Pseudotyped viral particles, compositions comprising pseudotyped viral particles and uses thereof

Abstract

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

Description

[0001] Related applications

[0002] This application claims the benefit of U.S. Provisional Application Serial No. 63 / 507,550, filed June 12, 2023, which is incorporated herein by reference in its entirety.

[0003] Reference sequence list submitted electronically

[0004] This application includes a sequence list, which is submitted electronically in XML format and incorporated herein by reference in its entirety. The XML copy created on May 29, 2024, is named “INH-027WO_SL” and has a size of 155,722 bytes. Background Technology

[0005] Vesicular stomatitis virus (VSV) is an enveloped, negative-sense RNA virus belonging to the genus Vesiculovirus of the family Rhabdovirus. This virus is an arbovirus that can infect insects, cattle, horses, and pigs. The VSV genome encodes five structural proteins, among which is a single transmembrane glycoprotein (G). Glycoproteins are classic type I membrane glycoproteins with an N-terminal signal peptide, an extracellular domain of approximately 450 amino acids, a single α-helix transmembrane segment, and a small intraviral C-terminal domain. The signal peptide is cleaved in the lumen of the endoplasmic reticulum, and the native glycoprotein is present in the extracellular domain, transmembrane domain, and intraviral domain.

[0006] G plays a crucial role in the initial steps of viral infection (Molecular and Cellular Aspects of Rhabdovirus Entry. Viruses 4, 117-139.), which is incorporated herein by reference in its entirety. First, this glycoprotein is responsible for viral attachment to specific receptors. After binding, the viral particle enters the cell via clathrin-mediated endocytosis. In the acidic environment of the endocytic vesicles, G triggers the fusion between the viral membrane and the endosomal membrane, releasing the genome into the cytosol for subsequent infection steps. Fusion is catalyzed by a large structural transition from the pre-fusion conformation to the post-fusion conformation induced by low pH, both of which are 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 reference is incorporated herein by reference in its entirety.

[0007] The G extracellular domain folds into three distinct domains: the fusion domain (FD), the Plek substrate homology domain (PHD), and the trimer domain (TrD). During structural transitions, FD, PHD, and TrD retain their tertiary structure. However, these domains undergo significant rearrangements in their relative orientations due to secondary changes in the refolded hinge segments (S1 to S5) during low-pH-induced conformational changes (Roche et al., 2006; Roche et al., 2007).

[0008] It has been shown that the low-density lipoprotein receptor (LDL-R) and other members of this receptor family act 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, the entire text of which is incorporated herein by reference). VSV-G can be used for pseudotypening of other viruses, and VSV-G pseudotyped lentiviruses (VSV-G-LV) exhibit the same broad tropism as VSV. However, this broad tropism can inhibit selective targeting to specific cell types. Therefore, there is a need to eliminate modified (mutated or mutant) VSV-G proteins that bind to the LDL receptor and can be used for viral pseudotypening. Embodiments of the present invention meet these and other needs.

[0009] Human CD7 is a cell surface glycoprotein belonging to the immunoglobulin superfamily with a molecular weight of approximately 40 kDa. CD7 is primarily expressed on the surface of most thymocytes, over 85% of peripheral blood T lymphocytes, and natural killer cells. The embodiments disclosed herein provide peptides and antibodies targeting CD7, compositions comprising the peptides and antibodies, and their uses.

[0010] CD8 (Cluster 8 of Differentiation) is a transmembrane glycoprotein and a specific marker for T cell subclasses, including cytotoxic T cells. Not bound by any particular theory, CD8 assembles into heterodimers of CD8α and CD8β subunits or homodimers of CD8α. The assembled dimerized CD8 complex, together with the T cell receptor (TCR), acts as a co-receptor 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 can reflect the progression of the immune response and can occur over time. The embodiments disclosed herein provide peptides and antibodies against CD8, compositions comprising the peptides and antibodies, and their uses. Summary of the Invention

[0011] In some embodiments, a VSV-G polypeptide is provided, which contains 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 in SEQ ID NO: 2.

[0012] In some embodiments, mutations at positions 8, 9, 10, 47, 50, 51, 179, 180, 182, 183, 184, 209, 347, 350, 352, 353, 354, or combinations thereof in SEQ ID NO: 2 involve substitutions for charged amino acids.

[0013] In some implementations, the charged amino acids are located at positions H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, or R354.

[0014] In some embodiments, the substitution of the charged amino acid is selected from D, E, K, or R.

[0015] In some embodiments, a VSV-G polypeptide is provided comprising the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, and further comprising 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 in SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5.

[0016] In some embodiments, a VSV-G polypeptide is provided comprising the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23, and further comprising 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.

[0017] In some implementations, viral particles comprising the VSV-G polypeptide as provided herein are provided.

[0018] In some implementations, the viral particles also include a targeting portion as provided herein.

[0019] In some implementations, the viral particles are pseudotyped lentiviruses as described herein.

[0020] In some implementations, the viral particles also contain nucleic acid molecules encoding heterologous molecules of interest, as provided herein.

[0021] In some implementations, the heterologous molecule of interest is a chimeric antigen receptor (“CAR”) as presented herein.

[0022] In some implementations, the chimeric antigen receptor includes an antigen-binding domain that binds to CD20 as provided herein.

[0023] In some implementations, the targeting portion binds to CD7 as provided herein.

[0024] In some implementations, the targeting portion binds to CD8 as provided herein.

[0025] In some embodiments, a method for delivering a heterologous molecule to a target cell is provided, the method comprising contacting the cell with a viral vector comprising:

[0026] a) VSV-G peptides as provided in this article;

[0027] b) The targeting portion that binds to the target cell; and

[0028] c) The nucleic acid molecule that encodes the heterologous molecule.

[0029] In some embodiments, a method is provided for delivering a heterologous molecule of interest to target cells in a subject, the method comprising administering a viral vector to the subject, the viral vector comprising:

[0030] a) VSV-G protein as provided in this article;

[0031] b) The targeting portion that binds to the target cell; and

[0032] c) The nucleic acid molecule that encodes the heterologous molecule.

[0033] In some implementations, the heterologous molecule is a chimeric antigen receptor as provided herein.

[0034] In some implementations, a method for treating a subject's cancer is provided, the method comprising administering a viral vector to the subject, the viral vector comprising:

[0035] a) VSV-G protein as provided in this article;

[0036] b) The targeting portion that binds to the target cell; and

[0037] c) The nucleic acid molecule that encodes the heterologous molecule.

[0038] In some implementations, the heterologous molecule is a chimeric antigen receptor as provided herein. Attached Figure Description

[0039] Figure 1A and Figure 1B The crystal structure of VSV-G combined with LDL-R is illustrated. Figure 1A The crystal structure of VSV-G bound to CR3 of LDL-R is illustrated. Figure 1B The crystal structure of VSV-G with CR2 bonded to LDL-R is illustrated.

[0040] Figure 2A and Figure 2B The effect of adding negatively charged amino acids to the VSV-G:LDL-R binding interface on native affinity and cohesion is illustrated. Figure 2A The titration of the VSV-G construct on SupT1 cells is illustrated. Figure 2B Examples are given by Figure 2A The functional titer of each construct is calculated by titration.

[0041] Figure 3 The comparison of extracellular domains of different VSV-G proteins from different strains is illustrated.

[0042] Figure 4 The effects of various VSV-G mutations on the serum stability of viral constructs combined with CD7 binding compounds are illustrated.

[0043] Figure 5 The effects of various VSV-G mutations on the serum stability of viral constructs combined with CD7 binding compounds are illustrated.

[0044] Figures 6A-6L Flow cytometry data of human PBMCs transduced with an exemplary vector containing a CD7 conjugate as disclosed herein are shown.

[0045] Figure 6M Flow cytometry data of human PBMCs transduced with an exemplary vector containing a CD7 conjugate as disclosed herein are shown.

[0046] Figure 7A -L shows flow cytometry data of non-human primate PBMCs transduced with an exemplary vector containing CD7 conjugates as disclosed herein.

[0047] Figure 7M Flow cytometry data of non-human primate PBMCs transduced with exemplary vectors containing CD7 conjugates as disclosed herein are shown.

[0048] Figure 8A Flow cytometry data of human PBMCs transduced with an exemplary vector containing a CD8 conjugate as disclosed herein are shown.

[0049] Figure 8B Flow cytometry data of non-human primate PBMCs transduced with exemplary vectors containing CD8 conjugates as disclosed herein are shown.

[0050] Figure 9A and Figure 9B Examples of GFP or CAR transduction in SupT1 cells using lentiviral particles with VSV-G pseudotypes carrying CD7 or CD8 conjugates, as provided herein. Figure 9A An example of GFP transduction is shown. Figure 9B An example of CAR transduction is given.

[0051] Figure 10A An example is VSV-G carrying a CD7 conjugate. The ability of pseudotyped lentiviral particles to transduce SupT1 cells and human and non-human primate PBMCs. Figure 10B The transduction of cells in the absence of CD7 binders is illustrated. Figure 10C Transduction of human and non-human primate PBMCs based on MOI calculated by SupT1 titration is illustrated. VSV-G This indicates a VSV-G polypeptide containing I182E, T214N, and T352A, which corresponds to the mature polypeptide (with I196E, T230N, and T368A mutations (with leader sequence and adjusted numbering)) of SEQ ID NO: 23 or SEQ ID NO: 25.

[0052] Figure 11A and Figure 11B This example illustrates VSV-G cells carrying CD7 binding compounds in a group of B cell lines compared to control SupT1 cells. Off-target transduction of pseudomorphic lentiviral particles. Figure 11A The data for GFP transduction are illustrated. Figure 11B Data on CAR20-T2A-GFP transduction are illustrated. VSV-G This indicates a VSV-G polypeptide containing the I182E, T214N, and T352A mutations as provided herein.

[0053] Figure 12A and Figure 12B Examples of VSV-G transgenics utilizing CD7 conjugates and CD20-CARs as provided herein are illustrated. Pseudotyped lentiviral particles kill Daudi lymphoma cells ( Figure 12A) or Raji lymphoma cells ( Figure 12B The CAR20 construct utilizes an antigen-binding domain comprising rituximab or, as provided herein, CD20AB1 SEQ ID NO 75 or 76.

[0054] Figure 13A and Figure 13B Examples of VSV-G transgenics utilizing CD7 conjugates and CD20-CARs as provided herein are illustrated. Pseudotyped lentiviral particles deplete the ability of B cells in huCD34 NSG mice. This is achieved through the inhibition of CD20 (… Figure 13A ) or CD19 ( Figure 13B The assessment of B cells is used to detect B cells.

[0055] Figure 14A and Figure 14B Examples of VSV-G transgenics utilizing CD7 conjugates and CD20-CARs as provided herein are illustrated. The ability of pseudomorphic lentiviral particles to prevent tumor formation in the body. Figure 14A The experimental design was described. Figure 14B Mice that received intravenous lentiviral particles as presented herein prior to Raji tumor infusion had significantly lower tumor burden than mice that received the control (GFP) vector or untreated mice. Tumor burden was measured via IVIS imaging.

[0056] Figure 15A and Figure 15B Examples of VSV-G transgenics utilizing CD7 conjugates and CD20-CARs as provided herein are illustrated. The ability of pseudomorphic lentiviral particles to eliminate Raji tumors established in the body. Figure 15A The experimental design was described. Figure 15B This study illustrates that, 6 days after Raji tumor infusion, the tumor burden in mice receiving intravenous lentiviral particles as described herein decreased to below the detection limit. Tumor burden was measured via IVIS imaging.

[0057] Figure 16 An example is illustrated by combining I182E with both I347G and T352E, or combining I182E with T352Q / E, thereby demonstrating a possible low-level additive benefit to additional variants. Detailed Implementation

[0058] This article provides a mutant VSV-G protein that can be used, for example, for pseudotypening viruses such as lentiviruses. In some embodiments, the pseudotyped virus-like particles are pseudotyped using viral glycoproteins of vesicular stomatitis New Jersey virus strain, vesicular stomatitis Indiana virus strain, vesicular stomatitis Aragos virus strain, vesicular stomatitis Malaba virus strain, or vesicular stomatitis Carajás virus strain.

[0059] Pseudotyped viruses containing mutant VSV-G proteins can be used in combination with target regions to promote the fusion of pseudotyped viruses with specific cells or tissues based on the expression of the target in the cells or tissues.

[0060] Unless otherwise defined, all technical and scientific terms have the same meaning as commonly understood by one of ordinary skill in the art to which the disclosed embodiments pertain.

[0061] As used herein, unless the context clearly indicates otherwise, the term "a" means "at least one" or "one or more".

[0062] As used herein, the term “about” means an approximate index value, and small variations will not significantly affect the practice of the disclosed embodiments. When numerical limits are used, the “about” index value may vary by ±10% and remain within the range of the disclosed embodiments unless the context otherwise specifies. Furthermore, when the phrase “about x to y” is used, the term “about” modifies both x and y unless the context otherwise specifies, and can be used interchangeably with the phrase “about x to about y”.

[0063] As used in this article regarding T cells, "activation" refers to the state of T cells that have been adequately stimulated to induce detectable cell proliferation. Activation can also be associated with induced cytokine production and detectable effector function. The term "activated T cell" primarily refers to T cells that are undergoing cell division.

[0064] As used in this article, “alleviating” a disease means reducing the severity of one or more symptoms of the disease.

[0065] 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 specific immune-competent cells, or both. Those skilled in the art will understand that any macromolecule, including virtually all proteins or peptides, can be used as an antigen. The term "antigen" may also refer to a molecule that antibodies or antibody-like molecules can bind to or recognize.

[0066] The terms “antibody molecule,” “antibody,” or “antigen-binding domain,” as used herein, refer to a polypeptide, such as an immunoglobulin chain or fragment thereof, containing at least one functional immunoglobulin variable domain sequence. An antibody molecule encompasses both antibodies (e.g., full-length antibodies) and antibody fragments. In some embodiments, an antibody molecule comprises an antigen-binding fragment or functional fragment of a full-length antibody or a full-length immunoglobulin chain. For example, a full-length antibody is a naturally occurring immunoglobulin (Ig) molecule (e.g., an IgG antibody) formed through a normal immunoglobulin gene fragment recombination process. In embodiments, an antibody molecule refers to the immunologically active antigen-binding portion of an immunoglobulin molecule, such as an antibody fragment. An antibody fragment, such as a functional fragment, comprises 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). The functional antibody fragment binds to the same antigen recognized by the intact (e.g., full-length) antibody. The terms "antibody fragment" or "functional fragment" also include separate fragments composed of variable regions, such as an "Fv" fragment composed of variable regions of a heavy chain and a light chain, or a recombinant single-chain polypeptide molecule ("scFv protein") in which the light chain variable regions and heavy chain variable regions are linked by peptide linkers. In some embodiments, the antibody fragment does not include antibody portions that do not have antigen-binding activity, such as Fc fragments or single amino acid residues. Exemplary antibody molecules include full-length antibodies and antibody fragments such as dAb (domain antibody), single-chain, Fab, Fab', and F(ab')2 fragments, and single-chain variable fragments (scFv).

[0067] The term "antibody molecule" also encompasses the entire or antigen-binding fragment of a domain antibody or single-domain antibody (also referred to as "sdAb" or "VHH"). Domain antibodies contain a VH or VL that can function as a standalone antibody fragment. Additionally, domain antibodies include antibodies containing only the heavy chain (HCAb). Domain antibodies also include the CH2 domain of IgG as a scaffold into which the CDR loop is grafted. 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 camel species such as llamas, but can also be synthesized using techniques well known in the art. The amino acid residue numbering of sdAbs or polypeptides follows the general numbering system for the VH domain, as given by Kabat et al. ("Sequence of proteins of immune interest," US Public Health Services, NIH Bethesda, MD, Publication 91, which is incorporated herein by reference in its entirety.). According to this designation, sdAb's FR1 contains amino acid residues at positions 1-30, sdAb's CDR1 contains amino acid residues at positions 31-36, sdAb's FR2 contains amino acids at positions 36-49, sdAb's CDR2 contains amino acid residues at positions 50-65, sdAb's FR3 contains amino acid residues at positions 66-94, sdAb's CDR3 contains amino acid residues at positions 95-102, and sdAb's FR4 contains amino acid residues at positions 103-113. Domain antibodies are also described in WO2004041862 and WO2016065323, each of which is incorporated herein by reference in its entirety. Domain antibodies can be targeting portions as described herein.

[0068] As used herein, unless otherwise stated, "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 that binds to a full-length antibody, such as a fragment retaining one or more CDR regions. Examples of antibody-binding fragments include, but are not limited to, Fab, Fab', F(ab')2, and Fv fragments; bivalent antibodies; linear antibodies; single-chain antibody molecules (e.g., sc-Fv); nanobodies (single-domain antibodies) formed from antibody fragments; and multispecific antibodies.

[0069] The “Fab fragment” consists of a light chain and a heavy chain of C… H It consists of 1 and variable regions. The heavy chain of the Fab molecule cannot form disulfide bonds with another heavy chain molecule.

[0070] The “Fc” region contains two C-cells that contain antibodies. H 2 and C H 3. Heavy chain segments of the structural domain. Two heavy chain segments are connected by two or more disulfide bonds and by C... H The hydrophobic interactions of the three structural domains remain together.

[0071] A “Fab” fragment contains a light chain and a portion or fragment of a heavy chain, wherein the portion or fragment of the heavy chain contains V. H Domain and C H 1. Structural domains and C H 1 and C H The region between the two domains allows interchain disulfide bonds to form between the two heavy chains of the two Fab' segments to form the F(ab')2 molecule.

[0072] The “F(ab')2 segment” contains two light chains and two heavy chains, with the heavy chains containing C. H 1 and C H Part of the constant region between the two structural domains allows for the formation of interchain disulfide bonds between the two heavy chains. Therefore, the F(ab')2 segment consists of two Fab' segments, which are held together by disulfide bonds between the two heavy chains.

[0073] The “Fv region” contains variable regions from both the heavy and light chains, but lacks constant regions.

[0074] The term "single-chain Fv" or "scFv" antibody refers to a V antibody containing an antibody. H Domain and V L Antibody fragments containing domains, wherein these domains are present within a single polypeptide chain. Typically, Fv polypeptides also contain domains intermediate between V and V. H Domain and V L A polypeptide linker between the domains enables scFv to form the structure required for antigen binding. For a review of scFv, see Pluckthun (1994), The Pharmacology of Monoclonal Antibodies, Vol. 113, edited by Rosenburg and Moore, Springer-Verlag, New York, pp. 269–315. See also International Patent Application Publication No. WO88 / 01649 and U.S. Patents Nos. 4,946,778 and 5,260,203.

[0075] Antibody molecules can be monospecific (e.g., monovalent or bivalent), bispecific (e.g., bivalent, trivalent, tetravalent, pentavalent, or hexavalent), trispecific (e.g., trivalent, tetravalent, pentavalent, or hexavalent), or have a higher level of specificity (e.g., tetraspecific) and / or a higher valence level than hexavalent. Antibody molecules may contain functional fragments of the light chain variable region and the heavy chain variable region, or the heavy and light chains may be fused together to form a single polypeptide.

[0076] Furthermore, antigens can be derived from recombinant or genomic DNA. Those skilled in the art will understand that any DNA containing a nucleotide sequence or a portion thereof encoding a protein that triggers an immune response therefore encodes the term "antigen" as used herein. Furthermore, those skilled in the art will understand that an antigen does not necessarily need to be encoded solely by the full-length nucleotide sequence of a gene. Moreover, those skilled in the art will understand that an antigen does not necessarily need to be encoded by a "gene" at all. It is evident that antigens can be synthesized or can be derived from biological samples. Such biological samples can include, but are not limited to, tissue samples, tumor samples, cells, or biological fluids.

[0077] In some embodiments, the monoclonal antibodies described herein also include camel-modified single-domain antibodies. See, for example, Muyldermans et al. (2001) Trends Biochem. Sci. 26:230; Reichmann et al. (1999) J. Immunol. Methods 231:25; WO 94 / 04678; WO 94 / 25591; U.S. Patent No. 6,005,079). In one embodiment, the present invention provides single-domain antibodies comprising two Vi molecules modified such that a single-domain antibody is formed. H Structural domain.

[0078] As used herein, the term "bivalent antibody" refers to a small antibody fragment having two antigen-binding sites, which contain fragments linked to the same polypeptide chain (V). H -V L or V L -V H The light chain variable structural domain (V) in ) L The heavy chain variable structural domain (V) HBy using linkers that are too short to allow pairing between two domains on the same strand, a domain is forced to pair with a complementary domain on another strand, creating two antigen-binding sites. Bivalent antibodies are described more comprehensively in, for example, EP 404,097; WO93 / 11161; and Holliger et al. (1993) Proc. Natl. Acad. Sci. USA 90: 6444-6448. For reviews of engineered antibody variants, see Holliger and Hudson (2005) Nat. Biotechnol. 23:1126-1136.

[0079] "Isolated antibody" refers to the purified state of a binding compound, and in such cases means that the molecule is substantially free of other biomolecules, such as nucleic acids, proteins, lipids, carbohydrates, or other materials such as cell debris and growth media. Generally, the term "isolated" is not intended to mean the complete absence of such materials or the absence of water, buffers, or salts, unless they are present in amounts that would substantially interfere with the experimental or therapeutic use of the binding compound as described herein.

[0080] As used herein, the term "monoclonal antibody" refers to a substantially homogeneous group of antibodies, meaning that the antibody molecules constituting the group are identical in amino acid sequence except that they may be present in small amounts with possible naturally occurring mutations and / or post-translational modifications. In contrast, conventional (polyclonal) antibody formulations typically comprise a variety of different antibodies having different amino acid sequences in their variable domains (particularly their CDRs) that are typically specific to different epitopes. The modifier "monoclonal" indicates the characteristic of antibodies obtained from a substantially homogeneous group of antibodies and should not be construed as requiring the antibody to be produced by any particular method. For example, the monoclonal antibody to be used according to the invention can be prepared by the hybridoma method first described by Kohler et al. (1975) Nature 256: 495, or by a recombinant DNA method (see, for example, U.S. Patent No. 4,816,567). Monoclonal antibodies can also be isolated from phage antibody libraries using techniques described, for example, those described in 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.

[0081] As used herein, the term "humanized antibody" refers to an antibody form containing sequences derived from both humans and non-humans (e.g., mice, rats). Generally, a humanized antibody will contain at least one and typically substantially all of two variable domains, wherein all or substantially all of the hypervariable loops correspond to those of non-human immunoglobulins, and all or substantially all of the frame (FR) regions are those of the human immunoglobulin sequence. A humanized antibody may optionally contain at least a portion (Fc) of the constant region of a human immunoglobulin.

