Pseudovirus particles, compositions containing them, and their use

Abstract

This specification provides a variant VSV-G polypeptide containing one or more mutations compared to the wild-type VSV-G polypeptide, a composition containing the same, and a method of using the same.

Description

[Technical Field]

[0001] (Related applications) This application claims the interests of U.S. Provisional Application No. 63 / 507,550, filed on 12 June 2023, which is incorporated herein by reference in its entirety.

[0002] (Reference to electronically submitted sequence listings) This application includes a sequence listing submitted electronically in XML format, the entirety of which is incorporated herein by reference. The XML copy, created on 29 May 2024, is named "INH-027WO_SL" and has a size of 155,722 bytes. [Background technology]

[0003] Vesicular stomatitis virus (VSV) is an enveloped minus-strand RNA virus belonging to the genus Becyclovirus in the family Rhabdoviridae. This virus is an arbovirus that can infect insects, cattle, horses, and pigs. The VSV genome encodes five structural proteins, including a single transmembrane glycoprotein (G). The glycoprotein is a classic type I membrane glycoprotein having an amino-terminal signal peptide, an ectodomain of approximately 450 amino acids, a single alpha-helical transmembrane segment, and a small intraviral carboxy-terminal domain. The signal peptide is cleaved within the lumen of the endoplasmic reticulum, and the native glycoprotein consists of the ectodomain, transmembrane domain, and intraviral domain.

[0004] G plays a crucial role in the early stages of viral infection (Molecular and Cellular Aspects of Rhabdovirus Entry. Viruses 4, 117-139.) (This document is incorporated herein in its entirety by reference). Firstly, it is involved in viral attachment to specific receptors. After binding, the virion enters the cell via the clathrin-mediated endocytosis pathway. In the acidic environment of the endocytic vesicle, G induces fusion of the viral membrane with the endosomal membrane, thereby releasing the genome into the cytoplasm for subsequent infection steps. Fusion is catalyzed by a large, low-pH-induced structural transition from the pre-fusion conformation to the post-fusion conformation (both trimers) (Roche, S., Bressanelli, S., Rey, FA, 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, FA, Gaudin, Y., and Bressanelli, S. (2007). Structure of the prefusion form of the vesicular stomatitis virus glycoprotein G. Science 315, 843-848; each of these is incorporated herein by reference in whole).

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

[0006] Low-density lipoprotein receptors (LDL-R) and other members of this receptor family have been shown to function 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 incorporated herein by reference in its entirety). VSV-G can be used to pseudotype other viruses, and VSV-G pseudotyped lentiviruses (VSV-G-LV) exhibit the same broad tropism as VSV. However, this broad tropism may inhibit selective targeting of specific cell types. Therefore, there is a need for a modified (mutant or variant) VSV-G protein that can be used to pseudotype a virus that inhibits binding to the LDL receptor. This embodiment satisfies these needs and other needs.

[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 primarily expressed on the surface of most thymocytes, more than 85% of peripheral blood T lymphocytes, and natural killer cells. Embodiments disclosed herein provide polypeptides and antibodies against CD7, compositions containing them, and their uses.

[0008] CD8 (differentiation cluster 8) is a transmembrane glycoprotein that is a specific marker for subclasses of T cells (including cytotoxic T cells). While not wishing to be bound by any particular theory, CD8 is assembled either as a heterodimer of CD8 alpha and CD8 beta subunits or as a CD8 alpha homodimer. The assembled dimeric CD8 complex functions as a co-receptor with the T cell receptor (TCR) to recognize antigen presentation by MHC class I cells. CD8 plays a role in T cell development and activation of mature T cells. Changes in T cell localization may reflect the progression of the immune response and may occur over time. Embodiments disclosed herein provide polypeptides and antibodies against CD8, compositions comprising them, and their uses. [Overview of the project]

[0009] In some embodiments, VSV-G polypeptides are provided, which contain mutations corresponding to mutations at positions 8, 9, 10, 47, 50, 51, 179, 180, 182, 183, 184, 209, 347, 350, 352, 353, 354 of SEQ ID NO: 2, or combinations thereof.

[0010] In some embodiments, mutations at positions 8, 9, 10, 47, 50, 51, 179, 180, 182, 183, 184, 209, 347, 350, 352, 353, 354 of SEQ ID NO: 2, or combinations thereof, include substitutions to charged amino acids.

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

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

[0013] In some embodiments, a VSV-G polypeptide is provided that comprises the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, and further comprises mutations corresponding to mutations at positions 8, 9, 10, 47, 50, 51, 179, 180, 182, 183, 184, 209, 347, 350, 352, 353, 354, or combinations 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 that comprises the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23, and further comprises mutations corresponding to mutations at positions 8, 9, 10, 47, 50, 51, 179, 180, 182, 183, 184, 209, 347, 350, 352, 353, 354, or combinations thereof, of SEQ ID NO: 22 or SEQ ID NO: 23.

[0015] In some embodiments, viral particles comprising the VSV-G polypeptide provided herein are provided.

[0016] In some embodiments, the virus particle further includes a targeting portion provided herein.

[0017] In some embodiments, the virus particles are pseudotyped lentiviruses provided herein.

[0018] In some embodiments, the virus particle further comprises a nucleic acid molecule encoding the heterogeneous molecule of interest provided herein.

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

[0020] In some embodiments, the chimeric antigen receptor includes an antigen-binding domain that binds to CD20, as provided herein.

[0021] In some embodiments, the targeting portion is coupled to the CD7 as provided herein.

[0022] In some embodiments, the targeting portion is coupled to the CD8 as provided herein.

[0023] In some embodiments, methods are provided for delivering heterologous molecules to target cells, and the methods involve the cells a) The VSV-G polypeptide provided herein, b) A targeting portion that binds to target cells, c) Including contact between a nucleic acid molecule encoding a heterologous molecule and a viral vector containing the above.

[0024] In some embodiments, methods are provided for delivering heterologous molecules to target cells in a subject, and the method is a) The VSV-G protein provided herein, b) A targeting portion that binds to target cells, c) Including administering a viral vector containing nucleic acid molecules encoding heterologous molecules to the target.

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

[0026] In some embodiments, a method for treating cancer in a subject is provided, and the method is a) The VSV-G protein provided herein, b) A targeting portion that binds to target cells, c) Including administering a viral vector containing nucleic acid molecules encoding heterologous molecules to the target.

[0027] In some embodiments, the heterologous molecule is a chimeric antigen receptor provided herein. [Brief explanation of the drawing]

[0028] [Figure 1A] The crystal structure of VSV-G bound to LDL-R is shown. Figure 1A shows the crystal structure of VSV-G bound to CR3 of LDL-R. [Figure 1B] Figure 1B shows the crystal structure of VSV-G bound to LDL-R.

[0029] [Figure 2A] This shows the effect of adding negatively charged amino acids to VSV-G. The LDL-R bond interacts with innate tropism and fusion. Figure 2A shows the titration of the VSV-G construct on SupT1 cells. [Figure 2B] This shows the effect of adding negatively charged amino acids to VSV-G. The LDL-R bond interacts with the innate tropism and fusion properties. Figure 2B shows the functional titer of each construct calculated from the titration in Figure 2A.

[0030] [Figure 3-1] This shows the alignment of ectodomains of different VSV-G proteins from different strains. [Figure 3-2] This shows the alignment of ectodomains of different VSV-G proteins from different strains. [Figure 3-3] This shows the alignment of ectodomains of different VSV-G proteins from different strains. [Figure 3-4] This shows the alignment of ectodomains of different VSV-G proteins from different strains.

[0031] [Figure 4]This study demonstrates the effects of various VSV-G mutations on the serum stability of viral constructs combined with a CD7 binder.

[0032] [Figure 5] This study demonstrates the effects of various VSV-G mutations on the serum stability of viral constructs combined with a CD7 binder.

[0033] [Figure 6A] Flow cytometry data of human PBMCs transduced with exemplary vectors containing the CD7 binder disclosed herein are shown. [Figure 6B] Flow cytometry data of human PBMCs transduced with exemplary vectors containing the CD7 binder disclosed herein are shown. [Figure 6C] Flow cytometry data of human PBMCs transduced with exemplary vectors containing the CD7 binder disclosed herein are shown. [Figure 6D] Flow cytometry data of human PBMCs transduced with exemplary vectors containing the CD7 binder disclosed herein are shown. [Figure 6E] Flow cytometry data of human PBMCs transduced with exemplary vectors containing the CD7 binder disclosed herein are shown. [Figure 6F] Flow cytometry data of human PBMCs transduced with exemplary vectors containing the CD7 binder disclosed herein are shown. [Figure 6G] Flow cytometry data of human PBMCs transduced with exemplary vectors containing the CD7 binder disclosed herein are shown. [Figure 6H] Flow cytometry data of human PBMCs transduced with exemplary vectors containing the CD7 binder disclosed herein are shown. [Figure 6I] Flow cytometry data of human PBMCs transduced with exemplary vectors containing the CD7 binder disclosed herein are shown. [Figure 6J] Flow cytometry data of human PBMCs transduced with exemplary vectors containing the CD7 binder disclosed herein are shown. [Figure 6K] Flow cytometry data of human PBMCs transduced with exemplary vectors containing the CD7 binder disclosed herein are shown. [Figure 6L] Flow cytometry data of human PBMCs transduced with exemplary vectors containing the CD7 binder disclosed herein are shown.

[0034] [Figure 6M] Flow cytometry data of human PBMCs transduced with exemplary vectors containing the CD7 binder disclosed herein are shown.

[0035] [Figure 7A] Flow cytometry data of non-human primate PBMCs transduced with exemplary vectors containing the CD7 binder disclosed herein are shown. [Figure 7B] Flow cytometry data of non-human primate PBMCs transduced with exemplary vectors containing the CD7 binder disclosed herein are shown. [Figure 7C] Flow cytometry data of non-human primate PBMCs transduced with exemplary vectors containing the CD7 binder disclosed herein are shown. [Figure 7D] Flow cytometry data of non-human primate PBMCs transduced with exemplary vectors containing the CD7 binder disclosed herein are shown. [Figure 7E] Flow cytometry data of non-human primate PBMCs transduced with exemplary vectors containing the CD7 binder disclosed herein are shown. [Figure 7F] Flow cytometry data of non-human primate PBMCs transduced with exemplary vectors containing the CD7 binder disclosed herein are shown. [Figure 7G]Flow cytometry data of non-human primate PBMCs transduced with exemplary vectors containing the CD7 binder disclosed herein are shown. [Figure 7H] Flow cytometry data of non-human primate PBMCs transduced with exemplary vectors containing the CD7 binder disclosed herein are shown. [Figure 7I] Flow cytometry data of non-human primate PBMCs transduced with exemplary vectors containing the CD7 binder disclosed herein are shown. [Figure 7J] Flow cytometry data of non-human primate PBMCs transduced with exemplary vectors containing the CD7 binder disclosed herein are shown. [Figure 7K] Flow cytometry data of non-human primate PBMCs transduced with exemplary vectors containing the CD7 binder disclosed herein are shown. [Figure 7L] Flow cytometry data of non-human primate PBMCs transduced with exemplary vectors containing the CD7 binder disclosed herein are shown.

[0036] [Figure 7M] Flow cytometry data of non-human primate PBMCs transduced with exemplary vectors containing the CD7 binder disclosed herein are shown.

[0037] [Figure 8A] Flow cytometry data of human PBMCs transduced with exemplary vectors containing the CD8 binder disclosed herein are shown.

[0038] [Figure 8B] Flow cytometry data of non-human primate PBMCs transduced with exemplary vectors containing the CD8 binder disclosed herein are shown.

[0039] [Figure 9A]This specification shows GFP or CAR transduction of SupT1 cells using VSV-G pseudotyped lentiviral particles possessing the CD7 or CD8 binder provided herein. Figure 9A shows GFP transduction. [Figure 9B] This specification shows GFP or CAR transduction of SupT1 cells using VSV-G pseudotyped lentiviral particles possessing the CD7 or CD8 binder provided herein. Figure 9B shows CAR transduction.

[0040] [Figure 10] Figure 10A shows the ability of VSV-G* pseudotyped lentivirus particles possessing the CD7 binder to transduce SupT1 cells, as well as human and non-human primate PBMCs. Figure 10B shows cell transduction in the absence of the CD7 binder. Figure 10C shows transduction of human and non-human primate PBMCs in terms of MOI calculated from SupT1 titration. VSV-G* represents the VSV-G polypeptide containing I182E, T214N, and T352A, which corresponds to the mature polypeptide of SEQ ID NO: 23 or SEQ ID NO: 25 (with I196E, T230N, and T368A mutations (with leader sequences and adjusted numbering)).

[0041] [Figure 11A] This shows off-target transduction of CD7 binder-containing VSV-G* pseudotyped lentiviral particles in a panel of B cell lines compared to control SupT1 cells. Figure 11A shows GFP transduction data. [Figure 11B] This shows off-target transduction of CD7 binder-containing VSV-G* pseudotyped lentiviral particles in a panel of B cell lines compared to control SupT1 cells. Figure 11B shows data for CAR20-T2A-GFP transduction. VSV-G* refers to the VSV-G polypeptide, including the I182E, T214N, and T352A mutations provided herein.

[0042] [Figure 12A]VSV-G* pseudotyped lentiviral particles utilizing the CD7 binder and CD20-CAR transgene provided herein demonstrate the ability to kill Daudi lymphoma cells (Figure 12A) or Raji lymphoma cells (Figure 12B). The CAR20 constructs utilized antigen-binding domains including rituximab or CD20AB1 SEQ ID NO: 75 or 76, as provided herein. [Figure 12B] VSV-G* pseudotyped lentiviral particles utilizing the CD7 binder and CD20-CAR transgene provided herein demonstrate the ability to kill Daudi lymphoma cells (Figure 12A) or Raji lymphoma cells (Figure 12B). The CAR20 constructs utilized antigen-binding domains including rituximab or CD20AB1 SEQ ID NO: 75 or 76, as provided herein.

[0043] [Figure 13A] VSV-G* pseudotyped lentiviral particles utilizing the CD7 binder and CD20-CAR transgene provided herein demonstrate the ability to deplete B cells in vivo in huCD34 NSG mice. B cells were detected by evaluation of CD20 (Figure 13A) or CD19 (Figure 13B). [Figure 13B] VSV-G* pseudotyped lentiviral particles utilizing the CD7 binder and CD20-CAR transgene provided herein demonstrate the ability to deplete B cells in vivo in huCD34 NSG mice. B cells were detected by evaluation of CD20 (Figure 13A) or CD19 (Figure 13B).

[0044] [Figure 14A] VSV-G* pseudotyped lentiviral particles utilizing the CD7 binder and CD20-CAR transgene provided herein demonstrate the ability to prevent tumorigenesis in vivo. Figure 14A shows the experimental design. [Figure 14B]VSV-G* pseudotyped lentiviral particles utilizing the CD7 binder and CD20-CAR transgene provided herein demonstrate the ability to prevent tumor formation in vivo. Figure 14B shows that mice treated with the iv lentiviral particles provided herein before Raji tumor injection had significantly lower tumor burdens than mice treated with the control (GFP) vector or untreated mice. Tumor burden measured by IVIS imaging.

[0045] [Figure 15A] The VSV-G* pseudotyped lentiviral particles utilizing the CD7 binder and CD20-CAR transgene provided herein exemplify the ability to eliminate established Raji tumors in vivo. Figure 15A shows the experimental design. [Figure 15B] The VSV-G* pseudotyped lentiviral particles utilizing the CD7 binder and CD20-CAR transgene provided herein exemplify the ability to eliminate established Raji tumors in vivo. Figure 15B shows that mice treated with the iv lentiviral particles provided herein 6 days after Raji tumor injection had their tumor load reduced to below the detection limit. Tumor load measured by IVIS imaging.

[0046] [Figure 16] We present pilot experiments combining I182E with both I347G and T352E, or with I182E in combination with T352Q / E, thus demonstrating a possible low level of additive benefit for further deformation. [Modes for carrying out the invention]

[0047] This specification provides mutant VSV-G proteins that can be used, for example, to pseudotype viruses such as lentiviruses. In some embodiments, pseudotyped virus-like particles are pseudotyped using viral glycoproteins of bullous stomatitis New Jersey virus strain, bullous stomatitis Indiana virus strain, bullous stomatitis Aragoas virus strain, bullous stomatitis Maraba virus strain, or bullous stomatitis Karajas virus strain.

[0048] Pseudotyped viruses containing the mutant VSV-G protein can be used in conjunction with a targeting moiety to facilitate fusion of the pseudotyped virus with specific cells or tissues based on the expression of targets on those cells or tissues.

[0049] Unless otherwise defined, all technical and scientific terms have the same meaning as they would be generally understood by those skilled in the art in the field to which the disclosed embodiments belong.

[0050] As used herein, the terms "a" or "an" mean "at least one" or "one or more" unless the context clearly indicates otherwise.

