Methods and compositions for modulating AAV infection

Abstract

Provided are genetically modified mammalian cells with enhanced permissiveness to adeno-associated virus (AAV) infection. The cells have increased levels of AAVR protein and reduced levels of SETDB1 protein relative to a corresponding cell that is not genetically modified. Also provide are methods of AAV delivery and methods of AAV titration using such cells.

Description

[0001]METHODS AND COMPOSITIONS FOR MODULATING AAV INFECTION CROSS-REFERENCE This application claims the benefit of U.S. Provisional Patent Application No.63 / 617,906 filed January 5, 2024 and U.S. Provisional Patent Application No.63 / 529,266 filed July 27, 2023, which applications are incorporated herein by reference in their entirety. GOVERNMENT RIGHTS This invention was made with Government support under contract AI130123 awarded by the National Institutes of Health. The Government has certain rights in the invention. INCORPORATION BY REFERENCE OF SEQUENCE LISTING PROVIDED AS AN XML FILE A Sequence Listing is provided herewith as a Sequence Listing XML, “STAN- 2117WO_SEQ_LIST.xml” created on July 19, 2024 and having a size of 64,990 bytes. The contents of the Sequence Listing XML are incorporated by reference herein in their entirety. INTRODUCTION Adeno-associated virus (AAV) vectored products are currently leading candidates for gene therapy applications with multiple approved products and many more in clinical trials. While AAV has been successfully used for gene delivery for many years, the receptor for this virus (AAVR) was only recently discovered. The multi-serotype AAV receptor (AAVR) has been shown to be critical for transduction both in vitro and in vivo for most AAV serotypes including the major serotypes used in the clinic. Overexpression of AAVR has also been shown to increase transduction in vitro for multiple AAV serotypes that are known to poorly transduce cells. However, there is a need for compositions and methods that can improve the efficacy and / or tropism of AAV infection, e.g., by enhancing the permissiveness of cells to AAV infection, relative to currently available methodologies – and there have been calls for development of methodologies to better characterize AAV product purity, e.g., for comparing lot-to-lot variation. Currently AAV lots may vary in ways that cannot be measured by current genome titer or capsid titer methods. Transduction requires the entry of rAAV vectors into the cells, the translocation of viral genomes to the nucleus and their conversion in double-stranded DNA, and, in addition, transcription of the transgene. To be meaningful, a functional titration assay should be performed in an in vitro system using a cell system that is maximally conducive to transduction by recombinant AAV. The above is provided herein, e.g., genetically modified cells described herein provide a robust functional titration assay - one that can, e.g., readout the ability of AAV to enter cells / express the encoded transgene, which gives a better proxy of the biological activity of the recombinant AAV preparation. SUMMARY The inventors discovered that surprising, unexpected levels of permissiveness to AAV are achieved when increased levels of AAVR protein are combined with decreased levels of SETDB1 protein. Such is achieved across a wide variety of AAV serotypes. Thus, provided are genetically modified mammalian cells with enhanced permissiveness to adeno-associated virus (AAV) infection, where the cell has increased levels of AAVR protein and reduced levels of SETDB1 protein (relative to a corresponding cell [otherwise equivalent / comparable cell] that is not genetically modified). Also provided are methods of AAV delivery. Such methods include contacting a subject genetically modified mammalian cell with an AAV particle that includes a DNA of interest (e.g., a DNA with a transgene of interest such as a non-coding RNA or a protein-coding transgene, e.g., a therapeutic protein, a cell marker such as GFP, luciferase, a drug selectable marker, and the like). The inventors also realized that because AAV transduction was so unexpectedly robust in cells with increased levels of AAVR protein and reduced levels of SETDB1 protein, the cells could be used to titrate AAV preparations based on function (i.e., functional titration) as opposed to titration based on physical characteristics of the AAV preparations. Thus, also provided are methods of titrating an AAV preparation. Such methods include contacting a population of subject genetically modified mammalian cells with an AAV preparation [in some cases with two or more (e.g., 3 or more, 4 or more, 5 or more) dilutions of the AAV preparation], and measuring a number and / or percentage of cells that were transduced by said contacting (in some cases, for each dilution). The inventors appreciate that in some cases, an AAV may include a transgene under the control of a promoter (e.g., a tissue specific promoter) that is not normally active in a subject genetically modified mammalian cell – and therefore, the transgene may not be expressed. For example, if a subject genetically modified mammalian cell is a HeLa cell and an AAV of interest expresses a transgene under the control of a tissue-specific promoter that is not active in HeLa cells, then the transgene may not be expressed the genetically modified cell. Thus, in some cases, a subject genetically modified mammalian cell includes CRISPRa components (e.g., a guide RNA, a CRISPR-Cas effector protein such as dCas9, dCas12a, and the like, and a transcription activating protein) for expression of viral (e.g., AAV) transgenes from an inverted terminal repeat (ITR). Such CRISPRa components provide for promoter- agnostic transduction by AAV, i.e., the CRISPRa components facilitate expression of an AAV transgene in a subject genetically modified mammalian cell regardless of the promoter to which the transgene is operably linked. BRIEF DESCRIPTION OF THE DRAWINGS The invention is best understood from the following detailed description when read in conjunction with the accompanying drawings. It is emphasized that, according to common practice, the various features of the drawings are not to-scale. On the contrary, the dimensions of the various features are arbitrarily expanded or reduced for clarity. Included in the drawings are the following figures. Fig.1A-1G. SETDB1 is a critical component of the HUSH complex responsible for suppression of recombinant AAV transgene expression. Fig.1A) HUSH complex component KO cells (FAM208A, MPP8, NP220, PPHLN1, or SETDB1) or WT HeLa cells were transduced with AAV2-CMV-Luc, AAV8-CMV-Luc, or AAV9-CMV-Luc at an MOI = 20,000 (4x108vg / well). Luciferase activity was determined at 48 hours post transduction. Ordinary one-way ANOVA with Dunnet post test (n=3 per group). Fig.1B) Testing transduction of different clonal SETDB1 KO lines. AAV2-CMV-GFP was used to transduce WT or SETDB1 KO clones (2-7, 2-10, and 2- 11) at an MOI = 20,000 (4x108vg / well). Luciferase activity was assessed at 48 hours post transduction. Fig.1C) Flow cytometry analysis of WT or SETDB1 KO cells transduced with AAV2-CMV-GFP at 48 hours post transduction. The number of transduced cells in each replicate was determined (Fig.1D) and the mean fluorescence intensity (MFI) was determined for each sample (Fig.1E). Fig.1F) Transduction of WT or SETDB1 KO cells by AAV4 expressing luciferase was determined at 72 hours after transduction at an MOI = 100,000 (2x109vg / well). Fig.1G) Transduction of WT or SETDB1 KO cells was assessed after transduction with AAV9-CMV-GFP or AAV9-CAG-GFP at an MOI=100,000 (2x109vg / well) after 48 hours. The number of GFP+ cells (transduction units; TU) per input viral genome (TU / vg) was reported. For multiple comparisons we used an ordinary one-way ANOVA with Dunnet posttest. For single comparisons we used an unpaired two-tailed t test. * p<0.05, ** p<0.01, ***p<0.001. Fig.2A-2E. Overexpression of the AAV receptor (AAVR) in conjunction with SETDB1 KO. Fig.2A) Lentivirus was generated using the pLenti-AAVR-FLAG plasmid. This was used to generate cell lines on both the HeLa WT background and the HeLa SETDB1 KO 2-7 background. Fig.2B) Transduction by AAV2, AAV8, and AAV9 encoding luciferase was compared in HeLa cells overexpressing AAVR were compared to WT HeLa cells. Transduction of HT1080, HeLa, HeLa SETDB1 KO 2-7, HeLa + AAVR clone #9, HeLa SETDB1 KO + AAVR clone #2 and clone #4 were compared. The transduction experiment was carried out using AAV2-CMV-GFP (Fig.2C), AAV9-CMV-GFP (Fig.2D), and AAV9-CAG-GFP (Fig.2E) at an MOI of 1,000 (2x107vg / well). Transduction was tracked over time and the number of transduced cells per viral genome (TU / vg) at 24 hours post transduction was reported. Fig.3A-3B. Functional titration of multiple AAV serotypes is possible using HeLa SETDB1 KO + AAVR cells. Fig.3A) HeLa, HeLa SETDB1 KO, HeLa + AAVR, and HeLa SETDB1 KO + AAVR cells were transduced with multiple AAV serotypes (AAV1 / 2 / 3 / 5 / 6 / 8 / 9- CMV-GFP and AAV9-CAG-GFP and AAV-PHP.eB-CAG-GFP) at an MOI = 1,000 (2x107vg / well). Transduction was tracked over time and the number of transduced cells per viral genome (TU / vg) at 24 hours post transduction was reported. Fig.3B) Transduction by each serotype was quantified at 24 hours post transduction. Fig.4A-4H. HeLa SETDB1 KO + AAVR cells can be efficiently transduced by multiple AAVR serotypes at different MOIs. Fig.4A) HeLa SETDB1 KO + AAVR cells were transduced with multiple AAV serotypes (AAV2 / 5 / 6 / 8 / 9 / 9-CAG) and WT cells were transduced with AAV9 at various multiplicities of infection (MOI) based on viral genomes per cell. Transduction was measured by live cell imaging and the number of infected cells is reported at 24 hours post transduction at each MOI. Fig.4B) HeLa SETDB1 KO + AAVR cells were transduced with various amounts of AAV based on viral genome (vg) and functional transduction was used to calculate a functional titer per well (TU / well) based on the number of GFP+ cells. A linear relationship between viral genome input and functional titer was established (R2values were calculated for each serotype). Using these relationships, the functional titers (TU / mL) were calculated for each AAV sample for an MOI = 1,000 (Fig.4C) or and MOI = 10,000 (Fig.4D). In a parallel experiment, WT HeLa or HeLa SETDB1 KO + AAVR cells were transduced with AAV2-GFP at different MOI. At 24 hours post transduction, flow cytometry was used to calculate the percentage of transduced cells (Fig.4E) and the mean fluorescent intensity of the transduced cells (Fig.4F) were reported for both cell types. AAV9-GFP was also used to transduce each cell population and the percentage of transduced cells (Fig.4G) and mean fluorescent intensity (Fig.4H) was reported. Statistical significance was determined using the Holm-Sidak method, with alpha = 0.05. Each row was analyzed individually, without assuming a consistent SD. * p<0.05, ** p<0.01, ***p<0.001. FIG.5 is a schematic illustration of one way to produce cells with reduced expression of SETDB1 and increased expression of AAVR. This workflow was used to generate the clonal cell lines used in the working examples herein. H1 HeLa cells (ATCC, CRL-1985) were used as the progenitor cell line. To generate the HeLa+AAVR clonal cell lines, cells were transduced with lentivirus generated using pLenti-AAVR-FLAG. After puromycin selection of the resistant population, these cells were single cell cloned to generate HeLa + AAVR-FLAG Clone #9. The generate the SETDB1 KO cell line HeLa cells were transfected with the PX458-sgRNA- SETDB1 plasmid, which contains Cas9 and sgRNA targeted SETDB1. Clonal cells were isolated by FACS and clone 2-7 was validated to be a SETDB1 KO by sequencing and western blot. This cell line was further modified by transduction with the AAVR-FLAG lentivirus and puromycin selection was performed. After selection this cell line was single cell cloned to generate HeLa SETDB1-KO + AAVR-FLAG Clone #4, which can be used for functional titration of recombinant AAV viral vectors. FIG.6 illustrates confirmation that the nucleotide sequence of the SETDB1 genomic locus was altered. FIG.7 illustrates a Western blot that was used to confirm SETDB1 knockout (KO) (resulting in reduced SETDB1 protein expression). FIG.8 is an example of titration of AAV9 at different time points. FIG.9A-9B Targeting AAV ITR using CRISPR activation to drive transgene expression. FIG.9A) Schematic of using CRISPR activation to target the conserved ITR of AAV to drive expression of the transgene. HeLa SETDB1 KO + AAVR cells were modified to express dCas9- VP64 and PP7-P65-HSF1 along with a guideRNA (gRNA) targeting various areas of the AAV ITR. FIG.9B) Multiple guide targetable sequences exist in the conserved AAV ITR, which allows for targeting of various sides using different gRNA including the 3 shown. The target site and PAM sequences are indicated (also see Table 1). The depicted ITR sequence is SEQ ID NO: 51. FIG.10A-10D Transduction of HeLa SETDB1 KO + AAVR + ITR activation cells. FIG. 10A) HeLa SETDB1 KO+AAVR+dCas9 cells with or without ITR guide #1 added to the cell line were transduced with AAV that had a universal promoter (AAV8-CMV-GFP) or a cell type specific promoter (AAV8-hSyn-mCh). Transduction is shown at 48 hours post transduction. FIG.10B) Transduction by AAV8-hSyn-mCh was tracked over time for HeLa SETDB1 KO+AAVR+dCas9 without a guide or with ITR guide #1, #2 or #3. Transduction was tracked over time and the transduction units (TU) per well are shown. FIG.10C) Transduction of HeLa SETDB1 KO+AAVR+dCas9 cells with or without ITR guides by AAV8-hSyn-mCh or AAV9- hSyn-mCh at 48 hours post transduction. The number of fluorescent cells was measured at 48 hours post transduction for either AAV serotype or mock transduced cells. FIG.10D) Testing specificity of HeLa SETDB1 KO+AAVR+dCas9+ITR guide cell lines using a plasmid transfection. pGL4, which lacks a promoter upstream of a Renilla luciferase (Rluc) gene, had the target sequence for each of the ITR gRNAs cloned upstream of the Rluc with a PAM sequence or with the PAM sequence mutated (which would prevent targeting by dCas9). Each cell line was transfected with the pGL4 plasmids and the ratio or PAM / PAMdel luciferase activity was reported. FIG.11A-11C Measuring transduction by AAV vectors with cell specific promoters. FIG. 11A) Transduction was measured by flow cytometry at 72 hours post transduction. Plots are shown for single cells with GFP / YFP transduction on the y-axis and mCherry transduction on the x-axis. FIG.11B) The percentage of transduced cells, as measured by flow cytometry, was calculated at 72 hours post transduction. FIG.11C) Transduction of WT HeLa cells, HeLa SETDB1 KO+AAVR+dCas9 and HeLa SETDB1 KO+AAVR+dCas9+ITR guide #1 by AAVs with cell type-specific promoters. Transduction was measured using live cell imaging at 72 hours post transduction. The number of transduced cells per well is reported. FIG.12 Schematic illustration of generation of clonal cell lines used in this study. HeLa cells (ATCC, CRL-1985) were used as the progenitor cell line. To generate the HeLa+AAVR clonal cell lines, cells were transduced with lentivirus generated using pLenti-AAVR-FLAG. After puromycin selection of the resistant population, these cells were single cell cloned to generate HeLa + AAVR-FLAG Clone #9. The generate the SETDB1 KO cell line HeLa cells were transfected with the PX458-sgRNA-SETDB1 plasmid, which contains Cas9 and sgRNA targeted SETDB1. Clonal cells were isolated by FACS and clone 2-7 was validated to be a SETDB1 KO by sequencing and western blot. This cell line was further modified by transduction with the AAVR-FLAG lentivirus and puromycin selection was performed. After selection this cell line was single cell cloned to generate HeLa SETDB1-KO + AAVR-FLAG Clone #4, which can be used for functional titration of recombinant AAV viral vectors. For the generation of the ITR activation cell lines, cells were first transduced with lentivirus generated using pLenti-dCas9-VP64-BLAST followed by blastmycin selection. After selection, cells were transduced with lentivirus generated using pLenti-CRISPRa-PP7-P65-HSF1-Zeo with guide ITR #1, #2, or #3 cloned into the guide scaffold. Cells were selected for Zeocin resistance followed by single cell selection based on transduction by AAV8-hSyn-mCh. This resulted in the production of HeLa SETDB1 KO+AAVR+CRISPRa+ITR guide #1, or #2 or #3, which allow for promoter agnostic transgene expression. FIG.13A-13C Schematic illustration of cloning procedures and plasmids used in the examples. DETAILED DESCRIPTION Before the present methods and compositions are described, it is to be understood that this invention is not limited to particular method or composition described, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting, since the scope of the present invention will be limited only by the appended claims. Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limits of that range is also specifically disclosed. Each smaller range between any stated value or intervening value in a stated range and any other stated or intervening value in that stated range is encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included or excluded in the range, and each range where either, neither or both limits are included in the smaller ranges is also encompassed within the invention, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the invention. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, some potential and preferred methods and materials are now described. All publications mentioned herein are incorporated herein by reference to disclose and describe the methods and / or materials in connection with which the publications are cited. It is understood that the present disclosure supersedes any disclosure of an incorporated publication to the extent there is a contradiction. As will be apparent to those of skill in the art upon reading this disclosure, each of the individual embodiments described and illustrated herein has discrete components and features which may be readily separated from or combined with the features of any of the other several embodiments without departing from the scope or spirit of the present invention. Any recited method can be carried out in the order of events recited or in any other order that is logically possible. It must be noted that as used herein and in the appended claims, the singular forms "a", "an", and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "a cell" includes a plurality of such cells and reference to "the peptide" includes reference to one or more peptides and equivalents thereof, e.g., polypeptides, known to those skilled in the art, and so forth. The publications discussed herein are provided solely for their disclosure prior to the filing date of the present application. Nothing herein is to be construed as an admission that the present invention is not entitled to antedate such publication by virtue of prior invention. Further, the dates of publication provided may be different from the actual publication dates which may need to be independently confirmed. Methods and compositions As noted above, the inventors have discovered that surprising, unexpected levels of permissiveness to AAV are achieved when increased levels of AAVR protein are combined with decreased levels of SETDB1 protein. Such is achieved across a wide variety of AAV serotypes. Thus, provided are genetically modified mammalian cells with enhanced permissiveness to adeno-associated virus (AAV) infection, where the cell has increased levels of AAVR protein and reduced levels of SETDB1 protein (relative to a corresponding cell [otherwise equivalent / comparable cell] that is not genetically modified). Also as noted above, the inventors appreciate that in some cases, an AAV may include a transgene under the control of a promoter (e.g., a tissue specific promoter) that is not normally active in a subject genetically modified mammalian cell – and therefore, the transgene may not be expressed. As such, in some cases, a subject genetically modified mammalian cell includes CRISPRa components (e.g., a CRISPRa fusion protein or a nucleic acid encoding it; and / or a guide RNA or a nucleic acid encoding it) for expression of viral transgenes, e.g., from an inverted terminal repeat (ITR) such as an AAV ITR. In some cases, a genetically modified mammalian cell has increased levels of AAVR protein, reduced levels of SETDB1 protein, and in addition includes CRIPSRa components for targeting an ITR sequence (e.g., an AAV ITR sequence). Also provided are methods of AAV delivery. Such methods include contacting a subject genetically modified mammalian cell with an AAV particle that includes a DNA of interest (e.g., a DNA with a transgene of interest such as a non-coding RNA or a protein-coding transgene, e.g., a therapeutic protein, a cell marker such as GFP, luciferase, a drug selectable marker, and the like). The inventors also realized that because AAV transduction was so unexpectedly robust in cells with increased levels of AAVR protein and reduced levels of SETDB1 protein, the cells could be used to titrate AAV preparations based on function (i.e., functional titration) as opposed to titration based on physical characteristics of the AAV preparations. Thus, also provided are methods of titrating an AAV preparation. Such methods include contacting a population of subject genetically modified mammalian cells with an AAV preparation [in some cases with two or more (e.g., 3 or more, 4 or more, 5 or more) dilutions of the AAV preparation], and measuring a number and / or percentage of cells that were transduced by said contacting (in some cases, for each dilution). i. AAVR protein Proteins / Genes The term “AAVR” is used herein to refer to the adeno-associated virus receptor. The inventors of this disclosure have discovered that adeno-associated virus (AAV) binds to the protein KIAA0319L, which is expressed by host cells (e.g., the cells that AAV will enter), and that the protein KIAA0319L functions as a receptor for AAV. The inventors have renamed the protein “KIAA0319L” to “AAV receptor” (AAVR). Wild type AAVR is a predicted type I transmembrane protein with a signal peptide (which directs AAVR to the secretory pathway of the cell), a MANEC domain (also sometimes referred to as a MANSC domain), and five Ig-like domains (polycystic kidney disease (PKD) domains 1-5). The transmembrane domain (TM) is located C-terminal to the MANEC and PKD domains (which are therefore part of the AAVR ectodomain), and is followed by a cytoplasmic tail (which includes subcellular targeting motifs – endocytic motifs). The cytoplasmic tail of the wild type AAVR protein directs trafficking of the protein from the plasma membrane to the trans-golgi network (TGN). Without being bound by theory, the inventors work in the examples section below suggests that an AAV particle binds to AAVR on the surface of a host cell, and because the cytoplasmic tail of the AAVR protein directs internalization of the AAVR protein (e.g., directs trafficking to the cell’s TGN) this allows internalization of the AAV particle that is bound to the AAVR protein (i.e., this provides entry for the AAV particle into the cell). An AAVR protein and variant AAVR polypeptides (e.g., a soluble AAVR, a mini-AAVR, etc., as described in more detail below) can be any AAVR protein. For example, suitable AAVR proteins (and corresponding variants) include those from any species, e.g., a mammalian AAVR protein, a rodent AAVR protein, a primate AAVR protein, a rat AAVR protein, a mouse AAVR protein, a pig AAVR protein, a cow AAVR protein, a sheep AAVR protein, a rabbit AAVR protein, a dog AAVR protein, a human AAVR protein, etc. Sequences for various wild type AAVR protein sequences (e.g., canine, bovine, sheep, equine, porcine, rodent, mouse, rat, feline, primate, monkey, ape, chimpanzee, and the like) can easily be found and are readily available to one of ordinary skill in the art. In some embodiments a subject AAVR is modified relative to a corresponding wild type AAVR (i.e., the AAVR polypeptide is a variant AAVR polypeptide having an amino acid sequence that is modified relative to the amino acid sequence of a corresponding wild type AAV protein). By “corresponding” wild type AAVR protein is meant a wild type AAVR protein from which the AAVR protein was or could have been derived (e.g., a wild type protein AAVR protein having high sequence identity to the variant AAVR polypeptide outside of the region(s) that is modified). For example, for a variant AAVR polypeptide that lacks a particular domain (e.g., a PKD domain) but is otherwise highly similar to a wild type mouse AAVR protein, the wild type mouse AAVR protein to which it is most similar may be considered to be a corresponding wild type AAVR protein. A corresponding wild type protein does not have to be 100% identical (e.g., can be 85% or more identical, 90% or more identical, 95% or more identical, 98% or more identical, 99% or more identical, etc.)