEQ ID NO: 4948), RVGSPHSKA (SEQ ID NO: 4949), GSCSPHRKA (SEQ ID NO: 4950), GSGSPHFLR (SEQ ID NO: 4951), GSGSPHSKW (SEQ ID NO: 4952), GSGSPHSKS (SEQ ID NO: 4953), GLLSPHWKA (SEQ ID NO: 4954), GSGSPHVRR (SEQ ID NO: 4955), GSGSPHSKV (SEQ ID NO: 4956), MSGSPHSKA (SEQ ID NO: 4957). RNGSPHSKA (SEQ ID NO: 4958), TSGSPHSKA (SEQ ID NO: 4959), ISGSPHSKA (SEQ ID NO: 4960), GPGSPHSKA (SEQ ID NO: 4961), GSGSPHSKT (SEQ ID NO: 4962), ESGSPHSKA (SEQ ID NO: 4963), SSGSPHSKA (SEQ ID NO: 4964), GNGSPHSKA (SEQ ID NO: 4965), ASGSPHSKA (SEQ ID NO: 4966), NSGSPHSKA (SEQ ID NO: 4967), ESGSPHSKA (SEQ ID NO: 4968), GGGSPHSKA (SEQ ID NO: 4969). KSGSPHSKA (SEQ ID NO: 4970), GGGSPHSKS (SEQ ID NO: 4971), GSGSPHSKG (SEQ ID NO: 4972), HSGSPHSKA (SEQ ID NO: 4973), GTGSPHSKA (SEQ ID NO: 4974), PSGSPHSKA (SEQ ID NO: 4975), GSVSPHGKA (SEQ ID NO: 4976), RSGSPHSKA (SEQ ID NO: 4977), GSGSPHTKA (SEQ ID NO: 4978), GIGSPHSK A (SEQ ID NO: 4979), WSGSPHSKA (SEQ ID NO: 4980), DSGSPHSKA (SEQ ID NO: 4981), IDGSPHSKA (SEQ ID NO: 4982), GSGSPHNKA (SEQ ID NO: 4983), GLGSPHSKS (SEQ ID NO: 4984), DAGSPHSKA (SEQ ID NO: 4985), DGGSPHSKA (SEQ ID NO: 4986), MEGSPHSKA (SEQ ID NO: 4987), ENGSPHSKA (SEQ ID NO: 4988).GSASPHSKA (SEQ ID NO: 4989), GNGSPHSKS (SEQ ID NO: 4990), KNGSPHSKA (SEQ ID NO: 4991), KEGSPHSKA (SEQ ID NO: 4992), AIGSPHSKA (SEQ ID NO: 4993), GSGSPHSKN (SEQ ID NO: 4994), GSGSPHAKA (SEQ ID NO: 4995), GHDSPHKIG (SEQ ID NO: 4996), GYDSPHKSG (SEQ ID NO: 4997), GHESPHKSG (SEQ ID NO: 4998), GHDSPHKTG (SEQ ID NO: 4999), GRGSPHKRG (SEQ ID NO: 5000), GQDSPHKSG (SEQ ID NO: 4908), GHDSPHKSL (SEQ ID NO: 5001), GHGSPHSKA (SEQ ID NO: 5002), GHDSPHKSE (SEQ ID NO: 5003), VSGSPHSKA (SEQ ID NO: 4913), GRDSPHKSG (SEQ ID NO: 5004), GNDSPHKSV (SEQ ID NO: 5005), GQDSPHKIG (SEQ ID NO: 5006), GHDSPHKSV (SEQ ID NO: 5007), GPDSPHKIG (SEQ ID NO: 5008), GPDSPHKSG (SEQ ID NO: 5009), GHDSPHKSW (SEQ ID NO: 5010). GHDSPHKSN (SEQ ID NO: 5011). GMGSPHSKT (SEQ ID NO: 5012). GHDSPHKHG (SEQ ID NO: 5013), GQVSPHKSG (SEQ ID NO: 5014), GDDSPHKSV (SEQ ID NO: 5015), GHNSPHKSG (SEQ ID NO: 5016), GNGSPI IKRG (SEQ ID NO: 5017), GHDSPHKYG (SEQ ID NO: 5018), GHDSPHKSQ (SEQ ID NO: 5019), GNDSPHKIG (SEQ ID NO: 5020), GHDSPHKSK (SEQ ID NO: 5021), GHDSPHKLW (SEQ ID NO: 5022), GHPSPHWKG (SEQ ID NO: 5023), GHDSPHKMG (SEQ ID NO: 5024), GHDSPHKMA (SEQ ID NO: 5025), or GHSSPHRSG (SEQ ID NO: 5026);(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i), e.g., any 2, 3, 4, 5, 6, 7, or 8 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no more than four modifications relative to any of the amino acid sequences in (i); or(iv) an amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).20. The AAV particle of any one of embodiments 1-19, wherein [N3] comprises SK, KA, KS. or SG.21. The AAV particle of any one of embodiments 1-20, wherein [N3] is or comprises SKA, KSG, or KYG.22. The AAV particle of any one of embodiments 1-21, wherein [N2]-[N3] comprises SPHSK (SEQ ID NO: 4701), SPHKS (SEQ ID NO: 4704), or SPHKY (SEQ ID NO: 4715).23. The AAV particle of any one of embodiments 1-22, wherein [N2]-[N3] is or comprises SPHSKA (SEQ ID NO: 941).2.4. The AAV particle of any one of embodiments 1-22, wherein [N2]-[N3] is or comprises SPHKSG (SEQ ID NO: 946).25. The AAV particle of any one of embodiments 1-22, wherein [N2]-[N3] is or comprises SPHKYG (SEQ ID NO: 966).26. The AAV particle of any one of embodiments 1-25, wherein [N1] comprises GS, SG, GH, or HD.27. The AAV particle of any one of embodiments 1-26, wherein [N1] is or comprises GSG.28. The AAV particle of any one of embodiments 1-26, wherein [N1] is or comprises GHD.29. The AAV particle of any one of embodiments 1 -23 or 26-27, wherein [N1]-[N2]-[N3] comprises SGSPHSK (SEQ ID NO: 4839).30. The AAV particle of any one of embodiments 1-22, 24, 26, or 28, wherein [N1]-[N2.]-[N3] comprises HDSPHKS (SEQ ID NO: 4840).31 . The AAV particle of any one of embodiments 1 -22 or 25-27, wherein [N1]-[N2]-[N3] comprises SGSPHKYG (SEQ ID NO: 5027).32. The AAV particle of any one of embodiments 1-8, 10, 12-23, 26-27, or 2.9, wherein [N1]-[N2.]- [N3] is or comprises GSGSPHSKA (SEQ ID NO: 4697).33. The AAV particle of any one of embodiments 1-9, 11-22, 24, 26, 28, or 30, wherein [N1]-[N2]- [N3] is or comprises GHDSPHKSG (SEQ ID NO: 4698).34. The AAV particle of any one of embodiments 1-8, 10, 12-22, 25-27, or 31, wherein [N1]-[N2]- [N3] is or comprises GSGSPHKYG (SEQ ID NO: 4927).35. The AAV particle of any one of embodiments 1-34, wherein [N1]-[N2]-[N3] replaces positions 453-455, numbered according to SEQ ID NO: 138.36. The AAV particle of any one of embodiments 1-35, wherein the AAV capsid variant comprises an amino acid other than Q at position 456 (e.g,, W, K, R, G, L, V, S, P, H, K, I, M, A, E, or F), an amino acid other than N at position 457 (e.g,, Y, C, K, T, H, R, D, V, S, P, G, W, E, F, A, I, M, Q, or L), an amino acid other than Q at position 458 (e.g. , G, K, H, R, T, L, D, A, P, I, F, V, M, W, Y, S, E, N, or Y), and / or an amino acid other than Q at position 459 (e.g., H, L, R, W, K, A, P, E, M, I, S, G, N, Y, C, V, T, D, or V), as numbered according to SEQ ID NO: 138.37. The AAV particle of any one of embodiments 1-36, wherein the AAV capsid variant comprises an amino acid other than Q at position 462 (e.g., W, K, R, G, L, V, S, P, H, K, I, M, A, E, or F), an amino acid other than N at position 463 (e.g., Y, C, K, T, H, R, D, V, S, P, G, W, E, F, A, I, M, Q, or L), an amino acid other than Q at position 464 (e.g., G, K, H, R, T, L, D, A, P, I, F, V, M, W, Y, S, E, N, or Y), and / or an amino acid other than Q at position 465 (e.g., H, L, R, W, K, A, P, E, M, I, S, G, N, Y, C, V, T, D, or V), as numbered according to SEQ ID NO: 981, 982, 36, 37, 39, 40, 42-46, 48, 49, 50. 52, 53, 56, or 57.38. The AAV particle of any one of embodiments 1 -37, wherein the AAV capsid variant comprises:(a) the amino acid Q at position 456, the amino acid N at position 457, the amino acid Q at position 458, and / or the amino acid Q at position 459, numbered according to SEQ ID NO: 138; or(b) the amino acid Q at position 462, the amino acid N at position 463. the amino acid Q at position 464, and / or the amino acid Q at position 465, numbered according to SEQ ID NO: 981, 982, 36, 37, 39, 40, 42-46, 48, 49, 50, 52, 53, 56, or 57.39. The AAV particle of any one of embodiments 1 -38, wherein the AAV capsid variant further comprises [N4], wherein [N4] comprises X7 X8 X9 X10, and wherein:(a) X7 is: Q. W, K. R, G, L, V, S, P, H, K, I. M, A, E, or F;(b) X8 is: N, Y, C, K, T. H, R, D, V, S, P, G, W, E, F, A. I, M, Q, or L;(c) X9 is: Q, G, K, H, R, T, L, D, A, P, I, F, V, M, W, Y, S, E, N, or Y; and(d) X10 is: Q, H, L, R, W, K, A, P. E, M, I, S, G, N, Y, C, V, T, D. or V; optionally wherein the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of the aforesaid amino acids in (a)-(d).40. The AAV particle of embodiment 39, wherein:(a) X7 of [N4] is Q or R:(b) X8 of [N4] is N orR;(c) X9 of [N4] is Q or R; and(d) X10 of [N4] is Q, L, or R.41. The AAV particle of embodiment 39 or 40, wherein [N4] is or comprises:(i) QNQQ (SEQ ID NO: 5028), WNQQ (SEQ ID NO: 5029), QYYV (SEQ ID NO: 5030), RRQQ (SEQ ID NO: 5031), GCGQ (SEQ ID NO: 5032), LRQQ (SEQ ID NO: 5033), RNQQ (SEQ ID NO: 5034), VNQQ (SEQ ID NO: 5035), FREQ (SEQ ID NO: 5036), FNQQ (SEQ ID NO: 5037), LLQQ (SEQ ID NO: 5038), SNQQ (SEQ ID NO: 5039), RL.QQ (SEQ ID NO: 5040), LNQQ (SEQ ID NO: 5041), QRKL (SEQ ID NO: 5042), LRRQ (SEQ ID NO: 5043), QRLR (SEQ ID NO: 5044). QRRL (SEQ ID NO: 5045), RRLQ (SEQ ID NO: 5046), RLRQ (SEQ ID NO: 5047), SKRQ (SEQ ID NO: 5048), QLYR (SEQ ID NO: 5049), QLTV (SEQ ID NO: 5050), QNKQ (SEQ ID NO: 5051), KNQQ (SEQ ID NO: 5052), QKQQ (SEQ ID NO: 5053), QTQQ (SEQ ID NO: 5054), QNHQ (SEQ ID NO: 5055), QHQQ (SEQ ID NO: 5056), QNQH (SEQ ID NO: 5057), QHRQ (SEQ ID NO: 5058), LTQQ (SEQ ID NO: 5059), QNQW (SEQ ID NO: 5060), QNTH (SEQ ID NO: 5061), RRRQ (SEQ ID NO: 5062), QYQQ (SEQ ID NO: 5063), QNDQ (SEQ ID NO: 5064), QNRH (SEQ ID NO: 5065), RDQQ (SEQ ID NO: 5066), PNLQ (SEQ ID NO: 5067), HVRQ (SEQ ID NO: 5068), PNQH (SEQ ID NO: 5069), HNQQ (SEQ ID NO: 5070), QSQQ (SEQ ID NO: 5071), QPAK (SEQ ID NO: 5072), QNLA (SEQ ID NO: 5073), QNQL (SEQ ID NO: 5074), QGQQ (SEQ ID NO: 5075), LNRQ (SEQ ID NO: 5076), QNPP (SEQ ID NO: 5077). QNLQ (SEQ ID NO: 5078), QDQE (SEQ ID NO: 5079), QDQQ (SEQ ID NO: 5080), HWQQ (SEQ ID NO: 5081), PNQQ (SEQ ID NO: 5082). PEQQ (SEQ ID NO: 5083), QRTM (SEQ ID NO: 5084), LHQH (SEQ ID NO: 5085), QHRI (SEQ ID NO: 5086), QYIH (SEQ ID NO: 5087), QKFE (SEQ ID NO: 5088), QFPS (SEQ ID NO: 5089), QNPL (SEQ ID NO: 5090), QAIK (SEQ ID NO: 5091), QNRQ (SEQ ID NO: 5092), QYQH (SEQ ID NO: 5093), QNPQ (SEQ ID NO: 5094), QHQL (SEQ ID NO: 5095), QSPP (SEQ ID NO: 5096), QAKL (SEQ ID NO: 5097), KSQQ (SEQ ID NO: 5098), QDRP (SEQ ID NO: 5099), QNLG (SEQ ID NO: 5100),QAFH (SEQ ID NO: 5101), QNAQ (SEQ ID NO: 5102), HNQL (SEQ ID NO: 5103), QKLN (SEQ ID NO: 5104), QNVQ (SEQ ID NO: 5105), QAQQ (SEQ ID NO: 5106), QTPP (SEQ ID NO: 5107), QPPA (SEQ ID NO: 5108). QERP (SEQ ID NO: 5109), QDLQ (SEQ ID NO: 5110), QAMH (SEQ ID NO: 5111), QHPS (SEQ ID NO: 5112), PGLQ (SEQ ID NO: 5113), QGIR (SEQ ID NO: 5114). QAPA (SEQ ID NO: 5115), QIPP (SEQ ID NO: 5116), QTQL (SEQ ID NO: 5117), QAPS (SEQ ID NO: 5118), QNTY (SEQ ID NO: 5119), QDKQ (SEQ ID NO: 5120), QNHL (SEQ ID NO: 5121), QIGM (SEQ ID NO: 5122), LNKQ (SEQ ID NO: 5123), PNQL (SEQ ID NO: 5124), QLQQ (SEQ ID NO: 5125), QRMS (SEQ ID NO: 5126), QGIL (SEQ ID NO: 5127), QDRQ (SEQ ID NO: 5128), RDWQ (SEQ ID NO: 5129), QERS (SEQ ID NO: 5130), QNYQ (SEQ ID NO: 5131), QRTC (SEQ ID NO: 5132), QIGH (SEQ ID NO: 5133), QGAI (SEQ ID NO: 5134), QVPP (SEQ ID NO: 5135), QVQQ (SEQ ID NO: 5136), LMRQ (SEQ ID NO: 5137), QYSV (SEQ ID NO: 5138), QAIT (SEQ ID NO: 5139), QKTL (SEQ ID NO: 5140), QLHH (SEQ ID NO: 5141), QNII (SEQ ID NO: 5142), QGHH (SEQ ID NO: 5143), QSKV (SEQ ID NO: 5144), QLPS (SEQ ID NO: 5145). 1GKQ (SEQ ID NO: 5146), QAIH (SEQ ID NO: 5147), QHGL (SEQ ID NO: 5148), QFMC (SEQ ID NO: 5149), QNQM (SEQ ID NO: 5150), QHLQ (SEQ ID NO: 5151). QPAR (SEQ ID NO: 5152), QSLQ (SEQ ID NO: 5153), QSQL (SEQ ID NO: 5154), HSQQ (SEQ ID NO: 5155), QMPS (SEQ ID NO: 5156), QGSL (SEQ ID NO: 5157), QVPA (SEQ ID NO: 5158), HYQQ (SEQ ID NO: 5159), QVPS (SEQ ID NO: 5160), RGEQ (SEQ ID NO: 5161), PGQQ (SEQ ID NO: 5162), LEQQ (SEQ ID NO: 5163), QNQS (SEQ ID NO: 5164), QKVI (SEQ ID NO: 5165), QNND (SEQ ID NO: 5166). QSVH (SEQ ID NO: 5167), QPLG (SEQ ID NO: 5168), HNQE (SEQ ID NO: 5169), QIQQ (SEQ ID NO: 5170). QVRN (SEQ ID NO: 5171). PSNQ (SEQ ID NO: 5172), QVGH (SEQ ID NO: 5173), QRDI (SEQ ID NO: 5174), QMPN (SEQ ID NO: 5175), RGLQ (SEQ ID NO: 5176), PSLQ (SEQ ID NO: 5177), QRDQ (SEQ ID NO: 5178), QAKG (SEQ ID NO: 5179), QSAH (SEQ ID NO: 5180), QSTM (SEQ ID NO: 5181), QREM (SEQ ID NO: 5182), QYRA (SEQ ID NO: 5183), QRQQ (SEQ ID NO: 5184), QWQQ (SEQ ID NO: 5185), QRMN (SEQ ID NO: 5186), GDSQ (SEQ ID NO: 5187), QK1S (SEQ ID NO: 5188), PSMQ (SEQ ID NO: 5189), SPRQ (SEQ ID NO: 5190), MEQQ (SEQ ID NO: 5191). QYQN (SEQ ID NO: 5192), QIRQ (SEQ ID NO: 5193). QSVQ (SEQ ID NO: 5194), RSQQ (SEQ ID NO: 5195), QNKL (SEQ ID NO: 5196), QIQH (SEQ ID NO: 5197), PRQQ (SEQ ID NO: 5198). HTQQ (SEQ ID NO: 5199), QRQH (SEQ ID NO: 5200), RNQE (SEQ ID NO: 5201), QSKQ (SEQ ID NO: 5202), QNQP (SEQ ID NO: 5203), QSPQ (SEQ ID NO: 5204), QTRQ (SEQ ID NO: 5205), QNLH (SEQ ID NO: 52.06), QNQE (SEQ ID NO: 5207), LNQP (SEQ ID NO: 5208), QNQD (SEQ ID NO: 5209), QNLL (SEQ ID NO: 5210), QLVI (SEQ ID NO: 5211), RTQE (SEQ ID NO: 5212), QTTIQ (SEQ ID NO: 5213), QDQH (SEQ ID NO: 5214), QSQH (SEQ ID NO: 5215), VRQQ (SEQ ID NO: 5216), A WQQ (SEQ ID NO: 5217). QSVP (SEQ ID NO: 5218), QNIQ (SEQ ID NO: 5219). LDQQ (SEQ ID NO: 5220), PDQQ (SEQ ID NO: 5221), ESQQ (SEQ ID NO: 5222), QRQL (SEQ ID NO: 5223), QIIV (SEQ ID NO: 5224), QKQS (SEQ ID NO: 5225), QSHQ (SEQ ID NO: 5226), QFVV (SEQ ID NO: 5227), QSQP (SEQ ID NO: 5228), QNEQ (SEQ ID NO: 5229), INQQ (SEQ IDNO: 5230), RNRQ (SEQ ID NO: 5231), RDQK (SEQ ID NO: 5232), QWKR (SEQ ID NO: 5233), ENRQ (SEQ ID NO: 5234), QTQP (SEQ ID NO: 5235), QKQL (SEQ ID NO: 5236), RNQL (SEQ ID NO: 5237), TSIQ (SEQ ID NO: 5238), QTVC (SEQ ID NO: 5239), QQIM (SEQ ID NO: 5240), LNHQ (SEQ ID NO: 52.41), QNQA (SEQ ID NO: 5242), QMIH (SEQ ID NO: 5243), RNHQ (SEQ ID NO: 5244), or QKMN (SEQ ID NO: 5245);(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i), e.g., any 2, or 3 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no more than four modifications relative to any of the amino acid sequences in (i); or(iv) an amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).42. The AAV particle of any one of embodiments 39-41, wherein [N1]-[N2]-[N3]-[N4] is or comprises:(i) the amino acid sequence of any of SEQ ID NOs: 1800-1808, 1832, 1833, 1835-1841, 1843-1845, 1848, 1851, 1852, 1854-2000, 2003, 2004, 2008-2241, 6421-6441, 6443-6456;(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i), e.g., any 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two. or three but no more than four modifications relative to any of the amino acid sequences in (i); or(iv) an amino acid sequence comprising one, two, or three but no more than four different amino acids, rela tive to any one of the amino acid sequences in (i).43. The AAV particle of any one of embodiments 39-42, wherein [N1]-[N2]-[N3]-[N4] is or comprises GSGSPHSKAQNQQ (SEQ ID NO: 1801).44. The AAV particle of any one of embodiments 39-42, wherein [N1]-[N2]-[N3]-[N4] is or comprises GHDSPHKSGQNQQ (SEQ ID NO: 1800).45. The AAV particle of any one of embodiments 39-42, wherein [N1]-[N2]-[N3]-[N4] is or comprises GSGSPHKYGQNQQT (SEQ ID NO: 910).46. The AAV particle of any one of embodiments 1-45, wherein the AAV capsid variant comprises an amino acid other than T at position 450 (e.g., S, Y, M, A, C, I, R, L, D, F, V, Q. N, H, E, or G), an amino acid other than I at position 451 (e.g., M, P, E, N, D, S, A, T, G, Q, F, V, L, C, H, R, W, or L), and / or an amino acid other than N at position 452 (e.g., M, E, G, Y, W, T, I, Q, F, V, A, L, I, P, K, R, H, S, D, or S), as numbered according to any one of SEQ ID NOs: 36-59, 138, 981, or 982.47. The AAV particle of any one of embodiments 1-46, wherein the AAV capsid variant comprises the amino acid T at position 450. the amino acid I at position 451. and / or the amino acid N at position 452, as numbered according to any one of SEQ ID NOs: 138, 981, or 982.48. The AAV particle of any one of embodiments 1 -47, wherein the AAV capsid variant further comprises [N0], wherein [N0] comprises XAXB. and Xc, and wherein:(a) XAis: T, S, Y, M, A, C. I, R, L, D, F, V, Q. N, H, E, or G;(b) XBis: I, M, P, E, N. D, S, A, T, G, Q, F, V, L, C, H, R, W, or L; and(c) Xcis: N, M, E, G, V. W, T, I, Q, F, V, A, L, I, P, K, R, H, S, D, or S: and optionally wherein the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of the aforesaid amino acids in (a)-(c).49. The AAV particle of embodiment 48, wherein [N0] is or comprises TIN, SMN, TIM, YLS, GLS, MPE, MEG, MEY, AEW, CEW, ANN, IPE. ADM, IEY, ADY, IET. MEW, CEY, RIN, MEI, LEY, ADW. IEI, DIM, FEQ, MEF, CDQ, LPE, IEN. MES, AEI, VEY, UN. TSN, IEV, MEM. AEV, MDA, VEW, AEQ, LEW, MEL, MET. MEA, IES, MEV, CEI, ATN, MDG, QEV, ADQ, NMN, IEM, ISN, TGN, QQQ, HDW, IEG, TII, TFP, TEK, EIN, TVN, TFN, SIN, TER, TSY, ELH, AIN, SVN, TDN, TFH, TVH, TEN, TSS, TID, TCN, NIN, TEH, AEM, AIK, TDK, TFK, SDQ, TEI, NTN, TET, SIK, TEL, TEA, TAN, TIY, TFS, TES, TTN, TED, TNN, EVH, TIS, TVR, TOR, TIK, NHI, TIP. ESD, TDL, TVP, T VI, AEH. NCL. TVK, NAD, TIT, NCV, TIR, NAL, VIN, HQ, TEF, TRE, QGE, SEK. NVN, GGE, EFV, SDK, TEQ, EVQ, TEY, NCW, TDV, SDI, NSI, NSL, EVV, TEP, SEL, TWQ, TEV, AVN, GVL, TLN, TEG, TRD, NAI, AEN, AET, ETA, NNL, or any dipeptide thereof.50. The AAV particle of embodiment 48 or 49, wherein [N0]-[N1]-[N2]-[N3]-[N4] is or comprises:(i) the amino acid sequence of any one of SEQ ID NOs: 2242-2886;(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i), e.g., any 2, 3, 4, 5, 6, 7, 8, 9, 10, 11. 12, 13, 14, or 15 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no more than four modifications relative to any of the amino acid sequences in (i); or(iv) an amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).51. The AAV particle of any one of embodiments 48-50. wherein [N0]-[N1]-[N2]-[N3]-[N4] is or comprises TINGSGSPHSKAQNQQ (SEQ ID NO: 2242).52. The AAV particle of any one of embodiments 48-50, wherein [N0]-[N1]-[N2] [N3]-[N4] is or comprises TINGHDSPHKSGQNQQ (SEQ ID NO: 2243).53. The AAV particle of any one of embodiments 48-52, wherein [N0]-[N1]-[N2]-[N3]-[N4] is or comprises TINGSGSPHKYGQNQQT (SEQ ID NO: 5246).54. The AAV particle of any one of embodiments 1-53, wherein [N1]-[N2]-[N3] is present in loop IV.55. The AAV particle of any one of embodiments 48-54, wherein [N0] and [N4] are present in loop IV.56. The AAV particle of any one of embodiments 48-55, wherein [N0] is present immediately subsequent to position 449, numbered according to SEQ ID NO: 138.57. The AAV particle of any one of embodiments 48-56, wherein [N0] is present immediately subsequent to position 449, numbered according to any one of SEQ ID NOs: 36-59, 981, or 982.58. The AAV particle of any one of embodiments 48-57, wherein [N0] replaces positions 450, 451, and 452. (e.g., T450, 1451, and N452), numbered according to SEQ ID NO: 138.59. The AAV particle of any one of embodiments 48-58, wherein [N0] replaces positions 450-452 (e.g., T450, 1451, and N452), numbered according to any one of SEQ ID NOs: 36-59, 981, or 982.60. The AAV particle of any one of embodiments 48-59, w'herein [N0] corresponds to positions 450- 452 of any one of SEQ ID NOs: 36-59, 138, 981 or 982.61. The AAV particle of any one of embodiments 48-60, wherein [N0] is present immediately subsequent to position 449 and wherein [N0] replaces positions 450-452 (e.g., T450, 1451, and N452), numbered according to SEQ ID NO: 138.62. The AAV particle of any one of embodiments 48-61, wherein [N0] is present immediately subsequent to position 449 and wherein [N0] replaces positions 450-452 (e.g., T450, 1451, and N452), numbered according to any one of SEQ ID NOs: 36-59, 981, or 982.63. The AAV particle of any one of embodiments 1-62, wherein [N1] is present immediately subsequent to position 452, numbered according to the amino acid sequence of SEQ ID NO: 138.64. The AAV particle of any one of embodiments 1 -63, wherein [N1] is present immediately subsequent to position 452, numbered according to SEQ ID NO: 981 or 982.65. The AAV particle of any one of embodiments 1-61, wherein [N1] replaces positions 453-455 (e.g,, G453, S454, and G455), numbered according to SEQ ID NO: 138.66. The AAV particle of any one of embodiments 1-64, wherein [N1] replaces positions 453 (e.g., G453), numbered according to SEQ ID NO: 138.67. The AAV particle of any one of embodiments 1-65, wherein [N1] replaces positions 453-455 (e.g., G453, S454, and G455), numbered according to SEQ ID NO: 981.68. The AAV particle of any one of embodiments 1-65 or 67, wherein [N1] replaces positions 453- 455, numbered according to SEQ ID NO: 982.69. The AAV particle of any one of embodiments 1-65, 67, or 68, wherein [N1] is present immediately subsequent to position 452. and wherein [N1] replaces positions 453-455 (e.g., G453, S454, and G455), numbered according to SEQ ID NO: 138,70. The AAV particle of any one of embodiments 1-64 or 66. wherein [N1] is present immediately subsequent to position 452 and wherein [N1] replaces positions 453 (e.g., G453), numbered according to SEQ ID NO: 138.71. The AAV particle of any one of embodiments 1 -64, 66 or 70, wherein [N1 ] is present immediately subsequent to position 452 and wherein [NT] replaces positions 453-455, numbered according to SEQ ID NO: 4, 36, 98i , or 982.72. The AAV particle of any one of embodiments 1-71, wherein [N1] corresponds to positions 453- 455, numbered according to any one of SEQ ID NOs: 4, 36-59, 981, or 982.7.3. The AAV particle of any one of embodiments 1 -72, wherein the AAV capsid variant comprises an amino acid other than S at position 454 and / or an amino acid oilier than G at position 455, numbered according to SEQ ID NO: 138, 981, or 982.74. The AAV particle of any one of embodiments 1-73, wherein the AAV capsid variant comprises the amino acid H at position 454 and the amino acid D at position 455, numbered according to SEQID NO: 138 or 982.75. The AAV particle of any one of embodiments 1 -74, wherein the AAV capsid variant comprises a substitution at position 454 (e.g., S454H) and / or a substitution at position 455 (e.g., G455D), numbered according io SEQ ID NO: 138.76. The AAV particle of any one of embodiments 1 -75, wherein the AAV capsid variant comprises the amino acid II at position 454 and the amino acid D at position 455, and further comprises the amino acid sequence SPHSKA (SEQ ID NO: 941) immediately subsequent to position 455. numbered according to SEQ ID NO: 138.77. The AAV particle of any one of embodiments 1-76, wherein the AAV capsid variant comprises the amino acid H at position 454 and the amino acid D at position 455, numbered according to SEQ ID NO: 982.78. The AAV particle of any one of embodiments 1-77, wherein the AAV capsid variant comprises the amino acid H at position 454 and the amino acid D at position 455, and further comprises the amino acid sequence SPHSKA (SEQ ID NO: 941) immediately subsequent to position 455, numbered according to SEQ ID NO: 982.79. The AAV particle of any one of embodiments 1-72, wherein the AAV capsid variant comprises the amino acid S at position 454 and the amino acid G at position 455, numbered according to SEQ ID NO: 138.80. The AAV particle of any one of embodiments 1-72 or 79, wherein the AAV capsid variant comprises the amino acid S at position 454 and the amino acid G at position 455, and further comprises the amino acid sequence SPHSKA (SEQ ID NO: 941) immediately subsequent to position 455, numbered according to SEQ ID NO: 138.81. The AAV particle of any one of embodiments 1 -72, 79, or 80, wherein the AAV capsid variant comprises the amino acid S at position 454 and the amino acid G at position 455, numbered according to SEQ ID NO: 981.82. The AAV particle of any one of embodiments 1-72 or 79-81, wherein the AAV capsid variant comprises the amino acid S at position 454 and the amino acid G at position 455, and further comprises the amino acid sequence SPHSKA (SEQ ID NO: 941) immediately subsequent to position 455, numbered according to SEQ ID NO: 981.83. The AAV particle of any one of embodiments 1-82, wherein [N2] is present immediately subsequent to position 455. numbered according to SEQ ID NO: 138.84. The AAV particle of any one of embodiments 1-83, wherein [N2] corresponds to positions 456- 458 (e.g., S456, P457, H458) of SEQ ID NO: 981 or 982.85. The AAV particle of any one of embodiments 1-83, wherein [N2] corresponds to positions 456- 458 (e.g., S456. P457, H458) of any one of SEQ ID NOs: 4 or 36-59.86. The AAV particle of any one of embodiments 1-85, wherein [N2]-[N3] is present immediately subsequent to position 455, numbered according to SEQ ID NO: 138.87. The AAV particle of any one of embodiments 1-86, wherein [N2] is present immediately subsequent to position 455, numbered according to SEQ ID NO: 4, 36, 981 , or 982.88. The AAV particle of any one of embodiments 1-87, wherein [N2]-[N3] is present immediately subsequent to position 455, numbered according to SEQ ID NO: 4, 36, 981. or 982.89. The AAV particle of any one of embodiments 1-88, wherein [N2]-[N3] corresponds to positions 456-461 (e.g., S456. P457, H458, S459, K460, A461) of SEQ ID NO: 981.90. The AAV particle of any one of embodiments 1-88, wherein [N2]-[N3] corresponds to positions 456-461 (e.g., S456, P457, H458, K459, S460, G461) of SEQ ID NO: 982.91. The AAV particle of any one of embodiments 1-90, wherein [N2] is present immediately subsequent to [N1],92. The AAV particle of any one of embodiments 1-64, 66, 70, or 71, wherein [N3] is present immediately subsequent to [N2] and replaces positions 454 and 455 (e.g., S454 and G455), numbered according to SEQ ID NO: 138.93. The AAV particle of any one of embodiments 1-1-64, 66, 70, 71, or 92, wherein [N3] is present immediately subsequent to [N1]-[N2] and replaces positions 454 and 455 (e.g., S454 and G455), numbered according to SEQ ID NO: 138.94. The AAV particle of any one of embodiments 39-93, wherein [N4] is present immediately subsequent to position 455, numbered according to SEQ ID NO: 138.95. The AAV particle of any one of embodiments 39-94. wherein [N4] replaces positions 456-459 (e.g., Q456, N457, Q458, and Q459), numbered according to SEQ ID NO: 138.96. The AAV particle of any one of embodiments 39-95, wherein [N4] corresponds to positions 462- 465 (e.g., Q462, N463, Q464, Q465) of SEQ ID NO: 4, 36. 981, or 982.97. The AAV particle of any one of embodiments 39-96, wherein [N2]-[N3]-[N4] replaces positions 456-459 (e.g., Q456, N457, Q458, and Q459), numbered according to SEQ ID NO: 138.98. The AAV particle of any one of embodiments 39-97, wherein [N2]-[N3]-[N4] is present immediately subsequent to position 455, and wherein [N2]-[N3]-[N4j replaces positions 456-459 (e.g., Q456, N457, Q458, and Q459), numbered according to SEQ ID NO: 138.99. The AAV particle of any one of embodiments 39-98, wherein [N2]-[N3]-[N4] corresponds to positions 456-465 (e.g., S456, P457, H458, S459, K460, A461, Q462, N463, Q464, Q465) of SEQ ID NO: 981.100. The AAV particle of any one of embodiments 39-98, wherein [N2]-[N3]-[N4] corresponds to positions 456-465 (e.g., S456, P457, H458, K459, S460, G461, Q462, N463, Q464, Q465) of SEQ ID NO: 982.101. The AAV particle of any one of embodiments 39-98, wherein [N2j-[N3]-[N4] corresponds to positions 456-465 of any one of SEQ ID NOs: 4 or 36-59.102. The AAV particle of any one of embodiments 39-101, wherein [N1]-[N2]-[N3]-[N4] replaces positions 453-459 (e.g., G453, S454, G455, Q456, N457, Q458, and Q459), numbered according to SEQ ID NO: 138.103. The AAV particle of any one of embodiments 39-102. wherein [N1]-[N2]-[N3]-[N4] is present immediately subsequent to position 452, and wherein [N1]-[N2]-[N3]-[N4] replaces positions 453-459 (e.g., G453, S454, G455, Q456, N457. Q458, and Q459), numbered according to SEQ ID NO: 138.104. The AAV particle of any one of embodiments 39-99, 102, or 103, wherein [N1]-[N2]-[N3]-[N4] corresponds to positions 453-465 (e.g., G453, S454, G455, S456, P457, H458, S459, K460, A461, Q462, N463, Q464, Q465) of SEQ ID NO: 981.105. The AAV particle of any one of embodiments 39-98, 100, 102, or 103, wherein [N1]-[N2]-[N3]- [N4] corresponds to positions 453-465 (e.g., G453, H454, D455, S456, P457, H458, K459, S460, G461, Q462, N463, Q464, Q465) of SEQ ID NO: 982.106. The AAV particle of any one of embodiments 39-98, 102, or 103. wherein [N1]-[N2]-[N3]-[N4] corresponds to positions 453-465 of any one of SEQ ID NOs: 4 or 36-59.107. The AAV particle of any one of embodiments 1-99 or 102-104, wherein [N1]-[N2]-[N3] corresponds to positions 453-461 (e.g., G453, S454, G455, S456, P457, H458, S459, K460, A461) of SEQ ID NO: 981.108. The AAV particle of any one of embodiments 1-98, 100, 102, 103, or 105, wherein [N1]-[N2J- [N3] corresponds to positions 453-461 (e.g., G453, H454, D455, S456, P457, H458, K459, S460, G461) of SEQ ID NO: 982.109. The AAV particle of any one of embodiments 39-98. 102, 103, or 106. wherein [N1]-[N2]-[N3] corresponds to positions 453-461 of any one of SEQ ID NOs: 36-59.110. The AAV particle of any one of embodiments 48-109, wherein [N0]-[N1]-[N2]-[N3]-[N4] replaces positions 450-459 (e.g., T450, 1451, N452, G453, S454, G455, Q456, N457. Q458, and Q459), numbered according to SEQ ID NO: 138.111. The AAV particle of any one of embodiments 48-110, wherein [N0]-[N1]-[N2]-[N3]~[N4] is present immediately subsequent to position 449, and wherein [N0]-[N1]-[N2]-[N3]-[N4] replaces positions 450-459 (e.g., T450, 1451 , N452, G453, S454, G455, Q4.56, N457. Q458, and Q459), numbered according to SEQ ID NO: 138.112. The AAV particle of any one of embodiments 48-99, 102-104, or 106, wherein [N0]-[N1]-[N2]-[N3]-[N4] corresponds to positions 450-465 (e.g,, T450, 1451. N452, G453, S454, G455, S456, P457.H458, S459, K460, A461, Q462, N463. Q464, Q465) of SEQ ID NO: 981.113. The AAV particle of any one of embodiments 48-98, 100. 102, 103. 105, or 108, wherein [N0]- [ N 1] -[ N 2 ]-[ N 3 ] -[ N4 ] corresponds to positions 450-465 (e.g., T450, 1451, N452, G453. H454, D455, S456, P457, H458, K459, S460, G461, Q462, N463, Q464, Q465) of SEQ ID NO: 982.114. The AAV particle of any one of embodiments 48-98, 102, 103, 106, or 109, wherein [N0]-[N1]-[N2]-[N3]-[N4] corresponds to positions 450-465 of any one of SEQ ID NOs: 36-59.115. The AAV particle of any one of embodiments 39-114, wherein [N4] replaces positions 462-465 (e.g,, Q462, N463, Q464, and Q465), numbered according to SEQ ID NO: 4, 36, 981, or 982.116. The AAV particle of any one of embodiments 39-115, wherein [N2]-[N3]-[N4] replaces positions 462-465 (e.g., Q462, N463, Q464, and Q465). numbered according to SEQ ID NO: 4, 36,981, or 982.117. The AAV particle of any one of embodiments 39-116, wherein [N2]-[N3]-[N4] is present immediately subsequent to position 455, and wherein [N2]-[N3]-[N4j replaces positions 462-465(e.g., Q462, N463, Q464, and Q465), numbered according to SEQ ID NO: 4, 36, 981, or 982.118. The AAV particle of any one of embodiments 1-117, wherein [N3] is present immediately subsequent to [N2J.119. The AAV particle of any one of embodiments 1-118, wherein the AAV capsid variant comprises. from N-terminus to C-terminus, [N2]-[N3].120. The AAV particle of any one of embodiments 1-119, wherein the AAV capsid variant comprises. from N-terminus to C-terminus, [N1]-[N2]-[N3],121. The AAV particle of any one of embodiments 48-120, wherein the AAV capsid variant comprises, from N-terminus to C-terminus, [N0]-[N1]-[N2]-[N3],122. The AAV particle of any one of embodiments 39-121 , wherein the AAV capsid variant comprises, from N-terminus to C-terminus, [N1]-[N2]-[N3]-[N4].123. The AAV particle of any one of embodiments 48-122, wherein the AAV capsid variant comprises, from N-terminus to C-terminus, [N0]-[N1]-[N2]-[N3]-[N4].124. The AAV particle of any one of the preceding embodiments, wherein the AAV capsid variant comprises an amino acid other T at position 460 (e.g., N, I, C, H, R. L, D, Y, A. M, Q, I, E, K, P, G or S), numbered according to SEQ ID NO: 138.125. The AAV particle of any one of the preceding embodiments, wherein the AAV capsid variant comprises the amino acid N, I. C, H, R, L, D, Y, A, M, Q, I, E, K. P, G or S at position 460, numbered according to SEQ ID NO: 138.126. The AAV particle of any one of the preceding embodiments, wherein the AAV capsid variant comprises an amino acid other T at position 466 (e.g., N, I, C, H, R, L , D, Y, A, M, Q, I, E, K, P, G or S), numbered according to any one of SEQ ID NOs: 36-59. 981, or 982.127. The AAV particle of any one of the preceding embodiments, wherein the AAV capsid variant comprises the amino acid N, I, C, H, R, L, D, Y, A, M, Q, I, E, K, P, G or S at position 466, numbered according to any one of SEQ ID NOs: 36-59, 981 or 982.128. The AAV particle of any one of the preceding embodiments, wherein the AAV capsid variant comprises an amino acid other K at position 449 (e.g., an E, an N, or a T), numbered according to any one of SEQ ID NOs: 36-59, 138, 981, or 982.129. The AAV particle of any one of the preceding embodiments, wherein the AAV capsid variant comprises the amino E, N, or T at position 449, numbered according to any one of SEQ ID NOs: 36- 59, 138, 981 or 982.130. An adeno-associated virus (AAV) particle comprising an AAV capsid variant (e,g., an AAV9 capsid variant) and a viral genome comprising a β-glucocerebiosidase 1 (GBA1)-encoding sequence (e.g., encoding a human GBA1 protein), wherein the AAV capsid variant comprises [A] [B] (SEQ ID NO: 4694), wherein:(i) [A] comprises the amino acid sequence of GSGSPH (SEQ ID NO: 4695); and(ii) [B] comprises Xi X2 X3 X4 X5 X6 X7, wherein:(a) XI is: S, C, F, or V;(b) X2 is: K, L, R, I, E, Y, V, or S;(c) X3 is: A. R, L. G, I, Y, S, F, or W;(d) X4 is: W, Q. R, G, L, V, S, or F;(e) X5 is: N. Y, R, C, K, or L;(f) X6 is: Q, G. K, R, T, L, or Y; and(g) X7 is: Q, L, R, or V; optionally wherein the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of the aforesaid amino acids in (a)-(g).131. The AAV particle of embodiment 130, wherein(a) X1 is S;(b) X2 is K or L;(c) X3 is: A, R, or L;(d) X4 is: Q or R;(e) X5 is: N or R;(f) X6 is: Q or R; and(g) X7 is: Q, L, or R.132. The AAV particle of embodiment 130 or 131, wherein [B] comprises:(i) SLLWNQQ (SEQ ID NO: 5247), SKAQYYV (SEQ ID NO: 5248), SKLRRQQ (SEQ ID NO: 5249), SIWQNQQ (SEQ ID NO: 5250), SKAGCGQ (SEQ ID NO: 5251), SRAQNQQ (SEQ ID NO: 5252), SKRLRQQ (SEQ ID NO: 5253), SLRRNQQ (SEQ ID NO: 5254), SRGRNQQ (SEQ ID NO: 5255), SEIVNQQ (SEQ ID NO: 5256), SSRRNQQ (SEQ ID NO: 5257), CLLQNQQ (SEQ ID NO: 5258), SKAFRLQ (SEQ ID NO: 5259), CLAQNQQ (SEQ ID NO: 5260), FLRQNQQ (SEQ ID NO: 5261), SLRFNQQ (SEQ ID NO: 5262), SYLRNQQ (SEQ ID NO: 5263), CSLQNQQ (SEQ ID NO: 5264), VLWQNQQ (SEQ ID NO: 5265), SKWLLQQ (SEQ ID NO: 5266), SLWSNQQ (SEQ ID NO: 5267), SKRRLQQ (SEQ ID NO: 5268), SVYLNQQ (SEQ ID NO: 5269), SLWLNQQ (SEQ ID NO: 5270), SKAQRKL (SEQ ID NO: 5271), SKALRRQ (SEQ ID NO: 5272), SKAQRLR (SEQ ID NO: 5273), SKAQNQQ (SEQ ID NO: 5274), SKAQRRL (SEQ ID NO: 5275), SKARRQQ (SEQ ID NO: 5276), SKARRLQ (SEQ ID NO: 5277), SKSRRQQ (SEQ ID NO: 5278). SKARLRQ (SEQ ID NO: 5279), SKASKRQ (SEQ ID NO: 5280), VRRQNQQ (SEQ ID NO: 5281), SKAQLYR (SEQ ID NO: 5282), SLFRNQQ (SEQ ID NO: 5283), SKAQLTV (SEQ ID NO: 5284);(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i), e.g., any 2, 3, 4, 5, or 6 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no more than four modifications relative to any of the amino acid sequences in (i); or(iv) an amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).133. The AAV particle of any one of embodiments 130-132, wherein [A][B] comprises:(i) GSGSPHSLLWNQQ (SEQ ID NO: 5285), GSGSPHSKAQYYV (SEQ ID NO: 2060), GSGSPHSKLRRQQ (SEQ ID NO: 2061), GSGSPHSIWQNQQ (SEQ ID NO: 5286), GSGSPHSK AGCGQ (SEQ ID NO: 2062), GSGSPHSR AQNQQ (SEQ ID NO: 2063), GSGSPHSKRLRQQ (SEQ ID NO: 2064), GSGSPHSLRRNQQ (SEQ ID NO: 2065). GSGSPHSRGRNQQ (SEQ ID NO: 2066), GSGSPHSEIVNQQ (SEQ ID NO: 5287), GSGSPHSSRRNQQ (SEQ ID NO: 2067), GSGSPHCLLQNQQ (SEQ ID NO: 5288), GSGSPHSKAFRLQ (SEQ ID NO: 2068), GSGSPHCLAQNQQ (SEQ ID NO: 5289),GSGSPHFLRQNQQ (SEQ ID NO: 2070), GSGSPHSLRFNQQ (SEQ ID NO: 2071), GSGSPHSYLRNQQ (SEQ ID NO: 5290), GSGSPHCSLQNQQ (SEQ ID NO: 5291), GSGSPHVLWQNQQ (SEQ ID NO: 5292), GSGSPHSKWLLQQ (SEQ ID NO: 2072), GSGSPHSLWSNQQ (SEQ ID NO: 5293). GSGSPHSKRRLQQ (SEQ ID NO: 2073), GSGSPHSVYLNQQ (SEQ ID NO: 5294), GSGSPHSLWLNQQ (SEQ ID NO: 5295), GSGSPHSKAQRKL (SEQ ID NO: 2074), GSGSPHSKALRRQ (SEQ ID NO: 2075), GSGSPHSKAQRLR (SEQ ID NO: 2076), GSGSPHSKAQNQQ (SEQ ID NO: 1801), GSGSPHSKAQRRL (SEQ ID NO: 2077), GSGSPHSKARRQQ (SEQ ID NO: 2078), GSGSPHSKARRLQ (SEQ ID NO: 2079), GSGSPHSKSRRQQ (SEQ ID NO: 2080), GSGSPHSKARLRQ (SEQ ID NO: 2082), GSGSPHSKASKRQ (SEQ ID NO: 2083), GSGSPHVRRQNQQ (SEQ ID NO: 2084), GSGSPHSKAQLYR (SEQ ID NO: 2085), GSGSPHSLFRNQQ (SEQ ID NO: 5296), GSGSPHSKAQLTV (SEQ ID NO: 2086);.