[0082] The term "fully human antibody" refers to an antibody that contains only the sequence of human immunoglobulin proteins. If produced in mice, mouse cells, or hybridomas derived from mouse cells, fully human antibodies may contain mouse glycans. Similarly, "mouse antibody" refers to an antibody that contains only the sequence of mouse immunoglobulins. Alternatively, if produced in rats, rat cells, or hybridomas derived from rat cells, fully human antibodies may contain rat glycans. Similarly, "rat antibody" refers to an antibody that contains only the sequence of rat immunoglobulins.

[0083] In some implementations, the basic antibody structural unit comprises a tetramer. Each tetramer comprises two pairs of identical polypeptide chains, each pair having a "light" chain (approximately 25 kDa) and a "heavy" chain (approximately 50 kDa to 70 kDa). The amino-terminal portion of each chain includes a variable region of approximately 100 to 110 or more amino acids, which is primarily responsible for antigen recognition. The carboxyl-terminal portion of the heavy chain may define a constant region primarily responsible for effector function. Typically, human light chains are classified as κ and λ light chains. Furthermore, human heavy chains are typically classified as μ, δ, γ, α, or ε, and antibody isotypes are defined as IgM, IgD, IgG, IgA, and IgE, respectively. Within both the light and heavy chains, the variable and constant regions are linked by a "J" region having approximately 12 or more amino acids, wherein the heavy chain also includes a "D" region having approximately 10 or more amino acids. See also Fundamental Immunology, Chapter 7 (edited by Paul, W., 2nd ed., Raven Press, NY (1989)).

[0084] The variable region of each light / heavy chain pair forms the antibody binding site. Therefore, in general, a complete antibody has two binding sites. However, in bifunctional or bispecific antibodies, the two binding sites are usually not the same.

[0085] Typically, the variable domains of both heavy and light chains contain three hypervariable regions, also known as complementarity-determining regions (CDRs), located within relatively conservative frame regions (FRs). CDRs are usually aligned with the frame regions to enable binding to specific epitopes. Generally, from the N-terminus to the C-terminus, the variable domains of both light and heavy chains contain FR1, CDR1, FR2, CDR2, FR3, CDR3, and FR4. The allocation of amino acids to each domain is usually based on the following definitions: Sequences of Proteins of Immunological Interest, Kabat et al.; National Institutes of Health, Bethesda, Md.; 5th edition; NIH Publ. No. 91-3242 (1991); Kabat (1978) Adv. Prot. Chem. 32:1-75; Kabat et al., (1977) J. Biol. Chem. 252:6609-6616; Chothia et al., (1987) J Mol. Biol. 196:901-917 or Chothia et al., (1989) Nature 342:878-883.

[0086] As used in this article, the term "hypervariate region" refers to the amino acid residues of the antibody responsible for antigen binding. The hypervariable region contains residues from the complementarity-determining region or the 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 edition Public Health Service, National Institutes of Health, Bethesda, Md.) and / or residues that form the hypervariable ring (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). CDRs may also be referred to by the IMGT system used to identify CDRs, described in Lefranc MP Unique database numbering system for immunogenetic analysis. Immunol Today (1997) 18:509. As used herein, the terms “frame” or “FR” residues refer to those variable domain residues other than the hypervariable region residues defined herein as CDR residues. CDRs provide most of the contact residues for antibody binding to antigens or epitopes. CDRs of interest may be derived from the variable heavy and light chain sequences of donor antibodies and include analogues of naturally occurring CDRs that also share or retain the same antigen-binding specificity and / or neutralizing capacity as the donor antibodies from which they are derived.

[0087] As used herein, "specific binding," "immune-specific binding," or "immune-specific binding" refers to an antibody binding to a predetermined antigen with a much higher affinity than to another antigen. In some embodiments, the antibody binds with an affinity of 10... -7 M or a smaller dissociation constant (K) D ) combines with the predetermined antigen, and this type of K D It is its K-type receptor that binds to non-specific antigens (e.g., BSA, casein, or another non-specific polypeptide). D At most 1 / 2.

[0088] Methods for determining mAb specificity and affinity through competitive inhibition can be found in the following literature: 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). These references are incorporated herein by reference in their entirety.

[0089] As used herein, the interchangeable terms “individual” or “subject” or “patient” mean any animal, including mammals such as mice, rats, other rodents, rabbits, dogs, cats, pigs, cattle, sheep, horses, or primates (such as humans). In some embodiments, the subject is a human. A “subject in need” means a subject who has been identified as needing treatment for a condition to be treated and is being treated with the specific intent to treat such a condition. These conditions can be any conditions, such as those described herein.

[0090] As used herein, the terms “comprise” (and any form of inclusion, such as “comprise”, “comprises”, and “comprised”), “have” (and any form of having, such as “have” and “has”), “include” (and any form of inclusion, such as “includes” and “include”), or “contains” (and any form of containing, such as “contains” and “contains”) are inclusive or open-ended and do not exclude additional, unlisted elements or method steps. Any step or composition using the transitional phrase “comprise” or “comprising” may also be described as being identical to that described by the transitional phrase “consisting of” or “consists”.

[0091] As used herein, the term “contact” means bringing two elements together in an in vitro or in vivo system. For example, “contacting” a virus or vector described herein with an individual or patient or cells includes administering a virus to an individual or patient, such as a human, and, for example, introducing a compound into a sample containing cells or a purified preparation containing cells.

[0092] As used herein, the terms “fusion” or “linkage” when referring to proteins with different domains or heterologous sequences mean that the protein domains are part of the same peptide chain and are linked to each other by peptide bonds or other covalent bonds. Domains or segments may be directly linked or fused to each other, or another domain or peptide sequence may be between two domains or sequences, and such sequences will still be considered fused or linked to each other. In some embodiments, the various domains or proteins provided herein are directly linked or fused to each other, or adapter sequences such as the glycine / serine sequences described herein link two domains together.

[0093] "Disease" is a state of health in which the animal is unable to maintain homeostasis, and in which the animal's health continues to deteriorate if the disease is not treated. In contrast, an animal's "symptom" is a state of health in which the animal is able to maintain homeostasis, but in which the animal's health is worse than it would be without the symptom. A symptom, if left untreated, does not necessarily lead to a further decline in the animal's health.

[0094] The terms "effective amount" or "therapeutic effective amount" are used interchangeably herein and refer to the amount of a compound, formulation, material, or composition as described herein that effectively achieves a particular biological outcome or provides a therapeutic or preventative benefit. Such an outcome may include, but is not limited to, the amount of immune cell activation that, when administered to a mammal, results in a detectable level of immune cell activation compared to that detected in the absence of the composition. Immune responses can be readily assessed using a wide range of methods recognized in the art. Those skilled in the art will understand that the amount of the composition administered herein varies and can be readily determined based on many factors, such as the disease or symptom being treated, the age and health and physical condition of the mammal being treated, the severity of the disease, the specific compound administered, etc.

[0095] "Encoding" refers to the inherent characteristics of a specific nucleotide sequence in a polynucleotide (such as a gene, cDNA, or mRNA) for use as a template in biological processes to synthesize other polymers and macromolecules having defined nucleotide sequences (i.e., rRNA, tRNA, and mRNA) or defined amino acid sequences, and the resulting biological characteristics. Therefore, if the transcription and translation of the mRNA corresponding to a gene produces a protein in a cell or other biological system, then the gene encodes that protein. Both the coding strand, whose nucleotide sequence is identical to the mRNA sequence and is typically provided in the sequence listing, and the non-coding strand, which serves as a template for transcription of the gene or cDNA, can be referred to as the protein or other product encoding that gene or cDNA.

[0096] "Expression vector" refers to a vector containing a recombinant polynucleotide that includes an expression control sequence operatively linked to a nucleotide sequence to be expressed. The expression vector contains sufficient cis-acting elements for expression; other elements for expression may be provided by a host cell or in an in vitro expression system. Expression vectors include all expression vectors known in the art, such as clomids, plasmids (e.g., naked or contained in liposomes) and viruses (e.g., Sendai virus, lentivirus, retrovirus, adenovirus, and adeno-associated virus) incorporating recombinant polynucleotides.

[0097] As used in this article, the phrase “ex vivo” in relation to transducing, transfecting or transforming cells means transducing, transfecting or transforming cells outside of a subject, i.e., removing cells from a subject prior to transducing, transfecting or transforming such cells.

[0098] As used herein, “identity” refers to the subunit sequence identity between two polymer molecules, such as two nucleic acid or amino acid molecules, or such as two polynucleotide or polypeptide molecules. Two amino acid sequences are identical when they have the same residue at the same position; for example, if each position in two polypeptide molecules is occupied by arginine, then they are identical at that position. The degree of identity, or similarity, between two amino acid or two nucleic acid sequences in an alignment is usually expressed as a percentage. Identity between two amino acid or two nucleic acid sequences is a direct function of the number of matching or identical positions; for example, if half of the positions in two sequences are identical, then the two sequences are 50% identical; if 90% of the positions (e.g., 9 out of 10) are matching or identical, then the two amino acid sequences are 90% identical.

[0099] "Substantially identical" means that the polypeptide or nucleic acid molecule exhibits at least 50% identity with 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 a sequence is at least 60%, 80%, or 85%, or 90%, 95%, or even 99% identical to the sequence used for comparison at the amino acid level or nucleic acid level. Other percentages of identity with respect to specific sequences are described herein.

[0100] Sequence identity can be measured / determined using sequence analysis software, such as the sequence analysis software package from Genetics Computer Group, University of Wisconsin Biotechnology Center, 1710 University Avenue, Madison, Wis. 53705, including the BLAST, BESTFIT, GAP, or PILEUP / PRETTYBOX programs. Such software matches identical or similar sequences by assigning degrees of homology to various substitutions, deletions, and / or other modifications. Conserved substitutions typically include those within the following groups: glycine, alanine; valine, isoleucine, leucine; aspartic acid, glutamic acid, asparagine, glutamine; serine, threonine; lysine, arginine; and phenylalanine, tyrosine. In exemplary methods for determining the degree of identity, the BLAST program can be used, where a probability score between e3 and e100 indicates closely related sequences. In some embodiments, sequence identity is determined using BLAST with default settings.

[0101] For the purposes of the embodiments provided herein, compositions comprising various proteins may, in some cases, contain amino acid sequences that have sequence identity with the amino acid sequences disclosed herein. Therefore, in some embodiments, depending on the specific sequence, the degree of sequence identity with the SEQ ID NO disclosed herein is preferably greater than 50% (e.g., 60%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or greater). Other identity percentages are also provided herein in addition to these percentages. Identity between peptides can be determined using an affine gap search with parameters gap opening penalty (12) and gap extension penalty = 1, as implemented in the MPSRCH program (Oxford Molecular).

[0102] These proteins, compared to publicly available proteins, may include one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) conserved amino acid substitutions, where one amino acid is replaced by another amino acid with a related side chain. Genetically encoded amino acids are generally classified into four families: (1) acidic, i.e., aspartic acid and glutamic acid; (2) basic, i.e., lysine, arginine, and histidine; (3) nonpolar, i.e., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, and tryptophan; and (4) uncharged polar, i.e., glycine, asparagine, glutamine, cysteine, serine, threonine, and tyrosine. Phenylalanine, tryptophan, and tyrosine are sometimes collectively classified as aromatic amino acids. Generally, substitution of a single amino acid within these families does not significantly affect biological activity. Proteins may have one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) single amino acid deletions relative to publicly available protein sequences. In addition to the publicly available protein sequence, the protein may also contain one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) insertions (e.g., each of 1, 2, 3, 4, or 5 amino acids). As presented herein, the variations may also be non-conservative.

[0103] As used in this article, the phrase “in vivo” in relation to transducing, transfecting, or transforming cells means transducing, transfecting, or transforming such cells in a subject without removing the cells from the subject prior to transducing, transfecting, or transforming them.

[0104] "Separated" means altered or removed from its natural state. For example, nucleic acids or peptides that are naturally present in living organisms are not "separated," but the same nucleic acids or peptides that are partially or completely separated from their natural counterparts are "separated." Separated nucleic acids or proteins can exist in a substantially purified form or in non-natural environments, such as, for example, host cells.

[0105] As used herein, “lentivirus” refers to a genus of the family Retroviridae capable of infecting non-dividing cells. Non-limiting examples of lentiviruses are HIV, SIV, and FIV. Vectors or virus-like particles derived from lentiviruses can be used to transduce cells and deliver genes or other molecules, enabling their expression in cells either in vitro (ex vivo) or in vivo.

[0106] As used herein, the term "modified" refers to an altered state or structure of a molecule or cell as presented herein. Molecules can be modified in many ways, including chemically, structurally, and functionally, such as through mutation, substitution, insertion, or deletion (e.g., internal deletion truncation). Cells can be modified by introducing nucleic acids or expressing heterologous proteins.

[0107] As used herein, the term "modulation" means mediating an increase or decrease in a subject's response level compared to the response level of a subject in the absence of treatment or the compound, and / or compared to the response level of other subjects who are otherwise identical but untreated. This term includes interfering with and / or influencing natural signals or responses, thereby mediating a beneficial therapeutic response in a subject (such as a human).

[0108] As used in this article, the following abbreviations for common nucleic acid bases are used: “A” for adenosine, “C” for cytosine, “G” for guanosine, “T” for thymidine, and “U” for uridine.

[0109] Unless otherwise specified, "nucleotide sequence encoding an amino acid sequence" includes all nucleotide sequences that are degenerate to each other and encode the same amino acid sequence. Phrases encoding protein or RNA may also contain introns, to the extent that nucleotide sequences encoding proteins may contain introns in some forms.

[0110] Nipah virus (NiV) is a member of the genus Henipavirus in the paramyxovirus family. Nipah virus is an enveloped virus with negatively polar RNA and a non-segmented RNA genome composed of a helical nucleocapsid. Two strains of Nipah virus include, but are not limited to, the Malaysian (MY) and Bangladeshi (BD) strains.

[0111] The term "oligonucleotide" usually refers to short polynucleotides. It should be understood that when a nucleotide sequence is represented by a DNA sequence (i.e., A, T, C, G), this also provides the corresponding RNA sequence (i.e., A, U, C, G) in which "U" replaces "T".

[0112] "Parenteral" administration of the composition includes techniques such as subcutaneous (sc), intravenous (iv), intramuscular (im), or intrasternal injection or infusion.

[0113] As used herein, the term "polynucleotide" is defined as a nucleotide chain. Furthermore, nucleic acids are polymers of nucleotides. Therefore, as used herein, the terms "nucleic acid" and "polynucleotide" are interchangeable. As used herein, polynucleotides include, but are not limited to, all nucleic acid sequences obtained by any method available in the art, including, but not limited to, recombinant methods, i.e., cloning nucleic acid sequences from recombinant libraries or cell genomes using cloning techniques and PCR, as well as synthetic methods.

[0114] As used herein, the terms “peptide,” “polypeptide,” and “protein” are used interchangeably and refer to compounds consisting of multiple amino acid residues covalently linked by peptide bonds. As used herein, the term refers to both short chains (which are also commonly referred to in the art as, for example, peptides, oligopeptides, and oligomers) and long chains (which are commonly referred to in the art as proteins, of which there are many types). “Polypeptide” includes, for example, biologically active fragments, substantially homologous polypeptides, oligopeptides, homodimers, heterodimers, variants of polypeptides, modified polypeptides, derivatives, analogs, fusion proteins, and so on. Polypeptides include natural peptides, recombinant peptides, synthetic peptides, or combinations thereof.

[0115] As used herein, the term "variant," when used to refer to a polynucleotide or polypeptide sequence, means that the variant has one or more changes compared to a reference sequence being compared. This change can be a mutation (substitution), deletion, or insertion. Variants can contain conserved or non-conserved mutations. For example, a variant VSV-G polypeptide is a VSV-G polypeptide that contains one or more changes compared to a reference VSV-G polypeptide. Various reference VSV-G polypeptides are provided herein. In some embodiments, the variant contains a mutation that modifies uncharged residues to charged residues. Non-limiting examples of such variants are provided herein. In some embodiments, the variant has 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 changes. The insertion of a consecutive number of amino acids is considered one change. For example, if a "GGG" peptide is inserted into a sequence to produce a variant without changing the inserted N-terminal or C-terminal residue, this is considered one change. However, if three consecutive amino acids in the reference sequence are changed to "GGG," this is considered three changes (mutations).

[0116] As used herein, the term "pseudotyped" or "pseudotyped viral particle" refers to a viral particle carrying a glycoprotein derived from another enveloped virus or a viral vector encoding an envelope glycoprotein from a virus different from its parent virus. Therefore, the host range of a vector particle can be expanded or altered depending on the type of cell surface receptor used by the glycoprotein. For example, viruses can be pseudotyped using VSV-G mutant proteins as presented herein or other viral glycoproteins (such as those presented herein).

[0117] Unless otherwise explicitly stated, the terms “pseudotyped viral particles” and “pseudotyped virus-like particles” as used herein are synonymous.

[0118] Unless otherwise explicitly stated, the terms “viral particle” and “pseudotyped viral particle” are used interchangeably as in this document.

[0119] As used herein with respect to antibodies, the term "specifically binding" refers to an antibody that recognizes a specific 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, this cross-species reactivity itself does not alter the antibody's specific classification. In another example, an antibody that specifically binds to an antigen may also bind to different allelic forms of the antigen. However, this cross-reactivity itself does not alter the antibody's specific classification. In some cases, the term "specifically binding" or "specifically binding" may be used in relation to the interaction of an antibody, protein, or peptide with a second chemical substance to mean that the interaction depends on the presence of a specific structure on the chemical substance (e.g., an antigenic determinant or epitope); for example, the antibody recognizes and binds to a specific protein structure, rather than a protein in general. If an antibody is specific for epitope "A," then in a reaction containing labeled "A" and an antibody, the presence of a molecule containing epitope A (or free, unlabeled A) will reduce the amount of labeled A that binds to the antibody. In some implementations, the targeting portion described herein that can be used to target viral particles containing mutant VSV-G protein can bind specifically to its target.

[0120] The term "subject" includes living organisms, including those that can elicit an immune response (e.g., mammals). As used herein, a "subject" or "patient" can be a 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 rodents. In some embodiments, the subject is a human.

[0121] As used in this article, the term "therapeutic" refers to treatment and / or prevention. Therapeutic effects are achieved by suppressing, alleviating, or eradicating a disease state.

[0122] As used herein, the terms “transfected,” “transformed,” or “transduced” refer to the process of transferring or introducing exogenous nucleic acids into cells. “Transfected,” “transformed,” or “transduced” cells are cells that have been transfected, transformed, or transduced with exogenous nucleic acids. Cells include primary subject cells and their progeny. In some embodiments, transfection, transformation, or transduction occurs in vivo.

[0123] As used herein, the term "treatment" means reducing the frequency or severity of at least one sign or symptom of a disease or condition experienced by a subject. As used herein, "inhibition" or "treatment" also includes delaying the development of symptoms associated with the condition and / or reducing the severity of such symptoms. These terms also include improving existing uncontrolled or harmful symptoms, preventing additional symptoms, and improving or preventing potential causes of such symptoms. Therefore, these terms indicate that beneficial outcomes have been achieved in vertebrate subjects who have a condition, disease, or symptom, or who have the potential to develop such a condition, disease, or symptom.

[0124] A "vector" is a composition of material containing isolated nucleic acids encoding proteins or peptides. Many 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, lentiviral vectors, etc.

[0125] "Carriers" or "delivery mediators" include viral particles, viruses, polylysine compounds, and liposomes that facilitate the transfer of nucleic acids into cells. Carriers or delivery mediators can also be used to deliver proteins or peptides into cells.

[0126] Scope: Throughout this disclosure, various aspects of the embodiments may be presented in a scope format. It should be understood that the scope format is for convenience and brevity only and should not be construed as an inflexible limitation. Therefore, the scope description should be considered as having specifically disclosed all possible sub-scopes and the individual values ​​within those scopes. For example, a scope such as 1 to 6 should be considered as having specifically disclosed sub-scopes such as 1 to 3, 1 to 4, 1 to 5, 2 to 4, 2 to 6, 3 to 6, etc., and the individual numbers within those scopes, such as 1, 2, 2.7, 3, 4, 5, 5.3, and 6. This applies regardless of the width of the scope. Unless otherwise expressly stated to the contrary, the disclosed scope also includes the endpoints of the scope.

[0127] Unbound by any particular theory, the embodiments described herein have shown that a mutant VSV-G protein containing a mutation at position 182 can be used for viral pseudotypening and transduction of cells when the virus contains a target region. Mutations to charged residues inhibit or reduce the affinity of VSV-G for its natural co-receptor LDL-R. The ability of other mutations to charged residues at other amino acid positions within the VSV-G protein to reduce the affinity of VSV-G for its natural co-receptor LDL-R has been tested. In some embodiments, the provided mutant VSV-G protein can be used to transduce target cells and deliver heterologous molecules to target cells.

[0128] In some embodiments, a VSV-G protein comprising a mutation at position 198 compared to SEQ ID NO: 1 or a mutation at position 182 compared to SEQ ID NO: 2 is provided. SEQ ID NO: 1 is the full-length protein, and SEQ ID NO: 2 is the extracellular domain of the VSV-G protein. The 16-mer signal peptide of MKCLLYLAFLFIGVNC (SEQ ID NO: 26), as shown at the N-terminus of SEQ ID NO: 1, is cleaved, leaving the protein of SEQ ID NO: 2. Therefore, although the mutation may be mentioned in the context of SEQ ID NO: 2, it should be understood that the mutation also occurs in the context of SEQ ID NO: 1 containing the leader sequence, and will therefore be a position number 16 positions higher than that described in 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 implementations, the mutation is the I182E mutation compared to SEQ ID NO: 2.

[0129] In some embodiments, a VSV-G protein comprising a mutation at position 198 compared to SEQ ID NO: 10 or a mutation at position 182 compared to SEQ ID NO: 11 is provided. SEQ ID NO: 10 is the full-length protein, and SEQ ID NO: 11 is the extracellular domain of the VSV-G protein. The 16-mer signal peptide of MLSYLIFALVVSPILG (SEQ ID NO: 27), as shown at the N-terminus of SEQ ID NO: 10, is cleaved, leaving the protein of SEQ ID NO: 11. Therefore, although the mutation may be mentioned in the context of SEQ ID NO: 11, it should be understood that the mutation also occurs in the context of SEQ ID NO: 10 containing the leader sequence, and will therefore be a position number 16 positions higher than that described in 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 implementations, the mutation is the T182E mutation compared to SEQ ID NO: 11.