[0051] Where used herein, the term “about” means that a number is an approximation and small variations will not significantly affect the implementation of the disclosed embodiment. Where numerical limitations are used, unless otherwise indicated by the context, “about” means that the number may vary by ±10% and remain within the range of the disclosed embodiment. Furthermore, where the phrase “about x to y” is used, the term “about” can be used interchangeably with the phrase “about x to y” unless both x and y are modified to indicate a different context.

[0052] When used herein in relation to T cells, "activation" refers to a state of T cells that have been sufficiently stimulated to induce detectable cell proliferation. Activation may also be associated with induced cytokine production and detectable effector function. The term "activated T cell" refers, among other things, to a T cell undergoing cell division.

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

[0054] As used herein, the term “antigen” is defined as a molecule that elicits an immune response. This immune response may involve antibody production, activation of cells with specific immunological capabilities, or both. Those skilled in the art will understand that virtually any macromolecule, including proteins or peptides, can function as an antigen. The term “antigen” may also refer to a molecule to which an antibody or antibody-like molecule can bind, or to which an antibody or antibody-like molecule recognizes.

[0055] The terms “antibody molecule,” “antibody,” or “antigen-binding domain,” when used herein, refer to a polypeptide, such as an immunoglobulin chain or fragment thereof, comprising at least one functional immunoglobulin variable domain sequence. Antibody molecules encompass antibodies (e.g., full-length antibodies) and antibody fragments. In some embodiments, an antibody molecule includes 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 a normal immunoglobulin gene fragment recombination process. In embodiments, an antibody molecule refers to an immunologically active antigen-binding portion of an immunoglobulin molecule, such as an antibody fragment. An antibody fragment, such as a functional fragment, includes a portion of an antibody, such as Fab, Fab', F(ab')2, F(ab)2, a variable fragment (Fv), a domain antibody (dAb), or a single-chain variable fragment (scFv). A functional antibody fragment binds to the same antigen recognized by an intact (e.g., full-length) antibody. The terms “antibody fragment” or “functional fragment” also include isolated fragments consisting of variable regions, e.g., “Fv” fragments consisting of heavy and light chain variable regions, or recombinant single-chain polypeptide molecules (“scFv proteins”) in which light and heavy chain variable regions are linked by a peptide linker. In some embodiments, an antibody fragment does not include an Fc fragment or a portion of the antibody that does not have antigen-binding activity, such as a single amino acid residue. Exemplary antibody molecules include full-length antibodies and antibody fragments, e.g., dAb (domain antibodies), single-chain, Fab, Fab', and F(ab')2 fragments, and single-chain variable fragments (scFv).

[0056] The term "antibody molecule" encompasses both the entire domain or single-domain antibody, or its antigen-binding fragment, which may also be referred to as "sdAb" or "VHH". Domain antibodies include either VH or VL, which can function as independent antibody fragments. Furthermore, domain antibodies include heavy-chain-only antibodies (HCAb). Domain antibodies also contain the CH2 domain of IgG as a basal scaffold on which the CDR loop is implanted. They can also generally be defined as polypeptides or proteins containing an amino acid sequence consisting 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 synthesized using techniques well known in the art. The numbering of amino acid residues in sdAb or polypeptides follows the general numbering of VH domains as presented by Kabat et al. ("Sequence of proteins of immunological interest," US Public Health Services, NIH Bethesda, MD, Publication No. 91 (incorporated herein by reference)). According to this numbering, FR1 of sdAb contains amino acid residues from positions 1 to 30, CDR1 of sdAb contains amino acid residues from positions 31 to 36, FR2 of sdAb contains amino acid residues from positions 36 to 49, CDR2 of sdAb contains amino acid residues from positions 50 to 65, FR3 of sdAb contains amino acid residues from positions 66 to 94, CDR3 of sdAb contains amino acid residues from positions 95 to 102, and FR4 of sdAb contains amino acid residues from positions 103 to 113. Domain antibodies are also described in International Publication Nos. 2004041862 and 2016065323, each of which is incorporated herein by reference. Domain antibodies may be targeted moieties as described herein.

[0057] As used herein, unless otherwise indicated, an "antibody fragment" or "antigen-binding fragment" refers to an antigen-binding fragment of an antibody, i.e., an antibody fragment that retains the ability to specifically bind to an antigen bound by the full-length antibody, for example, a fragment that retains 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., scFv); nanobodies (single-domain antibodies); and multispecific antibodies formed from antibody fragments.

[0058] A "Fab fragment" consists of one light chain and the C

[0062] , ,

[0061] , H , H , 1 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] The "Fc" region contains two heavy chain fragments that include the C H 2 and C H 3 domains. The two heavy chain fragments are held together by two or more disulfide bonds and by hydrophobic interactions of the C H 3 domains.

[0060] A "Fab’ fragment" contains one light chain, the V H domain and the C H 1 domain, and a portion or fragment of one heavy chain that contains the region between the C <00XX007>1 domain and the C H 2 domain, such that two Fab’ fragments can form an interchain disulfide bond between the two heavy chains of the two Fab’ fragments to form an F(ab’)2 molecule.

[0061] An "F(ab’)2 fragment" contains two light chains and two heavy chains, and the heavy chains contain a portion of the constant region such that an interchain disulfide bond is formed between the two heavy chains between the C H 1 and the C H 2 domains. Thus, an F(ab’)2 fragment is composed of two Fab’ fragments held together by an interchain disulfide bond between the two heavy chains. <00XX007>

[0062] The "Fv region" includes variable regions from both the heavy and light chains, but lacks a steady-state region.

[0063] The term "single-chain Fv" or "scFv" antibody refers to the V of the antibody. H and V L This refers to antibody fragments containing domains, which are present in a single polypeptide chain. Generally, Fv polypeptides contain V that allows scFv to form the desired structure for antigen binding. H Domain and V L It further includes a polypeptide linker between the domains. For an overview of scFv, see Pluckthun (1994) The Pharmacology of Monoclonal Antibodies, vol. 113, Rosenburg and Moore eds. Springer-Verlag, New York, pp. 269-315. See also International Publication No. 88 / 01649 and U.S. Patents Nos. 4,946,778 and 5,260,203.

[0064] Antibody molecules can have single specificity (e.g., monovalent or bivalent), bivalent specificity (e.g., bivalent, trivalent, tetravalent, pentavalent, or hexavalent), triple specificity (e.g., trivalent, tetravalent, pentavalent, or hexavalent), or higher-order specificity beyond hexavalent (e.g., tetravalent) and / or higher-order valency. Antibody molecules can contain functional fragments of the light chain variable region and functional fragments of the heavy chain variable region, or the heavy chain and light chain can be fused into a single polypeptide.

[0065] Furthermore, antigens may be derived from recombinant DNA or genomic DNA. Those skilled in the art will understand that, where the term “antigen” is used herein, any DNA containing a nucleotide sequence or a partial nucleotide sequence encoding a protein that triggers an immune response, thus encoding an “antigen.” Furthermore, those skilled in the art will understand that antigens do not need to be encoded solely by the full-length nucleotide sequence of a gene. Furthermore, those skilled in the art will understand that antigens do not need to be encoded by a “gene” at all. It is readily apparent that antigens can be synthesized and produced or derived from biological samples. Such biological samples may include, but are not limited to, tissue samples, tumor samples, cells, or biological fluids.

[0066] In certain embodiments, the monoclonal antibodies described herein also include camelized single-domain antibodies. See, for example, Muyldermans et al. (2001) Trends Biochem. Sci. 26-230, Reichmann et al. (1999) J. Immunol. Methods 231:25, International Publication No. 94 / 04678, International Publication No. 94 / 25591, and U.S. Patent No. 6,005,079. In one embodiment, the present invention relates to two V with modifications such that a single-domain antibody is formed. H We provide single-domain antibodies containing the domain.

[0067] As used herein, the term “diabody” refers to a small antibody fragment having two antigen-binding sites, the fragment being the same polypeptide chain (V H -V L or V L -V H ) Light chain variable domain (V L ) connected to the heavy chain variable domain (V H) includes. By using a linker that is too short to allow pairing between two domains on the same chain, the domains are forced to pair with a complementary domain on another chain, creating two antigen-binding sites. Diabodies are described in detail, for example, European Patent No. 404,097, International Publication No. 93 / 11161, and Holliger et al. (1993) Proc. Natl. Acad. Sci. USA 90:6444-6448. For an overview of engineered antibody variants, see Holliger and Hudson (2005) Nat. Biotechnol. 23:1126-1136.

[0068] "Isolated antibody" refers to the purified state of the conjugated compound, and in such context, means that the molecule substantially contains no other biological molecules such as nucleic acids, proteins, lipids, carbohydrates, or other materials such as cell debris and growth media. In general, the term "isolated" is not intended to mean the complete absence of such materials, or the absence of water, buffer, or salt, unless present in amounts that substantially prevent the experimental or therapeutic use of the conjugated compound described herein.

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

[0070] As used herein, the term “humanized antibody” refers to a form of antibody that contains sequences derived from both human and non-human (e.g., mouse, rat) antibodies. Generally, a humanized antibody contains substantially all of at least one, typically two, variable domains, all or substantially all of the hypervariable loops corresponding to those of a non-human immunoglobulin, and all or substantially all of the framework (FR) region being a human immunoglobulin sequence. A humanized antibody may optionally contain at least a portion of the constant region (Fc) of a human immunoglobulin.

[0071] The term "fully human antibody" refers to an antibody containing only human immunoglobulin protein sequences. Fully human antibodies may contain mouse carbohydrate chains when produced in mice, in mouse cells, or in hybridomas derived from mouse cells. Similarly, "mouse antibody" refers to an antibody containing only mouse immunoglobulin sequences. Alternatively, fully human antibodies may contain rat carbohydrate chains when produced in rats, in rat cells, or in hybridomas derived from rat cells. Similarly, "rat antibody" refers to an antibody containing only rat immunoglobulin sequences.

[0072] In some embodiments, the basic antibody structural unit comprises a tetramer. Each tetramer contains two identical polypeptide chain pairs, each pair having one "light" (approximately 25 kDa) chain and one "heavy" chain (approximately 50-70 kDa). The amino-terminal portion of each chain contains a variable region of approximately 100-110 or more amino acids, primarily involved in antigen recognition. The carboxyl-terminal portion of the heavy chain may define a constant region, primarily involved in 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 the antibody isotypes are defined as IgM, IgD, IgG, IgA, and IgE, respectively. Within the light and heavy chains, the variable and constant regions are linked by a "J" region of approximately 12 or more amino acids, and the heavy chain also contains a "D" region of approximately 10 or more amino acids. For general information, please refer to Fundamental Immunology Ch.7 (Paul, W., ed., 2nd ed., Raven Press, NY (1989)).

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

[0074] Typically, both the heavy and light chain variable domains contain three hypervariable regions (also called complementarity determining regions, CDRs) located within a relatively conserved framework region (FR). The CDRs are usually aligned by the framework region, enabling binding to specific epitopes. Generally, from the N-terminus to the C-terminus, both the light and heavy chain variable domains contain FR1, CDR1, FR2, CDR2, FR3, CDR3, and FR4. The amino acid assignments to each domain are generally as follows: Sequences of Proteins of Immunological Interest, Kabat, et al.; National Institutes of Health, Bethesda, Md.; 5 th ed.;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 according to the definition of 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 involved in antigen binding. The hypervariable region is defined as amino acid residues derived from the “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 The CDR also includes residues from Health, Bethesda, Md. and / or the "hypervariable loop" (i.e., residues 26-32 (CDRL1), 50-52 (CDRL2), and 91-96 (CDRL3) in the light chain variable domain and residues 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 CDR also includes Lefranc MP. Unique database numbering system for immunogenetic analysis. Immunol CDRs can be referenced according to the IMGT system for identification described in Today (1997) 18:509. As used herein, the terms “framework” or “FR” residues refer to variable domain residues other than the hypervariable region residues defined herein as CDR residues. CDRs provide the majority of contact residues for antibody binding to an antigen or epitope. The CDRs of interest may be derived from the variable heavy and light chain sequences of a donor antibody and include analogues of naturally occurring CDRs, which also share or retain the same antigen-binding specificity and / or neutralizing ability as the donor antibodies from which they are derived.

[0076] As used herein, “specific binding,” “immune-specific binding,” or “immunely binding” means an antibody that binds to a given antigen with a much higher affinity than another antigen. In some embodiments, the antibody is 10 -7 Dissociation constants (K) less than or equal to M D ) binds a predetermined antigen, and such K D Its K is for binding to nonspecific antigens (e.g., BSA, casein, or another nonspecific polypeptide). D It is at least twice as small.

[0077] Methods for determining the specificity and affinity of mAbs by competitive inhibition can be found in Harlow, et al., Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, 1988; Colligan et al., eds., Current Protocols in Immunology, Greene Publishing Assoc. and Wiley Interscience, NY, (1992, 1993); and Muller, Meth. Enzymol. 92:589 601 (1983), and these references are incorporated herein by reference.

[0078] As used herein, the terms “individual,” “subject,” or “patient” are interchangeable and mean any animal, including mice, rats, other rodents, rabbits, dogs, cats, pigs, cattle, sheep, horses, or mammals such as primates like humans. In some embodiments, the subject is human. The “subject in need of it” refers to a subject identified as needing treatment for a condition to be treated and being treated with the specific intention of treating such condition. The condition may be, for example, any of the conditions described herein.

[0079] As used herein, the terms “comprising” (and any conjugations of “comprising,” such as “comprise,” “comprises,” and “comprised,” “having” (and any conjugations of “having,” such as “have,” and “has,” “has,” “having,” “having,” “having,” “having,” “having,” “having,” “having,” “having,” and any conjugations of “having,” such as “havings,” and “having,” or “having,” “having,” are open or non-restrictive and do not exclude any additional elements or steps of method not described herein. Any step or composition using the transitional phrase “comprise” or “comprising” can also be said to describe the same thing using the transitional phrase “consisting of” or “consists.”

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

[0081] As used herein, the terms “fused” or “linked” used with respect to proteins having different domains or heterologous sequences mean that such protein domains are connected to one another by either peptide bonds or other covalent bonds and become part of the same peptide chain. Domains or sections may be directly linked or fused to one another, or another domain or peptide sequence may be between two domains or sequences, and such sequences will still be considered fused or linked to one another. In some embodiments, the various domains or proteins provided herein may be directly linked or fused to one another, or a linker sequence, such as the glycine / serine sequence described herein, may link two domains together.

[0082] A "disease" is a state of animal health in which the animal is unable to maintain homeostasis, and if the disease is not improved, the animal's health will continue to deteriorate. In contrast, a "disorder" in animals is a state of health in which the animal can maintain homeostasis, but the animal's health is less desirable than when the disorder is absent. If left untreated, a disorder does not necessarily lead to a further decline in the animal's health.

[0083] "Effective dose" or "therapeutic effective dose" means the amount of a compound, formulation, substance, or composition described herein that is effective in achieving a particular biological outcome or in producing a therapeutic or preventive effect. Such outcomes may include, but are not limited to, an amount that causes a detectable level of immune cell activation when administered to a mammal, compared to immune cell activation detected in the absence of the composition. The immune response can be readily assessed by a great many methods recognized in the art. Those skilled in the art will understand that the amounts of compositions administered herein vary and can be readily determined based on several factors, such as the disease or condition being treated, the age, health status, and physical condition of the mammal being treated, the severity of the disease, and the specific compound being administered.

[0084] "Code" refers to the inherent property of a particular sequence of nucleotides in a polynucleotide (e.g., a gene, cDNA, or mRNA) to function as a template for the synthesis of other polymers and macromolecules having either a specific sequence of nucleotides (i.e., rRNA, tRNA, and mRNA) or a specific sequence of amino acids in a biological process, as well as the biological properties derived therefrom. Thus, a gene codes for a protein when the transcription and translation of the mRNA corresponding to that gene produce a protein in a cell or other biological system. Both the coding strand, whose nucleotide sequence is identical to the mRNA sequence and is usually provided in a sequence listing, and the non-coding strand, which is used as a template for the transcription of a gene or cDNA, can be said to code for a protein or other product of that gene or cDNA.

[0085] An "expression vector" refers to a vector containing recombinant polynucleotides that include an expression control sequence operably ligated to the nucleotide sequence to be expressed. An expression vector contains sufficient cis-acting elements for expression, and other elements for expression can be supplied by host cells or in an in vitro expression system. Expression vectors include all known in the art, such as cosmids, plasmids (e.g., naked or liposome-containing) and viruses (e.g., Sendai virus, lentivirus, retrovirus, adenovirus, and adeno-associated virus) that incorporate recombinant polynucleotides.

[0086] As used herein, the term “ex vivo” in relation to cells transfected, transfected, or transformed ex vivo means cells that are transfected, transfected, or transformed outside of the subject, i.e., cells that are removed from the subject before such cells are transfected, transfected, or transformed.