(outside of region(s) that is modified), but the variant and corresponding wild type AAVR proteins can bind to an AAV particle, and retain enough sequence identity (outside of the region that is modified) that they can be considered homologous. The amino acid sequence of a “corresponding” wild type AAVR protein can be identified / evaluated using any convenient method (e.g., using any convenient sequence comparison / alignment software such as BLAST, MUSCLE, T-COFFEE, etc.). The wild type human AAVR protein amino acid sequence is depicted here, followed by various modified versions (variants) of the protein (subject variant AAVR polypeptides). Wild type human KIAA0319L (AAVR) *also known as “KIAA0319-like” and “dyslexia-associated protein” MEKRLGVKPNPASWILSGYYWQTSAKWLRSLYLFYTCFCFSVLWLSTDASES RCQQGKTQFGVGLRSGGENHLWLLEGTPSLQSCWAACCQDSACHVFWWL EGMCIQADCSRPQSCRAFRTHSSNSMLVFLKKFQTADDLGFLPEDDVPHLLG LGWNWASWRQSPPRAALRPAVSSSDQQSLIRKLQKRGSPSDVVTPIVTQHS KVNDSNELGGLTTSGSAEVHKAITISSPLTTDLTAELSGGPKNVSVQPEISEGL ATTPSTQQVKSSEKTQIAVPQPVAPSYSYATPTPQASFQSTSAPYPVIKELVV SAGESVQITLPKNEVQLNAYVLQEPPKGETYTYDWQLITHPRDYSGEMEGK HSQILKLSKLTPGLYEFKVIVEGQNAHGEGYVNVTVKPEPRKNRPPIAIVSPQ FQEISLPTTSTVIDGSQSTDDDKIVQYHWEELKGPLREEKISEDTAILKLSKLV PGNYTFSLTVVDSDGATNSTTANLTVNKAVDYPPVANAGPNQVITLPQNSIT LFGNQSTDDHGITSYEWSLSPSSKGKVVEMQGVRTPTLQLSAMQEGDYTY QLTVTDTIGQQATAQVTVIVQPENNKPPQADAGPDKELTLPVDSTTLDGSKS SDDQKIISYLWEKTQGPDGVQLENANSSVATVTGLQVGTYVFTLTVKDERNL QSQSSVNVIVKEEINKPPIAKITGNVVITLPTSTAELDGSKSSDDKGIVSYLWT RDEGSPAAGEVLNHSDHHPILFLSNLVEGTYTFHLKVTDAKGESDTDRTTVE VKPDPRKNNLVEIILDINVSQLTERLKGMFIRQIGVLLGVLDSDIIVQKIQPYTEQ STKMVFFVQNEPPHQIFKGHEVAAMLKSELRKQKADFLIFRALEVNTVTCQLN CSDHGHCDSFTKRCICDPFWMENFIKVQLRDGDSNCEWSVLYVIIATFVIVVA LGILSWTVICCCKRQKGKPKRKSKYKILDATDQESLELKPTSRAGIKQKGLLLS SSLMHSESELDSDDAIFTWPDREKGKLLHGQNGSVPNGQTPLKARSPREEIL (SEQ ID NO: 1) Domains (e.g., according to UniProt) (a) signal peptide (SP) (b) amino acids 49-127; MANEC domain (underline / italic) *also sometimes referred to as a MANSC domain (c) amino acids 312-401; PKD domain 1 (bold / underline) (d) amino acids 409-498; PKD domain 2 (bold / underline) (e) amino acids 504-594; PKD domain 3 (bold / underline) (f) amino acids 600-688; PKD domain 4 (bold / underline) (g) amino acids 694-785; PKD domain 5 (bold / underline) (h) amino acids 930-955; transmembrane domain (TM) (underline) *can be amino acids 933-953; 930-952; 930-955; 931-949 (i) amino acids 956-1049; cytoplasmic tail (with endocytic motifs) Delta-MANEC (deletion of MANEC domain) (also referred to as the MANEC domain) *dots (...) indicate deleted region MEKRLGVKPNPASWILSGYYWQTSAKWLRSLYLFYTCFCFSVLWLSTDASE.. .THSSNSMLVFLKKFQTADDLGFLPEDDVPHLLGLGWNWASWRQSPPRAAL RPAVSSSDQQSLIRKLQKRGSPSDVVTPIVTQHSKVNDSNELGGLTTSGSAE VHKAITISSPLTTDLTAELSGGPKNVSVQPEISEGLATTPSTQQVKSSEKTQIAV PQPVAPSYSYATPTPQASFQSTSAPYPVIKELVVSAGESVQITLPKNEVQLNA YVLQEPPKGETYTYDWQLITHPRDYSGEMEGKHSQILKLSKLTPGLYEFKVI VEGQNAHGEGYVNVTVKPEPRKNRPPIAIVSPQFQEISLPTTSTVIDGSQSTD DDKIVQYHWEELKGPLREEKISEDTAILKLSKLVPGNYTFSLTVVDSDGATNS TTANLTVNKAVDYPPVANAGPNQVITLPQNSITLFGNQSTDDHGITSYEWSL SPSSKGKVVEMQGVRTPTLQLSAMQEGDYTYQLTVTDTIGQQATAQVTVIV QPENNKPPQADAGPDKELTLPVDSTTLDGSKSSDDQKIISYLWEKTQGPDG VQLENANSSVATVTGLQVGTYVFTLTVKDERNLQSQSSVNVIVKEEINKPPIA KITGNVVITLPTSTAELDGSKSSDDKGIVSYLWTRDEGSPAAGEVLNHSDHH PILFLSNLVEGTYTFHLKVTDAKGESDTDRTTVEVKPDPRKNNLVEIILDINVS QLTERLKGMFIRQIGVLLGVLDSDIIVQKIQPYTEQSTKMVFFVQNEPPHQIFK GHEVAAMLKSELRKQKADFLIFRALEVNTVTCQLNCSDHGHCDSFTKRCICD PFWMENFIKVQLRDGDSNCEWSVLYVIIATFVIVVALGILSWTVICCCKRQKGK PKRKSKYKILDATDQESLELKPTSRAGIKQKGLLLSSSLMHSESELDSDDAIFT WPDREKGKLLHGQNGSVPNGQTPLKARSPREEIL (SEQ ID NO: 2) Deletion of PKD domains 1 and 2 *dots (...) indicate deleted region MEKRLGVKPNPASWILSGYYWQTSAKWLRSLYLFYTCFCFSVLWLSTDASES RCQQGKTQFGVGLRSGGENHLWLLEGTPSLQSCWAACCQDSACHVFWWL EGMCIQADCSRPQSCRAFRTHSSNSMLVFLKKFQTADDLGFLPEDDVPHLLG LGWNWASWRQSPPRAALRPAVSSSDQQSLIRKLQKRGSPSDVVTPIVTQHS KVNDSNELGGLTTSGSAEVHKAITISSPLTTDLTAELSGGPKNVSVQPEISEGL ATTPSTQQVKSSEKTQIAVPQPVAPSYSYATPTPQASFQSTSAPYPVIKEL...P PVANAGPNQVITLPQNSITLFGNQSTDDHGITSYEWSLSPSSKGKVVEMQGV RTPTLQLSAMQEGDYTYQLTVTDTIGQQATAQVTVIVQPENNKPPQADAGP DKELTLPVDSTTLDGSKSSDDQKIISYLWEKTQGPDGVQLENANSSVATVTG LQVGTYVFTLTVKDERNLQSQSSVNVIVKEEINKPPIAKITGNVVITLPTSTAEL DGSKSSDDKGIVSYLWTRDEGSPAAGEVLNHSDHHPILFLSNLVEGTYTFHL KVTDAKGESDTDRTTVEVKPDPRKNNLVEIILDINVSQLTERLKGMFIRQIGVL LGVLDSDIIVQKIQPYTEQSTKMVFFVQNEPPHQIFKGHEVAAMLKSELRKQK ADFLIFRALEVNTVTCQLNCSDHGHCDSFTKRCICDPFWMENFIKVQLRDGD SNCEWSVLYVIIATFVIVVALGILSWTVICCCKRQKGKPKRKSKYKILDATDQES LELKPTSRAGIKQKGLLLSSSLMHSESELDSDDAIFTWPDREKGKLLHGQNGS VPNGQTPLKARSPREEIL (SEQ ID NO: 3) Deletion of PKD domains 2 and 3 *dots (...) indicate deleted region MEKRLGVKPNPASWILSGYYWQTSAKWLRSLYLFYTCFCFSVLWLSTDASES RCQQGKTQFGVGLRSGGENHLWLLEGTPSLQSCWAACCQDSACHVFWWL EGMCIQADCSRPQSCRAFRTHSSNSMLVFLKKFQTADDLGFLPEDDVPHLLG LGWNWASWRQSPPRAALRPAVSSSDQQSLIRKLQKRGSPSDVVTPIVTQHS KVNDSNELGGLTTSGSAEVHKAITISSPLTTDLTAELSGGPKNVSVQPEISEGL ATTPSTQQVKSSEKTQIAVPQPVAPSYSYATPTPQASFQSTSAPYPVIKELVV SAGESVQITLPKNEVQLNAYVLQEPPKGETYTYDWQLITHPRDYSGEMEGK HSQILKLSKLTPGLYEFKVIVEGQNAHGEGYVNVTVKPEPRK...PPQADAGP DKELTLPVDSTTLDGSKSSDDQKIISYLWEKTQGPDGVQLENANSSVATVTG LQVGTYVFTLTVKDERNLQSQSSVNVIVKEEINKPPIAKITGNVVITLPTSTAEL DGSKSSDDKGIVSYLWTRDEGSPAAGEVLNHSDHHPILFLSNLVEGTYTFHL KVTDAKGESDTDRTTVEVKPDPRKNNLVEIILDINVSQLTERLKGMFIRQIGVL LGVLDSDIIVQKIQPYTEQSTKMVFFVQNEPPHQIFKGHEVAAMLKSELRKQK ADFLIFRALEVNTVTCQLNCSDHGHCDSFTKRCICDPFWMENFIKVQLRDGD SNCEWSVLYVIIATFVIVVALGILSWTVICCCKRQKGKPKRKSKYKILDATDQES LELKPTSRAGIKQKGLLLSSSLMHSESELDSDDAIFTWPDREKGKLLHGQNGS VPNGQTPLKARSPREEIL (SEQ ID NO: 4) Deletion of PKD domains 3 and 4 *dots (...) indicate deleted region MEKRLGVKPNPASWILSGYYWQTSAKWLRSLYLFYTCFCFSVLWLSTDASES RCQQGKTQFGVGLRSGGENHLWLLEGTPSLQSCWAACCQDSACHVFWWL EGMCIQADCSRPQSCRAFRTHSSNSMLVFLKKFQTADDLGFLPEDDVPHLLG LGWNWASWRQSPPRAALRPAVSSSDQQSLIRKLQKRGSPSDVVTPIVTQHS KVNDSNELGGLTTSGSAEVHKAITISSPLTTDLTAELSGGPKNVSVQPEISEGL ATTPSTQQVKSSEKTQIAVPQPVAPSYSYATPTPQASFQSTSAPYPVIKELVV SAGESVQITLPKNEVQLNAYVLQEPPKGETYTYDWQLITHPRDYSGEMEGK HSQILKLSKLTPGLYEFKVIVEGQNAHGEGYVNVTVKPEPRKNRPPIAIVSPQ FQEISLPTTSTVIDGSQSTDDDKIVQYHWEELKGPLREEKISEDTAILKLSKLV PGNYTFSLTVVDSDGATNSTTANLTVNKAVDYPP...IAKITGNVVITLPTSTAE LDGSKSSDDKGIVSYLWTRDEGSPAAGEVLNHSDHHPILFLSNLVEGTYTFH LKVTDAKGESDTDRTTVEVKPDPRKNNLVEIILDINVSQLTERLKGMFIRQIGV LLGVLDSDIIVQKIQPYTEQSTKMVFFVQNEPPHQIFKGHEVAAMLKSELRKQK ADFLIFRALEVNTVTCQLNCSDHGHCDSFTKRCICDPFWMENFIKVQLRDGD SNCEWSVLYVIIATFVIVVALGILSWTVICCCKRQKGKPKRKSKYKILDATDQES LELKPTSRAGIKQKGLLLSSSLMHSESELDSDDAIFTWPDREKGKLLHGQNGS VPNGQTPLKARSPREEIL (SEQ ID NO: 5) Deletion of PKD domains 4 and 5 *dots (...) indicate deleted region MEKRLGVKPNPASWILSGYYWQTSAKWLRSLYLFYTCFCFSVLWLSTDASES RCQQGKTQFGVGLRSGGENHLWLLEGTPSLQSCWAACCQDSACHVFWWL EGMCIQADCSRPQSCRAFRTHSSNSMLVFLKKFQTADDLGFLPEDDVPHLLG LGWNWASWRQSPPRAALRPAVSSSDQQSLIRKLQKRGSPSDVVTPIVTQHS KVNDSNELGGLTTSGSAEVHKAITISSPLTTDLTAELSGGPKNVSVQPEISEGL ATTPSTQQVKSSEKTQIAVPQPVAPSYSYATPTPQASFQSTSAPYPVIKELVV SAGESVQITLPKNEVQLNAYVLQEPPKGETYTYDWQLITHPRDYSGEMEGK HSQILKLSKLTPGLYEFKVIVEGQNAHGEGYVNVTVKPEPRKNRPPIAIVSPQ FQEISLPTTSTVIDGSQSTDDDKIVQYHWEELKGPLREEKISEDTAILKLSKLV PGNYTFSLTVVDSDGATNSTTANLTVNKAVDYPPVANAGPNQVITLPQNSIT LFGNQSTDDHGITSYEWSLSPSSKGKVVEMQGVRTPTLQLSAMQEGDYTY QLTVTDTIGQQATAQVTVIVQPENNK...NLVEIILDINVSQLTERLKGMFIRQIGV LLGVLDSDIIVQKIQPYTEQSTKMVFFVQNEPPHQIFKGHEVAAMLKSELRKQK ADFLIFRALEVNTVTCQLNCSDHGHCDSFTKRCICDPFWMENFIKVQLRDGD SNCEWSVLYVIIATFVIVVALGILSWTVICCCKRQKGKPKRKSKYKILDATDQES LELKPTSRAGIKQKGLLLSSSLMHSESELDSDDAIFTWPDREKGKLLHGQNGS VPNGQTPLKARSPREEIL (SEQ ID NO: 6) Example of a mini-AAVR *missing MANEC and PKDs 4-5 *dots (...) indicate deleted regions MEKRLGVKPNPASWILSGYYWQTSAKWLRSLYLFYTCFCFSVLWLSTDASE.. .VSAGESVQITLPKNEVQLNAYVLQEPPKGETYTYDWQLITHPRDYSGEMEG KHSQILKLSKLTPGLYEFKVIVEGQNAHGEGYVNVTVKPEPRKNRPPIAIVSP QFQEISLPTTSTVIDGSQSTDDDKIVQYHWEELKGPLREEKISEDTAILKLSKL VPGNYTFSLTVVDSDGATNSTTANLTVNKAVDYPPVANAGPNQVITLPQNSI TLFGNQSTDDHGITSYEWSLSPSSKGKVVEMQGVRTPTLQLSAMQEGDYTY QLTVTDTIGQQATAQVTVIVQPENNK...CEWSVLYVIIATFVIVVALGILSWTVIC CCKRQKGKPKRKSKYKILDATDQESLELKPTSRAGIKQKGLLLSSSLMHSESE LDSDDAIFTWPDREKGKLLHGQNGSVPNGQTPLKARSPREEIL (SEQ ID NO: 7) Example of PKD domains 1-5 (e.g., which can be used as (1) a soluble AAVR polypeptide, which sequence can be preceded by a signal peptide and encoded by nucleic acid, and / or which can be fused to a sequence that provides for solubility such as an MBP sequence; or (2) a variant AAVR polypeptide, which sequence can precede (a) a sequence that provides for presentation of all or a portion of the variant AAVR polypeptide on the surface of a cell and (b) a sequence that provides for trafficking of the AAVR polypeptide from the surface of the cell to a location within the cell, e.g., the TGN) VSAGESVQITLPKNEVQLNAYVLQEPPKGETYTYDWQLITHPRDYSGEMEG KHSQILKLSKLTPGLYEFKVIVEGQNAHGEGYVNVTVKPEPRKNRPPIAIVSP QFQEISLPTTSTVIDGSQSTDDDKIVQYHWEELKGPLREEKISEDTAILKLSKL VPGNYTFSLTVVDSDGATNSTTANLTVNKAVDYPPVANAGPNQVITLPQNSI TLFGNQSTDDHGITSYEWSLSPSSKGKVVEMQGVRTPTLQLSAMQEGDYTY QLTVTDTIGQQATAQVTVIVQPENNKPPQADAGPDKELTLPVDSTTLDGSKS SDDQKIISYLWEKTQGPDGVQLENANSSVATVTGLQVGTYVFTLTVKDERNL QSQSSVNVIVKEEINKPPIAKITGNVVITLPTSTAELDGSKSSDDKGIVSYLWT RDEGSPAAGEVLNHSDHHPILFLSNLVEGTYTFHLKVTDAKGESDTDRTTVE VKPDPR (SEQ ID NO: 8) Example of PKD domains 1-3 (e.g., which can be used as (1) a soluble AAVR polypeptide, which sequence can be preceded by a signal peptide and encoded by nucleic acid, and / or which can be fused to a sequence that provides for solubility such as an MBP sequence; or (2) a variant AAVR polypeptide, which sequence can precede (a) a sequence that provides for presentation of all or a portion of the variant AAVR polypeptide on the surface of a cell and (b) a sequence that provides for trafficking of the AAVR polypeptide from the surface of the cell to a location within the cell, e.g., the TGN) SAGESVQITLPKNEVQLNAYVLQEPPKGETYTYDWQLITHPRDYSGEMEGK HSQILKLSKLTPGLYEFKVIVEGQNAHGEGYVNVTVKPEPRKNRPPIAIVSPQ FQEISLPTTSTVIDGSQSTDDDKIVQYHWEELKGPLREEKISEDTAILKLSKLV PGNYTFSLTVVDSDGATNSTTANLTVNKAVDYPPVANAGPNQVITLPQNSIT LFGNQSTDDHGITSYEWSLSPSSKGKVVEMQGVRTPTLQLSAMQEGDYTY QLTVTDTIGQQATAQVTVIVQPE (SEQ ID NO: 9) Example of PKD domains 1-2 plus 5 (PKD domains 3-4 deleted) (e.g., which can be used as (1) a soluble AAVR polypeptide, which sequence can be preceded by a signal peptide and encoded by nucleic acid, and / or which can be fused to a sequence that provides for solubility such as an MBP sequence; or (2) a variant AAVR polypeptide, which sequence can precede (a) a sequence that provides for presentation of all or a portion of the variant AAVR polypeptide on the surface of a cell and (b) a sequence that provides for trafficking of the AAVR polypeptide from the surface of the cell to a location within the cell, e.g., the TGN) SAGESVQITLPKNEVQLNAYVLQEPPKGETYTYDWQLITHPRDYSGEMEGK HSQILKLSKLTPGLYEFKVIVEGQNAHGEGYVNVTVKPEPRKNRPPIAIVSPQ FQEISLPTTSTVIDGSQSTDDDKIVQYHWEELKGPLREEKISEDTAILKLSKLV PGNYTFSLTVVDSDGATNSTTANLTVNKA...INKPPIAKITGNVVITLPTSTAEL DGSKSSDDKGIVSYLWTRDEGSPAAGEVLNHSDHHPILFLSNLVEGTYTFHL KVTDAKGESDTDRTTVEVKPD (SEQ ID NO: 10) Example of PKD domains 1-2 plus 4 (PKD domains 3 and 5 deleted) (e.g., which can be used as (1) a soluble AAVR polypeptide, which sequence can be preceded by a signal peptide and encoded by nucleic acid, and / or which can be fused to a sequence that provides for solubility such as an MBP sequence; or (2) a variant AAVR polypeptide, which sequence can precede (a) a sequence that provides for presentation of all or a portion of the variant AAVR polypeptide on the surface of a cell and (b) a sequence that provides for trafficking of the AAVR polypeptide from the surface of the cell to a location within the cell, e.g., the TGN) SAGESVQITLPKNEVQLNAYVLQEPPKGETYTYDWQLITHPRDYSGEMEGK HSQILKLSKLTPGLYEFKVIVEGQNAHGEGYVNVTVKPEPRKNRPPIAIVSPQ FQEISLPTTSTVIDGSQSTDDDKIVQYHWEELKGPLREEKISEDTAILKLSKLV PGNYTFSLTVVDSDGATNSTTANLTVNKA...NNKPPQADAGPDKELTLPVDS TTLDGSKSSDDQKIISYLWEKTQGPDGVQLENANSSVATVTGLQVGTYVFTL TVKDERNLQSQSSVNVIVKEE (SEQ ID NO: 11) An AAVR polypeptide (e.g., a wild type AAVR polypeptide, a variant AAVR polypeptide, e.g., a soluble variant AAVR polypeptide) suitable for use in the compositions and methods provided specifically binds to AAV particles (e.g., binds to an AAV capsid protein). In other words, a suitable AAVR protein (e.g., a wild type AAVR polypeptide, a variant AAVR polypeptide, e.g., a soluble variant AAVR polypeptide) includes a portion of an AAVR protein that is sufficient to specifically bind an AAV particle (virion) at a recognizable affinity (e.g., a high affinity), which portion normally lies N-terminal to the transmembrane domain, or a fragment thereof that retains the binding activity. In some cases, domains (e.g., signal peptide, MANEC domain, PKD domains 1-5, transmembrane domain, cytoplasmic tail) of a subject AAVR polypeptide are 100% identical to the corresponding domains of a corresponding wild type AAVR protein, but this need not be the case. For example, when referring to the amino acid sequence of a PKD domain 1 of a subject AAVR polypeptide (e.g., a variant AAVR polypeptide, e.g., a soluble variant AAVR polypeptide), such a sequence can have 70% or more sequence identity (e.g., 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, 98% or more, 99% or more, 99.5% or more, or 100% sequence identity) with amino acids 312-401 of SEQ ID NO: 1 (or with corresponding amino acids of a corresponding wild type AAVR protein). When referring to the amino acid sequence of a PKD domain 2 of a subject AAVR polypeptide (e.g., a variant AAVR polypeptide, e.g., a soluble variant AAVR polypeptide), such a sequence can have 70% or more sequence identity (e.g., 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, 98% or more, 99% or more, 99.5% or more, or 100% sequence identity) with amino acids 409-498 of SEQ ID NO: 1 (or with corresponding amino acids of a corresponding wild type AAVR protein). When referring to the amino acid sequence of a PKD domain 3 of a subject AAVR polypeptide (e.g., a variant AAVR polypeptide, e.g., a soluble variant AAVR polypeptide), such a sequence can have 70% or more sequence identity (e.g., 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, 98% or more, 99% or more, 99.5% or more, or 100% sequence identity) with amino acids 504-594 of SEQ ID NO: 1 (or with corresponding amino acids of a corresponding wild type AAVR protein). When referring to the amino acid sequence of a PKD domain 4 of a subject AAVR polypeptide (e.g., a variant AAVR polypeptide, e.g., a soluble variant AAVR polypeptide), such a sequence can have 70% or more sequence identity (e.g., 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, 98% or more, 99% or more, 99.5% or more, or 100% sequence identity) with amino acids 600-688 of SEQ ID NO: 1 (or with corresponding amino acids of a corresponding wild type AAVR protein). When referring to the amino acid sequence of a PKD domain 5 of a subject AAVR polypeptide (e.g., a variant AAVR polypeptide, e.g., a soluble variant AAVR polypeptide), such a sequence can have 70% or more sequence identity (e.g., 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, 98% or more, 99% or more, 99.5% or more, or 100% sequence identity) with amino acids 694-785 of SEQ ID NO: 1 (or with corresponding amino acids of a corresponding wild type AAVR protein). When referring to the amino acid sequence of a MANEC domain of a subject AAVR polypeptide (e.g., a variant AAVR polypeptide, e.g., a soluble variant AAVR polypeptide), such a sequence can have 70% or more sequence identity (e.g., 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, 98% or more, 99% or more, 99.5% or more, or 100% sequence identity) with amino acids 49-127 of SEQ ID NO: 1 (or with corresponding amino acids of a corresponding wild type AAVR protein). When referring to the amino acid sequence of a cytoplasmic tail of a subject AAVR polypeptide (e.g., a variant AAVR polypeptide, e.g., a soluble variant AAVR polypeptide), such a sequence can have 70% or more sequence identity (e.g., 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, 98% or more, 99% or more, 99.5% or more, or 100% sequence identity) with amino acids 956-1049 of SEQ ID NO: 1 (or with corresponding amino acids of a corresponding wild type AAVR protein). It was previously demonstrated that function (e.g., binding to AAV) is lost when PKD domains 1-2 are lacking or when domains 2-3 are lacking, but not when PKD domains 3-4 or 4- 5 are lacking. In addition, PKD domains 1-3 are sufficient in order for an AAVR polypeptide to bind to AAV. Thus, when considering the combined data, PKD domain combinations of 1-2-3 and 1-2-5 were shown to be functional while PKD domain combinations of 3-4-5 and 1-4-5 were not. Additional previous work has also demonstrated that the AAVR protein retains function if only a single domain is missing (e.g., PKD domain 1, PKD domain 2, PKD domain 3, PKD domain 4, or PKD domain 5). Thus, a subject AAVR polypeptide (e.g., a variant AAVR polypeptide, e.g., a soluble variant AAVR polypeptide) can be suitable if it lacks PKD domain 1, but it should not also lack PKD domain 2. Likewise, a subject AAVR polypeptide (e.g., a variant AAVR polypeptide, e.g., a soluble variant AAVR polypeptide) can be suitable if it lacks PKD domain 2, but not if lacks either PKD domain 1 or PKD domain 3. Thus in some cases, a subject AAVR polypeptide (e.g., a variant AAVR polypeptide, e.g., a soluble variant AAVR polypeptide) lacks PKD domains 3 and 4 of a corresponding wild type AAVR protein. In some cases, a subject AAVR polypeptide (e.g., a variant AAVR polypeptide, e.g., a soluble variant AAVR polypeptide) lacks PKD domain 4 and 5 of a corresponding wild type AAVR protein. In some cases, a subject AAVR polypeptide (e.g., a variant AAVR polypeptide, e.g., a soluble variant AAVR polypeptide) lacks PKD domain 1 of a corresponding wild type AAVR protein. In some cases, a subject AAVR polypeptide (e.g., a variant AAVR polypeptide, e.g., a soluble variant AAVR polypeptide) lacks PKD domain 1 of a corresponding wild type AAVR protein, but does not also lack domain 2 (i.e., it includes a PKD domain 2 or functional equivalent thereof). In some cases a subject AAVR polypeptide (e.g., a variant AAVR polypeptide, e.g., a soluble variant AAVR polypeptide) lacks PKD domain 2 of a corresponding wild type AAVR protein. In some cases, a subject AAVR polypeptide (e.g., a variant AAVR polypeptide, e.g., a soluble variant AAVR polypeptide) lacks PKD domain 2 of a corresponding wild type AAVR protein, but does not also lack PDK domain 1 or PKD domain 3. In other words, if a suitable a subject AAVR polypeptide (e.g., a variant AAVR polypeptide, e.g., a soluble variant AAVR polypeptide) lacks PKD domain 2, it should include a PKD domain 1 and a PKD domain 3 (or functional equivalents thereof). In some cases a subject AAVR polypeptide (e.g., a variant AAVR polypeptide, e.g., a soluble variant AAVR polypeptide) lacks PKD domain 3 of a corresponding wild type AAVR protein, in some cases a subject AAVR polypeptide (e.g., a variant AAVR polypeptide, e.g., a soluble variant AAVR polypeptide) lacks PKD domain 4 of a corresponding wild type AAVR protein, and in some cases a subject AAVR polypeptide (e.g., a variant AAVR polypeptide, e.g., a soluble variant AAVR polypeptide) lacks PKD domain 5 of a corresponding wild type AAVR protein. A subject AAVR polypeptide (e.g., a variant AAVR polypeptide, e.g., a soluble variant AAVR polypeptide) can lack any combination of PKD domains as long as the remaining PKD domains provide for binding to AAV. In some cases, a subject variant AAVR polypeptide includes an amino acid change that alters the function of PKD domains 3 and 4 of a corresponding wild type AAVR protein. In some cases, a subject variant AAVR polypeptide includes an amino acid change that alters the function of PKD domain 4 and 5 of a corresponding wild type AAVR protein. In some cases, a subject variant AAVR polypeptide includes an amino acid change that alters the function of PKD domain 1 of a corresponding wild type AAVR protein, in some cases a subject variant AAVR polypeptide includes an amino acid change that alters the function of PKD domain 2 of a corresponding wild type AAVR protein, in some cases a subject variant AAVR polypeptide includes an amino acid change that alters the function of PKD domain 3 of a corresponding wild type AAVR protein, in some cases a subject variant AAVR polypeptide includes an amino acid change that alters the function of PKD domain 4 of a corresponding wild type AAVR protein, and in some cases a subject variant AAVR polypeptide includes an amino acid change that alters the function of PKD domain 5 of a corresponding wild type AAVR protein. In some cases, a subject variant AAVR polypeptide includes an amino acid change that alters the function of one or more domains of a corresponding wild type AAVR protein selected from: PKD domain 1, PKD domain 2, PKD domain 3, PKD domain 4, and PKD domain 5. In some cases, a subject variant AAVR polypeptide lacks one or more domains of a corresponding wild type AAVR protein selected from: PKD domain 1, PKD domain 2, PKD domain 3, PKD domain 4, and PKD domain 5. In some cases, a subject variant AAVR polypeptide includes an amino acid change that alters the function of one or more domains of a corresponding wild type AAVR protein selected from: signal peptide, MANEC domain, PDK domain 1, PKD domain 2, PKD domain 3, PKD domain 4, and PKD domain 5, transmembrane domain, and cytoplasmic tail. In some cases, a subject variant AAVR polypeptide lacks one or more domains of a corresponding wild type AAVR protein selected from: signal peptide, MANEC domain, PKD domain 1, PKD domain 2, PKD domain 3, PKD domain 4, and PKD domain 5, transmembrane domain, and cytoplasmic tail. In some cases, a subject AAVR polypeptide (e.g., a wild type AAVR polypeptide, a variant AAVR polypeptide, e.g., a soluble variant AAVR polypeptide) can include a PKD domain 2 (e.g., a PKD domain 2 that has 70% or more sequence identity, e.g., 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, 98% or more, 99% or more, 99.5% or more, or 100% sequence identity, with amino acids 409-498 of SEQ ID NO: 1, or with corresponding amino acids of a corresponding wild type AAVR protein) along with two other PKD domains (e.g., 1 and 3, 1 and 5, 1 and 4, 3 and 4, 3 and 5, or 4 and 5). In some cases, a subject AAVR polypeptide (e.g., a wild type AAVR polypeptide, a variant AAVR polypeptide, e.g., a soluble variant AAVR polypeptide) can include a PKD domain 2 (e.g., a PKD domain 2 that has 70% or more sequence identity, e.g., 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, 98% or more, 99% or more, 99.5% or more, or 100% sequence identity, with amino acids 409-498 of SEQ ID NO: 1, or with corresponding amino acids of a corresponding wild type AAVR protein); a PKD domain 1 (e.g., a PKD domain 1 that has 70% or more sequence identity, e.g., 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, 98% or more, 99% or more, 99.5% or more, or 100% sequence identity, with amino acids 312-401 of SEQ ID NO: 1, or with corresponding amino acids of a corresponding wild type AAVR protein); and a PKD domain 3 (e.g., a PKD domain 3 that has 70% or more sequence identity, e.g., 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, 98% or more, 99% or more, 99.5% or more, or 100% sequence identity, with amino acids 504-594 of SEQ ID NO: 1, or with corresponding amino acids of a corresponding wild type AAVR protein). In some cases the amino acid sequence of a subject AAVR polypeptide (e.g., a variant AAVR polypeptide, e.g., a soluble variant AAVR polypeptide) includes a PKD domain 1 that has 100% sequence identity with amino acids 312-401 of SEQ ID NO: 1 (or with corresponding amino acids of a corresponding wild type AAVR protein); a PKD domain 2 that has 100% sequence identity with amino acids 409-498 of SEQ ID NO: 1 (or with corresponding amino acids of a corresponding wild type AAVR protein); and a PKD domain 3 that has 100% sequence identity with amino acids 504-594 of SEQ ID NO: 1 (or with corresponding amino acids of a corresponding wild type AAVR protein). In some cases, a suitable AAVR protein includes PKD domains 1-3 (e.g., each having 70% or more sequence identity, e.g., 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, 98% or more, 99% or more, 99.5% or more, or 100% sequence identity, with amino acids 312-401, 409-498, and 504-594, respectively, of SEQ ID NO: 1, or with corresponding amino acids of a corresponding wild type AAVR protein). In some cases, the AAVR protein is a variant AAVR protein that includes PKD domains 1-3 (e.g., each having 70% or more sequence identity, e.g., 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, 98% or more, 99% or more, 99.5% or more, or 100% sequence identity, with amino acids 312-401, 409-498, and 504-594, respectively, of SEQ ID NO: 1, or with corresponding amino acids of a corresponding wild type AAVR protein) and lacks one or more PKD domains that are present in the wild type AAVR protein (e.g., lacks PKD domains 4-5, 5, or 4). In some cases, the AAVR protein includes PKD domains 1-3 (e.g., each having 70% or more sequence identity, e.g., 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, 98% or more, 99% or more, 99.5% or more, or 100% sequence identity, with amino acids 312-401, 409-498, and 504-594, respectively, of SEQ ID NO: 1, or with corresponding amino acids of a corresponding wild type AAVR protein) and the MANEC domain. In some cases, the AAVR protein is a variant AAVR protein that includes PKD domains 1-3 (e.g., each having 70% or more sequence identity, e.g., 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, 98% or more, 99% or more, 99.5% or more, or 100% sequence identity, with amino acids 312-401, 409-498, and 504-594, respectively, of SEQ ID NO: 1, or with corresponding amino acids of a corresponding wild type AAVR protein) and the MANEC domain and lacks one or more PKD domains that are present in the wild type AAVR protein (e.g., lacks PKD domains 4- 5, 5, or 4). In some cases, the AAVR protein is a variant AAVR protein that includes PKD domains 1-3 (e.g., each having 70% or more sequence identity, e.g., 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, 98% or more, 99% or more, 99.5% or more, or 100% sequence identity, with amino acids 312-401, 409-498, and 504-594, respectively, of SEQ ID NO: 1, or with corresponding amino acids of a corresponding wild type AAVR protein) and lacks the MANEC domain that is present in the wild type AAVR protein. In some cases, the AAVR protein is a variant AAVR protein that includes PKD domains 1-3 (e.g., each having 70% or more sequence identity, e.g., 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, 98% or more, 99% or more, 99.5% or more, or 100% sequence identity, with amino acids 312-401, 409-498, and 504-594, respectively, of