[0130] In some embodiments, a VSV-G protein comprising a mutation at position 198 compared to SEQ ID NO: 12 or a mutation at position 182 compared to SEQ ID NO: 13 is provided. SEQ ID NO: 12 is the full-length protein, and SEQ ID NO: 13 is the extracellular domain of the VSV-G protein. The 16-mer signal peptide of 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. Therefore, although the mutation may be mentioned in the context of SEQ ID NO: 13, it should be understood that the mutation also occurs in the context of SEQ ID NO: 12 containing the leader sequence, and will therefore be a position number 16 positions higher than that described in 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 implementations, the mutation is the A182E mutation compared to SEQ ID NO: 13.

[0131] In some embodiments, a VSV-G protein comprising a mutation at position 203 compared to SEQ ID NO: 14 or a mutation at position 182 compared to SEQ ID NO: 15 is provided. SEQ ID NO: 14 is the full-length protein, and SEQ ID NO: 15 is the extracellular domain of the VSV-G protein. The 21-mer signal peptide of MKMKMVIAGLILCIGILPAIG (SEQ ID NO: 29) as shown at the N-terminus of SEQ ID NO: 14 is cleaved, leaving the protein of SEQ ID NO: 15. Therefore, although the mutation may be mentioned in the context of SEQ ID NO: 15, it should be understood that the mutation also occurs in the context of SEQ ID NO: 14 containing the leader sequence, and will therefore be a position number 21 more than the position described in 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 implementations, the mutation is the V182E mutation compared to SEQ ID NO: 15.

[0132] In some embodiments, a VSV-G protein comprising a mutation at position 199 compared to SEQ ID NO: 16 or a mutation at position 182 compared to SEQ ID NO: 17 is provided. SEQ ID NO: 16 is the full-length protein, and SEQ ID NO: 17 is the extracellular domain of the VSV-G protein. The 17-mer signal peptide of MTPAFILCMLLAGSSWA (SEQ ID NO: 30), as shown at the N-terminus of SEQ ID NO: 16, is cleaved, leaving the protein of SEQ ID NO: 17. Therefore, although the mutation may be mentioned in the context of SEQ ID NO: 17, it should be understood that the mutation also occurs in the context of SEQ ID NO: 16 containing the leader sequence, and will therefore be a position number 17 more than the position described in 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 implementations, the mutation is the V182E mutation compared to SEQ ID NO: 17.

[0133] In some embodiments, a VSV-G protein comprising a mutation at position 199 compared to SEQ ID NO: 18 or a mutation at position 182 compared to SEQ ID NO: 19 is provided. SEQ ID NO: 18 is the full-length protein, and SEQ ID NO: 19 is the extracellular domain 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. Therefore, although the mutation may be mentioned in the context of SEQ ID NO: 19, it should be understood that the mutation also occurs in the context of SEQ ID NO: 18 containing the leader sequence, and will therefore be a position number 17 positions higher than that described in 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 implementations, the mutation is the V182E mutation compared to SEQ ID NO: 19.

[0134] In some embodiments, a VSV-G protein comprising a mutation at position 199 compared to SEQ ID NO: 20 or a mutation at position 182 compared to SEQ ID NO: 21 is provided. SEQ ID NO: 20 is the full-length protein, and SEQ ID NO: 21 is the extracellular domain of the VSV-G protein. The 17-mer signal peptide of MLVLYLLLSLLALGAQC (SEQ ID NO: 32), as shown at the N-terminus of SEQ ID NO: 20, is cleaved, leaving the protein of SEQ ID NO: 21. Therefore, although the mutation may be mentioned in the context of SEQ ID NO: 21, it should be understood that the mutation also occurs in the context of SEQ ID NO: 20 containing the leader sequence, and will therefore be a position number 17 positions higher than that described in 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 implementations, the mutation is the I182E mutation compared to SEQ ID NO: 21.

[0135] As used herein, when a peptide is considered to have a mutation compared to a reference sequence, this comparison is based on alignment performed using software such as BlastP, ClustalW, or ClustalOmega with default parameters. For example, position 182 can be found in SEQ ID NO: 2, and is also related to... Figure 3 Compare with other strains shown. Figure 3 Clustal alignments of the wild-type sequences of the extracellular domain of the VSV-G protein from various strains are shown. Bold and underlined residues are those aligned to position 182 of SEQ ID NO: 2 for each strain. SEQ ID NO: 2 refers to the extracellular domain of the VSV-G protein from the Indiana strain. SEQ ID NO: 11 refers to the extracellular domain of the VSV-G protein from the New Jersey strain. SEQ ID NO: 13 refers to the extracellular domain of the VSV-G protein from the Malabar strain. SEQ ID NO: 15 refers to the extracellular domain of the VSV-G protein from the Carajá strain. SEQ ID NO: 17 refers to the extracellular domain of the VSV-G protein from the Alagoa strain. SEQ ID NO: 19 refers to the extracellular domain of the VSV-G protein from the Cocal strain. SEQ ID NO: 21 refers to the extracellular domain of the VSV-G protein from the Morton strain. Therefore, residues that are compared with residue 182 of SEQ ID NO: 2 can also be mutated as provided herein.

[0136] 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.

[0137] 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.

[0138] Although the mutation may be described with reference to SEQ ID NO: 1 or SEQ ID NO: 2 (which is the VSV-G protein from the Indiana strain), the mutation can also be used in other strains of the VSV-G protein. For example, the mutation can be made in the New Jersey strain of VSV-G, the Malaba strain of VSV-G, the Carajás strain of VSV-G, the Alagoa strain of VSV-G, the Cocal strain of VSV-G, or the Morton strain of VSV-G. In some embodiments, the sequence of each strain is as provided herein. Examples of these strains 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 extracellular domains of the New Jersey strain of VSV-G are SEQ ID NO:10 and SEQ ID NO:11, respectively; the wild-type full-length or extracellular domains of the Malaba strain of VSV-G are SEQ ID NO:12 and SEQ ID NO:13, respectively; the wild-type full-length or extracellular domains of the Carajás strain of VSV-G are SEQ ID NO:14 and SEQ ID NO:15, respectively; the wild-type full-length or extracellular domains of the Alagoa strain of VSV-G are SEQ ID NO:16 and SEQ ID NO:17, respectively; the wild-type full-length or extracellular domains of the Cocal strain of VSV-G are SEQ ID NO:18 and SEQ ID NO:19, respectively; or the wild-type full-length or extracellular domains of the Morton strain of VSV-G are SEQ ID NO:20 and SEQ ID NO:21, respectively.

[0139] The VSV-G protein containing the 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 No. 2020 / 0216502, the entire contents of which are incorporated herein by reference. For example, the VSV-G protein may contain mutations at positions corresponding to positions 8, 47, 209, and / or 354 of SEQ ID NO: 2.

[0140] In some embodiments, the substitution at position 8 is made by any amino acid other than Y that is different from the amino acid indicated at that position in sequence SEQ ID NO: 2. In some embodiments, the substitution at position 8 is made by any amino acid other than H that is different from the amino acid indicated at that position in sequence SEQ ID NO: 2. In some embodiments, the substitution at position 8 is made by any amino acid other than Q that is different from the amino acid indicated at that position in sequence SEQ ID NO: 2. In some embodiments, the substitution at position 8 is made by any amino acid other than Y, H, or Q that is different from the amino acid indicated at that position in sequence SEQ ID NO: 2. 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 implementations, the substitution at position 8 is selected from H8A, H8I, H8V, H8L, etc.

[0141] In some embodiments, the substitution at position 209 is made by any amino acid other than H that is different from the amino acid indicated at that position in sequence SEQ ID NO: 2. In some embodiments, the substitution at position 209 is made by any amino acid other than Y that is different from the amino acid indicated at that position in sequence SEQ ID NO: 2. In some embodiments, the substitution at position 209 is made by any amino acid other than H or Y that is different from the amino acid indicated at that position in sequence SEQ ID NO: 2. In some embodiments, the substitution at position 209 is selected from alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glycine, isoleucine, valine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, or tryptophan.

[0142] In some embodiments, the substitution at position 47 is made by any amino acid other than K that is different from the amino acid indicated at that position in sequence SEQ ID NO: 2. In some embodiments, the substitution at position 47 is made by any amino acid other than R that is different from the amino acid indicated at that position in sequence SEQ ID NO: 2. In some embodiments, the substitution at position 47 is made by any amino acid other than K or R that is different from the amino acid indicated at that position in sequence SEQ ID NO: 2. 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.

[0143] In some embodiments, the substitution at position 354 is made by any amino acid other than K that is different from the amino acid indicated at that position in sequence SEQ ID NO: 2. In some embodiments, the substitution at position 354 is made by any amino acid other than R that is different from the amino acid indicated at that position in sequence SEQ ID NO: 2. In some embodiments, the substitution at position 354 is made by any amino acid other than K or R that is different from the amino acid indicated at that position in sequence SEQ ID NO: 2. 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.

[0144] In some embodiments, the substitution at position 47 or position 354, or at both positions 47 and 354, is independently replaced by A, G, F, N, or Q. In some embodiments, the substitution at position 47 or position 354, or at both positions 47 and 354, is independently A, Q, or N.

[0145] In some embodiments, the VSV-G protein may contain mutations at positions corresponding to positions 8, 47, 209, and / or 354. In some embodiments, the VSV-G protein may contain mutations at positions corresponding to position 8 as provided herein, at position 47 as provided herein, at position 209 as provided herein, and / or at position 354 as provided herein. In some embodiments, the VSV-G protein may contain mutations at positions corresponding to position 8 as provided herein and at position 47 as provided herein. In some embodiments, the VSV-G protein may contain mutations at positions corresponding to position 8 as provided herein and at position 209 as provided herein. In some embodiments, the VSV-G protein may contain mutations at positions corresponding to position 8 as provided herein and at position 354 as provided herein. In some embodiments, the VSV-G protein may contain mutations at positions corresponding to position 47 as provided herein and at position 209 as provided herein. In some embodiments, the VSV-G protein may contain mutations at positions corresponding to position 47 as provided herein and at position 354 as provided herein. In some embodiments, the VSV-G protein may contain mutations at the position corresponding to position 209 as provided herein and at position 354 as provided herein. In some embodiments, the VSV-G protein may contain mutations at the position corresponding to position 8 as provided herein, at position 47 as provided herein, and at position 209 as provided herein. In some embodiments, the VSV-G protein may contain mutations at the position corresponding to position 8 as provided herein, at position 47 as provided herein, and at position 354 as provided herein. In some embodiments, the VSV-G protein may contain mutations at the position corresponding to position 8 as provided herein, at position 209 as provided herein, and at position 354 as provided herein. In some embodiments, the VSV-G protein may contain mutations at the position corresponding to position 47 as provided herein, at position 209 as provided herein, and at position 354 as provided herein. In some implementations, the VSV-G protein may contain mutations at the position corresponding to position 8 as provided herein, at position 47 as provided herein, at position 209 as provided herein, and at position 354 as provided herein.

[0146] In some implementations, the substitution at position 8 is alanine, i.e., H8A.

[0147] In some implementations, the substitution at position 47 is Q, N, or A, i.e., K47Q, K47N, or K47A.

[0148] In some embodiments, the protein contains a substitution at position 8 and / or a substitution at position 47. In some embodiments, the protein contains a substitution at position 8 and a substitution at position 47. In some embodiments, the protein contains 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 comprises an H8A and / or K47Q mutation.

[0149] In some embodiments, the protein contains a mutation (substitution) at position 10. In some embodiments, the substitution / mutation is Q10A, Q10R, or Q10K.

[0150] In some non-limiting embodiments, the substitution at position 209 is A, namely Y209A.

[0151] In some non-limiting embodiments, the substitution at position 354 is A or Q, i.e., R354A or R354Q.

[0152] In some embodiments, the protein containing the 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 positions 8, 47, 209, and / or 354 of SEQ ID NO: 2. In some embodiments, the mutations in SEQ ID NO: 11 at positions similar to positions 8, 47, 209, and / or 354 of SEQ ID NO: 2 are as provided herein.

[0153] In some embodiments, the protein containing the 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 positions 8, 47, 209, and / or 354 of SEQ ID NO: 2. In some embodiments, the mutations in SEQ ID NO: 13 at positions similar to positions 8, 47, 209, and / or 354 of SEQ ID NO: 2 are as provided herein.

[0154] In some embodiments, the protein containing the 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 positions 8, 47, 209, and / or 354 of SEQ ID NO: 2. In some embodiments, the mutations in SEQ ID NO: 15 at positions similar to positions 8, 47, 209, and / or 354 of SEQ ID NO: 2 are as provided herein.

[0155] In some embodiments, the protein containing the 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 positions 8, 47, 209, and / or 354 of SEQ ID NO: 2. In some embodiments, the mutations in SEQ ID NO: 17 at positions similar to positions 8, 47, 209, and / or 354 of SEQ ID NO: 2 are as provided herein.

[0156] In some embodiments, the protein containing the 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 positions 8, 47, 209, and / or 354 of SEQ ID NO: 2. In some embodiments, the mutations in SEQ ID NO: 19 at positions similar to positions 8, 47, 209, and / or 354 of SEQ ID NO: 2 are as provided herein.

[0157] In some embodiments, the protein containing the 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 positions 8, 47, 209, and / or 354 of SEQ ID NO: 2. In some embodiments, the mutations in SEQ ID NO: 21 at positions similar to positions 8, 47, 209, and / or 354 of SEQ ID NO: 2 are as provided herein.

[0158] In some embodiments, the protein containing the mutation at position 182 compared to SEQ ID NO: 2 contains the 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 to SEQ ID NO: 2. 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 substitution at position 182 is an I182D or I182E mutation. In some embodiments, the mutation is I182D. In some embodiments, the mutation is I182E. In some embodiments, the mutation is I182S, I182H, I182T, I182Q, or I182N.

[0159] In some embodiments, VSV-G is provided, wherein the protein comprises the amino acid sequence of SEQ ID NO: 2 with 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 to SEQ ID NO: 2.

[0160] 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 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. In some embodiments, the VSV-G protein contains a T182S, T182H, T182Q, or T182N mutation.

[0161] 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 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. In some embodiments, the VSV-G protein contains an A182S, A182H, A182T, A182Q, or A182N mutation.

[0162] In some embodiments, a protein containing 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 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. In some embodiments, the VSV-G protein contains a V182S, V182H, V182T, V182Q, or V182N mutation.

[0163] In some embodiments, a protein containing 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 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. In some embodiments, the VSV-G protein contains a V182S, V182H, V182T, V182Q, or V182N mutation.

[0164] In some embodiments, a protein containing 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 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. In some embodiments, the VSV-G protein contains a V182S, V182H, V182T, V182Q, or V182N mutation.

[0165] In some embodiments, the protein containing 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 to SEQ ID NO: 21 (or SEQ ID NO: 20 if a full-length protein is used). In some embodiments, the polypeptide contains an I182D or I182E mutation. In some embodiments, the VSV-G protein contains an I182S, I182H, I182T, I182Q, or I182N mutation.

[0166] In some embodiments, a VSV-G protein is provided comprising 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 comprising, compared to SEQ ID NO: 2, 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, as provided herein. 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, comprise substitutions for charged amino acids. In some embodiments, the charged amino acids are as provided herein. In some embodiments, as provided herein, the VSV-G protein comprises 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. In some embodiments, as provided herein, 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 comprise substitutions to charged amino acids. In some embodiments, the charged amino acids are as provided herein. In some embodiments, the mutation at position H8 compared to SEQ ID NO: 2 is an H8D, H8E, H8K, or H8R substitution. In some embodiments, the mutation at position N9 compared to SEQ ID NO: 2 is an N9D, N9E, N9K, or N9R substitution. In some embodiments, the substitution at position Q10 compared to SEQ ID NO: 2 comprises a Q10D or Q10E substitution. In some embodiments, the substitution at position K47 compared to SEQ ID NO: 2 includes a K47D or K47E substitution. In some embodiments, the substitution at position K50 compared to SEQ ID NO: 2 includes a K50D or K50E substitution. In some embodiments, the mutation at position A51 compared to SEQ ID NO: 2 is an A51D, A51E, A51K, or A51R substitution.In some embodiments, the mutation at position S179 compared to SEQ ID NO: 2 is replaced by S179D, S179E, S179K, or S179R. In some embodiments, the mutation at position N180 compared to SEQ ID NO: 2 is replaced by N180D, N180E, N180K, or N180R. In some embodiments, the mutation at position I182 compared to SEQ ID NO: 2 is replaced by I182D, I182E, I182K, or I182R. In some embodiments, the mutation at position S183 compared to SEQ ID NO: 2 is replaced by S183D, S183E, S183K, or S183R. In some embodiments, the mutation at position M184 compared to SEQ ID NO: 2 is replaced by M184D, M184E, M184K, or M184R. In some embodiments, the mutation at position Y209 compared to SEQ ID NO: 2 is a substitution of Y209D, Y209E, Y209K, or Y209R. In some embodiments, the mutation at position I347 compared to SEQ ID NO: 2 is a substitution of I347D, I347E, I347K, or I347R. In some embodiments, the mutation at position T350 compared to SEQ ID NO: 2 is a substitution of T350D, T350E, T350K, or T350R. In some embodiments, the mutation at position T352 compared to SEQ ID NO: 2 is a substitution of T352D, T352E, T352K, or T352R. In some embodiments, the substitution at position E353 compared to SEQ ID NO: 2 includes a substitution of E353K or E353R. In some embodiments, the substitution at position R354 compared to SEQ ID NO: 2 includes substitutions of R354D or R354E.

[0167] In some embodiments, a VSV-G protein is provided, comprising the amino acid sequence of SEQ ID NO: 3, and further comprising, compared to SEQ ID NO: 3, a mutation corresponding to a mutation at positions 8, 9, 10, 47, 50, 51, 179, 180, 183, 184, 209, 347, 350, 352, 353, 354, or any combination thereof, as provided herein. In some embodiments, the mutation 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 to a charged amino acid. In some embodiments, the charged amino acid is as provided herein. In some embodiments, as provided herein, the VSV-G protein comprises substitutions 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. In some embodiments, as provided herein, substitutions 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, comprise substitutions to charged amino acids. In some embodiments, the charged amino acids are as provided herein. In some embodiments, the mutation at position H8 compared to SEQ ID NO: 3 is a substitution of H8D, H8E, H8K, or H8R. In some embodiments, the mutation at position N9 compared to SEQ ID NO: 3 is a substitution of N9D, N9E, N9K, or N9R. In some embodiments, the substitution at position Q10 compared to SEQ ID NO: 3 includes a substitution of Q10D or Q10E. In some embodiments, the substitution at position K47 compared to SEQ ID NO: 3 includes a substitution of K47D or K47E. In some embodiments, the substitution at position K50 compared to SEQ ID NO: 3 includes a substitution of K50D or K50E. In some embodiments, the mutation at position A51 compared to SEQ ID NO: 3 is a substitution of A51D, A51E, A51K, or A51R. In some embodiments, the mutation at position S179 compared to SEQ ID NO: 3 is a substitution of S179D, S179E, S179K, or S179R. In some implementations, the mutation at position N180 compared to SEQ ID NO: 3 is a substitution of N180D, N180E, N180K, or N180R.In some embodiments, the mutation at position S183 compared to SEQ ID NO: 3 is a substitution of S183D, S183E, S183K, or S183R. In some embodiments, the mutation at position M184 compared to SEQ ID NO: 3 is a substitution of M184D, M184E, M184K, or M184R. In some embodiments, the mutation at position Y209 compared to SEQ ID NO: 3 is a substitution of Y209D, Y209E, Y209K, or Y209R. In some embodiments, the mutation at position I347 compared to SEQ ID NO: 3 is a substitution of I347D, I347E, I347K, or I347R. In some embodiments, the mutation at position T350 compared to SEQ ID NO: 3 is a substitution of T350D, T350E, T350K, or T350R. In some embodiments, the mutation at position T352 compared to SEQ ID NO: 3 is a substitution of T352D, T352E, T352K, or T352R. In some embodiments, the substitution at position E353 compared to SEQ ID NO: 3 includes a substitution of E353K or E353R. In some embodiments, the substitution at position R354 compared to SEQ ID NO: 3 includes a substitution of R354D or R354E.

[0168] In some embodiments, a VSV-G protein is provided, comprising the amino acid sequence of SEQ ID NO: 4, and further comprising, compared to SEQ ID NO: 4, a mutation corresponding to a mutation at positions 8, 9, 10, 47, 50, 51, 179, 180, 183, 184, 209, 347, 350, 352, 353, 354, or any combination thereof, as provided herein. In some embodiments, the mutation 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 to a charged amino acid. In some embodiments, the charged amino acid is as provided herein. In some embodiments, as provided herein, the VSV-G protein comprises substitutions 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:4. In some embodiments, as provided herein, substitutions 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:4, comprise substitutions to charged amino acids. In some embodiments, the charged amino acids are as provided herein. In some embodiments, the mutation at position H8 compared to SEQ ID NO: 4 is a substitution of H8D, H8E, H8K, or H8R. In some embodiments, the mutation at position N9 compared to SEQ ID NO: 4 is a substitution of N9D, N9E, N9K, or N9R. In some embodiments, the substitution at position Q10 compared to SEQ ID NO: 4 includes a substitution of Q10D or Q10E. In some embodiments, the substitution at position K47 compared to SEQ ID NO: 4 includes a substitution of K47D or K47E. In some embodiments, the substitution at position K50 compared to SEQ ID NO: 4 includes a substitution of K50D or K50E. In some embodiments, the mutation at position A51 compared to SEQ ID NO: 4 is a substitution of A51D, A51E, A51K, or A51R. In some embodiments, the mutation at position S179 compared to SEQ ID NO: 4 is a substitution of S179D, S179E, S179K, or S179R. In some implementations, the mutation at position N180 compared to SEQ ID NO: 4 is a substitution of N180D, N180E, N180K, or N180R.In some embodiments, the mutation at position S183 compared to SEQ ID NO: 4 is a substitution of S183D, S183E, S183K, or S183R. In some embodiments, the mutation at position M184 compared to SEQ ID NO: 4 is a substitution of M184D, M184E, M184K, or M184R. In some embodiments, the mutation at position Y209 compared to SEQ ID NO: 4 is a substitution of Y209D, Y209E, Y209K, or Y209R. In some embodiments, the mutation at position I347 compared to SEQ ID NO: 4 is a substitution of I347D, I347E, I347K, or I347R. In some embodiments, the mutation at position T350 compared to SEQ ID NO: 4 is a substitution of T350D, T350E, T350K, or T350R. In some embodiments, the mutation at position T352 compared to SEQ ID NO: 4 is a substitution of T352D, T352E, T352K, or T352R. In some embodiments, the substitution at position E353 compared to SEQ ID NO: 4 includes a substitution of E353K or E353R. In some embodiments, the substitution at position R354 compared to SEQ ID NO: 4 includes a substitution of R354D or R354E.