(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i), e.g., any 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no more than four modifications relative to any of the amino acid sequences in (i); or(iv) an amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i)134. The AAV particle of any one of embodiments 130-133, wherein 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), numbered according to SEQ ID NO: 138.135. The AAV particle of any one of embodiments 130-134, wherein the AAV capsid variant further comprises an S at position 450 and an M at position 451, numbered according to SEQ ID NO: 138.136. The AAV particle of any one of embodiments 130-134, wherein the AAV capsid variant further comprises a Y at position 450, an L at position 451, and an S at position 452, numbered according to SEQ ID NO: 138.137. The AAV particle of any one of embodiments 130-134, wherein the AAV capsid variant further comprises a G at position 450, an L at position 451. and an S at position 452. numbered according to SEQ ID NO: 138.138. The AAV particle of any one of embodiments 130-137, wherein [A][B] is present in loop IV.139. The AAV particle of any one of embodiments 130-138, wherein [A] is present immediately subsequent to position 452, numbered according to SEQ ID NO: 138.140. The AAV particle of any one of embodiments 130-139, wherein [A] replaces positions 453-455(e.g,, G453, S454, G455), numbered according to SEQ ID NO: 138.141. The AAV particle of any one of embodiments 130-140, wherein [A] is present immediately subsequent to position 452, and wherein [A] replaces positions 453-455 (e.g., G453, S454, G455), numbered according io SEQ ID NO: 138.142. The AAV particle of any one of embodiments 130-141, wherein [B] is present immediately subsequent to [A],143. The AAV particle of any one of embodiments 130-142, wherein [B] replaces positions 456-459 (e.g., Q456, N457, Q458, Q459), numbered according to SEQ ID NO: 138.144. The AAV particle of any one of embodiments 130-143, wherein [A][B] replaces positions 453- 459 (e.g., G453, S454, G455, Q456. N457, Q458, Q459), numbered according to SEQ ID NO: 138.145. The AAV particle of any one of embodiments 130-144, wherein [A][B] is present immediately subsequent to position 452, and wherein [A] [B] replaces positions 453-459 (e.g., G453. S454, G455, Q456, N457, Q458, Q459), numbered according to SEQ ID NO: 138.146. The AAV particle of any one of embodiments 130-145, wherein the AAV capsid variant comprises, from N-terminus to C-terminus, [A][B].147. An adeno-associated virus (AAV) particle comprising an AAV capsid variant and a viral genome comprising a P-glucocerebrosidase 1 (GBA1)-encoding sequence (e.g., encoding a human GBA1 protein), wherein the AAV capsid variant comprises [A] [B] (SEQ ID NO: 4699), wherein:(i) [A] comprises X1 X2 X3 X4 X5 X6, wherein(a) X1 is T. M, A, C, I, R, L, D, F. V, Q, N, or H;(b) X2 is I. P, E, N, D, S, A, T, M, or Q;(c) X3 is N, E, G. Y, W, M, T, I, K, Q, F, S, V, A. or L;(d) X4 is G, D, R, or E;(e) X5 is H, Q, N, or D;(1) X6 is D or R;optionally wherein the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of the aforesaid amino acids in (a)-(f); and(ii) [B] comprises SPHKSG (SEQ ID NO: 946).148. The AAV particle of embodiment 147, wherein(a) X1 is: T, M, A, or I;(b) X2 is: E, I or D;(c) X3 is: N, Q, Y, I, M, or V; id) X4 is G.(e) X5 is H; and(f) X6 is D.149. The AAV particle of embodiment 147 or 148, wherein [A] comprises:(i) TINGHD (SEQ ID NO: 5297), MPEGHD (SEQ ID NO: 5298). MEGGHD (SEQ ID NO: 5299), MEYGHD (SEQ ID NO: 5300). AEWGHD (SEQ ID NO: 5301), CEWGHD (SEQ ID NO: 5302), ANNGQD (SEQ ID NO: 5303), IPEGHD (SEQ ID NO: 5304), ADMGHD (SEQ ID NO: 5305), IEYGHD (SEQ ID NO: 5306). ADYGHD (SEQ ID NO: 5307), IETGHD (SEQ ID NO: 5308), MEWGHD (SEQ ID NO: 5309), CEYGHD (SEQ ID NO: 5310), RINGHD (SEQ ID NO: 5311). MEIGHD (SEQ ID NO: 5312). LEYGHD (SEQ ID NO: 5313), ADWGHD (SEQ ID NO: 5314). IEIGIID (SEQ ID NO: 5315), TIKDND (SEQ ID NO: 5316), DIMGHD (SEQ ID NO: 5317), FEQGHD (SEQ ID NO: 5318), MEFGHD (SEQ ID NO: 5319), CDQGHD (SEQ ID NO: 5320), LPEGHD (SEQ ID NO: 5321), IENGHD (SEQ ID NO: 5322), MESGHD (SEQ ID NO: 5323), AEIGHD (SEQ ID NO: 5324), VEYGHD (SEQ ID NO: 5325), TSNGDD (SEQ ID NO: 5326), IEVGHD (SEQ ID NO: 5327), MEMGHD (SEQ ID NO: 5328), AEVGHD (SEQ ID NO: 5329), MDAGHD (SEQ ID NO: 5330), VEWGHD (SEQ ID NO: 5331), AEQGHD (SEQ ID NO: 5332), LEWGHD (SEQ ID NO: 5333), MELGHD (SEQ ID NO: 5334). METGHD (SEQ ID NO: 5335), MEAGHD (SEQ ID NO: 5336), TINRQR (SEQ ID NO: 5337), IESGHD (SEQ ID NO: 5338), TAKDHD (SEQ ID NO: 5339), MEVGHD (SEQ ID NO: 5340), CEIGHD (SEQ ID NO: 5341), ATNGHD (SEQ ID NO: 5342), NIDGGHD (SEQ ID NO: 5343), QEVGHD (SEQ ID NO: 5344). ADQGHD (SEQ ID NO: 5345), NMNGHD (SEQ ID NO: 5346), TPWEHD (SEQ ID NO: 5347), IEMGHD (SEQ ID NO: 5348), TANEHD (SEQ ID NO: 5349), QQQGHD (SEQ ID NO: 5350), TPQDHD (SEQ ID NO: 5351). HDWGHD (SEQ ID NO: 5352), IEGGIID (SEQ ID NO: 5353)(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i), e.g., any 2, 3, 4, or 5 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no more than four modifications relative to any of the amino acid sequences in (i); or(iv) an amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).150. The AAV particle of any one of embodiments 147-149, wherein [A][B] comprises:(i) TINGHDSPHKR (SEQ ID NO: 5354), MPEGHDSPHKS (SEQ ID NO: 5355), MEGGHDSPHKS (SEQ ID NO: 5356), MEYGHDSPHKS (SEQ ID NO: 5357), AEWGHDSPHKS (SEQ ID NO: 5358), CEWGHDSI-TIKS (SEQ ID NO: 5359). ANNGQDSPHKS (SEQ ID NO: 5360), IPEGHDSPHKS (SEQ ID NO: 5361), ADMGHDSPHKS (SEQ ID NO: 5362), IEYGHDSPHKS (SEQ ID NO: 5363), ADYGHDSPHKS (SEQ ID NO: 5364), IETGIIDSPHKS (SEQ ID NO: 5365), MEWGHDSPHKS (SEQ ID NO: 5366), CEYGHDSPHKS (SEQ ID NO: 5367), RINGED SPHKS (SEQ ID NO: 5368), MEIGHDSPHKS (SEQ ID NO: 5369), LEYGHDSPHKS (SEQ ID NO: 5370), ADWGHDSPHKS (SEQ ID NO: 5371), IEIGHDSPHKS (SEQ ID NO: 5372), TIKDNDSPHKS (SEQ ID NO: 5373), DIMGHDSPHKS (SEQ ID NO: 5374), FEQGHDSPHKS (SEQ ID NO: 5375), MEFGHDSPHKS (SEQ ID NO: 5376), CDQGHDSPHKS (SEQ ID NO: 5377), LPEGHDSPHKS (SEQ ID NO: 5378), IENGHDSPHKS (SEQ ID NO: 5379), MESGHDSPHKS (SEQ ID NO: 5380), AEIGHDSPHKS (SEQ ID NO: 5381), VEYGHDSPHKS (SEQ ID NO: 5382), TSNGDDSPHKS (SEQ ID NO: 5383), IEVGHDSPHKS (SEQ ID NO: 5384), MEMGHDSPHKS (SEQ ID NO: 5385), AEVGHDSPHKS (SEQ ID NO: 5386), MDAGHDSPHKS (SEQ ID NO: 5387), VEWGHDSPHKS (SEQ ID NO: 5388), AEQGHDSPHKS (SEQ ID NO: 5389), LEWGHDSPHKS (SEQ ID NO: 5390), MELGHDSI-TIKS (SEQ ID NO: 5391), METGHDSPHKS (SEQ ID NO: 5392), MEAGHDSPI IKS (SEQ ID NO: 5393), TINRQRSPHKS (SEQ ID NO: 5394). IESGIIDSPHKS (SEQ ID NO: 5395), TAKDHDSPHKS (SEQ ID NO: 5396), MEVGHDSPHKS (SEQ ID NO: 5397), CEIGHDSPHKS (SEQ ID NO: 5398), ATNGHDSPHKS (SEQ ID NO: 5399), MDGGHDSPHKS (SEQ ID NO: 5400), QEVGHDSPHKS (SEQ ID NO: 5401), ADQGHDSPHKS (SEQ ID NO: 5402), NMNGHDSPHKS (SEQ ID NO: 5403), TPWEHDSPHKS (SEQ ID NO: 5404), 1EMGHDSPHKS (SEQ ID NO: 5405), TANEHDSPHKS (SEQ ID NO: 5406), TINGHDSPHKS (SEQ ID NO: 5407), QQQGHDSPHKS (SEQ ID NO: 5408), TPQDHDSPHKS (SEQ ID NO: 5409), HDWGHDSPHKS (SEQ ID NO: 5410), IEGGHDSPHKS (SEQ ID NO: 5411)(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i), e.g., any 2, 3, 4. 5, 6, 7, 8. 9, or 10 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no more than four modifications relative to arty of the amino acid sequences in (i); or(iv) an amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).151. The AAV particle of any one of embodiments 147-150, wherein 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), Nat 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), numbered according to SEQ ID NO: 138.152. The AAV particle of any one of embodiments 147-151, wherein the AAV capsid variant further comprises an R at position 456, numbered according to SEQ ID NO: 138.153. The AAV particle of any one of embodiments 147-151, wherein the AAV capsid variant further comprises an L at position 456, numbered according to SEQ ID NO: 138.154. The AAV particle of any one of embodiments 147-153, wherein the AAV capsid variant further comprises an H at position 457 and an R at position 458, numbered according to SEQ ID NO: 138.155. The AAV particle of any one of embodiments 147-153, wherein the AAV capsid variant further comprises a K at position 457 and an N at position 460, numbered according to SEQ ID NO: 138.156. The AAV particle of any one of embodiments 147-153, wherein the AAV capsid variant further comprises a T at position 458, an H at position 459, and an S at position 460, numbered according to SEQ ID NO: 138.157. The AAV particle of any one of embodiments 147-151, wherein the AAV capsid variant further comprises an R at position 456, an R al position 457, and an R at position 458, numbered according to SEQ ID NO: 138.158. The AAV particle of any one of embodiments 147-157, wherein [A][B] is present in loop IV.159. The AAV particle of any one of embodiments 147-158, wherein [A] is present immediately subsequent to position 449, numbered according to SEQ ID NO: 138.160. The AAV particle of any one of embodiments 147-159, wherein [A] replaces positions 450-453 (e.g,, T450, 1451 , N452, G453), numbered according to SEQ ID NO: 138,161. The AAV particle of any one of embodiments 147-160, wherein [A] is present immediately subsequent to position 449, and wherein [A] replaces positions 450-453 (e.g., T450, 1451, N452,G453), numbered according to SEQ ID NO: 138.162. The AAV particle of any one of embodiments 147-161, wherein [A][B] replaces positions 450-455 (e.g., T450, 1451, N452, G453, S454, G455), numbered according to SEQ ID NO: 138.163. The AAV particle of any one of embodiments 147-162, wherein [A][B] is present immediately subsequent to position 449. and wherein [A][B] replaces positions 450-455 (e.g., T450, 1451. N452,G453, S454, G455). numbered according to SEQ ID NO: 138.164. The AAV particle of any one of embodiments 147-163, wherein [B] is present immediately subsequent [A], and replaces positions 454 and 455 (e.g., S454 and G455), numbered according to SEQ ID NO: 138.165. The AAV particle of any one of embodiments 147-164, wherein [B] is present immediately subsequent to position 455, numbered according to SEQ ID NO: 4, 36, 981, or 982.166. The AAV particle of any one of embodiments 147-165, wherein [B] is present immediately subsequent to [A],167. The AAV particle of any one of embodiments 147-166, wherein the AAV capsid variant comprises, from N-terminus to C -terminus, [A][B],168. An adeno-associated vims (AAV) particle comprising an AAV capsid variant (e.g., an AAV9 capsid variant) and a viral genome comprising a p-glucocerebrosidase 1 (GBA1)-encoding sequence(e.g„ encoding a human GBA1 protein), wherein the AAV capsid variant comprises an amino acid sequence having the following formula: [N1j-[N2]-[N3] (SEQ ID NO: 6407), wherein:(i) [N1] comprises X1, X2, and X3, wherein X2 is S and X3 is G;(ii) [N2] comprises the amino acid sequence SPH; and(iii) [N3 ] comprises X4, X5, and X6, wherein X5 is K.169. The AAV particle of embodiment 168, wherein:(i) X4 of [N3] is S, T, N, or A; and(ii) X5 of [N3] is A. V, T, S, G, R, L, or N; optionally wherein the AAV capsid variant comprises an amino acid modification, e.g.. a conseivative substitution, of any of the aforesaid amino acids in (i) or (ii).170. The AAV particle of embodiment 168 or 169, wherein X4 is S and / or X5 is A.171. The AAV particle of any one of embodiments 168-170, wherein [N3] comprises SK, TK, NK, AK, KA, K V, KT, KS, KG, KR, KL, or KN.172. The AAV particle of any one of embodiments 168-171, wherein [N3] is or comprises SKA, SK V, SKT, SKS, SKG, SKR, TKA, NKA, SKL, SKN, or AKA.173. The AAV particle of any one of embodiments 168-172, wherein [N3] is or comprises SKA.174. The AAV particle of any one of embodiments 168-173, wherein [N2]-[N3] comprises SPHSK (SEQ ID NO: 4701), SPHTK (SEQ ID NO: 4725), SPUNK (SEQ ID NO: 4726), or SI-TIAK (SEQ ID NO: 4727).175. The AAV particle of any one of embodiments 168-174, wherein [N2]-[N3] is or comprises:(i) SPHSKA (SEQ ID NO: 941), SPHSKV (SEQ ID NO: 4737), SPHSKT (SEQ ID NO: 4731), SPHSKS (SEQ ID NO: 962), SPHSKG (SEQ ID NO: 4732), SPHSKR (SEQ ID NO: 978), SPHTKA (SEQ ID NO: 4739), SPHNKA (SEQ ID NO: 4734), SPHSKL (SEQ ID NO: 960), SPHSKN (SEQ ID NO: 4735), or SPHAKA (SEQ ID NO: 4736);(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i), e.g., any 2, 3, 4, or 5 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no more than four modifications relative to any of the amino acid sequences in (i); or(iv) an amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).176. The AAV particle of any one of embodiments 168-175, wherein [N2]-[N3] is or comprises SPHSKA (SEQ ID NO: 941).177. The AAV particle of any one of embodiments 168-176, wherein the AAV capsid variant comprises an amino acid other than G at position 453 (e.g., M, T, I, E, S, A, N, V, L, K, H, P, R, W, or D), numbered according to SEQ ID NO: 138 or 981.178. The AAV particle of any one of embodiments 168-177, wherein the AAV capsid variant comprises the amino acid G at position 453, numbered according to SEQ ID NO: 138 or 981.179. The AAV particle of any one of embodiments 168-178, wherein X1 of [NT] is G, M, T, I, E, S, A, N, V, L, K, H, P, R, W, or D; optionally wherein the AAV capsid variant comprises an amino acid modification, e.g.. a conservative substitution, of any of the aforesaid amino acids.180. The AAV particle of any one of embodiments 168-179, wherein [N1] comprises SG, GS, MS, TS, IS, ES, SS, AS, NS, VS, LS, KS, HS, PS, RS, WS, or DS.181. The AAV particle of any one of embodiments 168-180, wherein [N1] is or comprises: GSG, MSG, TSG, ISG, ESG, SSG, ASG, NSG, VSG. LSG, KSG, HSG, PSG. RSG, WSG, or DSG.182. The AAV particle of any one of embodiments 168-181, wherein [N1] is or comprises GSG.183. The AAV particle of any one of embodiments 168-182, wherein [N1]-[N2] comprises SGSPH(SEQ ID NO: 4752).184. The AAV particle of any one of embodiments 168-183, wherein [N1]-[N2] is or comprises:(i) GSGSPH (SEQ ID NO: 4695), MSGSPH (SEQ ID NO: 4798), TSGSPH (SEQ ID NO: 4800), ISGSPH (SEQ ID NO: 4801), ESGSPH (SEQ ID NO: 4803), SSGSPH (SEQ ID NO: 4804), ASGSPH (SEQ ID NO: 4806), NSGSPH (SEQ ID NO: 4807), VSGSPH (SEQ ID NO: 4786). ESGSPH (SEQ ID NO: 4808), KSGSPH (SEQ ID NO: 4810), HSGSPH (SEQ ID NO: 4811), PSGSPH (SEQ ID NO: 4813), RSGSPH (SEQ ID NO: 4815), WSGSPH (SEQ ID NO: 4817). DSGSPH (SEQ ID NO: 4818);(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i), e.g., any 2. 3, 4, or 5 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no more than four modifications relative to any of the amino acid sequences in (i); or(iv) an amino acid sequence comprising one, two, or three but no more Ilian four different amino acids, rela tive to any one of the amino acid sequences in (i).185. The AAV particle of any one of embodiments 168-184, wherein [N1]-[N2]-[N3] is or comprises:(i) GSGSPHSKA (SEQ ID NO: 4697), GSGSPHSKV (SEQ ID NO: 4956), MSGSPHSKA (SEQ ID NO: 4957), TSGSPHSKA (SEQ ID NO: 4959), ISGSPHSKA (SEQ ID NO: 4960), GSGSPHSKT (SEQ ID NO: 4962), ESGSPHSKA (SEQ ID NO: 4963). SSGSPHSKA (SEQ ID NO: 4964), GSGSPHSKS (SEQ ID NO: 4953), ASGSPHSKA (SEQ ID NO: 4966). NSGSPHSKA (SEQ ID NO: 4967), VSGSPHSKA (SEQ ID NO: 4913), LSGSPHSKA (SEQ ID NO: 4968), KSGSPHSKA (SEQ ID NO: 4970), GSGSPHSKG (SEQ ID NO: 4972). GSGSPHSKR (SEQ ID NO: 4945), HSGSPHSKA (SEQ ID NO: 4973), PSGSPHSKA (SEQ ID NO: 4975), RSGSPHSKA (SEQ ID NO: 4977), GSGSPHTKA (SEQ ID NO: 4978), WSGSPHSKA (SEQ ID NO: 4980), DSGSPHSKA (SEQ ID NO: 4981), GSGSPHNKA (SEQ ID NO: 4983). GSGSPHSKT (SEQ ID NO: 4943), GSGSPHSKN (SEQ ID NO: 4994), or GSGSPHAKA (SEQ ID NO: 4995);(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i), e.g., any 2, 3, 4, 5, 6, 7, 8, or 9 amino acids, e.g., consecutive amino acids, thereof:(iii) an amino acid sequence comprising one, two, or three but no more than four modifications relative to any of the amino acid sequences in (i); or(iv) an amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).186. The AAV particle of any one of embodiments 168-185, wherein [N1]-[N2]-[N3] is or comprises GSGSPHSKA (SEQ ID NO: 4697).187. The AAV capsid variant of any one of embodiments 168-186, which comprises an amino acid other than Q at position 456 (e.g., R, P, H, L, K, I, G, S, M, or E), an amnio acid other than N at position 457 (e.g., D, V, S, P, T, G, Y, W, E, R, H, K, F, A, I, L, or M), an amino acid other than Q at position 458 (e.g., R, L, A, P, H, T, I, F, K, V, M, G, W, Y, S, E, N, or D), an amino acid other than Q at position 459 (e.g., H, K, A, L, P, E, M, I, S, N, R, Y, C, V, T, W, D, G), and / or an amino acid other than T at position 460 (e.g., I, N, S, H, R. L, D, Y, A. or Q), numbered according to SEQ ID NO: 138. i 88. The AAV particle of any one of embodiments 168-187, wherein the AAV capsid variant comprises an amino acid other than Q at position 462 (e.g., R, P, H, L, K, I, G, S, M, or E), an amino acid other than N at position 463 (e.g., D, V, S, P, T, G, Y, W, E, R, H, K, F, A, I, L , or M), an amino acid other than Q at position 464 (e.g., R, L, A. P, H. T, I, F, K, V, M, G, W, Y, S, E, N. or D), an amino acid other than Q at position 465 (e.g., H, K, A, L, P, E, M, I, S, N, R, Y, C. V, T, W, D, G), and / or an amino acid other than T at position 466 (e.g., I. N, S. H, R, L, D, Y, A, or Q), numbered according to SEQ ID NO: 981.189. The AAV particle of any one of embodiments 168-188, wherein the AAV capsid variant comprises the amino acid Q at position 456, the amino acid N at position 457, the amino acid Q at position 458, the amino acid Q at position 459, and / or the amino acid T at position 460, numbered according to SEQ ID NO: 138.190. The AAV particle of any one of embodiments 168-189, wherein the AAV capsid variant comprises the amino acid Q at position 462, the amino acid N at position 463, the amino acid Q at position 464. the amino acid Q at position 465, and / or the amino acid T at position 466, numbered according to SEQ ID NO: 981.191. The AAV particle of any one of embodiments 168-190, wherein the AAV capsid variant further comprises [N4] wherein [N4] comprises X7, X8, X9, X10, and X11, wherein:(a) X7 is Q, R, P, H, L, K, I, G, S, M, or E:(b) X8 is N, D, V, S, P, T, G, Y, W, E, R, H, K, F, A, 1, L, or M;(c) X9 is Q, R, L, A. P, H, T, I, F, K. V, M, G, W, Y, S, E, N, D;(d) X10 is Q, H, K, A, L, P. E, M, I, S, N, R, Y. C, V, T, W, D, G; and(e) X11 is T, I, N, S, H, R, L, D, Y, A, Q; optionally wherein the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of the aforesaid amino acids in (a)-(e).192. The AAV particle of embodiment 191, wherein [N4] is or comprises:(i) QNQQT (SEQ ID NO: 5412), QNRHT (SEQ ID NO: 5413), RDQQT (SEQ ID NO: 5414), PNLQT (SEQ ID NO: 5415), HVRQT (SEQ ID NO: 5416), PNQHT (SEQ ID NO: 5417), QSQQT (SEQ ID NO: 5418), QNQQI (SEQ ID NO: 5419), QPAKT (SEQ ID NO: 5420), QTQQN (SEQ ID NO: 5421), QNLAT (SEQ ID NO: 5422), QNQLT (SEQ ID NO: 5423), QGQQT (SEQ ID NO: 5424), LNRQS (SEQ ID NO: 5425), HNQQT (SEQ ID NO: 5426), QNPPT (SEQ ID NO: 5427), QNLQT (SEQ ID NO: 5428), QYQQT (SEQ ID NO: 5429), QDQET (SEQ ID NO: 5430), QNHQT (SEQ ID NO: 5431), QDQQT (SEQ ID NO: 5432), HWQQT (SEQ ID NO: 5433), PNQQT (SEQ ID NO: 5434), QNQLI (SEQ ID NO: 5435), PEQQT (SEQ ID NO: 5436), QRTMT (SEQ ID NO: 5437), QNQQH (SEQ ID NO: 5438), LHQHT (SEQ ID NO: 5439), QHRIT (SEQ ID NO: 5440), QYIHT (SEQ ID NO: 5441), QKFET (SEQ ID NO: 5442), QFPST (SEQ ID NO: 5443), HNQQR (SEQ ID NO: 5444). QAIKT (SEQ ID NO: 5445), QNRQT (SEQ ID NO: 5446), QYQHT (SEQ ID NO: 5447), QNPQS (SEQ ID NO: 5448), QHQLT (SEQ ID NO: 5449), QSPPT (SEQ ID NO: 5450), QAKL.T (SEQ ID NO: 5451). KSQQT (SEQ ID NO: 5452), QDRPT (SEQ ID NO: 5453), QSQQL (SEQ ID NO: 5454), QAFHT (SEQ ID NO: 5455), QKQQD (SEQ ID NO: 5456), QNAQT (SEQ ID NO: 5457), HNQLT (SEQ ID NO: 5458), QNQQY (SEQ ID NO: 5459), QKLNT (SEQ ID NO: 5460), QNVQT (SEQ ID NO: 5461), QAQQT (SEQ ID NO: 5462), QNLQA (SEQ ID NO: 5463), QTPPT (SEQ ID NO: 5464), QYQHA (SEQ ID NO: 5465), QGQQA (SEQ ID NO: 5466), QPPAT (SEQ ID NO: 5467), QERPT (SEQ ID NO: 5468), QDLQT (SEQ ID NO: 5469), QAMHT (SEQ ID NO: 5470), LNQQT (SEQ ID NO: 5471), QHPST (SEQ ID NO: 5472), PGLQT (SEQ ID NO: 5473), QGIRT (SEQ ID NO: 5474), QAPAT (SEQ ID NO: 5475), QSQQI (SEQ ID NO: 5476), QIPPT (SEQ ID NO: 5477), QTQLT (SEQ ID NO: 5478), QAPST (SEQ ID NO: 5479), QNTYA (SEQ ID NO: 5480), QNQHI (SEQ ID NO: 5481), QNHLT (SEQ ID NO: 5482), QIGMT (SEQ ID NO: 5483), LNKQT (SEQ ID NO: 5484), QLQQT (SEQ ID NO: 5485), QRMST (SEQ ID NO: 5486), QGILT (SEQ ID NO: 5487), QDRQT (SEQ ID NO: 5488), RDWQT (SEQ ID NO: 5489). QNTHD (SEQ ID NO: 5490), PNLQI (SEQ ID NO: 5491), QERST (SEQ ID NO: 5492), QNYQT (SEQ ID NO: 5493), QRTCT (SEQ ID NO: 5494), QIGHT (SEQ ID NO: 5495), QGAIT (SEQ ID NO: 5496), QVPPT (SEQ ID NO: 5497), QVQQI (SEQ ID NO: 5498), LMRQT (SEQ ID NO: 5499), QYSVT (SEQ ID NO: 5500), QAITT (SEQ ID NO: 5501), QKTLT (SEQ ID NO: 5502), QNQWT (SEQ ID NO: 5503), QLHHT (SEQ ID NO: 5504), QNIII (SEQ ID NO: 5505), QGHHT (SEQ ID NO: 5506), QSKVT (SEQ ID NO: 5507), QLPST (SEQ ID NO: 5508), 1GKQT (SEQ ID NO: 5509), QAIHT(SEQ ID NO: 5510), QHGLT (SEQ ID NO: 5511), QFMCT (SEQ ID NO: 5512), QHLQT (SEQ ID NO: 5513), QNHQN (SEQ ID NO: 5514), QPART (SEQ ID NO: 5515), QSLQT (SEQ ID NO: 5516), QSQLT (SEQ ID NO: 5517), QDRQS (SEQ ID NO: 5518), QMPST (SEQ ID NO: 5519), QGSLT (SEQ ID NO: 5520), QVPAT (SEQ ID NO: 5521), QDKQT (SEQ ID NO: 5522), HYQQT (SEQ ID NO: 5523), QVPST (SEQ ID NO: 5524), RGEQT (SEQ ID NO: 5525), PGQQT (SEQ ID NO: 552.6), QSLQI (SEQ ID NO: 5527), LEQQT (SEQ ID NO: 5528), QNQST (SEQ ID NO: 5529), QKVIT (SEQ ID NO: 5530). QNNDQ (SEQ ID NO: 5531), QSVHT (SEQ ID NO: 5532). QPLGT (SEQ ID NO: 5533), HNQET (SEQ ID NO: 5534), QNLQI (SEQ ID NO: 5535). QIQQT (SEQ ID NO: 5536), QVRNT (SEQ ID NO: 5537), PSNQT (SEQ ID NO: 5538), QVGHT (SEQ ID NO: 5539), QRDIT (SEQ ID NO: 5540), QMPNT (SEQ ID NO: 5541), RGLQT (SEQ ID NO: 5542), QKQQT (SEQ ID NO: 5543), PSLQT (SEQ ID NO: 5544), QRDQT (SEQ ID NO: 5545), QAKGT (SEQ ID NO: 5546), QSAHT (SEQ ID NO: 5547), QSTMT (SEQ ID NO: 5548), QREMT (SEQ ID NO: 5549), QYRAT (SEQ ID NO: 5550), QWQQT (SEQ ID NO: 5551), QRMNT (SEQ ID NO: 5552), GDSQT (SEQ ID NO: 5553), QKIST (SEQ ID NO: 5554), PSMQT (SEQ ID NO: 5555), SPRQT (SEQ ID NO: 5556), MEQQT (SEQ ID NO: 5557), QYQNT (SEQ ID NO: 5558). QHQQT (SEQ ID NO: 5559), INQQT (SEQ ID NO: 5560), PNQQH (SEQ ID NO: 5561), ENRQT (SEQ ID NO: 5562). QTQQA (SEQ ID NO: 5563), or QNQAT (SEQ ID NO: 5564);(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i), e.g., any 2. 3, or 4 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no more than four modifications relative to any of the amino acid sequences in (i); or(iv) an amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).193. The AAV particle of embodiment 191 or 192, wherein [N1]-[N2]-[N3]-[N4] is or comprises:(i) the amino acid sequence of any of SEQ ID NOs: 200 or 2887-3076;(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i), e.g., any 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or 13 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no more than four modifications relative to any of the amino acid sequences in (i); or(iv) an amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).194. The AAV particle of any one of embodiments 191-193, wherein [N1]-[N2]-[N3]-[N4] is or comprises GSGSPHSKAQNQQT (SEQ ID NO: 200).195. The AAV particle of any one of embodiments 191-193, wherein [N1]-[N2]-[N3]-[N4j is or comprises VSGSPHSKAQNQQT (SEQ ID NO: 903).196. The AAV particle of any one of embodiments 168-195, wherein the AAV capsid variant comprises an amino acid other than K at position 449 (e.g., T, E, or N), T at position 450 (e.g., S, E, A, N, V, Q, or G), an amino acid other than I at position 451 (e.g., F, E, V, L, D, S, C, T, A, N, H, R, G, or W), and / or an amino acid other than N at position 452 (e.g., I, P, K, R, H. S, M, Q, D, T, L, A, Y, V, F, E, W, or G). numbered according to SEQ ID NO: 138 or 981.197. The AAV particle of any one of embodiments 168-196, wherein the AAV capsid variant comprises the amnio acid K at position 449, the amino acid T at position 450, the amino acid I at position 451, and / or the amino acid N at position 452, numbered according to SEQ ID NO: 138 or 981.198. The AAV particle of any one of embodiments 168-197, wherein the AAV capsid variant further comprises [N0], wherein [N0] comprises XA, XB, Xc, and XD, wherein:(a) XAis K, T, E, or N;(b) XBis T, S, E, A, N, V, Q, or G;(c) XCis I, F, E, V, L, D, S, C, T. A, N, H, R, G, or W; and(d) XDis N, I, P, K, R, H, S, M, Q, D, T, L, A, Y, V, F, E, W, or G; optionally wherein the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of the aforesaid amino acids in (a)-(d).199. The AAV particle of embodiment 198, wherein [N0] is or comprises:(i) Kill (SEQ ID NO: 5565), KTFP (SEQ ID NO: 5566), KTEK (SEQ ID NO: 5567), KTVN (SEQ ID NO: 5568), KTFN (SEQ ID NO: 5569), KTIN (SEQ ID NO: 5570), TTIN (SEQ ID NO: 5571), KSIN (SEQ ID NO: 5572), KTER (SEQ ID NO: 5573), KELH (SEQ ID NO: 5574), KAIN (SEQ ID NO: 5575), KTDN (SEQ ID NO: 5576), KTFH (SEQ ID NO: 5577), KTSN (SEQ ID NO: 5578), F.TIN (SEQ ID NO: 5579), NTIN (SEQ ID NO: 5580), KTF.N (SEQ ID NO: 5581), KTSS (SEQ ID NO: 5582), KTCN (SEQ ID NO: 5583), KTEH (SEQ ID NO: 5584), KAEM (SEQ ID NO: 5585), KATN (SEQ ID NO: 5586). KAIK (SEQ ID NO: 5587), KTDK (SEQ ID NO: 5588), KTFK (SEQ ID NO: 5589), KSDQ (SEQ ID NO: 5590). KTEI (SEQ ID NO: 5591), KTID (SEQ ID NO: 5592), KNTN (SEQ ID NO: 5593), KTET (SEQ ID NO: 5594), KIEL (SEQ ID NO: 5595), KNIN (SEQ ID NO: 5596), KTEA (SEQ ID NO: 5597), KTAN (SEQ ID NO: 5598), NTIY (SEQ ID NO: 5599), KTFS (SEQ ID NO: 5600), KTES (SEQ ID NO: 5601), KTTN (SEQ ID NO: 5602), KTED (SEQ ID NO: 5603), KTNN (SEQ ID NO: 5604), KEVH (SEQ ID NO: 5605), KTIS (SEQ ID NO: 5606), KTVR (SEQ ID NO: 5607), KTDR (SEQ ID NO: 5608), ETIK (SEQ ID NO: 5609), KNHI(SEQ ID NO: 5610), KESD (SEQ ID NO: 5611), KTIK (SEQ ID NO: 5612), KTDL (SEQ ID NO: 5613), KTVP (SEQ ID NO: 5614), KTVI (SEQ ID NO: 5615). KAEH (SEQ ID NO: 5616), KNCL (SEQ ID NO: 5617), KTVK (SEQ ID NO: 5618), KNAD (SEQ ID NO: 5619), KTIT (SEQ ID NO: 5620), KNCV (SEQ ID NO: 5621), KNAL (SEQ ID NO: 5622). KVIN (SEQ ID NO: 5623), KTEF (SEQ ID NO: 5624), KTRE (SEQ ID NO: 5625), KQGE (SEQ ID NO: 5626), KSEK (SEQ ID NO: 5627), KNVN (SEQ ID NO: 562.8), KGGE (SEQ ID NO: 5629), KEFV (SEQ ID NO: 5630), KSDK (SEQ ID NO: 5631), KTEQ (SEQ ID NO: 5632), KEVQ (SEQ ID NO: 5633), KTEY (SEQ ID NO: 5634), KNOW (SEQ ID NO: 5635), KTDV (SEQ ID NO: 5636), KSDI (SEQ ID NO: 5637), KNSI (SEQ ID NO: 5638), KNSL (SEQ ID NO: 5639), KEW (SEQ ID NO: 5640), KEEP (SEQ ID NO: 5641), KSEL (SEQ ID NO: 5642), KTWQ (SEQ ID NO: 5643), KTEV (SEQ ID NO: 5644), KAVN (SEQ ID NO: 5645), KGVL (SEQ ID NO: 5646), KTEG (SEQ ID NO: 5647), KTRD (SEQ ID NO: 5648), KTGN (SEQ ID NO: 5649), KNAI (SEQ ID NO: 5650), KAEN (SEQ ID NO: 5651), KAET (SEQ ID NO: 5652), KTVH (SEQ ID NO: 5653), KETA (SEQ ID NO: 5654). KNNL (SEQ ID NO: 5655), EAIN (SEQ ID NO: 5656), KSLN (SEQ ID NO: 5657), KTIP (SEQ ID NO: 5658), orKTIH (SEQ ID NO: 5659);(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i). e.g., any 2. or 3 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no more than four modifications relative to any of the amino acid sequences in (i); or(iv) an amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).200. The AAV particle of embodiment 198 or 199, wherein [N0]-[NI]-[N2]-[N3]-[N4] is or comprises:(i) the amino acid sequence of any one of SEQ ID NOs: 3239-3526 or 3591-3605;(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i), e.g., any 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no more than four modifications relative to any of the amino acid sequences in (i); or(iv) an amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).201. The AAV particle of any one of embodiments 198-200, wherein [N0]-[N 1]-[N2]-[N3]-[N4] is or comprises KTINGSGSPHSKAQNQQT (SEQ ID NO: 5660).202. The AAV particle of any one of embodiments 198-200, wherein [N0]-[N1]-[N2]-[N3]-[N4] is or comprises KTERVSGSPHSKAQNQQT (SEQ ID NO: 3589).203. An adeno-associated virus (AAV) particle comprising an AAV capsid variant (e.g., an AAV9 capsid variant) and a viral genome comprising a p-glucocerebrosidase 1 (GBA1)-encoding sequence (e.g,, encoding a human GBA1 protein), wherein the AAV capsid variant comprises an amino acid sequence having the following formula: [N1]-[N2]-[N3] (SEQ ID NO: 6408), wherein:(i) [N1] comprises X1, X2, and X3, wherein X2 is an amino acid other than S and X3 is an amino acid other than G:(ii) [N2] comprises the amino acid sequence SPH: and(iii) [N3] comprises X4, X5, and X6, wherein X4 is K.204. The AAV particle of embodiment 203, wherein:optionally wherein the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of the aforesaid amino acids in (i) or (ii),2.05. The AAV particle of embodiment 203 or 204, wherein X5 is S and / or X6 is G.206. The AAV particle of any one of embodiments 203-205, wherein [N3] comprises KS, KI, KT, KR, KH, KY, KL, KM, SG, IG, TG, RG, SA, SL, SE, SV, SR, SW, SN, HG, YG, SQ, IV, SK, LW, MG, or MA.207. The AAV particle of any one of embodiments 203-206, wherein [N3] is or comprises KSG, K1G, KTG, KRG, KSA, KSL, KSE, KSV, KSR, KSW, KSN, KHG, KYG, KSQ, KIV, KSK, KLW, KMG, or KMA.208. The AAV particle of any one of embodiments 203-207, wherein [N3] is or comprises KSG.209. The AAV particle of any one of embodiments 203-208, wherein [N2]-[N3] comprises SPHKS (SEQ ID NO: 4704), SPHKI (SEQ ID NO: 4713), SPIIKT (SEQ ID NO: 4711), SPHKR (SEQ IDNO: 4717), NPHKS (SEQ ID NO: 5661). SPHKH (SEQ ID NO: 4728), SPHKY (SEQ ID NO: 4715).SPHKL (SEQ ID NO: 4714), or SPHKM (SEQ ID NO: 4729).210. The AAV particle of any one of embodiments 203-209, wherein [N2]-[N3] is or comprises:(i) SPHKSG (SEQ ID NO: 946), SPHK1G (SEQ ID NO: 958), SPHKTG (SEQ ID NO: 4738), SPHKRG (SEQ ID NO: 974), NPHKSG (SEQ ID NO: 5662), SPHKSA (SEQ ID NO: 977), SPURS; . (SEQ ID NO: 4740), SPHKSE (SEQ ID NO: 4741), SPHKSV (SEQ ID NO: 4742), SPHKSR (SEQ ID NO: 951), SPHKSW (SEQ ID NO: 4743), SPHKSN (SEQ ID NO: 4744), SPHKHG (SEQ ID NO: 4745), SPHKYG (SEQ ID NO: 966), SPHKSQ (SEQ ID NO: 4746), SPHKIV (SEQ ID NO: 5663), SPHKSK (SEQ ID NO: 4747), SPHKLW (SEQ ID NO: 4748), SPHKMG (SEQ ID NO: 4750), or SPHKMA (SEQ ID NO: 4751);(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i), e.g., any 2, 3, 4, or 5 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no more than four modifications relative to any of the amino acid sequences in (i); or(iv) an amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).211. The AAV particle of any one of embodiments 203-210, wherein [N2]-[N3] is or comprises SPHKSG (SEQ ID NO: 946).212. The AAV particle of any one of embodiments 203-211 , wherein the AAV capsid variant comprises an amino acid other than G at position 453 (e.g. , A, K, W, R, L , I, M, N, T, E, Q, Y, H, F, or V), numbered according to SEQ ID NO: 138 or 981.213. The AAV particle of any one of embodiments 203-212, wherein the AAV capsid variant comprises the amino acid G at position 453, numbered according to SEQ ID NO: 138 or 981.214. The AAV particle of any one of embodiments 203-214, wherein:(i) X1 of [N1] is G, A. K, W. R, L. 1, M, N, T, E, Q, Y, H, F, or V;(ii) X2 of [N1] is H, Y, R, Q. N, P. or D;(iii) X3 of [N1] is D, E, G, V, or N; optionally wherein the AAV capsid variant comprises an amino acid modification, e.g.. a conse rvative substitution, of any of the aforesaid amino acids in (i). (ii), or (iii).215. TheAAV particle of any one of embodiments 203-214, wherein X2 of [N1] is H and X3 of [N1] is D.216. The AAV particle of any one of embodiments 203-215, wherein X1 of [N1] is G, X2 of [N1] isH and X3 of [N 1] is D.217. The AAV particle of any one of embodiments 203-216, wherein [N1] comprises GH, HD, GY, GR, GQ, AH, GN, KH, GP, WH, PH, LH, IH, MH, GD, NH, TH, EH, QH, YH, HH, EH, VH. YD, HE. RG, QD, RD. ND, PD, QV, DD, I IN. or NG. 218. The AAV capsid variant of any one of embodiments 203-217, wherein [N1] is or comprises GHD, GYD, GHE, GRG, GQD, GRD, AHD, GND, KHD, GPD, WHD. RHD, LHD, GQV, IHD. MHD, GDD, GNH, NHD, TTID, GNG, EHD, QIID, YIID, HHD, FI ID, or VHD.219. The AAV particle of any one of embodiments 203-218, wherein [N1] is or comprises GHD.220. The AAV particle of any one of embodiments 203-219, wherein [N1]-[N2] comprises HDSPH (SEQ ID NO: 4703).221. The AAV particle of any one of embodiments 203-220, wherein [N1 ]-[N2] is or comprises:(i) GHDSPH (SEQ ID NO: 4784), GYDSPH (SEQ ID NO: 4829), GHESPH (SEQ ID NO: 4793), GRGSPH (SEQ ID NO: 4788), GHDNPH (SEQ ID NO: 5664), GQDSPH (SEQ ID NO: 4785), GRDSPH (SEQ ID NO: 4831), AHDSPH (SEQ ID NO: 5665), GNDSPH (SEQ ID NO: 4832), KHDSPH (SEQ ID NO: 5666). GPDSPH (SEQ ID NO: 4833), WHDSPH (SEQ ID NO: 5667), RHDSPH (SEQ ID NO: 5668), LHDSPH (SEQ ID NO: 5669), GQVSPH (SEQ ID NO: 4835), IHDSPH (SEQ ID NO: 5670), MHDSPH (SEQ ID NO: 5671), GDDSPH (SEQ ID NO: 4792), GIINSPI-I (SEQ ID NO: 4836), NTIDSPH (SEQ ID NO: 5672), TIIDSPH (SEQ ID NO: 5673), GNGSPH (SEQ ID NO: 4805), EHDSPH (SEQ ID NO: 5674), QHDSPH (SEQ ID NO: 5675), YHDSPH (SEQ ID NO: 5676), HHDSPH (SEQ ID NO: 5677), FHDSPH (SEQ ID NO: 5678), or VHDSPH (SEQ ID NO: 5679);(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i), e.g., any 2, 3, 4, or 5 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no more than four modifications relative to any- of the amino acid sequences in (i); or(iv) an amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).222. The AAV particle of any one of embodiments 203-221, wherein [N1]-[N2]-[N3] is or comprises:(i) GHDSPHKSG (SEQ ID NO: 4698), GIIDSPI I KIG (SEQ ID NO: 4996). GY DSPHKSG (SEQ ID NO: 4997), GHESPHKSG (SEQ ID NO: 4998), GHDSPHKTG (SEQ ID NO: 4999),GRGSPHKRG (SEQ ID NO: 5000), GHDNPHKSG (SEQ ID NO: 5680), GQDSPHKSG (SEQ IDNO: 4908), GHDSPHKSA (SEQ ID NO: 4940), GHDSPHKSL (SEQ ID NO: 5001), GHDSPHKSE(SEQ ID NO: 5003), GRDSPHKSG (SEQ ID NO: 5004), AHDSPHKSG (SEQ ID NO: 5681),GNDSPHKSV (SEQ ID NO: 5005), AHDSPHKIG (SEQ ID NO: 5682), GHESPHKSA (SEQ ID NO: 4939), GQDSPHKIG (SEQ ID NO: 5006), GHDSPHKSV (SEQ ID NO: 5007), GHDSPHKSR (SEQ ID NO: 4942), KHDSPHKSG (SEQ ID NO: 5683), GPDSPHKIG (SEQ ID NO: 5008), GPDSPHKSG (SEQ ID NO: 5009), GHDSPHKSW (SEQ ID NO: 5010), WHDSPHKSG (SEQ ID NO: 5684), RHDSPHKSG (SEQ ID NO: 5685), GHDSPHKSN (SEQ ID NO: 5011), GHDSPHKRG (SEQ ID NO: 4937), GHDSPHKRG (SEQ ID NO: 5013), LHDSPHKSG (SEQ ID NO: 5686), GQVSPHKSG (SEQ ID NO: 5014), IHDSPHKSG (SEQ ID NO: 5687), MHDSPHKSG (SEQ ID NO: 5688), GDDSPHKSV (SEQ ID NO: 5015), GHNSPHKSG (SEQ ID NO: 5016). NHDSPHKSG (SEQ ID NO: 5689), TI IDSPHKSG (SEQ ID NO: 5690), GNGSPHKRG (SEQ ID NO: 5017), EHDSPHKSG (SEQ ID NO: 5691), GHDSPHKYG (SEQ ID NO: 5018), GHDSPHKSQ (SEQ ID NO: 5019), QHDSPHKSG (SEQ ID NO: 5692), RHDSPHKIV (SEQ ID NO: 5693), YHDSPHKSG (SEQ ID NO: 5694), GNDSPHKIG (SEQ ID NO: 5020), HHDSPHKSG (SEQ ID NO: 5695), GHDSPHKSK (SEQ ID NO: 5021), FHDSPHKSG (SEQ ID NO: 5696), GHDSPHKLW (SEQ ID NO: 5022), VHDSPHKSG (SEQ ID NO: 5697), GHDSPHKMG (SEQ ID NO: 5024), GHDSPHKMA (SEQ ID NO: 5025), or GDDSPHKSG (SEQ ID NO: 4938);(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i), e.g., any 2. 