SEQ ID NO: 1, or with corresponding amino acids of a corresponding wild type AAVR protein), lacks the MANEC domain that is present in the wild type AAVR protein, and lacks one or more PKD domains that are present in the wild type AAVR protein (e.g., lacks PKD domains 4-5, 5, or 4). In some cases, a subject AAVR polypeptide (e.g., a wild type AAVR polypeptide, a variant AAVR polypeptide, e.g., a soluble variant AAVR polypeptide) can include a PKD domain 2 (e.g., a PKD domain 2 that has 70% or more sequence identity, e.g., 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, 98% or more, 99% or more, 99.5% or more, or 100% sequence identity, with amino acids 409-498 of SEQ ID NO: 1, or with corresponding amino acids of a corresponding wild type AAVR protein); a PKD domain 1 (e.g., a PKD domain 1 that has 70% or more sequence identity, e.g., 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, 98% or more, 99% or more, 99.5% or more, or 100% sequence identity, with amino acids 312-401 of SEQ ID NO: 1, or with corresponding amino acids of a corresponding wild type AAVR protein); and a PKD domain 5 (e.g., a PKD domain 5 that has 70% or more sequence identity, e.g., 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, 98% or more, 99% or more, 99.5% or more, or 100% sequence identity, with amino acids 694-785 of SEQ ID NO: 1, or with corresponding amino acids of a corresponding wild type AAVR protein). In some cases the amino acid sequence of a subject AAVR polypeptide (e.g., a variant AAVR polypeptide, e.g., a soluble variant AAVR polypeptide) includes a PKD domain 1 that has 100% sequence identity with amino acids 312-401 of SEQ ID NO: 1 (or with corresponding amino acids of a corresponding wild type AAVR protein); a PKD domain 2 that has 100% sequence identity with amino acids 409-498 of SEQ ID NO: 1 (or with corresponding amino acids of a corresponding wild type AAVR protein); and a PKD domain 5 that has 100% sequence identity with amino acids 694-785 of SEQ ID NO: 1 (or with corresponding amino acids of a corresponding wild type AAVR protein). In some cases, a suitable AAVR protein includes PKD domains 1-2 and 5 (e.g., each having 70% or more sequence identity, e.g., 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, 98% or more, 99% or more, 99.5% or more, or 100% sequence identity, with amino acids 312-401, 409-498, and 694-785, respectively, of SEQ ID NO: 1, or with corresponding amino acids of a corresponding wild type AAVR protein). In some cases, the AAVR protein is a variant AAVR protein that includes PKD domains 1-2 and 5 (e.g., each having 70% or more sequence identity, e.g., 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, 98% or more, 99% or more, 99.5% or more, or 100% sequence identity, with amino acids 312-401, 409-498, and 694-785, respectively, of SEQ ID NO: 1, or with corresponding amino acids of a corresponding wild type AAVR protein) and lacks one or more PKD domains that are present in the wild type AAVR protein (e.g., lacks PKD domains 3-4, 3, or 4). In some cases, the AAVR protein includes PKD domains 1-2 and 5 (e.g., each having 70% or more sequence identity, e.g., 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, 98% or more, 99% or more, 99.5% or more, or 100% sequence identity, with amino acids 312-401, 409-498, and 694-785, respectively, of SEQ ID NO: 1, or with corresponding amino acids of a corresponding wild type AAVR protein) and the MANEC domain. In some cases, the AAVR protein is a variant AAVR protein that includes PKD domains 1-2 and 5 (e.g., each having 70% or more sequence identity, e.g., 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, 98% or more, 99% or more, 99.5% or more, or 100% sequence identity, with amino acids 312-401, 409-498, and 694-785, respectively, of SEQ ID NO: 1, or with corresponding amino acids of a corresponding wild type AAVR protein) and the MANEC domain and lacks one or more PKD domains that are present in the wild type AAVR protein (e.g., lacks PKD domains 3-4, 3, or 4). In some cases, the AAVR protein is a variant AAVR protein that includes PKD domains 1-2 and 5 (e.g., each having 70% or more sequence identity, e.g., 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, 98% or more, 99% or more, 99.5% or more, or 100% sequence identity, with amino acids 312- 401, 409-498, and 694-785, respectively, of SEQ ID NO: 1, or with corresponding amino acids of a corresponding wild type AAVR protein) and lacks the MANEC domain that is present in the wild type AAVR protein. In some cases, the AAVR protein is a variant AAVR protein that includes PKD domains 1-2 and 5 (e.g., each having 70% or more sequence identity, e.g., 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, 98% or more, 99% or more, 99.5% or more, or 100% sequence identity, with amino acids 312-401, 409-498, and 694-785, respectively, of SEQ ID NO: 1, or with corresponding amino acids of a corresponding wild type AAVR protein), lacks the MANEC domain that is present in the wild type AAVR protein, and lacks one or more PKD domains that are present in the wild type AAVR protein (e.g., lacks PKD domains 3-4, 3, or 4). In some cases, a subject AAVR polypeptide (e.g., a wild type AAVR polypeptide, a variant AAVR polypeptide, e.g., a soluble variant AAVR polypeptide) can include a PKD domain 2 (e.g., a PKD domain 2 that has 70% or more sequence identity, e.g., 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, 98% or more, 99% or more, 99.5% or more, or 100% sequence identity, with amino acids 409-498 of SEQ ID NO: 1, or with corresponding amino acids of a corresponding wild type AAVR protein); a PKD domain 1 (e.g., a PKD domain 1 that has 70% or more sequence identity, e.g., 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, 98% or more, 99% or more, 99.5% or more, or 100% sequence identity, with amino acids 312-401 of SEQ ID NO: 1, or with corresponding amino acids of a corresponding wild type AAVR protein); and a PKD domain 4 (e.g., a PKD domain 4 that has 70% or more sequence identity, e.g., 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, 98% or more, 99% or more, 99.5% or more, or 100% sequence identity, with amino acids 600-688 of SEQ ID NO: 1, or with corresponding amino acids of a corresponding wild type AAVR protein). In some cases the amino acid sequence of a subject AAVR polypeptide (e.g., a variant AAVR polypeptide, e.g., a soluble variant AAVR polypeptide) includes a PKD domain 1 that has 100% sequence identity with amino acids 312-401 of SEQ ID NO: 1 (or with corresponding amino acids of a corresponding wild type AAVR protein); a PKD domain 2 that has 100% sequence identity with amino acids 409-498 of SEQ ID NO: 1 (or with corresponding amino acids of a corresponding wild type AAVR protein); and a PKD domain 4 that has 100% sequence identity with amino acids 600-688 of SEQ ID NO: 1 (or with corresponding amino acids of a corresponding wild type AAVR protein). In some cases, a suitable AAVR protein includes PKD domains 1-2 and 4 (e.g., each having 70% or more sequence identity, e.g., 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, 98% or more, 99% or more, 99.5% or more, or 100% sequence identity, with amino acids 312-401, 409-498, and 600-688, respectively, of SEQ ID NO: 1, or with corresponding amino acids of a corresponding wild type AAVR protein). In some cases, the AAVR protein is a variant AAVR protein that includes PKD domains 1-2 and 4 (e.g., each having 70% or more sequence identity, e.g., 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, 98% or more, 99% or more, 99.5% or more, or 100% sequence identity, with amino acids 312-401, 409-498, and 600-688, respectively, of SEQ ID NO: 1, or with corresponding amino acids of a corresponding wild type AAVR protein) and lacks one or more PKD domains that are present in the wild type AAVR protein (e.g., lacks PKD domains 3 and / or 5). In some cases, the AAVR protein includes PKD domains 1-2 and 4 (e.g., each having 70% or more sequence identity, e.g., 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, 98% or more, 99% or more, 99.5% or more, or 100% sequence identity, with amino acids 312-401, 409-498, and 600-688, respectively, of SEQ ID NO: 1, or with corresponding amino acids of a corresponding wild type AAVR protein) and the MANEC domain. In some cases, the AAVR protein is a variant AAVR protein that includes PKD domains 1-2 and 4 (e.g., each having 70% or more sequence identity, e.g., 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, 98% or more, 99% or more, 99.5% or more, or 100% sequence identity, with amino acids 312-401, 409-498, and 600-688, respectively, of SEQ ID NO: 1, or with corresponding amino acids of a corresponding wild type AAVR protein) and the MANEC domain and lacks one or more PKD domains that are present in the wild type AAVR protein (e.g., lacks PKD domains 3 and / or 5). In some cases, the AAVR protein is a variant AAVR protein that includes PKD domains 1-2 and 4 (e.g., each having 70% or more sequence identity, e.g., 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, 98% or more, 99% or more, 99.5% or more, or 100% sequence identity, with amino acids 312-401, 409-498, and 600-688, respectively, of SEQ ID NO: 1, or with corresponding amino acids of a corresponding wild type AAVR protein) and lacks the MANEC domain that is present in the wild type AAVR protein. In some cases, the AAVR protein is a variant AAVR protein that includes PKD domains 1-2 and 4 (e.g., each having 70% or more sequence identity, e.g., 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, 98% or more, 99% or more, 99.5% or more, or 100% sequence identity, with amino acids 312-401, 409-498, and 600-688, respectively, of SEQ ID NO: 1, or with corresponding amino acids of a corresponding wild type AAVR protein), lacks the MANEC domain that is present in the wild type AAVR protein, and lacks one or more PKD domains that are present in the wild type AAVR protein (e.g., lacks PKD domains 3 and / or 5). Transmembrane domain In some cases, a subject AAVR polypeptide (e.g., a wild type AAVR protein, a variant AAVR polypeptide) includes a transmembrane domain. For example, in some cases a subject AAVR polypeptide (e.g., a wild type AAVR protein, a variant AAVR polypeptide) is expressed in a cell to enhance the cell’s permissiveness to AAV infection. Strategies by which this can be accomplished include but are not limited to: increasing the overall amount of AAVR in the cell (e.g., via overexpression using a heterologous promoter, introducing protein directly into the cell, and the like), increasing the ability of the AAVR polypeptide to interact with AAV (e.g., increasing the binding affinity of the AAVR polypeptide for AAV, e.g., for a capsid protein of AAV), and modulating subcellular trafficking of the AAVR polypeptide (e.g., increasing trafficking of the AAVR protein from the cell surface to a subcellular location such as the TGN, modifying subcellular trafficking of the AAVR protein such that it traffics from the cell surface such to a subcellular location other than the TGN, such as the nucleus, etc.). When a subject method or composition is to be used in such a way that binding between a subject AAVR polypeptide (e.g., a wild type AAVR protein, a variant AAVR polypeptide) and an AAV particle is desirable (e.g., when enhancing the cell’s permissiveness to AAV infection), then the AAVR polypeptide will likely include a transmembrane domain in order to provide for presentation of all or a portion of the AAVR polypeptide on the surface of the target cell. Because it is also important for the AAVR polypeptide (e.g., a wild type AAVR protein, a variant AAVR polypeptide) to be able to traffic from the surface of the cell to a location within the cell (e.g., endocytic pathway, TGN, nucleus, cytoplasm, and the like), when a subject method or composition is to be used in such a way that binding between a subject AAVR polypeptide (e.g., a wild type AAVR protein, a variant AAVR polypeptide) and an AAV particle is desirable (e.g., when enhancing the cell’s permissiveness to AAV infection), then the AAVR polypeptide will likely include (i) an amino acid sequence that provides for presentation of all or a portion of the variant AAVR polypeptide on the surface of the target cell (e.g., a transmembrane domain), and (ii) an amino acid sequence that provides for trafficking of the AAVR polypeptide from the surface of the target cell to a location within the target cell (e.g., from the cell surface to the TGN, to endosomes, to the endocytic pathway, to the cytoplasm, to the nucleus, etc.).(e.g., the amino acids corresponding to the cytoplasmic tail, or a functional portion thereof, of the AAVR protein set forth in SEQ ID NO: 1). In some cases, an AAVR polypeptide can have additional sequences in the cytoplasmic tail (e.g., by incorporation of a fusion partner that provides for trafficking of the AAVR polypeptide from the surface of the target cell to a location within the target cell) or the cytoplasmic tail of the wild type AAVR protein can be replaced (e.g., by a fusion partner that provides for trafficking of the AAVR polypeptide from the surface of the target cell to a location within the target cell). As noted, in some embodiments, an AAVR polypeptide of the present disclosure is a fusion protein, e.g., fused in frame with a second polypeptide (a fusion partner). In some cases, the fusion partner provides for one or more of: protein tagging, protein isolation, protein trafficking, protein tracking, protein stability, and protein solubility. For example, in some cases the fusion partner is an epitope tag (e.g., His tag, FLAG tag, Myc tag, etc.), a fluorescent protein (e.g., GFP, YFP, RFP, BFP, etc.). With regard to an AAVR transmembrane domain, different transmembrane domain prediction programs were run on the wild type AAVR protein set forth in SEQ ID NO: 1, and the following overlapping amino acid regions were determined to define a transmembrane domain: 933-953; 930-952; 930-955; and 931-949. Thus, a transmembrane domain can be present at amino acids 930-955 (e.g., 933-953, 930-952, 930-955, and / or 931-949) of the wild type AAVR protein set forth in SEQ ID NO: 1. Thus, in some cases, a variant AAVR (e.g., a soluble AAVR) lacks amino acids 930-955, 933-953, 930-952, 930-955, and / or 931-949 of the wild type AAVR protein set forth in SEQ ID NO: 1, or the corresponding region of another wild type AAVR protein. It is to be understood that when a subject variant AAVR polypeptide (e.g., a soluble AAVR polypeptide) lacks a transmembrane domain, some amino acids from a transmembrane domain (e.g., an AAVR transmembrane domain) may still be present (e.g., some amino acids from the transmembrane domain may be retained, as long as the protein retains the desired function). When referring to the amino acid sequence of a transmembrane domain of a subject AAVR polypeptide (e.g., a variant AAVR polypeptide, e.g., a soluble variant AAVR polypeptide), such a sequence can have 70% or more sequence identity (e.g., 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, 98% or more, 99% or more, 99.5% or more, or 100% sequence identity) with amino acids 930-955 of SEQ ID NO: 1 (or with corresponding amino acids of a corresponding wild type AAVR protein). When referring to the amino acid sequence of a transmembrane domain of a subject AAVR polypeptide (e.g., a variant AAVR polypeptide, e.g., a soluble variant AAVR polypeptide), such a sequence can have 70% or more sequence identity (e.g., 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, 98% or more, 99% or more, 99.5% or more, or 100% sequence identity) with amino acids 933-953 of SEQ ID NO: 1 (or with corresponding amino acids of a corresponding wild type AAVR protein). When referring to the amino acid sequence of a transmembrane domain of a subject AAVR polypeptide (e.g., a variant AAVR polypeptide, e.g., a soluble variant AAVR polypeptide), such a sequence can have 70% or more sequence identity (e.g., 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, 98% or more, 99% or more, 99.5% or more, or 100% sequence identity) with amino acids 930-952 of SEQ ID NO: 1 (or with corresponding amino acids of a corresponding wild type AAVR protein). When referring to the amino acid sequence of a transmembrane domain of a subject AAVR polypeptide (e.g., a variant AAVR polypeptide, e.g., a soluble variant AAVR polypeptide), such a sequence can have 70% or more sequence identity (e.g., 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, 98% or more, 99% or more, 99.5% or more, or 100% sequence identity) with amino acids 930-955 of SEQ ID NO: 1 (or with corresponding amino acids of a corresponding wild type AAVR protein). When referring to the amino acid sequence of a transmembrane domain of a subject AAVR polypeptide (e.g., a variant AAVR polypeptide, e.g., a soluble variant AAVR polypeptide), such a sequence can have 70% or more sequence identity (e.g., 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, 98% or more, 99% or more, 99.5% or more, or 100% sequence identity) with amino acids 931-949 of SEQ ID NO: 1 (or with corresponding amino acids of a corresponding wild type AAVR protein). ii. SETDB1 protein SETDB1 is required for HUSH-mediated heterochromatin formation and gene silencing. SETDB1 Forms a complex with MBD1 and ATF7IP that represses transcription and couples DNA methylation and histone 'Lys-9' trimethylation. Wild type human SETDB1 (Uniprot Q15047) *also known as ESET; KG1T; KMT1E; TDRD21; H3-K9-HMTase4 MSSLPGCIGLDAATATVESEEIAELQQAVVEELGISMEELRHFIDEELEKMDCV QQRKKQLAELETWVIQKESEVAHVDQLFDDASRAVTNCESLVKDFYSKLGLQ YRDSSSEDESSRPTEIIEIPDEDDDVLSIDSGDAGSRTPKDQKLREAMAALRK SAQDVQKFMDAVNKKSSSQDLHKGTLSQMSGELSKDGDLIVSMRILGKKRTK TWHKGTLIAIQTVGPGKKYKVKFDNKGKSLLSGNHIAYDYHPPADKLYVGSRV VAKYKDGNQVWLYAGIVAETPNVKNKLRFLIFFDDGYASYVTQSELYPICRPL KKTWEDIEDISCRDFIEEYVTAYPNRPMVLLKSGQLIKTEWEGTWWKSRVEE VDGSLVRILFLDDKRCEWIYRGSTRLEPMFSMKTSSASALEKKQGQLRTRPN MGAVRSKGPVVQYTQDLTGTGTQFKPVEPPQPTAPPAPPFPPAPPLSPQAG DSDLESQLAQSRKQVAKKSTSFRPGSVGSGHSSPTSPALSENVSGGKPGIN QTYRSPLGSTASAPAPSALPAPPAPPVFHGMLERAPAEPSYRAPMEKLFYLP HVCSYTCLSRVRPMRNEQYRGKNPLLVPLLYDFRRMTARRRVNRKMGFHVI YKTPCGLCLRTMQEIERYLFETGCDFLFLEMFCLDPYVLVDRKFQPYKPFYYIL DITYGKEDVPLSCVNEIDTTPPPQVAYSKERIPGKGVFINTGPEFLVGCDCKD GCRDKSKCACHQLTIQATACTPGGQINPNSGYQYKRLEECLPTGVYECNKRC KCDPNMCTNRLVQHGLQVRLQLFKTQNKGWGIRCLDDIAKGSFVCIYAGKILT DDFADKEGLEMGDEYFANLDHIESVENFKEGYESDAPCSSDSSGVDLKDQE DGNSGTEDPEESNDDSSDDNFCKDEDFSTSSVWRSYATRRQTRGQKENGL SETTSKDSHPPDLGPPHIPVPPSIPVGGCNPPSSEETPKNKVASWLSCNSVS EGGFADSDSHSSFKTNEGGEGRAGGSRMEAEKASTSGLGIKDEGDIKQAKK EDTDDRNKMSVVTESSRNYGYNPSPVKPEGLRRPPSKTSMHQSRRLMASA QSNPDDVLTLSSSTESEGESGTSRKPTAGQTSATAVDSDDIQTISSGSEGDD FEDKKNMTGPMKRQVAVKSTRGFALKSTHGIAIKSTNMASVDKGESAPVRKN TRQFYDGEESCYIIDAKLEGNLGRYLNHSCSPNLFVQNVFVDTHDLRFPWVA FFASKRIRAGTELTWDYNYEVGSVEGKELLCCCGAIECRGRLL (SEQ ID NO: 12) Wild type mouse SETDB1 (Uniprot O88974) MSSLPGCMSLAAAPAAADSAEIAELQQAVVEELGISMEELRQYIDEELEKMDC IQQRKKQLAELETWVLQKESEVAYVDRLFDDASREVTNCESLVKDFYSKLGL QYHDSSSEDEASRPTEIIEIPDEDDDVLSIDSGDAGSRTPKDQKLREAMAALR KSAQDVQKFMDAVNKKSSSQDLHKGTLGQVSGELSKDGDLIVSMRILGKKRT KTWHKGTLIAIQTVGLGKKYKVKFDNKGKSLLSGNHIAYDYHPPADKLFVGSR VVAKYKDGNQVWLYAGIVAETPNVKNKLRFLIFFDDGYASYVTQSELYPICRP LKKTWEDIEDSSCRDFIEEYITAYPNRPMVLLKSGQLIKTEWEGTWWKSRVEE VDGSLVRILFLDDKRCEWIYRGSTRLEPMFSMKTSSASAMEKKQGGQLRTRP NMGAVRSKGPVVQYTQDLTGTGIQFKPMEPLQPIAPPAPLPIPPLSPQAADTD LESQLAQSRKQVAKKSTSFRPGSVGSGHSSPTSSTLSENVSAGKLGINQTYR SPLASVTSTPASAAPPVPPVPPGPPTPPGPPAPPGPLAPPAFHGMLERAPAE PSYRAPMEKLFYLPHVCSYTCLSRIRPMRNEQYRGKNPLLVPLLYDFRRMTA RRRVNRKMGFHVIYKTPCGLCLRTMQEIERYLFETGCDFLFLEMFCLDPYVLV DRKFQPFKPFYYILDITYGKEDVPLSCVNEIDTTPPPQVAYSKERIPGKGVFINT GPEFLVGCDCKDGCRDKSKCACHQLTIQATACTPGGQVNPNSGYQYKRLEE CLPTGVYECNKRCNCDPNMCTNRLVQHGLQVRLQLFKTQNKGWGIRCLDDI AKGSFVCIYAGKILTDDFADKEGLEMGDEYFANLDHIESVENFKEGYESDVPT SSDSSGVDMKDQEDGNSGSEDPEESNDDSSDDNFCKDEDFSTSSVWRSYA TRRQTRGQKENELSEMTSKDSRPPDLGPPHVPIPSSVSVGGCNPPSSEETP KNKVASWLSCNSVSEGGFADSDSRSSFKTSEGGDGRAGGGRGEAERASTS GLSFKDEGDNKQPKKEDPENRNKMPVVTEGSQNHGHNPPMKSEGLRRPAS KMSVLQSQRVVTSTQSNPDDILTLSSSTESEGESGTSRKPTAGHTSATAVDS DDIQTISSGSDGDDFEDKKNLSGPTKRQVAVKSTRGFALKSTHGIAIKSTNMA SVDKGESAPVRKNTRQFYDGEESCYIIDAKLEGNLGRYLNHSCSPNLFVQNV FVDTHDLRFPWVAFFASKRIRAGTELTWDYNYEVGSVEGKELLCCCGAIECR GRLL (SEQ ID NO: 13) iii. CRISPRa In some embodiments, an AAV vector is used to express a transgene (e.g., a transgene encoded by the AAV genome) in a subject genetically modified cell (e.g., in order to titrate the AAV preparation, e.g., to determine its titer). As such, in some cases, a subject genetically modified cell includes CRISPRa components (a CRISPRa fusion protein or a nucleic acid encoding it’; and / or a CRISPR-Cas guide RNA or a nucleic acid encoding it) that target an ITR sequence (e.g., an AAV ITR sequence) for the purpose of expressing target genes, e.g., a virally introduced transgene, (e.g., an AAV transgene). In some cases, the presence of CRISPRa components in a subject genetically modified cell is in addition to other perturbations of the cell – e.g., in addition to reduced levels of SETDB1 and increased levels of AAVR – as described elsewhere herein). In some cases, expression (also referred to herein as ‘overexpression’ because the expression is greater than what it would be in the absence of perturbation) is achieved using a CRISPRa fusion protein. Examples of such fusion proteins will be known to one of ordinary skill in the art and any convenient CRISPRa fusion protein can be used. A “CRISPRa fusion protein” includes a CRISPR-Cas effector protein (e.g., Cas9, Cas12a, dCas9, dCas12a, etc.) linked (covalently or non-covalently) to a transcription activating protein. In some cases, the CRISPRa fusion protein is fused to a transcription activating protein. In some cases, the CRISPRa fusion protein is linked (covalently or non-covalently) directly to the transcription activating protein. In some cases, the CRISPRa fusion protein is linked (covalently or non-covalently) indirectly to the transcription activating protein, e.g., by being linked a protein that recruits a transcription activating protein (see, e.g., Griffith et al., Cell Genom.2023 Sep 1;3(9):100387). Examples of CRISPR-Cas effector proteins will be readily available to one of ordinary skill in the art, and any convenient CRISPR-Cas effector protein can be used. In some embodiments, a subject CRISPR-Cas effector protein will be a Cas9 protein (e.g., Staphylococcus aureus Cas9 (saCas9), Streptococcus pyogenes Cas9 (SpyCas9), Neisseria meningitidis Cas9 (nmCas9), Streptococcus thermophilus Cas9 (stCas9), etc.). In some cases, a subject CRISPR-Cas effector protein will be a Cas12a protein. As would be understood by one of ordinary skill in the art, many variant forms of CRISPR-Cas effector proteins are known in the art, e.g., those harboring mutations that increase specificity (e.g., decrease off-targeting), and any convenient variant can be used. See, e.g., Vakulskas et al., Nat Med.2018 Aug;24(8):1216-1224; Kleinstiver et al., Nature.2016 Jan 28;529(7587):490-5; Yuen et al., Nucleic Acids Res.2022 Feb 22;50(3):1650-1660; Wei et al., FASEB J.2023 Aug;37(8):e23060; Tan et al., Proc Natl Acad Sci U S A.2019 Oct 15;116(42):20969-20976; Kleinstiver et al., Nat Biotechnol.2019 Mar;37(3):276-282; and DeWeirdt et al., Nat. Biotechnol. 