Pseudotyped virus particles, compositions containing same, and uses thereof

Abstract

Provided herein are mutant VSV-G polypeptides, compositions comprising same, and methods of using same.Also provided herein are polypeptides and compositions that bind CD7, and uses thereof.Also provided herein are polypeptides and compositions that bind CD8, and uses thereof.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Application No. 63 / 289,888, filed December 15, 2021, and U.S. Provisional Application No. 63 / 289,977, filed December 15, 2021, and U.S. Provisional Application No. 63 / 266,044, filed December 27, 2021, and U.S. Provisional Application No. 63 / 267,039, filed January 21, 2022, each of which is incorporated by reference in its entirety.

[0002] Reference to an electronically submitted sequence listing This application contains a Sequence Listing that has been submitted electronically in XML format and is incorporated herein by reference in its entirety. The XML copy was created on November 28, 2022, is named "148165.001402_SL.xml", and is 86.3 kilobytes in size. [Background technology]

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

[0004] G plays an important role in the early stages of viral infection (Molecular and Cellular Aspects of Rhabdovirus Entry. Viruses 4, 117-139.) (This document is incorporated herein by reference in its entirety). First, G is responsible for the attachment of the virus to a specific receptor. After binding, the virion enters the cell via the clathrin-mediated endocytosis pathway. In the acidic environment of the endocytic vesicle, G triggers the fusion of the viral membrane with the endosomal membrane, which releases the genome into the cytoplasm for the subsequent infection step. Fusion is catalyzed by a low-pH-induced large structural transition from a pre-fusion conformation to a post-fusion conformation, both of which are trimeric (Roche, S., Bressanelli, S., Rey, FA, and Gaudin, Y. (2006). Crystal structure of the low-pH form of the vesicular stomatitis virus glycoprotein G. Science 313, 187-191. Roche, S., Rey, FA, Gaudin, Y., and Bressanelli, S. (2007). Structure of the prefusion form of the vesicular stomatitis virus glycoprotein g. Science 315, 843-848), each of which is incorporated herein by reference in its entirety.

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

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

[0007] The human CD7 molecule is a cell surface glycoprotein belonging to the immunoglobulin superfamily and having a molecular weight of approximately 40 kDa. CD7 molecules are primarily expressed on the surface of most thymocytes, more than 85% of peripheral blood T lymphocytes, and natural killer cells. Embodiments disclosed herein provide polypeptides and antibodies against CD7, compositions comprising them, and uses thereof.

[0008] CD8 (cluster of differentiation 8) is a transmembrane glycoprotein that is a specific marker for subclasses of T cells (including cytotoxic T cells). Without wishing to be bound by theory, CD8 assembles as either a heterodimer of CD8 alpha and CD8 beta subunits or a CD8 alpha homodimer. The assembled dimeric CD8 complex functions as a coreceptor with the T cell receptor (TCR) to recognize antigens presented 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 an immune response and can occur over time. Embodiments disclosed herein provide polypeptides and antibodies against CD8, compositions comprising them, and uses thereof. Summary of the Invention

[0009] In some embodiments, a VSV-G polypeptide is provided. In some embodiments, the VSV-G polypeptide comprises a mutation at position 182 of SEQ ID NO:2. In some embodiments, the polypeptide comprises an I182E or I182D mutation compared to SEQ ID NO:2. In some embodiments, the VSV-G polypeptide comprises the sequence of SEQ ID NO:4. In some embodiments, the VSV-G polypeptide comprises the sequence of SEQ ID NO:5.

[0010] The VSV-G polypeptide further comprises a mutation in the VSV-G protein corresponding to positions 8, 10, 47, 209, and / or 354 compared to SEQ ID NO:2. In some embodiments, the VSV-G polypeptide comprises an H8A and / or K47Q substitution. In some embodiments, the VSV-G polypeptide comprises a substitution at position 10 compared to SEQ ID NO:2. In some embodiments, the substitution at position 10 is Q10A, Q10R, or Q10K.

[0011] In some embodiments, a VSV-G polypeptide is provided. In some embodiments, the VSV-G polypeptide comprises a substitution at position I182 and at least one of T214 and T352 of SEQ ID NO:2. In some embodiments, the VSV-G polypeptide comprises a substitution at positions I182, T214, and T352 of SEQ ID NO:2. In some embodiments, the VSV-G polypeptide comprises the sequence of SEQ ID NO:22. In some embodiments, the VSV-G polypeptide comprises the sequence of SEQ ID NO:23. In some embodiments, the VSV-G polypeptide comprises the sequence of SEQ ID NO:24. In some embodiments, the VSV-G polypeptide comprises the sequence of SEQ ID NO:25.

[0012] In some embodiments, a nucleic acid molecule is provided. In some embodiments, the nucleic acid molecule encodes a VSV-G polypeptide provided herein.

[0013] In some embodiments, a vector is provided that includes a nucleic acid molecule provided herein.

[0014] In some embodiments, a plasmid is provided that comprises a nucleic acid molecule provided herein.

[0015] In some embodiments, a viral particle is provided. In some embodiments, the viral particle comprises a VSV-G polypeptide provided herein. In some embodiments, the viral particle further comprises a targeting moiety. In some embodiments, the viral particle further comprises a nucleic acid molecule encoding a heterologous molecule of interest.

[0016] In some embodiments, a method for delivering a heterologous molecule of interest to a target cell is provided. In some embodiments, the method comprises contacting the cell with a viral vector comprising the VSV-G protein provided herein, a targeting moiety that binds to the target cell, and a nucleic acid molecule encoding the heterologous molecule of interest. In some embodiments, the heterologous molecule of interest is a chimeric antigen receptor.

[0017] In some embodiments, a method for delivering a heterologous molecule of interest to a target cell in a subject is provided. In some embodiments, the method comprises contacting the cell with a viral vector comprising the VSV-G protein provided herein, a targeting moiety that binds to the target cell, and a nucleic acid molecule encoding the heterologous molecule of interest. In some embodiments, the heterologous molecule of interest is a chimeric antigen receptor.

[0018] In some embodiments, a method for treating cancer in a subject is provided. In some embodiments, the method comprises contacting a cell with a viral vector comprising the VSV-G protein provided herein, a targeting moiety that binds to a target cell, and a nucleic acid molecule encoding a heterologous molecule of interest. In some embodiments, the heterologous molecule of interest is a chimeric antigen receptor.

[0019] In some embodiments, the targeting moiety of the viral particle binds to CD7. In some embodiments, the targeting moiety comprises a polypeptide comprising a heavy chain CDR1 having the amino acid sequence of SEQ ID NO: 35, a heavy chain CDR2 having the amino acid sequence of SEQ ID NO: 36, a heavy chain CDR3 having the amino acid sequence of SEQ ID NO: 37, a light chain CDR1 having the amino acid sequence of SEQ ID NO: 38, a light chain CDR2 having the amino acid sequence of SEQ ID NO: 39, and a light chain CDR3 having the amino acid sequence of SEQ ID NO: 40. In some embodiments, the targeting moiety comprises a polypeptide comprising a heavy chain variable region having the amino acid sequence of SEQ ID NO: 47 and a light chain variable region having the amino acid sequence of SEQ ID NO: 48.

[0020] A targeting moiety that binds CD7 comprises a sequence having at least 90% sequence identity to SEQ ID NO: 51, at least 95% sequence identity to SEQ ID NO: 51, at least 99% sequence identity to SEQ ID NO: 51, or a polypeptide comprising the sequence set forth in SEQ ID NO: 51. In some embodiments, a targeting moiety that binds CD7 comprises a polypeptide comprising the sequence of SEQ ID NO: 51.

[0021] A targeting moiety that binds CD7 comprises a sequence having at least 90% sequence identity to SEQ ID NO: 52, at least 95% sequence identity to SEQ ID NO: 52, at least 99% sequence identity to SEQ ID NO: 52, or a polypeptide comprising the sequence set forth in SEQ ID NO: 52. In some embodiments, a targeting moiety that binds CD7 comprises a polypeptide comprising the sequence of SEQ ID NO: 52.

[0022] In some embodiments, the targeting moiety of the viral particle binds to CD8. In some embodiments, the targeting moiety comprises a polypeptide comprising a heavy chain CDR1 having the amino acid sequence of SEQ ID NO: 55, a heavy chain CDR2 having the amino acid sequence of SEQ ID NO: 56, a heavy chain CDR3 having the amino acid sequence of SEQ ID NO: 57, a light chain CDR1 having the amino acid sequence of SEQ ID NO: 58, a light chain CDR2 having the amino acid sequence of SEQ ID NO: 59, and a light chain CDR3 having the amino acid sequence of SEQ ID NO: 60. In some embodiments, the targeting moiety comprises a polypeptide comprising a heavy chain variable region having the amino acid sequence of SEQ ID NO: 67 and a light chain variable region having the amino acid sequence of SEQ ID NO: 68.

[0023] A targeting moiety that binds CD8 comprises a sequence having at least 90% sequence identity to SEQ ID NO: 69, at least 95% sequence identity to SEQ ID NO: 69, at least 99% sequence identity to SEQ ID NO: 69, or a polypeptide comprising the sequence set forth in SEQ ID NO: 69. In some embodiments, a targeting moiety that binds CD7 comprises a polypeptide comprising the sequence of SEQ ID NO: 69.

[0024] A targeting moiety that binds CD7 comprises a sequence having at least 90% sequence identity to SEQ ID NO: 70, at least 95% sequence identity to SEQ ID NO: 70, at least 99% sequence identity to SEQ ID NO: 70, or a polypeptide comprising the sequence set forth in SEQ ID NO: 70. In some embodiments, a targeting moiety that binds CD7 comprises a polypeptide comprising the sequence of SEQ ID NO: 70.

[0025] In some embodiments, a method for delivering a heterologous molecule of interest to a target cell is provided. In some embodiments, the method comprises contacting a cell with a viral vector comprising a VSV-G protein provided herein, a targeting moiety provided herein that binds to the target cell, and a nucleic acid molecule encoding the heterologous molecule of interest. In some embodiments, the targeting moiety binds to CD7. In some embodiments, the targeting moiety binds to CB8. In some embodiments, the heterologous molecule of interest is a chimeric antigen receptor.

[0026] In some embodiments, a method for delivering a heterologous molecule of interest to a target cell in a subject is provided. In some embodiments, the method comprises contacting the cell with a viral vector comprising a VSV-G protein provided herein, a targeting moiety provided herein that binds to the target cell, and a nucleic acid molecule encoding the heterologous molecule of interest. In some embodiments, the targeting moiety binds to CD7. In some embodiments, the targeting moiety binds to CB8. In some embodiments, the heterologous molecule of interest is a chimeric antigen receptor.

[0027] In some embodiments, methods for treating cancer in a subject are provided. In some embodiments, the methods include contacting a cell with a viral vector comprising a VSV-G protein provided herein, a targeting moiety provided herein that binds to a target cell, and a nucleic acid molecule encoding a heterologous molecule of interest. In some embodiments, the targeting moiety binds to CD7. In some embodiments, the targeting moiety binds to CB8. In some embodiments, the heterologous molecule of interest is a chimeric antigen receptor. [Brief explanation of the drawings]

[0028] [Figure 1A] Crystal structure of VSV-G bound to LDL-R. Crystal structure of VSV-G bound to CR3 of LDL-R. [Figure 1B]Crystal structure of VSV-G bound to LDL-R. Crystal structure of VSV-G bound to CR2 of LDL-R. [Figure 2A] Figure 1 shows the effect of adding negatively charged amino acids to the VSV-G:LDL-R binding interface on native tropism and fusogenicity. Figure 2 shows titration of VSV-G constructs on SupT1 cells. [Figure 2B] Figure 2B shows the effect of adding negatively charged amino acids to the VSV-G:LDL-R binding interface on native tropism and fusogenicity. Figure 2C shows the functional titer of each construct calculated from the titrations in Figure 2A. [Figure 3] 1 shows an alignment of the ectodomains of different VSV-G proteins from different strains. [Figure 4] 1 shows the effect of various VSV-G mutations on the serum stability of viral constructs in combination with CD7 binders. [Figure 5] 1 shows the effect of various VSV-G mutations on the serum stability of viral constructs in combination with CD7 binders. [Figure 6A] 1 shows flow cytometry data of human PBMCs transduced with exemplary vectors comprising the CD7 binders disclosed herein. [Figure 6B] 1 shows flow cytometry data of human PBMCs transduced with exemplary vectors comprising the CD7 binders disclosed herein. [Figure 6C] 1 shows flow cytometry data of human PBMCs transduced with exemplary vectors comprising the CD7 binders disclosed herein. [Figure 6D] 1 shows flow cytometry data of human PBMCs transduced with exemplary vectors comprising the CD7 binders disclosed herein. [Figure 6E] 1 shows flow cytometry data of human PBMCs transduced with exemplary vectors comprising the CD7 binders disclosed herein. [Figure 6F] 1 shows flow cytometry data of human PBMCs transduced with exemplary vectors comprising the CD7 binders disclosed herein. [Figure 6G] 1 shows flow cytometry data of human PBMCs transduced with exemplary vectors comprising the CD7 binders disclosed herein. [Figure 6H] 1 shows flow cytometry data of human PBMCs transduced with exemplary vectors comprising the CD7 binders disclosed herein. [Figure 6I] 1 shows flow cytometry data of human PBMCs transduced with exemplary vectors comprising the CD7 binders disclosed herein. [Figure 6J] 1 shows flow cytometry data of human PBMCs transduced with exemplary vectors comprising the CD7 binders disclosed herein. [Figure 6K] 1 shows flow cytometry data of human PBMCs transduced with exemplary vectors comprising the CD7 binders disclosed herein. [Figure 6L] 1 shows flow cytometry data of human PBMCs transduced with exemplary vectors comprising the CD7 binders disclosed herein. [Figure 6M] 1 shows flow cytometry data of human PBMCs transduced with exemplary vectors comprising the CD7 binders disclosed herein. [Figure 7A] 1 shows flow cytometry data of non-human primate PBMCs transduced with exemplary vectors comprising the CD7 binders disclosed herein. [Figure 7B] 1 shows flow cytometry data of non-human primate PBMCs transduced with exemplary vectors comprising the CD7 binders disclosed herein. [Figure 7C] 1 shows flow cytometry data of non-human primate PBMCs transduced with exemplary vectors comprising the CD7 binders disclosed herein. [Figure 7D] 1 shows flow cytometry data of non-human primate PBMCs transduced with exemplary vectors comprising the CD7 binders disclosed herein. [Figure 7E]1 shows flow cytometry data of non-human primate PBMCs transduced with exemplary vectors comprising the CD7 binders disclosed herein. [Figure 7F] 1 shows flow cytometry data of non-human primate PBMCs transduced with exemplary vectors comprising the CD7 binders disclosed herein. [Figure 7G] 1 shows flow cytometry data of non-human primate PBMCs transduced with exemplary vectors comprising the CD7 binders disclosed herein. [Figure 7H] 1 shows flow cytometry data of non-human primate PBMCs transduced with exemplary vectors comprising the CD7 binders disclosed herein. [Figure 7I] 1 shows flow cytometry data of non-human primate PBMCs transduced with exemplary vectors comprising the CD7 binders disclosed herein. [Figure 7J] 1 shows flow cytometry data of non-human primate PBMCs transduced with exemplary vectors comprising the CD7 binders disclosed herein. [Figure 7K] 1 shows flow cytometry data of non-human primate PBMCs transduced with exemplary vectors comprising the CD7 binders disclosed herein. [Figure 7L] 1 shows flow cytometry data of non-human primate PBMCs transduced with exemplary vectors comprising the CD7 binders disclosed herein. [Figure 7M] 1 shows flow cytometry data of non-human primate PBMCs transduced with exemplary vectors comprising the CD7 binders disclosed herein. [Figure 8A] 1 shows flow cytometry data of human PBMCs transduced with exemplary vectors comprising the CD8 binders disclosed herein. [Figure 8B] 1 shows flow cytometry data of non-human primate PBMCs transduced with exemplary vectors comprising the CD8 binders disclosed herein. [Figure 9]1 shows GFP or CAR transduction of SupT1 cells using VSV-G pseudotyped lentiviral particles carrying CD7 or CD8 binders provided herein. A shows GFP transduction. B shows CAR transduction. [Figure 10] A shows the ability of VSV-G* pseudotyped lentiviral particles carrying a CD7 binder to transduce SupT1 cells as well as human and non-human primate PBMCs. B shows the transduction of cells in the absence of a CD7 binder. C shows the transduction of human and non-human primate PBMCs in terms of the MOI calculated from SupT1 titration. VSV-G* indicates a VSV-G polypeptide containing I182E, T214N, T352A, which corresponds to the mature polypeptide of SEQ ID NO: 23 or SEQ ID NO: 25 (with I196E, T230N, and T368A mutations (with leader sequence and numbering adjusted)). [Figure 11] Figure 1 shows off-target transduction of VSV-G* pseudotyped lentiviral particles carrying CD7 binders in a panel of B cell lines compared to control SupT1 cells. A shows data for GFP transduction. B shows data for CAR20-T2A-GFP transduction. VSV-G* represents a VSV-G polypeptide containing the I182E, T214N, and T352A mutations provided herein. [Figure 12] Figure 1 shows the ability of VSV-G* pseudotyped lentiviral particles utilizing a CD7 binder and a CD20-CAR transgene provided herein to kill Duadi lymphoma cells (A) or Raji lymphoma cells (B). The CAR20 construct utilized an antigen-binding domain comprising rituximab or CD20AB1 SEQ ID NO: 75 or 76, as provided herein. [Figure 13] Figure 1 shows the ability of VSV-G* pseudotyped lentiviral particles utilizing the CD7 binder and CD20-CAR transgene provided herein to deplete B cells in vivo in huCD34 NSG mice. B cells were detected by assessment of CD20 (A) or CD19 (B). [Figure 14A]1 shows the ability of VSV-G* pseudotyped lentiviral particles utilizing the CD7 binder and CD20-CAR transgene provided herein to prevent tumor formation in vivo. Illustrates the experimental design. [Figure 14B] Figure 1 shows the ability of VSV-G* pseudotyped lentiviral particles utilizing the CD7 binder and CD20-CAR transgene provided herein to prevent tumor formation in vivo. Figure 1 shows that mice receiving lentiviral particles provided herein via iv prior to Raji tumor injection had significantly lower tumor burden than mice receiving a control (GFP) vector or untreated mice. Tumor burden measured by IVIS imaging. [Figure 15A] 1 illustrates the ability of VSV-G* pseudotyped lentiviral particles utilizing the CD7 binder and CD20-CAR transgene provided herein to eliminate established Raji tumors in vivo. [Figure 15B] Figure 1 illustrates the ability of VSV-G* pseudotyped lentiviral particles utilizing the CD7 binder and CD20-CAR transgene provided herein to eliminate established Raji tumors in vivo. Mice receiving iv lentiviral particles provided herein 6 days after Raji tumor injection exhibited a reduction in tumor burden below the limit of detection. Tumor burden measured by IVIS imaging. DETAILED DESCRIPTION OF THE INVENTION

[0029] Provided herein are mutant VSV-G proteins that can be used to pseudotype 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 Alagoas virus strain, vesicular stomatitis Maraba virus strain, or vesicular stomatitis Carajas virus strain.

[0030] Pseudotyped viruses containing mutant VSV-G proteins can be used in conjunction with targeting moieties to promote fusion of the pseudotyped virus with specific cells or tissues based on the expression of the target on the cells or tissues.

[0031] 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 belong.

[0032] As used herein, the terms "a" or "an" mean "at least one" or "one or more," unless the context clearly indicates otherwise.

[0033] As used herein, the term "about" means that a numerical value is approximate and that small variations would not significantly affect the practice of the disclosed embodiments. When numerical limitations are used, unless the context dictates otherwise, "about" means that the numerical value can vary by ±10% and remain within the scope of the disclosed embodiments. Furthermore, when the phrase "about x to y" is provided, the term "about" modifies both x and y and can be used interchangeably with the phrase "about x to about y" unless the context dictates otherwise.

[0034] "Activated," as used herein with respect to T cells, refers to a state of T cells that has been stimulated sufficiently to induce detectable cell proliferation. Activation may also be associated with induced cytokine production and detectable effector function. The term "activated T cells" refers, inter alia, to T cells that are undergoing cell division.

[0035] As used herein, "alleviating" a disease means reducing the severity of one or more symptoms of the disease.

[0036] The term "antigen," as used herein, is defined as a molecule that elicits an immune response. This immune response may involve either antibody production, or activation of cells with specific immunological capabilities, or both. Those skilled in the art will understand that virtually any macromolecule, including any protein or peptide, can function as an antigen. The term "antigen" can also refer to a molecule that can be bound by or recognized by an antibody or antibody-like molecule.

[0037] The terms "antibody molecule," "antibody," or antigen-binding domain, as the terms are used herein, refer to a polypeptide, e.g., an immunoglobulin chain or fragment thereof, that comprises at least one functional immunoglobulin variable domain sequence. Antibody molecules include antibodies (e.g., full-length antibodies) and antibody fragments. In some embodiments, an antibody molecule comprises an antigen-binding or functional fragment of a full-length antibody or a full-length immunoglobulin chain. For example, a full-length antibody is an immunoglobulin (Ig) molecule (e.g., an IgG antibody) that occurs naturally or is formed by normal immunoglobulin gene fragment recombination processes. In embodiments, an antibody molecule refers to an immunologically active antigen-binding portion of an immunoglobulin molecule, such as an antibody fragment. Antibody fragments, e.g., functional fragments, include portions of an antibody, e.g., Fab, Fab', F(ab'), F(ab), variable fragment (Fv), domain antibody (dAb), or single-chain variable fragment (scFv). Functional antibody fragments bind to the same antigen recognized by an intact (e.g., full-length) antibody. The term "antibody fragment" or "functional fragment" also includes isolated fragments consisting of the variable regions, such as an "Fv" fragment consisting of the variable regions of the heavy and light chains, or a recombinant single-chain polypeptide molecule in which the variable regions of the light and heavy chains are connected by a peptide linker (an "scFv protein"). In some embodiments, an antibody fragment does not include a portion of an antibody that does not have antigen-binding activity, such as an Fc fragment or a single amino acid residue. Exemplary antibody molecules include full-length antibodies and antibody fragments, such as dAb (domain antibodies), single chain, Fab, Fab', and F(ab')2 fragments, and single-chain variable fragments (scFv).

[0038] The term "antibody molecule" also encompasses whole or antigen-binding fragments of domain or single-domain antibodies, which may also be referred to as "sdAb" or "VHH." Domain antibodies contain either VH or VL, which can function as independent antibody fragments. Furthermore, domain antibodies include heavy chain-only antibodies (HCAb). Domain antibodies also contain the CH2 domain of IgG as the basic scaffold onto which CDR loops are grafted. They can also be generally defined as polypeptides or proteins comprising an amino acid sequence consisting of four framework regions interrupted by three complementarity-determining regions, represented as FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4. sdAbs can be produced in camelids, such as llamas, but can also be produced synthetically using techniques well known in the art. The numbering of amino acid residues in an sdAb or polypeptide follows the general numbering of VH domains set forth by Kabat et al. ("Sequence of proteins of immunological interest," U.S. Public Health Services, NIH, Bethesda, MD, Publication No. 91, incorporated herein by reference). According to this numbering, FR1 of an sdAb comprises amino acid residues 1-30, CDR1 of an sdAb comprises amino acid residues 31-36, FR2 of an sdAb comprises amino acid residues 36-49, CDR2 of an sdAb comprises amino acid residues 50-65, FR3 of an sdAb comprises amino acid residues 66-94, CDR3 of an sdAb comprises amino acid residues 95-102, and FR4 of an sdAb comprises amino acid residues 103-113. Domain antibodies are also described in WO2004041862 and WO2016065323, each of which is incorporated herein by reference. Domain antibodies can be targeting moieties as described herein.

[0039] As used herein, unless otherwise indicated, "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 the antigen bound by the full-length antibody, e.g., a fragment that retains one or more CDR regions. Examples of antibody-binding fragments include, but are not limited to, Fab, Fab', F(ab'), and Fv fragments, diabodies, linear antibodies, single-chain antibody molecules (e.g., sc-Fv), nanobodies (single-domain antibodies), and multispecific antibodies formed from antibody fragments.

[0040] A "Fab fragment" is a fragment of one light chain and one heavy chain. H 1 and variable regions. The heavy chain of a Fab molecule cannot form disulfide bonds with another heavy chain molecule.

[0041] The "Fc" region is the C H 2 and C H The two heavy chain fragments contain two heavy chain fragments each containing a C3 domain. The two heavy chain fragments are held together by two or more disulfide bonds and by C H The three domains are held together by hydrophobic interactions.

[0042] A "Fab' fragment" is a fragment that contains one light chain, V, such that an interchain disulfide bond can form between the two heavy chains of two Fab' fragments to form an F(ab')2 molecule. H Domain and C H 1 domain, and C H 1 Domain and C H It contains a portion or fragment of one heavy chain containing the region between the two domains.

[0043] "F(ab')2 fragment" contains two light chains and two heavy chains, and the heavy chains contain a portion of the constant region of C such that an interchain disulfide bond is formed between the two heavy chains. H 1 and C H The F(ab')2 fragment is thus composed of two Fab' fragments held together by disulfide bonds between the two heavy chains.

[0044] The "Fv region" comprises the variable regions from both the heavy and light chains, but lacks the constant regions.

[0045] The term "single-chain Fv" or "scFv" antibody refers to the V of an antibody. H and V L Fv refers to an antibody fragment containing V domains, these domains being present in a single polypeptide chain. Generally, an Fv polypeptide contains V domains that enable the scFv to form the desired structure for antigen binding. H Domains and V L The scFv domains further comprise a polypeptide linker between them. For a review of scFvs, see Pluckthun (1994) THE PHARMACOLOGY OF MONOCLONAL ANTIBODIES, vol. 113, Rosenburg and Moore eds. Springer-Verlag, New York, pp. 269-315. See also International Patent Application Publication No. WO 88 / 01649 and U.S. Patent Nos. 4,946,778 and 5,260,203.

[0046] 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 order of specificity (e.g., tetravalent) and / or a higher order of valency than hexavalent. An antibody molecule can comprise a functional fragment of a light chain variable region and a functional fragment of a heavy chain variable region, or the heavy and light chains can be fused into a single polypeptide.

[0047] Furthermore, antigens can be derived from recombinant DNA or genomic DNA. Those skilled in the art will understand that, as the term "antigen" is used herein, any DNA containing a nucleotide sequence or a partial nucleotide sequence that encodes a protein that elicits an immune response therefore encodes an "antigen." Furthermore, those skilled in the art will understand that an antigen need not be encoded solely by the full-length nucleotide sequence of a gene. Furthermore, those skilled in the art will understand that an antigen need not be encoded by a "gene" at all. It is readily apparent that antigens can be synthetically produced or derived from biological samples. Such biological samples can include, but are not limited to, tissue samples, tumor samples, cells, or biological fluids.

[0048] In certain embodiments, the monoclonal antibodies herein also include camelized single domain antibodies. See, e.g., Muyldermans et al. (2001) Trends Biochem. Sci. 26:230; Reichmann et al. (1999) J. Immunol. Methods 231:25; WO94 / 04678; WO94 / 25591; U.S. Patent No. 6,005,079. In one embodiment, the present invention provides a method for the synthesis of camelized single domain antibodies by combining two V-domain antibodies with modifications such that single domain antibodies are formed. H A single domain antibody comprising the domain is provided.

[0049] As used herein, the term "diabody" refers to a small antibody fragment with two antigen-binding sites, which fragments are bound to the same polypeptide chain (V H -V L or V L -V H ) in the light chain variable domain (V L ) connected to the heavy chain variable domain (V H). By using a linker that is too short to allow pairing between the two domains on the same chain, the domains can be paired with the complementary domains of another chain and create two antigen-binding sites. Diabodies are described more fully in, for example, EP 404,097, WO 93 / 11161, and Holliger et al. (1993) Proc. Natl. Acad. Sci. USA 90:6444-6448. For a review of engineered antibody variants generally, see Holliger and Hudson (2005) Nat. Biotechnol. 23:1126-1136.

[0050] "Isolated antibody" refers to the purified state of the binding compound, and in that context means that the molecule is substantially free of other biological molecules, such as nucleic acids, proteins, lipids, carbohydrates, or other materials such as cellular debris and growth medium. In general, the term "isolated" is not intended to refer to the complete absence of such materials, or the absence of water, buffers, or salts, except when present in amounts that would substantially interfere with experimental or therapeutic uses of the binding compounds described herein.

[0051] As used herein, the term "monoclonal antibody" refers to a population of substantially homogeneous antibodies, i.e., the antibody molecules comprising the population are identical in amino acid sequence except for possible naturally occurring mutations and / or post-translational modifications that may be present in minor amounts. In contrast, conventional (polyclonal) antibody preparations typically contain a large number of different antibodies having different amino acid sequences in their variable domains, particularly their CDRs, which are often specific for different epitopes. The modifier "monoclonal" indicates the character of the antibody as being obtained from a substantially homogeneous antibody population and is not to be construed as requiring production of the antibody by any particular method. For example, monoclonal antibodies to be used in accordance with the present invention may be produced by the hybridoma method first described by Kohler et al. (1975) Nature 256:495, or may be produced by recombinant DNA methods (see, e.g., U.S. Pat. No. 4,816,567). "Monoclonal antibodies" may be isolated from phage antibody libraries using, for example, the techniques 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.

[0052] As used herein, the term "humanized antibody" refers to forms of antibodies that contain sequences derived from both human and non-human (e.g., mouse, rat) antibodies. Generally, humanized antibodies will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the hypervariable loops correspond to those of a non-human immunoglobulin and all or substantially all of the framework (FR) regions are those of a human immunoglobulin. Optionally, the humanized antibody may also comprise at least a portion of a human immunoglobulin constant region (Fc).

[0053] The term "fully human antibody" refers to an antibody that comprises only human immunoglobulin protein sequences. A fully human antibody may contain mouse carbohydrate chains if produced in a mouse, in a mouse cell, or in a hybridoma derived from a mouse cell. Similarly, a "mouse antibody" refers to an antibody that comprises only mouse immunoglobulin sequences. Alternatively, a fully human antibody may contain rat carbohydrate chains if produced in a rat, in a rat cell, or in a hybridoma derived from a rat cell. Similarly, a "rat antibody" refers to an antibody that comprises only rat immunoglobulin sequences.

[0054] In some embodiments, the basic antibody structural unit comprises a tetramer. Each tetramer comprises two identical pairs of polypeptide chains, each pair having one "light" chain (approximately 25 kDa) and one "heavy" chain (approximately 50-70 kDa). The amino-terminal portion of each chain contains a variable region of approximately 100-110 amino acids in length primarily responsible for antigen recognition. The carboxy-terminal portion of the heavy chain may define a constant region primarily responsible for effector function. Human light chains are typically classified as kappa and lambda light chains. Human heavy chains are further typically classified as mu, delta, gamma, alpha, or epsilon, and antibody isotypes are defined as IgM, IgD, IgG, IgA, and IgE, respectively. Within the light and heavy chains, the variable and constant regions are joined by a "J" region of approximately 12 or more amino acids, and the heavy chain also contains a "D" region of approximately 10 or more amino acids. See generally, Fundamental Immunology Ch. 7 (Paul, W., ed., 2nd ed. Raven Press, NY (1989)).

[0055] The variable regions of each light / heavy chain pair form the antibody binding site. Thus, an intact antibody generally has two binding sites. However, in bifunctional or bispecific antibodies, the two binding sites are generally not the same.

[0056] Typically, both heavy and light chain variable domains contain three hypervariable regions (also called complementarity-determining regions (CDRs)) located within relatively conserved framework regions (FRs). The CDRs are usually aligned by the framework regions, enabling binding to a specific epitope. Generally, from N- to C-terminus, both light and heavy chain variable domains contain FR1, CDR1, FR2, CDR2, FR3, CDR3, and FR4. The assignment of amino acids to each domain is generally based on the information in Sequences of Proteins of Immunological Interest, Kabat, et al.; National Institutes of Health, Bethesda, Md.; 5 th ed.; NIH Publ. No. 91-3242 (1991), Kabat (1978), Adv. Prot. Chem. 32:1-75, Kabat, et al., (1977) J. Biol. Chem. 252:6609-6616, Chothia, et al., (1987) J Mol. Biol. 196:901-917 or Chothia, et al., (1989) Nature 342:878-883.

[0057] As used herein, the term "hypervariable region" refers to the amino acid residues of an antibody that are responsible for antigen binding. The hypervariable region comprises amino acid residues from the "complementarity-determining regions" or "CDRs" (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; see Kabat et al. (1991) Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md.), and / or residues from the "hypervariable loops" (i.e., residues 26-32 (CDRL1), 50-52 (CDRL2), and 91-96 (CDRL3) in the light chain variable domain, and 26-32 (CDRH1), 53-55 (CDRH2), and 96-101 (CDRH3) in the heavy chain variable domain; Chothia and Lesk (1987) J. Mol. Biol. 196:901-917). CDRs may also be referred to according to the IMGT system for identifying CDRs, as described in Lefranc MP. Unique database numbering system for immunogenetic analysis. Immunol Today (1997) 18:509. As used herein, the term "framework" or "FR" residues refers to variable domain residues other than the hypervariable region residues defined herein as CDR residues. CDRs provide the majority of contact residues for antibody binding to antigen or epitope. CDRs of interest can be derived from the variable heavy and light chain sequences of a donor antibody, and include analogs of naturally occurring CDRs, which analogs also share or retain the same antigen-binding specificity and / or neutralizing ability as the donor antibody from which they are derived.

[0058] As used herein, "specific binding" or "immunospecific binding" or "immunospecifically binds" refers to an antibody that binds to a given antigen with much higher affinity than another antigen(s). In some embodiments, the antibody binds to a given antigen with much higher affinity than another antigen(s). -7 The dissociation constant (K D ) binds a given antigen, and such K D is its K for binding to a nonspecific antigen (e.g., BSA, casein, or another nonspecific polypeptide). D is at least two times smaller than

[0059] Methods for determining mAb specificity and affinity by competitive inhibition can be found in Harlow, et al., Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, 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 entireties).

[0060] As used herein, the terms "individual" or "subject" or "patient" are used interchangeably and refer to any animal, including mammals such as mice, rats, other rodents, rabbits, dogs, cats, pigs, cows, sheep, horses, or primates, such as humans. In some embodiments, the subject is a human. A subject "in need thereof" refers to a subject who has been identified as needing treatment for the condition being treated and who is treated with the specific intent of treating such condition. The condition may be, for example, any of the conditions described herein.

[0061] As used herein, the terms "comprising" (and any form of "comprising," such as "comprise," "comprises," and "comprised"), "having" (and any form of "have," such as "have" and "has"), "including" (and any form of "including," such as "includes" and "include"), or "containing" (and any form of "containing," such as "contains" and "contain") are inclusive or open-ended and do not exclude additional, unrecited elements or method steps. Any step or composition using the transitional phrase "comprise" or "comprising" can also be said to describe the same using the transitional phrase "consisting of" or "consists."

[0062] As used herein, the term "contacting" refers to the joining of two elements in an in vitro system or an in vivo system. For example, "contacting" a virus or vector described herein with an individual or patient or cell includes administering the virus to an individual or patient, such as a human, as well as introducing a compound into a sample containing, for example, a cell preparation or purified preparation containing the cell.

[0063] As used herein, the terms "fused" or "linked," when used in reference to proteins having different domains or heterologous sequences, mean that the protein domains are part of the same peptide chain, linked to each other either by peptide bonds or other covalent bonds. The domains or segments can be directly linked or fused to each other, or another domain or peptide sequence can be between the two domains or sequences, and such sequences would 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 a linker sequence, e.g., a glycine / serine sequence described herein, links the two domains together.

[0064] A "disease" is a state of health in an animal in which the animal is unable to maintain homeostasis and in which the animal's health continues to deteriorate if the disease is not ameliorated. In contrast, a "disorder" in an animal is a state of health in which the animal is able to maintain homeostasis, but the animal's health is not better than it would be in the absence of the disorder. If left untreated, a disorder does not necessarily cause a further decline in the animal's health.

[0065] "Effective amount" or "therapeutically effective amount," as used interchangeably herein, refer to an amount of a compound, formulation, material, or composition described herein that is effective to achieve a particular biological result or provide a therapeutic or prophylactic benefit. Such results may include, but are not limited to, an amount that, when administered to a mammal, causes a detectable level of immune cell activation compared to immune cell activation detected in the absence of the composition. Immune responses can be readily assessed by numerous art-recognized methods. One of skill in the art will understand that the amount of a composition administered herein will vary and can be readily determined based on several factors, such as the disease or condition being treated, the age, health, and physical condition of the mammal being treated, the severity of the disease, and the particular compound being administered.

[0066] "Encoding" refers to the inherent property of a particular sequence of nucleotides in a polynucleotide, such as a gene, cDNA, or mRNA, to serve as a template for the synthesis of other polymers and macromolecules in biological processes having either a defined sequence of nucleotides (i.e., rRNA, tRNA, and mRNA) or a defined sequence of amino acids, and biological properties derived therefrom. Thus, a gene encodes a protein when transcription and translation of the mRNA corresponding to that gene produces the protein in a cell or other biological system. Both the coding strand, whose nucleotide sequence is identical to the mRNA sequence and is usually provided in a sequence listing, and the non-coding strand, which is used as a template for transcription of the gene or cDNA, can be said to encode the protein or other product of that gene or cDNA.

[0067] An "expression vector" refers to a vector containing a recombinant polynucleotide comprising expression control sequences operably linked to a nucleotide sequence to be expressed. An expression vector contains sufficient cis-acting elements for expression; other elements for expression can be supplied by the host cell or in an in vitro expression system. Expression vectors include all those known in the art, such as cosmids, plasmids (e.g., naked or contained in liposomes), and viruses (e.g., Sendai virus, lentivirus, retrovirus, adenovirus, and adeno-associated virus) that incorporate the recombinant polynucleotide.

[0068] As used herein, the term "ex vivo" with respect to cells that are transduced, transfected, or transformed ex vivo refers to cells that are transduced, transfected, or transformed outside of a subject, i.e., cells that are removed from a subject before such cells are transduced, transfected, or transformed.

[0069] As used herein, "identity" refers to the subunit sequence identity between two polymers, such as between two nucleic acid or amino acid molecules, for example, between two polynucleotide or polypeptide molecules. If two amino acid sequences have the same residue at the same position, for example, if each position in two polypeptide molecules is occupied by arginine, they are identical at that position. The identity or degree to which two amino acid or two nucleic acid sequences have the same residue at the same position in an alignment is often expressed as a percentage. The identity between two amino acid or two nucleic acid sequences is a direct function of the number of matching or identical positions; for example, if half of the positions in the two sequences are identical, the two sequences are 50% identical, and if 90% (e.g., 9 out of 10) of the positions are matching or identical, the two amino acid sequences are 90% identical.

[0070] "Substantially identical" means that a polypeptide or nucleic acid molecule exhibits at least 50% identity to a reference amino acid sequence (e.g., any one of the amino acid sequences described herein) or nucleic acid sequence (e.g., any one of the nucleic acid sequences described herein). In some embodiments, such a sequence is at least 60%, 80%, or 85%, or 90%, 95%, or even 99% identical at the amino acid or nucleic acid level to the sequence used for comparison. Other identity percentages for specific sequences are described herein.