3, 4, 5, 6. 7, 8, or 9 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no more than four modifications relative to any of the amino acid sequences in (i); or(iv) an amino acid sequence comprising one, two, or three but no more Ilian four different amino acids, relative to any one of the amino acid sequences in (i).223. The AAV particle of any one of embodiments 203-222, wherein [N1]-[N2]-[N3] is or comprises GHDSPHKSG (SEQ ID NO: 4698).224. The AAV particle of any one of embodiments 203-223, wherein the AAV capsid variant comprises an amino acid other than Q at position 456 (e.g., R, P, H, K, L, V, A, E, or I), an amino acid other than N at position 457 (e.g., I, K, S, H, R, T, D, Y, L, W, F, A, Q, or M), an amino acid other than Q at position 458 (e.g,, R, V, K, P, Y, H, L, I, E, or M), an amino acid other than Q at position 459 (e.g., H, L, E, P, W, D, I, V, S, K, R, C, M, or N), and / or an amino acid other than T at position 460 (e.g., A, E, K, S, I, P, G, orN), numbered according to SEQ ID NO: 138.225. The AAV particle of any one of embodiments 203-224, wherein the AAV capsid variant comprises an amino acid other than Q at position 462 (e.g., R, P, H, K. L, V, A, E, or I), an amino acid other than N at position 463 (e.g., I, K, S, H, R, T, D, Y, L, W, F, A, Q, or M), an amino acid other than Q at position 464 (e.g., R, V, K, P, Y, H, L, I, E, or M), an amino acid other than Q atposition 465 (e.g., H, L, E, P, W, D, I, V, S, K, R, C, M, or N), and / or an amino acid other than T at position 466 (e.g., A, E, K, S, I, P, G, orN), numbered according to SEQ ID NO: 982.226. The AAV particle of any one of embodiments 203-225, wherein the AAV capsid variant comprises the amino acid Q at position 456, the amino acid N at position 457, the amino acid Q at position 458. the amino acid Q at position 459, and / or the amino acid T at position 460, numbered according to SEQ ID NO: 138.227. The AAV particle of any one of embodiments 203-226, wherein the AAV capsid variant comprises the amino acid Q at position 462, the amino acid N at position 463, the amino acid Q at position 464, the amino acid Q at position 465, and / or the amino acid T at position 466, numbered according to SEQ ID NO: 138.228. The AAV particle of any one of embodiments 203-227, wherein the AAV capsid variant further comprises [N4], wherein [N4] comprises X7, X8, X9, X10, and X11 , wherein:(a) X7 is Q, R, P, H, L, K, I, G, S, M, or E;(b) X8 is N, D, V, S, P, T. G, Y, W, E, R, H, K, F, A. I, L, or M;(c) X9 is Q. R, L, A, P, H, T, I, F. K, V, M. G, W. Y, S. E, N, D:(d) X10 is Q, H, K, A. L, P, E, M, I, S, N, R, Y, C, V, T, W, D, G; and(e) X11 is T, I, N, S, H, R. L, D, Y, A. Q; optionally wherein the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of the aforesaid amino acids in (a)-(e).229. The AAV particle of embodiment 228, wherein [N4] is or comprises:(i) QNQQT (SEQ ID NO: 5412), QIRQT (SEQ ID NO: 5698), QNQHA (SEQ ID NO: 5699), QKQQT (SEQ ID NO: 5543), QSVQT (SEQ ID NO: 5700), RSQQT (SEQ ID NO: 5701), QNKLE (SEQ ID NO: 5702), QNQQK (SEQ ID NO: 5703), QHQQA (SEQ ID NO: 5704), QIQHT (SEQ ID NO: 5705), PRQQT (SEQ ID NO: 5706), HTQQT (SEQ ID NO: 5707), QRQHT (SEQ ID NO: 5708), QSQQT (SEQ ID NO: 5418), QNQQS (SEQ ID NO: 5709), RNQET (SEQ ID NO: 5710). QTQLT (SEQ ID NO: 5478), KNQQT (SEQ ID NO: 5711), QDQQT (SEQ ID NO: 5432). HNQQT (SEQ ID NO: 5426), QNQLT (SEQ ID NO: 5423), QTQQT (SEQ ID NO: 5712), QTQQI (SEQ ID NO: 5713), QSKQA (SEQ ID NO: 5714), QNQPP (SEQ ID NO: 5715), QSPQT (SEQ ID NO: 5716), QNYQT (SEQ ID NO: 5493). QNHQT (SEQ ID NO: 5431), QNRQT (SEQ ID NO: 5446). QNQQG (SEQ ID NO: 5717), QNHLT (SEQ ID NO: 5482), QYQHT (SEQ ID NO: 5447). QNQWT (SEQ IDNO: 5503), QNQHT (SEQ ID NO: 5718), QTRQT (SEQ ID NO: 5719), QNLHT (SEQ ID NO: 5720), LNQQT (SEQ ID NO: 5471), QNQET (SEQ ID NO: 5721), QHLQT (SEQ ID NO: 5513), LNQPT (SEQ ID NO: 5722), QNQDT (SEQ ID NO: 5723), RNQQT (SEQ ID NO: 5724), QNLLT(SEQ ID NO: 5725), QLVIT (SEQ ID NO: 5726), RTQET (SEQ ID NO: 5727), QTHQT (SEQ ID NO: 5728), QNQPA (SEQ ID NO: 5729), QDQHT (SEQ ID NO: 5730), QSQHT (SEQ ID NO: 5731), RNQQI (SEQ ID NO: 5732), VRQQT (SEQ ID NO: 5733), QNQHS (SEQ ID NO: 5734), AWQQT (SEQ ID NO: 5735). QSVPT (SEQ ID NO: 5736). QNIQP (SEQ ID NO: 5737), QNHLN (SEQ ID NO: 5738), LDQQT (SEQ ID NO: 5739), PDQQS (SEQ ID NO: 5740), ESQQT (SEQ ID NO: 5741), QNKQT (SEQ ID NO: 5742). QRQLT (SEQ ID NO: 5743), QIIVT (SEQ ID NO: 5744), QKQST (SEQ ID NO: 5745), QSHQT (SEQ ID NO: 5746), QFWT (SEQ ID NO: 5747), QNLQT (SEQ ID NO: 5428), QNQQI (SEQ ID NO: 5419), QSQPT (SEQ ID NO: 5748), QNEQT (SEQ ID NO: 5749), QSLQT (SEQ ID NO: 5516), RNRQT (SEQ ID NO: 5750), QSKQT (SEQ ID NO: 5751), QNPLT (SEQ ID NO: 5752), RDQKT (SEQ ID NO: 5753), HNQQN (SEQ ID NO: 5754), QWKR.T (SEQ ID NO: 5755), QSQQI (SEQ ID NO: 5476), QAQQT (SEQ ID NO: 5462), QNHQI (SEQ ID NO: 5756), QNQQA (SEQ ID NO: 5757), QNQLN (SEQ ID NO: 5758), QTQPT (SEQ ID NO: 5759), INQQT (SEQ ID NO: 5560), QKQLT (SEQ ID NO: 5760), RNQLA (SEQ ID NO: 5761), RNQQS (SEQ ID NO: 5762), ISIQT (SEQ ID NO: 5763), QNQQN (SEQ ID NO: 5764), QSQQS (SEQ ID NO: 5765), QTVCT (SEQ ID NO: 5766), QYQQI (SEQ ID NO: 5767), QQIMT (SEQ ID NO: 5768), QNEQS (SEQ ID NO: 5769), LNHQT (SEQ ID NO: 5770), QMIHT (SEQ ID NO: 5771), RNHQS (SEQ ID NO: 5772), QKMNT (SEQ ID NO: 5773), QSQQN (SEQ ID NO: 5774), QYQHA (SEQ ID NO: 5465);(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i), e.g.. any 2, 3, or 4 amino acids, e.g.. consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no more than four modifications relative to any of the amino acid sequences in (i); or(iv) an amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).230. The AAV particle of embodiment 228 or 229, wherein [N1]-[N2]-[N3]-[N4] is or comprises:(i) the amino acid sequence of any of SEQ ID NOs: 201 or 3160-3237;(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i), e.g., any 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or 13 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no more than four modifications relative to any of the amino acid sequences in (i); or(iv) an amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).231. The AAV particle of any one of embodiments 228-230, wherein [N1]-[N2]-[N3]-[N4] is or comprises GHDSPHKSGQNQQT (SEQ ID NO: 201).232. The AAV particle of any one of embodiments 203-231, wherein the AAV capsid variant comprises an amino acid other than K at position 449 (e.g., T), T at position 450 (e.g., A, S, I, V, N, E, Y, C, G, W, or Q), an amino acid other titan I at position 451 (e.g., E, V, S, T, N, D, C, G, Q, L, P, A), and / or an amino acid other than N at position 452 (e.g., S, Y, I, K, F, T, D, E, G, V, L, A, M, Q, H, P, or R), numbered according to SEQ ID NO: 138 or 982.233. The AAV particle of any one of embodiments 203-232, wherein the AAV capsid variant comprises the amino acid K at position 449. the amino acid T at position 450, the amino acid I at position 451, and / or the amino acid N at position 452, numbered according to SEQ ID NO: 138 or 982.234. The AAV particle of any one of embodiments 203-233, wherein the AAV capsid variant further comprises [N0], wherein [N0] comprises XA, XB, Xc, and XD, wherein:(a) XAis K or T;(b) XBis T, A, S, I, V, N, E, Y, C, G, W, or Q;(c) Xcis I, E, V, S, T, N, D, C, G, Q, L, P, A; and(d) XDis N, S. Y. I, K, F, T, D, E, G, V, L. A, M, Q, H, P. or R ; optionally wherein the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of the aforesaid amino acids in (a)-(d).235. The AAV particle of embodiment 234, wherein [N0] is or comprises:(i) KAIN (SEQ ID NO: 5575), KT1N (SEQ ID NO: 5570), KTES (SEQ ID NO: 5601), TTIN (SEQ ID NO: 5571), KS1N (SEQ ID NO: 5572), KTVN (SEQ ID NO: 5568), KSIY (SEQ ID NO: 5775), KTSN (SEQ ID NO: 5578), KTTN (SEQ ID NO: 5602), KIIN (SEQ ID NO: 5776), KTIS (SEQ ID NO: 5606), KA1I (SEQ ID NO: 5777), KTIK (SEQ ID NO: 5612), KTEF (SEQ ID NO: 5624), KTIT (SEQ ID NO: 5620), KTNN (SEQ ID NO: 5604), KTID (SEQ ID NO: 5592), KAIS (SEQ ID NO: 5778), KTVD (SEQ ID NO: 5779), KTIE (SEQ ID NO: 5780), KTEG (SEQ ID NO: 5647), KVIN (SEQ ID NO: 5623), KAVN (SEQ ID NO: 5645), KT1Y (SEQ ID NO: 5781), KTDN (SEQ ID NO: 5576), KTCN (SEQ ID NO: 5583), KNW (SEQ ID NO: 5782), KIEL (SEQ ID NO: 5595), KTDA (SEQ ID NO: 5783). KTEV (SEQ ID NO: 5644), KSEL (SEQ ID NO: 5642), KTEM (SEQ ID NO: 5784), KTEQ (SEQ ID NO: 5632), KTII (SEQ ID NO: 5565), KIVN (SEQ ID NO: 5785), KTEK (SEQ ID NO: 5567), KEEN (SEQ ID NO: 5581), KIGN (SEQ ID NO: 5786), KEVM (SEQ ID NO: 5787), KYQV (SEQ ID NO: 5788), KTEA (SEQ ID NO: 5597), KATN (SEQ ID NO: 5586), KTEH (SEQ ID NO: 5584), KTVE (SEQ ID NO: 5789), KAID (SEQ ID NO: 5790), KTIM (SEQ ID NO: 5791), KEVG (SEQ ID NO: 5792), KSEM (SEQ ID NO: 5793), KAQQ (SEQ ID NO: 5794), KCGE (SEQ ID NO: 5795), KASN (SEQ ID NO: 5796), KTET (SEQ ID NO: 5594), KTIG (SEQ ID NO: 5797), KTDP (SEQ ID NO: 5798), KEL V (SEQ ID NO: 5799), KELM (SEQ ID NO:5800), KNEI (SEQ ID NO: 5801), KTPN (SEQ ID NO: 5802), KITN (SEQ ID NO: 5803), KTDI (SEQ ID NO: 5804), KTDQ (SEQ ID NO: 5805), KGIN (SEQ ID NO: 5806), KSET (SEQ ID NO: 5807), KSEK (SEQ ID NO: 5627), KWSA (SEQ ID NO: 5808), KELA (SEQ ID NO: 5809), KQTQ (SEQ ID NO: 5810), KGAD (SEQ ID NO: 5811), KVGE (SEQ ID NO: 5812), KANE (SEQ ID NO: 5813), KTDT (SEQ ID NO: 5814), KTCI (SEQ ID NO: 5815). KELR (SEQ ID NO: 5816). KCQI (SEQ ID NO: 5817), KGVM (SEQ ID NO: 5818), KA CD (SEQ ID NO: 5819), KNEE (SEQ ID NO: 5820), KAAE (SEQ ID NO: 5821), KGQN (SEQ ID NO: 5822), KNEE (SEQ ID NO: 5823), KTSI (SEQ ID NO: 5824), KAEH (SEQ ID NO: 5616), KCDQ (SEQ ID NO: 5825), KEIL (SEQ ID NO: 5826), KTER (SEQ ID NO: 5573), KNAI (SEQ ID NO: 5650), KTDK (SEQ ID NO: 5588), KTPD (SEQ ID NO: 5827), KTIH (SEQ ID NO: 5659), or KTEI (SEQ ID NO: 5591):(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i), e.g., any 2, or 3 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no more than four modifications relative to any of the amino acid sequences in (i); or(iv) an amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).236. The AAV particle of embodiment 234 or 235, wherein [N0]-[N1]-[N2]’[N3]-[N4] is or comprises:(i) the amino acid sequence of any one of SEQ ID NOs: 3606-3836;(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i), e.g., any 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no more than four modifications relative to any of the amino acid sequences in (i); or(iv) an amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).237. The AAV particle of any one of embodiments 234-236, wherein [N0]-[N1]-[N2]-[N3]-[N4] is or comprises KTINGHDSPHKSGQNQQT (SEQ ID NO: 5828).238. The AAV particle of any one of embodiments 234-236, wherein [N0]-[N 1]-[N2]-[N3]-[N4] is or comprises KAEIGHDSPIIKSGQNQQT (SEQ ID NO: 1754).239. The AAV particle of any one of embodiments 234-236, wherein [N0]-[N1]-[N2]-[N3]-[N4] is or comprises KTEKMSGSPHSKAQNQQT (SEQ ID NO: 3241).240. The AAV particle of any one of embodiments 168-239, wherein [N1]-[N2]-[N3] is present in loop IV, e.g., numbered according to SEQ ID NO: 4, 36, 138, 981, or 982.241. The AAV particle of any one of embodiments 198-202 or 234-240, wherein [N0] and [N4] are present in loop IV, e.g., numbered according to SEQ ID NO: 4, 36, 138, 981 , or 982.242. The AAV particle of any one of embodiments 198-202 or 234-241, wherein [N0] is present immediately subsequent to position 448, numbered according to the amino acid sequence of SEQ ID NO: 4. 36, 138, 981, or 982.243. The AAV particle of any one of embodiments 198-202 or 234-242, wherein [N0] replaces positions 449-452 (e.g., K449, T450, 1451, and N452), numbered according to SEQ ID NO: 4, 36,138, 981, or 982.244. The AAV particle of any one of embodiments 198-202 or 234-243, wherein [N0] is present immediately subsequent to position 448 and wherein [N0] replaces positions 449-452 (e.g., K449, T450, 1451, and N452), numbered according to SEQ ID NO: 4, 36, 138, 981, or 982,245. The AAV particle of any one of embodiments 198-202. or 234-244, wherein [N0] corresponds to positions 449-452 (e.g., K449, T450, 1451. and N452) of any one of SEQ ID NOs: 4, 36, 138, 981, or 982.246. The AAV particle of any one of embodiments 168-245, wherein [N1] is present immediately subsequent to position 452, numbered according to SEQ ID NO: 4, 36, 138, 981, or 982.247. The AAV particle of any one of embodiments 168-246, wherein [N1] replaces positions 453-455 (e.g., G453, S454, and G455), numbered according to SEQ ID NO: 4, 36, 138, 981, or 982.248. The AAV particle of any one of embodiments 168-246, wherein [N1] replaces position 453 (e.g., G453), numbered according to SEQ ID NO: 4, 36, 138, 981, or 982.249. The AAV particle of any one of embodiments 168-177, 179-181, 183-185. 187-193, 195-200, 202, or 240-246, wherein:(i) X1 of [N1] replaces position 453 (e.g., G453);(ii) X2 of [N1] corresponds to position 454 (e.g., S454); and(iii) X3 of [N1] corresponds to position 455 (e.g., G455), wherein (i), (ii), and (iii) are numbered according to SEQ ID NO: 138 or SEQ ID NO: 981250. The AAV particle of any one of embodiments 168-176, 178-201, or 240-246, wherein:(i) X1 of [N1] corresponds to position 453 (e.g., G453);(ii) X2. of [N1] corresponds to position 454 (e.g,, S454); and(iii) X3 of [N1] corresponds to position 455 (e.g., G455); wherein (i), (ii), and (iii) are numbered according to SEQ ID NO: 138 or SEQ ID NO: 981.251. The AAV particle of any one of embodiments 203-248, wherein:(i) X1 of [N1] corresponds to position 453 (e.g., G453):(ii) X2 of [N1] replaces position 454 (e.g., S454): and(iii) X3 of [N1] replaces position 455 (e.g., G455), wherein (i), (ii), and (iii) are numbered according to SEQ ID NO: 138 or SEQ ID NO: 982.252. The AAV particle of any one of embodiments 203-248 or 251 , wherein [N1 ] corresponds to positions 453-455 (e.g., G453, H454, D455) of SEQ ID NO 982.253. The AAV particle of any one of embodiments 168-176, 178-201, 240-247, or 2.50, wherein [N1] corresponds to positions 453-455 (e.g., G453. S454, G455) of SEQ ID NO: 138 or 981.2.54. The AAV particle of any one of embodiments 168-2.53, wherein [N2] is present immediately subsequent to position 455, numbered according to of SEQ ID NO: 4, 36, 138, 981, or 982.255. The AAV particle of any one of embodiments 168-254, wherein [N2] corresponds to positions 456-458 (e.g., S456, P457, and H458) of SEQ ID NO: 981 or 982.256. The AAV particle of any one of embodiments 168-254, wherein [N2] corresponds to positions 456-458 (e.g., S456, P457, and H458) of any one of SEQ ID NOs: 4 or 36-59.257. The AAV particle of any one of embodiments 168-256, wherein [N2] is present immediately subsequent to [N1].258. The AAV particle of any one of embodiments 168-202, 240-247, or 249-257, wherein [N3] corresponds to positions 459-460 (e.g., S459, K460. A461) of SEQ ID NO: 981.259. The AAV particle of any one of embodiments 168-202, 240-247, or 249-257, wherein [N3] corresponds to positions 459-460 (e.g., S459, K460, A461) of SEQ ID NO: 36, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 57, or 59.260. The AAV particle of any one of embodiments 168-259, wherein [N2]-[N3] is present immediately subsequent to position 455, numbered according to any one of SEQ ID NOs: 4, 36, 138, 981, or 982,261. The AAV particle of any one of embodiments 168-259, wherein [N2]-[N3] is present immediately subsequent to position 455, numbered according to SEQ ID NO: 981.262. The AAV particle of any one of embodiments 168-261, wherein [N2]-[N3] corresponds to positions 456-461 (e.g., S456, P457, H458, S459, K460, A461) of SEQ ID NO: 981.263. The AAV particle of any one of embodiments 168-262, wherein [N2]-[N3] corresponds to positions 456-461 (e.g., S456, P457, H458, S459, K460, A461) of any one of SEQ ID NOs: 36, 38, 39, 40, 41, 42, 43, 44, 45. 46, 47, 48, 49, 50, 51 , 52. 53, 54, 55, 57, or 59.264. The AAV particle of any one of embodiments 203-257 or 259-261, wherein [N3] corresponds to positions 459-460 (e.g., K459. S460, G461) of SEQ ID NO: 982.265. The AAV particle of any one of embodiments 203-257 or 259-261, wherein [N3] corresponds to positions 459-460 (e.g., K459, S460, G461) of SEQ ID NO: 37.266. The AAV particle of any one of embodiments 203-265, wherein [N2]-[N3] is present immediately subsequent to position 455, numbered according to SEQ ID NO: 982.267. The AAV particle of any one of embodiments 203-246, 248, 252, 255, 257, 260, 263-266, wherein [N3] replaces positions 454 and 455 (e.g., S454 and G455), numbered according to SEQ ID NO: 138.268. The AAV particle of any one of embodiments 203-246, 248, 252, 255, 257, 260, 263-267, wherein [N3] is present immediately subsequent to [N2] and replaces positions 454 and 455 (e.g.,S454 and G455), numbered according to SEQ ID NO: 138.269. The AAV particle of any one of embodiments 203-246, 248, 252, 255, 257, 260, 263-268, wherein [N3] is present immediately subsequent to [N1]-[N2] and replaces positions 454 and 455 (e.g., S454 and G455), numbered according to SEQ ID NO: 138.270. The AAV particle of any one of embodiments 203-257, 260, 264-269, wherein [N2]-[N3] corresponds to positions 456-461 (e.g., S456, P457, H458, K459, S460, G461) of SEQ ID NO: 982.271. The AAV particle of any one of embodiments 203-257, 260, 264-270, wherein [N2]-[N3] corresponds to positions 456-461 (e.g,, S456, P457, H458, K459, S460, G461) of SEQ ID NO: 37.272. The AAV particle of any one of embodiments 191-202 or 228-271, wherein [N4] is present immediately subsequent to position 455, numbered according to SEQ ID NO: 138.273. The AAV particle of any one of embodiments 191-202 or 228-272, wherein [N4] replaces positions 456-460 (e.g., Q456, N457, Q458, Q459, and T460), numbered according to SEQ ID NO: 138.274. The AAV particle of any one of embodiments 191 -202 or 228-273, wherein [N4] corresponds to positions 462-466 (e.g., Q462, N463, Q464, Q465, and T466) of SEQ ID NO: 981 or 982.275. The AAV particle of any one of embodiments 191-202. or 228-273, wherein [N4] corresponds to positions 462-466 of any one of SEQ ID NOs: 4 or 36-59.276. The AAV particle of any one of embodiments 191-202 or 228-274, wherein [N4] corresponds to positions 456-460 (e.g., Q456, N457, Q458, Q459, and T460) of SEQ ID NO: 138.277. The AAV particle of any one of embodiments 191-202 or 228-276, wherein [N2]-[N3]-[N4] replaces positions 456-460 (e.g., Q456, N457, Q458, Q459, and 1460), numbered according to SEQ ID NO: 138.278. The AAV particle of any one of embodiments 191-202 or 228-277, wherein [N2]-[N3]-[N4] is present immediately subsequent to position 455. and wherein [N2]-[N3]-[N4] replaces positions 456- 460 (e.g., Q456, N457, Q458, Q459, and T460), numbered according to SEQ ID NO: 138.279. The AAV particle of any one of embodiments 191-202 or 228-278, wherein [N1]-[N2]-[N3]-[N4] replaces positions 453-460 (e.g.. G453, S454, G455. Q456, N457, Q458, Q459. and T460), numbered according to SEQ ID NO: 138.280. The AAV particle of any one of embodiments 191-202 or 228-279, wherein [N1]-[N2]-[N3]-[N4] is present immediately subsequent to position 452, and wherein [N1]-[N2]-[N3]-[N4] replacespositions 453-460 (e.g., G453, S454, G455, Q456, N457, Q458, Q459, and T460), numbered according to SEQ ID NO: 138.281. The AAV particle of any one of embodiments 191-202, 240-247, 249, 250, 253-263, 266, or 272-280, wherein [N1]-[N2]-[N3]-[N4] corresponds to positions 453-466 (e.g., G453, S454, G455, S456, P457, H458, S459, K460. A461, Q462, N463, Q464. Q465, and T466) of SEQ ID NO: 981.282. The AAV particle of any one of embodiments 168-202, 240-247, 249, 250, 253-263, 266, or 272-280, wherein [N1]-[N2]-[N3] corresponds to positions 453-461 (e.g., G453, S454, G455. S456, P457, H458, S459, K460, A461) of SEQ ID NO: 981.283. The AAV particle of any one of embodiments 228-257, 260, 261, 264-282, wherein [N1]-[N2]- [N3]-[N4] corresponds to positions 453-466 (e.g., G453, H454, D455, S456, P457, H458, K459, S460, G461, Q462, N463, Q464, Q465, T466) of SEQ ID NO: 982.284. The AAV particle of any one of embodiments 203-257, 260, 261 , 264-283, wherein [N1]-[N2]- [N3] corresponds to positions 453-461 (e.g., G453, H454, D455, S456, P457, H458, K459, S460, G461 ) of SEQ ID NO: 982.285. The AAV particle of any one of embodiments 228-257, 260, 261, 264-282, wherein [N1]-[N2]-[N3]-[N4] corresponds to positions 453-466 of any one of SEQ ID NOs: 4 or 36-59.286. The AAV particle of any one of embodiments 198-202 or 234-286, wherein [N0]-|N l]-[N2j- [N3]-[N4] replaces positions 449-460 (e.g., K449, T450, 1451, N452, G453, S454, G455, Q456, N457, Q458, Q459, and T460), numbered according to SEQ ID NO: 138.287. The AAV particle of any one of embodiments 198-202 or 234-286, wherein [N0]-[N1]-[N2]- [N3]-[N4] is present immediately subsequent to position 448, and wherein [N0]-[N1]-[N2]-[N3]-[N4] replaces positions 449-460 (e.g., K449, T450, 1451, N452, G453, S454, G455, Q456, N457, Q458, Q459, and T460), numbered according to SEQ ID NO: 138.288. The AAV particle of any one of embodiments 198-202, 240-247, 249, 250, 253-263, 266, 272- 281, 286, or 287, wherein [N0]-[N1]-[N2]-[N3]-[N4] corresponds to positions 449-466 (e.g., K449, T450, 1451, N452, G453, S454, G455, S456, P457, H458, S459. K460, A461, Q462, N463. Q464, Q465, T466) of SEQ ID NO: 981.289. The AAV particle of any one of embodiments 234-257, 260, 261, 264-284, 286, or 287, wherein [N0]-[N1]-[N2]-[N3]-[N4] corresponds to positions 449-466 (e.g., K449, T450, 1451, N452, G453, H454, D455, S456, P457, H458, K459, S460, G461, Q462, N463, Q464, Q465, T466) of SEQ ID NO: 982.290. The AAV particle of any one of embodiments 234-257, 260, 261, 264-284, 286, or 287, wherein [N'O]-[N1]-[N2]-[N3]-[N4] corresponds to positions 449-466 of any one of SEQ ID NOs: 4 or 36-59.291. The AAV particle of any one of embodiments 191-202 or 228-290, wherein [N4] is present immediately subsequent to position 461, numbered according to SEQ ID NO: 4, 36, 981, or 982.292. The AAV particle of any one of embodiments 191-202 or 228-291, wherein [N4] replaces positions 462-466 (e.g., Q462, N463, Q464, Q465, and T466), numbered according to SEQ ID NO: 4, 36, 981, or 982.293. The AAV particle of any one of embodiments 191-202 or 228-292, wherein [N2]-[N3]-[N4] replaces positions 462-466 (e.g., Q462, N463, Q464, Q465, and T466), numbered according to SEQ ID NO: 4, 36, 981, or 982.294. The AAV particle of any one of embodiments 191-202 or 228-293, wherein [N2]-[N3]-[N4] is present immediately subsequent to position 455, and wherein [N2]-[N3]-[N4] replaces positions 462- 466 (e.g., Q462, N463, Q464, Q465, and T466), numbered according to SEQ ID NO: 4, 36, 981, or 982.295. The AAV particle of any one of embodiments 168-294, wherein the AAV capsid variant comprises, from N-terminus to C-terminus, [N2]-[N3].296. The AAV particle of any one of embodiments 168-295, wherein the AAV capsid variant comprises, from N-terminus to C-terminus, [N1]-[N2]-[N3].297. The AAV particle of any one of embodiments 168-296, wherein the AAV capsid variant comprises, from N-terminus to C-terminus, [N0]-[N1]-[N2]-[N3].298. The AAV particle of any one of embodiments 168-297, wherein the AAV capsid variant comprises, from N-terminus to C-terminus, [N1]-[N2]-[N3]-[N4J.299. The AAV particle of any one of embodiments 168-298, wherein the AAV capsid variant comprises, from N-terminus to C-terminus, [N0]-[N1]-[N2]-[N3]-[N4],300. An adeno-associated virus (AAV) particle comprising an AAV capsid variant (e,g., an AAV9 capsid variant) and a viral genome comprising a β-glucocerebrosidase 1 (GBA1)-encoding sequence (e.g,, encoding a human GBA1 protein), wherein the AAV capsid variant comprises the formula [A]- [B] (SEQ ID NO: 4696), wherein:(i) [A] comprises GSGSPH (SEQ ID NO: 4695); and(ii) [B] comprises X1 X2, X3, X4, and X5, wherein:(a) X1 is S, I, F, V, C, Y, W, R, P, L, Q, M, K, or G:(b) X2 is K, M, R, F, V, C, P, Y, L, W, G, N, S, T, I, or A;(c) X3 is A, Y, L, R, W, C, T, F, H, 1, P, M, K, S, V, G, Q, or N;(d) X4 is Q, M, F, K, H, R, C, W, P, V, L, G, S, Y, I, A, T, D, N, or E; and(e) X5 is A, N, Y, R, K, L, I, M, Q, S, C, W, F, T, G, V, or P; optionally wherein the AAV capsid variant comprises an amino acid modification, e.g., a conservative substitution, of any of the aforesaid amino acids in (a)-(e).301. The AAV particle of embodiment 300, wherein:(a) X1 is S, L, R, V, or P;(b) X2 is K, C, F . L, P, R, S. or V;(c) X3 is A, C, I . I, K, L, M, P, R, T, W, or Y:(d) X4 is Q, R, S. T, C. F, K, L, P or Y; and(e) X5 is N, R, S, T, K, M, Q or Y; optionally wherein the AAV capsid variant comprises an amnio acid modification, e.g., a conservative substitution, of any of the aforesaid amino acids in (a)-(e).302. The AAV particle of embodiment 300 or 301, wherein [B] comprises SKA, SMY, SKL, SKR, SKW, SRC, SFT, SKF, IVW, SKY, SCH, FPW, SKI, VYY, SLY, SKP, SRF, SRM, SVK, SWA, SLW, SFR, SKK, SYA, SCS, SGA, SFP, SFF, SMC, SKT. SGK, FYR, CRV, YGI, VNC, SLA, WSY, RWL, PSC, SSW, SKG, WW, SGC, STT, PKR, SKC, WAT, SFW, RIK, SKM, LRW, LPT, SYM, LLC, RCC, LCV, SYL, QGC, MAF, SFQ, SLC, RPW, RPR. SCP, SVR, SLP, VYH, SYT, LVY, YRY, SWL, CPA, SPP, RWT, PRK, PFV. SKS, WVA, SKV, CAL . SSC, SKN, LCT, STC, SKQ, KSG, SYY, SET, SCQ, FPF, SVF, GRY, AQA, AQN, YMN, AFY, LKR, RHR, AQK, WRL, CRN, TCN, FFL AQY. WQN, YFM, ARQ, HQN, IRR, YQN. YWN, AFS, FWN, AQC, MRN, KKN, APN, WKN, ARW, RPN, KVF, AFN, ACS, RLW, SRN, CPN, ACN, FRQ, PFN, FGN, CQN, LFW, IRK, KRN, RQN, VQN, IQN, AQR, PFR, AWN, RSY, LQN, WLN, RRA, AQT, GCT, RYT, TPN, ARM, CFL, PQN, WSN, FKN, KQN, APR, RYN, MIC, TQN, WKS, AAR, LTR, IRG, LVN,FQN, ACQ, WGL, ILR, QIN, ACI, ALR, AHA, CLN, AFV, AQF, RCN, MPC, KTS, PYN, AQS, TRN, LKN, AQM, CTN, PDN, RNY, ACR. CSV, ARI, LPK, SEQ, VRM, NSR, RKR, ARN, QRP, RW, GQN. YSN, QSN, AKG, CTS, FEN. AKK. KAQ. MYM, KAF, KLK, KRH, KWR, RCR, FTC, KFF, VWQ, KYF. KAR, CHQ, PWQ, KIR, YYQ, LYW, KPK, RFW, RMR, VKK, WAP, LAW, FRP, KKV, YAF, KAC, KRL, CSR. RCP, GAC, KFR, FFG, MCQ, KLF, KTR, GKR, YRQ, RVQ. GIQ, NCQ, KPF, LAW, KRS, SYQ, WLQ, KRR, KGC, KRY, GCQ, FTP, TTC, KRQ, KCF, VPQ, FWS, KFK. IKQ, KAP. FRY, KMI, RWQ, PTQ, KWK. YMR, KAA, LCQ, CCQ. CVQ, KLT, KLC, YLV, AFQ, KWG, KIL, FQI, KAL, KAH, LCL, PRQ, CPQ. VRY, VRC, KMP, KKT, LPY. YI-IQ, YTR, VYQ, RYQ, WLK, PAQ, MCT, PPD. WTQ, RKQ, KCS. FVQ. KLP, KSE, VAQ. LYQ, KVR, ALQ, SCT, KNS, KRK, CTQ, TCL, YAR, KQR, KRV, SGQ, YYS, LTC, CQS, KAK, KPQ, PFQ, KCT, or VFE.303. The AAV particle of any one of embodiments 300-302, wherein [B] comprises SKAQ (SEQ ID NO: 5829), SMYM (SEQ ID NO: 5830), SKAF (SEQ ID NO: 5831), SKLK (SEQ ID NO: 5832). SKRH (SEQ ID NO: 5833), SKWR (SEQ ID NO: 5834), SRCR (SEQ ID NO: 5835), SFTC (SEQ ID NO: 5836), SKFF (SEQ ID NO: 5837), IVWQ (SEQ ID NO: 5838), SKYF (SEQ ID NO: 5839), SKAR (SEQ ID NO: 5840). SCHQ (SEQ ID NO: 5841), FPWQ (SEQ ID NO: 5842), SKIR (SEQ ID NO: 5843). VYYQ (SEQ ID NO: 5844), SLYW (SEQ ID NO: 5845), SKPK (SEQ ID NO: 5846), SRFW (SEQ ID NO: 5847), SRMR (SEQ ID NO: 5848), SVKK (SEQ ID NO: 5849), SWAP (SEQ ID NO: 5850), SLWK (SEQ ID NO: 5851), SFRP (SEQ ID NO: 5852), SKKV (SEQ ID NO: 5853). SYAF (SEQ ID NO: 5854), SKAC (SEQ ID NO: 5855), SKRL (SEQ ID NO: 5856), SCSR (SEQ ID NO: 5857), SRCP (SEQ ID NO: 5858), SGAC (SEQ ID NO: 5859), SKFR (SEQ ID NO: 5860), SFPF (SEQ ID NO: 5861), SFFG (SEQ ID NO: 5862), SMCQ (SEQ ID NO: 5863), SKLF (SEQ ID NO: 5864), SKTR (SEQ ID NO: 5865), SGKR (SEQ ID NO: 5866), FYRQ (SEQ ID NO: 5867), CRVQ (SEQ ID NO: 5868), YGIQ (SEQ ID NO: 5869), VNCQ (SEQ ID NO: 5870), SKPF (SEQ ID NO: 5871), SLAW (SEQ ID NO: 5872), SKRS (SEQ ID NO: 5873), WSYQ (SEQ ID NO: 5874), RWLQ (SEQ ID NO: 5875), PSCQ (SEQ ID NO: 5876), SSWL (SEQ ID NO: 5877), SKRR (SEQ ID NO: 5878), SKGC (SEQ ID NO: 5879), VPWQ (SEQ ID NO: 5880), SKRY (SEQ ID NO: 5881), SGCQ (SEQ ID NO: 5882), SFTP (SEQ ID NO: 5883), STTC (SEQ ID NO: 5884), PKRQ (SEQ ID NO: 5885), SKCF (SEQ ID NO: 5886), WVPQ (SEQ ID NO: 5887), SFWS (SEQ ID NO: 5888), SKFK (SEQ ID NO: 5889). RIKQ (SEQ ID NO: 5890). SKAP (SEQ ID NO: 5891), SFRY (SEQ ID NO: 5892), SKMI (SEQ ID NO: 5893). LRWQ (SEQ ID NO: 5894), LPTQ (SEQ ID NO: 5895), SKWK (SEQ ID NO: 5896). SYMR (SEQ ID NO: 5897), SKAA (SEQ ID NO: 5898), LLCQ (SEQ ID NO: 5899), RCCQ (SEQ ID NO: 5900). LCVQ (SEQ ID NO: 5901), SKLT (SEQ ID NO: 5902), SKLC (SEQ ID NO: 5903), SYLV (SEQ ID NO: 5904), QGCQ (SEQ ID NO: 5905), MAFQ (SEQ ID NO: 5906), SKWG (SEQ ID NO: 5907), SKIL (SEQ ID NO: 5908), SFQI (SEQ ID NO: 5909), SKAL (SEQ ID NO: 5910), SKAH (SEQ ID NO: 5911), SLCL (SEQ ID NO: 5912), RPWQ (SEQ IDNO: 5913), RPRQ (SEQ ID NO: 5914), SCPQ (SEQ ID NO: 5915), SVRY (SEQ ID NO: 5916), SVRC (SEQ ID NO: 5917), SKMP (SEQ ID NO: 5918), SKKT (SEQ ID NO: 5919). SLPY (SEQ ID NO: 5920), VYHQ (SEQ ID NO: 5921). SYTR (SEQ ID NO: 5922), LVYQ (SEQ ID NO: 5923), YRYQ (SEQ ID NO: 5924), SWLK (SEQ ID NO: 592.5), CPAQ (SEQ ID NO: 5926), SMCT (SEQ ID NO: 5927), SPPD (SEQ ID NO: 5928), SKRN (SEQ ID NO: 5929), RWTQ (SEQ ID NO: 5930), PRKQ (SEQ ID NO: 5931), SKCS (SEQ ID NO: 5932). PFVQ (SEQ ID NO: 5933), SKLP (SEQ ID NO: 5934), SKSE (SEQ ID NO: 5935), WVAQ (SEQ ID NO: 5936), SLYQ (SEQ ID NO: 5937), SKVR (SEQ ID NO: 5938), CALQ (SEQ ID NO: 5939), SSCT (SEQ ID NO: 5940). SKNS (SEQ ID NO: 5941), SKRK (SEQ ID NO: 5942), LC'TQ (SEQ ID NO: 5943), STCL (SEQ ID NO: 5944), SY AR (SEQ ID NO: 5945), SKQR (SEQ ID NO: 5946), SKRV (SEQ ID NO: 5947), KSGQ (SEQ ID NO: 5948), SYYS (SEQ ID NO: 5949), SLTC (SEQ ID NO: 5950), SCQS (SEQ ID NO: 5951), SKAK (SEQ ID NO: 5952), SKPQ (SEQ ID NO: 5953), FPFQ (SEQ ID NO: 5954), SKCT (SEQ ID NO: 5955), SVFE (SEQ ID NO: 5956), GRYQ (SEQ ID NO: 5957), KAQA (SEQ ID NO: 5958), KAQN (SEQ ID NO: 5959), MYMN (SEQ ID NO: 5960), KAFY (SEQ ID NO: 5961). KLKR (SEQ ID NO: 5962), KRHR (SEQ ID NO: 5963), KAQK (SEQ ID NO: 5964), KWRL (SEQ ID NO: 5965), RCRN (SEQ ID NO: 5966), FTCN (SEQ ID NO: 5967), KFFI (SEQ ID NO: 5968), KAQY (SEQ ID NO: 5969). VWQN (SEQ ID NO: 5970), KYFM (SEQ ID NO: 5971), KARQ (SEQ ID NO: 5972). CHQN (SEQ ID NO: 5973), PWQN (SEQ ID NO: 5974), KIRR (SEQ ID NO: 5975), YYQN (SEQ ID NO: 5976), LYWN (SEQ ID NO: 5977), KPKR (SEQ ID NO: 5978), KAFS (SEQ ID NO: 5979), RFWN (SEQ ID NO: 5980), KAQC (SEQ ID NO: 5981), RMRN (SEQ ID NO: 5982), VKKN (SEQ ID NO: 5983), WAPN (SEQ ID NO: 5984), LWKN (SEQ ID NO: 5985), KARW (SEQ ID NO: 5986), FRPN (SEQ ID NO: 5987), KKVF (SEQ ID NO: 5988), YAFN (SEQ ID NO: 5989), KACS (SEQ ID NO: 5990), KRLW (SEQ ID NO: 5991), CSRN (SEQ ID NO: 5992), RCPN (SEQ ID NO: 5993), GACN (SEQ ID NO: 5994), KFRQ (SEQ ID NO: 5995), FPFN (SEQ ID NO: 5996), FFGN (SEQ ID NO: 5997), MCQN (SEQ ID NO: 5998), KLFW (SEQ ID NO: 5999), KTRK (SEQ ID NO: 6000), GKRN (SEQ ID NO: 6001), YRQN (SEQ ID NO: 6002), RVQN (SEQ ID NO: 6003), GIQN (SEQ ID NO: 6004), KAQR (SEQ ID NO: 6005), NCQN (SEQ ID NO: 6006), KPFR (SEQ ID NO: 6007), LAWN (SEQ ID NO: 6008), KRSY (SEQ ID NO: 6009), SYQN (SEQ ID NO: 6010). WLQN (SEQ ID NO: 6011), SCQN (SEQ ID NO: 6012), SWLN (SEQ ID NO: 6013), KRRA (SEQ ID NO: 6014), KAQT (SEQ ID NO: 6015). KGCT (SEQ ID NO: 6016), KRYT (SEQ ID NO: 6017), GCQN (SEQ ID NO: 6018), FTPN (SEQ ID NO: 6019), TTCN (SEQ ID NO: 6020), KARM (SEQ ID NO: 6021), KRQN (SEQ ID NO: 6022), KCFL (SEQ ID NO: 6023). VPQN (SEQ ID NO: 6024), FWSN (SEQ ID NO: 6025), KFKN (SEQ ID NO: 6026). IKQN (SEQ ID NO: 6027), KAPR (SEQ ID NO: 6028), FRYN (SEQ ID NO: 6029), KMIC (SEQ ID NO: 6030), RWQN (SEQ ID NO: 6031), PTQN (SEQ ID NO: 6032), KWKS (SEQ ID NO: 6033), YMRN (SEQ ID NO: 6034), KAAR (SEQ ID NO: 6035), LCQN (SEQ ID NO: 6036), CCQN (SEQ ID NO: 6037), CVQN (SEQ ID NO: 6038), KLTR (SEQ ID NO: 6039), KLCT (SEQ ID NO: 6040), KIRG (SEQ ID NO: 6041), YLVN (SEQ ID NO:6042), AFQN (SEQ ID NO: 6043), KACQ (SEQ ID NO: 6044). KWGL (SEQ ID NO: 6045), KILR (SEQ ID NO: 6046), FQIN (SEQ ID NO: 6047), KAC1 (SEQ ID NO: 6048). KALR (SEQ ID NO: 6049), KAHA (SEQ ID NO: 6050), LCLN (SEQ ID NO: 6051), KAFV (SEQ ID NO: 6052), PRQN (SEQ ID NO: 6053), CPQN (SEQ ID NO: 6054), KAQF (SEQ ID NO: 6055), VRYN (SEQ ID NO: 6056), VRCN (SEQ ID NO: 6057). KMPC (SEQ ID NO: 6058). KKTS (SEQ ID NO: 6059). LPYN (SEQ ID NO: 6060), YHQN (SEQ ID NO: 6061), KAQS (SEQ ID NO: 6062), YTRN (SEQ ID NO: 6063), VYQN (SEQ ID NO: 6064), RYQN (SEQ ID NO: 6065), WLKN (SEQ ID NO: 6066), KAQM (SEQ ID NO: 6067), PAQN (SEQ ID NO: 6068), MCTN (SEQ ID NO: 6069), PPDN (SEQ ID NO: 6070), KRNY (SEQ ID NO: 6071), WTQN (SEQ ID NO: 6072), KACR (SEQ ID NO: 6073), RKQN (SEQ ID NO: 6074), KCSV (SEQ ID NO: 6075), KARI (SEQ ID NO: 6076), FVQN (SEQ ID NO: 6077), KLPK (SEQ ID NO: 6078), KSEQ (SEQ ID NO: 6079), VAQN (SEQ ID NO: 6080), LYQN (SEQ ID NO: 6081), KVRM (SEQ ID NO: 6082), ALQN (SEQ ID NO: 6083), SCTN (SEQ ID NO: 6084), KN SR (SEQ ID NO: 6085), KRKR (SEQ ID NO: 6086). CTQN (SEQ ID NO: 6087), TCLN (SEQ ID NO: 6088), YARN (SEQ ID NO: 6089). KQRP (SEQ ID NO: 6090), KRVV (SEQ ID NO: 6091), SGQN (SEQ ID NO: 6092), YYSN (SEQ ID NO: 6093). ETON (SEQ ID NO: 6094), CQSN (SEQ ID NO: 6095), KAKG (SEQ ID NO: 6096), KPQN (SEQ ID NO: 6097). PFQN (SEQ ID NO: 6098), KCTS (SEQ ID NO: 6099), VFEN (SEQ ID NO: 6100), or KAKK (SEQ ID NO: 6101).304. The AAV particle of any one of embodiments 300-303, wherein [B] is or comprises:(i) SKAQA (SEQ ID NO: 6102), SKAQN (SEQ ID NO: 6103). SMYMN (SEQ ID NO: 6104), SKAFY (SEQ ID NO: 6105), SKLKR (SEQ ID NO: 6106), SKRHR (SEQ ID NO: 6107), SKAQK (SEQ ID NO: 6108), SKWRL (SEQ ID NO: 6109), SRCRN (SEQ ID NO: 6110), SFTCN (SEQ ID NO: 6111), SKFFI (SEQ ID NO: 6112), SKAQY (SEQ ID NO: 6113), IVWQN (SEQ ID NO: 6114), SKYFM (SEQ ID NO: 6115), SKARQ (SEQ ID NO: 6116), SCHQN (SEQ ID NO: 6117), FPWQN (SEQ ID NO: 6118), SKIRR (SEQ ID NO: 6119), VYYQN (SEQ ID NO: 6120), SLYWN (SEQ ID NO: 6121), SKPKR (SEQ ID NO: 6122), SKAFS (SEQ ID NO: 6123), SRFWN (SEQ ID NO: 6124), SKAQC (SEQ ID NO: 6125), SRMRN (SEQ ID NO: 6126). SVKKN (SEQ ID NO: 6127), SWAPN (SEQ ID NO: 6128). SLWKN (SEQ ID NO: 6129). SKARW (SEQ ID NO: 6130), SFRPN (SEQ ID NO: 6131), SKKVF (SEQ ID NO: 6132), SYAFN (SEQ ID NO: 6133), SKACS (SEQ ID NO: 6134), SKRLW (SEQ ID NO: 6135). SCSRN (SEQ ID NO: 6136), SRCPN (SEQ ID NO: 6137), SGACN (SEQ ID NO: 6138), SKFRQ (SEQ ID NO: 6139), SFPFN (SEQ ID NO: 6140), SFFGN (SEQ ID NO: 6141), SMCQN (SEQ ID NO: 6142), SKLFW (SEQ ID NO: 6143), SKTRK (SEQ ID NO: 6144), SGKRN (SEQ ID NO: 6145), FYRQN (SEQ ID NO: 6146), CRVQN (SEQ ID NO: 6147), YG1QN (SEQ ID NO: 6148), SKAQR (SEQ ID NO: 6149), VNCQN (SEQ ID NO: 6150), SKPFR (SEQ ID NO: 6151), SLAWN (SEQ ID NO: 6152), SKRSY (SEQ ID NO: 6153), WSYQN (SEQ ID NO: 6154), RWLQN (SEQ ID NO: 6155), PSCQN (SEQ ID NO:6156), SSWLN (SEQ ID NO: 6157), SKRRA (SEQ ID NO: 6158). SKAQT (SEQ ID NO: 6159), SKGCT (SEQ ID NO: 6160), VPWQN (SEQ ID NO: 6161), SKRYT (SEQ ID NO: 6162), SGCQN (SEQ ID NO: 6163), SFTPN (SEQ ID NO: 6164), STTCN (SEQ ID NO: 6165), SKARM (SEQ ID NO: 6166), PKRQN (SEQ ID NO: 6167), SKCFL (SEQ ID NO: 6168), WVPQN (SEQ ID NO: 6169), SFWSN (SEQ ID NO: 6170), SKFKN (SEQ ID NO: 6171), RIKQN (SEQ ID NO: 6172), SKAPR (SEQ ID NO: 6173), SFRYN (SEQ ID NO: 6174), SKMIC (SEQ ID NO: 6175), LRWQN (SEQ ID NO: 6176), LPTQN (SEQ ID