202139, 94–104. The amino acid sequences of two example wild-type Cas9 polypeptides (S. pyogenes and S. aureus are provided as SEQ ID NOs: 53 and 54. The amino acid sequence of an example wild-type Cas12a polypeptide (Acidaminococcus sp., strain BV3L6 (AsCas12a)) is provided as SEQ ID NO: 55. Other examples of Cas12a include, but are not limited to: LbCas12a and FnoCas12a, as well as AsCas12a ultra nuclease (see, e.g., Zhang et al., Nat Commun.2021 Jun 23;12(1):3908). In class 2 CRISPR systems, the functions of the effector complex (e.g., the cleavage of target DNA) are carried out by a single protein (which can be referred to as a CRISPR-Cas effector protein) – where the natural protein is an endonuclease (e.g., see Zetsche et al, Cell. 2015 Oct 22;163(3):759-71; Makarova et al, Nat Rev Microbiol.2015 Nov;13(11):722-36; Shmakov et al., Mol Cell.2015 Nov 5;60(3):385-97; Shmakov et al., Nat Rev Microbiol.2017 Mar;15(3):169-182: “Diversity and evolution of class 2 CRISPR-Cas systems”; and Koonin et al., Curr Opin Microbiol.2017 Jun:37:67-78). As such, the term “class 2 CRISPR-Cas protein” or “CRISPR-Cas effector protein” is used herein to encompass the effector protein from class 2 CRISPR systems – for example, type II CRISPR-Cas proteins (e.g., Cas9), type V CRISPR- Cas proteins (e.g., Cpf1 / Cas12a, C2c1 / Cas12b, C2C3 / Cas12c, Cas12d / CasY, Cas12e / CasX), and type VI CRISPR-Cas proteins (e.g., C2c2 / Cas13a, C2C7 / Cas13c, C2c6 / Cas13b). Class 2 CRISPR-Cas effector proteins include type II, type V, and type VI CRISPR-Cas proteins, but the term is also meant to encompass any class 2 CRISPR-Cas protein suitable for binding to a corresponding guide RNA and forming a ribonucleoprotein (RNP) complex. In some cases, the CRISPR-Cas effector protein (e.g., Cas9) is catalytically inactive (i.e., ‘dead’), which is referred to in the art as a dCas protein (e.g., dCas9). Such a protein will not exhibit the nuclease cleavage activity of the Cas effector protein, but the fusion protein (the CRISPRa fusion protein) will exhibit the activity of the protein to which the dCas protein is fused (i.e., the fusion partner - the transcription activating protein). Examples of mutations to produce a dCas effector protein will be known to one of ordinary skill in the art. For example, D10A / H840A of SpyCas9 as well as D908A and E993A of Cas12a have been employed. Examples of proteins (or fragments thereof) that can be used to increase transcription (i.e., transcription activating proteins) include but are not limited to: transcriptional activators such as VP16, VP64, VP48, VP64, VP160, p65 subdomain (e.g., from NFkB), Rta, VPR (which is a fusion of VP64, p65, and Rta), and activation domain of EDLL and / or TAL activation domain (e.g., for activity in plants); histone lysine methyltransferases such as SET1A, SET1B, MLL1 to 5, ASH1, SYMD2, NSD1, and the like; histone lysine demethylases such as JHDM2a / b, UTX, JMJD3, and the like; histone acetyltransferases such as GCN5, PCAF, CBP, p300, TAF1, TIP60 / PLIP, MOZ / MYST3, MORF / MYST4, SRC1, ACTR, P160, CLOCK, and the like; and DNA demethylases such as Ten-Eleven Translocation (TET) dioxygenase 1 (TET1CD), TET1, DME, DML1, DML2, ROS1, and the like. See, e.g., Chavez et al., Nat Methods.2015 Apr; 12(4): 326–328. In some cases, the CRISPRa system is a SAM system, which includes 3 components that form the DNA-binding complex: (1) a CRISPRa fusion protein (e.g., dCas9 fused to VP64), (2) MS2 aptamer(s) added to the guide RNA (forming a characteristic stem loop structure recognized by MS2), and (3) transcriptional activators P65 (Nuclear Factor NF-κB p65) and HSF1 (Heat Shock Factor 1) fused with an MS2-tag corresponding to the minimal aptamer-binding peptide of the MS2 coat protein. See, e.g., review articles such as Adli, Nat Commun.2018 May 15;9(1):1911; Becirovic, Cell Mol Life Sci. 2022 Feb 12;79(2):130; and Nidhi S, et al., Int J Mol Sci.2021 Mar 24;22(7):3327. In some embodiments, the CRISPR-Cas effector protein of the CRISPRa fusion protein is a dCas9. In some embodiments, the CRISPR-Cas effector protein of the CRISPRa fusion protein is a dCas12a. A subject CRISPRa fusion protein can include one or more NLSs, and a nucleic acid encoding a subject CRISPRa fusion protein will in some cases be codon optimized (for a desired type of cell). In some embodiments, a nucleic acid encoding the CRISPRa fusion protein is integrated into the genome of a subject genetically modified cell (e.g., one that has increased AAVR levels and decreased SETDB1 levels). In some embodiments, the nucleic acid encoding the CRISPRa fusion protein is extrachromosomal. In some cases, the nucleotide sequence encoding the CRISPRa fusion protein is operably linked to a constitutive promoter. In such cases, overexpression of an AAV transgene occurs in the presence of the appropriate guide RNA(s) [targeting the AAV ITR] – as such, overexpression of an AAV transgene can be initiated by introducing the guide RNA(s). In some cases, a subject genetically modified cell will include one or more (e.g., 1, 2, 3, 4, 5, 6, 1-10, 1- 8, 1-6, 1-5, 1-4, 1-3, 2-10, 2-8, 2-6, 2-5, 2-4, 3-10, 3-8, 3-6, 3-5, two or more, three or more, four or more, or five or more) guide RNAs (or nucleotide sequences that encode said guide RNAs) that target one or more AAV ITRs. In some such cases, the nucleotides sequence(s) encoding the guide RNA(s) are integrated into the genome of the subject genetically modified cell – as such, expression of a transgene can occur upon the introduction of an AAV encoding the transgene. In some cases, the nucleotide sequence encoding the CRISPRa fusion protein is operably linked to an inducible promoter, and overexpression of an AAV transgene occurs, in the presence the appropriate guide RNA(s) [targeting the AAV ITR], when the appropriate factor is present to induce expression of the CRISPRa fusion protein – as such, overexpression can be initiated by introducing the appropriate factor (e.g., doxycycline) to induce expression of the CRISPRa fusion protein. As would be understood to one of ordinary skill in the art, a CRISPRa fusion protein can be introduced into a cell directly as protein. A CRISPRa fusion protein can also be introduced as a nucleic encoding the protein (e.g., an RNA or a DNA such as an expression vector). In some cases, a CRISPRa fusion protein is introduced as an RNA encoding the protein (and the cell translates the RNA into protein). In some cases, a CRISPRa fusion protein is introduced as a DNA encoding the protein (and the cell expresses the protein via RNA transcription and translation into protein). In some cases, a sequence encoding the CRISPRa fusion protein (and / or one or more guide RNAs targeting an AAV ITR) is integrated into the genome of a subject genetically modified cell. A nucleic acid that binds to and thereby forms a complex with a CRISPR-Cas effector protein (e.g., a type II CRISPR-Cas effector protein – a Cas9 protein; a type V or type VI CRISPR-Cas protein; a Cas12a protein; etc.) (and thereby also can bind to a CRISPRa fusion protein) and targets the complex to a specific location within a target nucleic acid (e.g., target DNA) is referred to herein as a “guide RNA” or “CRISPR-Cas guide nucleic acid” or “CRISPR- Cas guide RNA.” It is understood that in some cases a guide nucleic acid includes both RNA and DNA nucleotides (i.e., is a hybrid molecule), but such a hybrid molecule is also referred to herein as a “guide nucleic acid” or “guide RNA.” A guide RNA includes a protein-binding region to bind to the CRISPR-Cas effector protein, and also includes a targeting region that provides target specificity to the complex (the RNP complex). The targeting region includes a guide sequence (also referred to herein as a targeting sequence), which is a nucleotide sequence that is complementary to a target sequence of a target nucleic acid (e.g., target DNA). The guide sequence (and the guide RNA) can therefore be said to “target” the target sequence. As an example from Table 1 below, guide RNA #1 can be said to target SEQ ID NO: 33, guide RNA #3 can be said to target SEQ ID NO: 40, while guide RNA #2 can be said to target SEQ ID NO: 48 (also see FIG.9B). As such, a CRISPR-Cas guide RNA of the present disclosure (e.g., a Cas9 guide RNA) can be said to target an AAV ITR (i.e., it hybridizes to a sequence of an AAV ITR - see, e.g., FIG.9B as well Tables 1 and 2 for examples). In some cases, the targeted AAV ITR includes the sequence of any of SEQ ID NOs: 26-50. In some cases, the targeted AAV ITR includes the sequence of any of SEQ ID NOs: 26-50 and 56-57. In some cases, the targeted AAV ITR includes the sequence of SEQ ID NO: 56 or 57. In some cases, the targeted AAV ITR includes the sequence of SEQ ID NO: 56. In some cases, the targeted AAV ITR includes the sequence of SEQ ID NO: 57. In other words, in some cases, a guide RNA targets any one of SEQ ID NOs: 26-50 and 56-57. In some cases, a guide RNA targets any one of SEQ ID NOs: 26-50. In some cases, a guide RNA targets SEQ ID NO: 56 or 57. In some cases, a guide RNA targets SEQ ID NO: 33. In some cases, a guide RNA targets SEQ ID NO: 40. In some cases, a guide RNA targets SEQ ID NO: 48. In some cases, a guide RNA targets any one of SEQ ID NOs: 33, 40, and 48. In some cases, the AAV ITR includes the sequence of SEQ ID NO: 52. In some cases, the AAV ITR includes the sequence of SEQ ID NO: 51 and / or the sequence of SEQ ID NO: 52. In some cases, the AAV ITR includes the sequence of SEQ ID NO: 51 and the sequence of SEQ ID NO: 52. In some cases, the AAV ITR includes the sequence of SEQ ID NO: 51 or the sequence of SEQ ID NO: 52. In other words, in some cases, a guide RNA targets SEQ ID NO: 51 and / or 52. In some cases, a guide RNA targets SEQ ID NO: 51 and 52. In some cases, a guide RNA targets SEQ ID NO: 51 or 52. In some cases, a guide RNA targets SEQ ID NO: 51. In some cases, a guide RNA targets SEQ ID NO: 52. A guide RNA can be referred to by the protein to which it corresponds. For example, when the CRISPR-Cas effector protein is a Cas9 protein, the corresponding guide RNA can be referred to as a “Cas9 guide RNA.” Likewise, as another example, when the CRISPR-Cas effector protein is a Cas12a protein, the corresponding guide RNA can be referred to as a “Cas12a guide RNA.” In some embodiments, a guide RNA includes two separate nucleic acid molecules: an “activator” and a “targeter” and is referred to herein as a “dual guide RNA”, a “double-molecule guide RNA”, a “two-molecule guide RNA”, or a “dgRNA.” In some embodiments, the guide RNA is one molecule (e.g., for some CRISPR-Cas effector proteins, the corresponding guide RNA is naturally a single molecule; and in some cases, an activator and targeter are artificially covalently linked to one another, e.g., via intervening nucleotides), and the guide RNA is referred to as a “single guide RNA”, a “single-molecule guide RNA,” a “one-molecule guide RNA”, or simply “sgRNA.” In some cases, two or more guide RNAs can be used, e.g., to target a CRISPRa fusion protein to more than one target sequence at the same time. For example, in some cases, two or more guide RNAs are used that target different sequences of a targeted region (e.g., a targeted ITR). As would be understood by one of ordinary skill in the art, the sequence targeted by a guide RNA is generally selected taking the protospacer adjacent motif (PAM) sequence into account. The PAM sequence and position relative to the target sequence varies depending on which CRISPR-Cas effector protein is used. For example, the PAM for SpyCas9 is NGG and the PAM for SaCas9 is NNGRR(T) [both positioned downstream of the targeted sequence], while the PAM for AsCas12a is TTTV (i.e., TTTA, TTTC, or TTTG) [positioned upstream of the targeted sequence]. PAMs for enhanced versions of Cas12a can include, for example, TTYN, VTTV, TRTV, TATM, and TGTM. As noted above, in some cases, the targeted sequence is a sequence of the AAV ITR of SEQ ID NO: 51. In some cases, the targeted sequence is a sequence of the AAV ITR of SEQ ID NO: 52, which is a reverse complement sequence of SEQ ID NO: 51. In some cases, the targeted sequence is a sequence of the AAV ITR of SEQ ID NO: 51 and / or SEQ ID NO: 52. In some cases, the targeted sequence is a sequence of the AAV ITR of SEQ ID NO: 51 and SEQ ID NO: 52. In some cases, the targeted sequence is a sequence of the AAV ITR of SEQ ID NO: 51 or SEQ ID NO: 52. See, e.g. : AAV ITR (See FIG.9B): aggaacccctagtgatggagttggccactccctctctgcgcgctcgctcgctcactgaggccgggcgaccaaaggtcgcccg acgcccgggctttgcccgggcggcctcagtgagcgagcgagcgcgcagagagggagtggccaactccatcactaggggtt cca (SEQ ID NO: 51) AAV ITR (reverse complement of the above – see FIG.9B): ctgcgcgctcgctcgctcactgaggccgcccgggcaaagcccgggcgtcgggcgacctttggtcgcccggcctcagtgagc gagcgagcgcgcagagagggagtggccaactccatcactaggggttcct (SEQ ID NO: 52) Examples of AAV ITR sequences that can be targeted using Cas9 guide RNAs include, but are not necessarily limited to, those listed in Table 1; while examples of AAV ITR sequences that can be targeted using Cas12a guide RNAs include, but are not necessarily limited to, those listed in Table 2 – also see FIG.9B. Table 1. List of AAV ITR sequences that can be targeted using SpyCas9 guide RNAs (PAM is NGG). “Guide1”, “Guide2”, and “Guide3” were targeted as proof of principle in the examples section below, see, e.g., FIG.9B. The listed sequences are target sequences of the AAV ITR sequences of SEQ ID NO: 51 and / or 52. SEQ ID PAM Target Sequence (5' to 3') Note SEQ ID PAM Target Sequence (5' to 3') Note NO: ” ” ” T a e . s o sequences a can e argee usng as12a. The listed sequences are target sequences of the AAV ITR sequences of SEQ ID NO: 51 and / or 52. SEQ ID PAM Target Sequence (5' to 3') NO In some embodiments, a nucleic acid encoding a guide RNA (i.e., a CRISPR-Cas guide RNA) is integrated into the genome of a subject genetically modified cell (e.g., one that has increased AAVR levels and decreased SETDB1 levels). In some embodiments, the nucleic acid encoding the guide RNA is extrachromosomal. In some cases, the nucleotide sequence encoding the guide RNA is operably linked to a promoter (e.g., a Pol III promoter such as U6 or H1). As noted elsewhere herein, in some cases, a subject genetically modified cell will include one or more (e.g., 1, 2, 3, 4, 5, 6, 1-10, 1- 8, 1-6, 1-5, 1-4, 1-3, 2-10, 2-8, 2-6, 2-5, 2-4, 3-10, 3-8, 3-6, 3-5, two or more, three or more, four or more, or five or more) guide RNAs (or nucleotide sequences that encode said guide RNAs) that target one or more AAV ITRs. In some such cases, the nucleotides sequence(s) encoding the guide RNA(s) are integrated into the genome of the subject genetically modified cell. As would be understood to one of ordinary skill in the art, the guide RNA can be introduced into a cell directly (e.g., as a RNA, as a DNA / RNA hybrid, and the like) or indirectly (e.g., as a nucleic acid encoding the RNA, e.g., a DNA such as an expression vector such as a viral or plasmid DNA). In some cases, a sequence encoding the guide RNA(s) is integrated into the genome of a subject genetically modified cell. iv. Nucleic acids The disclosure provides nucleic acids encoding a subject AAVR polypeptide (e.g., a wild type AAVR protein, a variant AAVR polypeptide), nucleic acids encoding: an RNAi agent that targets SETDB1; a site specific nuclease system that targets the SETDB1 genomic locus, e.g., Zinc Finger Nuclease (ZFN), TALEN, and / or CRISPR based systems (e.g., including CRISPR guide RNAs), a CRISPR based system (e.g., including CRISPR guide RNAs) that targets SETDB1 mRNA, vectors and host cells comprising subject nucleic acids, and recombinant techniques for the production of a subject AAVR polypeptide (e.g., a variant AAVR polypeptide, a wild type AAVR protein). In some cases, a nucleic acid encoding a subject AAVR is an RNA (e.g., an mRNA). In some cases, a nucleic acid encoding a subject AAVR is a DNA (e.g., where the sequence encoding the AAVR polypeptide is operably linked to a promoter, e.g., as part of an expression cassette, e.g., as part of an expression vector). Many vectors are available. The vector components generally include, but are not limited to, one or more of the following: a signal sequence, an origin of replication, one or more marker genes, an enhancer element, a promoter, and a transcription termination sequence. In some cases, as subject AAVR polypeptide (e.g., a variant AAVR polypeptide, a wild type AAVR protein) and / or an agent for reducing expression of SETDB1 is introduced into a cell (e.g., in vitro in culture, administered to an individual, and the like) by providing the AAVR polypeptide (e.g., a variant AAVR polypeptide, a wild type AAVR protein) and / or agent for reducing expression of SETDB1 as a nucleic acid (e.g., an RNA, e.g., an mRNA; or a DNA, e.g., a recombinant expression vector, a linear DNA, a circular DNA, a plasmid, a viral vector, etc.) encoding the AAVR polypeptide (e.g., a variant AAVR polypeptide, a wild type AAVR protein) and / or encoding the agent (e.g., RNAi agent, guide RNA, ZFN, CRISPR-Cas protein, TALEN, etc.). This disclosure provides such methods and also the nucleic acids for such methods. For example, an mRNA encoding a subject AAVR polypeptide (e.g., a variant AAVR polypeptide, a wild type AAVR protein) and / or an agent for reducing expression of SETDB1 can be introduced into a cell, and the cell can then express the translated protein. As another example, a DNA (e.g., a recombinant expression vector, a linear DNA, a circular DNA, a plasmid, a viral vector, etc.) encoding a subject AAVR polypeptide (e.g., a variant AAVR polypeptide, a wild type AAVR protein) and / or an agent for reducing expression of SETDB1 can be introduced into a cell and the cell can then produce the encoded protein. In some cases, a nucleic acid encoding a subject AAVR polypeptide (e.g., a variant AAVR polypeptide, a wild type AAVR protein) includes a nucleotide sequence encoding a signal sequence (e.g., upstream of and in frame with the nucleotide sequence that encodes the AAVR polypeptide). As would be readily recognized by one of ordinary skill in the art, a signal sequence as referred to here is an amino acid sequence at or near the amino terminus of a nascent protein that can be recognized by the signal recognition particle of a eukaryotic cell, resulting in transport of the protein into the secretory pathway of the cell. Any convenient signal sequence can be used. In some cases, a nucleic acid encoding a subject AAVR polypeptide (e.g., a variant AAVR polypeptide, a wild type AAVR protein) and / or an agent for reducing expression of SETDB1 is introduced into a cell (e.g., in vivo, ex vivo, in vitro) and the cell can then produce the encoded protein and / or RNA. In some cases, the cell is in vitro. In some cases, the cell is ex vivo. In some cases, the cell is in vivo. For example, in some cases, a nucleic acid encoding a AAVR polypeptide (e.g., a variant AAVR polypeptide, a wild type AAVR protein) and / or an agent for reducing expression of SETDB1 is introduced into a cell that is in vivo (e.g., in some cases, a nucleic acid encoding a AAVR polypeptide (e.g., a variant AAVR polypeptide, a wild type AAVR protein) and / or an agent for reducing expression of SETDB1 is introduced into a cell in vivo by administering the nucleic acid to an individual). In some cases, a nucleic acid encoding a subject AAVR polypeptide (e.g., a variant AAVR polypeptide, a wild type AAVR protein) and / or an agent for reducing expression of SETDB1 is introduced into a cell (e.g., ex vivo, in vitro) and the cell is then introduced into an individual. In some cases, the cell is autologous to the individual (e.g., the cell was isolated from the individual or is the progeny of a cell that was isolated from the individual). A "vector" or “expression vector” is a replicon, such as plasmid, phage, virus, or cosmid, to which another DNA segment, i.e. an “insert”, may be attached so as to bring about the replication of the attached segment in a cell. An “expression cassette” comprises a DNA coding sequence (e.g., a nucleotide sequence encoding a subject AAVR polypeptide) operably linked to a promoter. "Operably linked" refers to a juxtaposition wherein the components so described are in a relationship permitting them to function in their intended manner. For instance, a promoter is operably linked to a coding sequence (and likewise the coding sequence is operably linked to the promoter) if the promoter affects its transcription or expression. As would be readily understood by one of ordinary skill in the art, a nucleotide sequence can also be operably linked to other expression control elements such as enhancers (e.g., tissue specific enhancers). The terms “recombinant expression vector,” or “DNA construct” or “expression vector” and similar terms of the art are used interchangeably herein to refer to a DNA molecule comprising a vector and at least one insert. Recombinant expression vectors can be generated for the purpose of expressing and / or propagating the insert(s), or for the construction of other recombinant nucleotide sequences. The insert(s) (e.g., a nucleotide sequence encoding a subject AAVR polypeptide (e.g., a variant AAVR polypeptide, a wild type AAVR protein) and / or an agent for reducing expression of SETDB1) may or may not be operably linked to a promoter sequence and may or may not be operably linked to DNA regulatory sequences. Thus in some cases, a subject nucleic acid (e.g., an expression cassette, an expression vector, a plasmid, a viral vector, a circular vector, a linear vector, etc.) includes a nucleotide sequence encoding a subject AAVR polypeptide (e.g., a variant AAVR polypeptide, a wild type AAVR protein) and / or an agent for reducing expression of SETDB1 that is operably linked to a promoter (e.g., one that is operable in a desired cell type, e.g., a eukaryotic cell, a mammalian cell, a primate cell, a human cell, an immune cell, a leukocyte, a T cell, a CD8 T cell, a CD4 T cell, a memory / effector T cell, a B cell, an antigen presenting cell (APC), a dendritic cell, a macrophage, a monocyte, an NK cell, a stem cell, a hematopoietic stem cell, a pluripotent stem cell, a multipotent stem cell, a tissue restricted stem cell, a retinal cell, an hepatocyte, a hepatocyte precursor cell, a kidney cell, a muscle cell, a satellite cell, etc.). A promoter can be a constitutively active promoter (i.e., a promoter that is constitutively in an active / ”ON” state), it may be an inducible promoter (i.e., a promoter whose state, active / ”ON” or inactive / “OFF”, is controlled by an external stimulus, e.g., the presence of a particular temperature, compound, or protein.), it may be a spatially restricted promoter (i.e., transcriptional control element, enhancer, etc.)(e.g., tissue specific promoter, cell type specific promoter, etc.), and it may be a temporally restricted promoter (i.e., the promoter is in the “ON” state or “OFF” state during specific stages of embryonic development or during specific stages of a biological process, e.g., hair follicle cycle in mice). Suitable promoters can be derived from viruses and can therefore be referred to as viral promoters, or they can be derived from any organism, including prokaryotic or eukaryotic organisms. Suitable promoters can be used to drive expression by any RNA polymerase (e.g., pol I, pol II, pol III). Exemplary promoters include, but are not limited to the SV40 early promoter, mouse mammary tumor virus long terminal repeat (LTR) promoter; adenovirus major late promoter (Ad MLP); a herpes simplex virus (HSV) promoter, a cytomegalovirus (CMV) promoter such as the CMV immediate early promoter region (CMVIE), a rous sarcoma virus (RSV) promoter, EF1-alpha promoter, and the like. When referring to a nucleic acid encoding an RNAi agent (e.g., an shRNA, a microRNA, an siRNA) that targets AAVR, or a nucleic acid encoding a guide RNA, the nucleotide sequence encoding the RNAi agent or guide RNA can be operably linked to a pol III promoter such as a human U6 small nuclear promoter (U6) (Miyagishi et al. , Nature Biotechnology 20, 497 - 500 (2002)), an enhanced U6 promoter (e.g., Xia et al., Nucleic Acids Res.2003 Sep 1;31(17)), a human H1 promoter (H1), and the like. Examples of inducible promoters include, but are not limited toT7 RNA polymerase promoter, T3 RNA polymerase promoter, Isopropyl-beta-D-thiogalactopyranoside (IPTG)- regulated promoter, lactose induced promoter, heat shock promoter, Tetracycline-regulated promoter, Steroid-regulated promoter, Metal-regulated promoter, estrogen receptor-regulated promoter, etc. Inducible promoters can therefore be regulated by molecules including, but not limited to, doxycycline; RNA polymerase, e.g., T7 RNA polymerase; an estrogen receptor; an estrogen receptor fusion; etc. Suitable expression vectors include, but are not limited to, viral vectors (e.g., viral vectors based on vaccinia virus; poliovirus; adenovirus (see, e.g., Li et al., Invest Opthalmol Vis Sci 35:25432549, 1994; Borras et al., Gene Ther 6:515524, 1999; Li and Davidson, PNAS 92:77007704, 1995; Sakamoto et al., H Gene Ther 5:10881097, 1999; WO 94 / 12649, WO 93 / 03769; WO 93 / 19191; WO 94 / 28938; WO 95 / 11984 and WO 95 / 00655); adeno-associated virus (see, e.g., Ali et al., Hum Gene Ther 9:8186, 1998, Flannery et al., PNAS 94:69166921, 1997; Bennett et al., Invest Opthalmol Vis Sci 38:28572863, 1997; Jomary et al., Gene Ther 4:683690, 1997, Rolling et al., Hum Gene Ther 10:641648, 1999; Ali et al., Hum Mol Genet 5:591594, 1996; Srivastava in WO 93 / 09239, Samulski et al., J. Vir. (1989) 63:3822-3828; Mendelson et al., Virol. (1988) 166:154-165; and Flotte et al., PNAS (1993) 90:10613-10617); SV40; herpes simplex virus; human immunodeficiency virus (see, e.g., Miyoshi et al., PNAS 94:1031923, 1997; Takahashi et al., J Virol 73:78127816, 1999); a retroviral vector (e.g., Murine Leukemia Virus, spleen necrosis virus, and vectors derived from retroviruses such as Rous Sarcoma Virus, Harvey Sarcoma Virus, avian leukosis virus, a lentivirus, human immunodeficiency virus, myeloproliferative sarcoma virus, and mammary tumor virus); and the like. Numerous suitable expression vectors are known to those of skill in the art, and many are commercially available. The following vectors are provided by way of example; for eukaryotic host cells: pXT1, pSG5 (Stratagene), pSVK3, pBPV, pMSG, and pSVLSV40 (Pharmacia). However, any other vector may be used so long as it is compatible with the host cell. Depending on the host / vector system utilized, any of a number of suitable transcription and translation control elements, including constitutive and inducible promoters, transcription enhancer elements, transcription terminators, etc. may be used in the expression vector (see e.g., Bitter et al. (1987) Methods in Enzymology, 153:516-544). Also provided in this disclosure are cells that include a nucleic acid (e.g., as described above) that includes a nucleotide sequence encoding a subject AAVR polypeptide (e.g., a variant AAVR polypeptide, a wild type AAVR protein) and an agent for reducing expression of SETDB1 (or in some cases SETDB1 is reduced because the genomic locus encoding SETDB1 has been altered). Also provided in this disclosure are cells that include a nucleic acid (e.g., as described above) that includes a nucleotide sequence encoding an RNAi agent that targets an AAVR protein and an agent for reducing expression of SETDB1 (or in some cases SETDB1 is reduced because the genomic locus encoding SETDB1 has been altered) . Such a cell can be a cell from any organism (e.g., a bacterial cell, an archaeal cell, a cell of a single-cell eukaryotic organism, a plant cell, an algal cell, a fungal cell (e.g., a yeast cell), an animal cell, a cell from an invertebrate animal (e.g., fruit fly, mosquito, cnidarian, echinoderm, nematode, etc.), a cell from a vertebrate animal (e.g., fish, amphibian, reptile, bird, mammal), a cell from a mammal, a cell from a rodent, a cell from a human, etc.). Also provided are nucleic acids such as those described above that encode a CRISPRa fusion protein and / or a CRISPR-Cas guide RNA that targets an ITR sequence (e.g., an AAV ITR sequence). See elsewhere herein for additional discussion of CRIPSRa components, including discussion and examples of CRISPR-Cas guide RNAs that target an ITR sequence. v. Genetically modified cells The present disclosure provides genetically modified cells with increased levels of AAVR protein and reduced levels of SETDB1 protein relative to a corresponding cell