[0169] In some embodiments, a VSV-G protein is provided, comprising the amino acid sequence of SEQ ID NO: 5, and further comprising, compared to SEQ ID NO: 5, a mutation corresponding to a mutation at positions 8, 9, 10, 47, 50, 51, 179, 180, 183, 184, 209, 347, 350, 352, 353, 354, or any combination thereof, as provided herein. In some embodiments, the mutation 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, comprises a substitution to a charged amino acid. In some embodiments, the charged amino acid is as provided herein. In some embodiments, as provided herein, the VSV-G protein comprises substitutions 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:5. In some embodiments, as provided herein, substitutions 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:5, comprise substitutions to charged amino acids. In some embodiments, the charged amino acids are as provided herein. In some embodiments, the mutation at position H8 compared to SEQ ID NO: 5 is a substitution of H8D, H8E, H8K, or H8R. In some embodiments, the mutation at position N9 compared to SEQ ID NO: 5 is a substitution of N9D, N9E, N9K, or N9R. In some embodiments, the substitution at position Q10 compared to SEQ ID NO: 5 includes a substitution of Q10D or Q10E. In some embodiments, the substitution at position K47 compared to SEQ ID NO: 5 includes a substitution of K47D or K47E. In some embodiments, the substitution at position K50 compared to SEQ ID NO: 5 includes a substitution of K50D or K50E. In some embodiments, the mutation at position A51 compared to SEQ ID NO: 5 is a substitution of A51D, A51E, A51K, or A51R. In some embodiments, the mutation at position S179 compared to SEQ ID NO: 5 is a substitution of S179D, S179E, S179K, or S179R. In some implementations, the mutation at position N180 compared to SEQ ID NO: 5 is a substitution of N180D, N180E, N180K, or N180R.In some embodiments, the mutation at position S183 compared to SEQ ID NO: 5 is replaced by S183D, S183E, S183K, or S183R. In some embodiments, the mutation at position M184 compared to SEQ ID NO: 5 is replaced by M184D, M184E, M184K, or M184R. In some embodiments, the mutation at position Y209 compared to SEQ ID NO: 5 is replaced by Y209D, Y209E, Y209K, or Y209R. In some embodiments, the mutation at position I347 compared to SEQ ID NO: 5 is replaced by I347D, I347E, I347K, or I347R. In some embodiments, the mutation at position T350 compared to SEQ ID NO: 5 is replaced by T350D, T350E, T350K, or T350R. In some embodiments, the mutation at position T352 compared to SEQ ID NO: 5 is a substitution of T352D, T352E, T352K, or T352R. In some embodiments, the substitution at position E353 compared to SEQ ID NO: 5 includes a substitution of E353K or E353R. In some embodiments, the substitution at position R354 compared to SEQ ID NO: 5 includes a substitution of R354D or R354E.

[0170] In some embodiments, a VSV-G protein is provided, comprising the amino acid sequence of SEQ ID NO: 22, and further comprising, compared to SEQ ID NO: 22, a mutation corresponding to a mutation at positions 8, 9, 10, 47, 50, 51, 179, 180, 183, 184, 209, 347, 350, 353, 354, or any combination thereof, as provided herein. In some embodiments, the mutation 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, comprises a substitution to a charged amino acid. In some embodiments, the charged amino acid is as provided herein. In some embodiments, as provided herein, the VSV-G protein comprises substitutions 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: 22. In some embodiments, as provided herein, substitutions 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: 22, comprise substitutions to charged amino acids. In some embodiments, the charged amino acids are as provided herein. In some embodiments, the mutation at position H8 compared to SEQ ID NO: 22 is an H8D, H8E, H8K, or H8R substitution. In some embodiments, the mutation at position N9 compared to SEQ ID NO: 22 is a substitution of N9D, N9E, N9K, or N9R. In some embodiments, the substitution at position Q10 compared to SEQ ID NO: 22 includes a substitution of Q10D or Q10E. In some embodiments, the substitution at position K47 compared to SEQ ID NO: 22 includes a substitution of K47D or K47E. In some embodiments, the substitution at position K50 compared to SEQ ID NO: 22 includes a substitution of K50D or K50E. In some embodiments, the mutation at position A51 compared to SEQ ID NO: 22 is a substitution of A51D, A51E, A51K, or A51R. In some embodiments, the mutation at position S179 compared to SEQ ID NO: 22 is a substitution of S179D, S179E, S179K, or S179R. In some implementations, the mutation at position N180 compared to SEQ ID NO: 22 is a substitution of N180D, N180E, N180K, or N180R.In some embodiments, the mutation at position S183 compared to SEQ ID NO: 22 is a substitution of S183D, S183E, S183K, or S183R. In some embodiments, the mutation at position M184 compared to SEQ ID NO: 22 is a substitution of M184D, M184E, M184K, or M184R. In some embodiments, the mutation at position Y209 compared to SEQ ID NO: 22 is a substitution of Y209D, Y209E, Y209K, or Y209R. In some embodiments, the mutation at position I347 compared to SEQ ID NO: 22 is a substitution of I347D, I347E, I347K, or I347R. In some embodiments, the mutation at position T350 compared to SEQ ID NO: 22 is a substitution of T350D, T350E, T350K, or T350R. In some embodiments, the substitution at position E353 compared to SEQ ID NO: 22 includes E353K or E353R substitution. In some embodiments, the substitution at position R354 compared to SEQ ID NO: 22 includes R354D or R354E substitution.

[0171] In some embodiments, a VSV-G protein is provided, comprising the amino acid sequence of SEQ ID NO: 23, and further comprising, compared to SEQ ID NO: 23, a mutation corresponding to a mutation at positions 8, 9, 10, 47, 50, 51, 179, 180, 183, 184, 209, 347, 350, 353, 354, or any combination thereof, as provided herein. In some embodiments, the mutation 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, comprises a substitution to a charged amino acid. In some embodiments, the charged amino acid is as provided herein. In some embodiments, as provided herein, the VSV-G protein comprises substitutions 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: 23. In some embodiments, as provided herein, substitutions 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: 23, comprise substitutions to charged amino acids. In some embodiments, the charged amino acids are as provided herein. In some embodiments, the mutation at position H8 compared to SEQ ID NO: 23 is an H8D, H8E, H8K, or H8R substitution. In some embodiments, the mutation at position N9 compared to SEQ ID NO: 23 is an N9D, N9E, N9K, or N9R substitution. In some embodiments, the substitution at position Q10 compared to SEQ ID NO: 23 includes a Q10D or Q10E substitution. In some embodiments, the substitution at position K47 compared to SEQ ID NO: 23 includes a K47D or K47E substitution. In some embodiments, the substitution at position K50 compared to SEQ ID NO: 23 includes a K50D or K50E substitution. In some embodiments, the mutation at position A51 compared to SEQ ID NO: 23 is an A51D, A51E, A51K, or A51R substitution. In some embodiments, the mutation at position S179 compared to SEQ ID NO: 23 is an S179D, S179E, S179K, or S179R substitution. In some implementations, the mutation at position N180 compared to SEQ ID NO: 23 is a substitution of N180D, N180E, N180K, or N180R.In some embodiments, the mutation at position S183 compared to SEQ ID NO: 23 is a substitution of S183D, S183E, S183K, or S183R. In some embodiments, the mutation at position M184 compared to SEQ ID NO: 23 is a substitution of M184D, M184E, M184K, or M184R. In some embodiments, the mutation at position Y209 compared to SEQ ID NO: 23 is a substitution of Y209D, Y209E, Y209K, or Y209R. In some embodiments, the mutation at position I347 compared to SEQ ID NO: 23 is a substitution of I347D, I347E, I347K, or I347R. In some embodiments, the mutation at position T350 compared to SEQ ID NO: 23 is a substitution of T350D, T350E, T350K, or T350R. In some embodiments, the substitution at position E353 compared to SEQ ID NO: 23 includes substitutions of E353K or E353R. In some embodiments, the substitution at position R354 compared to SEQ ID NO: 23 includes substitutions of R354D or R354E.

[0172] Virus particles

[0173] The mutant VSV-G protein can be used, for example, for pseudotypening viruses (such as, but not limited to, lentiviruses). Therefore, in some embodiments, viral particles comprising the mutant VSV-G protein as provided herein are provided. In some embodiments, the viral particle comprises the VSV-G protein containing a mutation at position 198 compared to SEQ ID NO: 1. In some embodiments, a protein containing a mutation at position 182 compared to SEQ ID NO: 2 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 to SEQ ID NO: 2 (or SEQ ID NO: 1 if a full-length protein is used). In some embodiments, the peptide contains an I182D or I182E mutation compared to SEQ ID NO: 2. In some embodiments, the VSV-G protein contains an I182S, I182H, I182T, I182Q, or I182N mutation.

[0174] In some embodiments, the viral particle comprises a VSV-G protein containing a mutation at position 198 compared to SEQ ID NO: 10. 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 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: 11 (or SEQ ID NO: 10 if a full-length protein is used). In some embodiments, the polypeptide comprises a T182D or T182E mutation compared to SEQ ID NO: 11. In some implementations, the VSV-G protein contains T182S, T182H, T182Q, or T182N mutations.

[0175] In some embodiments, the viral particle comprises a VSV-G protein containing a mutation at position 198 compared to SEQ ID NO: 12. 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 to SEQ ID NO: 13 (or SEQ ID NO: 12 if a full-length protein is used). In some embodiments, the polypeptide comprises an A182D or A182E mutation compared to SEQ ID NO: 13. In some implementations, the VSV-G protein contains mutations of A182S, A182H, A182T, A182Q, or A182N.

[0176] In some embodiments, the viral particle comprises a VSV-G protein containing a mutation at position 203 compared to SEQ ID NO: 14. In some embodiments, a protein containing a mutation at position 182 compared to SEQ ID NO: 15 contains a mutation at position 182 and 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. In some embodiments, the polypeptide comprises a V182D or V182E mutation compared to SEQ ID NO: 15. In some implementations, the VSV-G protein contains mutations of V182S, V182H, V182T, V182Q, or V182N.

[0177] In some embodiments, the viral particle comprises a VSV-G protein containing a mutation at position 199 compared to SEQ ID NO: 16. In some embodiments, a protein containing 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 to SEQ ID NO: 17. In some embodiments, the polypeptide comprises a V182D or V182E mutation compared to SEQ ID NO: 17. In some implementations, the VSV-G protein contains mutations of V182S, V182H, V182T, V182Q, or V182N.

[0178] In some embodiments, the viral particle comprises a VSV-G protein containing a mutation at position 199 compared to SEQ ID NO: 18. In some embodiments, a protein containing 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 to SEQ ID NO: 19 (or SEQ ID NO: 18 if a full-length protein is used). In some embodiments, the polypeptide comprises a V182D or V182E mutation compared to SEQ ID NO: 19. In some implementations, the VSV-G protein contains mutations of V182S, V182H, V182T, V182Q, or V182N.

[0179] In some embodiments, the viral particle comprises a VSV-G protein containing a mutation at position 199 compared to SEQ ID NO: 20. In some embodiments, a protein containing 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 to SEQ ID NO: 21. In some embodiments, the polypeptide comprises an I182D or I182E mutation compared to SEQ ID NO: 21. In some implementations, the VSV-G protein contains I182S, I182H, I182T, I182Q, or I182N mutations.

[0180] In some embodiments, the VSV-G protein further comprises a mutation at the position corresponding to position 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 comprises a mutation corresponding to the T214N mutation compared to SEQ ID NO: 2. In some embodiments, the VSV-G protein comprises a mutation corresponding to the T352A mutation compared to SEQ ID NO: 2. In some embodiments, the VSV-G protein comprises both T214N and T352A mutations compared to SEQ ID NO: 2. These mutations may be combined with any other mutations as 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 comprises 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. These sequences are further illustrated below using leader sequences that are removed during protein processing.

[0181] VSV-G protein mutations I196D, T230N, and T368A (with leader sequence and adjusted numbering)

[0182] MKCLLYLAFLFIGVNCKFTIVFPHNQKGNWKNVPSNYHYCPSSSDLNWHNDLIGTALQVKMPKSHKAIQADGWMCHASKWVTTCDFRWYGPKYITHSIRSFTPSVEQCKESIEQTKQGTWLNPGFPPQSCGYATVTDAEAVIVQVTPHHVLVDEYTGEWVDSQFINGKCSNYICPTVHNSTTWHSDYKVKGLCDSNLDSMDITFFSEDGELSSLGKEGTGFRSNYFAYENGGKACKMQYCKHWGVRLPSGVWFEMADKDLFAAARFPECPEGSSISAPSQTSVDVSLIQDVERILDYSLCQETWSKIRAGLPISPVDLSYLAPKNPGTGPAFTIINGTLKYFETRYIRVDIAAPILSRMVGMISGTTAERELWDDWAPYEDVEIGPNGVLRTSSGYKFPLYMIGHGMLDSDLHLSSKAQVFEHPHIQDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCIKLKHTKKRQIYTDIEMNRLGK(SEQ ID NO:24)

[0183] VSV-G protein mutations: I182D, T214N, and T352A (without leader sequence)

[0184] KFTIVFPHNQKGNWKNVPSNYHYCPSSSDLNWHNDLIGTALQVKMPKSHKAIQADGWMCHASKWVTTCDFRWYGPKYITHSIRSFTPSVEQCKESIEQTKQGTWLNPGFPPQSCGYATVTDAEAVIVQVTPHHVLVDEYTGEWVDSQFINGKCSNYICPTVHNSTTWHSDYKVKGLCDSNLDSMDITFFSEDGELSSLGKEGTGFRSNYFAYENGGKACKMQYCKHWGVRLPSGVWFEMADKDLFAAARFPECPEGSSISAPSQTSVDVSLIQDVERILDYSLCQETWSKIRAGLPISPVDLSYLAPKNPGTGPAFTIINGTLKYFETRYIRVDIAAPILSRMVGMISGTTAERELWDDWAPYEDVEIGPNGVLRTSSGYKFPLYMIGHGMLDSDLHLSSKAQVFEHPHIQDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCIKLKHTKKRQIYTDIEMNRLGK(SEQ ID NO: 22)

[0185] VSV-G protein with I196E, T230N, and T368A mutations (with leader sequence and adjusted numbering)

[0186] MKCLLYLAFLFIGVNCKFTIVFPHNQKGNWKNVPSNYHYCPSSSDLNWHNDLIGTALQVKMPKSHKAIQADGWMCHASKWVTTCDFRWYGPKYITHSIRSFTPSVEQCKESIEQTKQGTWLNPGFPPQSCGYATVTDAEAVIVQVTPHHVLVDEYTGEWVDSQFINGKCSNYICPTVHNSTTWHSDYKVKGLCDSNLESMDITFFSEDGELSSLGKEGTGFRSNYFAYENGGKACKMQYCKHWGVRLPSGVWFEMADKDLFAAARFPECPEGSSISAPSQTSVDVSLIQDVERILDYSLCQETWSKIRAGLPISPVDLSYLAPKNPGTGPAFTIINGTLKYFETRYIRVDIAAPILSRMVGMISGTTAERELWDDWAPYEDVEIGPNGVLRTSSGYKFPLYMIGHGMLDSDLHLSSKAQVFEHPHIQDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCIKLKHTKKRQIYTDIEMNRLGK(SEQ ID NO:25)

[0187] VSV-G protein with I182E, T214N, and T352A mutations (without leader sequence)

[0188] KFTIVFPHNQKGNWKNVPSNYHYCPSSSDLNWHNDLIGTALQVKMPKSHKAIQADGWMCHASKWVTTCDFRWYGPKYITHSIRSFTPSVEQCKESIEQTKQGTWLNPGFPPQSCGYATVTDAEA VIVQVTPHHVLVDEYTGEWVDSQFINGKCSNYICPTVHNSTTWHSDYKVKGLCDSNLESMDITFFSEDGELSSLGKEGTGFRSNYFAYENGGKACKMQYCKHWGVRLPSGVWFEMADKDLFAAAR FPECPEGSSISAPSQTSVDVSLIQDVERILDYSLCQETWSKIRAGLPISPVDLSYLAPKNPGTGPAFTIINGTLKYFETRYIRVDIAAPILSRMVGMISGTTAERELWDDWAPYEDVEIGPNGVL RTSSGYKFPLYMIGGHGMLDSDLHLSSKAQVFEHPHIQDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLRVGIHLCIKLKHTKKRQIYTDIEMNRLGK (SEQ ID NO: 23)

[0189] Other strains of the VSV-G protein described herein may also contain mutations corresponding to T214N and / or T352A in SEQ ID NO: 2 and are shown in SEQ ID NO: 22 and SEQ ID NO: 23.

[0190] In some embodiments, the composition comprises mutations as described in Hwang et al., Gene Ther, Aug 2013; 20(8):807-15. (Epub, Jan 31, 2013), which is incorporated herein by reference in its entirety. For example, mutations may be at positions 230, 368, 66, and / or 162 corresponding to SEQ ID NO: 1. These positions would be 16 fewer than those in SEQ ID NO: 2 when the leader sequence is removed. In some embodiments, mutations at those positions are, for example, T230N, T368A, K66T, S162T, or any combination thereof. In some embodiments, the VSV-G protein comprises the T230N and T368A mutations. In some embodiments, the VSV-G polypeptide comprises K66T, S162T, T230N, and T368A. These positions are those corresponding to the positions in the full-length protein (SEQ ID NO: 1). In some embodiments, the VSV-G protein comprises the T230N mutation, the T368A mutation, the K66T mutation, the S162T mutation, or any combination thereof. In some embodiments, in addition to the mutation corresponding to position 182 of SEQ ID NO: 2, the VSV-G protein also comprises one or more mutations, such as those described in U.S. Patent Application Publication No. 20200216502, the entire contents of which are incorporated herein by reference. For example, the VSV-G protein may also comprise mutations at positions corresponding to positions 8, 47, 209, and / or 354 of SEQ ID NO: 2.

[0191] In some embodiments, the substitution at position 8 is made by any amino acid other than Y that is different from the amino acid indicated at that position in sequence SEQ ID NO: 2. In some embodiments, the substitution at position 209 is made by any amino acid other than H that is different from the amino acid indicated at that position in sequence SEQ ID NO: 2. In some embodiments, the substitution at position 47 is made by any amino acid other than K or R that is different from the amino acid indicated at that position in sequence SEQ ID NO: 2. In some embodiments, the substitution at position 354 is made by any amino acid other than K or R that is different from the amino acid indicated at that position in sequence SEQ ID NO: 2. In some embodiments, the substitution is located at position 47 or position 354, or at both positions 47 and 354, and 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.

[0192] In some embodiments, the viral particle comprises a VSV-G protein containing one or more mutations, wherein the mutation is a substitution to a charged amino acid. In some embodiments, the mutation comprises a substitution to an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with the amino acid sequence of SEQ ID NO: 2, and also comprises a charged amino acid 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, compared to SEQ ID NO: 2, the mutation involving the substitution of a charged amino acid is located at positions H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof.

[0193] In some embodiments, compared to SEQ ID NO: 2, the mutation comprising a substitution to a charged amino acid is located at position H8. In some embodiments, the VSV-G protein comprising a substitution to a charged amino acid at position H8 compared to SEQ ID NO: 2 also comprises one or more mutations comprising 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.

[0194] In some embodiments, compared to SEQ ID NO: 2, the mutation comprising a substitution to a charged amino acid is located at position N9. In some embodiments, the VSV-G protein comprising a substitution to a charged amino acid at position N9 compared to SEQ ID NO: 2 also comprises one or more mutations comprising 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.

[0195] In some embodiments, compared to SEQ ID NO: 2, the mutation comprising a substitution to a charged amino acid is located at position Q10. In some embodiments, the VSV-G protein comprising a substitution to a charged amino acid at position Q10 compared to SEQ ID NO: 2 also comprises one or more mutations comprising 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.

[0196] In some embodiments, compared to SEQ ID NO: 2, the mutation comprising a substitution to a charged amino acid is located at position K47. In some embodiments, the VSV-G protein comprising a substitution to a charged amino acid at position K47 compared to SEQ ID NO: 2 also comprises one or more mutations comprising 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.

[0197] In some embodiments, compared to SEQ ID NO: 2, the mutation comprising a substitution to a charged amino acid is located at position K50. In some embodiments, the VSV-G protein comprising a substitution to a charged amino acid at position K50 compared to SEQ ID NO: 2 also comprises one or more mutations comprising 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.

[0198] In some embodiments, compared to SEQ ID NO: 2, the mutation comprising a substitution to a charged amino acid is located at position A51. In some embodiments, the VSV-G protein comprising a substitution to a charged amino acid at position A51 compared to SEQ ID NO: 2 also comprises one or more mutations comprising 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.

[0199] In some embodiments, compared to SEQ ID NO: 2, the mutation comprising a substitution to a charged amino acid is located at position S179. In some embodiments, the VSV-G protein comprising a substitution to a charged amino acid at position S179 compared to SEQ ID NO: 2 also comprises one or more mutations comprising 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.

[0200] In some embodiments, compared to SEQ ID NO: 2, the mutation comprising a substitution to a charged amino acid is located at position N180. In some embodiments, the VSV-G protein comprising a substitution to a charged amino acid at position N180 compared to SEQ ID NO: 2 also comprises one or more mutations comprising 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.

[0201] In some embodiments, compared to SEQ ID NO: 2, the mutation comprising a substitution to a charged amino acid is located at position I182. In some embodiments, the VSV-G protein comprising a substitution to a charged amino acid at position I182 compared to SEQ ID NO: 2 also 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, R354, or any combination thereof.

[0202] In some embodiments, compared to SEQ ID NO: 2, the mutation comprising a substitution to a charged amino acid is located at position S183. In some embodiments, the VSV-G protein comprising a substitution to a charged amino acid at position S183 compared to SEQ ID NO: 2 also comprises one or more mutations comprising 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.

[0203] In some embodiments, compared to SEQ ID NO: 2, the mutation comprising a substitution to a charged amino acid is located at position M184. In some embodiments, the VSV-G protein comprising a substitution to a charged amino acid at position M184 compared to SEQ ID NO: 2 also comprises one or more mutations comprising 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.