NO: 6177), SKWKS (SEQ ID NO: 6178), SYMRN (SEQ ID NO: 6179), SKAAR (SEQ ID NO: 6180), LLC (QN (SEQ ID NO: 6181), RCCQN (SEQ ID NO: 6182), LCVQN (SEQ ID NO: 6183), SKLTR (SEQ ID NO: 6184), SKLCT (SEQ ID NO: 6185), SKIRG (SEQ ID NO: 6186), SYLVN (SEQ ID NO: 6187), QGCQN (SEQ ID NO: 6188), MAFQN (SEQ ID NO: 6189), SKACQ (SEQ ID NO: 6190), SKWGL (SEQ ID NO: 6191), SKILR (SEQ ID NO: 6192), SFQIN (SEQ ID NO: 6193), SKACI (SEQ ID NO: 6194), SKALR (SEQ ID NO: 6195), SKAHA (SEQ ID NO: 6196), SLCLN (SEQ ID NO: 6197). SKAFV (SEQ ID NO: 6198), RPWQN (SEQ ID NO: 6199), RPRQN (SEQ ID NO: 6200), SCPQN (SEQ ID NO: 6201), SKAQF (SEQ ID NO: 6202), SVRYN (SEQ ID NO: 6203), SVRCN (SEQ ID NO: 6204). SKMPC (SEQ ID NO: 6205), SKKTS (SEQ ID NO: 6206), SLPYN (SEQ ID NO: 6207), VYHQN (SEQ ID NO: 6208), SKAQS (SEQ ID NO: 6209), SYTRN (SEQ ID NO: 6210), LVYQN (SEQ ID NO: 6211), YRYQN (SEQ ID NO: 6212), SWLKN (SEQ ID NO: 6213), SKAQM (SEQ ID NO: 6214), CPAQN (SEQ ID NO: 6215). SMCTN (SEQ ID NO: 6216), SPPDN (SEQ ID NO: 6217), SKRNY (SEQ ID NO: 6218), RWTQN (SEQ ID NO: 6219), SKACR (SEQ ID NO: 6220), PRKQN (SEQ ID NO: 6221), SKCSV (SEQ ID NO: 6222), SKARI (SEQ ID NO: 6223), PFVQN (SEQ ID NO: 6224), SKLPK (SEQ ID NO: 6225), SKSEQ (SEQ ID NO: 6226), WVAQN (SEQ ID NO: 6227), SLYQN (SEQ ID NO: 6228), SKVRM (SEQ ID NO: 6229), CALQN (SEQ ID NO: 6230), SSCTN (SEQ ID NO: 6231), SKNSR (SEQ ID NO: 6232), SKRKR (SEQ ID NO: 6233), LCTQN (SEQ ID NO: 6234), STCLN (SEQ ID NO: 6235), SYARN (SEQ ID NO: 6236), SKQRP (SEQ ID NO: 6237), SKRVV (SEQ ID NO: 6238), KSGQN (SEQ ID NO: 6239), SYYSN (SEQ ID NO: 6240), SLTCN (SEQ ID NO: 6241), SCQSN (SEQ ID NO: 6242), SKAKG (SEQ ID NO: 6243), SKPQN (SEQ ID NO: 6244), FPFQN (SEQ ID NO: 6245), SKCTS (SEQ ID NO: 6246). SWEN (SEQ ID NO: 6247), SKAKK (SEQ ID NO: 6248), or GRYQN (SEQ ID NO: 6249);(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i), e.g., any 2, 3, or 4 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no more than four modifications relative to any of the amino acid sequences in (i); or(iv) an amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).305. The AAV particle of any one of embodiments 300-304, wherein [A]-[B] is or comprises:(i) GSGSPHSKAQA (SEQ ID NO: 6250), GSGSPHSKAQN (SEQ ID NO: 6251), GSGSPHSMYMN (SEQ ID NO: 6252), GSGSPHSKAFY (SEQ ID NO: 6253), GSGSPHSKLKR (SEQ ID NO: 6254), GSGSPHSKRHR (SEQ ID NO: 6255), GSGSPHSKAQK (SEQ ID NO: 6256), GSGSPHSKWRL (SEQ ID NO: 6257). GSGSPHSRCRN (SEQ ID NO: 6258), GSGSPHSFTCN (SEQ ID NO: 6259), GSGSPHSKFFI (SEQ ID NO: 6260), GSGSPHSKAQY (SEQ ID NO: 6261), GSGSPHTVWQN (SEQ ID NO: 6262), GSGSPHSKYFM (SEQ ID NO: 6263). GSGSPHSKARQ (SEQ ID NO: 6264), GSGSPHSCHQN (SEQ ID NO: 6265), GSGSPHFPWQN (SEQ ID NO: 6266), GSGSPI ISKIRR (SEQ ID NO: 6267), GSGSPHVYYQN (SEQ ID NO: 6268), GSGSPHSLYWN (SEQ ID NO: 6269), GSGSPHSKPKR (SEQ ID NO: 6270), GSGSPHSKAFS (SEQ ID NO: 6271), GSGSPHSRFWN (SEQ ID NO: 6272), GSGSPHSKAQC (SEQ ID NO: 6273), GSGSPHSRMRN (SEQ ID NO: 6274), GSGSPHSVKKN (SEQ ID NO: 6275), GSGSPHSWAPN (SEQ ID NO: 6276), GSGSPHSLWKN (SEQ ID NO: 6277), GSGSPHSKARW (SEQ ID NO: 6278), GSGSPHSFRPN (SEQ ID NO: 6279), GSGSPHSKKVF (SEQ ID NO: 6280), GSGSPHSYAFN (SEQ ID NO: 6281), GSGSPHSKACS (SEQ ID NO: 6282), GSGSPHSKRLW (SEQ ID NO: 6283), GSGSPHSCSRN (SEQ ID NO: 6284), GSGSPHSRCPN (SEQ ID NO: 6285), GSGSPHSGACN (SEQ ID NO: 6286), GSGSPHSKFRQ (SEQ ID NO: 6287), GSGSPHSFPFN (SEQ ID NO: 6288), GSGSPHSFFGN (SEQ ID NO: 6289), GSGSPHSMCQN (SEQ ID NO: 6290), GSGSPHSKLFW (SEQ ID NO: 6291), GSGSPHSKTRK (SEQ ID NO: 6292), GSGSPHSGKRN (SEQ ID NO: 6293), GSGSPHFYRQN (SEQ ID NO: 6294), GSGSPHCRVQN (SEQ ID NO: 6295), GSGSPHYGIQN (SEQ ID NO: 6296), GSGSPHSKAQR (SEQ ID NO: 6297). GSGSPHVNCQN (SEQ ID NO: 6298). GSGSPHSKPFR (SEQ ID NO: 6299), GSGSPHSLAWN (SEQ ID NO: 6300), GSGSPHSKRSY (SEQ ID NO: 6301), GSGSPHWSYQN (SEQ ID NO: 6302), GSGSPHRWLQN (SEQ ID NO: 6303), GSGSPHPSCQN (SEQ ID NO: 6304), GSGSPHSSWLN (SEQ ID NO: 6305), GSGSPHSKRRA (SEQ ID NO: 6306), GSGSPHSKAQT (SEQ ID NO: 6307), GSGSPHSKGCT (SEQ ID NO: 6308), GSGSPHVPWQN (SEQ ID NO: 6309), GSGSPHSKRYT (SEQ ID NO: 6310), GSGSPHSGCQN (SEQ ID NO: 6311), GSGSPHSFTPN (SEQ ID NO: 6312), GSGSPHSTTCN (SEQ ID NO: 6313), GSGSPHSKARM (SEQ ID NO: 6314), GSGSPHPKRQN (SEQ ID NO: 6315), GSGSPHSKCFL (SEQ ID NO: 6316), GSGSPHWVPQN (SEQ ID NO: 6317). GSGSPHSFWSN (SEQ ID NG: 6318), GSGSPHSKFKN (SEQ ID NO: 6319), GSGSPHRIKQN (SEQ ID NO: 6320), GSGSPHSKAPR (SEQ ID NO: 6321), GSGSPHSFRYN (SEQ ID NO: 632.2), GSGSPHSKMIC (SEQ ID NO: 6323), GSGSPHLRWQN (SEQ ID NO: 6324), GSGSPHLPTQN (SEQ ID NO: 6325), GSGSPHSKWKS (SEQ ID NO: 6326), GSGSPHSYMRN (SEQ ID NO: 6327), GSGSPHSK AAR (SEQ ID NO: 6328), GSGSPHLLCQN (SEQ ID NO: 6329), GSGSPI IRC CQN (SEQ ID NO: 6330), GSGSPHLCVQN (SEQ ID NO: 6331), GSGSPHSKLTR (SEQ ID NO: 6332), GSGSPHSKLCT (SEQ ID NO: 6333), GSGSPHSKIRG (SEQ ID NO: 6334), GSGSPHSYLVN (SEQ ID NO: 6335), GSGSPHQGCQN (SEQ ID NO: 6336), GSGSPHMAFQN (SEQ ID NO: 6337), GSGSPHSKACQ (SEQ ID NO: 6338), GSGSPHSK WGL (SEQ ID NO: 6339), GSGSPHSKILR (SEQ ID NO: 6340), GSGSPHSFQ1N (SEQ ID NO: 6341),GSGSPHSKACT (SEQ ID NO: 6342), GSGSPHSKALR (SEQ ID NO: 6343). GSGSPHSKAHA (SEQ ID NO: 6344), GSGSPHSLCLN (SEQ ID NO: 6345), GSGSPHSKAFV (SEQ ID NO: 6346), GSGSPHRPWQN (SEQ ID NO: 6347), GSGSPHRPRQN (SEQ ID NO: 6348), GSGSPHSCPQN (SEQ ID NO: 6349), GSGSPHSKAQF (SEQ ID NO: 6350), GSGSPHSVRYN (SEQ ID NO: 6351), GSGSPHSVRCN (SEQ ID NO: 6352), GSGSPHSKMPC (SEQ ID NO: 6353), GSGSPHSKKTS (SEQ ID NO: 6354), GSGSPHSLPYN (SEQ ID NO: 6355), GSGSPHVYHQN (SEQ ID NO: 6356), GSGSPHSKAQS (SEQ ID NO: 6357). GSGSPHSYTRN (SEQ ID NO: 6358), GSGSPHLVYQN (SEQ ID NO: 6359), GSGSPHYRYQN (SEQ ID NO: 6360), GSGSPHSWLKN (SEQ ID NO: 6361), GSGSPHSKAQM (SEQ ID NO: 6362), GSGSPHCPAQN (SEQ ID NO: 6363), GSGSPHSMCTN (SEQ ID NO: 6364), GSGSPHSPPDN (SEQ ID NO: 6365), GSGSPHSKRNY (SEQ ID NO: 6366), GSGSPHRWTQN (SEQ ID NO: 6367), GSGSPHSKACR (SEQ ID NO: 6368), GSGSPHPRKQN (SEQ ID NO: 6369), GSGSPHSKCSV (SEQ ID NO: 6370), GSGSPHSKARI (SEQ ID NO: 6371), GSGSPHPFVQN (SEQ ID NO: 6372), GSGSPHSKLPK (SEQ ID NO: 6373), GSGSPHSKSEQ (SEQ ID NO: 6374), GSGSPHWVAQN (SEQ ID NO: 6375), GSGSPHSLYQN (SEQ ID NO: 6376), GSGSPHSKVRM (SEQ ID NO: 6377), GSGSPHCALQN (SEQ ID NO: 6378), GSGSPHSSCTN (SEQ ID NO: 6379), GSGSPHSKNSR (SEQ ID NO: 6380), GSGSPHSKRKR (SEQ ID NO: 6381), GSGSPHLCTQN (SEQ ID NO: 6382), GSGSPHSTCLN (SEQ ID NO: 6383), GSGSPHSYARN (SEQ ID NO: 6384), GSGSPHSKQRP (SEQ ID NO: 6385). GSGSPHSKRW (SEQ ID NO: 6386), GSGSPHKSGQN (SEQ ID NO: 6387), GSGSPHSYYSN (SEQ ID NO: 6388), GSGSPHSLTCN (SEQ ID NO: 6389), GSGSPHSCQSN (SEQ ID NO: 6390), GSGSPHSKAKG (SEQ ID NO: 6391), GSGSPHSKPQN (SEQ ID NO: 6392), GSGSPHFPFQN (SEQ ID NO: 6393), GSGSPHSKCTS (SEQ ID NO: 6394), GSGSPHSVFEN (SEQ ID NO: 6395), GSGSPHSKAKK (SEQ ID NO: 6396), or GSGSPHGRYQN (SEQ ID NO: 6397);(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i), e.g., any 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no more than four modifications relative to any of the amino acid sequences in (i); or(iv) an amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i)306. The AAV particle of any one of embodiments 300-305, wherein [A]-[B] does not comprise the amino acid sequence of GSGSPHSKAQN (SEQ ID NO: 6251).307. The AAV particle of any one of embodiments 300-306, wherein the AAV capsid variant comprises one, two, or all of an amino acid other than Q at position 458 (e.g., R, C, S, W, L, F, Y, H, I, V, A, or P), an amino acid other than Q at position 459 (e.g., K, I, R, L or S), and / or an amino acid other than T at position 460 (e.g., R), numbered according to SEQ ID NO: 138.308. The AAV particle of any one of embodiments 300-307, wherein the AAV capsid variant comprises:(i) the amino acid R at position 458;(ii) tite amino acid W at position 458;(iii) the amino acid Y at position 458;(iv) the amino acid F at position 458;(v) the amino acid S at position 458;(vi) the amino acid C at position 458;(vii) the amino acid I at position 458;(viii) the amino acid L at position 458;(ix) the amino acid P at position 458;(x) the amino acid I at position 459;(xi) the amino acid H at position 458; or(xii) the amino acid V at position 458; wherein (i)-(xii) are numbered according to SEQ ID NO: 138.309. The AAV particle of any one of embodiments 300-307, wherein the AAV capsid variant comprises:(i) the amino acid R at position 458 and the amino acid K at position 459;(ii) the amino acid C at position 458 and the amino acid I at position 459;(iii) the amino acid S at position 458 and the amino acid R at position 459’(iv) the amino acid L at position 458 and the amino acid K at position 459;(v) the amino acid F at position 458 and the amino acid K at position 459;(vi) the amino acid C at position 458 and the amino acid R at position 459;(vii) the amino acid H at position 458 and the amino acid R at position 459;(viii) the amino acid I at position 458 and the amino acid L at position 459;(ix) the amino acid V at position 458 and the amino acid R at position 459;(x) the amino acid A at position 458 and the amino acid K at position 459;(xi) the amino acid I at position 458 and the amino acid K at position 459;(xii) the amino acid C at position 458 and the amino acid S at position 459; or(xiii) the amino acid C at position 458 and the amino acid L at position 459 wherein (i)-(xiii) are numbered according to SEQ ID NO: 138.310. The AAV particle of any one of embodiments 300-307, wherein the AAV capsid variant comprises the amino acid F at position 458, the amino acid K at position 459, and the amino acid R at position 460, numbered according to SEQ ID NO: 138.311. The AAV particle of any one of embodiments 300-310, wherein the AAV capsid variant comprises one, two, or all of an amino acid other than T at position 450 (e.g., Y. P, W, R, K, S, or F), an amino acid other than I at position 451 (e.g., R, S, Y, L, V, H, P, A, or F), and / or an amino acid other than N at position 452 (e.g.,V, W, A, T, F, Y, L, R, H, S, or M), numbered according to SEQ ID NO: 138.312. The AAV particle of any one of embodiments 300-311 , wherein the AAV capsid variant comprises the amino acid V at position 452. numbered according to SEQ ID NO: 138.313. The AAV particle of any one of embodiments 300-312, wherein the AAV capsid variant comprises the amino acid Y at position 450 and the amino acid V at position 452, numbered according to SEQ ID NO: 138.314. The AAV particle of any one of embodiments 300-312, wherein the AAV capsid variant comprises the amino acid R at position 450 and the amino acid Y at position 451, numbered according to SEQ ID NO: 138.315. The AAV particle of any one of embodiments 300-311 , wherein the AAV capsid variant comprises:(i) the amino acid P at position 450, the amino acid R at position 451, and the amino acid W at position 452;(ii) the amino acid Y at position 450, the amino acid S at position 451, and the amino acid A at position 452;(iii) the amino acid Y at position 450, the amino acid Y at position 451, and the amino acid T at position 452;(iv) the amino acid P at position 450, the amino acid R at position 451, and the amino acid F at position 452;(v) the amino acid W at position 450, the amino acid L at position 451, and the amino acid T at position 452;(vi) the amino acid R at position 450, the amino acid S at position 451, and the amino acid Y at position 452;(vii) the amino acid Y at position 450, the amino acid V at position 451. and the amino acid F at position 452;(viii) the amino acid K at position 450, the amino acid H at position 451, and the amino acid L at position 452;(ix) the amino acid P at position 450, the amino acid P at position 451, and the amino acid L at position 452;(x) the amino acid P at position 450, the amino acid A at position 451 , and the amino acid R at position 452;(xi) the amino acid S at position 450, the amino acid R at position 451, and the amino acid R at position 452;(xii) the amino acid F at position 450, the amino acid F at position 451, and the amino acid H at position 452;(xiii) the amino acid R at position 450, the amino acid F at position 451, and the amino acid S at position 452;(xiv) the amino acid Y at position 450, the amino acid S at position 451, and the amino acid M at position 452; or(xv) the amino acid P at position 450, the amino acid F at position 451, and the amino acid L. at position 452; wherein (i)-(xv) is numbered according to SEQ ID NO: 138.316. The AAV particle of any one of embodiments 300-315, wherein the AAV capsid variant comprises:(i) the amino acid sequence of any one of SEQ ID NOs: 3849-3982, 2984-4010, 4681-4693;(ii) an amino acid sequence comprising any portion of an amino acid sequence in (i). e.g., any 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 amino acids, e.g., consecutive amino acids, thereof;(iii) an amino acid sequence comprising one, two, or three but no more than four modifications relative to any of the amino acid sequences in (i); or(iv) an amino acid sequence comprising one, two, or three but no more than four different amino acids, relative to any one of the amino acid sequences in (i).317. The AAV particle of any one of embodiments 300-316, wherein the AAV capsid variant does not comprise the amino acid sequence of GSGSPHSKAQNQQ (SEQ ID NO: 1801) or GSGSPHSK AQNQQT (SEQ ID NO: 200).318. The AAV particle of any one of embodiments 300-317, wherein [A] -[B] is present in loop IV.319. The AAV particle of any one of embodiments 300-318, wherein [A] is present immediately subsequent to position 452, numbered according to SEQ ID NO: 138 or 981.320. The AAV particle of any one of embodiments 300-319, wherein [A] replaces positions 453-455(e.g., G453, S454, G455), numbered according to SEQ ID NO: 138 or 981321. The AAV particle of any one of embodiments 300-32.0, wherein [A] is present immediately subsequent to position 452. and wherein [A] replaces positions 453-455 (e.g., G453, S454, G455), numbered according to SEQ ID NO: 138 or 981.322. The AAV particle of any one of embodiments 300-32.1, wherein [B] is present immediately subsequent to [A],323. The AAV particle of any one of embodiments 300-322, wherein [Bj replaces positions 456 and457 (e.g., Q456, N457), numbered according to SEQ ID NO: 138.324. The AAV particle of any one of embodiments 300-323, wherein [ A]-[B] replaces positions 453-457 (e.g., G453, S454, G455, Q456, N457), numbered according to SEQ ID NO: 138.325. The AAV particle of any one of embodiments 300-324, wherein [A]-[B] is present immediately subsequent to position 452, and wherein [A]-[B] replaces positions 453-457 (e.g., G453, S454, G455, Q456, N457). numbered according to SEQ ID NO: 138.326. The AAV particle of any one of embodiments 300-325, wherein the AAV capsid variant comprises, from N -terminus to C-terminus, [A][BJ.327. The AAV particle of any one of the preceding embodiments, wherein the AAV capsid variant comprises at least one, at least two, at least three, or at least four (e.g., from 1-4 to 1-5) charged amino acid residues (e.g., acidic and / or basic amino acid residues) relative to SEQ ID NO: 138, which is present N-terminal to the amino acid sequence of SPH (e.g., within 1, 2, 3, 4, 5, or 6 amino acids from the start of the SPH amino acid sequence (e.g., within positions 450-455 numbered according to SEQ ID NO: 138)), optionally wherein the amino acid sequence of SPH is present at positions 456-458 numbered according to any one of SEQ ID NOs: 36-59, 981 , or 982.328. The AAV particle of embodiment 32.7, wherein the amino acid sequence of SPH is present al positions 456-458 numbered according to any one of SEQ ID NOs: 36-59, 981, or 982.329. The AAV particle of embodiment 327 or 328, wherein the AAV capsid variant comprises less than four, less than three, less than two (e.g., two or one) charged amino acid residues (e.g., acidic and / or basic amino acid residues) relative to SEQ ID NO: 138.330. The AAV particle of any one of embodiments 327-329, wherein the AAV capsid variant comprises one charged amino acid residues (e.g., an acidic or basic amino acid residue) relative to SEQ ID NO: 138, optionally at any one of positions 450-455 numbered relative to SEQ ID NO: 138,331. The AAV particle of any one of embodiments 327-330, wherein the charged amino acid residue is an acidic amino acid (e.g., D or E).332. The AAV particle of any one of embodiments 327-331, wherein the charged amino acid residue is a negatively charged amino acid (e.g., D or E).333. The AAV particle of any one of embodiments 327-332, wherein the charged amino acid residue is D.334. The AAV particle of any one of embodiments 327-333, wherein the charged amino acid residue is E.335. The AAV particle of any one of embodiments 327-334, wherein the charged amino acid residue is a basic amino acid (e.g., K, R, or H).336. The AAV particle of any one of embodiments 32.7-335, wherein the charged amino acid residue is a positively charged amino acid (e.g., K, R, or H).337. The AAV particle of any one of embodiments 327-336, wherein the charged amino acid residue is H.338. The AAV particle of any one of embodiments 327-337, wherein the charged amino acid residue is R.339. The AAV particle of any one of embodiments 327-338, wherein the charged amino acid residue is K.340. The AAV particle of any one of embodiments 327-339, wherein the AAV capsid variant comprises an acidic amino acid (e.g., E or D) and a basic amino acid (e.g., R, K, or H).341. The AAV particle of any one of embodiments 327-340, wherein at least one, two, three or four charged amino acid residues is present within 1, 2, 3, 4, 5, or 6 (e.g., 1 -6) amino acids from the start of the SPH amino acid sequence.342. The AAV particle of any one of embodiments 327-341, wherein the AAV capsid variant comprises two charged amino acid residues immediately preceding the amino acid sequence of SPH (e.g., at positions 454 and 455, numbered according to SEQ ID NO: 138 or SEQ ID NO: 982).343. The AAV particle of any one of embodiments 327-342, wherein the AAV capsid variant comprises a charged amino acid residue (e.g., E) within 1, 2, 3, 4, 5 (e.g., 5) amino acids from the start of the SPH amino acid sequence.344. The AAV particle of any one of embodiments 327-343, wherein the AAV capsid variant comprises a charged amino acid residue (e.g., E) at position 451, numbered according to any one of SEQ ID NO: 138, 981 , or 982.345. The AAV particle of any one of embodiments 327-344, wherein the AAV capsid variant comprises E at position 451, numbered according to any one of SEQ ID NOs: 138, 981 , or 982.346. The AAV particle of any one of embodiments 327-345, wherein the AAV capsid variant comprises a charged amino acid residue (e.g., R or K) at position 452, numbered according to any one of SEQ ID NOs: 138, 981, or 982.347. The AAV particle of any one of embodiments 327-346, wherein the AAV capsid variant comprises R at position 452, numbered according to SEQ ID NO: 138 or SEQ ID NO: 982.348. The AAV particle of any one of embodiments 327-347, wherein the AAV capsid variant comprises E at position 451 and R at position 452, numbered according to SEQ ID NO: 138 or SEQ ID NO: 982.349. The AAV particle of any one of embodiments 327-348, wherein the AAV capsid variant has decreased tropism for a liver cell or tissue, relative to the tropism of an AAV capsid comprising th amino acid sequence of SEQ ID NO: 138 or SEQ ID NO: 981.350. The AAV particle of any one of the preceding embodiments, wherein the AAV capsid variant comprises at least one, at least two, at least three, or at least four (e.g., from 1-4 to 1-5) charged amino acid residues (e.g., basic amino acid residues) relative to SEQ ID NO: 138, which is present C-terminal to the amino acid sequence of SPH (e.g., within 1, 2, 3, 4, 5, 6, or 7 amino acids from the end of the SPH amino acid sequence (e.g., within positions 459-465 numbered according to any one of SEQ ID NOs: 36-59, or 981)), optionally wherein the amino acid sequence of SPH is present at positions 456-458 numbered according to any one of SEQ ID NOs: 36-59, 981 , or 982.351. The AAV particle of embodiment 350, wherein the amino acid sequence of SPH is present at positions 456-458 numbered according to any one of SEQ ID NOs: 36-59, 981, or 982.352. The AAV particle of embodiment 350 or 351, wherein the AAV capsid variant comprises less than four, less than three, less than two (e.g., two or one) charged amino acid residues (e.g., basic amino acid residues) relative to SEQ ID NO: 138.353. The AAV particle of any one of embodiments 350-352, wherein the AAV capsid variant comprises one charged amino acid residues (e.g., a basic amino acid residue) relative to SEQ ID NO: 138, optionally at any one of positions 456-460 numbered relative to SEQ ID NO: 138 or at positions 462-466 numbered according to any one of SEQ ID NOs: 36-59, 981, or 982.354. The AAV particle of any one of embodiments 350-353, wherein the charged amino acid residue is a basic amino acid (e.g., R or K).355. The AAV particle of any one of embodiments 350-354, wherein the charged amino acid residue is a positively charged amino acid (e.g., R or K).356. The AAV particle of any one of embodiments 350-355, wherein the charged amino acid residue is R.357. The AAV particle of any one of embodiments 350-355, wherein the charged amino acid residue Is K.358. The AAV particle of any one of embodiments 350-357, wherein at least one, two, three or four charged amino acid residues is present within 1, 2, 3, 4, 5, 6, 7 (e.g., 1-7) amino acids from the end of the SPH amino acid sequence.359. The AAV particle of any one of embodiments 350-358, wherein the AAV capsid variant comprises a charged amino acid residue (e.g., K or R) immediately after the SPH sequence (e.g., at position 459 numbered according to SEQ ID NO: 981).360. The AAV particle of any one of embodiments 350-359, wherein the AAV capsid variant comprises a charged amino acid residue (e.g., K or R) at position 459, numbered according to SEQ ID NO: 138 or SEQ ID NO: 982.361. The AAV particle of any one of embodiments 350-360, wherein the AAV capsid variant comprises K at position 459, numbered according to SEQ ID NO: 981.362. The AAV particle of any one of embodiments 350-360, wherein the AAV capsid variant comprises R at position 459, numbered according to SEQ ID NO: 981.363. The AAV particle of any one of embodiments 350-362, wherein the AAV capsid variant comprises a charged amino acid residue (e.g., R or K) at one, two three, four, five, or all of positions460, 461, 462, 463, 464, and / or 465, numbered according to SEQ ID NO: 138 or 981.364. The AAV particle of any one of embodiments 300-326 or 350-363, wherein the AAV capsid variant has increased tropism for a liver ceil or tissue, relative to the tropism of an AAV capsid comprising the amino acid sequence of SEQ ID NO: 138,365. The AAV particle of any one of embodiments 300-326 or 350-364, wherein the AAV capsid variant is enriched at least 10, at least 15, at least 20, at least 25, at least 30, at least 35, at least 40, at least 45, at least 50, at least 55, at least 60, at least 65, at least 70, at least 75, at least 80, at least 85, at least 90, at least 95, at least 100, at least 105, at least 110, at least 115, at least 120, at least 125, at least 130, at least 135, at least 140, at least 150, at least 160, at least 170, at least 180, at least 190, or at least 200-fold, in the liver compared to an AAV capsid comprising SEQ ID NO: 138, e.g., when measured by an assay as described in Example 4.366. The AAV particle of any one of embodiments 300-326, 364, or 365, wherein the AAV capsid variant has reduced tropism for a CNS cell or tissue, e.g., a brain cell, brain tissue, spinal cord cell, or spinal cord tissue, relative to the tropism of an AAV capsid comprising the amino acid sequence of SEQ ID NO: 138.367. The AAV particle of any one of embodiments 300-326 or 364-366, wherein the AAV capsid variant shows preferential transduction in a liver region relative to the transduction in the brain and / or dorsal root ganglia (DRG).368. The AAV particle of any one of embodiments 300-326 or 364-367, wherein the AAV capsid variant shows preferential transduction in a liver region relative to the transduction in the heart and / or muscle (e.g., quadriceps).369. An adeno-associated virus (AAV) particle comprising an AAV capsid variant (e.g., an AAV9 capsid variant) and a viral genome comprising a P-glucocerebrosidase 1 (GBA1)-encoding sequence (e.g., encoding a human GBA1 protein), wherein the AAV capsid variant comprises:(a) the amino acid sequence of any of the sequences provided in Table 1, 2A, 2B, or 20-26;(b) an amino acid sequence comprising at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, or at least 17 consecutive amino acids from any one of the sequences provided in Table 1, 2A, 2B, or 20- 26; or(c) an amino acid sequence comprising at least one, at least two. or at least three but no more than four different amino acids, relative to any one of the sequences provided in Table 1, 2 A, 2B, or 20-26; or(d) an amino acid sequence comprising at least one, at least two, or at least three but no more than four modifications relative to the amino acid sequence of any one of the sequences provided in Table 1, 2A, 2B. or 20-26.370. An adeno-associated virus (AAV) particle comprising an AAV capsid variant (e.g., an AAV9 capsid variant) and a viral genome comprising a p-glucocerebrosidase 1 (GBA1)-encoding sequence (e.g., encoding a human GBA1 protein), wherein the AAV capsid variant comprises:(a) the amino acid sequence of any one of SEQ ID NOs: 945-980 or 985-986;(b) an amino acid sequence comprising at least 3, at least 4, or at least 5 consecutive amino acids from any one of SEQ ID NOs: 945-980 or 985-986; or(c) an amino acid sequence comprising at least one. at least two, or at least three but no more than four different amino acids, relative to the amino acid sequence of any one of SEQ ID NOs: 945- 980 or 985-986;(d) an amino sequence comprising at least one, at least two, or at least three but no more than four modifications relative to the amino acid sequence of any one of SEQ ID NOs: 945-980 or 985- 986.371. An adeno-associated virus (AAV) particle comprising an AAV capsid variant (e.g., an AAV9 capsid variant) and a viral genome comprising a p-glucocerebrosidase 1 (GBA1)-encoding sequence (e.g., encoding a human GBA1 protein), wherein the AAV capsid variant comprises:(a) the amino acid sequence of any one of SEQ ID NOs: 2, 200, 201, 941, 943, 204, 208, 404, or 903-909;(b) an amino acid sequence comprising at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, or at least 13 consecutive amino acids from any one of SEQ ID NOs: 2, 200, 201, 941 , 943, 204. 208, 404. or 903-909;(c) an amino acid sequence comprising at least one, at least two, or at least three but no more than four different amino acids, relative to the amino acid sequence of any one of SEQ ID NOs: 2, 200, 201, 941, 943, 204, 208, 404, or 903-909; or(d) an amino acid sequence comprising at least one, at least two, or at least three but no more than four modifications relative to the amino acid sequence of any one of SEQ ID NOs: 2, 200, 201, 941, 943, 204, 208, 404, or 903-909.372. An adeno-associated virus (AAV) particle comprising an AAV capsid variant (e.g., an AAV9 capsid variant) and a viral genome comprising a p-glucocerebrosidase 1 (GBA1)-encoding sequence (e.g., encoding a human GBA1 protein), wherein the AAV capsid variant comprises:(a) the amino acid sequence of any one of SEQ ID NOs: 3849-4051 or 4681 -4693;(b) an amino acid sequence comprising at least 3, at least 4, at least 5, at least 6, at least 7. at least 8. at least 9, at least 10, at least 11 , at least 12. at least 13, at least 14, at least 15, at least 16 or at least 17 consecutive amino acids from any one of SEQ ID NOs: 3849-4051 or 4681-4693;(c) an amino acid sequence comprising at least one, at least two, or at least three but no more than four different amino acids, relative to the amino acid sequence of any one of SEQ ID NOs: 3849- 4051 or 4681-4693; or(d) an amino acid sequence comprising at least one, at least two, or at least three but no more than four modifications relative to the amino acid sequence of any one of SEQ ID NOs: 3849-4051 or 4681-4693.373. An adeno-associated virus (AAV) particle comprising an AAV capsid variant (e.g., an AAV9 capsid variant) and a viral genome comprising a p-glucocerebrosidase 1 (GBA1)-encoding sequence (e.g., encoding a human GBA1 protein), wherein the AAV capsid variant comprises:(a) the amino acid sequence of any one of SEQ ID NOs: 4052-4092;(b) an amino acid sequence comprising at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least: 9, at least 10, at least 11, at least: 12, at: least 13, at least 14. at least 15. at least 16 or at: least 17 consecutive amino acids from any one of SEQ ID NOs: 4052-4092;(c) an amino acid sequence comprising at least one. at least two, or at least three but no more than four different amino acids, relative to the amino acid sequence of any one of SEQ ID NOs: 4052- 4092; or(d) an amino acid sequence comprising at least one, at least two, or at least three but no more than four modifications relative to the amino acid sequence of any one of SEQ ID NOs: 4052-4092.374. An adeno-associated virus (AAV) particle comprising an AAV capsid variant (e.g., an AAV9 capsid variant) and a viral genome comprising a p-glucocerebrosidase 1 (GBA1)-encoding sequence (e.g., encoding a human GBA1 protein), wherein the AAV capsid variant comprises:(a) the amino acid sequence of any one of SEQ ID NOs: 4056, 4058, 4059, 4062-4064, 4066, 4067, 4080, 4084, 4090, or 4095-4097;(b) an amino acid sequence comprising at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, al least 13, at least 14, at least 15. at least 16 or at least 17 consecutive amino acids from any one of SEQ ID NOs: 4056, 4058. 4059, 4062-4064, 4066, 4067, 4080, 4084, 4090, or 4095-4097;(c) an amino acid sequence comprising at least one, at least two, or at least three but no more than four different amino acids, relative to the amino acid sequence of any one of SEQ ID NOs: 4056,4058, 4059, 4062-4064, 4066, 4067, 4080, 4084, 4090, or 4095-4097; or(d) an amino acid sequence comprising at least one, at least two, or at least three but no more than four modifications relative to the amino acid sequence of any one of SEQ ID NOs: 4056, 4058,4059. 