[0087] As used herein, “identity” refers to the identity of subunit sequences between two nucleic acid molecules or amino acid molecules, or between two polymer molecules, such as two polynucleotide molecules or polypeptide molecules. Two amino acid sequences are identical at the same position if, for example, the position in each of two polypeptide molecules is occupied by arginine. The identity or degree to which two amino acids or two nucleic acid sequences have the same residue at the same position in their alignment is often expressed as a percentage. The identity between two amino acids or two nucleic acid sequences is a linear function of the number of matching or identical positions. For example, if half of the positions in two sequences are identical, the two sequences are 50% identical, and if 90% of the positions (e.g., 9 out of 10) are matching or identical, the two amino acid sequences are 90% identical.

[0088] "Substantially identical" means that a polypeptide or nucleic acid molecule exhibits at least 50% identity with respect to a reference amino acid sequence (e.g., any one of the amino acid sequences described herein) or nucleic acid sequence (e.g., any one of the nucleic acid sequences described herein). In some embodiments, such sequences are at least 60%, 80%, or 85%, or 90%, 95%, or even 99%, identical at the amino acid level or nucleic acid level to a sequence used for comparison. Other identity percentages for specific sequences are described herein.

[0089] Sequence identity can be measured / determined using sequence analysis software (e.g., 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 program). 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. An exemplary method for determining the degree of identity can be used with the BLAST program, where probability scores from e3 to e100 indicate closely related sequences. In some embodiments, sequence identity is determined by using BLAST with default settings.

[0090] The scope of embodiments provided herein includes compositions comprising various proteins, which may, in some cases, include amino acid sequences having sequence identity with the amino acid sequences disclosed herein. Therefore, in certain embodiments, depending on the specific 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) with respect to the sequence numbers disclosed herein. In addition to these percentages, other identity percentages are provided herein. Polypeptide identity can be determined by a Smith-Waterman homology search algorithm, such as that implemented in the MPSRCH program (Oxford Molecular), using an affine gap search with a parameter gap opening penalty of -12 and a gap elongation penalty of =1.

[0091] These proteins may contain one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) conserved amino acid substitutions, i.e., substitutions of one amino acid with another amino acid having a related side chain, compared to the disclosed proteins. Genetically encoded amino acids are generally divided into four families: (1) acidic, i.e., aspartates and glutamates; (2) basic, i.e., lysine, arginine, and histidine; (3) nonpolar, i.e., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, and tryptophan; and (4) non-charged, i.e., glycine, asparagine, glutamine, cysteine, serine, threonine, and tyrosine. Phenylalanine, tryptophan, and tyrosine are sometimes classified together as aromatic amino acids. In general, single amino acid substitutions within these families do not have a significant impact on biological activity. The protein may have one or more single amino acid deletions (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) compared to the disclosed protein sequence. The protein may also have one or more insertions (e.g., each of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) (e.g., each of 1, 2, 3, 4, or 5 amino acids) compared to the disclosed protein sequence. The changes may also be non-conservative as provided herein.

[0092] As used herein, the term "in vivo" with respect to cells transfected, transformed, or otherwise transfected in vivo means that the cells are transfected, transformed, or otherwise transfected within the subject, and that the cells have not been removed from the subject before being transfected, transfected, or transformed.

[0093] "Isolated" means modified or extracted from its natural state. For example, nucleic acids or peptides that are naturally present in living animals are not "isolated," but the same nucleic acids or peptides that have been partially or completely separated from their naturally occurring coexisting materials are "isolated." Isolated nucleic acids or proteins can exist in a substantially purified form or in a non-natural environment, such as a host cell.

[0094] As used herein, "lentivirus" refers to a genus of retroviridae capable of infecting non-dividing cells. Non-exclusive examples of lentiviruses include HIV, SIV, and FIV. Lentivirus-derived vectors or virus-like particles can be used to transduce cells, deliver genes or other molecules, and express them intracellularly, either in vitro (ex vivo) or in vivo.

[0095] The term "modified," as used herein, means an altered state or structure of a molecule or cell provided herein. Molecules can be modified in many ways, including chemical, structural, and functional modifications such as mutation, substitution, insertion, or deletion (e.g., internal deletion cleavage). Cells can be modified by the introduction of nucleic acids or the expression of heterologous proteins.

[0096] As used herein, the term “modulation” means mediating an increase or decrease in the response level of a subject compared to the response level of the subject in the absence of the treatment or compound, and / or compared to the response level of an otherwise identical but untreated subject. This term includes mediating a beneficial therapeutic response in a subject such as a human by disrupting and / or influencing a natural signal or response.

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

[0098] Unless otherwise specified, "nucleotide sequences encoding an amino acid sequence" includes all nucleotide sequences that encode the same amino acid sequence, including degenerate versions of each other. The phrase "nucleotide sequence encoding a protein or RNA" may include introns to the extent that a nucleotide sequence encoding a protein may contain introns in several versions.

[0099] Nipah virus (NiV) is a member of the genus Henipavirus in the family Paramyxoviridae. Nipah virus is a negative-strand polar enveloped virus with a non-segmented RNA genome consisting of a helical nucleocapsid. Two strains of Nipah virus exist, but are not limited to, the Malaysian (MY) strain and the Bangladesh (BD) strain.

[0100] The term "oligonucleotide" typically refers to a short polynucleotide. If a nucleotide sequence is represented by a DNA sequence (i.e., A, T, C, G), it is understood that this also provides a corresponding RNA sequence (i.e., A, U, C, G) where "T" is replaced by "U".

[0101] Parenteral administration of the composition includes, for example, subcutaneous (sc), intravenous (iv), intramuscular (im), or intrasternal injection, or infusion techniques.

[0102] As used herein, the term “polynucleotide” is defined as a chain of nucleotides. Furthermore, nucleic acids are polymers of nucleotides. Therefore, as used herein, the terms “nucleic acid” and “polynucleotide” are interchangeable. As used herein, polynucleotides include all nucleic acid sequences obtained by any method available in the art, including, but not limited to, recombinant methods, i.e., cloning of nucleic acid sequences from recombinant libraries or cell genomes using cloning techniques and PCR, etc.

[0103] As used herein, the terms “peptide,” “polypeptide,” and “protein” are interchangeable and refer to compounds composed of multiple amino acid residues covalently linked by peptide bonds. As used herein, this term refers to both short chains, also commonly referred to in the art as peptides, oligopeptides, and oligomers, and long chains, of which there are many types, commonly referred to in the art as proteins. Polypeptides include, for example, biologically active fragments, substantially homologous polypeptides, oligopeptides, homodimers, heterodimers, polypeptide variants, modified polypeptides, derivatives, analogs, and fusion proteins. Polypeptides include native peptides, recombinant peptides, synthetic peptides, or combinations thereof.

[0104] As used herein, the term “variant,” when used in reference to a polynucleotide or polypeptide sequence, means that a variant has one or more changes compared to the reference sequence being compared. Changes may be mutations (substitutions), deletions, or insertions. Variants may include conserved or non-conserved mutations. For example, a variant VSV-G polypeptide is a VSV-G polypeptide that has one or more changes compared to a reference VSV-G polypeptide. Various reference VSV-G polypeptides are provided herein. In some embodiments, a variant includes mutations that modify uncharged residues to charged residues. Non-limiting examples of such variants are provided herein. In some embodiments, a variant has one, two, three, four, five, six, seven, eight, nine, or ten changes. An insertion of a consecutive number of amino acids is considered one change. For example, if the peptide “GGG” is inserted into a sequence to create a variant without changing the residue at the N or C terminus of the insertion, this is considered one change. However, if three consecutive amino acids in the reference sequence change to "GGG", this is considered three changes (mutations).

[0105] The terms “pseudotype” or “pseudotyped viral particle,” as used herein, refer to viral particles having glycoproteins derived from another virus that has a viral vector encoding an envelope or envelope glycoprotein from a virus different from the parent virus. Thus, the host range of the vector particle can be expanded or modified depending on the type of cell surface receptor used by the glycoprotein. For example, a virus may be pseudotyped with the VSV-G variant protein provided herein, or other viral glycoproteins such as those provided herein.

[0106] The terms “pseudovirus particles” and “pseudovirus-like particles” are synonymous with each other as used herein, unless otherwise specified.

[0107] The terms “virus particle” and “pseudovirus particle” are synonymous with each other as used herein, unless otherwise specified.

[0108] Where used herein in relation to antibodies, the term “specifically binds” means that an antibody recognizes a particular antigen but substantially does not recognize or bind to other molecules in the 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. However, such interspecies reactivity does not in itself change the antibody’s classification as specific. In another example, an antibody that specifically binds to an antigen may also bind to different alleles of the antigen. However, such cross-reactivity does not in itself change the antibody’s classification as specific. In some cases, the term “specifically binds” or “specifically binds” can be used in relation to the interaction of an antibody, protein, or peptide with a second chemical species, meaning that the interaction depends on the presence of a specific structure on the chemical species (e.g., an antigenic determinant or epitope). For example, an antibody generally recognizes and binds to a specific protein structure rather than a protein. If an antibody is specific to epitope “A”, then in a reaction involving labeled “A” and the antibody, the presence of a molecule containing epitope A (or unlabeled free A) will reduce the amount of labeled A that binds to the antibody. In some embodiments, the targeting moieties described herein, which can be used to target viral particles containing mutant VSV-G proteins, are capable of specifically binding to those targets.

[0109] The term "subject" includes living organisms, including organisms (e.g., mammals) from which an immune response can be induced. As used herein, "subject" or "patient" may be human or a non-human mammal. Non-human mammals include, for example, livestock and pets such as sheep, cattle, pigs, dogs, non-human primates, cats, and mouse mammals. In some embodiments, the subject is human.

[0110] As used herein, “therapeutic” means treatment and / or prevention. Therapeutic effects are obtained by suppression, remission, or eradication of the disease state.

[0111] As used herein, the terms “transfected,” “transformed,” or “transduced” refer to the process by which an exogenous nucleic acid is transferred to or introduced into a cell. A “transfected,” “transformed,” or “transduced” cell is a cell that has been transfected, transformed, or transduced with an exogenous nucleic acid. Cells include primary target cells and their offspring. In some embodiments, transfection, transformation, or transduction is performed or carried out in vivo.

[0112] As used herein, “treating” a disease means reducing the frequency or severity of at least one sign or symptom of a disease or disorder experienced by a subject. As used herein, “inhibiting,” “treating,” or “curing” also include delaying the onset of symptoms associated with a disorder and / or reducing the severity of symptoms of such disorder. These terms further include improving existing uncontrolled or undesirable symptoms, preventing additional symptoms, and improving or preventing the underlying cause of such symptoms. Accordingly, these terms indicate that a beneficial outcome has been given to a vertebrate subject that has a disorder, disease or symptom, or is likely to develop such a disorder, disease or symptom.

[0113] A "vector" is a composition comprising isolated nucleic acids that encode a protein or 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 virus vectors, adenovirus vectors, adeno-associated virus vectors, retroviral vectors, and lentiviral vectors.

[0114] The "carrier" or "delivery vehicle" comprises viral particles, viruses, polylysine compounds, and liposomes, which facilitate the transfer of nucleic acids into cells. The carrier or delivery vehicle can also be used to deliver proteins or peptides to cells.

[0115] Scope: Throughout this disclosure, various aspects of the embodiments can be expressed in the form of a range. It should be understood that the range form is for convenience and brevity only and should not be interpreted as a definitive limitation. Therefore, the range should be considered to specifically disclose all possible subranges and the individual numbers within those ranges. For example, a range such as 1 to 6 should be considered to specifically disclose subranges such as 1 to 3, 1 to 4, 1 to 5, 2 to 4, 2 to 6, 3 to 6, and the individual numbers within those ranges, such as 1, 2, 2.7, 3, 4, 5, 5.3, and 6. This applies regardless of the width of the range. Unless otherwise explicitly stated, the disclosed range includes the endpoints of that range.

[0116] While not bound by any particular theory, the embodiments provided herein have been found to demonstrate that mutant VSV-G proteins containing a mutation at position 182 can be used to pseudotype the virus and transduce cells when the virus contains a targeting moiety. Mutations to charged residues inhibit or reduce the affinity of VSV-G to its native co-receptor, LDL-R. Additional mutations to charged residues at other amino acid positions within the VSV-G protein have been tested for their ability to reduce the affinity of VSV-G to its native co-receptor, LDL-R. In some embodiments, the provided mutant VSV-G proteins can be used to transduce target cells and deliver heterologous molecules to targeted cells.

[0117] In some embodiments, a VSV-G protein is provided that contains a mutation at position 198 compared to SEQ ID NO: 1, or at position 182 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 MKCLLYLAFLFIGVNC (SEQ ID NO: 26), shown at the N-terminus of SEQ ID NO: 1, is cleaved, leaving the protein of SEQ ID NO: 2 intact. Thus, the mutation may be mentioned in the context of SEQ ID NO: 2, but should be understood to also occur in the context of SEQ ID NO: 1, which contains the leader sequence, and therefore would be at a position number 16 more than the position listed for SEQ ID NO: 2. In some embodiments, the mutation inhibits or reduces the binding of the VSV-G protein to the LDL receptor (LDL-R). In some embodiments, the mutation is the I182D mutation compared to SEQ ID NO: 2. In some embodiments, the mutation is the I182E mutation compared to SEQ ID NO: 2.

[0118] In some embodiments, a VSV-G protein is provided with a mutation at position 198 compared to SEQ ID NO: 10, or at position 182 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 MLSYLIFALVVSPILG (SEQ ID NO: 27), shown at the N-terminus of SEQ ID NO: 10, is cleaved, leaving the protein of SEQ ID NO: 11 intact. Thus, the mutation may be mentioned in the context of SEQ ID NO: 11, but should be understood to also occur in the context of SEQ ID NO: 10, which contains the leader sequence, and therefore would be at a position number 16 higher than the position enumerated for SEQ ID NO: 11. In some embodiments, the mutation inhibits or reduces the binding of the VSV-G protein to the LDL receptor (LDL-R). In some embodiments, the mutation is the T182D mutation compared to SEQ ID NO: 11. In some embodiments, the mutation is the T182E mutation compared to SEQ ID NO: 11.

[0119] In some embodiments, VSV-G proteins are provided that contain a mutation at position 198 compared to SEQ ID NO: 12, or at position 182 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 MLRLFLFCFLALGAHS (SEQ ID NO: 28), shown at the N-terminus of SEQ ID NO: 12, is cleaved, leaving the protein of SEQ ID NO: 13 intact. Thus, the mutation may be mentioned in the context of SEQ ID NO: 13, but should be understood to also occur in the context of SEQ ID NO: 12, which contains the leader sequence, and therefore would be at a position number 16 higher than the position enumerated for SEQ ID NO: 13. In some embodiments, the mutation inhibits or reduces the binding of the VSV-G protein to the LDL receptor (LDL-R). In some embodiments, the mutation is the A182D mutation compared to SEQ ID NO: 13. In some embodiments, the mutation is the A182E mutation compared to SEQ ID NO: 13.

[0120] In some embodiments, a VSV-G protein is provided with a mutation at position 203 compared to SEQ ID NO: 14, or at position 182 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 MKMKMVIAGLILCIGILPAIG (SEQ ID NO: 29), shown at the N-terminus of SEQ ID NO: 14, is cleaved, leaving the protein of SEQ ID NO: 15 intact. Thus, the mutation may be mentioned in the context of SEQ ID NO: 15, but should be understood to also occur in the context of SEQ ID NO: 14, which contains the leader sequence, and therefore would be at a position number 21 higher than the position enumerated for SEQ ID NO: 15. In some embodiments, the mutation inhibits or reduces the binding of the VSV-G protein to the LDL receptor (LDL-R). In some embodiments, the mutation is the V182D mutation compared to SEQ ID NO: 15. In some embodiments, the mutation is the V182E mutation compared to SEQ ID NO: 15.

[0121] In some embodiments, a VSV-G protein is provided with a mutation at position 199 compared to SEQ ID NO: 16, or at position 182 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 MTPAFILCMLLAGSSWA (SEQ ID NO: 30), shown at the N-terminus of SEQ ID NO: 16, is cleaved, leaving the protein of SEQ ID NO: 17 intact. Therefore, the mutation may be mentioned in the context of SEQ ID NO: 17, but should be understood to also occur in the context of SEQ ID NO: 16, which contains the leader sequence, and thus would be a position number 17 higher than the position enumerated for SEQ ID NO: 17. In some embodiments, the mutation inhibits or reduces the binding of the VSV-G protein to the LDL receptor (LDL-R). In some embodiments, the mutation is the V182D mutation compared to SEQ ID NO: 17. In some embodiments, the mutation is the V182E mutation compared to SEQ ID NO: 17.