that is not genetically modified – and thereby the genetically modified cells exhibit enhanced / increased permissiveness to AAV. As would be readily understood by one of ordinary skill in the art, a “corresponding cell that is not genetically modified” is a cell that would be comparable but for the modifications that result in increased AAVR protein and decreased SETDB1. Thus, for example, the increased / decreased levels can be relative to the levels that were present in the same cell prior to the modification(s). As another example, the increased / decreased levels can be relative to the levels that are present in similar cells (e.g., cells from the same cell line) that are otherwise genetically identical to the modified cells. Non-limiting examples of genetically modified cells include cells with a heterologous nucleic acid encoding the AAVR (e.g., operably linked to a constitutive promoter), cells having an altered sequence in their genome at the SETDB1 locus, e.g., a knock-out cell, cells having an agent such as an RNAi or CRISPR agent that reduces SETDB1 protein levels by reducing SETDB1-encoding mRNA levels and / or blocking translation of SETDB1-encoding mRNA. As discussed elsewhere in more detail herein, in some cases, a subject genetically modified cell includes CRISPRa components (e.g., a CRISPRa fusion protein or a nucleic acid encoding it; and / or a CRISPR-Cas guide RNA or a nucleic acid encoding it, where the CRISPR- Cas guide RNA targets an ITR sequence such as an AAV ITR sequence). In some cases, a nucleic acid encoding a CRISPRa fusion protein is integrated into the cell’s genome. In some cases, the CRISPRa fusion protein is a Cas9 protein (e.g., a dCas9 protein), e.g., a SpyCas9, a SaCas9, etc., linked to (e.g., in some cases fused to) a transcriptional activator. In some cases, the CRISPRa fusion protein is a Cas12a protein (e.g., a dCas12a protein), linked to (e.g., in some cases fused to) a transcriptional activator. In some cases, a nucleic acid encoding a CRISPR-Cas guide RNA (e.g., a Cas9 guide RNA, a Cas12a guide RNA, etc.) (e.g., one that targets an AAV ITR sequence such as those of SEQ ID NOs: 26-50, e.g., 33, 40, or 48; one that targets an AAV ITR sequence such as those of SEQ ID NOs: 56 and 57; and the like) is integrated into the cell’s genome. In some cases, the CRISPR-Cas guide RNA targets SEQ ID NO: 33. In some cases, the CRISPR-Cas guide RNA targets SEQ ID NO: 40. In some cases, the CRISPR-Cas guide RNA targets SEQ ID NO: 48. In some cases, the CRISPR-Cas guide RNA targets any one of SEQ ID NOs: 26-50. In some cases, the CRISPR-Cas guide RNA targets any one of SEQ ID NOs: 33, 40, and 48. In some cases, the CRISPR-Cas guide RNA targets SEQ ID NO: 56. In some cases, the CRISPR-Cas guide RNA targets SEQ ID NO: 57. In some cases, the CRISPR-Cas guide RNA targets SEQ ID NO: 56 or 57. See the discussion in the “CRISPRa” section above for additional details and embodiments with respect to CRISPRa components. In some embodiments, a subject genetically modified cell is in vitro, e.g., is cell line (such as HeLa) that has been modified to express increased AAVR and reduced SETDB1. In some embodiments, a subject genetically modified cell is a mammalian cell or is derived from a mammalian cell. In some embodiments, a subject genetically modified host cell is a rodent cell (e.g., a mouse cell, a rat cell, and the like) or is derived from a rodent cell. In some embodiments, a subject genetically modified host cell is a human cell or is derived from a human cell. Examples of cells include but are not limited to: HeLa cells (e.g., American Type Culture Collection (ATCC) No. CCL-2), CHO cells (e.g., ATCC Nos. CRL9618, CCL61, CRL9096), 293 cells (e.g., ATCC No. CRL-1573), Vero cells, NIH 3T3 cells (e.g., ATCC No. CRL-1658), Huh-7 cells, BHK cells (e.g., ATCC No. CCLlO), PC12 cells (ATCC No. CRL1721), COS cells, COS-7 cells (ATCC No. CRL1651), RATl cells, mouse L cells (ATCC No. CCLl.3), human embryonic kidney (HEK) cells (ATCC No. CRL1573), HLHepG2 cells, Hut-78, Jurkat, HL-60, NK cell lines (e.g., NKL, NK92, and YTS), and the like. Examples of cells include but are not limited to:293, 3T3, 4T1, 721, 9L, A2780, A172, A20, A253, A431, A-549, A-673, ALC, B 16, B35, BCP-1, BEAS-2B, bEnd.3, BHK, BR 293, BT20, BT483, BxPC3, C2-C12, C.sub.3 h- 10T1 / 2, C6 / 36, C6, Cal-27, CHO, COR-L23, COS, COV-434, CML Tl, CMT, CRL7030, CT26, D17, DH82, DU145, DuCaP, EL4, EM2, EM3, EMT6, FM3, H1299, H69, HB54, HB55, HCA2, HEK-293, HeLa, Hepalclc7, HL-60, HMEC, Hs578T, HsS78Bst, HT-29, HTB2, HUVEC, Jurkat, J558L, JY, K562, Ku812, KCL22, KG1, KYO1, LNCap, Ma-Mel, MC-38, MCF-7, MCF-IOA, MDA-MB-231, MDA-MB-468, MDA-MB-435, MDCK, MG63, MOR / 0.2R, MONO-MAC 6, MRC5, MTD-1A, NCI-H69, NIH-3T3, NALM-1, NSO, NW-145, OPCN, OPCT, PNT-1A, PNT-2, Raji, RBL, RenCa, RIN-5F, RMA, Saos-2, SiHa, SKBR3, SKOV-3, T2, T-47D, T84, THP1, U373, U87, U937, VCaP, Vero, VERY, W138, WM39, WT-49, X63, YAC-1, and YAR cells. In some cases, a subject genetically modified cell is a HeLa cell. The present disclosure further provides progeny of a subject genetically modified cell, where the progeny can comprise the same exogenous nucleic acid or polypeptide as the subject genetically modified cell from which it was derived. The present disclosure further provides a composition comprising a subject genetically modified cell. Increased AAVR In some cases, a subject genetically modified cell includes a subject variant AAVR polypeptide (and / or a nucleic acid encoding the variant AAVR polypeptide, e.g., in some cases integrated into the genome). In some cases, a subject genetically modified cell includes a nucleic acid encoding an AAVR polypeptide (e.g., a wild type AAVR polypeptide, a AAVR polypeptide), where the nucleotide sequence encoding the AAVR polypeptide is operably linked to a heterologous promoter (i.e., a promoter with which it is not naturally in operable linkage – a promoter other than the AAVR promoter) (e.g., a constitutive promoter such as a CMV promoter, an EF1-alpha promoter, etc.; an inducible promoter; a tissue-specific promoter; a temporally regulated promoter; and the like). In some cases, the nucleotide sequence encoding the AAVR polypeptide is operably linked to a heterologous enhancer that modifies expression from the promoter to which it is operably linked. Thus, for example, cell lines can be developed with enhanced permissiveness to AAV infection (or with inducible permissiveness to AAV infection) by introducing into a cell a subject nucleic acid (e.g., having a nucleotide sequence encoding an AAVR polypeptide that is operably linked to a heterologous inducible promoter, e.g, heat shock promoter, Tetracycline-regulated promoter, Steroid-regulated promoter, Metal- regulated promoter, estrogen receptor-regulated promoter, etc.). In some cases the foreign nucleic acid (e.g., DNA) is incorporated (i.e., integrated) into the cell’s genome. In some cases, the foreign nucleic acid (e.g., DNA) is maintained episomally. In some cases, the foreign nucleic acid (e.g., DNA) is transiently present in the cell. In some embodiments, AAVR levels are increased using CRISPRa, e.g., to increase expression of AAVR from the cell’s endogenous AAVR locus. Reduced SETDB1 A subject genetically modified cell exhibits reduced levels of SETDB1 (has been genetically modified to expressed reduced amounts of SETDB1). Any convenient method can be used to reduce SETDB1 protein levels and many methods will be known to one of ordinary skill in the art. For example, in some cases, a subject genetically modified cell includes an RNAi agent (e.g., shRNA, siRNA, microRNA) or a nucleic acid encoding an RNAi agent (e.g., integrated into the genome) where the RNAi agent specifically targets the cell’s endogenous wild type SETDB1-encoding mRNA. Such reagents can decrease the SETDB1 mRNA levels and / or reduce translation from SETDB1 mRNA. SETDB1-encoding mRNA levels can also be reduced using CRISPR agents (e.g., CRISPRi, e.g., dCas9-fusion protein) that reduce transcription of SETDB1 mRNA from the endogenous SETDB1 locus. SETDB1-encoding mRNA levels can also be reduced using CRISPR agents (e.g., Cas13 agents) that target SETDB1 mRNA for cleavage and / or translation blocking. In some cases, reduced SETDB1 protein levels are achieved by altering the nucleotide sequence in the genomic locus that encodes the SETDB1 protein (e.g., a genomic deletion of an exon sequence encoding SETDB1). Such can be achieved using any convenient method – e.g., site-specific nuclease-based methods such as Zinc Finger Nucleases (ZFNs), TALENs, meganucleases, and CRISPR nucleases (e.g., Cas9) (including an appropriate guide RNA). Methods to reduce expression of a protein are known in the art and any convenient method can be used (e.g., altering the genomic nucleotide sequence encoding the protein, reducing levels of the mRNA encoding the protein, e.g., by reducing transcription and / or stability of the mRNA, and reducing translation of the mRNA into protein). In some cases, reduced expression of SETDB1 results from an altered nucleotide sequence (e.g., an altered genomic nucleotide sequence encoding SETDB1 - relative to the endogenous SETDB1 genomic locus of a corresponding wild type cell). Such alterations can be achieved, e.g., using nuclease-based gene editing (e.g., via a ZFN, a TALEN, a meganuclease, a CRIPSR system such as CRISPR-Cas9, and the like). In some cases, an altered genomic nucleotide sequence encoding SETDB1 includes a genomic deletion of an exon sequence encoding SETDB1. In some cases, reduced expression results from reducing levels of the mRNA encoding the SETDB1 protein, e.g., by reducing transcription and / or stability of the mRNA, and / or reducing translation of the mRNA into protein. (RNAi, CRISPRi, CRISPR-based RNA targeting, and the like). Reducing the levels of the mRNA and / or reducing translation of the mRNA into protein can be achieved, e.g., using CRISPR-based transcription reduction (e.g., CRISPRi), CRISPR-based RNA targeting (e.g., CRISPR-Cas13), RNA interference (e.g., using an RNAi agent such as siRNA, shRNA, miRNA), antisense oligonucleotides (e.g., LNAs), and the like. vi. Methods of use Methods are provided for enhancing permissiveness of a target cell to AAV infection (e.g., by increasing levels of AAVR and decreasing levels of SETDB1 in the cell). Aspects of the disclosure include methods of AAV delivery, which methods include contacting a subject genetically modified cell with an AAV particle (virion) that includes a nucleic acid of interest (e.g., a non-coding RNA such as an RNAi agent or a guide RNA, a DNA encoding a non- coding RNA such as an RNAi agent or guide RNA, a DNA encoding a protein such as a therapeutic protein, a protein for genome editing, a cell marker such as a luciferase, a fluorescent protein, a cell maker, etc.). In some cases, such a method also includes a step of generating the genetically modified cell by increasing the permissiveness of the cell to AAV infection (by increasing AAVR and decreasing SETDB1). The nucleic acid of interest (the heterologous nucleic acid) (e.g., that can be delivered via AAV after a cell’s permissiveness to AAV infection has been enhanced) can be any nucleic acid fragment adapted for introduction into a target cell. Suitable examples of nucleic acids of interest include promoter elements, coding sequences, e.g. therapeutic genes, marker genes, etc., control regions, trait-producing fragments, nucleic acid elements to accomplish gene disruption, as well as nucleic acids that do not encode for a polypeptide, including a polynucleotide that encodes a non-translated RNA, such as an RNAi agent (e.g., siRNA, shRNA, microRNA) that may play a role in RNA interference (RNAi) based gene expression control, or a CRISPR-Cas guide RNA. In some embodiments permissiveness of the cell to AAV infection is increased 1.1 fold or more (e.g., 1.2 fold or more, 1.5 fold or more, 2 fold or more, 2.5 fold or more, 3 fold or more, 5 fold or more, or 10 fold or more), e.g., compared to permissiveness of the cell or cell population, or a comparable cell or cell population prior to the method (or in the absence of the method). In some cases, a subject method includes measuring the increase in permissiveness to AAV infection. Target cells The cells of interest (i.e., “target cells”) are typically mammalian, where the term refers to any animal classified as a mammal, including humans, domestic and farm animals, and zoo, laboratory, sports, or pet animals, such as dogs, horses, cats, cows, mice, rats, rabbits, etc. In some embodiments, the target cell is a human cell. Target cells of interest include any cell susceptible to infection by a subject AAV virion (e.g., a recombinant AAV). In some cases, e.g., when the method is a method of delivering a heterologous nucleic acid to a target cell (e.g., delivering an AAV), the target cell can be a cell removed from an individual (e.g., a “primary” cell), or the target cell can be a tissue culture cell (e.g., from an established cell line). Examples of target cells include, but are not limited to, liver cells, pancreatic cells (e.g., islet cells: alpha cells, beta cells, delta cells, gamma cells, and / or epsilon cells), skeletal muscle cells, heart muscle cells, fibroblasts, retinal cells, synovial joint cells, lung cells, T cells, neurons, glial cells, stem cells, hematopoietic progenitor cells, neural progenitor cells, endothelial cells, and cancer cells. Exemplary stem cell target cells include, but are not limited to, hematopoietic stem cells, neural stem cells, neural crest stem cells, embryonic stem cells, induced pluripotent stem cells (iPS cells), mesenchymal stem cells, mesodermal stem cells, liver stem cells, pancreatic stem cells, muscle stem cells, and retinal stem cells. Target cells which are employed may be fresh, frozen, or have been subject to prior culture. They may be fetal, neonate, adult. Hematopoietic cells may be obtained from fetal liver, bone marrow, blood, particularly G-CSF or GM-CSF mobilized peripheral blood, or any other conventional source. The manner in which stem cells are separated from other cells of the hematopoietic or other lineage is not critical to this disclosure. As described above, a substantially homogeneous population of stem or progenitor cells may be obtained by selective isolation of cells free of markers associated with differentiated cells, while displaying epitopic characteristics associated with the stem cells. In some cases, a target cell is a genetically modified cell as described elsewhere herein. AAV delivery As noted above, in some embodiments, a subject method includes delivering an AAV particle to a subject genetically modified cell (e.g., one having increased levels of AAVR protein and reduced levels of SETDB1 protein). Such methods include contacting a subject genetically modified cell with an AAV particle that includes a nucleic acid (e.g., DNA) of interest. In some cases, the DNA of interest includes a nucleotide sequence that is operably linked to a promoter and encodes a non-coding RNA or a protein. In some cases, the nucleic acid (e.g., DNA) of interest includes a nucleotide sequence encoding a cell marker (e.g., a fluorescent protein, a luciferase, a drug selectable marker, and the like). In some cases, the AAV particle includes an AAV1, AAV2, AAV3, AAV5, AAV6, AAV8, AAV9, or AAV-PHP.eB capsid protein. Many AAV serotypes have been identified, cloned, sequenced, and converted into vectors, and at least 100 AAV variants have been isolated from non-primates, primates and humans. A subject AAV particle (e.g., for methods of delivering a heterologous nucleic acid, i.e., a nucleic acid of interest) can be of any serotype. Any convenient AAV serotype can be used. In some cases, the AAV used has AAV1, AAV2, AAV3, AAV3B, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, or AAV11 capsid protein. In some cases, the AAV used has an AAV1, AAV2, AAV3, AAV5, AAV6, AAV8, AAV9, or AAV-PHP.eB capsid protein. In some embodiments, the AAV is an AAVR-dependent serotype (i.e., has an AAVR-dependent capsid). In some cases, the AAV used has a AAV2 capsid. In some cases, the AAV used has a AAV1 capsid. In some cases, the AAV used has a AAV3 capsid. In some cases, the AAV used has a AAV4 capsid. In some cases, the AAV used does not have a AAV4 capsid. In some cases, the AAV used has a AAV5 capsid. In some cases, the AAV used has a AAV6 capsid. In some cases, the AAV used has a AAV7 capsid. In some cases, the AAV used has a AAV8 capsid. In some cases, the AAV used has a AAV9 capsid. In some cases, the AAV used has a AAV- PHP.B capsid. In some cases, the AAV used has a AAV-PHP.eB capsid. AAVs can be classified into clades (see, e.g., FIG.9; Gao et. al., J Virol.2004 Jun; 78(12): 6381–6388; U.S. Patent No.7,906,111, and U.S. Published Patent Application No. US 2003 / 0138772, the disclosures of which are incorporated herein by reference with respect to AAV sequences and their classification into various clades, especially the sequences and names of AAVs of Clade E). Any convenient AAV (AAV capsid) can be used, including engineered AAV variants. Contacting a target cell (e.g., a subject genetically modified cell) can include administering an AAV particle (virion) to a cell in vitro (e.g., in culture), ex vivo (e.g., a primary cell from an individual), or a cell in vivo (e.g., in vivo in an individual). AAV virions can be delivered using any convenient transduction techniques. If transduced in vitro or ex vivo a desired recipient cell (i.e., “target cell”) can be removed from the individual, treated to increase its permissiveness to AAV infection, and either reintroduced into the individual prior to contact with an AAV that includes the desired heterologous nucleic acid, or contacted with an AAV that includes the desired heterologous nucleic acid prior to reintroducing the cell back into the individual. As alternative to autologous cells, syngeneic or xenogeneic cells can be used if those cells will not generate an inappropriate immune response in the individual. "AAV" is an abbreviation for adeno-associated virus, and may be used to refer to the virus itself or derivatives thereof, and can be used to refer to a viral vector system for delivery of nucleic acids. The term covers all subtypes and both naturally occurring as well as recombinant and variant forms, except where specified otherwise. The abbreviation "rAAV" refers to recombinant adeno-associated virus, also referred to as a recombinant AAV vector (or "rAAV vector"). The term "AAV" includes any convenient AAV type, including variant types, e.g., AAV type 1 (AAV1), AAV type 2 (AAV2), AAV type 3 (AAV3), AAV type 4 (AAV4), AAV type 5 (AAV5), AAV type 6 (AAV6), AAV type 7 (AAV7), AAV type 8 (AAV8), AAV type 9 (AAV9), AAV-PHP.eB, AAV-PHP.B, avian AAV, bovine AAV, canine AAV, equine AAV, primate AAV, non-primate AAV, and ovine AAV. "Primate AAV" refers to AAV capable of infecting primates, "non-primate AAV" refers to AAV capable of infecting non-primate mammals, "bovine AAV" refers to AAV capable of infecting bovine mammals, etc. As would be clear to one of ordinary skill in the art, it is to be understood that the term “AAV vector” can be used to refer to the delivery system as a whole (e.g., a virion or population of virions), and can also be used to refer to a nucleic acid encoding the delivery system – i.e., one that includes a sequence that encodes a capsid polypeptide (i.e., a nucleic acid that includes a nucleotide sequence encoding a capsid polypeptide, also referred to as a AAV capsid protein or AAV capsid polypeptide – the terms “polypeptide” and “protein” are used interchangeably herein), depending on context. In some embodiments, a subject AAV vector is a variant (non-wild type) AAV vector (e.g., a nucleic acid can include a nucleotide sequence encoding a variant capsid polypeptide, also referred to as a variant AAV capsid protein or variant AAV capsid polypeptide). The AAV vectors (including variant AAV vectors) can also include a heterologous nucleic acid sequence not of AAV origin (e.g., as part of the nucleic acid insert). This heterologous nucleic acid sequence typically comprises a sequence of interest for the genetic transformation of a cell. In some cases, the heterologous nucleic acid sequence (the “nucleotide sequence of interest”) is flanked by at least one, and generally by two AAV inverted terminal repeat sequences (ITRs). The phrase "non-variant parent capsid polypeptides" (or “wild type capsid protein”) includes any naturally occurring AAV capsid polypeptides. In some embodiments, the non- variant parent capsid polypeptides include AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, bovine AAV and / or avian AAV capsid polypeptides. The term "substantially identical" in the context of variant AAV capsid polypeptides and non-variant parent capsid polypeptides refers to sequences with 1 or more amino acid changes. In some embodiments, these changes do not affect the packaging function of the capsid polypeptides. In some embodiments, substantially identical include variant AAV capsid polypeptides about 99%, about 98%, about 97%, about 96%, about 95%, about 94%, about 93%, about 92%, about 91%, or about 90% identical to non-variant parent capsid polypeptides. In some embodiments, the variant AAV capsid polypeptides can be substantially identical to non-variant parent capsid polypeptides over a subregion of the variant AAV capsid polypeptide, such as over about 25%, about 50%, about 75%, or about 90% of the total polypeptide sequence length. An "AAV virion" or "AAV virus" or "AAV viral particle" or "AAV vector particle" refers to a viral particle composed of at least one AAV capsid polypeptide (including both variant AAV capsid polypeptides and non-variant parent capsid polypeptides) and an encapsidated polynucleotide AAV transfer vector. If the particle comprises a heterologous nucleic acid (i.e. a polynucleotide other than a wild-type AAV genome, such as a transgene to be delivered to a mammalian cell), it can be referred to as an "AAV vector particle" or simply an "AAV vector". Thus, production of AAV virion or AAV particle necessarily includes production of AAV vector as such a vector is contained within an AAV virion or AAV particle. "Packaging" refers to a series of intracellular events resulting in the assembly of AAV virions or AAV particles which encapsidate a nucleic acid sequence and / or other therapeutic molecule. Packaging can refer to encapsidation of nucleic acid sequence and / or other therapeutic molecules into a capsid comprising the variant AAV capsid polypeptides described herein. The phrase "therapeutic molecule" as used herein can include nucleic acids (including, for example, vectors), polypeptides (including, for example, antibodies), and vaccines, as well as any other therapeutic molecule that could be packaged by the variant AAV capsid polypeptides of the invention. AAV "rep" and "cap" genes refer to polynucleotide sequences encoding replication and encapsidation proteins of adeno-associated virus (AAV). AAV rep (replication) and cap (capsid) are referred to herein as AAV "packaging genes." A "helper virus" for AAV refers to a virus allowing AAV (e.g. wild-type AAV) to be replicated and packaged by a mammalian cell. A variety of such helper viruses for AAV are known in the art, including adenoviruses, herpesviruses and poxviruses such as vaccinia. The adenoviruses encompass a number of different subgroups, although Adenovirus type 5 of subgroup C is most commonly used as a helper virus. Numerous adenoviruses of human, non- human mammalian and avian origin are known and available from depositories such as the ATCC. Viruses of the herpes family include, for example, herpes simplex viruses (HSV) and Epstein-Barr viruses (EBV), as well as cytomegaloviruses (CMV) and pseudorabies viruses (PRV); which are also available from depositories such as ATCC. "Helper virus function(s)" refers to function(s) encoded in a helper virus genome allowing AAV replication and packaging (in conjunction with other requirements for replication and packaging described herein). As described herein, "helper virus function" may be provided in a number of ways, including by providing helper virus or providing, for example, polynucleotide sequences encoding the requisite function(s) to a producer cell in trans. An "infectious" virion, virus or viral particle is one comprising a polynucleotide component deliverable into a cell tropic for the viral species. The term does not necessarily imply any replication capacity of the virus. As used herein, an "infectious" virus or viral particle is one that upon accessing a target cell, can infect a target cell, and can express a heterologous nucleic acid in a target cell. Thus, "infectivity" refers to the ability of a viral particle to access a target cell, enter a target cell, and express a heterologous nucleic acid in a target cell. Infectivity can refer to in vitro infectivity or in vivo infectivity. Assays for counting infectious viral particles are described elsewhere in this disclosure and in the art. Viral infectivity can be expressed as the ratio of infectious viral particles to total viral particles. Total viral particles can be expressed as the number of viral genome copies. The ability of a viral particle to express a heterologous nucleic acid in a cell can be referred to as "transduction." The ability of a viral particle to express a heterologous nucleic acid in a cell can be assayed using a number of techniques, including assessment of a marker gene, such as a green fluorescent protein (GFP) assay (e.g., where the virus comprises a nucleotide sequence encoding GFP), where GFP is produced in a cell infected with the viral particle and is detected and / or measured; or the measurement of a produced protein, for example by an enzyme-linked immunosorbent assay (ELISA) or