[0071] Sequence identity can be measured / determined using sequence analysis software (e.g., Sequence Analysis Software Package of the Genetics Computer Group, University of Wisconsin Biotechnology Center, 1710 University Avenue, Madison, Wis. 53705, BLAST, BESTFIT, GAP, or PILEUP / PRETTYBOX programs). Such software matches identical or similar sequences by assigning degrees of homology to various substitutions, deletions, and / or other modifications. Conservative substitutions typically include substitutions within the following groups: glycine, alanine, valine, isoleucine, leucine, aspartic acid, glutamic acid, asparagine, glutamine, serine, threonine, lysine, arginine, and phenylalanine, tyrosine. In an exemplary approach to determining the degree of identity, the BLAST program can be used, with a probability score of e3 to e100 indicating closely related sequences. In some embodiments, sequence identity is determined using BLAST with default settings.

[0072] The scope of the embodiments provided herein includes compositions comprising various proteins, which may, in some cases, comprise amino acid sequences having sequence identity to the amino acid sequences disclosed herein. Thus, in certain embodiments, depending on the particular sequence, the degree of sequence identity is preferably greater than 50% (e.g., 60%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more) to the SEQ ID NOs disclosed herein. In addition to these percentages, other identity percentages are provided herein. Identity between polypeptides can be determined by the Smith-Waterman homology search algorithm, as implemented in the MPSRCH program (Oxford Molecular), using an affine gap search with a gap opening penalty of -12 and a gap extension penalty of 1.

[0073] These proteins may contain one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) conservative amino acid substitutions, i.e., substitution of one amino acid with another amino acid having a related side chain, compared to the disclosed proteins. Genetically encoded amino acids are generally divided into four families: (1) acidic, i.e., aspartate, glutamate; (2) basic, i.e., lysine, arginine, histidine; (3) nonpolar, i.e., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan; and (4) uncharged polar, i.e., glycine, asparagine, glutamine, cysteine, serine, threonine, tyrosine. Phenylalanine, tryptophan, and tyrosine are sometimes classified together as aromatic amino acids. Generally, substitution of a single amino acid within these families does not significantly affect biological activity. The proteins can have one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) single amino acid deletions compared to the disclosed protein sequences. The proteins can also include one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) insertions (e.g., of 1, 2, 3, 4, or 5 amino acids each) relative to the disclosed protein sequences.

[0074] As used herein, the term "in vivo" with respect to cells that are transduced, transfected, or transformed in vivo refers to cells that are transduced, transfected, or transformed inside a subject and are not removed from the subject before such cells are transduced, transfected, or transformed.

[0075] "Isolated" means altered or removed from the natural state. For example, a nucleic acid or peptide naturally occurring in a living animal is not "isolated," but the same nucleic acid or peptide partially or completely separated from the coexisting materials of its natural state is "isolated." An isolated nucleic acid or protein can exist in a substantially purified form, or can exist in a non-native environment, such as, for example, a host cell.

[0076] As used herein, "lentivirus" refers to a genus of the Retroviridae family that can infect non-dividing cells. Non-limiting examples of lentiviruses include HIV, SIV, and FIV. Lentivirus-derived vectors or virus-like particles can be used to transduce cells, deliver genes or other molecules, and express them in cells either in vitro (ex vivo) or in vivo.

[0077] The term "modified," as used herein, refers to an altered state or structure of a molecule or cell provided herein. Molecules can be modified in many ways, including chemically, structurally, and functionally, such as by mutation, substitution, insertion, or deletion (e.g., internal deletion truncation). Cells can be modified by the introduction of a nucleic acid or the expression of a heterologous protein.

[0078] The term "modulate," as used herein, means to mediate an increase or decrease in the level of a response in a subject compared to the level of the response in the subject in the absence of a treatment or compound, and / or compared to the level of the response in an otherwise identical but untreated subject. The term encompasses mediating a beneficial therapeutic response in a subject, such as a human, by disrupting and / or affecting a natural signal or response.

[0079] As used herein, the following abbreviations for commonly occurring nucleobases are used: "A" refers to adenosine, "C" refers to cytosine, "G" refers to guanosine, "T" refers to thymidine, and "U" refers to uridine.

[0080] Unless otherwise specified, a "nucleotide sequence encoding an amino acid sequence" includes all nucleotide sequences that are degenerate versions of each other and that encode the same amino acid sequence. The phrase nucleotide sequence encoding a protein or RNA may include introns, to the extent that a nucleotide sequence that encodes a protein may, in some versions, contain intron(s).

[0081] "Nipah virus" (NiV) is a member of the genus Henipavirus in the family Paramyxoviridae. Nipah virus is an enveloped virus with negative-strand polarity 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) strain and the Bangladeshi (BD) strain.

[0082] The term "oligonucleotide" typically refers to a short polynucleotide.When a nucleotide sequence is represented by a DNA sequence (i.e., A, T, C, G), it is understood that this also provides the corresponding RNA sequence (i.e., A, U, C, G) in which "T" is replaced by "U".

[0083] "Parenteral" administration of the compositions includes, for example, subcutaneous (sc), intravenous (iv), intramuscular (im), or intrasternal injection or infusion techniques.

[0084] The term "polynucleotide," as used herein, is defined as a chain of nucleotides. Furthermore, a nucleic acid is a polymer of nucleotides. Thus, as used herein, the terms "nucleic acid" and "polynucleotide" are interchangeable. As used herein, polynucleotide includes 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 cellular genomes using cloning techniques and PCR, etc.

[0085] As used herein, the terms "peptide," "polypeptide," and "protein" are used interchangeably and refer to compounds composed of multiple amino acid residues covalently linked by peptide bonds. As used herein, the term refers to both short chains, also commonly referred to in the art as peptides, oligopeptides, and oligomers, and longer chains, commonly referred to in the art as proteins, of which there are many varieties. "Polypeptide" includes, inter alia, biologically active fragments, substantially homologous polypeptides, oligopeptides, homodimers, heterodimers, polypeptide variants, modified polypeptides, derivatives, analogs, and fusion proteins. Polypeptides include natural peptides, recombinant peptides, synthetic peptides, or combinations thereof.

[0086] The term "pseudotype" or "pseudotyped virus particle," as used herein, refers to a viral particle having glycoproteins derived from another virus, with the viral vector encoding an envelope or envelope glycoprotein from a virus different from the parent virus. Thus, the host range of the vector particle can be expanded or altered depending on the type of cell surface receptor used by the glycoprotein. For example, the virus can be pseudotyped with the VSV-G mutant protein provided herein, or other viral glycoproteins, such as those provided herein.

[0087] As used herein with respect to antibodies, the term "specifically binds" refers to an antibody that recognizes a specific antigen but does not substantially recognize or bind other molecules in a sample. For example, an antibody that specifically binds to an antigen from one species may also bind that antigen from one or more species. However, such cross-species reactivity, in and of itself, does not alter the antibody's classification as specific. In another example, an antibody that specifically binds to an antigen may also bind to different allelic forms of the antigen. However, such cross-reactivity, in and of itself, does not alter the antibody's classification as specific. In some cases, the terms "specific binding" or "specific binding" can be used in reference to the interaction of an antibody, protein, or peptide with a second chemical species, meaning that the interaction is dependent on the presence of a specific structure (e.g., an antigenic determinant or epitope) on the chemical species; for example, an antibody recognizes and binds to a specific protein structure rather than proteins in general. If an antibody is specific for epitope "A," in a reaction containing labeled "A" and an antibody, the presence of a molecule containing epitope A (or unlabeled free A) will reduce the amount of labeled A bound to the antibody. In some embodiments, the targeting moieties described herein that can be used to target viral particles containing mutant VSV-G proteins are capable of specifically binding their targets.

[0088] The term "subject" includes living organisms, including organisms in which an immune response can be elicited (e.g., mammals). As used herein, a "subject" or "patient" can be a human or non-human mammal. Non-human mammals include, for example, livestock and pets, such as ovine, bovine, porcine, canine, non-human primates, feline, and murine mammals. In some embodiments, the subject is a human.

[0089] As used herein, the term "therapeutic" means treatment and / or prophylaxis. A therapeutic effect is achieved by suppressing, ameliorating, or eradicating the disease state.

[0090] As used herein, the terms "transfected" or "transformed" or "transduced" refer to the process by which exogenous nucleic acid is transferred or introduced into a cell. A "transfected" or "transformed" or "transduced" cell is one that has been transfected, transformed, or transduced with exogenous nucleic acid. This cell includes the primary subject cell and its progeny. In some embodiments, transfection, transformation, or transduction is performed or takes place in vivo.

[0091] As used herein, "treating" a disease means reducing the frequency or severity of at least one sign or symptom of a disease or disorder experienced by a subject. As used herein, "inhibiting" or "treating" or "treatment" also includes postponing the onset of symptoms associated with a disorder and / or reducing the severity of symptoms of such a disorder. These terms further include ameliorating existing uncontrolled or unwanted symptoms, preventing additional symptoms, and ameliorating or preventing the underlying causes of such symptoms. Thus, these terms indicate a beneficial result being imparted to a vertebrate subject having a disorder, disease, or condition, or having a potential for developing such a disorder, disease, or condition.

[0092] A "vector" is a composition of matter comprising an isolated nucleic acid encoding a protein or peptide. Numerous vectors are known in the art, including, but not limited to, linear polynucleotides, plasmids, DNA, and RNA. Examples of viral vectors include, but are not limited to, Sendai virus vectors, adenovirus vectors, adeno-associated virus vectors, retrovirus vectors, lentivirus vectors, and the like.

[0093] "Carriers" or "delivery vehicles" include viral particles, viruses, polylysine compounds, and liposomes that facilitate the transfer of nucleic acids into cells. Carriers or delivery vehicles can also be used to deliver proteins or peptides to cells.

[0094] Ranges: Throughout this application, various aspects of the embodiments may be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values ​​within that range. For example, the description of a range such as 1 to 6 should be considered to have specifically disclosed subranges such as 1 to 3, 1 to 4, 1 to 5, 2 to 4, 2 to 6, 3 to 6, etc., as well as individual numerical values ​​within that range, such as 1, 2, 2.7, 3, 4, 5, 5.3, and 6. This applies regardless of the breadth of the range. Unless expressly stated otherwise, the disclosed ranges include the endpoints of the range.

[0095] Without being bound by any particular theory, the embodiments provided herein have been found to demonstrate that a mutant VSV-G protein containing a mutation at position 182 can be used to pseudotype viruses and transduce cells when the virus contains a targeting site. This mutation inhibits or reduces the affinity of VSV-G for its natural co-receptor, LDL-R. In some embodiments, the provided mutant VSV-G protein can be used to transduce target cells and deliver heterologous molecules to target cells.

[0096] In some embodiments, a VSV-G protein is provided that includes a mutation at position 198 compared to SEQ ID NO:1 or at position 182 compared to SEQ ID NO:2. SEQ ID NO:1 is the full-length protein, and SEQ ID NO:2 is the ectodomain of the VSV-G protein. The 16-mer signal peptide of MKCLLYLAFLFIGVNC (SEQ ID NO:26), shown at the N-terminus of SEQ ID NO:1, is cleaved, leaving the protein of SEQ ID NO:2. Thus, while mutations may be referred to in the context of SEQ ID NO:2, they should be understood to also be made in the context of SEQ ID NO:1, which contains the leader sequence, and thus will be 16 positions higher than the positions listed for SEQ ID NO:2. In some embodiments, the mutation inhibits or reduces binding of the VSV-G protein to the LDL receptor (LDL-R). In some embodiments, the mutation is an I182D mutation compared to SEQ ID NO:2. In some embodiments, the mutation is an I182E mutation compared to SEQ ID NO:2.

[0097] In some embodiments, a VSV-G protein is provided that includes a mutation at position 198 compared to SEQ ID NO: 10 or at position 182 compared to SEQ ID NO: 11. SEQ ID NO: 10 is the full-length protein, and SEQ ID NO: 11 is the ectodomain of the VSV-G protein. The 16-mer signal peptide of MLSYLIFALVVSPILG (SEQ ID NO: 27), shown at the N-terminus of SEQ ID NO: 10, is cleaved, leaving the protein of SEQ ID NO: 11. Thus, while mutations may be referred to in the context of SEQ ID NO: 11, they should be understood to also be made in the context of SEQ ID NO: 10, which contains the leader sequence, and thus will be 16 positions higher than the position recited for SEQ ID NO: 11. In some embodiments, the mutation inhibits or reduces binding of the VSV-G protein to the LDL receptor (LDL-R). In some embodiments, the mutation is a T182D mutation compared to SEQ ID NO: 11. In some embodiments, the mutation is a T182E mutation compared to SEQ ID NO: 11.

[0098] In some embodiments, a VSV-G protein is provided that includes a mutation at position 198 compared to SEQ ID NO: 12 or at position 182 compared to SEQ ID NO: 13. SEQ ID NO: 12 is the full-length protein, and SEQ ID NO: 13 is the ectodomain of the VSV-G protein. The 16-mer signal peptide 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. Thus, while mutations may be mentioned in the context of SEQ ID NO: 13, they should be understood to also be made in the context of SEQ ID NO: 12, which contains the leader sequence, and thus will be 16 positions higher than the positions listed for SEQ ID NO: 13. In some embodiments, the mutation inhibits or reduces binding of the VSV-G protein to the LDL receptor (LDL-R). In some embodiments, the mutation is an A182D mutation compared to SEQ ID NO: 13. In some embodiments, the mutation is an A182E mutation compared to SEQ ID NO: 13.

[0099] In some embodiments, a VSV-G protein is provided that includes a mutation at position 203 compared to SEQ ID NO: 14 or at position 182 compared to SEQ ID NO: 15. SEQ ID NO: 14 is the full-length protein, and SEQ ID NO: 15 is the ectodomain of the VSV-G protein. The 21-mer signal peptide of MKMKMVIAGLILCIGILPAIG (SEQ ID NO: 29), shown at the N-terminus of SEQ ID NO: 14, is cleaved, leaving the protein of SEQ ID NO: 15. Thus, while mutations may be mentioned in the context of SEQ ID NO: 15, they should be understood to also be made in the context of SEQ ID NO: 14, which contains the leader sequence, and thus will be 21 positions higher than the position recited for SEQ ID NO: 15. In some embodiments, the mutation inhibits or reduces binding of the VSV-G protein to the LDL receptor (LDL-R). In some embodiments, the mutation is a V182D mutation compared to SEQ ID NO: 15. In some embodiments, the mutation is a V182E mutation compared to SEQ ID NO: 15.

[0100] In some embodiments, a VSV-G protein is provided that includes a mutation at position 199 compared to SEQ ID NO: 16 or at position 182 compared to SEQ ID NO: 17. SEQ ID NO: 16 is the full-length protein, and SEQ ID NO: 17 is the ectodomain of the VSV-G protein. The 17-mer signal peptide of MTPAFILCMLLAGSSWA (SEQ ID NO: 30), shown at the N-terminus of SEQ ID NO: 16, is cleaved, leaving the protein of SEQ ID NO: 17. Thus, while mutations may be referred to in the context of SEQ ID NO: 17, they should be understood to also be made in the context of SEQ ID NO: 16 containing the leader sequence, and thus will be 17 positions higher than the position recited for SEQ ID NO: 17. In some embodiments, the mutation inhibits or reduces binding of the VSV-G protein to the LDL receptor (LDL-R). In some embodiments, the mutation is a V182D mutation compared to SEQ ID NO: 17. In some embodiments, the mutation is a V182E mutation compared to SEQ ID NO: 17.

[0101] In some embodiments, a VSV-G protein is provided that includes a mutation at position 199 compared to SEQ ID NO: 18 or at position 182 compared to SEQ ID NO: 19. SEQ ID NO: 18 is the full-length protein, and SEQ ID NO: 19 is the ectodomain of the VSV-G protein. The 17-mer signal peptide of 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. Thus, while mutations may be mentioned in the context of SEQ ID NO: 19, they should be understood to also be made in the context of SEQ ID NO: 18, which contains the leader sequence, and thus will be 17 positions higher than the position recited for SEQ ID NO: 19. In some embodiments, the mutation inhibits or reduces binding of the VSV-G protein to the LDL receptor (LDL-R). In some embodiments, the mutation is a V182D mutation compared to SEQ ID NO: 19. In some embodiments, the mutation is a V182E mutation compared to SEQ ID NO: 19.

[0102] In some embodiments, a VSV-G protein is provided that includes a mutation at position 199 compared to SEQ ID NO:20 or at position 182 compared to SEQ ID NO:21. SEQ ID NO:20 is the full-length protein, and SEQ ID NO:21 is the ectodomain of the VSV-G protein. The 17-mer signal peptide of MLVLYLLLSLLALGAQC (SEQ ID NO:32), shown at the N-terminus of SEQ ID NO:20, is cleaved, leaving the protein of SEQ ID NO:21. Thus, while mutations may be mentioned in the context of SEQ ID NO:21, they should be understood to also be made in the context of SEQ ID NO:20, which contains the leader sequence, and thus will be 17 positions higher than the position recited for SEQ ID NO:21. In some embodiments, the mutation inhibits or reduces binding of the VSV-G protein to the LDL receptor (LDL-R). In some embodiments, the mutation is an I182D mutation compared to SEQ ID NO:21. In some embodiments, the mutation is an I182E mutation compared to SEQ ID NO:21.

[0103] As used herein, when a polypeptide is said to have a mutation compared to a reference sequence, such comparison is based on an alignment, such as using BlastP, ClustalW, or ClutalOmega alignment software with default parameters. For example, position 182 can be found in SEQ ID NO: 2 and compared to other strains, as shown in Figure 3. Figure 3 shows a cluster alignment of wild-type sequences of the ectodomain of various strains of VSV-G protein. The bold and underlined residues are the residues aligned to position 182 of SEQ ID NO: 2 of various strains. SEQ ID NO: 2 refers to the ectodomain of the VSV-G protein of the Indiana strain. SEQ ID NO: 11 refers to the ectodomain of the VSV-G protein of the New Jersey strain. SEQ ID NO: 13 refers to the ectodomain of the VSV-G protein of the Maraba strain. SEQ ID NO: 15 refers to the ectodomain of the VSV-G protein of the Carajas strain. SEQ ID NO: 17 refers to the extracellular domain of the VSV-G protein of the Alagoa strain. SEQ ID NO: 19 refers to the ectodomain of the VSV-G protein of the Cocal strain. SEQ ID NO: 21 refers to the ectodomain of the VSV-G protein of the Moreton strain. Thus, the residue that aligns with residue 182 compared to SEQ ID NO: 2 can also be mutated as provided herein.

[0104] In some embodiments, the mutation at position 182 compared to SEQ ID NO: 2 is not an alanine. In some embodiments, the mutation at position 182 compared to SEQ ID NO: 2 is not a valine.

[0105] 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 relative to SEQ ID NO: 19 is V182S, V182H, V182T, V182Q, or V182N. In some embodiments, the mutation at position 182 relative 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.

[0106] The mutations may be described with reference to SEQ ID NO: 1 or SEQ ID NO: 2, which are VSV-G proteins from the Indiana strain, but the mutations may also be used in other strains of VSV-G proteins. For example, mutations may be made in the New Jersey strain of VSV-G, the Maraba strain of VSV-G, the Carajas strain of VSV-G, the Alagoa strain of VSV-G, the Kocal strain of VSV-G, or the Moreton strain of VSV-G. In some embodiments, the sequences for each are those provided herein. Examples of these may be found, for example, in U.S. Patent Application Publication No. 20200216502, which is incorporated herein by reference. For example, the wild-type full-length or ectodomain of the New Jersey strain of VSV-G is SEQ ID NO: 10 and SEQ ID NO: 11, respectively; the wild-type full-length or ectodomain of the Maraba strain of VSV-G is SEQ ID NO: 12 and SEQ ID NO: 13, respectively; the wild-type full-length or ectodomain of the Carajas strain of VSV-G is SEQ ID NO: 14 and SEQ ID NO: 15, respectively; the wild-type full-length or ectodomain of the Alagoa strain of VSV-G is SEQ ID NO: 16 and SEQ ID NO: 17, respectively; the wild-type full-length or ectodomain of the Kocal strain of VSV-G is SEQ ID NO: 18 and SEQ ID NO: 19, respectively; or the wild-type full-length or ectodomain of the Moreton strain of VSV-G is SEQ ID NO: 20 and SEQ ID NO: 21, respectively.

[0107] A VSV-G protein comprising a mutation at position 182 relative to SEQ ID NO:2 can also comprise other mutations, such as those described in U.S. Patent Application Publication No. 2020 / 0216502, which is incorporated by reference in its entirety. For example, the VSV-G protein can comprise mutations at positions corresponding to positions 8, 47, 209, and / or 354 of SEQ ID NO:2.

[0108] In some embodiments, the substitution at position 8 is with any amino acid different from the amino acid shown at that position in SEQ ID NO:2, except for Y. In some embodiments, the substitution at position 8 is with any amino acid different from the amino acid shown at that position in SEQ ID NO:2, except for H. In some embodiments, the substitution at position 8 is with any amino acid different from the amino acid shown at that position in SEQ ID NO:2, except for Q. In some embodiments, the substitution at position 8 is with any amino acid different from the amino acid shown at that position in SEQ ID NO:2, except for Y, H, or Q. In some embodiments, the substitution at position 8 is selected from alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glycine, isoleucine, valine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, or tryptophan. In some embodiments, the substitution at position 8 is selected from 8A, 8I, 8V, 8L, etc. In some embodiments, the substitution at position 8 is selected from H8A, H8I, H8V, H8L, etc.

[0109] In some embodiments, the substitution at position 209 is with any amino acid different from the amino acid shown at that position in SEQ ID NO: 2, except for H. In some embodiments, the substitution at position 209 is with any amino acid different from the amino acid shown at that position in SEQ ID NO: 2, except for Y. In some embodiments, the substitution at position 209 is with any amino acid different from the amino acid shown at that position in SEQ ID NO: 2, except for H or Y. In some embodiments, the substitution at position 209 is selected from alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, isoleucine, valine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, or tryptophan.

[0110] In some embodiments, the substitution at position 47 is with any amino acid different from the amino acid shown at that position in SEQ ID NO:2, except for K. In some embodiments, the substitution at position 47 is with any amino acid different from the amino acid shown at that position in SEQ ID NO:2, except for R. In some embodiments, the substitution at position 47 is with any amino acid different from the amino acid shown at that position in SEQ ID NO:2, except for K or R. In some embodiments, the substitution at position 47 is selected from alanine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, valine, leucine, methionine, phenylalanine, proline, serine, threonine, tryptophan, or tyrosine. In some embodiments, the substitution at position 47 is selected from A, G, F, N, or Q. In some embodiments, the substitution at position 47 is selected from Q or N.

[0111] In some embodiments, the substitution at position 354 is with any amino acid different from the amino acid shown at that position in SEQ ID NO:2, except for K. In some embodiments, the substitution at position 354 is with any amino acid different from the amino acid shown at that position in SEQ ID NO:2, except for R. In some embodiments, the substitution at position 354 is with any amino acid different from the amino acid shown at that position in SEQ ID NO:2, except for K or R. In some embodiments, the substitution at position 354 is selected from alanine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, valine, leucine, methionine, phenylalanine, proline, serine, threonine, tryptophan, or tyrosine. In some embodiments, the substitution at position 354 is selected from A, G, F, N, or Q.

[0112] In some embodiments, the substitutions are at positions 47 or 354, or at both positions 47 and 354, independently with A, G, F, N, or Q. In some embodiments, the substitutions at positions 47 or 354, or at both positions 47 and 354, are independently A, Q, or N.

[0113] In some embodiments, the VSV-G protein can comprise a mutation at a position corresponding to position 8, 47, 209, and / or 354. In some embodiments, the VSV-G protein can comprise a mutation at a position corresponding to position 8 provided herein, position 47 provided herein, position 209 provided herein, and / or position 354 provided herein. In some embodiments, the VSV-G protein can comprise a mutation at a position corresponding to position 8 provided herein and position 47 provided herein. In some embodiments, the VSV-G protein can comprise a mutation at a position corresponding to position 8 provided herein and position 209 provided herein. In some embodiments, the VSV-G protein can comprise a mutation at a position corresponding to position 8 provided herein and position 354 provided herein. In some embodiments, the VSV-G protein can comprise a mutation at a position corresponding to position 47 provided herein and position 209 provided herein. In some embodiments, the VSV-G protein can comprise a mutation at a position corresponding to position 47 provided herein and position 209 provided herein. In some embodiments, the VSV-G protein can comprise a mutation at a position corresponding to position 47 provided herein and position 354 provided herein. In some embodiments, the VSV-G protein can comprise a mutation at a position corresponding to position 209 as provided herein and at position 354 as provided herein. In some embodiments, the VSV-G protein can comprise a mutation at a 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 can comprise a mutation at a 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 can comprise a mutation at a 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 can comprise a mutation at a position corresponding to position 47 as provided herein, at position 209 as provided herein, and at position 354 as provided herein.In some embodiments, the VSV-G protein can include a mutation at a position corresponding to position 8 as provided herein, position 47 as provided herein, position 209 as provided herein, and position 354 as provided herein.

[0114] In some embodiments, the substitution at position 8 is an alanine, ie, H8A.

[0115] In some embodiments, the substitution at position 47 is Q or N or A, ie, K47Q or K47N or K47A.

[0116] In some embodiments, the protein comprises a substitution at position 8 and / or a substitution at position 47. In some embodiments, the protein comprises a substitution at position 8 and a substitution at position 47. In some embodiments, the protein comprises a substitution at position 8 or a substitution at position 47. In some embodiments, the substitution at position 8 and / or the substitution at position 47 comprises an H8A and / or a K47Q mutation.

[0117] In some embodiments, the protein comprises a mutation (substitution) at position 10. In some embodiments, the substitution / mutation is Q10A, Q10R, or Q10K.

[0118] In some non-limiting embodiments, the substitution at position 209 is A, ie, Y209A.

[0119] In some non-limiting embodiments, the substitution at position 354 is A or Q, ie, R354A or R354Q.

[0120] In some embodiments, a protein comprising a mutation at position 182 relative to SEQ ID NO:11 can also comprise other mutations, such as those described in U.S. Patent Application Publication No. 2020 / 0216502. For example, a VSV-G protein can comprise mutations at positions analogous 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 analogous to positions 8, 47, 209, and / or 354 of SEQ ID NO:2 are as provided herein.

[0121] In some embodiments, a protein comprising a mutation at position 182 relative to SEQ ID NO: 13 can also comprise other mutations, such as those described in U.S. Patent Application Publication No. 2020 / 0216502. For example, a VSV-G protein can comprise mutations at positions analogous 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 analogous to positions 8, 47, 209, and / or 354 of SEQ ID NO: 2 are as provided herein.

[0122] In some embodiments, a protein comprising a mutation at position 182 relative to SEQ ID NO: 15 can also comprise other mutations, such as those described in U.S. Patent Application Publication No. 2020 / 0216502. For example, a VSV-G protein can comprise mutations at positions analogous 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 analogous to positions 8, 47, 209, and / or 354 of SEQ ID NO: 2 are as provided herein.

[0123] In some embodiments, a protein comprising a mutation at position 182 relative to SEQ ID NO: 17 can also comprise other mutations, such as those described in U.S. Patent Application Publication No. 2020 / 0216502. For example, a VSV-G protein can comprise mutations at positions analogous 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 analogous to positions 8, 47, 209, and / or 354 of SEQ ID NO: 2 are as provided herein.

[0124] In some embodiments, a protein comprising a mutation at position 182 relative to SEQ ID NO: 19 can also comprise other mutations, such as those described in U.S. Patent Application Publication No. 2020 / 0216502. For example, a VSV-G protein can comprise mutations at positions analogous 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 analogous to positions 8, 47, 209, and / or 354 of SEQ ID NO: 2 are as provided herein.

[0125] In some embodiments, a protein comprising a mutation at position 182 relative to SEQ ID NO:21 can also comprise other mutations, such as those described in U.S. Patent Application Publication No. 2020 / 0216502. For example, a VSV-G protein can comprise mutations at positions analogous 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 analogous to positions 8, 47, 209, and / or 354 of SEQ ID NO:2 are as provided herein.

[0126] In some embodiments, the protein comprising a mutation at position 182 compared to SEQ ID NO:2 comprises 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 the full-length protein is used). In some embodiments, the protein is at least or about 80% identical to SEQ ID NO:2. In some embodiments, the protein is at least or about 85% identical to SEQ ID NO:2. In some embodiments, the protein is at least or about 90% identical to SEQ ID NO:2. In some embodiments, the protein is at least or about 95% identical to SEQ ID NO:2. In some embodiments, the mutation at position 182 is an I182D or I182E mutation. In some embodiments, the mutation is I182D. In some embodiments, the mutation is an I182E mutation. In some embodiments, the mutation is an I182S, I182H, I182T, I182Q, or I182N mutation.

[0127] In some embodiments, a VSV-G is provided wherein the protein comprises the amino acid sequence of SEQ ID NO:2 with a mutation at position 182 and 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.

[0128] In some embodiments, the protein comprising a mutation at position 182 compared to SEQ ID NO: 11 comprises 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 the full-length protein is used). In some embodiments, the polypeptide comprises a T182D or T182E mutation. In some embodiments, the VSV-G protein comprises a T182S, T182H, T182Q, or T182N mutation.

[0129] In some embodiments, the protein comprising a mutation at position 182 compared to SEQ ID NO: 13 comprises 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 the full-length protein is used). In some embodiments, the polypeptide comprises an A182D or A182E mutation. In some embodiments, the VSV-G protein comprises an A182S, A182H, A182T, A182Q, or A182N mutation.

[0130] In some embodiments, the protein comprising a mutation at position 182 compared to SEQ ID NO: 15 comprises 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 the full-length protein is used). In some embodiments, the polypeptide comprises a V182D or V182E mutation. In some embodiments, the VSV-G protein comprises a V182S, V182H, V182T, V182Q, or V182N mutation.

[0131] In some embodiments, the protein comprising a mutation at position 182 compared to SEQ ID NO: 17 comprises 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 the full-length protein is used). In some embodiments, the polypeptide comprises a V182D or V182E mutation. In some embodiments, the VSV-G protein comprises a V182S, V182H, V182T, V182Q, or V182N mutation.

[0132] In some embodiments, the protein comprising a mutation at position 182 compared to SEQ ID NO: 19 comprises 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 the full-length protein is used). In some embodiments, the polypeptide comprises a V182D or V182E mutation. In some embodiments, the VSV-G protein comprises a V182S, V182H, V182T, V182Q, or V182N mutation.

[0133] In some embodiments, the protein comprising a mutation at position 182 compared to SEQ ID NO:21 comprises 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 the full-length protein is used). In some embodiments, the polypeptide comprises an I182D or I182E mutation. In some embodiments, the VSV-G protein comprises an I182S, I182H, I182T, I182Q, or I182N mutation.

[0134] virus particles Mutant VSV-G proteins can be used to pseudotype viruses, such as, but not limited to, lentiviruses. Thus, in some embodiments, viral particles are provided that include the mutant VSV-G proteins provided herein. In some embodiments, the viral particles include a VSV-G protein that includes a mutation at position 198 compared to SEQ ID NO: 1. In some embodiments, a protein that includes a mutation at position 182 compared to SEQ ID NO: 2 includes 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 the full-length protein is used). In some embodiments, the polypeptide comprises an I182D or I182E mutation compared to SEQ ID NO: 2. In some embodiments, the VSV-G protein comprises an I182S, I182H, I182T, I182Q, or I182N mutation.

[0135] In some embodiments, the viral particle comprises a VSV-G protein comprising a mutation at position 198 compared to SEQ ID NO: 10. In some embodiments, the protein comprising a mutation at position 182 compared to SEQ ID NO: 11 comprises 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 the full-length protein is used). In some embodiments, the polypeptide comprises a T182D or T182E mutation compared to SEQ ID NO: 11. In some embodiments, the VSV-G protein comprises a T182S, T182H, T182Q, or T182N mutation.

[0136] In some embodiments, the viral particle comprises a VSV-G protein comprising a mutation at position 198 compared to SEQ ID NO: 12. In some embodiments, the protein comprising a mutation at position 182 compared to SEQ ID NO: 13 comprises 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 the full-length protein is used). In some embodiments, the polypeptide comprises an A182D or A182E mutation compared to SEQ ID NO: 13. In some embodiments, the VSV-G protein comprises an A182S, A182H, A182T, A182Q, or A182N mutation.

[0137] In some embodiments, the viral particle comprises a VSV-G protein comprising a mutation at position 203 compared to SEQ ID NO: 14. In some embodiments, the protein comprising a mutation at position 182 compared to SEQ ID NO: 15 comprises 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 the full-length protein is used). In some embodiments, the polypeptide comprises a V182D or V182E mutation compared to SEQ ID NO: 15. In some embodiments, the VSV-G protein comprises a V182S, V182H, V182T, V182Q, or V182N mutation.

[0138] In some embodiments, the viral particle comprises a VSV-G protein comprising a mutation at position 199 compared to SEQ ID NO: 16. In some embodiments, the protein comprising a mutation at position 182 compared to SEQ ID NO: 17 comprises 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 the full-length protein is used). In some embodiments, the polypeptide comprises a V182D or V182E mutation compared to SEQ ID NO: 17. In some embodiments, the VSV-G protein comprises a V182S, V182H, V182T, V182Q, or V182N mutation.

[0139] In some embodiments, the viral particle comprises a VSV-G protein comprising a mutation at position 199 compared to SEQ ID NO: 18. In some embodiments, the protein comprising a mutation at position 182 compared to SEQ ID NO: 19 comprises 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 the full-length protein is used). In some embodiments, the polypeptide comprises a V182D or V182E mutation compared to SEQ ID NO: 19. In some embodiments, the VSV-G protein comprises a V182S, V182H, V182T, V182Q, or V182N mutation.

[0140] In some embodiments, the viral particle comprises a VSV-G protein comprising a mutation at position 199 compared to SEQ ID NO: 20. In some embodiments, the protein comprising a mutation at position 182 compared to SEQ ID NO: 21 comprises 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 the full-length protein is used). In some embodiments, the polypeptide comprises an I182D or I182E mutation compared to SEQ ID NO: 21. In some embodiments, the VSV-G protein comprises an I182S, I182H, I182T, I182Q, or I182N mutation.

[0141] In some embodiments, the VSV-G protein further comprises a mutation at a 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 the T214N and T352A mutations compared to SEQ ID NO:2. These mutations can be combined with any other mutation provided herein. In some embodiments, the T214N and / or T352A mutations are combined with an I182E or I182D mutation. In some embodiments, the VSV-G protein comprises the amino acid sequence of SEQ ID NO:22 and SEQ ID NO:23, which combine an I182D or I182E mutation with the T214N and T352A mutations, respectively. The sequence is also shown below with the leader sequence removed during protein processing. VSV-G protein_I196D, T230N, and T368A mutations (with leader sequence, numbering adjusted) MKCLLYLAFLFIGVNCKFTIVFPHNQKGNWKNVPSNYHYCPSSSDLNWHNDLIGTALQVKMPKSHKAIQADGWMCHASKWVTTCDFRWYGPKYITHSIRSFTPSVEQCKESIEQTKQGTWLNPGFPPQS CGYATVTDAEAVIVQVTPHHVLVDEYTGEWVDSQFINGKCSNYICPTVHNSTTWHSDYKVKGLCDSNLDSMDITFFSEDGELSSLGKEGTGFRSNYFAYENGGKACKMQYCKHWGVRLPSGVWFEMADKD LFAAARFPECPEGSSISAPSQTSVDVSLIQDVERILDYSLCQETWSKIRAGLPISPVDLSYLAPKNPGTGPAFTIINGTLKYFETRYIRVDIAAPILSRMVGMISGTTAERELWDDWAPYEDVEIGPNGVLRTSSGYKFPLYMIGHGMLDSDLHLSSKAQVFEHPHIQDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCIKLKHTKKRQIYTDIEMNRLGK (SEQ ID NO: 24) VSV-G protein_I182D, T214N, and T352A mutations (leader sequence absent) KFTIVFPHNQKGNWKNVPSNYHYCPSSSDLNWHNDLIGTALQVKMPKSHKAIQADGWMCHASKWVTTCDFRWYGPKYITHSIRSFTPSVEQCKESIEQTKQGTWLNPGFPPQSCGYATVTDAEAV IVQVTPHHVLVDEYTGEWVDSQFINGKCSNYICPTVHNSTTWHSDYKVKGLCDSNLDSMDITFFSEDGELSSLGKEGTGFRSNYFAYENGGKACKMQYCKHWGVRLPSGVWFEMADKDLFAAARFP ECPEGSSISAPSQTSVDVSLIQDVERILDYSLCQETWSKIRAGLPISPVDLSYLAPKNPGTGPAFTIINGTLKYFETRYIRVDIAAPILSRMVGMISGTTAERELWDDWAPYEDVEIGPNGVLRTSSGYKFPLYMIGHGMLDSDLHLSSKAQVFEHPHIQDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCIKLKHTKKRQIYTDIEMNRLGK (SEQ ID NO: 22) VSV-G protein with I196E, T230N, and T368A mutations (with leader sequence and numbering adjusted) MKCLLYLAFLFIGVNCKFTIVFPHNQKGNWKNVPSNYHYCPSSSDLNWHNDLIGTALQVKMPKSHKAIQADGWMCHASKWVTTCDFRWYGPKYITHSIRSFTPSVEQCKESIEQTKQGTWLNPGFPPQS CGYATVTDAEAVIVQVTPHHVLVDEYTGEWVDSQFINGKCSNYICPTVHNSTTWHSDYKVKGLCDSNLESMDITFFSEDGELSSLGKEGTGFRSNYFAYENGGKACKMQYCKHWGVRLPSGVWFEMADKD LFAAARFPECPEGSSISAPSQTSVDVSLIQDVERILDYSLCQETWSKIRAGLPISPVDLSYLAPKNPGTGPAFTIINGTLKYFETRYIRVDIAAPILSRMVGMISGTTAERELWDDWAPYEDVEIGPNGVLRTSSGYKFPLYMIGHGMLDSDLHLSSKAQVFEHPHIQDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCIKLKHTKKRQIYTDIEMNRLGK (SEQ ID NO: 25) VSV-G protein (without leader sequence) with I182E, T214N, and T352A mutations KFTIVFPHNQKGNWKNVPSNYHYCPSSSDLNWHNDLIGTALQVKMPKSHKAIQADGWMCHASKWVTTCDFRWYGPKYITHSIRSFTPSVEQCKESIEQTKQGTWLNPGFPPQSCGYATVTDAEAV IVQVTPHHVLVDEYTGEWVDSQFINGKCSNYICPTVHNSTTWHSDYKVKGLCDSNLESMDITFFSEDGELSSLGKEGTGFRSNYFAYENGGKACKMQYCKHWGVRLPSGVWFEMADKDLFAAARFP ECPEGSSISAPSQTSVDVSLIQDVERILDYSLCQETWSKIRAGLPISPVDLSYLAPKNPGTGPAFTIINGTLKYFETRYIRVDIAAPILSRMVGMISGTTAERELWDDWAPYEDVEIGPNGVLRTSSGYKFPLYMIGHGMLDSDLHLSSKAQVFEHPHIQDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCIKLKHTKKRQIYTDIEMNRLGK (SEQ ID NO: 23) Other strains of the VSV-G protein described herein can also include mutations corresponding to T214N and / or T352A in SEQ ID NO:2, as well as the mutations shown in SEQ ID NO:22 and SEQ ID NO:23.

