Mutant polypeptide, composition containing the same, and uses thereof

Abstract

Provided herein are virus particles comprising a heterologous viral glycoprotein and a targeting moiety, wherein the targeting moiety comprises a polypeptide having the formula T-S1, where T is a target binding domain and S1 is a stalk portion. The stalk portion may include a variant Fc domain. The stalk portion may include a flexible polypeptide domain. The targeting moiety comprising the formula T-S1 is incorporated into the virus particle and such particle may assist in targeting a particular cell type. The present specification also provides a composition comprising the same, and methods of using the same.

Description

Technical Field

[0001] Related Applications This application claims the benefit of priority of U.S. Provisional Application No. 63 / 391,930, filed Jul. 25, 2022; U.S. Provisional Application No. 63 / 391,939, filed Jul. 25, 2022; U.S. Provisional Application No. 63 / 503,815, filed May 23, 2023; and U.S. Provisional Application No. 63 / 507,783, filed Jun. 13, 2023, the entire contents of each of which are hereby incorporated by reference.

[0002] Reference to Electronically Filed Sequence Listing This application includes a sequence listing that was electronically filed in XML format, the entire contents of which are hereby incorporated by reference. The name of this XML copy, created on Jul. 20, 2023, is INH_020WO_SL.xml, and the size is 114,351 bytes.

[0003] Embodiments provided herein relate to virus particles comprising a heterologous viral glycoprotein and a targeting moiety having the formula T-S1, wherein T is a target binding domain and S1 is a stalk moiety. The stalk moiety may include a variant Fc domain. The stalk moiety may include a flexible peptide domain. Embodiments provided herein further relate to compositions comprising the virus particles provided herein and methods of using the same.

Background Art

[0004] Vesicular stomatitis virus (VSV) is an enveloped negative-strand RNA virus belonging to the Vesiculovirus genus of the Rhabdoviridae family. 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 extracellular domain of approximately 450 amino acids, a single α-helix transmembrane segment, and a carboxy-terminal domain within the small virus. The signal peptide is cleaved in the lumen of the endoplasmic reticulum, and the native mature glycoprotein consists of an extracellular domain, a transmembrane domain, and an intra-viral domain.

[0005] G plays an important role in the initial steps of virus infection (Albertini, A.A.V., Baquero, E., Ferlin, A., and Gaudin, Y. (2012). Molecular and Cellular Aspects of Rhabdovirus Entry. Viruses 4, 117-139.), the entire content of which is incorporated herein by reference. First, it plays a role in attaching the virus to specific receptors. After binding, the virus particle enters the cell via the clathrin-mediated endocytosis pathway. In the acidic environment of the endocytic vesicle, G causes the fusion of the virus membrane and the endosome membrane, thereby releasing the genome into the cytoplasm for the next stage of infection. Fusion is catalyzed by a large structural transition from the prefusion conformation induced at low pH to the postfusion conformation, both of which are trimers (Roche, S., Bressanelli, S., Rey, F.A., and Gaudin, Y. (2006). Crystal structure of the low-pH form of the vesicular stomatitis virus glycoprotein G. Science 313, 187-191. Roche, S., Rey, F.A., Gaudin, Y., and Bressanelli, S. (2007). Structure of the prefusion form of the vesicular stomatitis virus glycoprotein g. Science 315, 843-848), the entire content of each of which is incorporated herein by reference.

[0006] The polypeptide chain of the G extracellular domain folds into three distinct domains: a fusion domain (FD), a pleckstrin homology domain (PHD), and a trimerization domain (TrD). During the structural transition, the FD, PHD, and TrD retain their tertiary structure. Nevertheless, they undergo large-scale reorganization in their relative orientation due to secondary changes (S1 to S5) in the hinge segments that are refolded during low-pH-induced conformational changes (Roche et al., 2006; Roche et al., 2007).

[0007] 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 hereby incorporated by reference in its entirety). VSV-G can be used to pseudotype other viruses, and VSV-G-pseudotyped lentivirus (VSV-G-LV) exhibits the same broad tropism as VSV. However, this broad tropism may inhibit the selective targeting of specific cell types. Therefore, there is a need for modified (mutated or mutant) VSV-G proteins that can be used for pseudotyped viruses that suppress binding to the LDL receptor. This embodiment meets these and other needs. SUMMARY OF THE INVENTION

[0008] In some embodiments, viral particles are provided. In some embodiments, the viral particles comprise a heterologous viral glycoprotein and a targeting moiety, the targeting moiety comprising a polypeptide having Formula TS1, wherein T is a target binding domain and S1 is a stalk portion.

[0009] In some embodiments, the stalk portion S1 comprises a variant Fc protein. In some embodiments, the variant Fc protein comprises a transmembrane domain such as, but not limited to, the CD8 or CD28 transmembrane domain. In some embodiments, the variant Fc protein comprises an effector mutation that inhibits the interaction of the Fc protein with an Fc interacting protein such as FcγR, C1q, FcRβ, or FcRn.

[0010] In some embodiments, the variant Fc protein is a variant IgG1 Fc protein comprising one or more mutations selected from the group consisting of L234A, L235A, N297A, P329G, I253A, H310A, and H435A.

[0011] In some embodiments, the variant IgG1 Fc protein comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 104, at least 85% identity to SEQ ID NO: 104, at least 90% identity to SEQ ID NO: 104, at least 95% identity to SEQ ID NO: 104, at least 98% identity to SEQ ID NO: 104, or at least 100% identity to SEQ ID NO: 104.

[0012] In some embodiments, the variant Fc protein is a variant IgG2 Fc protein comprising one or more mutations selected from the group consisting of N297A, P329G, I253A, H310A, and H435A.

[0013] In some embodiments, the variant Fc protein is a variant IgG4 Fc protein comprising one or more mutations selected from the group consisting of S228P, L235E, N297A, P329G, I253A, H310A, and H435A.

[0014] In some embodiments, the targeting moiety having the formula T-S1 comprises a stalk moiety S1 having the formula L1-Fc-L2-X1, wherein L1 is a linker or absent, Fc is a variant Fc protein, L2 is a linker or absent, X1 is a polypeptide comprising a transmembrane domain, and the targeting moiety having the formula T-S1 has the formula T-L1-Fc-L2-X1.

[0015] In some embodiments, the polypeptide comprising a transmembrane domain (X1) comprises a polypeptide having the formula ECD-T M -ICD, wherein ECD is an extracellular domain of a cell surface protein, or a fragment thereof, or absent; T M is a transmembrane domain of a transmembrane protein; ICD is an intracellular domain or a protein that facilitates incorporation of a targeting moiety into the envelope of a viral particle, or absent; wherein the targeting moiety having the formula T-L1-Fc-L2-X1 has the formula T-L1-Fc-L2-ECD-T M -ICD.

[0016] In some embodiments, the stalk moiety S1 comprises a moiety having the formula L3-X1, wherein L3 is a flexible peptide linker and X1 is a polypeptide comprising a transmembrane domain; wherein the targeting moiety having the formula T-S1 has the formula T-L3-X1.

[0017] In some embodiments, the polypeptide comprising a transmembrane domain (X1) comprises a polypeptide having the formula ECD-T M -ICD, wherein ECD is an extracellular domain of a cell surface protein, or a fragment thereof, or absent; T Mis the transmembrane domain of a transmembrane protein; ICD is a protein that promotes the incorporation of an intracellular domain or a targeting moiety into the envelope of a viral particle, or is absent; the targeting moiety having the formula T-L3-X1 is T-L3-ECD-T M - has the formula -ICD.

[0018] In some embodiments, the target moiety binds to CD7. In some embodiments, the targeting moiety comprises a polypeptide having a heavy chain variable region comprising HCDR1 of SEQ ID NO: 30, HCDR2 of SEQ ID NO: 31, and HCDR3 of SEQ ID NO: 32, or a variant of any of the forges. In some embodiments, the targeting moiety comprises a polypeptide having a light chain variable region comprising LCDR1 of SEQ ID NO: 33, LCDR2 of SEQ ID NO: 34, and LCDR3 of SEQ ID NO: 35, or a variant of any of the forges. In some embodiments, the heavy chain comprises a heavy chain variable region having at least 90% sequence identity to SEQ ID NO: 36. In some embodiments, the light chain comprises a light chain variable region having at least 90% sequence identity to SEQ ID NO: 37. In some embodiments, the targeting moiety that binds to CD7 comprises a polypeptide of a sequence having at least 90% sequence identity to SEQ ID NO: 38. In some embodiments, the targeting moiety that binds to CD7 comprises a polypeptide of a sequence having at least 90% sequence identity to SEQ ID NO: 39.

[0019] In some embodiments, the targeting moiety binds to CD8. In some embodiments, the targeting moiety comprises a polypeptide having a heavy chain variable region comprising HCDR1 of SEQ ID NO: 42, HCDR2 of SEQ ID NO: 43, and HCDR3 of SEQ ID NO: 44, or a variant of any of the forges. In some embodiments, the targeting moiety comprises a polypeptide having a light chain variable region comprising LCDR1 of SEQ ID NO: 45, LCDR2 of SEQ ID NO: 46, and LCDR3 of SEQ ID NO: 47, or a variant of any of the forges. In some embodiments, the heavy chain comprises a heavy chain variable region having at least 90% sequence identity to SEQ ID NO: 48. In some embodiments, the light chain comprises a light chain variable region having at least 90% sequence identity to SEQ ID NO: 49. In some embodiments, the targeting moiety that binds to CD8 comprises a polypeptide of a sequence having at least 90% sequence identity to SEQ ID NO: 50. In some embodiments, the targeting moiety that binds to CD8 comprises a polypeptide of a sequence having at least 90% sequence identity to SEQ ID NO: 51.

[0020] In some embodiments, the heterologous viral glycoprotein is the SVCV-G polypeptide provided herein.

[0021] In some embodiments, the heterologous viral glycoprotein is the VSV-G polypeptide. In some embodiments, the VSV-G polypeptide comprises substitutions at positions I182, T214, and T352 of SEQ ID NO: 2. In some embodiments, the substitution at position 182 is I182D or I182E. In some embodiments, the substitution at position 214 is T214N. In some embodiments, the substitution at position 352 is T352A.

[0022] In some embodiments, the viral particles provided herein further comprise a nucleic acid molecule encoding a heterologous molecule of interest. In some embodiments, the heterologous molecule of interest is as provided herein. In some embodiments, the heterologous molecule of interest is a CAR. In some embodiments, the CAR comprises an antigen-binding domain having a heavy-chain variable region with at least 95% identity to SEQ ID NO: 89 and a light-chain variable region with at least 95% identity to SEQ ID NO: 90. In some embodiments, the CAR comprises an antigen-binding domain having a heavy-chain variable region with at least 95% identity to SEQ ID NO: 94 and a light-chain variable region with at least 95% identity to SEQ ID NO: 95.