[0122] In some embodiments, a VSV-G protein is provided with a mutation at position 199 compared to SEQ ID NO: 18, or at position 182 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 MNFLLLTFIVLPLCSHA (SEQ ID NO: 31), shown at the N-terminus of SEQ ID NO: 18, is cleaved, leaving the protein of SEQ ID NO: 19 intact. Thus, the mutation may be mentioned in the context of SEQ ID NO: 19, but should be understood to also occur in the context of SEQ ID NO: 18, which contains the leader sequence, and therefore would be at a position number 17 higher than the position enumerated for SEQ ID NO: 19. In some embodiments, the mutation inhibits or reduces the binding of the VSV-G protein to the LDL receptor (LDL-R). In some embodiments, the mutation is the V182D mutation compared to SEQ ID NO: 19. In some embodiments, the mutation is the V182E mutation compared to SEQ ID NO: 19.

[0123] In some embodiments, a VSV-G protein is provided with a mutation at position 199 compared to SEQ ID NO: 20, or at position 182 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 MLVLYLLLSLLALGAQC (SEQ ID NO: 32), shown at the N-terminus of SEQ ID NO: 20, is cleaved, leaving the protein of SEQ ID NO: 21 intact. Thus, the mutation may be mentioned in the context of SEQ ID NO: 21, but should be understood to also occur in the context of SEQ ID NO: 20, which contains the leader sequence, and therefore would be at a position 17 more than the position listed for SEQ ID NO: 21. In some embodiments, the mutation inhibits or reduces the binding of the VSV-G protein to the LDL receptor (LDL-R). In some embodiments, the mutation is the I182D mutation compared to SEQ ID NO: 21. In some embodiments, the mutation is the I182E mutation compared to SEQ ID NO: 21.

[0124] Where used herein, when a polypeptide is said to have mutations compared to a reference sequence, such comparison is based on alignment, such as using BlastP, ClustalW, or ClutalOmega alignment software with default parameters. For example, position 182 can be found in SEQ ID NO: 2 and can also be found in comparison to other strains, as shown in Figure 3. Figure 3 shows cluster alignments of wild-type sequences of the ectodomains of various strains of the VSV-G protein. The residues in bold and underlined are the residues aligned to position 182 of SEQ ID NO: 2 in various strains. SEQ ID NO: 2 refers to the ectodomain of the VSV-G protein from the Indiana strain. SEQ ID NO: 11 refers to the ectodomain of the VSV-G protein from the New Jersey strain. SEQ ID NO: 13 refers to the ectodomain of the VSV-G protein from the Malaba strain. SEQ ID NO: 15 refers to the ectodomain of the VSV-G protein from the Karajas strain. SEQ ID NO: 17 refers to the extracellular domain of the VSV-G protein from the Alagoa strain. Sequence ID 19 refers to the ectodomain of the VSV-G protein from the Cocal strain. Sequence ID 21 refers to the ectodomain of the VSV-G protein from the Moreton strain. Therefore, the residue aligned at residue 182 compared to Sequence ID 2 can also be mutated as provided herein.

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

[0126] In some embodiments, the mutation at position 182 compared to SEQ ID NO: 2 is I182S, I182H, I182T, I182Q, or I182N. In some embodiments, the mutation at position 182 compared to SEQ ID NO: 11 is T182S, T182H, T182Q, or T182N. In some embodiments, the mutation at position 182 compared to SEQ ID NO: 13 is A182S, A182H, A182T, A182Q, or A182N. In some embodiments, the mutation at position 182 compared to SEQ ID NO: 15 is V182S, V182H, V182T, V182Q, or V182N. In some embodiments, the mutation at position 182 compared to SEQ ID NO: 17 is V182S, V182H, V182T, V182Q, or V182N. In some embodiments, the mutation at position 182 compared to SEQ ID NO: 19 is V182S, V182H, V182T, V182Q, or V182N. In some embodiments, the mutation at position 182 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] Mutations may be described with reference to SEQ ID NO: 1 or SEQ ID NO: 2, which are VSV-G proteins derived from the Indiana strain, but mutations can also be used in other strains of the VSV-G protein. For example, mutations can be produced in the VSV-G New Jersey strain, the VSV-G Malaba strain, the VSV-G Carajas strain, the VSV-G Alagoa strain, the VSV-G Kaukal strain, or the VSV-G Moreton strain. In some embodiments, each sequence is provided herein. Examples of these can be found, for example, in U.S. Patent Application Publication No. 20200216502, which is incorporated herein by reference. For example, the wild-type full-length or ectodomain of the VSV-G New Jersey strain is sequence number 10 and sequence number 11, respectively; the wild-type full-length or ectodomain of the VSV-G Malaba strain is sequence number 12 and sequence number 13, respectively; the wild-type full-length or ectodomain of the VSV-G Carajas strain is sequence number 14 and sequence number 15, respectively; the wild-type full-length or ectodomain of the VSV-G Alagoa strain is sequence number 16 and sequence number 17, respectively; the wild-type full-length or ectodomain of the VSV-G Kaukal strain is sequence number 18 and sequence number 19, respectively; or the wild-type full-length or ectodomain of the VSV-G Moreton strain is sequence number 20 and sequence number 21, respectively.

[0128] A VSV-G protein containing a mutation at position 182 compared to SEQ ID NO: 2 may also contain other mutations, such as those described in U.S. Patent Application Publication 2020 / 0216502 (which is incorporated herein by reference in its entirety). For example, a VSV-G protein may contain mutations at positions 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 shown at that position in SEQ ID NO: 2, except for Y. In some embodiments, the substitution at position 8 is by any amino acid different from the amino acid shown at that position in SEQ ID NO: 2, except for H. In some embodiments, the substitution at position 8 is by any amino acid different from the amino acid shown at that position in SEQ ID NO: 2, except for Q. In some embodiments, the substitution at position 8 is by any amino acid different from the amino acid shown at that position in SEQ ID NO: 2, except for 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, etc. In some embodiments, the substitution at position 8 is selected from H8A, H8I, H8V, H8L, etc.

[0130] In some embodiments, the substitution at position 209 is by any amino acid different from the amino acid shown at that position in SEQ ID NO: 2, except for H. In some embodiments, the substitution at position 209 is by any amino acid different from the amino acid shown at that position in SEQ ID NO: 2, except for Y. In some embodiments, the substitution at position 209 is by any amino acid different from the amino acid shown at that position in SEQ ID NO: 2, except for 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 any amino acid different from the amino acid shown at that position in SEQ ID NO: 2, except for K. In some embodiments, the substitution at position 47 is any amino acid different from the amino acid shown at that position in SEQ ID NO: 2, except for R. In some embodiments, the substitution at position 47 is any amino acid different from the amino acid shown at that position in SEQ ID NO: 2, except for 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 any amino acid different from the amino acid shown at that position in SEQ ID NO: 2, except for K. In some embodiments, the substitution at position 354 is any amino acid different from the amino acid shown at that position in SEQ ID NO: 2, except for R. In some embodiments, the substitution at position 354 is any amino acid different from the amino acid shown at that position in SEQ ID NO: 2, except for 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 354, or at both positions 47 and 354, independently substituted by A, G, F, N, or Q. In some embodiments, the substitution at position 47 or 354, or at both positions 47 and 354, is independently A, Q, or N.

[0134] In some embodiments, the VSV-G protein may contain mutations at positions 8, 47, 209, and / or 354. In some embodiments, the VSV-G protein may contain mutations at positions 8, 47, 209, and / or 354 provided herein. In some embodiments, the VSV-G protein may contain mutations at positions 8 and 47 provided herein. In some embodiments, the VSV-G protein may contain mutations at positions 8 and 209 provided herein. In some embodiments, the VSV-G protein may contain mutations at positions 8 and 354 provided herein. In some embodiments, the VSV-G protein may contain mutations at positions 47 and 209 provided herein. In some embodiments, the VSV-G protein may contain mutations at positions 47 and 354 provided herein. In some embodiments, the VSV-G protein may contain mutations at the position corresponding to position 209 and position 354 as provided herein. In some embodiments, the VSV-G protein may contain mutations at the position corresponding to position 8, position 47, and position 209 as provided herein. In some embodiments, the VSV-G protein may contain mutations at the position corresponding to position 8, position 47, and position 354 as provided herein. In some embodiments, the VSV-G protein may contain mutations at the position corresponding to position 8, position 209, and position 354 as provided herein. In some embodiments, the VSV-G protein may contain mutations at the position corresponding to position 47, position 209, and position 354 as provided herein.In some embodiments, the VSV-G protein may contain mutations at the position corresponding to position 8 provided herein, position 47 provided herein, position 209 provided herein, and position 354 provided herein.

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

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

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

[0138] In some embodiments, the protein contains 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, proteins containing a mutation at position 182 compared to SEQ ID NO: 11 may also contain other mutations, such as those described in U.S. Patent Application Publication No. 2020 / 0216502. For example, the VSV-G protein may contain mutations at positions similar to those at 8, 47, 209, and / or 354 of SEQ ID NO: 2. In some embodiments, mutations in SEQ ID NO: 11 at positions similar to those at 8, 47, 209, and / or 354 of SEQ ID NO: 2 are provided herein.

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

[0143] In some embodiments, proteins containing a mutation at position 182 compared to SEQ ID NO: 15 may also contain other mutations, such as those described in U.S. Patent Application Publication No. 2020 / 0216502. For example, the VSV-G protein may contain mutations at positions similar to those at 8, 47, 209, and / or 354 of SEQ ID NO: 2. In some embodiments, mutations in SEQ ID NO: 15 at positions similar to those at 8, 47, 209, and / or 354 of SEQ ID NO: 2 are provided herein.

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

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

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

[0147] In some embodiments, a protein containing a mutation at position 182 compared to SEQ ID NO: 2 is 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 to SEQ ID NO: 2 (or SEQ ID NO: 1 if a full-length protein is used). 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 the I182D or I182E mutation. In some embodiments, the mutation is I182D. In some embodiments, the mutation is the I182E mutation. In some embodiments, the mutation is the I182S, I182H, I182T, I182Q, or I182N mutation.

[0148] In some embodiments, VSV-G is provided, the protein comprising the amino acid sequence of SEQ ID NO: 2 having a mutation at position 182, and being 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 to SEQ ID NO: 2.

[0149] In some embodiments, a protein containing a mutation at position 182 compared to SEQ ID NO: 11 contains a mutation at position 182 and is 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 compared to SEQ ID NO: 11 (or SEQ ID NO: 10 if using the full-length protein). In some embodiments, the polypeptide contains a T182D or T182E mutation. In some embodiments, the VSV-G protein contains a T182S, T182H, T182Q, or T182N mutation.

[0150] In some embodiments, a protein containing a mutation at position 182 compared to SEQ ID NO: 13 contains a mutation at position 182 and is 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 compared to SEQ ID NO: 13 (or SEQ ID NO: 12 if using the full-length protein). In some embodiments, the polypeptide contains an A182D or A182E mutation. In some embodiments, the VSV-G protein contains an A182S, A182H, A182T, A182Q, or A182N mutation.

[0151] In some embodiments, a protein containing a mutation at position 182 compared to SEQ ID NO: 15 is at least 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 to SEQ ID NO: 15 (or SEQ ID NO: 14 if a full-length protein is used). In some embodiments, the polypeptide contains the V182D or V182E mutation. In some embodiments, the VSV-G protein contains the V182S, V182H, V182T, V182Q, or V182N mutation.

[0152] In some embodiments, a protein containing a mutation at position 182 compared to SEQ ID NO: 17 is 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 to SEQ ID NO: 17 (or SEQ ID NO: 16 if a full-length protein is used). In some embodiments, the polypeptide contains the V182D or V182E mutation. In some embodiments, the VSV-G protein contains the V182S, V182H, V182T, V182Q, or V182N mutation.

[0153] In some embodiments, a protein containing a mutation at position 182 compared to SEQ ID NO: 19 is 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 to SEQ ID NO: 19 (or SEQ ID NO: 18 if a full-length protein is used). In some embodiments, the polypeptide contains the V182D or V182E mutation. In some embodiments, the VSV-G protein contains the V182S, V182H, V182T, V182Q, or V182N mutation.

[0154] In some embodiments, a protein containing a mutation at position 182 compared to SEQ ID NO: 21 is at least 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 to SEQ ID NO: 21 (or SEQ ID NO: 20 if a full-length protein is used). In some embodiments, the polypeptide contains the I182D or I182E mutation. In some embodiments, the VSV-G protein contains the I182S, I182H, I182T, I182Q, or I182N mutation.

[0155] In some embodiments, as provided herein, a VSV-G protein is provided which 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 with the amino acid sequence of SEQ ID NO: 2, and further comprises mutations corresponding to mutations at positions 8, 9, 10, 47, 50, 51, 179, 180, 182, 183, 184, 209, 347, 350, 352, 353, 354, or any combination thereof, compared with SEQ ID NO: 2. In some embodiments, mutations at positions 8, 9, 10, 47, 50, 51, 179, 180, 182, 183, 184, 209, 347, 350, 352, 353, 354, or any combination thereof, compared to SEQ ID NO: 2, include substitutions to charged amino acids. In some embodiments, the charged amino acids are as provided herein. In some embodiments, the VSV-G protein includes substitutions at positions H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof, compared to SEQ ID NO: 2, as provided herein. In some embodiments, as provided herein, substitutions at the H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, R354 positions, or any combination thereof, compared to SEQ ID NO: 2, include substitutions to charged amino acids. In some embodiments, the charged amino acids are as provided herein. In some embodiments, substitutions at the H8 position compared to SEQ ID NO: 2 include H8D, H8E, H8K, or H8R substitutions. In some embodiments, substitutions at the N9 position compared to SEQ ID NO: 2 include N9D, N9E, N9K, or N9R substitutions. In some embodiments, substitutions at the Q10 position compared to SEQ ID NO: 2 include Q10D or Q10E substitutions. In some embodiments, substitutions at the K47 position compared to SEQ ID NO: 2 include K47D or K47E substitutions.In some embodiments, the substitution at position K50 compared to sequence number 2 includes the K50D or K50E substitution. In some embodiments, the substitution at position A51 compared to sequence number 2 includes the A51D, A51E, A51K, or A51R substitution. In some embodiments, the substitution at position S179 compared to sequence number 2 includes the S179D, S179E, S179K, or S179R substitution. In some embodiments, the substitution at position N180 compared to sequence number 2 includes the N180D, N180E, N180K, or N180R substitution. In some embodiments, the substitution at position I182 compared to sequence number 2 includes the I182D, I182E, I182K, or I182R substitution. In some embodiments, the substitution at position S183 compared to sequence number 2 includes the S183D, S183E, S183K, or S183R substitution. In some embodiments, substitutions at position M184 compared to sequence number 2 include the substitutions M184D, M184E, M184K, or M184R. In some embodiments, substitutions at position Y209 compared to sequence number 2 include the substitutions Y209D, Y209E, Y209K, or Y209R. In some embodiments, substitutions at position I347 compared to sequence number 2 include the substitutions I347D, I347E, I347K, or I347R. In some embodiments, substitutions at position T350 compared to sequence number 2 include the substitutions T350D, T350E, T350K, or T350R. In some embodiments, substitutions at position T352 compared to sequence number 2 include the substitutions T352D, T352E, T352K, or T352R. In some embodiments, substitutions at position E353 compared to sequence number 2 include the substitutions E353K or E353R. In some embodiments, the substitution at position R354 compared to SEQ ID NO: 2 includes the R354D or R354E substitution.

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

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

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

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

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

[0161] The mutant VSV-G protein can be used to pseudotype viruses, for example, lentiviruses, etc. Thus, in some embodiments, viral particles comprising the mutant VSV-G protein provided herein are provided. In some embodiments, the viral particles comprise a VSV-G protein having a mutation at position 198 compared to SEQ ID NO: 1. In some embodiments, a protein having a mutation at position 182 compared to SEQ ID NO: 2 is 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 to SEQ ID NO: 2 (or SEQ ID NO: 1 if a full-length protein is used) with the mutation at position 182. In some embodiments, the polypeptide contains the I182D or I182E mutation compared to SEQ ID NO: 2. In some embodiments, the VSV-G protein contains the I182S, I182H, I182T, I182Q, or I182N mutation.

[0162] In some embodiments, the viral particle contains a VSV-G protein with a mutation at position 198 compared to SEQ ID NO: 10. In some embodiments, the protein with a mutation at position 182 compared to SEQ ID NO: 11 contains a mutation at position 182 and is 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 compared to SEQ ID NO: 11 (or SEQ ID NO: 10 if a full-length protein is used). In some embodiments, the polypeptide contains a T182D or T182E mutation compared to SEQ ID NO: 11. In some embodiments, the VSV-G protein contains T182S, T182H, T182Q, or T182N mutations.

[0163] In some embodiments, the viral particle contains a VSV-G protein with a mutation at position 198 compared to SEQ ID NO: 12. In some embodiments, the protein with a mutation at position 182 compared to SEQ ID NO: 13 contains a mutation at position 182 and is 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 compared to SEQ ID NO: 13 (or SEQ ID NO: 12 if a full-length protein is used). In some embodiments, the polypeptide contains an A182D or A182E mutation compared to SEQ ID NO: 13. In some embodiments, the VSV-G protein includes A182S, A182H, A182T, A182Q, or A182N mutations.