[0204] In some embodiments, compared to SEQ ID NO: 2, the mutation comprising a substitution to a charged amino acid is located at position Y209. In some embodiments, the VSV-G protein comprising a substitution to a charged amino acid at position Y209 compared to SEQ ID NO: 2 also comprises one or more mutations comprising 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.

[0205] In some embodiments, compared to SEQ ID NO: 2, the mutation comprising a substitution to a charged amino acid is located at position I347. In some embodiments, the VSV-G protein comprising a substitution to a charged amino acid at position I347 compared to SEQ ID NO: 2 also comprises one or more mutations comprising 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.

[0206] In some embodiments, compared to SEQ ID NO: 2, the mutation comprising a substitution to a charged amino acid is located at position T350. In some embodiments, the VSV-G protein comprising a substitution to a charged amino acid at position T350 compared to SEQ ID NO: 2 also comprises one or more mutations comprising 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.

[0207] In some embodiments, compared to SEQ ID NO: 2, the mutation comprising a substitution to a charged amino acid is located at position T352. In some embodiments, the VSV-G protein comprising a substitution to a charged amino acid at position T352 compared to SEQ ID NO: 2 also comprises one or more mutations comprising 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.

[0208] In some embodiments, compared to SEQ ID NO: 2, the mutation involving the substitution of a charged amino acid is located at position E353. In some embodiments, the VSV-G protein containing the substitution of a charged amino acid at position E353 compared to SEQ ID NO: 2 also contains one or more mutations compared to SEQ ID NO: 2, which contain a substitution of 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.

[0209] In some embodiments, compared to SEQ ID NO: 2, the mutation comprising a substitution to a charged amino acid is located at position R354. In some embodiments, the VSV-G protein comprising a substitution to a charged amino acid at position R354 compared to SEQ ID NO: 2 also comprises one or more mutations comprising 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.

[0210] Substitution 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 substitution to any charged amino acid. In some embodiments, substitution includes substitution to acidic amino acids, including but not limited to aspartic acid (D) or glutamic acid (E). In some embodiments, substitution includes substitution to basic amino acids, including but not limited to lysine (K) or arginine (R). In some embodiments, where the original amino acid according to SEQ ID NO: 2 is an acidic amino acid (e.g., E353), substitution to charged amino acids may include substitution to another acidic amino acid (e.g., D), or substitution to a basic amino acid (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), substitution to the charged amino acid includes substitution to a basic amino acid (e.g., K or R). 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), substitution to the 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), substitution to the charged amino acid includes substitution to an acidic amino acid (e.g., D or E).

[0211] In some embodiments, compared to SEQ ID NO: 2, the mutation comprising a substitution to a charged amino acid is located at position H8, and the substitution is selected from D, E, K, or R. In some embodiments, the mutation at position H8 is H8D. In some embodiments, the mutation at position H8 is H8E. In some embodiments, the mutation at position H8 is H8K. In some embodiments, the mutation at position H8 is H8R. In some embodiments, the VSV-G protein comprising a mutation selected from H8D, H8E, H8K, or H8R at position H8 compared to SEQ ID NO: 2 further comprises one or more mutations comprising 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.

[0212] In some embodiments, compared to SEQ ID NO: 2, the mutation comprising a substitution to a charged amino acid is located at position N9, and the substitution is selected from D, E, K, or R. In some embodiments, the mutation at position N9 is N9D. In some embodiments, the mutation at position N9 is N9E. In some embodiments, the mutation at position N9 is N9K. In some embodiments, the mutation at position N9 is N9R. In some embodiments, the VSV-G protein comprising a mutation selected from N9D, N9E, N9K, or N9R at position N9 compared to SEQ ID NO: 2 further comprises one or more mutations comprising 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.

[0213] In some embodiments, compared to SEQ ID NO: 2, the mutation comprising a substitution to a charged amino acid is located at position Q10, and the substitution is selected from D or E. In some embodiments, the mutation at position Q10 is Q10D. In some embodiments, the mutation at position Q10 is Q10E. In some embodiments, the VSV-G protein comprising a mutation selected from Q10D or Q10E at position Q10 compared to SEQ ID NO: 2 further comprises one or more mutations comprising 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.

[0214] In some embodiments, compared to SEQ ID NO: 2, the mutation comprising a substitution to a charged amino acid is located at position K47, and the substitution is selected from D or E. In some embodiments, the mutation at position K47 is K47D. In some embodiments, the mutation at position K47 is K47E. In some embodiments, the VSV-G protein comprising a mutation selected from K47D or K47E at position K47 compared to SEQ ID NO: 2 further comprises one or more mutations comprising 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.

[0215] In some embodiments, compared to SEQ ID NO: 2, the mutation comprising a substitution to a charged amino acid is located at position K50, and the substitution is selected from D or E. In some embodiments, the mutation at position K50 is K50D. In some embodiments, the mutation at position K50 is K50E. In some embodiments, the VSV-G protein comprising a mutation selected from K50D or K50E at position K50 compared to SEQ ID NO: 2 further comprises one or more mutations comprising 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.

[0216] In some embodiments, compared to SEQ ID NO: 2, the mutation comprising a substitution for a charged amino acid is located at position A51, and the substitution is selected from D, E, K, or R. In some embodiments, the mutation at position A51 is A51D. In some embodiments, the mutation at position A51 is A51E. In some embodiments, the mutation at position A51 is A51K. In some embodiments, the mutation at position A51 is A51R. In some embodiments, the VSV-G protein containing a mutation selected from A51D, A51E, A51K, or A51R at position A51 compared to SEQ ID NO: 2 also contains one or more mutations compared to SEQ ID NO: 2, which contain a substitution of 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.

[0217] In some embodiments, compared to SEQ ID NO: 2, the mutation comprising a substitution of a charged amino acid is located at position S179, and the substitution is selected from D, E, K, or R. In some embodiments, the mutation at position S179 is S179D. In some embodiments, the mutation at position S179 is S179E. In some embodiments, the mutation at position S179 is S179K. In some embodiments, the mutation at position S179 is S179R. In some embodiments, the VSV-G protein containing a mutation selected from S179D, S179E, S179K, or S179R at position S179, compared to SEQ ID NO: 2, also contains one or more mutations compared to SEQ ID NO: 2, which contain a substitution of 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.

[0218] In some embodiments, compared to SEQ ID NO: 2, the mutation comprising a substitution of a charged amino acid is located at position N180, and the substitution is selected from D, E, K, or R. In some embodiments, the mutation at position N180 is N180D. In some embodiments, the mutation at position N180 is N180E. In some embodiments, the mutation at position N180 is N180K. In some embodiments, the mutation at position N180 is N180R. In some embodiments, the VSV-G protein containing a mutation selected from N180D, N180E, N180K, or N180R at position N180, compared to SEQ ID NO:2, also contains one or more mutations compared to SEQ ID NO:2, which contain a substitution of 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.

[0219] In some embodiments, compared to SEQ ID NO: 2, the mutation comprising a substitution of a charged amino acid is located at position I182, and the substitution is selected from D, E, K, or R. In some embodiments, the mutation at position I182 is I182D. In some embodiments, the mutation at position I182 is I182E. In some embodiments, the mutation at position I182 is I182K. In some embodiments, the mutation at position I182 is I182R. In some embodiments, the VSV-G protein containing a mutation selected from I182D, I182E, I182K, or I182R at position I182, compared to SEQ ID NO: 2, also contains one or more mutations compared to SEQ ID NO: 2, which contain a substitution of 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.

[0220] In some embodiments, compared to SEQ ID NO: 2, the mutation comprising a substitution of a charged amino acid is located at position S183, and the substitution is selected from D, E, K, or R. In some embodiments, the mutation at position S183 is S183D. In some embodiments, the mutation at position S183 is S183E. In some embodiments, the mutation at position S183 is S183K. In some embodiments, the mutation at position S183 is S183R. In some embodiments, the VSV-G protein containing a mutation selected from S183D, S183E, S183K, or S183R at position S183, compared to SEQ ID NO:2, also contains one or more mutations compared to SEQ ID NO:2, which contain a substitution of 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.

[0221] In some embodiments, compared to SEQ ID NO: 2, the mutation comprising a substitution of a charged amino acid is located at position M184, and the substitution is selected from D, E, K, or R. In some embodiments, the mutation at position M184 is M184D. In some embodiments, the mutation at position M184 is M184E. In some embodiments, the mutation at position M184 is M184K. In some embodiments, the mutation at position M184 is M184R. In some embodiments, the VSV-G protein containing a mutation selected from M184D, M184E, M184K, or M184R at position M184, compared to SEQ ID NO: 2, also contains one or more mutations compared to SEQ ID NO: 2, which contain a substitution of 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.

[0222] In some embodiments, compared to SEQ ID NO: 2, the mutation comprising a substitution of a charged amino acid is located at position Y209, and the substitution is selected from D, E, K, or R. In some embodiments, the mutation at position Y209 is Y209D. In some embodiments, the mutation at position Y209 is Y209E. In some embodiments, the mutation at position Y209 is Y209K. In some embodiments, the mutation at position Y209 is Y209R. In some embodiments, the VSV-G protein containing a mutation selected from Y209D, Y209E, Y209K, or Y209R at position Y209, compared to SEQ ID NO: 2, also contains one or more mutations compared to SEQ ID NO: 2, which contain a substitution of 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.

[0223] In some embodiments, compared to SEQ ID NO: 2, the mutation comprising a substitution of a charged amino acid is located at position I347, 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, the VSV-G protein containing a mutation selected from I347D, I347E, I347K, or I347R at position I347, compared to SEQ ID NO:2, also contains one or more mutations compared to SEQ ID NO:2, which contain a substitution of 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.

[0224] In some embodiments, compared to SEQ ID NO: 2, the mutation comprising a substitution of a charged amino acid is located at position T350, and the substitution is selected from D, E, K, or R. In some embodiments, the mutation at position T350 is T350D. In some embodiments, the mutation at position T350 is T350E. In some embodiments, the mutation at position T350 is T350K. In some embodiments, the mutation at position T350 is T350R. In some embodiments, the VSV-G protein containing a mutation selected from T350D, T350E, T350K, or T350R at position T350, compared to SEQ ID NO:2, also contains one or more mutations compared to SEQ ID NO:2, which contain a substitution of 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.

[0225] In some embodiments, compared to SEQ ID NO: 2, the mutation comprising a substitution of a charged amino acid is located at position T352, and the substitution is selected from D, E, K, or R. In some embodiments, the mutation at position T352 is T352D. In some embodiments, the mutation at position T352 is T352E. In some embodiments, the mutation at position T352 is T352K. In some embodiments, the mutation at position T352 is T352R. In some embodiments, the VSV-G protein containing a mutation selected from T352D, T352E, T352K, or T352R at position T352, compared to SEQ ID NO: 2, also contains one or more mutations compared to SEQ ID NO: 2, which contain a substitution of 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.

[0226] In some embodiments, compared to SEQ ID NO: 2, the mutation comprising a substitution to a charged amino acid is located at position E353, and the substitution is selected from K or R. In some embodiments, the mutation at position E353 is E353K. In some embodiments, the mutation at position E353 is E353R. In some embodiments, the VSV-G protein comprising a mutation selected from E353K or E353R at position E353 compared to SEQ ID NO: 2 further comprises one or more mutations comprising 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.

[0227] In some embodiments, compared to SEQ ID NO: 2, the mutation comprising a substitution to a charged amino acid is located at position R354, and the substitution is selected from D or E. In some embodiments, the mutation at position R354 is R354D. In some embodiments, the mutation at position R354 is R354E. In some embodiments, the VSV-G protein comprising a mutation selected from R354D or R354E at position R354 compared to SEQ ID NO: 2 further comprises one or more mutations comprising 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.

[0228] Table 1: Possibilities of charged amino acid positions and corresponding acceptable substitutions compared to SEQ ID NO: 2 .

[0229]

[0230] In some embodiments, the viral particle comprises a VSV-G protein containing one or more mutations, wherein the mutation is a substitution of a charged amino acid as described in Table 1. In some embodiments, the mutation containing the substitution of a charged amino acid is 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 described in Table 1. In some embodiments, the mutation containing the substitution of a charged amino acid is 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 described in Table 1.

[0231] It should be understood that any mutation of a specific residue as described in Table 1 may be combined with one or more additional mutations of other residues in Table 1. For example, in some embodiments, the viral particle contains the VSV-G protein containing the mutation at position H8 as described in Table 1, and also contains mutations at positions N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as described in Table 1. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position H8 as described in Table 1, and also contains at least one additional mutation selected from positions N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 1. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position H8 as described in Table 1, and also contains additional mutations selected from more than one position selected from positions N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 1.

[0232] In some embodiments, the viral particle contains a VSV-G protein containing a mutation at position N9 as described in Table 1, and also contains mutations at positions H8, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as described in Table 1. In some embodiments, the viral particle contains a VSV-G protein containing a mutation at position N9 as described in Table 1, and also contains at least one additional mutation selected from positions H8, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 1. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position N9 as described in Table 1, and also contains additional mutations at more than one position selected from H8, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353 or R354 as described in Table 1.

[0233] In some embodiments, the viral particle contains a VSV-G protein containing a mutation at position Q10 as described in Table 1, and also contains mutations at positions H8, N9, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as described in Table 1. In some embodiments, the viral particle contains a VSV-G protein containing a mutation at position Q10 as described in Table 1, and also contains at least one additional mutation selected from positions H8, N9, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 1. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position Q10 as described in Table 1, and also contains additional mutations at more than one position selected from H8, N9, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353 or R354 as described in Table 1.

[0234] In some embodiments, the viral particle contains a VSV-G protein containing a mutation at position K47 as described in Table 1, and also contains mutations at positions H8, N9, Q10, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as described in Table 1. In some embodiments, the viral particle contains a VSV-G protein containing a mutation at position K47 as described in Table 1, and also contains at least one additional mutation selected from positions H8, N9, Q10, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 1. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position K47 as described in Table 1, and also contains additional mutations at more than one position selected from H8, N9, Q10, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353 or R354 as described in Table 1.

[0235] In some embodiments, the viral particle contains a VSV-G protein containing a mutation at position K50 as described in Table 1, and also contains mutations at positions H8, N9, Q10, K47, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as described in Table 1. In some embodiments, the viral particle contains a VSV-G protein containing a mutation at position K50 as described in Table 1, and also contains at least one additional mutation selected from positions H8, N9, Q10, K47, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 1. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position K50 as described in Table 1, and also contains additional mutations at more than one position selected from H8, N9, Q10, K47, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353 or R354 as described in Table 1.

[0236] In some embodiments, the viral particle contains a VSV-G protein containing a mutation at position A51 as described in Table 1, and also contains mutations at positions H8, N9, Q10, K47, K50, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as described in Table 1. In some embodiments, the viral particle contains a VSV-G protein containing a mutation at position A51 as described in Table 1, and also contains at least one additional mutation selected from positions H8, N9, Q10, K47, K50, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 1. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position A51 as described in Table 1, and also contains additional mutations at more than one position selected from H8, N9, Q10, K47, K50, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353 or R354 as described in Table 1.

[0237] In some embodiments, the viral particle contains a VSV-G protein containing a mutation at position S179 as described in Table 1, and also contains mutations at positions H8, N9, Q10, K47, K50, A51, N180, I182, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as described in Table 1. In some embodiments, the viral particle contains a VSV-G protein containing a mutation at position S179 as described in Table 1, and also contains at least one additional mutation selected from positions H8, N9, Q10, K47, K50, A51, N180, I182, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 1. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position S179 as described in Table 1, and also contains additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, N180, I182, S183, M184, Y209, I347, T350, T352, E353 or R354 as described in Table 1.

[0238] In some embodiments, the viral particle contains a VSV-G protein containing a mutation at position N180 as described in Table 1, and also contains mutations at positions H8, N9, Q10, K47, K50, A51, S179, I182, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as described in Table 1. In some embodiments, the viral particle contains a VSV-G protein containing a mutation at position N180 as described in Table 1, and also contains at least one additional mutation selected from positions H8, N9, Q10, K47, K50, A51, S179, I182, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 1. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position N180 as described in Table 1, and also contains additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, I182, S183, M184, Y209, I347, T350, T352, E353 or R354 as described in Table 1.

[0239] In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position I182 as described in Table 1, and also contains mutations at positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as described in Table 1. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position I182 as described in Table 1, and also contains at least one additional mutation selected from positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 1. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position I182 as described in Table 1, and also contains additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353 or R354 as described in Table 1.

[0240] In some embodiments, the viral particle contains a VSV-G protein containing a mutation at position S183 as described in Table 1, and also contains mutations at positions H8, N9, Q10, K47, K50, A51, S179, N180, I182, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as described in Table 1. In some embodiments, the viral particle contains a VSV-G protein containing a mutation at position S183 as described in Table 1, and also contains at least one additional mutation selected from positions H8, N9, Q10, K47, K50, A51, S179, N180, I182, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 1. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position S183 as described in Table 1, and additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, N180, I182, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 1.

[0241] In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position M184 as described in Table 1, and also contains mutations at positions H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, Y209, I347, T350, T352, E353, R354, or any combination thereof as described in Table 1. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position M184 as described in Table 1, and also contains at least one additional mutation selected from positions H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, Y209, I347, T350, T352, E353, or R354 as described in Table 1. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position M184 as described in Table 1, and also contains additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, Y209, I347, T350, T352, E353 or R354 as described in Table 1.

[0242] In some embodiments, the viral particle contains a VSV-G protein containing a mutation at position Y209 as described in Table 1, and also contains mutations at positions H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, I347, T350, T352, E353, R354, or any combination thereof as described in Table 1. In some embodiments, the viral particle contains a VSV-G protein containing a mutation at position Y209 as described in Table 1, and also contains at least one additional mutation selected from positions H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, I347, T350, T352, E353, or R354 as described in Table 1. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position Y209 as described in Table 1, and also contains additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, I347, T350, T352, E353 or R354 as described in Table 1.

[0243] In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position I347 as described in Table 1, and also contains mutations at positions H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, T350, T352, E353, R354, or any combination thereof as described in Table 1. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position I347 as described in Table 1, and also contains at least one additional mutation selected from positions H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, T350, T352, E353, or R354 as described in Table 1. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position I347 as described in Table 1, and also contains additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, T350, T352, E353 or R354 as described in Table 1.

[0244] In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position T350 as described in Table 1, and also contains mutations at positions H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T352, E353, R354, or any combination thereof as described in Table 1. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position T350 as described in Table 1, and also contains at least one additional mutation selected from positions H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T352, E353, or R354 as described in Table 1. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position T350 as described in Table 1, and also contains additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T352, E353 or R354 as described in Table 1.

[0245] In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position T352 as described in Table 1, and also contains mutations at positions H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof as described in Table 1. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position T352 as described in Table 1, and also contains at least one additional mutation selected from positions H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, E353, or R354 as described in Table 1. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position T352 as described in Table 1, and also contains additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, E353 or R354 as described in Table 1.

[0246] In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position E353 as described in Table 1, and also contains mutations at positions H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, R354, or any combination thereof as described in Table 1. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position E353 as described in Table 1, and also contains at least one additional mutation selected from positions H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, or R354 as described in Table 1. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position E353 as described in Table 1, and also contains additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352 or R354 as described in Table 1.

[0247] In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position R354 as described in Table 1, and also contains mutations at positions H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353, or any combination thereof as described in Table 1. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position R354 as described in Table 1, and also contains at least one additional mutation selected from positions H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, or E353 as described in Table 1. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position R354 as described in Table 1, and also contains additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352 or E353 as described in Table 1.

[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 further comprises a substitution at position H8 for a charged amino acid 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, and further comprises a substitution at position H8 for a charged amino acid 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, and further comprises a substitution at position H8 for a charged amino acid 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, and further comprises a substitution at position H8 for a charged amino acid 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 of a charged amino acid at position H8 compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, further comprises one or more mutations, which comprise a substitution of a charged amino acid at positions N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof.

[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 further comprises a substitution at position N9 for a charged amino acid 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, and further comprises a substitution at position N9 for a charged amino acid 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, and further comprises a substitution at position N9 for a charged amino acid 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, and further comprises a substitution at position N9 for a charged amino acid 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 of 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, which comprise a substitution of 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.

[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 further comprises a substitution at position Q10 for a charged amino acid 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, and further comprises a substitution at position Q10 for a charged amino acid 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, and further comprises a substitution at position Q10 for a charged amino acid 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, and further comprises a substitution at position Q10 for a charged amino acid 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 of 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, which comprise a substitution of 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.

[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 further comprises a substitution at position K47 for a charged amino acid 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, and further comprises a substitution at position K47 for a charged amino acid 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, and further comprises a substitution at position K47 for a charged amino acid 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, and further comprises a substitution at position K47 for a charged amino acid 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 of 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, which comprise a substitution of 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.

[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 further comprises a substitution at position K50 for a charged amino acid 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, and further comprises a substitution at position K50 for a charged amino acid 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, and further comprises a substitution at position K50 for a charged amino acid 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, and further comprises a substitution at position K50 for a charged amino acid compared to SEQ ID NO: 5. In some embodiments, the VSV-G protein comprising the amino acid sequence SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 and having a substitution of 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, which comprise a substitution of 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.

[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 further comprises a substitution at position A51 for a charged amino acid 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, and further comprises a substitution at position A51 for a charged amino acid 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, and further comprises a substitution at position A51 for a charged amino acid 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, and further comprises a substitution at position A51 for a charged amino acid 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 of 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, which comprise a substitution of 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.

[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 further comprises a substitution at position S179 for a charged amino acid 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, and further comprises a substitution at position S179 for a charged amino acid 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, and further comprises a substitution at position S179 for a charged amino acid 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, and further comprises a substitution at position S179 for a charged amino acid 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 of 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, which comprise a substitution of 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.

[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 further comprises a substitution at position N180 for a charged amino acid 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, and further comprises a substitution at position N180 for a charged amino acid 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, and further comprises a substitution at position N180 for a charged amino acid 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, and further comprises a substitution at position N180 for a charged amino acid 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 of 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, which comprise a substitution of 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.

[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 further comprises a substitution at position S183 for a charged amino acid 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, and further comprises a substitution at position S183 for a charged amino acid 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, and further comprises a substitution at position S183 for a charged amino acid 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, and further comprises a substitution at position S183 for a charged amino acid 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 of 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, which comprise a substitution of 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.

[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 further comprises a substitution at position M184 for a charged amino acid 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, and further comprises a substitution at position M184 for a charged amino acid 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, and further comprises a substitution at position M184 for a charged amino acid 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, and further comprises a substitution at position M184 for a charged amino acid 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 of 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, which comprise a substitution of 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.