[0023] In some embodiments, the CAR comprises an antigen-binding domain having an amino acid sequence with at least 95% identity to SEQ ID NO: 92. In some embodiments, the CAR comprises an antigen-binding domain having an amino acid sequence with at least 95% identity to SEQ ID NO: 93. In some embodiments, the CAR comprises an antigen-binding domain having an amino acid sequence with at least 95% identity to SEQ ID NO: 96. In some embodiments, the CAR comprises an antigen-binding domain having an amino acid sequence with at least 95% identity to SEQ ID NO: 97.

[0024] In some embodiments, the CAR comprises an amino acid sequence having at least 85% identity, at least 90% identity, at least 95% identity, at least 99% identity, or at least 100% identity to SEQ ID NO: 99.

[0025] In some embodiments, a method of infecting a cell is provided. In some embodiments, the method comprises contacting the cell with the viral particles provided herein.

[0026] In some embodiments, methods of infecting cells in a subject are provided. In some embodiments, the method comprises administering to the subject a pharmaceutical composition comprising the viral particles provided herein.

[0027] In some embodiments, methods of delivering a heterologous molecule of interest to cells are provided. In some embodiments, the method comprises contacting the cells with the viral particles provided herein, wherein the viral particles comprise a nucleic acid molecule encoding the heterologous molecule of interest.

[0028] In some embodiments, methods of delivering a heterologous molecule of interest to cells of a subject are provided. In some embodiments, the method comprises administering to the subject the viral particles provided herein, wherein the viral particles comprise a nucleic acid molecule encoding the heterologous molecule of interest.

[0029] In some embodiments, methods of treating a disease or disorder in a subject are provided. In some embodiments, the method comprises administering to the subject the viral particles provided herein, wherein the viral particles comprise a nucleic acid molecule encoding a heterologous molecule of interest for treating the disease or disorder.

[0030] In some embodiments, methods of delivering a heterologous molecule to target cells are provided. In some embodiments, the method comprises contacting the cells with the viral particles provided herein, wherein the viral particles comprise a nucleic acid molecule encoding the heterologous molecule.

[0031] In some embodiments, viral particles are provided. In some embodiments, the viral particles include a targeting moiety that includes a heterologous viral glycoprotein and a polypeptide having the formula T-S1, where T is a target binding domain and S1 is a stalk portion. In some embodiments, the heterologous viral glycoprotein includes a sequence selected from SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 52, or SEQ ID NO: 53. In some embodiments, the targeting binding domain includes a sequence selected from SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 50, or SEQ ID NO: 51. In some embodiments, the stalk portion S1 includes a variant Fc protein that includes a sequence that is a variant of SEQ ID NO: 26, SEQ ID NO: 27, or SEQ ID NO: 28. In some embodiments, the variant of SEQ ID NO: 26 includes one or more mutations selected from the group consisting of L234A, L235A, N297A, P329G, I253A, H310A, and H435A. In some embodiments, the variant of SEQ ID NO: 27 includes one or more mutations selected from the group consisting of N297A, P329G, I253A, H310A, and H435A. In some embodiments, the variant of SEQ ID NO: 28 includes one or more mutations selected from the group consisting of S228P, L235E, N297A, P329G, I253A, H310A, and H435A. In some embodiments, the variant Fc protein further includes a transmembrane domain that includes a sequence selected from SEQ ID NO: 61 or SEQ ID NO: 62.

[0032] In some embodiments, virus particles are provided. In some embodiments, the virus particles comprise a targeting moiety comprising a heterologous viral glycoprotein and a polypeptide having the formula T-S1, wherein T is a target binding domain and S1 is a stalk portion. In some embodiments, the heterologous viral glycoprotein comprises a sequence selected from SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 52, or SEQ ID NO: 53. In some embodiments, the targeting binding domain comprises a sequence selected from SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 50, or SEQ ID NO: 51. In some embodiments, the stalk portion S1 comprises the formula L1-Fc-L2-X1, wherein L1 is a linker comprising a sequence selected from SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, or SEQ ID NO: 76, or is absent; Fc is a variant Fc protein comprising a sequence that is a variant of SEQ ID NO: 26, SEQ ID NO: 27, or SEQ ID NO: 28, L2 is a linker comprising a sequence selected from SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, or SEQ ID NO: 76, or is absent; X1 is a polypeptide comprising a transmembrane domain. In some embodiments, the variant of SEQ ID NO: 26 comprises one or more mutations selected from the group consisting of L234A, L235A, N297A, P329G, I253A, H310A, and H435A. In some embodiments, the variant of SEQ ID NO: 27 comprises one or more mutations selected from the group consisting of N297A, P329G, I253A, H310A, and H435A. In some embodiments, the variant of SEQ ID NO: 28 comprises one or more mutations selected from the group consisting of S228P, L235E, N297A, P329G, I253A, H310A and H435A. In some embodiments, the polypeptide comprising the transmembrane domain (X1) is ECD-T M -ICD having the formula, wherein ECD is an extracellular domain having a sequence selected from SEQ ID NO: 59 or SEQ ID NO: 60 or a fragment thereof, or is absent, T Mis a transmembrane domain having the sequence of SEQ ID NO: 61 or SEQ ID NO: 62 or a fragment thereof; ICD is an intracellular domain or protein that promotes the incorporation of the targeting moiety into the envelope of the viral particle, wherein ICD comprises an env incorporation motif comprising the amino acid sequence of SEQ ID NO: 63 or SEQ ID NO: 64, or ICD is absent.

[0033] In some embodiments, viral particles are provided. In some embodiments, the viral particle comprises a targeting moiety comprising a heterologous viral glycoprotein and a polypeptide having the formula T-S1, wherein T is a target binding domain and S1 is a stalk portion. In some embodiments, the heterologous viral glycoprotein comprises a sequence selected from the group consisting of SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 52, or SEQ ID NO: 53. In some embodiments, the targeting binding domain comprises a sequence selected from the group consisting of SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 50, or SEQ ID NO: 51. In some embodiments, the stalk portion S1 comprises the formula L1-Fc-L2-X1, wherein L1 is a linker comprising the sequence of SEQ ID NO: 55 or is absent; Fc is a variant Fc protein comprising a sequence that is a variant of SEQ ID NO: 26, SEQ ID NO: 27, or SEQ ID NO: 28, L2 is a linker comprising the sequence of SEQ ID NO: 55 or is absent; X1 is a polypeptide comprising a transmembrane domain. In some embodiments, the variant of SEQ ID NO: 26 comprises one or more mutations selected from the group consisting of L234A, L235A, N297A, P329G, I253A, H310A, and H435A. In some embodiments, the variant of SEQ ID NO: 27 comprises one or more mutations selected from the group consisting of N297A, P329G, I253A, H310A, and H435A. In some embodiments, the variant of SEQ ID NO: 28 comprises one or more mutations selected from the group consisting of S228P, L235E, N297A, P329G, I253A, H310A and H435A. In some embodiments, the polypeptide comprising the transmembrane domain (X1) is ECD-T M-having the formula of the ICD, wherein the ECD is an extracellular domain having SEQ ID NO: 60, or a fragment thereof, or is absent; T M is a transmembrane domain having the sequence of SEQ ID NO: 62 or a fragment thereof; the ICD is an intracellular domain or protein that promotes the incorporation of the targeting moiety into the envelope of the viral particle, wherein the ICD comprises an env incorporation motif comprising the amino acid sequence of SEQ ID NO: 63 or SEQ ID NO: 64, or the ICD is absent.

[0034] In some embodiments, viral particles are provided. In some embodiments, the viral particle comprises a targeting moiety comprising a heterologous viral glycoprotein and a polypeptide having the formula T-S1, wherein T is a target binding domain and S1 is a stalk portion. In some embodiments, the heterologous viral glycoprotein comprises a sequence selected from SEQ ID NO: 23 or SEQ ID NO: 25. In some embodiments, the target binding domain comprises SEQ ID NO: 39. In some embodiments, the stalk portion S1 comprises the formula L1-Fc-L2-X1, wherein L1 is a linker comprising the sequence of SEQ ID NO: 55; Fc is a variant Fc protein comprising the sequence of SEQ ID NO: 104, L2 is a linker and is absent; X1 is a polypeptide comprising a transmembrane domain. In some embodiments, the polypeptide comprising the transmembrane domain (X1) is ECD-T M -having the formula of the ICD, wherein the ECD is an extracellular domain having SEQ ID NO: 60; T M is a transmembrane domain having the sequence of SEQ ID NO: 62; the ICD is an intracellular domain or protein that promotes the incorporation of the targeting moiety into the envelope of the viral particle, wherein the ICD comprises an env incorporation motif comprising the amino acid sequence of SEQ ID NO: 63.

[0035] In some embodiments, viral particles are provided, where the viral particles comprise a heterologous viral glycoprotein and a targeting moiety. In some embodiments, the heterologous viral glycoprotein comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 23 or SEQ ID NO: 25, having at least 95% identity to SEQ ID NO: 23 or SEQ ID NO: 25, having at least 99% identity to SEQ ID NO: 23 or SEQ ID NO: 25, or having at least 100% identity to SEQ ID NO: 23 or SEQ ID NO: 25. In some embodiments, the targeting moiety comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 98, having at least 95% identity to SEQ ID NO: 98, having at least 99% identity to SEQ ID NO: 98, or having at least 100% identity to SEQ ID NO: 98.

[0036] In some embodiments, viral particles are provided, where the viral particles comprise a heterologous viral glycoprotein and a targeting moiety. In some embodiments, the heterologous viral glycoprotein comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 52 or SEQ ID NO: 53, having at least 95% identity to SEQ ID NO: 52 or SEQ ID NO: 53, having at least 99% identity to SEQ ID NO: 52 or SEQ ID NO: 53, or having at least 100% identity to SEQ ID NO: 52 or SEQ ID NO: 53. In some embodiments, the targeting moiety comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 98, having at least 95% identity to SEQ ID NO: 98, having at least 99% identity to SEQ ID NO: 98, or having at least 100% identity to SEQ ID NO: 98.

[0037] In some embodiments, viral particles are provided. In some embodiments, the viral particles comprise a targeting moiety comprising a heterologous viral glycoprotein and a polypeptide having the formula T-S1, wherein T is a target binding domain and S1 is a stalk portion. In some embodiments, the target binding domain comprises the amino acid sequence of SEQ ID NO: 38 or SEQ ID NO: 39. In some embodiments, the stalk portion S1 comprises the formula L3-X1, wherein L3 is a flexible peptide linker comprising the amino acid sequence of SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, or SEQ ID NO: 58, and X1 is a polypeptide linker comprising a transmembrane domain. In some embodiments, the polypeptide comprising the transmembrane domain (X1) is ECD-T M -ICD having the formula, wherein ECD is an extracellular domain comprising the amino acid sequence of SEQ ID NO: 59 or SEQ ID NO: 60 or a fragment thereof or is absent, and T M is a transmembrane domain comprising the amino acid sequence of SEQ ID NO: 61 or SEQ ID NO: 62, and ICD is an intracellular domain or protein that facilitates incorporation of the targeting moiety into the envelope of the viral particle, where ICD comprises an env incorporation motif comprising the amino acid sequence of SEQ ID NO: 63 or SEQ ID NO: 64 or ICD is absent.