[0164] In some embodiments, the viral particle contains a VSV-G protein with a mutation at position 203 compared to SEQ ID NO: 14. In some embodiments, the protein with a mutation at position 182 compared to SEQ ID NO: 15 contains a mutation at position 182 and is 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 compared to SEQ ID NO: 15 (or SEQ ID NO: 14 if a full-length protein is used). In some embodiments, the polypeptide contains a V182D or V182E mutation compared to SEQ ID NO: 15. In some embodiments, the VSV-G protein includes V182S, V182H, V182T, V182Q, or V182N mutations.

[0165] In some embodiments, the viral particle contains a VSV-G protein with a mutation at position 199 compared to SEQ ID NO: 16. In some embodiments, the protein with a mutation at position 182 compared to SEQ ID NO: 17 contains a mutation at position 182 and is 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 compared to SEQ ID NO: 17 (or SEQ ID NO: 16 if a full-length protein is used). In some embodiments, the polypeptide contains a V182D or V182E mutation compared to SEQ ID NO: 17. In some embodiments, the VSV-G protein includes V182S, V182H, V182T, V182Q, or V182N mutations.

[0166] In some embodiments, the viral particle contains a VSV-G protein with a mutation at position 199 compared to SEQ ID NO: 18. In some embodiments, the protein with a mutation at position 182 compared to SEQ ID NO: 19 contains a mutation at position 182 and is 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 compared to SEQ ID NO: 19 (or SEQ ID NO: 18 if a full-length protein is used). In some embodiments, the polypeptide contains a V182D or V182E mutation compared to SEQ ID NO: 19. In some embodiments, the VSV-G protein includes V182S, V182H, V182T, V182Q, or V182N mutations.

[0167] In some embodiments, the viral particle contains a VSV-G protein with a mutation at position 199 compared to SEQ ID NO: 20. In some embodiments, the protein with a mutation at position 182 compared to SEQ ID NO: 21 contains a mutation at position 182 and is 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 compared to SEQ ID NO: 21 (or SEQ ID NO: 20 if a full-length protein is used). In some embodiments, the polypeptide contains the I182D or I182E mutation compared to SEQ ID NO: 21. In some embodiments, the VSV-G protein contains I182S, I182H, I182T, I182Q, or I182N mutations.

[0168] In some embodiments, the VSV-G protein further includes mutations at positions corresponding to positions 214 and / or 352 of SEQ ID NO: 2. In some embodiments, the residue corresponding to position 214 of SEQ ID NO: 2 is T214. In some embodiments, the residue corresponding to position 352 of SEQ ID NO: 2 is T352. In some embodiments, the VSV-G protein includes a mutation corresponding to the T214N mutation compared to SEQ ID NO: 2. In some embodiments, the VSV-G protein includes a mutation corresponding to the T352A mutation compared to SEQ ID NO: 2. In some embodiments, the VSV-G protein includes the T214N and T352A mutations compared to SEQ ID NO: 2. These mutations can be combined with any other mutations provided herein. In some embodiments, the T214N and / or T352A mutations are combined with the I182E or I182D mutation. In some embodiments, the VSV-G protein includes the amino acid sequences of SEQ ID NO: 22 and SEQ ID NO: 23, which combine I182D or I182E with the T214N and T352A mutations, respectively. The sequences are also illustrated below, along with the leader sequences that are removed during protein processing. VSV-G protein_I196D, T230N, and T368A mutations (with leader sequences and adjusted numbering) MKCLLYLAFLFIGVNCKFTIVFPHNQKGNWKNVPSNYHYCPSSSDLNWHNDLIGTALQVKMPKSHKAIQADGWMCHASKWVTTCDFRWYGPKYITHSIRSFTPSVEQCKESIEQTKQGTWLNPGFPPQS CGYATVTDAEAVIVQVTPHHVLVDEYTGEWVDSQFINGKCSNYICPTVHNSTTWHSDYKVKGLCDSNLDSMDITFFSEDGELSSLGKEGTGFRSNYFAYENGGKACKMQYCKHWGVRLPSGVWFEMADKD LFAAARFPECPEGSSISAPSQTSVDVSLIQDVERILDYSLCQETWSKIRAGLPISPVDLSYLAPKNPGTGPAFTIINGTLKYFETRYIRVDIAAPILSRMVGMISGTTAERELWDDWAPYEDVEIGPNGVLRTSSGYKFPLYMIGHGMLDSDLHLSSKAQVFEHPHIQDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCIKLKHTKKRQIYTDIEMNRLGK(Sequence ID 24) VSV-G protein_I182D, T214N, and T352A mutations (no leader sequence) KFTIVFPHNQKGNWKNVPSNYHYCPSSSDLNWHNDLIGTALQVKMPKSHKAIQADGWMCHASKWVTTCDFRWYGPKYITHSIRSFTPSVEQCKESIEQTKQGTWLNPGFPPQSCGYATVTDAEAV IVQVTPHHVLVDEYTGEWVDSQFINGKCSNYICPTVHNSTTWHSDYKVKGLCDSNLDSMDITFFSEDGELSSLGKEGTGFRSNYFAYENGGKACKMQYCKHWGVRLPSGVWFEMADKDLFAAARFP ECPEGSSISAPSQTSVDVSLIQDVERILDYSLCQETWSKIRAGLPISPVDLSYLAPKNPGTGPAFTIINGTLKYFETRYIRVDIAAPILSRMVGMISGTTAERELWDDWAPYEDVEIGPNGVLRTSSGYKFPLYMIGHGMLDSDLHLSSKAQVFEHPHIQDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCIKLKHTKKRQIYTDIEMNRLGK(Sequence ID 22) VSV-G protein with I196E, T230N, and T368A mutations (with leader sequence and adjusted numbering) MKCLLYLAFLFIGVNCKFTIVFPHNQKGNWKNVPSNYHYCPSSSDLNWHNDLIGTALQVKMPKSHKAIQADGWMCHASKWVTTCDFRWYGPKYITHSIRSFTPSVEQCKESIEQTKQGTWLNPGFPPQS CGYATVTDAEAVIVQVTPHHVLVDEYTGEWVDSQFINGKCSNYICPTVHNSTTWHSDYKVKGLCDSNLESMDITFFSEDGELSSLGKEGTGFRSNYFAYENGGKACKMQYCKHWGVRLPSGVWFEMADKD LFAAARFPECPEGSSISAPSQTSVDVSLIQDVERILDYSLCQETWSKIRAGLPISPVDLSYLAPKNPGTGPAFTIINGTLKYFETRYIRVDIAAPILSRMVGMISGTTAERELWDDWAPYEDVEIGPNGVLRTSSGYKFPLYMIGHGMLDSDLHLSSKAQVFEHPHIQDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCIKLKHTKKRQIYTDIEMNRLGK(Sequence ID 25) VSV-G protein with I182E, T214N, and T352A mutations (no leader sequence) KFTIVFPHNQKGNWKNVPSNYHYCPSSSDLNWHNDLIGTALQVKMPKSHKAIQADGWMCHASKWVTTCDFRWYGPKYITHSIRSFTPSVEQCKESIEQTKQGTWLNPGFPPQSCGYATVTDAEAV IVQVTPHHVLVDEYTGEWVDSQFINGKCSNYICPTVHNSTTWHSDYKVKGLCDSNLESMDITFFSEDGELSSLGKEGTGFRSNYFAYENGGKACKMQYCKHWGVRLPSGVWFEMADKDLFAAARFP ECPEGSSISAPSQTSVDVSLIQDVERILDYSLCQETWSKIRAGLPISPVDLSYLAPKNPGTGPAFTIINGTLKYFETRYIRVDIAAPILSRMVGMISGTTAERELWDDWAPYEDVEIGPNGVLRTSSGYKFPLYMIGHGMLDSDLHLSSKAQVFEHPHIQDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCIKLKHTKKRQIYTDIEMNRLGK(Sequence ID 23)

[0169] Other strains of the VSV-G protein described herein may also include mutations corresponding to T214N and / or T352A in SEQ ID NO: 2, as well as the mutations shown in SEQ ID NOs: 22 and 23.

[0170] In some embodiments, the composition includes mutations as described in Hwang et al., Gene Ther 2013 Aug;20(8):807-15. (Epub 2013 Jan 31), the whole of which is incorporated herein by reference. For example, the mutations may be at positions 230, 368, 66, and / or 162, corresponding to SEQ ID NO: 1. If the leader sequence is removed, the positions are 16 positions fewer compared to SEQ ID NO: 2. 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 includes the T230N and T368A mutations. In some embodiments, the VSV-G polypeptide includes K66T, S162T, T230N, and T368A. These positions correspond to positions in the full-length protein (SEQ ID NO: 1). In some embodiments, the VSV-G protein includes the T230N mutation, the T368A mutation, the K66T mutation, the S162T mutation, or any combination thereof. In some embodiments, the VSV-G protein further includes one or more mutations in addition to the mutation corresponding to position 182 of SEQ ID NO: 2, such as that described in U.S. Patent Application Publication No. 20200216502 (which is incorporated herein by reference in its entirety). For example, the VSV-G protein may further include mutations at positions 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 shown at that position in SEQ ID NO: 2, except for Y. In some embodiments, the substitution at position 209 is by any amino acid different from the amino acid shown at that position in SEQ ID NO: 2, except for H. In some embodiments, the substitution at position 47 is by any amino acid different from the amino acid shown at that position in SEQ ID NO: 2, except for K or R. In some embodiments, the substitution at position 354 is by any amino acid different from the amino acid shown at that position in SEQ ID NO: 2, except for K or R. In some embodiments, the substitution at position 47 or 354, or both positions 47 and 354, is 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 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 contains 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 containing one or more mutations, the mutations being substitutions to charged amino acids. In some embodiments, the mutations include substitutions 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 with respect to the amino acid sequence of SEQ ID NO: 2, and further comprising charged amino acids at positions 8, 9, 10, 47, 50, 51, 179, 180, 182, 183, 184, 209, 347, 350, 352, 353, 354, or any combination thereof, compared to SEQ ID NO: 2. In some embodiments, mutations involving substitutions to charged amino acids are located at positions H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof, compared to SEQ ID NO: 2.

[0173] In some embodiments, the mutation, which includes a substitution to a charged amino acid, is located at position H8 compared to SEQ ID NO: 2. In some embodiments, the VSV-G protein, which includes a substitution to a charged amino acid at position H8 compared to SEQ ID NO: 2, further includes one or more mutations, which include a substitution to a charged amino acid at positions N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof, compared to SEQ ID NO: 2.

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

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

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

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

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

[0179] In some embodiments, the mutation, which includes a substitution to a charged amino acid, is located at position S179 compared to SEQ ID NO: 2. In some embodiments, the VSV-G protein, which includes a substitution to a charged amino acid at position S179 compared to SEQ ID NO: 2, further includes one or more mutations, which include a substitution to a charged amino acid at positions H8, N9, Q10, K47, K50, A51, N180, I182, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof, compared to SEQ ID NO: 2.

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

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

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

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

[0184] In some embodiments, the mutation, which includes a substitution to a charged amino acid, is located at position Y209 compared to SEQ ID NO: 2. In some embodiments, the VSV-G protein, which includes a substitution to a charged amino acid at position Y209 compared to SEQ ID NO: 2, further includes one or more mutations, which include a substitution to a charged amino acid at positions H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, I347, T350, T352, E353, R354, or any combination thereof, compared to SEQ ID NO: 2.

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

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

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

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

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

[0190] Substitutions of charged amino acids at positions H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof, compared to SEQ ID NO: 2, may include substitutions of any charged amino acid. In some embodiments, substitutions include substitutions of acidic amino acids, including but not limited to aspartic acid (D) or glutamic acid (E). In some embodiments, substitutions include substitutions of basic amino acids, 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), substitutions of charged amino acids may include substitutions of another acidic amino acid (e.g., D) or basic amino acids (e.g., K or R). In some embodiments, when 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 includes 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 include substitution to another basic amino acid (e.g., K or R) or substitution to an acidic amino acid (e.g., D or E). In some embodiments, when 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 includes substitution to an acidic amino acid (e.g., D or E).

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

[0192] In some embodiments, the mutation, which includes a substitution to a charged amino acid, is located at position N9 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, a VSV-G protein having a mutation at position N9 selected from N9D, N9E, N9K, or N9R compared to SEQ ID NO: 2 further includes one or more mutations, which include a substitution to a charged amino acid, at positions H8, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof, compared to SEQ ID NO: 2.

[0193] In some embodiments, the mutation, which includes a substitution to a charged amino acid, is located at position Q10 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, which includes a mutation at position Q10 selected from Q10D or Q10E compared to SEQ ID NO: 2, further includes one or more mutations, which include a substitution to a charged amino acid, at positions H8, N9, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof, compared to SEQ ID NO: 2.

[0194] In some embodiments, the mutation, which includes a substitution to a charged amino acid, is located at position K47 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, which includes a mutation at position K47 selected from K47D or K47E compared to SEQ ID NO: 2, further includes one or more mutations, which include a substitution to a charged amino acid, at positions H8, N9, Q10, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof, compared to SEQ ID NO: 2.

[0195] In some embodiments, the mutation, which includes a substitution to a charged amino acid, is located at position K50 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, which includes a mutation at position K50 selected from K50D or K50E compared to SEQ ID NO: 2, further includes one or more mutations, which include a substitution to a charged amino acid, at positions H8, N9, Q10, K47, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof, compared to SEQ ID NO: 2.

[0196] In some embodiments, the mutation, which includes a substitution to a charged amino acid, is located at position A51 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, a VSV-G protein containing a mutation at position A51, selected from A51D, A51E, A51K, or A51R compared to SEQ ID NO: 2, further includes one or more mutations, which include a substitution to a charged amino acid, at positions H8, N9, Q10, K47, K50, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof, compared to SEQ ID NO: 2.

[0197] In some embodiments, the mutation, which involves a substitution to a charged amino acid, is located at position S179 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, a VSV-G protein having a mutation at position S179 selected from S179D, S179E, S179K, or S179R compared to SEQ ID NO: 2 further includes one or more mutations, including substitutions to charged amino acids, at positions H8, N9, Q10, K47, K50, A51, N180, I182, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof, compared to SEQ ID NO: 2.

[0198] In some embodiments, the mutation, which involves a substitution to a charged amino acid, is located at position N180 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, a VSV-G protein having a mutation at position N180 selected from N180D, N180E, N180K, or N180R compared to SEQ ID NO: 2 further includes one or more mutations at positions H8, N9, Q10, K47, K50, A51, S179, I182, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof, that include a substitution to a charged amino acid.

[0199] In some embodiments, the mutation, which involves a substitution to a charged amino acid, is located at position I182 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, a VSV-G protein having a mutation at position I182 selected from I182D, I182E, I182K, or I182R compared to SEQ ID NO: 2 further includes one or more mutations at positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof, that include substitutions to charged amino acids.

[0200] In some embodiments, the mutation, which involves a substitution to a charged amino acid, is located at position S183 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, a VSV-G protein having a mutation at position S183 selected from S183D, S183E, S183K, or S183R compared to SEQ ID NO: 2 further includes one or more mutations, including substitutions to charged amino acids, at positions H8, N9, Q10, K47, K50, A51, S179, N180, I182, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof, compared to SEQ ID NO: 2.

[0201] In some embodiments, the mutation, which involves a substitution to a charged amino acid, is located at position M184 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, a VSV-G protein containing a mutation at position M184 selected from M184D, M184E, M184K, or M184R compared to SEQ ID NO: 2 further contains one or more mutations, compared to SEQ ID NO: 2, including substitutions to charged amino acids at positions H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, Y209, I347, T350, T352, E353, R354, or any combination thereof.

[0202] In some embodiments, the mutation, which involves a substitution to a charged amino acid, is located at position Y209 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, a VSV-G protein having a mutation at position Y209 selected from Y209D, Y209E, Y209K, or Y209R compared to SEQ ID NO: 2 further includes one or more mutations, including substitutions to charged amino acids, at positions H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, I347, T350, T352, E353, R354, or any combination thereof, compared to SEQ ID NO: 2.

[0203] In some embodiments, the mutation, which involves a substitution to a charged amino acid, is located at position I347 compared to SEQ ID NO: 2, and the substitution 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, a VSV-G protein having a mutation at position I347 selected from I347D, I347E, I347K, or I347R compared to SEQ ID NO: 2 further includes one or more mutations at positions H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, T350, T352, E353, R354, or any combination thereof, which include substitutions to charged amino acids.

[0204] In some embodiments, the mutation, which involves a substitution to a charged amino acid, is located at position T350 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, a VSV-G protein having a mutation at position T350 selected from T350D, T350E, T350K, or T350R compared to SEQ ID NO: 2 further includes one or more mutations at positions H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T352, E353, R354, or any combination thereof, that include substitutions to charged amino acids.