4062-4064, 4066, 4067, 4080, 4084, 4090, or 4095-4097.375. The AAV particle of embodiment 369 or 371, wherein the AAV capsid variant comprises an amino acid sequence comprising at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, or at least 13 consecutive amino acids from any one of SEQ ID NOs: 2, 200, 201, 941, 943, 204, 208, 404, or 903-909.376. The AAV particle of any one of embodiments 369-374, wherein the at least 3 consecutive amino acids comprise SPH.377. The AAV particle of any one of embodiments 369-371 or 376, wherein the at least 4 consecutive amino acids comprise SPHS (SEQ ID NO: 4700).378. The AAV particle of any one of embodiments 369-371, 376, or 377, wherein the at least 5 consecutive amino acids comprise SPHSK (SEQ ID NO: 4701),379. The AAV particle of any one of embodiments 369-371 or 376-378, wherein the at least 6 consecutive amino acids comprise SPHSKA (SEQ ID NO: 941).380. The AAV particle of embodiment 369-371, wherein the at least 3 consecutive amino acids comprise HDS.381. The AAV particle of any one of embodiments 369-371 or 380, wherein the at least 4 consecutive amino acids comprise HDSP (SEQ ID NO: 4702).382. The AAV particle of any one of embodiments 369-371, 380, or 381, wherein the at least 5 consecutive amino acids comprise HDSPH (SEQ ID NO: 4703).383. The AAV particle of any one of embodiments 369-371 or 380-382, wherein the at least 6 consecutive amino acids comprise HDSPHK (SEQ ID NO: 2).384. The AAV particle of any one of embodiments 369-371, wherein:(i) the at least 3 consecutive amino acids comprise SPH;(ii) the at least 4 consecutive amino acids comprise SPHK (SEQ ID NO: 6398);(iii) the at least 5 consecutive amino acids comprise SPHKY (SEQ ID NO: 4715); and / or(iv) the at least 6 consecutive amino acids comprise SPHKYG (SEQ ID NO: 966).385. The AAV particle of embodiment 369 or 371. wherein the AAV capsid variant comprises an amino acid sequence comprising at least one, at least two, or at least three but no more than four modifications relative to the amino acid sequence of any one of SEQ ID NOs: 2, 200, 201, 941, 943, 204, 208, 404, or 903-909.386. The AAV particle of any one of embodiments 369, 371, or 385, wherein the AAV capsid variant comprises an amino acid sequence comprising at least one, at least two, or at least three but no more than four modifications relative to the amino acid sequence of SPHSKA (SEQ ID NO: 941).387. The AAV particle of any one of embodiments 369, 371, or 385, wherein the AAV capsid variant comprises an amino acid sequence comprising at least one, at least two, or at least three but no more than four modifications relative to the amino acid sequence of HDSPHK (SEQ ID NO: 2).388. The AAV particle of any one of embodiments 369-371, 384, or 385, wherein the AAV capsid variant comprises an amino acid sequence comprising at least one. at least two, or at least three but no more than four modifications relative to the amino acid sequence of SPHKYG (SEQ ID NO: 966).389. The AAV particle of embodiment 370, wherein the AAV capsid variant comprises:(i) an amino acid sequence comprising at least one, at least two, or at least three but no more than four modifications, relative to the amino acid sequence of KTERVSGSPHSKAQNQQT (SEQ ID NO: 3589);(ii) an amino acid sequence comprising at least one, at least two. or at least three but no more than four modifications, relative to the amino acid sequence of KAEIGHDSPHKSGQNQQT (SEQ ID NO: 1754)(iii) an amino acid sequence comprising at least one, at least two, or at least three but no more than four modifications, relative to the amino acid sequence of KTEKMSGSPHSKAQNQQT (SEQ ID NO: 3241);(iv) an amino acid sequence comprising at least one, at least two, or at least three but no more than four modifications, relative to the amino acid sequence of KTINGHDSPHSKAQNLQT (SEQ ID NO: 4100); or(v) an amino acid sequence comprising at least one, at least two, or at least three but no more than four modifications, relative to the amino acid sequence of KTVNGHDSPHSKAQNQQT (SEQ ID NO: 4062).390. The AAV particle of embodiment 369 or 371. wherein the AAV capsid variant comprises an amino acid sequence comprising at least one. at least two, or at least three but no more than four different amino acids relative to the amino acid sequence of any one of SEQ ID NOs: 2, 200, 201, 941, 943, 204, 208, 404, or 903-909.391. The AAV particle of any one of embodiments 369, 371 , or 390, wherein the AAV capsid variant comprises an amino acid sequence comprising at least one, at least two, or at least three but no more than four different amino acids relative to the amino acid sequence of SPHSKA (SEQ ID NO: 941).392. The AAV particle of any one of embodiments 369, 371, or 390, wherein the AAV capsid variant comprises an amino acid sequence comprising at least one, at least two, or at least three but no more than four different amino acids relative to the amino acid sequence of HDSPHK (SEQ ID NO: 2).393. The AAV particle of any one of embodiments 369, 371, 384, or 390, wherein the AAV capsid variant comprises an amino acid sequence comprising at least one, at least two, or at least three but no more than four different amino acids relative to the amino acid sequence of SPHKYG (SEQ ID NO: 966).394. The AAV particle of embodiment 369, wherein the AAV capsid variant comprises:(i) an amino acid sequence comprising at least one, at least two, or at least three but no more than four different amino acids relative to the amino acid sequence of KTERVSGSPHSKAQNQQT (SEQ ID NO: 3589);(ii) an amino acid sequence comprising at least one, at least two, or at least three but no more than four different amino acids relative to the amino acid sequence of KAEIGHDSPHKSGQNQQT (SEQ ID NO: 1754);(iii) an amino acid sequence comprising at least one, at least two, or at least three but no more than four different amino acids relative to the amino acid sequence of KTEKMSGSPHSKAQNQQT (SEQ ID NO: 3241);(iv) an amino acid sequence comprising at least one, at least two, or at least three but no more than four different amino acids relative to the amino acid sequence of KTINGHDSPHSKAQNLQT (SEQ ID NO: 4100); or(v) an amino acid sequence comprising at least one, at least two, or at least three but no more than four different amino acids relative to the amino acid sequence of KTVNGHDSPHSKAQNQQT (SEQ ID NO: 4062).395. The AAV particle of any one of embodiments 1-129, 269, 271, 375-388, or 390-394, wherein the AAV capsid variant comprises the amino acid sequence of any one of SEQ ID NOs: 2, 200, 201, 941,943, 204, 208, 404, or 903-909.396. The AAV particle of any one of embodiments 295-297, 301-305, 313, 314, 318, 319, or 323, wherein the AAV capsid variant comprises the amino acid sequence of ERVSGSPHSKA (SEQ ID NO: 6399), optionally wherein the amino acid sequence is present immediately subsequent to position 450 and replaces positions 451-455 (e.g., 1451, N542, G453, S454, G455), numbered according to SEQ ID NO: 138.397. The AAV particle of any one of embodiments 369-371, 375-379, 385, 386, 389-391, or 394-396, wherein the AAV capsid variant comprises the amino acid sequence of KTERVSGSPHSKAQNQQT (SEQ ID NO: 3589), optionally wherein the amino acid sequence is present immediately subsequent to position 448 and replaces positions 449-460 (e.g., K449, T450, 1451, N452, G453, S454, G455, Q456, N457, Q458, Q459, T460), numbered according to SEQ ID NO: 138.398. The AAV particle of any one of embodiments 269-371, 375, 380-383, 385, 387, 389, 390, 393, or 394, wherein the AAV capsid variant comprises the amino acid sequence of AEIGHDSPHKSG (SEQ ID NO: 6400), optionally wherein the amino acid sequence is present immediately subsequent to position 449 and replaces positions 450-455 (e.g., T450, 1451, N452, G453, S454, G455), numbered according to SEQ ID NO: 138.399. The AAV particle of any one of embodiments 369-371, 375, 380-383, 385, 387, 389, 390, 393,394, or 398, wherein the AAV capsid variant comprises the amino acid sequence ofKAEIGHDSPHKSGQNQQT (SEQ ID NO: 1754), optionally wherein the amino acid sequence is present immediately subsequent to position 448 and replaces positions 449-460 (e.g., K449, T450, 1451, N452, G453, S454, G455, Q456, N457, Q458, Q459, T460), numbered according to SEQ ID NO: 138.400. The AAV particle of any one of embodiments 369-371, 375-379, 390, 391, or 395, wherein the AAV capsid variant comprises the amino acid sequence of EKMSGSPHSKA (SEQ ID NO: 6401), optionally wherein the amino acid sequence is present immediately subsequent to position 450 and replaces positions 451-455 (e.g., 1451. N452, G453, S454. G455). numbered according to SEQ ID NO: 138.401. The AAV particle of any one of embodiments 369-371, 375-379, 390, 391, or 395, wherein the AAV capsid variant comprises the amino acid sequence of KTEKMSGSPHSKAQNQQT (SEQ ID NO: 3241), optionally wherein the amino acid sequence is present immediately subsequent to position 448 and replaces positions 449-460 (e.g., K449, T450, 1451, N452, G453, S454, G455, Q456, N457, Q458, Q459, T460), numbered according to SEQ ID NO: 138.402. The AAV particle of any one of embodiments 369-371 , 375-379, 390, 391 , or 395, wherein the AAV capsid variant comprises the amino acid sequence of HDSPHSKAQNL (SEQ ID NO: 6402), optionally wherein the amino acid sequence is present immediately subsequent to position 453 and replaces positions 456-458 (e.g., Q456, N457, Q458), numbered according to SEQ ID NO: 138.403. The AAV particle of any one of embodiments 369-371, 375-379, 390, 391, or 395, wherein the AAV capsid variant comprises the amino acid sequence of KTINGHDSPHSKAQNLQT (SEQ ID NO: 4100), optionally wherein the amino acid sequence is present immediately subsequent to position 448 and replaces positions 449-460 (e.g., K449, T450, 1451 , N452, G453, S454, G455, Q456, N457, Q458, Q459, T460), numbered according to SEQ ID NO: 138.404. The AAV particle of any one of embodiments 369-371, 375-379, 390, 391, or 395, wherein the AAV capsid variant comprises the amino acid sequence of VNGHDSPHSKA (SEQ ID NO: 6403), optionally wherein the amino acid sequence is present immediately subsequent to position 450 and replaces positions 451-455 (e.g., 1451. N452, G453, S454. G455). numbered according to SEQ ID NO: 138.405. The AAV particle of any one of embodiments 369-371, 375-379, 390, 391, or 395, wherein the AAV capsid variant comprises the amino acid sequence of KTVNGHDSPHSKAQNQQT (SEQ ID NO: 4062), optionally wherein the amino acid sequence is present immediately subsequent to position448 and replaces positions 449-460 (e.g., K449, T450, 1451 , N452, G453, S454, G455, Q456, N457, Q458, Q459, T460), numbered according to SEQ ID NO: 138.406. The AAV particle of any one of embodiments 1-23, 26-29, 32, 35-43, 46-51 , 54-72, 69-89, 91, 94-99, 102-104, 107, 110-112, 115-129, 168-202. 02, 2.40-247. 2.49, 250, 253-263, 2.66, 272.-281, 286.288, 2.91-299, 327-363. 369-371 , 375-379, 385, 386, 390, 391. or 395, wherein the AAV capsid variant comprises an amino acid sequence encoded by: the nucleotide sequence of SEQ ID NO: 942: a nucleotide sequence comprising at least one, at least two, at least three, at least four, at least five, at least six, or at least seven modifications, e.g., substitutions (e.g., conservative substitutions), but no more than ten modifications, e.g., substitutions (e.g., conservative substitutions), relative to the nucleotide sequence of SEQ ID NO: 942; or a nucleotide sequence comprising at least one, at least two, at least three, at least four, at least five, at least six, or at least seven, but no more than ten different nucleotides relative to the nucleotide sequence of SEQ ID NO: 942.407. The AAV particle of any one of embodiments 1-9, 11, 12-22, 24, 26, 28, 30, 33, 35-42, 44, 46- 50, 52, 54-77, 83-88, 90-97, 100-103, 105, 110, 11 1, 113-129, 203-248, 251, 252, 254-257, 260, 261, 2.64-280, 283-287, 2.89-299, 327-363, 369, 369, 371, 380-383, 385, 386, 390, 392, or 395, wherein the AAV capsid variant comprises an amino acid sequence encoded by: the nucleotide sequence of SEQ ID NO: 3; a nucleotide sequence comprising at least one, at least two, at least three, at least four, at least five, at least six, or at least seven modifications, e.g.. substitutions (e.g., conservative substitutions), but no more than ten modifications, e.g., substitutions (e.g., conservative substitutions), relative to the nucleotide sequence of SEQ ID NO: 3; or a nucleotide sequence comprising at least one, at least two, at least three, at least four, at least five, at least six, or at least seven, but no more than ten different nucleotides relative to the nucleotide sequence of SEQ ID NO: 3.408. The AAV particle of any one of embodiments 1-23, 26-29, 32, 35-43, 46-51 , 54-72, 69-89, 91, 94-99, 102-104, 107, 110-112, 1 15-129, 168-202, 02, 240-247, 249, 250, 253-263, 266, 272-281, 286, 288, 291-299, 327-363, 369-371 , 375-379, 385, 386, 390, 391 , 395, or 406, wherein tbe nucleotide sequence encoding the capsid variant comprises the nucleotide sequence of SEQ ID NO: 942; a nucleotide sequence comprising at least one, at least two, at least three, at least four, at least five, at least six. or at least seven modifications, e.g., substitutions (e.g,, conservative substitutions), but no more than ten modifications, e.g., substitutions (e.g.. conservative substitutions), relative to the nucleotide sequence of SEQ ID NO: 942; or a nucleotide sequence comprising at least one, at least two, at least three, at least four, al least five, at least six, or at least seven, but no more than ten different nucleotides relative to the nucleotide sequence of SEQ ID NO: 942.409. The AAV particle of any one of embodiments 1-9, 11 , 12-22, 24, 26, 28, 30, 33, 35-42, 44, 46- 50, 52, 54-77, 83-88, 90-97, 100-103, 105, 110, 111 , 113-129, 203-248, 251, 252, 254-257, 260, 261, 264-280, 283-287, 289-299, 327-363, 369, 369, 371 , 380-383, 385, 386, 390, 392, 395, or 407, wherein the nucleotide sequence encoding the capsid variant comprises the nucleotide sequence of SEQ ID NO: 3; a nucleotide sequence comprising at least one, at least two. at least three, at least four, at least five, at least six, or at least seven modifications, e.g., substitutions (e.g.. conservative substitutions), but no more than ten modifications, e.g., substitutions (e.g., conservative substitutions), relative to the nucleotide sequence of SEQ ID NO: 3; or a nucleotide sequence comprising al least one, at least two, at least three, at least four, at least five, at least six, or at least seven, but no more than ten different nucleotides relative to the nucleotide sequence of SEQ ID NO: 3.410. The AAV particle of any one of embodiments 369-409, wherein the amino acid sequence is present in loop IV, e.g., relative to the amino acid sequence of SEQ ID NO: 138.411. The AAV particle of any one of embodiments 369-410, wherein the amino acid sequence is present immediately subsequent to position 448, 449, 450, 451, 452, 453, 454, or 455, numbered according to SEQ ID NO: 138.412. The AAV particle of any one of embodiments 369-411 , wherein the amino acid sequence replaces amino acids 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, and / or 460 (e.g., K449, T450, 1451, N452, G453, S454, G455. Q456, N457, Q458, Q459. and / or T460), numbered according SEQ ID NO: 138.413. The AAV particle of any one of embodiments 369-412, wherein the amino acid sequence is present immediately subsequent to position 455, numbered according to SEQ ID NO: 138.414. The AAV particle of any one of embodiments 369-413, wherein the amino acid sequence is present immediately subsequent to position 453, numbered according SEQ ID NO: 138.415. The AAV particle of any one of embodiments 1-2.3, 26-29, 32, 35-43, 46-51 , 54-72. 69-89, 91, 94-99, 102-104, 107, 110-112, 115-12.9, 168-202. 02, 2.40-247. 2.49, 250, 2.53-263. 2.66, 272-281, 286. 288, 291-299. 327-363, 369-371, 375-379, 385, 386, 390, 391, 395, 406, 408, or 410-413, wherein 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, according to SEQ ID NO: 138.436. The AAV particle of any one of embodiments 1-23, 26-29, 32, 35-43, 46-51, 54-72, 69-89, 91, 94-99, 102-104, 107, 110-112, 115-129. 168-202, 02, 240-247, 249, 250. 253-263, 266, 272-281, 286, 288, 291-299. 327-363, 369-371, 375-379, 385, 386, 390, 391 , 395, 406, 408, 410-413, or 415, wherein the AAV capsid variant the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is present immediately subsequent to position 455, numbered according to SEQ ID NO: 981.417. The AAV particle of embodiment 415 or 416, wherein the AAV capsid variant further comprises an amino acid other than I at position 451, an amino acid other than N at position 452, mid mi amino acid other than G at position 453, numbered according to any one of SEQ ID NOs: 36, 138, or 981.418. The AAV particle of any one of embodiments 415-417, wherein the AAV capsid variant further comprises E at position 451, R at position 452, and V at position 453, numbered according to any one of SEQ ID NOs: 36, 138, or 981.419. The AAV particle of any one of embodiments 415-418, wherein the AAV capsid variant further comprises the substitutions 145 IE, N452R, and G453V, numbered according to any one of SEQ ID NOs: 36. 138, or 981.420. The AAV particle of any one of embodiments 415-419, wherein the AAV capsid variant comprises:(i) E at position 451, R at position 452, and V at position 453, numbered according to any one of SEQ ID NOs: 36, 138, or 981; and(ii) the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is present immediately subsequent to position 455, numbered according to any one of SEQ ID NOs: 36, 138, or 981 (at amino acids 456-461 , numbered according to SEQ ID NO: 36 or 981).421. The AAV particle of embodiment 415 or 416, wherein the AAV capsid variant further comprises an amino acid other than I at position 451, an amino acid other than N at position 452, and / or G at position 453, numbered according to SEQ ID NO: 39 or 138.422. The AAV particle of any one of embodiments 415, 416, or 421, wherein the AAV capsid variant further comprises E at position 451, K at position 452, and / or M at position 453, numbered according to SEQ ID NO: 138 or 39.423. The AAV particle of any one of embodiments 415, 416, 421 , or 422, wherein the AAV capsid variant further comprises the substitutions 145 IE, N452K, and G453M, numbered according to SEQ ID NO: 39 or 138.424. The AAV particle of any one of embodiments 415, 416, or 421-423, wherein the AAV capsid variant comprises:(i) E al position 451, K at position 452. and M at position 453, numbered according to SEQ ID NO: 39 or 138; and(ii) the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is present immediately subsequent to position 455, numbered according to SEQ ID NO: 39 or 138.425. The AAV particle of embodiment 415 or 416, wherein the AAV capsid variant further comprises an amino acid other than S at position 454, an amino acid other than G at position 455. and / or Q at position 458, numbered according to SEQ ID NO: 138.426. The AAV particle of any one of embodiments 415, 416, or 425, wherein the AAV capsid variant further comprises H at position 454, D at position 455, and / or L at position 458, numbered according to SEQ ID NO: 138.427. The AAV particle of any one of embodiments 415, 416, 425, or 426, wherein the AAV capsid variant further comprises the substitutions S454H, G455D, and Q458L, numbered according to SEQ ID NO: 138.428. The AAV particle of any one of embodiments 415, 416, or 425-427, wherein the AAV capsid variant comprises:(i) H at position 454, D at position 455, and / or L at position 458, numbered according to SEQ ID NO: 138; and(ii) the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is present immediately subsequent to position 455, numbered according to SEQ ID NO: 138.429. The AAV particle of embodiment 415 or 416, wherein the AAV capsid variant further comprises an amino acid other than I at position 451, an amino acid oilier than S at position 454, and / or an amino acid other than G at position 455, numbered according to SEQ ID NO: 52 or 138.430. The AAV particle of any one of embodiments 415, 416, or 429, wherein the AAV capsid variant further comprises V at position 451, H at position 454, and / or D at position 455, numbered according to SEQ ID NO: 52 or 138.431. The AAV particle of any one of embodiments 415, 416, 429, or 430, wherein the AAV capsid variant further comprises the substitutions I451V, S454H, and / or G455D, numbered according to SEQ ID NO: 52 or 138.432. The AAV particle of any one of embodiments 415, 416, or 429-431, wherein the AAV capsid variant comprises:(i) V at position 451, H at position 454, and / or D at position 455, numbered according to SEQ ID NO: 52 or 138; and(ii) the amino acid sequence of SPHSKA (SEQ ID NO: 94 i), wherein the amino acid sequence is present immediately subsequent to position 455, numbered according to SEQ ID NO: 52 or 138.433. The AAV particle of any one of embodiments 1-9, 11, 12-22, 24, 26, 28, 30, 33, 35-42, 44, 46- 50, 52, 54-77, 83-88, 90-97. 100-103, 105, 110, 111, 113-129, 203-248, 251, 252, 254-257, 260, 261, 264-280, 2.83-287. 289-299. 327-363, 369, 369, 371, 380-383, 385, 386, 390. 392, 395. 407, 409-412, or 414, wherein the AAV capsid variant comprises the amino acid sequence of HDSPHK (SEQ ID NO: 2), wherein the amino acid sequence is present immediately subsequent to position 453, numbered according to the amino acid sequence of SEQ ID NO: 138.434. The AAV particle of any one of embodiments 1-9, 11, 12-22, 24, 26, 28, 30, 33, 35-42, 44, 46- 50, 52, 54-77, 83-88, 90-97, 100-103, 105, 110, 111, 113-129, 203-248, 251, 252, 254-257, 260, 261, 264-280, 283-287, 289-299, 327-363, 369, 369, 371 , 380-383, 385, 386, 390, 392, 395, 407, 409-412, 414, or 433, wherein the AAV capsid variant comprises the amino acid sequence of HDSPHK (SEQ ID NO: 2), wherein the amino acid sequence is present immediately subsequent to position 453, numbered according to the amino acid sequence of SEQ ID NO: 982.435. The AAV particle of any one of embodiments 1-9, 11, 12-22, 2.4, 2.6, 28, 30, 33, 35-42. 44, 46- 50, 52, 54-77. 83-88, 90-97, 100-103, 105, 110, 111, 113-129, 203-2.48, 251, 2.52, 254-257, 260, 261, 264-280, 283-287, 289-299, 327-363, 369, 369, 371, 380-383, 385, 386, 390, 392, 395, 407, 409-412, 414, 433, or 434, wherein the AAV capsid variant comprises tire amino acid sequence of SPHKSG (SEQ ID NO: 946), wherein the amino acid sequence is present immediately subsequent to position 455, numbered according to the amino acid sequence of SEQ ID NO: 982.436. The AAV particle of any one of embodiments 369-435, wherein the AAV capsid variant comprises:(i) the amino acid sequence of HDSPHSKA (SEQ ID NO: 4486), which is present immediately subsequent to position 453; and(ii) a deletion of amino acids SG at position 454 and 455; wherein (i) and (ii) are numbered according to SEQ ID NO: 138.437. The AAV particle of any one of embodiments 369-436, wherein the AAV capsid variant comprises the amino acids HD at position 454 and 455, and further comprises the amino acid sequence of SPHSKA (SEQ ID NO: 941), which is present immediately subsequent to position 455, numbered relative to SEQ ID NO: 138.438. The AAV particle of any one of embodiments 433-435, wherein the AAV capsid variant further comprises an amino acid other than T at position 450, an amino acid other than I at position 451, and an amino acid other than N at position 452, numbered according to SEQ ID NO: 138 or 982.439. The AAV particle of any one of embodiments 433-435 or 438, wherein the AAV capsid variant further comprises A at position 450, E at position 451 , and I at position 452, numbered according to SEQ ID NO: 138 or 982.440. The AAV particle of any one of embodiments 433-435, 438, or 439, wherein the AAV capsid variant further comprises the substitutions T450A, I451E, and N452I, numbered according to SEQ ID NO: 138 or 982.441. The AAV particle of any one of embodiments 433, 434, or 438-440, wherein the AAV capsid variant comprises:(i) A at position 450, E at position 451, and I at position 452, numbered according to SEQ IDNO: 138 or 982; and(ii) the amino acid sequence of HDSPHK (SEQ ID NO: 2), which is present immediately subsequent to positions 453. numbered according to SEQ ID NO: 138 or 982.442. The AAV particle of any one of embodiments 1-22, 25-27, 31, 34-42, 45-50, 53-63, 69. 79, 83- 86, 91-98, 102, 103, 110, 111. 118-129, 369-371, 384, 385, 390, 393, 395, 410-413, wherein the AAV capsid variant comprises the amino acid sequence of SPHKYG (SEQ ID NO: 966), wherein the amino acid sequence is present immediately subsequent to position 455, numbered according to the amino acid sequence of SEQ ID NO: 138.443. An adeno-associated vims (AAV) particle comprising an AAV capsid variant comprising the amino acid sequence of HDSPHK (SEQ ID NO: 2), wherein the amino acid sequence is present immediately subsequent to position 453, numbered according to the amino acid sequence of SEQ ID NO: 982, wherein the AAV particle further comprises a nucleic acid encoding a p-glucocerebrosidase 1 (GBA1) protein (e.g., a human GBA1 protein).444. An adeno-associated virus (AAV) particle comprising an AAV capsid variant and a nucleic acid encoding a β-glucocerebrosidase 1 (GBA1) protein (e.g.. a human GBA1 protein), wherein 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, numbered according to the amino acid sequence of SEQ ID NO: 981.445. An adeno-associated virus (AAV) particle comprising an AAV capsid variant comprising the amino acid sequence of HDSPHK (SEQ ID NO: 2), wherein the amino acid sequence is present immediately subsequent to position 453. numbered according to the amino acid sequence of SEQ ID NO: 37, and optionally further comprising:(i) one, two, or all of an amino acid other than T at position 450, an amino acid other than I at position 541, and / or an amino acid other than N at position 452, numbered according to SEQ ID NO: 138 or 37;(ii) one. two, or all of A at position 450, E at position 451, and / or I at position 452, numbered according to SEQ ID NO: 138 or 37; wherein the AAV particle further comprises a nucleic acid encoding a p-glucocerebrosidase 1 (GBA1) protein (e.g., a human GBA1 protein).446. An adeno-associated vims (AAV) particle comprising an AAV capsid variant comprising the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is present immediately subsequent to position 455, numbered according to the amino acid sequence of any one of SEQ ID NO: 36, 38-55, 57. or 59, wherein the AAV particle further comprises a nucleic acid encoding a p-glucocerebrosidase 1 (GBA1) protein (e.g., a human GBA1 protein).447. The AAV particle of any one of the preceding embodiments, wherein the AAV capsid variant further comprises:(i) a modification in loop I. II. VI and / or VIII; and / or(ii) a substitution at position K449, e.g., a K449R substitution, numbered according to SEQID NO: 138.448. The AAV particle of any one of the preceding embodiments, wherein the AAV capsid variant comprises an amino acid sequence comprising at least one, at least two, or at least three modifications, e.g., substitutions (e.g., conservative substitutions), but not more than 30, not more than 20, or not more than 10 modifications, e.g., substitutions (e.g., conservative substitutions), relative to the amino acid sequence of SEQ ID NO: 138.449. The AAV particle of any one of the preceding embodiments, wherein the AAV capsid variant comprises an amino acid sequence comprising at least one, at least two, or al least three, but no more than 30, not more than 20, or not more than 10 different amino acids relative to the amino acid sequence of SEQ ID NO: 138.450. The AAV particle of any one of the preceding embodiments, wherein the AAV capsid variant comprises an amino acid sequence with at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) sequence identity to SEQ ID NO: 138.451. The AAV particle of any one of the preceding embodiments, wherein the AAV capsid variant comprises an amino acid sequence with at least 98% identity to SEQ ID NO: 138.452. The AAV particle of any one of the preceding embodiments, wherein the AAV capsid variant comprises an amino acid sequence encoded by a sequence with at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) sequence identity to SEQ ID NO: 137.453. The AAV particle of any one of the preceding embodiments, wherein the nucleotide sequence encoding the capsid variant comprises a sequence with at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) sequence identity to SEQ ID NO: 137.454. The AAV particle of any one of the preceding embodiments, wherein the AAV capsid variant comprises a VP1 protein, a VP2 protein, a VP3 protein, or a combination thereof.455. The AAV particle of any one of embodiments 1-454, wherein the AAV capsid variant comprises the amino acid sequence corresponding to positions 138-742, e.g., a VP2, of SEQ ID NO: 981, 982, 36, or 4, or a sequence with at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) sequence identity thereto.456. The AAV particle of any one of embodiments 1 -455, wherein the AAV capsid variant comprises the amino acid sequence corresponding to positions 203-742, e.g, a VP3, of SEQ ID NO: 981, 982, 36, or 4, or a sequence with at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%. or at least 99%) sequence identity thereto.457. The AAV particle of any one of embodiments 1-456, wherein the AAV capsid variant comprises an amino acid sequence with at least 80% (e.g., at least 80%, al least 85%, at least 90%, at least 95%, al least 96%, at least 97%, at least 98%, or at least 99%) sequence identity to SEQ ID NO: 138.458. The AAV particle of any one of embodiments 1-457, wherein the AAV capsid variant comprises an amino acid sequence with at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) sequence identity to SEQ ID NO: 138.459. The AAV particle of any one of embodiments 1-23, 26-29, 32, 35-43, 46-51, 54-72, 69-89, 91, 94-99, 102-104, 107, 1 10- 112, 115-129, 168-202, 240-247, 249, 250, 253-263, 266, 272-281, 286, 288, 291-299, 327-363, 369-371, 375-379, 385, 386, 390, 391, 395, 406, 408, 410-413, 415-432, 444, or 446-458, wherein the AAV capsid variant comprises an amino acid sequence comprising at least 3, at least 4. at least 5, or at least 6 consecutive amino acids from the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein:(i) the at least 3 consecutive amino acids comprise SPH;(ii) the at least 4 consecutive amino acids comprise SPHS (SEQ ID NO: 4700);(iii) the at least 5 consecutive amino acids comprise SPHSK (SEQ ID NO: 4701); or(iv) the at least 6 consecutive amino acids comprise SPHSKA (SEQ ID NO: 941); wherein the AAV capsid variant comprises: (a) a VP1 protein comprising the amino acid sequence of SEQ ID NO: 981; (b) a VP2 protein comprising the amino acid sequence of positions 138-742 of SEQ ID NO: 981; (c) a VP3 protein comprising the amino acid sequence of positions 203- 742 of SEQ ID NO: 981 ; or (d) an amino acid sequence with at least 90% (e.g., at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) sequence Identity to any of the amino acid sequences in (a)-(c).460. The AAV particle of any one of embodiments 1-2.3, 26-29, 32, 35-43, 46-51 , 54-72, 69-89, 91, 94-99, 102-104, 107, 110-112, 115-129. 168-202, 240-247, 249, 250, 253-263, 266, 272-281, 286, 288, 291-299, 327-363, 369-371, 375-379, 385, 386, 390, 391, 395, 406, 408, 410-413, 415-432, 444, or 446-459, wherein the AAV capsid variant comprises an amino acid sequence comprising at least 3, at least 4, at least 5, or at least 6 consecutive amino acids from the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein:(i) the at least 3 consecutive amino acids comprise SPH;(ii) the at least 4 consecutive amino acids comprise SPHS (SEQ ID NO: 4700);(iii) the at least 5 consecutive amino acids comprise SPHSK (SEQ ID NO: 4701); or(iv) the at least 6 consecutive amino acids comprise SPHSKA (SEQ ID NO: 941); wherein the AAV capsid variant comprises an amino acid sequence at least 90% (e.g,, at least 90%, at least 95%, at least 96%. at least 97%, at least 98%, or at least 99%) to the amino acid sequence of SEQ ID NO: 981.461. The AAV particle of any one of embodiments 1-23, 26-29, 32, 35-43, 46-51, 54-72, 69-89, 91, 94-99, 102-104, 107, 110-112, 115-129. 168-202, 240-247, 249, 250, 253-263, 266, 272-281, 286, 288, 291-299, 327-363, 369-371, 375-379, 385, 386, 390, 391, 395, 406, 408, 410-413, 415-432, 444, or 446-460, wherein the AAV capsid variant comprises one or two, but no more than three substitutions relative to the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the AAV capsid variant comprises:(a) a VP1 protein comprising the amino acid sequence of SEQ ID NO: 981;(b) a VP2 protein comprising the amino acid sequence of positions 138-742 of SEQ ID NO: 981;(c) a VP3 protein comprising the amino acid sequence of positions 203-742 of SEQ ID NO: 981; or(d) an amino acid sequence with at least 90% (e.g, at least 90%, at: least 95%, at least 96%, at least 97%. at least 98%, or at least 99%) sequence identity to any of the amino acid sequences in (a)- (c).462. The AAV particle of any one of embodiments 1-23, 26-29, 32, 35-43, 46-51, 54-72, 69-89, 91, 94-99, 102-104, 107, 110-112, 115-129, 168-202, 240-247, 249, 250, 253-263, 266, 272-281, 286, 288, 291-299, 327-363, 369-371 , 375-379, 385, 386, 390, 391, 395, 406, 408, 410-413, 415-432, 444, or 446-461 , wherein the AAV capsid variant comprises one or two, but no more than three substitutions relative to the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the AAV capsid variant comprises an amino acid sequence at least 90% (e.g., at least 90%, at least 95%, at least 96%, at least 97%, at least 98%. or at least 99%) identical to the amino acid sequence of SEQ ID NO: 138 or SEQ ID NO: 981 .463. The AAV particle of any one of embodiments 459-462, wherein the amino acid sequence is present immediately subsequent to position 455. numbered according to SEQ ID NO: 138 or 981.464. The AAV particle of any one of embodiments 1-9, 11, 12-22, 24, 26, 28, 30, 33, 35-42, 44, 46- 50, 52, 54-77, 83-88, 90-97, 100-103, 105, 110, 111, 113-129, 203-248, 251, 252, 254-257, 260, 261, 264-280, 283-287, 289-299, 327-363, 369, 369, 371, 380-383, 385, 386, 390, 392, 395, 407, 409-412,414, 433-435, 438-441 , 443, 445, or 447-458, wherein the AAV capsid variant an amino acid sequence comprising at least 3, at least 4, at least 5, or at least 6 consecutive amino acids from the amino acid sequence of HDSPHK (SEQ ID NO: 2), wherein:(i) the at least 3 consecutive amino acids comprise HDS;(ii) the at least 4 consecutive amino acids comprise HDSP (SEQ ID NO: 4702);(iii) the at least 5 consecutive amino acids comprise HDSPH (SEQ ID NO: 4703); or(iv) the at least 6 consecutive amino acids comprise HDSPHK (SEQ ID NO: 2); wherein the AAV capsid variant comprises: (a) a VP1 protein comprising the amino acid sequence of SEQ ID NO: 982; (b) a VP2 protein comprising the amino acid sequence of positions 138-742 of SEQ ID NO: 982; (c) a VP3 protein comprising the amino acid sequence of positions 203- 742 of SEQ ID NO: 982; or (d) an amino acid sequence with at least 90% (e.g., at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) sequence identity to any of the amino acid sequences in (a)-(c).465. The AAV particle of any one of embodiments 1-9, 11, 12-22, 24, 26, 28, 30, 33, 35-42, 44, 46- 50, 52, 54-77, 83-88, 90-97, 100-103, 105, 110, 111, 113-129, 203-248, 251, 252, 254-257, 260, 261, 264-280, 283-287. 289-299. 327-363, 369, 369, 371, 380-383, 385, 386, 390. 392, 395. 407, 409-412, 414, 433-435, 438-441, 443, 445, 447-458, or 464, wherein the AAV capsid variant comprises an amino acid sequence comprising at least 3, at least 4, at least 5, or at least 6 consecutive amino acids from the amino acid sequence of HDSPHK (SEQ ID NO: 2), wherein:(i) the at least 3 consecutive amino acids comprise HDS;(ii) the at least 4 consecutive amino acids comprise HDSP (SEQ ID NO: 4702);(iii) the at least 5 consecutive amino acids comprise HDSPH (SEQ ID NO: 4703); or(iv) the at least 6 consecutive amino acids comprise HDSPHK (SEQ ID NO: 2); wherein the AAV capsid variant comprises an amino acid sequence at least 90% (e.g., at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence of SEQ ID NO: 982.466. The AAV particle of any one of embodiments 1-9, 11 , 12-22, 24, 26, 28, 30, 33, 35-42, 44, 46- 50, 52. 54-77, 83-88, 90-97, 100-103, 105, 110, 111 , 113-129, 203-248, 251, 252, 254-2.57, 260, 261, 264-2.80, 283-287, 289-299, 327-363, 369, 369, 371 , 380-383, 385, 386, 390, 392, 395, 407. 409-412,414, 433-435, 438-441, 443, 445. 447-458, 464, or 465, wherein the AAV capsid variant comprises one or two, but no more than three substitutions relative to the amino acid sequence of HDSPHK (SEQ ID NO: 2), wherein the AAV capsid variant comprises:(a) a VP1 protein comprising the amino acid sequence of SEQ ID NO: 982;(b) a VP2 protein comprising the amino acid sequence of positions 138-742 of SEQ ID NO: 982;(c) a VP3 protein comprising the amino acid sequence of positions 203-742 of SEQ ID NO:982; or(d) an amino acid sequence with at least 90% (e.g., at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) sequence identity to any of the amino acid sequences in (a)- (c),467. The AAV particle of any one of embodiments 1-9, 11, 12-22, 24, 26, 28, 30, 33, 35-42, 44, 46- 50, 52, 54-77, 83-88, 90-97, 100-103, 105, 110, 111, 113-129, 203-248, 251, 252, 254-257, 260, 261, 264-280, 283-287, 289-299, 327-363, 369, 369, 371, 380-383, 385, 386, 390, 392, 395, 407, 409-412, 414, 433-435, 438-441, 443, 445, 447-458, or 464-466, wherein the AAV capsid variant comprises one or two, but no more than three substitutions relative to the amino acid sequence of HDSPHK (SEQ ID NO: 2), wherein the AAV capsid variant comprises an amino acid sequence at least 90% (e.g., at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the amino acid sequence of SEQ ID NO: 982.468. The AAV particle of any one of embodiments 464-468, wherein the amino acid sequence is present immediately subsequent to position 453, numbered according to SEQ ID NO: 138 or 982.469. The AAV particle of any one of embodiments 1-468, wherein the AAV capsid variant comprises the amino acid sequence of SEQ ID NO: 981 or 982. or an amino acid sequence with at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98?% or at least 99%) sequence identity thereto.470. The AAV particle of any one of embodiments 1-469, wherein the AAV capsid variant comprises an amino acid sequence comprising at least one, at least two or at least three modifications, e.g., substitutions (e.g., conservative substitutions), but not more than 30, not more than 20 or not more than 10 modifications, e.g., substitutions (e.g., conservative substitutions), relative to the amino acid sequence of SEQ ID NO: 981 or 982.471. The AAV particle of any one of embodiments, 1 -470, wherein the AAV capsid variant comprises an amino acid sequence comprising at least one, at least two or at least three, but not more than 30, not more than 20 or not more than 10 different amino acids, relative to the amino acid sequence of SEQ ID NO: 981 or 982.472. The AAV particle of any one of embodiments 1-23, 26-29, 32, 35-43, 46-51, 54-72, 69-89, 91, 94-99, 102-104, 107, 110-112, 115-129, 168-202, 240-247, 249, 250, 253-263, 266, 272-281, 286, 288, 291-299, 327-363, 369-371, 375-379, 385, 386, 390, 391, 395, 406, 408, 410-413, 415-432, 444,446-463, or 469-471 , wherein the AAV capsid variant comprises the amino acid sequence of SEQ IDNO: 981, or an amino acid sequence with at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) sequence identity thereto.473. The AAV particle of any one of embodiments 1-23, 26-2.9, 32, 35-43, 46-51 , 54-72, 69-89, 91, 94-99, 102-104, 107, 110-112, 115-129, 168-202. 