[0038] In some embodiments, viral particles are provided. In some embodiments, the viral particles comprise a targeting moiety comprising a heterologous viral glycoprotein and a polypeptide having the formula T-S1, wherein T is a target binding domain and S1 is a stalk portion. In some embodiments, the target binding domain comprises the amino acid sequence of SEQ ID NO: 50 or SEQ ID NO: 51. In some embodiments, the stalk portion S1 comprises the formula L3-X1, wherein L3 is a flexible peptide linker comprising the amino acid sequence of SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, or SEQ ID NO: 58, and X1 is a polypeptide linker comprising a transmembrane domain. In some embodiments, the polypeptide comprising the transmembrane domain (X1) is ECD-T M- having the formula of ICD, wherein ECD is an extracellular domain comprising the amino acid sequence of SEQ ID NO: 59 or SEQ ID NO: 60, or a fragment thereof, or is absent, and T M is a transmembrane domain comprising the amino acid sequence of SEQ ID NO: 61 or SEQ ID NO: 62, and ICD is an intracellular domain or protein that promotes the incorporation of the targeting moiety into the envelope of the viral particle, wherein ICD comprises an env incorporation motif comprising the amino acid sequence of SEQ ID NO: 63 or SEQ ID NO: 64, or ICD is absent.

[0039] In some embodiments, viral particles are provided. In some embodiments, the viral particle comprises a targeting moiety comprising a heterologous viral glycoprotein and a polypeptide having the formula T-S1, wherein T is a target binding domain and S1 is a stalk portion. In some embodiments, the heterologous viral glycoprotein comprises the sequence of SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 52, or SEQ ID NO: 53. In some embodiments, the target binding domain comprises the amino acid sequence of SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 50, or SEQ ID NO: 51. In some embodiments, the stalk portion S1 comprises the formula L3-X1, wherein L3 is a flexible peptide linker comprising the amino acid sequence of SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, or SEQ ID NO: 58, and X1 is a polypeptide linker comprising a transmembrane domain. In some embodiments, the polypeptide comprising the transmembrane domain (X1) is ECD-T M - having the formula of ICD, wherein ECD is an extracellular domain comprising the amino acid sequence of SEQ ID NO: 59 or SEQ ID NO: 60, or a fragment thereof, or is absent, and T M is a transmembrane domain comprising the amino acid sequence of SEQ ID NO: 61 or SEQ ID NO: 62, and ICD is an intracellular domain or protein that promotes the incorporation of the targeting moiety into the envelope of the viral particle, wherein ICD comprises an env incorporation motif comprising the amino acid sequence of SEQ ID NO: 63 or SEQ ID NO: 64, or ICD is absent.

[0040] In some embodiments, viral particles are provided. In some embodiments, the viral particles include a targeting moiety comprising a heterologous viral glycoprotein and a polypeptide having the formula T-S1, wherein T is a target binding domain and S1 is a stalk portion. In some embodiments, the heterologous viral glycoprotein comprises the sequence of SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 52, or SEQ ID NO: 53. In some embodiments, the target binding domain comprises the amino acid sequence of SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 50, or SEQ ID NO: 51. In some embodiments, the stalk portion S1 comprises the formula L3-X1, wherein L3 is a flexible peptide linker comprising the amino acid sequence of SEQ ID NO: 55 and X1 is a polypeptide linker comprising a transmembrane domain. In some embodiments, the polypeptide comprising the transmembrane domain (X1) is ECD-T M -ICD, wherein ECD is an extracellular domain comprising the amino acid sequence of SEQ ID NO: 59 or SEQ ID NO: 60 or a fragment thereof or is absent, and T M is a transmembrane domain comprising the amino acid sequence of SEQ ID NO: 61 or SEQ ID NO: 62, and ICD is an intracellular domain or protein that facilitates incorporation of the targeting moiety into the envelope of the viral particle, where ICD comprises an env incorporation motif comprising the amino acid sequence of SEQ ID NO: 63 or SEQ ID NO: 64 or ICD is absent.

[0041] In some embodiments, viral particles are provided. In some embodiments, the viral particles comprise a targeting moiety comprising a heterologous viral glycoprotein and a polypeptide having the formula T-S1, wherein T is a target binding domain and S1 is a stalk portion. In some embodiments, the heterologous viral glycoprotein comprises the sequence of SEQ ID NO: 23 or SEQ ID NO: 25. In some embodiments, the target binding domain comprises the amino acid sequence of SEQ ID NO: 39. In some embodiments, the stalk portion S1 comprises the formula L3-X1, wherein L3 is a flexible peptide linker comprising the amino acid sequence of SEQ ID NO: 55 and X1 is a polypeptide linker comprising a transmembrane domain. In some embodiments, the polypeptide comprising the transmembrane domain (X1) is ECD-T M -ICD, wherein ECD is an extracellular domain comprising the amino acid sequence of SEQ ID NO: 59 and T M is a transmembrane domain comprising the amino acid sequence of SEQ ID NO: 61 and ICD is an intracellular domain or protein that facilitates incorporation of the targeting moiety into the envelope of the viral particle, wherein ICD comprises an env incorporation motif comprising the amino acid sequence of SEQ ID NO: 63 or SEQ ID NO: 64.

[0042] In some embodiments, viral particles are provided. In some embodiments, the viral particles comprise a targeting moiety comprising a heterologous viral glycoprotein and a polypeptide having the formula T-S1, wherein T is a target binding domain and S1 is a stalk portion. In some embodiments, the heterologous viral glycoprotein comprises the sequence of SEQ ID NO: 52 or SEQ ID NO: 53. In some embodiments, the target binding domain comprises the amino acid sequence of SEQ ID NO: 39. In some embodiments, the stalk portion S1 comprises the formula L3-X1, wherein L3 is a flexible peptide linker comprising the amino acid sequence of SEQ ID NO: 55 and X1 is a polypeptide linker comprising a transmembrane domain. In some embodiments, the polypeptide comprising the transmembrane domain (X1) is ECD-T M -ICD, wherein ECD is an extracellular domain comprising the amino acid sequence of SEQ ID NO: 59 and T Mis a transmembrane domain containing the amino acid sequence of SEQ ID NO: 61, and the ICD is an intracellular domain or protein that promotes the incorporation of the targeting moiety into the envelope of the viral particle, where the ICD contains an env incorporation motif containing the amino acid sequence of SEQ ID NO: 63 or SEQ ID NO: 64.

[0043] In some embodiments, the viral particles provided herein further comprise a nucleic acid molecule encoding a heterologous molecule of interest. In some embodiments, the heterologous molecule of interest is as provided herein. In some embodiments, the heterologous molecule of interest is a CAR. In some embodiments, the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 99, at least 90% identity to SEQ ID NO: 99, at least 95% identity to SEQ ID NO: 99, at least 99% identity to SEQ ID NO: 99, or at least 100% identity to SEQ ID NO: 99.

Brief Description of the Drawings

[0044]

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Mode for Carrying Out the Invention

[0045] Provided herein are virus particles comprising a heterologous viral glycoprotein and a targeting moiety, wherein the targeting moiety comprises a polypeptide having the formula T - S1, wherein T is a target binding domain and S1 is a stalk portion. In some embodiments, S1 comprises, for example, a mutant Fc polypeptide that can be linked to a transmembrane domain provided herein. In some embodiments, S1 comprises a flexible polypeptide provided herein. The mutant Fc polypeptide or flexible polypeptide can be incorporated into the virus particle to help facilitate targeting of the virus particle to a particular cell type.

[0046] Furthermore, the viral particles can include, for example, the VSV-G protein that can be used for pseudotyping of viruses such as lentiviruses. In some embodiments, the pseudotyped virus-like particles are pseudotyped using the viral glycoprotein of the Vesicular stomatitis New Jersey virus strain, the Vesicular stomatitis Indiana virus strain, the Vesicular stomatitis Aragua virus strain, the Vesicular stomatitis Maraba virus strain, or the Vesicular stomatitis Cocal virus strain. Examples of such proteins are provided herein.

[0047] Pseudotyped viruses containing mutant VSV-G proteins such as those provided herein can be used in combination with targeting moieties to facilitate fusion of the pseudotyped virus with a particular cell or tissue based on the expression of a target on the cell or tissue. As provided herein, the targeting moiety can be linked to an Fc protein, which can be called a stalk protein that includes a transmembrane domain that facilitates binding of the targeting moiety to the surface of the virus. In some embodiments, the Fc protein includes Fc effector mutations such as those provided herein.

[0048] 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.

[0049] As used herein, the term "a" or "an" means "at least one" or "one or more" unless the context clearly dictates otherwise.

[0050] As used herein, the term "about" means that a numerical value is an approximation and that minor variations do not materially affect the implementation of the disclosed embodiments. When numerical limitations are used, unless otherwise indicated by context, "about" means that the numerical value can vary by ±10% and still remain within the scope of the disclosed embodiments. Further, in the phrase "from about x to y," the term "about" modifies both x and y and can be used interchangeably with the phrase "from about x to about y" unless otherwise indicated by context.

[0051] As used herein, the terms "individual" or "subject" or "patient" are used interchangeably and mean any animal, including mammals such as mice, rats, other rodents, rabbits, dogs, cats, pigs, cows, sheep, horses, or primates such as humans.

[0052] As used herein, the terms "comprising" (and any form of comprising such as "comprise," "comprises," and "comprised"), "having" (and any form of having such as "have" and "has"), "including" (and any form of including such as "includes" and "include"), or "containing" (and any form of containing such as "contains" and "contain") are inclusive or 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 thing using the transitional phrase "consisting of" or "consists of."

[0053] As used herein, the term "contact" means bringing two elements together in an in vitro or in vivo system. For example, "contacting" a virus or vector described herein with an individual or patient or cell includes administering the virus to an individual or patient such as a human, and introducing a compound into a sample containing, for example, a cell preparation containing cells or a purified preparation.

[0054] As used herein, the terms "fusion" or "linkage" when used with respect to proteins having different domains or heterologous sequences mean that the protein domains are part of the same peptide chain connected to each other by peptide bonds or other covalent bonds. Domains or sections can be directly linked or fused to each other, or it is also possible for another domain or peptide sequence to be between the two domains or sequences, and such sequences are still considered to be 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 such as the glycine / serine sequence described herein links the two domains.