[0142] In some embodiments, the composition comprises a mutation described in Hwang et al., Gene Ther 2013 Aug;20(8):807-15. (Epub 2013 Jan 31), which is incorporated herein by reference in its entirety. For example, the mutations can be at positions 230, 368, 66, and / or 162, corresponding to SEQ ID NO: 1. These positions are 16 fewer than those of SEQ ID NO: 2 when the leader sequence is removed. In some embodiments, the mutations at these 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 correspond to those in the full-length protein (SEQ ID NO: 1). In some embodiments, the VSV-G protein comprises a T230N mutation, a T368A mutation, a K66T mutation, an S162T mutation, or any combination thereof. In some embodiments, the VSV-G protein further comprises one or more mutations in addition to the mutation corresponding to position 182 of SEQ ID NO:2, such as those described in U.S. Patent Application Publication No. 20200216502 (incorporated herein by reference in its entirety). For example, the VSV-G protein can further comprise mutations at positions corresponding to positions 8, 47, 209, and / or 354 of SEQ ID NO:2.

[0143] In some embodiments, the substitution at position 8 is with any amino acid different from the amino acid shown at that position in SEQ ID NO:2, except Y. In some embodiments, the substitution at position 209 is with any amino acid different from the amino acid shown at that position in SEQ ID NO:2, except H. In some embodiments, the substitution at position 47 is with any amino acid different from the amino acid shown at that position in SEQ ID NO:2, except K or R. In some embodiments, the substitution at position 354 is with any amino acid different from the amino acid shown at that position in SEQ ID NO:2, except K or R. In some embodiments, the substitution at positions 47 or 354, or both 47 and 354, is with 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 comprises a mutation (substitution) at position 10. In some embodiments, the substitution / mutation is Q10A, Q10R, or Q10K.

[0144] In some embodiments, the viral particle comprises a targeting moiety. The targeting moiety can be used to target viral particles comprising the mutant VSV-G protein to cells expressing a target to which the targeting moiety binds. In some embodiments, the targeting moiety is an antibody, an scFv antibody, an antigen-binding domain, ankyrin repeats (e.g., DARPIN), a VHH domain antibody, a nanobody, a single-domain antibody, an FN3 domain, or any combination thereof. The targeting moiety can be attached to the viral surface via an IgG Fc stalk. In some embodiments, the stalk comprises a transmembrane domain. In some embodiments, the transmembrane domain comprises a CD8 transmembrane domain. In some embodiments, the transmembrane domain comprises a CD28 transmembrane domain. In some embodiments, the targeting moiety is attached (fused or linked) to the envelope glycoprotein G or H of a virus of the Paramyxoviridae family, such as a morbillivirus, such as measles virus, or a henipavirus, such as Nipah virus, Cedar virus, or Hendra virus. In some embodiments, the targeting moiety is attached (fused or linked) to the glycoprotein of a virus of the Rhabdoviridae family, such as vesicular stomatitis New Jersey virus, vesicular stomatitis Indiana virus, vesicular stomatitis Alagoas virus, vesicular stomatitis Maraba virus, vesicular stomatitis Carajas virus, parainfluenza virus, Spodoptera frugiperda rhabdovirus isolate Sf G, Drosophila obscura sigma virus 10A, Wuhan insect virus 7, Perch virus, or spring viremia of carp virus. In some embodiments, the VSV protein is a mutant protein, such as those provided herein. In some embodiments, the targeting moiety is attached to the glycoprotein of a virus of the Filoviridae family, such as Ebola virus, or the glycoprotein of a virus of the Arenaviridae family, such as Machupo virus.

[0145] In some embodiments, the targeting moiety is an scFv. In some embodiments, the targeting moiety is a single domain antibody. In some embodiments, the targeting moiety is a VHH.

[0146] In some embodiments, the targeting moiety is selected from the group consisting of CD7, CD8, cKit (CD117), CD4, CD3, CD5, CD6, CD2, TCR alpha, TCR beta, TCR gamma, TCR delta, CD10, CD34, CD110, CD33, CD14, CD68, CCR7, CD62L, CD25, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, or CXCR3, a glycosylated CD43 epitope expressed on acute leukemia or lymphoma but not on hematopoietic progenitor cells, a glycosylated CD43 epitope expressed on non-hematopoietic cancers, kinase anchor protein 4 (AKAP-4), Adrenergic receptor beta 3 (ADRB3), AFP, anaplastic lymphoma kinase (ALK), androgen receptor, angiopoietin-binding cell surface receptor 2 (Tie2), autoantibodies to desmoglein 1 (Dsgl), autoantibodies to desmoglein 3 (Dsg3), B7H3 (CD276), biotin, bone marrow stromal cell antigen 2 (BST2), BST1 / CD157, cancer / testis antigen 1 (NY-ESO-1), cancer / testis antigen 2 (LAGE-1a), carbonic anhydrase IX (CA1X), carcinoembryonic antigen (CEA), CCCTC-binding factor (zinc finger protein)-like (BORIS or Brother of the Regulator of Imprinted Sites), CCR4, CD5, CD19, CD20, CD22, CD24, CD30, CD32 (FCGR2A), CD33, CD34, CD38, CD44v6, CD72, CD79a, CD79b, CD97, CD99, CD123, CD171, CD179a, CD179b-IGL11, CD200R, CD276 / B7H3, CD300 molecule-like family member f (CD300LF), CDH1-CD324, CDH6, CDH17, CDH19, chromosome X open reading frame 61 (CXORF61), claudin 6 (CLDN6), claudin l8.2 (CLD18A2 or CLDN18A.2), CMVpp65, C-MYC epitope tag, Cripto, CS1 (also called CD2 subset 1 or CRACC or SLAMF7 or CD319 or 19A24), CSF2RA (GM-CSFR-alpha), C-type lectin domain family 12 member A (CLEC12A), C-type lectin-like molecule-1 (CLL-1 or CLECL1), cyclin B1, cytochrome P450 IB 1 (CYP1B 1), DLL3, EBV-EBNA3c, EGF-bke module-containing mucin-like hormone receptor-like 2 (EMR2), elongation factor 2 variant (ELF2M), ephrin B2, ephrin type A receptor 2 (EphA2), epidermal growth factor receptor (EGFR), epidermal growth factor receptor variant III (EGFRviii), epithelial cell adhesion molecule (EPCAM), ERG, ETS translocation-variant gene 6 located on chromosome 12p (ETV6-AML), Fc fragment of IgA receptor (FCAR or CD89), Fc receptor-like 5 (FCRL5), fibroblast activation protein alpha (FAP), FITC, Fms-like tyrosine kinase 3 (FLT3), folate receptor alpha (FRa or FR1), folate receptor beta (FRb), follicle-stimulating hormone receptor ( FSHR), Fos-related antigen 1, fucosyl-GMl, G protein-coupled receptor class C group 5 member D (GPRC5D), G protein-coupled receptor 20 (GPR20), GAD, ganglioside G2 (GD2), ganglioside GD3 (aNeu5Ac(2-8)aNeu5Ac(2-3)bDGalp(l-4)bDGlcp(ll)Cer), ganglioside GM3 (aNeu5Ac(2-3)bDClalp(l-4)bDGlcp(ll)Cer), GD3, GFR alpha 4, glycoprotein 100 (gplOO), glypican-3 (GPC3), gonadotropin hormone receptor (CGHR or GR), GpA33, GpNMB, GPRC5D, guanylyl cyclase C (GCC), heat shock protein 70-2 mutant (muthsp70-2), hepatitis A virus cellular receptor 1 (HAVCR1), hexasaccharide moiety of globoH glycoceramide (GloboH), high molecular weight melanoma-associated antigen (HMWMAA), HIV-1 envelope glycoprotein, HLA, HLA-DOA, HLA-A, HLA-A2, HLA-B, HLA-C, HLA-DM, HLA-DOB, HLA-DP, HLA-DQ, HLA-DR, HLA-G, HTLV-1-Tax, human papillomavirus E6 (HPV E6), human papillomavirus E7 (HPV E7), human telomerase reverse transcriptase (hTERT), IgE, IL13Ra2, IL1 lRa, immunoglobulin lambda-like polypeptide 1 (IGLL1), influenza A hemagglutinin (HA), insulin-like growth factor 1 receptor (IGF-I receptor), interleukin-11 receptor alpha (IL-llRa), interleukin-13 receptor subunit alpha-2 (IL-13Ra2 or CD213A2), intestinal carboxylesterase, KIT (CD117), KSHV K8.1, KSHV-gH, LAMP1, legumain, leukocyte immunoglobulin-like receptor subfamily A member 2 (LILRA2), leukocyte-associated immunoglobulin-like receptor 1 (LAIR1), luteinizing hormone receptor (LHR), Lewis (Y) antigen, Lewis Ag, Livl, Locus K9 (LY6K), small conductance chloride channel, lymphocyte antigen 6 complex, lymphocyte antigen 75 (LY75), lymphocyte-specific protein tyrosine kinase (LCK), mammary differentiation antigen (NY-BR-1), melanoma antigen 1 recognized by T cells (MelanA or MARTI), melanoma-associated antigen 1 (MAGE-A1), melanoma cancer testis antigen-1 (MAD-CT-1), melanoma cancer testis antigen-2 (MAD-CT-2), melanoma inhibitor of apoptosis (ML-IAP), mesothelin, MPL, mucin 1 cell surface associated (MUC1), N-acetylglucosaminyl-transferase V (NA17), nectin-4, neural cell adhesion molecule (NCAM), NKG2D, NYBR1, O-acetyl-GD2 ganglioside (OAcGD2), olfactory receptor 51E2 (OR51E2), oncogene fusion protein (bcr-abl) consisting of breakpoint cluster region (BCR) and Abelson murine leukemia viral oncogene homolog 1 (Abl), P53 mutant, paired box protein Pax-3 (PAX3), paired box protein Pax-5 (PAX5), pannexin 3 (PANX3), PDL1, P-glycoprotein, placenta-specific 1 (PLAC1), platelet-derived growth factor receptor beta (PDGFR-beta), polysialic acid, proacrosin-binding protein sp32 (OY-TES1), prostase, prostate cancer tumor antigen-1 (PCT Al or galectin 8), prostate stem cell antigen (PSCA), prostate-specific membrane antigen (PSMA), prostatic acid phosphatase (PAP), prostein, protease serine 21 (testisin or PRSS21), proteasome (prosomal macropain) subunit beta type 9 (LMP2), PTK7, RasG12V, Ras homolog family member C (RhoC), rat sarcoma (Ras) mutant, receptor for advanced glycation end products (RAGE-1), receptor tyrosine kinase-like orphan receptor 1 (ROR1), receptor tyrosine-protein kinase ERBB2 or Her-22 / neu, renal ubiquitous 1 (RU1), renal ubiquitous 2 (RU2), sarcoma translocation breakpoint, serine 2 (TMPRSS2) ETS fusion gene, sialyl Lewis adhesion molecule (sLe), SLAMF4, SLAMF6, Slea (CA19.9 or sialyl Lewis antigen), sperm Subset protein 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 gamma alternative reading frame protein (TARP), TCR-beta 1 chain, TCR-beta 2 chain, TCR-delta chain, TCR gamma chain, TCR gamma-delta, telomerase, TGF-beta R2, antigen recognized by TNT antibodies, thyroid-stimulating hormone receptor (TSHR), Timl- / HVCR1, tissue factor 1 (TF1), Tn ag, Tn antigen ((Tn Ag) or (GalNAca-Ser / Thr)), TNF receptor family member B-cell maturation (BCMA), transglutaminase 5 (TGS5), transmembrane protease, TROP2, tumor endothelial marker 1 (TEM1 / CD248), tumor endothelial marker 7-related (TEM7R), tumor protein p53 (p53), tumor-associated glycoprotein 72 (TAG72), tyrosinase, tyrosinase-related protein 2 (TRP-2), uroplakin 2 (UPK2), vascular endothelial growth factor receptor 2 (VEGFR2), V-myc avian myelocytomatosis viral oncogene neuroblastoma-derived homolog (MYCN), Wilms tumor protein (WT1), or X antigen family member 1A (XAGE1). In some embodiments, the targeting moiety binds to CD7. In some embodiments, the targeting moiety binds to CD8.

[0147] In some embodiments, the targeting moiety binds to a target present on a cell, such as an immune cell. In some embodiments, the cell is an immune cell, for example, but not limited to, a T cell, a B cell, a NK cell, a dendritic cell, a neutrophil, a macrophage, a cancer cell, or, for example, a CD3+ T cell, a CD4+ T cell, a CD7+ T cell, a CD8+ T cell, a CD19+ B cell, a CD19+ cancer cell, a CD20+ B cell, a CD20+ cancer cell, a CD30+ lung epithelial cell, a CD34+ hematopoietic stem cell, a CD105+ endothelial cell, a CD105+ hematopoietic stem cell, a CD117+ hematopoietic stem cell, a CD133+ cancer cell, an EpCAM+ cancer cell, a GluA2+ neuron, a GluA4+ neuron, a hematopoietic stem cell, a hepatocyte, a Her2 / Neu+ cancer cell, an NKG2D+ natural killer cell, a SLC1A3+ astrocyte, or a SLC7A10+ adipocyte. In some embodiments, the cell is a T cell. In some embodiments, the cells are B cells. In some embodiments, the cells are CD7+ T cells and / or CD8+ T cells.

[0148] In some embodiments, the targeting moiety (polypeptide) is capable of binding to CD7.

[0149] In some embodiments, the polypeptide binds to CD7. In some embodiments, the polypeptide that binds to CD7 is an antibody that binds to non-human primate CD7. In some embodiments, the polypeptide that binds to CD7 is an antibody that binds to human CD7. The sequence of human CD7 (UniProtKB P09564) is as follows (SEQ ID NO: 33): MAGPPRLLLLPLLLALARGLPGALAAQEVQQSPHCTTVPVGASVNITCSTSGGLRGIYLRQLGPQPQDIIYYEDGVVPTTDRRFRGRIDFSGSQDNLTITMHRLQLSDTGTYTCQAITEVNVYGSGTLVLVTEEQSQGWHRCSDAPPRASALPAPPTGSALPDPQTASALPDPPAASALPAALAVISFLLGLGLGVACVLARTQIKKLCSWRDKNSAACVVYEDMSHSRCNTLSSPNQYQ (SEQ ID NO: 33).

[0150] In some embodiments, the CD7 to which the polypeptide binds is expressed on the surface of a cell. In some embodiments, the cell is an immune cell. In some embodiments, the immune cell is a CD7+ T cell, a CD4+ T cell, a CD8+ T cell, a NK cell, an alpha-beta T cell, a gamma-delta T cell, a lymphoid progenitor cell, a hematopoietic stem cell, a myeloid cell, a monocyte, a macrophage, a central memory T cell, an effector memory T cell, a stem cell-like memory T cell, a naive T cell, an activated T cell, a regulatory T cell (TReg), a terminally differentiated effector memory T cell (TEMRA), a resident memory T cell (TRM), or a CD8+CCR7+ T cell.

[0151] In some embodiments, the antibody comprises an Fc region. The Fc region can be linked to the heavy or light chain of the antibody. In some embodiments, the Fc region is an IgG Fc. In some embodiments, the IgG is selected from IgG1, IgG2, IgG3, or IgG4. In some embodiments, the IgG fc is an IgG1 Fc. In some embodiments, the antibody comprises the Fc constant region of SEQ ID NO: 34, as set forth below. ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 34)

[0152] In some embodiments, the IgG fc is an IgG2 Fc. In some embodiments, the antibody comprises the Fc constant region of SEQ ID NO: 71, as set forth below. STKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 71)

[0153] In some embodiments, the IgG fc is an IgG4 Fc. In some embodiments, the antibody comprises the Fc constant region of SEQ ID NO: 72, as set forth below. STKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK (SEQ ID NO: 72)

[0154] In some embodiments, provided herein are polypeptides (e.g., CD7-binding polypeptides). In some embodiments, provided herein are antibodies (e.g., anti-CD7 antibodies). In some embodiments, the antibody is a recombinant antibody that binds to CD7. In some embodiments, the CD7 protein is a human CD7 protein. In some embodiments, the CD7 protein is a non-human CD7 protein (e.g., mouse, rat, pig, dog, non-human primate). As used herein, the term "recombinant antibody" refers to an antibody that is not naturally occurring. In some embodiments, the term "recombinant antibody" refers to an antibody that has not been isolated from a human subject.

[0155] In some embodiments, an antibody or antigen-binding fragment thereof is provided, wherein the antibody or antibody fragment comprises a peptide selected from the table below, which shows the CDRs according to Chothia numbering: [Table 1]

[0156] In some embodiments, an antibody or antigen-binding fragment thereof is provided, wherein the antibody or antibody fragment comprises a peptide selected from the table below, which shows the CDRs according to Kabat numbering: [Table 2]

[0157] In some embodiments, an antibody or antigen-binding fragment thereof is provided, wherein the antibody or antibody fragment comprises a peptide selected from the table below, which shows the CDRs based on IMGT numbering: [Table 3]

[0158] In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises a heavy chain or light chain CDR provided in the table above. In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises a heavy chain or light chain CDR provided in the table above and binds to non-human primate CD7. In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises a heavy chain or light chain CDR provided in the table above and binds to human CD7. In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises a light chain CDR having a sequence selected from SEQ ID NOs: 38-40. In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises a light chain CDR having the sequence of SEQ ID NO: 38. In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises a light chain CDR having the sequence of SEQ ID NO: 39. In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises a light chain CDR having the sequence of SEQ ID NO: 40. In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises a heavy chain CDR having a sequence selected from SEQ ID NOs: 35-37. In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises a heavy chain CDR having the sequence of SEQ ID NO: 35. In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises a heavy chain CDR having the sequence of SEQ ID NO: 36. In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises a heavy chain CDR having the sequence of SEQ ID NO: 37. The CDRs referred to in embodiments throughout this specification can be interchanged with CDRs characterized by different formats, such as Kabat and IMGT.

[0159] In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises a light chain variable region having LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the sequence of SEQ ID NO: 38, LCDR2 has the sequence of SEQ ID NO: 39, and LCDR3 has the sequence of SEQ ID NO: 40.

[0160] In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises a light chain variable region having LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the sequence of SEQ ID NO: 46, LCDR2 has the sequence of YA, and LCDR3 has the sequence of SEQ ID NO: 40.

[0161] In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises a heavy chain variable region having HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the sequence of SEQ ID NO: 35, HCDR2 has the sequence of SEQ ID NO: 36, and HCDR3 has the sequence of SEQ ID NO: 37.

[0162] In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises a heavy chain variable region having HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the sequence of SEQ ID NO: 41, HCDR2 has the sequence of SEQ ID NO: 42, and HCDR3 has the sequence of SEQ ID NO: 37.

[0163] In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises a heavy chain variable region having HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the sequence of SEQ ID NO: 43, HCDR2 has the sequence of SEQ ID NO: 44, and HCDR3 has the sequence of SEQ ID NO: 45.

[0164] In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises (i) a light chain having any one of the above-listed combinations of LCDR1, LCDR2, and LCDR3 sequences, and (ii) a heavy chain having any one of the above-listed combinations of HCDR1, HCDR2, and HCDR3 sequences.

[0165] Different CDR motifs can be combined in any combination, including those not shown in the table above. For example, the following embodiments are provided as non-limiting examples of such combinations.

[0166] In some embodiments, the polypeptide, antibody, or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 38, the light chain CDR2 sequence has the amino acid sequence of SEQ ID NO: 39, and the light chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 40; and (ii) a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 35, the heavy chain CDR2 sequence has the amino acid sequence of SEQ ID NO: 36, and the heavy chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 37, or a variant of any of the foregoing.

[0167] In some embodiments, the polypeptide, antibody, or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 38, the light chain CDR2 sequence has the amino acid sequence of SEQ ID NO: 39, and the light chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 40; and (ii) a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 41, the heavy chain CDR2 sequence has the amino acid sequence of SEQ ID NO: 42, and the heavy chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 37, or a variant of any of the foregoing.

[0168] In some embodiments, the polypeptide, antibody, or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 46, the light chain CDR2 sequence has the amino acid sequence of YA, and the light chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 40; and (ii) a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 43, the heavy chain CDR2 sequence has the amino acid sequence of SEQ ID NO: 44, and the heavy chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 45, or a variant of any of the foregoing.

[0169] In some embodiments, the light chain variable region CDR1 is replaced with any of other light chain CDR1 sequences. In some embodiments, the light chain variable region CDR2 is replaced with any of other light chain CDR2 sequences. In some embodiments, the light chain variable region CDR3 is replaced with any of other light chain CDR3 sequences. In some embodiments, the heavy chain variable region CDR1 is replaced with any of other heavy chain CDR1 sequences. In some embodiments, the heavy chain variable region CDR2 is replaced with any of other heavy chain CDR2 sequences. In some embodiments, the heavy chain variable region CDR3 is replaced with any of other heavy chain CDR3 sequences.

[0170] In some embodiments, the polypeptide comprises a heavy chain variable region peptide having one of the following sequences, or a variant thereof: [Table 4]

[0171] In some embodiments, the polypeptide comprises a light chain variable region peptide having one of the following sequences, or a variant thereof: [Table 5]

[0172] In some embodiments, the polypeptide, antibody, or antigen-binding fragment thereof comprises V of SEQ ID NO:47 H In some embodiments, the polypeptide, antibody, or antigen-binding fragment thereof comprises a peptide selected from the group consisting of V of SEQ ID NO:48. L In some embodiments, the polypeptide, antibody, or antigen-binding fragment thereof comprises a V H Peptides and V L Contains peptides, V H The peptide comprises the sequence of SEQ ID NO: 47, or a variant thereof, and L The peptide comprises the sequence of SEQ ID NO: 48, or a variant thereof. In some embodiments, the polypeptide, antibody, or antigen-binding fragment thereof comprises V H Peptides and V L Contains peptides, V H The peptide comprises the sequence of SEQ ID NO: 47, or a variant thereof, and L The peptide comprises the sequence of SEQ ID NO: 48, or a variant thereof, and the polypeptide, antibody, or antigen-binding fragment thereof binds to non-human primate CD7. In some embodiments, the polypeptide, antibody, or antigen-binding fragment thereof binds to V H Peptides and V L Contains peptides, V H The peptide comprises the sequence of SEQ ID NO: 47, or a variant thereof, and L The peptide comprises the sequence of SEQ ID NO: 48, or a variant thereof, and the polypeptide, antibody, or antigen-binding fragment thereof binds to human CD7. H The peptide comprises the sequence of SEQ ID NO: 47, L The peptide comprises the sequence of SEQ ID NO:48.

[0173] The VH and VL sequences may be in any format, including, but not limited to, an scFv format in which the VH and VL regions are linked by a peptide linker. Examples of peptide linkers that may be used to link the various peptides provided herein include, but are not limited to, (GGGGS) n(SEQ ID NO: 49), wherein each n is independently 1 to 5. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 3. In some embodiments, n is 4. In some embodiments, n is 5. In some embodiments, the variable regions are not linked by a peptide linker. In some embodiments, the polypeptide comprises SEQ ID NO: 47 and SEQ ID NO: 48.

[0174] In some embodiments, the VH and VL polypeptides are linked to an Fc region. In some embodiments, the Fc region is as provided herein. In some embodiments, the Fc region comprises the amino acid sequence of SEQ ID NO:34, SEQ ID NO:71, or SEQ ID NO:72, as provided herein. A heavy chain can be linked to an Fc region as provided herein. Non-limiting mutations within the Fc region are provided herein. In some embodiments, the Fc region further comprises a transmembrane domain. Examples of transmembrane domains include, but are not limited to, a CD8 or CD28 ("CD8 / CD28") transmembrane domain. In some embodiments, the Fc region further comprises a CD8 transmembrane domain. In some embodiments, the Fc region further comprises a CD28 transmembrane domain. In some embodiments, an Fc region comprising a transmembrane domain further comprises an Env integration motif. In some embodiments, an Fc region comprising a CD8 / CD28 transmembrane domain further comprises an Env integration motif. In some embodiments, the VH and VL polypeptides provided herein are linked to an Fc region comprising a transmembrane domain. In some embodiments, the VH and VL polypeptides provided herein are linked to an Fc region comprising a CD8 / CD28 transmembrane domain. In some embodiments, the VH and VL polypeptides provided herein are linked to an Fc region comprising a CD8 / CD28 transmembrane domain and an Env integration motif. In some embodiments, the VH and VL polypeptides provided herein linked to an Fc region comprising a CD8 / CD28 transmembrane domain are anchored to the plasma membrane on the surface of a cell. In some embodiments, the cell is an immune cell, such as those provided herein. In some embodiments, a VH having the sequence set forth in SEQ ID NO: 47 and a VL having the sequence set forth in SEQ ID NO: 48 are linked to an Fc region comprising a transmembrane domain. In some embodiments, a VH having the sequence set forth in SEQ ID NO: 47 and a VL having the sequence set forth in SEQ ID NO: 48 are linked to an Fc region comprising a CD8 / CD28 transmembrane domain.In some embodiments, a VH having the sequence set forth in SEQ ID NO: 47 and a VL having the sequence set forth in SEQ ID NO: 48 are linked to an Fc region comprising a CD8 / CD28 transmembrane domain and an Env integration motif. In some embodiments, a VH having the sequence set forth in SEQ ID NO: 47 and a VL having the sequence set forth in SEQ ID NO: 48 linked to an Fc region comprising a CD8 / CD28 transmembrane domain are anchored to the plasma membrane on the surface of a cell. In some embodiments, the cell is an immune cell, such as those provided herein.

[0175] In some embodiments, a V comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO:47. H peptides, and V comprising a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO:48. L In some embodiments, the peptide is linked to an Fc region comprising a transmembrane domain. In some embodiments, the V comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 47. H peptides, and V comprising a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO:48. L In some embodiments, the peptide is linked to an Fc region comprising a CD8 / CD28 transmembrane domain. In some embodiments, the V comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 47. Hpeptides, and V comprising a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO:48. L The peptide is linked to an Fc region comprising a CD8 / CD28 transmembrane domain and an Env integration motif. In some embodiments, a V peptide comprising a sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 47 linked to an Fc region comprising a CD8 / CD28 transmembrane domain. H peptides, and V comprising a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO:48. L The peptide is anchored to the plasma membrane on the surface of the cell. In some embodiments, the cell is an immune cell, such as those provided herein.

[0176] In some embodiments, the polypeptide is H Peptides and V L Contains peptides, V H The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 47, and L The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO:48.

[0177] In some embodiments, the polypeptide is H Peptides and V L Contains peptides, V HThe peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 47, and L The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 48, with the proviso that V H Peptides and V L The peptide comprises a light chain CDR having the sequence of SEQ ID NO: 38-40 and / or a heavy chain CDR having the sequence of SEQ ID NO: 35-37. H Peptides and V L Contains peptides, V H The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 47, and L The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 48, with the proviso that V H Peptides and V L The peptide comprises a light chain CDR1 having the sequence of SEQ ID NO: 38, a light chain CDR2 having the sequence of SEQ ID NO: 39, a light chain CDR3 having the sequence of SEQ ID NO: 40, and / or a heavy chain CDR1 having the sequence of SEQ ID NO: 35, a heavy chain CDR2 having the sequence of SEQ ID NO: 36, and a heavy chain CDR3 having the sequence of SEQ ID NO: 37. In some embodiments, V H or V L The CDRs in the chains are as shown in the combinations provided herein.

[0178] In some embodiments, the polypeptide is H Peptides and V L Contains peptides, V HThe peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 47, and L The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 48, with the proviso that V L The peptide comprises an LCDR1 having the sequence of SEQ ID NO: 38, an LCDR2 having the sequence of SEQ ID NO: 39, and an LCDR3 having the sequence of SEQ ID NO: 40, H The peptide comprises an HCDR1 having the sequence of SEQ ID NO:35, an HCDR2 having the sequence of SEQ ID NO:36, and an HCDR3 having the sequence of SEQ ID NO:37.

[0179] In some embodiments, the polypeptide is H Peptides and V L Contains peptides, V H The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 47, and L The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 48, with the proviso that V L The peptide comprises an LCDR1 having the sequence of SEQ ID NO: 38, which contains at most one conservative amino acid substitution; an LCDR2 having the sequence of SEQ ID NO: 39, which contains at most one conservative amino acid substitution; and an LCDR3 having the sequence of SEQ ID NO: 40, which contains at most one conservative amino acid substitution; HThe peptide comprises an HCDR1 having the sequence of SEQ ID NO: 35, which contains at most one conservative amino acid substitution; an HCDR2 having the sequence of SEQ ID NO: 36, which contains at most one conservative amino acid substitution; and an HCDR3 having the sequence of SEQ ID NO: 37, which contains at most one conservative amino acid substitution.

[0180] In some embodiments, the polypeptide is H Peptides and V L Contains peptides, V H The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 47, and L The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 48, with the proviso that V H Peptides and V L The peptide comprises a light chain CDR1 having the sequence of SEQ ID NO: 38, a light chain CDR2 having the sequence of SEQ ID NO: 39, a light chain CDR1 having the sequence of SEQ ID NO: 40, and / or a heavy chain CDR1 having the sequence of SEQ ID NO: 41, a heavy chain CDR2 having the sequence of SEQ ID NO: 42, and a heavy chain CDR3 having the sequence of SEQ ID NO: 37. In some embodiments, V H or V L The CDRs in the chains are as shown in the combinations provided herein.

[0181] In some embodiments, the polypeptide is H Peptides and V L Contains peptides, V H The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 47, and LThe peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 48, with the proviso that V L The peptide comprises an LCDR1 having the sequence of SEQ ID NO: 38, an LCDR2 having the sequence of SEQ ID NO: 39, and an LCDR3 having the sequence of SEQ ID NO: 40, H The peptide comprises an HCDR1 having the sequence of SEQ ID NO: 41, an HCDR2 having the sequence of SEQ ID NO: 42, and an HCDR3 having the sequence of SEQ ID NO: 37.

[0182] In some embodiments, the polypeptide is H Peptides and V L Contains peptides, V H The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 47, and L The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 48, with the proviso that V L The peptide comprises an LCDR1 having the sequence of SEQ ID NO: 38, which contains at most one conservative amino acid substitution; an LCDR2 having the sequence of SEQ ID NO: 39, which contains at most one conservative amino acid substitution; and an LCDR3 having the sequence of SEQ ID NO: 40, which contains at most one conservative amino acid substitution; H The peptide comprises an HCDR1 having the sequence of SEQ ID NO: 41, which contains at most one conservative amino acid substitution; an HCDR2 having the sequence of SEQ ID NO: 42, which contains at most one conservative amino acid substitution; and an HCDR3 having the sequence of SEQ ID NO: 37, which contains at most one conservative amino acid substitution.

[0183] In some embodiments, the polypeptide isH Peptides and V L Contains peptides, V H The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 47, and L The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 48, with the proviso that V H Peptides and V L The peptide comprises a light chain CDR1 having the sequence of SEQ ID NO: 46, a light chain CDR2 having the sequence of YA, a light chain CDR1 having the sequence of SEQ ID NO: 40, and / or a heavy chain CDR1 having the sequence of SEQ ID NO: 43, a heavy chain CDR2 having the sequence of SEQ ID NO: 44, and a heavy chain CDR3 having the sequence of SEQ ID NO: 45. In some embodiments, V H or V L The CDRs in the chains are as shown in the combinations provided herein.

[0184] In some embodiments, the polypeptide is H Peptides and V L Contains peptides, V H The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 47, and L The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 48, with the proviso that V L The peptide comprises an LCDR1 having the sequence of SEQ ID NO: 46, an LCDR2 having the sequence of YA, and an LCDR3 having the sequence of SEQ ID NO: 40, and V H The peptide comprises an HCDR1 having the sequence of SEQ ID NO:43, an HCDR2 having the sequence of SEQ ID NO:44, and an HCDR3 having the sequence of SEQ ID NO:45.

[0185] In some embodiments, the polypeptide is H Peptides and V L Contains peptides, V H The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 47, and L The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 48, with the proviso that V L The peptide comprises an LCDR1 having the sequence of SEQ ID NO: 46, which contains at most one conservative amino acid substitution; an LCDR2 having the sequence of YA, which contains at most one conservative amino acid substitution; and an LCDR3 having the sequence of SEQ ID NO: 40, which contains at most one conservative amino acid substitution; H The peptide comprises an HCDR1 having the sequence of SEQ ID NO: 43, which contains at most one conservative amino acid substitution; an HCDR2 having the sequence of SEQ ID NO: 44, which contains at most one conservative amino acid substitution; and an HCDR3 having the sequence of SEQ ID NO: 45, which contains at most one conservative amino acid substitution.

[0186] In some embodiments, the polypeptide is H Peptides and V L Contains peptides, V H The peptide comprises the sequence of SEQ ID NO: 47, L The peptide comprises the sequence of SEQ ID NO:48.

[0187] In some embodiments, the polypeptides provided herein bind to non-human primate CD7. In some embodiments, the polypeptides provided herein bind to human CD7.

[0188] As provided herein, the different polypeptides described herein (V H or V L ) may be linked by a peptide linker or may not be linked by a peptide linker but instead form a contiguous sequence. In some embodiments, the peptide linker is (GGGGS) n (SEQ ID NO: 49), wherein each n is independently 1 to 5. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 3. In some embodiments, n is 4. In some embodiments, n is 5. The linked peptide format comprises V H -ZV L or V L -ZV H wherein Z is a peptide linker. In some embodiments, Z is (GGGGS) n (SEQ ID NO: 49), wherein each n is independently 1 to 5.

[0189] In some embodiments, V L -ZV H The polypeptide comprising a connecting peptide of the formula: comprises a heavy chain variable region set forth in SEQ ID NO: 47, linked to a light chain variable region set forth in SEQ ID NO: 48 via the linker sequence GGGGSGGGGSGGGGSGGGGS (SEQ ID NO: 50). In some embodiments, the polypeptide comprises a V H V connected to L The polypeptide comprising has the sequence shown below: DILLTQSPAILSVSPGERVSFSCRASQSIGTSIHWYQQRTNDSPRLLIKYASESISGIPSRFSGSGSGTDFTLSINSVESEDIADYYCQQSNSWPTTFGGGTKLEIKR GGGGSGGGGSGGGGSGGGGSQVQLQQPGAELVKPGASVKLSCKASGYPFTSYWIHWVKQRPGRGLEWLGRIDPNSGDTKYNEKFKNKATLTVDKSSTTAYMQLSSLTS EDSAVYYCARSPYYSNDNSMDYWGQGTSVTVSS (SEQ ID NO: 51).

[0190] In some embodiments, the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 51. In some embodiments, the polypeptide comprises a sequence that is at least 90% identical to the sequence of SEQ ID NO: 51. In some embodiments, the polypeptide comprises a sequence that is at least 95% identical to the sequence of SEQ ID NO: 51. In some embodiments, the polypeptide comprises a sequence that is at least 99% identical to the sequence of SEQ ID NO: 51. In some embodiments, the polypeptide comprises the sequence set forth in SEQ ID NO: 51. In some embodiments, the polypeptide set forth in SEQ ID NO: 51 is an antibody or antigen-binding fragment thereof. In some embodiments, the antibody is an anti-CD7 antibody.

[0191] In some embodiments, V H -ZV L The polypeptide comprising a connecting peptide of the formula: comprises a light chain variable region set forth in SEQ ID NO: 48, linked to a heavy chain variable region set forth in SEQ ID NO: 49 via the linker sequence GGGGSGGGGSGGGGSGGGGS (SEQ ID NO: 50). In some embodiments, the polypeptide comprises a V L V connected to H The polypeptide comprising has the sequence shown below: QVQLQQPGAELVKPGASVKLSCKASGYPFTSYWIHWVKQRPGRGLEWLGRIDPNSGDTKYNEKFKNKATLTVDKSSTTAYMQLSSLTSEDSAVYYCARSPYYSNDNSMDYWGQGTSVTVSSGGGGSGGGGSGGGGSGGGGSDILLTQSPAILSVSPGERVSFSCRASQSIGTSIHWYQQRTNDSPRLLIKYASESISGIPSRFSGSGSGTDFTLSINSVESEDIADYYCQQSNSWPTTFGGGTKLEIKR (SEQ ID NO: 52)

[0192] In some embodiments, the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 52. In some embodiments, the polypeptide comprises a sequence that is at least 90% identical to the sequence of SEQ ID NO: 52. In some embodiments, the polypeptide comprises a sequence that is at least 95% identical to the sequence of SEQ ID NO: 52. In some embodiments, the polypeptide comprises a sequence that is at least 99% identical to the sequence of SEQ ID NO: 52. In some embodiments, the polypeptide set forth in SEQ ID NO: 52 is an antibody or antigen-binding fragment thereof. In some embodiments, the antibody is an anti-CD7 antibody. In some embodiments, the anti-CD7 antibody binds to non-human primate CD7. In some embodiments, the anti-CD7 antibody binds to human CD7.

[0193] In some embodiments, the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 51 and comprises an Fc region such as those provided herein. In some embodiments, the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 51 and comprises an Fc region such as those provided herein and a transmembrane domain such as those provided herein. In some embodiments, the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 51, and comprises an Fc region such as those provided herein, and a CD8 / CD28 transmembrane domain. In some embodiments, the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 51, and comprises an Fc region such as those provided herein, a transmembrane domain such as those provided herein, and an Env integration motif.

[0194] In some embodiments, the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 52 and comprises an Fc region such as those provided herein. In some embodiments, the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 52 and comprises an Fc region such as those provided herein and a transmembrane domain such as those provided herein. In some embodiments, the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 52 and comprises an Fc region such as those provided herein, and a CD8 / CD28 transmembrane domain. In some embodiments, the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 52 and comprises an Fc region such as those provided herein, a transmembrane domain such as those provided herein, and an Env integration motif.

[0195] As provided herein, polypeptides, antibodies, or antigen-binding fragments thereof may be sequence variants.

[0196] The polypeptide or antibody sequence can be modified to produce a human IgG antibody. The sequences provided herein can be modified to produce other types of antibodies by conversion. The CDRs can also be linked to other antibodies, proteins, or molecules to create antibody fragments that bind CD7.

[0197] In some embodiments, a polypeptide or antibody provided herein is a targeting moiety on the surface of an engineered viral particle. In some embodiments, the targeting moiety enables binding to a target cell. In some embodiments, the targeting moiety is a CD7-binding moiety, such as a polypeptide or antibody provided herein. In some embodiments, the targeting moiety comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 51. In some embodiments, the targeting moiety comprises a sequence that is at least 90% identical to the sequence of SEQ ID NO: 51. In some embodiments, the targeting moiety comprises a sequence that is at least 95% identical to the sequence of SEQ ID NO: 51. In some embodiments, the targeting moiety comprises a sequence that is at least 99% identical to the sequence of SEQ ID NO: 51. In some embodiments, the targeting moiety comprises the sequence set forth in SEQ ID NO: 51. In some embodiments, the targeting moiety set forth in SEQ ID NO: 51 is an antibody or an antigen-binding fragment thereof. In some embodiments, the targeting moiety is an anti-CD7 antibody.

[0198] In some embodiments, a polypeptide or antibody provided herein is a targeting moiety on the surface of an engineered viral particle. In some embodiments, the engineered viral particle is a pseudotyped virus-like particle. In some embodiments, the targeting moiety enables binding to a target cell. In some embodiments, the targeting moiety is a CD7-binding moiety, such as a polypeptide or antibody provided herein. In some embodiments, the targeting moiety comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 52. In some embodiments, the targeting moiety comprises a sequence that is at least 90% identical to the sequence of SEQ ID NO: 52. In some embodiments, the targeting moiety comprises a sequence that is at least 95% identical to the sequence of SEQ ID NO: 52. In some embodiments, the targeting moiety comprises a sequence that is at least 99% identical to the sequence of SEQ ID NO: 52. In some embodiments, the targeting moiety comprises the sequence set forth in SEQ ID NO: 52. In some embodiments, the targeting moiety set forth in SEQ ID NO: 52 is an antibody or antigen-binding fragment thereof. In some embodiments, the targeting moiety is an anti-CD7 antibody. In some embodiments, the anti-CD7 antibody binds to non-human primate CD7. In some embodiments, the anti-CD7 antibody binds to human CD7.