240-247, 249, 250, 253-263, 266, 272-281, 286, 288, 291-299, 327-363, 369-371, 375-379, 385, 386, 390, 391, 395, 406, 408, 410-413, 415-432, 444, 446-463, or 469-472, wherein the AAV capsid variant comprises an amino acid sequence comprising al least one, at least two or al least three modifications, e.g., substitutions (e.g., conservative substitutions), but not more than 30, not more than 20 or not more than 10 modifications, e.g., substitutions (e.g., conservative substitutions), relative to the amino acid sequence of SEQ ID NO: 981.474. The AAV particle of any one of embodiments 1-23, 26-29, 32, 35-43, 46-51, 54-72, 69-89, 91, 94-99, 102-104, 107, 110-1 12, 115-129, 168-202, 240-247, 249, 250, 253-263, 266, 272-281, 286, 288, 291-299, 327-363, 369-371, 375-379, 385, 386, 390, 391, 395, 406, 408, 410-413, 415-432, 444, 446-463, or 469-473, wherein the AAV capsid variant comprises an amino acid sequence comprising at least one, at least two or at least three, but not more than 30, not more than 20 or not more than 10 different amino acids, relative to the amino acid sequence of SEQ ID NO: 981.475. The AAV particle of any one of embodiments 1-9, 11, 12-22, 24, 26, 28. 30, 33, 35-42, 44, 46-50, 52, 54-77, 83-88, 90-97, 100-103, 105, 110, 111, 113-129, 203-248, 251, 252, 254-257, 260, 261,264-280, 283-287, 289-299, 327-363, 369, 369, 371, 380-383, 385, 386, 390, 392, 395, 407, 409-412,414, 433-435, 438-441, 443, 445, 447-458, or 464-471, wherein the AAV capsid variant comprises the amino acid sequence of SEQ ID NO: 982, or an amino acid sequence with at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least99%) sequence identity thereto.476. The AAV particle of any one of embodiments 1-9, 11 , 12-22, 24, 2.6, 28, 30, 33, 35-42. 44, 46-50, 52, 54-77, 83-88, 90-97, 100-103, 105, 110, 111 , 113-129, 203-248, 251, 2.52, 254-257, 260, 261264-280, 283-287, 289-299, 327-363, 369, 369, 371 , 380-383, 385, 386, 390, 392. 395, 407, 409-412,414, 433-435, 438-441, 443, 445, 447-458, 464-471, or 475, wherein three AAV capsid variant comprises an amino acid sequence comprising at least one, at least two or at least three modifications, e.g., substitutions (e.g., conservative substitutions), but not more than 30, not more than 20 or not more than 10 modifications, e.g., substitutions (e.g., conservative substitutions), relative to the amino acid sequence of SEQ ID NO: 982.477. The AAV particle of any one of embodiments 1-9, 11, 12-22, 24, 26, 28, 30, 33, 35-42, 44, 46- 50, 52, 54-77, 83-88, 90-97, 100-103, 105, 110, 111 , 113-129, 203-248, 251, 252, 254-257, 260, 261, 264-280, 283-287, 289-299, 327-363, 369, 369, 371 , 380-383, 385, 386, 390, 392, 395, 407, 409-412, 414, 433-435, 438-441 , 443, 445, 447-458, 464-471 , 475, or 476, wherein the AAV capsid variant comprises an amino acid sequence comprising at least one, at least two or at least three, but not more than 30, not more than 2.0 or not more than 10 different amino acids, relative to the amino acid sequence of SEQ ID NO: 982.478. The AAV particle of any one of embodiments 1-477, wherein the AAV capsid variant comprises an amino acid sequence encoded by the nucleotide sequence of SEQ ID NO: 983 or 984, or a nucleotide sequence with at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) sequence identity thereto.479. The AAV particle of any one of embodiments 1-478, wherein the nucleotide sequence encoding the capsid variant comprises the nucleotide sequence of SEQ ID NOs: 983 or 984, or a nucleotide sequence with at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) sequence identity thereto.480. The AAV particle of any one of embodiments 1-23, 26-29, 32. 35-43, 46-51, 54-72, 69-89, 91, 94-99, 102-104, 107, 110-112, 115-129, 168-202, 02, 240-247, 249. 250, 253-263, 266, 272-281, 286, 288, 291-299, 327-363, 369-371, 375-379, 385, 386, 390, 391, 395, 406, 408, 410-413, 415-432, 444, 446-463, 469-474, 478, or 479, wherein the nucleotide sequence encoding the capsid variant comprises the nucleotide sequence of SEQ ID NO: 983, or a nucleotide sequence with at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) sequence identity thereto.481. The AAV particle of any one of embodiments 1-9, 11 , 12-22, 24, 26, 28, 30, 33, 35-42, 44, 46- 50, 52, 54-77. 83-88, 90-97, 100-103, 105, 110, 111 , 113-129, 203-248, 251, 252, 254-257, 260, 261, 264-280, 283-287, 289-299, 327-363, 369, 369, 371. 380-383, 385, 386, 390, 392. 395, 407. 409-412, 414, 433-435, 438-441 , 443, 445, 447-458, 464-471 , or 475-479, wherein the nucleotide sequence encoding the capsid variant comprises the nucleotide sequence of SEQ ID NO: 984, or a nucleotide sequence with at least 80% (e.g., al least 80%, at least 85%. at least 90%, at least 95%, al least 96%, at least 97%, at least 98%, or al least 99%) sequence identity thereto.482. The AAV particle of any one of the preceding embodiments, wherein the nucleotide sequence encoding the capsid variant is codon optimized.483. An adeno-associated virus (AAV) particle of any one of embodiments 1-23, 26-29, 32, 35-43, 46-51 , 54-72, 69-89, 91, 94-99, 102-104, 107, 110-112, 115-129, 168-202, 02, 240-247, 249, 250, 253-263, 266, 272-281 , 286, 288, 291-299, 327-363, 369-371 , 375-379, 385, 386, 390, 391 , 395, 406, 408, 410-413, 415-432, 444, 446-463, 469-474, 478-480, or 482, and further comprising an amino acid sequence at least 95% identical to SEQ ID NO: 981.484. An adeno-associated virus (AAV) particle comprising an AAV capsid variant and a nucleic acid encoding a p-glucocerebrosidase 1 (GBA1) protein (e.g.. a human GBA1 protein), wherein the AAV capsid variant comprises the amino acid sequence of SEQ ID NO: 981.485. The AAV particle of embodiment 483 or 484, wherein the nucleotide sequence encoding the AAV capsid variant comprises the nucleotide sequence of SEQ ID NO: 983, or a nucleotide sequence at least 90%, at least 95%, or at least 99% identical thereto.486. The AAV particle of any one of embodiments 1-9, 11, 12-22, 24, 26, 28, 30, 33, 35-42, 44, 46-50, 52, 54-77, 83-88, 90-97, 100-103, 105, 110, 11 1, 113-129, 203-248, 251, 252, 254-257. 260, 261,264-280, 2.83-287, 289-299. 327-363, 369, 369, 371, 380-383, 385, 386, 390, 392, 395, 407, 409-412,414, 433-435, 438-441, 443, 445, 447-458, 464-471, 475-479, 481 , or 482, and further comprising an amino acid sequence at least 95% identical to SEQ ID NO: 982.487. An adeno-associated virus (AAV) particle comprising an AAV capsid variant and a nucleic acid encoding a P-glucocerebrosidase 1 (GBA1) protein (e.g., a human GBA1 protein), wherein the AAV capsid variant comprises the amino acid sequence of SEQ ID NO: 982.488. The AAV particle of embodiment 486 or 487, wherein the nucleotide sequence encoding the AAV capsid variant comprises the nucleotide sequence of SEQ ID NO: 984, or a nucleotide sequence at least 90%, at least 95%, or at least 99% identical thereto.489. An adeno-associated virus (AAV) particle comprising an AAV capsid variant and a nucleic acid encoding a P-glucocerebrosidase 1 (GBA1) protein (e.g., a human GBA1 protein), wherein the AAV capsid variant comprises an amino acid sequence encoded by the nucleotide sequence of SEQ ID NOs: 983 or 984, or a nucleotide sequence at least 95% identical thereto.490. An adeno-associated virus ( AAV) particle comprising an AAV capsid variant and a nucleic acid encoding a p-glucocerebrosidase 1 (GBA1) protein (e.g., a human GBA1 protein), wherein the AAV capsid variant comprises the amino acid sequence of any one of SEQ ID NOs: 4 or 36-59, optionally wherein the AAV capsid variant comprises the amino acid sequence of SEQ ID NO: 4 or 36.491. An adeno-associated vims (AAV) particle comprising an AAV capsid variant and a nucleic acid encoding a P-glucocerebrosidase 1 (GBA1) protein (e.g., a human GBA1 protein), wherein the AAV capsid variant comprises an amino acid sequence encoded by the nucleotide sequence of any one ofSEQ ID NOs: 12-35, or a nucleotide sequence at least 95% identical thereto.492. The AAV particle of 490 or 491. wherein the nucleotide sequence encoding the AAV capsid variant comprises the nucleotide sequence of any one of SEQ ID NOs: 12-35, or a nucleotide sequence at least 95% identical thereto.493. The AAV particle of any one of embodiments 1-299, 369-371, or 375-492, which has an increased tropism for a CNS cell or tissue, e.g., a brain cell, brain tissue, spinal cord cell, or spinal cord tissue, relative to the tropism of an AAV particle comprising a capsid comprising the amino acid sequence of SEQ ID NO: 138.494. The AAV particle of any one of embodiments 1-129, 168-299, 369-371 , or 375-493, which transduces a brain region, e.g., a midbrain region (e.g., the hippocampus, or thalamus) or the brain stem, optionally wherein the level of transduction is at least 5, at least 10. at least 15. at least 2.0, at least 25, at least 30, at least 35, at least 40, at least 45. at least 50, at least 55, at least 60, or at least 65- fold greater as compared to an AAV particle comprising a capsid of SEQ ID NO: 138, e.g., when measured by an assay, e.g., an immunohistochemistry assay or a qPCR assay, e.g., as described in Example 2.495. The AAV particle of any one of embodiments 1-129, 168-299, 369-371, or 375-494, which transduces a brain region, e.g., a midbrain region (e.g., the hippocampus, or thalamus) or the brain stem, optionally wherein the level of transduction is at least 30, at least 35, at least 40, at least 45, at least 50, at least 55, at least 60, or at least 65-fold greater as compared to an AAV particle comprising a capsid of SEQ ID NO: 138, e.g., when measured by an assay, e.g., an immunohistochemistry assay or a qPCR assay, e.g., as described in Example 2.496. The AAV particle of any one of embodiments 1-129, 168-299, 369-371, or 375-495, which is enriched at least 3. at least 4, at least 5, at least 6, at least 7. at least 8, at least 9, or at least 10-fold, in the brain compared to an AAV particle comprising a capsid of SEQ ID NO: 138, e.g., when measured by an assay as described in Example 1.497. The AAV particle of any one of embodiments 1-129, 168-299, 369-371, or 375-496, which is enriched at least 20, at least 25, at least 30, at least 35, at least 40, at least 45, at least 50, at least 55, atleast 60, at least 65, at least 70, at least 75, at least 80 or at least 85-fold, in the brain compared to anAAV particle comprising a capsid of SEQ ID NO: 138, e.g., when measured by an assay as described in Example 1.498. The AAV particle of any one of embodiments 1-129, 168-299, 369-371, or 375-497, which is enriched in the brain of at least two to at least three species, e.g., a non-human primate and rodent(e.g., mouse), e.g., as compared to an AAV particle comprising a capsid of SEQ ID NO: 138.499. The AAV particle of any one of embodiments 1-129, 168-299, 369-371, or 375-498, which is enriched at least 10, at least 15, at least 20, at least 25, at least 30, at least 35, at least 40, at least 45, at least 50, at least 55, at least 60, at least 65, at least 70, at least 75, at least 80, at least 85, at least 90, at least 95, at least 100, at least 105, at least 115, at least 120, at least 125, at least 130, at least 135, at least 140, at least 145, at least 150, at least 155, at least 160, at least 165, at least 170, at least 175, at least 180, at least 190, at least 200, at least 205, or at least 210-fold, in the brain of at least two to at least three species, e.g., a non-human primate and rodent (e.g., mouse), compared to an AAV particle comprising a capsid of SEQ ID NO: 138, e.g., when measured by an assay as described in Example 1 or 5.500. The AAV particle of embodiment 498 or 499. wherein the at least two to at least three species are Macaco fascicularis, Chlorocebus sabaeus, Callithrixjacchus, and / or mouse (e.g., BALB / c mice, C57B1 / 6 mice, and / or CD-I outbred mice).501. The AAV particle of any one of embodiments 130-146, 369, 410-414, 447-454, 457, 458, 482, or 493, which is enriched at least 2, at least 2.5, at least 3, at least 3.5, at least 4, at least 4.5, at least 5, at least 5.5, at least 6, at least 6.5, at least 7, at least 7.5, or at least 8-fold, in the brain compared to an AAV particle comprising a capsid of SEQ ID NO: 981, e.g., when measured by an assay as described in Example 3.502. The AAV particle of any one of embodiments 147-167, 369, 410-414, 447-454, 457, 458, 482, or493, which is enriched at least 2, at least 2.5, at least 3, at least 3.5. at least 4, at least 4.5, at least 5, or at least 5.5-fold, in the brain compared to an AAV particle comprising a capsid of SEQ ID NO: 982, e.g., when measured by an assay as described in Example 3.503. The AAV particle of any one of embodiments 1-129, 168-299, 369-371, or 375-500, which delivers an increased level of a pay load to a brain region, optionally wherein the level of the pay load is increased by at least 10, at least 12, at least 15, at least 20, at least 25, at least 30, at least 35, at least 40, at least 45, at least 50, at least 55, at least 60, at least 65, or at least 70-fold, as compared to anAAV particle comprising a capsid of SEQ ID NO: 138, e.g.. when measured by an assay, e.g., a qRT-PCR or a qPCR assay (e.g., as described in Example 2 or 8).504. The AAV particle of any one of embodiments 1-129, 168-299, 369-371, 375-500, or 503, which delivers an increased level of viral genomes to a b rain region, optionally wherein the level of viral genomes is increased by at least 5. at least 10, at least 15, at least 17, at least 18, at least 19, at least20, at least 25, at least 30. at least 35, at least 40, at least 45, or at least 50-fold, as compared to an AAV particle comprising a capsid of SEQ ID NO: 138, e,g„ when measured by an assay, e.g., a qRT-PCR or a qPCR assay (e.g., as described in Example 2 or 8).505. The AAV particle of embodiment 503 or 504, wherein the brain region is a midbrain region (e.g., the hippocampus or thalamus), frontal cortex, temporal cortex, motor cortex, cerebral cortex, caudate, putamen, dentate nucleus, substantia nigra, or the brainstem.506. The AAV particle of any one of embodiments 1-129, 168-299, 369-371 , 375-500, or 503-505, which is enriched at least 4, at least 5, at least 10, at least 15, at least 20, at least 25, at least 30, or at least 35 -fold, in the spinal cord compared to an AAV particle comprising a capsid of SEQ ID NO: 138, e.g., when measured by an assay as described in Example 1 or 8, optionally wherein the region of the spinal cord is a thoracic spinal cord region, cervical spinal cord region, C5 ventral horn region, lumbar spinal cord region, or L5 ventral horn region.507. The AAV particle of any one of embodiments 1-129, 168-299, 369-371, 375-500, or 503-506, which shows preferential transduction in a brain region relative to the transduction in the dorsal root ganglia (DRG).508. The AAV particle of any one of embodiments 1-129, 168-299, 369-371, 375-500, or 503-507, which show's preferential transduction in a brain region relative to the liver.509. The AAV particle of any one of embodiments 1-129, 168-299, 369-371, 375-500, or 503-508, which shows preferential transduction in a brain region relative to the transduction in the heart.510. The AAV particle of any one of embodiments 1-129, 168-299, 369-371, 375-500, or 503-509, which shows preferential transduction in a brain region relative to the transduction in the dorsal root ganglia (DRG) and the heart.511. The AAV particle of any one of the preceding embodiments, which is capable of transducing non-neuronal cells, e.g., glial cells (e.g., oligodendrocytes or astrocytes).512. The AAV particle of embodiment 511, w'herein the non-neuronal cells comprise glial cells, oligodendrocytes (e.g., Olig2 positive oligodendrocytes), or astrocytes (e.g., Olig2 positive astrocytes).513. The AAV particle of any one of the preceding embodiments, which is capable of transducing Olig2 positive cells, e.g.. Olig2 positive astrocytes or Olig2 positive oligodendrocy tes.514. The AAV particle of any one of embodiments 369, 373, 447-454, 457, 458, or 482, which has increased tropism for a heart cell or tissue, e.g., a heart ventricle or heart atrium, relative to the tropism of an AAV particle comprising a capsid of SEQ ID NO: 138.515. The AAV particle of any one of embodiments 369, 373, 447-454, 457, 458, 482, or 514, which is enriched at least 4, at least 5, at least 8, at least 10, at least 1 1, at least 12, at least 13, at least 14, at least 18, at least 19, at least 20, at least 21, at least 22, at least 24, at least 25, at least 27, at least 31, at least 33, or at least 34-fold, in the heart compared to an AAV particle comprising a capsid of SEQ IDNO: 138, e.g., when measured by an assay as described in Example 4.516. The AAV particle of any one of embodiments 369, 374, 447-454, 457, 458, 482, which lias an increased tropism for a muscle cell or tissue (e.g., a quadriceps ceil or a quadriceps tissue), relative to the tropism of an AAV particle comprising a capsid comprising the amino acid sequence of SEQ ID NO: 138.517. The AAV particle of any one of embodiments 369, 374, 447-454, 457, 458, 482, which is enriched at least 4, at least 5, at least 8, at least 12, at least 17, at least 18, at least 20, at least 26, at least 27, at least 28, at least 30, or at least 36-fold, in the muscle compared to an AAV particle comprising a capsid of SEQ ID NO: 138, e.g., when measured by an assay as described in Example 4.518. The AAV particle of embodiment 516 or 517, wherein the muscle cell or tissue is a heart muscle(e.g,, a heart ventricle or a heart atrium, or both), a quadriceps muscle, or both.519. The AAV particle of any one of the preceding embodiments, which is isolated and / or recombinant.[Embodiments 520-585 are intentionally absent.]586. The AAV particle of any one of the preceding embodiments, wherein the viral genome comprises a promoter operably linked to the GB A-encoding sequence.587. The AAV particle of embodiment 586, wherein the promoter is human elongation factor 1α- subunit (EF1α), cytomegalovirus (CMV) immediate-early enhancer and / or promoter, chicken 0-actin (CBA), CAG, CAG derivative, β glucuronidase (GUSB), or ubiquitin C (UBC), neuron-specific enolase (NSE), platelet-derived growth factor (PDGF), platelet-derived growth factor B-cltain (PDGF-0), intercellular adhesion molecule 2 (ICAM-2), synapsin (Syn), melhyl-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 nβ2, preproenkephalin (PPE), enkephalin (Enk) and excitatory amino acid transporter 2 (EAAT2), glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), a cardiovascular promoter (e.g., αMHC, cTnT, and CMV-MLC2k), a liver promoter (e.g., hAAT, TBG), a skeletal muscle promoter (e.g., desmin, MCK, C512) or a fragment, e.g., a truncation, or a functional variant thereof.[Embodiments 588 and 589 are intentionally absent,]590. The AAV particle of any one of embodiments 586-589, wherein the viral genome further comprises a polyadenylation (poly A) sequence.591. The AAV particle of any one of embodiments 586-590, wherein the viral genome further comprises an inverted terminal repeat (ITR) sequence.592. The AAV particle of any one of embodiments 586-591, wherein the viral genome comprises an ITR sequence positioned 5’ relative to the nucleotide sequence encoding the GBA1 protein (e.g., the human GBA1 protein).593. The AAV particle of any one of embodiments 586-592, wherein the viral genome comprises an ITR sequence positioned 3’ relative to the nucleotide sequence encoding the GBA1 protein (e.g., the human GBA1 protein).594. The AAV particle of any one of embodiments 586-593, wherein the viral genome comprises an ITR sequence positioned 5' relative to the nucleotide sequence encoding the GBA1 protein (e.g., the human GBA1 protein) and an ITR sequence positioned 3’ relative to the nucleotide sequence encoding the GBA1 protein (e.g., the human GBA1 protein).595. The AAV particle of any one of embodiments 586-594, wherein the viral genome further comprises an enhancer, a Kozak sequence, an intron region, and / or an exon region.596. The AAV particle of any one of embodiments 586-594, 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 GBA1 protein encoded by the viral genome in a cell or tissue where the corresponding miRNA is expressed.597. The AAV particle of embodiment 596, wherein the encoded miRNA binding site is fully complementary or partially complementary to a miRNA expressed in a cell or tissue of the DRG, liver, heart, hematopoietic lineage, or a combination thereof.598. The AAV particle of embodiment 596 or 597, wherein the encoded miR binding site modulates, e.g., reduces, expression of the encoded GBA1 protein in a cell or tissue of the DRG, liver, heart, hematopoietic lineage, or a combination thereof.599. The AAV particle of any one of embodiments 586-598, wherein the viral genome comprises at least 1-5 copies of the encoded miR binding site, e.g., at least 1, at least 2, at least 3, at least 4, or at least 5 copies.600. The AAV particle of any one of embodiments 586-599, 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, at least two, at least three, or all of the copies comprise a different miR binding site.601. The AAV particle of embodiment 600, wherein the 3 copies of the encoded miR binding sites are continuous (e.g., not separated by a spacer), or are separated by a spacer, optionally wherein the spacer comprises the nucleotide sequence of GATAGTTA, or a nucleotide sequence having at least one, at least two. or at least three modifications, e.g., substitutions (e.g., conservative substitutions), but no more than four modifications, e.g., substitutions (e.g., conservative substitutions), relative to the nucleotide sequence of GATAGTTA.602. The AAV particle of any one of embodiments 586-601, 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, at least two, at least three, or all of the copies comprise a different miR binding site.603. The AAV particle of embodiment 602, wherein the at least 4 copies of the encoded miR binding sites are continuous (i.e., not separated by a spacer).603a. The AAV particle of embodiment 602, wherein the at least 4 copies of the encoded miR binding site are separated by a spacer.604. The AAV particle of any one of embodiments 596-603a, 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: the encoded miR183 binding site comprises the nucleotide sequence of SEQ ID NO: 1847, or a nucleotide sequence substantially identical (e.g., having at least 70% at least 75%, at least 80%, at least 85% at least 90%, at least 92%, at least 95%, at least 97% at least 98%, or at least 99% sequence identity) thereto; or a nucleotide sequence having at least one, at least two, at least three, at least four, at least five, at least six, or at least 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: 1847.[Embodiments 605-608 are intentionally absent.]609. The AAV particle of any one of embodiments 586-604, wherein the viral genome comprises an encoded miR183 binding site.610. The AAV particle of any one of embodiments 586-609, wherein the viral genome comprises at least 1-5 copies, e.g., 1, 2, or 3 copies of a miR 183 binding site, optionally wherein each copy is continuous (re., not separated by a spacer), or each copy is separated by a spacer, optionally wherein the spacer comprises the nucleotide sequence of GATAGTTA, or a nucleotide sequence having at least one, at least two, or at least three modifications, e.g., substitutions (e.g., conservative substitutions), but no more than four modifications, e.g., substitutions (e.g., conservative substitutions), relative to the nucleotide sequence of GATAGTTA. The AAV particle of embodiment 609 or 610, wherein the encoded miR 183 binding site comprises the nucleotide sequence of SEQ ID NO: 1847, or a nucleotide sequence substantially identical (e.g., having at least 70%, at least 75% at least 80%. at least 85%, at least 90%, at least 92%, at least 95%, at least 97%, at least 98%, or at least 99% sequence identity) thereto; or a nucleotide sequence having at least one, at least two, at least three, at least four, at least five, at least six, or at least 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: 1847.612. The AAV particle of any one of embodiments 586-611, wherein the viral genome comprises:(A) (i) a first encoded miR 183 binding site comprising the nucleotide sequence of SEQ ID NO: 1847, or a nucleotide sequence substantially identical (e.g., having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%. at least 92%, at least 95%, at least 97%, at least 98%. or at least 99% sequence identity) thereto; or a nucleotide sequence having at least one, at least two, at least three, at least four, at least five, at least six, or at least 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: 1847;(ii) a first spacer comprising the nucleotide sequence of GATAGTTA, or a nucleotide sequence having at least one, at least two, or at least three modifications, e.g., substitutions (e.g., conservative substitutions), but no more than four modifications, e.g., substitutions (e.g., conservative substitutions), relative to the nucleotide sequence of GATAGTTA; and(iii) a second encoded miR183 binding site comprising the nucleotide sequence of SEQ ID NO: 1847, or a nucleotide sequence substantially identical (e.g., having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 92%, at least 95%, at least 97%, at least 98%, or at least 99% sequence identity ) thereto; or a nucleotide sequence having at least one, at least two, at least three, at least four, at least five, at least six, or at least 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: 1847; or(B) (i) a first encoded miR183 binding site comprising the nucleotide sequence of SEQ ID NO: 1847, or a nucleotide sequence substantially identical (e.g., having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 92%, at least 95%, at least 97%, at least 98%, or at least 99% sequence identity) thereto; or a nucleotide sequence having at least one, at least two, at least three, at least four, at least five, at least six, or at least 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: 1847;(ii) a first spacer comprising the nucleotide sequence of GATAGTTA, or a nucleotide sequence having at least one, at least two, or at least three modifications, e.g,, substitutions (e.g., conservative substitutions), but no more than four modifications, e.g., substitutions (e.g., conservative substitutions), relative to GATAGTTA;(iii) a second encoded miR183 binding site comprising the nucleotide sequence of SEQ ID NO: 1847, or a nucleotide sequence substantially identical (e.g., having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%. at least 92%, at least 95%, at least 97%, at least 98%. or at least 99% sequence identity) thereto; or a nucleotide sequence having at least one, at least two, at least three, at least four, at least five, at least six, or at least 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: 1847;(iv) a second spacer comprising the nucleotide sequence of GATAGTTA, or a nucleotide sequence having at least one, at least two, or at least three modifications, e.g,, substitutions (e.g., conservative substitutions), but no more than four modifications, e.g., substitutions (e.g., conservative substitutions), relative to the nucleotide sequence of GATAGTTA; and(v) a third encoded miR183 binding site comprising the nucleotide sequence of SEQ ID NO: 1847, or a nucleotide sequence substantially identical (e.g., having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 92%, al least 95%, at least 97%, at least 98%, or at least 99% sequence identity) thereto; or a nucleotide sequence having at least one, at least two, at least three, at least four, at least five, at least six, or at least 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: 1847.[Embodiment 613 is intentionally absent.]614. The AAV particle of any one of embodiments 586-612, wherein the viral genome is single stranded.615. The AAV particle of any one of embodiments 586-612, wherein the viral genome self- complementary.616. The AAV particle of any one of embodiments 586-615, w'herein 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 (e.g., a Rep78 and aRep52 protein).617. The AAV particle of any one of embodiments 586-615, wherein the AAV particle 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 (e.g., a Rep78 and a Rep52 protein).618. The AAV particle of embodiment 616 or 617, wherein the Rep78 protein, the Rep68 protein, the Rep52 protein, and / or the Rep40 protein are encoded by al least one Rep gene.619. The AAV particle of any one of embodiments 586-618, wherein the viral genome further comprises a nucleic acid sequence encoding the AAV capsid variant of the AAV particle of any one of embodiments 1-519, 566, or 574.620. The AAV particle of any one of embodiments 575-519, wherein the AAV particle is an isolated and / or recombinant AAV particle.[Embodiment 621 is intentionally absent.]622. A cell, e.g., a host cell, comprising the AAV particle of any one of the preceding embodiments.623. The cell of embodiment 622, wherein the cell is a mammalian cell or an insect cell.624. The cell of embodiment 622 or 623, wherein the cell is a ceil of a brain region or a spinal cord region, optionally a cell of the brain stem, hippocampus, or thalamus.625. The ceil of any one of embodiments 622-624, wherein the cell is a neuron, a sensory neuron, a motor neuron, an astrocyte, a glial cell, oligodendrocyte, or a muscle cell (e.g.. a cell of the heart, diaphragm, or quadriceps).[Embodiment 626 is intentionally absent.]627. A method of making an AAV particle, comprising(i) providing a host cell comprising a viral genome comprising a GBA1 -encoding sequence; and(ii) incubating the host ceil under conditions suitable to encapsulate the viral genome in the AAV capsid variant as described in any one of embodiments 1-620; thereby making the AAV particle.62.8. The method of embodiment 627, further comprising, prior to step (i), introducing a first nucleic acid molecule comprising the viral genome into the host cell.629. The method of embodiment 628, wherein the host cell comprises a second nucleic acid encoding the capsid variant.630. The method of embodiment 629, wherein the second nucleic add molecule is introduced into the host cell prior to, concurrently with, or after the first nucleic acid molecule.631. A pharmaceutical composition comprising the AAV particle of any one of embodiments 1-620, and a pharmaceutically acceptable excipient.632. A method of delivering GBA1 to a cell or tissue (e.g., a CNS cell or CNS tissue), comprising administering an effective amount of the pharmaceutical composition of embodiment 631 or the AAV particle of any one of embodiments 1-620.633. The method of embodiment 632, 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, cerebellar cortex, cerebral cortex, brain stem, hippocampus, or thalamus.634. The method of embodiment 632 or 633, wherein the cell is a neuron, a sensory neuron, a motor neuron, an astrocyte, a glial cell, or an oligodendrocyte.[Embodiment 635 is intentionally absent.]636. The method of any one of embodiments 632-634, wherein the cell or tissue is within a subject,637. The method of embodiment 636, wherein the subject lias, has been diagnosed with having, or is at risk of having a genetic disorder, e.g., a monogenic disorder or a polygenic disorder.638. The method of embodiment 636 or 637, wherein the subject lias, has been diagnosed with having, or is at risk of having a neurological, e.g., a neurodegenerative disorder.[Embodiment 639 is intentionally absent.]640. The method of embodiment 636 or 637, wherein the subject has, has been diagnosed with having, or is at risk of having a muscular disorder or a neuromuscular disorder.641. 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 631 or the AAV particle of any one of embodiments 1-620.642. 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 thepharmaceutical composition of embodiment 631 or the AAV particle of any one of embodiments 1- 620.643. A method of treating a subject having or diagnosed with having a muscular disorder or a neuromuscular disorder, comprising administering to the subject an effective amount of the pharmaceutical composition of embodiment 631 or the AAV particle of any one of embodiments 1- 620.[Embodiment 644 is intentionally absent.]645. The method of any one of embodiments 637-643, wherein the genetic disorder, neurological disorder, neurodegenerative disorder, muscular disorder, or neuromuscular disorder is Huntington’s Disease, Amyotrophic Lateral Sclerosis (ALS), Gaucher Disease, Dementia with Lewy Bodies, Lewy Body Dementia, Parkinson’s disease, Parkinson’s disease dementia, Spinal Muscular Atrophy, Alzheimer’s Disease, a leukodystrophy (e.g., Alexander disease, autosomal dominant leukodystrophy w ith autonomic diseases (ADLD), Pure Autonomic Failure, Canavan disease, cerebrotendinous xanthomatosis (CTX), metachromatic leukodystrophy (MLD), Pelizaeus-Merzbacher disease, or Refsum disease.646. The method of any one of embodiments 641-645, where treating comprises prevention of progression of the disorder in the subject.647. The method of any one of embodiments 636-646, wherein the subject is a human.648. The method of any one of embodiments 636-647, wherein the AAV particle is administered to the subject intravenously, via intra-cistema magna injection (ICM), intracerebrally, intrathecallv, intracerebroventricularly, via intraparenchymal administration, intraarterially, or intramuscularly.649. The method of any one of embodiments 636-648, wherein 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.650. The method of any one of embodiments 636-649. wherein the AAV particle is administered to the subject intravenously.651. The method of any one of embodiments 636-650, wherein the AAV particle is administered to the subject via intra-cistema magna injection (ICM).652. The method of any one of embodiments 636-651, wherein the AAV particle is administered to the subject intraarterially.[Embodiment 653 is intentionally absent.]654. The method of any one of embodiments 648-652, wherein administration of the AAV particle results in an increased presence, level, and / or activity of a GBA1 gene, mRNA, protein, or a combination thereof.655. The pharmaceutical composition of embodiment 631 or the AAV particle of any one of embodiments 1-620 for use in a method of delivering a GBA1-encoding sequence to a cell or tissue.656. The pharmaceutical composition of embodiment 631 or the AAV particle of any one of embodiments 1-620 for use in a method of treating a genetic disorder, a neurological disorder, a neurodegenerative disorder, a muscular disorder, or a neuromuscular disorder.657. The pharmaceutical composition of embodiment 631 or the AAV particle of any one of embodiments 1-620 for use in the manufacture of a medicament.658. Use of the pharma...

