Compositions and methods for generation and secretion of AAV particles

Abstract

Disclosed herein are variant membrane-associated accessory proteins (MAAPs) and methods of using variant MAAP variants to generate AAV particles and improve AAV secretion and / or AAV egress.

Description

COMPOSITIONS AND METHODS FOR GENERATION AND SECRETION OF AAV PARTICLESI. CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Application No. 63 / 624,779 filed 24 January 2024 and to U.S. Provisional Application No. 63 / 653,271 filed 30 May 2024, each of which is incorporated herein by reference in its entirety.II. REFERENCE TO THE SEQUENCE LISTING

[0002] The Sequence Listing submitted 24 January 2025 as an XML file named “23-3002- WO_SL”, created on 24 January 2025 and having a size of 909,312 bytes is hereby incorporated by reference pursuant to 37 C.F.R. § 1.52(e)(5).III. BACKGROUND OF THE INVENTION

[0003] Recombinant adeno-associated virus (rAAV) vectors are a leading gene delivery platform, and several rAAV-mediated therapies have recently been approved. Despite these advances in the clinic, rAAV vector manufacturing remains a challenge. Adeno-associated viruses (AAV) are non-enveloped, parvoviruses that rely on a helper virus for transitioning from a latent to lytic cycle. Upon co-infection with a helper such as adenovirus, herpesvirus, or papillomavirus, the dependoparvovirus AAV undergoes a transition from latent to lytic life cycle, exploiting the hijacked host cell machinery. A significant nucleolar buildup of AAV particles has been demonstrated following synthesis and replication of the single-stranded DNA (ssDNA) AAV genome, capsid assembly and packaging, all of which occur within nuclear loci. Notably, unlike other autonomous parvoviruses that undergo a lytic cycle, AAV does not induce marked cytopathic effects (CPE). Nevertheless, some recombinant AAV serotypes appear to be secreted into cell culture media prior to lysis, albeit with variable efficiency. Although the cellular egress of virions is thought to be primarily driven by overexpression of Adenoviral or Herpesvirus proteins, exactly how AAV exits the cell upon transitioning into this phase of replication was previously unclear.

[0004] Because AAVs are commonly used for gene therapy, understanding the mechanism driving cellular secretion of AAVs and extracellular vesicles generally is needed. Accordingly, there is a need to improve the manufacturing of AAV for gene therapy and / or gene editing applications.IV. BRIEF SUMMARY OF THE INVENTION

[0005] Disclosed herein is a variant membrane-associated accessory protein (MAAP) comprising the sequence of any one of SEQ ID NO:331 - SEQ ID NO:360.

[0006] Disclosed herein is a variant membrane-associated accessory protein (MAAP) comprising the sequence of any one of SEQ ID NO:346 - SEQ ID NO:360. In an aspect of any one of SEQ ID NO:346 - SEQ ID NO:360, each amino acid at positions 4-12 can comprise any amino acid.

[0007] Disclosed herein is a variant membrane-associated accessory protein (MAAP) with a mutation at one or more of positions 4-12, positions 49-57, and / or positions 87-95 with respect to the amino acid sequence of SEQ ID NO:01 or SEQ ID NO:31.

[0008] Disclosed herein is a variant membrane-associated accessory protein (MAAP) with a mutation at one or more of positions 4-12, positions 49-57, and / or positions 87-95 with respect to the amino acid sequence of SEQ ID NO:02 or SEQ ID NO:32.

[0009] Disclosed herein is a variant membrane-associated accessory protein (MAAP) with a mutation at one or more of positions 4-12, positions 49-57, and / or positions 87-95 with respect to the amino acid sequence of SEQ ID NO: 03.

[0010] Disclosed herein is a variant membrane-associated accessory protein (MAAP) with a mutation at one or more of positions 4-12, positions 49-57, and / or positions 87-95 with respect to the amino acid sequence of SEQ ID NO:04 or SEQ ID NO:34.

[0011] Disclosed herein is a variant membrane-associated accessory protein (MAAP) with a mutation at one or more of positions 4-12, positions 49-57, and / or positions 87-95 with respect to the amino acid sequence of SEQ ID NO: 05 or SEQ ID NO:35.

[0012] Disclosed herein is a variant membrane-associated accessory protein (MAAP) with a mutation at one or more of positions 4-12, positions 49-57, and / or positions 87-95 with respect to the amino acid sequence of SEQ ID NO:06 or SEQ ID NO:36.

[0013] Disclosed herein is a variant membrane-associated accessory protein (MAAP) with a mutation at one or more of positions 4-12, positions 49-57, and / or positions 87-95 with respect to the amino acid sequence of SEQ ID NO:07 or SEQ ID NO:37.

[0014] Disclosed herein is a variant membrane-associated accessory protein (MAAP) with a mutation at one or more of positions 4-12, positions 49-57, and / or positions 87-95 with respect to the amino acid sequence of SEQ ID NO: 08 or SEQ ID NO:38.

[0015] Disclosed herein is a variant membrane-associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:361 or SEQ ID NO:615.

[0016] Disclosed herein is a nucleic acid comprising a nucleotide sequence encoding a disclosed variant membrane-associated accessory protein (MAAP). Disclosed herein is a nucleic acid encoding a disclosed variant membrane-associated accessory protein (MAAP).

[0017] Disclosed herein is a variant membrane-associated accessory protein (MAAP) with a mutation at one or more of positions 4-12, positions 49-57, and / or positions 87-95 with respect to the amino acid sequence of SEQ ID NO:09 or SEQ ID NO:39.

[0018] Disclosed herein is a variant membrane-associated accessory protein (MAAP) with a mutation at one or more of positions 4-12, positions 49-57, and / or positions 87-95 with respect to the amino acid sequence of SEQ ID NO: 10 or SEQ ID NO:40.

[0019] Disclosed herein is a variant membrane-associated accessory protein (MAAP) with a mutation at one or more of positions 4-12, positions 49-57, and / or positions 87-95 with respect to the amino acid sequence of SEQ ID NO: 11 or SEQ ID NO:41.

[0020] Disclosed herein is a variant membrane-associated accessory protein (MAAP) with a mutation at one or more of positions 4-12, positions 49-57, and / or positions 87-95 with respect to the amino acid sequence of SEQ ID NO: 12 or SEQ ID NO:42.

[0021] Disclosed herein is a variant membrane-associated accessory protein (MAAP) with a mutation at one or more of positions 4-12, positions 49-57, and / or positions 87-95 with respect to the amino acid sequence of SEQ ID NO: 13 or SEQ ID NO:43.

[0022] Disclosed herein is a variant membrane-associated accessory protein (MAAP) with a mutation at one or more of positions 4-12, positions 49-57, and / or positions 87-95 with respect to the amino acid sequence of SEQ ID NO: 14 or SEQ ID NO:44.

[0023] Disclosed herein is a variant membrane-associated accessory protein (MAAP) with a mutation at one or more of positions 4-12, positions 49-57, and / or positions 87-95 with respect to the amino acid sequence of SEQ ID NO: 15 or SEQ ID NO:45.

[0024] Disclosed herein is a producer cell comprising a disclosed nucleic acid encoding a disclosed MAAP. Disclosed herein is a producer cell expressing a disclosed nucleic acid encoding a disclosed MAAP.

[0025] Disclosed herein is a method of generating AAV particles, the method comprising: delivering to one or more cells genetically modified to express a variant MAAP (i) a nucleic acid comprising a nucleotide sequence encoding an AAV capsid; and (ii) an rAAV comprising a nucleotide sequence encoding one or more transgenes or one or more gene products; culturing in a suitable culture medium the one or more cells; and harvesting from the culture medium the AAV particles secreted by the cells.

[0026] Disclosed herein is a method of increasing AAV secretion, the method comprising delivering to one or more cells a disclosed nucleic acid or a disclosed rAAV; and culturing in a suitable culture medium the one or more cells, wherein a disclosed encoded variant MAAPis expressed during the culturing step, wherein the secretion of AAV is increased compared to the secretion of AAV in the one or more cells having wild-type MAAP.V. BRIEF DESCRIPTION OF THE FIGURES

[0027] FIG. 1A is a schematic of the WT AAV genome showing Rep and Cap genes with MAAP encoded in a +1 open reading frame in the VP1 region.

[0028] FIG. IB shows a sequence alignment of the MAAPs from AAV serotypes 1 to 13 along with AAVrh.8 and AAVrh.10. An annotated multiple-sequence alignment of the AAP sequences of 15 AAV serotypes is shown. Various regions are annotated above the alignment. Predicted secondary structural (SS) elements (strand, helix) for the sequence and amino acid numbering are displayed below the alignments.

[0029] FIG. 2 shows the AlphaFol d2 Prediction of MAAP8 in ribbon view. Highlighted regions denote library locations (Library 1, Library 2, and Library 3).

[0030] FIG. 3A - FIG. 3D shows the overview of the directed evolution strategy. FIG. 3A shows a schematic of the rAAV genome containing the MAAP library under the control of an EFla promoter with an HRPT1 stuff er sequence to ensure optimal genome size. FIG. 3B shows the workflow demonstration of the parental virus generation in suspension cells. FIG. 3C shows that transfection passaging track relied on output from the parental virus to be subcloned before transfection into HEKG2 cells for virus preparation. FIG. 3D show that within the serial viral passaging track, virus from the parental round was cycled on new HEKG2 cells.

[0031] FIG. 4 shows the enrichment plots of the transfection track of serial passaging across the cycled libraries, (e.g., for each round of evolution). On the Y-axis is fold enrichment (% abundance of a given sequence in one round compared to the % abundance of that same sequence in a prior round). On the X-axis is read depth (i.e., the number of reads a given sequence has by next generation sequencing). Crosshairs are set at (102, 10°) as an arbitrary cutoff, with 100 reads chosen as sufficient, and a fold change of 1 denotes no change in abundance between rounds. The arrow represents the wildtype sequence in that respective library (left (Library 1), middle (Library 2), and right (Library 3)). The top panels represent Round 1, while the bottom panels represent Round 2.

[0032] FIG. 5 shows the enrichment plots of the infectious track of serial passaging across the cycled libraries, (e.g., for each round of evolution). On the Y-axis is fold enrichment (% abundance of a given sequence in one round compared to the % abundance of that same sequence in a prior round). On the X-axis is read depth (i.e., the number of reads a given sequence has by next generation sequencing). Crosshairs are set at (102, 10°) as an arbitrary cutoff, 100 reads was chosen as sufficient, and a fold change of 1 denotes no change inabundance between rounds. The arrow represents the wildtype sequence in that respective library (left (Library 1), middle (Library 2), and right (Library 3)). The top panels represent Round 1, while the bottom panels represent Round 2.

[0033] FIG. 6A - FIG. 6C show the commonalities between the transfection track of serial passaging and infectious track of serial passaging. Venn diagrams of the overlap between the transfection and infectious passaging tracks for Library 1 (FIG. 6A), Library 2 (FIG. 6B), and Library 3 (FIG. 6C). A subset of the overlap (top sequences) is listed in Table 2 (Library 1), Table 3 (Library 2), and Table 4 (Library 3).

[0034] FIG. 7A - FIG. 7B shows rescue of MAAP secretion with total DNase protected viral genomes quantified in the supernatant for AAV8 (FIG. 7A) and AAV9 (FIG. 7B) represented as a percent of the total vector produced (black). Total DNase protected viral genomes quantified in the cell lysate represented as a percent of the total vector produced (grey).

[0035] FIG. 8 shows that in addition to improving the titers of secreted virus, the evolved variants improve the percentage of secreted viral genomes.

[0036] FIG. 9 shows that total viral genomes were calculated, and the percentage of secreted viral genomes was determined by dividing the viral genomes in the supernatant by the total viral genomes produced (supernatant + cell lysate).

[0037] FIG. 10 shows the data normalized to the natural MAAP control and fold-change in secretion, which was calculated by dividing the percent secreted for each variant by the natural MAAP condition,

[0038] FIG. 11A - FIG. 11B show the evolved MAAP candidates Improved secreted capsid concentration. To quantify capsid concentration, virus conditioned supernatant was analyzed using an AAV9-specific ELISA (ADK9). Capsid concentrations were interpolated from a standard curve generated with known AAV9 capsid quantities

[0039] FIG. 12 shows that mass photometry revealed comparable particle heterogeneity for AAVs secreted with evolved variants. Mass photometry revealed that AAV particle heterogeneity produced using engineered MAAP trans-complementation was comparable to that of control MAAP. Three days post-transfection, viral particles were purified from the cell culture supernatant using AAVX affinity purification. The samples were then buffer- exchanged and analyzed via mass photometry.

[0040] FIG. 13 shows that viruses produced using engineered MAAP variants had no significant differences in transduction efficiency compared to controls. AAV9 particles containing a CBa-driven luciferase transgene were generated in HEK293 cells using MAAP trans-complementation with the engineered variants. HEK293 cells were subsequentlytransduced at a multiplicity of infection of 1E5, and luminescence was measured 72 hours posttransduction. FIG. 13 shows that no significant differences in transduction efficiency were observed.

[0041] FIG. 14A - FIG. 14B show evolved candidates are predicted to have increased amphipathicity and correspondingly more robust cell membrane interactions. Helical wheel schematics show increasingly structured amphipathic helices corroborated by a greater hydrophobicity score. Helical wheels were generated using pepwheel by EMBOSS with the amphipathic residue option on. Hydrophobicity scores were generated using HeliQuest). Computational structural prediction indicated that evolved MAAP candidates appear more structured in the engineered region, confirming the increased propensity to form an alpha-helix. The C-terminal region of the MAAP protein was modeled using AlphaFold3, highlighting structural convergence in the engineered sequences.

[0042] FIG. 15 shows the scrambled region from the library is denoted in blue.

[0043] FIG. 16 provides a schematic of lentivirus transfer plasmid. In FIG. 16, the following apply: 5’ LTR (Long Terminal Repeat of HIV-1); HIV-1 (Packaging Signal from HIV-1); RRE (Rev response element); gp41 (gp-41 antigen); cPPT / CTS (central polypurine tract and central termination sequence of HIV-1); 4x Tet Operator (Tet operator for rTetR gene); mCMV promoter (human cytomegalovirus immediate early promoter); MAAP8 and variants thereof (MAAP from AAV serotype 8 and variants of said protein); UbC promoter (Human Ubiquitin C promoter); rTetR (Tet-On system, binds to the Tet Operators to modulate transcription); IRES (internal ribosome entry site of encephalomyocarditis virus); BSD (blasticidin resistance gene), and 3 ’LTR (long terminal repeat from HIV-1).

[0044] FIG. 17 shows that stable MAAP expressing cell lines demonstrating selective induction. Monoclonal isolates of TetOn-MAAP-HA producer cells were subject to doxycycline (Doxy.) or control treatment. 48 hours post treatment, cells were lysed with RIPA buffer supplemented with HALT protease inhibitors. Immunoblotting was performed to identify positive clones, with clones 1 - 4 representing individual monoclonal isolates.

[0045] FIG. 18 shows the timing of MAAP induction modulated AAV secretion. Induction of MAAP at different timepoints demonstrates differences in viral titers. X-axis indicates time of tetracycline addition

[0046] FIG. 19A - FIG. 19D show that the experimental array revealed optimal transfection and induction conditions for enhanced rAAV production. Four parameters were evaluated for their role in improving AAV secretion in a MAAP8 inducible setting. Parameters evaluated include concentration of Rep / Cap plasmid (FIG. 19A), time of induction post-transfection(FIG. 19B), doxycycline concentration (FIG. 19C), and time of harvest post-induction (FIG. 19D) Asterisk denotes optimal conditions while the dotted line denotes baseline from triple transfection.VI. DETAILED DESCRIPTION OF THE INVENTION

[0047] The present disclosure describes isolated nucleic acids, viral vectors, viral capsid proteins, viral particles, plasmids, cells, kits, pharmaceutical formulations, and compositions thereof and methods of using the disclosed compositions. It is to be understood that the inventive aspects of which are not limited to specific synthetic methods unless otherwise specified, or to particular reagents unless otherwise specified, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular aspects only and is not intended to be limiting. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, example methods and materials are now described.

[0048] 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. 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.A. DEFINITIONS

[0049] Before the present compounds, compositions, articles, systems, devices, vectors, and / or methods are disclosed and described, it is to be understood that they are not limited to specific synthetic methods unless otherwise specified, or to particular reagents unless otherwise specified, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular aspects only and is not intended to be limiting. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, example methods and materials are now described.

[0050] This disclosure describes inventive concepts with reference to specific examples. However, the intent is to cover all modifications, equivalents, and alternatives of the inventive concepts that are consistent with this disclosure.

[0051] As used in the specification and the appended claims, the singular forms “a”, “an”, and “the” include plural referents unless the context clearly dictates otherwise.

[0052] The phrase “consisting essentially of’ limits the scope of a claim to the recited components in a composition or the recited steps in a method as well as those that do notmaterially affect the basic and novel characteristic or characteristics of the claimed composition or claimed method. The phrase “consisting of’ excludes any component, step, or element that is not recited in the claim. The phrase “comprising” is synonymous with “including”, “containing”, or “characterized by”, and is inclusive or open-ended. “Comprising” does not exclude additional, unrecited components or steps.

[0053] In an aspect, when referring to any numerical value, the term “about” means a value falling within a range that is ± 10% of the stated value.

[0054] Ranges can be expressed herein as from “about” one particular value, and / or to “about” another particular value. When such a range is expressed, a further aspect includes from the one particular value and / or to the other particular value. Similarly, when values are expressed as approximations, by use of the antecedent “about,” it will be understood that the particular value forms a further aspect. It will be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint and independently of the other endpoint. It is also understood that there are a number of values disclosed herein, and that each value is also herein disclosed as “about” that particular value in addition to the value itself. For example, if the value “10” is disclosed, then “about 10” is also disclosed. It is also understood that each unit between two particular units are also disclosed. For example, if 10 and 15 are disclosed, then 11, 12, 13, and 14 are also disclosed.

[0055] In an aspect, the term “approximately” or “about,” as applied to one or more values of interest, refers to a value that is similar to a stated reference value. In an aspect, the term “approximately” or “about” refers to a range of values that fall within 25%, 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, or less in either direction of the stated reference value unless otherwise stated or otherwise evident from the context.

[0056] In an aspect, the term “in vitro” refers to events or experiments that occur in an artificial environment, e.g., in a petri dish, test tube, cell culture, etc., rather than within a multicellular organism. In an aspect, the term “in vivo” refers to events or experiments that occur within a multicellular organism.

[0057] In an aspect, the term “comparable” in the context of a particular value and a reference value means that the particular value is consistent with the reference value, or that the deviation from the reference value (above or below) is at most 10%.

[0058] References in the specification and concluding claims to parts by weight of a particular element or component in a composition denotes the weight relationship between the element or component and any other elements or components in the composition or article for which apart by weight is expressed. Thus, in a compound containing 2 parts by weight component X and 5 parts by weight component Y, X and Y are present at a weight ratio of 2:5, and are present in such ratio regardless of whether additional components are contained in the compound.

[0059] In an aspect, the terms “optional” or “optionally” means that the subsequently described event or circumstance can or cannot occur, and that the description includes instances where said event or circumstance occurs and instances where it does not. In an aspect, a disclosed method can optionally comprise one or more additional steps, such as, for example, repeating an administering step or altering an administering step.

[0060] In an aspect, the term “subject” refers to the target of administration. In an aspect, a subject can be a human being. The term “subject” includes domesticated animals (e.g., cats, dogs, etc.), livestock (e.g., cattle, horses, pigs, sheep, goats, etc.), and laboratory animals (e.g., mouse, rabbit, rat, guinea pig, fruit fly, etc.). Thus, the subject of the herein disclosed methods can be a vertebrate, such as a mammal, a fish, a bird, a reptile, or an amphibian. Alternatively, the subject of the herein disclosed methods can be a human, non-human primate, horse, pig, rabbit, dog, sheep, goat, cow, cat, guinea pig, or rodent. The term does not denote a particular age or sex, and thus, adult and child subjects, as well as fetuses, whether male or female, are intended to be covered. In an aspect, a subject can be a human patient. In an aspect, a subject can have a disease, a disorder, an infection, a symptom, and / or a complication, be suspected of having a disease, a disease, a disorder, an infection, a symptom, and / or a complication, or be at risk of developing a disease, a disorder, an infection, a symptom, and / or a complication. For example, a subject can have risk factors for developing a disease, a disorder, an infection, a symptom, and / or a complication. Risk factors can include, but are not limited to the following: cancer, chronic kidney disease, chronic obstructive pulmonary disease, an immunocompromised state (weakened immune system) from solid organ transplant, obesity (body mass index [BMI] of 30 or higher), serious heart conditions (e.g., heart failure, coronary artery disease, or cardiomyopathies), sickle cell disease, diabetes mellitus, asthma (moderate- to-severe), cerebrovascular disease (i.e., disease that affects blood vessels and blood supply to the brain), cystic fibrosis, hypertension or high blood pressure, immunocompromised state (weakened immune system) from blood or bone marrow transplant, immune deficiencies, HIV, use of corticosteroids, or use of other immune weakening medicines, neurologic conditions (e.g. dementia, Alzheimer’s), liver disease, pregnancy, pulmonary fibrosis (having damaged or scarred lung tissues), tobacco use, smoking, thalassemia. A subject can be at risk due to genetic predisposition, employment type (e.g., a health care worker, a miner), attendance at a specific location (e.g., school), attendance at social events (e.g., sporting events, concerns, religiousservices, political rallies and events, social justice rallies, marches, and events, etc.), by use of public transportation or public services, exposure to natural and man-made disasters (e.g., Chernobyl, 9 / 11 attacks, etc.).