[0199] In some embodiments, the polypeptide comprises a sequence having the sequence set forth in SEQ ID NO:51 and comprises an Fc region such as those provided herein. In some embodiments, the polypeptide comprises a sequence having the sequence set forth in SEQ ID NO:51 and comprises an Fc region such as those provided herein and a transmembrane domain such as those provided herein. In some embodiments, the polypeptide comprises a sequence having the sequence set forth in SEQ ID NO:51 and comprises an Fc region such as those provided herein and a CD8 / CD28 transmembrane domain. In some embodiments, the polypeptide comprises a sequence having the sequence set forth in SEQ ID NO:51 and comprises an Fc region such as those provided herein, a transmembrane domain such as those provided herein, and an Env integration motif.

[0200] In some embodiments, the polypeptide comprises a sequence having the sequence set forth in SEQ ID NO: 52 and comprises an Fc region such as those provided herein. In some embodiments, the polypeptide comprises a sequence having the sequence set forth in SEQ ID NO: 52 and comprises an Fc region such as those provided herein and a transmembrane domain such as those provided herein. In some embodiments, the polypeptide comprises a sequence having the sequence set forth in SEQ ID NO: 52 and comprises an Fc region such as those provided herein and a CD8 / CD28 transmembrane domain. In some embodiments, the polypeptide comprises a sequence having the sequence set forth in SEQ ID NO: 52 and comprises an Fc region such as those provided herein, a transmembrane domain such as those provided herein, and an Env integration motif.

[0201] In some embodiments, the targeting moiety (polypeptide) is capable of binding to CD8.

[0202] In some embodiments, the polypeptide binds to CD8. In some embodiments, the polypeptide binds to CD8-alpha. In some embodiments, the polypeptide binds to CD8-beta. In some embodiments, the polypeptide binds to a CD8 heterodimer. In some embodiments, the CD8 heterodimer comprises CD8-alpha and CD8-beta subunits. In some embodiments, the polypeptide binds to a CD8-alpha homodimer. In some embodiments, the polypeptide that binds to CD8 is an antibody that binds to non-human primate CD8. In some embodiments, the antibody that binds to non-human primate CD8 is an antibody that binds to non-human primate CD8-alpha. In some embodiments, the antibody that binds to non-human primate CD8 is an antibody that binds to non-human primate CD8-beta. In some embodiments, the antibody that binds to non-human primate CD8 is an antibody that binds to non-human primate CD8-alpha homodimer. In some embodiments, the antibody that binds to non-human primate CD8 is an antibody that binds to non-human primate CD8 heterodimer. In some embodiments, the polypeptide that binds to CD8 is an antibody that binds to human CD8. In some embodiments, the antibody that binds to human CD8 is an antibody that binds to human CD8-alpha. In some embodiments, the antibody that binds to human CD8 is an antibody that binds to human CD8-beta. In some embodiments, the antibody that binds to human CD8 is an antibody that binds to human CD8-alpha homodimer. In some embodiments, the antibody that binds to human CD8 is an antibody that binds to human CD8 heterodimer. The sequence of human CD8-alpha (UniProtKB Q8TAW8) is as follows (SEQ ID NO: 53): MALPVTALLLPLALLLHAARPSQFRVSPLDRTWNLGETVELKCQVLLSNPTSGCSWLFQPRGAAASPTFLLYLSQNKPKAAEGLDTQRFSGKRLGDTFVLTLSDFRRENEGCYFCSALSNSIMYFSHFVPVFLPAKPTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCNHRNRRRVCKCPRPVVKSGDKPSLSARYV (SEQ ID NO: 53).

[0203] The sequence of human CD8-beta (UniProtKB Q8TD28) is as follows (SEQ ID NO: 54): MRPRLWLLLAAQLTVLHGNSVLQQTPAYIKVQTNKMVMLSCEAKISLSNMRIYWLRQRQAPSSDSHHEFLALWDSAKGTIHGEEVEQEKIAVFRDASRFILNLTSVKPEDSGIYFCMIVGSPELTFGKGTQLSVVDFLPTTAQPTKKSTLKKRVCRLPRPETQKGPLCSPITLGLLVAGVLVLLVSLGVAIHLCCRRRRARLRFMKQLYK (SEQ ID NO: 54).

[0204] In some embodiments, the CD8 to which the polypeptide binds is expressed on the surface of a cell. In some embodiments, the cell is an immune cell. In some embodiments, the immune cell is a CD7+ T cell, a CD4+ T cell, a CD8+ T cell, a NK cell, an alpha-beta T cell, a gamma-delta T cell, a lymphoid progenitor cell, a hematopoietic stem cell, a myeloid cell, a monocyte, a macrophage, a central memory T cell, an effector memory T cell, a stem cell-like memory T cell, a naive T cell, an activated T cell, a regulatory T cell (TReg), a terminally differentiated effector memory T cell (TEMRA), a resident memory T cell (TRM), or a CD8+CCR7+ T cell. In some embodiments, the cell is a CD8+ T cell. In some embodiments, the cell is a CD8+ cell.

[0205] In some embodiments, the antibody comprises an Fc region. The Fc region can be linked to the heavy or light chain of the antibody. In some embodiments, the Fc region is an IgG Fc. In some embodiments, the IgG is selected from IgG1, IgG2, IgG3, or IgG4. In some embodiments, the IgG Fc is an IgG1 Fc. In some embodiments, the antibody comprises an Fc constant region as described below. ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 34)

[0206] In some embodiments, the IgG fc is an IgG2 Fc. In some embodiments, the antibody comprises the Fc constant region of SEQ ID NO: 71, as set forth below. STKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 71)

[0207] In some embodiments, the IgG fc is an IgG4 Fc. In some embodiments, the antibody comprises the Fc constant region of SEQ ID NO: 72, as set forth below. STKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK (SEQ ID NO: 72)

[0208] In some embodiments, provided herein are polypeptides (e.g., CD8-binding polypeptides). In some embodiments, provided herein are antibodies (e.g., anti-CD8 antibodies). In some embodiments, the antibody is a recombinant antibody that binds to CD8. In some embodiments, the CD8 protein is a human CD8 protein. In some embodiments, the CD8 protein is a non-human CD8 protein (e.g., mouse, rat, pig, dog, non-human primate). As used herein, the term "recombinant antibody" refers to an antibody that is not naturally occurring. In some embodiments, the term "recombinant antibody" refers to an antibody that has not been isolated from a human subject.

[0209] In some embodiments, an antibody or antigen-binding fragment thereof is provided, wherein the antibody or antibody fragment comprises a peptide selected from the table below, which shows the CDRs according to Chothia numbering: [Table 6]

[0210] In some embodiments, an antibody or antigen-binding fragment thereof is provided, wherein the antibody or antibody fragment comprises a peptide selected from the table below, which shows the CDRs according to Kabat numbering: [Table 7]

[0211] In some embodiments, an antibody or antigen-binding fragment thereof is provided, wherein the antibody or antibody fragment comprises a peptide selected from the table below, which shows the CDRs based on IMGT numbering: [Table 8]

[0212] In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises a heavy chain or light chain CDR provided in the table above. In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises a heavy chain or light chain CDR provided in the table above and binds to non-human primate CD8. In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises a heavy chain or light chain CDR provided in the table above and binds to human CD8. In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises a light chain CDR having a sequence selected from SEQ ID NOs: 58-60. In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises a light chain CDR having the sequence of SEQ ID NO: 58. In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises a light chain CDR having the sequence of SEQ ID NO: 59. In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises a light chain CDR having the sequence of SEQ ID NO: 60. In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises a heavy chain CDR having a sequence selected from SEQ ID NOs: 55-57. In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises a heavy chain CDR having the sequence of SEQ ID NO: 55. In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises a heavy chain CDR having the sequence of SEQ ID NO: 56. In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises a heavy chain CDR having the sequence of SEQ ID NO: 57. The CDRs referred to in embodiments throughout this specification can be interchanged with CDRs characterized by different formats, such as Kabat and IMGT.

[0213] In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises a light chain variable region having LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the sequence of SEQ ID NO: 58, LCDR2 has the sequence of SEQ ID NO: 59, and LCDR3 has the sequence of SEQ ID NO: 60.

[0214] In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises a light chain variable region having LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the sequence of SEQ ID NO: 66, LCDR2 has the sequence of LA, and LCDR3 has the sequence of SEQ ID NO: 60.

[0215] In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises a heavy chain variable region having HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the sequence of SEQ ID NO: 55, HCDR2 has the sequence of SEQ ID NO: 56, and HCDR3 has the sequence of SEQ ID NO: 57.

[0216] In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises a heavy chain variable region having HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the sequence of SEQ ID NO: 61, HCDR2 has the sequence of SEQ ID NO: 62, and HCDR3 has the sequence of SEQ ID NO: 57.

[0217] In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises a heavy chain variable region having HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the sequence of SEQ ID NO: 63, HCDR2 has the sequence of SEQ ID NO: 64, and HCDR3 has the sequence of SEQ ID NO: 65.

[0218] In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises (i) a light chain having any one of the above-listed combinations of LCDR1, LCDR2, and LCDR3 sequences, and (ii) a heavy chain having any one of the above-listed combinations of HCDR1, HCDR2, and HCDR3 sequences.

[0219] Different CDR motifs can be combined in any combination, including those not shown in the table above. For example, the following embodiments are provided as non-limiting examples of such combinations.

[0220] In some embodiments, the polypeptide, antibody, or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 58, the light chain CDR2 sequence has the amino acid sequence of SEQ ID NO: 59, and the light chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 60; and (ii) a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 55, the heavy chain CDR2 sequence has the amino acid sequence of SEQ ID NO: 56, and the heavy chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 57, or a variant of any of the foregoing.

[0221] In some embodiments, the polypeptide, antibody, or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 58, the light chain CDR2 sequence has the amino acid sequence of SEQ ID NO: 59, and the light chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 60; and (ii) a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 61, the heavy chain CDR2 sequence has the amino acid sequence of SEQ ID NO: 62, and the heavy chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 57, or a variant of any of the foregoing.

[0222] In some embodiments, the polypeptide, antibody, or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 66, the light chain CDR2 has the amino acid sequence of LA, and the light chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 60; and (ii) a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 63, the heavy chain CDR2 sequence has the amino acid sequence of SEQ ID NO: 64, and the heavy chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 65, or a variant of any of the foregoing.

[0223] In some embodiments, the light chain variable region CDR1 is replaced with any of other light chain CDR1 sequences. In some embodiments, the light chain variable region CDR2 is replaced with any of other light chain CDR2 sequences. In some embodiments, the light chain variable region CDR3 is replaced with any of other light chain CDR3 sequences. In some embodiments, the heavy chain variable region CDR1 is replaced with any of other heavy chain CDR1 sequences. In some embodiments, the heavy chain variable region CDR2 is replaced with any of other heavy chain CDR2 sequences. In some embodiments, the heavy chain variable region CDR3 is replaced with any of other heavy chain CDR3 sequences.

[0224] In some embodiments, the polypeptide comprises a heavy chain variable region peptide having one of the following sequences, or a variant thereof: [Table 9]

[0225] In some embodiments, the polypeptide comprises a light chain variable region peptide having one of the following sequences, or a variant thereof: [Table 10]

[0226] In some embodiments, the polypeptide, antibody, or antigen-binding fragment thereof comprises V of SEQ ID NO:67 H In some embodiments, the polypeptide, antibody, or antigen-binding fragment thereof comprises a peptide selected from the group consisting of V of SEQ ID NO:68. L In some embodiments, the polypeptide, antibody, or antigen-binding fragment thereof comprises a V H Peptides and V L Contains peptides, V H The peptide comprises the sequence of SEQ ID NO: 67, or a variant thereof, and L In some embodiments, the polypeptide, antibody, or antigen-binding fragment thereof comprises the sequence of V H Peptides and V L Contains peptides, V H The peptide comprises the sequence of SEQ ID NO: 67, or a variant thereof, and L The peptide comprises the sequence of SEQ ID NO: 68, or a variant thereof, and the polypeptide, antibody, or antigen-binding fragment thereof binds to non-human primate CD8. In some embodiments, the polypeptide, antibody, or antigen-binding fragment thereof binds to V H Peptides and V L Contains peptides, V H The peptide comprises the sequence of SEQ ID NO: 67, or a variant thereof, and L The peptide comprises the sequence of SEQ ID NO: 68, or a variant thereof, and the polypeptide, antibody, or antigen-binding fragment thereof binds to human CD8. H The peptide comprises the sequence of SEQ ID NO: 67, L The peptide comprises the sequence of SEQ ID NO:68.

[0227] The VH and VL sequences may be in any format, including, but not limited to, an scFv format in which the VH and VL regions are linked by a peptide linker. Examples of peptide linkers that may be used to link the various peptides provided herein include, but are not limited to, (GGGGS) n(SEQ ID NO: 49), wherein each n is independently 1 to 5. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 3. In some embodiments, n is 4. In some embodiments, n is 5. In some embodiments, the variable regions are not linked by a peptide linker. In some embodiments, the polypeptide comprises SEQ ID NO: 67 and SEQ ID NO: 68.

[0228] In some embodiments, the VH and VL polypeptides are linked to an Fc region. In some embodiments, the Fc region is as provided herein. As provided herein, a heavy chain can be linked to an Fc region. Non-limiting mutations within the Fc region are provided herein. In some embodiments, the Fc region further comprises a transmembrane domain. Examples of transmembrane domains include, but are not limited to, a CD8 / CD28 transmembrane domain. In some embodiments, the Fc region further comprises a CD8 or CD28 ("CD8 / CD28") transmembrane domain. In some embodiments, the Fc region further comprises a CD8 transmembrane domain. In some embodiments, the Fc region further comprises a CD28 transmembrane domain. In some embodiments, an Fc region comprising a transmembrane domain further comprises an Env integration motif. In some embodiments, an Fc region comprising a CD8 / CD28 transmembrane domain further comprises an Env integration motif. In some embodiments, the VH and VL polypeptides provided herein are linked to an Fc region comprising a transmembrane domain. In some embodiments, the VH and VL polypeptides provided herein are linked to an Fc region comprising a CD8 / CD28 transmembrane domain. In some embodiments, the VH and VL polypeptides provided herein are linked to an Fc region comprising a CD8 / CD28 transmembrane domain and an Env integration motif. In some embodiments, the VH and VL polypeptides provided herein linked to an Fc region comprising a CD8 / CD28 transmembrane domain are anchored to the plasma membrane on the surface of a cell. In some embodiments, the cell is an immune cell, such as those provided herein. In some embodiments, a VH having the sequence set forth in SEQ ID NO: 67 and a VL having the sequence set forth in SEQ ID NO: 68 are linked to an Fc region comprising a transmembrane domain. In some embodiments, a VH having the sequence set forth in SEQ ID NO: 67 and a VL having the sequence set forth in SEQ ID NO: 68 are linked to an Fc region comprising a CD8 / CD28 transmembrane domain. In some embodiments, a VH having the sequence set forth in SEQ ID NO: 67 and a VL having the sequence set forth in SEQ ID NO: 68 are linked to an Fc region comprising a CD8 / CD28 transmembrane domain and an Env integration motif.In some embodiments, a VH having the sequence set forth in SEQ ID NO: 67 and a VL having the sequence set forth in SEQ ID NO: 68 linked to an Fc region comprising a CD8 / CD28 transmembrane domain are anchored to the plasma membrane on the surface of a cell. In some embodiments, the cell is an immune cell, such as those provided herein.

[0229] In some embodiments, a V comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 67. H peptides, and V comprising a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 68. L In some embodiments, the peptide is linked to an Fc region comprising a transmembrane domain. In some embodiments, the V comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 67. H peptides, and V comprising a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 68. L In some embodiments, the peptide is linked to an Fc region comprising a CD8 / CD28 transmembrane domain. In some embodiments, the V comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 67. H peptides, and V comprising a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 68. LThe peptide is linked to an Fc region comprising a CD8 / CD28 transmembrane domain and an Env integration motif. In some embodiments, a V peptide comprising a sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 67 linked to an Fc region comprising a CD8 / CD28 transmembrane domain. H peptides, and V comprising a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 68. L The peptide is anchored to the plasma membrane on the surface of the cell. In some embodiments, the cell is an immune cell, such as those provided herein.

[0230] In some embodiments, the polypeptide is H Peptides and V L Contains peptides, V H The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 67, and L The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO:68.

[0231] In some embodiments, the polypeptide is H Peptides and V L Contains peptides, V H The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 67, and LThe peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 68, with the proviso that V H Peptides and V L The peptide comprises a light chain CDR having the sequence of SEQ ID NO: 58-60 and / or a heavy chain CDR having the sequence of SEQ ID NO: 55-57. H Peptides and V L Contains peptides, V H The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 67, and L The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 68, with the proviso that V H Peptides and V L The peptide comprises a light chain CDR1 having the sequence of SEQ ID NO: 58, a light chain CDR2 having the sequence of SEQ ID NO: 59, a light chain CDR3 having the sequence of SEQ ID NO: 60, and / or a heavy chain CDR1 having the sequence of SEQ ID NO: 55, a heavy chain CDR2 having the sequence of SEQ ID NO: 56, and a heavy chain CDR3 having the sequence of SEQ ID NO: 57. In some embodiments, V H or V L The CDRs in the chains are as shown in the combinations provided herein.

[0232] In some embodiments, the polypeptide is H Peptides and V L Contains peptides, V H The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 67, and LThe peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 68, with the proviso that V L The peptide comprises an LCDR1 having the sequence of SEQ ID NO: 58, an LCDR2 having the sequence of SEQ ID NO: 59, and an LCDR3 having the sequence of SEQ ID NO: 60, H The peptide comprises an HCDR1 having the sequence of SEQ ID NO:55, an HCDR2 having the sequence of SEQ ID NO:56, and an HCDR3 having the sequence of SEQ ID NO:57.

[0233] In some embodiments, the polypeptide is H Peptides and V L Contains peptides, V H The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 67, and L The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 68, with the proviso that V L The peptide comprises an LCDR1 having the sequence of SEQ ID NO: 58, which contains at most one conservative amino acid substitution; an LCDR2 having the sequence of SEQ ID NO: 59, which contains at most one conservative amino acid substitution; and an LCDR3 having the sequence of SEQ ID NO: 60, which contains at most one conservative amino acid substitution; H The peptide comprises an HCDR1 having the sequence of SEQ ID NO: 55, which contains at most one conservative amino acid substitution; an HCDR2 having the sequence of SEQ ID NO: 56, which contains at most one conservative amino acid substitution; and an HCDR3 having the sequence of SEQ ID NO: 57, which contains at most one conservative amino acid substitution.

[0234] In some embodiments, the polypeptide isH Peptides and V L Contains peptides, V H The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 67, and L The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 68, with the proviso that V H Peptides and V L The peptide comprises a light chain CDR1 having the sequence of SEQ ID NO: 58, a light chain CDR2 having the sequence of SEQ ID NO: 59, a light chain CDR3 having the sequence of SEQ ID NO: 60, and / or a heavy chain CDR1 having the sequence of SEQ ID NO: 61, a heavy chain CDR2 having the sequence of SEQ ID NO: 62, and a heavy chain CDR3 having the sequence of SEQ ID NO: 57. In some embodiments, V H or V L The CDRs in the chains are as shown in the combinations provided herein.

[0235] In some embodiments, the polypeptide is H Peptides and V L Contains peptides, V H The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 67, and L The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 68, with the proviso that V L The peptide comprises an LCDR1 having the sequence of SEQ ID NO: 58, an LCDR2 having the sequence of SEQ ID NO: 59, and an LCDR3 having the sequence of SEQ ID NO: 60, HThe peptide comprises an HCDR1 having the sequence of SEQ ID NO: 61, an HCDR2 having the sequence of SEQ ID NO: 62, and an HCDR3 having the sequence of SEQ ID NO: 57.

[0236] In some embodiments, the polypeptide is H Peptides and V L Contains peptides, V H The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 67, and L The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 68, with the proviso that V L The peptide comprises an LCDR1 having the sequence of SEQ ID NO: 58, which contains at most one conservative amino acid substitution; an LCDR2 having the sequence of SEQ ID NO: 59, which contains at most one conservative amino acid substitution; and an LCDR3 having the sequence of SEQ ID NO: 60, which contains at most one conservative amino acid substitution; H The peptide comprises an HCDR1 having the sequence of SEQ ID NO: 61, which contains at most one conservative amino acid substitution; an HCDR2 having the sequence of SEQ ID NO: 62, which contains at most one conservative amino acid substitution; and an HCDR3 having the sequence of SEQ ID NO: 57, which contains at most one conservative amino acid substitution.

[0237] In some embodiments, the polypeptide is H Peptides and V L Contains peptides, V H The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 67, and LThe peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 68, with the proviso that V H Peptides and V L The peptide comprises a light chain CDR1 having the sequence of SEQ ID NO: 66, a light chain CDR2 having the sequence of LA, a light chain CDR3 having the sequence of SEQ ID NO: 60, and / or a heavy chain CDR1 having the sequence of SEQ ID NO: 63, a heavy chain CDR2 having the sequence of SEQ ID NO: 64, and a heavy chain CDR3 having the sequence of SEQ ID NO: 65. In some embodiments, V H or V L The CDRs in the chains are as shown in the combinations provided herein.

[0238] In some embodiments, the polypeptide is H Peptides and V L Contains peptides, V H The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 67, and L The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 68, with the proviso that V L The peptide comprises an LCDR1 having the sequence of SEQ ID NO: 66, an LCDR2 having the sequence of LA, and an LCDR3 having the sequence of SEQ ID NO: 60, and V H The peptide comprises an HCDR1 having the sequence of SEQ ID NO:63, an HCDR2 having the sequence of SEQ ID NO:64, and an HCDR3 having the sequence of SEQ ID NO:65.

[0239] In some embodiments, the polypeptide is H Peptides and V L Contains peptides, V HThe peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 67, and L The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 68, with the proviso that V L The peptide comprises an LCDR1 having the sequence of SEQ ID NO: 66, which contains at most one conservative amino acid substitution; an LCDR2 having the sequence of LA, which contains at most one conservative amino acid substitution; and an LCDR3 having the sequence of SEQ ID NO: 60, which contains at most one conservative amino acid substitution; H The peptide comprises an HCDR1 having the sequence of SEQ ID NO: 63, which contains at most one conservative amino acid substitution; an HCDR2 having the sequence of SEQ ID NO: 64, which contains at most one conservative amino acid substitution; and an HCDR3 having the sequence of SEQ ID NO: 65, which contains at most one conservative amino acid substitution.

[0240] In some embodiments, the polypeptide is H Peptides and V L Contains peptides, V H The peptide comprises the sequence of SEQ ID NO: 67, L The peptide comprises the sequence of SEQ ID NO:68.

[0241] In some embodiments, the polypeptides provided herein bind to non-human primate CD8. In some embodiments, the polypeptides provided herein bind to human CD8.

[0242] As provided herein, the different polypeptides described herein (V H or V L) may be linked by a peptide linker or may not be linked by a peptide linker but instead form a contiguous sequence. In some embodiments, the peptide linker is (GGGGS) n (SEQ ID NO: 49), wherein each n is independently 1 to 5. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 3. In some embodiments, n is 4. In some embodiments, n is 5. The linked peptide format comprises V H -ZV L or V L -ZV H wherein Z is a peptide linker. In some embodiments, Z is (GGGGS) n (SEQ ID NO: 49), wherein each n is independently 1 to 5.

[0243] In some embodiments, V L -ZV H The polypeptide comprising a connecting peptide of the formula: comprises a heavy chain variable region set forth in SEQ ID NO: 67, linked to a light chain variable region set forth in SEQ ID NO: 68 via the linker sequence GGGGSGGGGSGGGGSGGGGS (SEQ ID NO: 50). In some embodiments, the polypeptide comprises a V H V connected to L The polypeptide comprising has the sequence shown below: NIVLTQSPASLAVSLGQRATISCRASESVDGFGNSFMNWYQQKPGQSPKLLIYLASNLESGVPARFSGSGSRTDFTLTIDPVEADDAATYYCQQNNEDPYTFGGGTKLEIKRGGGGSGGGGSGGGGSGGGGSEVQLQQSGPELVKPGASVKISCKASRYTFTDYNLHWVKLSHEKSLEWIGFIYPYNGGTGYNQKFKNKAKLTVDYSSSTAYMELRSLTSVDAAVYYCARDHRYNEGVSFDYWGQGTTLTVSS (SEQ ID NO: 69).

[0244] In some embodiments, the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 69. In some embodiments, the polypeptide comprises a sequence that is at least 90% identical to the sequence of SEQ ID NO: 69. In some embodiments, the polypeptide comprises a sequence that is at least 95% identical to the sequence of SEQ ID NO: 69. In some embodiments, the polypeptide comprises a sequence that is at least 99% identical to the sequence of SEQ ID NO: 69. In some embodiments, the polypeptide comprises the sequence set forth in SEQ ID NO: 69. In some embodiments, the polypeptide set forth in SEQ ID NO: 69 is an antibody or antigen-binding fragment thereof. In some embodiments, the antibody is an anti-CD8 antibody.

[0245] In some embodiments, V H -ZV L The polypeptide comprising a connecting peptide of the formula: comprises a light chain variable region set forth in SEQ ID NO: 68, linked to a heavy chain variable region set forth in SEQ ID NO: 67 via the linker sequence GGGGSGGGGSGGGGSGGGGS (SEQ ID NO: 50). In some embodiments, the polypeptide comprises a V L V connected to H The polypeptide comprising has the sequence shown below: EVQLQQSGPELVKPGASVKISCKASRYTFTDYNLHWVKLSHEKSLEWIGFIYPYNGGTGYNQKFKNKAKLTVDYSSSTAYMELRSLTSVDAAVYYCARDHryNEGVSFDYWGQGTTLTVSSGGGGSGGGGSGGGGSGGGGSNIVLTQSPASLAVSLGQRATISCRASESVDGFGNSFMNWYQQKPGQSPKLLIYLASNLESGVPARFSGSGSRTDFTLTIDPVEADDAATYYCQQNNEDPYTFGGGTKLEIKR (SEQ ID NO: 70).

[0246] In some embodiments, the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 70. In some embodiments, the polypeptide comprises a sequence that is at least 90% identical to the sequence of SEQ ID NO: 70. In some embodiments, the polypeptide comprises a sequence that is at least 95% identical to the sequence of SEQ ID NO: 70. In some embodiments, the polypeptide comprises a sequence that is at least 99% identical to the sequence of SEQ ID NO: 70. In some embodiments, the polypeptide set forth in SEQ ID NO: 70 is an antibody or antigen-binding fragment thereof. In some embodiments, the antibody is an anti-CD8 antibody. In some embodiments, the anti-CD8 antibody binds to non-human primate CD8. In some embodiments, the anti-CD8 antibody binds to human CD8.

[0247] In some embodiments, the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 69 and comprises an Fc region such as those provided herein. In some embodiments, the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 69 and comprises an Fc region such as those provided herein and a transmembrane domain such as those provided herein. In some embodiments, the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 69 and comprises an Fc region such as those provided herein, and a CD8 / CD28 transmembrane domain. In some embodiments, the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 69 and comprises an Fc region such as those provided herein, a transmembrane domain such as those provided herein, and an Env integration motif.

[0248] In some embodiments, the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 70 and comprises an Fc region such as those provided herein. In some embodiments, the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 70 and comprises an Fc region such as those provided herein and a transmembrane domain such as those provided herein. In some embodiments, the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 70, and comprises an Fc region such as those provided herein, and a CD8 / CD28 transmembrane domain. In some embodiments, the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 70, and comprises an Fc region such as those provided herein, a transmembrane domain such as those provided herein, and an Env integration motif.

[0249] As provided herein, polypeptides, antibodies, or antigen-binding fragments thereof may be sequence variants.

[0250] The polypeptide or antibody sequence can be modified to produce a human IgG antibody. The sequences provided herein can be modified to produce other types of antibodies by conversion. The CDRs can also be linked to other antibodies, proteins, or molecules to create antibody fragments that bind CD8.

[0251] In some embodiments, a polypeptide or antibody provided herein is a targeting moiety on the surface of an engineered viral particle. In some embodiments, the targeting moiety enables binding to a target cell. In some embodiments, the targeting moiety is a CD8-binding moiety, such as a polypeptide or antibody provided herein. In some embodiments, the targeting moiety comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO: 69. In some embodiments, the targeting moiety comprises a sequence that is at least 90% identical to the sequence of SEQ ID NO: 69. In some embodiments, the targeting moiety comprises a sequence that is at least 95% identical to the sequence of SEQ ID NO: 69. In some embodiments, the targeting moiety comprises a sequence that is at least 99% identical to the sequence of SEQ ID NO: 69. In some embodiments, the targeting moiety set forth in SEQ ID NO: 69 is an antibody or antigen-binding fragment thereof. In some embodiments, the targeting moiety is an anti-CD8 antibody.

[0252] In some embodiments, a polypeptide or antibody provided herein is a targeting moiety on the surface of an engineered viral particle. In some embodiments, the engineered viral particle is a pseudotyped virus-like particle. In some embodiments, the targeting moiety enables binding to a target cell. In some embodiments, the targeting moiety is a CD8-binding moiety, such as a polypeptide or antibody provided herein. In some embodiments, the targeting moiety comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO:70. In some embodiments, the targeting moiety comprises a sequence that is at least 90% identical to the sequence of SEQ ID NO:70. In some embodiments, the targeting moiety comprises a sequence that is at least 95% identical to the sequence of SEQ ID NO:70. In some embodiments, the targeting moiety comprises a sequence that is at least 99% identical to the sequence of SEQ ID NO:70. In some embodiments, the targeting moiety comprises the sequence set forth in SEQ ID NO:70. In some embodiments, the targeting moiety set forth in SEQ ID NO: 70 is an antibody or antigen-binding fragment thereof. In some embodiments, the targeting moiety is an anti-CD8 antibody. In some embodiments, the anti-CD8 antibody binds to non-human primate CD8. In some embodiments, the anti-CD8 antibody binds to human CD8.

[0253] In some embodiments, the polypeptide comprises a sequence having the sequence set forth in SEQ ID NO: 69 and comprises an Fc region such as those provided herein. In some embodiments, the polypeptide comprises a sequence having the sequence set forth in SEQ ID NO: 69 and comprises an Fc region such as those provided herein and a transmembrane domain such as those provided herein. In some embodiments, the polypeptide comprises a sequence having the sequence set forth in SEQ ID NO: 69 and comprises an Fc region such as those provided herein and a CD8 / CD28 transmembrane domain. In some embodiments, the polypeptide comprises a sequence having the sequence set forth in SEQ ID NO: 69 and comprises an Fc region such as those provided herein, a transmembrane domain such as those provided herein, and an Env integration motif.

[0254] In some embodiments, the polypeptide comprises a sequence having the sequence set forth in SEQ ID NO: 70 and comprises an Fc region such as those provided herein. In some embodiments, the polypeptide comprises a sequence having the sequence set forth in SEQ ID NO: 70 and comprises an Fc region such as those provided herein and a transmembrane domain such as those provided herein. In some embodiments, the polypeptide comprises a sequence having the sequence set forth in SEQ ID NO: 70 and comprises an Fc region such as those provided herein and a CD8 / CD28 transmembrane domain. In some embodiments, the polypeptide comprises a sequence having the sequence set forth in SEQ ID NO: 70 and comprises an Fc region such as those provided herein, a transmembrane domain such as those provided herein, and an Env integration motif.

[0255] Although binders that bind to CD7 and CD8 have been demonstrated, in part, using mutant VSV-G proteins, other fusogenic proteins can be used in place of VSV-G proteins. For example, in some embodiments, pseudotyped virus-like particles can be pseudotyped with viral glycoproteins other than VSV-G.

[0256] In some embodiments, the virus particles can be pseudotyped using viral glycoproteins, for example, from VSV. In some embodiments, the virus particles can be pseudotyped using viral glycoproteins, for example, from a virus of the Paramyxoviridae family. In some embodiments, the pseudotyped virus-like particles are pseudotyped using viral glycoproteins of a morbillivirus, such as measles virus. In some embodiments, the pseudotyped virus-like particles are pseudotyped using viral glycoproteins of measles virus. In some embodiments, the pseudotyped virus-like particles are pseudotyped using viral glycoproteins of a henipavirus, such as Nipah virus, Cedar virus, or Hendra virus. In some embodiments, the pseudotyped virus-like particles are pseudotyped using viral glycoproteins of Nipah virus. In some embodiments, the polypeptides or antibodies provided herein are linked via a linker to the envelope glycoprotein G or H of a virus of the Paramyxoviridae family. In some embodiments, the virus of the Paramyxoviridae family is a morbillivirus, such as measles virus. In some embodiments, the virus of the Paramyxoviridae family is a Henipavirus, such as a Nipah virus, a Cedar virus, or a Hendra virus.

[0257] In some embodiments, pseudotyped virus-like particles comprising targeting moieties provided herein are pseudotyped with a viral glycoprotein of a virus of the Rhabdoviridae family. In some embodiments, the pseudotyped virus-like particles are pseudotyped using a viral glycoprotein of vesicular stomatitis New Jersey virus, vesicular stomatitis Indiana virus, vesicular stomatitis Alagoas virus, vesicular stomatitis Maraba virus, or vesicular stomatitis Carajas virus. In some embodiments, the polypeptide or antibody provided herein is linked to the glycoprotein of a virus of the Rhabdoviridae family via a linker. In some embodiments, the virus of the Rhabdoviridae family is vesicular stomatitis New Jersey virus, vesicular stomatitis Indiana virus, vesicular stomatitis Alagoas virus, vesicular stomatitis Maraba virus, or vesicular stomatitis Carajas virus.

[0258] In some embodiments, pseudotyped virus-like particles comprising a targeting moiety provided herein are pseudotyped with a viral glycoprotein of a parainfluenza virus, a Spodoptera frugiperda virus, a Drosophila obscura sigma virus, a Wuhan insect virus 7, a spring viremia of carp virus, or a perch virus. In some embodiments, a polypeptide or antibody provided herein is linked to a glycoprotein of a virus of the Rhabdoviridae family via a linker. In some embodiments, the virus of the Rhabdoviridae family is a parainfluenza virus. In some embodiments, the virus of the Rhabdoviridae family is a Spodoptera frugiperda virus. In some embodiments, the virus of the Rhabdoviridae family is a Drosophila obscura sigma virus. In some embodiments, the virus of the Rhabdoviridae family is a Wuhan insect virus 7. In some embodiments, the virus of the Rhabdoviridae family is a spring viremia of carp virus. In some embodiments, the virus of the Rhabdoviridae family is a perch virus. In some embodiments, the polypeptide or antibody provided herein is linked to Parainfluenza virus glycoprotein via a linker.In some embodiments, the polypeptide or antibody provided herein is linked to Spodoptera frugiperda rhabdovirus isolate Sf G virus glycoprotein via a linker.

[0259] In some embodiments, the pseudotyped virus-like particles comprising the targeting moieties provided herein are pseudotyped with a viral glycoprotein of a virus of the Arenaviridae family. In some embodiments, the pseudotyped virus-like particles are pseudotyped using a viral glycoprotein of a Machupo virus. In some embodiments, the polypeptide or antibody provided herein is linked to the glycoprotein of a virus of the Arenaviridae family via a linker. In some embodiments, the virus of the Arenaviridae family is a Machupo virus.

[0260] In some embodiments, viral particles comprising a mutant VSV-G protein (or other viral glycoruptein) and / or targeting moiety provided herein comprise a nucleic acid molecule encoding a heterologous molecule of interest or "cargo." For example, a heterologous molecule of interest is meant to refer to any product that can be encoded by a nucleic acid molecule. As non-limiting examples, "cargo" or "heterologous molecule of interest" can refer to an siRNA, shRNA, a peptide, a polypeptide, a protein, a viral payload, a viral genome, or a combination thereof. In some embodiments, the polypeptide is a chimeric antigen receptor ("CAR"). In some embodiments, the heterologous molecule of interest is an siRNA, shRNA, a non-coding RNA (e.g., a guide RNA for a CRISPR system), a peptide, a polypeptide, a protein, a viral payload, a viral genome, a chimeric antigen receptor ("CAR"), or a combination thereof. In some embodiments, the heterologous molecule of interest is a CAR.

[0261] As used herein, "chimeric antigen receptor" or "CAR" refers to an antigen-binding domain that is fused directly or indirectly (e.g., via a hinge or transmembrane domain) to an intracellular signaling domain that is capable of activating or stimulating an immune cell. Most commonly, the extracellular binding domain of a CAR is composed of a single-chain variable fragment (scFv) derived from fusing the variable heavy and light regions of a murine or humanized monoclonal antibody. Alternatively, an scFv derived from a Fab (not from an antibody, but obtained, for example, from a Fab library) may be used. In various embodiments, the scFv is fused to a transmembrane domain and then to an intracellular signaling domain. However, the antigen-binding domain can be any molecule capable of binding to a target on a cell. For example, the antigen-binding domain of a CAR can be an antibody, an scFv antibody, an antigen-binding domain, ankyrin repeats (e.g., DARPIN), a VHH domain antibody, a nanobody, a single domain antibody, an FN3 domain, or and any combination thereof. In some embodiments, CARs include those that provide only a CD3ζ signal upon antigen binding. In some embodiments, CARs include those that provide both costimulation (e.g., CD28 or CD137) and activation (CD3ζ). In some embodiments, CARs include those that provide multiple costimulation (e.g., CD28 and CD137) and activation (CD3ζ). In various embodiments, CARs are selected to have high affinity or avidity for the antigen. In some embodiments, the antigen binding domain binds to CD20. In some embodiments, the antigen binding domain comprises a CD20 antibody or fragment thereof. In some embodiments, the antibody fragment is, but is not limited to, an scFv antibody, an antigen binding domain, an ankyrin repeat (e.g., DARPIN), a VHH domain antibody, a nanobody, a single domain antibody, an FN3 domain, or any combination thereof.

[0262] In some embodiments, the antigen binding domain of the CAR is V H Domain, V L Domain, or VH Domain and V L In some embodiments, the V H A domain comprises an amino acid sequence having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 73, or any value or range therebetween. EVQLVESGGGLVQPGRSLRLSCAASGFTFNDYAMHWVRQAPGKGLEWVSTISWNSGSIGYADSVKGRFTISRDNAKKSLYLQMNSLRAEDTALYYCAKDIQYGNYYYGMDVWGQGTTVTVSS (SEQ ID NO: 73) In some embodiments, V H The V domain comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 73. In some embodiments, the V H The V domain comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 73. In some embodiments, the V H The V domain comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 73. In some embodiments, the V H The V domain comprises an amino acid sequence having at least 99% identity to SEQ ID NO: 73. In some embodiments, the V H The domain comprises an amino acid sequence having the sequence of SEQ ID NO:73.

[0263] In some embodiments, V L A domain comprises an amino acid sequence having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 74, or any value or range therebetween. EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPITFGQGTRLEIK (SEQ ID NO: 74) In some embodiments, V L The V domain comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 74. In some embodiments, the V L The V domain comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 74. In some embodiments, the V L The V domain comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 74. In some embodiments, the V L The V domain comprises an amino acid sequence having at least 99% identity to SEQ ID NO: 74. In some embodiments, the V L The domain comprises an amino acid sequence having the sequence of SEQ ID NO:74.