[0055] A "disease" is a health state of an animal in which the animal cannot maintain homeostasis, and if the disease is not improved, the health of the animal continues to deteriorate. In contrast, a "disorder" of an animal refers to a health state in which the animal can maintain homeostasis, but the health state of the animal is less favorable than in the absence of the disorder. Even if the disorder is left untreated, the disorder does not necessarily further degrade the health state of the animal.

[0056] "Effective amount" or "therapeutically effective amount" are used interchangeably herein and refer to the amount of a compound, formulation, substance, or composition described herein that is effective to achieve a particular biological result or to provide a therapeutic or prophylactic benefit. Such results can include, but are not limited to, an amount that causes a detectable level of immune cell activation when administered to a mammal as compared to immune cell activation detected in the absence of the composition. The immune response can be readily evaluated by a number of methods known in the art. One of ordinary skill in the art will understand that the amount of the composition administered herein will vary and can be readily determined based on a number of factors, including the disease or condition being treated, the age and health and physical condition of the mammal being treated, the severity of the disease, the particular compound being administered, and the like.

[0057] "Encoding" refers to the unique property of a specific sequence of nucleotides in a polynucleotide, such as a gene, cDNA, or mRNA, and the biological properties resulting therefrom, which functions as a template for the synthesis of other polymers and macromolecules in a biological process having either a defined sequence of nucleotides (i.e., rRNA, tRNA, and mRNA) or a defined sequence of amino acids. Thus, a gene encodes a protein when transcription and translation of the mRNA corresponding to that gene results in the production of the protein in a cell or other biological system. Both a nucleotide sequence that is identical to the mRNA sequence, the coding strand, which is typically provided in the 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.

[0058] As used herein, an "expression vector" refers to a vector containing a recombinant polynucleotide comprising an expression control sequence operably linked to a nucleotide sequence to be expressed. The expression vector contains cis-acting elements sufficient for expression, and other elements for expression can be provided by the host cell or in an in vitro expression system. Expression vectors include all expression vectors known in the art, such as cosmids, plasmids (e.g., in naked form or contained in liposomes) and viruses (e.g., Sendai virus, lentivirus, retrovirus, adenovirus, and adeno-associated virus) that incorporate the recombinant polynucleotide.

[0059] As used herein, the term "ex vivo" with respect to a cell that has been transduced, transfected or transformed ex vivo refers to a cell that has been transduced, transfected or transformed outside the subject, i.e., a cell that has been removed from the subject prior to such transduction, transfection, or transformation.

[0060] As used herein, "identity" refers to the identity of the subunit sequences between two nucleic acid molecules or amino acid molecules, e.g., between two polymer molecules such as between two polynucleotide molecules or polypeptide molecules. When two amino acid sequences have the same residue at the same position, e.g., when each position of two polypeptide molecules is occupied by arginine, they are identical at that position. The identity or degree to which two amino acid sequences 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 sequences or two nucleic acid sequences depends directly on the number of matching or identical positions, e.g., if half of the positions of 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.

[0061] "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 sequences are at least 60%, 80%, or 85%, or 90%, 95%, or even 99% identical at the amino acid or nucleic acid level to the sequences used for comparison. Other percentage identities for specific sequences are described herein.

[0062] Sequence identity can be measured / determined using sequence analysis software (e.g., the 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 aligns identical or similar sequences by assigning degrees of homology to various substitutions, deletions, and / or other modifications. Conservative substitutions typically include substitutions within the group of glycine, alanine, valine, isoleucine, leucine, aspartic acid, glutamic acid, asparagine, glutamine, serine, threonine, lysine, arginine, and phenylalanine, tyrosine. In an exemplary method of measuring the degree of identity, the BLAST program, which shows sequences with probability scores of e3 to e100 for closely related sequences, can be used. In some embodiments, sequence identity is determined using BLAST with default settings.

[0063] To the extent that embodiments provided herein include compositions containing various proteins, these proteins may, in some cases, include amino acid sequences having sequence identity with 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) relative to the sequence numbers disclosed herein. In addition to these percentages, other percentages of identity are also provided herein. The identity between polypeptides can be determined by the Smith-Waterman homology search algorithm implemented in the MPSRCH program (Oxford Molecular) using an affine gap search with parameters of gap open penalty = -12 and gap extension penalty = 1.

[0064] These proteins may include one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) conservative amino acid substitutions compared to the disclosed proteins, i.e., substitutions of one amino acid with another amino acid having a related side chain. Genetically encoded amino acids are generally classified into four families. (1) Acidic, i.e., aspartic acid, glutamic acid, (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 may also be grouped together as aromatic amino acids. Usually, substitution of a single amino acid within these families does not significantly affect biological activity. The protein may have one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) single amino acid deletions relative to the disclosed protein sequence. The protein may also include one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) insertions (e.g., each of 1, 2, 3, 4, or 5 amino acids) relative to the disclosed protein sequence.

[0065] As used herein, the phrase "in vivo" with respect to a cell that has been transduced, transfected, or transformed in vivo means a cell that has been transduced, transfected, or transformed in a subject in which the cell has not been removed from the subject prior to such transduction, transfection, or transformation.

[0066] "Isolated" means altered or removed from its natural state. For example, a nucleic acid or peptide that naturally occurs in a living animal is not "isolated," but the same nucleic acid or peptide is "isolated" if it has been partially or completely separated from its natural coexisting materials. An isolated nucleic acid or protein can exist in a substantially purified form or in a non-natural environment such as, for example, a host cell.

[0067] As used herein, the term "lentivirus" refers to a genus of the Retroviridae family that can infect non-dividing cells. Non-limiting examples of lentiviruses are HIV, SIV, and FIV. Vectors or virus-like particles derived from lentiviruses can be used to transduce cells to deliver genes or other molecules and express them intracellularly in vitro (ex vivo) or in vivo.

[0068] As used herein, the term "modified" means an altered state or structure of a molecule or cell provided herein. A molecule can be modified in various ways, such as chemically, structurally, and functionally, by mutations, substitutions, insertions, or deletions (e.g., internal deletions, truncations). A cell can be modified through the introduction of nucleic acids or the expression of heterologous proteins.

[0069] As used herein, the term "modulate" encompasses mediating an increase or decrease in the response level of a subject as compared to the response level of the subject in the absence of treatment or compound and / or as compared to the response level of a subject that is otherwise identical but not receiving treatment. This term means to disrupt and / or affect the original signal or response, thereby mediating a beneficial therapeutic response in a subject such as a human.

[0070] Unless otherwise indicated, "nucleotide sequences encoding an amino acid sequence" are degenerate versions of each other and include all nucleotide sequences encoding the same amino acid sequence. The phrase "nucleotide sequence encoding a protein or RNA" can include introns to the extent that the nucleotide sequence encoding the protein can contain introns in some versions.

[0071] The term "oligonucleotide" usually refers to short polynucleotides. When the nucleotide sequence is represented by a DNA sequence (i.e., A, T, C, G), it is also understood to provide the corresponding RNA sequence (i.e., A, U, C, G) in which "T" is replaced by "U".

[0072] "Parenteral" administration of a composition includes, for example, subcutaneous (s.c.), intravenous (i.v.), intramuscular (i.m.), or intrasternal injection, or infusion techniques.

[0073] As used herein, the term "polynucleotide" is defined as a chain of nucleotides. Further, a nucleic acid is a polymer of nucleotides. Thus, the terms "nucleic acid" and "polynucleotide" as used herein are interchangeable. As used herein, polynucleotides include, but are not limited to, all nucleic acid sequences obtained by any method available in the art, and these methods include recombinant methods, i.e., cloning techniques and PCR, etc., cloning of nucleic acid sequences from recombinant libraries or cell genomes and synthetic means, but are not limited thereto.

[0074] As used herein, the terms "peptide", "polypeptide", and "protein" are used interchangeably and refer to a compound composed of a plurality of amino acid residues covalently linked by peptide bonds. As used herein, the term refers to both short chains, which are generally also called peptides, oligopeptides, and oligomers in the art, and long chains, which are generally called proteins in the art, and there are many types thereof. "Polypeptides" include, for example, among others, biologically active fragments, substantially homologous polypeptides, oligopeptides, homodimers, heterodimers, variants of polypeptides, modified polypeptides, derivatives, analogs, fusion proteins, etc. Polypeptides include natural peptides, recombinant peptides, synthetic peptides, or combinations thereof.

[0075] As used herein, the terms "heterologous viral structural protein" and "heterologous viral glycoprotein" are used synonymously and interchangeably unless expressly provided otherwise. Thus, unless expressly stated otherwise, embodiments referring to a "heterologous viral structural protein" are understood to refer to a "heterologous viral glycoprotein" and vice versa.

[0076] As used herein, the term "pseudotype" or "pseudotyped virus particle" refers to a virus particle having a glycoprotein derived from another virus with an envelope, or a viral vector encoding an envelope glycoprotein from a virus different from the parental 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, as provided herein, viruses can be pseudotyped using the VSV-G mutant protein.

[0077] As used herein with respect to an antibody, the term "specifically binds" means an antibody that recognizes a particular antigen but does not substantially recognize or bind other molecules in a sample. For example, an antibody that specifically binds an antigen from one species may also bind that antigen from one or more other species. However, such cross-species reactivity per se does not alter the classification of the antibody as specific. In another example, an antibody that specifically binds an antigen may also bind different allelic forms of the antigen. However, such cross-reactivity per se does not alter the classification of the antibody as specific. In some cases, the terms "specific binding" or "specifically binds" are used with respect to the interaction of an antibody, protein, or peptide with a second chemical species, and mean that the interaction depends on the presence of a particular structure (e.g., an antigenic determinant or epitope) on the chemical species; for example, an antibody recognizes and binds to a particular protein structure rather than proteins in general. If an antibody is specific for epitope "A", the presence of a molecule containing epitope A (or unlabeled free A) during a reaction containing the label "A" and the antibody will decrease the amount of labeled A that binds to the antibody. In some embodiments, the targeting moieties described herein that can be used to target viral particles, including mutant VSV-G protein, or other viral structural proteins used to pseudotype a virus, can specifically bind to that target.

[0078] The term "subject" includes a living organism (e.g., a mammal) that can elicit an immune response. As used herein, "subject" or "patient" refers to a human or non-human mammal. Non-human mammals include, for example, mammals such as sheep, cows, pigs, dogs, non-human primates, cats, and rodents, as well as domestic animals and pets. In some embodiments, the subject is a human.

[0079] As used herein, the term "therapeutic" means treatment and / or prevention. A therapeutic effect is obtained by suppression, remission, or eradication of a medical condition.

[0080] As used herein, the terms "transfected", "transformed", or "transduced" refer to the process by which exogenous nucleic acid is transferred or introduced into a cell. A "transfected", "transformed", or "transduced" cell is a cell that has been transfected, transformed, or transduced with exogenous nucleic acid. This cell includes primary subject cells and their progeny. In some embodiments, transfection, transformation, or transduction occurs or is performed in vivo.