fluorescence-activated cell sorting (FACS). A "replication-competent" virion or virus (e.g. a replication-competent AAV) refers to an infectious phenotypically wild-type virus, and is replicable in an infected cell (i.e. in the presence of a helper virus or helper virus functions). In the case of AAV, replication competence generally requires the presence of functional AAV packaging genes. In some embodiments, AAV vectors, as described herein, lack of one or more AAV packaging genes and are replication-incompetent in mammalian cells (especially in human cells). In some embodiments, AAV vectors lack any AAV packaging gene sequences, minimizing the possibility of generating replication competent AAV by recombination between AAV packaging genes and an incoming AAV vector. In many embodiments, AAV vector preparations as described herein are those containing few if any replication competent AAV (rcAAV, also referred to as RCA) (e.g., less than about 1 rcAAV per 10.sup.2 AAV particles, less than about 1 rcAAV per 10.sup.4 AAV particles, less than about 1 rcAAV per 10.sup.8 AAV particles, less than about 1 rcAAV per 10.sup.12 AAV particles, or no rcAAV). vii. Titration Provided are methods and compositions of functionally titrating an adeno-associated virus (AAV) preparation – i.e., determining a functional titer of the preparation. Such methods include contacting a population of subject genetically modified cells (i.e., having increased AAVR and decreased SETDB1) with an AAV preparation (e.g., one with any serotype / capsid of interest – see above for examples), and determining a functional titer of the AAV preparation. Such determination includes measuring the number and / or percentage of cells that were transduced. A titer can be calculated, for example, by determining the number of cells transduced per volume used. Such a titer will be based on a functional measurement as opposed to a physical measurement, e.g., one based on number of viral genomes, one based on number of capsids, etc. In some cases, such methods include contact with two or more (e.g., 3 or more, 4 or more, or 5 or more) different dilutions (e.g., serial dilutions) of the AAV preparation. As such, the determination of functional titer can include measuring the number and / or percentage of cells that were transduced for each of said different dilutions. A titer and then be calculated, for example, by finding the slope when plotting the number of transduced cells vs. the volume of AAV preparation used (from the dilutions). In some cases, measuring the number and / or percentage of cells that were transduced includes evaluating expression of a transgene encoded by the AAV. For example, an AAV can encode, as a transgene, a marker such as a fluorescent protein (e.g. GFP, BFP, CFP, RFP, and the like) and the number and / or percentage of cells that were transduced can be measured by evaluating the number of cells expressing the transgene (e.g., counting the number and / or percentage of cells expressing GFP). In some cases, the transgene is expressed in the cells by a CRISPRa fusion protein. For example, in some cases, subject genetically modified cells (having increased AAVR and decreased SETDB1) also include CRISPRa components (e.g., include a nucleic acid encoding a CRISPRa fusion protein, e.g., a dCas9 fused to a transcriptional activator, and also include a CRISPR-Cas guide RNA that targets an AAV ITR sequence) – and a population of such cells are contacted with an AAV preparation, where the AAV include a transgene sequence. The transgene sequence is expressed (e.g., from the AAV ITR) by the CRISPRa fusion protein of the genetically modified cells – and therefore a number of transduced cells can be counted by evaluating expression of the transgene (e.g., by counting the number of cells expressing a fluorescent protein). Genetically modified cells of this disclosure (i.e., having increased AAVR and decreased SETDB1) can also be used for testing anti-AAV neutralizing antibody titers in patients prior to gene therapy treatment (e.g., testing whether a patient is likely to mount an immune response to AAV-based gene therapy by measuring their anti-AAV neutralizing antibody titers). For example, anti-AAV neutralizing antibodies (NAbs) can be assessed using in vitro cell-based transduction inhibition (TI) assays. Cell-based NAb (also known as transduction inhibition (TI)) assays have been used in clinical studies to evaluate preexisting antibodies to AAV capsid for enrollment purposes. See, e.g., Cao et al., Gene Ther 30, 150–159 (2023), for information related to cell-based TI assays. A functional cell-based TI assay has the advantage of detecting neutralization activity by directly measuring the impact on AAV transduction, however, this assay is more challenging to manage as an enrollment assay. Using genetically modified cells of this disclosure for such assays can help overcome such challenges. As such, provided are methods and compositions for testing anti-AAV neutralizing antibody titers in sample from an individual (e.g., a blood sample). Such methods include contacting a population of subject genetically modified cells (i.e., having increased AAVR and decreased SETDB1) with (i) an AAV preparation (e.g., one with any serotype / capsid of interest), and (ii) a sample from an individual (e.g., a blood sample), and measuring an amount (e.g. a titer) of anti-AAV neutralizing antibody(ies) present in the sample. In some cases, the ‘measuring’ includes determining / measuring an amount of AAV transduction in the presence of the sample. This measured amount can be compared to a control (e.g., a measured amount of AAV transduction in the absence of the sample from the individual and / or a measured amount of AAV transduction in the presence of a comparable sample that is known to not include neutralizing antibodies). In some cases, the measurement of anti-AAV neutralizing antibody(ies) present in the sample from the individual is used to determine whether the individual is suitable for an AAV- based therapy. If an individual is determined to be suitable, such a method can also include a step of delivering an AAV-based therapy to the individual. viii. Kits Also within the scope of the disclosure are kits comprising the compositions (e.g., variant AAVR polypeptides, nucleic acids encoding AAVR polypeptides, reagents for reducing SETDB1 levels (e.g., RNAi, ZFN, TALEN, and / or CRISPR-based reagents), and formulations / compositions thereof) of the disclosure and instructions for use. Also within the scope of the disclosure are kits that further include CRISPRa components (such as one or more guide RNAs (e.g., 2 or more, 3 or more, 4 or more, 5 or more, 1-10, 1-5, 1-3, 2-10, 2-5, 3- 10, 3-5, 1, 2, 3, 4, or 5) (and / or nucleic acids encoding them) that target an AAV ITR sequence(s), a CRISPRa fusion protein and / or a nucleic acid that encodes it), and formulations / compositions thereof, of the disclosure and instructions for use. The kit can further contain a least one additional reagent, e.g., one or more AAV vectors, etc. Kits typically include a label indicating the intended use of the contents of the kit. The term label includes any writing, or recorded material supplied on or with the kit, or which otherwise accompanies the kit. ix. Definitions In the description herein, a number of terms conventionally used in the field are utilized. In order to provide a clear and consistent understanding of the specification and claims, and the scope to be given to such terms, the following definitions are provided. The terms "polypeptide," "peptide" and "protein" are used interchangeably herein to refer to a polymer of amino acid residues. The terms also apply to amino acid polymers in which one or more amino acid residue is an artificial chemical mimetic of a corresponding naturally occurring amino acid, as well as to naturally occurring amino acid polymers and non- naturally occurring amino acid polymer. The term "amino acid" refers to naturally occurring and synthetic amino acids, as well as amino acid analogs and amino acid mimetics that function in a manner similar to the naturally occurring amino acids. Naturally occurring amino acids are those encoded by the genetic code, as well as those amino acids that are later modified, e.g., hydroxyproline, gamma- carboxyglutamate, and O-phosphoserine. Amino acid analogs refers to compounds that have the same basic chemical structure as a naturally occurring amino acid, i.e., an .alpha. carbon that is bound to a hydrogen, a carboxyl group, an amino group, and an R group, e.g., homoserine, norleucine, methionine sulfoxide, methionine methyl sulfonium. Such analogs have modified R groups (e.g., norleucine) or modified peptide backbones, but retain the same basic chemical structure as a naturally occurring amino acid. Amino acid mimetics refers to chemical compounds that have a structure that is different from the general chemical structure of an amino acid, but that functions in a manner similar to a naturally occurring amino acid. The terms “recipient”, “individual”, “subject”, “host”, and “patient”, are used interchangeably herein and refer to any mammalian subject for whom diagnosis, treatment, or therapy is desired, particularly humans. "Mammal" for purposes of treatment refers to any animal classified as a mammal, including humans, domestic and farm animals, and zoo, sports, or pet animals, such as dogs, horses, cats, cows, sheep, goats, pigs, etc. In some embodiments, the mammal is human. The terms “specific binding,” “specifically binds,” and the like, refer to non-covalent or covalent preferential binding to a molecule relative to other molecules or moieties in a solution or reaction mixture (e.g., an AAV can specifically bind to a particular polypeptide (e.g., AAVR) relative to other available polypeptides). In some embodiments, the affinity of one molecule for another molecule to which it specifically binds is characterized by a KD(dissociation constant) of 10-5M or less (e.g., 10-6M or less, 10-7M or less, 10-8M or less, 10-9M or less, 10-10M or less, 10-11M or less, 10-12M or less, 10-13M or less, 10-14M or less, 10-15M or less, or 10-16M or less). "Affinity" refers to the strength of binding, increased binding affinity being correlated with a lower KD. The term “specific binding member” as used herein refers to a member of a specific binding pair (i.e., two molecules, usually two different molecules, where one of the molecules, e.g., a first specific binding member, through non-covalent means specifically binds to the other molecule, e.g., a second specific binding member). AAVR and AAV (e.g., an AAV capsid protein) can be considered a specific binding pair. As used herein, the term “correlates,” or “correlates with,” and like terms, refers to a statistical association between instances of two events, where events include numbers, data sets, and the like. For example, when the events involve numbers, a positive correlation (also referred to herein as a “direct correlation”) means that as one increases, the other increases as well. A negative correlation (also referred to herein as an “inverse correlation”) means that as one increases, the other decreases. "Dosage unit" refers to physically discrete units suited as unitary dosages for the particular individual to be treated (e.g., a dosage unit of an AAVR polypeptide that will help increase the permissiveness of a target cell to AAV infection). Each unit can contain a predetermined quantity of active compound(s) calculated to produce the desired therapeutic effect(s) in association with the required pharmaceutical carrier. The specification for the dosage unit forms can be dictated by (a) the unique characteristics of the active compound(s) and the particular therapeutic effect(s) to be achieved, and (b) the limitations inherent in the art of compounding such active compound(s). "Pharmaceutically acceptable excipient” means an excipient that is useful in preparing a pharmaceutical composition that is generally safe, non-toxic, and desirable, and includes excipients that are acceptable for veterinary use as well as those for human pharmaceutical use. Such excipients can be solid, liquid, semisolid, or, in the case of an aerosol composition, gaseous. The terms "pharmaceutically acceptable", "physiologically tolerable" and grammatical variations thereof, as they refer to compositions, carriers, diluents and reagents, are used interchangeably and represent that the materials are capable of administration to or upon a human without the production of undesirable physiological effects to a degree that would prohibit administration of the composition. A "therapeutically effective amount" means the amount that, when administered to a subject for treating a disease or condition, is sufficient to effect treatment for that disease or condition. The terms "treatment", "treating", "treat" and the like are used herein to generally refer to obtaining a desired pharmacologic and / or physiologic effect (e.g., increased permissiveness of a cell to AAV infection). Unless specifically indicated to the contrary, the term "conjugate" as described and claimed herein is defined as a heterogeneous molecule formed by the covalent attachment of one or more antibody fragment(s) to one or more polymer molecule(s), wherein the heterogeneous molecule is water soluble, i.e. soluble in physiological fluids such as blood, and wherein the heterogeneous molecule is free of any structured aggregate. A conjugate of interest is PEG (e.g., a subject AAVR polypeptide can be PEGylated, or a delivery vehicle for an AAVR polypeptide such as a nanoparticle, can be conjugated to PEG). In the context of the foregoing definition, the term "structured aggregate" refers to (1) any aggregate of molecules in aqueous solution having a spheroid or spheroid shell structure, such that the heterogeneous molecule is not in a micelle or other emulsion structure, and is not anchored to a lipid bilayer, vesicle or liposome; and (2) any aggregate of molecules in solid or insolubilized form, such as a chromatography bead matrix, that does not release the heterogeneous molecule into solution upon contact with an aqueous phase. Accordingly, the term "conjugate" as defined herein encompasses the aforementioned heterogeneous molecule in a precipitate, sediment, bioerodible matrix or other solid capable of releasing the heterogeneous molecule into aqueous solution upon hydration of the solid. EXAMPLES OF NON-LIMITING ASPECTS OF THE DISCLOSURE Aspects, including embodiments, of the present subject matter described above may be beneficial alone or in combination, with one or more other aspects or embodiments. Without limiting the foregoing description, certain non-limiting aspects of the disclosure are provided below (see SET A and SET B). As will be apparent to those of skill in the art upon reading this disclosure, each of the individually numbered aspects may be used or combined with any of the preceding or following individually numbered aspects. This is intended to provide support for all such combinations of aspects and is not limited to combinations of aspects explicitly provided below: SET A 1. A genetically modified mammalian cell with enhanced permissiveness to adeno- associated virus (AAV) infection, wherein said cell has increased levels of AAVR protein and reduced levels of SETDB1 protein relative to a corresponding cell that is not genetically modified. 2. The cell of 1, wherein the cell comprises an altered nucleotide sequence in the genomic locus that encodes the SETDB1 protein. 3. The cell of 2, wherein the altered nucleotide sequence is a genomic deletion of an exon sequence encoding SETDB1. 4. The cell of 1, wherein the cell comprises an RNAi agent or CRISPR-based agent that causes the reduced levels of the SETDB1 protein. 5. The cell of 4, wherein the RNAi agent or CRISPR-based agent is integrated into the genome of the genetically modified cell. 6. The cell of any one of 1-5, wherein the cell comprises a heterologous DNA molecule comprising a nucleotide sequence encoding the AAVR protein. 7. The cell of 6, wherein the nucleotide sequence encoding the AAVR protein is operably linked to a promoter that is also part of the heterologous DNA molecule. 8. The cell of 7, wherein the promoter is a constitutive promoter. 9. The cell of 7, wherein the promoter is a inducible promoter. 10. The cell of any one of 6-9, wherein said heterologous DNA molecule is integrated into the genome of the cell. 11. The cell of any one of 1-10, wherein said cell is a rodent cell or a human cell. 12. A method of adeno-associated virus (AAV) delivery, comprising: contacting the genetically modified mammalian cell of any one of 1-11 with an AAV particle that comprises a DNA of interest. 13. The method of 12, wherein the DNA of interest comprises a nucleotide sequence that is operably linked to a promoter and encodes a non-coding RNA or a protein. 14. The method of 12, wherein the DNA of interest comprises a nucleotide sequence encoding a cell marker. 15. The method of 14, wherein the cell marker is a fluorescent protein, a luciferase, or a drug selectable marker. 16. The method of any one of 12-15, wherein the AAV particle comprises an AAV1, AAV2, AAV3, AAV5, AAV6, AAV8, AAV9, or AAV-PHP.eB capsid protein. 17. A method of functionally titrating an adeno-associated virus (AAV) preparation, comprising: contacting a population of the genetically modified mammalian cell of any one of 1-11 with an AAV preparation, and determining a functional titer of the AAV preparation, comprising measuring the number and / or percentage of cells that were transduced by said contacting. 18. The method of 17, wherein the method comprises contacting said population with two or more (e.g., 3 or more, 4 or more, or 5 or more) different dilutions of the AAV preparation, and wherein said determining comprises measuring the number and / or percentage of cells that were transduced by said contacting for each of said different dilutions. SET B 1. A genetically modified mammalian cell with enhanced permissiveness to adeno- associated virus (AAV) infection, wherein said cell has increased levels of AAVR protein and reduced levels of SETDB1 protein relative to a corresponding cell that is not genetically modified. 2. The cell of 1, wherein the cell comprises an altered nucleotide sequence in the genomic locus that encodes the SETDB1 protein. 3. The cell of 2, wherein the altered nucleotide sequence is a genomic deletion of an exon sequence encoding SETDB1. 4. The cell of 1, wherein the cell comprises an RNAi agent or CRISPR-based agent that causes the reduced levels of the SETDB1 protein. 5. The cell of 4, wherein the RNAi agent or CRISPR-based agent is integrated into the genome of the genetically modified cell. 6. The cell of any one of 1-5, wherein the cell comprises a heterologous DNA molecule comprising a nucleotide sequence encoding the AAVR protein. 7. The cell of 6, wherein the nucleotide sequence encoding the AAVR protein is operably linked to a promoter that is also part of the heterologous DNA molecule. 8. The cell of 7, wherein the promoter is a constitutive promoter. 9. The cell of 7, wherein the promoter is a inducible promoter. 10. The cell of any one of 6-9, wherein said heterologous DNA molecule is integrated into the genome of the cell. 11. The cell of any one of 1-10, wherein said cell is a rodent cell or a human cell. 12. The cell of any one of 1-11, further comprising a CRISPR-Cas guide RNA and / or a nucleic acid encoding the CRISPR-Cas guide RNA, wherein the CRISPR-Cas guide RNA targets an AAV ITR. 13. The cell of 12, wherein the CRISPR-Cas guide RNA is a Cas9 guide RNA or a Cas12a guide RNA. 14. The cell of 12, wherein the CRISPR-Cas guide RNA is a Cas9 guide RNA that targets the sequence of any one of SEQ ID NOs: 26-50. 15. The cell of 12, wherein the CRISPR-Cas guide RNA is a Cas12a guide RNA that targets the sequence of SEQ ID NO: 56 or 57. 16. The cell of any one of 12-15, wherein the nucleic acid encoding the CRISPR-Cas guide RNA is integrated into the cell’s genome. 17. The cell of any one of 1-16, further comprising a CRISPRa fusion protein or a nucleic acid sequence encoding the CRISPRa fusion protein. 18. The cell of 17, wherein the CRISPRa fusion protein comprises a dCas9 protein fused to a transcriptional activator protein. 19. The cell of 17 or 18, wherein the nucleic acid encoding the CRISPRa fusion protein is integrated into the cell’s genome. 20. A method of adeno-associated virus (AAV) delivery, comprising: contacting the genetically modified mammalian cell of any one of 1-19 with an AAV particle that comprises a DNA of interest. 21. The method of 20, wherein the DNA of interest comprises a nucleotide sequence that is operably linked to a promoter and encodes a non-coding RNA or a protein. 22. The method of 20, wherein the DNA of interest comprises a nucleotide sequence encoding a cell marker. 23. The method of 22, wherein the cell marker is a fluorescent protein, a luciferase, or a drug selectable marker. 24. The method of any one of 20-23, wherein the AAV particle comprises an AAV1, AAV2, AAV3, AAV5, AAV6, AAV8, AAV9, or AAV-PHP.eB capsid protein. 25. A method of functionally titrating an adeno-associated virus (AAV) preparation, comprising: contacting a population of the genetically modified mammalian cell of any one of 1-19 with an AAV preparation, and determining a functional titer of the AAV preparation, comprising measuring the number and / or percentage of cells that were transduced by said contacting. 26. The method of 25, wherein the method comprises contacting said population with two or more (e.g., 3 or more, 4 or more, or 5 or more) different dilutions of the AAV preparation, and wherein said determining comprises measuring the number and / or percentage of cells that were transduced by said contacting for each of said different dilutions. 27. The method of 26, wherein said measuring comprises evaluating expression of a transgene by a CRISPRa fusion protein. The invention now being fully described, it will be apparent to one of ordinary skill in the art that various changes and modifications can be made without departing from the spirit or scope of the invention. EXPERIMENTAL The following examples are put forth so as to provide those of ordinary skill in the art with a complete disclosure and description of how to make and use the present invention, and are not intended to limit the scope of what the inventors regard as their invention nor are they intended to represent that the experiments below are all or the only experiments performed. Efforts have been made to ensure accuracy with respect to numbers used (e.g., amounts, temperature, etc.) but some experimental errors and deviations should be accounted for. Unless indicated otherwise, parts are parts by weight, molecular weight is weight average molecular weight, temperature is in degrees Centigrade, and pressure is at or near atmospheric. All publications and patent applications cited in this specification are herein incorporated by reference as if each individual publication or patent application were specifically and individually indicated to be incorporated by reference. The present invention has been described in terms of particular embodiments found or proposed by the present inventor to comprise preferred modes for the practice of the invention. It will be appreciated by those of skill in the art that, in light of the present disclosure, numerous modifications and changes can be made in the particular embodiments exemplified without departing from the intended scope of the invention. For example, due to codon redundancy, changes can be made in the underlying DNA sequence without affecting the protein sequence. Moreover, due to biological functional equivalency considerations, changes can be made in protein structure without affecting the biological action in kind or amount. All such modifications are intended to be included within the scope of the appended claims. Example 1 The results provided here demonstrate that the subject genetically modified cells (e.g., mammalian cells) can be beneficial in research applications (e.g., for producing consistent results between AAV lots or experiments) as well as in clinical applications (e.g., to ensure quality of AAV-based therapeutics). Recently, a role for the HUSH complex in silencing gene expression of retrotransposons, lentivirus, retroviral DNA, and more recently Adeno-associated virus has been uncovered. In order to determine what components of the HUSH complex were critical for inhibiting AAV transduction and transgene expression, clonal KOs of multiple HUSH complex components were generated (FAM208A, MPP8, NP220, PPHLN1, and SETDB1). Cells were transduced with AAV2, AAV8, or AAV9 expressing Firefly luciferase (luc) at an MOI of 20,000 and luciferase activity was assessed at 48 hr post transduction (Fig.1a). We found that there was a significant increase in transduction when compared to wild- type (WT) cells in the SETDB1-KO cells after transduction with all three serotypes. NP220-KO cells also had increased transduction compared to WT cells when transduced by AAV9-luc. We went on to test multiple single cell clones of SETDB1 KO, which all showed significantly increased transduction by AAV2-luc when compared to WT cells (Fig.1b). We selected SETDB1 KO clone 2-7 to continue all future experiments, which will now be referred to as SETDB1 KO. In order to determine if expression of other transgenes would also be increased in SETDB1 KO cells, we transduced WT and KO SETDB1 KO cells with AAV2-GFP and assessed transduction by flow cytometry at 48 hours post transduction (Fig.1c). We found that that there was a significant increase in both the number of transduced cells (Fig.1d) and the mean fluorescent intensity in the transduced cell population (Fig.1e). In order to