Claims

CLAIMSWhat is claimed is:1 . An adeno-associated virus (AAV) particle comprising: a) an AAV capsid variant comprising an amino acid sequence having the following formula: [N1]-[N2]-[N3], wherein:(i) optionally [N1] comprises X1, X2, and X3, wherein at least one of X1, X2, or X3 is G;(ii) [N2] comprises the amino acid sequence of SPH; and(iii) [N3] comprises X4, X5, and X6, wherein at least one of X4, X5, or X6 is a basic amino acid; and b) a viral genome comprising a p-glucocerebrosidase 1 (GBA1)-encoding sequence.

2. The AAV particle of claim 1, wherein the amino acid sequence [N1]-[N2]-[N3] is in hypervariable loop IV of the AAV capsid variant.The AAV particle of claim 1 or claim 2. wherein the AAV capsid variant is an AAV9 capsid variant.

4. The AAV particle of any one of claims 1-3, wherein [N 1] comprises X1, X2, and X3, wherein at least one of X1, X2, or X3 is G.

5. The AAV particle of any one of claims 1-4, wherein [N2]-[N3] comprises the amino acid sequence of SPHSKA (SEQ ID NO: 941).

6. An adeno-associated virus (AAV) particle comprising a viral genome comprising a β - glucocerebrosidase 1 (GBA1)-encoding sequence and an AAV9 capsid variant comprising the amino acid sequence of SPHSKA (SEQ ID NO: 941).

7. The AAV particle of claim 6. wherein the amino acid sequence of SPHSKA (SEQ ID NO: 941) is in hypervariable loop IV of the AAV9 capsid variant.

8. The AAV particle of claim 6 or claim 7, wherein the amino acid sequence of SPHSKA ( SEQ ID NO: 941) is present immediately subsequent to an amino acid position corresponding to position 455 of SEQ ID NO: 4 or SEQ ID NO: 36.

9. The AAV particle of any one of claims 6-8, wherein the AAV9 capsid variant further comprises one, two, or all of: an N at an amino acid position corresponding to position 452, an E at an aminoacid position corresponding to position 451, and / or a V at an amino acid position corresponding to position 453 of SEQ ID NO: 4.

10. The AAV particle of claim any one of claims 6-9, wherein the AAV9 capsid variant comprises the amino acid sequence of KTENVSGSPHSKAQNQQT (SEQ ID NO: 3272).

11. The AAV particle of any one of claims 6-10, wherein the AAV9 capsid variant comprises:(i) a VP1 protein comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 4;(ii) a VP2 protein comprising an amino acid sequence having at least 90% identity to positions 138-742 of SEQ ID NO: 4; and / or(iii) a VP3 protein comprising an amino acid sequence having at least 90% identity to positions 203-742 of SEQ ID NO: 4.

12. The AAV particle of any one of claims 6-11. wherein the AAV9 capsid variant comprises:(i) a VP1 protein comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 4;(ii) a VP2 protein comprising an amino acid sequence having at least 95% identity to positions 138-742 SEQ ID NO: 4; and / or(iii) a VP3 protein comprising an amino acid sequence having at least 95% identity to positions 203-742 of SEQ ID NO: 4.

13. The AAV particle of any one of claims 6-12, wherein the AAV9 capsid variant comprises :(i) a VP1 protein comprising an amino acid sequence having at least 99% identity to SEQ ID NO: 4;(ii) a VP2 protein comprising an amino acid sequence having at least 99% identity to positions 138-742 of SEQ ID NO: 4; and / or(iii) a VP3 protein comprising an amino acid sequence having at least 99% identity to positions 203-742 of SEQ ID NO: 4.

14. The AAV particle of any one of claims 6-13, wherein the AAV9 capsid variant comprises:(i) a VP1 protein comprising the amino acid sequence of SEQ ID NO: 4;(ii) a VP2 protein comprising the amino acid sequence of positions 138-742 of SEQ ID NO: 4; and / or(iii) a VP3 protein comprising the amino acid sequence of positions 203-742 of SEQ ID NO:4.

15. The AAV particle of any one of claims 6-13. wherein the AAV9 capsid variant comprises:(i) the amino acid sequence of SPHSKA (SEQ ID NO: 941), wherein the amino acid sequence is present immediately subsequent to an amino acid position corresponding to position 455 of SEQ ID NO: 4:(ii) an E at an amino acid position corresponding to position 451 and a V at an amino acid position corresponding to position 453 of SEQ ID NO: 4; and(iii) no other modifications relative to wild type AAV9.

16. The AAV particle of any one of claims 6-8, wherein the AAV9 capsid variant further comprises one, two, or all of: an E at an amino acid position corresponding to position 451 , an R at an amino acid position corresponding to position 452, and / or a V at an amino acid position corresponding to position 453 of SEQ ID NO: 36.

17. The AAV particle of any one of claims 6-8 and 16, wherein the A.AV9 capsid variant comprises the amino acid sequence of KTERVSGSPHSK.AQNQQT (SEQ ID NO: 3589).

18. The AAV particle of any one of claims 6-8, 16, and 17, wherein the AAV9 capsid variant comprises:(i) a VP1 protein comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 36;(ii) a VP2 protein comprising an amino acid sequence having at least 90% identity to positions 138-742 SEQ ID NO: 36; and / or(iii) a VP3 protein comprising an amino acid sequence having at least 90% identity to positions 203-742 of SEQ ID NO: 36.

19. The AAV particle of any one of claims 6-8 and 16-18, wherein the AAV9 capsid variant comprises:(i) a VP1 protein comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 36;(ii) a VP2 protein comprising an amino acid sequence liaving at least 95% identity to positions 138-742 SEQ ID NO: 36; and / or(iii) a VP3 protein comprising an amino acid sequence liaving at least 95% identity to positions 203-742 of SEQ ID NO: 36.

20. The AAV particle of any one of claims 6-8 and 16-19, wherein the AAV9 capsid variant comprises:(i) a VP1 protein comprising an amino acid sequence having at least 99% identity to SEQ IDNO: 36;(ii) a VP2 protein comprising an amino acid sequence having at least 99% identity to positions 138-742 of SEQ ID NO: 36; and / or(iii) a VP3 protein comprising an amino acid sequence having at least 99% identity to positions 203-742 of SEQ ID NO: 36.

21. The AAV particle of any one of claims 6-8 and 16-20, wherein the AAV9 capsid variant comprises:(i) a VP1 protein comprising the amino acid sequence of SEQ ID NO: 36;(ii) a VP2 protein comprising the amino acid sequence of positions 138-742 of SEQ ID NO: 36; and / or(iii) a VP3 protein comprising the amino acid sequence of positions 203-742 of SEQ ID NO: 36.

22. The AAV particle of any one of claims 6-8 and 16-20, wherein the AAV9 capsid variant comprises:(i) the amino acid sequence SPHSKA (SEQ ID NO: 941 ), wherein the amino acid sequence is present immediately subsequent to an amino acid position corresponding to position 455 of SEQ ID NO: 36;(ii) an E at an amino acid position corresponding to position 451, an R at an amino acid position corresponding to position 452, and a V at an amino acid position corresponding to position 453 of SEQ ID NO: 36; and(iii) no other modifications relative to wild type AAV9.

23. The AAV particle of any one of claims 1-4, wherein [N1]-[N2]-[N3] is present immediately subsequent to a position corresponding to the amino acid position 452 of SEQ ID NO: 982; and wherein the AAV capsid variant comprises an amino acid sequence at least 90% identical, e.g., at least 91%, at least 92%. at least 93%, at least 94%, at least 95%, at least 96%. at least 97%, at least 98%, at least 99%, or 100% identical, to the amino acid sequence of SEQ ID NO: 982, e.g., to positions 203-742 of SEQ ID NO: 982,24. The AAV particle of claim 23, wherein [N1] comprises GHD.

25. The AAV particle of claim 23 or claim 24, wherein [N1] comprises the amino acid G at a position corresponding to position 453, the amino acid H at position 454, and the amino acid D at position 455 of SEQ ID NO: 138 or SEQ ID NO: 982.

26. The AAV particle of any one of claims 23-25, wherein [N3] comprises KSG.

27. The AAV particle of any one of claims 23-26, wherein the AAV capsid variant comprises:(i) a VP1 protein comprising the amino acid sequence of SEQ ID NO:

982. or an amino acid sequence having at least 90% identity to SEQ ID NO: 982;(ii) a VP2 protein comprising the amino acid sequence of positions 138-742 of SEQ ID NO:982 or an amino acid sequence having at least 90% identity to positions 138-742 SEQ ID NO: 982; or(iii) a VP3 protein comprising the amino acid sequence of positions 203-742 of SEQ ID NO:982 or an amino acid sequence having at least 90% identity to positions 203-742 of SEQ ID NO: 982.

28. The AAV particle of any one of claims 23-27, wherein the AAV capsid variant comprises:(i) a ATI protein comprising the amino acid sequence of SEQ ID NO: 982 or an amino acid sequence having at least 95% identity to SEQ ID NO: 982;(ii) a VP2 protein comprising the amino acid sequence of positions 138-742 of SEQ ID NO: 982 or an amino acid sequence having at least 95% identity to positions 138-742 SEQ ID NO: 982; or(iii) a VP3 protein comprising the amino acid sequence of positions 2.03-742. of SEQ ID NO:

982. or an amino acid sequence having at least 95% identity to positions 203-742 of SEQ ID NO: 982.

29. The AAV particle of any one of claims 23-28, wherein the AAV capsid variant comprises:(i) a VP1 protein comprising the amino acid sequence of SEQ ID NO: 982 or an amino acid sequence having at least 99% identity to SEQ ID NO: 982;(ii) a VP2 protein comprising the amino acid sequence of positions 138-742 of SEQ ID NO: 982 or an amino acid sequence having at least 99% identity to positions 138-742 SEQ ID NO: 982; or(iii) a VP3 protein comprising the amino acid sequence of positions 203-742 of SEQ ID NO: 982 or an amino acid sequence having at least 99% identity to positions 203-742 of SEQ ID NO: 982.

30. The AAV particle of any one of claims 23-29, wherein the AAV capsid variant comprises:(i) a VP1 protein comprising the amino acid sequence of SEQ ID NO: 982;(ii) a AT2 protein comprising the amino acid sequence of positions 138-742. of SEQ ID NO: 982; or(iii) a VP3 protein comprising the amino acid sequence of positions 203-742 of SEQ ID NO: 982.

31. The AAV particle of any one of claims 1-30, wherein the viral genome encodes a wildtype GBA1 protein.

32. The AAV particle of any one of claims 1-31, wherein the viral genome does not encode a hemagglutinin (HA) tag.

33. The AAV particle of any one of claims 1-32, wherein the viral genome encodes a human GBA1 protein, a dog GBA1 protein, or an equine GBA1 protein.

34. The AAV particle of claim 33, wherein the viral genome encodes a human GBA1 protein, optionally wherein the human GBA1 protein comprises the amino acid sequence of SEQ ID NO: 1775.

35. The AAV particle of any one of claims 1-34, wherein the GBA1-encoding sequence comprises a nucleotide sequence that is at least 90% identical (e.g., at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to SEQ ID NO: 2002.

36. The AAV particle of any one of claims 1 -35, wherein the GBA1-encoding sequence comprises a nucleotide sequence that is at least 95% (e.g., at least 95%, at least 96%, at least 97%. at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 2002.

37. The AAV particle of any one of claims 1-36, wherein the GBA1-encoding sequence comprises the nucleotide sequence of SEQ ID NO: 2002.

38. The AAV particle of any one of claims 1-37, wherein the GBA1-encoding sequence encodes a signal sequence comprising an amino acid sequence that is at least 90% identical to SEQ ID: 2005.

39. The AAV particle of claim 38, wherein the signal sequence comprises the amino acid sequence of SEQ ID NO: 2005.

40. The AAV particle of any one of claims 1-39, wherein the GBA1-encoding sequence comprises a nucleotide sequence that is at least 90% identical (e.g,, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%. at least 96%, at least 97%, at least 98%, at least 99%. or 100% identical) to SEQ ID NO: 2001.

41. The AAV particle of claim 40, wherein the GBA1-encoding sequence comprises SEQ ID NO: 2001.

42. The AAV particle of any one of claims 1-41, wherein the viral genome further comprises a miRNA (miR) binding site that modulates expression of the encoded GBA1 protein in a cell or tissue of the DRG, liver, heart, hematopoietic lineage, or a combination thereof43. The AAV particle of any one of claims 1-42, wherein the viral genome further comprises a promoter operably linked to the GBA1 -encoding sequence.

44. The AAV particle of claim 43, wherein the promoter is at least 90% identical (e.g., at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the nucleotide sequence of SEQ ID NO: 1834.

45. The AAV particle of claim 43, wherein the promoter comprises the nucleotide sequence of SEQ ID NO: 1834.

46. The AAV particle of any one of claims 1 -45, wherein the viral genome further comprises an enhancer.

47. The AAV particle of claim 46, wherein the enhancer compri ses a CMV immediate-early (CMVie) enhancer.

48. The AAV particle of claim 47, wherein the CMVie enhancer is at least 90% identical (e.g., at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the nucleotide sequence of SEQ ID NO: 1831.

49. The AAV particle of claim 47, wherein the CMVie enhancer comprises the nucleotide sequence of SEQ ID NO: 1831.

50. The AAV particle of any one of claims 1-49, wherein the viral genome further comprises an intron.51 . The AAV particle of claim 50, wherein the intron is at least 90% identical (e.g., at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the nucleotide sequence of SEQ ID NO: 1842.

52. The AAV particle of claim 50, wherein the intron comprises the nucleotide sequence of SEQ ID NO: 1842.

53. The AAV particle of any one of claims 1-52, wherein the viral genome further comprises a polyadenylation (poly A) region.

54. The AAV particle of claim 53, wherein the poly A region is at least 90% identical (e.g., at least 90%, at least 91%, at least 92%. at least 93%, at least 94%, at least 95%, at least 96%. at least 97%, at least 98%, at least 99%, or 100% identical) to the nucleotide sequence of SEQ ID NO: 1846.

55. The AAV particle of claim 53, wherein the poly A region comprises the nucleotide sequence of SEQ ID NO: 1846.

56. The AAV particle of any one of claims 1-55, wherein the viral genome further comprises an inverted terminal repeat (ITR).

57. The AAV particle of claim 56, wherein the ITR is at least 90% identical (e.g., at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical) to the nucleotide sequence of SEQ ID NO: 1829 or SEQ ID NO: 1830.

58. The AAV particle of claim 56, wherein the ITR comprises the nucleotide sequence of SEQ ID NO: 1829 or SEQ ID NO: 1830.

59. The AAV particle of claim 56, wherein the viral genome comprises a 5’ ITR and a 3’ ITR, wherein the 5 ’ ITR comprises the nucleotide sequence of SEQ ID NO: 1829 and the 3 ’ ITR comprises the nucleotide sequence of SEQ ID NO: 1830.

60. The AAV particle of any one of claims 1-59, wherein the viral genome further comprises one or more miR183 binding sites.61 . The AAV particle of claim 60 wherein the viral genome comprises four miR 183 binding sites.

62. The AAV particle of claim 61, wherein each of the four miR183 binding sites comprises at least 70% identity to the nucleotide sequence of SEQ ID NO: 1847, optionally wherein each of the four miR183 binding sites comprises the nucleotide sequence of SEQ ID NO: 1847.

63. The AAV particle of any one of claims 1-60, wherein the viral genome further comprises a miR183 binding site series that comprises a sequence at least 95% (e.g., at least 95%, at least 96%, atleast 97%, at least 98%, at least 99%, or 100%) identical to the nucleotide sequence of SEQ ID NO: 1849.

64. The AAV particle of claim 63, wherein the miR183 binding site series comprises a nucleotide sequence of SEQ ID NO: 1849.

65. The AAV particle of any one of claims 1-34, wherein the viral genome comprises, in 5’ to 3’ order:(i) a 5’ inverted terminal repeal (ITR);(ii) a promoter;(iii) the GBA1-encoding sequence, wherein the GBA1-encoding sequence comprises the nucleotide sequence of SEQ ID NO: 2002 or a nucleotide sequence at least 90% identical (e.g., at least 93% identical) to SEQ ID NO: 2002; and(iv) a 3’ ITR.

66. The AAV particle of any one of claims 1 -34, wherein the viral genome comprises, in 5’ to 3’ order:(i) a 5' inverted terminal repeat (ITR);(ii) a promoter;(iii) the GBA1-encoding sequence, wherein the GBA1-encoding sequence comprises the nucleotide sequence of SEQ ID NO: 2001 or a nucleotide sequence al least 90% identical (e.g., at least 94% identical) to SEQ ID NO: 2001; and(iv) a 3’ ITR.

67. The AAV particle of any one of claims 1-34, wherein the viral genome comprises:(i) a 5’ inverted terminal repeat (ITR);(ii) a CMV immediate-early (CMVie) enhancer comprising the nucleotide sequence SEQ ID NO: 1831 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1831;(iii) a chicken beta actin (CB A) promoter comprising the nucleotide sequence of SEQ ID NO: 1834 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%. at least 98%, or at least 99% identical) to SEQ ID NO: 1834;(iv) an intron comprising the nucleotide sequence of SEQ ID NO: 1842 or a nucleotide sequence at least 95% identical (e.g., at least 95%, al least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1842;(v) the GBA1 -encoding sequence, wherein the GBA1-encoding sequence comprises the nucleotide sequence of SEQ ID NO: 2002 or a nucleotide sequence at least 90% identical (e.g., at least 93% identical) to SEQ ID NO: 2002; and(vi ) a 3 ’ ITR68. The AAV particle of any one of claims 1-34, wherein the viral genome comprises:(i) a 5’ inverted terminal repeal (ITR);(ii) a CMV immediate-early (CMVie) enhancer comprising the nucleotide sequence SEQ ID NO: 1831 or a nucleotide sequence at least 95% identical (e.g., at least 95%. at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1831;(iii) a chicken beta actin (CBA) promoter comprising the nucleotide sequence of SEQ ID NO: 1834 or a nucleotide sequence at least 95% identical (e.g., at least 95% at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1834;(iv) an intron comprising the nucleotide sequence of SEQ ID NO: 1842 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1842; and(v) the GBA1-encoding sequence, wherein the GBA1 -encoding sequence comprises the nucleotide sequence of SEQ ID NO: 2001 or a nucleotide sequence at least 90% identical (e.g., at least 94% identical) to SEQ ID NO: 2001 and(vi) a 3 ' ITR.

69. The AAV particle of any one of claims 1-34, wherein the viral genome comprises:(i) a 5 ’ inverted terminal repeat (ITR);(ii) a CMV immediate-early (CMVre) enhancer comprising the nucleotide sequence SEQ ID NO: 1831 or a nucleotide sequence at least 95% identical to SEQ ID NO: 1831;(iii) a chicken beta actin (CBA) promoter comprising the nucleotide sequence of SEQ ID NO: 1834 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1834;(iv) an intron comprising the nucleotide sequence of SEQ ID NO: 1842 or a nucleotide sequence at least 95% identical (e.g.. at least 95%, at least 96%, at least 97%, at least 98%. or at least 99% identical) to SEQ ID NO: 1842;(v) the GBA1-encoding sequence, wherein the GBA1-encoding sequence comprises the nucleotide sequence of SEQ ID NO: 2002 or a nucleotide sequence at least 90% identical (e.g., at least 93% identical) to SEQ ID NO: 2002;(vi) a polyadenylation (poly A) region comprising the nucleotide sequence of SEQ ID NO: 1846 or a nucleotide sequence at least 95% identical to SEQ ID NO: 1846; and(vii) a 3’ H R.

70. The AAV particle of any one of claims 1-34, wherein the viral genome comprises, in 5’ to 3 order:(i) a 5’ inverted terminal repeat (ITR);(ii) a CMV immediate-early (CMVie) enhancer comprising the nucleotide sequence SEQ ID NO: 1831 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1831;(iii) a chicken beta actin (CBA) promoter comprising the nucleotide sequence of SEQ ID NO: 1834 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1834;(iv) an intron comprising the nucleotide sequence of SEQ ID NO: 1842 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1842;(v) the GBA1-encoding sequence, wherein the GBA1-encoding sequence comprises the nucleotide sequence of SEQ ID NO: 2001 or a nucleotide sequence at least 90% identical (e.g., at least 94% identical) to SEQ ID NO: 2001;(vi) a polyadenylation (polyA) region comprising the nucleotide sequence of SEQ ID NO: 1846 or a nucleotide sequence at least 95% identical to SEQ ID NO: 1846; and(vii) a 3’ ITR.

71. The AAV particle of any one of claims 1-34, wherein the viral genome comprises, in 5’ to 3’ order:(i) a 5’ inverted terminal repeat (ITR) comprising the nucleotide sequence of SEQ ID NO: 1829 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1829;(ii) a CMV immediate-early (CMVie) enhancer comprising the nucleotide sequence SEQ ID NO: 1831 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1831;(iii) a chicken beta actin (CBA) promoter comprising the nucleotide sequence of SEQ ID NO: 1834 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%. at least 98%, or at least 99% identical) to SEQ ID NO: 1834;(iv) an intron comprising the nucleotide sequence of SEQ ID NO: 1842 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1842;(v) the GBA1-encoding sequence, wherein the GBA1 -encoding sequence comprises the nucleotide sequence of SEQ ID NO: 2002 or a nucleotide sequence at least 90% identical (e.g., at least 93% identical) to SEQ ID NO: 2002;(vi) a poly adenylation (poly A) region comprising the nucleotide sequence of SEQ ID NO: 1846 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1846; and(vii) a 3’ ITR comprising the nucleotide sequence of SEQ ID NO: 1830 or a nucleotide sequence at least 95% identical to SEQ ID NO: 1830,72. The AAV particle of any one of claims 1-34, wherein the viral genome comprises:(i) a 5’ inverted terminal repeal (ITR) comprising the nucleotide sequence of SEQ ID NO: 1829 or a nucleotide sequence at least 95% identical (e.g., al ieast 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1829;(ii) a CMV immediate-early (CMVie) enhancer comprising the nucleotide sequence SEQ ID NO: 1831 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at ieast 99% identical) to SEQ ID NO: 1831;(iii) a chicken beta actin (CBA) promoter comprising the nucleotide sequence of SEQ ID NO: 1834 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1834;(iv) an intron comprising the nucleotide sequence of SEQ ID NO: 1842 or a nucleotide sequence at ieast 95% identical (e.g., at least 95%, at least 96%. at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1842;(v) the GBA1-encoding sequence, wherein the GBA1-encoding sequence comprises the nucleotide sequence of SEQ ID NO: 2001 or a nucleotide sequence al least 90% identical (e.g., at least 94% identical) to SEQ ID NO: 2001;(vi) a poly adenylation (poly A) region comprising the nucleotide sequence of SEQ ID NO: 1846 or a nucleotide sequence at ieast 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1846; and(vii) a 3’ ITR comprising the nucleotide sequence of SEQ ID NO: 1830 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1830.