[0081] "Treat" or "treatment" of a disease, as the term is used herein, means reducing the frequency or severity of at least one sign or symptom of a disease or disorder experienced by a subject.

[0082] A "vector" is a composition of matter that includes an isolated nucleic acid encoding a protein or peptide. A number of 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.

[0083] A "carrier" or "delivery vehicle" includes viral particles, viruses, polylysine compounds, and liposomes, which facilitate the transfer of nucleic acid into cells. A carrier or delivery vehicle can also be used to deliver a protein or peptide to a cell.

[0084] Scope: Throughout this disclosure, various aspects of the embodiments can be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation. Thus, the description of a range should be considered to specifically disclose all possible sub-ranges as well as the individual numerical values within that range. For example, a description of a range such as 1 to 6 should be considered to specifically disclose sub-ranges such as 1 to 3, 1 to 4, 1 to 5, 2 to 4, 2 to 6, 3 to 6, etc., as well as the individual numerical values within that range, such as 1, 2, 2.7, 3, 4, 5, 5.3, and 6. This applies regardless of the width of the range. Unless explicitly stated to the contrary, the disclosed ranges include the endpoints of the range.

[0085] In some embodiments, a polypeptide comprising a variant Fc polypeptide is provided. In some embodiments, the variant Fc polypeptide is a variant of an Fc polypeptide comprising the amino acid sequence of SEQ ID NO: 26 (IgG1 Fc), SEQ ID NO: 27 (IgG2 Fc), or SEQ ID NO: 28 (IgG4 Fc). In some embodiments, the variant comprises an N-terminal deletion. In some embodiments, the N-terminal deletion does not include up to 100 amino acid residues from the N-terminus of SEQ ID NO: 26, SEQ ID NO: 27, or SEQ ID NO: 28. In some embodiments, the N-terminal deletion does not include up to 98 amino acid residues counted from the N-terminus of SEQ ID NO: 26, SEQ ID NO: 27, or SEQ ID NO: 28. In some embodiments, the N-terminal deletion does not include 98 amino acid residues counted from the N-terminus of SEQ ID NO: 26, SEQ ID NO: 27, or SEQ ID NO: 28. In some embodiments, the N-terminal deletion does not include 98 amino acid residues counted from the N-terminus of SEQ ID NO: 26. In some embodiments, the N-terminal deletion does not include 90 to 98 amino acid residues counted from the N-terminus of SEQ ID NO: 26, SEQ ID NO: 27, or SEQ ID NO: 28. In some embodiments, the N-terminal deletion does not include 75 to 98 amino acid residues counted from the N-terminus of SEQ ID NO: 26, SEQ ID NO: 27, or SEQ ID NO: 28. In some embodiments, the N-terminal deletion does not include 60 to 98 amino acid residues counted from the N-terminus of SEQ ID NO: 26, SEQ ID NO: 27, or SEQ ID NO: 28. In some embodiments, the N-terminal deletion does not include 50 to 98 amino acid residues counted from the N-terminus of SEQ ID NO: 26, SEQ ID NO: 27, or SEQ ID NO: 28. In some embodiments, the N-terminal deletion does not include 40 to 98 amino acid residues counted from the N-terminus of SEQ ID NO: 26, SEQ ID NO: 27, or SEQ ID NO: 28. In some embodiments, the N-terminal deletion does not include 30 to 98 amino acid residues counted from the N-terminus of SEQ ID NO: 26, SEQ ID NO: 27, or SEQ ID NO: 28. In some embodiments, the N-terminal deletion does not include 10 to 98 amino acid residues counted from the N-terminus of SEQ ID NO: 26, SEQ ID NO: 27, or SEQ ID NO: 28. In some embodiments, the N-terminal deletion does not include 5 to 98 amino acid residues counted from the N-terminus of SEQ ID NO: 26, SEQ ID NO: 27, or SEQ ID NO: 28.In some embodiments, the N-terminal deletion does not include 1 to 98 amino acid residues counted from the N-terminus of SEQ ID NO: 26, SEQ ID NO: 27, or SEQ ID NO: 28. In some embodiments, the variant Fc polypeptide does not include the following amino acid sequence. ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKV (SEQ ID NO: 105).

[0086] In some embodiments, the variant Fc polypeptide does not include any of the sequences of SEQ ID NO: 105. In some embodiments, the variant Fc polypeptide does not include the entire sequence of SEQ ID NO: 15. As used herein, the phrase "counting from the N-terminus" with respect to an N-terminal deletion of a reference sequence means treating the first residue of the reference sequence as residue 1, even if the first residue has a different number under a numbering scheme such as the EU numbering scheme of the Fc polypeptide. Thus, for example, the phrase "the N-terminal deletion does not include 3 amino acid residues counting from the N-terminus of SEQ ID NO: 26" refers to the deletion of the residues "ASK" because they are the first three residues of SEQ ID NO: 26. In some embodiments, the variant Fc polypeptide includes the amino acid sequence of SEQ ID NO: 103. In some embodiments, the variant Fc polypeptides provided herein, with or without an N-terminal deletion, include one or more mutations at positions corresponding to L234, L235, M297, P329, I253, H310, or H435. The positions refer to the EU numbering of the Fc polypeptide. In some embodiments, the variant Fc polypeptides provided herein, with or without an N-terminal deletion, include one or more mutations at positions corresponding to L234, L235, M297, P329, I253, H310, and H435. In some embodiments, the variant Fc polypeptides provided herein, with or without an N-terminal deletion, include mutations at positions corresponding to L234 and L235. In some embodiments, the variant Fc polypeptides provided herein, with or without an N-terminal deletion, include a mutation at the position corresponding to M297. In some embodiments, the variant Fc polypeptides provided herein, with or without an N-terminal deletion, include a mutation at the position corresponding to P329. In some embodiments, the variant Fc polypeptides provided herein, with or without an N-terminal deletion, include a mutation at the position corresponding to I253. In some embodiments, the variant Fc polypeptides provided herein, with or without an N-terminal deletion, include a mutation at the position corresponding to H310.In some embodiments, the variant Fc polypeptide with or without an N-terminal deletion provided herein comprises a mutation at the position corresponding to H435. In some embodiments, the variant Fc polypeptide with or without an N-terminal deletion provided herein comprises one or more mutations corresponding to L234A, L235A, M297A, P329G, I253A, H310A, or H435A. In some embodiments, the variant Fc polypeptide with or without an N-terminal deletion provided herein comprises mutations corresponding to L234A, L235A, M297A, P329G, I253A, H310A, and H435A. In some embodiments, the Fc variant polypeptide is at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 103, provided that the Fc variant does not comprise the amino acid sequence of SEQ ID NO: 105 and the variant comprises one or more mutations corresponding to L234A, L235A, M297A, P329G, I253A, H310A, or H435A, and comprises an amino acid sequence. In some embodiments, the Fc variant polypeptide is at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 103, provided that the Fc variant does not comprise the amino acid sequence of SEQ ID NO: 105 and the variant comprises mutations corresponding to 234A, L235A, M297A, P329G, I253A, H310A, and H435A, and comprises an amino acid sequence. In some embodiments, the Fc variant polypeptide is at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 104, provided that the Fc variant does not comprise the amino acid sequence of SEQ ID NO: 105, and comprises an amino acid sequence. In some embodiments, the Fc variant polypeptide comprises the sequence of SEQ ID NO: 104, provided that the Fc variant does not comprise the amino acid sequence of SEQ ID NO: 105.As used herein, positions referred to in connection with an Fc polypeptide refer to positions according to the EU numbering scheme, which is known in the art. For example, in the polypeptide of SEQ ID NO: 104, position 234 refers to residue 19 of SEQ ID NO: 104, position 235 refers to residue 20 of SEQ ID NO: 104, and so on.

[0087] As provided herein, in some embodiments, an Fc variant can be fused or linked to another protein, e.g., a targeting moiety. An Fc variant can also be fused or linked to a transmembrane domain and / or an intracellular domain, thereby allowing insertion into a cell membrane or viral envelope, e.g., the envelope of a lentivirus. In some embodiments, the targeting moiety is linked or fused to the N-terminus of the Fc variant polypeptide. In some embodiments, the Fc variant polypeptide is linked to a transmembrane domain at the C-terminus of the Fc variant polypeptide.

[0088] In some embodiments, provided are virus particles comprising a variant Fc polypeptide provided herein, such as those described herein including those above and below.

[0089] Virus particles comprising a heterologous viral glycoprotein and a targeting moiety In some embodiments, virus particles are provided that include a heterologous viral glycoprotein and a targeting moiety. In some embodiments, the targeting moiety includes a polypeptide having the formula T-S1, where T is a target binding domain and S1 is a stalk portion. In some embodiments, S1 includes a variant Fc protein, and the variant Fc protein includes a transmembrane domain such as, but not limited to, the CD8 or CD28 transmembrane domain. Thus, in some embodiments, the stalk portion S1 includes the N-terminal to C-terminal orientation of the variant Fc-transmembrane domain. In some embodiments, the variant Fc protein includes an effector mutation, and the effector mutation inhibits the interaction of the Fc protein with an Fc interacting protein such as FcγR, C1q, FcRβ, or FcRn.

[0090] In some embodiments, the S1 stalk portion is attached to the surface of the virus particle via a transmembrane domain. For example, the transmembrane domain can pass through the envelope of an enveloped virus (e.g., a lentivirus or other virus provided herein) or be inserted into the envelope thereof. Thus, the stalk portion of S1 linked to the transmembrane domain is presented on the outer surface of the enveloped virus.

[0091] In some embodiments, the variant Fc protein is a variant of an IgG1 Fc, IgG2 Fc, or IgG4 Fc protein. In some embodiments, the variant Fc protein includes a variant of the sequence of SEQ ID NO: 26 (IgG1 Fc), SEQ ID NO: 27 (IgG2 Fc), or SEQ ID NO: 28 (IgG4 Fc).