[0205] In some embodiments, the mutation, which involves a substitution to a charged amino acid, is located at position T352 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, a VSV-G protein containing a mutation at position T352 selected from T352D, T352E, T352K, or T352R compared to SEQ ID NO: 2 further contains one or more mutations, including substitutions to charged amino acids, at positions H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof, compared to SEQ ID NO: 2.

[0206] In some embodiments, the mutation, which includes a substitution to a charged amino acid, is located at position E353 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, which includes a mutation at position E353 selected from E353K or E353R compared to SEQ ID NO: 2, further includes one or more mutations, which include a substitution to a charged amino acid, at positions H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, R354, or any combination thereof, compared to SEQ ID NO: 2.

[0207] In some embodiments, the mutation, which includes a substitution to a charged amino acid, is located at position R354 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, which includes a mutation at position R354 selected from R354D or R354E compared to SEQ ID NO: 2, further includes one or more mutations, which include a substitution to a charged amino acid, at positions H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, or any combination thereof, compared to SEQ ID NO: 2.

[0208] TIFF2026520753000002.tif118170

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

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

[0211] In some embodiments, the viral particle comprises a VSV-G protein with a mutation at the N9 position, as shown in Table 1, and further comprises a mutation at the H8, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, R354 positions, or any combination thereof, as shown in Table 1. In some embodiments, the viral particle comprises a VSV-G protein with a mutation at the N9 position, as shown 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 shown in Table 1. In some embodiments, the viral particle comprises a VSV-G protein with a mutation at the N9 position, as shown in Table 1, and further comprises additional mutations at one or more positions selected from H8, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, or R354, as shown in Table 1.

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

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

[0214] In some embodiments, the viral particle comprises a VSV-G protein with a mutation at the K50 position, as shown in Table 1, and further comprises mutations at the H8, N9, Q10, K47, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, R354 positions, or any combination thereof, as shown in Table 1. In some embodiments, the viral particle comprises a VSV-G protein with a mutation at the K50 position, as shown 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 shown in Table 1. In some embodiments, the viral particle comprises a VSV-G protein with a mutation at the K50 position, as shown in Table 1, and further comprises additional mutations at one or more positions selected from H8, N9, Q10, K47, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, or R354, as shown in Table 1.

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

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

[0217] In some embodiments, the viral particle comprises a VSV-G protein with a mutation at position N180, as shown in Table 1, and further comprises mutations at positions H8, N9, Q10, K47, K50, A51, S179, I182, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof, as shown in Table 1. In some embodiments, the viral particle comprises a VSV-G protein with a mutation at position N180, as shown 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 shown in Table 1. In some embodiments, the viral particle comprises a VSV-G protein with a mutation at position N180, as shown in Table 1, and further comprises additional mutations at one or more positions selected from H8, N9, Q10, K47, K50, A51, S179, I182, S183, M184, Y209, I347, T350, T352, E353, or R354, as shown in Table 1.

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

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

[0220] In some embodiments, the viral particle comprises a VSV-G protein with a mutation at position M184, as shown in Table 1, and further comprises mutations at positions H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, Y209, I347, T350, T352, E353, R354, or any combination thereof, as shown in Table 1. In some embodiments, the viral particle comprises a VSV-G protein with a mutation at position M184, as shown 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 shown in Table 1. In some embodiments, the viral particle comprises a VSV-G protein with a mutation at position M184, as shown in Table 1, and further comprises additional mutations at one or more positions selected from H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, Y209, I347, T350, T352, E353, or R354, as shown in Table 1.

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

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

[0223] In some embodiments, the viral particle comprises a VSV-G protein with a mutation at the T350 position, as shown in Table 1, and further comprises mutations at the H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T352, E353, R354 positions, or any combination thereof, as shown in Table 1. In some embodiments, the viral particle comprises a VSV-G protein with a mutation at the T350 position, as shown 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 shown in Table 1. In some embodiments, the viral particle comprises a VSV-G protein with a mutation at position T350, as shown in Table 1, and further comprises additional mutations at one or more positions selected from H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T352, E353, or R354, as shown in Table 1.

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

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

[0226] In some embodiments, the viral particle comprises a VSV-G protein with a mutation at the R354 position, as shown in Table 1, and further comprises mutations at the H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353 positions, or any combination thereof, as shown in Table 1. In some embodiments, the viral particle comprises a VSV-G protein with a mutation at the R354 position, as shown 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 shown in Table 1. In some embodiments, the viral particle comprises a VSV-G protein with a mutation at position R354, as shown in Table 1, and further comprises additional mutations at one or more positions selected from H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, or E353, as shown in Table 1.

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

[0243] Substitutions of charged amino acids at positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof, compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, may include substitutions of any charged amino acid. In some embodiments, substitutions include substitutions of acidic amino acids, including but not limited to aspartic acid (D) or glutamic acid (E). In some embodiments, substitutions include substitutions of basic amino acids, 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), substitutions of charged amino acids may include substitutions of another acidic amino acid (e.g., D) or basic amino acids (e.g., K or R). In some embodiments, when 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 includes 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 include substitution to another basic amino acid (e.g., K or R) or substitution to an acidic amino acid (e.g., D or E). In some embodiments, when 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 includes substitution to an acidic amino acid (e.g., D or E).

[0244] In some embodiments, the viral particle comprises a VSV-G protein containing the 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 the H8 position compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, where the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 3, and a substitution to a charged amino acid at the H8 position compared to SEQ ID NO: 3, where the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 4, and a substitution to a charged amino acid at the H8 position compared to SEQ ID NO: 4, where the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 5, and a substitution to a charged amino acid at the H8 position compared to SEQ ID NO: 5, where the charged amino acid is selected from D, E, K, or R. In some embodiments, the mutation at the H8 position is H8D. In some embodiments, the mutation at the H8 position is H8E. In some embodiments, the mutation at the H8 position is H8K. In some embodiments, the mutation at the H8 position is H8R. In some embodiments, a 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 the H8 position selected from H8D, H8E, H8K, or H8R compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, further comprises one or more mutations comprising substitutions to charged amino acids at positions N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof, 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 containing 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 compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, the charged amino acid being selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 3, and a substitution to a charged amino acid at position N9 compared to SEQ ID NO: 3, the charged amino acid being selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 4, and a substitution to a charged amino acid at position N9 compared to SEQ ID NO: 4, the charged amino acid being selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 5, and a substitution to a charged amino acid at position N9 compared to SEQ ID NO: 5, the charged amino acid being 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, a 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 selected from N9D, N9E, N9K, or N9R 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 positions H8, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof, 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 containing 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 compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, where the charged amino acid is selected from D or E. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 3, and a substitution to a charged amino acid at position Q10 compared to SEQ ID NO: 3, where the charged amino acid is selected from D or E. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 4, and a substitution to a charged amino acid at position Q10 compared to SEQ ID NO: 4, where the charged amino acid is selected from D or E. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 5, and a substitution to a charged amino acid at position Q10 compared to SEQ ID NO: 5, where 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, a 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 selected from Q10D or Q10E compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, further comprises one or more mutations comprising substitutions to charged amino acids at positions H8, N9, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof.

[0247] In some embodiments, the viral particle comprises a VSV-G protein containing 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 compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, the charged amino acid being selected from D or E. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 3, and a substitution to a charged amino acid at position K47 compared to SEQ ID NO: 3, the charged amino acid being selected from D or E. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 4, and a substitution to a charged amino acid at position K47 compared to SEQ ID NO: 4, the charged amino acid being selected from D or E. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 5, and a substitution to a charged amino acid at position K47 compared to SEQ ID NO: 5, the charged amino acid being 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, a VSV-G protein comprising the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 comprises a mutation at position K47 selected from K47D or K47E compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, and further comprises one or more mutations comprising a substitution to a charged amino acid at positions H8, N9, Q10, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof 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 containing 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 compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, the charged amino acid being selected from D or E. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 3, and a substitution to a charged amino acid at position K50 compared to SEQ ID NO: 3, the charged amino acid being selected from D or E. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 4, and a substitution to a charged amino acid at position K50 compared to SEQ ID NO: 4, the charged amino acid being selected from D or E. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 5, and a substitution to a charged amino acid at position K50 compared to SEQ ID NO: 5, the charged amino acid being 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, a 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 the K50 position selected from K50D or K50E compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, further comprises one or more mutations comprising substitutions to charged amino acids at the H8, N9, Q10, K47, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, R354 positions, or any combination thereof, 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 containing 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 A51 compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, the charged amino acid being selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 3, and a substitution to a charged amino acid at position A51 compared to SEQ ID NO: 3, the charged amino acid being selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 4, and a substitution to a charged amino acid at position A51 compared to SEQ ID NO: 4, the charged amino acid being selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 5, and a substitution to a charged amino acid at position A51 compared to SEQ ID NO: 5, the charged amino acid being 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, a 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 selected from A51D, A51E, A51K, or A51R compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, further comprises one or more mutations comprising substitutions to charged amino acids at positions H8, N9, Q10, K47, K50, S179, N180, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof.

[0250] In some embodiments, the viral particle comprises a VSV-G protein containing 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 compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, the charged amino acid being selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 3, and a substitution to a charged amino acid at position S179 compared to SEQ ID NO: 3, the charged amino acid being selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 4, and a substitution to a charged amino acid at position S179 compared to SEQ ID NO: 4, the charged amino acid being selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 5, and a substitution to a charged amino acid at position S179 compared to SEQ ID NO: 5, the charged amino acid being 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, a 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 selected from S179D, S179E, S179K, or S179R 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 positions H8, N9, Q10, K47, K50, A51, N180, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof, 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 containing 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 compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, the charged amino acid being selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 3, and a substitution to a charged amino acid at position N180 compared to SEQ ID NO: 3, the charged amino acid being selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 4, and a substitution to a charged amino acid at position N180 compared to SEQ ID NO: 4, the charged amino acid being selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 5, and a substitution to a charged amino acid at position N180 compared to SEQ ID NO: 5, the charged amino acid being 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, a 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 selected from N180D, N180E, N180K, or N180R compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, further comprises one or more mutations comprising substitutions to charged amino acids at positions H8, N9, Q10, K47, K50, A51, S179, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof.

[0252] In some embodiments, the viral particle comprises a VSV-G protein containing 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 compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, the charged amino acid being selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 3, and a substitution to a charged amino acid at position S183 compared to SEQ ID NO: 3, the charged amino acid being selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 4, and a substitution to a charged amino acid at position S183 compared to SEQ ID NO: 4, the charged amino acid being selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 5, and a substitution to a charged amino acid at position S183 compared to SEQ ID NO: 5, the charged amino acid being 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, a 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 selected from S183D, S183E, S183K, or S183R compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, further comprises one or more mutations comprising substitutions to charged amino acids at positions H8, N9, Q10, K47, K50, A51, S179, N180, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof, 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 containing 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 compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, the charged amino acid being selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 3, and a substitution to a charged amino acid at position M184 compared to SEQ ID NO: 3, the charged amino acid being selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 4, and a substitution to a charged amino acid at position M184 compared to SEQ ID NO: 4, the charged amino acid being selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 5, and a substitution to a charged amino acid at position M184 compared to SEQ ID NO: 5, the charged amino acid being 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, a 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 M184 selected from M184D, M184E, M184K, or M184R compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, further comprises one or more mutations comprising substitutions to charged amino acids at positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, Y209, I347, T350, T352, E353, R354, or any combination thereof, 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 containing 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 compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, the charged amino acid being selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 3, and a substitution to a charged amino acid at position Y209 compared to SEQ ID NO: 3, the charged amino acid being selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 4, and a substitution to a charged amino acid at position Y209 compared to SEQ ID NO: 4, the charged amino acid being selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 5, and a substitution to a charged amino acid at position Y209 compared to SEQ ID NO: 5, the charged amino acid being 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, a 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 selected from Y209D, Y209E, Y209K, or Y209R compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, further comprises one or more mutations comprising substitutions to charged amino acids at positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, I347, T350, T352, E353, R354, or any combination thereof, 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 containing 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 compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, the charged amino acid being selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 3, and a substitution to a charged amino acid at position I347 compared to SEQ ID NO: 3, the charged amino acid being selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 4, and a substitution to a charged amino acid at position I347 compared to SEQ ID NO: 4, the charged amino acid being selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 5, and a substitution to a charged amino acid at position I347 compared to SEQ ID NO: 5, the charged amino acid being 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, a 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 selected from I347D, I347E, I347K, or I347R compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, further comprises one or more mutations comprising substitutions to charged amino acids at positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, T350, T352, E353, R354, or any combination thereof, 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 containing 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 compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, the charged amino acid being selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 3, and a substitution to a charged amino acid at position T350 compared to SEQ ID NO: 3, the charged amino acid being selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 4, and a substitution to a charged amino acid at position T350 compared to SEQ ID NO: 4, the charged amino acid being selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 5, and a substitution to a charged amino acid at position T350 compared to SEQ ID NO: 5, the charged amino acid being 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, a 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 selected from T350D, T350E, T350K, or T350R compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, further comprises one or more mutations comprising substitutions to charged amino acids at positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T352, E353, R354, or any combination thereof.

[0257] In some embodiments, the viral particle comprises a VSV-G protein containing 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 compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, the charged amino acid being selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 3, and a substitution to a charged amino acid at position T352 compared to SEQ ID NO: 3, the charged amino acid being selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 4, and a substitution to a charged amino acid at position T352 compared to SEQ ID NO: 4, the charged amino acid being selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 5, and a substitution to a charged amino acid at position T352 compared to SEQ ID NO: 5, the charged amino acid being 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, a 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 selected from T352D, T352E, T352K, or T352R compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, further comprises one or more mutations comprising substitutions to charged amino acids at positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof.

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

[0259] In some embodiments, the viral particle comprises a VSV-G protein containing 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 compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, the charged amino acid being selected from D or E. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 3, and a substitution to a charged amino acid at position R354 compared to SEQ ID NO: 3, the charged amino acid being selected from D or E. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 4, and a substitution to a charged amino acid at position R354 compared to SEQ ID NO: 4, the charged amino acid being selected from D or E. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 5, and a substitution to a charged amino acid at position R354 compared to SEQ ID NO: 5, the charged amino acid being 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, a 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 selected from R354D or R354E compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, further comprises one or more mutations comprising substitutions to charged amino acids at positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, or any combination thereof.

[0260] TIFF2026520753000003.tif112170

[0261] In some embodiments, the viral particle contains a VSV-G protein containing one or more mutations, the mutations being substitutions to charged amino acids as listed in Table 2. In some embodiments, the mutations containing substitutions to charged amino acids are located at positions 8, 9, 10, 47, 50, 51, 179, 180, 183, 184, 209, 347, 350, 352, 353, 354, or any combination thereof, as listed in Table 2. In some embodiments, the mutations containing substitutions to charged amino acids are located at positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof, as listed in Table 2.

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

[0263] In some embodiments, the viral particle comprises a VSV-G protein with a mutation at the N9 position, as shown in Table 2, and further comprises mutations at the H8, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, R354 positions, or any combination thereof, as shown in Table 2. In some embodiments, the viral particle comprises a VSV-G protein with a mutation at the N9 position, as shown 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 shown in Table 2. In some embodiments, the viral particle comprises a VSV-G protein with a mutation at the N9 position, as shown in Table 2, and further comprises additional mutations at one or more positions selected from H8, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, or R354, as shown in Table 2.

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

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

[0266] In some embodiments, the viral particle comprises a VSV-G protein with a mutation at the K50 position, as shown in Table 2, and further comprises mutations at the H8, N9, Q10, K47, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, R354 positions, or any combination thereof, as shown in Table 2. In some embodiments, the viral particle comprises a VSV-G protein with a mutation at the K50 position, as shown 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 shown in Table 2. In some embodiments, the viral particle comprises a VSV-G protein with a mutation at the K50 position, as shown in Table 2, and further comprises additional mutations at one or more positions selected from H8, N9, Q10, K47, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, or R354, as shown in Table 2.

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

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

[0269] In some embodiments, the viral particle comprises a VSV-G protein with a mutation at position N180, as shown in Table 2, and further comprises mutations at positions H8, N9, Q10, K47, K50, A51, S179, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof, as shown in Table 2. In some embodiments, the viral particle comprises a VSV-G protein with a mutation at position N180, as shown 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 shown in Table 2. In some embodiments, the viral particle comprises a VSV-G protein with a mutation at position N180, as shown in Table 2, and further comprises additional mutations at one or more positions selected from H8, N9, Q10, K47, K50, A51, S179, S183, M184, Y209, I347, T350, T352, E353, or R354, as shown in Table 2.