73. The AAV particle of any one of claims 1-34, wherein the viral genome comprises the nucleotide sequence of SEQ ID NO: 2.006 or a nucleotide sequence at least 90% identical (e.g., at least 97% identical) to SEQ ID NO: 2006.

74. The AAV particle of claim 73, wherein the viral genome comprises the nucleotide sequence of SEQ ID NO: 2006.

75. The AAV particle of claim 74, wherein the viral genome consists of the nucleotide sequence of SEQ ID NO: 2006.

76. The AAV particle of any one of claims 1-34, wherein the viral genome comprises, in 5’ to 3’ order:(i) a 5’ inverted terminal repeat (ITR);(ii) a promoter;(iii) the GBA1-encoding sequence, wherein the GBA1-encoding sequence comprises the nucleotide sequence of SEQ ID NO: 2002 or a nucleotide sequence at least 90% identical (e.g., at least 93% identical) to SEQ ID NO: 2002;(iv) at least one miR 183 binding site; and(v) a 3’ ITR.

77. The AAV particle of any one of claims 1 -34, wherein the viral genome comprises, in 5’ to 3’ order:(i) a 5’ inverted terminal repeat (ITR);(ii) a promoter;(iii) the GBA1-encoding sequence, wherein the GBA1-encoding sequence comprises the nucleotide sequence of SEQ ID NO: 2001 or a nucleotide sequence at least 90% identical (e.g., at least 94% identical) to SEQ ID NO: 2001;(iv) at least one miR183 binding site; and(v) a 3’ ITR.

78. The AAV particle of any one of claims 1-34, wherein the viral genome comprises, in 5’ to 3’ order:(i) a 5’ inverted terminal repeat (ITR);(ii) a promoter;(iii) the GBA1-encoding sequence, wherein the GBA1-encoding sequence comprises the nucleotide sequence of SEQ ID NO: 2002 or a nucleotide sequence at least 90% identical (e.g.. at least 93% identical) to SEQ ID NO: 2.002;(iv) at least one miR 183 binding site series comprising at least one miR183 binding site and at least one spacer sequence; and(v) a 3’ ITR.

79. The AAV particle of any one of claims 1-34, wherein the viral genome comprises, in 5’ to 3’ order:(i) a 5’ inverted terminal repeat ( ITR);(ii) a promoter;(iii) the GBA1-encoding sequence, wherein the GBA1-encoding sequence comprises the nucleotide sequence of SEQ ID NO: 2001 or a nucleotide sequence at least 90% identical (e.g., at least 94% identical) to SEQ ID NO: 2.001 ;(iv) at least one miR183 binding site series comprising at least one miR183 binding site and at least one spacer sequence; and(v) a 3’ ITR.

80. The AAV particle of any one of claims 1-34, wherein the viral genome comprises, in 5’ to 3’ order:(i) a 5’ inverted terminal repeat ( ITR );(ii) a CMV immediate-early (CMVie) enhancer comprising the nucleotide sequence SEQ ID NO: 1831 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1831;(iii) a chicken beta actin (CBA) promoter comprising the nucleotide sequence of SEQ ID NO: 1834 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1834;(iv) an intron comprising the nucleotide sequence of SEQ ID NO: 1842 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%. at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1842;(v) the GBA1-encoding sequence, wherein the GBA1-encoding sequence comprises the nucleotide sequence of SEQ ID NO: 2002 or a nucleotide sequence at least 90% identical (e.g., at least 93% identical) to SEQ ID NO: 2002;(vi) at least one miR183 binding site; and(vii) a 3 ’ ITR.

81. The AAV particle of any one of claims 1-34, wherein the viral genome comprises, in 5’ to 3’ order:(i) a 5’ inverted terminal repeat (ITR);(ii) a CMV immediate-early (CMVie) enhancer comprising the nucleotide sequence SEQ ID NO: 1831 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1831;(iii) a chicken beta actin (CBA) promoter comprising the nucleotide sequence of SEQ ID NO: 1834 or a nucleotide sequence at least 95% identical (e.g., al least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1834;(iv) an intron comprising the nucleotide sequence of SEQ ID NO: 1842 or a nucleotide sequence at least 95% identical to SEQ ID NO: 1842;(v) the GBA1 -encoding sequence, wherein the GBA1-encoding sequence comprises the nucleotide sequence of SEQ ID NO: 2001 or a nucleotide sequence at least 90% identical (e.g., at least 94% identical) to SEQ ID NO: 2001 ;(vi) at least one miR183 binding site: and(vii) a 3 ’ ITR.

82. The AAV particle of any one of claims 1-34, wherein the viral genome comprises, in 5’ to 3’ order:(i) a 5’ inverted terminal repeat (ITR);(ii) a CMV immediate-early (CMVie) enhancer comprising the nucleotide sequence SEQ ID NO: 1831 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1831;(iii) a chicken beta actin (CBA) promoter comprising the nucleotide sequence of SEQ ID NO: 1834 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1834;(iv) an intron comprising the nucleotide sequence of SEQ ID NO: 1842 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%. at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1842;(v) the GB Al -encoding sequence, wherein the GBA1 -encoding sequence comprises the nucleotide sequence of SEQ ID NO: 2002 or a nucleotide sequence al least 90% identical (e.g., at least 93% identical) to SEQ ID NO: 2002;(vi) a miR183 binding site series comprising the nucleotide sequence of SEQ ID NO: 1849 or a nucleotide sequence at least 90% identical to SEQ ID NO: 1849; and(vii) a 3 ’ ITR.

83. The AAV particle of any one of claims 1-34, wherein the viral genome comprises, in 5’ to 3’ order:(i) a 5’ inverted terminal repeat (ITR);(ii) a CMV immediate-early (CMVie) enhancer comprising the nucleotide sequence SEQ ID NO: 1831 or a nucleotide sequence at least: 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1831;(iii) a chicken beta actin (CBA) promoter comprising the nucleotide sequence of SEQ ID NO: 1834 or a nucleotide sequence at least 95% identical (e.g., al least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1834;(iv) an intron comprising the nucleotide sequence of SEQ ID NO: 1842 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1842;(v) the GBA1-encoding sequence, wherein the GBA1-encoding sequence comprises the nucleotide sequence of SEQ ID NO: 2001 or a nucleotide sequence at least 90% identical (e.g., at least 94% identical) to SEQ ID NO: 2001 ;(vi) a miR 183 binding site series comprising the nucleotide sequence of SEQ ID NO: 1849 or a nucleotide sequence at least 90% identical (e.g., at least 90%. at least 91%, at least 92%, at least 93%, at least 94%, at least 95%. at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1849; and(vii) a 3 ’ ITR.

84. The AAV particle of any one of claims 1-34, wherein the viral genome comprises, in 5’ to 3’ order:(i) a 5’ inverted terminal repeat (ITR) comprising the nucleotide sequence of SEQ ID NO:1829 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1829;(ii) a CMV immediate-early (CMVie) enhancer comprising the nucleotide sequence of SEQ ID NO: 1831 or a nucleotide sequence at least 95% identical (e.g. , at least 95%, at least 96%, at least 97%. at least 98%, or at least 99% identical) to SEQ ID NO: 1831;(iii) a chicken beta actin (CBA) promoter comprising the nucleotide sequence of SEQ ID NO: 1834 or a nucleotide sequence at least 95% identical (e.g., at least 95%. at least 96%, at least 97%, at least 98%. or at least 99% identical) to SEQ ID NO: 1834;(iv) an intron comprising the nucleotide sequence of SEQ ID NO: 1842 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1842;(v) the GBA1-encoding sequence, wherein the GBA1-encoding sequence comprises the nucleotide sequence of SEQ ID NO: 2002 or a nucleotide sequence at least 90% identical (e.g., at least 93% identical) to SEQ ID NO: 2002;(vi) at least one miR183 binding site comprising the nucleotide sequence of SEQ ID NO: 1847;(vii) a polyadenylation (poly A) region comprising the nucleotide sequence of SEQ ID NO: 1846 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%. at least 98%, or at least 99% identical) to SEQ ID NO: 1846; and(viii) a 3’ ITR comprising the nucleotide sequence of SEQ ID NO: 1830 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1830.

85. The AAV particle of any one of claims 1-34, wherein the viral genome comprises, in 5’ to 3’ order:(i) a 5’ inverted terminal repeat (ITR) comprising the nucleotide sequence of SEQ ID NO: 1829 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1829;(ii) a CMV immediate-early (CMVie) enhancer comprising the nucleotide sequence of SEQ ID NO: 1831 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%. at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1831;(iii) a chicken beta actin (CBA) promoter comprising the nucleotide sequence of SEQ ID NO: 1834 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1834;(iv) an intron comprising the nucleotide sequence of SEQ ID NO: 1842 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1842;(v) the GBA1-encoding sequence, wherein the GBA1 -encoding sequence comprises the nucleotide sequence of SEQ ID NO: 2001 or a nucleotide sequence at least 90% identical (e.g., at least 94% identical) to SEQ ID NO: 2001;(vi) at least one miRl 83 binding site comprising the nucleotide sequence of SEQ ID NO: 1847;(vii) a polyadenylation (polyA) region comprising the nucleotide sequence of SEQ ID NO: 1846 or a nucleotide sequence at least 95% identical (e.g., at least 95%. at least 96%, at least 97%, at least 98%. or at least 99% identical) to SEQ ID NO: 1846; and(viii) a 3’ ITR comprising the nucleotide sequence of SEQ ID NO: 1830 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1830.

86. The AAV particle of any one of claims 1-34, wherein the viral genome comprises, in 5’ to 3’ order:(i) a 5’ inverted terminal repeat (ITR) comprising the nucleotide sequence of SEQ ID NO: 1829 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1829;(ii) a CMV immediate-early (CMVie) enhancer comprising the nucleotide sequence of SEQ ID NO: 1831 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%. at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1831;(iii) a chicken beta actin (CBA) promoter comprising the nucleotide sequence of SEQ ID NO: 1834 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical) to SEQ ID NO: 1834;(iv) an intron comprising the nucleotide sequence of SEQ ID NO: 1842 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1842;(v) the GBA1 -encoding sequence, wherein the GBA1-encoding sequence comprises the nucleotide sequence of SEQ ID NO: 2.002 or a nucleotide sequence at least 90% identical (e.g.. at least 93% identical) to SEQ ID NO: 2.002;(vi) a rmR183 binding site series comprising the nucleotide sequence of SEQ ID NO: 1849 or a nucleotide sequence at least 90% identical (e.g.. at least 90%, at least 91%, al least 92?% at least 93?% at least 94%, at least 95%, at least 96%, al least 97%, at least 98%, or at least 99% identical) io SEQ ID NO: 1849;(vii) a poly adenylation (poly A) region comprising the nucleotide sequence of SEQ ID NO: 1846 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%. or at least 99% identical) to SEQ ID NO: 1846; and(viii) a 3’ ITR comprising the nucleotide sequence of SEQ ID NO: 1830 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1830.

87. The AAV particle of any one of claims 1 -34, wherein the viral genome comprises, in 5 ’ to 3 ’ order:(i) a 5’ inverted terminal repeat (ITR) comprising the nucleotide sequence of SEQ ID NO: 1829 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1829;(ii) a CMV immediate-early (CMVie) enhancer comprising the nucleotide sequence of SEQ ID NO: 1831 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1831;(iii) a chicken beta actin (CBA) promoter comprising the nucleotide sequence of SEQ ID NO: 1834 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1834;(iv) an intron comprising the nucleotide sequence of SEQ ID NO: 1842 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%, at least 98%. or at least 99% identical) to SEQ ID NO: 1842;(v) the GBA1-encoding sequence, wherein the GBA1-encoding sequence comprises the nucleotide sequence of SEQ ID NO: 2001 or a nucleotide sequence at least 90% identical (e.g., at least 94% identical) to SEQ ID NO: 2001;(vi) a miR183 binding site series comprising the nucleotide sequence of SEQ ID NO: 1849 or a nucleotide sequence at least 90% identical (e.g., at least 90%, at least 91%, at least 92%, at least93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1849;(vii) a polyadenvlation (poly A) region comprising the nucleotide sequence of SEQ ID NO: 1846 or a nucleotide sequence at least 95% identical (e.g., at least 95%, at least 96%, at least 97%. at least 98%, or at least 99% identical) to SEQ ID NO: 1846; and(viii) a 3' ITR comprising the nucleotide sequence of SEQ ID NO: 1830 or a nucleotide sequence at least 95% identical (e.g., at least 95%, al least 96% at least 97%, at least 98%, or at least 99% identical) to SEQ ID NO: 1830.

88. The AAV particle of claim 87, wherein:(i) the 5’ ITR comprises the nucleotide sequence of SEQ ID NO: 1829;(ii) the CMVie enhancer comprises the nucleotide sequence of SEQ ID NO: 1831;(iii) the CBA promoter comprises the nucleotide sequence of SEQ ID NO: 1834;(iv) the intron comprises the nucleotide sequence of SEQ ID NO: 1842;(v) the GBA1-encoding sequence comprises the nucleotide sequence of SEQ ID NO: 2001;(vi) the miR183 binding site series comprises the nucleotide sequence of SEQ ID NO: 1849;(vii) the poly A region comprises the nucleotide sequence of SEQ ID NO: 1846; and(viii) the 3’ ITR comprises the nucleotide sequence of SEQ ID NO: 1830.

89. The AAV particle of any one of claims 1-34, wherein the viral genome comprises the nucleotide sequence of SEQ ID NO: 2007 or a nucleotide sequence at least 90% identical (e.g., al least 97% identical) to SEQ ID NO: 2007.

90. The AAV particle of claim 89, wherein the viral genome comprises the nucleotide sequence of SEQ ID NO: 2007.91 . The AAV particle of claim 90, wherein the viral genome consists of the nucleotide sequence of SEQ ID NO: 2007.

92. An adeno-associated vims (AAV) particle comprising a viral genome comprising the nucleotide sequence of SEQ ID NO: 2.001 and an AAV capsid variant comprising:(i) a VP1 protein comprising the amino acid sequence of SEQ ID NO: 4;(ii) a VP2 protein comprising the amino acid sequence of positions 138-742 of SEQ ID NO: 4; and / or(iii) a VP3 protein comprising the amino acid sequence of positions 203-742 of SEQ ID NO:4.

93. An adeno-associated virus (AAV) particle comprising a viral genome comprising the nucleotide sequence of SEQ ID NO: 2001 and an AAV capsid variant comprising:(i) a VP1 protein comprising the amino acid sequence of SEQ ID NO: 36;(ii) a VP2 protein comprising the amino acid sequence of positions 138-742. of SEQ ID NO:36; and / or(iii) a VP3 protein comprising the amino acid sequence of positions 203-742 of SEQ ID NO:36.

94. An adeno-associated virus (AAV) particle comprising a viral genome comprising the nucleotide sequence of SEQ ID NO: 2002 and an AAV capsid variant comprising:(i) a VP1 protein comprising the amino acid sequence of SEQ ID NO: 4;(ii) a VP2 protein comprising the amino acid sequence of positions 138-742 of SEQ ID NO:4; and / or(iii) a VP3 protein comprising the amino acid sequence of positions 203-742 of SEQ ID NO: 4.

95. An adeno-associated virus (AAV) particle comprising a viral genome comprising the nucleotide sequence of SEQ ID NO: 2002 and an AAV capsid variant comprising:(i) a VP1 protein comprising the amino acid sequence of SEQ ID NO: 36;(ii) a VP2 protein comprising the amino acid sequence of positions 138-742 of SEQ ID NO: 36; and / or(iii) a VP3 protein comprising the amino acid sequence of positions 203-742 of SEQ ID NO: 36.

96. A ceil comprising the AAV particle of any one of claims 1-95, optionally wherein the cell is a mammalian cell (e.g., an HEK293 ceil), an insect cell (e.g., an Sf9 cell), or a bacterial ceil.

97. A method of making the AAV particle of any one of claims 1-95, the method comprising:(i) providing a cell comprising the viral genome comprising a GBA1 -encoding sequence and a nucleic acid encoding the AAV capsid variant; and(ii) incubating the cell under conditions suitable to encapsulate the viral genome in the AAV capsid variant; thereby making the AAV particle.

98. The method of claim 97, wherein the viral genome comprises(a) the nucleotide sequence of SEQ ID NO: 2006 or a nucleotide sequence at least 90% identical (e.g., at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) thereto; or(b) the nucleotide sequence of SEQ ID NO: 2007 or a nucleotide sequence at least 90% identical (e.g., at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) thereto; and wherein the AAV capsid variant comprises:(i) a VP1 protein comprising the amino acid sequence of SEQ ID NO: 4 or an amino acid sequence having at least 90% identity (e.g., at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity) to SEQ ID NO: 4;(ii) a VP2 protein comprising the amino acid sequence of positions 138-742 of SEQ ID NO: 4 or an amino acid sequence having at least 90% identity (e.g., at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity) to positions 138-742 SEQ ID NO: 4; or(iii) a VP3 protein comprising the amino acid sequence of positions 203-742 of SEQ ID NO: 4 or an amino acid sequence having at least 90% identity (e.g., at least 90%, at least 91%, at least 92%. at least 93%, at least 94%, at least 95%, at least 96%. at least 97%, at least 98%, or at least 99% identity) to positions 203-742 of SEQ ID NO: 4.

99. The method of claim 97, wherein the viral genome comprises(a) the nucleotide sequence of SEQ ID NO: 2006 or a nucleotide sequence at least 90% identical (e.g., at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) thereto; or(b) the nucleotide sequence of SEQ ID NO: 2007 or a nucleotide sequence at least 90% identical (e.g., at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) thereto; and wherein the AAV capsid variant comprises the amino acid sequence of SEQ ID NO: 4, the amino acid sequence of positions 138-742 of SEQ ID NO: 4, and / or the amino acid sequence of positions 203-742 of SEQ ID NO: 4.

100. The method of claim 97, wherein the viral genome comprises:(a) the nucleotide sequence of SEQ ID NO: 2006 or a nucleotide sequence at least 90% identical (e.g., at least 90%. at least 91%, at least 92%, at least 93%, at least 94%. at least 95%, at least 96%. at least 97%, at least 98%, or at least 99% identical) thereto; or(b) the nucleotide sequence of SEQ ID NO: 2007 or a nucleotide sequence at least 90% identical (e.g., at least 90%. at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) thereto; and wherein the AAV capsid variant comprises:(i) a VP1 protein comprising the amino acid sequence of SEQ ID NO: 36 or an amino acid sequence having at least 90% identity (e.g., at least 90%, at least 91%. at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity) to SEQ ID NO: 36;(ii) a VP2 protein comprising the amino acid sequence of positions 138-742 of SEQ ID NO: 36 or an amino acid sequence having at least 90% identity (e.g., at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity) to positions 138-742 SEQ ID NO: 36; and / or(iii) a VP3 protein comprising the amino acid sequence of positions 203-742 of SEQ ID NO: 36 or an amino acid sequence having at least 90% identity (e.g., at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity) to positions 203-742 of SEQ ID NO: 36.

101. The method of claim 97, wherein the viral genome comprises:(a) the nucleotide sequence of SEQ ID NO: 2006 or a nucleotide sequence at least 90% identical (e.g., at least 90%, at least 91%, at least 92%. at least 93%, at least 94%, al least 95%, at least 96%. at least 97%, at least 98%, or at least 99% identical) thereto; or(b) the nucleotide sequence of SEQ ID NO: 2007 or a nucleotide sequence at least 90% identical (e.g., at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) thereto; and wherein the AAV capsid variant comprises the amino acid sequence of SEQ ID NO: 36, the amino acid sequence of positions 138-742 of SEQ ID NO: 36, and / or the amino acid sequence of positions 203-742 of SEQ ID NO: 36.

102. The method of claim 97, wherein the viral genome comprises:(a) the nucleotide sequence of SEQ ID NO: 2.006 or a nucleotide sequence at least 90% identical (e.g., at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical) thereto; or(b) the nucleotide sequence of SEQ ID NO: 2007 or a nucleotide sequence at least 90% identical (e.g., at least 90%. at least 91%, at least 92%, al least 93%, at least 94%. at least 95%, at least 96%. at least 97%, at least 98%, or at least 99% identical) thereto; and wherein the AAV capsid variant comprises:(i) a VP1 protein comprising the amino acid sequence of SEQ ID NO: 982 or an amino acid sequence having at least 90% identity (e.g., at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity) to SEQ ID NO: 982;(ii) a VP2 protein comprising the amino acid sequence of positions 138-742. of SEQ ID NO: 982 or an amino acid sequence having at least 90% identity (e.g,, at least 90%, at least 91%, at least 92?% at least 93%, at least 94%, at least 95%, al least 96%, at least 97%, at least 98%, or at least 99% identity ) to positrons 138-742 SEQ ID NO: 982; and / or(iii) a VP3 protein comprising the amino acid sequence of positions 203-742 of SEQ ID NO: 982 or an amino acid sequence having at least 90% identity (e.g., at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity) to positions 203-742 of SEQ ID NO: 982.

103. The method of claim 97, wherein the viral genome comprises:(a) the nucleotide sequence of SEQ ID NO: 2006 or a nucleotide sequence at least 90% identical (e.g., at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, al least 98%, or at least 99% identical) thereto; or(b) the nucleotide sequence of SEQ ID NO: 2007 or a nucleotide sequence at least 90% identical (e.g., at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%. at least 97%, at least 98%, or at least 99% identical) thereto; and wherein the AAV capsid variant comprises the amino acid sequence of SEQ ID NO:

982. the amino acid sequence of positions 138-742 of SEQ ID NO: 982, and / or the amino acid sequence of positions 203-742 of SEQ ID NO: 982.

104. The method of any one of claims 97-103, further comprising, prior to step (i), introducing a first nucleic acid molecule comprising the viral genome into the cell.

105. The method of any one of claims 97-104, wherein the cell comprises a second nucleic acid molecule encoding the AAV capsid variant.

106. The method of claim 105, further comprisi ng, prior to step (i), introducing the second nucleic acid into the cell.

107. The method of any one of claims 97-106. wherein the cell comprises a mammalian cell (e.g., an HEK293 cell), an insect cell (e.g., an Sf9 cell), or a bacterial cell.

108. A pharmaceutical composition comprising the AAV particle of any one of claims 1-95. and a pharmaceutically acceptable excipient.

109. A pharmaceutical composition comprising the AAV particle of any one of claims 5-22 and a pharmaceutically acceptable excipient.

110. A pliarmaceutical composition comprising the AAV particle of any one of claims 9-15, 92. and 94, and a pharmaceutically acceptable excipient.

111. A pharmacal composition comprising the AAV particle of any one of claims 16-22, 93, and95, and a pharmaceutically acceptable excipient.

112. A method of delivering an AAV particle encoding a GBA1 protein to a subject, comprising administering to the subject an effective amount of the pharmaceutical composition of any one of claims 108-111 or the AAV particle of any one of claims 1-95,113. The method of claim 112, wherein the subject has, lias been diagnosed with having, or is at risk of having a GBA1 -related disorder, optionally wherein the GBA1-related disorder is a GBA1 -related neurodegenerative or neuromuscular disorder, further optionally wherein the GBA1 -related disorder is Parkinson’s Disease (PD), Parkinson’s Disease Dementia (PDD), Gaucher Disease (GD) (e.g., GD type 1, 2, or 3), Dementia with Lewy Bodies (DLB), Lewy Body Dementia (LBD), Multiple System Atrophy (MSA), Alzheimer’s Disease (AD), Amyotrophic Lateral Sclerosis (ALS), Pure Autonomic Failure, Neurodegeneration with brain iron accumulation, type 1 (NB1A 1), or Hallervorden-Spatz Syndrome.

114. The method of claim 112 or claim 113, wherein the subject has, has been diagnosed with having, or is at risk of having Parkinson’s Disease (PD).

115. A method of treating a subject hatring or diagnosed with having a GBA1-related disorder, comprising administering to the subject an effective amount of the pliarmaceutical composition anyone of claims 108-111 or the AAV particle of any one of claims 1-95.

116. A method of treating a subject having or diagnosed with having a GBA1 -related disorder, comprising administering to the subject an effective amount of the pharmacal composition of any one of claims 109-111 or the AAV particle of any one of claims 5-22.

117. A method of treating a subject having or diagnosed with having a GBA1-related disorder, comprising administering to the subject an effective amount of the pharmaceutical composition of claim 110 or the AAV particle of any one of claims 9-15, 92, and 94.

118. A method of treating a subject having or diagnosed with having a GBA1-related disorder, comprising administering to the subject an effective amount of the pharmaceutical composition of claim 111 or the AAV particle of any one of claims 16-22, 93, and 95.

119. The method of any one of claims 115-118, wherein the GBA1 -related disorder is a GBA1-related neurodegenerative or neuromuscular disorder, optionally wherein the GBA1-related disorder is Parkinson’s Disease (PD), Parkinson’s Disease Dementia (PDD), Gaucher Disease (GD) (e.g., GD type 1, 2, or 3), Dementia with Lewy Bodies (DLB), Lewy Body Dementia (LBD), Multiple System Atrophy (MSA), Alzheimer’s Disease (AD), Amyotrophic Lateral Sclerosis (ALS), Pure Autonomic Failure, Neurodegeneration with brain iron accumulation, type 1 (NBIA 1), or Hallervorden- Spatz Syndrome.

120. The method of claim 119, wherein the GBA1 -related neurodegenerative or neuromuscular disorder is Parkinson’s Disease (PD).

121. The method of claim 119. wherein the GBA1-related neurodegenerative or neuromuscular disorder is Gaucher Disease (GD) (e.g., GD type 1, 2. or 3).

122. The method of claim 121, wherein the GBA1-related neurodegenerative or neuromuscular disorder is GD type 1.

123. The method of claim 121, wherein the GBA1-related neurodegenerative or neuromuscular disorder is GD type 2.

124. The method of claim 121, wherein the GBA1-related neurodegenerative or neuromuscular disorder is GD type 3.

125. The method of claim 119, wherein the GBA1-related neurodegenerative or neuromuscular disorder is Dementia with Lewy Bothes (DLB).

126. The method of claim 119, wherein the GBA1-related neurodegenerative or neuromuscular disorder is Lewy Body Dementia (LBD).

127. A method of treating a subject having Parkinson’s Disease (PD) or diagnosed with having PD, comprising administering to the subject an effective amount of the pharmaceutical composition of any one of claims 108-111 or the AAV particle of any one of claims 1 -95.

128. A method of treating a subject having Parkinson’s Disease (PD) or diagnosed with having PD, comprising administering to the subject an effective amount of the pharmaceutical composition of claim any one of claims 109-111 or the AAV particle of tiny one of claims 5-22.

129. A method of treating a subject having Parkinson’s Disease (PD) or diagnosed with having PD, comprising administering to the subject an effec tive amount of the pharmaceutical composition of claim 110 or the AAV particle of any one of claims 9-15, 92, and 94.

130. A method of treating a subject having Parkinson’s Disease (PD) or diagnosed with having PD, comprising administering to the subject an effective amount of the pharmaceutical composition of claim 1 11 or the AAV particle of any one of claims 16-22, 93, and 95.

131. A method of treating a subject having Gaucher Disease (GD) (e.g., GD type 1 , 2, or 3) or diagnosed with having Gaucher Disease (GD) (e.g., GD type 1, 2, or 3), comprising administering to the subject an effective amount of the pharmaceutical composition of any one of claims 108-111 or the AAV particle of any one of claims 1-95.

132. A method of treating a subject having Gaucher Disease (GD) (e.g., GD type 1, 2, or 3) or diagnosed with having Gaucher Disease (GD) (e.g., GD type 1, 2, or 3), comprising administering to the subject an effective amount of the pharmaceutical composition of claim 109-111 or the AAV particle of any one of claims 5-22.

133. A method of treating a subject having Gaucher Disease (GD) (e.g., GD type 1, 2, or 3) or diagnosed with having Gaucher Disease (GD) (e.g., GD type 1, 2, or 3), comprising administering to the subject an effective amount of the pharmaceutical composition of claim 110 or the AAV particle of any one of claims 9-15, 92, and 94.

134. A method of treating a subject having Gaucher Disease (GD) (e.g., GD type 1, 2. or 3) or diagnosed with having Gaucher Disease (GD) (e.g., GD type 1, 2, or 3), comprising administering to the subject an effective amount of the pharmaceutical composition of claim 111 or the AAV particle of any one of claims 16-22, 93, and 95.

135. The method of any one of claims 131-134, wherein the GD is GD type 1.

136. The method of any one of claims 131-134, wherein the GD is GD type 2.

137. The method of any one of claims 131-134, wherein the GD is GD type 3.

138. A method of treating a subject hatring Lewy Body Dementia (I., ED), comprising administering to the subject an effective amount of the pharmaceutical composition of any one of claims 108-111 or the AAV particle of any one of claims 1-95.

139. A method of treating a subject having Lewy Body Dementia (LED), comprising administering to the subject an effective amount of the pharmaceutical composition of claim 109-111 or the AAV particle of any one of claims 5-22.

140. A method of treating a subject having Lewy Body Dementia (LED), comprising administering to the subject an effective amount of the pharmaceutical composition of claim 111 or the AAV particle of any one of claims 9-15, 92, and 94.

141. A method of treating a subject having Lewy' Body Dementia (LED), comprising administering to the subject an effective amount of the plrarmacentical composition of claim 111 or the AAV particle of any one of claims 16-22, 93, and 95.

142. A method of treating a subject having Dementia with Lewy Bodies (DLB), comprising administering to the subject an effective amount of the pharmaceutical composition of any one of claims 108-111 or the AAV particle of any one of claims 1-95.

143. A method of treating a subject having Dementia with Lewy Bodies (DLB), comprising administering to the subject an effective amount of the pharmaceutical composition of claim 109-111 or the AAV particle of any one of claims 5-22.

144. A method of treating a subject having Dementia with Lewy Bodies (DLB), comprising administering to the subject an effective amount of the plrarmacentical composition of claim 111 or the AAV particle of any one of claims 9-15, 92. and 94.

145. A method of treating a subject having Dementia with Lewy Bodies (DLB), comprising administering to the subject an effective amount of the pharmaceutical composition of claim 111 or the AAV particle of any one of claims 16-22, 93, and 95.

146. The method of any one of claims 112-145, wherein the subject Iras one or more mutations in the GBA1 gene.

147. The method of any one of claims 112-146, wherein the subject has lower GCase activity as compared to GCase activity in an individual who does not have a GBA1-related disorder, optionally wherein the level of GCase activity is measured by a 4-MUG assay or a SensoLyte Blue Glucocerebrosidase assay.

148. The method of any one of claims 115-147, wherein the treating results in prevention of progression of the disorder in the subject.

149. The method of any one of claims 115-148, wherein the treating results in amelioration of at least one symptom of the disorder and / or a change in one or more biomarkers of the disorder.

150. The method of claim 149. wherein the one or more biomarkers comprises a GCase activity, a level of glucocerebroside and other glycolipids, (e.g.. within immune cells such as macrophages), a level of synuclein aggregates (e.g.. Lewy bodies), a level of neurofilament light chain, or a combination thereof.

151. The method of claim 149. wherein the at least one symptom comprises developmental delay, progressive encephalopathy, progressive dementia, ataxia, myoclonus, oculomotor dysfunction, bulbar palsy, generalized weakness, trembling of a limb, depression, visual hallucinations, cognitive decline, or a combination thereof.

152. The method of any one of claims 112-151, wherein the subject is a human.

153. The method of any one of claims 112-152, wherein the AAV particle is delivered to a cell, tissue, or region of the CNS, e.g., a region of the brain or spinal cord, e.g., the parenchyma, the cortex, substantia nigra, caudate cerebellum, striatum, corpus callosum, cerebellum, brain stem caudate- putamen. thalamus, superior colliculus, the spinal cord, or a combination thereof, wherein the AAV particle or pharmaceutical composition is delivered via intravenous administration.

154. The method of any one of claims 112-153, further comprising evaluating, e.g., measuring, the level of GBA1 expression, e.g., GBA1 gene expression. GBA1 mRNA expression, and / or GBA1 protein expression, in the subject, e.g., in a cell, tissue, or fluid of the subject.

155. The method of any one of claims 112-154, wherein the level of GBA1 protein expression is measured by an ELISA, a Western blot, or an immunohistochemistry assay.

156. The method of claim 154 or claim 155, wherein evaluating the level of GBA1 expression is performed prior to and subsequent to administration of the AAV, optionally wherein the level of GBA1 expression prior to administration is compared to the level of GBA1 expression subsequent to administration.

157. The method of any one of claims 154-156, comprising evaluating foe level of GBA1 expression in a cell or tissue of the central nervous system (e.g., parenchyma).

158. The method of claim 156 or claim 157, wherein foe subject’s level of GBA1 protein expression subsequent to administration is increased relative to the subject’s level of GBA1 protein expression prior to administration.

159. The method of any one of claims 1 12-158, further comprising evaluating, e.g., measuring, the level of GCase activity in the subject.

160. The method of any one of claims 112-159, wherein the administration results in an increase in:(i) GCase activity in a cell, tissue, (e.g., a cell or tissue of the CNS. e.g., the cortex, striatum, thalamus, cerebellum, and / or brainstem), and / or fluid (e.g.. CSF and / or serum) of the subject, optionally wherein GCase activity in the subject subsequent to the administration is increased by at least 2-fold, at least 3-fold, at least 4-fold, or at least 5-fold relative to GCase activity in the subject prior to the administration;(ii) viral genomes (VG) per ceil level in a CNS tissue (e.g., the cortex, striatum, thalamus, cerebellum, brainstem, and / or spinal cord) of the subject, optionally wherein the subject’s VG per cell level in the CNS tissue is increased by greater than 50 VG per cell relative to the subject’s VG per cell level in a peripheral tissue; and / or(iii) GBA1 mRNA expression in a cell or tissue (e.g., a cell or tissue of the CNS, e.g., the cortex, thalamus, and / or brainstem) of the subject, optionally wherein GBA1 mRNA expression in the subject subsequent to the administration is increased by at least 100-1300-fold as compared to GBA1 mRNA expression in the subject prior to foe administration.

161. The method of any one of claims 115-160, further comprising administering to the subject an additional agent suitable for treatment or prevention of the GBA1 -related disorder, optionally wherein the additional agent comprises enzyme replacement therapy (ERT) (e.g., imiglucerase, velaglucerase alfa, or tahglucerase alfa); substrate reduction therapy (SRT) (e.g.,elighistat or miglustat), levodopa, carbidopa, Safinamide. a dopamine agonist (e.g., quetiapine, clozapine, pramipexole, rotigotine, or ropinirole), an anticholinergic (e.g., benztropine or trihexyphenidyl), a cholinesterase inhibitor (e.g., rivastigmine, donepezil, or galantamine), an N- methyl-d-aspartate (NMDA receptor antagonist (e.g., memantine), or a combination thereof.

162. The method of any one of claims 112-161, farther comprising administering a blood transfusion to the subject.

163. The method of any one of claims 112-161, further comprising administering an immunosuppressant to the subject.

164. The method of claim 162, wherein the immunosuppressant comprises a corticosteroid (e.g., prednisone, prednisolone, methylprednisolone, and / or dexamethasone), rapamycin, mycophenolate mofetil, tacrolimus, rituximab, and / or eculizumab hydroxychloroquine.

165. The pharmaceutical composition of any one of claims 108-111 or the AAV particle of any one of claims 1-95, for use in the treatment of a GBA1-related disorder; optionally wherein the GBA1- related disorder is Parkinson’s Disease (PD), Parkinson’s Disease Dementia (PDD), Gaucher Disease (GD) (e.g.. GD type 1, 2, or 3), Dementia with Lewy' Bodies (LBD), Lewy Body Dementia (LBD), Multiple System Atrophy (MSA), Alzheimer’s Disease (AD), Amyotrophic Lateral Sclerosis (ALS), Pure Autonomic Failure, Neurodegeneration with brain iron accumulation, type 1 (NBIA 1), or Hallervorden-Spatz Syndrome.

166. The pharmaceutical composition or the AAV particle of claim 165, wherein the GBA1-related disorder is Gaucher Disease (GD) (e.g., GD type 1, 2, or 3).

167. The pharmaceutical composition or the AAV particle of claim 166, wherein the GD is GD type 1.

168. The pharmaceutical composition or the AAV particle of claim 166, wherein the GD is GD type2.

169. The pharmaceutical composition or the AAV particle of claim 166, wherein the GD is GD type170. The pharmaceutical composition or the AAV particle of claim 165. wherein the GBA1-related disorder is Parkinson’s Disease (PD).

171. The pharmaceutical composition orthe AAV particle of claim 165, wherein the GBA1-related disorder is LBD.

172. The pharmaceutical composition or the AAV particle of claim 165, wherein the GBA1-related disorder is DLB.

173. Use of the pharmaceutical composition of any one of claims 108-111 or the AAV particle of any one of claims 1-95 in the manufacture of a medicament for the treatment of a GBA1-related disorder; optionally wherein the GBA1-related disorder is Parkinson’s Disease (PD), Parkinson’s Disease Dementia (PDD), Gaucher Disease (GD) (e.g., GD type 1, 2, or 3), Dementia with Lewy Bodies (DLB), Lewy Body Dementia (LBD), Multiple System Atrophy (MSA), Alzheimer’s Disease (AD), Amyotrophic Lateral Sclerosis (ALS), Pure Autonomic Failure, Neurodegeneration with brain iron accumulation, type 1 (NBIA 1), or Hallervorden-Spatz Syndrome.

174. The use of claim 173. wherein the GBA1-related disorder is PD.

175. The use of claim 173, wherein the GBA1 -related disorder is Gaucher Disease (GD) (e.g,, GD type 1, 2, or 3).

176. The use of claim 175, wherein the GD is GD type 1.

177. The use of claim 175, wherein the GD is GD type 2.

178. The use of claim 175, wherein the GD is GD type 3.

179. The use of claim 173, wherein the GBA1-related disorder is LBD.

180. The use of claim 173, wherein the GBA1-related disorder is DLB,