[0092] In some embodiments, the variant Fc protein is a variant IgG1 Fc protein (SEQ ID NO: 26). In some embodiments, the variant IgG1 Fc protein corresponds to a mutation selected from the group consisting of L234A, L235A, N297A, P329G, I253A, H310A, and H435A of SEQ ID NO: 26, and is numbered according to the Kabat EU numbering index described in Edelman, G M et al. “The covalent structure of an entire gammaG immunoglobulin molecule.” Proceedings of the National Academy of Sciences of the United States of America vol.63,1(1969):78 - 85.doi:10.1073 / pnas.63.1.78, the entirety of which is incorporated herein by reference. Any of the mutations L234A, L235A, N297A, P329G, I253A, H310A, and H435A of SEQ ID NO: 26 may or may not be present, and the mutations may be combined in any combination. In some embodiments, the variant IgG1 Fc protein comprises mutations corresponding to L234A and L235A of SEQ ID NO: 26. In some embodiments, the variant IgG1 Fc protein comprises a mutation corresponding to N297A of SEQ ID NO: 26. In some embodiments, the variant IgG1 Fc protein comprises a mutation corresponding to P329G of SEQ ID NO: 26. In some embodiments, the variant IgG1 Fc protein comprises mutations corresponding to L234A, L235A, N297A, and P329G of SEQ ID NO: 26. In some embodiments, the variant IgG1 Fc protein comprises a mutation corresponding to I253A of SEQ ID NO: 26. In some embodiments, the variant IgG1 Fc protein comprises a mutation corresponding to H310A of SEQ ID NO: 26. In some embodiments, the variant IgG1 Fc protein comprises a mutation corresponding to H435A of SEQ ID NO: 26.In some embodiments, the variant IgG1 Fc protein comprises mutations corresponding to I253A, H310A, and H435A of SEQ ID NO: 26. In some embodiments, the variant IgG1 Fc protein comprises mutations corresponding to L234A, L235A, N297A, P329G, I253A, H310A, and H435A of SEQ ID NO: 26.

[0093] In some embodiments, the variant Fc protein comprising the variant IgG1 Fc protein comprises a truncation of the IgG1 Fc sequence. The truncation can include the deletion of any number of amino acids from the N-terminus, C-terminus, or both of the IgG1 Fc sequence. In some embodiments, the variant Fc protein comprising the variant IgG1 Fc protein comprises a truncation of SEQ ID NO: 26. The truncation can include the deletion of any number of amino acids from the N-terminus, C-terminus, or both of SEQ ID NO: 26. In some embodiments, the truncation includes the deletion of amino acids from the N-terminus of SEQ ID NO: 26. In some embodiments, the truncation includes the deletion of amino acids from the C-terminus of SEQ ID NO: 26. In some embodiments, the truncation can include the deletion of amino acids from both the N-terminus and C-terminus of SEQ ID NO: 26. In some embodiments, the truncation of SEQ ID NO: 26 comprises the amino acid sequence of SEQ ID NO: 103: EPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 103).

[0094] In some embodiments, the variant IgG1 Fc protein comprises one or more mutations relative to SEQ ID NO: 103 selected from the group consisting of L19A, L20A, N82A, P114G, I38A, H95A, and H220A. It should be understood that positions L19, L20, N82, P114, I38, H95, and H220 refer only to SEQ ID NO: 103. One of ordinary skill in the art will readily recognize that positions L234, L235, N297, P329, I253, H310, and H435, numbered according to the Kabat EU numbering system, correspond to positions L19, L20, N82, P114, I38, H95, and H220 of SEQ ID NO: 103, respectively. Any of the mutations L19A, L20A, N82A, P114G, I38A, H95A, and H220A of SEQ ID NO: 103 may or may not be present, and these mutations can be combined in any combination. In some embodiments, the variant IgG1 Fc protein comprises mutations corresponding to L19A and L20A of SEQ ID NO: 103. In some embodiments, the variant IgG1 Fc protein comprises a mutation corresponding to N82A of SEQ ID NO: 103. In some embodiments, the variant IgG1 Fc comprises a mutation corresponding to P114G of SEQ ID NO: 103. In some embodiments, the variant IgG1 Fc comprises mutations corresponding to L19A, L20A, N82A, and P114G of SEQ ID NO: 103. In some embodiments, the variant IgG1 Fc protein comprises a mutation corresponding to I38A of SEQ ID NO: 103. In some embodiments, the variant IgG1 Fc protein comprises a mutation corresponding to H95A of SEQ ID NO: 103. In some embodiments, the variant IgG1 Fc protein comprises a mutation corresponding to H220A of SEQ ID NO: 103. In some embodiments, the variant IgG1 Fc protein comprises mutations corresponding to I38A, H95A, and H220A of SEQ ID NO: 103. In some embodiments, the variant IgG1 Fc protein comprises mutations corresponding to L19A, L20A, N82A, P114G, I38A, H95A, and H220A of SEQ ID NO: 103.In some embodiments, the variant IgG1 Fc protein comprises mutations corresponding to each of L19A, L20A, N82A, P114G, I38A, H95A, and H220A of SEQ ID NO: 103. An exemplary variant IgG1 protein comprising each of L19A, L20A, N82A, P114G, I38A, H95A, and H220A is shown below in the amino acid sequence of SEQ ID NO: 104:. EPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMASRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLAQDWLNGKEYKCKVSNKALGAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNAYTQKSLSLSPGK (SEQ ID NO: 104).

[0095] In some embodiments, the variant Fc protein is a variant IgG2 Fc protein (SEQ ID NO: 27). In some embodiments, the variant IgG2 Fc protein is selected from the group consisting of N297A, P329G, I253A, H310A, and H435A at positions corresponding to SEQ ID NO: 27 and contains one or more mutations numbered according to the Kabat EU numbering index. Any of the mutations N297A, P329G, I253A, H310A, and H435A of SEQ ID NO: 27 may or may not be present, and the mutations may be combined in any combination. In some embodiments, the variant IgG2 Fc protein contains a mutation corresponding to N297A of SEQ ID NO: 27. In some embodiments, the variant IgG2 Fc protein contains a mutation corresponding to P329G of SEQ ID NO: 27. In some embodiments, the variant IgG2 Fc protein contains mutations corresponding to N297A and P329G of SEQ ID NO: 27. In some embodiments, the variant IgG2 Fc protein contains a mutation corresponding to I253A of SEQ ID NO: 27. In some embodiments, the variant IgG2 Fc protein contains a mutation corresponding to H310A of SEQ ID NO: 27. In some embodiments, the variant IgG2 Fc protein contains a mutation corresponding to H435A of SEQ ID NO: 27. In some embodiments, the variant IgG2 Fc protein contains mutations corresponding to I253A, H310A, and H435A of SEQ ID NO: 27.

[0096] In some embodiments, the variant Fc protein comprising the variant IgG2 Fc protein comprises a truncation of the IgG2 Fc sequence. The truncation can include a deletion of any number of amino acids from the N-terminus, C-terminus, or both of the IgG2 Fc sequence. In some embodiments, the variant Fc protein comprising the variant IgG2 Fc protein comprises the truncation of SEQ ID NO:27. The truncation can include a deletion of any number of amino acids from the N-terminus, C-terminus, or both of SEQ ID NO:27. In some embodiments, the truncation includes a deletion of amino acids from the N-terminus of SEQ ID NO:27. In some embodiments, the truncation includes a deletion of amino acids from the C-terminus of SEQ ID NO:27. In some embodiments, the truncation can include a deletion of amino acids from both the N-terminus and C-terminus of SEQ ID NO:27.

[0097] In some embodiments, the variant Fc protein is a variant IgG4 Fc protein (SEQ ID NO: 28). In some embodiments, the variant IgG4 Fc protein is selected from the group consisting of S228P, L235E, N297A, P329G, I253A, H310A, and H435A at positions corresponding to SEQ ID NO: 28 and includes one or more mutations numbered according to the Kabat EU numbering index. Any of the mutations S228P, L235E, N297A, P329G, I253A, H310A, and H435A of SEQ ID NO: 28 may or may not be present, and the mutations may be combined in any combination. In some embodiments, the variant IgG4 Fc protein includes a mutation corresponding to S228P of SEQ ID NO: 28. In some embodiments, the variant IgG4 Fc protein includes a mutation corresponding to L235E of SEQ ID NO: 28. In some embodiments, the variant IgG4 Fc protein includes a mutation corresponding to N297A of SEQ ID NO: 28. In some embodiments, the variant IgG4 Fc protein includes a mutation corresponding to P329G of SEQ ID NO: 28. In some embodiments, the variant IgG4 Fc protein includes mutations corresponding to S228P, L235E, N297A, and P329G of SEQ ID NO: 28. In some embodiments, the variant IgG4 Fc protein includes a mutation corresponding to I253A of SEQ ID NO: 28. In some embodiments, the variant IgG4 Fc protein includes a mutation corresponding to H310A of SEQ ID NO: 28. In some embodiments, the variant IgG4 Fc protein includes a mutation corresponding to H435A of SEQ ID NO: 28. In some embodiments, the variant IgG4 Fc protein includes mutations corresponding to I253A, H310A, and H435A of SEQ ID NO: 28.

[0098] In some embodiments, the variant Fc protein comprising the variant IgG4 Fc protein comprises a truncation of the IgG4 Fc sequence. The truncation may include a deletion of any number of amino acids from the N-terminus, C-terminus, or both of the IgG4 Fc sequence. In some embodiments, the variant Fc protein comprising the variant IgG4 Fc protein comprises the truncation of SEQ ID NO: 28. The truncation may include a deletion of any number of amino acids from the N-terminus, C-terminus, or both of SEQ ID NO: 28. In some embodiments, the truncation includes a deletion of amino acids from the N-terminus of SEQ ID NO: 28. In some embodiments, the truncation includes a deletion of amino acids from the C-terminus of SEQ ID NO: 28. In some embodiments, the truncation may include a deletion of amino acids from both the N-terminus and C-terminus of SEQ ID NO: 28.

[0099] In some embodiments, the stalk portion S1 comprising the variant Fc protein is given by the formula L1-Fc-L2-X1, where L1 is a linker or absent; Fc is a variant Fc protein; L2 is a linker or absent; and X1 is a polypeptide comprising a transmembrane domain. Thus, the targeting portion comprising the formula T-S1 may also be given by the formula T-L1-Fc-L2-X1, where T is a target binding domain; L1 is a linker or absent; Fc is a variant Fc protein; L2 is a linker or absent; and X1 is a polypeptide comprising a transmembrane domain. Thus, it should be understood that in some embodiments, the stalk portion S1 may be given by the formula L1-Fc-L2-X1. In some embodiments, the target binding domain T is as provided herein. In some embodiments, the variant Fc protein is as provided herein.