determine if the transduction phenotype seen in SETDB1 KO cells was receptor dependent, we assessed transduction by AAV4, which has been shown to transduce cells in an AAVR-independent manner. We found that transduction by AAV4 was significantly increased in SETDB1 KO cell (Fig.1f), suggesting that the SETDB1 KO phenotype is receptor independent. We also wanted to determine if the promoter used to drive the expression of the transgene was important for the observed phenotype. Since it has been recently reported that the HUSH complex specifically silences intronless genes, we compared transduction of WT and SETDB1 KO cells with AAV9 with either a CMV, which is intronless, or CAG, which contains the chicken beta-actin intron (Fig.1g). We found that the difference in transduction using the AAV9-CAG-GFP was similar in the WT and SETDB1 KO cells, suggesting SETDB1 is not silencing the CAG-GFP transgene as efficiently as the CMV-GFP transgene. After demonstrating that SETDB1 KO cells have significantly better transduction for many AAV serotypes and multiple transgenes, we wanted to determine if combination of SETDB1 KO and AAVR overexpression could produce a cell line that could be efficiently transduced by recombinant AAV vectors. We had previously generated AAVR overexpressing cell lines using the pLenti-AAVR-FLAG construct (Fig.2a). These cell lines have enhanced transduction by multiple AAV serotypes, especially those without a well-defined secondary attachment factor, such as AAV8 and AAV9 (Fig 2b). We went on to generate clonal cell lines that overexpress AAVR only (HeLa+AAVR clone #9) or that have SETDB1 KO with AAVR overexpression (HeLa SETDB1 KO + AAVR clone #2 and clone #4). We tested the transduction of HT1080 cells, which have been described as more permissible to AAV transduction, along with HeLa cells, SETDB1 KO, cells overexpressing AAVR and SETDB1 KO with AAVR overexpression. When transduced with AAV2-CMV-GFP (Fig.2c) there was little difference between groups, although the most transduction was seen in SETDB1 KO cells. When transduction with AAV9-CMV-GFP (Fig.2d) was assessed at 24 hours, we found SETDB1 KO cells had a 5.4-fold increase in transduction and HeLa+AAVR cells had a 22-fold increase in transduction. Both HeLa SETDB1 KO + AAVR clones had much higher transduction with clone #2 having a 757-fold increase and clone #4 having a 1161-fold increase in transduction compared to WT cells. These fold changes would suggest a more than additive increase in transduction, suggesting a synergistic effect of SETDB1 KO with AAVR overexpression. We also tested transduction in these cells using AAV9-CAG-GFP (Fig.2e). As expected, there was little difference in the WT versus SETDB1-KO cells (1.6-fold), while HeLa+AAVR cells showed a 29-fold increase in transduction. Again, both SETDB1 KO + AAVR clones showed a large increase in transduction (clone #2, 198-fold; clone #4, 245-fold). Thus, the combination of reduced expression of SETDB1 (e.g., via SETDB1 KO) and increased expression of AAVR (e.g., via overexpression of AAVR) resulted in unexpectedly high levels of permissiveness to AAV. These data suggested that the combination of reduced expression of SETDB1 (e.g., via SETDB1 KO) and increased expression of AAVR (e.g., via overexpression of AAVR) would be a good candidate for functional titration of recombinant AAV vectors. We went on to further characterize transduction using HeLa SETDB1 KO + AAVR clone #4 (now referred to as HeLa SETDB1 KO + AAVR). In order to test the HeLa SETDB1 KO + AAVR cell line for transduction by multiple AAV serotypes we tested AAV1, AAV2, AAV3, AAV5, AAV6, AAV8, AAV9 with a CMV-GFP transgene and AAV9 and AAV-PHP.eB with a CAG-GFP transgene and tracked transduction over time using an MOI of 1,000 vg (viral genomes) per cell. Transduction was tracked every hour for 24 hours (Fig.3a). All AAV serotypes tested showed significant increases in transduction in the HeLa SETDB1 KO + AAVR cells compared to WT cells or cells only overexpressing AAVR. Transduction at 24 hours showed a clear benefit of the combination cell line in the functional titration of AAV (Fig.3b). Thus, the combination of reduced expression of SETDB1 (e.g., via SETDB1 KO) and increased expression of AAVR (e.g., via overexpression of AAVR) ((e.g., a SETDB1 KO + AAVR cell line) can be used to perform functional titration of AAV vectors, which previously were unable to be titrated in cell culture systems. We wanted to demonstrate the ability to dilute AAV and titrate different serotypes using the HeLa SETDB1 + AAVR cell line. To do this we titrated AAV2, 5, 6, 8, and 9 with a CMV- GFP transgene along with AAV9 encoding a CAG-GFP transgene at and MOI of 100,000 vg per cell to 1 vg per cell at 10-fold dilutions. All serotypes were titrated on HeLa SETDB1 + AAVR while AAV9-CMV-GFP was also titrated on WT HeLa cells. Transduction events were calculated at 24 hours post transduction (Fig.4a). We found that the titer of each AAV serotype could be correlated with MOI for all serotypes when using HeLa SETDB1 KO + AAVR cells, while WT cells were not transduced well at any MOI tested. To use the HeLa SETDB1 KO + AAVR cells for calculation of functional transduction units in the AAV stock solutions used, we plotted the input titer (vg / well) against the functional titer in transduction units per well (TU / well). This produced a linear relationship for AAV2 (R2=0.938), AAV5 (R2=0.986), AAV6 (R2=0.907), AAV8 (R2=0.835), AAV9 (R2=0.968), AAV9- CAG (R2=0.982) in HeLa SETDB1 KO + AAVR cells. While HeLa (WT) cells did not show a correlation for AAV9 (R2=0.002). This functional titer (TU / mL) for each AAV stock solution used was calculated using the MOI = 1,000 (C) and 10,000 (D) points, which gave similar results. This shows the ability to use HeLa SETDB1 KO + AAVR cells to determine a functional titer for multiple AAV serotypes. This should hold true for titration of all AAVR dependent serotypes. For AAV with other transgenes, alternative functional readout assays could be used based on immunofluorescence, ELISA, or other relevant assays. To show alternative methods of quantification, transduction of AAV2 and AAV9 was also accessed by flow cytometry. Transduction by AAV2 was measured at 24 hours post transduction at each MOI (vg / cell) and the percentage of GFP+ cells was calculated (Fig.4e). The mean fluorescent intensity (MFI), which correlated to the amount of transgene expression in a transduced cell, was also calculated for all GFP+ cells at each MOI (Fig.4f). We found that the SETDB1 KO + AAVR cells were better transduced by AAV2 at lower MOIs, although there was not a large difference in % of cells transduced. There was a significant difference in the MFI of infected cells at all MOI tested, suggesting that this cell line allows for higher levels of per-cell transgene expression. In parallel, flow cytometry was also used to assess transfection by AAV9 and the percentage of transduced cells (Fig.4g) and MFI of GFP fluorescence in transduced cells (Fig.4h) were measured. Only a small number of cells were found to be transduced in WT HeLa cells at MOI 100,000 and 10,000. There were significant differences in the number of transduced cells and the MFI of transduced cells in the HeLa SETDB1 KO + AAVR cells compared to WT HeLa cells at these MOIs. The quantification by flow cytometry correlates well with the transduction seen using live cell imaging. Methods Construction of plasmids The AAVR full length construct was previously generated as described (Pillay et al., Nature 530, 108–112 (2016)). In short, the Gibson assembly reaction kit (New England Biolabs, UK) was used to insert the gene of interest into a lentiviral-based vector, pLenti-CMV-Puro- DEST (w118-1) (plasmid #17452), digested with EcoRV to remove the DEST cassette (a gift from Eric Campeau)10. AAVR was amplified from a KIAA0319L cDNA clone (clone ID # 3843301) (purchased from GE Dharmacon, Lafayette, CO), which was later corrected to match the annotated human genome. The following primers were used to generate PCR products from the human KIAA0319L cDNA to be cloned directly into pLenti CMV Puro DEST. The reverse primer added a 1x FLAG tag to the gene: AAVR full-length: 5′- ATGTGTGGTGGAATTCTGCAGATACCATGGAGAAGAGGCTGGG – 3′ (SEQ ID NO: 14) and 5′- CGGCCGCCACTGTGCTGGATTTACTTATCGTCGTCATCCTTGTAATCCAGGATCTCCTCCC GC – 3’ (SEQ ID NO: 15). This produced the plasmid pLenti-AAVR-FLAG-PURO, which has now been deposited at Addgene by our lab (Plasmid #166716). A sgRNA (CGTCCTCAGAGCTACTGTCC) (SEQ ID NO: 16) was selected to target the SETDB1 gene on chromosome 1 at position 150930029 on the negative strand. This sgRNA was cloned into the pSpCas9(BB)-2A-GFP. pSpCas9(BB)-2A-GFP (PX458) was a gift from Feng Zhang (Addgene plasmid # 48138; http: / / n2t.net / addgene:48138 ; RRID:Addgene_48138). This produced the plasmid PX458-sgRNA-SETDB1. Cell lines production H1-HeLa were obtained from ATCC (CRL-1958). HT-1080 cells were obtained from ATCC (CCL-121).293FT were obtained from ThermoFisher (R70007). Cells were grown in DMEM^+^10% FBS ^+ pen / strep (D10) (ThermoFisher, 11995073; Sigma, 4333). AAVR overexpressing cells were previously generated as described above. In short, lentivirus was produced using pLenti-AAVR-FLAG-PURO and 293FT cells and utilized to transduce the respective cell lines overnight. Cells stably expressing the gene of interest were selected by treatment with 1–3 μg / ml puromycin over 2 days (InvivoGen). SETDB1-KO cells were generated through transfection of the PX458-sgRNA-SETDB1 plasmid into H1-HeLa cells. After 2 days, GFP+ cells were single cell sorted into individual wells of a 96-well plate at the Stanford Shared FACS facility. After individual cell clones were isolated, SETDB1 KO was confirmed by western blot and Sanger sequencing an amplified genome fragment around the target site. SETDB1-KO clone 2-7 was used further modifications. To generate the H1-HeLa SETDB1-KO + AAVR cell line, SETDB1-KO clone 2-7 was transduced with lentivirus generated using pLenti-AAVR-FLAG-PURO and 293FT cells. After 48 hours, cells were selected using puromycin (InvivoGen). Cells were grown and resuspended in 90% FBS and 10% DMSO and banked in liquid nitrogen for future use. To isolated clonal cell lines, populations of H1-Hela + AAVR and H1-HeLa SETDB1-KO + AAVR were each single cell sorted into 396-well plates per line at the Stanford Shared FACS facility. After single colonies grew, cells were replica plated into 2x 96-well plates. Clones were selected for high transfectability by transduction with scAAV9-GFP (UNC Vector Core) at an MOI=1,000. Clones with high percentage of GFP transduction were grown to large scale and HeLa SETDB1-KO + AAVR clone #4 was selected for high transfectability and general growth characteristics. Workflow of cell line development is outlined in FIG.5. Transduction experiments Purified, titered stocks of recombinant AAV1, AAV2, AAV3, AAV4, AAV6, AAV8 and AAV9 vectors encoding reporter genes under the CMV promoter were purchased from the University of North Carolina Chapel Hill Gene Therapy Center Vector Core. AAV vectors encoding EGFP were self-complementary and those encoding firefly luciferase single-stranded. Purified, titered stocks of recombinant, single-stranded AAV9 and AAV-PHP.eB vectors encoding GFP under the CAG promoter were obtained from Addgene. pAAV-CAG-GFP was a gift from Edward Boyden (Addgene viral prep # 37825-AAV9 and Addgene viral prep # 37825- PHPeB; “http:” followed by “ / / ” followed by “n2t.” followed by “net / addgene” followed by “:37825”; RRID:Addgene_37825 and). All input titers were determined by the supplier using qPCR to detect viral genomes (vg) in the sample. AAV transduction experiments were carried out in 96-well plates with cells plated in 200µl of DMEM+10%FBS+Pen / Strep at day -1 to obtain an approximate density of 50-70% confluence at the time of transduction. The approximate number of cells at the time of transduction was 2x104vg / well. AAV was diluted in 50µl of DMEM at the specified MOI based on viral genomes and added to the 96-well plates. Functional titers were calculated by determining the number of transduction events (GFP+ cells) at 24 hours post transduction and dividing this by the input volume of the AAV stock virus to calculate vg / mL. For firefly luciferase experiment, luciferase activity was assessed using the Luciferase Assay System (Promega, E1500). Luciferase activity was read using a Glomax luciferase plate reader (Promega). GFP fluorescence was tracked over time using the Incucyte S3 Live Cell Analysis Instrument (Sartorius). Confluence and fluorescence were tracked every 1-2 hours and the number of GFP+ cells in each well were calculated using the Incucyte Analysis Software. The number of GFP+ cells measured by the Incucyte are described as transduction units (TU). In some experiments, transduction was assessed by flow cytometry on a LSRFortessa X-20 (BD Biosciences) and % of GFP+ singlet cells were calculated. Mean fluorescent intensity (MFI) was calculated for the GFP+ cell populations only. FIG.6 illustrates confirmation that the nucleotide sequence of the SETDB1 genomic locus was altered. FIG.7 illustrates a Western blot that was used to confirm SETDB1 knockout (KO) (resulting in reduced SETDB1 protein expression). FIG.8 is an example of titration of AAV9 at different time points. Example 2 Adeno-associated virus (AAV) vectored products are currently leading candidates for gene therapy applications with multiple approved products and many more in clinical trials. Currently, about 50% of AAV gene therapy vectors in clinical trials include a promoter that is cell type-specific1. There is ongoing research identifying and characterizing promoters that can increase specificity of AAV vectors beyond what can be done with capsid modification2. One issue that arises from the use cell type-specific promoters is that in vitro titration often requires use of primary cells for testing of AAV vectors in vitro. The addition of promoter-specific CRISPR activation (CRISPRa) mediated transgene expression has been shown to allow for AAVs with cell type-specific prompters to transduce cells that would normally not be transduced3. This method currently requires the production of a new cell line for each AAV promoter to be tested. Development of a universal cell line that allows for promoter agnostic transduction by AAV would be a useful tool for performing functional titration of AAV in a research or clinical setting. We have developed a cell line that builds of our current technology that incorporated AAV receptor (AAVR) overexpression with HUSH complex inactivation. This cell line includes CRISPR activation (CRISPRa) machinery that is targeted to the AAV inverted terminal repeat (ITR) using guide RNAs (gRNA) specific to this conserved sequence. This cell line will allow for efficient in vitro transduction by most serotypes of AAVs and allows for the use of both universal and cell-type specific promoters. In order to make a cell line that allows for promoter agnostic transduction, we incorporated dCas9-VP64, which was developed for CRISPR activation (CRISPRa)4, into our cell line that was optimized to allow for efficient in vitro titration by most AAV serotypes (HeLa SETB1 KO+AAVR) (Fig.1a). We the introduced additional factors that will increase transcriptional activation (PP7, p65, and HSF1) that will be delivered with the specific guide RNA (gRNA) based on previous studies that have shown this to increase targeted gene expression5. We designed gRNA that targeted various regions of the AAV2 ITR, which is used for most gene therapy vectors and should be conserved through most AAVs that are being use in research and in a clinical setting (Fig.1b). We went on to single cell clone and characterize cell lines that incorporated ITR targeting guides #1, #2, and #3 to produce HeLa SETDB1 KO+AAVR+CRISPRa+ITR guide #1, #2, and #3 cells. Cell lines developed above were tested using a AAV8 that expresses a transgene with either a universal promoter (CMV) or a neuronal specific promoter (hSyn)6,7. HeLa SETDB1 KO+AAVR+CRISPRa cells with or without ITR guide#1 were transduced with AAV8-CMV-GFP or AAV8-hSyn-mCh (Fig.2a). Transduction was assessed at 48 hours post transduction, which showed efficient transduction in both cell lines with the CMV promoter, while the hSyn promoter containing AAV only transduced the cell line containing the ITR targeting gRNA. In order to compare targeting of the ITR by different guides, cell lines with incorporated ITR guides #1, #2, and #3 were transduced with AAV8-hSyn-mCh and transduction was tracked over time (Fig. 2b). Cells without gRNA showed no transduction, while ITR guide #1 showed the highest levels of transduction followed by ITR guide #3 then ITR guide #2. Showing that targeting the ITR with any of the 3 selected guides allowed for transduction using AAV encoding a transgene downstream of the cell type-specific hSyn promoter. Each of these cell lines was single cell cloned to identify cells that were highly transduced by AAV9-hSyn-mCh. These cell lines were used for the remaining experiments. Each clonal cell line was transduced with AAV8-hSyn-mCh or AAV9-hSyn-mCh (Fig.2c). All three cell lines were efficiently transduced compared to the cell line that did not have a gRNA present. In order to test the specificity of each cell line, we generated plasmids that did not have a promoter present upstream of a Renilla luciferase (Rluc) gene but incorporated a target sequence for one of the ITR gRNAs. We also generated plasmids that incorporated the guide sequence but did not include the PAM sequence required for Cas9 targeting as a negative control. HeLa SETDB1 KO+AAVR+CRISPRa without a gRNA or with ITR guides #1, #2, or #3 were transfected with plasmids that contained one of the 3 target sequences with or without a PAM sequence. The ratio of PAM containing versus PAM deleted (PAMdel) was reported for each cell line (Fig.2d). This data shows that gene expression for each cell line is specific for the guide RNA that is incorporated. The previous experiments suggested that the HeLa SETDB1+AAVR+CRIPRa+ITR guide #1 has the best transduction using AAV with the hSyn promoter. To test the ability of this cell line to measure in vitro transduction by additional AAVs, we tested transduction using multiple AAV serotypes (AAV-DJ, AAV8, AAV5, AAV1, AAV9) with various cell type-specific promoters (hSyn, CaMKIIa, D2SP, hMORp). HeLa SETDB1+AAVR+CRIPRa with or without ITR guide #1 were transduced and transduction was measured at 72 hours by flow cytometry (Fig.3a). The percentage of transduce cells was measured (Fig.3b), and there were low levels of transduction for many of the AAVs in the cell line without the ITR #1 gRNA, but the transduction was significantly higher with the ITR #1 gRNA present. This includes no measurable transduction for AAV5-hMORp-eYFP, AAV1-hMORp-eYFP, and AAV9-hSyn-mCh without the guide present. We also measured transduction using live cell imaging for the same AAVs along with AAVs that had universal promoter (CMV and CAG) (Fig.3c). We found that the detection of transduced cells was reduced for many of the AAVs tested using this system with efficient detection of transduction for the cell type-specific promoters only in the cells with the ITR guide #1. The newly developed cell lines that incorporate the CRISPRa driven transgene expression with the cell line that incorporates AAV receptor overexpression and HUSH complex inactivation will allow for in vitro titration of most AAV vectors used in research and in clinical development. This universal cell line will allow for efficient transduction using most AAVs without requiring cell lines that transduce well in vitro or the use of broadly active promoters. Methods Plasmid The CRISPR activation plasmid used to generate the parental cell line was lenti-dCAS9- VP64_Blast (Addgene plasmid #61425)4. The additional transcription factors and guide RNA were delivered using the pXPR_502 (Addgene plasmid #96923)5. Guide RNAs targeting the AAV2 ITR were cloned into pXPR_502 targeting the sequences (CCGACGCCCGGGCTTTGCCC (SEQ ID NO: 33), AGTGGCCAACTCCATCACTA (SEQ ID NO: 48), and CACTGAGGCCGGGCGACCAA (SEQ ID NO: 40)). The puromycin resistance gene was replaced by BleoR resistance gene, which confers resistance to the bleomycin / phleomycin family of antibotics including Zeocin. Cloning was performed using Gibson assembly using a synthetic DNA construct as an insert. To test the specificity of the ITR targeting guides, pGL4.10[luc2] (Promega, E6651) was modified to include the target sequence for the gRNAs used for each of the cell lines with or without the PAM sequence modified: Target Sequence SEQ ID NO Cell line production H1 HeLa SETDB1 KO+AAVR clone #4 were used as the progenitor cell line for all cell lines used for the ITR activation cell line development. Cells were first transduced with lentivirus generated with plent-dCAS9-VP64_Blast plasmid. Cells were selected using blastmycin for ~1 week. After selection, cells were transduced with lentivirus generated using pXPR_502 + ITR guide #1, #2 or #3, which contain a Zeocin resistance gene. Cells were selected using Zeocin for ~2 weeks. Cell lines were tested as a population, followed by future single cell cloning using FACS. Single cell clones were tested for transduction using AAV8-hSyn-mCh, and highly transducible cell lines selected that included each of the gRNAs, resulted in the HeLa SETDB1 KO+AAVR+CRISPRa+ITR guide #1, #2, and #3 cell lines that were tested. Transduction and transfection experiments Purified, titered stocks of AAV were used for all experiments. AAV8-hSyn-mCh and AAV9-hSyn-mCh were obtained for the UNC vector core. AAV-DJ-hSyn1-EYFP, AAV8-hSyn- eYFP, AAV-DJ-CaMKIIa-eYFP, AAV8-CaMKIIa-eYFP-NRN, AAV8-D2SP-eYFP-WPRE, AAV5- hMORp-eYF,P AAV5-hMORp-eYFP, AAV8-hSyn-mChAAV9-hSyn-mCh, AAV-DJ-CMV-hrGFP, and AAV-DJ-CAG-hrGFP were obtained for the Stanford Gene Vector and Virus Core. Cells were transduced in 96-well plates and transduction was measured by flow cytometry (BD LSR II.UV) at a terminal endpoint and tracked over time using and Incucyte live-cell imager (Sartorius). Transfection with the pGL4-Rluc vectors was performed to determine specificity for the guide ITR containing cell lines. Cells were transduced with each of the plasmids that had the guide target sequence incorporated with or without a mutated PAM sequence. After 48 hours, Renilla luciferase activity was assessed using the Renilla luciferase assay system (Promega, E2820) and the Luciferase activity was read using a Glomax luciferase plate reader (Promega). References 1. Au, H. K. E., Isalan, M. & Mielcarek, M. Gene therapy advances: A meta-analysis of AAV usage in clinical settings. Front. Med. (Lausanne) 8, (2022). 2. Domenger, C. & Grimm, D. Next-generation AAV vectors-do not judge a virus (only) by its cover. Hum. Mol. Genet.28, R3–R14 (2019). 3. https: / / www.cell.com / molecular-therapy-family / methods / fulltext / S2329-0501(19)30031-2. 4. Konermann, S. et al. Genome-scale transcriptional activation by an engineered CRISPR- Cas9 complex. Nature 517, 583–588 (2015). 5. Sanson, K. R. et al. Optimized libraries for CRISPR-Cas9 genetic screens with multiple modalities. Nat. Commun.9, 1–15 (2018). 6. Kügler, S. et al. Neuron-specific expression of therapeutic proteins: evaluation of different cellular promoters in recombinant adenoviral vectors. Mol. Cell. Neurosci.17, 78–96 (2001). 7. Kügler, S., Lingor, P., Schöll, U., Zolotukhin, S. & Bähr, M. Differential transgene expression in brain cells in vivo and in vitro from AAV-2 vectors with small transcriptional control units. Virology 311, 89–95 (2003). Although the foregoing invention has been described in some detail by way of illustration and example for purposes of clarity of understanding, it is readily apparent to those of ordinary skill in the art in light of the teachings of this invention that certain changes and modifications may be made thereto without departing from the spirit or scope of the appended claims. Accordingly, the preceding merely illustrates the principles of the invention. It will be appreciated that those skilled in the art will be able to devise various arrangements which, although not explicitly described or shown herein, embody the principles of the invention and are included within its spirit and scope. Furthermore, all examples and conditional language recited herein are principally intended to aid the reader in understanding the principles of the invention and the concepts contributed by the inventors to furthering the art, and are to be construed as being without limitation to such specifically recited examples and conditions. Moreover, all statements herein reciting principles, aspects, and embodiments of the invention as well as specific examples thereof, are intended to encompass both structural and functional equivalents thereof. Additionally, it is intended that such equivalents include both currently known equivalents and equivalents developed in the future, i.e., any elements developed that perform the same function, regardless of structure. Moreover, nothing disclosed herein is intended to be dedicated to the public regardless of whether such disclosure is explicitly recited in the claims. The scope of the present invention, therefore, is not intended to be limited to the exemplary embodiments shown and described herein. Rather, the scope and spirit of present invention is embodied by the appended claims. In the claims, 35 U.S.C. §112(f) or 35 U.S.C. §112(6) is expressly defined as being invoked for a limitation in the claim only when the exact phrase "means for" or the exact phrase "step for" is recited at the beginning of such limitation in the claim; if such exact phrase is not used in a limitation in the claim, then 35 U.S.C. § 112 (f) or 35 U.S.C. §112(6) is not invoked.