[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 further comprises a substitution at position Y209 for a charged amino acid 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, and further comprises a substitution at position Y209 for a charged amino acid 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, and further comprises a substitution at position Y209 for a charged amino acid 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, and further comprises a substitution at position Y209 for a charged amino acid 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 of 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, which comprise a substitution of 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.

[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 further comprises a substitution at position I347 for a charged amino acid 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, and further comprises a substitution at position I347 for a charged amino acid 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, and further comprises a substitution at position I347 for a charged amino acid 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, and further comprises a substitution at position I347 for a charged amino acid 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 of 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, which comprise a substitution of 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.

[0260] 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 further comprises a substitution at position T350 for a charged amino acid 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, and further comprises a substitution at position T350 for a charged amino acid 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, and further comprises a substitution at position T350 for a charged amino acid 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, and further comprises a substitution at position T350 for a charged amino acid 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 of 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, which comprise a substitution of 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.

[0261] 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 further comprises a substitution at position T352 for a charged amino acid 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, and further comprises a substitution at position T352 for a charged amino acid 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, and further comprises a substitution at position T352 for a charged amino acid 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, and further comprises a substitution at position T352 for a charged amino acid 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 of 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, which comprise a substitution of 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.

[0262] 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 further comprises a substitution at position E353 for a charged amino acid 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, and further comprises a substitution at position E353 for a charged amino acid 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, and further comprises a substitution at position E353 for a charged amino acid 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 of 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, which comprise a substitution of 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.

[0263] 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 further comprises a substitution at position R354 for a charged amino acid 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, and further comprises a substitution at position R354 for a charged amino acid 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, and further comprises a substitution at position R354 for a charged amino acid 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, and further comprises a substitution at position R354 for a charged amino acid 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 of 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, which comprise a substitution of 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.

[0264] Substitution 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 substitution to any charged amino acid. In some embodiments, substitution includes substitution to acidic amino acids, including but not limited to aspartic acid (D) or glutamic acid (E). In some embodiments, substitution includes substitution to basic amino acids, including but not limited to lysine (K) or arginine (R). In some embodiments, where the original amino acid according to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 is an acidic amino acid (e.g., E353), substitution to charged amino acids may include substitution to another acidic amino acid (e.g., D), or substitution to a basic amino acid (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), substitution to the charged amino acid includes substitution to a basic amino acid (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 a basic amino acid (e.g., Q10, K47, K50, or R354), substitution to the 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), substitution to the charged amino acid includes substitution to an acidic amino acid (e.g., D or E).

[0265] In some embodiments, the viral particle comprises an amino acid sequence containing SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 4, and a VSV-G protein with a substituted charged amino acid at position H8 compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises an amino acid sequence containing SEQ ID NO: 3, and a VSV-G protein with a substituted charged amino acid at position H8 compared to SEQ ID NO: 3, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises an amino acid sequence containing SEQ ID NO: 4, and a VSV-G protein with a substituted charged amino acid at position H8 compared to SEQ ID NO: 4, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises the amino acid sequence of SEQ ID NO: 5, and a VSV-G protein with a substitution of a charged amino acid at position H8 compared to SEQ ID NO: 5, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the mutation at position H8 is H8D. In some embodiments, the mutation at position H8 is H8E. In some embodiments, the mutation at position H8 is H8K. In some embodiments, the mutation at position H8 is H8R. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 and a mutation selected from H8D, H8E, H8K, or H8R at position H8 compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, further comprising one or more mutations compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, which comprises a substitution of a charged amino acid at positions N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof.

[0266] 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 at position N9 for a charged amino acid compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 3, and a substitution at position N9 for a charged amino acid compared to SEQ ID NO: 3, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 4, and a substitution at position N9 for a charged amino acid compared to SEQ ID NO: 4, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises the VSV-G protein containing the amino acid sequence of SEQ ID NO: 5, and a substitution at position N9 for a charged amino acid selected from D, E, K, or R compared to SEQ ID NO: 5. In some embodiments, the mutation at position N9 is N9D. In some embodiments, the mutation at position N9 is N9E. In some embodiments, the mutation at position N9 is N9K. In some embodiments, the mutation at position N9 is N9R. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 and a mutation selected from N9D, N9E, N9K, or N9R at position N9 compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, further comprising one or more mutations compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, which comprises a substitution of 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.

[0267] 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 at position Q10 for a charged amino acid compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, wherein the charged amino acid is selected from D or E. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 3, and a substitution at position Q10 for a charged amino acid compared to SEQ ID NO: 3, wherein the charged amino acid is selected from D or E. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 4, and a substitution at position Q10 for a charged amino acid compared to SEQ ID NO: 4, wherein the charged amino acid is selected from D or E. In some embodiments, the viral particle comprises the VSV-G protein containing the amino acid sequence of SEQ ID NO: 5, and a substitution at position Q10 for a charged amino acid, wherein the charged amino acid is selected from D or E. In some embodiments, the mutation at position Q10 is Q10D. In some embodiments, the mutation at position Q10 is Q10E. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 and a mutation selected from Q10D or Q10E at position Q10 compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, further comprising one or more mutations compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, which comprises a substitution of 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.

[0268] 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 at position K47 for a charged amino acid compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, wherein the charged amino acid is selected from D or E. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 3, and a substitution at position K47 for a charged amino acid compared to SEQ ID NO: 3, wherein the charged amino acid is selected from D or E. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 4, and a substitution at position K47 for a charged amino acid compared to SEQ ID NO: 4, wherein the charged amino acid is selected from D or E. In some embodiments, the viral particle comprises the VSV-G protein containing the amino acid sequence of SEQ ID NO: 5, and a substitution at position K47 for a charged amino acid, wherein the charged amino acid is selected from D or E, compared to SEQ ID NO: 5. In some embodiments, the mutation at position K47 is K47D. In some embodiments, the mutation at position K47 is K47E. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 and a mutation selected from K47D or K47E at position K47 compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, further comprising one or more mutations compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, which comprises a substitution of 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.

[0269] 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 at position K50 for a charged amino acid compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, wherein the charged amino acid is selected from D or E. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 3, and a substitution at position K50 for a charged amino acid compared to SEQ ID NO: 3, wherein the charged amino acid is selected from D or E. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 4, and a substitution at position K50 for a charged amino acid compared to SEQ ID NO: 4, wherein the charged amino acid is selected from D or E. In some embodiments, the viral particle comprises the VSV-G protein containing the amino acid sequence of SEQ ID NO: 5, and a substitution at position K50 for a charged amino acid, wherein the charged amino acid is selected from D or E, compared to SEQ ID NO: 5. In some embodiments, the mutation at position K50 is K50D. In some embodiments, the mutation at position K50 is K50E. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 and a mutation selected from K50D or K50E at position K50 compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, further comprising one or more mutations compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, which comprises a substitution of 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.

[0270] 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 at position A51 for a charged amino acid compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 3, and a substitution at position A51 for a charged amino acid compared to SEQ ID NO: 3, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 4, and a substitution at position A51 for a charged amino acid compared to SEQ ID NO: 4, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises the VSV-G protein containing the amino acid sequence of SEQ ID NO: 5, and a substitution at position A51 for a charged amino acid, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the mutation at position A51 is A51D. In some embodiments, the mutation at position A51 is A51E. In some embodiments, the mutation at position A51 is A51K. In some embodiments, the mutation at position A51 is A51R. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 and a mutation selected from A51D, A51E, A51K, or A51R at position A51 compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, further comprising one or more mutations compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, which comprises a substitution of 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.

[0271] 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 at position S179 for a charged amino acid compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 3, and a substitution at position S179 for a charged amino acid compared to SEQ ID NO: 3, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 4, and a substitution at position S179 for a charged amino acid compared to SEQ ID NO: 4, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises the VSV-G protein containing the amino acid sequence of SEQ ID NO: 5, and a substitution at position S179 for a charged amino acid, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the mutation at position S179 is S179D. In some embodiments, the mutation at position S179 is S179E. In some embodiments, the mutation at position S179 is S179K. In some embodiments, the mutation at position S179 is S179R. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 and a mutation selected from S179D, S179E, S179K, or S179R at position S179 compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, further comprising one or more mutations compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, which comprises a substitution of 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.

[0272] 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 at position N180 for a charged amino acid compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 3, and a substitution at position N180 for a charged amino acid compared to SEQ ID NO: 3, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 4, and a substitution at position N180 for a charged amino acid compared to SEQ ID NO: 4, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises the VSV-G protein containing the amino acid sequence of SEQ ID NO: 5, and a substitution at position N180 for a charged amino acid, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the mutation at position N180 is N180D. In some embodiments, the mutation at position N180 is N180E. In some embodiments, the mutation at position N180 is N180K. In some embodiments, the mutation at position N180 is N180R. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 and a mutation selected from N180D, N180E, N180K, or N180R at position N180 compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, further comprising one or more mutations compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, which comprises a substitution of 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.

[0273] 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 at position S183 for a charged amino acid compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 3, and a substitution at position S183 for a charged amino acid compared to SEQ ID NO: 3, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 4, and a substitution at position S183 for a charged amino acid compared to SEQ ID NO: 4, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises the VSV-G protein containing the amino acid sequence of SEQ ID NO: 5, and a substitution at position S183 for a charged amino acid, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the mutation at position S183 is S183D. In some embodiments, the mutation at position S183 is S183E. In some embodiments, the mutation at position S183 is S183K. In some embodiments, the mutation at position S183 is S183R. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 and a mutation selected from S183D, S183E, S183K, or S183R at position S183 compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, further comprising one or more mutations compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, which comprises a substitution of 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.

[0274] 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 at position M184 for a charged amino acid compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 3, and a substitution at position M184 for a charged amino acid compared to SEQ ID NO: 3, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 4, and a substitution at position M184 for a charged amino acid compared to SEQ ID NO: 4, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises the VSV-G protein containing the amino acid sequence of SEQ ID NO: 5, and a substitution at position M184 for a charged amino acid, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the mutation at position M184 is M184D. In some embodiments, the mutation at position M184 is M184E. In some embodiments, the mutation at position M184 is M184K. In some embodiments, the mutation at position M184 is M184R. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 and a mutation selected from M184D, M184E, M184K, or M184R at position M184 compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, further comprising one or more mutations compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, which comprises a substitution of 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.

[0275] 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 at position Y209 for a charged amino acid compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 3, and a substitution at position Y209 for a charged amino acid compared to SEQ ID NO: 3, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 4, and a substitution at position Y209 for a charged amino acid compared to SEQ ID NO: 4, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises the VSV-G protein containing the amino acid sequence of SEQ ID NO: 5, and a substitution at position Y209 for a charged amino acid, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the mutation at position Y209 is Y209D. In some embodiments, the mutation at position Y209 is Y209E. In some embodiments, the mutation at position Y209 is Y209K. In some embodiments, the mutation at position Y209 is Y209R. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 and a mutation selected from Y209D, Y209E, Y209K, or Y209R at position Y209 compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, further comprising one or more mutations compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, which comprises a substitution of 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.

[0276] 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 at position I347 for a charged amino acid compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 3, and a substitution at position I347 for a charged amino acid compared to SEQ ID NO: 3, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 4, and a substitution at position I347 for a charged amino acid compared to SEQ ID NO: 4, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises the VSV-G protein containing the amino acid sequence of SEQ ID NO: 5, and a substitution at position I347 for a charged amino acid, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the mutation at position I347 is I347D. In some embodiments, the mutation at position I347 is I347E. In some embodiments, the mutation at position I347 is I347K. In some embodiments, the mutation at position I347 is I347R. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 and a mutation selected from I347D, I347E, I347K, or I347R at position I347 compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, further comprising one or more mutations compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, which comprises a substitution of 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.

[0277] In some embodiments, the viral particle comprises an amino acid sequence containing SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, and a VSV-G protein with a substituted charged amino acid at position T350 compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises an amino acid sequence containing SEQ ID NO: 3, and a VSV-G protein with a substituted charged amino acid at position T350 compared to SEQ ID NO: 3, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises an amino acid sequence containing SEQ ID NO: 4, and a VSV-G protein with a substituted charged amino acid at position T350 compared to SEQ ID NO: 4, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises the amino acid sequence of SEQ ID NO: 5, and a VSV-G protein with a substituted charged amino acid at position T350 compared to SEQ ID NO: 5, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the mutation at position T350 is T350D. In some embodiments, the mutation at position T350 is T350E. In some embodiments, the mutation at position T350 is T350K. In some embodiments, the mutation at position T350 is T350R. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 and a mutation selected from T350D, T350E, T350K, or T350R at position T350 compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, further comprising one or more mutations compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, which comprises a substitution of 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.

[0278] 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 at position T352 for a charged amino acid compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 3, and a substitution at position T352 for a charged amino acid compared to SEQ ID NO: 3, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 4, and a substitution at position T352 for a charged amino acid compared to SEQ ID NO: 4, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises the VSV-G protein containing the amino acid sequence of SEQ ID NO: 5, and a substitution at position T352 for a charged amino acid, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the mutation at position T352 is T352D. In some embodiments, the mutation at position T352 is T352E. In some embodiments, the mutation at position T352 is T352K. In some embodiments, the mutation at position T352 is T352R. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 and a mutation selected from T352D, T352E, T352K, or T352R at position T352 compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, further comprising one or more mutations compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, which comprises a substitution of 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.

[0279] 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 at position E353 for a charged amino acid compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, wherein the charged amino acid is selected from K or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 3, and a substitution at position E353 for a charged amino acid compared to SEQ ID NO: 3, wherein the charged amino acid is selected from K or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 4, and a substitution at position E353 for a charged amino acid compared to SEQ ID NO: 4, wherein the charged amino acid is selected from K or R. In some embodiments, the viral particle comprises the VSV-G protein containing the amino acid sequence of SEQ ID NO: 5, and a substitution at position E353 for a charged amino acid selected from K or R compared to SEQ ID NO: 5. In some embodiments, the mutation at position E353 is E353K. In some embodiments, the mutation at position E353 is E353R. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 and a mutation selected from E353K or E353R at position E353 compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, further comprising one or more mutations compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, which comprises a substitution of 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.

[0280] 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 at position R354 for a charged amino acid compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, wherein the charged amino acid is selected from D or E. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 3, and a substitution at position R354 for a charged amino acid compared to SEQ ID NO: 3, wherein the charged amino acid is selected from D or E. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 4, and a substitution at position R354 for a charged amino acid compared to SEQ ID NO: 4, wherein the charged amino acid is selected from D or E. In some embodiments, the viral particle comprises the VSV-G protein containing the amino acid sequence of SEQ ID NO: 5, and a substitution at position R354 for a charged amino acid, wherein the charged amino acid is selected from D or E, compared to SEQ ID NO: 5. In some embodiments, the mutation at position R354 is R354D. In some embodiments, the mutation at position R354 is R354E. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 and a mutation selected from R354D or R354E at position R354 compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, further comprising one or more mutations compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, which comprise a substitution of 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.

[0281] Table 2: Charged amino acid positions compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 Energy and corresponding acceptable substitution .

[0282]

[0283] In some embodiments, the viral particle contains a VSV-G protein with one or more mutations, wherein the mutation is a substitution of a charged amino acid as described in Table 2. In some embodiments, the mutation containing the substitution of a charged amino acid is located at positions 8, 9, 10, 47, 50, 51, 179, 180, 183, 184, 209, 347, 350, 352, 353, 354, or any combination thereof, as described in Table 2. In some embodiments, the mutation containing the substitution of a charged amino acid is located at positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof, as described in Table 2.

[0284] It should be understood that any mutation of a specific residue as described in Table 2 may be combined with one or more additional mutations of other residues in Table 2. For example, in some embodiments, the viral particle contains the VSV-G protein containing a mutation at position H8 as described in Table 2, and also contains mutations at positions N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as described in Table 2. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position H8 as described in Table 2, and also contains at least one additional mutation selected from positions N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 2. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position H8 as described in Table 2, and also contains additional mutations selected from more than one position selected from positions N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 2.

[0285] In some embodiments, the viral particle contains a VSV-G protein containing a mutation at position N9 as described in Table 2, and also contains mutations at positions H8, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as described in Table 2. In some embodiments, the viral particle contains a VSV-G protein containing a mutation at position N9 as described in Table 2, and also contains at least one additional mutation selected from positions H8, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 2. In some implementations, the viral particle contains the VSV-G protein, which contains a mutation at position N9 as described in Table 2, and also contains additional mutations at more than one position selected from H8, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353 or R354 as described in Table 2.

[0286] In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position Q10 as described in Table 2, and also contains mutations at positions H8, N9, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as described in Table 2. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position Q10 as described in Table 2, and also contains at least one additional mutation selected from positions H8, N9, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 2. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position Q10 as described in Table 2, and also contains additional mutations at more than one position selected from H8, N9, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353 or R354 as described in Table 2.

[0287] In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position K47 as described in Table 2, and also contains mutations at positions H8, N9, Q10, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as described in Table 2. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position K47 as described in Table 2, and also contains at least one additional mutation selected from positions H8, N9, Q10, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 2. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position K47 as described in Table 2, and also contains additional mutations at more than one position selected from H8, N9, Q10, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353 or R354 as described in Table 2.

[0288] In some embodiments, the viral particle contains a VSV-G protein containing a mutation at position K50 as described in Table 2, and also contains mutations at positions H8, N9, Q10, K47, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as described in Table 2. In some embodiments, the viral particle contains a VSV-G protein containing a mutation at position K50 as described in Table 2, and also contains at least one additional mutation selected from positions H8, N9, Q10, K47, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 2. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position K50 as described in Table 2, and also contains additional mutations at more than one position selected from H8, N9, Q10, K47, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353 or R354 as described in Table 2.

[0289] In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position A51 as described in Table 2, and also contains mutations at positions H8, N9, Q10, K47, K50, S179, N180, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as described in Table 2. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position A51 as described in Table 2, and also contains at least one additional mutation selected from positions H8, N9, Q10, K47, K50, S179, N180, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 2. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position A51 as described in Table 2, and also contains additional mutations at more than one position selected from H8, N9, Q10, K47, K50, S179, N180, S183, M184, Y209, I347, T350, T352, E353 or R354 as described in Table 2.

[0290] In some embodiments, the viral particle contains a VSV-G protein containing a mutation at position S179 as described in Table 2, and also contains mutations at positions H8, N9, Q10, K47, K50, A51, N180, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as described in Table 2. In some embodiments, the viral particle contains a VSV-G protein containing a mutation at position S179 as described in Table 2, and also contains at least one additional mutation selected from positions H8, N9, Q10, K47, K50, A51, N180, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 2. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position S179 as described in Table 2, and also contains additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, N180, S183, M184, Y209, I347, T350, T352, E353 or R354 as described in Table 2.

[0291] In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position N180 as described in Table 2, and also contains mutations at positions H8, N9, Q10, K47, K50, A51, S179, S183, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as described in Table 2. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position N180 as described in Table 2, and also contains at least one additional mutation selected from positions H8, N9, Q10, K47, K50, A51, S179, S183, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 2. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position N180 as described in Table 2, and also contains additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, S183, M184, Y209, I347, T350, T352, E353 or R354 as described in Table 2.

[0292] In some embodiments, the viral particle contains a VSV-G protein containing a mutation at position S183 as described in Table 2, and also contains mutations at positions H8, N9, Q10, K47, K50, A51, S179, N180, M184, Y209, I347, T350, T352, E353, R354, or any combination thereof as described in Table 2. In some embodiments, the viral particle contains a VSV-G protein containing a mutation at position S183 as described in Table 2, and also contains at least one additional mutation selected from positions H8, N9, Q10, K47, K50, A51, S179, N180, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 2. In some implementations, the viral particle contains the VSV-G protein, which contains a mutation at position S183 as described in Table 2, and additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, N180, M184, Y209, I347, T350, T352, E353, or R354 as described in Table 2.

[0293] In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position M184 as described in Table 2, and also contains mutations at positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, Y209, I347, T350, T352, E353, R354, or any combination thereof as described in Table 2. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position M184 as described in Table 2, and also contains at least one additional mutation selected from positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, Y209, I347, T350, T352, E353, or R354 as described in Table 2. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position M184 as described in Table 2, and also contains additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, N180, S183, Y209, I347, T350, T352, E353 or R354 as described in Table 2.

[0294] In some embodiments, the viral particle contains a VSV-G protein containing a mutation at position Y209 as described in Table 2, and also contains mutations at positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, I347, T350, T352, E353, R354, or any combination thereof as described in Table 2. In some embodiments, the viral particle contains a VSV-G protein containing a mutation at position Y209 as described in Table 2, and also contains at least one additional mutation selected from positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, I347, T350, T352, E353, or R354 as described in Table 2. In some implementations, the viral particle contains the VSV-G protein, which contains a mutation at position Y209 as described in Table 2, and also contains additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, I347, T350, T352, E353 or R354 as described in Table 2.

[0295] In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position I347 as described in Table 2, and also contains mutations at positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, T350, T352, E353, R354, or any combination thereof as described in Table 2. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position I347 as described in Table 2, and also contains at least one additional mutation selected from positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, T350, T352, E353, or R354 as described in Table 2. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position I347 as described in Table 2, and also contains additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, T350, T352, E353 or R354 as described in Table 2.

[0296] In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position T350 as described in Table 2, and also contains mutations at positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T352, E353, R354, or any combination thereof as described in Table 2. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position T350 as described in Table 2, and also contains at least one additional mutation selected from positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T352, E353, or R354 as described in Table 2. In some implementations, the viral particle contains the VSV-G protein, which contains a mutation at position T350 as described in Table 2, and also contains additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T352, E353 or R354 as described in Table 2.

[0297] In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position T352 as described in Table 2, and also contains mutations at positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof as described in Table 2. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position T352 as described in Table 2, and also contains at least one additional mutation selected from positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, or R354 as described in Table 2. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position T352 as described in Table 2, and also contains additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353 or R354 as described in Table 2.

[0298] In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position E353 as described in Table 2, and also contains mutations at positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, R354, or any combination thereof as described in Table 2. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position E353 as described in Table 2, and also contains at least one additional mutation selected from positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, or R354 as described in Table 2. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position E353 as described in Table 2, and also contains additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352 or R354 as described in Table 2.

[0299] In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position R354 as described in Table 2, and also contains mutations at positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, E353, or any combination thereof as described in Table 2. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position R354 as described in Table 2, and also contains at least one additional mutation selected from positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352, or E353 as described in Table 2. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position R354 as described in Table 2, and also contains additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, T352 or E353 as described in Table 2.

