Pseudotyped viral particles, compositions comprising the same, and uses thereof

Abstract

Provided for herein are variant VSV-G polypeptides comprising one or more mutations as compared to wild type VSV-G polypeptides, compositions comprising the same, and methods of using the same.

Description

INH-027WO PATENT PSEUDOTYPED VIRAL PARTICLES, COMPOSITIONS COMPRISING THE SAME, AND USES THEREOF RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Application Ser. No.63 / 507,550 filed June 12, 2023, which is hereby incorporated by reference in its entirety. REFERENCE TO SEQUENCE LISTING SUBMITTED ELECTRONICALLY

[0002] The instant application contains a Sequence Listing which has been submitted electronically in XML format and is hereby incorporated by reference in its entirety. Said XML copy, created on May 29, 2024, is named “INH-027WO_SL” and is 155,722 bytes in size. BACKGROUND

[0003] Vesicular stomatitis virus (VSV) is an enveloped, negative-strand RNA virus that belongs to the Vesiculovirus genus of the Rhabdovirus family. It is an arbovirus which can infect insects, cattle, horses and pigs. VSV genome encodes five structural proteins among which include a single transmembrane glycoprotein (G). The glycoprotein is a classic type I membrane glycoprotein with an amino-terminal signal peptide, an ectodomain of about 450 amino acids, a single alpha helical transmembrane segment and a small intraviral carboxy- terminal domain. The signal peptide is cleaved in the lumen of the endoplasmic reticulum and the native glycoprotein consists in the ectodomain, the transmembrane domain and the intraviral domain.

[0004] G plays a critical role during the initial steps of virus infection (Molecular and Cellular Aspects of Rhabdovirus Entry. Viruses 4, 117-139.), which is hereby incorporated by reference in its entirety. First, it is responsible for virus attachment to specific receptors. After binding, virions enter the cell by a clathrin-mediated endocytic pathway. In the acidic environment of the endocytic vesicle, G triggers the fusion between the viral and endosomal membranes, which releases the genome in the cytosol for the subsequent steps of infection. Fusion is catalyzed by a low-pH-induced large structural transition from a pre-toward a post-fusion conformation which are both trimeric (Roche, S., Bressanelli, S., Rey, F. A., and Gaudin, Y. (2006). Crystal structure of the low-pH form of the vesicular stomatitis virus glycoprotein G. Science 313, 187- 191. Roche, S., Rey, F. A., Gaudin, Y., and Bressanelli, S. (2007). Structure of the prefusion 1 IPTS / 128573217.2INH-027WO PATENT form of the vesicular stomatitis virus glycoprotein g. Science 315, 843-848), each of which is hereby incorporated by reference in its entirety).

[0005] The polypeptide chain of G ectodomain folds into three distinct domains which are the fusion domain (FD), the pleckstrin homology domain (PHD), and the trimerization domain (TrD). During the structural transition, the FD, the PHD and the TrD retain their tertiary structure. Nevertheless, they undergo large rearrangements in their relative orientation due to secondary changes in hinge segments (S1 to S5) which refold during the low-pH induced conformational change (Roche et al., 2006; Roche et al., 2007).

[0006] It has been shown that low-density lipoprotein receptor (LDL-R) and other members of this receptor family serve as VSV receptors (Finkelshtein, D., Werman, A., Novick, D., Barak, S., and Rubinstein, M. (2013). LDL receptor and its family members serve as the cellular receptors for vesicular stomatitis virus. Proceedings of the National Academy of Sciences of the United States of America 110, 7306-7311, which is hereby incorporated by reference in its entirety). VSV-G can be used for pseudotyping other viruses and VSV-G-pseudotyped lentiviruses (VSV-G-LVs) exhibit the same broad tropism as VSV. However, this broad tropism can inhibit the selective targeting of specific cell types. Therefore, there is a need, for modified (mutated or mutant) VSV-G proteins that can be used to pseudotype viruses that abrogate its binding to the LDL receptor. The present embodiments, fulfill these needs as well as others.

[0007] The human CD7 molecule is a cell surface glycoprotein with a molecular weight of approximately 40 kDa belonging to the immunoglobulin superfamily. The CD7 molecule is mainly expressed on the surface of most thymocytes, more than 85% of the surface of peripheral blood T lymphocytes and the surface of natural killer cells. The embodiments disclosed herein provide for polypeptide and antibodies against CD7, compositions comprising the same, and uses thereof.

[0008] CD8 (cluster of differentiation 8) is a transmembrane glycoprotein which is a specific marker for a subclass of T-cells (which includes cytotoxic T-cells). Without wishing to be bound to a particular theory, CD8 assembles as either a heterodimer of the CD8 alpha and CD8 beta subunits or a CD8 alpha homodimer. The assembled dimeric CD8 complex acts as a co- receptor together with the T cell receptor (TCR) to recognize antigen presentation by MHC class I cells. CD8 plays a role in the development of T-cells and activation of mature T-cells. Changes in T-cell localization can reflect the progression of an immune response and can occur over time. The embodiments disclosed herein provide for polypeptide and antibodies against 2 IPTS / 128573217.2INH-027WO PATENT CD8, compositions comprising the same, and uses thereof. BRIEF SUMMARY

[0009] In some embodiments, a VSV-G polypeptide is provided, the VSV-G polypeptide comprising a mutation that corresponds to a mutation at position 8, 9, 10, 47, 50, 51, 179, 180, 182, 183, 184, 209, 347, 350, 352, 353, 354, or a combination thereof, of SEQ ID NO: 2.

[0010] In some embodiments, the mutation at position 8, 9, 10, 47, 50, 51, 179, 180, 182, 183, 184, 209, 347, 350, 352, 353, 354, or a combination thereof of SEQ ID NO: 2 comprises a substitution to a charged amino acid.

[0011] In some embodiments, the charged amino acid is at position H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, or R354.

[0012] In some embodiments, the substitution to the charged amino acid is selected from D, E, K, or R.

[0013] In some embodiments, a VSV-G polypeptide is provided comprising an amino acid sequence of SEQ ID NO 3, SEQ ID NO 4, or SEQ ID NO 5, further comprising a mutation that corresponds to a mutation at position 8, 9, 10, 47, 50, 51, 179, 180, 182, 183, 184, 209, 347, 350, 352, 353, 354, or a combination thereof of SEQ ID NO 3, SEQ ID NO 4, or SEQ ID NO 5.

[0014] In some embodiments, a VSV-G polypeptide is provided comprising an amino acid sequence of SEQ ID NO 22 or SEQ ID NO 23, further comprising a mutation that corresponds to a mutation at position 8, 9, 10, 47, 50, 51, 179, 180, 182, 183, 184, 209, 347, 350, 352, 353, 354, or a combination thereof of SEQ ID NO 22 or SEQ ID NO 23.

[0015] In some embodiments, a viral particle is provided comprising a VSV-G polypeptide as provided for herein.

[0016] In some embodiments, the viral particle further comprises a targeting moiety as provided for herein.

[0017] In some embodiments, the viral particle is a pseudotyped lentivirus as provided for herein.

[0018] In some embodiments, the viral particle further comprises a nucleic acid molecule encoding a heterologous molecule of interest as provided for herein.

[0019] In some embodiments, the heterologous molecule of interest is a chimeric antigen receptor (“CAR”) as provided for herein.

[0020] In some embodiments, the chimeric antigen receptor comprises an antigen binding 3 IPTS / 128573217.2INH-027WO PATENT domain that binds to CD20 as provided for herein.

[0021] In some embodiments, the targeting moiety binds to CD7 as provided for herein.

[0022] In some embodiments, the targeting moiety binds to CD8 as provided for herein.

[0023] In some embodiments, a method of delivering a heterologous molecule to a target cell is provided, the method comprising contacting the cell with a viral vector comprising: a) a VSV-G polypeptide as provided for herein; b) a targeting moiety that binds to the target cell; and c) a nucleic acid molecule encoding the heterologous molecule.

[0024] In some embodiments, a method of delivering a heterologous molecule of interest to a target cell in a subject is provided, the method comprising administering to the subject a viral vector comprising: a) a VSV-G protein as provided for herein; b) a targeting moiety that binds to the target cell; and c) a nucleic acid molecule encoding the heterologous molecule.

[0025] In some embodiments, the heterologous molecule is a chimeric antigen receptor as provided for herein.

[0026] In some embodiments, a method of treating cancer in a subject is provided, the method comprising administering to the subject a viral vector comprising: a) a VSV-G protein as provided for herein; b) a targeting moiety that binds to the target cell; and c) a nucleic acid molecule encoding the heterologous molecule.

[0027] In some embodiments, the heterologous molecule is a chimeric antigen receptor as provided for herein. BRIEF DESCRIPTION OF FIGURES

[0028] FIG.1A and FIG.1B illustrate crystal structures of VSV-G bound to LDL-R. FIG.1A illustrates the crystal structure of VSV-G bound to CR3 of the LDL-R. FIG.1B illustrates the crystal structure of VSV-G bound to CR2 of the LDL-R.

[0029] FIG. 2A and FIG. 2B illustrate the effect of adding negatively charged amino acids to the VSV-G:LDL-R binding interface on native tropism and fusogenicity. FIG. 2A illustrates the titration of VSV-G constructs on SupT1 cells. FIG. 2B illustrates functional titer of each construct calculated from the titration in FIG.2A.

[0030] FIG. 3 illustrates an alignment of the ectodomains of different VSV-G proteins from 4 IPTS / 128573217.2INH-027WO PATENT different strains.

[0031] FIG.4 illustrates the effect of various VSV-G mutations on the serum stability of viral constructs in combination with a CD7 binder.

[0032] FIG.5 illustrates the effect of various VSV-G mutations on the serum stability of viral constructs in combination with a CD7 binder.

[0033] FIG. 6A-L show flow cytometry data of human PBMCs transduced with exemplary vectors comprising CD7 binders as disclosed herein.

[0034] FIG. 6M shows flow cytometry data of human PBMCs transduced with exemplary vectors comprising CD7 binders as disclosed herein.

[0035] FIG.7A-L shows flow cytometry data of non-human primate PBMCs transduced with exemplary vectors comprising CD7 binders as disclosed herein.

[0036] FIG. 7M shows flow cytometry data of non-human primate PBMCs transduced with exemplary vectors comprising CD7 binders as disclosed herein.

[0037] FIG. 8A shows flow cytometry data of human PBMCs transduced with exemplary vectors comprising CD8 binders as disclosed herein.

[0038] FIG. 8B shows flow cytometry data of non-human primate PBMCs transduced with exemplary vectors comprising CD8 binders as disclosed herein.

[0039] FIG.9A and FIG.9B illustrate GFP or CAR transduction of SupT1 cells utilizing VSV- G pseudotyped lentiviral particles harboring CD7 or CD8 binders as provided for herein. FIG. 9A illustrates GFP transduction. FIG.9B illustrates CAR transduction.

[0040] FIG.10A illustrates the ability of VSV-G* pseudotyped lentiviral particles harboring a CD7 binder to transduce SupT1 cells as well as human and non-human primate PBMCs. FIG. 10B illustrates the transduction of cells in the absence of the CD7 binder. FIG.10C illustrates the transduction of human and non-human primate PBMCs in terms of MOI calculated from SupT1 titration. VSV-G* denotes VSV-G polypeptide comprising I182E, T214N, T352A, which corresponds to a mature polypeptide of SEQ ID NO: 23 or SEQ ID NO: 25 (with I196E, T230N and T368A mutations (with leader sequence and adjusted numbering).

[0041] FIG. 11A and FIG. 11B illustrate the off target transduction of VSV-G* pseudotyped lentiviral particles harboring a CD7 binder in a panel of B-cell cell lines as compared to control SupT1 cells. FIG.11A illustrates the data for GFP transduction. FIG.11B illustrates the data for CAR20-T2A-GFP transduction. VSV-G* denotes a VSV-G polypeptide comprising I182E, T214N, and T352A mutations as provided for herein.

[0042] FIG.12A and FIG.12B illustrate the ability of VSV-G* pseudotyped lentiviral particles 5 IPTS / 128573217.2INH-027WO PATENT utilizing CD7 binders and a CD20-CAR transgene as provided for herein to kill Daudi lymphoma cells (FIG. 12A) or Raji lymphoma cells (FIG. 12B). CAR20 constructs utilized antigen binding domains comprising rituximab, or CD20AB1 SEQ ID NOs 75 or 76 as provided for herein.

[0043] FIG.13A and FIG.13B illustrate the ability of VSV-G* pseudotyped lentiviral particles utilizing CD7 binders and a CD20-CAR transgene as provided for herein to deplete B-cells in vivo in huCD34 NSG mice. B-cells were detected via assessment for CD20 (FIG. 13A) or CD19 (FIG.13B).

[0044] FIG.14A and FIG.14B illustrate the ability of VSV-G* pseudotyped lentiviral particles utilizing CD7 binders and a CD20-CAR transgene as provided for herein to prevent tumor formation in vivo. FIG. 14A depicts the experimental design. FIG. 14B illustrates that mice receiving i.v. lentiviral particles as provided for herein prior to Raji tumor infusion had significantly lower tumor burden than mice receiving control (GFP) vector or untreated mice. Tumor burden measured via IVIS imaging.

[0045] FIG.15A and FIG.15B illustrate the ability of VSV-G* pseudotyped lentiviral particles utilizing CD7 binders and a CD20-CAR transgene as provided for herein to eliminate established Raji tumors in vivo. FIG. 15A depicts the experimental design. FIG. 15B illustrates that mice receiving i.v. lentiviral particles as provided for herein after 6 days after Raji tumor infusion had their tumor burdens diminished below the limit of detection. Tumor burden measured via IVIS imaging.

[0046] FIG. 16 illustrates a pilot experiment which combines I182E with both I347G and T352E or I182E with T352Q / E, thus showing a possible low level of additive benefit to additional variations. DETAILED DESCRIPTION

[0047] Provided for herein are mutant VSV-G proteins that can be used, for example, to pseudotype a virus, such as a lentivirus. In some embodiments, the pseudotyped viral-like particles are pseudotyped using viral glycoproteins of a vesicular stomatitis New Jersey virus strain, a vesicular stomatitis Indiana virus strain, a vesicular stomatitis Alagoas virus strain, a vesicular stromatitis Maraba virus strain, or a vesicular stomatitis Carajas virus strain.

[0048] The pseudotyped viruses comprising the mutant VSV-G proteins can be used in conjunction with a targeting moiety to facilitate the fusion of the pseudotyped virus with a specific cell or tissue based on the expression of the target on the cell or the tissue. 6 IPTS / 128573217.2INH-027WO PATENT

[0049] Unless defined otherwise, all technical and scientific terms have the same meaning as is commonly understood by one of ordinary skill in the art to which the embodiments disclosed belongs.

[0050] As used herein, the terms “a” or “an” means that “at least one” or “one or more” unless the context clearly indicates otherwise.

[0051] As used herein, the term “about” means that the numerical value is approximate and small variations would not significantly affect the practice of the disclosed embodiments. Where a numerical limitation is used, unless indicated otherwise by the context, “about” means the numerical value can vary by ±10% and remain within the scope of the disclosed embodiments. Additionally, where a phrase recites “about x to y,” the term “about” modifies both x and y and can be used interchangeably with the phrase “about x to about y” unless context dictates differently.

[0052] “Activation,” as used herein in reference to a T cell, refers to the state of a T cell that has been sufficiently stimulated to induce detectable cellular proliferation. Activation can also be associated with induced cytokine production, and detectable effector functions. The term “activated T cells” refers to, among other things, T cells that are undergoing cell division.

[0053] As used herein, to “alleviate” a disease means reducing the severity of one or more symptoms of the disease.

[0054] The term “antigen” as used herein is defined as a molecule that provokes an immune response. This immune response may involve either antibody production, or the activation of specific immunologically-competent cells, or both. The skilled artisan will understand that any macromolecule, including virtually all proteins or peptides, can serve as an antigen. The term “antigen” can also refer to a molecule that an antibody or antibody-like molecule can bind to or is recognized by the antibody or antibody-like molecule.

[0055] The term “antibody molecule,” “antibody” or antigen binding domain, as that term is used herein, refers to a polypeptide, e.g., an immunoglobulin chain or fragment thereof, comprising at least one functional immunoglobulin variable domain sequence. An antibody molecule encompasses antibodies (e.g., full-length antibodies) and antibody fragments. In some embodiments, an antibody molecule comprises an antigen binding or functional fragment of a full-length antibody, or a full-length immunoglobulin chain. For example, a full-length antibody is an immunoglobulin (Ig) molecule (e.g., an IgG antibody) that is naturally occurring or formed by normal immunoglobulin gene fragment recombinatorial processes. In embodiments, an antibody molecule refers to an immunologically active, antigen binding 7 IPTS / 128573217.2INH-027WO PATENT portion of an immunoglobulin molecule, such as an antibody fragment. An antibody fragment, e.g., functional fragment, comprises a portion of an antibody, e.g., Fab, Fab′, F(ab′)2, F(ab)2, variable fragment (Fv), domain antibody (dAb), or single chain variable fragment (scFv). A functional antibody fragment binds to the same antigen as that recognized by the intact (e.g., full-length) antibody. The terms “antibody fragment” or “functional fragment” also include isolated fragments consisting of the variable regions, such as the “Fv” fragments consisting of the variable regions of the heavy and light chains or recombinant single chain polypeptide molecules in which light and heavy variable regions are connected by a peptide linker (“scFv proteins”). In some embodiments, an antibody fragment does not include portions of antibodies without antigen binding activity, such as Fc fragments or single amino acid residues. Exemplary antibody molecules include full-length antibodies and antibody fragments, e.g., dAb (domain antibody), single chain, Fab, Fab’, and F(ab’)2 fragments, and single chain variable fragments (scFvs).

[0056] The term “antibody molecule” also encompasses whole or antigen binding fragments of domain, or single domain, antibodies, which can also be referred to as “sdAb” or “VHH.” Domain antibodies comprise either VH or VL that can act as stand-alone, antibody fragments. Additionally, domain antibodies include heavy-chain-only antibodies (HCAbs). Domain antibodies also include a CH2 domain of an IgG as the base scaffold into which CDR loops are grafted. It can also be generally defined as a polypeptide or protein comprising an amino acid sequence that is comprised of four framework regions interrupted by three complementarity determining regions. This is represented as FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4. sdAbs can be produced in camelids such as llamas, but can also be synthetically generated using techniques that are well known in the art. The numbering of the amino acid residues of a sdAb or polypeptide is according to the general numbering for VH domains given by Kabat et al. ("Sequence of proteins of immunological interest," US Public Health Services, NIH Bethesda, MD, Publication No. 91, which is hereby incorporated by reference). According to this numbering, FR1 of a sdAb comprises the amino acid residues at positions 1-30, CDR1 of a sdAb comprises the amino acid residues at positions 31-36, FR2 of a sdAb comprises the amino acids at positions 36-49, CDR2 of a sdAb comprises the amino acid residues at positions 50- 65, FR3 of a sdAb comprises the amino acid residues at positions 66-94, CDR3 of a sdAb comprises the amino acid residues at positions 95-102, and FR4 of a sdAb comprises the amino acid residues at positions 103-113. Domain antibodies are also described in WO2004041862 and WO2016065323, each of which is hereby incorporated by reference. The domain 8 IPTS / 128573217.2INH-027WO PATENT antibodies can be a targeting moiety as described herein.

[0057] As used herein, unless otherwise indicated, “antibody fragment” or “antigen binding fragment” refers to antigen binding fragments of antibodies, i.e. antibody fragments that retain the ability to bind specifically to the antigen bound by the full-length antibody, e.g. fragments that retain one or more CDR regions. Examples of antibody binding fragments include, but are not limited to, Fab, Fab', F(ab')2, and Fv fragments; diabodies; linear antibodies; single- chain antibody molecules, e.g., sc-Fv; nanobodies (single domain antibody) and multispecific antibodies formed from antibody fragments.

[0058] A “Fab fragment” is comprised of one light chain and the CH1 and variable regions of one heavy chain. The heavy chain of a Fab molecule cannot form a disulfide bond with another heavy chain molecule.

[0059] An “Fc” region contains two heavy chain fragments comprising the CH2 and CH3 domains of an antibody. The two heavy chain fragments are held together by two or more disulfide bonds and by hydrophobic interactions of the CH3 domains.

[0060] A “Fab' fragment” contains one light chain and a portion or fragment of one heavy chain that contains the VH domain and the C H1 domain and also the region between the CH1 and C H2 domains, such that an interchain disulfide bond can be formed between the two heavy chains of two Fab' fragments to form a F(ab') 2 molecule.

[0061] A “F(ab')2 fragment” contains two light chains and two heavy chains containing a portion of the constant region between the CH1 and CH2 domains, such that an interchain disulfide bond is formed between the two heavy chains. A F(ab')2 fragment thus is composed of two Fab' fragments that are held together by a disulfide bond between the two heavy chains.

[0062] The “Fv region” comprises the variable regions from both the heavy and light chains, but lacks the constant regions.

[0063] The term “single-chain Fv” or “scFv” antibody refers to antibody fragments comprising the VH and VL domains of an antibody, wherein these domains are present in a single polypeptide chain. Generally, the Fv polypeptide further comprises a polypeptide linker between the VH and VL domains which enables the scFv to form the desired structure for antigen binding. For a review of scFv, see Pluckthun (1994) THEPHARMACOLOGY OFMONOCLONAL ANTIBODIES, vol.113, Rosenburg and Moore eds. Springer-Verlag, New York, pp. 269-315. See also, International Patent Application Publication No. WO 88 / 01649 and U.S. Pat. Nos.4,946, 778 and 5,260,203.

[0064] Antibody molecules can be monospecific (e.g., monovalent or bivalent), bispecific 9 IPTS / 128573217.2INH-027WO PATENT (e.g., bivalent, trivalent, tetravalent, pentavalent, or hexavalent), trispecific (e.g., trivalent, tetravalent, pentavalent, or hexavalent), or with higher orders of specificity (e.g, tetraspecific) and / or higher orders of valency beyond hexavalency. An antibody molecule can comprise a functional fragment of a light chain variable region and a functional fragment of a heavy chain variable region, or heavy and light chains may be fused together into a single polypeptide.

[0065] Furthermore, antigens can be derived from recombinant or genomic DNA. A skilled artisan will understand that any DNA, which comprises a nucleotide sequences or a partial nucleotide sequence encoding a protein that elicits an immune response therefore encodes an “antigen” as that term is used herein. Furthermore, one skilled in the art will understand that an antigen need not be encoded solely by a full length nucleotide sequence of a gene. Moreover, a skilled artisan will understand that an antigen need not be encoded by a “gene” at all. It is readily apparent that an antigen can be generated synthesized or can be derived from a biological sample. Such a biological sample can include, but is not limited to a tissue sample, a tumor sample, a cell or a biological fluid.

[0066] In certain embodiments, monoclonal antibodies herein also include camelized single domain antibodies. See, e.g., Muyldermans et al. (2001) Trends Biochem. Sci. 26:230; Reichmann et al. (1999) J. Immunol. Methods 231:25; WO 94 / 04678; WO 94 / 25591; U.S. Pat. No.6,005,079). In one embodiment, the present invention provides single domain antibodies comprising two VH domains with modifications such that single domain antibodies are formed.

[0067] As used herein, the term “diabodies” refers to small antibody fragments with two antigen-binding sites, which fragments comprise a heavy chain variable domain (VH) connected to a light chain variable domain (VL) in the same polypeptide chain (VH-VL or VL- VH). By using a linker that is too short to allow pairing between the two domains on the same chain, the domains are forced to pair with the complementary domains of another chain and create two antigen-binding sites. Diabodies are described more fully in, e.g., EP 404,097; WO 93 / 11161; and Holliger et al. (1993) Proc. Natl. Acad. Sci. USA 90: 6444-6448. For a review of engineered antibody variants generally see Holliger and Hudson (2005) Nat. Biotechnol. 23:1126-1136.

[0068] “Isolated antibody” refers to the purification status of a binding compound and in such context means the molecule is substantially free of other biological molecules such as nucleic acids, proteins, lipids, carbohydrates, or other material such as cellular debris and growth media. Generally, the term “isolated” is not intended to refer to a complete absence of such material or to an absence of water, buffers, or salts, unless they are present in amounts that 10 IPTS / 128573217.2INH-027WO PATENT substantially interfere with experimental or therapeutic use of the binding compound as described herein.

[0069] The term “monoclonal antibody”, as used herein, refers to population of substantially homogeneous antibodies, i.e., the antibody molecules comprising the population are identical in amino acid sequence except for possible naturally occurring mutations and / or post- translational modifications that may be present in minor amounts. In contrast, conventional (polyclonal) antibody preparations typically include a multitude of different antibodies having different amino acid sequences in their variable domains, particularly their CDRs, that are often specific for different epitopes. The modifier “monoclonal” indicates the character of the antibody as being obtained from a substantially homogeneous population of antibodies, and is not to be construed as requiring production of the antibody by any particular method. For example, the monoclonal antibodies to be used in accordance with the present invention may be made by the hybridoma method first described by Kohler et al. (1975) Nature 256: 495, or may be made by recombinant DNA methods (see, e.g., U.S. Pat. No. 4,816,567). The “monoclonal antibodies” may also be isolated from phage antibody libraries using the techniques described in Clackson et al. (1991) Nature 352: 624-628 and Marks et al. (1991) J. Mol. Biol. 222: 581-597, for example. See also Presta (2005) J. Allergy Clin. Immunol. 116:731.

[0070] As used herein, the term “humanized antibody” refers to forms of antibodies that contain sequences from both human and non-human (e.g., murine, rat) antibodies. In general, the humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the hypervariable loops correspond to those of a non-human immunoglobulin, and all or substantially all of the framework (FR) regions are those of a human immunoglobulin sequence. The humanized antibody may optionally comprise at least a portion of a human immunoglobulin constant region (Fc).

[0071] The term “fully human antibody” refers to an antibody that comprises human immunoglobulin protein sequences only. A fully human antibody may contain murine carbohydrate chains if produced in a mouse, in a mouse cell, or in a hybridoma derived from a mouse cell. Similarly, “mouse antibody” refers to an antibody that comprises mouse immunoglobulin sequences only. Alternatively, a fully human antibody may contain rat carbohydrate chains if produced in a rat, in a rat cell, or in a hybridoma derived from a rat cell. Similarly, “rat antibody” refers to an antibody that comprises rat immunoglobulin sequences only. 11 IPTS / 128573217.2INH-027WO PATENT

[0072] In some embodiments, the basic antibody structural unit comprises a tetramer. Each tetramer includes two identical pairs of polypeptide chains, each pair having one “light” (about 25 kDa) and one “heavy” chain (about 50-70 kDa). The amino-terminal portion of each chain includes a variable region of about 100 to 110 or more amino acids primarily responsible for antigen recognition. The carboxy-terminal portion of the heavy chain may define a constant region primarily responsible for effector function. Typically, human light chains are classified as kappa and lambda light chains. Furthermore, human heavy chains are typically classified as mu, delta, gamma, alpha, or epsilon, and define the antibody's isotype as IgM, IgD, IgG, IgA, and IgE, respectively. Within light and heavy chains, the variable and constant regions are joined by a “J” region of about 12 or more amino acids, with the heavy chain also including a “D” region of about 10 more amino acids. See generally, Fundamental Immunology Ch. 7 (Paul, W., ed., 2nd ed. Raven Press, N.Y. (1989).