[0264] In some embodiments, the antigen binding domain of the CAR is V H Domain and V L In some embodiments, the V H and V L The domains are not linked by a linker peptide. H and V L The domains are linked by a linker peptide, such as those provided herein, including but not limited to: (GGGGS) n (SEQ ID NO: 49), wherein each n is independently 1 to 5. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 3. In some embodiments, n is 4. In some embodiments, n is 5.

[0265] In some embodiments, V H Domain and V LThe antigen binding domain of the CAR comprises a V domain having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 73. H domain and having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 74. L In some embodiments, V H Domain and V L The antigen binding domain of the CAR comprises a V domain having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 73. H V domain and having at least 90% identity to SEQ ID NO: 74 L In some embodiments, V H Domain and V L The antigen binding domain of the CAR comprises a V domain having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 73. H V domain and having at least 95% identity to SEQ ID NO: 74 L In some embodiments, V H Domain and V L The antigen binding domain of the CAR comprises a V domain having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 73. H V domain and having at least 98% identity to SEQ ID NO: 74 L In some embodiments, V H Domain and V LThe antigen binding domain of the CAR comprises a V domain having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 73. H V domain and having at least 99% identity to SEQ ID NO: 74 L In some embodiments, V H Domain and V L The antigen binding domain of the CAR comprises a V domain having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 73. H V domain and having the sequence of SEQ ID NO: 74 L In some embodiments, V H Domain and V L The antigen-binding domain of the CAR comprises a V domain having at least 90% identity to SEQ ID NO: 73 H domain and having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 74. L In some embodiments, V H Domain and V L The antigen-binding domain of the CAR comprises a V domain having at least 95% identity to SEQ ID NO: 73. H domain and having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 74. L In some embodiments, V H Domain and V L The antigen-binding domain of the CAR comprises a V domain having at least 98% identity to SEQ ID NO: 73. Hdomain and having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 74. L In some embodiments, V H Domain and V L The antigen-binding domain of the CAR comprises a V domain having at least 99% identity to SEQ ID NO: 73. H domain and having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 74. L In some embodiments, V H Domain and V L The antigen-binding domain of the CAR comprises a V domain having the amino acid sequence of SEQ ID NO: 73. H domain and having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 74. L In some embodiments, V H Domain and V L The antigen-binding domain of the CAR comprises a V domain having at least 90% identity to SEQ ID NO: 73 H V domain and having at least 90% identity to SEQ ID NO: 74 L In some embodiments, V H Domain and V L The antigen-binding domain of the CAR comprises a V domain having at least 95% identity to SEQ ID NO: 73. H V domain and having at least 90% identity to SEQ ID NO: 74 L In some embodiments, V H Domain and V L The antigen-binding domain of the CAR comprises a V domain having at least 90% identity to SEQ ID NO: 73 HV domain and having at least 95% identity to SEQ ID NO: 74 L In some embodiments, V H Domain and V L The antigen-binding domain of the CAR comprises a V domain having at least 95% identity to SEQ ID NO: 73. H V domain and having at least 95% identity to SEQ ID NO: 74 L In some embodiments, V H Domain and V L The antigen-binding domain of the CAR comprises a V domain having at least 98% identity to SEQ ID NO: 73. H V domain and having at least 98% identity to SEQ ID NO: 74 L In some embodiments, V H Domain and V L The antigen-binding domain of the CAR comprises a V domain having at least 99% identity to SEQ ID NO: 73. H V domain and having at least 99% identity to SEQ ID NO: 74 L In some embodiments, V H Domain and V L The antigen-binding domain of the CAR comprises a V domain having the amino acid sequence of SEQ ID NO: 73. H V domain and having the amino acid sequence of SEQ ID NO: 74 L Includes:

[0266] In some embodiments, the antigen binding domain of the CAR is V H -ZV L where V H is a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 73, Z is a linker comprising the amino acid sequence GGGGSGGGSGGGGS (SEQ ID NO: 77), and V L is a light chain variable region comprising the amino acid sequence of SEQ ID NO: 74. In some embodiments, V H -ZV L The antigen binding domain of the CAR comprising the formula has the amino acid sequence shown below: EVQLVESGGGLVQPGRSLRLSCAASGFTFNDYAMHWVRQAPGKGLEWVSTISWNSGSIGYADSVKGRFTISRDNAKKSLYLQMNSLRAEDTALYYCAKDIQYGNYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPITFGQGTRLEIK (SEQ ID NO: 75)

[0267] In some embodiments, the antigen binding domain of the CAR comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the sequence of SEQ ID NO: 75. In some embodiments, the antigen binding domain of the CAR comprises an amino acid sequence having at least 90% identity to the sequence of SEQ ID NO: 75. In some embodiments, the antigen binding domain of the CAR comprises an amino acid sequence having at least 95% identity to the sequence of SEQ ID NO: 75. In some embodiments, the antigen binding domain of the CAR comprises an amino acid sequence having at least 98% identity to the sequence of SEQ ID NO: 75. In some embodiments, the antigen binding domain of the CAR comprises an amino acid sequence having at least 99% identity to the sequence of SEQ ID NO: 75. In some embodiments, the antigen binding domain of the CAR comprises the amino acid sequence of SEQ ID NO: 75.

[0268] In some embodiments, the antigen binding domain of the CAR is V L -ZV H where V L is a light chain variable region comprising the amino acid sequence of SEQ ID NO: 74, Z is a linker comprising the amino acid sequence GGGGSGGGSGGGGS (SEQ ID NO: 77), and V H is a light chain variable region comprising the amino acid sequence of SEQ ID NO: 73. In some embodiments, V L -ZV HThe antigen binding domain of the CAR comprising the formula has the amino acid sequence shown below: EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPITFGQGTRLEIKGGGGSGGGGSGGGGSEVQLVESGGGLVQPGRSLRLSCAASGFTFNDYAMHWVRQAPGKGLEWVSTISWNSGSIGYADSVKGRFTISRDNAKKSLYLQMNSLRAEDTALYYCAKDIQYGNYYYGMDVWGQGTTVTVSS (SEQ ID NO: 76)

[0269] In some embodiments, the antigen binding domain of a CAR comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the sequence of SEQ ID NO: 76. In some embodiments, the antigen binding domain of a CAR comprises an amino acid sequence having at least 90% identity to the sequence of SEQ ID NO: 76. In some embodiments, the antigen binding domain of a CAR comprises an amino acid sequence having at least 95% identity to the sequence of SEQ ID NO: 76. In some embodiments, the antigen binding domain of a CAR comprises an amino acid sequence having at least 98% identity to the sequence of SEQ ID NO: 76. In some embodiments, the antigen binding domain of a CAR comprises an amino acid sequence having at least 99% identity to the sequence of SEQ ID NO: 76. In some embodiments, the antigen binding domain of a CAR comprises the amino acid sequence of SEQ ID NO: 76.

[0270] In some embodiments, the antigen binding domain of the CAR is V H Domain, V L Domain, or V H Domain and V L In some embodiments, the V HA domain comprises an amino acid sequence having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 78, or any value or range therebetween. DIVLTQSPAILSASPGEKVTMTCRASSSVNYMDWYQKKPGSSPKPWIYATSNLASGVPARFSGSGSGTSYSLTISRVEAEDAATYYCQQWSFNPPTFGGGTKLEIKGSTS (SEQ ID NO: 78) In some embodiments, V H The V domain comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 78. In some embodiments, the V H The V domain comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 78. In some embodiments, the V H The V domain comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 78. In some embodiments, the V H The V domain comprises an amino acid sequence having at least 99% identity to SEQ ID NO: 78. In some embodiments, the V H The domain comprises an amino acid sequence having the sequence of SEQ ID NO:78.

[0271] In some embodiments, V L A domain comprises an amino acid sequence having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 79, or any value or range therebetween. EVQLQQSGAELVKPGASVKMSCKASGYTFTSYNMHWVKQTPGQGLEWIGAIYPGNGDTSYNQKFKGKATLTADKSSSTAYMQLSSLTSEDSADYYCARSNYYGSSYWFFDVWGAGTTVTVSS (SEQ ID NO: 79) In some embodiments, V LThe V domain comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 79. In some embodiments, the V L The V domain comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 79. In some embodiments, the V L The V domain comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 79. In some embodiments, the V L The V domain comprises an amino acid sequence having at least 99% identity to SEQ ID NO: 79. In some embodiments, the V L The domain comprises an amino acid sequence having the sequence of SEQ ID NO:79.

[0272] In some embodiments, V H Domain and V L The antigen binding domain of the CAR comprises a V domain having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 78. H domain and having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 79. L In some embodiments, V H Domain and V L The antigen binding domain of the CAR comprises a V domain having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 78. H V domain and having at least 90% identity to SEQ ID NO: 79 L In some embodiments, V H Domain and V LThe antigen binding domain of the CAR comprises a V domain having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 78. H V domain and having at least 95% identity to SEQ ID NO: 79 L In some embodiments, V H Domain and V L The antigen binding domain of the CAR comprises a V domain having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 78. H V domain and having at least 98% identity to SEQ ID NO: 79 L In some embodiments, V H Domain and V L The antigen binding domain of the CAR comprises a V domain having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 78. H V domain and having at least 99% identity to SEQ ID NO: 79 L In some embodiments, V H Domain and V L The antigen binding domain of the CAR comprises a V domain having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 78. H V domain and having the sequence of SEQ ID NO: 79 L In some embodiments, V H Domain and V L The antigen-binding domain of the CAR comprises a V domain having at least 90% identity to SEQ ID NO: 78 Hdomain and having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 79. L In some embodiments, V H Domain and V L The antigen-binding domain of the CAR comprises a V domain having at least 95% identity to SEQ ID NO: 78 H domain and having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 79. L In some embodiments, V H Domain and V L The antigen-binding domain of the CAR comprises a V domain having at least 98% identity to SEQ ID NO: 78 H domain and having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 79. L In some embodiments, V H Domain and V L The antigen-binding domain of the CAR comprises a V domain having at least 99% identity to SEQ ID NO: 78 H domain and having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 79. L In some embodiments, V H Domain and V L The antigen-binding domain of the CAR comprises a V domain having the amino acid sequence of SEQ ID NO: 78. Hdomain and having at least 75%, 80%, 85%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 79. L In some embodiments, V H Domain and V L The antigen-binding domain of the CAR comprises a V domain having at least 90% identity to SEQ ID NO: 78 H V domain and having at least 90% identity to SEQ ID NO: 79 L In some embodiments, V H Domain and V L The antigen-binding domain of the CAR comprises a V domain having at least 95% identity to SEQ ID NO: 78 H V domain and having at least 90% identity to SEQ ID NO: 79 L In some embodiments, V H Domain and V L The antigen-binding domain of the CAR comprises a V domain having at least 90% identity to SEQ ID NO: 78 H V domain and having at least 95% identity to SEQ ID NO: 79 L In some embodiments, V H Domain and V L The antigen-binding domain of the CAR comprises a V domain having at least 95% identity to SEQ ID NO: 78 H V domain and having at least 95% identity to SEQ ID NO: 79 L In some embodiments, V H Domain and V L The antigen-binding domain of the CAR comprises a V domain having at least 98% identity to SEQ ID NO: 78 H V domain and having at least 98% identity to SEQ ID NO: 79 L In some embodiments, V H Domain and V LThe antigen-binding domain of the CAR comprises a V domain having at least 99% identity to SEQ ID NO: 78 H V domain and having at least 99% identity to SEQ ID NO: 79 L In some embodiments, V H Domain and V L The antigen-binding domain of the CAR comprises a V domain having the amino acid sequence of SEQ ID NO: 78. H V domain and having the amino acid sequence of SEQ ID NO: 79 L Includes:

[0273] In some embodiments, the antigen binding domain of the CAR is V H -ZV L where V H is a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 78, Z is a linker comprising the amino acid sequence GGGGSGGGSGGGGS (SEQ ID NO: 77), and V L is a light chain variable region comprising the amino acid sequence of SEQ ID NO: 79. In some embodiments, V H -ZV L The antigen binding domain of the CAR comprising the formula has the amino acid sequence shown below: DIVLTQSPAILSASPGEKVTMTCRASSSVNYMDWYQKKPGSSPKPWIYATSNLASGVPARFSGSGSGTSYSLTISRVEAEDAATYYCQQWSFNPPTFGGGTKLEIKGSTSGGGGSGGGGSGGGGSSEVQLQQSGAELVKPGASVKMSCKASGYTFTSYNMHWVKQTPGQGLEWIGAIYPGNGDTSYNQKFKGKATLTADKSSSTAYMQLSSLTSEDSADYYCARSNYYGSSYWFFDVWGAGTTVTVSS (SEQ ID NO: 80)

[0274] In some embodiments, the antigen binding domain of the CAR comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the sequence of SEQ ID NO: 80. In some embodiments, the antigen binding domain of the CAR comprises an amino acid sequence having at least 90% identity to the sequence of SEQ ID NO: 80. In some embodiments, the antigen binding domain of the CAR comprises an amino acid sequence having at least 95% identity to the sequence of SEQ ID NO: 80. In some embodiments, the antigen binding domain of the CAR comprises an amino acid sequence having at least 98% identity to the sequence of SEQ ID NO: 80. In some embodiments, the antigen binding domain of the CAR comprises an amino acid sequence having at least 99% identity to the sequence of SEQ ID NO: 80. In some embodiments, the antigen binding domain of the CAR comprises the amino acid sequence of SEQ ID NO: 80.

[0275] In some embodiments, the antigen binding domain of the CAR is V L -ZV H where V L is a light chain variable region comprising the amino acid sequence of SEQ ID NO: 79, Z is a linker comprising the amino acid sequence GGGGSGGGSGGGGS (SEQ ID NO: 77), and V H is a light chain variable region comprising the amino acid sequence of SEQ ID NO: 78. In some embodiments, V L -ZV H The antigen binding domain of the CAR comprising the formula has the amino acid sequence shown below: SEVQLQQSGAELVKPGASVKMSCKASGYTFTSYNMHWVKQTPGQGLEWIGAIYPGNGDTSYNQKFKGKATLTADKSSSTAYMQLSSLTSEDSADYYCARSNYYGSSYWFFDVWGAGTTVTVSSGGGGSGGGGSGGGGSDIVLTQSPAILSASPGEKVTMTCRASSSVNYMDWYQKKPGSSPKPWIYATSNLASGVPARFSGSGSGTSYSLTISRVEAEDAATYYCQQWSFNPPTFGGGTKLEIKGSTS (SEQ ID NO: 81)

[0276] In some embodiments, the antigen binding domain of a CAR comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the sequence of SEQ ID NO: 81. In some embodiments, the antigen binding domain of a CAR comprises an amino acid sequence having at least 90% identity to the sequence of SEQ ID NO: 81. In some embodiments, the antigen binding domain of a CAR comprises an amino acid sequence having at least 95% identity to the sequence of SEQ ID NO: 81. In some embodiments, the antigen binding domain of a CAR comprises an amino acid sequence having at least 98% identity to the sequence of SEQ ID NO: 81. In some embodiments, the antigen binding domain of a CAR comprises an amino acid sequence having at least 99% identity to the sequence of SEQ ID NO: 81. In some embodiments, the antigen binding domain of a CAR comprises the amino acid sequence of SEQ ID NO: 81.

[0277] In some embodiments, the antigen-binding domain of the CAR comprises rituximab, ocrelizumab, obinutuzumab, ofatumumab, ibritumomab tiuxetan, tositumomab, or ublituximab. In some embodiments, the antigen-binding domain comprises rituximab. In some embodiments, the antigen-binding domain comprises ofatumumab. In some embodiments, the CAR also comprises a 4-1BB domain. These are merely exemplary in nature and are not intended to be limiting; any chimeric antigen receptor can be delivered in conjunction with the viral particles and vectors provided herein. These are non-limiting examples of CARs; any CAR construct can be encoded by a nucleic acid molecule.

[0278] In some embodiments, the pseudotyped virus particle further comprises a heterologous nucleic acid molecule encoding a cargo of interest. The nucleic acid molecule may be useful for regulating the expression of a target gene. In some embodiments, the cargo can be used to regulate cellular activity or express a protein that is transported to the surface of the target cell. Thus, in some embodiments, the nucleic acid may comprise an siRNA or shRNA. The nucleic acid may also encode a cargo of interest. Thus, in some embodiments, the cargo of interest may comprise a polypeptide or a portion thereof, a protein or a portion thereof, a chimeric antigen receptor or a portion thereof, or a tumor antigen or a portion thereof. In some embodiments, the cargo of interest is an antibody that can be produced by the virus and then secreted by cells infected with the virus. The term "protein" may refer to any polypeptide that performs a natural function in a cellular environment. Thus, in some embodiments, the protein encoded by the nucleic acid cargo of interest may comprise an enzyme, a nuclear receptor, a transporter, a ribosomal protein, a membrane-bound protein, a cytoplasmic protein, a G protein-coupled receptor, a voltage-gated ion channel, a secreted protein, a mitochondrial protein, a cytokine, a chimeric antigen receptor, a tumor antigen, or a portion or chimeric species thereof.

[0279] Without being bound by any particular theory, viral particles containing the mutant VSV-G proteins or other viral glycoproteins provided herein that contain a targeting moiety can be used to express a heterologous molecule of interest in target cells. Thus, for example, a CAR can be expressed in T cells targeted by viral particles pseudotyped with the VSV-G proteins provided herein. When T cells are the intended target, the viral particles can contain a targeting moiety that binds to a target on the surface of the T cell, such as, but not limited to, CD2, CD3, CD4, CD5, CD7, or CD8. In some embodiments, the target is CD2. In some embodiments, the target is CD3. In some embodiments, the target is CD4. In some embodiments, the target is CD5. In some embodiments, the target is CD6. In some embodiments, the target is CD7. In some embodiments, the target is CD8.

[0280] Also provided herein are viral particles comprising a targeting moiety that binds to CD7 or CD8, or pharmaceutical compositions comprising the same. Some viral particles comprise a targeting moiety that binds to CD7. Some viral particles comprise a targeting moiety that binds to CD7.

[0281] In some embodiments, the viral particle comprising a targeting moiety that binds to CD7 or CD8 is a pseudotyped viral particle. The viral particle can be pseudotyped with a viral glycoprotein, such as, but not limited to, those described herein. In some embodiments, the viral particle is pseudotyped with a VSV-G protein or a variant thereof, including, but not limited to, those provided herein. The targeting moiety can be any antibody or binder that binds to CD7 or CD8. Non-limiting examples are provided herein.

[0282] In addition to being pseudotyped, viral particles containing targeting sites that bind to CD7 or CD8 can contain a heterologous nucleic acid molecule encoding a molecule of interest. This can be, for example, siRNA, shRNA, non-coding RNA (e.g., guide RNA for CRISPR systems), peptide, polypeptide, protein, viral payload, viral genome, or a combination thereof. In some embodiments, the heterologous molecule of interest is a chimeric antigen receptor ("CAR").

[0283] In some embodiments, the pseudotyped viral particles are recombinant lentivirus. In some embodiments, the recombinant pseudotyped viral particles are replication competent. In some embodiments, the recombinant pseudotyped viral particles are replication incompetent.

[0284] In some embodiments, pharmaceutical compositions are provided that include any of the compositions, particles, or components provided herein, such as envelope pseudotyped viral particles or vectors provided herein, i.e., particles comprising the VSV-G mutant proteins or other viral glycoproteins provided herein, or particles comprising the targeting moieties and / or heterologous nucleic acid molecules provided herein.

[0285] In some embodiments, methods for delivering a cargo of interest to a cell are provided, hi some embodiments, the methods comprise contacting the cell with a pseudotyped virus-like particle or viral vector provided herein, or a pharmaceutical composition comprising same.

[0286] In some embodiments, a method for delivering a cargo of interest to a cell in a subject is provided. In some embodiments, the method comprises administering to a subject a pseudotyped virus-like particle or viral vector provided herein, or a pharmaceutical composition comprising the same. In some embodiments, the cargo is a chimeric antigen receptor or as otherwise defined herein.

[0287] In some embodiments, a method for delivering a chimeric antigen receptor to T cells in a subject is provided. In some embodiments, the method comprises administering to a subject a pseudotyped virus-like particle or viral vector provided herein, or a pharmaceutical composition comprising the same, wherein the pseudotyped virus-like particle or viral vector comprises a heterologous nucleic acid molecule encoding the chimeric antigen receptor.

[0288] Provided herein are nucleic acid molecules that encode the mutant VSV-G proteins provided herein.

[0289] Also provided herein are nucleic acid molecules that encode targeting moieties, such as those provided herein.

[0290] Methods for producing virus-like particles or vectors are also provided. In some embodiments, the methods include producing virus-like particles or vectors comprising a mutant VSV-G protein or other viral glycoprotein. In some embodiments, the methods include transfecting or transducing a packaging cell line with a nucleic acid molecule encoding a mutant VSV-G protein or another viral glycoprotein provided herein under conditions sufficient to produce the pseudotyped virus-like particle or viral vector. In some embodiments, the methods include transfecting or transducing a packaging cell line with a plurality of nucleic acid molecules provided herein under conditions sufficient to produce the pseudotyped virus-like particle or viral vector, and optionally with a targeting moiety, such as one that binds to a target antigen, such as those provided herein. In some embodiments, the targeting moiety binds to CD7 or CD8. In some embodiments, the targeting moiety comprises a sequence that binds to CD7 or CD8, such as those provided herein. In some embodiments, the method further comprises isolating the pseudotyped virus-like particle or viral vector. In some embodiments, the nucleic acid molecule also comprises a nucleic acid molecule encoding a targeting moiety and / or cargo to be delivered by the produced viral vector.

[0291] Thus, in some embodiments, cells are provided that contain heterologous nucleic acid molecules encoding components for producing a virus. Packaging cell lines are known in the art and can be modified with molecules of interest to produce viral particles of interest.

[0292] For example, cells or cell populations are provided that contain one or more heterologous nucleic acid molecules encoding a targeting moiety and / or a viral glycoprotein. In some embodiments, the cells contain a heterologous nucleic acid molecule encoding a targeting moiety and a viral glycoprotein. In some embodiments, the heterologous nucleic acid molecule comprises a nucleic acid sequence encoding a targeting moiety that binds to CD7 or CD8. In some embodiments, the encoded targeting moiety comprises an amino acid sequence provided herein. In some embodiments, the encoded viral glycoprotein is any viral glycoprotein that can function as a fusogenic protein to facilitate entry of viral particles into cells that express CD7 or CD8. In some embodiments, the viral glycoprotein is a wild-type or mutant VSV-G protein, such as those provided herein. Other viral glycoproteins that can be encoded are also described herein and can be used.

[0293] The viral particles provided herein can be produced or generated, for example, by culturing cells under conditions sufficient to generate viral particles. In some embodiments, the cells are referred to as packaging cell lines, which provide viral components for generating viral particles. These can be structural or nonstructural viral components or proteins.

[0294] Also provided herein are methods for treating cancer in a subject. In some embodiments, the methods comprise administering to the subject a pseudotyped virus-like particle or viral vector provided herein, or a pharmaceutical composition comprising the same, wherein the pseudotyped virus-like particle or viral vector comprises a heterologous nucleic acid molecule encoding a chimeric antigen receptor.

[0295] Also provided herein are methods of treating a disease in a subject in need thereof.

[0296] In some embodiments, provided methods include, but are not limited to, methods of treating a disease in a subject in need thereof, comprising administering to the subject a viral particle(s) provided herein to treat the disease.

[0297] In certain embodiments, the disease is cancer. In addition, the compositions provided herein can be used in methods for the treatment of any condition associated with cancer, such as a cell-mediated immune response against tumor cell(s), where it is desirable to treat or alleviate the disease. Types of cancer to be treated include, but are not limited to, carcinoma, blastoma, sarcoma, certain leukemia or lymphoid malignancies, benign and malignant tumors, malignant tumors such as sarcoma, carcinoma, and melanoma. Other exemplary cancers include, but are not limited to, 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, and the like. In some embodiments, the cancer is a carcinoma, blastoma, sarcoma, leukemia, lymphoid malignancy, 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. The cancer can be a non-solid tumor (such as a hematological tumor) or a solid tumor. Adult tumors / cancers and pediatric tumors / cancers are also included. In one embodiment, the cancer is a hematological tumor. In one embodiment, the cancer is a carcinoma. In one embodiment, the cancer is a sarcoma. In one embodiment, the cancer is a leukemia. In one embodiment, the cancer is a solid tumor.

[0298] A solid tumor is an abnormal mass of tissue that usually does not contain cysts or liquid areas. Solid tumors can be benign or malignant. Different types of solid tumors are named according to the type of cells that form them (e.g., sarcoma, carcinoma, and lymphoma). Examples of solid tumors, such as sarcomas and carcinomas, include fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteosarcoma, synovium, mesothelioma, Ewing's tumor, leiomyosarcoma, rhabdomyosarcoma, colon cancer, lymphoid malignancies, pancreatic cancer, breast cancer, lung cancer, ovarian cancer, prostate cancer, hepatocellular carcinoma, squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, sweat gland carcinoma, medullary thyroid carcinoma, papillary thyroid carcinoma, pheochromocytoma, sebaceous gland carcinoma, papillary carcinoma, papillary adenocarcinoma, medullary carcinoma, bronchogenic carcinoma, renal cell carcinoma, hepatoma, gallbladder carcin ... These include ductal carcinoma, choriocarcinoma, Wilms' tumor, cervical cancer, testicular tumor, seminoma, bladder cancer, melanoma, CNS tumors (gliomas (including brainstem glioma and mixed glioma), glioblastoma (also known as glioblastoma multiforme), astrocytoma, CNS lymphoma, germ cell tumor, medulloblastoma, schwannoma / craniopharyngioma, ependymoma, pinealoma, hemangioblastoma, acoustic neuroma, oligodendroglioma, meningeal hemangioma, neuroblastoma, retinoblastoma, and brain metastases).

[0299] Carcinomas amenable to therapy by the methods disclosed herein include, but are not limited to, esophageal carcinoma, hepatocellular carcinoma, basal cell carcinoma (a form of skin cancer), squamous cell carcinoma (various tissues), bladder carcinoma including transitional cell carcinoma (a malignant tumor of the bladder), bronchogenic carcinoma, colon cancer, colorectal carcinoma, gastric cancer, lung cancer including small cell and non-small cell carcinoma of the lung, adrenocortical carcinoma, thyroid carcinoma, pancreatic cancer, breast cancer, ovarian cancer, prostate cancer, adenocarcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma, papillary adenocarcinoma, cystadenocarcinoma, medullary carcinoma, renal cell carcinoma, ductal carcinoma in situ or bile duct carcinoma, choriocarcinoma, seminoma, embryonal carcinoma, Wilms' tumor, cervical cancer, uterine cancer, testicular cancer, osteogenic carcinoma, epithelial carcinoma, and nasopharyngeal carcinoma.

[0300] In certain exemplary embodiments, the compositions provided herein can be used in methods for treating myeloma or a condition related to myeloma. Examples of myeloma or a condition related to myeloma include, but are not limited to, light chain myeloma, non-secretory myeloma, monoclonal gammopathy of undetermined significance (MGUS), plasmacytoma (e.g., solitary, multiple solitary, extramedullary plasmacytoma), amyloidosis, and multiple myeloma. In some embodiments, methods for treating multiple myeloma are provided. In some embodiments, the multiple myeloma is refractory myeloma. In some embodiments, the multiple myeloma is relapsed myeloma.

[0301] In certain exemplary embodiments, the in vivo modified immune cells produced using the compositions provided herein are used to treat melanoma or a condition associated with melanoma. Examples of melanoma or a condition associated with melanoma include, but are not limited to, superficial spreading melanoma, nodular melanoma, lentigo maligna melanoma, acral lentigo melanoma, amelanotic, or skin melanoma (e.g., cutaneous, ocular, vulvar, vaginal, or rectal melanoma). In some embodiments, the melanoma is cutaneous melanoma. In some embodiments, the melanoma is refractory melanoma. In some embodiments, the melanoma is recurrent melanoma.

[0302] In some embodiments, the compositions provided herein are used to treat sarcoma or a sarcoma-related condition. Examples of sarcoma or a sarcoma-related condition include, but are not limited to, angiosarcoma, chondrosarcoma, chordoma, endothelial sarcoma, Ewing's sarcoma, fibrosarcoma, gastrointestinal stromal tumor, leiomyosarcoma, liposarcoma, lymphangiosarcoma, lymphangioendothelioma, mesothelioma, malignant peripheral nerve sheath tumor, myxosarcoma, osteogenic sarcoma, osteosarcoma, pleomorphic sarcoma, rhabdomyosarcoma, synovium, and other soft tissue sarcomas. In some embodiments, the sarcoma is synovial sarcoma. In some embodiments, the sarcoma is a liposarcoma, such as myxoid / round cell liposarcoma, differentiated / dedifferentiated liposarcoma, or pleomorphic liposarcoma. In some embodiments, the sarcoma is myxoid / round cell liposarcoma. In some embodiments, the sarcoma is a refractory sarcoma. In some embodiments, the sarcoma is a recurrent sarcoma.

[0303] In some embodiments, the subject has been treated with a therapeutic agent targeted to the disease or condition, e.g., tumor, prior to administration of the composition. In some aspects, the subject is refractory or non-responsive to other therapeutic agents. In some embodiments, the subject has persistent or recurrent disease after treatment with another therapeutic intervention, including, for example, chemotherapy, radiation therapy, and / or hematopoietic stem cell transplantation (HSCT), e.g., allogeneic HSCT. In some embodiments, administration effectively treats the subject despite the subject having become resistant to another therapy.

[0304] In some embodiments, the subject responds to the other therapeutic agent, and treatment with the therapeutic agent reduces the disease burden. In some aspects, the subject initially responds to the therapeutic agent but exhibits a recurrence of the disease or condition over time. In some embodiments, the subject has not relapsed. In some such embodiments, the subject is determined to be at risk of relapse, such as at high risk of relapse, and therefore the composition is administered prophylactically, e.g., to reduce the likelihood of relapse or prevent relapse. In some aspects, the subject has not received prior treatment with another therapeutic agent.

[0305] The composition can be administered by any convenient method known to those skilled in the art. For example, the composition can be administered to a subject by aerosol inhalation, injection, ingestion, transfusion, implantation, or transplantation. The compositions described herein can be administered to a patient by intra-arterial, subcutaneous, intradermal, intratumoral, intranodal, intramedullary, intramuscular, intravenous (iv) injection, intraperitoneal, intranasal, intracranial, or intraosseous administration. In other cases, the composition is directly injected into the subject at the site of a local disease, lymph node, organ, tumor, or the like.

[0306] For the prevention or treatment of disease, the appropriate dosage will depend on the type of disease being treated, the severity and course of the disease, whether the composition is being administered for prophylactic or therapeutic purposes, previous therapy, the subject's clinical history and response to treatment, and the discretion of the attending physician. The compositions, in some embodiments, are suitably administered to the subject at one time or over a series of treatments.

[0307] In some embodiments, the composition is administered as part of a combination therapy, e.g., simultaneously with another therapeutic intervention, such as an antibody or produced cell or receptor or agent, e.g., a cytotoxic agent or therapeutic agent, or sequentially in any order. In some embodiments, the composition(s) are co-administered in conjunction with another therapeutic intervention, simultaneously with one or more additional therapeutic agents, or sequentially in any order. In some contexts, the composition is co-administered with another therapy sufficiently close in time so that the composition enhances the effect of one or more additional therapeutic agents, or vice versa. In some embodiments, the composition is administered before one or more additional therapeutic agents. In some embodiments, the composition is administered after one or more additional therapeutic agents. In some embodiments, the one or more additional agents include a cytokine, such as IL-2, for example, to enhance durability. In some embodiments, the method includes administration of a chemotherapeutic agent. In some embodiments, the method does not include administration of a chemotherapeutic agent.

[0308] In certain embodiments, the composition may be administered to a subject in combination with an immune checkpoint antibody (e.g., an anti-PD1, anti-CTLA-4, or anti-PDL1 antibody). For example, the viral vector may be administered in combination with, for example, an antibody or antibody fragment that targets PD-1 (programmed cell death 1 protein). Examples of anti-PD-1 antibodies include, but are not limited to, pembrolizumab (KEYTRUDA®, formerly lambrolizumab, also known as MK-3475), and nivolumab (BMS-936558, MDX-1106, ONO-4538, OPDIVO®), or an antigen-binding fragment thereof. In certain embodiments, the composition may be administered in combination with an anti-PD-L1 antibody or an antigen-binding fragment thereof. Examples of anti-PD-L1 antibodies include, but are not limited to, BMS-936559, MPDL3280A (TECENTRIQ®, atezolizumab), and MEDI4736 (durvalumab, Imfinzi). In certain embodiments, the compositions may be administered in combination with an anti-CTLA-4 antibody or antigen-binding fragment thereof. An example of an anti-CTLA-4 antibody includes, but is not limited to, ipilimumab (trade name Yervoy). Other types of immune checkpoint modulators may also be used, including, but not limited to, small molecules, siRNA, miRNA, and CRISPR systems. The immune checkpoint modulator may be administered before, after, or simultaneously with the viral vector. In certain embodiments, a combination therapy including an immune checkpoint modulator may increase the therapeutic efficacy of a therapy including a composition provided herein. Other therapeutic agents may be administered simultaneously, before, or after the compositions provided herein are administered to a subject.

[0309] In certain embodiments, the subject receives a second-line treatment, including, but not limited to, chemotherapy, radiation therapy, surgery, and drug therapy. In some embodiments, the subject is not provided with a second-line treatment.

[0310] In some embodiments, the method is performed without a lymphodepletion step, such as administration of cyclophosphamide and / or fludarabine.

[0311] In some embodiments, after administration of the composition, the subject can undergo a conditioning therapy to kill certain immune cells that are not transduced with the CAR encoded by the composition. This can be done by including a selectable marker encoded by the nucleic acid cargo of interest. In some embodiments, the conditioning therapy comprises administering an effective amount of cyclophosphamide to the subject. In some embodiments, the conditioning therapy comprises administering an effective amount of fludarabine to the subject. In some embodiments, the conditioning therapy comprises administering an effective amount of a combination of cyclophosphamide and fludarabine to the subject.

[0312] In some embodiments, certain dosing regimens of the present disclosure include a lymphodepletion step following administration of the composition. In exemplary embodiments, the lymphodepletion step includes administration of cyclophosphamide and / or fludarabine.

[0313] In some embodiments, the lymphodepletion step comprises administration of cyclophosphamide at a dose of about 200 mg / m² / day to about 2000 mg / m² / day (e.g., 200 mg / m² / day, 300 mg / m² / day, or 500 mg / m² / day). In exemplary embodiments, the dose of cyclophosphamide is about 300 mg / m² / day. In some embodiments, the lymphodepletion step comprises administration of fludarabine at a dose of about 20 mg / m² / day to about 900 mg / m² / day (e.g., 20 mg / m² / day, 25 mg / m² / day, 30 mg / m² / day, or 60 mg / m² / day). In exemplary embodiments, the dose of fludarabine is about 30 mg / m² / day.

[0314] In some embodiments, the lymphodepletion step comprises administration of cyclophosphamide at a dose of about 200 mg / m² / day to about 2000 mg / m² / day (e.g., 200 mg / m² / day, 300 mg / m² / day, or 500 mg / m² / day) and fludarabine at a dose of about 20 mg / m² / day to about 900 mg / m² / day (e.g., 20 mg / m² / day, 25 mg / m² / day, 30 mg / m² / day, or 60 mg / m² / day). In an exemplary embodiment, the lymphodepletion step comprises administration of cyclophosphamide at a dose of about 300 mg / m² / day and fludarabine at a dose of about 30 mg / m² / day.

[0315] In an exemplary embodiment, the dose of cyclophosphamide is 300 mg / m2 / day for three days and the dose of fludarabine is 30 mg / m2 / day for three days.

[0316] It is known in the art that one of the adverse effects of using CAR T cells can be the onset of immune activation known as cytokine release syndrome (CRS). CRS is immune activation that leads to an increase in inflammatory cytokines. CRS is a known target toxicity, and its occurrence likely correlates with efficacy. Clinical and laboratory measures range from mild CRS (systemic symptoms and / or grade 2 organ toxicity) to severe CRS (sCRS; grade 3 or higher organ toxicity, aggressive clinical intervention, and / or potentially life-threatening). Clinical features include high fever, malaise, fatigue, myalgia, nausea, anorexia, tachycardia / hypotension, capillary leak, cardiac dysfunction, renal dysfunction, liver failure, and disseminated intravascular coagulation. Dramatic increases in cytokines, including interferon-gamma, granulocyte-macrophage colony-stimulating factor, IL-10, and IL-6, have been shown after CAR T cell infusion. One CRS signature is elevated cytokines, including IL-6 (severe elevation), IFN-gamma, TNF-alpha (moderate elevation), and IL-2 (mild elevation). Elevated clinically available inflammatory markers, including ferritin and C-reactive protein (CRP), have also been observed to correlate with CRS syndrome. The presence of CRS generally correlates with proliferation of adoptively transferred cells and progressive immune activation. It has been demonstrated that the degree of CRS severity is determined by the disease burden at the time of infusion, as patients with a high tumor burden experience more sCRS.

[0317] Therefore, in some embodiments, the method includes an appropriate CRS management strategy for alleviating the physiological symptoms of uncontrolled inflammation after the diagnosis of CRS without compromising the anti-tumor efficacy of in vivo generated cells (e.g., CAR T cells). CRS management strategies are known in the art. For example, systemic corticosteroids may be administered to rapidly ameliorate the symptoms of sCRS (e.g., grade 3 CRS) without impairing the initial anti-tumor response.

[0318] In some embodiments, an anti-IL-6R antibody may be administered. An example of an anti-IL-6R antibody is the monoclonal antibody tocilizumab, also known as atlizumab (commercially available as Actemra or RoActemra), approved by the Food and Drug Administration. Tocilizumab is a humanized monoclonal antibody against the interleukin-6 receptor (IL-6R). Administration of tocilizumab has demonstrated almost immediate reversal of CRS.

[0319] CRS is generally managed based on the severity of the syndrome observed, and interventions are tailored accordingly. CRS management decisions may be based on clinical signs and symptoms and response to interventions, and not solely on laboratory values.

[0320] Mild to moderate cases are generally treated with symptom management using fluid therapy, nonsteroidal anti-inflammatory drugs (NSAIDs), and antihistamines as needed for adequate symptom relief. More severe cases include patients with any degree of hemodynamic instability, in which case administration of tocilizumab is recommended. First-line management of CRS may, in some embodiments, be tocilizumab at a labeled dose of 8 mg / kg IV over 60 minutes (not to exceed 800 mg / dose), which may be repeated every 8 hours. If the response to the first dose of tocilizumab is suboptimal, additional doses of tocilizumab may be considered. Tocilizumab can be administered alone or in combination with corticosteroid therapy. Patients with persistent or progressive CRS symptoms, inadequate clinical improvement within 12–18 hours, or poor response to tocilizumab may be treated with high-dose corticosteroid therapy, typically hydrocortisone 100 mg IV or methylprednisolone 1–2 mg / kg. In patients with more severe hemodynamic instability or more severe respiratory symptoms, patients may receive high-dose corticosteroid therapy earlier in the course of CRS. CRS management guidance may be based on published standards (Lee et al. (2019) Biol Blood Marrow Transplant, doi.org / 10.1016 / j.bbmt.2018.12.758; Neelapu et al. (2018) Nat Rev Clin Oncology, 15:47; Teachey et al. (2016) Cancer Discov, 6(6):664–679).