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

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

[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 further comprises a substitution at position Q10 for a charged amino acid 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, and further comprises a substitution at position Q10 for a charged amino acid 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, and further comprises a substitution at position Q10 for a charged amino acid 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 of a charged amino acid at position Q10 compared to SEQ ID NO: 22 or SEQ ID NO: 23, further comprises one or more mutations, which comprise a substitution of a charged amino acid at positions H8, N9, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof.

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

[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 further comprises a substitution at position K50 for a charged amino acid 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, and further comprises a substitution at position K50 for a charged amino acid 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, and further comprises a substitution at position K50 for a charged amino acid 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 of a charged amino acid at position K50 compared to SEQ ID NO: 22 or SEQ ID NO: 23, further comprises one or more mutations, which comprise a substitution of a charged amino acid at positions H8, N9, Q10, K47, A51, S179, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof.

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

[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 further comprises a substitution at position N180 for a charged amino acid 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, and further comprises a substitution at position N180 for a charged amino acid 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, and further comprises a substitution at position N180 for a charged amino acid 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 of a charged amino acid at position N180 compared to SEQ ID NO: 22 or SEQ ID NO: 23, further comprises one or more mutations, which comprise a substitution of a charged amino acid at positions H8, N9, Q10, K47, K50, A51, S179, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof.

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

[0309] 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 further comprises a substitution at position M184 for a charged amino acid 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, and further comprises a substitution at position M184 for a charged amino acid compared to SEQ ID NO: 23. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 23, and further comprises a substitution at position M184 for a charged amino acid 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 of a charged amino acid at position M184 compared to SEQ ID NO: 22 or SEQ ID NO: 23, further comprises one or more mutations, which comprise a substitution of a charged amino acid at positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, Y209, I347, T350, E353, R354, or any combination thereof.

[0310] 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 further comprises a substitution at position Y209 for a charged amino acid 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, and further comprises a substitution at position Y209 for a charged amino acid compared to SEQ ID NO: 23. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 23, and further comprises a substitution at position Y209 for a charged amino acid 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 of a charged amino acid at position Y209 compared to SEQ ID NO: 22 or SEQ ID NO: 23, further comprises one or more mutations, which comprise a substitution of a charged amino acid at positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, I347, T350, E353, R354, or any combination thereof.

[0311] 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 further comprises a substitution at position I347 for a charged amino acid 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, and further comprises a substitution at position I347 for a charged amino acid compared to SEQ ID NO: 23. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 23, and further comprises a substitution at position I347 for a charged amino acid 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 of a charged amino acid at position I347 compared to SEQ ID NO: 22 or SEQ ID NO: 23, further comprises one or more mutations, which comprise a substitution of a charged amino acid at positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, T350, E353, R354, or any combination thereof.

[0312] 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 further comprises a substitution at position T350 for a charged amino acid 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, and further comprises a substitution at position T350 for a charged amino acid 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, and further comprises a substitution at position T350 for a charged amino acid 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 of a charged amino acid at position T350 compared to SEQ ID NO: 22 or SEQ ID NO: 23, further comprises one or more mutations, which comprise a substitution of a charged amino acid at positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, E353, R354, or any combination thereof.

[0313] 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 further comprises a substitution at position E353 for a charged amino acid 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, and further comprises a substitution at position E353 for a charged amino acid compared to SEQ ID NO: 23. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 23, and further comprises a substitution at position E353 for a charged amino acid 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 of a charged amino acid at position E353 compared to SEQ ID NO: 22 or SEQ ID NO: 23, further comprises one or more mutations, which comprise a substitution of a charged amino acid at positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, R354, or any combination thereof.

[0314] 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 further comprises a substitution at position R354 for a charged amino acid 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, and further comprises a substitution at position R354 for a charged amino acid 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, and further comprises a substitution at position R354 for a charged amino acid 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 of a charged amino acid at position R354 compared to SEQ ID NO: 22 or SEQ ID NO: 23, further comprises one or more mutations, which comprise a substitution of a charged amino acid at positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353 or any combination thereof.

[0315] Substitution of charged amino acids 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: 22 or SEQ ID NO: 23 may include substitution to any charged amino acid. In some embodiments, substitution includes substitution to acidic amino acids, including but not limited to aspartic acid (D) or glutamic acid (E). In some embodiments, substitution includes substitution to basic amino acids, including but not limited to lysine (K) or arginine (R). In some embodiments, where the original amino acid according to SEQ ID NO: 22 or SEQ ID NO: 23 is an acidic amino acid (e.g., E353), substitution to charged amino acids may include substitution to another acidic amino acid (e.g., D), or substitution to a basic amino acid (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), substitution to the charged amino acid includes substitution to a basic amino acid (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 a basic amino acid (e.g., Q10, K47, K50, or R354), substitution to the 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), substitution to the charged amino acid includes substitution to an acidic amino acid (e.g., D or E).

[0316] 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 at position H8 for a charged amino acid compared to SEQ ID NO: 22 or SEQ ID NO: 23, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 22, and a substitution at position H8 for a charged amino acid compared to SEQ ID NO: 22, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 23, and a substitution at position H8 for a charged amino acid compared to SEQ ID NO: 23, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the mutation at position H8 is H8D. In some embodiments, the mutation at position H8 is H8E. In some embodiments, the mutation at position H8 is H8K. In some embodiments, the mutation at position H8 is H8R. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a mutation selected from H8D, H8E, H8K, or H8R at position H8 compared to SEQ ID NO: 22 or SEQ ID NO: 23, further comprises one or more mutations compared to SEQ ID NO: 23, which comprise a substitution of a charged amino acid at positions N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof.

[0317] 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 at position N9 for a charged amino acid compared to SEQ ID NO: 22 or SEQ ID NO: 23, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 22, and a substitution at position N9 for a charged amino acid compared to SEQ ID NO: 22, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 23, and a substitution at position N9 for a charged amino acid compared to SEQ ID NO: 23, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the mutation at position N9 is N9D. In some embodiments, the mutation at position N9 is N9E. In some embodiments, the mutation at position N9 is N9K. In some embodiments, the mutation at position N9 is N9R. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a mutation selected from N9D, N9E, N9K, or N9R at position N9 compared to SEQ ID NO: 22 or SEQ ID NO: 23, further comprising one or more mutations compared to SEQ ID NO: 23, which comprise a substitution of a charged amino acid at positions H8, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof.

[0318] 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 at position Q10 for a charged amino acid compared to SEQ ID NO: 22 or SEQ ID NO: 23, wherein the charged amino acid is selected from D or E. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 22, and a substitution at position Q10 for a charged amino acid compared to SEQ ID NO: 22, wherein the charged amino acid is selected from D or E. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 23, and a substitution at position Q10 for a charged amino acid compared to SEQ ID NO: 23, wherein the charged amino acid is selected from D or E. In some embodiments, the mutation at position Q10 is Q10D. In some embodiments, the mutation at position Q10 is Q10E. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a mutation selected from Q10D or Q10E at position Q10 compared to SEQ ID NO: 22 or SEQ ID NO: 23, further comprising one or more mutations compared to SEQ ID NO: 22 or SEQ ID NO: 23, the one or more mutations comprising a substitution of a charged amino acid at positions H8, N9, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, R354 or any combination thereof.

[0319] 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 at position K47 for a charged amino acid compared to SEQ ID NO: 22 or SEQ ID NO: 23, wherein the charged amino acid is selected from D or E. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 22, and a substitution at position K47 for a charged amino acid compared to SEQ ID NO: 22, wherein the charged amino acid is selected from D or E. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 23, and a substitution at position K47 for a charged amino acid compared to SEQ ID NO: 23, wherein the charged amino acid is selected from D or E. In some embodiments, the mutation at position K47 is K47D. In some embodiments, the mutation at position K47 is K47E. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a mutation selected from K47D or K47E at position K47 compared to SEQ ID NO: 22 or SEQ ID NO: 23, further comprising one or more mutations compared to SEQ ID NO: 22 or SEQ ID NO: 23, the one or more mutations comprising a substitution of a charged amino acid at positions H8, N9, Q10, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, R354 or any combination thereof.

[0320] 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 at position K50 for a charged amino acid compared to SEQ ID NO: 22 or SEQ ID NO: 23, wherein the charged amino acid is selected from D or E. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 22, and a substitution at position K50 for a charged amino acid compared to SEQ ID NO: 22, wherein the charged amino acid is selected from D or E. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 23, and a substitution at position K50 for a charged amino acid compared to SEQ ID NO: 23, wherein the charged amino acid is selected from D or E. In some embodiments, the mutation at position K50 is K50D. In some embodiments, the mutation at position K50 is K50E. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a mutation selected from K50D or K50E at position K50 compared to SEQ ID NO: 22 or SEQ ID NO: 23, further comprising one or more mutations compared to SEQ ID NO: 22 or SEQ ID NO: 23, the one or more mutations comprising a substitution of a charged amino acid at positions H8, N9, Q10, K47, A51, S179, N180, S183, M184, Y209, I347, T350, E353, R354 or any combination thereof.

[0321] 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 at position A51 for a charged amino acid compared to SEQ ID NO: 22 or SEQ ID NO: 23, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 22, and a substitution at position A51 for a charged amino acid compared to SEQ ID NO: 22, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 23, and a substitution at position A51 for a charged amino acid compared to SEQ ID NO: 23, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the mutation at position A51 is A51D. In some embodiments, the mutation at position A51 is A51E. In some embodiments, the mutation at position A51 is A51K. In some embodiments, the mutation at position A51 is A51R. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO:22 or SEQ ID NO:23 and a mutation selected from A51D, A51E, A51K, or A51R at position A51 compared to SEQ ID NO:22 or SEQ ID NO:23 further comprises one or more mutations compared to SEQ ID NO:23, which comprise a substitution of a charged amino acid at positions H8, N9, Q10, K47, K50, S179, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof.

[0322] 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 at position S179 for a charged amino acid compared to SEQ ID NO: 22 or SEQ ID NO: 23, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 22, and a substitution at position S179 for a charged amino acid compared to SEQ ID NO: 22, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 23, and a substitution at position S179 for a charged amino acid compared to SEQ ID NO: 23, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the mutation at position S179 is S179D. In some embodiments, the mutation at position S179 is S179E. In some embodiments, the mutation at position S179 is S179K. In some embodiments, the mutation at position S179 is S179R. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a mutation selected from S179D, S179E, S179K, or S179R at position S179 compared to SEQ ID NO: 22 or SEQ ID NO: 23, further comprises one or more mutations compared to SEQ ID NO: 23, which comprise a substitution of a charged amino acid at positions H8, N9, Q10, K47, K50, A51, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof.

[0323] 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 at position N180 for a charged amino acid compared to SEQ ID NO: 22 or SEQ ID NO: 23, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 22, and a substitution at position N180 for a charged amino acid compared to SEQ ID NO: 22, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 23, and a substitution at position N180 for a charged amino acid compared to SEQ ID NO: 23, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the mutation at position N180 is N180D. In some embodiments, the mutation at position N180 is N180E. In some embodiments, the mutation at position N180 is N180K. In some embodiments, the mutation at position N180 is N180R. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a mutation selected from N180D, N180E, N180K, or N180R at position N180 compared to SEQ ID NO: 22 or SEQ ID NO: 23, further comprises one or more mutations compared to SEQ ID NO: 23, which comprise a substitution of a charged amino acid at positions H8, N9, Q10, K47, K50, A51, S179, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof.

[0324] 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 at position S183 for a charged amino acid compared to SEQ ID NO: 22 or SEQ ID NO: 23, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 22, and a substitution at position S183 for a charged amino acid compared to SEQ ID NO: 22, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 23, and a substitution at position S183 for a charged amino acid compared to SEQ ID NO: 23, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the mutation at position S183 is S183D. In some embodiments, the mutation at position S183 is S183E. In some embodiments, the mutation at position S183 is S183K. In some embodiments, the mutation at position S183 is S183R. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a mutation selected from S183D, S183E, S183K, or S183R at position S183 compared to SEQ ID NO: 22 or SEQ ID NO: 23, further comprises one or more mutations compared to SEQ ID NO: 23, which comprise a substitution of a charged amino acid at positions H8, N9, Q10, K47, K50, A51, S179, N180, M184, Y209, I347, T350, E353, R354, or any combination thereof.

[0325] 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 at position M184 for a charged amino acid compared to SEQ ID NO: 22 or SEQ ID NO: 23, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 22, and a substitution at position M184 for a charged amino acid compared to SEQ ID NO: 22, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 23, and a substitution at position M184 for a charged amino acid compared to SEQ ID NO: 23, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the mutation at position M184 is M184D. In some embodiments, the mutation at position M184 is M184E. In some embodiments, the mutation at position M184 is M184K. In some embodiments, the mutation at position M184 is M184R. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a mutation selected from M184D, M184E, M184K, or M184R at position M184 compared to SEQ ID NO: 22 or SEQ ID NO: 23, further comprises one or more mutations compared to SEQ ID NO: 23, which comprise a substitution of a charged amino acid at positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, Y209, I347, T350, E353, R354, or any combination thereof.

[0326] 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 at position Y209 for a charged amino acid compared to SEQ ID NO: 22 or SEQ ID NO: 23, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 22, and a substitution at position Y209 for a charged amino acid compared to SEQ ID NO: 22, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 23, and a substitution at position Y209 for a charged amino acid compared to SEQ ID NO: 23, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the mutation at position Y209 is Y209D. In some embodiments, the mutation at position Y209 is Y209E. In some embodiments, the mutation at position Y209 is Y209K. In some embodiments, the mutation at position Y209 is Y209R. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a mutation selected from Y209D, Y209E, Y209K, or Y209R at position Y209 compared to SEQ ID NO: 22 or SEQ ID NO: 23, further comprises one or more mutations compared to SEQ ID NO: 23, which comprise a substitution of a charged amino acid at positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, I347, T350, E353, R354, or any combination thereof.

[0327] 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 at position I347 for a charged amino acid compared to SEQ ID NO: 22 or SEQ ID NO: 23, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 22, and a substitution at position I347 for a charged amino acid compared to SEQ ID NO: 22, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 23, and a substitution at position I347 for a charged amino acid compared to SEQ ID NO: 23, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the mutation at position I347 is I347D. In some embodiments, the mutation at position I347 is I347E. In some embodiments, the mutation at position I347 is I347K. In some embodiments, the mutation at position I347 is I347R. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a mutation selected from I347D, I347E, I347K, or I347R at position I347 compared to SEQ ID NO: 22 or SEQ ID NO: 23, further comprises one or more mutations compared to SEQ ID NO: 23, which comprise a substitution of a charged amino acid at positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, T350, E353, R354, or any combination thereof.

[0328] In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 22 and SEQ ID NO: 23, and a substitution at position T350 for a charged amino acid compared to SEQ ID NO: 22 or SEQ ID NO: 23, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 22, and a substitution at position T350 for a charged amino acid compared to SEQ ID NO: 22, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 23, and a substitution at position T350 for a charged amino acid compared to SEQ ID NO: 23, wherein the charged amino acid is selected from D, E, K, or R. In some embodiments, the mutation at position T350 is T350D. In some embodiments, the mutation at position T350 is T350E. In some embodiments, the mutation at position T350 is T350K. In some embodiments, the mutation at position T350 is T350R. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a mutation selected from T350D, T350E, T350K, or T350R at position T350 compared to SEQ ID NO: 22 or SEQ ID NO: 23, further comprises one or more mutations compared to SEQ ID NO: 23, which comprise a substitution of a charged amino acid at positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, E353, R354, or any combination thereof.

[0329] 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 at position E353 for a charged amino acid compared to SEQ ID NO: 22 or SEQ ID NO: 23, wherein the charged amino acid is selected from K or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 22, and a substitution at position E353 for a charged amino acid compared to SEQ ID NO: 22, wherein the charged amino acid is selected from K or R. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 23, and a substitution at position E353 for a charged amino acid compared to SEQ ID NO: 23, wherein the charged amino acid is selected from K or R. In some embodiments, the mutation at position E353 is E353K. In some embodiments, the mutation at position E353 is E353R. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a mutation selected from E353K or E353R at position E353 compared to SEQ ID NO: 22 or SEQ ID NO: 23, further comprising one or more mutations compared to SEQ ID NO: 22 or SEQ ID NO: 23, the one or more mutations comprising a substitution of a charged amino acid at positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, R354 or any combination thereof.

[0330] 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 at position R354 for a charged amino acid compared to SEQ ID NO: 22 or SEQ ID NO: 23, wherein the charged amino acid is selected from D or E. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 22, and a substitution at position R354 for a charged amino acid compared to SEQ ID NO: 22, wherein the charged amino acid is selected from D or E. In some embodiments, the viral particle comprises a VSV-G protein containing the amino acid sequence of SEQ ID NO: 23, and a substitution at position R354 for a charged amino acid compared to SEQ ID NO: 23, wherein the charged amino acid is selected from D or E. In some embodiments, the mutation at position R354 is R354D. In some embodiments, the mutation at position R354 is R354E. In some embodiments, the VSV-G protein comprising the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 23 and a mutation selected from R354D or R354E at position R354 compared to SEQ ID NO: 22 or SEQ ID NO: 23, further comprising one or more mutations compared to SEQ ID NO: 22 or SEQ ID NO: 23, the one or more mutations comprising a substitution of a charged amino acid at positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353 or any combination thereof.

[0331] Table 3: Charged amino acid positions compared to SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5 Energy and corresponding acceptable substitution .

[0332]

[0333] In some embodiments, the viral particle comprises a VSV-G protein containing one or more mutations, wherein the mutation is a substitution of a charged amino acid as described in Table 3. In some embodiments, the mutation containing the substitution of a charged amino acid is located at positions 8, 9, 10, 47, 50, 51, 179, 180, 183, 184, 209, 347, 350, 353, 354, or any combination thereof, as described in Table 3. In some embodiments, the mutation containing the substitution of a charged amino acid is located at positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof, as described in Table 3.

[0334] It should be understood that any mutation of a specific residue as described in Table 3 may be combined with one or more additional mutations of other residues in Table 3. For example, in some embodiments, the viral particle contains the VSV-G protein containing a mutation at position H8 as described in Table 3, and also contains mutations at positions N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof as described in Table 3. In some embodiments, the viral particle contains the VSV-G protein, which contains the mutation at position H8 as described in Table 3, and also contains at least one additional mutation selected from N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, or R354 as described in Table 3. In some embodiments, the viral particle contains the VSV-G protein, which contains the mutation at position H8 as described in Table 3, and also contains additional mutations selected from more than one of N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, or R354 as described in Table 3.

[0335] In some embodiments, the viral particle contains a VSV-G protein containing a mutation at position N9 as described in Table 3, and also contains mutations at positions H8, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof as described in Table 3. In some embodiments, the viral particle contains a VSV-G protein containing a mutation at position N9 as described in Table 3, and also contains at least one additional mutation selected from positions H8, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, or R354 as described in Table 3. In some implementations, the viral particle contains the VSV-G protein, which contains a mutation at position N9 as described in Table 3, and also contains additional mutations at more than one position selected from H8, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353 or R354 as described in Table 3.

[0336] In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position Q10 as described in Table 3, and also contains mutations at positions H8, N9, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof as described in Table 3. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position Q10 as described in Table 3, and also contains at least one additional mutation at a position selected from H8, N9, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, or R354 as described in Table 3. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position Q10 as described in Table 3, and also contains additional mutations at more than one position selected from H8, N9, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353 or R354 as described in Table 3.

[0337] In some embodiments, the viral particle contains a VSV-G protein containing a mutation at position K47 as described in Table 3, and also contains mutations at positions H8, N9, Q10, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof as described in Table 3. In some embodiments, the viral particle contains a VSV-G protein containing a mutation at position K47 as described in Table 3, and also contains at least one additional mutation selected from positions H8, N9, Q10, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, or R354 as described in Table 3. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position K47 as described in Table 3, and also contains additional mutations at more than one position selected from H8, N9, Q10, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353 or R354 as described in Table 3.

[0338] In some embodiments, the viral particle contains a VSV-G protein containing a mutation at position K50 as described in Table 3, and also contains mutations at positions H8, N9, Q10, K47, A51, S179, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof as described in Table 3. In some embodiments, the viral particle contains a VSV-G protein containing a mutation at position K50 as described in Table 3, and also contains at least one additional mutation selected from positions H8, N9, Q10, K47, A51, S179, N180, S183, M184, Y209, I347, T350, E353, or R354 as described in Table 3. In some implementations, the viral particle contains the VSV-G protein, which contains a mutation at position K50 as described in Table 3, and also contains additional mutations at more than one position selected from H8, N9, Q10, K47, A51, S179, N180, S183, M184, Y209, I347, T350, E353 or R354 as described in Table 3.

[0339] In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position A51 as described in Table 3, and also contains mutations at positions H8, N9, Q10, K47, K50, S179, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof as described in Table 3. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position A51 as described in Table 3, and also contains at least one additional mutation selected from positions H8, N9, Q10, K47, K50, S179, N180, S183, M184, Y209, I347, T350, E353, or R354 as described in Table 3. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position A51 as described in Table 3, and also contains additional mutations at more than one position selected from H8, N9, Q10, K47, K50, S179, N180, S183, M184, Y209, I347, T350, E353 or R354 as described in Table 3.

[0340] In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position S179 as described in Table 3, and also contains mutations at positions H8, N9, Q10, K47, K50, A51, N180, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof as described in Table 3. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position S179 as described in Table 3, and also contains at least one additional mutation selected from positions H8, N9, Q10, K47, K50, A51, N180, S183, M184, Y209, I347, T350, E353, or R354 as described in Table 3. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position S179 as described in Table 3, and also contains additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, N180, S183, M184, Y209, I347, T350, E353 or R354 as described in Table 3.

[0341] In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position N180 as described in Table 3, and also contains mutations at positions H8, N9, Q10, K47, K50, A51, S179, S183, M184, Y209, I347, T350, E353, R354, or any combination thereof as described in Table 3. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position N180 as described in Table 3, and also contains at least one additional mutation selected from positions H8, N9, Q10, K47, K50, A51, S179, S183, M184, Y209, I347, T350, E353, or R354 as described in Table 3. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position N180 as described in Table 3, and also contains additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, S183, M184, Y209, I347, T350, E353 or R354 as described in Table 3.