[0073] The variable regions of each light / heavy chain pair form the antibody binding site. Thus, in general, an intact antibody has two binding sites. However, in bifunctional or bispecific antibodies, the two binding sites are, in general, not the same.

[0074] Typically, the variable domains of both the heavy and light chains comprise three hypervariable regions, also called complementarity determining regions (CDRs), located within relatively conserved framework regions (FR). The CDRs are usually aligned by the framework regions, enabling binding to a specific epitope. In general, from N-terminal to C- terminal, both light and heavy chains variable domains comprise FR1, CDR1, FR2, CDR2, FR3, CDR3 and FR4. The assignment of amino acids to each domain is, generally, in accordance with the definitions of Sequences of Proteins of Immunological Interest, Kabat, et al.; National Institutes of Health, Bethesda, Md. ; 5thed.; NIH Publ. No.91-3242 (1991); Kabat (1978) Adv. Prot. Chem.32:1-75; Kabat, et al., (1977) J. Biol. Chem.252:6609-6616; Chothia, et al., (1987) J Mol. Biol.196:901-917 or Chothia, et al., (1989) Nature 342:878-883.

[0075] As used herein, the term “hypervariable region” refers to the amino acid residues of an antibody that are responsible for antigen-binding. The hypervariable region comprises amino acid residues from a “complementarity determining region” or “CDR” (i.e. residues 24-34 (CDRL1), 50-56 (CDRL2) and 89-97 (CDRL3) in the light chain variable domain and residues 31-35 (CDRH1), 50-65 (CDRH2) and 95-102 (CDRH3) in the heavy chain variable domain; Kabat et al. (1991) Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md.) and / or those residues from a “hypervariable loop” (i.e. residues 26-32 (CDRL1), 50-52 (CDRL2) and 91-96 (CDRL3) in 12 IPTS / 128573217.2INH-027WO PATENT the light chain variable domain and 26-32 (CDRH1), 53-55 (CDRH2) and 96-101 (CDRH3) in the heavy chain variable domain; Chothia and Lesk (1987) J. Mol. Biol. 196: 901-917). The CDRs can also be referenced according to the IMGT system for the identification of CDRs, which is described in Lefranc MP. Unique database numbering system for immunogenetic analysis. Immunol Today (1997) 18:509. As used herein, the term “framework” or “FR” residues refers to those variable domain residues other than the hypervariable region residues defined herein as CDR residues. CDRs provide the majority of contact residues for the binding of the antibody to the antigen or epitope. CDRs of interest can be derived from donor antibody variable heavy and light chain sequences, and include analogs of the naturally occurring CDRs, which analogs also share or retain the same antigen binding specificity and / or neutralizing ability as the donor antibody from which they were derived.

[0076] As used herein, “specific binding” or “immunospecific binding” or “binds immunospecifically” refer to antibody binding to a predetermined antigen at a much higher affinity than for another antigen(s). In some embodiments, the antibody binds the predetermined antigen with a dissociation constant (KD) of 10-7M or less, and such KD is at least two-fold less than its KD for binding to a non-specific antigen (e.g., BSA, casein, or another non-specific polypeptide).

[0077] Methods for determining mAb specificity and affinity by competitive inhibition can be found in Harlow, et al., Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1988), Colligan et al., eds., Current Protocols in Immunology, Greene Publishing Assoc. and Wiley Interscience, N.Y., (1992, 1993), and Muller, Meth. Enzymol.92:589601 (1983), which references are entirely incorporated herein by reference.

[0078] As used herein, the term “individual” or “subject,” or “patient” used interchangeably, means any animal, including mammals, such as mice, rats, other rodents, rabbits, dogs, cats, swine, cattle, sheep, horses, or primates, such as humans. In some embodiments, the subject is a human. A subject that is “in need thereof” refers to a subject that has been identified as requiring treatment for the condition that is to be treated and is treated with the specific intent of treating such condition. The conditions can be, for example, any of the conditions described herein.

[0079] As used herein, the terms “comprising” (and any form of comprising, such as “comprise”, “comprises”, and “comprised”), “having” (and any form of having, such as “have” and “has”), “including” (and any form of including, such as “includes” and “include”), or “containing” (and any form of containing, such as “contains” and “contain”), are inclusive or 13 IPTS / 128573217.2INH-027WO PATENT open-ended and do not exclude additional, unrecited elements or method steps. Any step or composition that uses the transitional phrase of “comprise” or “comprising” can also be said to describe the same with the transitional phase of “consisting of” or “consists.”

[0080] As used herein, the term “contacting” means bringing together of two elements in an in vitro system or an in vivo system. For example, “contacting” virus or vector described herein with an individual or patient or cell includes the administration of the virus to an individual or patient, such as a human, as well as, for example, introducing a compound into a sample containing a cellular or purified preparation containing the cell.

[0081] As used herein, the term “fused” or “linked” when used in reference to a protein having different domains or heterologous sequences means that the protein domains are part of the same peptide chain that are connected to one another with either peptide bonds or other covalent bonding. The domains or section can be linked or fused directly to one another or another domain or peptide sequence can be between the two domains or sequences and such sequences would still be considered to be fused or linked to one another. In some embodiments, the various domains or proteins provided for herein are linked or fused directly to one another or a linker sequences, such as the glycine / serine sequences described herein link the two domains together.

[0082] A “disease” is a state of health of an animal wherein the animal cannot maintain homeostasis, and wherein if the disease is not ameliorated then the animal’s health continues to deteriorate. In contrast, a “disorder” in an animal is a state of health in which the animal is able to maintain homeostasis, but in which the animal’s state of health is less favorable than it would be in the absence of the disorder. Left untreated, a disorder does not necessarily cause a further decrease in the animal’s state of health.

[0083] “Effective amount” or “therapeutically effective amount” are used interchangeably herein, and refer to an amount of a compound, formulation, material, or composition, as described herein effective to achieve a particular biological result or provides a therapeutic or prophylactic benefit. Such results may include, but are not limited to an amount that when administered to a mammal, causes a detectable level of immune cell activation compared to the immune cell activation detected in the absence of the composition. The immune response can be readily assessed by a plethora of art-recognized methods. The skilled artisan would understand that the amount of the composition administered herein varies and can be readily determined based on a number of factors such as the disease or condition being treated, the age and health and physical condition of the mammal being treated, the severity of the disease, the 14 IPTS / 128573217.2INH-027WO PATENT particular compound being administered, and the like.

[0084] “Encoding” refers to the inherent property of specific sequences of nucleotides in a polynucleotide, such as a gene, a cDNA, or an mRNA, to serve as templates for synthesis of other polymers and macromolecules in biological processes having either a defined sequence of nucleotides (i.e., rRNA, tRNA and mRNA) or a defined sequence of amino acids and the biological properties resulting therefrom. Thus, a gene encodes a protein if transcription and translation of mRNA corresponding to that gene produces the protein in a cell or other biological system. Both the coding strand, the nucleotide sequence of which is identical to the mRNA sequence and is usually provided in sequence listings, and the non-coding strand, used as the template for transcription of a gene or cDNA, can be referred to as encoding the protein or other product of that gene or cDNA.

[0085] “Expression vector” refers to a vector comprising a recombinant polynucleotide comprising expression control sequences operatively linked to a nucleotide sequence to be expressed. An expression vector comprises sufficient cis-acting elements for expression; other elements for expression can be supplied by the host cell or in an in vitro expression system. Expression vectors include all those known in the art, such as cosmids, plasmids (e.g., naked or contained in liposomes) and viruses (e.g., Sendai viruses, lentiviruses, retroviruses, adenoviruses, and adeno-associated viruses) that incorporate the recombinant polynucleotide.

[0086] As used herein, the phrase “ex vivo” in reference to a cell being transduced, transfected or transformed ex vivo, refers to a cell being transduced, transfected or transformed outside of the subject, that is with the cells being removed from the subject before such cells are transduced, transfected or transformed.

[0087] “Identity” as used herein refers to the subunit sequence identity between two polymeric molecules such as between two nucleic acid or amino acid molecules, such as, between two polynucleotide or polypeptide molecules. When two amino acid sequences have the same residues at the same positions; e.g., if a position in each of two polypeptide molecules is occupied by an Arginine, then they are identical at that position. The identity or extent to which two amino acid or two nucleic acid sequences have the same residues at the same positions in an alignment is often expressed as a percentage. The identity between two amino acid or two nucleic acid sequences is a direct function of the number of matching or identical positions; e.g., if half of the positions in two sequences are identical, the two sequences are 50% identical; if 90% of the positions (e.g., 9 of 10), are matched or identical, the two amino acids sequences are 90% identical. 15 IPTS / 128573217.2INH-027WO PATENT

[0088] By "substantially identical" is meant a polypeptide or nucleic acid molecule exhibiting at least 50% identity to a reference amino acid sequence (for example, any one of the amino acid sequences described herein) or nucleic acid sequence (for example, any one of the nucleic acid sequences described herein). In some embodiments, such a sequence is at least 60%, 80% or 85%, or 90%, 95% or even 99% identical at the amino acid level or nucleic acid to the sequence used for comparison. Other percentages of identity in reference to specific sequences are described herein.

[0089] Sequence identity can be measured / determined using sequence analysis software (for example, Sequence Analysis Software Package of the Genetics Computer Group, University of Wisconsin Biotechnology Center, 1710 University Avenue, Madison, Wis.53705, BLAST, BESTFIT, GAP, or PILEUP / PRETTYBOX programs). Such software matches identical or similar sequences by assigning degrees of homology to various substitutions, deletions, and / or other modifications. Conservative substitutions typically include substitutions within the following groups: glycine, alanine; valine, isoleucine, leucine; aspartic acid, glutamic acid, asparagine, glutamine; serine, threonine; lysine, arginine; and phenylalanine, tyrosine. In an exemplary approach to determining the degree of identity, a BLAST program may be used, with a probability score between e3 and e100 indicating a closely related sequence. In some embodiments, sequence identity is determined by using BLAST with the default settings.

[0090] To the extent embodiments provided for herein, includes composition comprising various proteins, these proteins may, in some instances, comprise amino acid sequences that have sequence identity to the amino acid sequences disclosed herein. Therefore, in certain embodiments, depending on the particular sequence, the degree of sequence identity is preferably greater than 50% (e.g. 60%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more) to the SEQ ID NOs disclosed herein. In addition to these percentages, other percentages of identity are provided for herein. Identity between polypeptides can be determined by the Smith-Waterman homology search algorithm as implemented in the MPSRCH program (Oxford Molecular), using an affine gap search with parameters gap open penalty – 12 and gap extension penalty = 1.

[0091] These proteins may, compared to the disclosed proteins, include one or more (e.g.1, 2, 3,4, 5, 6, 7, 8, 9, 10, etc.) conservative amino acid replacements i.e. replacements of one amino acid with another which has a related side chain. Genetically-encoded amino acids are generally divided into four families: (1) acidic i.e. aspartate, glutamate; (2) basic i.e. lysine, arginine, histidine; (3) non polar i.e. alanine, valine, leucine, isoleucine, proline, phenylalanine, 16 IPTS / 128573217.2INH-027WO PATENT methionine, tryptophan; and (4) uncharged polar i.e. glycine, asparagine, glutamine, cysteine, serine, threonine, tyrosine. Phenylalanine, tryptophan, and tyrosine are sometimes classified jointly as aromatic amino acids. In general, Substitution of single amino acids within these families does not have a major effect on the biological activity. The proteins may have one or more (e.g.1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) single amino acid deletions relative to the disclosed protein sequences. The proteins may also include one or more (e.g.1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) insertions (e.g. each of 1, 2, 3, 4 or 5 amino acids) relative to the disclosed protein sequences. The changes may also be non-conservative as provided for herein.

[0092] As used herein, the phrase “in vivo” in reference to a cell being transduced, transfected or transformed in vivo, refers to a cell being transduced, transfected or transformed in the subject without the cells being removed from the subject before such cells are transduced, transfected or transformed.

[0093] “Isolated” means altered or removed from the natural state. For example, a nucleic acid or a peptide naturally present in a living animal is not “isolated,” but the same nucleic acid or peptide partially or completely separated from the coexisting materials of its natural state is “isolated.” An isolated nucleic acid or protein can exist in substantially purified form, or can exist in a non-native environment such as, for example, a host cell.

[0094] A “lentivirus” as used herein refers to a genus of the Retroviridae family that is able to infect non-dividing cells. Non-limiting examples of lentiviruses are HIV, SIV, and FIV. Vectors or viral-like particles derived from lentiviruses can be used to transduce cells and deliver genes or other molecules and have them expressed in a cell either in vitro (ex-vivo) or in vivo.

[0095] By the term “modified” as used herein, is meant a changed state or structure of a molecule or cell as provided herein. Molecules may be modified in many ways, including chemically, structurally, and functionally, such as mutations, substitutions, insertions, or deletions (e.g. internal deletions truncations). Cells may be modified through the introduction of nucleic acids or the expression of heterologous proteins.

[0096] By the term “modulating,” as used herein, is meant mediating an increase or decrease in the level of a response in a subject compared with the level of a response in the subject in the absence of a treatment or compound, and / or compared with the level of a response in an otherwise identical but untreated subject. The term encompasses perturbing and / or affecting a native signal or response thereby mediating a beneficial therapeutic response in a subject, such as, a human. 17 IPTS / 128573217.2INH-027WO PATENT

[0097] As used herein, the following abbreviations for the commonly occurring nucleic acid bases are used: “A” refers to adenosine, “C” refers to cytosine, “G” refers to guanosine, “T” refers to thymidine, and “U” refers to uridine.

[0098] Unless otherwise specified, a “nucleotide sequence encoding an amino acid sequence” includes all nucleotide sequences that are degenerate versions of each other and that encode the same amino acid sequence. The phrase nucleotide sequence that encodes a protein or an RNA may also include introns to the extent that the nucleotide sequence encoding the protein may in some version contain an intron(s).

[0099] The “Nipah virus” (NiV) is member of the family Paramyxoviridae, genus Henipavirus. Nipah virus is an enveloped virus with negative-stranded polarity and a non-segmented RNA genome consisting of helical nucleocapsids. Two strains of Nipah virus include, but are not limited to, the Malaysian (MY) and the Bangladesh (BD) strains.

[0100] The term “oligonucleotide” typically refers to short polynucleotides. It will be understood that when a nucleotide sequence is represented by a DNA sequence (i.e., A, T, C, G), this also provides the corresponding RNA sequence (i.e., A, U, C, G) in which “U” replaces “T.”

[0101] “Parenteral” administration of a composition includes, e.g., subcutaneous (s.c.), intravenous (i.v.), intramuscular (i.m.), or intrasternal injection, or infusion techniques.

[0102] The term “polynucleotide” as used herein is defined as a chain of nucleotides. Furthermore, nucleic acids are polymers of nucleotides. Thus, the terms “nucleic acids” and “polynucleotides” as used herein are interchangeable. As used herein polynucleotides include, but are not limited to, all nucleic acid sequences which are obtained by any methods available in the art, including, without limitation, recombinant methods, i.e., the cloning of nucleic acid sequences from a recombinant library or a cell genome, using cloning technology and PCR, and the like, and by synthetic means.

[0103] As used herein, the terms “peptide,” “polypeptide,” and “protein” are used interchangeably, and refer to a compound comprised of a plurality of amino acid residues covalently linked by peptide bonds. As used herein, the term refers to both short chains, which also commonly are referred to in the art as peptides, oligopeptides and oligomers, for example, and to longer chains, which generally are referred to in the art as proteins, of which there are many types. “Polypeptides” include, for example, biologically active fragments, substantially homologous polypeptides, oligopeptides, homodimers, heterodimers, variants of polypeptides, modified polypeptides, derivatives, analogs, fusion proteins, among others. The polypeptides 18 IPTS / 128573217.2INH-027WO PATENT include natural peptides, recombinant peptides, synthetic peptides, or a combination thereof.

[0104] As used herein, the term “variant” when used in reference to polynucleotide or polypeptide sequence means that the variant has one or more changes as compared to the reference sequence to which it is being compared. The change can be a mutation (substitution), deletion, or insertion. The variant can comprise a conservative mutation or a non-conservative mutation. For example, a variant VSV-G polypeptide is a VSV-G polypeptide that comprises one more changes as compared to the reference VSV-G polypeptide. There are various reference VSV-G polypeptides provided for herein. In some embodiments, the variant comprises a mutation that modifies a non-charged residue to a charged residue. Non-limiting examples are provided for herein for such variants. In some embodiments, the variants have 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 changes. An insertion of a contiguous number of amino acids is considered 1 change. For example, if the peptide of “GGG” is inserted into a sequence to create a variant without changing the residues to the N or C terminus of the insertion, this is considered one change. However, if three consecutive amino acids in the reference sequence are changed to “GGG” this would be considered 3 changes (mutations).

[0105] The term “pseudotyped” or “pseudotyped viral particle”, as used herein, refers to a viral particle bearing glycoproteins derived from other viruses having envelopes or a viral vector encoding envelope glycoproteins from a virus that is different from the parental virus. The host range of the vector particles can thus be expanded or altered depending on the type of cell surface receptor used by the glycoprotein. For example, a virus can be pseudotyped with a VSV-G mutant protein as provided for herein or other virus glycoproteins, such as those provided for herein.

[0106] The terms “pseudotyped viral particle” and “pseudotyped viral-like particle”, as used herein, are synonymous with each other unless explicitly stated otherwise.

[0107] The terms “viral particle” and “pseudotyped viral particle”, as used herein, are synonymous with each other unless explicitly stated otherwise.

[0108] By the term “specifically binds,” as used herein with respect to an antibody, is meant an antibody which recognizes a specific antigen, but does not substantially recognize or bind other molecules in a sample. For example, an antibody that specifically binds to an antigen from one species may also bind to that antigen from one or more species. But, such cross- species reactivity does not itself alter the classification of an antibody as specific. In another example, an antibody that specifically binds to an antigen may also bind to different allelic forms of the antigen. However, such cross reactivity does not itself alter the classification of 19 IPTS / 128573217.2INH-027WO PATENT an antibody as specific. In some instances, the terms “specific binding” or “specifically binding,” can be used in reference to the interaction of an antibody, a protein, or a peptide with a second chemical species, to mean that the interaction is dependent upon the presence of a particular structure (e.g., an antigenic determinant or epitope) on the chemical species; for example, an antibody recognizes and binds to a specific protein structure rather than to proteins generally. If an antibody is specific for epitope “A”, the presence of a molecule containing epitope A (or free, unlabeled A), in a reaction containing labeled “A” and the antibody, will reduce the amount of labeled A bound to the antibody. In some embodiments, the targeting moieties described herein that can be used to target the viral particles comprising the mutant VSV-G protein can specifically bind to their target.

[0109] The term “subject” includes living organisms, including those in which an immune response can be elicited (e.g., mammals). A “subject” or “patient,” as used therein, may be a human or non-human mammal. Non-human mammals include, for example, livestock and pets, such as ovine, bovine, porcine, canine, non-human primates, feline and murine mammals. In some embodiments, the subject is human.

[0110] The term “therapeutic” as used herein means a treatment and / or prophylaxis. A therapeutic effect is obtained by suppression, remission, or eradication of a disease state.

[0111] The term “transfected” or “transformed” or “transduced” as used herein refers to a process by which exogenous nucleic acid is transferred or introduced into a cell. A “transfected” or “transformed” or “transduced” cell is one which has been transfected, transformed or transduced with exogenous nucleic acid. The cell includes the primary subject cell and its progeny. In some embodiments, the transfection, transformation, or transduction is performed or occurs in vivo.

[0112] To “treat” a disease as the term is used herein, means to reduce the frequency or severity of at least one sign or symptom of a disease or disorder experienced by a subject. As used herein, “inhibit” or “treat” or “treatment” also includes a postponement of development of the symptoms associated with a disorder and / or a reduction in the severity of the symptoms of such disorder. The terms further include ameliorating existing uncontrolled or unwanted symptoms, preventing additional symptoms, and ameliorating or preventing the underlying causes of such symptoms. Thus, the terms denote that a beneficial result has been conferred on a vertebrate subject with a disorder, disease or symptom, or with the potential to develop such a disorder, disease or symptom.

[0113] A “vector” is a composition of matter which comprises an isolated nucleic acid 20 IPTS / 128573217.2INH-027WO PATENT encoding a protein or a peptide. Numerous vectors are known in the art including, but not limited to, linear polynucleotides, plasmids, DNA, and RNA. Examples of viral vectors include, but are not limited to, Sendai viral vectors, adenoviral vectors, adeno-associated virus vectors, retroviral vectors, lentiviral vectors, and the like.

[0114] A “carrier” or “delivery vehicle” includes viral particles, viruses, polylysine compounds, and liposomes, which facilitate transfer of nucleic acid into cells. A carrier or delivery vehicle can also be used to deliver a protein or peptide to a cell.

[0115] Ranges: throughout this disclosure, various aspects of the embodiments can be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 2.7, 3, 4, 5, 5.3, and 6. This applies regardless of the breadth of the range. Unless otherwise explicitly stated to the contrary, a range that is disclosed also includes the endpoints of the range.

[0116] Without being bound to any particular theory, the embodiments provided for herein have been found to show that a mutant VSV-G protein comprising a mutation at position 182 can be used to pseudotype a virus and transduce a cell when the virus comprises a targeting moiety. The mutation to a charged residue inhibits or reduces the VSV-G affinity to its natural co-receptor, the LDL-R. Additional mutations to charged residues at other amino acid positions within the VSV-G protein were tested for their ability to reduce the VSV-G affinity to its natural co-receptor, the LDL-R. The mutant VSV-G proteins as provided can be used, in some embodiments, to transduce a target cell and deliver a heterologous molecule to the targeted cells.

[0117] In some embodiments, a VSV-G protein is provided that comprises a mutation at position 198 as compared to SEQ ID NO: 1 or at position 182 as compared to SEQ ID NO: 2. SEQ ID NO: 1 is the full length protein and SEQ ID NO: 2 is the ectodomain of the VSV-G protein. The 16-mer signal peptide of MKCLLYLAFLFIGVNC (SEQ ID NO: 26) as shown at the N-terminus of SEQ ID NO: 1 is cleaved leaving a protein of SEQ ID NO: 2. Thus, although a mutation may be referred to in the context of SEQ ID NO: 2, it should be understood to also be made in the context of SEQ ID NO: 1, which contains the leader sequence, and thus 21 IPTS / 128573217.2INH-027WO PATENT would be a position number that is 16 more than the position recited for SEQ ID NO: 2. In some embodiments, the mutation inhibits or decreases the binding of the VSV-G protein to the LDL receptor (LDL-R). In some embodiments, the mutation is a I182D mutation as compared to SEQ ID NO: 2. In some embodiments, the mutation is a I182E mutation as compared to SEQ ID NO: 2.

[0118] In some embodiments, a VSV-G protein is provided that comprises a mutation at position 198 as compared to SEQ ID NO: 10 or at position 182 as compared to SEQ ID NO: 11. SEQ ID NO: 10 is the full length protein and SEQ ID NO: 11 is the ectodomain of the VSV-G protein. The 16-mer signal peptide of MLSYLIFALVVSPILG (SEQ ID NO: 27) as shown at the N-terminus of SEQ ID NO: 10 is cleaved leaving a protein of SEQ ID NO: 11. Thus, although a mutation may be referred to in the context of SEQ ID NO: 11, it should be understood to also be made in the context of SEQ ID NO: 10, which contains the leader sequence, and thus would be a position number that is 16 more than the position recited for SEQ ID NO: 11. In some embodiments, the mutation inhibits or decreases the binding of the VSV-G protein to the LDL receptor (LDL-R). In some embodiments, the mutation is a T182D mutation as compared to SEQ ID NO: 11. In some embodiments, the mutation is a T182E mutation as compared to SEQ ID NO: 11.

[0119] In some embodiments, a VSV-G protein is provided that comprises a mutation at position 198 as compared to SEQ ID NO: 12 or at position 182 as compared to SEQ ID NO: 13. SEQ ID NO: 12 is the full length protein and SEQ ID NO: 13 is the ectodomain of the VSV-G protein. The 16-mer signal peptide of MLRLFLFCFLALGAHS (SEQ ID NO: 28) as shown at the N-terminus of SEQ ID NO: 12 is cleaved leaving a protein of SEQ ID NO: 13. Thus, although a mutation may be referred to in the context of SEQ ID NO: 13, it should be understood to also be made in the context of SEQ ID NO: 12, which contains the leader sequence, and thus would be a position number that is 16 more than the position recited for SEQ ID NO: 13. In some embodiments, the mutation inhibits or decreases the binding of the VSV-G protein to the LDL receptor (LDL-R). In some embodiments, the mutation is a A182D mutation as compared to SEQ ID NO: 13. In some embodiments, the mutation is a A182E mutation as compared to SEQ ID NO: 13.

[0120] In some embodiments, a VSV-G protein is provided that comprises a mutation at position 203 as compared to SEQ ID NO: 14 or at position 182 as compared to SEQ ID NO: 15. SEQ ID NO: 14 is the full length protein and SEQ ID NO: 15 is the ectodomain of the VSV-G protein. The 21-mer signal peptide of MKMKMVIAGLILCIGILPAIG (SEQ ID NO: 22 IPTS / 128573217.2INH-027WO PATENT 29) as shown at the N-terminus of SEQ ID NO: 14 is cleaved leaving a protein of SEQ ID NO: 15. Thus, although a mutation may be referred to in the context of SEQ ID NO: 15, it should be understood to also be made in the context of SEQ ID NO: 14, which contains the leader sequence, and thus would be a position number that is 21 more than the position recited for SEQ ID NO: 15. In some embodiments, the mutation inhibits or decreases the binding of the VSV-G protein to the LDL receptor (LDL-R). In some embodiments, the mutation is a V182D mutation as compared to SEQ ID NO: 15. In some embodiments, the mutation is a V182E mutation as compared to SEQ ID NO: 15.

[0121] In some embodiments, a VSV-G protein is provided that comprises a mutation at position 199 as compared to SEQ ID NO: 16 or at position 182 as compared to SEQ ID NO: 17. SEQ ID NO: 16 is the full length protein and SEQ ID NO: 17 is the ectodomain of the VSV-G protein. The 17-mer signal peptide of MTPAFILCMLLAGSSWA (SEQ ID NO: 30) as shown at the N-terminus of SEQ ID NO: 16 is cleaved leaving a protein of SEQ ID NO: 17. Thus, although a mutation may be referred to in the context of SEQ ID NO: 17, it should be understood to also be made in the context of SEQ ID NO: 16, which contains the leader sequence, and thus would be a position number that is 17 more than the position recited for SEQ ID NO: 17. In some embodiments, the mutation inhibits or decreases the binding of the VSV-G protein to the LDL receptor (LDL-R). In some embodiments, the mutation is a V182D mutation as compared to SEQ ID NO: 17. In some embodiments, the mutation is a V182E mutation as compared to SEQ ID NO: 17.