[0321] Consistent with the clinical manifestations of CRS, features consistent with macrophage activation syndrome (MAS) or hemophagocytic lymphohistiocytosis (HLH) have been observed in patients treated with CAR-T therapy (Henter, 2007). MAS appears to be a response to immune activation resulting from CRS and should therefore be considered a manifestation of CRS. MAS resembles HLH, which is also a response to immune stimulation. The clinical syndrome of MAS is characterized by high-grade, unremitting fever, cytopenias affecting at least two of three blood systems, and hepatosplenomegaly. This is associated with elevated serum ferritin, soluble interleukin-2 receptor, and triglycerides, as well as decreased circulating natural killer (NK) activity.

[0322] In some embodiments, methods are provided for treating cancer in a subject in need thereof, the method comprising administering to the subject any of the compositions, such as viral particle(s), provided herein.

[0323] The compositions disclosed herein can include pharmaceutical compositions, for example, including a pharmaceutically acceptable carrier and / or a pharmaceutical formulation.

[0324] The term "pharmaceutical formulation" refers to a preparation in a form that allows the biological activity of the active ingredient contained therein to be effective and that does not contain any additional ingredients that are unacceptably toxic to the subject to which the formulation will be administered. A "pharmaceutically acceptable carrier" refers to ingredients in a pharmaceutical formulation, other than the active ingredient, that are non-toxic to the subject. Pharmaceutically acceptable carriers include, but are not limited to, buffers, excipients, stabilizers, or preservatives. In some embodiments, the choice of carrier is determined in part by the particular cell and / or method of administration. Accordingly, a variety of suitable formulations exist. For example, the pharmaceutical composition can contain a preservative. Suitable preservatives can include, for example, methylparaben, propylparaben, sodium benzoate, and benzalkonium chloride. In some embodiments, a mixture of two or more preservatives is used. The preservative or mixtures thereof are typically present in an amount of about 0.0001% to about 2% by weight of the total composition. Carriers are described, for example, by Remington's Pharmaceutical Sciences 16th edition, Osol, A. Ed. (1980).Pharmaceutically acceptable carriers are generally non-toxic to recipients at the dosages and concentrations employed and include, but are not limited to, buffers such as phosphate, citrate, and other organic acids; antioxidants including ascorbic acid and methionine; preservatives (such as octadecyldimethylbenzylammonium chloride; hexamethonium chloride; benzalkonium chloride; benzethonium chloride; phenol, butyl, or benzyl alcohol; alkyl parabens such as methyl or propyl paraben; catechol; resorcinol; cyclohexanol; 3-pentanol; and m-cresol); low molecular weight (less than about 10 residues) polypeptides; serum albumin; hydrophilic polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, histidine, arginine, or lysine; monosaccharides, disaccharides, and other carbohydrates including glucose, mannose, or dextrins; chelating agents such as EDTA; sugars such as sucrose, mannitol, trehalose, or sorbitol; salt-forming counterions such as sodium; metal complexes (e.g., Zn-protein complexes); and / or non-ionic surfactants such as polyethylene glycol (PEG).

[0325] In some embodiments, a buffering agent is included in the composition. Suitable buffering agents include, for example, citric acid, sodium citrate, phosphoric acid, potassium phosphate, and various other acids and salts. In some embodiments, a mixture of two or more buffering agents is used. The buffering agent or mixture thereof is typically present in an amount of about 0.001% to about 4% by weight of the total composition. Methods for preparing administrable pharmaceutical compositions are known. Exemplary methods are described in more detail, for example, in Remington: The Science and Practice of Pharmacy, Lippincott Williams & Wilkins; 21st ed. (May 1, 2005).

[0326] The formulation may comprise an aqueous solution. The formulation or composition may also contain one or more active ingredients useful for the particular indication, disease, or condition being treated with the composition, preferably those with complementary activities, where the activities do not adversely affect each other. Such active ingredients are preferably present in combination in amounts effective for the intended purpose. Thus, in some embodiments, the pharmaceutical composition further comprises another pharmaceutically active agent or drug, such as a chemotherapeutic agent, e.g., asparaginase, busulfan, carboplatin, cisplatin, daunorubicin, doxorubicin, fluorouracil, gemcitabine, hydroxyurea, methotrexate, paclitaxel, rituximab, vinblastine, and / or vincristine. In some embodiments, the pharmaceutical composition contains the composition in an amount effective to treat or prevent the disease or condition, e.g., a therapeutically or prophylactically effective amount. In some embodiments, therapeutic or prophylactic effectiveness is monitored by periodic evaluation of the treated subject. The desired dosage can be delivered by a single bolus administration of the composition, multiple boluses of the composition, or a continuous infusion of the composition. In some embodiments, the pharmaceutical composition does not comprise a chemotherapeutic agent.

[0327] Formulations include those for oral, intravenous, intraperitoneal, subcutaneous, pulmonary, transdermal, intramuscular, intranasal, buccal, sublingual, or suppository administration. In some embodiments, the compositions are administered parenterally. As used herein, the term "parenteral" includes intravenous, intramuscular, subcutaneous, rectal, vaginal, and intraperitoneal administration. In some embodiments, the compositions are administered to a subject using peripheral systemic delivery via intravenous, intraperitoneal, or subcutaneous injection. In some embodiments, the compositions are provided as sterile liquid preparations, such as isotonic aqueous solutions, suspensions, emulsions, dispersions, or viscous compositions, which may, in some aspects, be buffered to a selected pH. Liquid preparations are typically easier to prepare than gels, other viscous compositions, and solid compositions. Furthermore, liquid compositions are somewhat more convenient to administer, particularly by injection. On the other hand, viscous compositions can be formulated within an appropriate viscosity range to provide longer contact periods with specific tissues. A liquid or viscous composition can contain a carrier, which can be a solvent or dispersion medium containing, for example, water, saline, phosphate buffered saline, polyol (e.g., glycerol, propylene glycol, liquid polyethylene glycol), and suitable mixtures thereof.

[0328] Sterile injectable solutions can be prepared by incorporating the composition into a mixture with a suitable carrier, diluent, or excipient, such as sterile water, saline, glucose, dextrose, etc. The composition can contain auxiliary substances, such as wetting agents, dispersing agents, or emulsifying agents (e.g., methylcellulose), pH buffering agents, gelling or viscosity-enhancing additives, preservatives, flavoring agents, and / or dyes, depending on the route of administration and the desired preparation. Standard texts can be consulted in some embodiments to prepare suitable preparations.

[0329] Various additives that enhance the stability and sterility of the compositions can be added, including antimicrobial preservatives, antioxidants, chelating agents, and buffers. Prevention of microbial activity can be ensured by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, and sorbic acid. Prolonged absorption of the injectable pharmaceutical form can be brought about by the use of agents delaying absorption, for example, aluminum monostearate and gelatin.

[0330] Preparations to be used for internal administration are generally sterile, which may be readily accomplished, for example, by filtration through sterile filtration membranes.

[0331] The embodiments provided herein can be used for many purposes, as pseudotyped viruses capable of fusing with target cells can be used to deliver genes of interest or other heterologous sequences.

[0332] Enumeration of Embodiments In some embodiments, the following embodiments are provided: 1. A VSV-G polypeptide comprising a mutation corresponding to the mutation at position 182 of SEQ ID NO:2. 2. The VSV-G polypeptide of embodiment 1, wherein the protein comprises the amino acid sequence of SEQ ID NO: 2 with a mutation at position 182 and has at least 70% identity to SEQ ID NO: 2. 3. The VSV-G polypeptide of embodiment 1 or 2, wherein the polypeptide comprises an I182E or I182D mutation compared to SEQ ID NO: 2. 4. A VSV-G polypeptide according to any one of embodiments 1 to 3, wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 1 with a mutation at position 198 and at least 70% identity to SEQ ID NO: 2. 5. A VSV-G polypeptide according to any one of embodiments 1 to 4, wherein the polypeptide comprises a mutation corresponding to I182D or I182E compared to the sequence of SEQ ID NO: 2. 6. The VSV-G polypeptide of any one of embodiments 1 to 5, wherein the polypeptide comprises an amino acid sequence 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 the amino acid sequence of SEQ ID NO:4. 7. The VSV-G polypeptide of any one of embodiments 1 to 5, wherein the polypeptide comprises the sequence of SEQ ID NO: 4. 8. The VSV polypeptide of any one of embodiments 1 to 5, wherein the polypeptide comprises an amino acid sequence that 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 the amino acid sequence of SEQ ID NO:5. 9. The VSV-G polypeptide of any one of embodiments 1 to 5, wherein the polypeptide comprises the sequence of SEQ ID NO: 5. 10. A VSV-G polypeptide according to any one of embodiments 1 to 9, further comprising a mutation in the VSV-G protein corresponding to the mutation described in US2020 / 0216502, the entire contents of which are incorporated herein by reference. 11. A VSV-G polypeptide according to any one of embodiments 1 to 10, further comprising mutations in the VSV-G protein corresponding to positions 8, 10, 47, 209, and / or 354 compared to SEQ ID NO: 2. 12. The VSV-G polypeptide of any one of embodiments 1 to 11, further comprising a mutation corresponding to position 8 of SEQ ID NO:2, wherein said mutation is any amino acid different from the amino acid shown at that position in SEQ ID NO:2, except for Y. 13. The VSV-G polypeptide of any one of embodiments 1 to 12, further comprising a mutation corresponding to position 209 of SEQ ID NO:2, wherein the mutation is any amino acid different from the amino acid shown at that position in SEQ ID NO:2, except for H. 14. The VSV-G polypeptide of any one of embodiments 1 to 13, further comprising a mutation corresponding to position 47 of SEQ ID NO:2, wherein the mutation is any amino acid different from the amino acid shown at that position in SEQ ID NO:2, except for K or R. 15. The VSV-G polypeptide of any one of embodiments 1 to 14, further comprising a mutation corresponding to position 354 of SEQ ID NO:2, wherein said mutation is any amino acid different from the amino acid shown at that position in SEQ ID NO:2, except for K or R. 16. The VSV-G polypeptide of any one of embodiments 1 to 15, further comprising a mutation corresponding to position 10 of SEQ ID NO:2, wherein the mutation is any amino acid different from the amino acid shown at that position in SEQ ID NO:2, except for Q or N. 17. The VSV-G polypeptide of any one of embodiments 1 to 16, wherein the protein comprises a substitution at position 47 or 354, or at both positions 47 and 354, each position independently substituted with A, G, F, Q, or N. 18. The VSV-G polypeptide of any one of embodiments 1 to 17, wherein the protein comprises a substitution at position 8, wherein the substitution is H8A, H8I, H8V, H8L, or the like. 19. The VSV-G polypeptide of any one of embodiments 1 to 18, wherein the protein comprises a substitution at position 47, wherein the substitution is K47Q or K47N. 20. The VSV-G polypeptide of any one of embodiments 1 to 19, wherein the protein comprises the substitution H8A and / or the K47Q mutation. 21. The VSV-G polypeptide of any one of embodiments 1 to 20, wherein the protein comprises a substitution at position 10, such as a Q10A, Q10R, or Q10K substitution. 22. The VSV-G polypeptide of any one of embodiments 1 to 21, further comprising a mutation corresponding to the mutation at position 214 and / or 352 of SEQ ID NO: 2. 23. The VSV-G polypeptide of embodiment 22, wherein the polypeptide comprises a T214N and / or a T352A mutation. 24. A VSV-G polypeptide comprising a substitution at position I182 and at least one of T214 and T352 of SEQ ID NO:2. 25. The VSV-G polypeptide of embodiment 24, wherein the polypeptide comprises substitutions at positions I182, T214, and T352 of SEQ ID NO:2. 26. The VSV-G polypeptide of embodiment 24 or 25, wherein the substitution at position 182 is I182D or I182E, the substitution at position 214 is T214N, and the substitution at position 352 is T352A. 27. The VSV-G polypeptide of any one of embodiments 24 to 26, wherein the polypeptide comprises the sequence of SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, or SEQ ID NO: 25. 28. The VSV-G polypeptide of any one of embodiments 24 to 26, wherein the polypeptide comprises the sequence of SEQ ID NO: 22. 29. The VSV-G polypeptide of any one of embodiments 24 to 26, wherein the polypeptide comprises the sequence of SEQ ID NO: 23. 30. The VSV-G polypeptide of any one of embodiments 24 to 26, wherein the polypeptide comprises the sequence of SEQ ID NO: 24. 31. The VSV-G polypeptide of any one of embodiments 24 to 26, wherein the polypeptide comprises the sequence of SEQ ID NO: 25. 32. A nucleic acid molecule encoding a VSV-G polypeptide according to any one of embodiments 1 to 31. 33. A vector comprising the nucleic acid molecule of embodiment 32. 34. A plasmid comprising the nucleic acid molecule of embodiment 32. 35. A viral particle comprising a polypeptide according to any one of embodiments 1 to 31. 36. The viral particle of embodiment 35, further comprising a targeting moiety. 37. The viral particle of embodiment 35 or 36, wherein the viral particle is a pseudotyped lentivirus. 38. A viral particle according to any one of embodiments 35 to 37, wherein the viral particle further comprises a nucleic acid molecule encoding a heterologous molecule of interest. 39. The viral particle of embodiment 38, wherein the heterologous molecule of interest is an siRNA, shRNA, non-coding RNA (e.g., a guide RNA for a CRISPR system), a peptide, a polypeptide, a protein, a viral payload, a viral genome, or a combination thereof. 40. The viral particle of embodiment 38 or 39, wherein the heterologous molecule of interest is a chimeric antigen receptor ("CAR"). 41. The viral particle of any one of embodiments 35-40, wherein the targeting moiety binds to an immune cell, such as a T cell, a B cell, an NK cell, a dendritic cell, a neutrophil, a macrophage, a cancer cell, or, for example, a CD3+ T cell, a CD4+ T cell, a CD7+ T cell, a CD8+ T cell, a CD19+ B cell, a CD19+ cancer cell, a CD20+ B cell, a CD20+ cancer cell, a CD30+ lung epithelial cell, a CD34+ hematopoietic stem cell, a CD105+ endothelial cell, a CD105+ hematopoietic stem cell, a CD117+ hematopoietic stem cell, a CD133+ cancer cell, an EpCAM+ cancer cell, a GluA2+ neuron, a GluA4+ neuron, a hematopoietic stem cell, a hepatocyte, a Her2 / Neu+ cancer cell, an NKG2D+ natural killer cell, a SLC1A3+ astrocyte, or a SLC7A10+ adipocyte. 42. The targeting moiety is selected from the group consisting of CD7, CD8, cKit (CD117), CD4, CD3, CD5, CD6, CD2, TCR alpha, TCR beta, TCR gamma, TCR delta, CD10, CD34, CD110, CD33, CD14, CD68, CCR7, CD62L, CD25, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, or CXCR3, a glycosylated CD43 epitope expressed on acute leukemia or lymphoma but not on hematopoietic progenitor cells, a glycosylated CD43 epitope expressed on non-hematopoietic cancers, kinase anchor protein 4 (AKAP-4), address Antigens include: ADRB3, AFP, anaplastic lymphoma kinase (ALK), androgen receptor, angiopoietin-binding cell surface receptor 2 (Tie2), autoantibodies to desmoglein 1 (Dsgl), autoantibodies to desmoglein 3 (Dsg3), B7H3 (CD276), biotin, bone marrow stromal cell antigen 2 (BST2), BST1 / CD157, cancer / testis antigen 1 (NY-ESO-1), cancer / testis antigen 2 (LAGE-1a), carbonic anhydrase IX (CA1X), carcinoembryonic antigen (CEA), CCCTC-binding factor (zinc finger protein)-like (BORIS or Brother of the Regulator of Imprinted Sites), CCR4, CD5, CD19, CD20, CD22, CD24, CD30, CD32 (FCGR2A), CD33, CD34, CD38, CD44v6, CD72, CD79a, CD79b, CD97, CD99, CD123, CD171, CD179a, CD179b-IGL11, CD200R, CD276 / B7H3, CD300 molecule-like family member f (CD300LF), CDH1-CD324, CDH6, CDH17, CDH19, chromosome X open reading frame 61 (CXORF61), claudin 6 (CLDN6), claudin l8.2 (CLD18A2 or CLDN18A.2), CMVpp65, C-MYC epitope tag, Cripto, CS1 (also called CD2 subset 1 or CRACC or SLAMF7 or CD319 or 19A24), CSF2RA (GM-CSFR-alpha), C-type lectin domain family 12 member A (CLEC12A), C-type lectin-like molecule-1 (CLL-1 or CLECL1), cyclin B1, cytochrome P450 IB 1 (CYP1B 1), DLL3, EBV-EBNA3c, EGF-bke module-containing mucin-like hormone receptor-like 2 (EMR2), elongation factor 2 variant (ELF2M), ephrin B2, ephrin type A receptor 2 (EphA2), epidermal growth factor receptor (EGFR), epidermal growth factor receptor variant III (EGFRviii), epithelial cell adhesion molecule (EPCAM), ERG, ETS translocation-variant gene 6 located on chromosome 12p (ETV6-AML), Fc fragment of IgA receptor (FCAR or CD89), Fc receptor-like 5 (FCRL5), fibroblast activation protein alpha (FAP), FITC, Fms-like tyrosine kinase 3 (FLT3), folate receptor alpha (FRa or FR1), folate receptor beta (FRb), follicle-stimulating hormone receptor ( FSHR), Fos-related antigen 1, fucosyl-GMl, G protein-coupled receptor class C group 5 member D (GPRC5D), G protein-coupled receptor 20 (GPR20), GAD, ganglioside G2 (GD2), ganglioside GD3 (aNeu5Ac(2-8)aNeu5Ac(2-3)bDGalp(l-4)bDGlcp(ll)Cer), ganglioside GM3 (aNeu5Ac(2-3)bDClalp(l-4)bDGlcp(ll)Cer), GD3, GFR alpha 4, glycoprotein 100 (gplOO), glypican-3 (GPC3), gonadotropin hormone receptor (CGHR or GR), GpA33, GpNMB, GPRC5D, guanylyl cyclase C (GCC), heat shock protein 70-2 mutant (muthsp70-2), hepatitis A virus cellular receptor 1 (HAVCR1), hexasaccharide moiety of globoH glycoceramide (GloboH), high molecular weight melanoma-associated antigen (HMWMAA), HIV-1 envelope glycoprotein, HLA, HLA-DOA, HLA-A, HLA-A2, HLA-B, HLA-C, HLA-DM, HLA-DOB, HLA-DP, HLA-DQ, HLA-DR, HLA-G, HTLV-1-Tax, human papillomavirus E6 (HPV E6), human papillomavirus E7 (HPV E7), human telomerase reverse transcriptase (hTERT), IgE, IL13Ra2, IL1 lRa, immunoglobulin lambda-like polypeptide 1 (IGLL1), influenza A hemagglutinin (HA), insulin-like growth factor 1 receptor (IGF-I receptor), interleukin-11 receptor alpha (IL-llRa), interleukin-13 receptor subunit alpha-2 (IL-13Ra2 or CD213A2), intestinal carboxylesterase, KIT (CD117), KSHV K8.1, KSHV-gH, LAMP1, legumain, leukocyte immunoglobulin-like receptor subfamily A member 2 (LILRA2), leukocyte-associated immunoglobulin-like receptor 1 (LAIR1), luteinizing hormone receptor (LHR), Lewis (Y) antigen, Lewis Ag, Livl, Locus K9 (LY6K), small conductance chloride channel, lymphocyte antigen 6 complex, lymphocyte antigen 75 (LY75), lymphocyte-specific protein tyrosine kinase (LCK), mammary differentiation antigen (NY-BR-1), melanoma antigen 1 recognized by T cells (MelanA or MARTI), melanoma-associated antigen 1 (MAGE-A1), melanoma cancer testis antigen-1 (MAD-CT-1), melanoma cancer testis antigen-2 (MAD-CT-2), melanoma inhibitor of apoptosis (ML-IAP), mesothelin, MPL, mucin 1 cell surface associated (MUC1), N-acetylglucosaminyl-transferase V (NA17), nectin-4, neural cell adhesion molecule (NCAM), NKG2D, NYBR1, O-acetyl-GD2 ganglioside (OAcGD2), olfactory receptor 51E2 (OR51E2), oncogene fusion protein (bcr-abl) consisting of breakpoint cluster region (BCR) and Abelson murine leukemia viral oncogene homolog 1 (Abl), P53 mutant, paired box protein Pax-3 (PAX3), paired box protein Pax-5 (PAX5), pannexin 3 (PANX3), PDL1, P-glycoprotein, placenta-specific 1 (PLAC1), platelet-derived growth factor receptor beta (PDGFR-beta), polysialic acid, proacrosin-binding protein sp32 (OY-TES1), prostase, prostate cancer tumor antigen-1 (PCT Al or galectin 8), prostate stem cell antigen (PSCA), prostate-specific membrane antigen (PSMA), prostatic acid phosphatase (PAP), prostein, protease serine 21 (testisin or PRSS21), proteasome (prosomal macropain) subunit beta type 9 (LMP2), PTK7, RasG12V, Ras homolog family member C (RhoC), rat sarcoma (Ras) mutant, receptor for advanced glycation end products (RAGE-1), receptor tyrosine kinase-like orphan receptor 1 (ROR1), receptor tyrosine-protein kinase ERBB2 or Her-22 / neu, renal ubiquitous 1 (RU1), renal ubiquitous 2 (RU2), sarcoma translocation breakpoint, serine 2 (TMPRSS2) ETS fusion gene, sialyl Lewis adhesion molecule (sLe), SLAMF4, SLAMF6, Slea (CA19.9 or sialyl Lewis antigen), sperm Subset protein 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 gamma alternative reading frame protein (TARP), TCR-beta 1 chain, TCR-beta 2 chain, TCR-delta chain, TCR gamma chain, TCR gamma-delta, telomerase, TGF-beta R2, antigen recognized by TNT antibodies, thyroid-stimulating hormone receptor (TSHR), Timl- / HVCR1, tissue factor 1 (TF1), Tn 42. The viral particle of any one of embodiments 35-41, which binds to ag, Tn antigen ((Tn Ag) or (GalNAca-Ser / Thr)), TNF receptor family member B-cell maturation (BCMA), transglutaminase 5 (TGS5), transmembrane protease, TROP2, tumor endothelial marker 1 (TEM1 / CD248), tumor endothelial marker 7-related (TEM7R), tumor protein p53 (p53), tumor-associated glycoprotein 72 (TAG72), tyrosinase, tyrosinase-related protein 2 (TRP-2), uroplakin 2 (UPK2), vascular endothelial growth factor receptor 2 (VEGFR2), V-myc avian myelocytomatosis viral oncogene neuroblastoma-derived homolog (MYCN), Wilms tumor protein (WT1), or X antigen family member 1A (XAGE1). 43. The viral particle of any one of embodiments 35 to 42, wherein the targeting moiety is an antibody, an scFv antibody, an antigen-binding domain, ankyrin repeats (e.g., DARPIN), a VHH domain antibody, a nanobody, a single domain antibody, an FN3 domain, or any combination thereof. 44. The targeting moiety is: IgG Fc stalk, envelope glycoprotein G or H of a virus of the Paramyxoviridae family, such as a morbillivirus, such as measles virus, or a henipavirus, such as Nipah virus, Cedar virus, or Hendra virus; glycoproteins of viruses of the family Rhabdoviridae, such as vesicular stomatitis New Jersey virus, vesicular stomatitis Indiana virus, vesicular stomatitis Alagoas virus, vesicular stomatitis Maraba virus, vesicular stomatitis Carajas virus, parainfluenza virus, Spodoptera frugiperda rhabdovirus isolate Sf G, Drosophila obscura sigma virus 10A, Wuhan insect virus 7, Perch virus, or carp spring viremia virus; glycoproteins of viruses in the Filoviridae family, such as Ebola virus, or 44. The virus particle of any one of embodiments 35 to 43, which is attached to the viral surface via a glycoprotein of a virus of the Arenaviridae family, such as Machupo virus. 45. The viral particle of embodiment 44, wherein the stalk comprises a transmembrane domain, such as, but not limited to, a CD8 or CD28 transmembrane domain. 46. ​​A method for delivering a heterologous molecule to a target cell, said method comprising contacting said cell with a viral vector, said viral vector comprising: a) a VSV-G protein according to any one of embodiments 1 to 31; b) a targeting moiety that binds to said target cell; c) a nucleic acid molecule encoding said heterologous molecule. 47. The method of embodiment 46, wherein the target cell is an immune cell, a T cell, a B cell, an NK cell, a dendritic cell, a neutrophil, a macrophage, a cancer cell, or, for example, a CD3+ T cell, a CD4+ T cell, a CD7+ T cell, a CD8+ T cell, a CD19+ B cell, a CD19+ cancer cell, a CD20+ B cell, a CD30+ lung epithelial cell, a CD34+ hematopoietic stem cell, a CD105+ endothelial cell, a CD105+ hematopoietic stem cell, a CD117+ hematopoietic stem cell, a CD133+ cancer cell, an EpCAM+ cancer cell, a GluA2+ neuron, a GluA4+ neuron, a hematopoietic stem cell, a hepatocyte, a Her2 / Neu+ cancer cell, an NKG2D+ natural killer cell, an SLC1A3+ astrocyte, or an SLC7A10+ adipocyte. 48. The targeting moiety is selected from the group consisting of CD7, CD8, cKit (CD117), CD4, CD3, CD5, CD6, CD2, TCR alpha, TCR beta, TCR gamma, TCR delta, CD10, CD34, CD110, CD33, CD14, CD68, CCR7, CD62L, CD25, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, and CXCR3 on the target cell, 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, and kinase anchor protein 4 (AKAP-4). , adrenoceptor beta 3 (ADRB3), AFP, anaplastic lymphoma kinase (ALK), androgen receptor, angiopoietin-binding cell surface receptor 2 (Tie2), autoantibodies to desmoglein 1 (Dsgl), autoantibodies to desmoglein 3 (Dsg3), B7H3 (CD276), biotin, bone marrow stromal cell antigen 2 (BST2), BST1 / CD157, cancer / testis antigen 1 (NY-ESO-1), cancer / testis antigen 2 (LAGE-1a), carbonic anhydrase IX (CA1X), carcinoembryonic antigen (CEA), CCCTC-binding factor (zinc finger protein)-like (BORIS or Brother of the Regulator of Imprinted Sites), CCR4, CD5, CD19, CD20, CD22, CD24, CD30, CD32 (FCGR2A), CD33, CD34, CD38, CD44v6, CD72, CD79a, CD79b, CD97, CD99, CD123, CD171, CD179a, CD179b-IGL11, CD200R, CD276 / B7H3, CD300 molecule-like family member f (CD300LF), CDH1-CD324, CDH6, CDH17, CDH19, chromosome X open reading frame 61 (CXORF61), claudin 6 (CLDN6), claudin l8.2 (CLD18A2 or CLDN18A.2), CMVpp65, C-MYC epitope tag, Cripto, CS1 (also called CD2 subset 1 or CRACC or SLAMF7 or CD319 or 19A24), CSF2RA (GM-CSFR-alpha), C-type lectin domain family 12 member A (CLEC12A), C-type lectin-like molecule-1 (CLL-1 or CLECL1), cyclin B1, cytochrome P450 IB 1 (CYP1B 1), DLL3, EBV-EBNA3c, EGF-bke module-containing mucin-like hormone receptor-like 2 (EMR2), elongation factor 2 variant (ELF2M), ephrin B2, ephrin type A receptor 2 (EphA2), epidermal growth factor receptor (EGFR), epidermal growth factor receptor variant III (EGFRviii), epithelial cell adhesion molecule (EPCAM), ERG, ETS translocation-variant gene 6 located on chromosome 12p (ETV6-AML), Fc fragment of IgA receptor (FCAR or CD89), Fc receptor-like 5 (FCRL5), fibroblast activation protein alpha (FAP), FITC, Fms-like tyrosine kinase 3 (FLT3), folate receptor alpha (FRa or FR1), folate receptor beta (FRb), follicle-stimulating hormone receptor ( FSHR), Fos-related antigen 1, fucosyl-GMl, G protein-coupled receptor class C group 5 member D (GPRC5D), G protein-coupled receptor 20 (GPR20), GAD, ganglioside G2 (GD2), ganglioside GD3 (aNeu5Ac(2-8)aNeu5Ac(2-3)bDGalp(l-4)bDGlcp(ll)Cer), ganglioside GM3 (aNeu5Ac(2-3)bDClalp(l-4)bDGlcp(ll)Cer), GD3, GFR alpha 4, glycoprotein 100 (gplOO), glypican-3 (GPC3), gonadotropin hormone receptor (CGHR or GR), GpA33, GpNMB, GPRC5D, guanylyl cyclase C (GCC), heat shock protein 70-2 mutant (muthsp70-2), hepatitis A virus cellular receptor 1 (HAVCR1), hexasaccharide moiety of globoH glycoceramide (GloboH), high molecular weight melanoma-associated antigen (HMWMAA), HIV-1 envelope glycoprotein, HLA, HLA-DOA, HLA-A, HLA-A2, HLA-B, HLA-C, HLA-DM, HLA-DOB, HLA-DP, HLA-DQ, HLA-DR, HLA-G, HTLV-1-Tax, human papillomavirus E6 (HPV E6), human papillomavirus E7 (HPV E7), human telomerase reverse transcriptase (hTERT), IgE, IL13Ra2, IL1 lRa, immunoglobulin lambda-like polypeptide 1 (IGLL1), influenza A hemagglutinin (HA), insulin-like growth factor 1 receptor (IGF-I receptor), interleukin-11 receptor alpha (IL-llRa), interleukin-13 receptor subunit alpha-2 (IL-13Ra2 or CD213A2), intestinal carboxylesterase, KIT (CD117), KSHV K8.1, KSHV-gH, LAMP1, legumain, leukocyte immunoglobulin-like receptor subfamily A member 2 (LILRA2), leukocyte-associated immunoglobulin-like receptor 1 (LAIR1), luteinizing hormone receptor (LHR), Lewis (Y) antigen, Lewis Ag, Livl, Locus K9 (LY6K), small conductance chloride channel, lymphocyte antigen 6 complex, lymphocyte antigen 75 (LY75), lymphocyte-specific protein tyrosine kinase (LCK), mammary differentiation antigen (NY-BR-1), melanoma antigen 1 recognized by T cells (MelanA or MARTI), melanoma-associated antigen 1 (MAGE-A1), melanoma cancer testis antigen-1 (MAD-CT-1), melanoma cancer testis antigen-2 (MAD-CT-2), melanoma inhibitor of apoptosis (ML-IAP), mesothelin, MPL, mucin 1 cell surface associated (MUC1), N-acetylglucosaminyl-transferase V (NA17), nectin-4, neural cell adhesion molecule (NCAM), NKG2D, NYBR1, O-acetyl-GD2 ganglioside (OAcGD2), olfactory receptor 51E2 (OR51E2), oncogene fusion protein (bcr-abl) consisting of breakpoint cluster region (BCR) and Abelson murine leukemia viral oncogene homolog 1 (Abl), P53 mutant, paired box protein Pax-3 (PAX3), paired box protein Pax-5 (PAX5), pannexin 3 (PANX3), PDL1, P-glycoprotein, placenta-specific 1 (PLAC1), platelet-derived growth factor receptor beta (PDGFR-beta), polysialic acid, proacrosin-binding protein sp32 (OY-TES1), prostase, prostate cancer tumor antigen-1 (PCT Al or galectin 8), prostate stem cell antigen (PSCA), prostate-specific membrane antigen (PSMA), prostatic acid phosphatase (PAP), prostein, protease serine 21 (testisin or PRSS21), proteasome (prosomal macropain) subunit beta type 9 (LMP2), PTK7, RasG12V, Ras homolog family member C (RhoC), rat sarcoma (Ras) mutant, receptor for advanced glycation end products (RAGE-1), receptor tyrosine kinase-like orphan receptor 1 (ROR1), receptor tyrosine-protein kinase ERBB2 or Her-22 / neu, renal ubiquitous 1 (RU1), renal ubiquitous 2 (RU2), sarcoma translocation breakpoint, serine 2 (TMPRSS2) ETS fusion gene, sialyl Lewis adhesion molecule (sLe), SLAMF4, SLAMF6, Slea (CA19.9 or sialyl Lewis antigen), sperm Subset protein 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 gamma alternative reading frame protein (TARP), TCR-beta 1 chain, TCR-beta 2 chain, TCR-delta chain, TCR gamma chain, TCR gamma-delta, telomerase, TGF-beta R2, antigen recognized by TNT antibodies, thyroid-stimulating hormone receptor (TSHR), Timl- / HVCR1, tissue factor 1 (TF1), Tn 48. The method of embodiment 46 or 47, wherein the antibody binds to ag, Tn antigen ((Tn Ag) or (GalNAca-Ser / Thr)), TNF receptor family member B-cell maturation (BCMA), transglutaminase 5 (TGS5), transmembrane protease, TROP2, tumor endothelial marker 1 (TEM1 / CD248), tumor endothelial marker 7-related (TEM7R), tumor protein p53 (p53), tumor-associated glycoprotein 72 (TAG72), tyrosinase, tyrosinase-related protein 2 (TRP-2), uroplakin 2 (UPK2), vascular endothelial growth factor receptor 2 (VEGFR2), V-myc avian myelocytomatosis viral oncogene neuroblastoma-derived homolog (MYCN), Wilms tumor protein (WT1), or X antigen family member 1A (XAGE1). 49. A method of delivering a heterologous molecule to a target cell in a subject, the method comprising administering to the subject a viral vector, the viral vector comprising: a) a VSV-G polypeptide according to any one of embodiments 1 to 31; b) a targeting moiety that binds to said target cell; c) a nucleic acid molecule encoding said heterologous molecule. 50. The method of embodiment 49, wherein the target cell is an immune cell, a T cell, a B cell, an NK cell, a dendritic cell, a neutrophil, a macrophage, a cancer cell, or, for example, a CD3+ T cell, a CD4+ T cell, a CD7+ T cell, a CD8+ T cell, a CD19+ B cell, a CD19+ cancer cell, a CD20+ B cell, a CD20+ cancer cell, a CD30+ lung epithelial cell, a CD34+ hematopoietic stem cell, a CD105+ endothelial cell, a CD105+ hematopoietic stem cell, a CD117+ hematopoietic stem cell, a CD133+ cancer cell, an EpCAM+ cancer cell, a GluA2+ neuron, a GluA4+ neuron, a hematopoietic stem cell, a hepatocyte, a Her2 / Neu+ cancer cell, an NKG2D+ natural killer cell, an SLC1A3+ astrocyte, or an SLC7A10+ adipocyte. 51. The targeting moiety is selected from the group consisting of CD7, CD8, cKit (CD117), CD4, CD3, CD5, CD6, CD2, TCR alpha, TCR beta, TCR gamma, TCR delta, CD10, CD34, CD110, CD33, CD14, CD68, CCR7, CD62L, CD25, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, and CXCR3 on the target cell, 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, and kinase anchor protein 4 (AKAP-4). , adrenoceptor beta 3 (ADRB3), AFP, anaplastic lymphoma kinase (ALK), androgen receptor, angiopoietin-binding cell surface receptor 2 (Tie2), autoantibodies to desmoglein 1 (Dsgl), autoantibodies to desmoglein 3 (Dsg3), B7H3 (CD276), biotin, bone marrow stromal cell antigen 2 (BST2), BST1 / CD157, cancer / testis antigen 1 (NY-ESO-1), cancer / testis antigen 2 (LAGE-1a), carbonic anhydrase IX (CA1X), carcinoembryonic antigen (CEA), CCCTC-binding factor (zinc finger protein)-like (BORIS or Brother of the Regulator of Imprinted Sites), CCR4, CD5, CD19, CD20, CD22, CD24, CD30, CD32 (FCGR2A), CD33, CD34, CD38, CD44v6, CD72, CD79a, CD79b, CD97, CD99, CD123, CD171, CD179a, CD179b-IGL11, CD200R, CD276 / B7H3, CD300 molecule-like family member f (CD300LF), CDH1-CD324, CDH6, CDH17, CDH19, chromosome X open reading frame 61 (CXORF61), claudin 6 (CLDN6), claudin l8.2 (CLD18A2 or CLDN18A.2), CMVpp65, C-MYC epitope tag, Cripto, CS1 (also called CD2 subset 1 or CRACC or SLAMF7 or CD319 or 19A24), CSF2RA (GM-CSFR-alpha), C-type lectin domain family 12 member A (CLEC12A), C-type lectin-like molecule-1 (CLL-1 or CLECL1), cyclin B1, cytochrome P450 IB 1 (CYP1B 1), DLL3, EBV-EBNA3c, EGF-bke module-containing mucin-like hormone receptor-like 2 (EMR2), elongation factor 2 variant (ELF2M), ephrin B2, ephrin type A receptor 2 (EphA2), epidermal growth factor receptor (EGFR), epidermal growth factor receptor variant III (EGFRviii), epithelial cell adhesion molecule (EPCAM), ERG, ETS translocation-variant gene 6 located on chromosome 12p (ETV6-AML), Fc fragment of IgA receptor (FCAR or CD89), Fc receptor-like 5 (FCRL5), fibroblast activation protein alpha (FAP), FITC, Fms-like tyrosine kinase 3 (FLT3), folate receptor alpha (FRa or FR1), folate receptor beta (FRb), follicle-stimulating hormone receptor ( FSHR), Fos-related antigen 1, fucosyl-GMl, G protein-coupled receptor class C group 5 member D (GPRC5D), G protein-coupled receptor 20 (GPR20), GAD, ganglioside G2 (GD2), ganglioside GD3 (aNeu5Ac(2-8)aNeu5Ac(2-3)bDGalp(l-4)bDGlcp(ll)Cer), ganglioside GM3 (aNeu5Ac(2-3)bDClalp(l-4)bDGlcp(ll)Cer), GD3, GFR alpha 4, glycoprotein 100 (gplOO), glypican-3 (GPC3), gonadotropin hormone receptor (CGHR or GR), GpA33, GpNMB, GPRC5D, guanylyl cyclase C (GCC), heat shock protein 70-2 mutant (muthsp70-2), hepatitis A virus cellular receptor 1 (HAVCR1), hexasaccharide moiety of globoH glycoceramide (GloboH), high molecular weight melanoma-associated antigen (HMWMAA), HIV-1 envelope glycoprotein, HLA, HLA-DOA, HLA-A, HLA-A2, HLA-B, HLA-C, HLA-DM, HLA-DOB, HLA-DP, HLA-DQ, HLA-DR, HLA-G, HTLV-1-Tax, human papillomavirus E6 (HPV E6), human papillomavirus E7 (HPV E7), human telomerase reverse transcriptase (hTERT), IgE, IL13Ra2, IL1 lRa, immunoglobulin lambda-like polypeptide 1 (IGLL1), influenza A hemagglutinin (HA), insulin-like growth factor 1 receptor (IGF-I receptor), interleukin-11 receptor alpha (IL-llRa), interleukin-13 receptor subunit alpha-2 (IL-13Ra2 or CD213A2), intestinal carboxylesterase, KIT (CD117), KSHV K8.1, KSHV-gH, LAMP1, legumain, leukocyte immunoglobulin-like receptor subfamily A member 2 (LILRA2), leukocyte-associated immunoglobulin-like receptor 1 (LAIR1), luteinizing hormone receptor (LHR), Lewis (Y) antigen, Lewis Ag, Livl, Locus K9 (LY6K), small conductance chloride channel, lymphocyte antigen 6 complex, lymphocyte antigen 75 (LY75), lymphocyte-specific protein tyrosine kinase (LCK), mammary differentiation antigen (NY-BR-1), melanoma antigen 1 recognized by T cells (MelanA or MARTI), melanoma-associated antigen 1 (MAGE-A1), melanoma cancer testis antigen-1 (MAD-CT-1), melanoma cancer testis antigen-2 (MAD-CT-2), melanoma inhibitor of apoptosis (ML-IAP), mesothelin, MPL, mucin 1 cell surface associated (MUC1), N-acetylglucosaminyl-transferase V (NA17), nectin-4, neural cell adhesion molecule (NCAM), NKG2D, NYBR1, O-acetyl-GD2 ganglioside (OAcGD2), olfactory receptor 51E2 (OR51E2), oncogene fusion protein (bcr-abl) consisting of breakpoint cluster region (BCR) and Abelson murine leukemia viral oncogene homolog 1 (Abl), P53 mutant, paired box protein Pax-3 (PAX3), paired box protein Pax-5 (PAX5), pannexin 3 (PANX3), PDL1, P-glycoprotein, placenta-specific 1 (PLAC1), platelet-derived growth factor receptor beta (PDGFR-beta), polysialic acid, proacrosin-binding protein sp32 (OY-TES1), prostase, prostate cancer tumor antigen-1 (PCT Al or galectin 8), prostate stem cell antigen (PSCA), prostate-specific membrane antigen (PSMA), prostatic acid phosphatase (PAP), prostein, protease serine 21 (testisin or PRSS21), proteasome (prosomal macropain) subunit beta type 9 (LMP2), PTK7, RasG12V, Ras homolog family member C (RhoC), rat sarcoma (Ras) mutant, receptor for advanced glycation end products (RAGE-1), receptor tyrosine kinase-like orphan receptor 1 (ROR1), receptor tyrosine-protein kinase ERBB2 or Her-22 / neu, renal ubiquitous 1 (RU1), renal ubiquitous 2 (RU2), sarcoma translocation breakpoint, serine 2 (TMPRSS2) ETS fusion gene, sialyl Lewis adhesion molecule (sLe), SLAMF4, SLAMF6, Slea (CA19.9 or sialyl Lewis antigen), sperm Subset protein 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 gamma alternative reading frame protein (TARP), TCR-beta 1 chain, TCR-beta 2 chain, TCR-delta chain, TCR gamma chain, TCR gamma-delta, telomerase, TGF-beta R2, antigen recognized by TNT antibodies, thyroid-stimulating hormone receptor (TSHR), Timl- / HVCR1, tissue factor 1 (TF1), Tn 51. The method of embodiment 49 or 50, wherein the antibody binds to ag, Tn antigen ((Tn Ag) or (GalNAca-Ser / Thr)), TNF receptor family member B-cell maturation (BCMA), transglutaminase 5 (TGS5), transmembrane protease, TROP2, tumor endothelial marker 1 (TEM1 / CD248), tumor endothelial marker 7-related (TEM7R), tumor protein p53 (p53), tumor-associated glycoprotein 72 (TAG72), tyrosinase, tyrosinase-related protein 2 (TRP-2), uroplakin 2 (UPK2), vascular endothelial growth factor receptor 2 (VEGFR2), V-myc avian myelocytomatosis viral oncogene neuroblastoma-derived homolog (MYCN), Wilms tumor protein (WT1), or X antigen family member 1A (XAGE1). 52. The viral particle of any one of embodiments 46 to 51, wherein the heterologous molecule is an siRNA, shRNA, non-coding RNA (e.g., a guide RNA for a CRISPR system), a peptide, a polypeptide, a protein, a viral payload, a viral genome, or a combination thereof, such as a chimeric antigen receptor ("CAR"). 53. A method of treating cancer in a subject, the method comprising administering to the subject a viral vector, the viral vector comprising: a) a VSV-G polypeptide according to any one of embodiments 1 to 31; b) a targeting moiety that binds to said target cell; c) a nucleic acid molecule encoding said heterologous molecule. 54. The method of embodiment 53, wherein the heterologous molecule is a chimeric antigen receptor. 55. The method of embodiment 53 or 54, wherein the target cell is an immune cell, a T cell, a B cell, an NK cell, a dendritic cell, a neutrophil, a macrophage, a cancer cell, or, for example, a CD3+ T cell, a CD4+ T cell, a CD7+ T cell, a CD8+ T cell, a CD19+ B cell, a CD19+ cancer cell, a CD20+ B cell, a CD30+ lung epithelial cell, a CD34+ hematopoietic stem cell, a CD105+ endothelial cell, a CD105+ hematopoietic stem cell, a CD117+ hematopoietic stem cell, a CD133+ cancer cell, an EpCAM+ cancer cell, a GluA2+ neuron, a GluA4+ neuron, a hematopoietic stem cell, a hepatocyte, a Her2 / Neu+ cancer cell, an NKG2D+ natural killer cell, an SLC1A3+ astrocyte, or an SLC7A10+ adipocyte. 56. The targeting moiety is selected from the group consisting of CD7, CD8, cKit (CD117), CD4, CD3, CD5, CD6, CD2, TCR alpha, TCR beta, TCR gamma, TCR delta, CD10, CD34, CD110, CD33, CD14, CD68, CCR7, CD62L, CD25, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, and CXCR3 on the target cell, 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, and kinase anchor protein 4 (AKAP-4). , adrenoceptor beta 3 (ADRB3), AFP, anaplastic lymphoma kinase (ALK), androgen receptor, angiopoietin-binding cell surface receptor 2 (Tie2), autoantibodies to desmoglein 1 (Dsgl), autoantibodies to desmoglein 3 (Dsg3), B7H3 (CD276), biotin, bone marrow stromal cell antigen 2 (BST2), BST1 / CD157, cancer / testis antigen 1 (NY-ESO-1), cancer / testis antigen 2 (LAGE-1a), carbonic anhydrase IX (CA1X), carcinoembryonic antigen (CEA), CCCTC-binding factor (zinc finger protein)-like (BORIS or Brother of the Regulator of Imprinted Sites), CCR4, CD5, CD19, CD20, CD22, CD24, CD30, CD32 (FCGR2A), CD33, CD34, CD38, CD44v6, CD72, CD79a, CD79b, CD97, CD99, CD123, CD171, CD179a, CD179b-IGL11, CD200R, CD276 / B7H3, CD300 molecule-like family member f (CD300LF), CDH1-CD324, CDH6, CDH17, CDH19, chromosome X open reading frame 61 (CXORF61), claudin 6 (CLDN6), claudin l8.2 (CLD18A2 or CLDN18A.2), CMVpp65, C-MYC epitope tag, Cripto, CS1 (also called CD2 subset 1 or CRACC or SLAMF7 or CD319 or 19A24), CSF2RA (GM-CSFR-alpha), C-type lectin domain family 12 member A (CLEC12A), C-type lectin-like molecule-1 (CLL-1 or CLECL1), cyclin B1, cytochrome P450 IB 1 (CYP1B 1), DLL3, EBV-EBNA3c, EGF-bke module-containing mucin-like hormone receptor-like 2 (EMR2), elongation factor 2 variant (ELF2M), ephrin B2, ephrin type A receptor 2 (EphA2), epidermal growth factor receptor (EGFR), epidermal growth factor receptor variant III (EGFRviii), epithelial cell adhesion molecule (EPCAM), ERG, ETS translocation-variant gene 6 located on chromosome 12p (ETV6-AML), Fc fragment of IgA receptor (FCAR or CD89), Fc receptor-like 5 (FCRL5), fibroblast activation protein alpha (FAP), FITC, Fms-like tyrosine kinase 3 (FLT3), folate receptor alpha (FRa or FR1), folate receptor beta (FRb), follicle-stimulating hormone receptor ( FSHR), Fos-related antigen 1, fucosyl-GMl, G protein-coupled receptor class C group 5 member D (GPRC5D), G protein-coupled receptor 20 (GPR20), GAD, ganglioside G2 (GD2), ganglioside GD3 (aNeu5Ac(2-8)aNeu5Ac(2-3)bDGalp(l-4)bDGlcp(ll)Cer), ganglioside GM3 (aNeu5Ac(2-3)bDClalp(l-4)bDGlcp(ll)Cer), GD3, GFR alpha 4, glycoprotein 100 (gplOO), glypican-3 (GPC3), gonadotropin hormone receptor (CGHR or GR), GpA33, GpNMB, GPRC5D, guanylyl cyclase C (GCC), heat shock protein 70-2 mutant (muthsp70-2), hepatitis A virus cellular receptor 1 (HAVCR1), hexasaccharide moiety of globoH glycoceramide (GloboH), high molecular weight melanoma-associated antigen (HMWMAA), HIV-1 envelope glycoprotein, HLA, HLA-DOA, HLA-A, HLA-A2, HLA-B, HLA-C, HLA-DM, HLA-DOB, HLA-DP, HLA-DQ, HLA-DR, HLA-G, HTLV-1-Tax, human papillomavirus E6 (HPV E6), human papillomavirus E7 (HPV E7), human telomerase reverse transcriptase (hTERT), IgE, IL13Ra2, IL1 lRa, immunoglobulin lambda-like polypeptide 1 (IGLL1), influenza A hemagglutinin (HA), insulin-like growth factor 1 receptor (IGF-I receptor), interleukin-11 receptor alpha (IL-llRa), interleukin-13 receptor subunit alpha-2 (IL-13Ra2 or CD213A2), intestinal carboxylesterase, KIT (CD117), KSHV K8.1, KSHV-gH, LAMP1, legumain, leukocyte immunoglobulin-like receptor subfamily A member 2 (LILRA2), leukocyte-associated immunoglobulin-like receptor 1 (LAIR1), luteinizing hormone receptor (LHR), Lewis (Y) antigen, Lewis Ag, Livl, Locus K9 (LY6K), small conductance chloride channel, lymphocyte antigen 6 complex, lymphocyte antigen 75 (LY75), lymphocyte-specific protein tyrosine kinase (LCK), mammary differentiation antigen (NY-BR-1), melanoma antigen 1 recognized by T cells (MelanA or MARTI), melanoma-associated antigen 1 (MAGE-A1), melanoma cancer testis antigen-1 (MAD-CT-1), melanoma cancer testis antigen-2 (MAD-CT-2), melanoma inhibitor of apoptosis (ML-IAP), mesothelin, MPL, mucin 1 cell surface associated (MUC1), N-acetylglucosaminyl-transferase V (NA17), nectin-4, neural cell adhesion molecule (NCAM), NKG2D, NYBR1, O-acetyl-GD2 ganglioside (OAcGD2), olfactory receptor 51E2 (OR51E2), oncogene fusion protein (bcr-abl) consisting of breakpoint cluster region (BCR) and Abelson murine leukemia viral oncogene homolog 1 (Abl), P53 mutant, paired box protein Pax-3 (PAX3), paired box protein Pax-5 (PAX5), pannexin 3 (PANX3), PDL1, P-glycoprotein, placenta-specific 1 (PLAC1), platelet-derived growth factor receptor beta (PDGFR-beta), polysialic acid, proacrosin-binding protein sp32 (OY-TES1), prostase, prostate cancer tumor antigen-1 (PCT Al or galectin 8), prostate stem cell antigen (PSCA), prostate-specific membrane antigen (PSMA), prostatic acid phosphatase (PAP), prostein, protease serine 21 (testisin or PRSS21), proteasome (prosomal macropain) subunit beta type 9 (LMP2), PTK7, RasG12V, Ras homolog family member C (RhoC), rat sarcoma (Ras) mutant, receptor for advanced glycation end products (RAGE-1), receptor tyrosine kinase-like orphan receptor 1 (ROR1), receptor tyrosine-protein kinase ERBB2 or Her-22 / neu, renal ubiquitous 1 (RU1), renal ubiquitous 2 (RU2), sarcoma translocation breakpoint, serine 2 (TMPRSS2) ETS fusion gene, sialyl Lewis adhesion molecule (sLe), SLAMF4, SLAMF6, Slea (CA19.9 or sialyl Lewis antigen), sperm Subset protein 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 gamma alternative reading frame protein (TARP), TCR-beta 1 chain, TCR-beta 2 chain, TCR-delta chain, TCR gamma chain, TCR gamma-delta, telomerase, TGF-beta R2, antigen recognized by TNT antibodies, thyroid-stimulating hormone receptor (TSHR), Timl- / HVCR1, tissue factor 1 (TF1), Tn 56. The method of any one of embodiments 53-55, wherein the antibody binds to ag, Tn antigen ((Tn Ag) or (GalNAca-Ser / Thr)), TNF receptor family member B-cell maturation (BCMA), transglutaminase 5 (TGS5), transmembrane protease, TROP2, tumor endothelial marker 1 (TEM1 / CD248), tumor endothelial marker 7-related (TEM7R), tumor protein p53 (p53), tumor-associated glycoprotein 72 (TAG72), tyrosinase, tyrosinase-related protein 2 (TRP-2), uroplakin 2 (UPK2), vascular endothelial growth factor receptor 2 (VEGFR2), V-myc avian myelocytomatosis viral oncogene neuroblastoma-derived homolog (MYCN), Wilms tumor protein (WT1), or X antigen family member 1A (XAGE1). 57. The method of any one of embodiments 53-56, wherein the cancer is a cancer provided herein, such as a T-cell or B-cell disorder. 58. A viral particle according to any one of embodiments 35 to 45, wherein the targeting moiety binds to CD7. 59. The viral particle of embodiment 58, wherein the targeting moiety that binds to CD7 comprises a polypeptide comprising: (i) a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 35, the heavy chain CDR2 sequence has the amino acid sequence of SEQ ID NO: 36, and the heavy chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 37, or any variant thereof; and (ii) a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 38, the light chain CDR2 sequence has the amino acid sequence of SEQ ID NO: 39, and the light chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 40, or any variant thereof. 60. The viral particle of embodiment 59, wherein the heavy chain comprises a heavy chain variable region having at least 90% sequence identity to SEQ ID NO: 47, and wherein the polypeptide maintains the sequences of HCDR1 set forth in SEQ ID NO: 35, HCDR2 set forth in SEQ ID NO: 36, and HCDR3 set forth in SEQ ID NO: 37. 61. The viral particle of embodiment 59 or 60, wherein the light chain comprises a light chain variable region having at least 90% sequence identity to SEQ ID NO: 48, and wherein the polypeptide maintains the sequences of LCDR1 set forth in SEQ ID NO: 38, LCDR2 set forth in SEQ ID NO: 39, and LCDR3 set forth in SEQ ID NO: 40. 62. A viral particle described in any one of embodiments 59 to 61, wherein the polypeptide comprises a heavy chain and a light chain, the heavy chain comprising a heavy chain variable region having at least 90% sequence identity to SEQ ID NO: 47, and a light chain variable region of the light chain having at least 90% sequence identity to SEQ ID NO: 48, and the polypeptide maintains the seque...