[0061] In an aspect, “effective amount” and “amount effective” can refer to an amount that is sufficient to achieve the desired result such as, for example, the treatment and / or prevention of a disease, a disorder, an infection, a symptom, and / or a complication, or a suspected disease, disorder, infection, symptom, and / or complication. For example, a “therapeutically effective amount” refers to an amount (i.e., vector genome / body weight or vg / kg) that is sufficient to achieve the desired therapeutic result or to have an effect on undesired symptoms, but is generally insufficient to cause adverse side effects. In an aspect, “therapeutically effective amount” means an amount of a disclosed composition that (i) treats the particular disease, disorder, and / or infection, (ii) attenuates, ameliorates, or eliminates one or more symptoms of the particular disease, condition, and / or disorder, or (iii) delays the onset of one or more symptoms of the particular disease, condition, and / or disorder described herein. The specific therapeutically effective dose level for any particular patient will depend upon a variety of factors including the disorder being treated and the severity of the disorder; the specific disclosed compositions and / or a pharmaceutical preparation comprising one or more disclosed compositions, or methods employed; the age, body weight, general health, sex and diet of the patient; the time of administration; the route of administration; the rate of excretion of the disclosed compositions and / or a pharmaceutical preparation comprising one or more disclosed compositions employed; the duration of the treatment; drugs used in combination or coincidental with a disclosed compositions and / or a pharmaceutical preparation comprising one or more disclosed compositions employed, and other like factors well known in the medical arts. For example, it is well within the skill of the art to start doses of a disclosed composition and / or a pharmaceutical preparation comprising one or more disclosed composition at levels lower than those required to achieve the desired therapeutic effect and to gradually increase the dosage until the desired effect is achieved. If desired, then the effective daily dose can be divided into multiple doses for purposes of administration. Consequently, a single dose of a disclosed compositions and / or a pharmaceutical preparation comprising one or more disclosed compositions, or methods can contain such amounts or submultiples thereof to make up the daily dose. The dosage can be adjusted by the individual physician in the event of any contraindications. Dosage can vary, and can be administered in one or more dose administrations daily, for one or several days. Guidance can be found in the literature for appropriate dosages for given classes of pharmaceutical products. In further various aspects, apreparation can be administered in a “prophylactically effective amount”; that is, an amount effective for prevention of a disease, a disorder, an infection, a symptom, and / or a complication.

[0062] In an aspect, “control” refers a standard or reference condition, against which results are compared (e.g., WT MAAP expression). In an aspect, a control is used at the same time as a test variable or subject to provide a comparison. In an aspect, a control is a historical control that has been performed previously, a result or amount that has been previously known, or an otherwise existing record. A control may can be a positive or negative control.

[0063] In an aspect, a therapeutically effective amount of disclosed vector can be delivered via intravenous (IV) administration and can comprise a range of about 1 x IO10vg / kg to about 2 x 1014vg / kg. In an aspect, for example, a disclosed vector can be administered at a dose of about 1 x 1011to about 8 x 1013vg / kg or about 1 x 1012to about 8 x 1013vg / kg. In an aspect, a disclosed vector can be administered at a dose of about 1 x 1013to about 6 x 1013vg / kg. In an aspect, a disclosed vector can be administered at a dose of at least about 1 x IO10, at least about 5 x IO10, at least about 1 x 1011, at least about 5 x 1011, at least about 1 x 1012, at least about 5 x 1012, at least about 1 x 1013, at least about 5 x 1013, or at least about 1 x 1014vg / kg. In an aspect, a disclosed vector can be administered at a dose of no more than about 1 x IO10, no more than about 5 x IO10, no more than about 1 x 1011, no more than about 5 x 1011, no more than about 1 x 1012, no more than about 5 x 1012, no more than about 1 x 1013, no more than about 5 x 1013, or no more than about 1 x 1014vg / kg. In an aspect, a disclosed vector can be administered at a dose of about 1 x 1012vg / kg. In an aspect, a disclosed vector can be administered at a dose of about 1 x 1011vg / kg. In an aspect, a therapeutically effective amount of disclosed vector can be delivered via intravenous (IV) administration and can comprise a range of about 1 x 1012vg per subject total to about 1 x 1017vg per subject total. In an aspect, a therapeutically effective amount of disclosed vector can be delivered via intravenous (IV) administration and can comprise a range of about 1 x 1012vg per subject total, about 1 x 1013vg per subject total, about 1 x 1014vg per subject total, about 1 x 1015vg per subject total, about 1 x 1016vg per subject total, or about 1 x 1017vg per subject total. In an aspect, a disclosed vector can be administered in a single dose, or in multiple doses (such as 2, 3, 4, 5, 6, 7, 8, 9 or 10 doses) as needed for the desired therapeutic results. In an aspect, a therapeutically effective amount of disclosed vector can comprise a range determined by a skilled person. In an aspect, a therapeutically effective amount of disclosed vector can be delivered via intravenous (IV) administration and can comprise a range of about 1 x 1012vg per subject total to about 1 x 1017vg per subject total. In an aspect, a therapeutically effective amount of disclosed vector can be delivered via intravenous (IV) administration and can comprise a range of about 1 x1012vg per subject total, about 1 x 1013vg per subject total, about 1 x 1014vg per subject total, about 1 x 1015vg per subject total, about 1 x 1016vg per subject total, or about 1 x 1017vg per subject total.

[0064] In an aspect, the term “diagnosed” means having been subjected to a physical examination by a person of skill, for example, a physician, and found to have a disease, a disorder, an infection, a symptom, and / or a complication that can be diagnosed or treated by one or more of the disclosed nucleic acids, the disclosed vectors, the disclosed capsid proteins, the disclosed variant MAAPs, and disclosed compositions thereof, the disclosed pharmaceutical preparations, and / or the disclosed methods. For example, “suspected of having” can mean having been subjected to a physical examination by a person of skill, for example, a physician, and found to have a condition that can likely be treated by one or more of the disclosed nucleic acids, the disclosed vectors, the disclosed capsid proteins, the disclosed variant MAAPs, and disclosed compositions thereof, the disclosed pharmaceutical preparations, and / or the disclosed methods.

[0065] The words “treat” or “treating” or “treatment” refer to therapeutic or medical treatment wherein the object is to slow down (lessen), ameliorate, and / or diminish an undesired physiological change, disease, pathological condition, or disorder in a subject. In an aspect, beneficial or desired clinical results include, but are not limited to, alleviation of symptoms, diminishment of extent of disease, stabilized (i.e., not worsening) state of disease, delay or slowing of disease progression, amelioration or palliation of the disease state, and remission (whether partial or total), whether detectable or undetectable. “Treatment” can also mean prolonging survival as compared to expected survival if not receiving treatment. Treatment may not necessarily result in the complete clearance of an infection but may reduce or minimize complications, the side effects, and / or the progression of a disease, a disorder, an infection, a symptom, and / or a complication. The success or otherwise of treatment can be monitored by physical examination of the subject as well as cytopathological, DNA, and / or mRNA detection techniques. The words “treat” or “treating” or “treatment” include palliative treatment, that is, treatment designed for the relief of symptoms rather than the curing of the disease, pathological condition, or disorder; preventative treatment, that is, treatment directed to minimizing or partially or completely inhibiting the development of the associated disease, pathological condition, or disorder; and supportive treatment, that is, treatment employed to supplement another specific therapy directed toward the improvement of the associated disease, pathological condition, or disorder. In various aspects, the term covers any treatment of a subject, including a mammal (e.g., a human), and includes: (i) preventing the undesiredphysiological change, disease, pathological condition, or disorder from occurring in a subject that can be predisposed to the disease but has not yet been diagnosed as having it; (ii) inhibiting the physiological change, disease, pathological condition, or disorder, z.e., arresting its development; or (iii) relieving the physiological change, disease, pathological condition, or disorder, z.e., causing regression of the disease. For example, in an aspect, treating an infection can reduce the severity of an established infection in a subject by 1%- 100% as compared to a control (such as, for example, a subject not having the disease, the disorder, the infection, the symptom, and / or the complication. In an aspect, treating can refer to a 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% reduction in the severity of an established disease, disorder, infection, symptom, and / or complication. In an aspect, treating can refer to 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100% reduction of one or more symptoms. It is understood that treatment does not necessarily refer to a cure or complete ablation or eradication of the disease, disorder, infection, symptom, and / or complication. However, in an aspect, treatment can refer to a cure or complete ablation or eradication of the disease, disorder, infection, symptom, and / or complication.

[0066] Methods and techniques to monitor a subject’s response to a disclosed method can comprise qualitative (or subjective) means as well as quantitative (or objective) means. In an aspect, qualitative means (or subjective means) can comprise a subject’s own perspective. For example, a subject can report how he / she is feeling, whether he / she has experienced improvements and / or setbacks, whether he / she has experienced an amelioration or an intensification of one or more symptoms, or a combination thereof. In an aspect, quantitative means (or objective means) can comprise methods and techniques that include, but are not limited to, the following: (i) fluid analysis (e.g., tests of a subject’s fluids including but not limited to aqueous humor and vitreous humor, bile, blood, blood serum, breast milk, cerebrospinal fluid, cerumen (earwax), digestive fluids, endolymph and perilymph, female ejaculate, gastric juice, mucus (including nasal drainage and phlegm), peritoneal fluid, pleural fluid, saliva, sebum (skin oil), semen, sweat, synovial fluid, tears, vaginal secretion, vomit, and urine), (ii) imaging (e.g., ordinary x-rays, ultrasonography, radioisotope (nuclear) scanning, computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), and angiography), (iii) endoscopy (e.g., laryngoscopy, bronchoscopy, esophagoscopy, gastroscopy, GI endoscopy, coloscopy, cystoscopy, hysteroscopy, arthroscopy, laparoscopy, mediastinoscopy, and thoracoscopy), (iv) analysis of organ activity(e.g., electrocardiography (ECG), electroencephalography (EEG), and pulse oximetry), (v) biopsy (e.g., removal of tissue samples for microscopic evaluation), and (vi) genetic testing.

[0067] A “patient” refers to a subject afflicted with a disease, disorder, infection, symptom, and / or complication. In an aspect, a patient can refer to a subject that has been diagnosed with or is suspected of having a disease, disorder, infection, symptom, and / or complication. In an aspect, a patient can refer to a subject that has been diagnosed with or is suspected of having an established disease, disorder, infection, symptom, and / or complication and is seeking treatment or receiving treatment.

[0068] In an aspect, the term “prevent” or “preventing” or “prevention” refers to precluding, averting, obviating, forestalling, stopping, or hindering something from happening, especially by advance action. It is understood that where reduce, inhibit, or prevent are used herein, unless specifically indicated otherwise, the use of the other two words is also expressly disclosed. In an aspect, preventing a disease, disorder, infection, symptom, and / or complication is intended. The words “prevent” and “preventing” and “prevention” also refer to prophylactic or preventative measures for protecting or precluding a subject (e.g., an individual) not having a given infection related complication from progressing to that complication. Individuals in which prevention is required include those who have an infection.

[0069] In an aspect, the terms “administering” and “administration” refer to any method of providing one or more of the disclosed nucleic acids, the disclosed vectors, the disclosed capsid proteins, the disclosed variant MAAPs, and disclosed compositions thereof, the disclosed pharmaceutical preparations, and / or the disclosed methods to a subject. Such methods are well known to those skilled in the art and include, but are not limited to, the following: oral administration, transdermal administration, administration by inhalation, nasal administration, topical administration, intravaginal administration, ophthalmic administration, intraaural administration, otic administration, inter utero administration, intracerebral administration, rectal administration, sublingual administration, buccal administration, and parenteral administration, including injectable such as intravenous administration, intra-arterial administration, intramuscular administration, and subcutaneous administration. Administration can be continuous or intermittent.

[0070] In an aspect, “modifying the method” can comprise modifying or changing one or more features or aspects of one or more steps of a disclosed method. For example, in an aspect, a method can be altered by changing the amount of one or more of the disclosed nucleic acids, the disclosed vectors, the disclosed capsid proteins, the disclosed variant MAAPs, and disclosed compositions thereof, or the disclosed pharmaceutical preparations administered to asubject, or by changing the frequency of administration, or by changing the duration of time of administration or between administrations to a subject.

[0071] In an aspect, “concurrently” means (1) simultaneously in time, or (2) at different times during the course of a common treatment schedule.

[0072] In an aspect, the term “contacting” refers to bringing one or more of the disclosed nucleic acids, the disclosed vectors, the disclosed capsid proteins, the disclosed variant MAAPs, and disclosed compositions thereof, the disclosed pharmaceutical preparations, and / or the disclosed methods with a target area or intended target area in such a manner that the one or more disclosed nucleic acids, vectors, compositions, and / or pharmaceutical preparation can exert an effect on the intended target or targeted area either directly or indirectly.

[0073] In an aspect, “determining” can refer to measuring or ascertaining the presence and severity of a disease, disorder, infection, symptom, and / or complication. Methods and techniques used to determining the presence and / or severity of a disease, disorder, infection, symptom, and / or complication are typically known to the medical arts. For example, the art is familiar with the ways to identify and / or diagnose the presence, severity, or both of a disease, disorder, infection, symptom, and / or complication.

[0074] In an aspect, the term “pharmaceutically acceptable carrier” refers to sterile aqueous or nonaqueous solutions, dispersions, suspensions or emulsions, as well as sterile powders for reconstitution into sterile injectable solutions or dispersions just prior to use. Examples of suitable aqueous and nonaqueous carriers, diluents, solvents, or vehicles include water, ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol and the like), carboxymethylcellulose and suitable mixtures thereof, vegetable oils (such as olive oil) and injectable organic esters such as ethyl oleate. In an aspect, a pharmaceutical carrier employed can be a solid, liquid, or gas. In an aspect, examples of solid carriers can include lactose, terra alba, sucrose, talc, gelatin, agar, pectin, acacia, magnesium stearate, and stearic acid. In an aspect, examples of liquid carriers can include sugar syrup, peanut oil, olive oil, and water. In an aspect, examples of gaseous carriers can include carbon dioxide and nitrogen. In preparing a disclosed composition for oral dosage form, any convenient pharmaceutical media can be employed. For example, water, glycols, oils, alcohols, flavoring agents, preservatives, coloring agents and the like can be used to form oral liquid preparations such as suspensions, elixirs and solutions; while carriers such as starches, sugars, microcrystalline cellulose, diluents, granulating agents, lubricants, binders, disintegrating agents, and the like can be used to form oral solid preparations such as powders, capsules and tablets. Because of their ease of administration, tablets and capsules are the preferred oral dosage units whereby solidpharmaceutical carriers are employed. Optionally, tablets can be coated by standard aqueous or nonaqueous techniques. Proper fluidity can be maintained, for example, by the use of coating materials such as lecithin, by the maintenance of the required particle size in the case of dispersions and by the use of surfactants. These compositions can also contain adjuvants such as preservatives, wetting agents, emulsifying agents and dispersing agents. Prevention of the action of microorganisms can be ensured by the inclusion of various antibacterial and antifungal agents such as paraben, chlorobutanol, phenol, sorbic acid and the like. It can also be desirable to include isotonic agents such as sugars, sodium chloride and the like. Prolonged absorption of the injectable pharmaceutical form can be brought about by the inclusion of agents, such as aluminum monostearate and gelatin, which delay absorption. Injectable depot forms are made by forming microencapsule matrices of the drug in biodegradable polymers such as polylactide-polyglycolide, poly(orthoesters) and poly(anhydrides). Depending upon the ratio of drug to polymer and the nature of the particular polymer employed, the rate of drug release can be controlled. Depot injectable formulations are also prepared by entrapping the drug in liposomes or microemulsions that are compatible with body tissues. The injectable formulations can be sterilized, for example, by filtration through a bacterial-retaining filter or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved or dispersed in sterile water or other sterile injectable media just prior to use. Suitable inert carriers can include sugars such as lactose. Desirably, at least 95% by weight of the particles of the active ingredient have an effective particle size in the range of 0.01 to 10 micrometers.

[0075] In an aspect, the term “derivative” refers to a compound having a structure derived from the structure of a parent compound and whose structure is sufficiently similar to those disclosed herein and based upon that similarity, would be expected by one skilled in the art to exhibit the same or similar activities and utilities as the claimed compounds, or to induce, as a precursor, the same or similar activities and utilities as the claimed compounds.

[0076] In an aspect, the term “analog” refers to a compound having a structure derived from the structure of a parent compound and whose structure is sufficiently similar to those disclosed herein and based upon that similarity, would be expected by one skilled in the art to exhibit the same or similar activities and utilities as the claimed compounds, or to induce, as a precursor, the same or similar activities and utilities as the claimed compounds.

[0077] In an aspect, AAV genomes or AAV vectors, when present in a suitable producer cell and in the presence of AAV Rep and Cap proteins, can replicate and package into viral particles, particularly infectious viral particles. AAV “rep” and “cap” genes refer topolynucleotide sequences encoding replication and encapsidation proteins of adeno-associated virus. AAV rep and cap are referred to herein as AAV “packaging genes.”

[0078] In an aspect, “adeno-associated virus” or “AAV” refers to a viral particle consisting of at least one AAV capsid protein VP1, VP2, and / or VP3, preferably all capsid proteins of a wild-type AAV, and an encapsidated polynucleotide AAV genome or AAV vector. An AAV of the invention can typically be a recombinant AAV. An AAV can be a non-naturally occurring AAV. The AAV can comprise one or more heterologous polynucleotides, i.e., polynucleotides other than wild-type AAV polynucleotides, such as transgenes. An example of a transgene is a therapeutic gene.

[0079] In an aspect, “recombinant,” as applied to a polynucleotide means that the polynucleotide is the product of various combinations of cloning, restriction or ligation steps, and other procedures that result in a construct that is distinct from a polynucleotide found in nature. In an aspect, a recombinant virus can be a viral particle comprising a recombinant polynucleotide.

[0080] In an aspect, “AAV” is an abbreviation for adeno-associated virus, and may be used to refer to the virus itself or derivatives thereof. The term covers all subtypes and both naturally occurring and recombinant form.

[0081] A “helper virus” for AAV refers to a virus that allows 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. 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.

[0082] In an aspect, “helper virus function” can refer to function (or functions) encoded in a helper virus genome that allow AAV replication and packaging (in conjunction with other requirements for replication and packaging described herein). In an aspect, “helper virus function” can 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.

[0083] In an aspect, “transfer plasmid” or “pTransfer” contains the viral genome. The pTransfer further comprises two ITRs, a transgene, gene of interest, and / or payload, a promoter, and one or more cis-regulatory elements (e.g., Lox sites, WPRE, poly A, etc.).

[0084] In an aspect, a “control element” or “control sequence” is a nucleotide sequence involved in an interaction of molecules that contributes to the functional regulation of a polynucleotide, including replication, duplication, transcription, splicing, translation, or degradation of the polynucleotide. The regulation may affect the frequency, speed, or specificity of the process, and may be enhancing or inhibitory in nature. Control elements known in the art include, for example, transcriptional regulatory sequences such as promoters and enhancers. A promoter is a DNA region capable under certain conditions of binding RNA polymerase and initiating transcription of a coding region usually located downstream (in the 3’ direction) from the promoter.

[0085] In an aspect, a “transgene” is a polynucleotide encoding a gene that is delivered to a cell by a vector.

[0086] A “gene” refers to a polynucleotide containing at least one open reading frame that is capable of encoding a particular gene product after being transcribed, and sometimes also translated. The term “gene” or “coding sequence” refers to a nucleotide sequence in vitro or in vivo that encodes a gene product. In some instances, the gene consists or consists essentially of coding sequence, that is, sequence that encodes the gene product. In other instances, the gene comprises additional, non-coding, sequence that permits, facilitates or directs the cellular expression machinery to express the encoded product. Such sequences can include, but are not limited to promoters, enhancers, transcriptional termination and / or poly(A) addition signals, and elements that affect transcript processing and / or stability. A gene may or may not include regions preceding and following the coding region, e.g. 5’ untranslated (5’ UTR) or “leader” sequences and 3’ UTR or “trailer” sequences, as well as intervening sequences (introns) between individual coding segments (exons).

[0087] A “gene product” is a molecule resulting from expression of a particular gene or fragment thereof. Gene products can include, for example, a polypeptide, an aptamer, an interfering RNA, an mRNA, and the like. A “gene product” can be a polypeptide, peptide, protein or interfering RNA including short interfering RNA (siRNA), miRNA or small hairpin RNA (shRNA). In an aspect, a disclosed gene product can be a therapeutic gene product, e.g., a therapeutic protein or a therapeutic RNA.

[0088] In an aspect, a “therapeutic gene” refers to a gene that, when expressed, produces a therapeutic gene product that confers a beneficial effect on the cell or tissue in which it ispresent, or on a mammal in which the gene is expressed. Examples of beneficial effects include amelioration of a sign or symptom of a condition or disease, prevention or inhibition of a condition or disease, or conferral of a desired characteristic. Therapeutic genes include, but are not limited to, genes that correct a genetic deficiency in a cell or mammal.

[0089] AAV can be replication competent or replication incompetent. By “replication competent” is meant that the virus or viral particle is infectious and capable of replication in a suitable infected cell. In an aspect, the disclosed AAV can be replication-incompetent.

[0090] In an aspect, the term “viral vector” refers to a nucleic acid vector construct that includes at least one element of viral origin and has the capacity to be packaged into a viral particle. The viral vector can contain a nucleic acid (e.g., a transgene, a gene of interest, and / or a payload) encoding a polypeptide as described herein in place of non-essential viral genes. The vector and / or particle can be utilized for the purpose of transferring nucleic acids into cells either in vitro or in vivo. Numerous forms of viral vectors are known in the art.

[0091] In an aspect, an “expression vector” is a vector comprising a region which encodes a polypeptide of interest, and is used for effecting the expression of the protein in an intended target cell. An expression vector also comprises control elements operatively linked to the encoding region to facilitate expression of the protein in the target. The combination of control elements and a gene or genes to which they are operably linked for expression is sometimes referred to as an “expression cassette,” a large number of which are known and available in the art or can be readily constructed from components that are available in the art.

[0092] In an aspect, an “AAV virus” or “AAV viral particle” refers to a viral particle composed of at least one AAV capsid protein such as VP1 (typically by all of the capsid proteins of a wild- type AAV) and an encapsidated polynucleotide rAAV vector. If the particle comprises a heterologous polynucleotide (i.e. a polynucleotide other than a wild-type AAV genome, such as a transgene to be delivered to a mammalian cell), it is typically referred to as a “recombinant AAV vector particle” or simply a “rAAV vector”. Thus, production of a rAAV particle necessarily includes production of a rAAV vector, as such a vector is contained within a rAAV particle.

[0093] In an aspect, “viral capsid polypeptide” refers to the proteinaceous shell or coat of a viral particle. A viral capsid polypeptide permits packaging or assembly of the capsid polypeptide into a viral particle that is competent for delivery of nucleic acid to the host cell. Capsids function to encapsidate, protect, transport, and release into a host cell a viral genome. Capsids are generally comprised of oligomeric structural subunits of a polypeptide of the viral capsid polypeptides.

[0094] In an aspect, “encap si dated” means enclosed within a viral capsid. As an example, the AAV genome comprises three overlapping sequences which encode capsid proteins, VP1, VP2 and VP3, which start from one promoter, p40. The AAV capsid is composed of a mixture of VP1, VP2, and VP3 totaling 60 monomers arranged in icosahedral symmetry in a ratio of 1 : 1 : 10.

[0095] In an aspect, “packaging” refers to a series of intracellular events that result in the assembly and encapsidation of an AAV particle.