[0342] In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position S183 as described in Table 3, and also contains mutations at positions H8, N9, Q10, K47, K50, A51, S179, N180, M184, Y209, I347, T350, E353, R354, or any combination thereof as described in Table 3. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position S183 as described in Table 3, and also contains at least one additional mutation selected from positions H8, N9, Q10, K47, K50, A51, S179, N180, M184, Y209, I347, T350, E353, or R354 as described in Table 3. In some implementations, the viral particle contains the VSV-G protein, which contains a mutation at position S183 as described in Table 3, and additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, N180, M184, Y209, I347, T350, E353, or R354 as described in Table 3.

[0343] In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position M184 as described in Table 3, and also contains mutations at positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, Y209, I347, T350, E353, R354, or any combination thereof as described in Table 3. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position M184 as described in Table 3, and also contains at least one additional mutation selected from positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, Y209, I347, T350, E353, or R354 as described in Table 3. In some implementations, the viral particle contains the VSV-G protein, which contains a mutation at position M184 as described in Table 3, and also contains additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, N180, S183, Y209, I347, T350, E353 or R354 as described in Table 3.

[0344] In some embodiments, the viral particle contains a VSV-G protein containing a mutation at position Y209 as described in Table 3, and also contains mutations at positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, I347, T350, E353, R354, or any combination thereof as described in Table 3. In some embodiments, the viral particle contains a VSV-G protein containing a mutation at position Y209 as described in Table 3, and also contains at least one additional mutation selected from positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, I347, T350, E353, or R354 as described in Table 3. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position Y209 as described in Table 3, and also contains additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, I347, T350, E353 or R354 as described in Table 3.

[0345] In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position I347 as described in Table 3, and also contains mutations at positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, T350, E353, R354, or any combination thereof as described in Table 3. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position I347 as described in Table 3, and also contains at least one additional mutation selected from positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, T350, E353, or R354 as described in Table 3. In some implementations, the viral particle contains the VSV-G protein, which contains a mutation at position I347 as described in Table 3, and also contains additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, T350, E353 or R354 as described in Table 3.

[0346] In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position T350 as described in Table 3, and also contains mutations at positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, E353, R354, or any combination thereof as described in Table 3. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position T350 as described in Table 3, and also contains at least one additional mutation selected from positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, E353, or R354 as described in Table 3. In some implementations, the viral particle contains the VSV-G protein, which contains a mutation at position T350 as described in Table 3, and also contains additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, E353 or R354 as described in Table 3.

[0347] In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position E353 as described in Table 3, and also contains mutations at positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, R354, or any combination thereof as described in Table 3. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position E353 as described in Table 3, and also contains at least one additional mutation selected from positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, or R354 as described in Table 3. In some implementations, the viral particle contains the VSV-G protein, which contains a mutation at position E353 as described in Table 3, and also contains additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350 or R354 as described in Table 3.

[0348] In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position R354 as described in Table 3, and also contains mutations at positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, E353, or any combination thereof as described in Table 3. In some embodiments, the viral particle contains the VSV-G protein, which contains a mutation at position R354 as described in Table 3, and also contains at least one additional mutation selected from positions H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350, or E353 as described in Table 3. In some implementations, the viral particle contains the VSV-G protein, which contains a mutation at position R354 as described in Table 3, and also contains additional mutations at more than one position selected from H8, N9, Q10, K47, K50, A51, S179, N180, S183, M184, Y209, I347, T350 or E353 as described in Table 3.

[0349] In any embodiment of this document, the VSV-G protein may also contain 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 mutation is a substitution 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.

[0350] As provided herein, any mutation (i.e., substitution) described herein may be combined with any other mutation described herein. For example, in some embodiments, a VSV-G protein, as provided herein, is provided that comprises 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 also comprises a mutation at positions 8, 9, 10, 47, 50, 51, 179, 180, 182, 184, 209, 347, 350, 352, 353, 354, or any combination thereof, wherein the mutation is a substitution to an alanine residue.

[0351] As provided herein, any mutation (i.e., substitution) described herein may be combined with any other mutation described herein. For example, in some embodiments, a VSV-G protein, as provided herein, is provided that comprises 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 also comprises a mutation at positions 8, 9, 10, 47, 50, 51, 179, 180, 182, 184, 209, 347, 350, 352, 353, 354, or any combination thereof, wherein the mutation is a substitution to a glycine residue.

[0352] As provided herein, any mutation (i.e., substitution) described herein may be combined with any other mutation described herein. For example, in some embodiments, a VSV-G protein, as provided herein, is provided that comprises 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 also comprises a mutation at positions 8, 9, 10, 47, 50, 51, 179, 180, 182, 184, 209, 347, 350, 352, 353, 354, or any combination thereof, wherein the mutation is a substitution to a glutamine residue.

[0353] In some embodiments, the VSV-G protein provided herein contains the H8A mutation, and also contains 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.

[0354] In some embodiments, the VSV-G protein provided herein contains the N9A mutation, and also contains 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.

[0355] In some embodiments, the VSV-G protein provided herein contains the H8A mutation, and also contains 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.

[0356] In some embodiments, the VSV-G protein provided herein contains the Q10A mutation, and also contains 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.

[0357] In some embodiments, the VSV-G protein provided herein contains the K47A mutation, and also contains 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.

[0358] In some embodiments, the VSV-G protein provided herein contains the K50A mutation, and also contains 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.

[0359] In some embodiments, the VSV-G protein provided herein contains the K51A mutation, and also contains 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.

[0360] In some embodiments, the VSV-G protein provided herein contains the S179A mutation, and also contains 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.

[0361] In some embodiments, the VSV-G protein provided herein contains the N180A mutation, and also contains 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.

[0362] In some embodiments, the VSV-G protein provided herein contains the I182A mutation, and also contains 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.

[0363] In some embodiments, the VSV-G protein provided herein contains the M184A mutation, and also contains 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.

[0364] In some embodiments, the VSV-G protein provided herein contains the Y209A mutation, and also contains 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.

[0365] In some embodiments, the VSV-G protein provided herein contains the I347A mutation, and also contains 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.

[0366] In some embodiments, the VSV-G protein provided herein contains the I347G mutation, and also contains 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.

[0367] In some embodiments, the VSV-G protein provided herein contains the T350A mutation, and also contains 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.

[0368] In some embodiments, the VSV-G protein provided herein contains the T352A mutation, and also contains 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.

[0369] In some embodiments, the VSV-G protein provided herein contains the T352Q mutation, and also contains 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.

[0370] In some embodiments, the VSV-G protein provided herein contains the E353A mutation, and also contains 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.

[0371] In some embodiments, the VSV-G protein provided herein contains the R354A mutation, and also contains 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 any combination thereof.

[0372] In some embodiments, the VSV-G protein provided herein contains the I182E mutation and also contains the I347G mutation, the T352E mutation, or any combination thereof. In some embodiments, the VSV-G protein provided herein contains the I347G mutation and also contains the I182E mutation, the T352E mutation, or any combination thereof. In some embodiments, the T352E mutation is combined with either 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 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 may be combined with any other mutations provided herein.

[0373] As provided herein, the sequences 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 contain the extracellular domain of the VSV-G polypeptide sequence, wherein the leader peptide has been cleaved. Therefore, although specific embodiments have been 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 cover the corresponding full-length VSV-G protein sequences. Therefore, in some embodiments, the embodiment belonging to SEQ ID NO: 2 also applies to SEQ ID NO: 1, wherein the amino acid numbers are updated to reflect the presence of the leader peptide. In some embodiments, the embodiment belonging to SEQ ID NO: 22 also applies to SEQ ID NO: 24, wherein the amino acid numbers are updated to reflect the presence of the leader peptide. In some embodiments, the embodiment belonging to SEQ ID NO: 23 also applies to SEQ ID NO: 25, wherein the amino acid numbers are updated to reflect the presence of the leader peptide. In some embodiments, the embodiment belonging to SEQ ID NO: 3 further comprises the 16-meric signal peptide of SEQ ID NO: 26, wherein the amino acid numbering for the mutation described in SEQ ID NO: 3 is updated to reflect the presence of the leader peptide. In some embodiments, the embodiment belonging to SEQ ID NO: 4 further comprises the 16-meric signal peptide of SEQ ID NO: 26, wherein the amino acid numbering for the mutation described in SEQ ID NO: 4 is updated to reflect the presence of the leader peptide. In some embodiments, the embodiment belonging to SEQ ID NO: 5 further comprises the 16-meric signal peptide of SEQ ID NO: 26, wherein the amino acid numbering for the mutation described in SEQ ID NO: 5 is updated to reflect the presence of the leader peptide.

[0374] Furthermore, although mutations can be described 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 (which are derived from or originate from the Indiana strain of VSV-G protein), mutations can also be used in other strains of the VSV-G protein. For example, mutations can be made in the New Jersey strain of VSV-G, the Malaba strain of VSV-G, the Carajás strain of VSV-G, the Alagoa strain of VSV-G, the Cocal strain of VSV-G, or the Morton strain of VSV-G. In some embodiments, the sequence of each strain is as provided herein. Examples of such strains 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 extracellular domains of the New Jersey strain of VSV-G are SEQ ID NO: 10 and SEQ ID NO: 11, respectively; the wild-type full-length or extracellular domains of the Malaba strain of VSV-G are SEQ ID NO: 12 and SEQ ID NO: 13, respectively; the wild-type full-length or extracellular domains of the Carajá strain of VSV-G are SEQ ID NO: 14 and SEQ ID NO: 15, respectively; the wild-type full-length or extracellular domains of the Alagoa strain of VSV-G are SEQ ID NO: 16 and SEQ ID NO: 17, respectively; the wild-type full-length or extracellular domains of the Cocal strain of VSV-G are SEQ ID NO: 18 and SEQ ID NO: 19, respectively; or the wild-type full-length or extracellular domains of the Morton strain of VSV-G are SEQ ID NO: 20 and SEQ ID NO: 21, respectively.

[0375] Targeted portion

[0376] In some embodiments, the viral particle includes a targeting portion. The targeting portion can be used to target a viral particle containing the mutant VSV-G protein to a cell expressing a target to which the targeting portion binds. In some embodiments, the targeting portion is an antibody, scFv antibody, antigen-binding domain, an ankyrin repeat sequence (e.g., DARPIN), VHH domain antibody, nanobody, single-domain antibody, FN3 domain, or any combination thereof. The targeting portion can be attached to the viral surface via an IgG Fc stem. In some embodiments, the stem includes a transmembrane domain. In some embodiments, the transmembrane domain includes a CD8 transmembrane domain. In some embodiments, the transmembrane domain includes a CD28 transmembrane domain. In some embodiments, the targeting portion is attached (fused to or linked) to the envelope glycoprotein G or H of a virus of the Paramyxoviridae family, such as a measlesvirus, or a Hennipa virus, such as Nipah virus, cedar virus, or Hendra virus. In some embodiments, the targeting portion may attach (fuse or link) to a glycoprotein of a virus belonging to the Rhabdoviridae family, such as vesicular stomatitis virus (VSV), vesicular stomatitis virus (VSV), vesicular stomatitis virus (VSV), vesicular stomatitis virus (VSV), vesicular stomatitis virus (VSV), parainfluenza virus, fall armyworm rhabdovirus isolate Sf G, Drosophila sigmavirus 10A, Wuhan insect virus 7, perch virus, or carp spring viremia virus. In some embodiments, the VSV protein is a mutant protein, such as those described herein. In some embodiments, the targeting portion attaches to a glycoprotein of a virus belonging to the Filoviridae family (such as Ebola virus) or a virus belonging to the Arenaviridae family (such as Machupo virus).

[0377] In some implementations, the targeting moiety is scFv. In some implementations, the targeting moiety is a single-domain antibody. In some implementations, the targeting moiety is VHH.

[0378] In some implementations, the targeting portion binds to the following: CD7, CD8, cKit (CD117), CD4, CD3...

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 or combinations thereof in SEQ ID NO: 2, 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 or combinations thereof in SEQ ID NO: 2 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 H8, N9, Q10, K47, K50, A51, S179, N180, I182, S183, M184, Y209, I347, T350, T352, E353 or R354 of SEQ ID NO:

2.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

5.

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

3.

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

4.

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

5.

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 combinations thereof comprises a substitution to a charged amino acid selected from the group consisting of 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, the variant comprising a mutation corresponding to a mutation at positions 8, 9, 10, 47, 50, 51, 179, 180, 183, 184, 209, 347, 350, 353, 354 or combinations thereof in SEQ ID NO: 22 or SEQ ID NO:

23.

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

22.

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

23.

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 combinations thereof comprises a substitution to a charged amino acid selected from the group consisting of 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 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, or any combination thereof, compared to 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 viral particle comprising a polypeptide according to any one of claims 1 to 32.

35. The viral particle of claim 36, wherein the viral particle further comprises a targeting portion.

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

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

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

39. The viral particle according to any one of claims 34 to 38, wherein the targeting portion binds to: CD7, CD8, cKit (CD117), CD4, CD3, CD5, CD6, CD2, TCRα, TCRβ, TCRγ, TCRδ, CD10, CD34, CD110, CD33, CD14, CD68, CCR7, CD62L, CD25, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7 or CXCR3, a glycosylated CD43 epitope expressed on acute leukemia or lymphoma but not on hematopoietic progenitor cells, a glycosylated CD43 epitope expressed on non-hematopoietic cancers, kinase-anchored protein 4 (AKAP-4), adrenaline receptor β3 (ADRB3), AFP, anaplastic lymphoma kinase (ALK), androgen receptor, angiopoietin-binding cell surface receptor 2 (TIP). 2) Anti-desmosome 1 (Dsgl) autoantibody, anti-desmosome 3 (Dsg3) autoantibody, B7H3 (CD276), biotin, bone marrow stromal cell antigen 2 (BST2), BST1 / CD157; cancer / testis antigen 1 (NY-ESO-1), cancer / testis antigen 2 (LAGE-la), carbonic anhydrase IX (CAIX), carcinoembryonic antigen (CEA), CCCTC binding factor (zinc finger protein)-like (BORIS or imprinted site regulator sibling factor), CCR4, CD5, CD19, CD20, CD22, CD24, CD30, CD32 (FCG) R2A), CD33, CD34, CD38, CD44v6, CD72, CD79a, CD79b, CD97, CD99, CD123, CD171, CD179a, CD179b-IGLll, CD200R, CD276 / B7H3, CD300 molecular-like family member f (CD300LF), CDH1-CD324, CDH6, CDH17, CDH19, chromosome X open reading frame 61 (CXORF61), sealing protein 6 (CLDN6), sealing protein 18.2 (CLD18A2 or CLDN18A.2), CMV pp65, C-MYC epitope tag, Cripto, CS1 (also known as CD2 subset 1 or CRACC or SLAMF7 or CD319 or 19A24), CSF2RA (GM-CSFR-α), 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 2 containing mucin-like hormone receptor-like receptor (EMR2), Elongation factor 2 mutant (ELF2M), liver glycoside B2, liver glycoside A receptor 2 (EphA2), epidermal growth factor receptor (EGFR), epidermal growth factor receptor variant III (EGFRviii), epidermal cell adhesion molecule (EPCAM), ERG, ETS translocation variant gene 6 located on chromosome 12p (ETV6-AML), Fc fragment of IgA receptor (FCAR or CD89), Fc receptor-like 5 (FCRL5), fibroblast activating protein α (FAP), FITC, Fms-like tyrosine kinase 3 (FLT3), folate receptor α (FRa or FR1), folate receptor β (FRb), follicle-stimulating hormone receptor (FSHR) Fos-related antigen 1, fucose-GM1, G protein-coupled receptor class C5 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(11)Cer), ganglioside GM3 (aNeu5Ac(2-3)bDClalp(1-4)bDGlcp(11)Cer), GD3, GFRα4, glycoprotein 100 (gplOO), phosphatidylinositol proteoglycan-3 (GPC3), gonadotropin receptor (CGHR or GR), GpA33, GpNMB, GPRC5D, guanylate cyclase C (GCC), mutant heat shock protein 70-2 (mut HSP70-2), Hepatitis A Virus Receptor 1 (HAVCR1), the hexasaccharide moiety of globoH glycosylceramide (GloboH), high molecular weight melanoma-associated antigen (HMWMAA), HIV1 envelope glycoprotein, HLA, HLA-DOA, HLA-A, HLA-A2, HLA-B, HLA-C, HLA-DM, HLA-DOB, HLA-DP, HLA-DQ, HLA-DR, HLA-G, HTLV1-Tax, Human Papillomavirus E6 (HPV E6), Human Papillomavirus E7 (HPV E7), Human Telomerase Reverse Transcriptase (hTERT), IgE, IL13Ra2, IL1 lRa, immunoglobulin λ-like polypeptide 1 (IGLL1), influenza A hemagglutinin (HA), insulin-like growth factor 1 receptor (IGF-I receptor), interleukin 11 receptor α (IL-11Ra), interleukin 13 receptor subunit α-2 (IL-13Ra2 or CD213A2), intestinal carboxylesterase, KIT (CD117), KSHVK8.1, KSHV-gH, LAMP1, pod protein, leukocyte immunoglobulin-like receptor subfamily A member 2 (LILRA2), leukocyte-associated immunoglobulin-like receptor 1 (LAIR1), luteinizing hormone receptor (LHR), Lewis (Y) antigen, Lews Ag, Livl, locus K 9 (LY6K), low-conductivity chloride channels, lymphocyte antigen 6 complex, lymphocyte antigen 75 (LY75), lymphocyte-specific protein tyrosine kinase (LCK), breast differentiation antigen (NY-BR-1), T-cell recognized melanoma antigen 1 (MelanA or MARTI), melanoma-associated antigen 1 (MAGE-A1), melanoma cancer testis antigen-1 (MAD-CT-1), melanoma cancer testis antigen-2 (MAD-CT-2), melanoma cell apoptosis inhibitor (ML-IAP), mesothelin, MPL, cell surface-associated mucin 1 (MUC1), N-acetylglucosamine transferase V (NA17), adhesion protein-4, neural cell adhesion molecule (NCAM), NK G2D, NYBR1, o-acetyl-GD2 ganglioside (OAcGD2), olfactory receptor 51E2 (OR51E2), oncogene fusion protein composed of breakpoint cluster region (BCR) and Abelson murine leukemia virus oncogene homolog 1 (Abl) (bcr-abl), P53 mutant, pairing box protein Pax-3 (PAX3), pairing box protein Pax-5 (PAX5), pan-connector protein 3 (PANX3), PDL1, P-glycoprotein, placenta-specific 1 (PLAC1), platelet-derived growth factor receptor β (PDGFR-β), polysialic acid, proapocrine-binding protein sp32 (OY-TES1), prostate enzyme, prostate cancer tumor antigen-1 (PCT) Al or galactohemagglutinin 8), prostate stem cell antigen (PSCA), prostate-specific membrane antigen (PSMA), prostate acid phosphatase (PAP), Prostein, serine protease 21 (Testisin or PRSS21), proteasome macropain subunit βType 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 universal protein 1 (RU1), renal universal protein 2 (RU2), sarcoma translocation breakpoint, serine 2 (TMPRSS2) ETS fusion gene, sialic acid Lewis adhesion molecule (sLe), SLAMF4, SLAMF6, Slea (CA19.9 or sialic acid Lewis antigen), spermin 17 (SPA17), T cell recognized squamous cell carcinoma antigen 3 (SART3), stage-specific embryonic antigen-4 (SSEA-4), STEAP1, survivin, synovial sarcoma X breakpoint 2 (SSX2), TCR γ-substituted reading frame protein (TARP), TCR-β1 chain, TCR-β2 chain, TCR-δ chain, TCR-γ chain, TCRγ-δ, telomerase, TGFβR2, antigen recognized by TNT antibody, thyroid-stimulating hormone receptor (TSHR), Timol / HVCR1, tissue factor 1 (TF1), Tn ag, Tn antigen ((Tn) (Ag) or (GalNAca-Ser / Thr)), TNF receptor family member B cell maturation (BCMA), transglutaminase 5 (TGS5), transmembrane protease, TROP2, tumor endothelial marker 1 (TEM1 / CD248), tumor endothelial marker 7 associated (TEM7R), tumor protein p53 (p53), tumor-associated glycoprotein 72 (TAG72), tyrosinase, tyrosinase-associated protein 2 (TRP-2), urolytic protein 2 (UPK2), vascular endothelial growth factor receptor 2 (VEGFR2), V-myc avian myeloma virus oncogene neuroblastoma-derived homolog (MYCN), Wilms tumor protein (WT1) or X antigen family member 1A (XAGE1).

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

41. The viral particle of claim 40, wherein the targeting portion binding to CD7 comprises a polypeptide, the polypeptide comprising a sequence having at least 90% sequence identity with SEQ ID NO: 52, at least 95% sequence identity with SEQ ID NO: 52, at least 99% sequence identity with SEQ ID NO: 52, or a sequence as shown in SEQ ID NO:

52.

42. The viral particle according to any one of claims 34 to 41, wherein the targeting portion is attached to the viral surface by means of: IgG Fc stem; The envelope glycoprotein G or H of viruses of the Paramyxoviridae family, such as measlesviruses, such as measlesviruses, or Hennipaviruses, such as Nipah virus, cedar virus, or Hendra virus. Glycoproteins of viruses in the Rhabdoviridae family, such as vesicular stomatitis virus (VSDV), vesicular stomatitis virus (VSDV), vesicular stomatitis virus (VSDV), vesicular stomatitis virus (VSDV), vesicular stomatitis virus (VSDV), parainfluenza virus, fall armyworm rhabdovirus isolate Sf G, Drosophila sigmavirus 10A, Wuhan insect virus 7, perch virus, or carp spring viremia virus; Glycoproteins of viruses in the Filoviridae family, such as Ebola virus; or Glycoproteins of viruses in the Arenaviridae family, such as Machupo virus.

43. A method for delivering a heterologous molecule to a target cell, the method comprising contacting the cell with a viral vector, the viral vector comprising: a) The variant VSV-G protein according to any one of claims 1 to 32; b) The targeting portion that binds to the target cells; and c) Nucleic acid molecules that encode the heterologous molecule.

44. A method of delivering a heterologous molecule to target cells in a subject, the method comprising administering a viral vector to the subject, the viral vector comprising: a) The variant VSV-G polypeptide according to any one of claims 1 to 32; b) The targeting portion that binds to the target cells; and c) Nucleic acid molecules that encode the heterologous molecule.

45. The method according to any one of claims 43 to 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 of treating cancer in a subject, the method comprising administering a viral vector to the subject, the viral vector comprising: a) The variant VSV-G polypeptide according to any one of claims 1 to 32; b) The targeting portion that binds to the target cells; and c) Nucleic acid molecules that encode the heterologous molecule.

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

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

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