[0122] In some embodiments, a VSV-G protein is provided that comprises a mutation at position 199 as compared to SEQ ID NO: 18 or at position 182 as compared to SEQ ID NO: 19. SEQ ID NO: 18 is the full length protein and SEQ ID NO: 19 is the ectodomain of the VSV-G protein. The 17-mer signal peptide of MNFLLLTFIVLPLCSHA (SEQ ID NO: 31) as shown at the N-terminus of SEQ ID NO: 18 is cleaved leaving a protein of SEQ ID NO: 19. Thus, although a mutation may be referred to in the context of SEQ ID NO: 19, it should be understood to also be made in the context of SEQ ID NO: 18, which contains the leader sequence, and thus would be a position number that is 17 more than the position recited for SEQ ID NO: 19. In some embodiments, the mutation inhibits or decreases the binding of the VSV-G protein to the LDL receptor (LDL-R). In some embodiments, the mutation is a V182D mutation as compared to SEQ ID NO: 19. In some embodiments, the mutation is a V182E mutation as compared to SEQ ID NO: 19.

[0123] In some embodiments, a VSV-G protein is provided that comprises a mutation at 23 IPTS / 128573217.2INH-027WO PATENT position 199 as compared to SEQ ID NO: 20 or at position 182 as compared to SEQ ID NO: 21. SEQ ID NO: 20 is the full length protein and SEQ ID NO: 21 is the ectodomain of the VSV-G protein. The 17-mer signal peptide of MLVLYLLLSLLALGAQC (SEQ ID NO: 32) as shown at the N-terminus of SEQ ID NO: 20 is cleaved leaving a protein of SEQ ID NO: 21. Thus, although a mutation may be referred to in the context of SEQ ID NO: 21, it should be understood to also be made in the context of SEQ ID NO: 20, which contains the leader sequence, and thus would be a position number that is 17 more than the position recited for SEQ ID NO: 21. In some embodiments, the mutation inhibits or decreases the binding of the VSV-G protein to the LDL receptor (LDL-R). In some embodiments, the mutation is a I182D mutation as compared to SEQ ID NO: 21. In some embodiments, the mutation is a I182E mutation as compared to SEQ ID NO: 21.

[0124] As used herein, when a polypeptide is said to have a mutation as compared to a reference sequence, such comparison is based on an alignment such as using BlastP or ClustalW or ClutalOmega alignment software using default parameters. For example, position 182 can be found in SEQ ID NO: 2 and also as compared to the other strains as illustrated in FIG.3. FIG.3 illustrates a clustal alignment of the wild-type sequences of the ectodomains of the various strains of the VSV-G protein. The residue that is bolded and underlined are the residues that align to position 182 of SEQ ID NO: 2 of the various strains. SEQ ID NO: 2 refers to ectodomain of the VSV-G protein of the Indiana strain. SEQ ID NO: 11 refers to ectodomain of the VSV-G protein of the New Jersey strain. SEQ ID NO: 13 refers to ectodomain of the VSV-G protein of the Marraba strain. SEQ ID NO: 15 refers to ectodomain of the VSV-G protein of the Carajas strain. SEQ ID NO: 17 refers to ectodomain of the VSV- G protein of the Alagoa strain. SEQ ID NO: 19 refers to ectodomain of the VSV-G protein of the Cocal strain. SEQ ID NO: 21 refers to ectodomain of the VSV-G protein of the Morreton strain. Accordingly, the residue that aligns to residues 182 as compared to SEQ ID NO: 2 can also be mutated as provided for herein.

[0125] In some embodiments, the mutation at position 182 as compared to SEQ ID NO: 2 is not an alanine. In some embodiments, the mutation at position 182 as compared to SEQ ID NO: 2 is not a valine.

[0126] In some embodiments, the mutation at position 182 as compared to SEQ ID NO: 2 is I182S, I182H, I182T, I182Q, or I182N. In some embodiments, the mutation at position 182 as compared to SEQ ID NO: 11 is T182S, T182H, T182Q, or T182N. In some embodiments, the mutation at position 182 as compared to SEQ ID NO: 13 is A182S, A182H, A182T, A182Q, 24 IPTS / 128573217.2INH-027WO PATENT or A182N. In some embodiments, the mutation at position 182 as compared to SEQ ID NO: 15 is V182S, V182H, V182T, V182Q, or V182N. In some embodiments, the mutation at position 182 as compared to SEQ ID NO: 17 is V182S, V182H, V182T, V182Q, or V182N. In some embodiments, the mutation at position 182 as compared to SEQ ID NO: 19 is V182S, V182H, V182T, V182Q, or V182N. In some embodiments, the mutation at position 182 as compared to SEQ ID NO: 21 is I182S, I182H, I182T, I182Q, or I182N. In some embodiments, the mutation at position 182 is not a hydrophobic residue. In some embodiments, the mutation at position 182 is a charged residue. In some embodiments, the mutation at position 182 is a negatively charged residue.

[0127] Although, the mutations may be described in reference to SEQ ID NO: 1 or SEQ ID NO: 2, which is the VSV-G protein from the Indiana strain, the mutation can also be used in other strains of the VSV-G protein. For example, the mutation can be made in the New Jersey Strain of VSV-G, the Marraba strain of VSV-G, the Carajas strain of VSV-G, the Alagoa strain of VSV-G, the Cocal strain of VSV-G, or the Morreton strain of VSV-G. In some embodiments, the sequences of each are as provided herein. Examples of these can be found, for example in U.S. Patent Application Publication No. 20200216502, which is hereby incorporated by reference. For example, the wild-type full length or ectodomain of the New Jersey Strain of VSV-G are SEQ ID NO: 10 and SEQ ID NO: 11, respectively, the wild-type full length or ectodomain of Marraba strain of VSV-G are SEQ ID NO: 12 and SEQ ID NO: 13, respectively, the wild-type full length or ectodomain of Carajas strain of VSV-G are SEQ ID NO: 14 and SEQ ID NO: 15, respectively, the wild-type full length or ectodomain of Alagoa strain of VSV-G are SEQ ID NO: 16 and SEQ ID NO: 17, respectively, the wild-type full length or ectodomain of Cocal strain of VSV-G are SEQ ID NO: 18 and SEQ ID NO: 19, respectively, or the wild-type full length or ectodomain of Morreton strain of VSV-G are SEQ ID NO: 20 and SEQ ID NO: 21, respectively.

[0128] A VSV-G protein comprising a mutation at position 182 as compared to SEQ ID NO: 2 can also comprise other mutations, such as those described in U.S. Patent Application Publication No.2020 / 0216502, which is hereby incorporated by reference in its entirety. For example, the VSV-G protein can comprise a mutation at a position that corresponds to positions of 8, 47, 209 and / or 354 of SEQ ID NO: 2.

[0129] In some embodiments, the substitution at position 8 is by any amino acid different from the amino acid indicated at that position in the sequence SEQ ID NO: 2, except Y. In some embodiments, the substitution at position 8 is by any amino acid different from the amino acid 25 IPTS / 128573217.2INH-027WO PATENT indicated at that position in the sequence SEQ ID NO: 2, except H. In some embodiments, the substitution at position 8 is by any amino acid different from the amino acid indicated at that position in the sequence SEQ ID NO: 2, except Q. In some embodiments, the substitution at position 8 is by any amino acid different from the amino acid indicated at that position in the sequence SEQ ID NO: 2, except Y or H or Q. In some embodiments, the substitution at position 8 is selected from alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glycine, isoleucine, valine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, or tryptophan. In some embodiments, the substitution at position 8 is selected from 8A, 8I, 8V, 8L, and the like. In some embodiments, the substitution at position 8 is selected from H8A, H8I, H8V, H8L, and the like.

[0130] In some embodiments, the substitution at position 209 is by any amino acid different from the amino acid indicated at that position in the sequence SEQ ID NO: 2, except H. In some embodiments, the substitution at position 209 is by any amino acid different from the amino acid indicated at that position in the sequence SEQ ID NO: 2, except Y. In some embodiments, the substitution at position 209 is by any amino acid different from the amino acid indicated at that position in the sequence SEQ ID NO: 2, except H or Y. In some embodiments, the substitution at position 209 is selected from alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, isoleucine, valine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, or tryptophan.

[0131] In some embodiments, the substitution at position 47 is by any amino acid different from the amino acid indicated at that position in the sequence SEQ ID NO: 2, except K. In some embodiments, the substitution at position 47 is by any amino acid different from the amino acid indicated at that position in the sequence SEQ ID NO: 2, except R. In some embodiments, the substitution at position 47 is by any amino acid different from the amino acid indicated at that position in the sequence SEQ ID NO: 2, except K or R. In some embodiments, the substitution at position 47 is selected from alanine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, valine, leucine, methionine, phenylalanine, proline, serine, threonine, tryptophan, or tyrosine. In some embodiments, the substitution at position 47 is selected from A, G, F, N, or Q. In some embodiments, the substitution at position 47 is selected from Q or N.

[0132] In some embodiments, the substitution at position 354 is by any amino acid different from the amino acid indicated at that position in the sequence SEQ ID NO: 2, except K. In some embodiments, the substitution at position 354 is by any amino acid different from the 26 IPTS / 128573217.2INH-027WO PATENT amino acid indicated at that position in the sequence SEQ ID NO: 2, except R. In some embodiments, the substitution at position 354 is by any amino acid different from the amino acid indicated at that position in the sequence SEQ ID NO: 2, except K or R. In some embodiments, the substitution at position 354 is selected from alanine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, valine, leucine, methionine, phenylalanine, proline, serine, threonine, tryptophan, or tyrosine. In some embodiments, the substitution at position 354 is selected from A, G, F, N, or Q.

[0133] In some embodiments, the substitution is at position 47 or at position 354, or at both positions 47 and 354 are, independently, substituted by A, G, F, N or Q. In some embodiments, the substitution at position 47 or at position 354, or at both positions 47 and 354 is, independently, A or Q or N.

[0134] In some embodiments, the VSV-G protein can comprise a mutation at a position that corresponds to positions of 8, 47, 209 and / or 354. In some embodiments, the VSV-G protein can comprise a mutation at a position that corresponds to position 8 as provided for herein, at position 47 as provided for herein, at position 209 as provided for herein, and / or position 354 as provided for herein. In some embodiments, the VSV-G protein can comprise a mutation at a position that corresponds to position 8 as provided for herein and at position 47 as provided for herein. In some embodiments, the VSV-G protein can comprise a mutation at a position that corresponds to position 8 as provided for herein and at position 209 as provided for herein. In some embodiments, the VSV-G protein can comprise a mutation at a position that corresponds to position 8 as provided for herein and at position 354 as provided for herein. In some embodiments, the VSV-G protein can comprise a mutation at a position that corresponds to position 47 as provided for herein and at position 209 as provided for herein. In some embodiments, the VSV-G protein can comprise a mutation at a position that corresponds to position 47 as provided for herein and at position 354 as provided for herein. In some embodiments, the VSV-G protein can comprise a mutation at a position that corresponds to position 209 as provided for herein and at position 354 as provided for herein. In some embodiments, the VSV-G protein can comprise a mutation at a position that corresponds to position 8 as provided for herein, at position 47 as provided for herein, and position 209 as provided for herein. In some embodiments, the VSV-G protein can comprise a mutation at a position that corresponds to position 8 as provided for herein, at position 47 as provided for herein, and position 354 as provided for herein. In some embodiments, the VSV-G protein can comprise a mutation at a position that corresponds to position 8 as provided for herein, at 27 IPTS / 128573217.2INH-027WO PATENT position 209 as provided for herein, and position 354 as provided for herein. In some embodiments, the VSV-G protein can comprise a mutation at a position that corresponds to position 47 as provided for herein, at position 209 as provided for herein, and position 354 as provided for herein. In some embodiments, the VSV-G protein can comprise a mutation at a position that corresponds to position 8 as provided for herein, at position 47 as provided for herein, at position 209 as provided for herein, and at position 354 as provided for herein.

[0135] In some embodiments, the substitution at position 8 is an alanine, i.e., H8A.

[0136] In some embodiments, the substitution at position 47 is Q or N or A, i.e., K47Q or K47N or K47A.

[0137] In some embodiments, the protein comprises a substitution at position 8 and / or a substitution at position 47. In some embodiments, the protein comprises a substitution at position 8 and a substitution at position 47. In some embodiments, the protein comprises a substitution at position 8 or a substitution at position 47. In some embodiments, the substitution at position 8 and / or a substitution at position 47 comprises a H8A and / or K47Q mutation.

[0138] In some embodiments, the protein comprises a mutation (substitution) at position 10. In some embodiments, the substitution / mutation is Q10A, Q10R, or Q10K.

[0139] In some non-limiting embodiments, the substitution at position 209 is A, i.e., Y209A.

[0140] In some non-limiting embodiments, the substitution at position 354 is A or Q, i.e. R354A or R354Q.

[0141] In some embodiments, a protein comprising a mutation at position 182 as compared to SEQ ID NO: 11 can also comprise other mutations, such as those described in U.S. Patent Application Publication No.2020 / 0216502. For example, the VSV-G protein can comprise a mutation at a position analogous to positions of 8, 47, 209 and / or 354 of SEQ ID NO: 2. In some embodiments, the mutation in SEQ ID NO: 11 at a position analogous to positions of 8, 47, 209 and / or 354 of SEQ ID NO: 2 are as provided for herein.

[0142] In some embodiments, a protein comprising a mutation at position 182 as compared to SEQ ID NO: 13 can also comprise other mutations, such as those described in U.S. Patent Application Publication No.2020 / 0216502. For example, the VSV-G protein can comprise a mutation at a position analogous to positions of 8, 47, 209 and / or 354 of SEQ ID NO: 2. In some embodiments, the mutation in SEQ ID NO: 13 at a position analogous to positions of 8, 47, 209 and / or 354 of SEQ ID NO: 2 are as provided for herein.

[0143] In some embodiments, a protein comprising a mutation at position 182 as compared to SEQ ID NO: 15 can also comprise other mutations, such as those described in U.S. Patent 28 IPTS / 128573217.2INH-027WO PATENT Application Publication No.2020 / 0216502. For example, the VSV-G protein can comprise a mutation at a position analogous to positions of 8, 47, 209 and / or 354 of SEQ ID NO: 2. In some embodiments, the mutation in SEQ ID NO: 15 at a position analogous to positions of 8, 47, 209 and / or 354 of SEQ ID NO: 2 are as provided for herein.

[0144] In some embodiments, a protein comprising a mutation at position 182 as compared to SEQ ID NO: 17 can also comprise other mutations, such as those described in U.S. Patent Application Publication No.2020 / 0216502. For example, the VSV-G protein can comprise a mutation at a position analogous to positions of 8, 47, 209 and / or 354 of SEQ ID NO: 2. In some embodiments, the mutation in SEQ ID NO: 17 at a position analogous to positions of 8, 47, 209 and / or 354 of SEQ ID NO: 2 are as provided for herein.

[0145] In some embodiments, a protein comprising a mutation at position 182 as compared to SEQ ID NO: 19 can also comprise other mutations, such as those described in U.S. Patent Application Publication No.2020 / 0216502. For example, the VSV-G protein can comprise a mutation at a position analogous to positions of 8, 47, 209 and / or 354 of SEQ ID NO: 2. In some embodiments, the mutation in SEQ ID NO: 19 at a position analogous to positions of 8, 47, 209 and / or 354 of SEQ ID NO: 2 are as provided for herein.

[0146] In some embodiments, a protein comprising a mutation at position 182 as compared to SEQ ID NO: 21 can also comprise other mutations, such as those described in U.S. Patent Application Publication No.2020 / 0216502. For example, the VSV-G protein can comprise a mutation at a position analogous to positions of 8, 47, 209 and / or 354 of SEQ ID NO: 2. In some embodiments, the mutation in SEQ ID NO: 21 at a position analogous to positions of 8, 47, 209 and / or 354 of SEQ ID NO: 2 are as provided for herein.

[0147] In some embodiments, a protein comprising a mutation at position 182 as compared to SEQ ID NO: 2 comprises a mutation at position 182 and at least, or about, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical as compared to SEQ ID NO: 2 (or SEQ ID NO: 1 if using the full length protein). In some embodiments, the protein is at least, or about, 80% identical to SEQ ID NO: 2. In some embodiments, the protein is at least, or about, 85% identical to SEQ ID NO: 2. In some embodiments, the protein is at least, or about, 90% identical to SEQ ID NO: 2. In some embodiments, the protein is at least, or about, 95% identical to SEQ ID NO: 2. In some embodiments, the mutation at position 182 is I182D or I182E mutation. In some embodiments, the mutation is I182D. In some embodiments, the mutation is I182E mutation. In some embodiments, the mutation is I182S, 29 IPTS / 128573217.2INH-027WO PATENT I182H, I182T, I182Q, or I182N mutation.

[0148] In some embodiments, a VSV-G is provided wherein the protein comprises the amino acid sequence of SEQ ID NO: 2 with a mutation at position 182 and at least, or about, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical as compared to SEQ ID NO: 2.

[0149] In some embodiments, a protein comprising a mutation at position 182 as compared to SEQ ID NO: 11 comprises a mutation at position 182 and at least, or about, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical as compared to SEQ ID NO: 11 (or SEQ ID NO: 10 if using the full length protein). In some embodiments, the polypeptide comprises a T182D or T182E mutation. In some embodiments, the VSV-G protein comprises a T182S, T182H, T182Q, or T182N mutation.

[0150] In some embodiments, a protein comprising a mutation at position 182 as compared to SEQ ID NO: 13 comprises a mutation at position 182 and at least, or about, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical as compared to SEQ ID NO: 13 (or SEQ ID NO: 12 if using the full length protein). In some embodiments, the polypeptide comprises a A182D or A182E mutation. In some embodiments, the VSV-G protein comprises a A182S, A182H, A182T, A182Q, or A182N mutation.

[0151] In some embodiments, a protein comprising a mutation at position 182 as compared to SEQ ID NO: 15 comprises a mutation at position 182 and at least, or about, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical as compared to SEQ ID NO: 15 (or SEQ ID NO: 14 if using the full length protein). In some embodiments, the polypeptide comprises a V182D or V182E mutation. In some embodiments, the VSV-G protein comprises a V182S, V182H, V182T, V182Q, or V182N mutation.

[0152] In some embodiments, a protein comprising a mutation at position 182 as compared to SEQ ID NO: 17 comprises a mutation at position 182 and at least, or about, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical as compared to SEQ ID NO: 17 (or SEQ ID NO: 16 if using the full length protein). In some embodiments, the polypeptide comprises a V182D or V182E mutation. In some embodiments, the VSV-G 30 IPTS / 128573217.2INH-027WO PATENT protein comprises a V182S, V182H, V182T, V182Q, or V182N mutation.

[0153] In some embodiments, a protein comprising a mutation at position 182 as compared to SEQ ID NO: 19 comprises a mutation at position 182 and at least, or about, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical as compared to SEQ ID NO: 19 (or SEQ ID NO: 18 if using the full length protein). In some embodiments, the polypeptide comprises a V182D or V182E mutation. In some embodiments, the VSV-G protein comprises a V182S, V182H, V182T, V182Q, or V182N mutation.

[0154] In some embodiments, a protein comprising a mutation at position 182 as compared to SEQ ID NO: 21 comprises a mutation at position 182 and at least, or about, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical as compared to SEQ ID NO: 21 (or SEQ ID NO: 20 if using the full length protein). In some embodiments, the polypeptide comprises a I182D or I182E mutation. In some embodiments, the VSV-G protein comprises a I182S, I182H, I182T, I182Q, or I182N mutation.

[0155] In some embodiments, a VSV-G protein is provided that comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to the amino acid sequence of SEQ ID NO: 2, and further comprises a mutation that corresponds to a mutation at position 8, 9, 10, 47, 50, 51, 179, 180, 182, 183, 184, 209, 347, 350, 352, 353, 354, or any combination thereof as compared to SEQ ID NO: 2, as provided for herein. In some embodiments, the mutation at position 8, 9, 10, 47, 50, 51, 179, 180, 182, 183, 184, 209, 347, 350, 352, 353, 354, or any combination thereof as compared to SEQ ID NO: 2 comprises a substitution to a charged amino acid. In some embodiments, the charged amino acid is as provided for herein. In some embodiments, the VSV-G protein comprises a substitution at position H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 2, as provided for herein. In some embodiments, the substitution at position H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 2, as provided for herein, comprises a substitution to a charged amino acid. In some embodiments, the charged amino acid is as provided for herein. In some embodiments, the substitution at position H8 as compared to SEQ ID NO: 2 comprises a H8D, H8E, H8K, or H8R substitution. In some embodiments, the substitution at position N9 as compared to SEQ ID NO: 2 comprises a N9D, 31 IPTS / 128573217.2INH-027WO PATENT N9E, N9K, or N9R substitution. In some embodiments, the substitution at position Q10 as compared to SEQ ID NO: 2 comprises a Q10D or Q10E substitution. In some embodiments, the substitution at position K47 as compared to SEQ ID NO: 2 comprises a K47D or K47E substitution. In some embodiments, the substitution at position K50 as compared to SEQ ID NO: 2 comprises a K50D or K50E substitution. In some embodiments, the substitution at position A51 as compared to SEQ ID NO: 2 comprises a A51D, A51E, A51K, or A51R substitution. In some embodiments, the substitution at position S179 as compared to SEQ ID NO: 2 comprises a S179D, S179E, S179K, or S179R substitution. In some embodiments, the substitution at position N180 as compared to SEQ ID NO: 2 comprises a N180D, N180E, N180K, or N180R substitution. In some embodiments, the substitution at position I182 as compared to SEQ ID NO: 2 comprises a I182D, I182E, I182K, or I182R substitution. In some embodiments, the substitution at position S183 as compared to SEQ ID NO: 2 comprises a S183D, S183E, S183K, or S183R substitution. In some embodiments, the substitution at position M184 as compared to SEQ ID NO: 2 comprises a M184D, M184E, M184K, or M184R substitution. In some embodiments, the substitution at position Y209 as compared to SEQ ID NO: 2 comprises a Y209D, Y209E, Y209K, or Y209R substitution. In some embodiments, the substitution at position I347 as compared to SEQ ID NO: 2 comprises a I347D, I347E, I347K, or I347R substitution. In some embodiments, the substitution at position T350 as compared to SEQ ID NO: 2 comprises a T350D, T350E, T350K, or T350R substitution. In some embodiments, the substitution at position T352 as compared to SEQ ID NO: 2 comprises a T352D, T352E, T352K, or T352R substitution. In some embodiments, the substitution at position E353 as compared to SEQ ID NO: 2 comprises a E353K or E353R substitution. In some embodiments, the substitution at position R354 as compared to SEQ ID NO: 2 comprises a R354D or R354E substitution.

[0156] In some embodiments, a VSV-G protein is provided that comprises the amino acid sequence of SEQ ID NO: 3 and further comprises a mutation that corresponds to a mutation at position 8, 9, 10, 47, 50, 51, 179, 180, 183, 184, 209, 347, 350, 352, 353, 354, or any combination thereof as compared to SEQ ID NO: 3, as provided for herein. In some embodiments, the mutation at position 8, 9, 10, 47, 50, 51, 179, 180, 183, 184, 209, 347, 350, 352, 353, 354, or any combination thereof as compared to SEQ ID NO: 3 comprises a substitution to a charged amino acid. In some embodiments, the charged amino acid is as provided for herein. In some embodiments, the VSV-G protein comprises a substitution at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, 32 IPTS / 128573217.2INH-027WO PATENT E353, R354, or any combination thereof as compared to SEQ ID NO: 3, as provided for herein. In some embodiments, the substitution at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 3, as provided for herein, comprises a substitution to a charged amino acid. In some embodiments, the charged amino acid is as provided for herein. In some embodiments, the substitution at position H8 as compared to SEQ ID NO: 3 comprises a H8D, H8E, H8K, or H8R substitution. In some embodiments, the substitution at position N9 as compared to SEQ ID NO: 3 comprises a N9D, N9E, N9K, or N9R substitution. In some embodiments, the substitution at position Q10 as compared to SEQ ID NO: 3 comprises a Q10D or Q10E substitution. In some embodiments, the substitution at position K47 as compared to SEQ ID NO: 3 comprises a K47D or K47E substitution. In some embodiments, the substitution at position K50 as compared to SEQ ID NO: 3 comprises a K50D or K50E substitution. In some embodiments, the substitution at position A51 as compared to SEQ ID NO: 3 comprises a A51D, A51E, A51K, or A51R substitution. In some embodiments, the substitution at position S179 as compared to SEQ ID NO: 3 comprises a S179D, S179E, S179K, or S179R substitution. In some embodiments, the substitution at position N180 as compared to SEQ ID NO: 3 comprises a N180D, N180E, N180K, or N180R substitution. In some embodiments, the substitution at position S183 as compared to SEQ ID NO: 3 comprises a S183D, S183E, S183K, or S183R substitution. In some embodiments, the substitution at position M184 as compared to SEQ ID NO: 3 comprises a M184D, M184E, M184K, or M184R substitution. In some embodiments, the substitution at position Y209 as compared to SEQ ID NO: 3 comprises a Y209D, Y209E, Y209K, or Y209R substitution. In some embodiments, the substitution at position I347 as compared to SEQ ID NO: 3 comprises a I347D, I347E, I347K, or I347R substitution. In some embodiments, the substitution at position T350 as compared to SEQ ID NO: 3 comprises a T350D, T350E, T350K, or T350R substitution. In some embodiments, the substitution at position T352 as compared to SEQ ID NO: 3 comprises a T352D, T352E, T352K, or T352R substitution. In some embodiments, the substitution at position E353 as compared to SEQ ID NO: 3 comprises a E353K or E353R substitution. In some embodiments, the substitution at position R354 as compared to SEQ ID NO: 3 comprises a R354D or R354E substitution.