[0096] In an aspect, “payload” refers to a nucleic acid that is encapsidated within a viral vector, e.g., an AAV vector. A payload nucleic acid can encode a polypeptide, an inhibitory RNA, an antibody or antibody reagent, an oligonucleotide, or a miRNA. In an aspect, a “payload” refers to one or more polynucleotides or polynucleotide regions encoded by or within a viral genome or an expression product of such polynucleotide or polynucleotide region, e.g., a transgene, a polynucleotide encoding a polypeptide or multi-polypeptide or a modulatory nucleic acid or regulatory nucleic acid. In an aspect, a disclosed payload can comprise any nucleic acid that is useful for modulating the expression in a target cell transduced or contacted with the AAV particle carrying the payload. In an aspect, modulation can be by supplementation of the payload in a target cell or tissue. In an aspect, modulation can be gene replacement of the payload in a target cell or tissue. In an aspect, modulation can be by inhibition using a modulatory nucleic acid of the payload in a target cell or tissue. In an aspect, a disclosed payload can comprise a combination of coding and non-coding nucleic acid sequences, and can be codon-optimized. In an aspect, a payload can comprise one or more regulatable elements. In an aspect, a disclosed payload can encode a messenger RNA (mRNA) can be encoded by a disclosed payload. In an aspect, a disclosed payload can encode a gene therapy product. A gene therapy product can comprise a polypeptide, RNA molecule, or other gene product that, when expressed in a target cell, provides a desired therapeutic effect. In an aspect, a gene therapy product can comprise a substitute for a non-functional gene that is absent or mutated. In an aspect, a disclosed payload nucleic acid can encode a transgene having a beneficial or desirable gene product.

[0097] In an aspect, the term “polypeptide” refers to a polymer of amino acids. The terms “protein” and “polypeptide” are used interchangeably herein. A peptide is a relatively short polypeptide, typically between about 2 and 60 amino acids in length. Polypeptides used herein typically contain amino acids such as the 20 L-amino acids that are most commonly found in proteins. However, other amino acids and / or amino acid analogs known in the art can be used. One or more of the amino acids in a polypeptide can be modified, for example, by the additionof a chemical entity such as a carbohydrate group, a phosphate group, a fatty acid group, a linker for conjugation, functionalization, etc. A polypeptide that has a nonpolypeptide moiety covalently or noncovalently associated therewith is still considered a “polypeptide.” Exemplary modifications include glycosylation and palmitoylation. Polypeptides can be purified from natural sources, produced using recombinant DNA technology or synthesized through chemical means such as conventional solid phase peptide synthesis, etc. The term “polypeptide sequence” or “amino acid sequence” can refer to the polypeptide material itself and / or to the sequence information (i.e., the succession of letters or three letter codes used as abbreviations for amino acid names) that biochemically characterizes a polypeptide. A polypeptide sequence presented herein is presented in an N- terminal to C-terminal direction unless otherwise indicated.

[0098] A variant amino acid or DNA sequence (a disclosed variant MAAP) can be at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or more, identical to a native or reference sequence (e.g., WT MAAP). The degree of homology (percent identity) between a native and a mutant sequence can be determined, for example, by comparing the two sequences using computer programs commonly employed for this purpose, e.g., that are freely available on the world wide web (e.g., BLASTp or BLASTn with default settings). Alterations of the native amino acid sequence can be accomplished by any of a number of techniques known to one of skill in the art. Mutations can be introduced, for example, at particular loci by synthesizing oligonucleotides containing a mutant sequence, flanked by restriction sites permitting ligation to fragments of the native sequence. Following ligation, the resulting reconstructed sequence encodes an analog having the desired amino acid insertion, substitution, or deletion. Alternatively, oligonucleotide-directed site-specific mutagenesis procedures can be employed to provide an altered nucleotide sequence having particular codons altered according to the substitution, deletion, or insertion required. Techniques for making such alterations are well established. Any cysteine residue not involved in maintaining the proper conformation of a polypeptide also can be substituted, generally with serine, to improve the oxidative stability of the molecule and prevent aberrant crosslinking. Conversely, cysteine bond(s) can be added to a polypeptide to improve its stability or facilitate oligomerization.

[0099] In an aspect, “polynucleotide sequence” can refer to the polynucleotide material itself and / or to the sequence information (i.e., the succession of letters used as abbreviations for bases) that biochemically characterizes a specific nucleic acid. A polynucleotide sequence presented herein is presented in a 5’ to 3’ direction unless otherwise indicated.

[0100] In an aspect, the term “corresponding to,” when used in reference to an amino acid or polynucleotide sequence means that a given amino acid or polynucleotide sequence in one polypeptide or polynucleotide molecule has structural properties, functional properties, or both that are similar relative to an amino acid or polynucleotide sequence in a similar location in another polypeptide or polynucleotide molecule. Homologues of a given polypeptide in different species “correspond to” each other, as do regions or domains of homologous polypeptides from different species. Similarly, capsid polypeptides of different serotypes of viral vectors, including but not limited to adeno- associated virus (AAV) vectors, “correspond to” each other, as do regions of such polypeptides, defined, for example by alignment of their amino acid sequences. While other alignment parameters can be used to define such regions, for the avoidance of doubt, alignment can be performed using BLAST® (Basic Local Alignment Search Tool) using default parameters.

[0101] In an aspect, “operably linked” means that expression of a gene or a transgene is under the control of a promoter with which it is spatially connected. A promoter can be positioned 5’ (upstream) or 3’ (downstream) of a gene under its control. The distance between the promoter and a gene can be approximately the same as the distance between that promoter and the gene it controls in the gene from which the promoter is derived. As is known in the art, variation in this distance can be accommodated without loss of promoter function.

[0102] In an aspect, “promoter” or “promoters” are known to the art. Depending on the level and tissue-specific expression desired, a variety of promoter elements can be used. A promoter can be tissue-specific or ubiquitous and can be constitutive or inducible, depending on the pattern of the gene expression desired. A promoter can be native or foreign and can be a natural or a synthetic sequence. By foreign, it is intended that the transcriptional initiation region is not found in the wild-type host into which the transcriptional initiation region is introduced.

[0103] In an aspect, an “isolated” biological component (such as a nucleic acid, protein, or virus) has been substantially separated or purified away from other biological components (e.g., other chromosomal and extra-chromosomal DNA and RNA, proteins and / or organelles). Nucleic acids, proteins, and / or viruses that have been “isolated” include nucleic acids, proteins, and viruses purified by standard purification methods. The term also embraces nucleic acids, proteins, and viruses prepared by recombinant expression in a host cell, as well as chemically synthesized nucleic acids or proteins. The term “isolated” (or purified) does not require absolute purity; rather, it is intended as a relative term. Thus, for example, an isolated or purified nucleic acid, protein, virus, or other active compound is one that is isolated in whole or in part from associated nucleic acids, proteins, and other contaminants. In an aspect, theterm “substantially purified” refers to a nucleic acid, protein, virus or other active compound that has been isolated from a cell, cell culture medium, or other crude preparation and subjected to fractionation to remove various components of the initial preparation, such as proteins, cellular debris, and other components.

[0104] “Sequence identity” and “sequence similarity” can be determined by alignment of two peptide or two nucleotide sequences using global or local alignment algorithms. Sequences may then be referred to as “substantially identical” or “essentially similar” when they are optimally aligned. For example, sequence similarity or identity can be determined by searching against databases such as FASTA, BLAST, etc., but hits should be retrieved and aligned pairwise to compare sequence identity. Two proteins or two protein domains, or two nucleic acid sequences can have “substantial sequence identity” if the percentage sequence identity is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99% or more, preferably 90%, 95%, 98%, 99% or more. Such sequences are also referred to as “variants” herein, e.g., other variants of MAAP. It should be understood that sequence with substantial sequence identity do not necessarily have the same length and may differ in length. For example, sequences that have the same nucleotide sequence but of which one has additional nucleotides on the 3’- and / or 5 ’-side are 100% identical.

[0105] A “codon-optimized” nucleic acid refers to a nucleic acid sequence that has been altered such that the codons are optimal for expression in a particular system (such as a particular species or group of species). For example, a nucleic acid sequence can be optimized for expression in mammalian cells or in a particular mammalian species (such as human cells). Codon optimization does not alter the amino acid sequence of the encoded protein.

[0106] Disclosed are the components to be used to prepare one or more of the disclosed nucleic acids, the disclosed vectors, the disclosed capsid proteins, disclosed vectors, disclosed plasmids or compositions thereof, and / or the disclosed pharmaceutical preparations used within the methods disclosed herein. These and other materials are disclosed herein, and it is understood that when combinations, subsets, interactions, groups, etc. of these materials are disclosed that while specific reference of each various individual and collective combinations and permutation of these compounds cannot be explicitly disclosed, each is specifically contemplated and described herein. For example, if a particular compound is disclosed and discussed and a number of modifications that can be made to a number of molecules including the compounds are discussed, specifically contemplated is each and every combination and permutation of the compound and the modifications that are possible unless specifically indicated to the contrary. Thus, if a class of molecules A, B, and C are disclosed as well as aclass of molecules D, E, and F and an example of a combination molecule, A-D is disclosed, then even if each is not individually recited each is individually and collectively contemplated meaning combinations, A-E, A-F, B-D, B-E, B-F, C-D, C-E, and C-F are considered disclosed. Likewise, any subset or combination of these is also disclosed. Thus, for example, the subgroup of A-E, B-F, and C-E would be considered disclosed. This concept applies to all aspects of this application including, but not limited to, steps in methods of making and using the compositions of the invention. Thus, if there are a variety of additional steps that can be performed it is understood that each of these additional steps can be performed with any specific aspects or combination of aspects of the methods of the invention.B. COMPOSITIONS1. VARIANT MEMBRANE -ASSOCIATED ACCESSORY PROTEINS (MAAPs)

[0107] Disclosed herein is a variant membrane-associated accessory protein (MAAP).

[0108] Disclosed herein is a variant membrane-associated accessory protein (MAAP) listed in Table 1A or Table IB.

[0109] Disclosed herein is a variant MAAP comprising about 110 to about 130 amino acids. Disclosed herein is a variant MAAP comprising between 110 amino acids and 120 amino acids. Disclosed herein is a variant MAAP comprising between 120 amino acids and 130 amino acids. Disclosed herein is a variant membrane-associated accessory protein (MAAP) comprising the sequence of any one of SEQ ID NO:331 - SEQ ID NO:360. In an aspect of any one of SEQ ID NO:331 - SEQ ID NO:360, each amino acid at positions 4-12 can comprise any amino acid. In an aspect of any one of SEQ ID NO:331 - SEQ ID NO:360, each amino acid at positions 49-57 can comprise any amino acid. In an aspect of any one of SEQ ID NO:331 - SEQ ID NO:360, each amino acid at positions 87-95 can comprise any amino acid. In an aspect of any one of SEQ ID NO:331 - SEQ ID NO:360, each of X4X5X6X7X8X9X10X11X12 can comprise any amino acid, each of X49X50X51X52X53X54X55X56X57 can comprise any amino acid, and each of X87X88X89X90X91X92X93X94X95 can comprise any amino acid. In an aspect, Table 1A provides the amino acid sequence for each of SEQ ID NO:331 - SEQ ID NO:360, which identify three separate 9 amino acid regions targeted for directed evolution of MAAP variants. In an aspect, Table 1A provides the amino acid sequence for each of SEQ ID NO:331 - SEQ ID NO:360, which identify the 9 amino acid regions targeted for Library 1 (e.g., Table 2), Library 2 (e.g., Table 3), and Library 3 (e.g., Table 4). Disclosed herein is a variant MAAP comprising a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to any one of SEQ ID NO:331 - SEQ ID NO:360.Table 1A - Amino Acid Sequences for MAAPs of Various AAVs with Leucine StartCodons

[0110] Disclosed herein is a variant membrane-associated accessory protein (MAAP) comprising the sequence of any one of SEQ ID NO:346 - SEQ ID NO:360. In an aspect of any one of SEQ ID NO:346 - SEQ ID NO:360, each amino acid at positions 4-12 can comprise any amino acid. In an aspect of any one of SEQ ID NO:346 - SEQ ID NO:360, each amino acid at positions 49-57 can comprise any amino acid. In an aspect of any one of SEQ ID NO:346 - SEQ ID NO:360, each amino acid at positions 87-95 can comprise any amino acid. In an aspect of any one of SEQ ID NO:346 - SEQ ID NO:360, each of X4X5X6X7X8X9X10X11X12 can comprise any amino acid, each of X49X50X51X52X53X54X55X56X57 can comprise any amino acid, and each of X87X88X89X90X91X92X93X94X95 can comprise any amino acid. In an aspect, Table IB providesthe amino acid sequence for each of SEQ ID NO:346 - SEQ ID NO:360, which identify three separate 9 amino acid regions targeted for directed evolution of MAAP variants. In an aspect, Table IB provides the amino acid sequence for each of SEQ ID NO:346 - SEQ ID NO:360, which identify the 9 amino acid regions targeted for Library 1 (e.g., Table 2), Library 2 (e.g., Table 3), and Library 3 (e.g., Table 4). Disclosed herein is a variant MAAP comprising a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to any one of SEQ ID NO:346 - SEQ ID NO:360.Table IB - Amino Acid Sequences for MAAPs of Various AAVs with Methionine StartCodonsTable 2 - Wild-Type Amino Acid and Nucleic Acid Sequences for Library 1 (MAAPs in Various AAVs)Table 3 - Wild-Type Amino Acid and Nucleic Acid Sequences for Library 2 (MAAPs inVarious AAVs)Table 4 - Wild-Type Amino Acid and Nucleic Acid Sequences for Library 3 (MAAPs inVarious AAVs)MAAP1 Variants

[0111] Disclosed herein is a variant membrane-associated accessory protein (MAAP) with a mutation at one or more of positions 4-12, positions 49-57, and / or positions 87-95 with respect to the amino acid sequence of SEQ ID NO:01 or SEQ ID NO: 31. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:01 or SEQ ID NO:31 and having one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:01 or SEQ ID NO:31 with one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:01 or SEQ ID NO:31, wherein positions 4-12 comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200, wherein positions 49-57 comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238, or wherein positions 87-95 comprise the sequence set forth inany one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:01 or SEQ ID NO:31, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 4-12. In an aspect, the disclosed amino acid sequence at positions 4-12 can comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:01 or SEQ ID NO:31, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 49-57. In an aspect, the disclosed amino acid sequence at positions 49-57 can comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:01 or SEQ ID NO:31, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising one or more mutations at positions 87-95. In an aspect, the disclosed amino acid sequence at positions 87-95 can comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising a mutation at one or more positions in the sequence of SEQ ID NO:61, SEQ ID NO: 62, or SEQ ID NO: 63.

[0112] Disclosed herein is a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:01 or SEQ ID NO:31. Disclosed herein is a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:01 or SEQ ID NO:31, wherein one or more mutations occur at positions 4-12, at positions 49-57, or at positions 87-95. Disclosed herein is a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:01 or SEQ ID NO:31, wherein one or more mutations occur in the sequence set forth in SEQ ID NO:61, SEQ ID NO:62, or SEQ ID NO:63.

[0113] In an aspect, the sequence set forth in SEQ ID NO:01 can be encoded by the sequence set forth in SEQ ID NO: 16. In an aspect, the sequence set forth in SEQ ID NO:31 can be encoded by the sequence set forth in SEQ ID NO:46. In an aspect, the sequence set forth in SEQ ID NO:61 can be encoded by the sequence set forth in SEQ ID NO: 106. In an aspect, the sequence set forth in SEQ ID NO: 62 can be encoded by the sequence set forth in SEQ ID NO: 107. In an aspect, the sequence set forth in SEQ ID NO:63 can be encoded by the sequence set forth in SEQ ID NO: 108.

[0114] Disclosed herein is a variant MAAP identified by a disclosed method and comprising a mutation at one or more of positions 4-12, positions 49-57, and / or positions 87-95 with respect to the amino acid sequence of SEQ ID NO:01 or SEQ ID NO:31. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:01 or SEQ ID NO:31 and having one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:01 or SEQ ID NO:31 with one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:01 or SEQ ID NO:31, wherein positions 4-12 comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200, wherein positions 49-57 comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238, or wherein positions 87-95 comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288.

[0115] Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:01 or SEQ ID NO:31, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:01 or SEQ ID NO:31, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:01 or SEQ ID NO:31, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:01 or SEQ ID NO:31, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:01 or SEQ ID NO:31, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:01 or SEQ IDN0:31, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288.MAAP2 Variants

[0116] Disclosed herein is a variant membrane-associated accessory protein (MAAP) with a mutation at one or more of positions 4-12, positions 49-57, and / or positions 87-95 with respect to the amino acid sequence of SEQ ID NO:02 or SEQ ID NO:32. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:02 or SEQ ID NO:32 and having one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:02 or SEQ ID NO:32 with one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:02 or SEQ ID NO:32, wherein positions 4-12 comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200, wherein positions 49-57 comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238, or wherein positions 87-95 comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:02 or SEQ ID NO:32, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 4-12. In an aspect, the disclosed amino acid sequence at positions 4-12 can comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:02 or SEQ ID NO:32, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 49-57. In an aspect, the disclosed amino acid sequence at positions 49-57 can comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:02 or SEQ ID NO:32, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising one or more mutations at positions 87-95. In an aspect, the disclosed amino acid sequence at positions 87-95 can comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant membraneassociated accessory protein (MAAP) comprising a mutation at one or more positions in the sequence of SEQ ID NO:64, SEQ ID NO:65, or SEQ ID NO:66.

[0117] Disclosed herein is a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:02 or SEQ ID NO:32. Disclosed herein is a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:02 or SEQ ID NO:32, wherein one or more mutations occur at positions 4-12, at positions 49-57, or at positions 87-95. Disclosed herein is a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 02 or SEQ ID NO:32, wherein one or more mutations occur in the sequence set forth in SEQ ID NO:64, SEQ ID NO:65, or SEQ ID NO:66.

[0118] In an aspect, the sequence set forth in SEQ ID NO: 02 can be encoded by the sequence set forth in SEQ ID NO: 17. In an aspect, the sequence set forth in SEQ ID NO:32 can be encoded by the sequence set forth in SEQ ID NO:47. In an aspect, the sequence set forth in SEQ ID NO:61 can be encoded by the sequence set forth in SEQ ID NO: 109. In an aspect, the sequence set forth in SEQ ID NO: 62 can be encoded by the sequence set forth in SEQ ID NO: 110. In an aspect, the sequence set forth in SEQ ID NO:63 can be encoded by the sequence set forth in SEQ ID NO: 111.

[0119] Disclosed herein is a variant MAAP identified by a disclosed method and comprising a mutation at one or more of positions 4-12, positions 49-57, and / or positions 87-95 with respect to the amino acid sequence of SEQ ID NO:02 or SEQ ID NO:32. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:02 or SEQ ID NO:32 and having one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:02 or SEQ ID NO:32 with one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:02 or SEQ ID NO:32, wherein positions 4-12 comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200, wherein positions 49-57 comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238, or wherein positions 87-95 comprise the sequence set forth inany one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:02 or SEQ ID NO:32, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:02 or SEQ ID NO:32, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:02 or SEQ ID NO:32, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:02 or SEQ ID NO:32, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:02 or SEQ ID NO:32, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:02 or SEQ ID NO:32, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288.MAAP3 Variants

[0120] Disclosed herein is a variant membrane-associated accessory protein (MAAP) with a mutation at one or more of positions 4-12, positions 49-57, and / or positions 87-95 with respect to the amino acid sequence of SEQ ID NO:03. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:03 or SEQ ID NO:33 and having one or more mutations at positions 4-12, positions 49-57, or positions 87- 95. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 03 or SEQ ID NO:33 with one or more mutations at positions 4- 12, positions 49-57, or positions 87-95. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:03 or SEQ ID NO:33, wherein positions 4-12 comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200, wherein positions 49-57 comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238, or wherein positions 87-95 comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:03 or SEQ ID NO:33, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 4-12. In an aspect, the disclosed amino acid sequence at positions4-12 can comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:03 or SEQ ID NO:33, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 49-57. In an aspect, the disclosed amino acid sequence at positions 49-57 can comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:03 or SEQ ID NO:33, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising one or more mutations at positions 87-95. In an aspect, the disclosed amino acid sequence at positions 87-95 can comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising a mutation at one or more positions in the sequence of SEQ ID NO:67, SEQ ID NO: 68, or SEQ ID NO: 69.

[0121] Disclosed herein is a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:03 or SEQ ID NO:33. Disclosed herein is a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:03 or SEQ ID NO:33, wherein one or more mutations occur at positions 4-12, at positions 49-57, or at positions 87-95. Disclosed herein is a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 03 or SEQ ID NO:33, wherein one or more mutations occur in the sequence set forth in SEQ ID NO:67, SEQ ID NO:68, or SEQ ID NO:69.

[0122] In an aspect, the sequence set forth in SEQ ID NO: 03 can be encoded by the sequence set forth in SEQ ID NO: 18. In an aspect, the sequence set forth in SEQ ID NO:33 can be encoded by the sequence set forth in SEQ ID NO:48. In an aspect, the sequence set forth in SEQ ID NO: 67 can be encoded by the sequence set forth in SEQ ID NO: 112. In an aspect, the sequence set forth in SEQ ID NO: 68 can be encoded by the sequence set forth in SEQ IDNO: 113. In an aspect, the sequence set forth in SEQ ID NO: 69 can be encoded by the sequence set forth in SEQ ID NO114.

[0123] Disclosed herein is a variant MAAP identified by a disclosed method and comprising a mutation at one or more of positions 4-12, positions 49-57, and / or positions 87-95 with respect to the amino acid sequence of SEQ ID NO:03 or SEQ ID NO:33. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:03 or SEQ ID NO:33 and having one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:03 or SEQ ID NO:33 with one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:03 or SEQ ID NO:33, wherein positions 4-12 comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200, wherein positions 49-57 comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238, or wherein positions 87-95 comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:03 or SEQ ID NO:33, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:03 or SEQ ID NO:33, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:03 or SEQ ID NO:33, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:03 or SEQ ID NO:33, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:03 or SEQ ID NO:33, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:03 or SEQ ID NO:33, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288.MAAP4 Variants

[0124] Disclosed herein is a variant membrane-associated accessory protein (MAAP) with a mutation at one or more of positions 4-12, positions 49-57, and / or positions 87-95 with respect to the amino acid sequence of SEQ ID NO:04 or SEQ ID NO:34. Disclosed herein is a variantmembrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:04 or SEQ ID NO:34 and having one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:04 or SEQ ID NO:34 with one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:04 or SEQ ID NO:34, wherein positions 4-12 comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200, wherein positions 49-57 comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238, or wherein positions 87-95 comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:04 or SEQ ID NO:34, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 4-12. In an aspect, the disclosed amino acid sequence at positions 4-12 can comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:04 or SEQ ID NO:34, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 49-57. In an aspect, the disclosed amino acid sequence at positions 49-57 can comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:04 or SEQ ID NO:34, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising one or more mutations at positions 87-95. In an aspect, the disclosed amino acid sequence at positions 87-95 can comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising a mutation at one or more positions in the sequence of SEQ ID NO: 70, SEQ ID NO: 71, or SEQ ID NO: 72.