Claims

1. A VSV-G polypeptide comprising a mutation corresponding to the mutation at position 182 of SEQ ID NO: 2, wherein the mutation is a substitution of D, E, S, H, T, Q, N, or A at position 182 of SEQ ID NO:

2.

2. The VSV-G polypeptide according to Claim 1, wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 2 having a mutation at position 182, and is at least 95% identical to SEQ ID NO:

2.

3. The VSV-G polypeptide according to claim 1, wherein the polypeptide comprises the I182E or I182D mutation compared to SEQ ID NO:

2.

4. The VSV-G polypeptide according to claim 1, wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 1 having a mutation at position 198 and is at least 70% identical to SEQ ID NO:

2.

5. The VSV-G polypeptide according to claim 1, wherein the polypeptide comprises a mutation corresponding to I182D or I182E when compared to the sequence of SEQ ID NO:

2.

6. The VSV-G polypeptide according to claim 1, wherein the polypeptide comprises at least 95% of the same amino acid sequence as the sequence of SEQ ID NO:

4.

7. The VSV-G polypeptide according to claim 1, wherein the polypeptide comprises the amino acid sequence of SEQ ID NO:

4.

8. The VSV-G polypeptide according to claim 1, wherein the polypeptide comprises at least 95% of the same amino acid sequence as the sequence of SEQ ID NO:

5.

9. The VSV-G polypeptide according to claim 1, wherein the polypeptide comprises the amino acid sequence of SEQ ID NO:

5.

10. The VSV-G polypeptide according to claim 1, further comprising mutations of the VSV-G polypeptide corresponding to positions 8, 10, 47, 209, and / or 354 compared to SEQ ID NO:

2.

11. The VSV-G polypeptide according to claim 1, further comprising a mutation corresponding to position 8 of SEQ ID NO: 2, wherein the mutation is any amino acid different from the amino acid shown at that position in SEQ ID NO: 2, except for Y.

12. The VSV-G polypeptide according to claim 1, further comprising a mutation corresponding to position 209 of SEQ ID NO: 2, wherein the mutation is any amino acid different from the amino acid shown at that position in SEQ ID NO: 2, except for H.

13. The VSV-G polypeptide according to claim 1, further comprising a mutation corresponding to position 47 of SEQ ID NO: 2, wherein the mutation is any amino acid different from the amino acid shown at that position in SEQ ID NO: 2, except for K or R.

14. The VSV-G polypeptide according to claim 1, further comprising a mutation corresponding to position 354 of SEQ ID NO: 2, wherein the mutation is any amino acid different from the amino acid shown at that position in SEQ ID NO: 2, except for K or R.

15. The VSV-G polypeptide according to claim 1, further comprising a mutation corresponding to position 10 of SEQ ID NO: 2, wherein the mutation is any amino acid different from the amino acid shown at that position in SEQ ID NO: 2, except for Q or N.

16. The VSV-G polypeptide according to claim 1, wherein the polypeptide further comprises substitutions at position 47, position 354, or both positions 47 and 354, each position independently substituted with A, G, F, Q, or N.

17. The VSV-G polypeptide according to claim 1, wherein the polypeptide further comprises a substitution at the 8-position, the substitution being H8A, H8I, H8V, H8L, and the like.

18. The VSV-G polypeptide according to claim 1, wherein the polypeptide further comprises a substitution at the 47th position, and the substitution is K47Q or K47N.

19. The VSV-G polypeptide according to claim 1, wherein the polypeptide further comprises a substituted H8A and / or K47Q mutation.

20. The VSV-G polypeptide according to claim 1, wherein the polypeptide further comprises a Q10A, Q10R, or Q10K substitution.

21. The VSV-G polypeptide according to claim 1, further comprising mutations corresponding to the mutations at position 214 and / or 352 of SEQ ID NO:

2.

22. The VSV-G polypeptide according to claim 21, wherein the polypeptide comprises the T214N and / or T352A mutation.

23. A VSV-G polypeptide comprising a substitution at position I182 of SEQ ID NO: 2 and at least one of T214 and T352, wherein the mutation at position 182 is I182D, I182E, I182S, I182H, I182T, I182Q, I182N, or I182A compared to SEQ ID NO:

2.

24. The VSV-G polypeptide according to claim 23, wherein the polypeptide comprises substitutions at positions I182, T214, and T352 of SEQ ID NO:

2.

25. The VSV-G polypeptide according to claim 23, wherein the substitution at position 182 is I182D or I182E, the substitution at position 214 is T214N, and the substitution at position 352 is T352A.

26. The VSV-G polypeptide according to claim 23, wherein the polypeptide comprises the sequence of SEQ ID NO: 23, SEQ ID NO: 22, SEQ ID NO: 24, or SEQ ID NO:

25.

27. The VSV-G polypeptide according to claim 23, wherein the polypeptide comprises the sequence of sequence number 23.

28. The VSV-G polypeptide according to claim 23, wherein the polypeptide comprises the sequence of sequence number 22.

29. The VSV-G polypeptide according to claim 23, wherein the polypeptide comprises the sequence of sequence number 24.

30. The VSV-G polypeptide according to claim 23, wherein the polypeptide comprises the sequence of sequence number 25.

31. A nucleic acid molecule encoding the VSV-G polypeptide described in claim 1.

32. A vector comprising the nucleic acid molecule described in claim 31.

33. A plasmid comprising the nucleic acid molecule described in claim 31.

34. A virus particle comprising the polypeptide described in any one of claims 1 to 30.

35. The virus particle according to claim 34, further comprising a targeting site.

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

37. The virus particle according to claim 34, wherein the virus particle further comprises a nucleic acid molecule encoding a target heterologous molecule.

38. The viral particle according to claim 37, wherein the target heterogeneous molecule is an siRNA, shRNA, non-coding RNA (e.g., guide RNA for the CRISPR system), peptide, polypeptide, protein, viral payload, viral genome, or a combination thereof.

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

40. The virus particle according to claim 39, wherein the chimeric antigen receptor includes an antigen-binding domain that binds to CD20.

41. The virus particle according to claim 34, wherein the targeting site binds to immune cells, T cells, B cells, NK cells, dendritic cells, neutrophils, macrophages, cancer cells, CD3+ T cells, CD4+ T cells, CD7+ T cells, CD8+ T cells, CD19+ B cells, CD19+ cancer cells, CD20+ B cells, CD20+ cancer cells, CD30+ lung epithelial cells, CD34+ hematopoietic stem cells, CD105+ endothelial cells, CD105+ hematopoietic stem cells, CD117+ hematopoietic stem cells, CD133+ cancer cells, EpCAM+ cancer cells, GluA2+ neurons, GluA4+ neurons, hematopoietic stem cells, hepatocytes, Her2 / Neu+ cancer cells, NKG2D+ natural killer cells, SLC1A3+ astrocytes, or SLC7A10+ adipocytes.

42. The targeting sites include CD7, CD8, cKit (CD117), CD4, CD3, CD5, CD6, CD2, TCR alpha, TCR beta, TCR gamma, TCR delta, CD10, CD34, CD110, CD33, CD14, CD68, CCR7, CD62L, CD25, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, or CXCR3, glycosylated CD43 epitope expressed on acute leukemia or lymphoma but not on hematopoietic progenitor cells, glycosylated CD43 epitope expressed on non-hematopoietic carcinomas, kinase anchor protein 4 (AKAP-4), and adrenaline Autoantibodies against desmoglein receptor beta-3 (ADRB3), AFP, anaplastic lymphoma kinase (ALK), androgen receptor, angiopoietin-binding cell surface receptor 2 (Tie2), desmoglein 1 (Dsgl), desmoglein 3 (Dsg3), B7H3 (CD276), biotin, bone marrow stromal cell antigen 2 (BST2), BST1 / CD157, cancer / testis antigen 1 (NY-ESO-1), cancer / testis antigen 2 (LAGE-la), carbonic anhydrase IX (CA1X), carcinoembryonic antigen (CEA), CCCTC-binding factor (zinc finger protein)-like (BORIS or Brother of the Regulator of lmprinted Sites), CCR4, CD5, CD19, CD20, CD22, CD24, CD30, CD32 (FCGR2A), CD33, CD34, CD38, CD44v6, CD72, CD79a, CD79b, CD97, CD99, CD123, CD171, CD179a, CD179b-IGLL, CD200R, CD276 / B7H3, CD300 molecule-like family member f (CD300LF), CDH1-CD324, CDH6, CDH17, CDH19, chromosome X open reading frame 61 (CXORF61), claudin 6 (CLDN6), claudin 18.2 (CLD18A2 or CLDN18A.2), CMVpp65, C-MYC epitope tag, Crypto, CS1 (also known as CD2 subset 1, CRACC, SLAMF7, CD319, or 19A24), CSF2RA (GM-CSFR-alpha), C-type lectin domain family 12 member A (CLEC12A), C-type lectin-like molecule-1 (CLL-1 or CLECL1), cyclin BL, cytochrome P450 IB 1 (CYP1B) 1) DLL3, EBV-EBNA3c, EGF-bke module-containing mucin-like hormone receptor 2 (EMR2), elongation factor 2 mutant (ELF2M), ephrin B2, ephrin type A receptor 2 (EphA2), epidermal growth factor receptor (EGFR), epidermal growth factor receptor variant III (EGFRviiii), epidermal cell adhesion molecule (EPCAM), ERG, ETS translocation-variant gene 6 located on chromosome 12p (ETV6-AML), IgA receptor Fc fragment (FCAR or CD89), Fc receptor-like 5 (FCRL5), fibroblast-activating protein alpha (FAP), FITC, Fms-like tyrosine kinase 3 (FLT3), folate receptor alpha (FRa or FR1), folate receptor beta (FRb), follicle-stimulating hormone receptor (F SHR), Fos-related antigen 1, fucosyl-GMl, G protein-coupled receptor class C group 5 member D (GPRC5D), G protein-coupled receptor 20 (GPR20), GAD, ganglioside G2 (GD2), ganglioside GD3 (aNeu5Ac(2-8)aNeu5Ac(2-3)bDGalp(l-4)bDGlcp(l-l)Cer), ganglioside GM3 ( aNeu5Ac(2-3)bDCLarp(l-4)bDGlcp(l-l)Cer), GD3, GFR alpha 4, glycoprotein 100 (gplOO), glypican-3 (GPC3), gonadotropin hormone receptor (CGHR or GR), GpA33, GpNMB, GPRC5D, guanylyl cyclase C (GCC), heat shock protein 70-2 variant (muthsp70-2), hepatitis A virus cell receptor 1 (HAVCR1), hexasaccharide portion of globeH glycoceramide (GloboH), high molecular weight melanoma-associated antigen (HMWMAA), HIV1 envelope glycoprotein, HLA, HLA-DOA, HLA-A, HLA-A2, HLA-B, HLA-C, HLA-DM, HLA-DOB, HLA-DP, HLA-DQ, HLA-DR, HLA-G, HTLV-Tax, human papillomavirus E6 (HPV E6), human papillomavirus E7 (HPV E7), human telomerase reverse transcriptase (hTERT), IgE, IL13Ra2, IL lRa, immunoglobulin lambda-like polypeptide 1 (IGLL1), influenza A hemagglutinin (HA), insulin-like growth factor 1 receptor (IGF-I receptor), interleukin-11 receptor alpha (IL-llRa), interleukin-13 receptor subunit alpha-2 (IL-13Ra2 or CD213A2), intestinal carboxylesterase, KIT (CD117), KSHV K8.1, KSHV-gH, LAMP1, Legmain, leukocyte immunoglobulin-like receptor subfamily A member 2 (LILRA2), leukocyte-associated immunoglobulin-like receptor 1 (LAIR1), luteinizing hormone receptor (LHR), Lewis (Y) antigen, Lewis Ag, Livl, Locus K9 (LY6K), low-conductance chloride channel, lymphocyte antigen 6 complex, lymphocyte antigen 75 (LY75), lymphocyte-specific protein tyrosine kinase (LCK), mammary gland differentiation antigen (NY-BR-1), melanoma antigen 1 recognized by T cells (MelanA or MARTI), melanoma-associated antigen 1 (MAGE-A1), melanoma carcinoma testis antigen-1 (MAD-CT-1), melanoma carcinoma testis antigen-2 (MAD-CT-2), apoptosis-induced melanoma inhibitor (ML-IAP), mesoserine, MPL, mucin 1 cell surface-associated (MUC1), N-acetylglucosaminyl-transferase V (NA17), nectin-4, nerve cell adhesion molecule (NCAM), NKG2D, NYBR1, Oncogene fusion protein (bcr-abl) consisting of O-acetyl-GD2 ganglioside (OAcGD2), olfactory receptor 51E2 (OR51E2), cleavage cluster region (BCR), and Abelson mouse leukemia virus oncogene homolog 1 (Abl), P53 variant, paired box protein Pax-3 (PAX3), paired box protein Pax-5 (PAX5), panexin 3 (PANX3), PDL1, P-glycoprotein, placenta-specific 1 (PLAC1), platelet-derived growth factor receptor beta (PDGFR-beta), polysialic acid, proacrosin-binding protein sp32 (OY-TES1), prostase, prostate cancer tumor antigen-1 (PCT A-l or galectin-8), prostate stem cell antigen (PSCA), prostate-specific membrane antigen (PSMA), prostatic acid phosphatase (PAP), prostain, protease serine 21 (testicin or PRSS21), proteasome (prosomal macropain) subunit beta-9 (LMP2), PTK7, RasG12V, Ras homolog family member C (RhoC), rat sarcoma (Ras) mutant, advanced glycation end product receptor (RAGE-1), receptor tyrosine kinase-like orphan receptor 1 (ROR1), receptor tyrosine-protein kinase ERBB2 or Her-22 / neu, renal ubiquitous receptor 1 (RU1), renal ubiquitous receptor 2 (RU2), sarcoma translocation breakpoint, serine 2 (TMPRSS2) ETS fusion gene, sialyl Lewis adhesion molecule (sLe), SLAMF4, SLAMF6, Slea (CA19.9 or sialyl Lewis antigen), sperm Sub-protein 17 (SPA17), squamous cell carcinoma antigen 3 recognized by T cells (SART3), stage-specific embryonic antigen-4 (SSEA-4), STEAP1, Survivin, synovial sarcoma X-section 2 (SSX2), TCR gamma surrogate leading frame protein (TARP), TCR-beta 1 chain, TCR-beta 2 chain, TCR-delta chain, TCR gamma chain, TCR gamma-delta, telomerase, TGF-beta R2, antigen recognized by TNT antibody, thyroid-stimulating hormone receptor (TSHR), Timl- / HVCR1, tissue factor 1 (TF1), Tn The viral particle according to claim 34, which binds to ag, Tn antigen ((Tn Ag) or (GalNAca-Ser / Thr)), TNF receptor family member B cell maturation (BCMA), transglutaminase 5 (TGS5), transmembrane protease, TROP2, tumor endothelial marker 1 (TEM1 / CD248), tumor endothelial marker 7-related (TEM7R), tumor protein p53 (p53), tumor-associated glycoprotein 72 (TAG72), tyrosinase, tyrosinase-related protein 2 (TRP-2), uroplakin 2 (UPK2), vascular endothelial growth factor receptor 2 (VEGFR2), V-myc avian myelocytosis virus oncogene neuroblastoma-derived homolog (MYCN), Wilms tumor protein (WT1), or X antigen family member 1A (XAGE1).

43. The virus particle according to claim 42, wherein the targeting site binds to CD7.

44. The virus particle according to claim 43, wherein the targeting site that binds to CD7 comprises a polypeptide 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 the sequence shown in SEQ ID NO:

52.

45. The virus particle according to claim 42, wherein the targeting site binds to CD8.

46. The virus particle according to claim 45, wherein the targeting site that binds to CD8 comprises a sequence having at least 90% sequence identity with respect to SEQ ID NO: 69, at least 95% sequence identity with respect to SEQ ID NO: 69, at least 99% sequence identity with respect to SEQ ID NO: 69, or a polypeptide comprising the sequence shown in SEQ ID NO:

69.

47. The viral particle according to claim 34, wherein the targeting site is an antibody, an scFv antibody, an antigen-binding domain, an ankyrin repeat (e.g., DARPIN), a VHH domain antibody, a nanobody, a single-domain antibody, an FN3 domain, or any combination thereof.

48. The aforementioned target site is IG FcStork, Envelope glycoproteins G or H of viruses belonging to the Paramyxoviridae family, such as morbilliviruses including measles virus, or henipaviruses such as nipah virus, cedar virus, or hendra virus. Glycoproteins of viruses of the Rhabdoviridae family, such as bullous stomatitis New Jersey virus, bullous stomatitis Indiana virus, bullous stomatitis Aragoas virus, bullous stomatitis Maraba virus, bullous stomatitis Karajas virus, parainfluenza virus, Spodoptera frugiperda rhabdovirus isolate Sf G, Drosophila obscura sigmavirus 10A, Wuhan insect virus 7, perch virus, or koi spring viremia virus. Glycoproteins of viruses of the Filoviridae family, such as the Ebola virus, or The virus particle according to claim 34, which attaches to the surface of a virus via a glycoprotein of a virus of the family Arenaviridae, such as Machupovirus.

49. The virus particle according to claim 48, wherein the stalk comprises a CD8 or CD28 transmembrane domain.

50. A method for delivering a heterologous molecule to a target cell in vitro or ex vivo, wherein the method includes contacting the cell with a viral vector, and the viral vector is a) A VSV-G polypeptide according to any one of claims 1 to 30, b) A targeting site that binds to the target cell, c) The method comprising a nucleic acid molecule encoding the heterologous molecule.

51. The method according to claim 50, wherein the target cells are immune cells, T cells, B cells, NK cells, dendritic cells, neutrophils, macrophages, cancer cells, CD3+ T cells, CD4+ T cells, CD7+ T cells, CD8+ T cells, CD19+ B cells, CD19+ cancer cells, CD20+ B cells, CD20+ cancer cells, CD30+ lung epithelial cells, CD34+ hematopoietic stem cells, CD105+ endothelial cells, CD105+ hematopoietic stem cells, CD117+ hematopoietic stem cells, CD133+ cancer cells, EpCAM+ cancer cells, GluA2+ neurons, GluA4+ neurons, hematopoietic stem cells, hepatocytes, Her2 / Neu+ cancer cells, NKG2D+ natural killer cells, SLC1A3+ astrocytic cells, or SLC7A10+ adipocytes.

52. The targeting sites include CD7, CD8, cKit (CD117), CD4, CD3, CD5, CD6, CD2, TCR alpha, TCR beta, TCR gamma, TCR delta, CD10, CD34, CD110, CD33, CD14, CD68, CCR7, CD62L, CD25, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, or CXCR3 on the target cells, a glycosylated CD43 epitope expressed on acute leukemia or lymphoma but not on hematopoietic progenitor cells, a glycosylated CD43 epitope expressed on non-hematopoietic carcinomas, kinase anchor protein 4 (AKAP-4), and Autoantibodies against drainage receptor beta-3 (ADRB3), AFP, anaplastic lymphoma kinase (ALK), androgen receptor, angiopoietin-binding cell surface receptor 2 (Tie2), desmoglein 1 (Dsgl), desmoglein 3 (Dsg3), B7H3 (CD276), biotin, bone marrow stromal cell antigen 2 (BST2), BST1 / CD157, cancer / testis antigen 1 (NY-ESO-1), cancer / testis antigen 2 (LAGE-la), carbonic anhydrase IX (CA1X), carcinoembryonic antigen (CEA), and CCCTC-binding factor (zinc finger protein)-like (BORIS or Brother of the Regulator of lmprinted Sites), CCR4, CD5, CD19, CD20, CD22, CD24, CD30, CD32 (FCGR2A), CD33, CD34, CD38, CD44v6, CD72, CD79a, CD79b, CD97, CD99, CD123, CD171, CD179a, CD179b-IGLL, CD200R, CD276 / B7H3, CD300 molecule-like family member f (CD300LF), CDH1-CD324, CDH6, CDH17, CDH19, chromosome X open reading frame 61 (CXORF61), claudin 6 (CLDN6), claudin 18.2 (CLD18A2 or CLDN18A.2), CMVpp65, C-MYC epitope tag, Crypto, CS1 (also known as CD2 subset 1, CRACC, SLAMF7, CD319, or 19A24), CSF2RA (GM-CSFR-alpha), C-type lectin domain family 12 member A (CLEC12A), C-type lectin-like molecule-1 (CLL-1 or CLECL1), cyclin BL, cytochrome P450 IB 1 (CYP1B) 1) DLL3, EBV-EBNA3c, EGF-bke module-containing mucin-like hormone receptor 2 (EMR2), elongation factor 2 mutant (ELF2M), ephrin B2, ephrin type A receptor 2 (EphA2), epidermal growth factor receptor (EGFR), epidermal growth factor receptor variant III (EGFRviiii), epidermal cell adhesion molecule (EPCAM), ERG, ETS translocation-variant gene 6 located on chromosome 12p (ETV6-AML), IgA receptor Fc fragment (FCAR or CD89), Fc receptor-like 5 (FCRL5), fibroblast-activating protein alpha (FAP), FITC, Fms-like tyrosine kinase 3 (FLT3), folate receptor alpha (FRa or FR1), folate receptor beta (FRb), follicle-stimulating hormone receptor (F SHR), Fos-related antigen 1, fucosyl-GMl, G protein-coupled receptor class C group 5 member D (GPRC5D), G protein-coupled receptor 20 (GPR20), GAD, ganglioside G2 (GD2), ganglioside GD3 (aNeu5Ac(2-8)aNeu5Ac(2-3)bDGalp(l-4)bDGlcp(l-l)Cer), ganglioside GM3 ( aNeu5Ac(2-3)bDCLarp(l-4)bDGlcp(l-l)Cer), GD3, GFR alpha 4, glycoprotein 100 (gplOO), glypican-3 (GPC3), gonadotropin hormone receptor (CGHR or GR), GpA33, GpNMB, GPRC5D, guanylyl cyclase C (GCC), heat shock protein 70-2 variant (muthsp70-2), hepatitis A virus cell receptor 1 (HAVCR1), hexasaccharide portion of globeH glycoceramide (GloboH), high molecular weight melanoma-associated antigen (HMWMAA), HIV1 envelope glycoprotein, HLA, HLA-DOA, HLA-A, HLA-A2, HLA-B, HLA-C, HLA-DM, HLA-DOB, HLA-DP, HLA-DQ, HLA-DR, HLA-G, HTLV-Tax, human papillomavirus E6 (HPV E6), human papillomavirus E7 (HPV E7), human telomerase reverse transcriptase (hTERT), IgE, IL13Ra2, IL lRa, immunoglobulin lambda-like polypeptide 1 (IGLL1), influenza A hemagglutinin (HA), insulin-like growth factor 1 receptor (IGF-I receptor), interleukin-11 receptor alpha (IL-llRa), interleukin-13 receptor subunit alpha-2 (IL-13Ra2 or CD213A2), intestinal carboxylesterase, KIT (CD117), KSHV K8.1, KSHV-gH, LAMP1, Legmain, leukocyte immunoglobulin-like receptor subfamily A member 2 (LILRA2), leukocyte-associated immunoglobulin-like receptor 1 (LAIR1), luteinizing hormone receptor (LHR), Lewis (Y) antigen, Lewis Ag, Livl, Locus K9 (LY6K), low-conductance chloride channel, lymphocyte antigen 6 complex, lymphocyte antigen 75 (LY75), lymphocyte-specific protein tyrosine kinase (LCK), mammary gland differentiation antigen (NY-BR-1), melanoma antigen 1 recognized by T cells (MelanA or MARTI), melanoma-associated antigen 1 (MAGE-A1), melanoma carcinoma testis antigen-1 (MAD-CT-1), melanoma carcinoma testis antigen-2 (MAD-CT-2), apoptosis-induced melanoma inhibitor (ML-IAP), mesoserine, MPL, mucin 1 cell surface-associated (MUC1), N-acetylglucosaminyl-transferase V (NA17), nectin-4, nerve cell adhesion molecule (NCAM), NKG2D, NYBR1, Oncogene fusion protein (bcr-abl) consisting of O-acetyl-GD2 ganglioside (OAcGD2), olfactory receptor 51E2 (OR51E2), cleavage cluster region (BCR), and Abelson mouse leukemia virus oncogene homolog 1 (Abl), P53 variant, paired box protein Pax-3 (PAX3), paired box protein Pax-5 (PAX5), panexin 3 (PANX3), PDL1, P-glycoprotein, placenta-specific 1 (PLAC1), platelet-derived growth factor receptor beta (PDGFR-beta), polysialic acid, proacrosin-binding protein sp32 (OY-TES1), prostase, prostate cancer tumor antigen-1 (PCT A-l or galectin-8), prostate stem cell antigen (PSCA), prostate-specific membrane antigen (PSMA), prostatic acid phosphatase (PAP), prostain, protease serine 21 (testicin or PRSS21), proteasome (prosomal macropain) subunit beta-9 (LMP2), PTK7, RasG12V, Ras homolog family member C (RhoC), rat sarcoma (Ras) mutant, advanced glycation end product receptor (RAGE-1), receptor tyrosine kinase-like orphan receptor 1 (ROR1), receptor tyrosine-protein kinase ERBB2 or Her-22 / neu, renal ubiquitous receptor 1 (RU1), renal ubiquitous receptor 2 (RU2), sarcoma translocation breakpoint, serine 2 (TMPRSS2) ETS fusion gene, sialyl Lewis adhesion molecule (sLe), SLAMF4, SLAMF6, Slea (CA19.9 or sialyl Lewis antigen), sperm Sub-protein 17 (SPA17), squamous cell carcinoma antigen 3 recognized by T cells (SART3), stage-specific embryonic antigen-4 (SSEA-4), STEAP1, Survivin, synovial sarcoma X-section 2 (SSX2), TCR gamma surrogate leading frame protein (TARP), TCR-beta 1 chain, TCR-beta 2 chain, TCR-delta chain, TCR gamma chain, TCR gamma-delta, telomerase, TGF-beta R2, antigen recognized by TNT antibody, thyroid-stimulating hormone receptor (TSHR), Timl- / HVCR1, tissue factor 1 (TF1), Tn The method according to claim 50, wherein the binding is to ag, Tn antigen ((Tn Ag) or (GalNAca-Ser / Thr)), TNF receptor family member B cell maturation (BCMA), transglutaminase 5 (TGS5), transmembrane protease, TROP2, tumor endothelial marker 1 (TEM1 / CD248), tumor endothelial marker 7-related (TEM7R), tumor protein p53 (p53), tumor-associated glycoprotein 72 (TAG72), tyrosinase, tyrosinase-related protein 2 (TRP-2), uroplakin 2 (UPK2), vascular endothelial growth factor receptor 2 (VEGFR2), V-myc avian myelocytosis virus oncogene neuroblastoma-derived homolog (MYCN), Wilms tumor protein (WT1), or X antigen family member 1A (XAGE1).