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

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

[0272] In some embodiments, the viral particle comprises a VSV-G protein with a mutation at the Y209 position, as shown in Table 2, and further comprises mutations at the H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, I347, T350, T352, E353, R354 positions, or any combination thereof, as shown in Table 2. In some embodiments, the viral particle comprises a VSV-G protein with a mutation at the Y209 position, as shown 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 shown in Table 2. In some embodiments, the viral particle comprises a VSV-G protein with a mutation at position Y209, as shown in Table 2, and further comprises additional mutations at one or more positions selected from H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, I347, T350, T352, E353, or R354, as shown in Table 2.

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

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

[0275] In some embodiments, the viral particle comprises a VSV-G protein with a mutation at the T352 position, as shown in Table 2, and further comprises mutations at the H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, R354 positions, or any combination thereof, as shown in Table 2. In some embodiments, the viral particle comprises a VSV-G protein with a mutation at the T352 position, as shown 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 shown in Table 2. In some embodiments, the viral particle comprises a VSV-G protein with a mutation at position T352, as shown in Table 2, and further comprises additional mutations at one or more positions selected from H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, or R354, as shown in Table 2.

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

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

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

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

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

[0281] In some embodiments, the viral particles comprise a VSV-G protein containing the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23, further comprising a substitution of a charged amino acid at the K47 position compared to SEQ ID NO: 22 or SEQ ID NO: 23. In some embodiments, the VSV-G protein, which includes 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 compared to SEQ ID NO: 22 or SEQ ID NO: 23, further includes one or more mutations, which include substitutions to a charged amino acid at positions H8, N9, Q10, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof, compared to SEQ ID NO: 22 or SEQ ID NO: 23.

[0282] In some embodiments, the viral particles comprise a VSV-G protein containing the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23, further comprising a substitution of a charged amino acid at the K50 position compared to SEQ ID NO: 22 or SEQ ID NO: 23. In some embodiments, the viral particles comprise a VSV-G protein containing the amino acid sequence of SEQ ID NO: 22, further comprising a substitution of a charged amino acid at the K50 position compared to SEQ ID NO: 22. In some embodiments, the viral particles comprise a VSV-G protein containing the amino acid sequence of SEQ ID NO: 23, further comprising a substitution of a charged amino acid at the K50 position compared to SEQ ID NO: 23. In some embodiments, the VSV-G protein, which includes 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 compared to SEQ ID NO: 22 or SEQ ID NO: 23, further includes one or more mutations, which include substitutions to a charged amino acid at positions H8, N9, Q10, K47, A51, S179, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof, compared to SEQ ID NO: 22 or SEQ ID NO: 23.

[0283] In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23, further comprising a substitution of a charged amino acid at position A51 compared to SEQ ID NO: 22 or SEQ ID NO: 23. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 22, further comprising a substitution of a charged amino acid at position A51 compared to SEQ ID NO: 22. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 23, further comprising a substitution of a charged amino acid at position A51 compared to SEQ ID NO: 23. In some embodiments, the VSV-G protein, which includes 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 compared to SEQ ID NO: 22 or SEQ ID NO: 23, further includes one or more mutations, which include substitutions to a charged amino acid at positions H8, N9, Q10, K47, K50, S179, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof, compared to SEQ ID NO: 22 or SEQ ID NO: 23.

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

[0285] In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23, further comprising a substitution of a charged amino acid at position N180 compared to SEQ ID NO: 22 or SEQ ID NO: 23. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 22, further comprising a substitution of a charged amino acid at position N180 compared to SEQ ID NO: 22. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 23, further comprising a substitution of a charged amino acid at position N180 compared to SEQ ID NO: 23. In some embodiments, the VSV-G protein, which includes 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 compared to SEQ ID NO: 22 or SEQ ID NO: 23, further includes one or more mutations, which include substitutions to a charged amino acid at positions H8, N9, Q10, K47, K50, A51, S179, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof, compared to SEQ ID NO: 22 or SEQ ID NO: 23.

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

[0287] In some embodiments, the viral particles comprise a VSV-G protein containing the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23, further comprising a substitution of a charged amino acid at position M184 compared to SEQ ID NO: 22 or SEQ ID NO: 23. In some embodiments, the VSV-G protein, which includes 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 compared to SEQ ID NO: 22 or SEQ ID NO: 23, further includes one or more mutations, which include substitutions to charged amino acids at positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, Y209, I347, T350, E353, R354, or any combination thereof, compared to SEQ ID NO: 22 or SEQ ID NO: 23.

[0288] In some embodiments, the virus particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23, further comprising a substitution of a charged amino acid at position Y209 compared to SEQ ID NO: 22 or SEQ ID NO: 23. In some embodiments, the virus particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 22, further comprising a substitution of a charged amino acid at position Y209 compared to SEQ ID NO: 22. In some embodiments, the virus particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 23, further comprising a substitution of a charged amino acid at position Y209 compared to SEQ ID NO: 23. In some embodiments, the VSV-G protein, which includes 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 compared to SEQ ID NO: 22 or SEQ ID NO: 23, further includes one or more mutations, which include substitutions to a charged amino acid at positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, I347, T350, E353, R354, or any combination thereof, compared to SEQ ID NO: 22 or SEQ ID NO: 23.

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

[0290] In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23, further comprising a substitution of a charged amino acid at position T350 compared to SEQ ID NO: 22 or SEQ ID NO: 23. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 22, further comprising a substitution of a charged amino acid at position T350 compared to SEQ ID NO: 22. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 23, further comprising a substitution of a charged amino acid at position T350 compared to SEQ ID NO: 23. In some embodiments, the VSV-G protein, which includes 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 compared to SEQ ID NO: 22 or SEQ ID NO: 23, further includes one or more mutations, which include substitutions to a charged amino acid at positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, E353, R354, or any combination thereof, compared to SEQ ID NO: 22 or SEQ ID NO: 23.

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

[0292] In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23, further comprising a substitution of a charged amino acid at position R354 compared to SEQ ID NO: 22 or SEQ ID NO: 23. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 22, further comprising a substitution of a charged amino acid at position R354 compared to SEQ ID NO: 22. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 23, further comprising a substitution of a charged amino acid at position R354 compared to SEQ ID NO: 23. In some embodiments, the VSV-G protein, which includes 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 compared to SEQ ID NO: 22 or SEQ ID NO: 23, further includes one or more mutations, which include substitutions to charged amino acids at positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, or any combination thereof, compared to SEQ ID NO: 22 or SEQ ID NO: 23.

[0293] Substitutions of charged amino acids in H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof, compared to SEQ ID NO: 22 or SEQ ID NO: 23, may include substitutions of any charged amino acid. In some embodiments, substitutions include substitutions of acidic amino acids, including but not limited to aspartic acid (D) or glutamic acid (E). In some embodiments, substitutions include substitutions of basic amino acids, 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), substitutions of charged amino acids may include substitutions of another acidic amino acid (e.g., D) or basic amino acids (e.g., K or R). In some embodiments, when 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 includes 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 include substitution to another basic amino acid (e.g., K or R) or substitution to an acidic amino acid (e.g., D or E). In some embodiments, when 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 includes substitution to an acidic amino acid (e.g., D or E).

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

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

[0296] In some embodiments, the viral particle comprises a VSV-G protein containing 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 compared to SEQ ID NO: 22 or SEQ ID NO: 23, the charged amino acid being selected from D or E. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 22, and a substitution to a charged amino acid at position Q10 compared to SEQ ID NO: 22, the charged amino acid being selected from D or E. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 23, and a substitution to a charged amino acid at position Q10 compared to SEQ ID NO: 23, the charged amino acid being 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, a VSV-G protein comprising the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23, and a mutation at position Q10 selected from Q10D or Q10E compared to SEQ ID NO: 22 or SEQ ID NO: 23, further comprises one or more mutations comprising substitutions to charged amino acids at positions H8, N9, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof, compared to SEQ ID NO: 22 or SEQ ID NO: 23.

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

[0298] In some embodiments, the viral particle comprises a VSV-G protein containing 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 compared to SEQ ID NO: 22 or SEQ ID NO: 23, the charged amino acid being selected from D or E. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 22, and a substitution to a charged amino acid at position K50 compared to SEQ ID NO: 22, the charged amino acid being selected from D or E. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 23, and a substitution to a charged amino acid at position K50 compared to SEQ ID NO: 23, the charged amino acid being 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, a VSV-G protein comprising the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23, and a mutation at the K50 position selected from K50D or K50E compared to SEQ ID NO: 22 or SEQ ID NO: 23, further comprises one or more mutations comprising substitutions to charged amino acids at the H8, N9, Q10, K47, A51, S179, N180, S183, M184, Y209, I347, T350, E353, R354 positions, or any combination thereof, compared to SEQ ID NO: 22 or SEQ ID NO: 23.

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

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

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

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

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

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

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

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

[0307] In some embodiments, the viral particle comprises a VSV-G protein containing 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 compared to SEQ ID NO: 22 or SEQ ID NO: 23, the charged amino acid being selected from K or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 22, and a substitution to a charged amino acid at position E353 compared to SEQ ID NO: 22, the charged amino acid being selected from K or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 23, and a substitution to a charged amino acid at position E353 compared to SEQ ID NO: 23, the charged amino acid being 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, a VSV-G protein comprising the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23, and a mutation at position E353 selected from E353K or E353R compared to SEQ ID NO: 22 or SEQ ID NO: 23, further comprises one or more mutations comprising substitutions to charged amino acids at positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, R354, or any combination thereof, compared to SEQ ID NO: 22 or SEQ ID NO: 23.

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

[0309] TIFF2026520753000004.tif107170

[0310] In some embodiments, the viral particle comprises a VSV-G protein containing one or more mutations, the mutations being substitutions to charged amino acids as listed in Table 3. In some embodiments, the mutations containing substitutions to charged amino acids are located at positions 8, 9, 10, 47, 50, 51, 179, 180, 183, 184, 209, 347, 350, 353, 354, or any combination thereof, as listed in Table 3. In some embodiments, the mutations containing substitutions to charged amino acids are located at positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof, as listed in Table 3.

[0311] It should be understood that any of the mutations for specific residues listed in Table 3 may be combined with one or more additional mutations for other residues in Table 3. For example, in some embodiments, the viral particle comprises a VSV-G protein with a mutation at the H8 position as listed in Table 3, and further comprises mutations at the N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, R354 positions, or any combination thereof, as listed in Table 3. In some embodiments, the viral particle comprises a VSV-G protein with a mutation at the H8 position, as shown in Table 3, and further comprises additional mutations at one or more positions selected from N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, or R354, as shown in Table 3.

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

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

[0314] In some embodiments, the viral particle comprises a VSV-G protein with a mutation at the K47 position, as shown in Table 3, and further comprises mutations at the H8, N9, Q10, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, R354 positions, or any combination thereof, as shown in Table 3. In some embodiments, the viral particle comprises a VSV-G protein with a mutation at the K47 position, as shown 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 shown in Table 3. In some embodiments, the viral particle comprises a VSV-G protein with a mutation at the K47 position, as shown in Table 3, and further comprises additional mutations at one or more positions selected from H8, N9, Q10, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, or R354, as shown in Table 3.

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

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

[0317] In some embodiments, the viral particle comprises a VSV-G protein with a mutation at position S179, as shown in Table 3, and further comprises mutations at positions H8, N9, Q10, K47, K50, A51, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof, as shown in Table 3. In some embodiments, the viral particle comprises a VSV-G protein with a mutation at position S179, as shown in Table 3, and further comprises additional mutations at one or more positions selected from H8, N9, Q10, K47, K50, A51, N180, S183, M184, Y209, I347, T350, E353, or R354, as shown in Table 3.

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

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

[0320] In some embodiments, the viral particle comprises a VSV-G protein with a mutation at position M184, as shown in Table 3, and further comprises mutations at positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, Y209, I347, T350, E353, R354, or any combination thereof, as shown in Table 3. In some embodiments, the viral particle comprises a VSV-G protein with a mutation at position M184, as shown 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 shown in Table 3. In some embodiments, the viral particle comprises a VSV-G protein with a mutation at position M184, as shown in Table 3, and further comprises additional mutations at one or more positions selected from H8, N9, Q10, K47, K50, A51, S179, N180, S183, Y209, I347, T350, E353, or R354, as shown in Table 3.

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

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

[0323] In some embodiments, the viral particle comprises a VSV-G protein with a mutation at the T350 position, as shown in Table 3, and further comprises mutations at the H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, E353, R354 positions, or any combination thereof, as shown in Table 3. In some embodiments, the viral particle comprises a VSV-G protein with a mutation at the T350 position, as shown 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 shown in Table 3. In some embodiments, the viral particle comprises a VSV-G protein with a mutation at position T350, as shown in Table 3, and further comprises additional mutations at one or more positions selected from H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, E353, or R354, as shown in Table 3.

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

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

[0326] In any of the embodiments herein, the VSV-G protein may further include mutations at positions 8, 9, 10, 47, 50, 51, 179, 180, 182, 184, 209, 347, 350, 352, 353, 354, or any combination thereof, wherein the mutations are substitutions for 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 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 herein, any of the mutations (i.e., substitutions) described herein may be combined with any other mutations described herein. For example, in some embodiments, as provided herein, a VSV-G protein is provided comprising a mutation to a charged amino acid at positions 8, 9, 10, 47, 50, 51, 179, 180, 182, 184, 209, 347, 350, 352, 353, 354, or any combination thereof, and further comprising a mutation at positions 8, 9, 10, 47, 50, 51, 179, 180, 182, 184, 209, 347, 350, 352, 353, 354, or any combination thereof, where the mutation is a substitution to an alanine residue.

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

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

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

[0331] In some embodiments, the VSV-G protein provided herein includes the N9A mutation, and further includes the H8A mutation, Q10A mutation, K47A mutation, K50A mutation, K51A mutation, S179A mutation, N180A mutation, I182A mutation, M184A mutation, Y209A mutation, I347A, I347G mutation, T350A mutation, T352A mutation, T352Q mutation, E353A mutation, or R354A mutation, or any combination thereof.

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

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

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

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

[0336] In some embodiments, the VSV-G protein provided herein comprises the K51A mutation, and further comprises the N9A mutation, Q10A mutation, K47A mutation, K50A mutation, H8A mutation, S179A mutation, N180A mutation, I182A mutation, M184A mutation, Y209A mutation, I347A, I347G mutation, T350A mutation, T352A mutation, T352Q mutation, E353A mutation, or R354A mutation, or any combination thereof.

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

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

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

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

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

[0342] In some embodiments, the VSV-G protein provided herein includes the I347A mutation, and further includes the N9A mutation, Q10A mutation, K47A mutation, K50A mutation, K51A mutation, S179A mutation, N180A mutation, I182A mutation, M184A mutation, Y209A mutation, H8A, I347G mutation, T350A mutation, T352A mutation, T352Q mutation, E353A mutation, or R354A mutation, or any combination thereof.

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

[0344] In some embodiments, the VSV-G protein provided herein comprises the T350A mutation, and further comprises the N9A mutation, Q10A mutation, K47A mutation, K50A mutation, K51A mutation, S179A mutation, N180A mutation, I182A mutation, M184A mutation, Y209A mutation, I347A, I347G mutation, H8A mutation, T352A mutation, T352Q mutation, E353A mutation, or R354A mutation, or any combination thereof.

[0345] In some embodiments, the VSV-G protein provided herein comprises the T352A mutation, and further comprises the N9A mutation, Q10A mutation, K47A mutation, K50A mutation, K51A mutation, S179A mutation, N180A mutation, I182A mutation, M184A mutation, Y209A mutation, I347A, I347G mutation, T350A mutation, H8A mutation, T352Q mutation, E353A mutation, or R354A mutation, or any combination thereof.

[0346] In some embodiments, the VSV-G protein provided herein comprises the T352Q mutation, and further comprises the N9A mutation, Q10A mutation, K47A mutation, K50A mutation, K51A mutation, S179A mutation, N180A mutation, I182A mutation, M184A mutation, Y209A mutation, I347A, I347G mutation, T350A mutation, T352A mutation, H8A mutation, E353A mutation, or R354A mutation, or any combination thereof.

[0347] In some embodiments, the VSV-G protein provided herein comprises the E353A mutation and further comprises the N9A mutation, Q10A mutation, K47A mutation, K50A mutation, K51A mutation, S179A mutation, N180A mutation, I182A mutation, M184A mutation, Y209A mutation, I347A, I347G mutation, T350A mutation, T352A mutation, T352Q mutation, H8A mutation, or R354A mutation, or any combination thereof.

[0348] In some embodiments, the VSV-G protein provided herein comprises the R354A mutation and further comprises the N9A mutation, Q10A mutation, K47A mutation, K50A mutation, K51A mutation, S179A mutation, N180A mutation, I182A mutation, M184A mutation, Y209A mutation, I347A, I347G mutation, T350A mutation, T352A mutation, T352Q mutation, H8A mutation, or H8A mutation, or any combination thereof.