[0157] In some embodiments, a VSV-G protein is provided that comprises the amino acid sequence of SEQ ID NO: 4 and further comprises a mutation that corresponds to a mutation at position 8, 9, 10, 47, 50, 51, 179, 180, 183, 184, 209, 347, 350, 352, 353, 354, or any 33 IPTS / 128573217.2INH-027WO PATENT combination thereof as compared to SEQ ID NO: 4, as provided for herein. In some embodiments, the mutation at position 8, 9, 10, 47, 50, 51, 179, 180, 183, 184, 209, 347, 350, 352, 353, 354, or any combination thereof as compared to SEQ ID NO: 4 comprises a substitution to a charged amino acid. In some embodiments, the charged amino acid is as provided for herein. In some embodiments, the VSV-G protein comprises a substitution at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 4, as provided for herein. In some embodiments, the substitution at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 4, as provided for herein, comprises a substitution to a charged amino acid. In some embodiments, the charged amino acid is as provided for herein. In some embodiments, the substitution at position H8 as compared to SEQ ID NO: 4 comprises a H8D, H8E, H8K, or H8R substitution. In some embodiments, the substitution at position N9 as compared to SEQ ID NO: 4 comprises a N9D, N9E, N9K, or N9R substitution. In some embodiments, the substitution at position Q10 as compared to SEQ ID NO: 4 comprises a Q10D or Q10E substitution. In some embodiments, the substitution at position K47 as compared to SEQ ID NO: 4 comprises a K47D or K47E substitution. In some embodiments, the substitution at position K50 as compared to SEQ ID NO: 4 comprises a K50D or K50E substitution. In some embodiments, the substitution at position A51 as compared to SEQ ID NO: 4 comprises a A51D, A51E, A51K, or A51R substitution. In some embodiments, the substitution at position S179 as compared to SEQ ID NO: 4 comprises a S179D, S179E, S179K, or S179R substitution. In some embodiments, the substitution at position N180 as compared to SEQ ID NO: 4 comprises a N180D, N180E, N180K, or N180R substitution. In some embodiments, the substitution at position S183 as compared to SEQ ID NO: 4 comprises a S183D, S183E, S183K, or S183R substitution. In some embodiments, the substitution at position M184 as compared to SEQ ID NO: 4 comprises a M184D, M184E, M184K, or M184R substitution. In some embodiments, the substitution at position Y209 as compared to SEQ ID NO: 4 comprises a Y209D, Y209E, Y209K, or Y209R substitution. In some embodiments, the substitution at position I347 as compared to SEQ ID NO: 4 comprises a I347D, I347E, I347K, or I347R substitution. In some embodiments, the substitution at position T350 as compared to SEQ ID NO: 4 comprises a T350D, T350E, T350K, or T350R substitution. In some embodiments, the substitution at position T352 as compared to SEQ ID NO: 4 comprises a T352D, T352E, T352K, or T352R substitution. In some embodiments, the substitution at position E353 as 34 IPTS / 128573217.2INH-027WO PATENT compared to SEQ ID NO: 4 comprises a E353K or E353R substitution. In some embodiments, the substitution at position R354 as compared to SEQ ID NO: 4 comprises a R354D or R354E substitution.

[0158] In some embodiments, a VSV-G protein is provided that comprises the amino acid sequence of SEQ ID NO: 5 and further comprises a mutation that corresponds to a mutation at position 8, 9, 10, 47, 50, 51, 179, 180, 183, 184, 209, 347, 350, 352, 353, 354, or any combination thereof as compared to SEQ ID NO: 5, as provided for herein. In some embodiments, the mutation at position 8, 9, 10, 47, 50, 51, 179, 180, 183, 184, 209, 347, 350, 352, 353, 354, or any combination thereof as compared to SEQ ID NO: 5 comprises a substitution to a charged amino acid. In some embodiments, the charged amino acid is as provided for herein. In some embodiments, the VSV-G protein comprises a substitution at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 5, as provided for herein. In some embodiments, the substitution at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 5, as provided for herein, comprises a substitution to a charged amino acid. In some embodiments, the charged amino acid is as provided for herein. In some embodiments, the substitution at position H8 as compared to SEQ ID NO: 5 comprises a H8D, H8E, H8K, or H8R substitution. In some embodiments, the substitution at position N9 as compared to SEQ ID NO: 5 comprises a N9D, N9E, N9K, or N9R substitution. In some embodiments, the substitution at position Q10 as compared to SEQ ID NO: 5 comprises a Q10D or Q10E substitution. In some embodiments, the substitution at position K47 as compared to SEQ ID NO: 5 comprises a K47D or K47E substitution. In some embodiments, the substitution at position K50 as compared to SEQ ID NO: 5 comprises a K50D or K50E substitution. In some embodiments, the substitution at position A51 as compared to SEQ ID NO: 5 comprises a A51D, A51E, A51K, or A51R substitution. In some embodiments, the substitution at position S179 as compared to SEQ ID NO: 5 comprises a S179D, S179E, S179K, or S179R substitution. In some embodiments, the substitution at position N180 as compared to SEQ ID NO: 5 comprises a N180D, N180E, N180K, or N180R substitution. In some embodiments, the substitution at position S183 as compared to SEQ ID NO: 5 comprises a S183D, S183E, S183K, or S183R substitution. In some embodiments, the substitution at position M184 as compared to SEQ ID NO: 5 comprises a M184D, M184E, M184K, or M184R substitution. In some embodiments, the substitution at position Y209 as compared to SEQ ID NO: 5 comprises 35 IPTS / 128573217.2INH-027WO PATENT a Y209D, Y209E, Y209K, or Y209R substitution. In some embodiments, the substitution at position I347 as compared to SEQ ID NO: 5 comprises a I347D, I347E, I347K, or I347R substitution. In some embodiments, the substitution at position T350 as compared to SEQ ID NO: 5 comprises a T350D, T350E, T350K, or T350R substitution. In some embodiments, the substitution at position T352 as compared to SEQ ID NO: 5 comprises a T352D, T352E, T352K, or T352R substitution. In some embodiments, the substitution at position E353 as compared to SEQ ID NO: 5 comprises a E353K or E353R substitution. In some embodiments, the substitution at position R354 as compared to SEQ ID NO: 5 comprises a R354D or R354E substitution.

[0159] In some embodiments, a VSV-G protein is provided that comprises the amino acid sequence of SEQ ID NO: 22 and further comprises a mutation that corresponds to a mutation at position 8, 9, 10, 47, 50, 51, 179, 180, 183, 184, 209, 347, 350, 353, 354, or any combination thereof as compared to SEQ ID NO: 22, as provided for herein. In some embodiments, the mutation at position 8, 9, 10, 47, 50, 51, 179, 180, 183, 184, 209, 347, 350, 353, 354, or any combination thereof as compared to SEQ ID NO: 22 comprises a substitution to a charged amino acid. In some embodiments, the charged amino acid is as provided for herein. In some embodiments, the VSV-G protein comprises a substitution at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof as compared to SEQ ID NO: 22, as provided for herein. In some embodiments, the substitution at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof as compared to SEQ ID NO: 22, as provided for herein, comprises a substitution to a charged amino acid. In some embodiments, the charged amino acid is as provided for herein. In some embodiments, the substitution at position H8 as compared to SEQ ID NO: 22 comprises a H8D, H8E, H8K, or H8R substitution. In some embodiments, the substitution at position N9 as compared to SEQ ID NO: 22 comprises a N9D, N9E, N9K, or N9R substitution. In some embodiments, the substitution at position Q10 as compared to SEQ ID NO: 22 comprises a Q10D or Q10E substitution. In some embodiments, the substitution at position K47 as compared to SEQ ID NO: 22 comprises a K47D or K47E substitution. In some embodiments, the substitution at position K50 as compared to SEQ ID NO: 22 comprises a K50D or K50E substitution. In some embodiments, the substitution at position A51 as compared to SEQ ID NO: 22 comprises a A51D, A51E, A51K, or A51R substitution. In some embodiments, the substitution at position S179 as compared to SEQ ID NO: 22 comprises a S179D, S179E, S179K, or S179R substitution. In some embodiments, the 36 IPTS / 128573217.2INH-027WO PATENT substitution at position N180 as compared to SEQ ID NO: 22 comprises a N180D, N180E, N180K, or N180R substitution. In some embodiments, the substitution at position S183 as compared to SEQ ID NO: 22 comprises a S183D, S183E, S183K, or S183R substitution. In some embodiments, the substitution at position M184 as compared to SEQ ID NO: 22 comprises a M184D, M184E, M184K, or M184R substitution. In some embodiments, the substitution at position Y209 as compared to SEQ ID NO: 22 comprises a Y209D, Y209E, Y209K, or Y209R substitution. In some embodiments, the substitution at position I347 as compared to SEQ ID NO: 22 comprises a I347D, I347E, I347K, or I347R substitution. In some embodiments, the substitution at position T350 as compared to SEQ ID NO: 22 comprises a T350D, T350E, T350K, or T350R substitution. In some embodiments, the substitution at position E353 as compared to SEQ ID NO: 22 comprises a E353K or E353R substitution. In some embodiments, the substitution at position R354 as compared to SEQ ID NO: 22 comprises a R354D or R354E substitution.

[0160] In some embodiments, a VSV-G protein is provided that comprises the amino acid sequence of SEQ ID NO: 23 and further comprises a mutation that corresponds to a mutation at position 8, 9, 10, 47, 50, 51, 179, 180, 183, 184, 209, 347, 350, 353, 354, or any combination thereof as compared to SEQ ID NO: 23, as provided for herein. In some embodiments, the mutation at position 8, 9, 10, 47, 50, 51, 179, 180, 183, 184, 209, 347, 350, 353, 354, or any combination thereof as compared to SEQ ID NO: 23 comprises a substitution to a charged amino acid. In some embodiments, the charged amino acid is as provided for herein. In some embodiments, the VSV-G protein comprises a substitution at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof as compared to SEQ ID NO: 23, as provided for herein. In some embodiments, the substitution at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof as compared to SEQ ID NO: 23, as provided for herein, comprises a substitution to a charged amino acid. In some embodiments, the charged amino acid is as provided for herein. In some embodiments, the substitution at position H8 as compared to SEQ ID NO: 23 comprises a H8D, H8E, H8K, or H8R substitution. In some embodiments, the substitution at position N9 as compared to SEQ ID NO: 23 comprises a N9D, N9E, N9K, or N9R substitution. In some embodiments, the substitution at position Q10 as compared to SEQ ID NO: 23 comprises a Q10D or Q10E substitution. In some embodiments, the substitution at position K47 as compared to SEQ ID NO: 23 comprises a K47D or K47E substitution. In some embodiments, the substitution at position K50 as compared to SEQ ID 37 IPTS / 128573217.2INH-027WO PATENT NO: 23 comprises a K50D or K50E substitution. In some embodiments, the substitution at position A51 as compared to SEQ ID NO: 23 comprises a A51D, A51E, A51K, or A51R substitution. In some embodiments, the substitution at position S179 as compared to SEQ ID NO: 23 comprises a S179D, S179E, S179K, or S179R substitution. In some embodiments, the substitution at position N180 as compared to SEQ ID NO: 23 comprises a N180D, N180E, N180K, or N180R substitution. In some embodiments, the substitution at position S183 as compared to SEQ ID NO: 23 comprises a S183D, S183E, S183K, or S183R substitution. In some embodiments, the substitution at position M184 as compared to SEQ ID NO: 23 comprises a M184D, M184E, M184K, or M184R substitution. In some embodiments, the substitution at position Y209 as compared to SEQ ID NO: 23 comprises a Y209D, Y209E, Y209K, or Y209R substitution. In some embodiments, the substitution at position I347 as compared to SEQ ID NO: 23 comprises a I347D, I347E, I347K, or I347R substitution. In some embodiments, the substitution at position T350 as compared to SEQ ID NO: 23 comprises a T350D, T350E, T350K, or T350R substitution. In some embodiments, the substitution at position E353 as compared to SEQ ID NO: 23 comprises a E353K or E353R substitution. In some embodiments, the substitution at position R354 as compared to SEQ ID NO: 23 comprises a R354D or R354E substitution. Viral Particles

[0161] The mutant VSV-G proteins can be used, for example, to pseudotype a virus, such as, but not limited to a lentivirus. Accordingly, in some embodiments, a viral particle comprising a mutant VSV-G protein as provided herein are provided. In some embodiments, the viral particle comprises a VSV-G protein comprising a mutation at position 198 as compared to SEQ ID NO: 1. In some embodiments, a protein comprising a mutation at position 182 as compared to SEQ ID NO: 2 comprises a mutation at position 182 and at least, or about, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical as compared to SEQ ID NO: 2 (or SEQ ID NO: 1 if using the full length protein). In some embodiments, the polypeptide comprises a I182D or I182E mutation as compared to SEQ ID NO: 2. In some embodiments, the VSV-G protein comprises a I182S, I182H, I182T, I182Q, or I182N mutation.

[0162] In some embodiments, the viral particle comprises a VSV-G protein comprising a mutation at position 198 as compared to SEQ ID NO: 10. In some embodiments, a protein 38 IPTS / 128573217.2INH-027WO PATENT comprising a mutation at position 182 as compared to SEQ ID NO: 11 comprises a mutation at position 182 and at least, or about, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical as compared to SEQ ID NO: 11 (or SEQ ID NO: 10 if using the full length protein). In some embodiments, the polypeptide comprises a T182D or T182E mutation as compared to SEQ ID NO: 11. In some embodiments, the VSV-G protein comprises a T182S, T182H, T182Q, or T182N mutation.

[0163] In some embodiments, the viral particle comprises a VSV-G protein comprising a mutation at position 198 as compared to SEQ ID NO: 12. In some embodiments, a protein comprising a mutation at position 182 as compared to SEQ ID NO: 13 comprises a mutation at position 182 and at least, or about, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical as compared to SEQ ID NO: 13 (or SEQ ID NO: 12 if using the full length protein). In some embodiments, the polypeptide comprises a A182D or A182E mutation as compared to SEQ ID NO: 13. In some embodiments, the VSV-G protein comprises a A182S, A182H, A182T, A182Q, or A182N mutation.

[0164] In some embodiments, the viral particle comprises a VSV-G protein comprising a mutation at position 203 as compared to SEQ ID NO: 14. In some embodiments, a protein comprising a mutation at position 182 as compared to SEQ ID NO: 15 comprises a mutation at position 182 and at least, or about, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical as compared to SEQ ID NO: 15 (or SEQ ID NO: 14 if using the full length protein). In some embodiments, the polypeptide comprises a V182D or V182E mutation as compared to SEQ ID NO: 15. In some embodiments, the VSV-G protein comprises a V182S, V182H, V182T, V182Q, or V182N mutation.

[0165] In some embodiments, the viral particle comprises a VSV-G protein comprising a mutation at position 199 as compared to SEQ ID NO: 16. In some embodiments, a protein comprising a mutation at position 182 as compared to SEQ ID NO: 17 comprises a mutation at position 182 and at least, or about, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical as compared to SEQ ID NO: 17 (or SEQ ID NO: 16 if using the full length protein). In some embodiments, the polypeptide comprises a V182D or V182E mutation as compared to SEQ ID NO: 17. In some embodiments, the VSV-G protein 39 IPTS / 128573217.2INH-027WO PATENT comprises a V182S, V182H, V182T, V182Q, or V182N mutation.

[0166] In some embodiments, the viral particle comprises a VSV-G protein comprising a mutation at position 199 as compared to SEQ ID NO: 18. In some embodiments, a protein comprising a mutation at position 182 as compared to SEQ ID NO: 19 comprises a mutation at position 182 and at least, or about, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical as compared to SEQ ID NO: 19 (or SEQ ID NO: 18 if using the full length protein). In some embodiments, the polypeptide comprises a V182D or V182E mutation as compared to SEQ ID NO: 19. In some embodiments, the VSV-G protein comprises a V182S, V182H, V182T, V182Q, or V182N mutation.

[0167] In some embodiments, the viral particle comprises a VSV-G protein comprising a mutation at position 199 as compared to SEQ ID NO: 20. In some embodiments, a protein comprising a mutation at position 182 as compared to SEQ ID NO: 21 comprises a mutation at position 182 and at least, or about, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical as compared to SEQ ID NO: 21 (or SEQ ID NO: 20 if using the full length protein). In some embodiments, the polypeptide comprises a I182D or I182E mutation as compared to SEQ ID NO: 21. In some embodiments, the VSV-G protein comprises a I182S, I182H, I182T, I182Q, or I182N mutation.

[0168] In some embodiments, the VSV-G protein further comprises a mutation at position that corresponds to positions 214 and / or 352 of SEQ ID NO: 2. In some embodiments, the residue that corresponds to position 214 of SEQ ID NO: 2 is T214. In some embodiments, the residue that corresponds to position 352 of SEQ ID NO: is T352. In some embodiments, the VSV-G protein comprises mutation that corresponds to T214N mutation as compared to SEQ ID NO: 2. In some embodiments, the VSV-G protein comprises mutation that corresponds to T352A mutation as compared to SEQ ID NO: 2. In some embodiments, the VSV-G protein comprises a T214N and T352A mutations as compared to SEQ ID NO: 2. These mutations can be combined with any other mutations as provided for herein. In some embodiments, the T214N and / or T352A mutations are combined with the I182E or I182D mutations. In some embodiments, a VSV-G protein comprises an amino acid sequence of SEQ ID NO: 22 and SEQ ID NO: 23, which combines the I182D or I182E, respectively, with the T214N and T352A mutations. The sequences are also illustrated below with the leader sequences, which are removed during protein processing. 40 IPTS / 128573217.2INH-027WO PATENT VSV-G Protein_ I196D, T230N and T368A mutations (with leader sequence and adjusted numbering) MKCLLYLAFLFIGVNCKFTIVFPHNQKGNWKNVPSNYHYCPSSSDLNWHND LIGTALQVKMPKSHKAIQADGWMCHASKWVTTCDFRWYGPKYITHSIRSFTP SVEQCKESIEQTKQGTWLNPGFPPQSCGYATVTDAEAVIVQVTPHHVLVDEY TGEWVDSQFINGKCSNYICPTVHNSTTWHSDYKVKGLCDSNLDSMDITFFSE DGELSSLGKEGTGFRSNYFAYENGGKACKMQYCKHWGVRLPSGVWFEMAD KDLFAAARFPECPEGSSISAPSQTSVDVSLIQDVERILDYSLCQETWSKIRAGLP ISPVDLSYLAPKNPGTGPAFTIINGTLKYFETRYIRVDIAAPILSRMVGMISGTT AERELWDDWAPYEDVEIGPNGVLRTSSGYKFPLYMIGHGMLDSDLHLSSKA QVFEHPHIQDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIG LIIGLFLVLRVGIHLCIKLKHTKKRQIYTDIEMNRLGK (SEQ ID NO: 24) VSV-G Protein_I182D, T214N and T352A mutations (without leader sequence) KFTIVFPHNQKGNWKNVPSNYHYCPSSSDLNWHNDLIGTALQVKMPKSHKAI QADGWMCHASKWVTTCDFRWYGPKYITHSIRSFTPSVEQCKESIEQTKQGT WLNPGFPPQSCGYATVTDAEAVIVQVTPHHVLVDEYTGEWVDSQFINGKCS NYICPTVHNSTTWHSDYKVKGLCDSNLDSMDITFFSEDGELSSLGKEGTGFRS NYFAYENGGKACKMQYCKHWGVRLPSGVWFEMADKDLFAAARFPECPEGS SISAPSQTSVDVSLIQDVERILDYSLCQETWSKIRAGLPISPVDLSYLAPKNPGT GPAFTIINGTLKYFETRYIRVDIAAPILSRMVGMISGTTAERELWDDWAPYED VEIGPNGVLRTSSGYKFPLYMIGHGMLDSDLHLSSKAQVFEHPHIQDAASQLP DDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCIK LKHTKKRQIYTDIEMNRLGK (SEQ ID NO: 22) VSV-G Protein with I196E, T230N and T368A mutations (with leader sequence and adjusted numbering) MKCLLYLAFLFIGVNCKFTIVFPHNQKGNWKNVPSNYHYCPSSSDLNWHND LIGTALQVKMPKSHKAIQADGWMCHASKWVTTCDFRWYGPKYITHSIRSFTP SVEQCKESIEQTKQGTWLNPGFPPQSCGYATVTDAEAVIVQVTPHHVLVDEY TGEWVDSQFINGKCSNYICPTVHNSTTWHSDYKVKGLCDSNLESMDITFFSE DGELSSLGKEGTGFRSNYFAYENGGKACKMQYCKHWGVRLPSGVWFEMAD 41 IPTS / 128573217.2INH-027WO PATENT KDLFAAARFPECPEGSSISAPSQTSVDVSLIQDVERILDYSLCQETWSKIRAGLP ISPVDLSYLAPKNPGTGPAFTIINGTLKYFETRYIRVDIAAPILSRMVGMISGTT AERELWDDWAPYEDVEIGPNGVLRTSSGYKFPLYMIGHGMLDSDLHLSSKA QVFEHPHIQDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIG LIIGLFLVLRVGIHLCIKLKHTKKRQIYTDIEMNRLGK (SEQ ID NO: 25) VSV-G Protein with I182E, T214N and T352A mutations (without leader sequences) KFTIVFPHNQKGNWKNVPSNYHYCPSSSDLNWHNDLIGTALQVKMPKSHKAI QADGWMCHASKWVTTCDFRWYGPKYITHSIRSFTPSVEQCKESIEQTKQGT WLNPGFPPQSCGYATVTDAEAVIVQVTPHHVLVDEYTGEWVDSQFINGKCS NYICPTVHNSTTWHSDYKVKGLCDSNLESMDITFFSEDGELSSLGKEGTGFRS NYFAYENGGKACKMQYCKHWGVRLPSGVWFEMADKDLFAAARFPECPEGS SISAPSQTSVDVSLIQDVERILDYSLCQETWSKIRAGLPISPVDLSYLAPKNPGT GPAFTIINGTLKYFETRYIRVDIAAPILSRMVGMISGTTAERELWDDWAPYED VEIGPNGVLRTSSGYKFPLYMIGHGMLDSDLHLSSKAQVFEHPHIQDAASQLP DDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCIK LKHTKKRQIYTDIEMNRLGK (SEQ ID NO: 23)

[0169] The other strains of the VSV-G protein as described herein can also comprises the mutations that correspond to T214N and / or T352A in SEQ ID NO: 2 and as illustrated in SEQ ID NO: 22 and SEQ ID NO: 23.

[0170] In some embodiments, the composition comprises a mutation as described in Hwang et al., Gene Ther 2013 Aug;20(8):807-15. (Epub 2013 Jan 31), which is hereby incorporated by reference in its entirety. For example, the mutations can be. at positions 230, 368, 66, and / or 162 that corresponds to SEQ ID NO: 1. The positions will be 16 positions less as compared to SEQ ID NO: 2, when the leader sequence is removed. In some embodiments, the mutations at those positions are, for example, T230N, T368A, K66T, S162T, or any combination thereof. In some embodiments, the VSV-G protein comprises a T230N and a T368A mutation. In some embodiments, the VSV-G polypeptide comprises a K66T, S162T, T230N, and a T368A. These positions are those that correspond to the positions in the full length protein (SEQ ID NO: 1). In some embodiments, the VSV-G protein comprises T230N mutation, a T368A mutation, a K66T mutation, a S162T mutation, or any combination thereof. In some embodiments, the VSV-G protein further comprises one or more mutations in addition to the mutation that 42 IPTS / 128573217.2INH-027WO PATENT corresponds to position 182 of SEQ ID NO: 2, such as those described in U.S. Patent Application Publication No. 20200216502, which is hereby incorporated by reference in its entirety. For example, the VSV-G protein can further comprise a mutation at a position that corresponds to positions of 8, 47, 209 and / or 354 of SEQ ID NO: 2.

[0171] In some embodiments, the substitution at position 8 is by any amino acid different from the amino acid indicated at that position in the sequence SEQ ID NO: 2, except Y. In some embodiments, the substitution at position 209 is by any amino acid different from the amino acid indicated at that position in the sequence SEQ ID NO: 2, except H. In some embodiments, the substitution at position 47 is by any amino acid different from the amino acid indicated at that position in the sequence SEQ ID NO: 2, except K or R. In some embodiments, the substitution at position 354 is by any amino acid different from the amino acid indicated at that position in the sequence SEQ ID NO: 2, except K or R. In some embodiments, the substitution is at position 47 or at position 354, or at both positions 47 and 354 are substituted by A, G, F or Q. In some embodiments, the substitution is A or Q. In some embodiments, the substitution at position 8 is an alanine, i.e., H8A. In some embodiments, the substitution at position 47 is Q or N, i.e., K47Q or K47N. In some embodiments, the protein comprises a mutation (substitution) at position 10. In some embodiments, the substitution / mutation is Q10A, Q10R, or Q10K.

[0172] In some embodiments, the viral particle comprises a VSV-G protein comprising one or more mutations, wherein the mutation is a substitution to a charged amino acid. In some embodiments, the mutation comprising a substitution to an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to the amino acid sequence of SEQ ID NO: 2, and further comprising a charged amino acid at position 8, 9, 10, 47, 50, 51, 179, 180, 182, 183, 184, 209, 347, 350, 352, 353, 354, or any combination thereof as compared to SEQ ID NO: 2. In some embodiments, the mutation comprising a substitution to a charged amino acid is at position H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 2.

[0173] In some embodiments, the mutation comprising a substitution to a charged amino acid is at position H8 as compared to SEQ ID NO: 2. In some embodiments, the VSV-G protein comprising a substitution to a charged amino acid at position H8 as compared to SEQ ID NO: 2 further comprises one or more mutations comprising a substitution to a charged amino acid at position N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, 43 IPTS / 128573217.2INH-027WO PATENT E353, R354, or any combination thereof as compared to SEQ ID NO: 2.

[0174] In some embodiments, the mutation comprising a substitution to a charged amino acid is at position N9 as compared to SEQ ID NO: 2. In some embodiments, the VSV-G protein comprising a substitution to a charged amino acid at position N9 as compared to SEQ ID NO: 2 further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 2.

[0175] In some embodiments, the mutation comprising a substitution to a charged amino acid is at position Q10 as compared to SEQ ID NO: 2. In some embodiments, the VSV-G protein comprising a substitution to a charged amino acid at position Q10 as compared to SEQ ID NO: 2 further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 2.

[0176] In some embodiments, the mutation comprising a substitution to a charged amino acid is at position K47 as compared to SEQ ID NO: 2. In some embodiments, the VSV-G protein comprising a substitution to a charged amino acid at position K47 as compared to SEQ ID NO: 2 further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 2.

[0177] In some embodiments, the mutation comprising a substitution to a charged amino acid is at position K50 as compared to SEQ ID NO: 2. In some embodiments, the VSV-G protein comprising a substitution to a charged amino acid at position K50 as compared to SEQ ID NO: 2 further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 2.

[0178] In some embodiments, the mutation comprising a substitution to a charged amino acid is at position A51 as compared to SEQ ID NO: 2. In some embodiments, the VSV-G protein comprising a substitution to a charged amino acid at position A51 as compared to SEQ ID NO: 2 further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 2.

[0179] In some embodiments, the mutation comprising a substitution to a charged amino acid is at position S179 as compared to SEQ ID NO: 2. In some embodiments, the VSV-G protein 44 IPTS / 128573217.2INH-027WO PATENT comprising a substitution to a charged amino acid at position S179 as compared to SEQ ID NO: 2 further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, N180, I182, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 2.

[0180] In some embodiments, the mutation comprising a substitution to a charged amino acid is at position N180 as compared to SEQ ID NO: 2. In some embodiments, the VSV-G protein comprising a substitution to a charged amino acid at position N180 as compared to SEQ ID NO: 2 further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, I182, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 2.

[0181] In some embodiments, the mutation comprising a substitution to a charged amino acid is at position I182 as compared to SEQ ID NO: 2. In some embodiments, the VSV-G protein comprising a substitution to a charged amino acid at position I182 as compared to SEQ ID NO: 2 further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 2.

[0182] In some embodiments, the mutation comprising a substitution to a charged amino acid is at position S183 as compared to SEQ ID NO: 2. In some embodiments, the VSV-G protein comprising a substitution to a charged amino acid at position S183 as compared to SEQ ID NO: 2 further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, N180, I182, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 2.