[0125] Disclosed herein is a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:04 or SEQ ID NO:34. Disclosed herein is a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, atleast 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:04 or SEQ ID NO:34, wherein one or more mutations occur at positions 4-12, at positions 49-57, or at positions 87-95. Disclosed herein is a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 04 or SEQ ID NO:34, wherein one or more mutations occur in the sequence set forth in SEQ ID NO:70, SEQ ID NO:71, or SEQ ID NO:72.

[0126] In an aspect, the sequence set forth in SEQ ID NO: 04 can be encoded by the sequence set forth in SEQ ID NO: 19. In an aspect, the sequence set forth in SEQ ID NO:34 can be encoded by the sequence set forth in SEQ ID NO:49. In an aspect, the sequence set forth in SEQ ID NO:70 can be encoded by the sequence set forth in SEQ ID NO: 115. In an aspect, the sequence set forth in SEQ ID NO:71 can be encoded by the sequence set forth in SEQ ID NO: 116. In an aspect, the sequence set forth in SEQ ID NO:72 can be encoded by the sequence set forth in SEQ ID NO: 117.

[0127] Disclosed herein is a variant MAAP identified by a disclosed method and comprising a mutation at one or more of positions 4-12, positions 49-57, and / or positions 87-95 with respect to the amino acid sequence of SEQ ID NO:04 or SEQ ID NO:34. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:04 or SEQ ID NO:34 and having one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:04 or SEQ ID NO:34 with one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:04 or SEQ ID NO:34, wherein positions 4-12 comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200, wherein positions 49-57 comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238, or wherein positions 87-95 comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:04 or SEQ ID NO:34, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:04 or SEQ ID NO:34, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:04 or SEQ ID NO:34,wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:04 or SEQ ID NO:34, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:04 or SEQ ID NO:34, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:04 or SEQ ID NO:34, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288.MAAP5 Variants

[0128] Disclosed herein is a variant membrane-associated accessory protein (MAAP) with a mutation at one or more of positions 4-12, positions 49-57, and / or positions 87-95 with respect to the amino acid sequence of SEQ ID NO:05 or SEQ ID NO:35. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:05 or SEQ ID NO:35 and having one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:05 or SEQ ID NO:35 with one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:05 or SEQ ID NO:35, wherein positions 4-12 comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200, wherein positions 49-57 comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238, or wherein positions 87-95 comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:05 or SEQ ID NO:30, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 4-12. In an aspect, the disclosed amino acid sequence at positions 4-12 can comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:05 or SEQ ID NO:35, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 49-57. In an aspect, the disclosed amino acid sequence at positions 49-57 can comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238. Disclosedherein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:05 or SEQ ID NO:35, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising one or more mutations at positions 87-95. In an aspect, the disclosed amino acid sequence at positions 87-95 can comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising a mutation at one or more positions in the sequence of SEQ ID NO: 73, SEQ ID NO: 74, or SEQ ID NO: 75.

[0129] Disclosed herein is a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:05 or SEQ ID NO:35. Disclosed herein is a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:05 or SEQ ID NO:35, wherein one or more mutations occur at positions 4-12, at positions 49-57, or at positions 87-95. Disclosed herein is a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 05 or SEQ ID NO:35, wherein one or more mutations occur in the sequence set forth in SEQ ID NO:73, SEQ ID NO:74, or SEQ ID NO:75.

[0130] In an aspect, the sequence set forth in SEQ ID NO: 05 can be encoded by the sequence set forth in SEQ ID NO:20. In an aspect, the sequence set forth in SEQ ID NO:38 can be encoded by the sequence set forth in SEQ ID NO: 50. In an aspect, the sequence set forth in SEQ ID NO: 73 can be encoded by the sequence set forth in SEQ ID NO: 118. In an aspect, the sequence set forth in SEQ ID NO: 74 can be encoded by the sequence set forth in SEQ ID NO: 119. In an aspect, the sequence set forth in SEQ ID NO:75 can be encoded by the sequence set forth in SEQ ID NO: 120.

[0131] Disclosed herein is a variant MAAP identified by a disclosed method and comprising a mutation at one or more of positions 4-12, positions 49-57, and / or positions 87-95 with respect to the amino acid sequence of SEQ ID NO:05 or SEQ ID NO:35. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:05 or SEQ ID NO:35 and having one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant MAAP identified by a disclosed method andcomprising the sequence of SEQ ID NO:05 or SEQ ID NO:35 with one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:05 or SEQ ID NO:35, wherein positions 4-12 comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200, wherein positions 49-57 comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238, or wherein positions 87-95 comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:05 or SEQ ID NO:35, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:05 or SEQ ID NO:35, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:05 or SEQ ID NO:35, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:05 or SEQ ID NO:35, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:05 or SEQ ID NO:35, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:05 or SEQ ID NO:35, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288.MAAP6 Variants

[0132] Disclosed herein is a variant membrane-associated accessory protein (MAAP) with a mutation at one or more of positions 4-12, positions 49-57, and / or positions 87-95 with respect to the amino acid sequence of SEQ ID NO:06 or SEQ ID NO:36. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:06 and having one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:06 or SEQ ID NO:36 with one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:06 or SEQ ID NO:36, wherein positions 4-12 comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200, wherein positions 49-57 comprise the sequence set forth in any one of SEQ IDNO:201 - SEQ ID NO:238, or wherein positions 87-95 comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288.

[0133] Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:06 or SEQ ID NO:36, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 4- 12. In an aspect, the disclosed amino acid sequence at positions 4-12 can comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:06 or SEQ ID NO:36, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 49-57. In an aspect, the disclosed amino acid sequence at positions 49-57 can comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:06 or SEQ ID NO:36, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising one or more mutations at positions 87-95. In an aspect, the disclosed amino acid sequence at positions 87-95 can comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising a mutation at one or more positions in the sequence of SEQ ID NO:76, SEQ ID NO:77, or SEQ ID NO:78.

[0134] Disclosed herein is a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:06 or SEQ ID NO:36. Disclosed herein is a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:06 or SEQ ID NO:36, wherein one or more mutations occur at positions 4-12, at positions 49-57, or at positions 87-95. Disclosed herein is a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 06or SEQ ID NO: 36, wherein one or more mutations occur in the sequence set forth in SEQ ID NO:76, SEQ ID NO:77, or SEQ ID NO:78.

[0135] In an aspect, the sequence set forth in SEQ ID NO:06 can be encoded by the sequence set forth in SEQ ID NO:21. In an aspect, the sequence set forth in SEQ ID NO:36 can be encoded by the sequence set forth in SEQ ID NO:51. In an aspect, the sequence set forth in SEQ ID NO:76 can be encoded by the sequence set forth in SEQ ID NO: 121. In an aspect, the sequence set forth in SEQ ID NO:77 can be encoded by the sequence set forth in SEQ ID NO: 122. In an aspect, the sequence set forth in SEQ ID NO:78 can be encoded by the sequence set forth in SEQ ID NO: 123.

[0136] Disclosed herein is a variant MAAP identified by a disclosed method and comprising a mutation at one or more of positions 4-12, positions 49-57, and / or positions 87-95 with respect to the amino acid sequence of SEQ ID NO:06 or SEQ ID NO:36. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:06 or SEQ ID NO:36 and having one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:06 or SEQ ID NO:36 with one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:06 or SEQ ID NO:36, wherein positions 4-12 comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200, wherein positions 49-57 comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238, or wherein positions 87-95 comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:06 or SEQ ID NO:36, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:06 or SEQ ID NO:36, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:06 or SEQ ID NO:36, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:06 or SEQ ID NO:36, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:06 or SEQ ID NO:36, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238.Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:06 or SEQ ID NO:36, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288.MAAP7 Variants

[0137] Disclosed herein is a variant membrane-associated accessory protein (MAAP) with a mutation at one or more of positions 4-12, positions 49-57, and / or positions 87-95 with respect to the amino acid sequence of SEQ ID NO:07 or SEQ ID NO:37. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:07 or SEQ ID NO:37 and having one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:07 or SEQ ID NO:37 with one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:07 or SEQ ID NO:37, wherein positions 4-12 comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200, wherein positions 49-57 comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238, or wherein positions 87-95 comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:07 or SEQ ID NO:37, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 4-12. In an aspect, the disclosed amino acid sequence at positions 4-12 can comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:07 or SEQ ID NO:37, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 49-57. In an aspect, the disclosed amino acid sequence at positions 49-57 can comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:07 or SEQ ID NO:37, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising one or more mutations at positions 87-95. In an aspect, the disclosed amino acid sequence at positions 87-95 can comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant membraneassociated accessory protein (MAAP) comprising a mutation at one or more positions in the sequence of SEQ ID NO: 79, SEQ ID NO: 80, or SEQ ID NO:81.

[0138] Disclosed herein is a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:07 or SEQ ID NO:37. Disclosed herein is a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:07 or SEQ ID NO:37, wherein one or more mutations occur at positions 4-12, at positions 49-57, or at positions 87-95. Disclosed herein is a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 07 or SEQ ID NO: 37, wherein one or more mutations occur in the sequence set forth in SEQ ID NO:79, SEQ ID NO:80, or SEQ ID NO:81.

[0139] In an aspect, the sequence set forth in SEQ ID NO: 07 can be encoded by the sequence set forth in SEQ ID NO:22. In an aspect, the sequence set forth in SEQ ID NO:37 can be encoded by the sequence set forth in SEQ ID NO: 52. In an aspect, the sequence set forth in SEQ ID NO:79 can be encoded by the sequence set forth in SEQ ID NO: 124. In an aspect, the sequence set forth in SEQ ID NO: 80 can be encoded by the sequence set forth in SEQ ID NO: 125. In an aspect, the sequence set forth in SEQ ID NO: 81 can be encoded by the sequence set forth in SEQ ID NO: 126.

[0140] Disclosed herein is a variant MAAP identified by a disclosed method and comprising a mutation at one or more of positions 4-12, positions 49-57, and / or positions 87-95 with respect to the amino acid sequence of SEQ ID NO:07 or SEQ ID NO:37. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:07 or SEQ ID NO:37 and having one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:07 or SEQ ID NO:37 with one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:07 or SEQ ID NO:37, wherein positions 4-12 comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200, wherein positions 49-57 comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238, or wherein positions 87-95 comprise the sequence set forth inany one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:07 or SEQ ID NO:37, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:07 or SEQ ID NO:37, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:07 or SEQ ID NO:37, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:07 or SEQ ID NO:37, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:07 or SEQ ID NO:37, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:07 or SEQ ID NO:37, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288.MAAP8 Variants

[0141] Disclosed herein is a variant membrane-associated accessory protein (MAAP) with a mutation at one or more of positions 4-12, positions 49-57, and / or positions 87-95 with respect to the amino acid sequence of SEQ ID NO:08 or SEQ ID NO:38. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:08 and having one or more mutations at one of positions 4-12, positions 49-57, or positions 87- 95. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 08 or SEQ ID NO:38 with one or more mutations at one of positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:08 or SEQ ID NO:38, wherein positions 4-12 comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200, wherein positions 49-57 comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238, or wherein positions 87-95 comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288.

[0142] Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:08 or SEQ ID NO:38, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 4-12. In an aspect, the disclosed amino acid sequence at positions 4-12 can comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200.

[0143] Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:08 or SEQ ID NO:38, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 49-57. In an aspect, the disclosed amino acid sequence at positions 49-57 can comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:08 or SEQ ID NO:38, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising one or more mutations at positions 87-95. In an aspect, the disclosed amino acid sequence at positions 87-95 can comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising a mutation at one or more positions in the sequence of SEQ ID NO:82, SEQ ID NO:83, or SEQ ID NO:84.

[0144] Disclosed herein is a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:08 or SEQ ID NO:38. Disclosed herein is a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:08 or SEQ ID NO:38, wherein one or more mutations occur at positions 4-12, at positions 49-57, or at positions 87-95. Disclosed herein is a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 08 or SEQ ID NO: 38, wherein one or more mutations occur in the sequence set forth in SEQ ID NO:82, SEQ ID NO:83, or SEQ ID NO:84.

[0145] In an aspect, the sequence set forth in SEQ ID NO:08 can be encoded by the sequence set forth in SEQ ID NO:23. In an aspect, the sequence set forth in SEQ ID NO:38 can be encoded by the sequence set forth in SEQ ID NO: 53. In an aspect, the sequence set forth in SEQ ID NO:82 can be encoded by the sequence set forth in SEQ ID NO: 127. In an aspect, the sequence set forth in SEQ ID NO: 83 can be encoded by the sequence set forth in SEQ IDNO: 128. In an aspect, the sequence set forth in SEQ ID NO: 84 can be encoded by the sequence set forth in SEQ ID NO: 129.

[0146] Disclosed herein is a variant MAAP identified by a disclosed method and comprising a mutation at one or more of positions 4-12, positions 49-57, and / or positions 87-95 with respect to the amino acid sequence of SEQ ID NO: 08 or SEQ ID NO:38.

[0147] Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 08 or SEQ ID NO:38 and having one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:08 or SEQ ID NO:38 with one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:08 or SEQ ID NO:38, wherein positions 4-12 comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200, wherein positions 49-57 comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238, or wherein positions 87-95 comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:08 or SEQ ID NO:38, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:08 or SEQ ID NO:38, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:08 or SEQ ID NO:38, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:08 or SEQ ID NO:38, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:08 or SEQ ID NO:38, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:08 or SEQ ID NO:38, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288.

[0148] Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of any one of SEQ ID NO:289 - SEQ ID NO:298. In an aspect, the sequence set forth in SEQ ID NO:289 can be encoded by the sequence set forth in SEQ ID NO:299. In an aspect, the sequence set forth in SEQ ID NO:290 can be encoded by thesequence set forth in SEQ ID NO:300. In an aspect, the sequence set forth in SEQ ID NO:291 can be encoded by the sequence set forth in SEQ ID NO:301. In an aspect, the sequence set forth in SEQ ID NO:292 can be encoded by the sequence set forth in SEQ ID NO:302. In an aspect, the sequence set forth in SEQ ID NO:293 can be encoded by the sequence set forth in SEQ ID NO:303. In an aspect, the sequence set forth in SEQ ID NO:294 can be encoded by the sequence set forth in SEQ ID NO:304. In an aspect, the sequence set forth in SEQ ID NO:295 can be encoded by the sequence set forth in SEQ ID NO:305. In an aspect, the sequence set forth in SEQ ID NO:296 can be encoded by the sequence set forth in SEQ ID NO:306. In an aspect, the sequence set forth in SEQ ID NO:297 can be encoded by the sequence set forth in SEQ ID NO:307. In an aspect, the sequence set forth in SEQ ID NO:298 can be encoded by the sequence set forth in SEQ ID NO: 308.

[0149] Disclosed herein is a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90, at least 95%, or more than 95% identity to the sequence set forth in any one of SEQ ID NO:289 - SEQ ID NO:298. Disclosed herein is a variant membrane associated accessory protein (MAAP) encoded by a nucleic acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90, at least 95%, or more than 95% identity to the sequence set forth in any one of SEQ ID NO:299 - SEQ ID NO:308.

[0150] Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of any one of SEQ ID NO:309 - SEQ ID NO:319. Disclosed herein is a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90, at least 95%, or more than 95% identity to the sequence set forth in any one of SEQ ID NO: 309 - SEQ ID NO:319.

[0151] In an aspect, the sequence set forth in SEQ ID NO: 309 can be encoded by the sequence set forth in SEQ ID NO:320. In an aspect, the sequence set forth in SEQ ID NO:310 can be encoded by the sequence set forth in SEQ ID NO:321. In an aspect, the sequence set forth in SEQ ID NO:311 can be encoded by the sequence set forth in SEQ ID NO:322. In an aspect, the sequence set forth in SEQ ID NO: 312 can be encoded by the sequence set forth in SEQ ID NO:323. In an aspect, the sequence set forth in SEQ ID NO:313 can be encoded by the sequence set forth in SEQ ID NO:324. In an aspect, the sequence set forth in SEQ ID NO:314 can be encoded by the sequence set forth in SEQ ID NO:325. In an aspect, the sequence set forth in SEQ ID NO:315 can be encoded by the sequence set forth in SEQ ID NO:326. In anaspect, the sequence set forth in SEQ ID NO:316 can be encoded by the sequence set forth in SEQ ID NO:327. In an aspect, the sequence set forth in SEQ ID NO:317 can be encoded by the sequence set forth in SEQ ID NO:328. In an aspect, the sequence set forth in SEQ ID NO:318 can be encoded by the sequence set forth in SEQ ID NO:329. In an aspect, the sequence set forth in SEQ ID NO:319 can be encoded by the sequence set forth in SEQ ID NO:330.

[0152] Disclosed herein is a variant membrane associated accessory protein (MAAP) encoded by a nucleic acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90, at least 95%, or more than 95% identity to the sequence set forth in any one of SEQ ID NO:320 - SEQ ID NO:330.

[0153] Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of any one of SEQ ID NO:362 - SEQ ID NO:472. Disclosed herein is a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90, at least 95%, or more than 95% identity to the sequence set forth in any one of SEQ ID NO: 362- SEQ ID NO:472.

[0154] Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of any one of SEQ ID NO:331 - SEQ ID NO:345 or SEQ ID NO:346- SEQ ID NO:360. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising a sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90, at least 95%, or more than 95% identity to the sequence set forth in any one of SEQ ID NO:331 - SEQ ID NO:345 or SEQ ID NO:346 - SEQ ID NO:360.

[0155] Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of any one of SEQ ID NO:473 - SEQ ID NO:610. Disclosed herein is a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90, at least 95%, or more than 95% identity to the sequence set forth in any one of SEQ ID NO:473- SEQ ID NO:610.

[0156] Disclosed herein is a variant membrane-associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:361 or SEQ ID NO:615. Table 5 provides the sequence of SEQ ID NO:361 and SEQ ID NO:615. In an aspect of SEQ ID NO:361 or SEQ ID NO:615, each amino acid at positions 4-12 can comprise any amino acid. In an aspect of SEQ ID NO:361 or SEQ ID NO:615, each amino acid at positions 87-95 can comprise anyamino acid. In an aspect of any one of SEQ ID NO:331 - SEQ ID NO:345, each of X4X5X6X7X8X9X10X11X12 can comprise any amino acid, and each of X87X88X89X90X91X92X93X94X95 can comprise any amino acid.Table 5 - Amino Acid Sequences for MAAP8 with Region 1 and Region 3 VariantsMAAP9 Variants

[0157] Disclosed herein is a variant membrane-associated accessory protein (MAAP) with a mutation at one or more of positions 4-12, positions 49-57, and / or positions 87-95 with respect to the amino acid sequence of SEQ ID NO:09 or SEQ ID NO:39. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:09 or SEQ ID NO:39 and having one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:09 or SEQ ID NO:39 with one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:09 or SEQ ID NO:39, wherein positions 4-12 comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200, wherein positions 49-57 comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238, or wherein positions 87-95 comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:09 or SEQ ID NO:39, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 4-12. In an aspect, the disclosed amino acid sequence at positions 4-12 can comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant membrane associated accessory protein (MAAP)comprising the sequence of SEQ ID NO:09 or SEQ ID NO:39, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 49-57. In an aspect, the disclosed amino acid sequence at positions 49-57 can comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:09 or SEQ ID NO:39, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising one or more mutations at positions 87-95. In an aspect, the disclosed amino acid sequence at positions 87-95 can comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising a mutation at one or more positions in the sequence of SEQ ID NO:85, SEQ ID NO:86, or SEQ ID NO:87.

[0158] Disclosed herein is a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:09 or SEQ ID NO:39. Disclosed herein is a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:09 or SEQ ID NO:39, wherein one or more mutations occur at positions 4-12, at positions 49-57, or at positions 87-95. Disclosed herein is a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 09 or SEQ ID NO: 39, wherein one or more mutations occur in the sequence set forth in SEQ ID NO:85, SEQ ID NO:86, or SEQ ID NO:87.

[0159] In an aspect, the sequence set forth in SEQ ID NO:09 can be encoded by the sequence set forth in SEQ ID NO:24. In an aspect, the sequence set forth in SEQ ID NO:39 can be encoded by the sequence set forth in SEQ ID NO: 54. In an aspect, the sequence set forth in SEQ ID NO:85 can be encoded by the sequence set forth in SEQ ID NO: 130. In an aspect, the sequence set forth in SEQ ID NO: 86 can be encoded by the sequence set forth in SEQ ID NO: 131. In an aspect, the sequence set forth in SEQ ID NO: 87 can be encoded by the sequence set forth in SEQ ID NO: 132.

[0160] Disclosed herein is a variant MAAP identified by a disclosed method and comprising a mutation at one or more of positions 4-12, positions 49-57, and / or positions 87-95 with respect to the amino acid sequence of SEQ ID NO:09 or SEQ ID NO:39. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:09 or SEQ ID NO:39 and having one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:09 or SEQ ID NO:39 with one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:09 or SEQ ID NO:39, wherein positions 4-12 comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200, wherein positions 49-57 comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238, or wherein positions 87-95 comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:09 or SEQ ID NO:39, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:09 or SEQ ID NO:39, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:09 or SEQ ID NO:39, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:09 or SEQ ID NO:39, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:09 or SEQ ID NO:39, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO:09 or SEQ ID NO:39, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288.MAAP10 Variants

[0161] Disclosed herein is a variant membrane-associated accessory protein (MAAP) with a mutation at one or more of positions 4-12, positions 49-57, and / or positions 87-95 with respect to the amino acid sequence of SEQ ID NO: 10 or SEQ ID NO:40. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 10 or SEQ ID NO:40 and having one or more mutations at positions 4-12, positions 49-57, orpositions 87-95. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 10 or SEQ ID NO:40 with one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 10 or SEQ ID NO:40, wherein positions 4-12 comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200, wherein positions 49-57 comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238, or wherein positions 87-95 comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 10 or SEQ ID NO:40, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 4-12. In an aspect, the disclosed amino acid sequence at positions 4-12 can comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 10 or SEQ ID NO:40, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 49-57. In an aspect, the disclosed amino acid sequence at positions 49-57 can comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 10 or SEQ ID NO:40, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising one or more mutations at positions 87-95. In an aspect, the disclosed amino acid sequence at positions 87-95 can comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising a mutation at one or more positions in the sequence of SEQ ID NO:88, SEQ ID NO:89, or SEQ ID NO:90.