[0100] In some embodiments, L1 and L2 are each independently a polypeptide linker. In some embodiments, the polypeptide linker is (GGGGA) n(SEQ ID NO: 54), (GGGGS) n (SEQ ID NO: 55), (EAAAK) n (SEQ ID NO: 73), A(EAAAK) n A(SEQ ID NO: 74), (XP) n including (SEQ ID NO: 75), where X includes Ala, Lys, or Glu, GSAGAAGSGEF (SEQ ID NO: 56), KESGSVSSEQLAQFRSLD (SEQ ID NO: 57), EGKSSGSGSESKST (SEQ ID NO: 58), AEAAAKEAAAKA (SEQ ID NO: 76), or combinations thereof, and each n is independently 1 - 5. In some embodiments, each n is independently 1. In some embodiments, each n is independently 2. In some embodiments, each n is independently 3. In some embodiments, each n is independently 4. In some embodiments, each n is independently 5. In some embodiments, each n is independently greater than 5. In some embodiments, L1 is absent. In some embodiments, L1 is (GGGGA) n (SEQ ID NO: 54) or (GGGGS) n (SEQ ID NO: 55), and each n is independently 1 - 5. In some embodiments, L1 is (GGGGA) n (SEQ ID NO: 54) or (GGGGS) n (SEQ ID NO: 55), and each n is independently 1. In some embodiments, L1 is (GGGGA) n (SEQ ID NO: 54) or (GGGGS) n (SEQ ID NO: 55), and each n is independently 2. In some embodiments, L1 is (GGGGA) n (SEQ ID NO: 54) or (GGGGS) n (SEQ ID NO: 55), and each n is independently 3. In some embodiments, L1 is (GGGGA) n (SEQ ID NO: 54) or (GGGGS) n (SEQ ID NO: 55), and each n is independently 4. In some embodiments, L1 is (GGGGA) n (SEQ ID NO: 54) or (GGGGS) n(SEQ ID NO: 55), where each n is independently 5. In some embodiments, L1 is (GGGGA) n (SEQ ID NO: 54) or (GGGGS) n (SEQ ID NO: 55), where each n is independently greater than 5. In some embodiments, L2 is absent. In some embodiments, L2 is (GGGGA) n (SEQ ID NO: 54) or (GGGGS) n (SEQ ID NO: 55), where each n is independently from 1 to 5. In some embodiments, L2 is (GGGGA) n (SEQ ID NO: 54) or (GGGGS) n (SEQ ID NO: 55), where each n is independently 1. In some embodiments, L2 is (GGGGA) n (SEQ ID NO: 54) or (GGGGS) n (SEQ ID NO: 55), where each n is independently 2. In some embodiments, L2 is (GGGGA) n (SEQ ID NO: 54) or (GGGGS) n (SEQ ID NO: 55), where each n is independently 3. In some embodiments, L2 is (GGGGA) n (SEQ ID NO: 54) or (GGGGS) n (SEQ ID NO: 55), where each n is independently 4. In some embodiments, L2 is (GGGGA) n (SEQ ID NO: 54) or (GGGGS) n (SEQ ID NO: 55), where each n is independently 5. In some embodiments, L2 is (GGGGA) n (SEQ ID NO: 54) or (GGGGS) n (SEQ ID NO: 55), where each n is independently greater than 5.

[0101] In some embodiments, X1 comprises a polypeptide having the formula ECD-T M -ICD, wherein ECD is the extracellular domain of a cell surface protein, or a fragment thereof, or is absent; T Mis the transmembrane domain of a transmembrane protein; ICD is a protein that promotes the incorporation of the intracellular domain of the protein or the targeting moiety into the envelope of the viral particle, or is absent. Thus, in some embodiments, the targeting moiety, which may be given by the formula T-L1-Fc-L2-X1, includes the formula T-S1 which may be given by the formula T-L1-Fc-L2-ECD-T M -ICD (wherein T is a target binding domain); L1 is a linker or is absent; Fc is a variant Fc protein; L2 is a linker or is absent; ECD is the extracellular domain of a cell surface protein or a fragment thereof, or is absent; T M is the transmembrane domain of a transmembrane protein; ICD is a protein that promotes the incorporation of the intracellular domain of the protein or the targeting moiety into the envelope of the viral particle, or is absent. Thus, in some embodiments, the stalk portion S1 may be given by the formula L1-Fc-L2-ECD-T M -ICD. It should be understood that in some embodiments, the stalk portion S1 may be given by the formula L1-Fc-L2-ECD-T

[0102] In some embodiments, the stalk portion S1 does not include a mutant Fc region. In some embodiments, the stalk portion S1 is given by the formula L3-X1, wherein L3 is a flexible peptide linker and X1 is a polypeptide comprising a transmembrane domain provided herein. Thus, in some embodiments, the targeting moiety comprising the formula T-S1 may be given by the formula T-L3-X1, wherein T is a target binding domain, L3 is a flexible peptide linker, and X1 is a polypeptide comprising a transmembrane domain provided herein. Thus, it should be understood that in some embodiments, the stalk portion S1 may be given by the formula L3-X1. In some embodiments, the S1 stalk portion is bound to the surface of the viral particle via a transmembrane domain.

[0103] In some embodiments, the flexible peptide linker L3 can be any flexible peptide linker. In some embodiments, L3 is (GGGGA) n (SEQ ID NO: 54), (GGGGS) n (SEQ ID NO: 55), GSAGSAAGSGEF (SEQ ID NO: 56), KESGSVSSEQLAQFRSLD (SEQ ID NO: 57), EGKSSGSGSESKST (SEQ ID NO: 58), or any combination thereof, and is selected from the group of flexible linkers including but not limited to these, where each n is independently an integer selected from 1 to 4. In some embodiments, each n is independently an integer selected from 1 to 4, 1 to 5, 1 to 6, 1 to 7, 1 to 8, 1 to 9, or 1 to 10. 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, n is 6. In some embodiments, n is 7. In some embodiments, n is 8. In some embodiments, n is 9. In some embodiments, n is 10. In some embodiments, each n is independently greater than 10. In some embodiments, L3 is (GGGGA) n (SEQ ID NO: 54) and n is 1. In some embodiments, L3 is (GGGGA) n (SEQ ID NO: 54) and n is 2. In some embodiments, L3 is (GGGGA) n (SEQ ID NO: 54) and n is 3. In some embodiments, L3 is (GGGGA) n (SEQ ID NO: 54) and n is 4. In some embodiments, L3 is (GGGGA) n (SEQ ID NO: 54) and n is 5. In some embodiments, L3 is (GGGGA) n (SEQ ID NO: 54) and n is 6. In some embodiments, L3 is (GGGGA) n (SEQ ID NO: 54) and n is 7. In some embodiments, L3 is (GGGGA) n(SEQ ID NO: 54), and n is 8. In some embodiments, L3 is (GGGGA) n (SEQ ID NO: 54), and n is 9. In some embodiments, L3 is (GGGGA) n (SEQ ID NO: 54), and n is 10. In some embodiments, L3 is (GGGGA) n (SEQ ID NO: 54), and n is greater than 10. In some embodiments, L3 is (GGGGS) n (SEQ ID NO: 55), and n is 1. In some embodiments, L3 is (GGGGS) n (SEQ ID NO: 55), and n is 2. In some embodiments, L3 is (GGGGS) n (SEQ ID NO: 55), and n is 3. In some embodiments, L3 is (GGGGS) n (SEQ ID NO: 55), and n is 4. In some embodiments, L3 is (GGGGS) n (SEQ ID NO: 55), and n is 5. In some embodiments, L3 is (GGGGS) n (SEQ ID NO: 55), and n is 6. In some embodiments, L3 is (GGGGS) n (SEQ ID NO: 55), and n is 7. In some embodiments, L3 is (GGGGS) n (SEQ ID NO: 55), and n is 8. In some embodiments, L3 is (GGGGS) n (SEQ ID NO: 55), and n is 9. In some embodiments, L3 is (GGGGS) n (SEQ ID NO: 55), and n is 10. In some embodiments, L3 is (GGGGA) n (SEQ ID NO: 55), and n is greater than 10. In some embodiments, L3 is GSAGSAAGSGEF (SEQ ID NO: 56). In some embodiments, L3 is KESGSVSSEQLAQFRSLD (SEQ ID NO: 57). In some embodiments, L3 is EGKSSGSGSESKST (SEQ ID NO: 58).

[0104] In some embodiments, the flexible peptide linker L3 can be any flexible peptide linker. In some embodiments, L3 is (GGGGA) n (SEQ ID NO: 54), (GGGGS) n (SEQ ID NO: 55), GSAGSAAGSGEF (SEQ ID NO: 56), KESGSVSSEQLAQFRSLD (SEQ ID NO: 57), EGKSSGSGSESKST (SEQ ID NO: 58), or any combination thereof, and is selected from the group of flexible linkers, where each n is independently an integer selected from 1 to 4. 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, L3 is (GGGGA) n and n is 1. In some embodiments, L3 is (GGGGA) n (SEQ ID NO: 54) and n is 2. In some embodiments, L3 is (GGGGA) n (SEQ ID NO: 54) and n is 3. In some embodiments, L3 is (GGGGA) n (SEQ ID NO: 54) and n is 4. In some embodiments, L3 is (GGGGS) n (SEQ ID NO: 55) and n is 1. In some embodiments, L3 is (GGGGS) n (SEQ ID NO: 55) and n is 2. In some embodiments, L3 is (GGGGS) n (SEQ ID NO: 55) and n is 3. In some embodiments, L3 is (GGGGS) n (SEQ ID NO: 55) and n is 4. In some embodiments, L3 is GSAGSAAGSGEF (SEQ ID NO: 56). In some embodiments, L3 is KESGSVSSEQLAQFRSLD (SEQ ID NO: 57). In some embodiments, L3 is EGKSSGSGSESKST (SEQ ID NO: 58).

[0105] In some embodiments, L3 is (GGGGA) n (SEQ ID NO: 54), (GGGGS) nSelected from the group of flexible linkers including, but not limited to, (SEQ ID NO: 55), GSAGSAAGSGEF (SEQ ID NO: 56), KESGSVSSEQLAQFRSLD (SEQ ID NO: 57), EGKSSGSGSESKST (SEQ ID NO: 58), or any combination thereof, each n is independently an integer selected from 1, 2, or 4. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 4. In some embodiments, L3 is (GGGGA) n (SEQ ID NO: 54), and n is 1. In some embodiments, L3 is (GGGGA) n (SEQ ID NO: 54), and n is 2. In some embodiments, L3 is (GGGGA) n (SEQ ID NO: 54), and n is 4. In some embodiments, L3 is (GGGGS) n (SEQ ID NO: 55), and n is 1. In some embodiments, L3 is (GGGGS) n (SEQ ID NO: 55), and n is 2. In some embodiments, L3 is (GGGGS) n (SEQ ID NO: 55), and n is 4. In some embodiments, L3 is GSAGSAAGSGEF (SEQ ID NO: 56). In some embodiments, L3 is KESGSVSSEQLAQFRSLD (SEQ ID NO: 57). In some embodiments, L3 is EGKSSGSGSESKST (SEQ ID NO: 58).