[0183] In some embodiments, the mutation comprising a substitution to a charged amino acid is at position M184 as compared to SEQ ID NO: 2. In some embodiments, the VSV-G protein comprising a substitution to a charged amino acid at position M184 as compared to SEQ ID NO: 2 further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, Y209, I347, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 2.

[0184] In some embodiments, the mutation comprising a substitution to a charged amino acid is at position Y209 as compared to SEQ ID NO: 2. In some embodiments, the VSV-G protein comprising a substitution to a charged amino acid at position Y209 as compared to SEQ ID NO: 2 further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, I347, T350, 45 IPTS / 128573217.2INH-027WO PATENT T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 2.

[0185] In some embodiments, the mutation comprising a substitution to a charged amino acid is at position I347 as compared to SEQ ID NO: 2. In some embodiments, the VSV-G protein comprising a substitution to a charged amino acid at position I347 as compared to SEQ ID NO: 2 further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 2.

[0186] In some embodiments, the mutation comprising a substitution to a charged amino acid is at position T350 as compared to SEQ ID NO: 2. In some embodiments, the VSV-G protein comprising a substitution to a charged amino acid at position T350 as compared to SEQ ID NO: 2 further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 2.

[0187] In some embodiments, the mutation comprising a substitution to a charged amino acid is at position T352 as compared to SEQ ID NO: 2. In some embodiments, the VSV-G protein comprising a substitution to a charged amino acid at position T352 as compared to SEQ ID NO: 2 further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof as compared to SEQ ID NO: 2.

[0188] In some embodiments, the mutation comprising a substitution to a charged amino acid is at position E353 as compared to SEQ ID NO: 2. In some embodiments, the VSV-G protein comprising a substitution to a charged amino acid at position E353 as compared to SEQ ID NO: 2 further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, R354, or any combination thereof as compared to SEQ ID NO: 2.

[0189] In some embodiments, the mutation comprising a substitution to a charged amino acid is at position R354 as compared to SEQ ID NO: 2. In some embodiments, the VSV-G protein comprising a substitution to a charged amino acid at position R354 as compared to SEQ ID NO: 2 further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, or any combination thereof as compared to SEQ ID NO: 2.

[0190] The substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination 46 IPTS / 128573217.2INH-027WO PATENT thereof as compared to SEQ ID NO: 2 may comprise a substitution to any charged amino acid. In some embodiments, the substitution comprises a substitution to an acidic amino acid, including but not limited to aspartate (D), or glutamate (E). In some embodiments, the substitution comprises a substitution to a basic amino acid, including but not limited to lysine (K) or arginine (R). In embodiments where the original amino acid according to SEQ ID NO: 2 is an acidic amino acid (e.g. E353), the substitution to a charged amino acid may comprise a substitution to another acid amino acid (e.g. D), or a substitution to a basic amino acid (e.g. K or R). In some embodiments, where the original amino acid according to SEQ ID NO: 2 is an acidic amino acid (e.g. E353), the substitution to a charged amino acid comprises a substitution to a basic amino acid (e.g. K or R). In embodiments where the original amino acid according to SEQ ID NO: 2 is a basic amino acid (e.g. Q10, K47, K50, or R354), the substitution to a charged amino acid may comprise a substitution to another basic amino acid (e.g. K or R), a substitution to an acidic amino acid (e.g. D or E). In some embodiments, where the original amino acid according to SEQ ID NO: 2 is a basic amino acid (e.g. Q10, K47, K50, or R354), the substitution to a charged amino acid comprises a substitution to an acidic amino acid (e.g. D or E),

[0191] In some embodiments, the mutation comprising a substitution to a charged amino acid is at position H8 as compared to SEQ ID NO: 2, and the substitution is selected from D, E, K, or R. In some embodiments, the mutation at position H8 is H8D. In some embodiments, the mutation at position H8 is H8E. In some embodiments, the mutation at position H8 is H8K. In some embodiments, the mutation at position H8 is H8R. In some embodiments, the VSV- G protein comprising a mutation at position H8 as compared to SEQ ID NO: 2 selected from H8D, H8E, H8K, or H8R, further comprises one or more mutations comprising a substitution to a charged amino acid at position N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 2.

[0192] In some embodiments, the mutation comprising a substitution to a charged amino acid is at position N9 as compared to SEQ ID NO: 2, and the substitution is selected from D, E, K, or R. In some embodiments, the mutation at position N9 is N9D. In some embodiments, the mutation at position N9 is N9E. In some embodiments, the mutation at position N9 is N9K. In some embodiments, the mutation at position N9 is N9R. In some embodiments, the VSV- G protein comprising a mutation at position N9 as compared to SEQ ID NO: 2 selected from N9D, N9E, N9K, or N9R, further comprises one or more mutations comprising a substitution 47 IPTS / 128573217.2INH-027WO PATENT to a charged amino acid at position H8, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 2.

[0193] In some embodiments, the mutation comprising a substitution to a charged amino acid is at position Q10 as compared to SEQ ID NO: 2, and the substitution is selected from D or E. In some embodiments, the mutation at position Q10 is Q10D. In some embodiments, the mutation at position Q10 is Q10E. In some embodiments, the VSV-G protein comprising a mutation at position Q10 as compared to SEQ ID NO: 2 selected from Q10D or Q10E, further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 2.

[0194] In some embodiments, the mutation comprising a substitution to a charged amino acid is at position K47 as compared to SEQ ID NO: 2, and the substitution is selected from D or E. In some embodiments, the mutation at position K47 is K47D. In some embodiments, the mutation at position K47 is K47E. In some embodiments, the VSV-G protein comprising a mutation at position K47 as compared to SEQ ID NO: 2 selected from K47D or K47E, further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 2.

[0195] In some embodiments, the mutation comprising a substitution to a charged amino acid is at position K50 as compared to SEQ ID NO: 2, and the substitution is selected from D, or E. In some embodiments, the mutation at position K50 is K50D. In some embodiments, the mutation at position K50 is K50E. In some embodiments, the VSV-G protein comprising a mutation at position K50 as compared to SEQ ID NO: 2 selected from K50D or K50E, further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 2.

[0196] In some embodiments, the mutation comprising a substitution to a charged amino acid is at position A51 as compared to SEQ ID NO: 2, and the substitution is selected from D, E, K, or R. In some embodiments, the mutation at position A51 is A51D. In some embodiments, the mutation at position A51 is A51E. In some embodiments, the mutation at position A51 is A51K. In some embodiments, the mutation at position A51 is A51R. In some embodiments, the VSV-G protein comprising a mutation at position A51 as compared to SEQ ID NO: 2 48 IPTS / 128573217.2INH-027WO PATENT selected from A51D, A51E, A51K, or A51R, further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 2.

[0197] In some embodiments, the mutation comprising a substitution to a charged amino acid is at position S179 as compared to SEQ ID NO: 2, and the substitution is selected from D, E, K, or R. In some embodiments, the mutation at position S179 is S179D. In some embodiments, the mutation at position S179 is S179E. In some embodiments, the mutation at position S179 is S179K. In some embodiments, the mutation at position S179 is S179R. In some embodiments, the VSV-G protein comprising a mutation at position S179 as compared to SEQ ID NO: 2 selected from S179D, S179E, S179K, or S179R, further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, N180, I182, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 2.

[0198] In some embodiments, the mutation comprising a substitution to a charged amino acid is at position N180 as compared to SEQ ID NO: 2, and the substitution is selected from D, E, K, or R. In some embodiments, the mutation at position N180 is N180D. In some embodiments, the mutation at position N180 is N180E. In some embodiments, the mutation at position N180 is N180K. In some embodiments, the mutation at position N180 is N180R. In some embodiments, the VSV-G protein comprising a mutation at position N180 as compared to SEQ ID NO: 2 selected from N180D, N180E, N180K, or N180R, further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, I182, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 2.

[0199] In some embodiments, the mutation comprising a substitution to a charged amino acid is at position I182 as compared to SEQ ID NO: 2, and the substitution is selected from D, E, K, or R. In some embodiments, the mutation at position I182 is I182D. In some embodiments, the mutation at position I182 is I182E. In some embodiments, the mutation at position I182 is I182K. In some embodiments, the mutation at position I182 is I182R. In some embodiments, the VSV-G protein comprising a mutation at position I182 as compared to SEQ ID NO: 2 selected from I182D, I182E, I182K, or I182R, further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof 49 IPTS / 128573217.2INH-027WO PATENT as compared to SEQ ID NO: 2.

[0200] In some embodiments, the mutation comprising a substitution to a charged amino acid is at position S183 as compared to SEQ ID NO: 2, and the substitution is selected from D, E, K, or R. In some embodiments, the mutation at position S183 is S183D. In some embodiments, the mutation at position S183 is S183E. In some embodiments, the mutation at position S183 is S183K. In some embodiments, the mutation at position S183 is S183R. In some embodiments, the VSV-G protein comprising a mutation at position S183 as compared to SEQ ID NO: 2 selected from S183D, S183E, S183K, or S183R, further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, N180, I182, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 2.

[0201] In some embodiments, the mutation comprising a substitution to a charged amino acid is at position M184 as compared to SEQ ID NO: 2, and the substitution is selected from D, E, K, or R. In some embodiments, the mutation at position M184 is M184D. In some embodiments, the mutation at position M184 is M184E. In some embodiments, the mutation at position M184 is M184K. In some embodiments, the mutation at position M184 is M184R. In some embodiments, the VSV-G protein comprising a mutation at position M184 as compared to SEQ ID NO: 2 selected from M184D, M184E, M184K, or M184R, further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, Y209, I347, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 2.

[0202] In some embodiments, the mutation comprising a substitution to a charged amino acid is at position Y209 as compared to SEQ ID NO: 2, and the substitution is selected from D, E, K, or R. In some embodiments, the mutation at position Y209 is Y209D. In some embodiments, the mutation at position Y209 is Y209E. In some embodiments, the mutation at position Y209 is Y209K. In some embodiments, the mutation at position Y209 is Y209R. In some embodiments, the VSV-G protein comprising a mutation at position Y209 as compared to SEQ ID NO: 2 selected from Y209D, Y209E, Y209K, or Y209R, further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, I347, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 2.

[0203] In some embodiments, the mutation comprising a substitution to a charged amino acid is at position I347 as compared to SEQ ID NO: 2, and the substitution is selected from D, E, 50 IPTS / 128573217.2INH-027WO PATENT K, or R. In some embodiments, the mutation at position I347 is I347D. In some embodiments, the mutation at position I347 is I347E. In some embodiments, the mutation at position I347 is I347K. In some embodiments, the mutation at position I347 is I347R. In some embodiments, the VSV-G protein comprising a mutation at position I347 as compared to SEQ ID NO: 2 selected from I347D, I347E, I347K, or I347R, further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 2.

[0204] In some embodiments, the mutation comprising a substitution to a charged amino acid is at position T350 as compared to SEQ ID NO: 2, and the substitution is selected from D, E, K, or R. In some embodiments, the mutation at position T350 is T350D. In some embodiments, the mutation at position T350 is T350E. In some embodiments, the mutation at position T350 is T350K. In some embodiments, the mutation at position T350 is T350R. In some embodiments, the VSV-G protein comprising a mutation at position T350 as compared to SEQ ID NO: 2 selected from T350D, T350E, T350K, or T350R, further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 2.

[0205] In some embodiments, the mutation comprising a substitution to a charged amino acid is at position T352 as compared to SEQ ID NO: 2, and the substitution is selected from D, E, K, or R. In some embodiments, the mutation at position T352 is T352D. In some embodiments, the mutation at position T352 is T352E. In some embodiments, the mutation at position T352 is T352K. In some embodiments, the mutation at position T352 is T352R. In some embodiments, the VSV-G protein comprising a mutation at position T352 as compared to SEQ ID NO: 2 selected from T352D, T352E, T352K, or T352R, further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof as compared to SEQ ID NO: 2.

[0206] In some embodiments, the mutation comprising a substitution to a charged amino acid is at position E353 as compared to SEQ ID NO: 2, and the substitution is selected from K, or R. In some embodiments, the mutation at position E353 is E353K. In some embodiments, the mutation at position E353 is E353R. In some embodiments, the VSV-G protein comprising a mutation at position E353 as compared to SEQ ID NO: 2 selected from E353K or E353R, 51 IPTS / 128573217.2INH-027WO PATENT further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, R354, or any combination thereof as compared to SEQ ID NO: 2.

[0207] In some embodiments, the mutation comprising a substitution to a charged amino acid is at position R354 as compared to SEQ ID NO: 2, and the substitution is selected from D, or E. In some embodiments, the mutation at position R354 is R354D. In some embodiments, the mutation at position R354 is R354E. In some embodiments, the VSV-G protein comprising a mutation at position R354 as compared to SEQ ID NO: 2 selected from R354D or R354E, further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, or any combination thereof as compared to SEQ ID NO: 2.

[0208] Table 1: Charged amino acid position possibilities and corresponding acceptable substitutions as compared to SEQ ID NO: 2. Position Acceptable Substitution G52 IPTS / 128573217.2INH-027WO PATENT R354 R354D, R354E

[0209] In some embodiments, the viral particle comprises a VSV-G protein comprising one or more mutations, wherein the mutation is a substitution to a charged amino acid as described in Table 1. In some embodiments, the mutation comprising a substitution to a charged amino acid is at position 8, 9, 10, 47, 50, 51, 179, 180, 182, 183, 184, 209, 347, 350, 352, 353, 354, or any combination thereof as described in Table 1. In some embodiments, the mutation comprising a substitution to a charged amino acid is at position H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as described in Table 1.

[0210] It is to be understood that any of the mutations for a particular residue as described in Table 1 may be combined with one or more additional mutations for the other residues in Table 1. For example, in some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position H8 as described in Table 1, and further comprises a mutation at position N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as described in Table 1. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position H8 as described in Table 1, and further comprises at least one additional mutation at a position selected from N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 1. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position H8 as described in Table 1, and further comprises additional mutations at more than one position selected from N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 1.

[0211] In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position N9 as described in Table 1, and further comprises a mutation at position H8, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as described in Table 1. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position N9 as described in Table 1, and further comprises at least one additional mutation at a position selected from H8, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 1. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position N9 as described in Table 1, and further comprises additional 53 IPTS / 128573217.2INH-027WO PATENT mutations at more than one position selected from H8, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 1.

[0212] In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position Q10 as described in Table 1, and further comprises a mutation at position H8, N9, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as described in Table 1. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position Q10 as described in Table 1, and further comprises at least one additional mutation at a position selected from H8, N9, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 1. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position Q10 as described in Table 1, and further comprises additional mutations at more than one position selected from H8, N9, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 1.

[0213] In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position K47 as described in Table 1, and further comprises a mutation at position H8, N9, Q10, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as described in Table 1. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position K47 as described in Table 1, and further comprises at least one additional mutation at a position selected from H8, N9, Q10, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 1. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position K47 as described in Table 1, and further comprises additional mutations at more than one position selected from H8, N9, Q10, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 1.

[0214] In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position K50 as described in Table 1, and further comprises a mutation at position H8, N9, Q10, K47, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as described in Table 1. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position K50 as described in Table 1, and further comprises at least one additional mutation at a position selected from H8, N9, Q10, K47, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 1. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position K50 as described in Table 1, and further comprises additional 54 IPTS / 128573217.2INH-027WO PATENT mutations at more than one position selected from H8, N9, Q10, K47, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 1.

[0215] In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position A51 as described in Table 1, and further comprises a mutation at position H8, N9, Q10, K47, K50, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as described in Table 1. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position A51 as described in Table 1, and further comprises at least one additional mutation at a position selected from H8, N9, Q10, K47, K50, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 1. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position A51 as described in Table 1, and further comprises additional mutations at more than one position selected from H8, N9, Q10, K47, K50, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 1.

[0216] In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position S179 as described in Table 1, and further comprises a mutation at position H8, N9, Q10, K47, K50, A51, N180, I182, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as described in Table 1. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position S179 as described in Table 1, and further comprises at least one additional mutation at a position selected from H8, N9, Q10, K47, K50, A51, N180, I182, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 1. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position S179 as described in Table 1, and further comprises additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, N180, I182, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 1.

[0217] In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position N180 as described in Table 1, and further comprises a mutation at position H8, N9, Q10, K47, K50, A51, S179, I182, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as described in Table 1. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position N180 as described in Table 1, and further comprises at least one additional mutation at a position selected from H8, N9, Q10, K47, K50, A51, S179, I182, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 1. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position N180 as described in Table 1, and further comprises additional mutations 55 IPTS / 128573217.2INH-027WO PATENT at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, I182, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 1.

[0218] In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position I182 as described in Table 1, and further comprises a mutation at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as described in Table 1. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position I182 as described in Table 1, and further comprises at least one additional mutation at a position selected from H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 1. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position I182 as described in Table 1, and further comprises additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 1.

[0219] In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position S183 as described in Table 1, and further comprises a mutation at position H8, N9, Q10, K47, K50, A51, S179, N180, I182, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as described in Table 1. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position S183 as described in Table 1, and further comprises at least one additional mutation at a position selected from H8, N9, Q10, K47, K50, A51, S179, N180, I182, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 1. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position S183 as described in Table 1, and further additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, N180, I182, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 1.

[0220] In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position M184 as described in Table 1, and further comprises a mutation at position H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, Y209, I347, T350, T352, E353, R354, or any combination thereof as described in Table 1. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position M184 as described in Table 1, and further comprises at least one additional mutation at a position selected from H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, Y209, I347, T350, T352, E353, or R354 as described in Table 1. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position M184 as described in Table 1, and further comprises additional mutations 56 IPTS / 128573217.2INH-027WO PATENT at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, Y209, I347, T350, T352, E353, or R354 as described in Table 1.

[0221] In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position Y209 as described in Table 1, and further comprises a mutation at position H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, I347, T350, T352, E353, R354, or any combination thereof as described in Table 1. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position Y209 as described in Table 1, and further comprises at least one additional mutation at a position selected from H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, I347, T350, T352, E353, or R354 as described in Table 1. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position Y209 as described in Table 1, and further comprises additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, I347, T350, T352, E353, or R354 as described in Table 1.

[0222] In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position I347 as described in Table 1, and further comprises a mutation at position H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, T350, T352, E353, R354, or any combination thereof as described in Table 1. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position I347 as described in Table 1, and further comprises at least one additional mutation at a position selected from H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, T350, T352, E353, or R354 as described in Table 1. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position I347 as described in Table 1, and further comprises additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, T350, T352, E353, or R354 as described in Table 1.

[0223] In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position T350 as described in Table 1, and further comprises a mutation at position H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T352, E353, R354, or any combination thereof as described in Table 1. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position T350 as described in Table 1, and further comprises at least one additional mutation at a position selected from H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T352, E353, or R354 as described in Table 1. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position T350 as described in Table 1, and further comprises additional mutations 57 IPTS / 128573217.2INH-027WO PATENT at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T352, E353, or R354 as described in Table 1.

[0224] In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position T352 as described in Table 1, and further comprises a mutation at position H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof as described in Table 1. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position T352 as described in Table 1, and further comprises at least one additional mutation at a position selected from H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, E353, or R354 as described in Table 1. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position T352 as described in Table 1, and further comprises additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, E353, or R354 as described in Table 1.

[0225] In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position E353 as described in Table 1, and further comprises a mutation at position H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, R354, or any combination thereof as described in Table 1. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position E353 as described in Table 1, and further comprises at least one additional mutation at a position selected from H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, or R354 as described in Table 1. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position E353 as described in Table 1, and further comprises additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, or R354 as described in Table 1.

[0226] In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position R354 as described in Table 1, and further comprises a mutation at position H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, or any combination thereof as described in Table 1. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position R354 as described in Table 1, and further comprises at least one additional mutation at a position selected from H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, or E353 as described in Table 1. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position R354 as described in Table 1, and further comprises additional mutations 58 IPTS / 128573217.2INH-027WO PATENT at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, or E353 as described in Table 1.

[0227] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, and further comprises a substitution to a charged amino acid at position H8 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3 and further comprises a substitution to a charged amino acid is at position H8 as compared to SEQ ID NO: 3. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 4 and further comprises a substitution to a charged amino acid is at position H8 as compared to SEQ ID NO: 4. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 5 and further comprises a substitution to a charged amino acid is at position H8 as compared to SEQ ID NO: 5. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 and a substitution to a charged amino acid at position H8 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 further comprises one or more mutations comprising a substitution to a charged amino acid at position N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 3. SEQ ID NO: 4, or SEQ ID NO: 5.

[0228] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, and further comprises a substitution to a charged amino acid at position N9 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3 and further comprises a substitution to a charged amino acid is at position N9 as compared to SEQ ID NO: 3. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 4 and further comprises a substitution to a charged amino acid is at position N9 as compared to SEQ ID NO: 4. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 5 and further comprises a substitution to a charged amino acid is at position N9 as compared to SEQ ID NO: 5. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 and a substitution to a charged amino acid at position N9 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 further comprises one or more 59 IPTS / 128573217.2INH-027WO PATENT mutations comprising a substitution to a charged amino acid at position H8, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5.

[0229] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, and further comprises a substitution to a charged amino acid at position Q10 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3 and further comprises a substitution to a charged amino acid is at position Q10 as compared to SEQ ID NO: 3. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 4 and further comprises a substitution to a charged amino acid is at position Q10 as compared to SEQ ID NO: 4. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 5 and further comprises a substitution to a charged amino acid is at position Q10 as compared to SEQ ID NO: 5. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 and a substitution to a charged amino acid at position Q10 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5.

[0230] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, and further comprises a substitution to a charged amino acid at position K47 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3 and further comprises a substitution to a charged amino acid is at position K47 as compared to SEQ ID NO: 3. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 4 and further comprises a substitution to a charged amino acid is at position K47 as compared to SEQ ID NO: 4. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 5 and further comprises a substitution to a charged amino acid is at position K47 as compared to SEQ ID NO: 5. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 and a substitution to a charged amino acid at position K47 as 60 IPTS / 128573217.2INH-027WO PATENT compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5.

[0231] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, and further comprises a substitution to a charged amino acid at position K50 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3 and further comprises a substitution to a charged amino acid is at position K50 as compared to SEQ ID NO: 3. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 4 and further comprises a substitution to a charged amino acid is at position K50 as compared to SEQ ID NO: 4. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 5 and further comprises a substitution to a charged amino acid is at position K50 as compared to SEQ ID NO: 5. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4 or SEQ ID NO: 5 and a substitution to a charged amino acid at position K50 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5.

[0232] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, and further comprises a substitution to a charged amino acid at position A51 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3 and further comprises a substitution to a charged amino acid is at position A51 as compared to SEQ ID NO: 3. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 4 and further comprises a substitution to a charged amino acid is at position A51 as compared to SEQ ID NO: 4. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 5 and further comprises a substitution to a charged amino acid is at position A51 as compared to SEQ ID NO: 5. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 3, SEQ 61 IPTS / 128573217.2INH-027WO PATENT ID NO: 4, or SEQ ID NO: 5 and a substitution to a charged amino acid at position A51 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, S179, N180, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5.

[0233] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, and further comprises a substitution to a charged amino acid at position S179 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3 and further comprises a substitution to a charged amino acid is at position S179 as compared to SEQ ID NO: 3. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 4 and further comprises a substitution to a charged amino acid is at position S179 as compared to SEQ ID NO: 4. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 5 and further comprises a substitution to a charged amino acid is at position S179 as compared to SEQ ID NO: 5. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 and a substitution to a charged amino acid at position S179 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, N180, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5.

[0234] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, and further comprises a substitution to a charged amino acid at position N180 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3 and further comprises a substitution to a charged amino acid is at position N180 as compared to SEQ ID NO: 3. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 4 and further comprises a substitution to a charged amino acid is at position N180 as compared to SEQ ID NO: 4. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 5 and further comprises a substitution to a charged amino acid is at position N180 as compared to SEQ ID 62 IPTS / 128573217.2INH-027WO PATENT NO: 5. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 and a substitution to a charged amino acid at position N180 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5.

[0235] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, and further comprises a substitution to a charged amino acid at position S183 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3 and further comprises a substitution to a charged amino acid is at position S183 as compared to SEQ ID NO: 3. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 4 and further comprises a substitution to a charged amino acid is at position S183 as compared to SEQ ID NO: 4. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 5 and further comprises a substitution to a charged amino acid is at position S183 as compared to SEQ ID NO: 5. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 and a substitution to a charged amino acid at position S183 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, N180, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5.

[0236] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, and further comprises a substitution to a charged amino acid at position M184 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3 and further comprises a substitution to a charged amino acid is at position M184 as compared to SEQ ID NO: 3. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 4 and further comprises a substitution to a charged amino acid is at position M184 as compared to SEQ ID NO: 4. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 5 and further 63 IPTS / 128573217.2INH-027WO PATENT comprises a substitution to a charged amino acid is at position M184 as compared to SEQ ID NO: 5. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 and a substitution to a charged amino acid at position M184 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, Y209, I347, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5.

[0237] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, and further comprises a substitution to a charged amino acid at position Y209 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3 and further comprises a substitution to a charged amino acid is at position Y209 as compared to SEQ ID NO: 3. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 4 and further comprises a substitution to a charged amino acid is at position Y209 as compared to SEQ ID NO: 4. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 5 and further comprises a substitution to a charged amino acid is at position Y209 as compared to SEQ ID NO: 5. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 and a substitution to a charged amino acid at position Y209 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, I347, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5.

[0238] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, and further comprises a substitution to a charged amino acid at position I347 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3 and further comprises a substitution to a charged amino acid is at position I347 as compared to SEQ ID NO: 3. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 4 and further comprises a substitution to a charged amino acid is at position I347 as compared to SEQ ID NO: 4. In some embodiments the viral particle comprises a VSV-G 64 IPTS / 128573217.2INH-027WO PATENT protein comprising an amino acid sequence of SEQ ID NO: 5 and further comprises a substitution to a charged amino acid is at position I347 as compared to SEQ ID NO: 5. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 and a substitution to a charged amino acid at position I347 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5.

[0239] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, and further comprises a substitution to a charged amino acid at position T350 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3 and further comprises a substitution to a charged amino acid is at position T350 as compared to SEQ ID NO: 3. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 4 and further comprises a substitution to a charged amino acid is at position T350 as compared to SEQ ID NO: 4. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 5 and further comprises a substitution to a charged amino acid is at position T350 as compared to SEQ ID NO: 5. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 and a substitution to a charged amino acid at position T350 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5.

[0240] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, and further comprises a substitution to a charged amino acid at position T352 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3 and further comprises a substitution to a charged amino acid is at position T352 as compared to SEQ ID NO: 3. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 4 and further comprises a substitution to a charged amino acid is at 65 IPTS / 128573217.2INH-027WO PATENT position T352 as compared to SEQ ID NO: 4. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 5 and further comprises a substitution to a charged amino acid is at position T352 as compared to SEQ ID NO: 5. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 and a substitution to a charged amino acid at position T352 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5.

[0241] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, and further comprises a substitution to a charged amino acid at position E353 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3 and further comprises a substitution to a charged amino acid is at position E353 as compared to SEQ ID NO: 3. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 4 and further comprises a substitution to a charged amino acid is at position E353 as compared to SEQ ID NO: 4. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 5 and further comprises a substitution to a charged amino acid is at position E353 as compared to SEQ ID NO: 5. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 and a substitution to a charged amino acid at position E353 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, R354, or any combination thereof as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5.