[0162] Disclosed herein is a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 10 or SEQ ID NO:40. Disclosed herein is a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 10 or SEQ ID NO:40, wherein one ormore mutations occur at positions 4-12, at positions 49-57, or at positions 87-95. Disclosed herein is a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 10 or SEQ ID NO:40, wherein one or more mutations occur in the sequence set forth in SEQ ID NO:88, SEQ ID NO:89, or SEQ ID NO:90.

[0163] In an aspect, the sequence set forth in SEQ ID NO: 10 can be encoded by the sequence set forth in SEQ ID NO:25. In an aspect, the sequence set forth in SEQ ID NO:40 can be encoded by the sequence set forth in SEQ ID NO: 55. In an aspect, the sequence set forth in SEQ ID NO:88 can be encoded by the sequence set forth in SEQ ID NO: 133. In an aspect, the sequence set forth in SEQ ID NO: 89 can be encoded by the sequence set forth in SEQ ID NO: 134. In an aspect, the sequence set forth in SEQ ID NO:90 can be encoded by the sequence set forth in SEQ ID NO: 135.

[0164] Disclosed herein is a variant MAAP identified by a disclosed method and comprising a mutation at one or more of positions 4-12, positions 49-57, and / or positions 87-95 with respect to the amino acid sequence of SEQ ID NO: 10 or SEQ ID NO:40. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 10 or SEQ ID NO:40 and having one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 10 or SEQ ID NO:40 with one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 10 or SEQ ID NO:40, wherein positions 4-12 comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200, wherein positions 49-57 comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238, or wherein positions 87-95 comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 10 or SEQ ID NO:40, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 10 or SEQ ID NO:40, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 10 or SEQ ID NO:40, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant MAAP identified by a disclosed method and comprising thesequence of SEQ ID NO: 10 or SEQ ID NO:40, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 10 or SEQ ID NO:40, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 10 or SEQ ID NO:40, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288.MAAP11 Variants

[0165] Disclosed herein is a variant membrane-associated accessory protein (MAAP) with a mutation at one or more of positions 4-12, positions 49-57, and / or positions 87-95 with respect to the amino acid sequence of SEQ ID NO: 11 or SEQ ID NO:41. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 11 or SEQ ID NO:41 and having one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 11 or SEQ ID NO:41 with one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 11 or SEQ ID NO:41, wherein positions 4-12 comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200, wherein positions 49-57 comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238, or wherein positions 87-95 comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 11 or SEQ ID NO:41, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 4-12. In an aspect, the disclosed amino acid sequence at positions 4-12 can comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 11 or SEQ ID NO:41, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 49-57. In an aspect, the disclosed amino acid sequence at positions 49-57 can comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 11 or SEQ ID NO:41, wherein positions 87-95 comprise the sequence set forthin SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising one or more mutations at positions 87-95. In an aspect, the disclosed amino acid sequence at positions 87-95 can comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising a mutation at one or more positions in the sequence of SEQ ID NO:91, SEQ ID NO: 92, or SEQ ID NO: 93.

[0166] Disclosed herein is a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 11 or SEQ ID NO:41. Disclosed herein is a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 11 or SEQ ID NO:41, wherein one or more mutations occur at positions 4-12, at positions 49-57, or at positions 87-95. Disclosed herein is a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 11 or SEQ ID NO:41, wherein one or more mutations occur in the sequence set forth in SEQ ID NO:91, SEQ ID NO:92, or SEQ ID NO:93.

[0167] In an aspect, the sequence set forth in SEQ ID NO: 11 can be encoded by the sequence set forth in SEQ ID NO:26. In an aspect, the sequence set forth in SEQ ID NO:41 can be encoded by the sequence set forth in SEQ ID NO: 56. In an aspect, the sequence set forth in SEQ ID NO:91 can be encoded by the sequence set forth in SEQ ID NO: 136. In an aspect, the sequence set forth in SEQ ID NO: 92 can be encoded by the sequence set forth in SEQ ID NO: 137. In an aspect, the sequence set forth in SEQ ID NO:93 can be encoded by the sequence set forth in SEQ ID NO: 138.

[0168] Disclosed herein is a variant MAAP identified by a disclosed method and comprising a mutation at one or more of positions 4-12, positions 49-57, and / or positions 87-95 with respect to the amino acid sequence of SEQ ID NO: 11 or SEQ ID NO:41. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 11 or SEQ ID NO:41 and having one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 11 or SEQ ID NO:41 with one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant MAAPidentified by a disclosed method and comprising the sequence of SEQ ID NO: 11 or SEQ ID NO:41, wherein positions 4-12 comprise the sequence set forth in any one of SEQ ID NO: 151- SEQ ID NO:200, wherein positions 49-57 comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238, or wherein positions 87-95 comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 11 or SEQ ID NO:41, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 11 or SEQ ID NO:41, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 11 or SEQ ID NO:41, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 11 or SEQ ID NO:41, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 11 or SEQ ID NO:41, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 11 or SEQ ID NO:41, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288.MAAP12 Variants

[0169] Disclosed herein is a variant membrane-associated accessory protein (MAAP) with a mutation at one or more of positions 4-12, positions 49-57, and / or positions 87-95 with respect to the amino acid sequence of SEQ ID NO: 12 or SEQ ID NO:42. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 12 or SEQ ID NO:42 and having one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 12 or SEQ ID NO:42 with one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 12 or SEQ ID NO:42, wherein positions 4-12 comprise the sequence set forth in any one of SEQ ID NO: 151- SEQ ID NO:200, wherein positions 49-57 comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238, or wherein positions 87-95 comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant membraneassociated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 12 or SEQ ID NO:42, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 4-12. In an aspect, the disclosed amino acid sequence at positions 4-12 can comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 12 or SEQ ID NO:42, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 49-57. In an aspect, the disclosed amino acid sequence at positions 49-57 can comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 12 or SEQ ID NO:42, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising one or more mutations at positions 87-95. In an aspect, the disclosed amino acid sequence at positions 87-95 can comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising a mutation at one or more positions in the sequence of SEQ ID NO:94, SEQ ID NO:95, or SEQ ID NO:96.

[0170] Disclosed herein is a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 12 or SEQ ID NO:42. Disclosed herein is a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 12 or SEQ ID NO:42, wherein one or more mutations occur at positions 4-12, at positions 49-57, or at positions 87-95. Disclosed herein is a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 12 or SEQ ID NO:42, wherein one or more mutations occur in the sequence set forth in SEQ ID NO:94, SEQ ID NO:95, or SEQ ID NO:96.

[0171] In an aspect, the sequence set forth in SEQ ID NO: 12 can be encoded by the sequence set forth in SEQ ID NO:27. In an aspect, the sequence set forth in SEQ ID NO:42 can beencoded by the sequence set forth in SEQ ID NO: 57. In an aspect, the sequence set forth in SEQ ID NO: 94 can be encoded by the sequence set forth in SEQ ID NO: 139. In an aspect, the sequence set forth in SEQ ID NO: 95 can be encoded by the sequence set forth in SEQ ID NO: 140. In an aspect, the sequence set forth in SEQ ID NO:96 can be encoded by the sequence set forth in SEQ ID NO: 141.

[0172] Disclosed herein is a variant MAAP identified by a disclosed method and comprising a mutation at one or more of positions 4-12, positions 49-57, and / or positions 87-95 with respect to the amino acid sequence of SEQ ID NO: 12 or SEQ ID NO:42. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 12 or SEQ ID NO:42 and having one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 12 or SEQ ID NO:42 with one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 12 or SEQ ID NO:42, wherein positions 4-12 comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200, wherein positions 49-57 comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238, or wherein positions 87-95 comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 12 or SEQ ID NO:42, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 12 or SEQ ID NO:42, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 12 or SEQ ID NO:42, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 12 or SEQ ID NO:42, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 12 or SEQ ID NO:42, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 12 or SEQ ID NO:42, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288.MAAP13 Variants

[0173] Disclosed herein is a variant membrane-associated accessory protein (MAAP) with a mutation at one or more of positions 4-12, positions 49-57, and / or positions 87-95 with respect to the amino acid sequence of SEQ ID NO: 13 or SEQ ID NO:43. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 13 or SEQ ID NO:43 and having one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 13 or SEQ ID NO:43 with one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 13 or SEQ ID NO:43, wherein positions 4-12 comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200, wherein positions 49-57 comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238, or wherein positions 87-95 comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 13 or SEQ ID NO:43, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 4-12. In an aspect, the disclosed amino acid sequence at positions 4-12 can comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 13 or SEQ ID NO:43, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 49-57. In an aspect, the disclosed amino acid sequence at positions 49-57 can comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 13 or SEQ ID NO:43, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising one or more mutations at positions 87-95. In an aspect, the disclosed amino acid sequence at positions 87-95 can comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising a mutation at one or more positions in the sequence of SEQ ID NO: 97, SEQ ID NO: 98, or SEQ ID NO: 99.

[0174] Disclosed herein is a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 13 or SEQ ID NO:43. Disclosed herein is a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 13 or SEQ ID NO:43, wherein one or more mutations occur at positions 4-12, at positions 49-57, or at positions 87-95. Disclosed herein is a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 13 or SEQ ID NO:43, wherein one or more mutations occur in the sequence set forth in SEQ ID NO:97, SEQ ID NO:98, or SEQ ID NO:99.

[0175] In an aspect, the sequence set forth in SEQ ID NO: 153 can be encoded by the sequence set forth in SEQ ID NO:28. In an aspect, the sequence set forth in SEQ ID NO:43 can be encoded by the sequence set forth in SEQ ID NO: 58. In an aspect, the sequence set forth in SEQ ID NO: 97 can be encoded by the sequence set forth in SEQ ID NO: 142. In an aspect, the sequence set forth in SEQ ID NO: 98 can be encoded by the sequence set forth in SEQ ID NO: 143. In an aspect, the sequence set forth in SEQ ID NO: 99 can be encoded by the sequence set forth in SEQ ID NO: 144.

[0176] Disclosed herein is a variant MAAP identified by a disclosed method and comprising a mutation at one or more of positions 4-12, positions 49-57, and / or positions 87-95 with respect to the amino acid sequence of SEQ ID NO: 13 or SEQ ID NO:43. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 13 or SEQ ID NO:43 and having one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 13 or SEQ ID NO:43 with one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 13 or SEQ ID NO:43, wherein positions 4-12 comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200, wherein positions 49-57 comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238, or wherein positions 87-95 comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 13 or SEQ ID NO:43,wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 13 or SEQ ID NO:43, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 13 or SEQ ID NO:43, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 13 or SEQ ID NO:43, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 13 or SEQ ID NO:43, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 13 or SEQ ID NO:43, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288.MAAPrh.8 Variants

[0177] Disclosed herein is a variant membrane-associated accessory protein (MAAP) with a mutation at one or more of positions 4-12, positions 49-57, and / or positions 87-95 with respect to the amino acid sequence of SEQ ID NO: 14 or SEQ ID NO:44. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 14 or SEQ ID NO:44and having one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 14 or SEQ ID NO:44 with one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 14 or SEQ ID NO:44, wherein positions 4-12 comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200, wherein positions 49-57 comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238, or wherein positions 87-95 comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 14 or SEQ ID NO:44, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 4-12. In an aspect, the disclosed amino acid sequence at positions 4-12 can comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant membrane associated accessory protein (MAAP)comprising the sequence of SEQ ID NO: 14 or SEQ ID NO:44, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 49-57. In an aspect, the disclosed amino acid sequence at positions 49-57 can comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 14 or SEQ ID NO:44, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising one or more mutations at positions 87-95. In an aspect, the disclosed amino acid sequence at positions 87-95 can comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising a mutation at one or more positions in the sequence of SEQ ID NO: 100, SEQ ID NO: 101, or SEQ ID NO: 102.

[0178] Disclosed herein is a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 14 or SEQ ID NO:44. Disclosed herein is a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 14 or SEQ ID NO:44, wherein one or more mutations occur at positions 4-12, at positions 49-57, or at positions 87-95. Disclosed herein is a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 14 or SEQ ID NO:44, wherein one or more mutations occur in the sequence set forth in SEQ ID NO: 100, SEQ ID NO: 101, or SEQ ID NO: 102.

[0179] In an aspect, the sequence set forth in SEQ ID NO: 14 can be encoded by the sequence set forth in SEQ ID NO:29. In an aspect, the sequence set forth in SEQ ID NO:44 can be encoded by the sequence set forth in SEQ ID NO: 59. In an aspect, the sequence set forth in SEQ ID NO: 100 can be encoded by the sequence set forth in SEQ ID NO: 145. In an aspect, the sequence set forth in SEQ ID NO: 101 can be encoded by the sequence set forth in SEQ ID NO: 146. In an aspect, the sequence set forth in SEQ ID NO: 102 can be encoded by the sequence set forth in SEQ ID NO: 147.

[0180] Disclosed herein is a variant MAAP identified by a disclosed method and comprising a mutation at one or more of positions 4-12, positions 49-57, and / or positions 87-95 with respect to the amino acid sequence of SEQ ID NO: 14 or SEQ ID NO:44. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 14 or SEQ ID NO:44 and having one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 14 or SEQ ID NO:44with one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 14 or SEQ ID NO:44, wherein positions 4-12 comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200, wherein positions 49-57 comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238, or wherein positions 87-95 comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 14 or SEQ ID NO:44, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 14 or SEQ ID NO:44, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 14 or SEQ ID NO:44, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 14 or SEQ ID NO:44, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 14 or SEQ ID NO:44, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 14 or SEQ ID NO:44, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288.MAAPrh.10 Variants

[0181] Disclosed herein is a variant membrane-associated accessory protein (MAAP) with a mutation at one or more of positions 4-12, positions 49-57, and / or positions 87-95 with respect to the amino acid sequence of SEQ ID NO: 15 or SEQ ID NO:45. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 15 or SEQ ID NO:45 and having one or more mutations at positions 4-12, positions 49-57, orpositions 87-95. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 15 or SEQ ID NO:45 with one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 15 or SEQ ID NO:45, wherein positions 4-12 comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200, wherein positions 49-57 comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238, or wherein positions 87-95 comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 15 or SEQ ID NO:45, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 4-12. In an aspect, the disclosed amino acid sequence at positions 4-12 can comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 15 or SEQ ID NO:45, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 49-57. In an aspect, the disclosed amino acid sequence at positions 49-57 can comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 15 or SEQ ID NO:45, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising one or more mutations at positions 87-95. In an aspect, the disclosed amino acid sequence at positions 87-95 can comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288.

[0182] Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising a mutation at one or more positions in the sequence of SEQ ID NO: 103, SEQ ID NO: 104, or SEQ ID NO: 105. Disclosed herein is a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 15 or SEQ ID NO:45. Disclosed herein is a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 15 or SEQ ID NO:45,wherein one or more mutations occur at positions 4-12, at positions 49-57, or at positions 87- 95. Disclosed herein is a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 15 or SEQ ID NO:45, wherein one or more mutations occur in the sequence set forth in SEQ ID NO: 103, SEQ ID NO: 104, or SEQ ID NO: 105. In an aspect, the sequence set forth in SEQ ID NO: 15 can be encoded by the sequence set forth in SEQ ID NO:30. In an aspect, the sequence set forth in SEQ ID NO:45 can be encoded by the sequence set forth in SEQ ID NO:60. In an aspect, the sequence set forth in SEQ ID NO: 103 can be encoded by the sequence set forth in SEQ ID NO: 148. In an aspect, the sequence set forth in SEQ ID NO: 104 can be encoded by the sequence set forth in SEQ ID NO: 149. In an aspect, the sequence set forth in SEQ ID NO: 105 can be encoded by the sequence set forth in SEQ ID NO: 150.

[0183] Disclosed herein is a variant MAAP identified by a disclosed method and comprising a mutation at one or more of positions 4-12, positions 49-57, and / or positions 87-95 with respect to the amino acid sequence of SEQ ID NO: 15 or SEQ ID NO:45. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 15 or SEQ ID NO:45 and having one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 15 or SEQ ID NO:45 with one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 15 or SEQ ID NO:45, wherein positions 4-12 comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200, wherein positions 49-57 comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238, or wherein positions 87-95 comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 15 or SEQ ID NO:45, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 15 or SEQ ID NO:45, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 15 or SEQ ID NO:45, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 15 or SEQ ID NO:45, wherein positions 4-12 comprise the sequenceset forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 15 or SEQ ID NO:45, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a variant MAAP identified by a disclosed method and comprising the sequence of SEQ ID NO: 15 or SEQ ID NO:45, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288.

[0184] In an aspect, a disclosed variant MAAP or expression of a disclosed variant MAAP in a cell can increase AAV egress. In an aspect, a disclosed AAV egress can be increased with the variant MAAP. In an aspect, a disclosed increase in AAV egress can comprise at least a 10%, 15%, 20%, 25%, 30%, 35, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100% (i.e., two-fold), 200%, 300%, 400%, 500%, or more than a 500% increase when compared to a control level (e.g., achieved by WT MAAP) or a level achieved in the absence of expression of the variant MAAP. In an aspect, a disclosed increase in AAV egress can comprise at least a 2-fold, a 3-fold, a 4-fold, a 5-fold, or more than 5-fold increase when compared to a control level (e.g., achieved by WT MAAP) or a level achieved in the absence of expression of the variant MAAP.

[0185] In an aspect, a disclosed variant MAAP or expression of a disclosed variant MAAP in a cell can modulate the rate or efficiency of AAV particle secretion. In an aspect, a disclosed rate or efficiency of AAV particle secretion can be modulated. In an aspect, modulating the rate or efficiency of AAV particle secretion can comprise increasing the rate of efficiency of AAV particle secretion. In an aspect, modulating the rate or efficiency of AAV particle secretion can comprise decreasing the rate of efficiency of AAV particle secretion.

[0186] In an aspect, a disclosed variant MAAP or expression of a disclosed variant MAAP in a cell can improve AAV capsid integrity. In an aspect, a disclosed AAV capsid integrity in a producer cell can be improved. In an aspect, a disclosed improvement in AAV capsid integrity can at least a 10%, 15%, 20%, 25%, 30%, 35, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100% (i.e., two-fold), 200%, 300%, 400%, 500%, or more than a 500% increase when compared to a control level (e.g., achieved by WT MAAP) or a level achieved in the absence of expression of the variant MAAP. In an aspect, a disclosed improvement of AAV capsid integrity can comprise at least a 2-fold, a 3-fold, a 4-fold, a 5-fold, or more than 5-fold increase when compared to a control level (e.g., achieved by WT MAAP) or a level achieved in the absence of expression of the variant MAAP.

[0187] In an aspect, a disclosed variant MAAP or expression of a disclosed variant MAAP in a cell can increase the stability of one or more viral proteins. In an aspect, a disclosed stabilityof one or more viral proteins can be increased. In an aspect, a disclosed increase in the stability of the one or more viral proteins can comprise at least a 10%, 15%, 20%, 25%, 30%, 35, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100% (i.e., two-fold), 200%, 300%, 400%, 500%, or more than a 500% increase when compared to a control level (e.g., achieved by WT MAAP) or a level achieved in the absence of expression of the variant MAAP. In an aspect, a disclosed increase in the stability of the one or more viral proteins can comprise at least a 2-fold, a 3 -fold, a 4-fold, a 5-fold, or more than 5-fold increase when compared to a control level (e.g., achieved by WT MAAP) or a level achieved in the absence of expression of the variant MAAP.

[0188] In an aspect, a disclosed variant MAAP or expression of a disclosed variant MAAP in a cell can decrease the degradation of the AAV capsid and / or viral proteins. In an aspect, a disclosed degradation of the AAV capsid and / or viral proteins can be decreased. In an aspect, a disclosed decrease in the stability of the one or more viral proteins can comprise at least a 10%, 15%, 20%, 25%, 30%, 35, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100% (i.e., two-fold), 200%, 300%, 400%, 500%, or more than a 500% when compared to a control level (e.g., achieved by WT MAAP) or a level achieved in the absence of expression of the variant MAAP. In an aspect, a disclosed decrease in the stability of the one or more viral proteins can comprise at least a 2-fold, a 3-fold, a 4-fold, a 5-fold, or more than 5-fold increase when compared to a control level (e.g., achieved by WT MAAP) or a level achieved in the absence of expression of the variant MAAP.

[0189] In an aspect, a disclosed variant MAAP or expression of a disclosed variant MAAP in a cell can increase AAV production. In an aspect, a disclosed AAV production in a producer cell can be increased. In an aspect, a disclosed AAV production can comprise at least a 10%, 15%, 20%, 25%, 30%, 35, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100% (i.e., two-fold), 200%, 300%, 400%, 500%, or more than a 500% increase when compared to a control level (e.g., achieved by WT MAAP) or a level achieved in the absence of expression of the variant MAAP. In an aspect, a disclosed production of AAV from the producer cell can comprise at least a 2-fold, a 3-fold, a 4-fold, a 5-fold, or more than 5-fold increase when compared to a control level (e.g., achieved by WT MAAP) or a level achieved in the absence of expression of the variant MAAP.

[0190] In an aspect, a disclosed variant MAAP or expression of a disclosed variant MAAP in a cell can enhance virion secretion from a producer cell. In an aspect, a disclosed virion secretion from a producer cell can be enhanced. In an aspect, a disclosed enhancement in virion secretion can comprise at least a 10%, 15%, 20%, 25%, 30%, 35, 40%, 45%, 50%, 55%, 60%,65%, 70%, 75%, 80%, 85%, 90%, 95%, 100% (i.e., two-fold), 200%, 300%, 400%, 500%, or more than a 500% increase when compared to a control level (e.g., achieved by WT MAAP) or a level achieved in the absence of expression of the variant MAAP. In an aspect, a disclosed enhancement in virion secretion can comprise at least a 2-fold, a 3-fold, a 4-fold, a 5-fold, or more than 5-fold increase when compared to a control level (e.g., achieved by WT MAAP) or a level achieved in the absence of expression of the variant MAAP.