Claims

CLAIMS What is claimed is:

1. A genetically modified mammalian cell with enhanced permissiveness to adeno- associated virus (AAV) infection, wherein said cell has increased levels of AAVR protein and reduced levels of SETDB1 protein relative to a corresponding cell that is not genetically modified.

2. The cell of claim 1, wherein the cell comprises an altered nucleotide sequence in the genomic locus that encodes the SETDB1 protein.

3. The cell of claim 2, wherein the altered nucleotide sequence is a genomic deletion of an exon sequence encoding SETDB1.

4. The cell of claim 1, wherein the cell comprises an RNAi agent or CRISPR-based agent that causes the reduced levels of the SETDB1 protein.

5. The cell of claim 4, wherein the RNAi agent or CRISPR-based agent is integrated into the genome of the genetically modified cell.

6. The cell of any one of claims 1-5, wherein the cell comprises a heterologous DNA molecule comprising a nucleotide sequence encoding the AAVR protein.

7. The cell of claim 6, wherein the nucleotide sequence encoding the AAVR protein is operably linked to a promoter that is also part of the heterologous DNA molecule.

8. The cell of claim 7, wherein the promoter is a constitutive promoter.

9. The cell of claim 7, wherein the promoter is a inducible promoter.

10. The cell of any one of claims 6-9, wherein said heterologous DNA molecule is integrated into the genome of the cell.

11. The cell of any one of claims 1-10, wherein said cell is a rodent cell or a human cell.

12. The cell of any one of claims 1-11, further comprising a CRISPR-Cas guide RNA and / or a nucleic acid encoding the CRISPR-Cas guide RNA, wherein the CRISPR-Cas guide RNA targets an AAV ITR.

13. The cell of claim 12, wherein the CRISPR-Cas guide RNA is a Cas9 guide RNA or a Cas12a guide RNA.

14. The cell of claim 12, wherein the CRISPR-Cas guide RNA is a Cas9 guide RNA that targets the sequence of any one of SEQ ID NOs: 26-50.

15. The cell of claim 12, wherein the CRISPR-Cas guide RNA is a Cas12a guide RNA that targets the sequence of SEQ ID NO: 56 or 57.

16. The cell of any one of claims 12-15, wherein the nucleic acid encoding the CRISPR-Cas guide RNA is integrated into the cell’s genome.

17. The cell of any one of claims 1-16, further comprising a CRISPRa fusion protein or a nucleic acid sequence encoding the CRISPRa fusion protein.

18. The cell of claim 17, wherein the CRISPRa fusion protein comprises a dCas9 protein fused to a transcriptional activator protein.

19. The cell of claim 17 or claim 18, wherein the nucleic acid encoding the CRISPRa fusion protein is integrated into the cell’s genome.

20. A method of adeno-associated virus (AAV) delivery, comprising: contacting the genetically modified mammalian cell of any one of claims 1-19 with an AAV particle that comprises a DNA of interest.

21. The method of claim 20, wherein the DNA of interest comprises a nucleotide sequence that is operably linked to a promoter and encodes a non-coding RNA or a protein.

22. The method of claim 20, wherein the DNA of interest comprises a nucleotide sequence encoding a cell marker.

23. The method of claim 22, wherein the cell marker is a fluorescent protein, a luciferase, or a drug selectable marker.

24. The method of any one of claims 20-23, wherein the AAV particle comprises an AAV1, AAV2, AAV3, AAV5, AAV6, AAV8, AAV9, or AAV-PHP.eB capsid protein.

25. A method of functionally titrating an adeno-associated virus (AAV) preparation, comprising: contacting a population of the genetically modified mammalian cell of any one of claims 1-19 with an AAV preparation, and determining a functional titer of the AAV preparation, comprising measuring the number and / or percentage of cells that were transduced by said contacting.

26. The method of claim 25, wherein the method comprises contacting said population with two or more (e.g., 3 or more, 4 or more, or 5 or more) different dilutions of the AAV preparation, and wherein said determining comprises measuring the number and / or percentage of cells that were transduced by said contacting for each of said different dilutions.

27. The method of claim 26, wherein said measuring comprises evaluating expression of a transgene by a CRISPRa fusion protein.