[0349] In some embodiments, the VSV-G protein provided herein includes the I182E mutation, and further includes the I347G mutation, the T352E mutation, or a combination thereof. In some embodiments, the VSV-G protein provided herein includes the I347G mutation, and further includes the I182E mutation, the T352E mutation, or a combination thereof. In some embodiments, the T352E mutation is combined with the I182E or I347G mutation. In some embodiments, the I182E mutation is combined with the I347G mutation. In some embodiments, the I182E mutation is combined with the T352E mutation. In some embodiments, the I347G mutation is combined with the T352E mutation. In some embodiments, the I182E mutation is combined with the T352Q mutation. In some embodiments, the I182E mutation is combined with the T352E mutation. As provided herein, these mutations can be combined with any other mutations provided herein.

[0350] As provided herein, the sequences of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 22, and SEQ ID NO: 23 include the ectodomain of the VSV-G polypeptide sequence, and the leader peptide is cleaved. Therefore, while specific embodiments are provided with reference to SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 22, and SEQ ID NO: 23, it should be understood that these embodiments also encompass their respective full-length VSV-G protein sequences. Accordingly, in some embodiments, the embodiment relating to SEQ ID NO: 2 also applies to SEQ ID NO: 1, and the amino acid numbering is updated to reflect the presence of the leader peptide. In some embodiments, the embodiment relating to SEQ ID NO: 22 also applies to SEQ ID NO: 24, and the amino acid numbering is updated to reflect the presence of the leader peptide. In some embodiments, the embodiment relating to SEQ ID NO: 23 also applies to SEQ ID NO: 25, and the amino acid numbering is updated to reflect the presence of the leader peptide. In some embodiments, the embodiment relating to SEQ ID NO: 3 further includes the 16-mer signal peptide of SEQ ID NO: 26, and the amino acid numbering of the mutation described for SEQ ID NO: 3 is updated to reflect the presence of the leader peptide. In some embodiments, the embodiment relating to SEQ ID NO: 4 further comprises the hexameric signal peptide of SEQ ID NO: 26, and the amino acid numbering of the mutation described for SEQ ID NO: 4 is updated to reflect the presence of the leader peptide. In some embodiments, the embodiment relating to SEQ ID NO: 5 further comprises the hexameric signal peptide of SEQ ID NO: 26, and the amino acid numbering of the mutation described for SEQ ID NO: 5 is updated to reflect the presence of the leader peptide.

[0351] Furthermore, while the mutations may be described with reference to the VSV-G protein derived from the Indiana strain, or to Sequence ID No. 2, Sequence ID No. 3, Sequence ID No. 4, Sequence ID No. 5, Sequence ID No. 22, and Sequence ID No. 23 derived therefrom, the mutations can also be used in other strains of the VSV-G protein. For example, the mutations can be produced in the VSV-G New Jersey strain, the VSV-G Malaba strain, the VSV-G Carajas strain, the VSV-G Alagoa strain, the VSV-G Kaukal strain, or the VSV-G Moreton strain. In some embodiments, each sequence is provided herein. Examples of these can be found, for example, in U.S. Patent Application Publication No. 20200216502, which is incorporated herein by reference. For example, the wild-type full-length or ectodomain of the VSV-G New Jersey strain is sequence number 10 and sequence number 11, respectively; the wild-type full-length or ectodomain of the VSV-G Malaba strain is sequence number 12 and sequence number 13, respectively; the wild-type full-length or ectodomain of the VSV-G Carajas strain is sequence number 14 and sequence number 15, respectively; the wild-type full-length or ectodomain of the VSV-G Alagoa strain is sequence number 16 and sequence number 17, respectively; the wild-type full-length or ectodomain of the VSV-G Kaukal strain is sequence number 18 and sequence number 19, respectively; or the wild-type full-length or ectodomain of the VSV-G Moreton strain is sequence number 20 and sequence number 21, respectively. targeting part

[0352] In some embodiments, the viral particle includes a targeting moiety. The targeting moiety can be used to target the viral particle containing the mutant VSV-G protein to cells expressing a target to which the targeting moiety binds. In some embodiments, the targeting moiety is an antibody, scFv antibody, antigen-binding domain, ankyrin repeat (e.g., DARPIN), VHH domain antibody, nanobody, single-domain antibody, FN3 domain, or any combination thereof. The targeting moiety may attach to the...

Claims

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

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

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

2.

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

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

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

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

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

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

10. The variant VSV-G polypeptide according to claim 2, wherein the mutation to the charged amino acid at position A51 is A51D, A51E, A51K, or A51R.

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

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

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

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

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

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

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

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

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

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

21. The variant VSV-G polypeptide according to claim 2, wherein the mutation to the charged amino acid at position R354 is R354D or R354E.

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

23. A variant VSV-G polypeptide comprising the variant amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, including mutations corresponding to mutations at positions 8, 9, 10, 47, 50, 51, 179, 180, 183, 184, 209, 347, 350, 352, 353, 354, or combinations thereof.

24. The variant VSV-G polypeptide according to claim 23, wherein the variant VSV-G polypeptide comprises a variant of the amino acid sequence of SEQ ID NO: 3, which includes mutations corresponding to mutations at positions 8, 9, 10, 47, 50, 51, 179, 180, 183, 184, 209, 347, 350, 352, 353, 354 of SEQ ID NO: 3, or combinations thereof.

25. The variant VSV-G polypeptide according to claim 23, wherein the variant VSV-G polypeptide comprises a variant of the amino acid sequence of SEQ ID NO: 4, which includes mutations corresponding to mutations at positions 8, 9, 10, 47, 50, 51, 179, 180, 183, 184, 209, 347, 350, 352, 353, 354 of SEQ ID NO: 4, or combinations thereof.

26. The variant VSV-G polypeptide according to claim 23, wherein the variant VSV-G polypeptide comprises a variant of the amino acid sequence of SEQ ID NO: 5, which includes mutations corresponding to mutations at positions 8, 9, 10, 47, 50, 51, 179, 180, 183, 184, 209, 347, 350, 352, 353, 354 of SEQ ID NO: 5, or combinations thereof.

27. The variant VSV-G polypeptide according to any one of claims 23 to 26, wherein the mutation at positions 8, 9, 10, 47, 50, 51, 179, 180, 182, 183, 184, 209, 347, 350, 352, 353, 354, or any 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, which includes mutations corresponding to mutations at positions 8, 9, 10, 47, 50, 51, 179, 180, 183, 184, 209, 347, 350, 353, 354, or combinations thereof.

29. The variant VSV-G polypeptide according to claim 28, wherein the variant VSV-G polypeptide comprises a variant of the amino acid sequence of SEQ ID NO: 22, which includes mutations corresponding to mutations at positions 8, 9, 10, 47, 50, 51, 179, 180, 183, 184, 209, 347, 350, 353, 354, or combinations thereof.

30. The variant VSV-G polypeptide according to claim 28, wherein the variant VSV-G polypeptide comprises the amino acid sequence of SEQ ID NO: 23, which includes mutations corresponding to mutations at positions 8, 9, 10, 47, 50, 51, 179, 180, 183, 184, 209, 347, 350, 353, 354, or combinations thereof.

31. The variant VSV-G polypeptide according to any one of claims 28 to 30, wherein the mutation at positions 8, 9, 10, 47, 50, 51, 179, 180, 182, 183, 184, 209, 347, 350, 352, 353, 354, or any 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 with the amino acid sequence of SEQ ID NO: 2, and further comprises mutations corresponding to mutations at positions 8, 9, 10, 47, 50, 51, 179, 180, 182, 183, 184, 209, 347, 350, 352, 353, 354, or any combination thereof, compared with SEQ ID NO:

2.

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

34. A virus particle comprising the polypeptide described in any one of claims 1 to 32.

35. The virus particle according to claim 36, further comprising a targeted portion.

36. The virus particle according to claim 34 or 35, wherein the virus particle is a pseudotyped lentivirus.

37. The virus particle according to any one of claims 34 to 36, wherein the virus particle further comprises a nucleic acid molecule encoding a target heterologous molecule.

38. The viral particle according to claim 37, wherein the aforementioned heterogeneous molecule is a chimeric antigen receptor ("CAR").

39. The targeted portion is a glycosylation expressed on 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, which is expressed on acute leukemia or lymphoma but not on hematopoietic progenitor cells. CD43 epitope, glycosylated CD43 epitope expressed on non-hematopoietic malignancies, kinase anchor protein 4 (AKAP-4), adrenergic receptor beta-3 (ADRB3), AFP, anaplastic lymphoma kinase (ALK), androgen receptor, angiopoietin-binding cell surface receptor 2 (Tie2), autoantibodies against desmoglein 1 (Dsg1), autoantibodies against desmoglein 3 (Dsg3), B7H3 (CD276), biotin, bone marrow stromal cell antibodies Original 2 (BST2), BST1 / CD157, cancer / testicular antigen 1 (NY-ESO-1), cancer / testicular antigen 2 (LAGE-la), carbonic anhydrase IX (CA1X), carcinoembryonic antigen (CEA), CCCTC binding factor (zinc finger protein)-like (sibling of BORIS or imprint site regulator), CCR4, CD5, CD19, CD20, CD22, CD24, CD30, CD32 (FCGR2A), CD33, CD34, CD38, CD44v6, CD7 2. CD79a, CD79b, CD97, CD99, CD123, CD171, CD179a, CD179b-IGLL, 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), claudin 18.2 (CLD18A2 or CLDN18A.2), CMVpp65, C-MYC epitope tag, crypto, CS1 (also known 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 B1, cytochrome P450 IB 1 (CYP1B 1) DLL3, EBV-EBNA3c, EGF-bke module-containing mucin-like hormone receptor 2 (EMR2), elongation factor 2 mutant (ELF2M), ephrin B2, ephrin type A receptor 2 (EphA2), epidermal growth factor receptor (EGFR), epidermal growth factor receptor variant III (EGFRviiii), epidermal cell adhesion molecule (EPCAM), ERG, ETS translocation-variant gene 6 located on chromosome 12p (ETV6-AML), IgA receptor Fc fragment (FCAR or CD89), Fc receptor-like 5 (FCRL5), fibroblast-activating protein alpha (FAP), FITC, Fms-like tyrosine kinase 3 (FLT3), folate receptor alpha (FRa or FR1), folate receptor beta (FRb), follicle-stimulating hormone receptor (FS HR), 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(1-4)bDGlcp(1-1)Cer), ganglioside G M3 (aNeu5Ac(2-3)bDCLarp(1-4)bDGlcp(1-1)Cer), GD3, GFR alpha 4, glycoprotein 100 (gp100), glypican-3 (GPC3), gonadotropin receptor (CGHR or GR), GpA33, GpNMB, GPRC5D, guanylyl cyclase C (GCC), heat shock protein 70-2 variant (mut hsp70-2), hepatitis A virus cell receptor1 (HAVCR1), hexasaccharide portion of globeH glycoceramide (GloboH), high molecular weight malignant 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, HTLV-Tax, human papillomavirus E6 (HPV E6), human papillomavirus E7 (HPV E7), human telomerase reverse transcriptase (hTERT), IgE, IL13Ra2, IL 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 carboxylesterase, KIT (CD117), KSHV K8.1, KSHV-gH, LAMP1, regmine, leukocyte immunoglobulin-like receptor subfamily A member 2 (LILRA2), leukocyte-associated immunoglobulin-like receptor 1 (LAIR1), luteinizing hormone receptor (LHR), Lewis (Y) antigen, Lewis Ag, Livl, gene locus K9 (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), malignant melanoma antigen 1 recognized by T cells (MelanA or MARTI), malignant melanoma-associated antigen 1 (MAGE-A1), malignant melanoma carcinoma testis antigen-1 (MAD-CT-1), malignant melanoma carcinoma testis antigen-2 (MAD-CT-2), apoptosis inhibitor of malignant melanoma (ML-IAP), mesothelin, MPL, mucin 1 cell surface-bound (MUC1), N-acetylglucosaminyl-transferase V (NA17), nectin-4, nerve cell adhesion molecule (NCAM), NKG2D, NYBR1, O-acetyl-GD2 ganglioside (OAcGD2), olfactory receptor 51E2 (OR51E2), cleavage cluster region (BCR), and oncogene fusion protein consisting of Abelson mouse leukemia virus oncogene homolog 1 (Abl) (bcr-abl), P53 variant, paired box protein Pax-3 (PAX3), paired box protein Pax-5 (PAX5), panexin 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 cancer tumor antigen-1 (PCT A-1 or galectin 8), prostate stem cell antigen (PSCA), prostate-specific membrane antigen (PSMA), prostatic acid phosphatase (PAP), prostain, protease serine 21 (testicin or PRSS21), proteasome (prosomal macropain) subunit beta type 9 (LMP2), PTK7, RasG12V, Ras homolog family member C (RhoC), rat sarcoma (Ras) mutant, receptor for advanced glycation end products (RAGE-1), receptor tyrosine kinase-like orphan receptor 1 (ROR1), receptor tyrosine-protein kinase ERBB2 or Her-22 / neu, renal ubiquitous receptor 1 (RU1), renal ubiquitous receptor 2 (RU2), sarcoma translocation breakpoint, serine 2 (TMPRSS2) ETS fusion gene, sialyl Lewis adhesion molecule (sLe), SLAMF4, SLAMF6, Slea (CA19.9 or sialyl Lewis antigen), sperm protein T cell-recognized squamous cell carcinoma antigen 3 (SART3), stage-specific embryonic antigen-4 (SSEA-4), STEAP1, Survivin, synovial sarcoma X-section 2 (SSX2), TCR gamma surrogate leading frame protein (TARP), TCR-beta 1 chain, TCR-beta 2 chain, TCR-delta chain, TCR-gamma chain, TCR-gamma-delta, telomerase, TGF-beta R2, antigens recognized by TNT antibody, thyroid-stimulating hormone receptor (TSHR), Timl- / HVCR1, tissue factor 1 (TF1), Tn A viral particle according to any one of claims 34 to 38, which binds to 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 myeloblastosis virus oncogene neuroblastoma-derived homolog (MYCN), Wilms tumor protein (WT1), or X antigen family member 1A (XAGE1).

40. The virus particle according to claim 39, wherein the targeted portion binds to CD7.

41. The virus particle according to claim 40, wherein the targeted portion that binds to CD7 comprises a polypeptide having at least 90% sequence identity with SEQ ID NO: 52, a sequence having at least 95% sequence identity with SEQ ID NO: 52, a sequence having at least 99% sequence identity with SEQ ID NO: 52, or the sequence shown in SEQ ID NO:

52.

42. The target portion, IgG FcStork; Envelope glycoproteins G or H of viruses belonging to the Paramyxoviridae family, such as morbilliviruses including measles virus, or henipaviruses such as nipah virus, cedar virus, or hendra virus; Glycoproteins of viruses of the Rhabdoviridae family, such as bullous stomatitis New Jersey virus, bullous stomatitis Indiana virus, bullous stomatitis Aragoas virus, bullous stomatitis Maraba virus, bullous stomatitis Karajas virus, parainfluenza virus, armyworm rhabdovirus isolate Sf G, drosophila Sigma virus 10A, Wuhan insect virus 7, perch virus, or carp spring viremia virus; Glycoproteins of viruses of the Filoviridae family, such as the Ebola virus; or A virus particle according to any one of claims 34 to 41, which attaches to the surface of a virus via a glycoprotein of a virus of the family Arenaviridae, such as Machupovirus.

43. A method for delivering a heterologous molecule to a target cell, wherein the method involves the cell being a) A variant VSV-G protein according to any one of claims 1 to 32, b) A targeting portion that binds to the target cell, c) A method comprising contacting a viral vector containing a nucleic acid molecule encoding the heterologous molecule.

44. A method for delivering heterologous molecules to target cells in a subject, wherein the method is a) A variant VSV-G polypeptide according to any one of claims 1 to 32, b) A targeting portion that binds to the target cell, c) A method comprising administering a viral vector containing a nucleic acid molecule encoding the heterologous molecule to the subject.

45. The method according to claim 43 or 44, wherein the heterologous molecule is siRNA, shRNA, non-coding RNA, peptide, polypeptide, protein, viral payload, viral genome, chimeric antigen receptor ("CAR"), or a combination thereof.

46. A method for treating cancer in a subject, wherein the method is a) A variant VSV-G polypeptide according to any one of claims 1 to 32, b) A targeting portion that binds to target cells, c) A method comprising administering a viral vector containing a nucleic acid molecule encoding a heterologous molecule to the subject.

47. The method according to claim 46, wherein the heterologous molecule is a chimeric antigen receptor.

48. The method according to claim 46 or 47, wherein the cancer is carcinoma, blastoma, sarcoma, leukemia, lymphoid malignancy, benign tumor, malignant tumor, sarcoma, carcinoma, malignant melanoma, breast cancer, prostate cancer, ovarian cancer, cervical cancer, skin cancer, pancreatic cancer, colorectal cancer, kidney cancer, liver cancer, brain tumor, lymphoma, leukemia, lung cancer, thyroid cancer, B-cell related cancer, or T-cell related cancer.

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