[0191] In an aspect, a disclosed variant MAAP or expression of a disclosed MAAP variant in a cell can increase AAV packaging. In an aspect, a disclosed AAV packaging in a producer cell can be increased. In an aspect, a disclosed increase in AAV packaging can comprise at least a 10%, 15%, 20%, 25%, 30%, 35, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100% (i.e., two-fold), 200%, 300%, 400%, 500%, or more than a 500% increase when compared to a control level (e.g., achieved by WT MAAP) or a level achieved in the absence of expression of the variant MAAP. In an aspect, a disclosed increase in AAV packaging can comprise at least a 2-fold, a 3 -fold, a 4-fold, a 5-fold, or more than 5-fold increase when compared to a control level (e.g., achieved by WT MAAP) or a level achieved in the absence of expression of the variant MAAP.

[0192] In an aspect, a disclosed variant MAAP or expression of a disclosed MAAP variant in a cell can increase the overall titer and ratio of secreted vector genomes. In an aspect, a disclosed overall titer and ratio of secreted vector genomes can be increased. In an aspect, a disclosed increase in the overall titer and ratio of secreted vector genomes can comprise at least a 10%, 15%, 20%, 25%, 30%, 35, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100% (i.e., two-fold), 200%, 300%, 400%, 500%, or more than a 500% increase when compared to a control level (e.g., achieved by WT MAAP) or a level achieved in the absence of expression of the variant MAAP. In an aspect, a disclosed increase in the overall titer and ratio of secreted vector genomes can comprise at least a 2-fold, a 3-fold, a 4-fold, a 5- fold, or more than 5-fold increase when compared to a control level (e.g., achieved by WT MAAP) or a level achieved in the absence of expression of the variant MAAP.

[0193] In an aspect, a disclosed variant MAAP or expression of a disclosed MAAP variant in a cell can promote AAV secretion from a producer cell. In an aspect, a disclosed AAV secretion from a producer cell can be promoted. In an aspect, a disclosed AAV secretion from a producer cell can comprise at least a 10%, 15%, 20%, 25%, 30%, 35, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100% (i.e., two-fold), 200%, 300%, 400%, 500%, or more than a 500% increase when compared to a control level (e.g., achieved by WT MAAP) or a level achieved in the absence of expression of the variant MAAP. In an aspect, adisclosed increase in AAV secretion from a producer cell can comprise at least a 2-fold, a 3- fold, a 4-fold, a 5-fold, or more than 5-fold increase when compared to a control level (e.g., achieved by WT MAAP) or a level achieved in the absence of expression of the variant MAAP.

[0194] In an aspect, a disclosed variant MAAP or expression of a disclosed MAAP variant in a cell can increase production of AAV virions from a producer cell. In an aspect, a disclosed production of virions from a producer cell can be increased. In an aspect, a disclosed increase in production of AAV virions can comprise at least a 10%, 15%, 20%, 25%, 30%, 35, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100% (i.e., two-fold), 200%, 300%, 400%, 500%, or more than a 500% increase when compared to a control level (e.g., achieved by WT MAAP) or a level achieved in the absence of expression of the variant MAAP. In an aspect, a disclosed increase in production of AAV virions can comprise at least a 2-fold, a 3-fold, a 4-fold, a 5-fold, or more than 5-fold increase when compared to a control level (e.g., achieved by WT MAAP) or a level achieved in the absence of expression of the variant MAAP.

[0195] In an aspect, a disclosed variant MAAP or expression of a disclosed variant MAAP in a cell can increase AAV secretion from a producer cell during packaging. In an aspect, a disclosed AAV secretion from a producer cell during packaging can be increased. In an aspect, a disclosed increase in AAV secretion can comprise at least a 10%, 15%, 20%, 25%, 30%, 35, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100% (i.e., two-fold), 200%, 300%, 400%, 500%, or more than a 500% increase when compared to a control level (e.g., achieved by WT MAAP) or a level achieved in the absence of expression of the variant MAAP. In an aspect, a disclosed increase in AAV secretion can comprise at least a 2-fold, a 3-fold, a 4-fold, a 5-fold, or more than 5-fold increase when compared to a control level (e.g., achieved by WT MAAP) or a level achieved in the absence of expression of the variant MAAP.

[0196] In an aspect, a disclosed variant MAAP or expression of a disclosed variant MAAP also increase EV-associated genome titers and / or increase EV secretion by the one or more cells. In an aspect, a disclosed variant MAAP or expression of a disclosed variant MAAP can increase EV-associated genome titers and / or EV secretion by one or more producer cells. In an aspect of a disclosed method, expression of a disclosed variant MAAP can increase EV-associated genome titers and / or EV secretion by one or more producer cells by at least a 10%, 15%, 20%, 25%, 30%, 35, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100% (i.e., two-fold), 200%, 300%, 400%, 500%, or more than a 500% when compared to a control level (e.g., achieved by WT MAAP) or a level achieved in the absence of expression of the variant MAAP. In an aspect, a disclosed increase in EV-associated genome titers and / or in EV secretion by one or more producer cells can comprise at least a 2-fold, a 3-fold, a 4-fold, a 5-fold, or more than 5-fold increase when compared to a control level (e.g., achieved by WT MAAP) or a level achieved in the absence of expression of the variant MAAP. In an aspect of a disclosed method, the number of AAV particles physically enclosed within EVs is increased, the number of AAV particles physically attached to the surface of the EVs is increased, or both.

[0197] In an aspect, a disclosed variant MAAP can be used to improve the manufacturing of rAAV for gene therapy applications and / or gene editing applications in a subject in need thereof. In an aspect, a disclosed variant MAAP can be covalently attached or non-covalently attached to one or more of a polypeptide, a glycopeptide, a polysaccharide, a glycolipid, a lipid, or a nucleic acid polymer, or to a combination thereof. In an aspect, a disclosed variant MAAP can be covalently attached or non-covalently attached to one or more therapeutic agents. In an aspect, a disclosed variant MAAP can increase secretion of an AAV having a different serotype. For example, a disclosed variant MAAP8 can increase secretion of AAV9 or AAV2 or AAV4 or any other AAV. In an aspect, a disclosed variant MAAP acts independent of AAV serotype.Table 6 - Amino Acid Sequences for Wild-Type MAAPs with LEU Start CodonTable 7 - Amino Acid Sequences for Wild-Type MAAPs with MET Start Codon2. NUCLEIC ACIDS

[0198] Disclosed herein is a nucleic acid comprising a nucleotide sequence encoding a disclosed variant membrane-associated accessory protein (MAAP). Disclosed herein is a nucleic acid encoding a disclosed variant membrane-associated accessory protein (MAAP).

[0199] Disclosed herein is a nucleic acid comprising a nucleotide sequence encoding a variant membrane-associated accessory protein (MAAP) comprising the sequence of any one of SEQ ID NO:331 - SEQ ID NO:360. In an aspect of any one of SEQ ID NO:331 - SEQ ID NO:360, each amino acid at positions 4-12 can comprise any amino acid. In an aspect of any one of SEQ ID NO:331 - SEQ ID NO:360, each amino acid at positions 49-57 can comprise any amino acid. In an aspect of any one of SEQ ID NO:331 - SEQ ID NO:360, each amino acid at positions 87-95 can comprise any amino acid. In an aspect of any one of SEQ ID NO:331 - SEQ ID NO:360, each of X4X5X6X7X8X9X10X11X12 can comprise any amino acid, each of X49X50X51X52X53X54X55X56X57 can comprise any amino acid, and each of X87X88X89X90X91X92X93X94X95 can comprise any amino acid. In an aspect, Table 1A provides the amino acid sequence for each of SEQ ID NO:331 - SEQ ID NO:360, which identify threeseparate 9 amino acid regions targeted for directed evolution of MAAP variants. In an aspect, Table 1A provides the amino acid sequence for each of SEQ ID NO:331 - SEQ ID NO:360, which identify the 9 amino acid regions targeted for Library 1 (e.g., Table 2), Library 2 (e.g., Table 3), and Library 3 (e.g., Table 4). Disclosed herein is a sequence encoding a variant MAAP comprising a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to any one of SEQ ID NO:331 - SEQ ID NO:360.

[0200] Disclosed herein is a nucleic acid comprising a nucleotide sequence encoding a variant membrane-associated accessory protein (MAAP) comprising the sequence of any one of SEQ ID NO:346 - SEQ ID NO:360. In an aspect of any one of SEQ ID NO:346 - SEQ ID NO:360, each amino acid at positions 4-12 can comprise any amino acid. In an aspect of any one of SEQ ID NO:346 - SEQ ID NO:360, each amino acid at positions 49-57 can comprise any amino acid. In an aspect of any one of SEQ ID NO:346 - SEQ ID NO:360, each amino acid at positions 87-95 can comprise any amino acid. In an aspect of any one of SEQ ID NO:346 - SEQ ID NO:360, each of X4X5X6X7X8X9X10X11X12 can comprise any amino acid, each of X49X50X51X52X53X54X55X56X57 can comprise any amino acid, and each of X87X88X89X90X91X92X93X94X95 can comprise any amino acid. In an aspect, Table IB provides the amino acid sequence for each of SEQ ID NO:346 - SEQ ID NO:360, which identify three separate 9 amino acid regions targeted for directed evolution of MAAP variants. In an aspect, Table IB provides the amino acid sequence for each of SEQ ID NO:346 - SEQ ID NO:360, which identify the 9 amino acid regions targeted for Library 1 (e.g., Table 2), Library 2 (e.g., Table 3), and Library 3 (e.g., Table 4). Disclosed herein is a nucleic acid comprising a nucleotide sequence encoding a variant MAAP comprising a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to any one of SEQ ID NO:346 - SEQ ID NO:360.MAAP1 Variants

[0201] Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein from AAV1 (MAAP1).

[0202] Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:01 or SEQ ID NO:31. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:01 or SEQ ID NO:31 and having one or more mutations at positions 4-12,positions 49-57, or positions 87-95. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:01 or SEQ ID NO:31 with one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:01 or SEQ ID NO:31, wherein positions 4-12 comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200, wherein positions 49-57 comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238, or wherein positions 87-95 comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:01 or SEQ ID NO:31, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 4-12. In an aspect, the disclosed amino acid sequence at positions 4-12 can comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 01 or SEQ ID NO:31, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 49-57. In an aspect, the disclosed amino acid sequence at positions 49-57 can comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:01 or SEQ ID NO:31, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising one or more mutations at positions 87-95. In an aspect, the disclosed amino acid sequence at positions 87-95 can comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising a mutation at one or more positions in the sequence of SEQ ID NO:61, SEQ ID NO:62, or SEQ ID NO:63. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:01 or SEQ ID NO:31, wherein one or more mutations occur at positions 4-12, at positions 49-57, or at positions 87-95. Disclosed herein is a nucleic acid encoding avariant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:01 or SEQ ID NO:31, wherein one or more mutations occur in the sequence set forth in SEQ ID NO:82, the sequence set forth in SEQ ID NO:83, or the sequence set forth in SEQ ID NO:84.

[0203] In an aspect, the sequence set forth in SEQ ID NO:01 can be encoded by the sequence set forth in SEQ ID NO: 16. In an aspect, the sequence set forth in SEQ ID NO:31 can be encoded by the sequence set forth in SEQ ID NO:46. In an aspect, the sequence set forth in SEQ ID NO:61 can be encoded by the sequence set forth in SEQ ID NO: 106. In an aspect, the sequence set forth in SEQ ID NO: 62 can be encoded by the sequence set forth in SEQ ID NO: 107. In an aspect, the sequence set forth in SEQ ID NO:63 can be encoded by the sequence set forth in SEQ ID NO: 108.MAAP2 Variants

[0204] Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein from AAV2 (MAAP2).

[0205] Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:02 or SEQ ID NO:32. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:02 or SEQ ID NO:32 and having one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:02 or SEQ ID NO:32 with one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:02 or SEQ ID NO:32, wherein positions 4-12 comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200, wherein positions 49-57 comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238, or wherein positions 87-95 comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:02 or SEQ ID NO:32, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 4-12. In anaspect, the disclosed amino acid sequence at positions 4-12 can comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:02 or SEQ ID NO:32, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 49-57. In an aspect, the disclosed amino acid sequence at positions 49-57 can comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:02 or SEQ ID NO:32, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising one or more mutations at positions 87-95. In an aspect, the disclosed amino acid sequence at positions 87-95 can comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising a mutation at one or more positions in the sequence of SEQ ID NO:64, SEQ ID NO:65, or SEQ ID NO:66. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:02 or SEQ ID NO:32, wherein one or more mutations occur at positions 4-12, at positions 49-57, or at positions 87-95. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:02 or SEQ ID NO:32, wherein one or more mutations occur in the sequence set forth in SEQ ID NO:64, the sequence set forth in SEQ ID NO:65, or the sequence set forth in SEQ ID NO:66.

[0206] In an aspect, the sequence set forth in SEQ ID NO: 02 can be encoded by the sequence set forth in SEQ ID NO: 17. In an aspect, the sequence set forth in SEQ ID NO:32 can be encoded by the sequence set forth in SEQ ID NO:47. In an aspect, the sequence set forth in SEQ ID NO:61 can be encoded by the sequence set forth in SEQ ID NO: 109. In an aspect, the sequence set forth in SEQ ID NO: 62 can be encoded by the sequence set forth in SEQ ID NO: 110. In an aspect, the sequence set forth in SEQ ID NO:63 can be encoded by the sequence set forth in SEQ ID NO: 111.MAAP3 Variants

[0207] Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein from AAV3 (MAAP3).

[0208] Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:03 or SEQ ID NO:33. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 03 or SEQ ID NO:33 and having one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:03 or SEQ ID NO:33 with one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:03 or SEQ ID NO:33, wherein positions 4-12 comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200, wherein positions 49-57 comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238, or wherein positions 87-95 comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:03 or SEQ ID NO:33, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 4-12. In an aspect, the disclosed amino acid sequence at positions 4-12 can comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:03 or SEQ ID NO:33, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 49-57. In an aspect, the disclosed amino acid sequence at positions 49-57 can comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:03 or SEQ ID NO:33, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising one or more mutations atpositions 87-95. In an aspect, the disclosed amino acid sequence at positions 87-95 can comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising a mutation at one or more positions in the sequence of SEQ ID NO:67, SEQ ID NO:68, or SEQ ID NO:69. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 03 or SEQ ID NO:33, wherein one or more mutations occur at positions 4-12, at positions 49-57, or at positions 87-95. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 03 or SEQ ID NO:33, wherein one or more mutations occur in the sequence set forth in SEQ ID NO: 67, the sequence set forth in SEQ ID NO: 180, or the sequence set forth in SEQ ID NO: 181.

[0209] In an aspect, the sequence set forth in SEQ ID NO: 03 can be encoded by the sequence set forth in SEQ ID NO: 18. In an aspect, the sequence set forth in SEQ ID NO:33 can be encoded by the sequence set forth in SEQ ID NO:48. In an aspect, the sequence set forth in SEQ ID NO:67 can be encoded by the sequence set forth in SEQ ID NO: 112. In an aspect, the sequence set forth in SEQ ID NO: 68 can be encoded by the sequence set forth in SEQ ID NO: 113. In an aspect, the sequence set forth in SEQ ID NO: 69 can be encoded by the sequence set forth in SEQ ID NO: 114.MAAP4 Variants

[0210] Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein from AAV4 (MAAP4).

[0211] Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:04 or SEQ ID NO:34. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:04 or SEQ ID NO:34 and having one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:04 or SEQ ID NO:34 with one or more mutations at positions 4-12, positions 49-57, or positions87-95. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:04 or SEQ ID NO:34, wherein positions 4-12 comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200, wherein positions 49-57 comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238, or wherein positions 87-95 comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:04 or SEQ ID NO:34, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 4-12. In an aspect, the disclosed amino acid sequence at positions 4-12 can comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:04 or SEQ ID NO:34, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 49-57. In an aspect, the disclosed amino acid sequence at positions 49-57 can comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:04 or SEQ ID NO:34, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising one or more mutations at positions 87-95. In an aspect, the disclosed amino acid sequence at positions 87-95 can comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising a mutation at one or more positions in the sequence of SEQ ID NO:70, SEQ ID NO:71, or SEQ ID NO:72. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:04 or SEQ ID NO:34, wherein one or more mutations occur at positions 4-12, at positions 49-57, or at positions 87-95. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence setforth in SEQ ID NO:04 or SEQ ID NO:34, wherein one or more mutations occur in the sequence set forth in SEQ ID NO:70, the sequence set forth in SEQ ID NO:71, or the sequence set forth in SEQ ID NO:72.

[0212] In an aspect, the sequence set forth in SEQ ID NO: 04 can be encoded by the sequence set forth in SEQ ID NO: 19. In an aspect, the sequence set forth in SEQ ID NO:34 can be encoded by the sequence set forth in SEQ ID NO:49. In an aspect, the sequence set forth in SEQ ID NO:70 can be encoded by the sequence set forth in SEQ ID NO: 115. In an aspect, the sequence set forth in SEQ ID NO:71 can be encoded by the sequence set forth in SEQ ID NO: 116. In an aspect, the sequence set forth in SEQ ID NO:72 can be encoded by the sequence set forth in SEQ ID NO: 117.MAAP5 Variants

[0213] Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein from AAV5 (MAAP5).

[0214] Disclosed herein is a nucleic acid encoding variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:05 or SEQ ID NO:35. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 05 or SEQ ID NO:35 and having one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:05 or SEQ ID NO:35 with one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:05 or SEQ ID NO:35, wherein positions 4-12 comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200, wherein positions 49-57 comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238, or wherein positions 87-95 comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:05 or SEQ ID NO:35, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 4-12. In an aspect, the disclosed amino acid sequence at positions 4-12 can comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a nucleic acid encoding a variantmembrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:05 or SEQ ID NO:35, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 49-57. In an aspect, the disclosed amino acid sequence at positions 49-57 can comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:05 or SEQ ID NO:35, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising one or more mutations at positions 87-95. In an aspect, the disclosed amino acid sequence at positions 87-95 can comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising a mutation at one or more positions in the sequence of SEQ ID NO: 73, SEQ ID NO: 74, or SEQ ID NO: 75. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:05 or SEQ ID NO:35, wherein one or more mutations occur at positions 4-12, at positions 49-57, or at positions 87-95. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 05 or SEQ ID NO:35, wherein one or more mutations occur in the sequence set forth in SEQ ID NO: 73, the sequence set forth in SEQ ID NO: 74, or the sequence set forth in SEQ ID NO: 75.

[0215] In an aspect, the sequence set forth in SEQ ID NO:05 can be encoded by the sequence set forth in SEQ ID NO:20. In an aspect, the sequence set forth in SEQ ID NO:38 can be encoded by the sequence set forth in SEQ ID NO: 50. In an aspect, the sequence set forth in SEQ ID NO: 73 can be encoded by the sequence set forth in SEQ ID NO: 118. In an aspect, the sequence set forth in SEQ ID NO: 74 can be encoded by the sequence set forth in SEQ ID NO: 119. In an aspect, the sequence set forth in SEQ ID NO:75 can be encoded by the sequence set forth in SEQ ID NO: 120.MAAP6 Variants

[0216] Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein from AAV6 (MAAP6).

[0217] Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:06 or SEQ ID NO:36. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 06 or SEQ ID NO:36 and having one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:06 or SEQ ID NO:36 with one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:06 or SEQ ID NO:36, wherein positions 4-12 comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200, wherein positions 49-57 comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238, or wherein positions 87-95 comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:06 or SEQ ID NO:36, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 4-12. In an aspect, the disclosed amino acid sequence at positions 4-12 can comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:06 or SEQ ID NO:36, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 49-57. In an aspect, the disclosed amino acid sequence at positions 49-57 can comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:06 or SEQ ID NO:36, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising one or more mutations at positions 87-95. In an aspect, the disclosed amino acid sequence at positions 87-95 can comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP)comprising a mutation at one or more positions in the sequence of SEQ ID NO:76, SEQ ID NO:77, or SEQ ID NO:78. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 06 or SEQ ID NO: 36, wherein one or more mutations occur at positions 4-12, at positions 49-57, or at positions 87-95. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 06 or SEQ ID NO: 36, wherein one or more mutations occur in the sequence set forth in SEQ ID NO:76, the sequence set forth in SEQ ID NO:77, or the sequence set forth in SEQ ID NO: 78.

[0218] In an aspect, the sequence set forth in SEQ ID NO: 06 can be encoded by the sequence set forth in SEQ ID NO:21. In an aspect, the sequence set forth in SEQ ID NO:36 can be encoded by the sequence set forth in SEQ ID NO:51. In an aspect, the sequence set forth in SEQ ID NO:76 can be encoded by the sequence set forth in SEQ ID NO: 121. In an aspect, the sequence set forth in SEQ ID NO:77 can be encoded by the sequence set forth in SEQ ID NO: 122. In an aspect, the sequence set forth in SEQ ID NO:78 can be encoded by the sequence set forth in SEQ ID NO: 123.MAAP7 Variants

[0219] Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein from AAV7 (MAAP7).

[0220] Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:07 or SEQ ID NO:37. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 07 or SEQ ID NO:37 and having one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:07 or SEQ ID NO:37 with one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:07 or SEQ ID NO:37, wherein positions 4-12 comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ IDN0:200, wherein positions 49-57 comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238, or wherein positions 87-95 comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:07 or SEQ ID NO:37, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 4-12. In an aspect, the disclosed amino acid sequence at positions 4-12 can comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:07 or SEQ ID NO:37, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 49-57. In an aspect, the disclosed amino acid sequence at positions 49-57 can comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:07 or SEQ ID NO:37, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising one or more mutations at positions 87-95. In an aspect, the disclosed amino acid sequence at positions 87-95 can comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising a mutation at one or more positions in the sequence of SEQ ID NO:79, SEQ ID NO:80, or SEQ ID NO:81. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 07 or SEQ ID NO: 37, wherein one or more mutations occur at positions 4-12, at positions 49-57, or at positions 87-95. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 07 or SEQ ID NO: 37, wherein one or more mutations occur in the sequence set forth in SEQ ID NO:79, the sequence set forth in SEQ ID NO:80, or the sequence set forth in SEQ ID NO:81.

[0221] In an aspect, the sequence set forth in SEQ ID NO: 07 can be encoded by the sequence set forth in SEQ ID NO:22. In an aspect, the sequence set forth in SEQ ID NO:37 can be encoded by the sequence set forth in SEQ ID NO: 52. In an aspect, the sequence set forth in SEQ ID NO:79 can be encoded by the sequence set forth in SEQ ID NO: 124. In an aspect, the sequence set forth in SEQ ID NO: 80 can be encoded by the sequence set forth in SEQ ID NO: 125. In an aspect, the sequence set forth in SEQ ID NO: 81 can be encoded by the sequence set forth in SEQ ID NO: 126.MAAP8 Variants

[0222] Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein from AAV8 (MAAP8).