53. A composition for delivering heterologous molecules to target cells in a subject, a) A VSV-G polypeptide according to any one of claims 1 to 30, b) A targeting site that binds to the target cell, c) A composition comprising a viral vector, which comprises a nucleic acid molecule encoding the heterologous molecule.

54. The composition according to claim 53, wherein the target cells are immune cells, T cells, B cells, NK cells, dendritic cells, neutrophils, macrophages, cancer cells, CD3+ T cells, CD4+ T cells, CD7+ T cells, CD8+ T cells, CD19+ B cells, CD19+ cancer cells, CD20+ B cells, CD20+ cancer cells, CD30+ lung epithelial cells, CD34+ hematopoietic stem cells, CD105+ endothelial cells, CD105+ hematopoietic stem cells, CD117+ hematopoietic stem cells, CD133+ cancer cells, EpCAM+ cancer cells, GluA2+ neurons, GluA4+ neurons, hematopoietic stem cells, hepatocytes, Her2 / Neu+ cancer cells, NKG2D+ natural killer cells, SLC1A3+ astrocytic cells, or SLC7A10+ adipocytes.

55. The targeting sites include CD7, CD8, cKit (CD117), CD4, CD3, CD5, CD6, CD2, TCR alpha, TCR beta, TCR gamma, TCR delta, CD10, CD34, CD110, CD33, CD14, CD68, CCR7, CD62L, CD25, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, or CXCR3 on the target cells, a glycosylated CD43 epitope expressed on acute leukemia or lymphoma but not on hematopoietic progenitor cells, a glycosylated CD43 epitope expressed on non-hematopoietic carcinomas, kinase anchor protein 4 (AKAP-4), and Autoantibodies against drainage receptor beta-3 (ADRB3), AFP, anaplastic lymphoma kinase (ALK), androgen receptor, angiopoietin-binding cell surface receptor 2 (Tie2), desmoglein 1 (Dsgl), desmoglein 3 (Dsg3), B7H3 (CD276), biotin, bone marrow stromal cell antigen 2 (BST2), BST1 / CD157, cancer / testis antigen 1 (NY-ESO-1), cancer / testis antigen 2 (LAGE-la), carbonic anhydrase IX (CA1X), carcinoembryonic antigen (CEA), and CCCTC-binding factor (zinc finger protein)-like (BORIS or Brother of the Regulator of lmprinted Sites), CCR4, CD5, CD19, CD20, CD22, CD24, CD30, CD32 (FCGR2A), CD33, CD34, CD38, CD44v6, CD72, CD79a, CD79b, CD97, CD99, CD123, CD171, CD179a, CD179b-IGLL, CD200R, CD276 / B7H3, CD300 molecule-like family member f (CD300LF), CDH1-CD324, CDH6, CDH17, CDH19, chromosome X open reading frame 61 (CXORF61), claudin 6 (CLDN6), claudin 18.2 (CLD18A2 or CLDN18A.2), CMVpp65, C-MYC epitope tag, Crypto, CS1 (also known as CD2 subset 1, CRACC, SLAMF7, CD319, or 19A24), CSF2RA (GM-CSFR-alpha), C-type lectin domain family 12 member A (CLEC12A), C-type lectin-like molecule-1 (CLL-1 or CLECL1), cyclin BL, cytochrome P450 IB 1 (CYP1B) 1) DLL3, EBV-EBNA3c, EGF-bke module-containing mucin-like hormone receptor 2 (EMR2), elongation factor 2 mutant (ELF2M), ephrin B2, ephrin type A receptor 2 (EphA2), epidermal growth factor receptor (EGFR), epidermal growth factor receptor variant III (EGFRviiii), epidermal cell adhesion molecule (EPCAM), ERG, ETS translocation-variant gene 6 located on chromosome 12p (ETV6-AML), IgA receptor Fc fragment (FCAR or CD89), Fc receptor-like 5 (FCRL5), fibroblast-activating protein alpha (FAP), FITC, Fms-like tyrosine kinase 3 (FLT3), folate receptor alpha (FRa or FR1), folate receptor beta (FRb), follicle-stimulating hormone receptor (F SHR), Fos-related antigen 1, fucosyl-GMl, G protein-coupled receptor class C group 5 member D (GPRC5D), G protein-coupled receptor 20 (GPR20), GAD, ganglioside G2 (GD2), ganglioside GD3 (aNeu5Ac(2-8)aNeu5Ac(2-3)bDGalp(l-4)bDGlcp(l-l)Cer), ganglioside GM3 ( aNeu5Ac(2-3)bDCLarp(l-4)bDGlcp(l-l)Cer), GD3, GFR alpha 4, glycoprotein 100 (gplOO), glypican-3 (GPC3), gonadotropin hormone receptor (CGHR or GR), GpA33, GpNMB, GPRC5D, guanylyl cyclase C (GCC), heat shock protein 70-2 variant (muthsp70-2), hepatitis A virus cell receptor 1 (HAVCR1), hexasaccharide portion of globeH glycoceramide (GloboH), high molecular weight melanoma-associated antigen (HMWMAA), HIV1 envelope glycoprotein, HLA, HLA-DOA, HLA-A, HLA-A2, HLA-B, HLA-C, HLA-DM, HLA-DOB, HLA-DP, HLA-DQ, HLA-DR, HLA-G, HTLV-Tax, human papillomavirus E6 (HPV E6), human papillomavirus E7 (HPV E7), human telomerase reverse transcriptase (hTERT), IgE, IL13Ra2, IL lRa, immunoglobulin lambda-like polypeptide 1 (IGLL1), influenza A hemagglutinin (HA), insulin-like growth factor 1 receptor (IGF-I receptor), interleukin-11 receptor alpha (IL-llRa), interleukin-13 receptor subunit alpha-2 (IL-13Ra2 or CD213A2), intestinal carboxylesterase, KIT (CD117), KSHV K8.1, KSHV-gH, LAMP1, Legmain, leukocyte immunoglobulin-like receptor subfamily A member 2 (LILRA2), leukocyte-associated immunoglobulin-like receptor 1 (LAIR1), luteinizing hormone receptor (LHR), Lewis (Y) antigen, Lewis Ag, Livl, Locus K9 (LY6K), low-conductance chloride channel, lymphocyte antigen 6 complex, lymphocyte antigen 75 (LY75), lymphocyte-specific protein tyrosine kinase (LCK), mammary gland differentiation antigen (NY-BR-1), melanoma antigen 1 recognized by T cells (MelanA or MARTI), melanoma-associated antigen 1 (MAGE-A1), melanoma carcinoma testis antigen-1 (MAD-CT-1), melanoma carcinoma testis antigen-2 (MAD-CT-2), apoptosis-induced melanoma inhibitor (ML-IAP), mesoserine, MPL, mucin 1 cell surface-associated (MUC1), N-acetylglucosaminyl-transferase V (NA17), nectin-4, nerve cell adhesion molecule (NCAM), NKG2D, NYBR1, Oncogene fusion protein (bcr-abl) consisting of O-acetyl-GD2 ganglioside (OAcGD2), olfactory receptor 51E2 (OR51E2), cleavage cluster region (BCR), and Abelson mouse leukemia virus oncogene homolog 1 (Abl), P53 variant, paired box protein Pax-3 (PAX3), paired box protein Pax-5 (PAX5), panexin 3 (PANX3), PDL1, P-glycoprotein, placenta-specific 1 (PLAC1), platelet-derived growth factor receptor beta (PDGFR-beta), polysialic acid, proacrosin-binding protein sp32 (OY-TES1), prostase, prostate cancer tumor antigen-1 (PCT A-l or galectin-8), prostate stem cell antigen (PSCA), prostate-specific membrane antigen (PSMA), prostatic acid phosphatase (PAP), prostain, protease serine 21 (testicin or PRSS21), proteasome (prosomal macropain) subunit beta-9 (LMP2), PTK7, RasG12V, Ras homolog family member C (RhoC), rat sarcoma (Ras) mutant, advanced glycation end product receptor (RAGE-1), receptor tyrosine kinase-like orphan receptor 1 (ROR1), receptor tyrosine-protein kinase ERBB2 or Her-22 / neu, renal ubiquitous receptor 1 (RU1), renal ubiquitous receptor 2 (RU2), sarcoma translocation breakpoint, serine 2 (TMPRSS2) ETS fusion gene, sialyl Lewis adhesion molecule (sLe), SLAMF4, SLAMF6, Slea (CA19.9 or sialyl Lewis antigen), sperm Sub-protein 17 (SPA17), squamous cell carcinoma antigen 3 recognized by T cells (SART3), stage-specific embryonic antigen-4 (SSEA-4), STEAP1, Survivin, synovial sarcoma X-section 2 (SSX2), TCR gamma surrogate leading frame protein (TARP), TCR-beta 1 chain, TCR-beta 2 chain, TCR-delta chain, TCR gamma chain, TCR gamma-delta, telomerase, TGF-beta R2, antigen recognized by TNT antibody, thyroid-stimulating hormone receptor (TSHR), Timl- / HVCR1, tissue factor 1 (TF1), Tn The composition according to claim 53, which binds to ag, Tn antigen ((Tn Ag) or (GalNAca-Ser / Thr)), TNF receptor family member B cell maturation (BCMA), transglutaminase 5 (TGS5), transmembrane protease, TROP2, tumor endothelial marker 1 (TEM1 / CD248), tumor endothelial marker 7-related (TEM7R), tumor protein p53 (p53), tumor-associated glycoprotein 72 (TAG72), tyrosinase, tyrosinase-related protein 2 (TRP-2), uroplakin 2 (UPK2), vascular endothelial growth factor receptor 2 (VEGFR2), V-myc avian myelocytosis virus oncogene neuroblastoma-derived homolog (MYCN), Wilms tumor protein (WT1), or X antigen family member 1A (XAGE1).

56. The method according to claim 50, 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.

57. A composition for treating cancer, a) A VSV-G polypeptide according to any one of claims 1 to 30, b) A targeting site that binds to the target cell, c) A nucleic acid molecule that encodes the aforementioned heterogeneous molecule, A composition containing a viral vector.

58. The composition according to claim 57, wherein the heterologous molecule is a chimeric antigen receptor.

59. The composition according to claim 57, wherein the target cells are immune cells, T cells, B cells, NK cells, dendritic cells, neutrophils, macrophages, cancer cells, or, for example, CD3+ T cells, CD4+ T cells, CD7+ T cells, CD8+ T cells, CD19+ B cells, CD19+ cancer cells, CD20+ B cells, CD30+ lung epithelial cells, CD34+ hematopoietic stem cells, CD105+ endothelial cells, CD105+ hematopoietic stem cells, CD117+ hematopoietic stem cells, CD133+ cancer cells, EpCAM+ cancer cells, GluA2+ neurons, GluA4+ neurons, hematopoietic stem cells, hepatocytes, Her2 / Neu+ cancer cells, NKG2D+ natural killer cells, SLC1A3+ astrocytic cells, or SLC7A10+ adipocytes.

60. The targeting sites include CD7, CD8, cKit (CD117), CD4, CD3, CD5, CD6, CD2, TCR alpha, TCR beta, TCR gamma, TCR delta, CD10, CD34, CD110, CD33, CD14, CD68, CCR7, CD62L, CD25, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, or CXCR3 on the target cells, a glycosylated CD43 epitope expressed on acute leukemia or lymphoma but not on hematopoietic progenitor cells, a glycosylated CD43 epitope expressed on non-hematopoietic carcinomas, kinase anchor protein 4 (AKAP-4), and Autoantibodies against drainage receptor beta-3 (ADRB3), AFP, anaplastic lymphoma kinase (ALK), androgen receptor, angiopoietin-binding cell surface receptor 2 (Tie2), desmoglein 1 (Dsgl), desmoglein 3 (Dsg3), B7H3 (CD276), biotin, bone marrow stromal cell antigen 2 (BST2), BST1 / CD157, cancer / testis antigen 1 (NY-ESO-1), cancer / testis antigen 2 (LAGE-la), carbonic anhydrase IX (CA1X), carcinoembryonic antigen (CEA), and CCCTC-binding factor (zinc finger protein)-like (BORIS or Brother of the Regulator of lmprinted Sites), CCR4, CD5, CD19, CD20, CD22, CD24, CD30, CD32 (FCGR2A), CD33, CD34, CD38, CD44v6, CD72, CD79a, CD79b, CD97, CD99, CD123, CD171, CD179a, CD179b-IGLL, CD200R, CD276 / B7H3, CD300 molecule-like family member f (CD300LF), CDH1-CD324, CDH6, CDH17, CDH19, chromosome X open reading frame 61 (CXORF61), claudin 6 (CLDN6), claudin 18.2 (CLD18A2 or CLDN18A.2), CMVpp65, C-MYC epitope tag, Crypto, CS1 (also known as CD2 subset 1, CRACC, SLAMF7, CD319, or 19A24), CSF2RA (GM-CSFR-alpha), C-type lectin domain family 12 member A (CLEC12A), C-type lectin-like molecule-1 (CLL-1 or CLECL1), cyclin BL, cytochrome P450 IB 1 (CYP1B) 1) DLL3, EBV-EBNA3c, EGF-bke module-containing mucin-like hormone receptor 2 (EMR2), elongation factor 2 mutant (ELF2M), ephrin B2, ephrin type A receptor 2 (EphA2), epidermal growth factor receptor (EGFR), epidermal growth factor receptor variant III (EGFRviiii), epidermal cell adhesion molecule (EPCAM), ERG, ETS translocation-variant gene 6 located on chromosome 12p (ETV6-AML), IgA receptor Fc fragment (FCAR or CD89), Fc receptor-like 5 (FCRL5), fibroblast-activating protein alpha (FAP), FITC, Fms-like tyrosine kinase 3 (FLT3), folate receptor alpha (FRa or FR1), folate receptor beta (FRb), follicle-stimulating hormone receptor (F SHR), Fos-related antigen 1, fucosyl-GMl, G protein-coupled receptor class C group 5 member D (GPRC5D), G protein-coupled receptor 20 (GPR20), GAD, ganglioside G2 (GD2), ganglioside GD3 (aNeu5Ac(2-8)aNeu5Ac(2-3)bDGalp(l-4)bDGlcp(l-l)Cer), ganglioside GM3 ( aNeu5Ac(2-3)bDCLarp(l-4)bDGlcp(l-l)Cer), GD3, GFR alpha 4, glycoprotein 100 (gplOO), glypican-3 (GPC3), gonadotropin hormone receptor (CGHR or GR), GpA33, GpNMB, GPRC5D, guanylyl cyclase C (GCC), heat shock protein 70-2 variant (muthsp70-2), hepatitis A virus cell receptor 1 (HAVCR1), hexasaccharide portion of globeH glycoceramide (GloboH), high molecular weight melanoma-associated antigen (HMWMAA), HIV1 envelope glycoprotein, HLA, HLA-DOA, HLA-A, HLA-A2, HLA-B, HLA-C, HLA-DM, HLA-DOB, HLA-DP, HLA-DQ, HLA-DR, HLA-G, HTLV-Tax, human papillomavirus E6 (HPV E6), human papillomavirus E7 (HPV E7), human telomerase reverse transcriptase (hTERT), IgE, IL13Ra2, IL lRa, immunoglobulin lambda-like polypeptide 1 (IGLL1), influenza A hemagglutinin (HA), insulin-like growth factor 1 receptor (IGF-I receptor), interleukin-11 receptor alpha (IL-llRa), interleukin-13 receptor subunit alpha-2 (IL-13Ra2 or CD213A2), intestinal carboxylesterase, KIT (CD117), KSHV K8.1, KSHV-gH, LAMP1, Legmain, leukocyte immunoglobulin-like receptor subfamily A member 2 (LILRA2), leukocyte-associated immunoglobulin-like receptor 1 (LAIR1), luteinizing hormone receptor (LHR), Lewis (Y) antigen, Lewis Ag, Livl, Locus K9 (LY6K), low-conductance chloride channel, lymphocyte antigen 6 complex, lymphocyte antigen 75 (LY75), lymphocyte-specific protein tyrosine kinase (LCK), mammary gland differentiation antigen (NY-BR-1), melanoma antigen 1 recognized by T cells (MelanA or MARTI), melanoma-associated antigen 1 (MAGE-A1), melanoma carcinoma testis antigen-1 (MAD-CT-1), melanoma carcinoma testis antigen-2 (MAD-CT-2), apoptosis-induced melanoma inhibitor (ML-IAP), mesoserine, MPL, mucin 1 cell surface-associated (MUC1), N-acetylglucosaminyl-transferase V (NA17), nectin-4, nerve cell adhesion molecule (NCAM), NKG2D, NYBR1, Oncogene fusion protein (bcr-abl) consisting of O-acetyl-GD2 ganglioside (OAcGD2), olfactory receptor 51E2 (OR51E2), cleavage cluster region (BCR), and Abelson mouse leukemia virus oncogene homolog 1 (Abl), P53 variant, paired box protein Pax-3 (PAX3), paired box protein Pax-5 (PAX5), panexin 3 (PANX3), PDL1, P-glycoprotein, placenta-specific 1 (PLAC1), platelet-derived growth factor receptor beta (PDGFR-beta), polysialic acid, proacrosin-binding protein sp32 (OY-TES1), prostase, prostate cancer tumor antigen-1 (PCT A-l or galectin-8), prostate stem cell antigen (PSCA), prostate-specific membrane antigen (PSMA), prostatic acid phosphatase (PAP), prostain, protease serine 21 (testicin or PRSS21), proteasome (prosomal macropain) subunit beta-9 (LMP2), PTK7, RasG12V, Ras homolog family member C (RhoC), rat sarcoma (Ras) mutant, advanced glycation end product receptor (RAGE-1), receptor tyrosine kinase-like orphan receptor 1 (ROR1), receptor tyrosine-protein kinase ERBB2 or Her-22 / neu, renal ubiquitous receptor 1 (RU1), renal ubiquitous receptor 2 (RU2), sarcoma translocation breakpoint, serine 2 (TMPRSS2) ETS fusion gene, sialyl Lewis adhesion molecule (sLe), SLAMF4, SLAMF6, Slea (CA19.9 or sialyl Lewis antigen), sperm Sub-protein 17 (SPA17), squamous cell carcinoma antigen 3 recognized by T cells (SART3), stage-specific embryonic antigen-4 (SSEA-4), STEAP1, Survivin, synovial sarcoma X-section 2 (SSX2), TCR gamma surrogate leading frame protein (TARP), TCR-beta 1 chain, TCR-beta 2 chain, TCR-delta chain, TCR gamma chain, TCR gamma-delta, telomerase, TGF-beta R2, antigen recognized by TNT antibody, thyroid-stimulating hormone receptor (TSHR), Timl- / HVCR1, tissue factor 1 (TF1), Tn The composition according to claim 57, which binds to ag, Tn antigen ((Tn Ag) or (GalNAca-Ser / Thr)), TNF receptor family member B cell maturation (BCMA), transglutaminase 5 (TGS5), transmembrane protease, TROP2, tumor endothelial marker 1 (TEM1 / CD248), tumor endothelial marker 7-related (TEM7R), tumor protein p53 (p53), tumor-associated glycoprotein 72 (TAG72), tyrosinase, tyrosinase-related protein 2 (TRP-2), uroplakin 2 (UPK2), vascular endothelial growth factor receptor 2 (VEGFR2), V-myc avian myelocytosis virus oncogene neuroblastoma-derived homolog (MYCN), Wilms tumor protein (WT1), or X antigen family member 1A (XAGE1).

61. The composition according to claim 57, wherein the cancer is a carcinoma, blastoma, sarcoma, leukemia, lymphoid malignancy, benign tumor, malignancy, 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.

62. A viral particle containing a targeting site that binds to CD7 or CD8, or a pharmaceutical composition containing the same, i) The target site that binds to CD7 is A polypeptide comprising: (i) a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 35, the heavy chain CDR2 sequence has the amino acid sequence of SEQ ID NO: 36, and the heavy chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 37, or any variant thereof; and (ii) a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 38, the light chain CDR2 sequence has the amino acid sequence of SEQ ID NO: 39, and the light chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 40, or any variant thereof; A heavy chain comprising a heavy chain variable region having at least 90% sequence identity with SEQ ID NO: 47, wherein the polypeptide maintains the sequences of HCDR1 shown in SEQ ID NO: 35, HCDR2 shown in SEQ ID NO: 36, and HCDR3 shown in SEQ ID NO:

37. A light chain comprising a light chain variable region having at least 90% sequence identity with SEQ ID NO: 48, wherein the polypeptide maintains the sequences of LCDR1 shown in SEQ ID NO: 38, LCDR2 shown in SEQ ID NO: 39, and LCDR3 shown in SEQ ID NO:

40. The polypeptide comprises a heavy chain and a light chain, the polypeptide comprising a heavy chain variable region having at least 90% sequence identity with SEQ ID NO: 47, and a light chain variable region having at least 90% sequence identity with SEQ ID NO: 48, and the polypeptide maintains the sequences of HCDR1 shown in SEQ ID NO: 35, HCDR2 shown in SEQ ID NO: 36, HCDR3 shown in SEQ ID NO: 37, LCDR1 shown in SEQ ID NO: 38, LCD2 shown in SEQ ID NO: 39, and LCDR3 shown in SEQ ID NO:

40. A light chain and a heavy chain, the heavy chain having a variable heavy chain region having at least 90% sequence identity with SEQ ID NO: 47, and the light chain having a variable light chain region having at least 90% sequence identity with SEQ ID NO: 48, A heavy chain variable region of the heavy chain having at least 95% sequence identity with sequence number 47, and a light chain variable region of the light chain having at least 95% sequence identity with sequence number 48, A heavy chain variable region of the heavy chain having at least 99% sequence identity with respect to sequence number 47, and a light chain variable region of the light chain having at least 99% sequence identity with respect to sequence number 48, A heavy chain variable region including SEQ ID NO: 47, a light chain variable region including SEQ ID NO: 48, a sequence having at least 90% sequence identity to SEQ ID NO: 51, at least 95% sequence identity to SEQ ID NO: 51, at least 99% sequence identity to SEQ ID NO: 51, or a polypeptide containing the sequence shown in SEQ ID NO: 51, A polypeptide containing a sequence that has at least 90% sequence identity with SEQ ID NO: 52, or at least 95% sequence identity with SEQ ID NO: 52, or at least 99% sequence identity with SEQ ID NO: 52, or a polypeptide containing the sequence shown in SEQ ID NO: 52, or ii) The target site that binds to CD8 is A polypeptide comprising: (ii) a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 55, the heavy chain CDR2 sequence has the amino acid sequence of SEQ ID NO: 56, and the heavy chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 57, or any variant thereof; and (ii) a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 58, the light chain CDR2 sequence has the amino acid sequence of SEQ ID NO: 59, and the light chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 60, or any variant thereof; A heavy chain comprising a heavy chain variable region having at least 90% sequence identity with SEQ ID NO: 67, wherein the polypeptide maintains the sequences of HCDR1 shown in SEQ ID NO: 55, HCDR2 shown in SEQ ID NO: 56, and HCDR3 shown in SEQ ID NO:

57. A light chain comprising a light chain variable region having at least 90% sequence identity with SEQ ID NO: 68, wherein the polypeptide maintains the sequences of LCDR1 shown in SEQ ID NO: 58, LCDR2 shown in SEQ ID NO: 59, and LCDR3 shown in SEQ ID NO:

60. A polypeptide comprising a heavy chain and a light chain, wherein the heavy chain has a heavy chain variable region having at least 90% sequence identity with SEQ ID NO: 67, and the light chain has a light chain variable region having at least 90% sequence identity with SEQ ID NO: 68, wherein the polypeptide maintains the sequences of HCDR1 shown in SEQ ID NO: 55, HCDR2 shown in SEQ ID NO: 56, HCDR3 shown in SEQ ID NO: 57, LCDR1 shown in SEQ ID NO: 58, LCD2 shown in SEQ ID NO: 59, and LCDR3 shown in SEQ ID NO:

60. A polypeptide comprising a light chain and a heavy chain, including a heavy chain variable region of a heavy chain having at least 90% sequence identity with SEQ ID NO: 67, and a light chain variable region of a light chain having at least 90% sequence identity with SEQ ID NO:

68. A polypeptide comprising a light chain and a heavy chain, including a heavy chain variable region of a heavy chain having at least 95% sequence identity with SEQ ID NO: 67, and a light chain variable region of a light chain having at least 95% sequence identity with SEQ ID NO:

68. A polypeptide comprising a heavy chain and a heavy chain, including a heavy chain variable region having at least 99% sequence identity with SEQ ID NO: 67, and a light chain variable region having at least 99% sequence identity with SEQ ID NO:

68. A polypeptide comprising a light chain and a heavy chain, wherein the heavy chain variable region comprises SEQ ID NO: 67, and the light chain variable region comprises SEQ ID NO: 68, A sequence having at least 90% sequence identity with SEQ ID NO: 69, at least 95% sequence identity with SEQ ID NO: 69, at least 99% sequence identity with SEQ ID NO: 69, or a polypeptide containing the sequence shown in SEQ ID NO: 69, A virus particle comprising a polypeptide having at least 90% sequence identity with SEQ ID NO: 70, at least 95% sequence identity with SEQ ID NO: 70, or at least 99% sequence identity with SEQ ID NO: 70, or a sequence represented by SEQ ID NO: 70, or the pharmaceutical composition comprising the same.

63. The virus particle according to claim 62, or a pharmaceutical composition containing the same, wherein the virus particle comprises a heterogeneous fusion protein, such as a glycoprotein from those provided herein.

64. The viral particle according to claim 63, or a pharmaceutical composition containing the same, wherein the fusionable protein is a VSV-G protein or a mutant VSV-G protein or another viral glycoprotein.

65. The viral particle according to claim 64, or a pharmaceutical composition containing the mutant VSV-G protein, comprising the polypeptide according to any one of claims 1 to 30.

66. The virus particle according to claim 62, or a pharmaceutical composition containing the same, wherein the virus particle comprises a nucleic acid molecule encoding a chimeric antigen receptor.

67. A composition for delivering a heterologous molecule to CD7+ or CD8+ target cells, or for treating cancer in a target, comprising a pseudotyped viral vector comprising a targeting site that specifically binds to CD7 or CD8 on the target cell, and a nucleic acid molecule encoding the heterologous molecule, i) The target site that binds to CD7 is A polypeptide comprising: (i) a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 35, the heavy chain CDR2 sequence has the amino acid sequence of SEQ ID NO: 36, and the heavy chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 37, or any variant thereof; and (ii) a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 38, the light chain CDR2 sequence has the amino acid sequence of SEQ ID NO: 39, and the light chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 40, or any variant thereof; A heavy chain comprising a heavy chain variable region having at least 90% sequence identity with SEQ ID NO: 47, wherein the polypeptide maintains the sequences of HCDR1 shown in SEQ ID NO: 35, HCDR2 shown in SEQ ID NO: 36, and HCDR3 shown in SEQ ID NO:

37. A light chain comprising a light chain variable region having at least 90% sequence identity with SEQ ID NO: 48, wherein the polypeptide maintains the sequences of LCDR1 shown in SEQ ID NO: 38, LCDR2 shown in SEQ ID NO: 39, and LCDR3 shown in SEQ ID NO:

40. The polypeptide comprises a heavy chain and a light chain, the polypeptide comprising a heavy chain variable region having at least 90% sequence identity with SEQ ID NO: 47, and a light chain variable region having at least 90% sequence identity with SEQ ID NO: 48, and the polypeptide maintains the sequences of HCDR1 shown in SEQ ID NO: 35, HCDR2 shown in SEQ ID NO: 36, HCDR3 shown in SEQ ID NO: 37, LCDR1 shown in SEQ ID NO: 38, LCD2 shown in SEQ ID NO: 39, and LCDR3 shown in SEQ ID NO:

40. A light chain and a heavy chain, the heavy chain having a variable heavy chain region having at least 90% sequence identity with SEQ ID NO: 47, and the light chain having a variable light chain region having at least 90% sequence identity with SEQ ID NO: 48, A heavy chain variable region of the heavy chain having at least 95% sequence identity with sequence number 47, and a light chain variable region of the light chain having at least 95% sequence identity with sequence number 48, A heavy chain variable region of the heavy chain having at least 99% sequence identity with respect to sequence number 47, and a light chain variable region of the light chain having at least 99% sequence identity with respect to sequence number 48, A heavy chain variable region including SEQ ID NO: 47, a light chain variable region including SEQ ID NO: 48, a sequence having at least 90% sequence identity to SEQ ID NO: 51, at least 95% sequence identity to SEQ ID NO: 51, at least 99% sequence identity to SEQ ID NO: 51, or a polypeptide containing the sequence shown in SEQ ID NO: 51, A polypeptide containing a sequence that has at least 90% sequence identity with SEQ ID NO: 52, or at least 95% sequence identity with SEQ ID NO: 52, or at least 99% sequence identity with SEQ ID NO: 52, or a polypeptide containing the sequence shown in SEQ ID NO: 52, or ii) The target site that binds to CD8 is A polypeptide comprising: (ii) a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 55, the heavy chain CDR2 sequence has the amino acid sequence of SEQ ID NO: 56, and the heavy chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 57, or any variant thereof; and (ii) a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 58, the light chain CDR2 sequence has the amino acid sequence of SEQ ID NO: 59, and the light chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 60, or any variant thereof; A heavy chain comprising a heavy chain variable region having at least 90% sequence identity with SEQ ID NO: 67, wherein the polypeptide maintains the sequences of HCDR1 shown in SEQ ID NO: 55, HCDR2 shown in SEQ ID NO: 56, and HCDR3 shown in SEQ ID NO:

57. A light chain comprising a light chain variable region having at least 90% sequence identity with SEQ ID NO: 68, wherein the polypeptide maintains the sequences of LCDR1 shown in SEQ ID NO: 58, LCDR2 shown in SEQ ID NO: 59, and LCDR3 shown in SEQ ID NO:

60. A polypeptide comprising a heavy chain and a light chain, wherein the heavy chain comprises a heavy chain variable region having at least 90% sequence identity with SEQ ID NO: 67, and a light chain variable region having at least 90% sequence identity with SEQ ID NO: 68, wherein the polypeptide comprises HCDR1 shown in SEQ ID NO: 55, HCDR2 shown in SEQ ID NO: 56, HCDR3 shown in SEQ ID NO: 57, LCDR1 shown in SEQ ID NO: 58, and LCD2 shown in SEQ ID NO:

59. and the polypeptide that maintains the sequence of LCDR3 shown in Sequence ID No. 60, A polypeptide comprising a light chain and a heavy chain, including a heavy chain variable region of a heavy chain having at least 90% sequence identity with SEQ ID NO: 67, and a light chain variable region of a light chain having at least 90% sequence identity with SEQ ID NO:

68. A polypeptide comprising a light chain and a heavy chain, including a heavy chain variable region of a heavy chain having at least 95% sequence identity with SEQ ID NO: 67, and a light chain variable region of a light chain having at least 95% sequence identity with SEQ ID NO:

68. A polypeptide comprising a heavy chain and a heavy chain, including a heavy chain variable region having at least 99% sequence identity with SEQ ID NO: 67, and a light chain variable region having at least 99% sequence identity with SEQ ID NO:

68. A polypeptide comprising a light chain and a heavy chain, wherein the heavy chain variable region comprises SEQ ID NO: 67, and the light chain variable region comprises SEQ ID NO: 68, A sequence having at least 90% sequence identity with SEQ ID NO: 69, at least 95% sequence identity with SEQ ID NO: 69, at least 99% sequence identity with SEQ ID NO: 69, or a polypeptide containing the sequence shown in SEQ ID NO: 69, The composition comprising a polypeptide having at least 90% sequence identity with SEQ ID NO: 70, at least 95% sequence identity with SEQ ID NO: 70, at least 99% sequence identity with SEQ ID NO: 70, or a sequence represented by SEQ ID NO:

70.

68. A cell comprising one or more heterogeneous nucleic acid molecules encoding a targeting site and a viral glycoprotein, wherein the heterogeneous nucleic acid molecules include a nucleic acid sequence encoding a targeting site that binds to CD7 or CD8, i) The target site that binds to CD7 is A polypeptide comprising: (i) a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 35, the heavy chain CDR2 sequence has the amino acid sequence of SEQ ID NO: 36, and the heavy chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 37, or any variant thereof; and (ii) a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 38, the light chain CDR2 sequence has the amino acid sequence of SEQ ID NO: 39, and the light chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 40, or any variant thereof; A heavy chain comprising a heavy chain variable region having at least 90% sequence identity with SEQ ID NO: 47, wherein the polypeptide maintains the sequences of HCDR1 shown in SEQ ID NO: 35, HCDR2 shown in SEQ ID NO: 36, and HCDR3 shown in SEQ ID NO:

37. A light chain comprising a light chain variable region having at least 90% sequence identity with SEQ ID NO: 48, wherein the polypeptide maintains the sequences of LCDR1 shown in SEQ ID NO: 38, LCDR2 shown in SEQ ID NO: 39, and LCDR3 shown in SEQ ID NO:

40. The polypeptide comprises a heavy chain and a light chain, the polypeptide comprising a heavy chain variable region having at least 90% sequence identity with SEQ ID NO: 47, and a light chain variable region having at least 90% sequence identity with SEQ ID NO: 48, and the polypeptide maintains the sequences of HCDR1 shown in SEQ ID NO: 35, HCDR2 shown in SEQ ID NO: 36, HCDR3 shown in SEQ ID NO: 37, LCDR1 shown in SEQ ID NO: 38, LCD2 shown in SEQ ID NO: 39, and LCDR3 shown in SEQ ID NO:

40. A light chain and a heavy chain, the heavy chain having a variable heavy chain region having at least 90% sequence identity with SEQ ID NO: 47, and the light chain having a variable light chain region having at least 90% sequence identity with SEQ ID NO: 48, A heavy chain variable region of the heavy chain having at least 95% sequence identity with sequence number 47, and a light chain variable region of the light chain having at least 95% sequence identity with sequence number 48, A heavy chain variable region of the heavy chain having at least 99% sequence identity with respect to sequence number 47, and a light chain variable region of the light chain having at least 99% sequence identity with respect to sequence number 48, A heavy chain variable region including SEQ ID NO: 47, a light chain variable region including SEQ ID NO: 48, a sequence having at least 90% sequence identity to SEQ ID NO: 51, at least 95% sequence identity to SEQ ID NO: 51, at least 99% sequence identity to SEQ ID NO: 51, or a polypeptide containing the sequence shown in SEQ ID NO: 51, A polypeptide containing a sequence that has at least 90% sequence identity with SEQ ID NO: 52, or at least 95% sequence identity with SEQ ID NO: 52, or at least 99% sequence identity with SEQ ID NO: 52, or a polypeptide containing the sequence shown in SEQ ID NO: 52, or ii) The target site that binds to CD8 is A polypeptide comprising: (ii) a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 55, the heavy chain CDR2 sequence has the amino acid sequence of SEQ ID NO: 56, and the heavy chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 57, or any variant thereof; and (ii) a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 58, the light chain CDR2 sequence has the amino acid sequence of SEQ ID NO: 59, and the light chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 60, or any variant thereof; A heavy chain comprising a heavy chain variable region having at least 90% sequence identity with SEQ ID NO: 67, wherein the polypeptide maintains the sequences of HCDR1 shown in SEQ ID NO: 55, HCDR2 shown in SEQ ID NO: 56, and HCDR3 shown in SEQ ID NO:

57. A light chain comprising a light chain variable region having at least 90% sequence identity with SEQ ID NO: 68, wherein the polypeptide maintains the sequences of LCDR1 shown in SEQ ID NO: 58, LCDR2 shown in SEQ ID NO: 59, and LCDR3 shown in SEQ ID NO:

60. A polypeptide comprising a heavy chain and a light chain, wherein the heavy chain has a heavy chain variable region having at least 90% sequence identity with SEQ ID NO: 67, and the light chain has a light chain variable region having at least 90% sequence identity with SEQ ID NO: 68, wherein the polypeptide maintains the sequences of HCDR1 shown in SEQ ID NO: 55, HCDR2 shown in SEQ ID NO: 56, HCDR3 shown in SEQ ID NO: 57, LCDR1 shown in SEQ ID NO: 58, LCD2 shown in SEQ ID NO: 59, and LCDR3 shown in SEQ ID NO:

60. A polypeptide comprising a light chain and a heavy chain, including a heavy chain variable region of a heavy chain having at least 90% sequence identity with SEQ ID NO: 67, and a light chain variable region of a light chain having at least 90% sequence identity with SEQ ID NO:

68. A polypeptide comprising a light chain and a heavy chain, including a heavy chain variable region of a heavy chain having at least 95% sequence identity with SEQ ID NO: 67, and a light chain variable region of a light chain having at least 95% sequence identity with SEQ ID NO:

68. A polypeptide comprising a heavy chain and a heavy chain, including a heavy chain variable region having at least 99% sequence identity with SEQ ID NO: 67, and a light chain variable region having at least 99% sequence identity with SEQ ID NO:

68. A polypeptide comprising a light chain and a heavy chain, wherein the heavy chain variable region comprises SEQ ID NO: 67, and the light chain variable region comprises SEQ ID NO: 68, A sequence having at least 90% sequence identity with SEQ ID NO: 69, at least 95% sequence identity with SEQ ID NO: 69, at least 99% sequence identity with SEQ ID NO: 69, or a polypeptide containing the sequence shown in SEQ ID NO: 69, The cell comprising a polypeptide having at least 90% sequence identity with SEQ ID NO: 70, at least 95% sequence identity with SEQ ID NO: 70, at least 99% sequence identity with SEQ ID NO: 70, or a sequence represented by SEQ ID NO:

70.

69. A cell comprising the nucleic acid molecule described in claim 31, the vector described in claim 32, or the plasmid described in claim 33.

70. A method for producing viral particles, comprising culturing the cells described in claim 69 under conditions sufficient to produce the viral particles.

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