[0242] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, and further comprises a substitution to a charged amino acid at position R354 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3 and further comprises a substitution to a charged amino acid is at position R354 as compared to SEQ ID NO: 3. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid 66 IPTS / 128573217.2INH-027WO PATENT sequence of SEQ ID NO: 4 and further comprises a substitution to a charged amino acid is at position R354 as compared to SEQ ID NO: 4. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 5 and further comprises a substitution to a charged amino acid is at position R354 as compared to SEQ ID NO: 5. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 and a substitution to a charged amino acid at position R354 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, or any combination thereof as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5.

[0243] The substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 may comprise a substitution to any charged amino acid. In some embodiments, the substitution comprises a substitution to an acidic amino acid, including but not limited to aspartate (D) or glutamate (E). In some embodiments, the substitution comprises a substitution to a basic amino acid, including but not limited to lysine (K) or arginine (R). In embodiments where the original amino acid according to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 is an acidic amino acid (e.g. E353), the substitution to a charged amino acid may comprise a substitution to another acidic amino acid (e.g. D), or a substitution to a basic amino acid (e.g. K or R). In some embodiments, where the original amino acid according to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 is an acidic amino acid (e.g. E353), the substitution to a charged amino acid comprises a substitution to a basic amino acid (e.g. K or R). In embodiments where the original amino acid according to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 is a basic amino acid (e.g. Q10, K47, K50, or R354), the substitution to a charged amino acid may comprise a substitution to another basic amino acid (e.g. K or R), or a substitution to an acidic amino acid (e.g. D or E). In some embodiments, where the original amino acid according to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 is a basic amino acid (e.g. Q10, K47, K50, or R354), the substitution to a charged amino acid comprises a substitution to an acidic amino acid (e.g. D or E).

[0244] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 4, and a substitution to a charged amino acid at position H8 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments 67 IPTS / 128573217.2INH-027WO PATENT the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3 and a substitution to a charged amino acid at position H8 as compared to SEQ ID NO: 3, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 4 and a substitution to a charged amino acid at position H8 as compared to SEQ ID NO: 4, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 5 and a substitution to a charged amino acid at position H8 as compared to SEQ ID NO: 5, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the mutation at position H8 is H8D. In some embodiments, the mutation at position H8 is H8E. In some embodiments, the mutation at position H8 is H8K. In some embodiments, the mutation at position H8 is H8R. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 and a mutation at position H8 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 selected from H8D, H8E, H8K, or H8R, further comprises one or more mutations comprising a substitution to a charged amino acid at position N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5.

[0245] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, and a substitution to a charged amino acid at position N9 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3 and a substitution to a charged amino acid at position N9 as compared to SEQ ID NO: 3, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 4 and a substitution to a charged amino acid at position N9 as compared to SEQ ID NO: 4, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 5 and a substitution to a charged amino acid at position N9 as compared to SEQ ID NO: 5, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the mutation at position N9 is N9D. In some embodiments, the mutation at position N9 is N9E. In some embodiments, the mutation at position N9 is N9K. In some embodiments, the mutation at 68 IPTS / 128573217.2INH-027WO PATENT position N9 is N9R. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 and a mutation at position N9 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 selected from N9D, N9E, N9K, or N9R, further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5.

[0246] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, and a substitution to a charged amino acid at position Q10 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, wherein the charged amino acid is selected from D or E. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3 and a substitution to a charged amino acid at position Q10 as compared to SEQ ID NO: 3, wherein the charged amino acid is selected from D or E. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 4 and a substitution to a charged amino acid at position Q10 as compared to SEQ ID NO: 4, wherein the charged amino acid is selected from D or E. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 5 and a substitution to a charged amino acid at position Q10 as compared to SEQ ID NO: 5, wherein the charged amino acid is selected from D or E. In some embodiments, the mutation at position Q10 is Q10D. In some embodiments, the mutation at position Q10 is Q10E. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 and a mutation at position Q10 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 selected from Q10D or Q10E, further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5.

[0247] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, and a substitution to a charged amino acid at position K47 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, wherein the charged amino acid is selected from D or E. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3 and a substitution to a charged amino acid at position K47 as compared to SEQ ID NO: 3, 69 IPTS / 128573217.2INH-027WO PATENT wherein the charged amino acid is selected from D or E. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 4 and a substitution to a charged amino acid at position K47 as compared to SEQ ID NO: 4, wherein the charged amino acid is selected from D or E. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 5 and a substitution to a charged amino acid at position K47 as compared to SEQ ID NO: 5, wherein the charged amino acid is selected from D or E. In some embodiments, the mutation at position K47 is K47D. In some embodiments, the mutation at position K47 is K47E. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 an da mutation at position K47 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 selected from K47D or K47E, further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5.

[0248] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, and a substitution to a charged amino acid at position K50 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, wherein the charged amino acid is selected from D or E. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3 and a substitution to a charged amino acid at position K50 as compared to SEQ ID NO: 3, wherein the charged amino acid is selected from D or E. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 4 and a substitution to a charged amino acid at position K50 as compared to SEQ ID NO: 4, wherein the charged amino acid is selected from D or E. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 5 and a substitution to a charged amino acid at position K50 as compared to SEQ ID NO: 5, wherein the charged amino acid is selected from D or E. In some embodiments, the mutation at position K50 is K50D. In some embodiments, the mutation at position K50 is K50E. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 and a mutation at position K50 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 selected from K50D or K50E, further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination 70 IPTS / 128573217.2INH-027WO PATENT thereof as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5.

[0249] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, and a substitution to a charged amino acid at position A51 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3 and a substitution to a charged amino acid at position A51 as compared to SEQ ID NO: 3, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 4 and a substitution to a charged amino acid at position A51 as compared to SEQ ID NO: 4, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 5 and a substitution to a charged amino acid at position A51 as compared to SEQ ID NO: 5, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the mutation at position A51 is A51D. In some embodiments, the mutation at position A51 is A51E. In some embodiments, the mutation at position A51 is A51K. In some embodiments, the mutation at position A51 is A51R. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 and a mutation at position A51 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 selected from A51D, A51E, A51K, or A51R, further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, S179, N180, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5.

[0250] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, and a substitution to a charged amino acid at position S179 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3 and a substitution to a charged amino acid at position S179 as compared to SEQ ID NO: 3, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 4 and a substitution to a charged amino acid at position S179 as compared to SEQ ID NO: 4, wherein the charged amino acid is selected from D, E, K, or R. In some 71 IPTS / 128573217.2INH-027WO PATENT embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 5 and a substitution to a charged amino acid at position S179 as compared to SEQ ID NO: 5, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the mutation at position S179 is S179D. In some embodiments, the mutation at position S179 is S179E. In some embodiments, the mutation at position S179 is S179K. In some embodiments, the mutation at position S179 is S179R. In some embodiments, the VSV- G protein comprising the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 and a mutation at position S179 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 selected from S179D, S179E, S179K, or S179R, further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, N180, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5.

[0251] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, and a substitution to a charged amino acid at position N180 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3 and a substitution to a charged amino acid at position N180 as compared to SEQ ID NO: 3, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 4 and a substitution to a charged amino acid at position N180 as compared to SEQ ID NO: 4, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 5 and a substitution to a charged amino acid at position N180 as compared to SEQ ID NO: 5, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the mutation at position N180 is N180D. In some embodiments, the mutation at position N180 is N180E. In some embodiments, the mutation at position N180 is N180K. In some embodiments, the mutation at position N180 is N180R. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 and a mutation at position N180 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 selected from N180D, N180E, N180K, or N180R, further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination 72 IPTS / 128573217.2INH-027WO PATENT thereof as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5.

[0252] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, and a substitution to a charged amino acid at position S183 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, whereing the charged amino acid is selected from D, E, K, or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3 and a substitution to a charged amino acid at position S183 as compared to SEQ ID NO: 3, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 4 and a substitution to a charged amino acid at position S183 as compared to SEQ ID NO: 4, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 5 and a substitution to a charged amino acid at position S183 as compared to SEQ ID NO: 5, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the mutation at position S183 is S183D. In some embodiments, the mutation at position S183 is S183E. In some embodiments, the mutation at position S183 is S183K. In some embodiments, the mutation at position S183 is S183R. In some embodiments, the VSV- G protein comprising the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 and a mutation at position S183 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 selected from S183D, S183E, S183K, or S183R, further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, N180, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5.

[0253] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, and a substitution to a charged amino acid at position M184 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3 and a substitution to a charged amino acid at position M184 as compared to SEQ ID NO: 3, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 4 and a substitution to a charged amino acid at position M184 as compared to SEQ ID NO: 4, wherein the charged amino acid is selected from D, E, K, or R. In some 73 IPTS / 128573217.2INH-027WO PATENT embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 5 and a substitution to a charged amino acid at position M184 as compared to SEQ ID NO: 5, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the mutation at position M184 is M184D. In some embodiments, the mutation at position M184 is M184E. In some embodiments, the mutation at position M184 is M184K. In some embodiments, the mutation at position M184 is M184R. In some embodiments, the VSV-G protein comprising the amino aicd sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 and a mutation at position M184 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 selected from M184D, M184E, M184K, or M184R, further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, Y209, I347, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5.

[0254] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, and a substitution to a charged amino acid at position Y209 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3 and a substitution to a charged amino acid at position Y209 as compared to SEQ ID NO: 3, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 4 and a substitution to a charged amino acid at position Y209 as compared to SEQ ID NO: 4, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 5 and a substitution to a charged amino acid at position Y209 as compared to SEQ ID NO: 5, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the mutation at position Y209 is Y209D. In some embodiments, the mutation at position Y209 is Y209E. In some embodiments, the mutation at position Y209 is Y209K. In some embodiments, the mutation at position Y209 is Y209R. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 and a mutation at position Y209 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 selected from Y209D, Y209E, Y209K, or Y209R, further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, I347, T350, T352, E353, R354, or any combination 74 IPTS / 128573217.2INH-027WO PATENT thereof as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5.

[0255] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, and a substitution to a charged amino acid at position I347 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3 and a substitution to a charged amino acid at position I347 as compared to SEQ ID NO: 3, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 4 and a substitution to a charged amino acid at position I347 as compared to SEQ ID NO: 4, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 5 and a substitution to a charged amino acid at position I347 as compared to SEQ ID NO: 5, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the mutation at position I347 is I347D. In some embodiments, the mutation at position I347 is I347E. In some embodiments, the mutation at position I347 is I347K. In some embodiments, the mutation at position I347 is I347R. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 and a mutation at position I347 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 selected from I347D, I347E, I347K, or I347R, further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, T350, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5.

[0256] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3 SEQ ID NO: 4, or SEQ ID NO: 5, and a substitution to a charged amino acid at position T350 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3 and a substitution to a charged amino acid at position T350 as compared to SEQ ID NO: 3, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 4 and a substitution to a charged amino acid at position T350 as compared to SEQ ID NO: 4, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments the viral 75 IPTS / 128573217.2INH-027WO PATENT particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 5 and a substitution to a charged amino acid at position T350 as compared to SEQ ID NO: 5, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the mutation at position T350 is T350D. In some embodiments, the mutation at position T350 is T350E. In some embodiments, the mutation at position T350 is T350K. In some embodiments, the mutation at position T350 is T350R. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 and a mutation at position T350 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 selected from T350D, T350E, T350K, or T350R, further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T352, E353, R354, or any combination thereof as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5.

[0257] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, and a substitution to a charged amino acid at position T352 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3 and a substitution to a charged amino acid at position T352 as compared to SEQ ID NO: 3, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 4 and a substitution to a charged amino acid at position T352 as compared to SEQ ID NO: 4, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 5 and a substitution to a charged amino acid at position T352 as compared to SEQ ID NO: 5, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the mutation at position T352 is T352D. In some embodiments, the mutation at position T352 is T352E. In some embodiments, the mutation at position T352 is T352K. In some embodiments, the mutation at position T352 is T352R. In some embodiments, the VSV- G protein comprising the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 and a mutation at position T352 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 selected from T352D, T352E, T352K, or T352R, further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination 76 IPTS / 128573217.2INH-027WO PATENT thereof as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5.

[0258] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, and a substitution to a charged amino acid at position E353 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, wherein the charged amino acid is selected from K, or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3 and a substitution to a charged amino acid at position E353 as compared to SEQ ID NO: 3, wherein the charged amino acid is selected from K, or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 4 and a substitution to a charged amino acid at position E353 as compared to SEQ ID NO: 4, wherein the charged amino acid is selected from K, or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 5 and a substitution to a charged amino acid at position E353 as compared to SEQ ID NO: 5, wherein the charged amino acid is selected from K, or R. In some embodiments, the mutation at position E353 is E353K. In some embodiments, the mutation at position E353 is E353R. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 and a mutation at position E353 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 selected from E353K or E353R, further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, R354, or any combination thereof as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5.

[0259] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, and a substitution to a charged amino acid at position R354 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, wherein the charged amino acid is selected from D, or E. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 3 and a substitution to a charged amino acid at position R354 as compared to SEQ ID NO: 3, wherein the charged amino acid is selected from D, or E. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 4 and a substitution to a charged amino acid at position R354 as compared to SEQ ID NO: 4, wherein the charged amino acid is selected from D, or E. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 5 and a substitution to a charged amino acid at position R354 as compared to SEQ ID NO: 5, wherein 77 IPTS / 128573217.2INH-027WO PATENT the charged amino acid is selected from D, or E. In some embodiments, the mutation at position R354 is R354D. In some embodiments, the mutation at position R354 is R354E. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 and a mutation at position R354 as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 selected from R354D or R354E, further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, or any combination thereof as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5.

[0260] Table 2: Charged amino acid position possibilities and corresponding acceptable substitutions as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. Applicable SEQ ID NO: Position Acceptable Substitution SE ID NO 3 4 5 H8 H8D H8E H8K H8R H8A ,78 IPTS / 128573217.2INH-027WO PATENT SEQ ID NO: 3, 4, or 5 R354 R354D, R354E

[0261] In some embodiments, the viral particle comprises a VSV-G protein comprising one or more mutations, wherein the mutation is a substitution to a charged amino acid as described in Table 2. In some embodiments, the mutation comprising a substitution to a charged amino acid is at position 8, 9, 10, 47, 50, 51, 179, 180, 183, 184, 209, 347, 350, 352, 353, 354, or any combination thereof as described in Table 2. In some embodiments, the mutation comprising a substitution to a charged amino acid is at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as described in Table 2.

[0262] It is to be understood that any of the mutations for a particular residue as described in Table 2 may be combined with one or more additional mutations for the other residues in Table 2. For example, in some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position H8 as described in Table 2, and further comprises a mutation at position N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as described in Table 2. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position H8 as described in Table 2, and further comprises at least one additional mutation at a position selected from N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 2. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position H8 as described in Table 2, and further comprises additional mutations at more than one position selected from N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 2.

[0263] In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position N9 as described in Table 2, and further comprises a mutation at position H8, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as described in Table 2. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position N9 as described in Table 2, and further comprises at least one additional mutation at a position selected from H8, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 2. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position N9 as described in Table 2, and further comprises additional mutations at 79 IPTS / 128573217.2INH-027WO PATENT more than one position selected from H8, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 2.

[0264] In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position Q10 as described in Table 2, and further comprises a mutation at position H8, N9, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as described in Table 2. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position Q10 as described in Table 2, and further comprises at least one additional mutation at a position selected from H8, N9, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 2. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position Q10 as described in Table 2, and further comprises additional mutations at more than one position selected from H8, N9, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 2.

[0265] In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position K47 as described in Table 2, and further comprises a mutation at position H8, N9, Q10, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as described in Table 2. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position K47 as described in Table 2, and further comprises at least one additional mutation at a position selected from H8, N9, Q10, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 2. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position K47 as described in Table 2, and further comprises additional mutations at more than one position selected from H8, N9, Q10, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 2.

[0266] In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position K50 as described in Table 2, and further comprises a mutation at position H8, N9, Q10, K47, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as described in Table 2. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position K50 as described in Table 2, and further comprises at least one additional mutation at a position selected from H8, N9, Q10, K47, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 2. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position K50 as described in Table 2, and further comprises additional mutations 80 IPTS / 128573217.2INH-027WO PATENT at more than one position selected from H8, N9, Q10, K47, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 2.

[0267] In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position A51 as described in Table 2, and further comprises a mutation at position H8, N9, Q10, K47, K50, S179, N180, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as described in Table 2. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position A51 as described in Table 2, and further comprises at least one additional mutation at a position selected from H8, N9, Q10, K47, K50, S179, N180, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 2. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position A51 as described in Table 2, and further comprises additional mutations at more than one position selected from H8, N9, Q10, K47, K50, S179, N180, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 2.

[0268] In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position S179 as described in Table 2, and further comprises a mutation at position H8, N9, Q10, K47, K50, A51, N180, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as described in Table 2. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position S179 as described in Table 2, and further comprises at least one additional mutation at a position selected from H8, N9, Q10, K47, K50, A51, N180, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 2. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position S179 as described in Table 2, and further comprises additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, N180, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 2.

[0269] In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position N180 as described in Table 2, and further comprises a mutation at position H8, N9, Q10, K47, K50, A51, S179, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as described in Table 2. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position N180 as described in Table 2, and further comprises at least one additional mutation at a position selected from H8, N9, Q10, K47, K50, A51, S179, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 2. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position N180 as described in Table 2, and further comprises additional mutations 81 IPTS / 128573217.2INH-027WO PATENT at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 2.

[0270] In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position S183 as described in Table 2, and further comprises a mutation at position H8, N9, Q10, K47, K50, A51, S179, N180, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as described in Table 2. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position S183 as described in Table 2, and further comprises at least one additional mutation at a position selected from H8, N9, Q10, K47, K50, A51, S179, N180, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 2. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position S183 as described in Table 2, and further additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, N180, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 2.

[0271] In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position M184 as described in Table 2, and further comprises a mutation at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, Y209, I347, T350, T352, E353, R354, or any combination thereof as described in Table 2. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position M184 as described in Table 2, and further comprises at least one additional mutation at a position selected from H8, N9, Q10, K47, K50, A51, S179, N180, S183, Y209, I347, T350, T352, E353, or R354 as described in Table 2. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position M184 as described in Table 2, and further comprises additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, N180, S183, Y209, I347, T350, T352, E353, or R354 as described in Table 2.

[0272] In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position Y209 as described in Table 2, and further comprises a mutation at position H8, N9, Q10, K47, K50, A51, S179, N180 , S183, M184, I347, T350, T352, E353, R354, or any combination thereof as described in Table 2. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position Y209 as described in Table 2, and further comprises at least one additional mutation at a position selected from H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, I347, T350, T352, E353, or R354 as described in Table 2. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position Y209 as described in Table 2, and further comprises additional mutations 82 IPTS / 128573217.2INH-027WO PATENT at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, I347, T350, T352, E353, or R354 as described in Table 2.

[0273] In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position I347 as described in Table 2, and further comprises a mutation at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, T350, T352, E353, R354, or any combination thereof as described in Table 2. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position I347 as described in Table 2, and further comprises at least one additional mutation at a position selected from H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, T350, T352, E353, or R354 as described in Table 2. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position I347 as described in Table 2, and further comprises additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, T350, T352, E353, or R354 as described in Table 2.

[0274] In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position T350 as described in Table 2, and further comprises a mutation at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T352, E353, R354, or any combination thereof as described in Table 2. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position T350 as described in Table 2, and further comprises at least one additional mutation at a position selected from H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T352, E353, or R354 as described in Table 2. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position T350 as described in Table 2, and further comprises additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T352, E353, or R354 as described in Table 2.

[0275] In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position T352 as described in Table 2, and further comprises a mutation at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof as described in Table 2. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position T352 as described in Table 2, and further comprises at least one additional mutation at a position selected from H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, or R354 as described in Table 2. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position T352 as described in Table 2, and further comprises additional mutations 83 IPTS / 128573217.2INH-027WO PATENT at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, or R354 as described in Table 2.

[0276] In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position E353 as described in Table 2, and further comprises a mutation at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, R354, or any combination thereof as described in Table 2. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position E353 as described in Table 2, and further comprises at least one additional mutation at a position selected from H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, or R354 as described in Table 2. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position E353 as described in Table 2, and further comprises additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, or R354 as described in Table 2.

[0277] In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position R354 as described in Table 2, and further comprises a mutation at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, or any combination thereof as described in Table 2. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position R354 as described in Table 2, and further comprises at least one additional mutation at a position selected from H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, or E353 as described in Table 2. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position R354 as described in Table 2, and further comprises additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, or E353 as described in Table 2.

[0278] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23, and further comprises a substitution to a charged amino acid at position H8 as compared to SEQ ID NO: 22 or SEQ ID NO: 23. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 and further comprises a substitution to a charged amino acid is at position H8 as compared to SEQ ID NO: 22. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 23 and further comprises a substitution to a charged amino acid is at position H8 as compared to SEQ ID NO: 23. In some embodiments, the VSV-G protein comprising a substitution to a charged amino acid at 84 IPTS / 128573217.2INH-027WO PATENT position H8 as compared to SEQ ID NO: 22 or SEQ ID NO: 23 further comprises one or more mutations comprising a substitution to a charged amino acid at position N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof as compared to SEQ ID NO: 22 or SEQ ID NO: 23.

[0279] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and further comprises a substitution to a charged amino acid at position N9 as compared to SEQ ID NO: 22 or SEQ ID NO: 23. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 and further comprises a substitution to a charged amino acid is at position N9 as compared to SEQ ID NO: 22. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 23 and further comprises a substitution to a charged amino acid is at position N9 as compared to SEQ ID NO: 23. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a substitution to a charged amino acid at position N9 as compared to SEQ ID NO: 22 or SEQ ID NO: 23 further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof as compared to SEQ ID NO: 22 or SEQ ID NO: 23.

[0280] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and further comprises a substitution to a charged amino acid at position Q10 as compared to SEQ ID NO: 22 or SEQ ID NO: 23. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 and further comprises a substitution to a charged amino acid is at position Q10 as compared to SEQ ID NO: 22. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 23 and further comprises a substitution to a charged amino acid is at position Q10 as compared to SEQ ID NO: 23. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a substitution to a charged amino acid at position Q10 as compared to SEQ ID NO: 22 or SEQ ID NO: 23 further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof as compared to SEQ ID NO: 22 or SEQ ID NO: 23.

[0281] In some embodiments the viral particle comprises a VSV-G protein comprising an 85 IPTS / 128573217.2INH-027WO PATENT amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and further comprises a substitution to a charged amino acid at position K47 as compared to SEQ ID NO: 22 or SEQ ID NO: 23. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 and further comprises a substitution to a charged amino acid is at position K47 as compared to SEQ ID NO: 22. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 23 and further comprises a substitution to a charged amino acid is at position K47 as compared to SEQ ID NO: 23. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a substitution to a charged amino acid at position K47 as compared to SEQ ID NO: 22 or SEQ ID NO: 23 further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof as compared to SEQ ID NO: 22 or SEQ ID NO: 23.

[0282] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and further comprises a substitution to a charged amino acid at position K50 as compared to SEQ ID NO: 22 or SEQ ID NO: 23. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 and further comprises a substitution to a charged amino acid is at position K50 as compared to SEQ ID NO: 22. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 23 and further comprises a substitution to a charged amino acid is at position K50 as compared to SEQ ID NO: 23. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a substitution to a charged amino acid at position K50 as compared to SEQ ID NO: 22 or SEQ ID NO: 23 further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, A51, S179, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof as compared to SEQ ID NO: 22 or SEQ ID NO: 23.

[0283] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and further comprises a substitution to a charged amino acid at position A51 as compared to SEQ ID NO: 22 or SEQ ID NO: 23. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 and further comprises a substitution to a charged amino acid is at position A51 as compared to SEQ ID NO: 22. In some embodiments the viral particle 86 IPTS / 128573217.2INH-027WO PATENT comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 23 and further comprises a substitution to a charged amino acid is at position A51 as compared to SEQ ID NO: 23. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a substitution to a charged amino acid at position A51 as compared to SEQ ID NO: 22 or SEQ ID NO: 23 further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, S179, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof as compared to SEQ ID NO: 22 or SEQ ID NO: 23.

[0284] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and further comprises a substitution to a charged amino acid at position S179 as compared to SEQ ID NO: 22 or SEQ ID NO: 23. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 and further comprises a substitution to a charged amino acid is at position S179 as compared to SEQ ID NO: 22. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 23 and further comprises a substitution to a charged amino acid is at position S179 as compared to SEQ ID NO: 23. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a substitution to a charged amino acid at position S179 as compared to SEQ ID NO: 22 or SEQ ID NO: 23 further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof as compared to SEQ ID NO: 22 or SEQ ID NO: 23.

[0285] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and further comprises a substitution to a charged amino acid at position N180 as compared to SEQ ID NO: 22 or SEQ ID NO: 23. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 and further comprises a substitution to a charged amino acid is at position N180 as compared to SEQ ID NO: 22. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 23 and further comprises a substitution to a charged amino acid is at position N180 as compared to SEQ ID NO: 23. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a substitution to a charged amino acid at position N180 as compared to SEQ ID NO: 22 or SEQ ID NO: 23 further comprises one or more mutations 87 IPTS / 128573217.2INH-027WO PATENT comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof as compared to SEQ ID NO: 22 or SEQ ID NO: 23.

[0286] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and further comprises a substitution to a charged amino acid at position S183 as compared to SEQ ID NO: 22 or SEQ ID NO: 23. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 and further comprises a substitution to a charged amino acid is at position S183 as compared to SEQ ID NO: 22. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 23 and further comprises a substitution to a charged amino acid is at position S183 as compared to SEQ ID NO: 23. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a substitution to a charged amino acid at position S183 as compared to SEQ ID NO: 22 or SEQ ID NO: 23 further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, N180, M184, Y209, I347, T350, E353, R354, or any combination thereof as compared to SEQ ID NO: 22 or SEQ ID NO: 23.

[0287] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and further comprises a substitution to a charged amino acid at position M184 as compared to SEQ ID NO: 22 or SEQ ID NO: 23. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 and further comprises a substitution to a charged amino acid is at position M184 as compared to SEQ ID NO: 22. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 23 and further comprises a substitution to a charged amino acid is at position M184 as compared to SEQ ID NO: 23. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a substitution to a charged amino acid at position M184 as compared to SEQ ID NO: 22 or SEQ ID NO: 23 further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, Y209, I347, T350, E353, R354, or any combination thereof as compared to SEQ ID NO: 22 or SEQ ID NO: 23.

[0288] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and further comprises a substitution 88 IPTS / 128573217.2INH-027WO PATENT to a charged amino acid at position Y209 as compared to SEQ ID NO: 22 or SEQ ID NO: 23. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 and further comprises a substitution to a charged amino acid is at position Y209 as compared to SEQ ID NO: 22. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 23 and further comprises a substitution to a charged amino acid is at position Y209 as compared to SEQ ID NO: 23. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a substitution to a charged amino acid at position Y209 as compared to SEQ ID NO: 22 or SEQ ID NO: 23 further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, I347, T350, E353, R354, or any combination thereof as compared to SEQ ID NO: 22 or SEQ ID NO: 23.