[0223] Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:08 or SEQ ID NO:38. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 08 or SEQ ID NO:38 and having one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:08 or SEQ ID NO:38 with one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:08 or SEQ ID NO:38, wherein positions 4-12 comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200, wherein positions 49-57 comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238, or wherein positions 87-95 comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:08 or SEQ ID NO:38, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 4-12. In an aspect, the disclosed amino acid sequence at positions 4-12 can comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:08 or SEQ ID NO:38, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a nucleic acid encoding a variant membraneassociated accessory protein (MAAP) having one or more mutations at positions 49-57. In an aspect, the disclosed amino acid sequence at positions 49-57 can comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:08 or SEQ ID NO:38, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising one or more mutations at positions 87-95. In an aspect, the disclosed amino acid sequence at positions 87-95 can comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising one or more mutations at one or more positions in the sequence of SEQ ID NO:82, SEQ ID NO:83, or SEQ ID NO:84. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 08 or SEQ ID NO: 38, wherein one or more mutations occur at positions 4-12, at positions 49-57, or at positions 87- 95. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 08 or SEQ ID NO: 38, wherein one or more mutations occur in the sequence set forth in SEQ ID NO: 82, the sequence set forth in SEQ ID NO: 83, or the sequence set forth in SEQ ID NO:84.

[0224] In an aspect, the sequence set forth in SEQ ID NO: 08 can be encoded by the sequence set forth in SEQ ID NO:23. In an aspect, the sequence set forth in SEQ ID NO:38 can be encoded by the sequence set forth in SEQ ID NO: 53. In an aspect, the sequence set forth in SEQ ID NO:82 can be encoded by the sequence set forth in SEQ ID NO: 127. In an aspect, the sequence set forth in SEQ ID NO: 83 can be encoded by the sequence set forth in SEQ ID NO: 128. In an aspect, the sequence set forth in SEQ ID NO: 84 can be encoded by the sequence set forth in SEQ ID NO: 129.

[0225] Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of any one of SEQ ID NO:289 - SEQ ID NO:298. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising a sequence having at least 50%, at least 55%, at least 60%, at least 65%,at least 70%, at least 75%, at least 80%, at least 85%, at least 90, at least 95%, or more than 95% identity to the sequence set forth in any one of SEQ ID NO:289 - SEQ ID NO:298.

[0226] Disclosed herein is a nucleic acid comprising sequence set forth in any one of SEQ ID NO:299 - SEQ ID NO:308. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) and comprising sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90, at least 95%, or more than 95% identity to the sequence set forth in any one of SEQ ID NO:299 - SEQ ID NO:308.

[0227] In an aspect, the sequence set forth in SEQ ID NO:299 can encode the sequence set forth in SEQ ID NO:289. In an aspect, the sequence set forth in SEQ ID NO:300 can encode the sequence set forth in SEQ ID NO:290. In an aspect, the sequence set forth in SEQ ID NO:301 can encode the sequence set forth in SEQ ID NO:291. In an aspect, the sequence set forth in SEQ ID NO:302 can encode the sequence set forth in SEQ ID NO:292. In an aspect, the sequence set forth in SEQ ID NO:303 can encode the sequence set forth in SEQ ID NO:293. In an aspect, the sequence set forth in SEQ ID NO: 304 can encode the sequence set forth in SEQ ID NO:294. In an aspect, the sequence set forth in SEQ ID NO:305 can encode the sequence set forth in SEQ ID NO:295. In an aspect, the sequence set forth in SEQ ID NO:306 can encode the sequence set forth in SEQ ID NO:296. In an aspect, the sequence set forth in SEQ ID NO:307 can encode the sequence set forth in SEQ ID NO:297. In an aspect, the sequence set forth in SEQ ID NO:308 can encode the sequence set forth in SEQ ID NO:298.

[0228] Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of any one of SEQ ID NO:309 - SEQ ID NO:319. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising a sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90, at least 95%, or more than 95% identity to the sequence set forth in any one of SEQ ID NO:309 - SEQ ID NO:319.

[0229] Disclosed herein is a nucleic acid comprising the sequence set forth in any one of SEQ ID NO:320 - SEQ ID NO:330. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) and comprising sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90, at least 95%, or more than 95% identity to the sequence set forth in any one of SEQ ID NO:320 - SEQ ID NO:330. In an aspect, the sequence set forth in SEQ ID NO:320 can encode the sequence set forth in SEQ ID NO:309. In an aspect, the sequence set forth in SEQ ID NO:321 can encode the sequence set forth in SEQ ID NO:310. In an aspect, the sequence setforth in SEQ ID NO:322 can encode the sequence set forth in SEQ ID NO:311. In an aspect, the sequence set forth in SEQ ID NO:323 can encode the sequence set forth in SEQ ID NO:312. In an aspect, the sequence set forth in SEQ ID NO:324 can encode the sequence set forth in SEQ ID NO:313. In an aspect, the sequence set forth in SEQ ID NO:325 can encode the sequence set forth in SEQ ID NO:314. In an aspect, the sequence set forth in SEQ ID NO:326 can encode the sequence set forth in SEQ ID NO:315. In an aspect, the sequence set forth in SEQ ID NO:327 can encode the sequence set forth in SEQ ID NO:316. In an aspect, the sequence set forth in SEQ ID NO:328 can encode the sequence set forth in SEQ ID NO:317. In an aspect, the sequence set forth in SEQ ID NO:329 can encode the sequence set forth in SEQ ID NO:318. In an aspect, the sequence set forth in SEQ ID NO:330 can encode the sequence set forth in SEQ ID NO:319.

[0230] Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of any one of SEQ ID NO:331 - SEQ ID NO:345 or SEQ ID NO:346 - SEQ ID NO:360. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising a sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90, at least 95%, or more than 95% identity to the sequence set forth in any one of SEQ ID NO:331 - SEQ ID NO:345 or SEQ ID NO:346 - SEQ ID NO:360.

[0231] Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of any one of SEQ ID NO:362- SEQ ID NO:472. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising a sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90, at least 95%, or more than 95% identity to the sequence set forth in any one of SEQ ID NO:362 - SEQ ID NO:472.

[0232] Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of any one of SEQ ID NO:473 - SEQ ID NO:610. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising a sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90, at least 95%, or more than 95% identity to the sequence set forth in any one of SEQ ID NO:473 - SEQ ID NO:610.

[0233] Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:345 or SEQ ID NO:615. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising a sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least70%, at least 75%, at least 80%, at least 85%, at least 90, at least 95%, or more than 95% identity to the sequence set forth in of SEQ ID NO:345 or SEQ ID NO:615.MAAP9 Variants

[0234] Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein from AAV9 (MAAP9).

[0235] Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO:09 or SEQ ID NO:39. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 09 or SEQ ID NO:39 and having one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:09 or SEQ ID NO:39 with one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:09 or SEQ ID NO:39, wherein positions 4-12 comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200, wherein positions 49-57 comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238, or wherein positions 87-95 comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:09 or SEQ ID NO:39, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 4-12. In an aspect, the disclosed amino acid sequence at positions 4-12 can comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:09 or SEQ ID NO:39, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 49-57. In an aspect, the disclosed amino acid sequence at positions 49-57 can comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO:09 or SEQ ID NO:39, wherein positions 87-95 comprise the sequence set forthin SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising one or more mutations at positions 87-95. In an aspect, the disclosed amino acid sequence at positions 87-95 can comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising a mutation at one or more positions in the sequence of SEQ ID NO: 85, SEQ ID NO:86, or SEQ ID NO:87. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 09 or SEQ ID NO: 39, wherein one or more mutations occur at positions 4-12, at positions 49-57, or at positions 87-95. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 09 or SEQ ID NO: 39, wherein one or more mutations occur in the sequence set forth in SEQ ID NO: 197, the sequence set forth in SEQ ID NO: 198, or the sequence set forth in SEQ ID NO: 199.

[0236] In an aspect, the sequence set forth in SEQ ID NO: 09 can be encoded by the sequence set forth in SEQ ID NO:24. In an aspect, the sequence set forth in SEQ ID NO:39 can be encoded by the sequence set forth in SEQ ID NO: 54. In an aspect, the sequence set forth in SEQ ID NO:85 can be encoded by the sequence set forth in SEQ ID NO: 130. In an aspect, the sequence set forth in SEQ ID NO: 86 can be encoded by the sequence set forth in SEQ ID NO: 131. In an aspect, the sequence set forth in SEQ ID NO: 87 can be encoded by the sequence set forth in SEQ ID NO: 132.MAAP10 Variants

[0237] Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein from AAV10 (MAAP 10).

[0238] Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 10 or SEQ ID NO:40. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 10 or SEQ ID NO:40 and having one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a nucleic acid encoding a variantmembrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 10 or SEQ ID NO:40 with one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 10 or SEQ ID NO:40, wherein positions 4-12 comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200, wherein positions 49-57 comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238, or wherein positions 87-95 comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 10 or SEQ ID NO:40, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 4-12. In an aspect, the disclosed amino acid sequence at positions 4-12 can comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 10 or SEQ ID NO:40, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 49-57. In an aspect, the disclosed amino acid sequence at positions 49-57 can comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 10 or SEQ ID NO:40, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising one or more mutations at positions 87-95. In an aspect, the disclosed amino acid sequence at positions 87-95 can comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising a mutation at one or more positions in the sequence of SEQ ID NO:88, SEQ ID NO:89, or SEQ ID NO:90. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 10 or SEQ ID NO:40, wherein one or more mutations occur at positions 4-12, at positions 49-57, or at positions 87-95. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP)having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 10 or SEQ ID NO:40, wherein one or more mutations occur in the sequence set forth in SEQ ID NO:88, the sequence set forth in SEQ ID NO:89, or the sequence set forth in SEQ ID NO:90.

[0239] In an aspect, the sequence set forth in SEQ ID NO: 10 can be encoded by the sequence set forth in SEQ ID NO:25. In an aspect, the sequence set forth in SEQ ID NO:40 can be encoded by the sequence set forth in SEQ ID NO: 55. In an aspect, the sequence set forth in SEQ ID NO:88 can be encoded by the sequence set forth in SEQ ID NO: 133. In an aspect, the sequence set forth in SEQ ID NO: 89 can be encoded by the sequence set forth in SEQ ID NO: 134. In an aspect, the sequence set forth in SEQ ID NO:90 can be encoded by the sequence set forth in SEQ ID NO: 135.MAAP11 Variants

[0240] Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein from AAV11 (MAAP11).

[0241] Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 11 or SEQ ID NO:41. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 11 or SEQ ID NO:41 and having one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 11 or SEQ ID NO:41 with one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 11 or SEQ ID NO:41, wherein positions 4-12 comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200, wherein positions 49-57 comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238, or wherein positions 87-95 comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 11 or SEQ ID NO:41, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 4-12. In anaspect, the disclosed amino acid sequence at positions 4-12 can comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 11 or SEQ ID NO:41, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 49-57. In an aspect, the disclosed amino acid sequence at positions 49-57 can comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 11 or SEQ ID NO:41, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising one or more mutations at positions 87-95. In an aspect, the disclosed amino acid sequence at positions 87-95 can comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising a mutation at one or more positions in the sequence of SEQ ID NO:91, SEQ ID NO:92, or SEQ ID NO:93. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 11 or SEQ ID NO:41, wherein one or more mutations occur at positions 4-12, at positions 49-57, or at positions 87-95. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 11 or SEQ ID NO:41, wherein one or more mutations occur in the sequence set forth in SEQ ID NO:203, the sequence set forth in SEQ ID NO:204, or the sequence set forth in SEQ ID NO:205.

[0242] In an aspect, the sequence set forth in SEQ ID NO: 11 can be encoded by the sequence set forth in SEQ ID NO:26. In an aspect, the sequence set forth in SEQ ID NO:41 can be encoded by the sequence set forth in SEQ ID NO: 56. In an aspect, the sequence set forth in SEQ ID NO:91 can be encoded by the sequence set forth in SEQ ID NO: 136. In an aspect, the sequence set forth in SEQ ID NO: 92 can be encoded by the sequence set forth in SEQ ID NO: 137. In an aspect, the sequence set forth in SEQ ID NO:93 can be encoded by the sequence set forth in SEQ ID NO: 138.MAAP12 Variants

[0243] Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein from AAV12 (MAAP12).

[0244] Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 12 or SEQ ID NO:42. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 12 or SEQ ID NO:42 and having one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 12 or SEQ ID NO:42 with one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 12 or SEQ ID NO:42, wherein positions 4-12 comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200, wherein positions 49-57 comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238, or wherein positions 87-95 comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 12 or SEQ ID NO:42, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 4-12. In an aspect, the disclosed amino acid sequence at positions 4-12 can comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 12 or SEQ ID NO:42, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 49-57. In an aspect, the disclosed amino acid sequence at positions 49-57 can comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 12 or SEQ ID NO:42, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising one or more mutations atpositions 87-95. In an aspect, the disclosed amino acid sequence at positions 87-95 can comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising a mutation at one or more positions in the sequence of SEQ ID NO:94, SEQ ID NO:95, or SEQ ID NO:96. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 12 or SEQ ID NO:42, wherein one or more mutations occur at positions 4-12, at positions 49-57, or at positions 87-95. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 12 or SEQ ID NO:42, wherein one or more mutations occur in the sequence set forth in SEQ ID NO:94, the sequence set forth in SEQ ID NO:95, or the sequence set forth in SEQ ID NO:96.

[0245] In an aspect, the sequence set forth in SEQ ID NO: 12 can be encoded by the sequence set forth in SEQ ID NO:27. In an aspect, the sequence set forth in SEQ ID NO:42 can be encoded by the sequence set forth in SEQ ID NO: 57. In an aspect, the sequence set forth in SEQ ID NO:94 can be encoded by the sequence set forth in SEQ ID NO: 139. In an aspect, the sequence set forth in SEQ ID NO: 95 can be encoded by the sequence set forth in SEQ ID NO: 140. In an aspect, the sequence set forth in SEQ ID NO:96 can be encoded by the sequence set forth in SEQ ID NO: 141.MAAP13 Variants

[0246] Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein from AAV13 (MAAP 13).

[0247] Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 13 or SEQ ID NO:43. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 13 or SEQ ID NO:43 and having one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 13 or SEQ ID NO:43 with one or more mutations at positions 4-12, positions 49-57, or positions87-95. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 13 or SEQ ID NO:43, wherein positions 4-12 comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200, wherein positions 49-57 comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238, or wherein positions 87-95 comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 13 or SEQ ID NO:43, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 4-12. In an aspect, the disclosed amino acid sequence at positions 4-12 can comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 13 or SEQ ID NO:43, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 49-57. In an aspect, the disclosed amino acid sequence at positions 49-57 can comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 13 or SEQ ID NO:43, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising one or more mutations at positions 87-95. In an aspect, the disclosed amino acid sequence at positions 87-95 can comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising a mutation at one or more positions in the sequence of SEQ ID NO:97, SEQ ID NO:98, or SEQ ID NO:99. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 13 or SEQ ID NO:43, wherein one or more mutations occur at positions 4-12, at positions 49-57, or at positions 87-95. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence setforth in SEQ ID NO: 13 or SEQ ID NO:43, wherein one or more mutations occur in the sequence set forth in SEQ ID NO: 97, the sequence set forth in SEQ ID NO: 98, or the sequence set forth in SEQ ID NO:99.

[0248] In an aspect, the sequence set forth in SEQ ID NO: 13 can be encoded by the sequence set forth in SEQ ID NO:28. In an aspect, the sequence set forth in SEQ ID NO:43 can be encoded by the sequence set forth in SEQ ID NO: 58. In an aspect, the sequence set forth in SEQ ID NO:97 can be encoded by the sequence set forth in SEQ ID NO: 142. In an aspect, the sequence set forth in SEQ ID NO: 98 can be encoded by the sequence set forth in SEQ ID NO: 143. In an aspect, the sequence set forth in SEQ ID NO: 99 can be encoded by the sequence set forth in SEQ ID NO: 144.MAAPrh.8 Variants

[0249] Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein from AAVrh.8 (MAAPrh.8).

[0250] Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 14 or SEQ ID NO:44. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 14 or SEQ ID NO:44 and having one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 14 or SEQ ID NO:44 with one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 14 or SEQ ID NO:44, wherein positions 4-12 comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200, wherein positions 49-57 comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238, or wherein positions 87-95 comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 14 or SEQ ID NO:44, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 4-12. In an aspect, the disclosed amino acid sequence at positions 4-12 can comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a nucleic acid encodinga variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 14 or SEQ ID NO:44, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 49-57. In an aspect, the disclosed amino acid sequence at positions 49-57 can comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 14 or SEQ ID NO:44, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising one or more mutations at positions 87-95. In an aspect, the disclosed amino acid sequence at positions 87-95 can comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising a mutation at one or more positions in the sequence of SEQ ID NO: 100, SEQ ID NO: 101, or SEQ ID NO: 102. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 14 or SEQ ID NO:44, wherein one or more mutations occur at positions 4-12, at positions 49-57, or at positions 87-95. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 14 or SEQ ID NO:44, wherein one or more mutations occur in the sequence set forth in SEQ ID NO: 100, the sequence set forth in SEQ ID NO: 101, or the sequence set forth in SEQ ID NO: 102.

[0251] In an aspect, the sequence set forth in SEQ ID NO: 14 can be encoded by the sequence set forth in SEQ ID NO:29. In an aspect, the sequence set forth in SEQ ID NO:44 can be encoded by the sequence set forth in SEQ ID NO: 59. In an aspect, the sequence set forth in SEQ ID NO: 100 can be encoded by the sequence set forth in SEQ ID NO: 145. In an aspect, the sequence set forth in SEQ ID NO: 101 can be encoded by the sequence set forth in SEQ ID NO: 146. In an aspect, the sequence set forth in SEQ ID NO: 102 can be encoded by the sequence set forth in SEQ ID NO: 147.MAAPrh.10 Variants

[0252] Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein from AAVrh.10 (MAAPrh.10).

[0253] Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 15 or SEQ ID NO:45. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 15 or SEQ ID NO:45 and having one or more mutations at positions 4-12, positions 49-57, or positions 87-95. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 15 or SEQ ID NO:45 one or more mutations at positions 4-12, positions 49-57, or positions 87- 95. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 15 or SEQ ID NO:45, wherein positions 4-12 comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200, wherein positions 49-57 comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238, or wherein positions 87-95 comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 15 or SEQ ID NO:45, wherein positions 4-12 comprise the sequence set forth in SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 4-12. In an aspect, the disclosed amino acid sequence at positions 4-12 can comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 15 or SEQ ID NO:45, wherein positions 49-57 comprise the sequence set forth in SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having one or more mutations at positions 49-57. In an aspect, the disclosed amino acid sequence at positions 49-57 can comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising the sequence of SEQ ID NO: 15 or SEQ ID NO:45, wherein positions 87-95 comprise the sequence set forth in SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising one or more mutations atpositions 87-95. In an aspect, the disclosed amino acid sequence at positions 87-95 can comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) comprising a mutation at one or more positions in the sequence of SEQ ID NO: 103, SEQ ID NO: 104, or SEQ ID NO: 105. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 15 or SEQ ID NO:45, wherein one or more mutations occur at positions 4-12, at positions 49-57, or at positions 87-95. Disclosed herein is a nucleic acid encoding a variant membrane associated accessory protein (MAAP) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or more than 95% identity to the sequence set forth in SEQ ID NO: 15 or SEQ ID NO:45, wherein one or more mutations occur in the sequence set forth in SEQ ID NO: 103, the sequence set forth in SEQ ID NO: 104, or the sequence set forth in SEQ ID NO: 105.

[0254] In an aspect, the sequence set forth in SEQ ID NO: 15 can be encoded by the sequence set forth in SEQ ID NO:30. In an aspect, the sequence set forth in SEQ ID NO:45 can be encoded by the sequence set forth in SEQ ID NO:60. In an aspect, the sequence set forth in SEQ ID NO: 103 can be encoded by the sequence set forth in SEQ ID NO: 148. In an aspect, the sequence set forth in SEQ ID NO: 104 can be encoded by the sequence set forth in SEQ ID NO: 149. In an aspect, the sequence set forth in SEQ ID NO: 105 can be encoded by the sequence set forth in SEQ ID NO: 150.Table 8 - Nucleic Acid Sequences for Wild-Type MAAPs with Leucine Start CodonTable 9 - Nucleic Acid Sequences for Wild-Type MAAPs with Methionine Start Codon

[0255] In an aspect, a disclosed isolated nucleic acid can comprise the sequence for one or more regulatory elements. For example, a disclosed regulatory element can comprise a promoter operably linked to a disclosed isolated nucleic acid, wherein the promoter drives the expression of a disclosed variant MAAP.

[0256] In an aspect, a disclosed isolated nucleic acid can comprise the sequence for at least one of polypeptide, a glycopeptide, a polysaccharide, a glycolipid, a lipid, or a nucleic acid polymer, or a combination thereof. In an aspect, a disclosed isolated nucleic acid can comprise the sequence for at least one therapeutic agent. In an aspect, a disclosed therapeutic agent can be an oligonucleotide therapeutic agent. In an aspect, a disclosed oligonucleotide therapeutic agent can be a single-stranded or double-stranded DNA, iRNA, shRNA, siRNA, mRNA, noncoding RNA (ncRNA), an antisense molecule, miRNA, a morpholino, a peptide-nucleic acid (PNA), or an analog or conjugate thereof. In an aspect, a disclosed therapeutic agent can be an ASO or an RNAi. In an aspect, a disclosed nucleic acid-based molecule can comprise one or more modifications at any position applicable. In an aspect, a disclosed therapeutic agent can comprise a CRISPR-based endonuclease (e.g., Cas9). In an aspect, a disclosed CRISPR-based endonuclease can be derived from a CRISPR / Cas type I, type II, or type III system.

[0257] In an aspect, a disclosed nucleic acid comprising a nucleotide sequence encoding a disclosed variant membrane-associated accessory protein (MAAP) can increase secretion from a cell of an AAV having a different serotype. For example, a disclosed isolated nucleic acid comprising a nucleotide sequence encoding a disclosed variant membrane-associated accessory protein from AAV8 (MAAP8) can increase secretion from a cell of AAV9 or AAV2 or AAV4 or any other AAV. In an aspect, a disclosed nucleic acid comprising a nucleotide sequence encoding a disclosed variant membrane-associated accessory protein (MAAP) can increase AAV secretion from a cell independent of AAV serotype.

[0258] In an aspect, a disclosed nucleic acid encoding a disclosed variant membrane-associated accessory protein (MAAP) can increase secretion from a cell of an AAV having a different serotype. For example, a disclosed nucleic acid encoding a disclosed variant membrane- associated accessory protein from AAV8 (MAAP8) can increase secretion from a cell of AAV9 or AAV2 or AAV4 or any other AAV. In an aspect, a disclosed nucleic acid encoding a disclosed variant membrane-associated accessory protein (MAAP) can increase AAV secretion from a cell independent of AAV serotype.

[0259] In an aspect, a disclosed nucleic acid encoding a disclosed variant membrane-associated accessory protein (MAAP) can increase and / or can improve packaging. In an aspect, packaging can refer to a series of intracellular events that result in the assembly and encapsidation of an AAV particle. In an aspect, packaging is increased and / or improved in the presence of a disclosed variant MAAP.

[0260] In an aspect, a disclosed nucleic acid comprising a nucleotide sequence encoding a disclosed variant MAAP can further comprise and / or can be operably linked to one or more regulatory elements. In an aspect, “operably linked” refers to a juxtaposition where the components described are in a relationship permitting them to function in their intended manner. For example, a control element or regulatory element “operably linked” to a functional element is associated in such a way that expression and / or activity of the functional element is achieved under conditions compatible with the control element. In an aspect, a promotor can be operably linked to a disclosed nucleic acid. For example, in an aspect, disclosed regulatory elements can comprise promoters, enhancers, internal ribosomal entry sites (IRES), and other expression control elements (e.g., transcription termination signals, such as polyadenylation signals and poly-U sequences, Woodchuck Hepatitis Virus (WHV) Posttranscriptional Regulator Element (WPRE), triplex from MALAT1, the PRE of Hepatitis B virus (HPRE), and an iron response element). Regulatory elements can include those that direct constitutive expression of a nucleotide sequence in many types of host cells and those that direct expression of the nucleotide sequence only in certain host cells (e.g., tissue-specific regulatory sequences- lung cells, liver cells, spleen cells, etc.).

[0261] In an aspect, a disclosed promoter can be tissue-specific or ubiquitous and can be constitutive or inducible, depending on the pattern of the expression desired. A promoter can be native or foreign and can be a natural or a synthetic sequence. By foreign, it is intended that the transcriptional initiation region is not found in the wild-type host into which the transcriptional initiation region is introduced. In an aspect, a disclosed promoter can be a promoter / enhancer. In an aspect, a disclosed promoter for the disclosed nucleic acid can be anendogenous promoter. In an aspect, a disclosed endogenous promoter can be an endogenous promoter / enhancer. In an aspect, a disclosed endogenous promoter or a disclosed endogenous promoter / enhancer can generally be obtained from a non-coding region upstream of a transcription initiation site of a gene of interest. In an aspect, a disclosed endogenous promoter or a disclosed endogenous promoter / enhancer can be used for constitutive expression of a disclosed gene.

[0262] Tissue-specific promoters are known to the art and include, but are not limited to, neuron-specific promoters, muscle-specific promoters, liver-specific promoters, skeletal muscle-specific promoters, lung-specific promoters, spleen-specific promoters, and heartspecific promoters. Ubiquitous / constitutive promoters are known to the art and include, but are not limited to, a CMV major immediate-early enhancer / chicken beta-actin promoter, a cytomegalovirus (CMV) major immediate-early promoter, an Elongation Factor 1-a (EFl -a) promoter, a simian vacuolating virus 40 (S V40) promoter, an AmpR promoter, a PyK promoter, a human ubiquitin C gene (Ubc) promoter, a MFG promoter, a human beta actin promoter, a CAG promoter, a EGR1 promoter, a FerH promoter, a FerL promoter, a GRP78 promoter, a GRP94 promoter, a HSP70 promoter, a P-kin promoter, a murine phosphoglycerate kinase (mPGK) or human PGK (hPGK) promoter, a ROSA promoter, human Ubiquitin B promoter, a Rous sarcoma virus promoter, or any other natural or synthetic ubiquitous / constitutive promoters.

[0263] In an aspect, a disclosed promoter can be inducible. For example, a disclosed inducible promoter can be a tetracycline ON promoter. In an aspect, inducibility can be governed by one or more parameters including, for example, those listed in Table 13.

[0264] “Tissue-specific promoters” are known to the art and include, but are not limited to, neuron-specific promoters, muscle-specific promoters, liver-specific promoters, skeletal muscle-specific promoters, and heart-specific promoters.

[0265] “Neuron-specific promoters” are known to the art and include, but are not limited to, the synapsin I (SYN) promoter, the calcium / calmodulin-dependent protein kinase II promoter, the tubulin alpha I promoter, the neuron-specific enolase promoter, and the platelet-derived growth factor beta chain promoter.

[0266] “Liver-specific promoters” are known to the art and include, but are not limited to, the al-microglobulin / bikunin enhancer / thyroid hormone-binding globulin promoter, the human albumin (hALB) promoter, the thyroid hormone-binding globulin promoter, thyroxin binding globulin promoter, the a- 1 -anti -trypsin promoter, the bovine albumin (bAlb) promoter, the murine albumin (mAlb) promoter, the human al -antitrypsin (hAAT) promoter, theApoEhAAT promoter composed of the ApoE enhancer and the hAAT promoter, the transthyretin (TTR) promoter, the liver fatty acid binding protein promoter, the hepatitis B virus (HBV) promoter, the DC 172 promoter consisting of the hAAT promoter and the al- microglobulin enhancer, the DC 190 promoter containing the human albumin promoter and the prothrombin enhancer, and other natural and synthetic liver-specific promoters.

[0267] “Muscle-specific promoters” are known to the art and include, but are not limited to, the MHCK7 promoter, the muscle creatine kinase (MCK) promoter / enhancer, the slow isoform of troponin I (TnIS) promoter, the MYODI promoter, the MYLK2 promoter, the SPc5- 12 promoter, the desmin (Des) promoter, the unc45b promoter, and other natural and synthetic muscle-specific promoters.

[0268] “Skeletal muscle-specific promoters” are known to the art and include, but are not limited to, the HSA promoter, the human a-skeletal actin promoter.

[0269] “Heart-specific promoters” are known to the art and include, but art not limited to, the MYH6 promoter, the TNNI3 promoter, the cardiac troponin C (cTnC) promoter, the alphamyosin heavy chain (a-MHC) promoter, myosin light chain 2 (MLC-2), and the MYBPC3 promoter.

[0270] In an aspect, a “ubiquitous / constitutive promoter” refer to a promoter that allows for continual transcription of its associated gene. A ubiquitous / constitutive promoter is always active and can be used to express genes in a wide range of cells and tissues, including, but not limited to, the liver, kidney, skeletal muscle, cardiac muscle, smooth muscle, diaphragm muscle, brain, spinal cord, endothelial cells, intestinal cells, pulmonary cells (e.g., smooth muscle or epithelium), peritoneal epithelial cells, and fibroblasts. Ubiquitous / constitutive promoters include, but are not limited to, a CMV major immediate-early enhancer / chicken beta-actin promoter, a cytomegalovirus (CMV) major immediate-early promoter, an Elongation Factor 1-a (EFla) promoter, a simian vacuolating virus 40 (SV40) promoter, an AmpR promoter, a PyK promoter, a human ubiquitin C gene (Ubc) promoter, a MFG promoter, a human beta actin promoter, a CAG promoter, a EGR1 promoter, a FerH promoter, a FerL promoter, a GRP78 promoter, a GRP94 promoter, a HSP70 promoter, a [3-kin promoter, a murine phosphoglycerate kinase (mPGK) or human PGK (hPGK) promoter, a ROSA promoter, human Ubiquitin B promoter, a Rous sarcoma virus promoter, or any other natural or synthetic ubiquitous / constitutive promoters.

[0271] In an aspect, an “inducible promoter” refers to a promoter that can be regulated by positive or negative control. Factors that can regulate an inducible promoter include, but areI l lnot limited to, chemical agents (e.g., the metallothionein promoter or a hormone inducible promoter), temperature, and light.3. CELLS

[0272] Disclosed herein is a producer cell comprising a disclosed nucleic acid encoding a disclosed MAAP. Disclosed herein is a producer cell expressing a disclosed nucleic acid encoding a disclosed MAAP. Disclosed herein is a producer cell comprising a disclosed viral vector. Disclosed herein is a producer cell comprising a rAAV vector particle. Disclosed herein are producer cells used to perform and / or effect a disclosed method. Disclosed herein are producer cells used to perform and / or effect a disclosed method of directed evolution of MAAP. Disclosed herein are producer cells used to perform and / or effect a disclosed method of generating AAV particles. Disclosed herein are producer cells used to perform and / or effect a disclosed method of increasing AAV secretion. Disclosed herein are producer cells used to perform and / or effect a disclosed method of delivering a payload. Disclosed herein are producer cells capable of generating AAV having a disclosed variant MAAP.

[0273] In an aspect, when expressed in a disclosed cell or a disclosed producer cell, a disclosed variant MAAP can increase production of rAAV virions from the producer cell. For example, in an aspect, an increase in production can comprise at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 100% (or two-fold), at least 2.5-fold, at least 5-fold, at least 10-fold, or more than 10-fold, increase than the level of production when the producer cell expresses wildtype MAAP. In an aspect, at least 50%, at least 55%, at least 60%, at least 70%, at least 80%, at least 90%, or more than 90%, of the rAAV virions can be secreted into the culture medium in which the producer cell is cultured.

[0274] Suitable producer cells can include known mammalian cell lines or modified cell lines. Suitable mammalian cell lines can include 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. CCL10), PC12 cells (ATCC No. CRL1721), COS cells, COS-7 cells (ATCC No. CRL1651), RATI cells, mouse L cells (ATCC No. CCLI.3), human embryonic kidney (HEK) cells (ATCC No. CRL1573), HEK 293T cells, HLHepG2 cells, and others known to the art.

[0275] In an aspect, a disclosed producer cell can be genetically modified. For example, in an aspect, a disclosed producer cell can comprise a helper virus that can provide helper functions for AAV replication, or a helper recombinant vector that comprises a nucleotide sequenceencoding helper functions. Although adenovirus is commonly employed, other helper viruses can also be used as is known in the art. In an aspect, a requisite helper virus function can be isolated genetically from a helper virus and the encoding genes can be used to provide helper virus functions in trans. In an aspect, disclosed AAV vector elements and the helper virus (or helper virus functions) can be introduced into the host cell either simultaneously or sequentially in any order.

[0276] In an aspect, a disclosed cell or producer cell can be genetically modified with one or more disclosed nucleic acids encoding one or more disclosed variant MAAPs. In an aspect, a disclosed nucleic acid encoding one or more disclosed variant MAAPs can be integrated into the genome of a genetically modified mammalian cell.

[0277] Disclosed herein is a cell comprising a disclosed AAV having a variant MAAP. Disclosed herein is a cell comprising a disclosed capsid having a disclosed variant MAAP. Disclosed herein is a cell comprising a disclosed nucleic acid encoding a disclosed MAAP. Disclosed herein is a cell expressing a disclosed nucleic acid encoding a disclosed MAAP. Disclosed herein is a cell comprising a disclosed viral vector. Disclosed herein is a cell comprising a rAAV vector particle. Disclosed herein are cells used to perform and / or effect a disclosed method. Disclosed herein are cells used to perform and / or effect a disclosed method of directed evolution of MAAP. Disclosed herein are cells used to perform and / or effect a disclosed method of generating AAV particles. Disclosed herein are cells used to perform and / or effect a disclosed method of increasing AAV secretion. Disclosed herein are cells used to perform and / or effect a disclosed method of delivering a payload. Disclosed herein are producer cells capable of generating AAV having a disclosed variant MAAP. Disclosed herein is a cell comprising a disclosed AAV having a variant MAAP. Disclosed herein is a cell comprising a disclosed capsid having a disclosed variant MAAP. In an aspect, a disclosed cell or a disclosed producer cell can be used to produce an AAV virion or rAAV virion.4. VECTORS AND VECTOR PARTICLES

[0278] Disclosed herein is a vector comprising a disclosed isolated nucleic acid. Disclosed herein is a vector comprising a disclosed variant MAAP. Disclosed herein is an AAV vector comprising a disclosed isolated nucleic acid. Disclosed herein is a AAV vector comprising a disclosed variant MAAP. Disclosed herein is a AAV vector comprising a capsid having a disclosed variant MAAP. Disclosed herein is a AAV vector for use in a disclosed method including methods of delivering a payload and methods of treating a subject in need thereof. Disclosed herein is a recombinant AAV vector. In an aspect, a disclosed rAAV vector can comprise a polynucleotide sequence not of AAV origin (i.e., a polynucleotide heterologous toAAV), which can be a sequence of interest for the genetic transformation of a cell. In general, the heterologous polynucleotide is flanked by at least one, and generally by two AAV inverted terminal repeat sequences (ITRs). In an aspect, a disclosed rAAV vector can encompass both rAAV vector particles and rAAV vector plasmids. In an aspect, a disclosed “AAV virus” or “AAV viral particle” or “rAAV vector particle” can refer to a viral particle having at least one AAV capsid protein (typically by all of the capsid proteins of a wild-type AAV) and an encapsidated polynucleotide rAAV vector. In an aspect, if the particle comprises a heterologous polynucleotide (i.e. a polynucleotide other than a wild-type AAV genome, such as a transgene to be delivered to a mammalian cell), it is typically referred to as an “rAAV vector particle” or simply an “rAAV vector”. In an aspect, production of rAAV particle necessarily can include production of rAAV vector, as such a vector is contained within an rAAV particle.

[0279] Disclosed herein is a viral vector encoding a disclosed AAV capsid polypeptide. Disclosed herein is a rAAV vector particle comprising a disclosed AAV capsid polypeptide.

[0280] Disclosed herein is a rAAV vector particle comprising a nucleic acid sequence encoding a transgene, and, optionally, a transgene encoding a payload. In an aspect, a disclosed transgene can be operably linked to a disclosed nucleic acid sequence encoding a disclosed variant MAAP. In an aspect, a disclosed transgene can be provided on a second nucleic acid not operably linked to a disclosed nucleic acid encoding a disclosed variant MAAP.

[0281] In an aspect, a disclosed AAV vector can comprise a variant capsid protein. Capsid proteins and variant capsid proteins are known to the art.

[0282] In an aspect, a disclosed AAV vector can be AAV1, AAV2, AAV3 (including 3a and 3b), AAV4, AAV5, AAV6, AAV7, AAV8, AAVrh8, AAV9, AAV10, AAVrhlO, AAV11, AAV12, AAV13, AAVrh39, AAVrh43, or AAVcy.7. In an aspect, a disclosed AAV vector can be bovine AAV, caprine AAV, canine AAV, equine AAV, ovine AAV, avian AAV, primate AAV, or non-primate AAV. In an aspect, a disclosed AAV vector can be AAV-DJ, AAV-HAE1, AAV-HAE2, AAVM41, AAV-1829, AAV2 Y / F, AAV2 T / V, AAV2i8, AAV2.5, AAV9.45, AAV9.61, AAV-B1, AAV-AS, AAV9.45A-String (e.g., AAV9.45-AS), AAV9.45Angiopep, AAV9.47-Angiopep, AAV9.47-AS, AAV-PHP.B, AAV-PHP.eB, AAV- PHP.S, AAV-F, AAVcc.47, or AAVcc.81.

[0283] In an aspect, a disclosed AAV vector can comprise one or more regulatory elements. A disclosed vector can comprise a ubiquitous promoter operably linked to a disclosed isolated nucleic acid, wherein the ubiquitous promoter drives the expression of a disclosed transgene or gene of interest, a disclosed encoded polypeptide or nucleic acid, a disclosed encodedtherapeutic agent, or both. A disclosed vector can comprise a tissue specific promoter operably linked to a disclosed isolated nucleic acid, wherein the tissue specific promoter drives the expression of a disclosed transgene or gene of interest, a disclosed encoded polypeptide, a disclosed encoded therapeutic agent, or both.

[0284] In an aspect, a disclosed vector or a disclosed AAV vector can be formulated for administration via one or more routes. Such routes are well known to those skilled in the art and include, but are not limited to, the following: oral administration, transdermal administration, administration by inhalation, nasal administration, topical administration, intravaginal administration, ophthalmic administration, intraaural administration, otic administration, inter utero administration, intracerebral administration, rectal administration, sublingual administration, buccal administration, and parenteral administration, including injectable such as intravenous administration, intra-arterial administration, intramuscular administration, and subcutaneous administration. Administration of a disclosed vector can be continuous or intermittent.

[0285] In an aspect, a disclosed vector can be used in a disclosed method. In an aspect, a disclosed vector can be used in a disclosed of generating and / or making AAV or a disclosed method of increasing AAV secretion and / or egress.5. PHARMACEUTICAL FORMULATIONS

[0286] Disclosed herein is a pharmaceutical formulation comprising a disclosed AAV in a pharmaceutically acceptable carrier. Disclosed herein is a pharmaceutical formulation comprising a disclosed vector in a pharmaceutically acceptable carrier. Disclosed herein is a pharmaceutical formulation comprising a disclosed nucleic acid in a pharmaceutically acceptable carrier.

[0287] In an aspect, a disclosed pharmaceutical formulation can be administered to a subject in need thereof. In an aspect, a disclosed AAV can comprise an AAV having a variant MAAP. Variant MAAPs are disclosed herein. In an aspect, a disclosed pharmaceutical formulation can be administered to a subject in need thereof to deliver a payload. In an aspect, a disclosed pharmaceutical formulation can be administered to a subject in need thereof to treat and / or prevent a disease or disorder. Pharmaceutically acceptable carriers are known to the art and are discussed supra.

[0288] In an aspect, a disclosed pharmaceutical formulation can be formulated for administration via one or more routes. Such routes are well known to those skilled in the art and include, but are not limited to, the following: oral administration, transdermal administration, administration by inhalation, nasal administration, topical administration,intravaginal administration, ophthalmic administration, intraaural administration, otic administration, inter utero administration, intracerebral administration, rectal administration, sublingual administration, buccal administration, and parenteral administration, including injectable such as intravenous administration, intra-arterial administration, intramuscular administration, and subcutaneous administration. Administration of a disclosed pharmaceutical formulation can be continuous or intermittent.

[0289] In an aspect, a disclosed pharmaceutical formulation can be used in a disclosed method. In an aspect, a disclosed pharmaceutical formulation can be used in a disclosed method of delivering a payload.6. KITS

[0290] Disclosed herein is a kit comprising one or more disclosed compositions. In an aspect, a composition of a disclosed kit can comprise a disclosed isolated nucleic acid, a disclosed plasmid, a disclosed variant MAAP, a disclosed producer cell, a disclosed genetically modified producer cell, a disclosed AAV comprising a capsid having a variant MAAP, a disclosed vector, a disclosed pharmaceutical composition, or a combination thereof. In an aspect, a disclosed kit can comprise a combination of one or more active agents. In an aspect, a disclosed kit can comprise at least two components constituting the kit. Together, the components constitute a functional unit for a given purpose (such as, for example, performing directed evolution on MAAPs, generating AAV particles, increasing AAV secretion, or delivering a payload). Individual member components can be physically packaged together or separately. For example, a disclosed kit comprising an instruction for using the kit may or may not physically include the instruction with other individual member components. Instead, the instruction can be supplied as a separate member component, either in a paper form or an electronic form that can be supplied on computer readable memory device or downloaded from an internet website, or as recorded presentation. In an aspect, a disclosed kit for use in a disclosed method can comprise one or more containers holding a disclosed composition (i.e., a disclosed MAAP, a disclosed nucleic acid, a disclosed cell, a disclosed AAV, a disclosed vector, a disclosed plasmid, a disclosed pr...

Claims

VIII. CLAIMSWhat is claimed is:

1. A variant membrane-associated accessory protein (MAAP) with at least one variant sequence at one of positions 4-12, positions 49-57, or positions 87-95 with respect to the amino acid sequence of SEQ ID NO: 08.

2. The variant MAAP of Claim 1, wherein positions 4-12 comprise the sequence set forth in any one of SEQ ID NO: 151 - SEQ ID NO:200.

3. The variant MAAP of Claim 1, wherein positions 49-57 comprise the sequence set forth in any one of SEQ ID NO:201 - SEQ ID NO:238.

4. The variant MAAP of Claim 1, wherein positions 87-95 comprise the sequence set forth in any one of SEQ ID NO:239 - SEQ ID NO:288.

5. The variant MAAP of Claim 1, comprising the amino acid sequence of any one of SEQ IDNO:309 - SEQ ID NO:319.

6. The variant MAAP of Claim 1, comprising the amino acid sequence of any one of SEQ IDNO:289 - SEQ ID NO:298.

7. A variant membrane-associated accessory protein (MAAP) with a variant sequence at one of positions 4-12 and at positions 87-95 with respect to the amino acid sequence of SEQ ID NO:08.

8. The variant MAAP of Claim 7, comprising the amino acid sequence of any one of SEQ IDNO:362 - SEQ ID NO:472.

9. A nucleic acid comprising a nucleotide sequence encoding the variant MAAP of any one ofClaims 1 - 9.

10. The nucleic acid of Claim 9, wherein the nucleotide sequence encoding the variant MAAP comprises the sequence set forth in SEQ ID NO:299 - SEQ ID NO:308 or SEQ ID NO:320 - SEQ ID NO:330.

11. The nucleic acid of Claim 9 or Claim 10, wherein the nucleotide sequence encoding the variant MAAP is operably linked to a promoter.

12. The nucleic acid of Claim 11, wherein the promoter comprises a cell-specific promoter, a constitutive promoter, or an inducible promoter.

13. A eukaryotic cell, comprising: the nucleic acid of any one of Claims 9 - 12.

14. The eukaryotic cell of Claim 13, wherein the nucleic acid is integrated into the genomicDNA of the cell.

15. The eukaryotic cell of Claim 13, further comprising one or more nucleic acids comprising a nucleotide sequence encoding AAV cap and rep gene products.

16. The eukaryotic cell of Claim 15, wherein the one or more nucleic acids are integrated into the genomic DNA of the cell.

17. The eukaryotic cell of Claim 16, further comprising a recombinant adeno- associated virus(rAAV), wherein the rAAV comprises a nucleotide sequence encoding one or more heterologous gene products.

18. The eukaryotic cell of Claim 17, wherein the one or more heterologous gene products comprises a polypeptide and / or a nucleic acid.

19. A method of generating rAAV, the method comprising: culturing in a suitable culture medium the eukaryotic cell of any one of Claims 17 - 18 under conditions such that rAAV is generated.

20. The method of Claim 19, further comprising harvesting from the culture medium rAAV secreted from the eukaryotic cell.

21. A recombinant adeno-associated virus (rAAV) comprising the nucleic acid of any one of Claims 9 - 12.

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