[0289] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and further comprises a substitution to a charged amino acid at position I347 as compared to SEQ ID NO: 22 or SEQ ID NO: 23. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 and further comprises a substitution to a charged amino acid is at position I347 as compared to SEQ ID NO: 22. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 23 and further comprises a substitution to a charged amino acid is at position I347 as compared to SEQ ID NO: 23. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a substitution to a charged amino acid at position I347 as compared to SEQ ID NO: 22 or SEQ ID NO: 23 further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, T350, E353, R354, or any combination thereof as compared to SEQ ID NO: 22 or SEQ ID NO: 23.

[0290] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and further comprises a substitution to a charged amino acid at position T350 as compared to SEQ ID NO: 22 or SEQ ID NO: 23. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 and further comprises a substitution to a charged amino acid is at position T350 as compared to SEQ ID NO: 22. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 23 and further 89 IPTS / 128573217.2INH-027WO PATENT comprises a substitution to a charged amino acid is at position T350 as compared to SEQ ID NO: 23. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a substitution to a charged amino acid at position T350 as compared to SEQ ID NO: 22 or SEQ ID NO: 23 further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, E353, R354, or any combination thereof as compared to SEQ ID NO: 22 or SEQ ID NO: 23.

[0291] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and further comprises a substitution to a charged amino acid at position E353 as compared to SEQ ID NO: 22 or SEQ ID NO: 23. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 and further comprises a substitution to a charged amino acid is at position E353 as compared to SEQ ID NO: 22. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 23 and further comprises a substitution to a charged amino acid is at position E353 as compared to SEQ ID NO: 23. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a substitution to a charged amino acid at position E353 as compared to SEQ ID NO: 22 or SEQ ID NO: 23 further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, R354, or any combination thereof as compared to SEQ ID NO: 22 or SEQ ID NO: 23.

[0292] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and further comprises a substitution to a charged amino acid at position R354 as compared to SEQ ID NO: 22 or SEQ ID NO: 23. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 and further comprises a substitution to a charged amino acid is at position R354 as compared to SEQ ID NO: 22. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 23 and further comprises a substitution to a charged amino acid is at position R354 as compared to SEQ ID NO: 23. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a substitution to a charged amino acid at position R354 as compared to SEQ ID NO: 22 or SEQ ID NO: 23 further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, 90 IPTS / 128573217.2INH-027WO PATENT S179, N180, S183, M184, Y209, I347, T350, E353, or any combination thereof as compared to SEQ ID NO: 22 or SEQ ID NO: 23.

[0293] The substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof as compared to SEQ ID NO: 22 or SEQ ID NO: 23 may comprise a substitution to any charged amino acid. In some embodiments, the substitution comprises a substitution to an acidic amino acid, including but not limited to aspartate (D) or glutamate (E). In some embodiments, the substitution comprises a substitution to a basic amino acid, including but not limited to lysine (K) or arginine (R). In embodiments where the original amino acid according to SEQ ID NO: 22 or SEQ ID NO: 23 is an acidic amino acid (e.g. E353), the substitution to a charged amino acid may comprise a substitution to another acid amino acid (e.g. D), or a substitution to a basic amino acid (e.g. K or R). In some embodiments, where the original amino acid according to SEQ ID NO: 22 or SEQ ID NO: 23 is an acidic amino acid (e.g. E353), the substitution to a charged amino acid comprises a substitution to a basic amino acid (e.g. K or R). In embodiments where the original amino acid according to SEQ ID NO: 22 or SEQ ID NO: 23 is a basic amino acid (e.g. Q10, K47, K50, or R354), the substitution to a charged amino acid may comprise a substitution to another basic amino acid (e.g. K or R), or a substitution to an acidic amino acid (e.g. D or E). In some embodiments, where the original amino acid according to SEQ ID NO: 22 or SEQ ID NO: 23 is a basic amino acid (e.g. Q10, K47, K50, or R354), the substitution to a charged amino acid comprises a substitution to an acidic amino acid (e.g. D or E),

[0294] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a substitution to a charged amino acid at position H8 as compared to SEQ ID NO: 22 or SEQ ID NO: 23, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 and a substitution to a charged amino acid at position H8 as compared to SEQ ID NO: 22, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 23 and a substitution to a charged amino acid at position H8 as compared to SEQ ID NO: 23, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the mutation at position H8 is H8D. In some embodiments, the mutation at position H8 is H8E. In some embodiments, the mutation at position H8 is H8K. In some embodiments, the mutation at 91 IPTS / 128573217.2INH-027WO PATENT position H8 is H8R. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a mutation at position H8 as compared to SEQ ID NO: 22 or SEQ ID NO: 23 selected from H8D, H8E, H8K, or H8R, further comprises one or more mutations comprising a substitution to a charged amino acid at position N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof as compared to SEQ ID NO: 22 or SEQ ID NO: 23.

[0295] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a substitution to a charged amino acid at position N9 as compared to SEQ ID NO: 22 or SEQ ID NO: 23, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 and a substitution to a charged amino acid at position N9 as compared to SEQ ID NO: 22, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 23 and a substitution to a charged amino acid at position N9 as compared to SEQ ID NO: 23, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the mutation at position N9 is N9D. In some embodiments, the mutation at position N9 is N9E. In some embodiments, the mutation at position N9 is N9K. In some embodiments, the mutation at position N9 is N9R. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a mutation at position N9 as compared to SEQ ID NO: 22 or SEQ ID NO: 23 selected from N9D, N9E, N9K, or N9R, further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof as compared to SEQ ID NO: 22 or SEQ ID NO: 23.

[0296] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a substitution to a charged amino acid at position Q10 as compared to SEQ ID NO: 22 or SEQ ID NO: 23, wherein the charged amino acid is selected from D or E. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 and a substitution to a charged amino acid at position Q10 as compared to SEQ ID NO: 22, wherein the charged amino acid is selected from D or E. In some embodiments the viral particle comprises a VSV- G protein comprising an amino acid sequence of SEQ ID NO: 23 and a substitution to a charged amino acid at position Q10 as compared to SEQ ID NO: 23, wherein the charged amino acid 92 IPTS / 128573217.2INH-027WO PATENT is selected from D or E. In some embodiments, the mutation at position Q10 is Q10D. In some embodiments, the mutation at position Q10 is Q10E. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a mutation at position Q10 as compared to SEQ ID NO: 22 or SEQ ID NO: 23 selected from Q10D or Q10E, further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof as compared to SEQ ID NO: 22 or SEQ ID NO: 23.

[0297] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a substitution to a charged amino acid at position K47 as compared to SEQ ID NO: 22 or SEQ ID NO: 23, wherein the charged amino acid is selected from D or E. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 and a substitution to a charged amino acid at position K47 as compared to SEQ ID NO: 22, wherein the charged amino acid is selected from D or E. In some embodiments the viral particle comprises a VSV- G protein comprising an amino acid sequence of SEQ ID NO: 23 and a substitution to a charged amino acid at position K47 as compared to SEQ ID NO: 23, wherein the charged amino acid is selected from D or E. In some embodiments, the mutation at position K47 is K47D. In some embodiments, the mutation at position K47 is K47E. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a mutation at position K47 as compared to SEQ ID NO: 22 or SEQ ID NO: 23 selected from K47D or K47E, further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof as compared to SEQ ID NO: 22 or SEQ ID NO: 23.

[0298] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a substitution to a charged amino acid at position K50 as compared to SEQ ID NO: 22 or SEQ ID NO: 23, wherein the charged amino acid is selected from D or E. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 and a substitution to a charged amino acid at position K50 as compared to SEQ ID NO: 22, wherein the charged amino acid is selected from D or E. In some embodiments the viral particle comprises a VSV- G protein comprising an amino acid sequence of SEQ ID NO: 23 and a substitution to a charged amino acid at position K50 as compared to SEQ ID NO: 23, wherein the charged amino acid is selected from D or E. In some embodiments, the mutation at position K50 is K50D. In some 93 IPTS / 128573217.2INH-027WO PATENT embodiments, the mutation at position K50 is K50E. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a mutation at position K50 as compared to SEQ ID NO: 22 or SEQ ID NO: 23 selected from K50D or K50E, further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, A51, S179, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof as compared to SEQ ID NO: 22 or SEQ ID NO: 23.

[0299] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a substitution to a charged amino acid at position A51 as compared to SEQ ID NO: 22 or SEQ ID NO: 23, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 and a substitution to a charged amino acid at position A51 as compared to SEQ ID NO: 22, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 23 and a substitution to a charged amino acid at position A51 as compared to SEQ ID NO: 23, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the mutation at position A51 is A51D. In some embodiments, the mutation at position A51 is A51E. In some embodiments, the mutation at position A51 is A51K. In some embodiments, the mutation at position A51 is A51R. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a mutation at position A51 as compared to SEQ ID NO: 22 or SEQ ID NO: 23 selected from A51D, A51E, A51K, or A51R, further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, S179, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof as compared to SEQ ID NO: 22 or SEQ ID NO: 23.

[0300] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a substitution to a charged amino acid at position S179 as compared to SEQ ID NO: 22 or SEQ ID NO: 23, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 and a substitution to a charged amino acid at position S179 as compared to SEQ ID NO: 22, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 23 and a substitution to a charged amino acid at position S179 as compared to SEQ ID NO: 23, wherein 94 IPTS / 128573217.2INH-027WO PATENT the charged amino acid is selected from D, E, K, or R. In some embodiments, the mutation at position S179 is S179D. In some embodiments, the mutation at position S179 is S179E. In some embodiments, the mutation at position S179 is S179K. In some embodiments, the mutation at position S179 is S179R. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a mutation at position S179 as compared to SEQ ID NO: 22 or SEQ ID NO: 23 selected from S179D, S179E, S179K, or S179R, further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof as compared to SEQ ID NO: 22 or SEQ ID NO: 23.

[0301] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a substitution to a charged amino acid at position N180 as compared to SEQ ID NO: 22 or SEQ ID NO: 23, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 and a substitution to a charged amino acid at position N180 as compared to SEQ ID NO: 22, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 23 and a substitution to a charged amino acid at position N180 as compared to SEQ ID NO: 23, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the mutation at position N180 is N180D. In some embodiments, the mutation at position N180 is N180E. In some embodiments, the mutation at position N180 is N180K. In some embodiments, the mutation at position N180 is N180R. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a mutation at position N180 as compared to SEQ ID NO: 22 or SEQ ID NO: 23 selected from N180D, N180E, N180K, or N180R, further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof as compared to SEQ ID NO: 22 or SEQ ID NO: 23.

[0302] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a substitution to a charged amino acid at position S183 as compared to SEQ ID NO: 22 or SEQ ID NO: 23, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 and a substitution to a charged amino acid at position S183 as compared to SEQ ID NO: 22, wherein 95 IPTS / 128573217.2INH-027WO PATENT the charged amino acid is selected from D, E, K, or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 23 and a substitution to a charged amino acid at position S183 as compared to SEQ ID NO: 23, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the mutation at position S183 is S183D. In some embodiments, the mutation at position S183 is S183E. In some embodiments, the mutation at position S183 is S183K. In some embodiments, the mutation at position S183 is S183R. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a mutation at position S183 as compared to SEQ ID NO: 22 or SEQ ID NO: 23 selected from S183D, S183E, S183K, or S183R, further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, N180, M184, Y209, I347, T350, E353, R354, or any combination thereof as compared to SEQ ID NO: 22 or SEQ ID NO: 23.

[0303] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a substitution to a charged amino acid at position M184 as compared to SEQ ID NO: 22 or SEQ ID NO: 23, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 and a substitution to a charged amino acid at position M184 as compared to SEQ ID NO: 22, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 23 and a substitution to a charged amino acid at position M184 as compared to SEQ ID NO: 23, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the mutation at position M184 is M184D. In some embodiments, the mutation at position M184 is M184E. In some embodiments, the mutation at position M184 is M184K. In some embodiments, the mutation at position M184 is M184R. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a mutation at position M184 as compared to SEQ ID NO: 22 or SEQ ID NO: 23 selected from M184D, M184E, M184K, or M184R, further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, Y209, I347, T350, E353, R354, or any combination thereof as compared to SEQ ID NO: 22 or SEQ ID NO: 23.

[0304] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a substitution to a charged 96 IPTS / 128573217.2INH-027WO PATENT amino acid at position Y209 as compared to SEQ ID NO: 22 or SEQ ID NO: 23, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 and a substitution to a charged amino acid at position Y209 as compared to SEQ ID NO: 22, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 23 and a substitution to a charged amino acid at position Y209 as compared to SEQ ID NO: 23, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the mutation at position Y209 is Y209D. In some embodiments, the mutation at position Y209 is Y209E. In some embodiments, the mutation at position Y209 is Y209K. In some embodiments, the mutation at position Y209 is Y209R. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a mutation at position Y209 as compared to SEQ ID NO: 22 or SEQ ID NO: 23 selected from Y209D, Y209E, Y209K, or Y209R, further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, I347, T350, E353, R354, or any combination thereof as compared to SEQ ID NO: 22 or SEQ ID NO: 23.

[0305] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a substitution to a charged amino acid at position I347 as compared to SEQ ID NO: 22 or SEQ ID NO: 23, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 and a substitution to a charged amino acid at position I347 as compared to SEQ ID NO: 22, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 23 and a substitution to a charged amino acid at position I347 as compared to SEQ ID NO: 23, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the mutation at position I347 is I347D. In some embodiments, the mutation at position I347 is I347E. In some embodiments, the mutation at position I347 is I347K. In some embodiments, the mutation at position I347 is I347R. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a mutation at position I347 as compared to SEQ ID NO: 22 or SEQ ID NO: 23 selected from I347D, I347E, I347K, or I347R, further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, T350, E353, R354, or any 97 IPTS / 128573217.2INH-027WO PATENT combination thereof as compared to SEQ ID NO: 22 or SEQ ID NO: 23.

[0306] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 SEQ ID NO: 23 and a substitution to a charged amino acid at position T350 as compared to SEQ ID NO: 22 or SEQ ID NO: 23, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 and a substitution to a charged amino acid at position T350 as compared to SEQ ID NO: 22, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 23 and a substitution to a charged amino acid at position T350 as compared to SEQ ID NO: 23, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the mutation at position T350 is T350D. In some embodiments, the mutation at position T350 is T350E. In some embodiments, the mutation at position T350 is T350K. In some embodiments, the mutation at position T350 is T350R. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a mutation at position T350 as compared to SEQ ID NO: 22 or SEQ ID NO: 23 selected from T350D, T350E, T350K, or T350R, further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, E353, R354, or any combination thereof as compared to SEQ ID NO: 22 or SEQ ID NO: 23.

[0307] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a substitution to a charged amino acid at position E353 as compared to SEQ ID NO: 22 or SEQ ID NO: 23, wherein the charged amino acid is selected from K or R. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 and a substitution to a charged amino acid at position E353 as compared to SEQ ID NO: 22, wherein the charged amino acid is selected from K, or R. In some embodiments the viral particle comprises a VSV- G protein comprising an amino acid sequence of SEQ ID NO: 23 and a substitution to a charged amino acid at position E353 as compared to SEQ ID NO: 23, wherein the charged amino acid is selected from K, or R. In some embodiments, the mutation at position E353 is E353K. In some embodiments, the mutation at position E353 is E353R. In some embodiments, the VSV- G protein comprising the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a mutation at position E353 as compared to SEQ ID NO: 22 or SEQ ID NO: 23 selected from E353K or E353R, further comprises one or more mutations comprising a substitution to a 98 IPTS / 128573217.2INH-027WO PATENT charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, R354, or any combination thereof as compared to SEQ ID NO: 22 or SEQ ID NO: 23.

[0308] In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a substitution to a charged amino acid at position R354 as compared to SEQ ID NO: 22 or SEQ ID NO: 23, wherein the charged amino acid is selected from D or E. In some embodiments the viral particle comprises a VSV-G protein comprising an amino acid sequence of SEQ ID NO: 22 and a substitution to a charged amino acid at position R354 as compared to SEQ ID NO: 22, wherein the charged amino acid is selected from D or E. In some embodiments the viral particle comprises a VSV- G protein comprising an amino acid sequence of SEQ ID NO: 23 and a substitution to a charged amino acid at position R354 as compared to SEQ ID NO: 23, wherein the charged amino acid is selected from D or E. In some embodiments, the mutation at position R354 is R354D. In some embodiments, the mutation at position R354 is R354E. In some embodiments, the VSV- G protein comprising the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a mutation at position R354 as compared to SEQ ID NO: 22 or SEQ ID NO: 23 selected from R354D or R354E, further comprises one or more mutations comprising a substitution to a charged amino acid at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, or any combination thereof as compared to SEQ ID NO: 22 or SEQ ID NO: 23.

[0309] Table 3: Charged amino acid position possibilities and corresponding acceptable substitutions as compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. Applicable SEQ ID NO: Position Acceptable Substitution99 IPTS / 128573217.2INH-027WO PATENT SEQ ID NO: 22 or 23 S183 S183D, S183E, S183K, S183R

[0310] In some embodiments, the viral particle comprises a VSV-G protein comprising one or more mutations, wherein the mutation is a substitution to a charged amino acid as described in Table 3. In some embodiments, the mutation comprising a substitution to a charged amino acid is at position 8, 9, 10, 47, 50, 51, 179, 180, 183, 184, 209, 347, 350, 353, 354, or any combination thereof as described in Table 3. In some embodiments, the mutation comprising a substitution to a charged amino acid is at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof as described in Table 3.

[0311] It is to be understood that any of the mutations for a particular residue as described in Table 3 may be combined with one or more additional mutations for the other residues in Table 3. For example, in some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position H8 as described in Table 3, and further comprises a mutation at position N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof as described in Table 3. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position H8 as described in Table 3, and further comprises at least one additional mutation at a position selected from N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, or R354 as described in Table 3. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position H8 as described in Table 3 and further comprises additional mutations at more than one position selected from N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, or R354 as described in Table 3. 100 IPTS / 128573217.2INH-027WO PATENT

[0312] In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position N9 as described in Table 3, and further comprises a mutation at position H8, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof as described in Table 3. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position N9 as described in Table 3, and further comprises at least one additional mutation at a position selected from H8, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, or R354 as described in Table 3. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position N9 as described in Table 3, and further comprises additional mutations at more than one position selected from H8, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, or R354 as described in Table 3.

[0313] In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position Q10 as described in Table 3, and further comprises a mutation at position H8, N9, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof as described in Table 3. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position Q10 as described in Table 3, and further comprises at least one additional mutation at a position selected from H8, N9, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, or R354 as described in Table 3. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position Q10 as described in Table 3, and further comprises additional mutations at more than one position selected from H8, N9, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, or R354 as described in Table 3.

[0314] In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position K47 as described in Table 3, and further comprises a mutation at position H8, N9, Q10, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof as described in Table 3. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position K47 as described in Table 3, and further comprises at least one additional mutation at a position selected from H8, N9, Q10, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, or R354 as described in Table 3. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position K47 as described in Table 3, and further comprises additional mutations at more than one position selected from H8, N9, Q10, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, or R354 as described in Table 3. 101 IPTS / 128573217.2INH-027WO PATENT

[0315] In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position K50 as described in Table 3, and further comprises a mutation at position H8, N9, Q10, K47, A51, S179, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof as described in Table 3. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position K50 as described in Table 3, and further comprises at least one additional mutation at a position selected from H8, N9, Q10, K47, A51, S179, N180, S183, M184, Y209, I347, T350, E353, or R354 as described in Table 3. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position K50 as described in Table 3, and further comprises additional mutations at more than one position selected from H8, N9, Q10, K47, A51, S179, N180, S183, M184, Y209, I347, T350, E353, or R354 as described in Table 3.

[0316] In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position A51 as described in Table 3, and further comprises a mutation at position H8, N9, Q10, K47, K50, S179, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof as described in Table 3. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position A51 as described in Table 3, and further comprises at least one additional mutation at a position selected from H8, N9, Q10, K47, K50, S179, N180, S183, M184, Y209, I347, T350, E353, or R354 as described in Table 3. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position A51 as described in Table 3, and further comprises additional mutations at more than one position selected from H8, N9, Q10, K47, K50, S179, N180, S183, M184, Y209, I347, T350, E353, or R354 as described in Table 3.

[0317] In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position S179 as described in Table 3, and further comprises a mutation at position H8, N9, Q10, K47, K50, A51, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof as described in Table 3. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position S179 as described in Table 3, and further comprises at least one additional mutation at a position selected from H8, N9, Q10, K47, K50, A51, N180, S183, M184, Y209, I347, T350, E353, or R354 as described in Table 3. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position S179 as described in Table 3, and further comprises additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, N180, S183, M184, Y209, I347, T350, E353, or R354 as described in Table 3. 102 IPTS / 128573217.2INH-027WO PATENT

[0318] In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position N180 as described in Table 3, and further comprises a mutation at position H8, N9, Q10, K47, K50, A51, S179, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof as described in Table 3. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position N180 as described in Table 3, and further comprises at least one additional mutation at a position selected from H8, N9, Q10, K47, K50, A51, S179, S183, M184, Y209, I347, T350, E353, or R354 as described in Table 3. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position N180 as described in Table 3, and further comprises additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, S183, M184, Y209, I347, T350, E353, or R354 as described in Table 3.

[0319] In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position S183 as described in Table 3, and further comprises a mutation at position H8, N9, Q10, K47, K50, A51, S179, N180, M184, Y209, I347, T350, E353, R354, or any combination thereof as described in Table 3. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position S183 as described in Table 3, and further comprises at least one additional mutation at a position selected from H8, N9, Q10, K47, K50, A51, S179, N180, M184, Y209, I347, T350, E353, or R354 as described in Table 3. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position S183 as described in Table 3, and further additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, N180, M184, Y209, I347, T350, E353, or R354 as described in Table 3.

[0320] In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position M184 as described in Table 3, and further comprises a mutation at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, Y209, I347, T350, E353, R354, or any combination thereof as described in Table 3. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position M184 as described in Table 3, and further comprises at least one additional mutation at a position selected from H8, N9, Q10, K47, K50, A51, S179, N180, S183, Y209, I347, T350, E353, or R354 as described in Table 3. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position M184 as described in Table 3, and further comprises additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, N180, S183, Y209, I347, T350, E353, or R354 as described in Table 3. 103 IPTS / 128573217.2INH-027WO PATENT

[0321] In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position Y209 as described in Table 3, and further comprises a mutation at position H8, N9, Q10, K47, K50, A51, S179, N180 , S183, M184, I347, T350, E353, R354, or any combination thereof as described in Table 3. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position Y209 as described in Table 3, and further comprises at least one additional mutation at a position selected from H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, I347, T350, E353, or R354 as described in Table 3. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position Y209 as described in Table 3, and further comprises additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, I347, T350, E353, or R354 as described in Table 3.

[0322] In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position I347 as described in Table 3, and further comprises a mutation at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, T350, E353, R354, or any combination thereof as described in Table 3. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position I347 as described in Table 3, and further comprises at least one additional mutation at a position selected from H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, T350, E353, or R354 as described in Table 3. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position I347 as described in Table 3, and further comprises additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, T350, E353, or R354 as described in Table 3.

[0323] In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position T350 as described in Table 3, and further comprises a mutation at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, E353, R354, or any combination thereof as described in Table 3. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position T350 as described in Table 3, and further comprises at least one additional mutation at a position selected from H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, E353, or R354 as described in Table 3. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position T350 as described in Table 3, and further comprises additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, E353, or R354 as described in Table 3. 104 IPTS / 128573217.2INH-027WO PATENT

[0324] In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position E353 as described in Table 3, and further comprises a mutation at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, R354, or any combination thereof as described in Table 3. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position E353 as described in Table 3, and further comprises at least one additional mutation at a position selected from H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, or R354 as described in Table 3. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position E353 as described in Table 3, and further comprises additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, or R354 as described in Table 3.

[0325] In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position R354 as described in Table 3, and further comprises a mutation at position H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, or any combination thereof as described in Table 3. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position R354 as described in Table 3, and further comprises at least one additional mutation at a position selected from H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, or E353 as described in Table 3. In some embodiments the viral particle comprises a VSV-G protein comprising a mutation at position R354 as described in Table 3, and further comprises additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, or E353 as described in Table 3.

[0326] In any of the embodiments herein, the VSV-G protein may further comprise a mutation at position 8, 9, 10, 47, 50, 51, 179, 180, 182, 184, 209, 347, 350, 352, 353, 354, or any combination thereof wherein the mutation is a substitution to an alanine (A), glycine (G), glutamine (Q), or a combination thereof. In some embodiments, the substitution at position 8 is H8A. In some embodiments, the substitution at position 9 is N9A. In some embodiments, the substitution at position 10 is Q10A. In some embodiments, the substitution at position 47 is K47A. In some embodiments, the substitution at position 47 is K47Q. In some embodiments, the substitution at position 50 is K50A. In some embodiments, the substitution at position 179 is S179A. In some embodiments, the substitution at position 180 is N180A. In some embodiments, the substitution at position 182 is I182A. In some embodiments, the substitution at position 184 is M184A. In some embodiments, the substitution at position 209 is Y209A. In 105 IPTS / 128573217.2INH-027WO PATENT some embodiments, the substitution at position 347 is I347A. In some embodiments, the substitution at position 347 is I347G. In some embodiments, the substitution at position 350 is T350A. In some embodiments, the substitution at position 353 is E353A. In some embodiments, the substitution at position 352 is T352A. In some embodiments, the substitution at position 352 is T352Q. In some embodiments, the substitution at position 354 is R354A.

[0327] As provided for herein, any of the mutations (i.e. substitutions) described herein may be combined with any other mutation described herein. For example, in some embodiments, a VSV-G protein is provided comprising a mutation to a charged amino acid at position 8, 9, 10, 47, 50, 51, 179, 180, 182, 184, 209, 347, 350, 352, 353, 354, or any combination thereof as provided for herein, and further comprising a mutation at position 8, 9, 10, 47, 50, 51, 179, 180, 182, 184, 209, 347, 350, 352, 353, 354, or any combination thereof wherein the mutation is a substitution to an alanine residue as provided for herein.

[0328] As provided for herein, any of the mutations (i.e. substitutions) described herein may be combined with any other mutation described herein. For example, in some embodiments, a VSV-G protein is provided comprising a mutation to a charged amino acid at position 8, 9, 10, 47, 50, 51, 179, 180, 182, 184, 209, 347, 350, 352, 353, 354, or any combination thereof as provided for herein, and further comprising a mutation at position 8, 9, 10, 47, 50, 51, 179, 180, 182, 184, 209, 347, 350, 352, 353, 354, or any combination thereof wherein the mutation is a substitution to an glycine residue as provided for herein.

[0329] As provided for herein, any of the mutations (i.e. substitutions) described herein may be combined with any other mutation described herein. For example, in some embodiments, a VSV-G protein is provided comprising a mutation to a charged amino acid at position 8, 9, 10, 47, 50, 51, 179, 180, 182, 184, 209, 347, 350, 352, 353, 354, or any combination thereof as provided for herein, and further comprising a mutation at position 8, 9, 10, 47, 50, 51, 179, 180, 182, 184, 209, 347, 350, 352, 353, 354, or any combination thereof wherein the mutation is a substitution to an glutamine residue as provided for herein.

[0330] In some embodiments, the VSV-G protein provided for herein comprises a H8A mutation and further comprises an N9A mutation, a Q10A mutation, a K47A mutation, a K50A mutation, a K51A mutation, an S179A mutation, an N180A mutation, an I182A mutation, an M184A mutation, a Y209A mutation, an I347A, an I347G mutation, a T350A mutation, a T352A mutation, a T352Q mutation, an E353A mutation, or an R354A mutation, or any combination thereof.

[0331] In some embodiments, the VSV-G protein provided for herein comprises an N9A 106 IPTS / 128573217.2INH-027WO PATENT mutation and further comprises an H8A mutation, a Q10A mutation, a K47A mutation, a K50A mutation, a K51A mutation, an S179A mutation, an N180A mutation, an I182A mutation, an M184A mutation, a Y209A mutation, an I347A, an I347G mutation, a T350A mutation, a T352A mutation, a T352Q mutation, an E353A mutation, or an R354A mutation, or any combination thereof.

[0332] In some embodiments, the VSV-G protein provided for herein comprises a H8A mutation and further comprises an N9A mutation, a Q10A mutation, a K47A mutation, a K50A mutation, a K51A mutation, an S179A mutation, an N180A mutation, an I182A mutation, an M184A mutation, a Y209A mutation, an I347A, an I347G mutation, a T350A mutation, a T352A mutation, a T352Q mutation, an E353A mutation, or an R354A mutation, or any combination thereof.

[0333] In some embodiments, the VSV-G protein provided for herein comprises a Q10A mutation and further comprises an N9A mutation, a H8A mutation, a K47A mutation, a K50A mutation, a K51A mutation, an S179A mutation, an N180A mutation, an I182A mutation, an M184A mutation, a Y209A mutation, an I347A, an I347G mutation, a T350A mutation, a T352A mutation, a T352Q mutation, an E353A mutation, or an R354A mutation, or any combination thereof.

[0334] In some embodiments, the VSV-G protein provided for herein comprises a K47A mutation and further comprises an N9A mutation, a Q10A mutation, a H8A mutation, a K50A mutation, a K51A mutation, an S179A mutation, an N180A mutation, an I182A mutation, an M184A mutation, a Y209A mutation, an I347A, an I347G mutation, a T350A mutation, a T352A mutation, a T352Q mutation, an E353A mutation, or an R354A mutation, or any combination thereof.

[0335] In some embodiments, the VSV-G protein provided for herein comprises a K50A mutation and further comprises an N9A mutation, a Q10A mutation, a K47A mutation, a H8A mutation, a K51A mutation, an S179A mutation, an N180A mutation, an I182A mutation, an M184A mutation, a Y209A mutation, an I347A, an I347G mutation, a T350A mutation, a T352A mutation, a T352Q mutation, an E353A mutation, or an R354A mutation, or any combination thereof.

[0336] In some embodiments, the VSV-G protein provided for herein comprises a K51A mutation and further comprises an N9A mutation, a Q10A mutation, a K47A mutation, a K50A mutation, a H8A mutation, an S179A mutation, an N180A mutation, an I182A mutation, an M184A mutation, a Y209A mutation, an I347A, an I347G mutation, a T350A mutation, a 107 IPTS / 128573217.2INH-027WO PATENT T352A mutation, a T352Q mutation, an E353A mutation, or an R354A mutation, or any combination thereof.

[0337] In some embodiments, the VSV-G protein provided for herein comprises a S179A mutation and further comprises an N9A mutation, a Q10A mutation, a K47A mutation, a K50A mutation, a K51A mutation, an H8A mutation, an N180A mutation, an I182A mutation, an M184A mutation, a Y209A mutation, an I347A, an I347G mutation, a T350A mutation, a T352A mutation, a T352Q mutation, an E353A mutation, or an R354A mutation, or any combination thereof.

[0338] In some embodiments, the VSV-G protein provided for herein comprises a N180A mutation and further comprises an N9A mutation, a Q10A mutation, a K47A mutation, a K50A mutation, a K51A mutation, an S179A mutation, an H8A mutation, an I182A mutation, an M184A mutation, a Y209A mutation, an I347A, an I347G mutation, a T350A mutation, a T352A mutation, a T352Q mutation, an E353A mutation, or an R354A mutation, or any combination thereof.

[0339] In some embodiments, the VSV-G protein provided for herein comprises a I182A mutation and further comprises an N9A mutation, a Q10A mutation, a K47A mutation, a K50A mutation, a K51A mutation, an S179A mutation, an N180A mutation, an H8A mutation, an M184A mutation, a Y209A mutation, an I347A, an I347G mutation, a T350A mutation, a T352A mutation, a T352Q mutation, an E353A mutation, or an R354A mutation, or any combination thereof.

[0340] In some embodiments, the VSV-G protein provided for herein comprises a M184A mutation and further comprises an N9A mutation, a Q10A mutation, a K47A mutation, a K50A mutation, a K51A mutation, an S179A mutation, an N180A mutation, an I182A mutation, an H8A mutation, a Y209A mutation, an I347A, an I347G mutation, a T350A mutation, a T352A mutation, a T352Q mutation, an E353A mutation, or an R354A mutation, or any combination thereof.

[0341] In some embodiments, the VSV-G protein provided for herein comprises a Y209A mutation and further comprises an N9A mutation, a Q10A mutation, a K47A mutation, a K50A mutation, a K51A mutation, an S179A mutation, an N180A mutation, an I182A mutation, an M184A mutation, a H8A mutation, an I347A, an I347G mutation, a T350A mutation, a T352A mutation, a T352Q mutation, an E353A mutation, or an R354A mutation, or any combination thereof.

[0342] In some embodiments, the VSV-G protein provided for herein comprises a I347A 108 IPTS / 128573217.2INH-027WO PATENT mutation and further comprises an N9A mutation, a Q10A mutation, a K47A mutation, a K50A mutation, a K51A mutation, an S179A mutation, an N180A mutation, an I182A mutation, an M184A mutation, a Y209A mutation, an H8A, an I347G mutation, a T350A mutation, a T352A mutation, a T352Q mutation, an E353A mutation, or an R354A mutation, or any combination thereof.

[0343] In some embodiments, the VSV-G protein provided for herein comprises a I347G mutation and further comprises an N9A mutation, a Q10A mutation, a K47A mutation, a K50A mutation, a K51A mutation, an S179A mutation, an N180A mutation, an I182A mutation, an M184A mutation, a Y209A mutation, an I347A, an H8A mutation, a T350A mutation, a T352A mutation, a T352Q mutation, an E353A mutation, or an R354A mutation, or any combination thereof.

[0344] In some embodiments, the VSV-G protein provided for herein comprises a T350A mutation and further comprises an N9A mutation, a Q10A mutation, a K47A mutation, a K50A mutation, a K51A mutation, an S179A mutation, an N180A mutation, an I182A mutation, an M184A mutation, a Y209A mutation, an I347A, an I347G mutation, a H8A mutation, a T352A mutation, a T352Q mutation, an E353A mutati...

Claims

INH-027WO PATENT What is Claimed:

1. A variant VSV-G polypeptide comprising a mutation that corresponds to a mutation at position 8, 9, 10, 47, 50, 51, 179, 180, 182, 183, 184, 209, 347, 350, 352, 353, 354, or a combination thereof, of SEQ ID NO: 2, provided that the mutation is not a I182E mutation, a I182A mutation, or a I182D mutation.

2. The variant VSV-G polypeptide of claim 1, wherein the mutation at position 8, 9, 10, 47, 50, 51, 179, 180, 182, 183, 184, 209, 347, 350, 352, 353, 354, or a combination thereof, of SEQ ID NO: 2 comprises a substitution to a charged amino acid.

3. The variant VSV-G polypeptide of claim 2, wherein the charged amino acid corresponds to the position of H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, or R354 of SEQ ID NO:

2.

4. The variant VSV-G polypeptide of claim 2, wherein the substitution to the charged amino acid is D, E, K, or R.

5. The variant VSV-G polypeptide of claim 2, wherein the mutation to a charged amino acid at position H8 is H8D, H8E, H8K, or H8R.

6. The variant VSV-G polypeptide of claim 2, wherein the mutation to a charged amino acid at position N9 is N9D, N9E, N9K, or N9R.

7. The variant VSV-G polypeptide of claim 2, wherein the mutation to a charged amino acid at position Q10 is Q10D, or Q10E.

8. The variant VSV-G polypeptide of claim 2, wherein the mutation to a charged amino acid at position K47 is K47D or K47E.

9. The variant VSV-G polypeptide of claim 2, wherein the mutation to a charged amino acid at position K50 is K50D or K50E.

10. The variant VSV-G polypeptide of claim 2, wherein the mutation to a charged amino 218 IPTS / 128573217.2INH-027WO PATENT acid at position A51 is A51D, A51E, A51K, or A51R.

11. The variant VSV-G polypeptide of claim 2, wherein the mutation to a charged amino acid at position S179 is S179D, S179E, S179K, or S179R.

12. The variant VSV-G polypeptide of claim 2, wherein the mutation to a charged amino acid at position N180 is N180D, N180E, or N180K.

13. The variant VSV-G polypeptide of claim 2, wherein the mutation to a charged amino acid at position I182 is I182D, I182K, or I182R.

14. The variant VSV-G polypeptide of claim 2, wherein the mutation to a charged amino acid at position S183 is S183D, S183E, S183K, or S183R.

15. The variant VSV-G polypeptide of claim 2, wherein the mutation to a charged amino acid at position M184 is M184D, M184E, M184K, or M184R.

16. The variant VSV-G polypeptide of claim 2, wherein the mutation to a charged amino acid at position Y209 is Y209D, Y209E, Y209K, or Y209R.

17. The variant VSV-G polypeptide of claim 2, wherein the mutation to a charged amino acid at position I347 is I347D, I347E, I347K, or I347R.

18. The variant VSV-G polypeptide of claim 2, wherein the mutation to a charged amino acid at position T350 is T350D T350E T350K, or T350R.

19. The variant VSV-G polypeptide of claim 2, wherein the mutation to a charged amino acid at position T352 is T352D, T352E, T352K, or T352R.

20. The variant VSV-G polypeptide of claim 2, wherein the mutation to a charged amino acid at position E353 is E353K or E353R.

21. The variant VSV-G polypeptide of claim 2, wherein the mutation to a charged amino 219 IPTS / 128573217.2INH-027WO PATENT acid at position R354 is R354D or R354E.

22. The variant VSV-G polypeptide of claim 1, wherein the mutation is a substitution to an alanine (A), glycine (G), glutamine (Q), or a combination thereof.

23. A variant VSV-G polypeptide comprising a variant amino acid sequence of SEQ ID NO 3, SEQ ID NO 4, or SEQ ID NO 5 comprising a mutation that corresponds to a mutation at position 8, 9, 10, 47, 50, 51, 179, 180, 183, 184, 209, 347, 350, 352, 353, 354, or a combination thereof, of SEQ ID NO 3, SEQ ID NO 4, or SEQ ID NO 5.

24. The variant VSV-G polypeptide of claim 23, wherein the variant VSV-G polypeptide comprises a variant of the amino acid sequence of SEQ ID NO 3 comprising a mutation that corresponds to a mutation at position 8, 9, 10, 47, 50, 51, 179, 180, 183, 184, 209, 347, 350, 352, 353, 354, or a combination thereof, of SEQ ID NO 3.

25. The variant VSV-G polypeptide of claim 23, wherein the variant VSV-G polypeptide comprises a variant of the amino acid sequence of SEQ ID NO 4 comprising a mutation that corresponds to a mutation at position 8, 9, 10, 47, 50, 51, 179, 180, 183, 184, 209, 347, 350, 352, 353, 354, or a combination thereof, of SEQ ID NO 4.

26. The variant VSV-G polypeptide of claim 23, wherein the variant VSV-G polypeptide comprises a variant of the amino acid sequence of SEQ ID NO 5 comprising a mutation that corresponds to a mutation at position 8, 9, 10, 47, 50, 51, 179, 180, 183, 184, 209, 347, 350, 352, 353, 354, or a combination thereof of SEQ ID NO 5.

27. The variant VSV-G polypeptide of any one of claims 23-26, wherein the mutation at position 8, 9, 10, 47, 50, 51, 179, 180, 182, 183, 184, 209, 347, 350, 352, 353, 354, or a combination thereof comprises a substitution to a charged amino acid selected from H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, or R354.

28. A variant VSV-G polypeptide comprising a variant of the amino acid sequence of SEQ ID NO 22 or SEQ ID NO 23 comprising a mutation that corresponds to a mutation at position 8, 9, 10, 47, 50, 51, 179, 180, 183, 184, 209, 347, 350, 353, 354, or a combination thereof of 220 IPTS / 128573217.2INH-027WO PATENT SEQ ID NO 22 or SEQ ID NO 23. 29: The variant VSV-G polypeptide of claim 28, wherein the variant VSV-G polypeptide comprises a variant of the amino acid sequence of SEQ ID NO 22 comprising a mutation that corresponds to a mutation at position 8, 9, 10, 47, 50, 51, 179, 180, 183, 184, 209, 347, 350, 353, 354, or a combination thereof of SEQ ID NO 22.

30. The variant VSV-G polypeptide of claim 28, wherein the variant VSV-G polypeptide comprises an amino acid sequence of SEQ ID NO 23 comprising a mutation that corresponds to a mutation at position 8, 9, 10, 47, 50, 51, 179, 180, 183, 184, 209, 347, 350, 353, 354, or a combination thereof of SEQ ID NO 23.

31. The variant VSV-G polypeptide of any one of claims 28-30, wherein the mutation at position 8, 9, 10, 47, 50, 51, 179, 180, 182, 183, 184, 209, 347, 350, 352, 353, 354, or a combination thereof comprises a substitution to a charged amino acid selected from H8, N9, Q10, K47, K50, A51, S179, N180,, S183, M184, Y209, I347, T350,, E353, or R354.

32. A variant VSV-G polypeptide, wherein the variant amino acid sequence has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to the amino acid sequence of SEQ ID NO: 2, and further comprises a mutation that corresponds to a mutation at position 8, 9, 10, 47, 50, 51, 179, 180, 182, 183, 184, 209, 347, 350, 352, 353, 354, or any combination thereof as compared to SEQ ID NO:

2.

33. A nucleic acid molecule encoding the variant VSV-G polypeptide of any one of claims 1-32.

34. A viral particle comprising the polypeptide of any one of claims 1-32.

35. The viral particle of claim 36, further comprising a targeting moiety.

36. The viral particle of claims 34 or 35, wherein the viral particle is a pseudotyped lentivirus. 221 IPTS / 128573217.2INH-027WO PATENT 37. The viral particle of any one of claims 34-36, wherein the viral particle further comprises a nucleic acid molecule encoding a heterologous molecule of interest.

38. The viral particle of claim 37, wherein the heterologous molecule of interest is a chimeric antigen receptor (“CAR”).

39. The viral particle of any one of claims 34-38, wherein the targeting moiety binds to CD7, CD8, cKit (CD117), CD4, CD3, CD5, CD6, CD2, TCR alpha, TCR beta, TCR gamma, TCR delta, CD10, CD34, CD110, CD33, CD14, CD68, CCR7, CD62L, CD25, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, or CXCR3, A glycosylated CD43 epitope expressed on acute leukemia or lymphoma but not on hematopoietic progenitors, A glycosylated CD43 epitope expressed on non-hematopoietic cancers, A kinase anchor protein 4 (AKAP-4), Adrenoceptor beta 3 (ADRB3), AFP, Anaplastic lymphoma kinase (ALK), Androgen receptor, Angiopoietin- binding cell surface receptor 2 (Tie 2), Auto antibody to desmoglein 1 (Dsgl), Auto antibody to desmoglein 3 (Dsg3), B7H3 (CD276), Biotin, Bone marrow stromal cell antigen 2 (BST2), BST1 / CD157, Cancer / testis antigen 1 (NY-ESO-1), Cancer / testis antigen 2 (LAGE-la), Carbonic anhydrase IX (CA1X), Carcinoembryonic antigen (CEA), CCCTC-Binding Factor (Zinc Finger Protein)-Like (BORIS or Brother of the Regulator of lmprinted Sites), CCR4, CD5, CD19, CD20, CD22, CD24, CD30, CD32 (FCGR2A), CD33, CD34, CD38, CD44v6, CD72, CD79a, CD79b, CD97, CD99, CD123, CD171, CD179a, CD179b-IGLll, CD200R, CD276 / B7H3, CD300 molecule-like family member f (CD300LF), CDH1-CD324, CDH6, CDH17, CDH19, Chromosome X open reading frame 61 (CXORF61), Claudin 6 (CLDN6), Claudinl8.2 (CLD18A2 or CLDN18A.2), CMV pp65, C-MYC epitope Tag, Cripto, CS1 (also referred to as CD2 subset 1 or CRACC or SLAMF7 or CD319 or 19A24), CSF2RA (GM- CSFR-alpha), C-type lectin domain family 12 member A (CLEC12A), C-type lectin-like molecule-1 (CLL-1 or CLECL1), Cyclin Bl, Cytochrome P450 IB 1 (CYP1B 1), DLL3, EBV- EBNA3c, EGF-bke module- containing mucin-like hormone receptor-like 2 (EMR2), Elongation factor 2 mutated (ELF2M), Ephrin B2, Ephrin type-A receptor 2 (EphA2), Epidermal growth factor receptor (EGFR), Epidermal growth factor receptor variant III (EGFRviii), Epithelial cell adhesion molecule (EPCAM), ERG, ETS translocation-variant gene 6 located on chromosome 12p (ETV6-AML), Fc fragment of IgA receptor (FCAR or CD89), Fc receptor-like 5 (FCRL5), Fibroblast activation protein alpha (FAP), FITC, Fms Like Tyrosine Kinase 3 (FLT3), Folate receptor alpha (FRa or FR1), Folate receptor beta (FRb), 222 IPTS / 128573217.2INH-027WO PATENT Follicle stimulating hormone receptor (FSHR), Fos-related antigen 1, Fucosyl-GMl, G protein coupled receptor class C group 5 member D (GPRC5D), G protein-coupled receptor 20 (GPR20), GAD, Ganglioside G2 (GD2) , Ganglioside GD3 (aNeu5Ac(2-8)aNeu5Ac(2- 3)bDGalp(l-4 )bDGlcp(l-l)Cer), Ganglioside GM3 (aNeu5Ac(2-3)bDClalp(l- 4)bDGlcp(l- l)Cer), GD3, GFRalpha4, Glycoprotein 100 (gplOO), Glypican-3 (GPC3), Gonadotropin Hormone receptor (CGHR or GR), GpA33, GpNMB, GPRC5D, Guanylyl cyclase C (GCC), Heat shock protein 70-2 mutated (mut hsp70-2), Hepatitis A virus cellular receptor 1 (HAVCR1), Hexasaccharide portion of globoH glycoceramide (GloboH), High molecular weight-melanoma associated antigen (HMWMAA), HIV1 envelope glycoprotein, HLA, HLA- DOA, HLA-A, HLA-A2, HLA-B, HLA-C, HLA-DM, HLA-DOB, HLA-DP, HLA-DQ, HLA- DR, HLA-G, HTLVl-Tax, Human papilloma virus E6 (HPV E6), Human papilloma virus E7 (HPV E7), Human Telomerase reverse transcriptase (hTERT), IgE, IL13Ra2, ILl lRa, Immunoglobulin lambda-like polypeptide 1 (IGLL1), Influenza A hemagglutinin (HA), Insulin-like growth factor 1 receptor (IGF-I receptor), Interleukin 11 receptor alpha (IL-llRa), Interleukin- 13 receptor subunit alpha-2 (IL-13Ra2 or CD213A2), Intestinal carboxyl esterase, KIT (CD117), KSHV K8.1, KSHV-gH, LAMP1 , Legumain, Leukocyte immunoglobulin-like receptor subfamily A member 2 (LILRA2), Leukocyte-associated immunoglobulin-like receptor 1 (LAIR1), Leutenizing hormone receptor (LHR), Lewis(Y) antigen, Lews Ag, Livl, Locus K 9 (LY6K), Low conductance chloride channel, Lymphocyte antigen 6 complex, Lymphocyte antigen 75 (LY75), Lymphocyte-specific protein tyrosine kinase (LCK), Mammary gland differentiation antigen (NY-BR-1), Melanoma antigen recognized by T cells 1 (MelanA or MARTI), Melanoma- associated antigen 1 (MAGE-A1), Melanoma cancer testis antigen-1 (MAD-CT-1), Melanoma cancer testis antigen-2 (MAD-CT-2), Melanoma inhibitor of apoptosis (ML-IAP), Mesothelin, MPL, Mucin 1 cell surface associated (MUC1), N-Acetyl glucosaminyl-transferase V (NA17), Nectin-4, Neural cell adhesion molecule (NCAM), NKG2D, NYBR1, O-acetyl-GD2 ganglioside (OAcGD2), Olfactory receptor 51E2 (OR51E2), Oncogene fusion protein consisting of breakpoint cluster region (BCR) and Abelson murine leukemia viral oncogene homolog 1 (Abl) (bcr-abl), P53 mutant, Paired box protein Pax-3 (PAX3), Paired box protein Pax-5 (PAX5), Pannexin 3 (PANX3), PDL1, P-glycoprotein, Placenta-specific 1 (PLAC1), Platelet-derived growth factor receptor beta (PDGFR-beta), Polysialic acid, Proacrosin binding protein sp32 (OY-TES1), Prostase, Prostate carcinoma tumor antigen-1 (PCT A-l or Galectin 8), Prostate stem cell antigen (PSCA), Prostate-specific membrane antigen (PSMA), Prostatic acid phosphatase (PAP), Prostein, Protease Serine 21 223 IPTS / 128573217.2INH-027WO PATENT (Testisin or PRSS21), Proteasome (Prosome Macropain) Subunit Beta Type 9 (LMP2), PTK7, Ras G12V, Ras Homolog Family Member C (RhoC), Rat sarcoma (Ras) mutant, Receptor for Advanced Gly cation Endproducts (RAGE-1), Receptor tyrosine kinase-like orphan receptor 1 (ROR1), Receptor tyrosine-protein kinase ERBB2 or Her-22 / neu, Renal ubiquitous 1 (RU1), Renal ubiquitous 2 (RU2), Sarcoma translocation breakpoints, Serine 2 (TMPRSS2) ETS fusion gene, Sialyl Lewis adhesion molecule (sLe), SLAMF4, SLAMF6, Slea (CA19.9 or Sialyl Lewis Antigen), Sperm protein 17 (SPA17), Squamous Cell Carcinoma Antigen Recognized By T Cells 3 (SART3), Stage-specific embryonic antigen-4 (SSEA-4), STEAP1, Survivin, Synovial sarcoma X breakpoint 2 (SSX2), TCR Gamma Alternate Reading Frame Protein (TARP), TCR-beta1 chain, TCR-beta2 chain, TCR-delta chain, TCR-gamma chain, TCRgamma-delta, Telomerase, TGFbetaR2, The antigen recognized by TNT antibody, Thyroid stimulating hormone receptor (TSHR), Timl- / HVCR1, Tissue Factor 1 (TF1), Tn ag, Tn antigen ((Tn Ag) or (GalNAca-Ser / Thr)), TNF receptor family member B cell maturation (BCMA), Transglutaminase 5 (TGS5), Transmembrane protease, TROP2, Tumor endothelial marker 1 (TEM1 / CD248), Tumor endothelial marker 7-related (TEM7R), Tumor protein p53 (p53), Tumor-associated glycoprotein 72 (TAG72), Tyrosinase, Tyrosinase-related protein 2 (TRP-2), Uroplakin 2 (UPK2), Vascular endothelial growth factor receptor 2 (VEGFR2), V- myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN), Wilms tumor protein (WT1), or X Antigen Family Member 1A (XAGE1).

40. The viral particle of claim 39, wherein the targeting moiety binds to CD7.

41. The viral particle of claim 40, wherein the targeting moiety that binds to CD7 comprises a polypeptide comprising a sequence having at least 90% sequence identity to SEQ ID NO: 52, having at least 95% sequence identity to SEQ ID NO: 52, having at least 99% sequence identity to SEQ ID NO: 52, or a sequence as set forth in SEQ ID NO:

52.

42. The viral particle of any one of claims 34-41, wherein the targeting moiety is attached to the viral surface through an IgG Fc stalk; an envelope glycoprotein G or H of a virus of the Paramyxoviridae family, such as a morbillivirus, such as Measles virus, or a henipavirus, such as Nipah virus, Cedar virus, or Hendra virus; 224 IPTS / 128573217.2INH-027WO PATENT a glycoprotein of a virus of the Rhabdoviridae family, such as a vesicular stomatitis New Jersey virus, a vesicular stomatitis Indiana virus, a vesicular stomatitis Alagoas virus, a vesicular stromatitis Maraba virus, a vesicular stomatitis Carajas virus, Parainfluenza virus, Spodoptera frugiperda rhabdovirus isolate Sf G, Drosophila obscura sigmavirus 10A, Wuhan insect virus 7, Perch virus, or Spring viremia of carp virus; a glycoprotein of a virus of the Filoviridae family, such as Ebola virus; or a glycoprotein of a virus of the Arenaviridae family, such as Machupo virus.

43. A method of delivering a heterologous molecule to a target cell, the method comprising contacting the cell with a viral vector comprising: a) the variant VSV-G protein of any one of claims 1-32; b) a targeting moiety that binds to the target cell; and c) a nucleic acid molecule encoding the heterologous molecule.

44. A method of delivering a heterologous molecule to a target cell in a subject, the method comprising administering to the subject a viral vector comprising: a) the variant VSV-G polypeptide of any one of claims 1-32; b) a targeting moiety that binds to the target cell; and c) a nucleic acid molecule encoding the heterologous molecule.

45. The method of any one of claims 43-44, wherein the heterologous molecule is an siRNA, an shRNA, a non-coding RNA, a peptide, a polypeptide, a protein, a viral payload, a viral genome, a chimeric antigen receptor (“CAR”) or a combination thereof.

46. A method of treating cancer in a subject, the method comprising administering to the subject a viral vector comprising: a) the variant VSV-G polypeptide of any one of claims 1-32; b) a targeting moiety that binds to the target cell; and c) a nucleic acid molecule encoding the heterologous molecule.

47. The method of claim 46, wherein the heterologous molecule is a chimeric antigen receptor. 225 IPTS / 128573217.2INH-027WO PATENT 48. The method of any one of claims 46-47, wherein the cancer is carcinoma, blastoma, sarcoma, leukemia, lymphoid malignancies, benign tumors, malignant tumors, sarcoma, carcinoma, melanoma, breast cancer, prostate cancer, ovarian cancer, cervical cancer, skin cancer, pancreatic cancer, colorectal cancer, renal cancer, liver cancer, brain cancer, lymphoma, leukemia, lung cancer, thyroid cancer, B cell related cancers or T cell related cancers. 226 IPTS / 128573217.2

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