[0106] In some embodiments, X1 is ECD-T M -ICD having a polypeptide of the formula, wherein ECD is the extracellular domain of a cell surface protein, or a fragment thereof, or is absent; T M is the transmembrane domain of a transmembrane protein; ICD is the intracellular domain of a protein, or a protein that promotes the incorporation of a targeting moiety into the envelope of a viral particle, or is absent. Thus, in some embodiments, the targeting moiety, which may be given by the formula T-L3-X1, including the formula T-S1, is the formula T-L3-ECD-T M-May also be provided by an ICD, where T is a target binding domain, L3 is a flexible peptide linker, ECD is the extracellular domain of a cell surface protein, or a fragment thereof, or is absent; T M is the transmembrane domain of a transmembrane protein; ICD is the intracellular domain of a protein, or a protein that promotes the incorporation of a targeting moiety into the envelope of a viral particle, or is absent. Thus, in some embodiments, it should be understood that the stalk portion S1 may be provided by the formula L1-Fc-L2-ECD-TM-ICD.

[0107] In some embodiments, the ECD does not exist. In some embodiments, the ECD can be any suitable extracellular domain or fragment thereof. In some embodiments, the ECD is derived from a protein different from the transmembrane domain. The ECD domain can be the entire ECD domain or a fragment thereof. In some embodiments, the ECD domain is the ECD domain of CD8 or CD28, or a fragment thereof. In some embodiments, the ECD domain is the CD8 ECD domain or a fragment thereof. In some embodiments, the CD8 ECD domain comprises the polypeptide of FVPVFLPAKPTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACD (SEQ ID NO: 59). In some embodiments, the CD8 ECD domain consists of, or consists essentially of, the polypeptide of FVPVFLPAKPTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACD (SEQ ID NO: 59). In some embodiments, the ECD domain comprises a polypeptide that is 25 to 45 amino acids in length. In some embodiments, the ECD comprises a polypeptide that is at least, or about 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the peptide of FVPVFLPAKPTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACD (SEQ ID NO: 59). In some embodiments, the ECD domain is the ECD domain of CD28 or a fragment thereof. In some embodiments, the CD28 ECD domain comprises the polypeptide of KIEVMYPPPYLDNEKSNGTIIHVKGKHLCPSPLFPGPSKP (SEQ ID NO: 60). In some embodiments, the CD28 ECD domain consists of, or consists essentially of, the polypeptide of KIEVMYPPPYLDNEKSNGTIIHVKGKHLCPSPLFPGPSKP (SEQ ID NO: 60). In some embodiments, the ECD domain comprises a polypeptide that is 25 to 45 amino acids in length.In some embodiments, the ECD comprises a polypeptide that is at least, or about 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the peptide of KIEVMYPPPYLDNEKSNGTIIHVKGKHLCPSPLFPGPSKP (SEQ ID NO: 60).

[0108] In some embodiments, T M can be any suitable transmembrane domain or fragment thereof. In some embodiments, T M domain is the T M domain of CD8 or CD28, or a fragment thereof. In some embodiments, T M domain is the CD8 T M domain, or a fragment thereof. In some embodiments, the CD8 T M domain comprises the polypeptide of IYIWAPLAGTCGVLLLSLVITLYCNHRN (SEQ ID NO: 61). In some embodiments, the CD8 T M domain consists of, or consists essentially of, the polypeptide of IYIWAPLAGTCGVLLLSLVITLYCNHRN (SEQ ID NO: 61). In some embodiments, T M comprises a polypeptide that is at least, or about 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the peptide of IYIWAPLAGTCGVLLLSLVITLYCNHRN (SEQ ID NO: 61). In some embodiments, T M domain is the T M domain of CD28, or a fragment thereof. In some embodiments, the T M domain of CD28 comprises the polypeptide of FWVLVVVGGVLACYSLLVTVAFIIFWV (SEQ ID NO: 62). In some embodiments, the T M domain of CD28 consists of, or consists essentially of, the polypeptide of FWVLVVVGGVLACYSLLVTVAFIIFWV (SEQ ID NO: 62). In some embodiments, T Mcomprises a polypeptide that is at least, or about 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the peptide of SWVLVVVGGVLACYSLLVTVAFIIFWV (SEQ ID NO: 62).

[0109] In some embodiments, T M domain is derived from the same protein as the ECD. In some embodiments, T M domain is derived from a protein different from the ECD. In some embodiments, T M domain is the T M domain of CD8, or CD28, or a fragment thereof, and the ECD domain is the ECD domain of CD8, or CD28, or a fragment thereof. In some embodiments, T M domain is at least, or about 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the peptide of IYIWAPLAGTCGVLLLSLVITLYCNHRN (SEQ ID NO: 61), and the ECD domain is at least, or about 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the peptide of FVPVFLPAKPTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACD (SEQ ID NO: 59). In some embodiments, T M domain is at least, or about 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the peptide of IYIWAPLAGTCGVLLLSLVITLYCNHRN (SEQ ID NO: 61), and the ECD domain is at least, or about 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the peptide of KIEVMYPPPYLDNEKSNGTIIHVKGKHLCPSPLFPGPSKP (SEQ ID NO: 60). In some embodiments, T MThe domain is at least, or about 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the peptide of FWVLVVVGGVLACYSLLVTVAFIIFWV (SEQ ID NO: 62), and the ECD domain is at least, or about 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the peptide of FVPVFLPAKPTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACD (SEQ ID NO: 59). In some embodiments, T M The domain is at least, or about 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the peptide of FWVLVVVGGVLACYSLLVTVAFIIFWV (SEQ ID NO: 62), and the ECD domain is at least, or about 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to the peptide of KIEVMYPPPYLDNEKSNGTIIHVKGKHLCPSPLFPGPSKP (SEQ ID NO: 60).

[0110] In some embodiments, the transmembrane domain is linked to the intracellular domain (ICD) of a transmembrane protein, or a fragment thereof. In some embodiments, the ICD is absent. In some embodiments, the ICD is derived from the same or a different protein as the TM domain. In some embodiments, the ICD comprises an Env incorporation motif. The Env incorporation motif can be a molecule, such as a polypeptide, that helps to facilitate the incorporation of the protein into the viral envelope. Non-limiting examples of Env incorporation motifs are polypeptides that include the amino acid sequence of NRVRQGYS (SEQ ID NO: 63). This is a non-limiting example, and other peptide sequences, such as, but not limited to, GGTETSQVAPA (SEQ ID NO: 64), can be used. In some embodiments, the Env incorporation motif comprises the amino acid sequence of SEQ ID NO: 63, SEQ ID NO: 64, or a combination thereof. In some embodiments, the Env incorporation motif comprises the amino acid sequence of SEQ ID NO: 63. In some embodiments, the Env incorporation motif comprises the amino acid sequence of SEQ ID NO: 64.

[0111] In some embodiments, the target binding domain "T" is any polypeptide or polynucleotide that can be used to bind to a desired target. In some embodiments, T is any polypeptide, polynucleotide, or fragment thereof, and is expressed in acute leukemia or lymphoma but not in hematopoietic progenitor cells, including 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 in acute leukemia or lymphoma but not in hematopoietic progenitor cells; a glycosylated CD43 epitope expressed in non-hematopoietic cancer; kinase anchor protein 4 (AKAP-4); adrenergic receptor beta 3 (ADRB3); AFP; anaplastic lymphoma kinase (ALK); androgen receptor; angiopoietin-binding cell surface receptor 2 (Tie 2); autoantibody against desmoglein 1 (Dsgl); autoantibody against 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 homolog of 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-IGLll; CD200R; CD276 / B7H3; CD300 molecule-like family member f (CD300LF); CDH1-CD324; CDH6; CDH17; CDH19; chromosome X open reading frame 61 (CXORF61); claudin 6 (CLDN6); claudin 18.2 (CLD18A2 or CLDN18A.2); CMV pp65; C-MYC epitope tag; Cripto;CS1 (also known as CD2 subset 1 or CRACC or SLAMF7 or CD319 or 19A24); CSF2RA (GM-CSFR-alpha); C-type lectin domain family 12 member A (CLEC12A); C-type lectin-like molecule 1 (CLL-1 or CLECL1); Cyclin B1; Cytochrome P450 1B1 (CYP1B1); DLL3; EBV-EBNA3c; EGF-bke module-containing mucin-like hormone receptor-like 2 (EMR2); Mutated elongation factor 2 (ELF2M); Ephrin B2; Ephrin 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); Folic acid receptor alpha (FRa or FR1); Folic acid receptor beta (FRb); Follicle-stimulating hormone receptor (FSHR); Fos-related antigen 1; Fucosyl GM1; G protein-coupled receptor class C group 5 member D (GPRC5D); G protein-coupled receptor 20 (GPR20); GAD; Ganglioside G2 (GD2); Ganglioside GD3 (aNeu5Ac(2-8)aNeu5Ac(2-3)bDGalp(1-4)bDGlcp(1-1)Cer); Ganglioside GM3 (aNeu5Ac(2-3)bDClalp(1-4)bDGlcp(1-1)Cer); GD3; GFR alpha 4; Glycoprotein 100 (gp100); Glypican-3 (GPC3); Gonadotropin hormone receptor (CGHR or GR); GpA33; GpNMB; GPRC5D; Guanylate cyclase C (GCC); Heat shock protein 70-2 mutation (mut hsp70-2); Hepatitis A virus cellular receptor 1 (HAVCR1); Hexasaccharide moiety of globoH glycosphingolipid (GloboH); High molecular weight melanoma-associated antigen (HMWMAA): HIV1 envelope glycoprotein; HLA; HLA-DOA; HLA-A; HLA-A2; HLA-B; HLA-C; HLA-DM; HLA-DOB; HLA-DP;HLA-DQ; HLA-DR; HLA-G; HTLVl-Tax; Human Papillomavirus E6 (HPV E6); Human Papillomavirus E7 (HPV E7); Human Telomerase Reverse Transcriptase (hTERT); IgE; IL13Ra2; ILl lRa; Immunoglobulin Lambda-like Polypeptide 1 (IGLL1); Influenza A Hemagglutinin (HA); Insulin-like Growth Factor 1 Receptor (IGF-I Receptor); Interleukin 11 Receptor Alpha (IL-llRa); Interleukin-13 Receptor Subunit Alpha-2 (IL-13Ra2 or CD213A2); Intestinal 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 K 9 (LY6K); Low 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 Recognized by T Cells 1 (MelanA or MARTI); Melanoma-associated Antigen 1 (MAGE-A1); Melanoma Cancer Testis Antigen 1 (MAD-CT-1); Melanoma Cancer Testis Antigen 2 (MAD-CT-2); Melanoma Inhibitor of Apoptosis (ML-IAP); Mesothelin; MPL; Mucin 1 Cell Surface-associated (MUC1); N-acetylglucosaminyltransferase V (NA17); Necltin4; Neural Cell Adhesion Molecule (NCAM); NKG2D; NYBR1; O-acetyl-GD2 Ganglioside (OAcGD2); Olfactory Receptor 51E2 (OR51E2); Oncogene Fusion Protein Consisting of Breakpoint Cluster Region (BCR) and Abelson Murine Leukemia Virus Oncogene Homolog 1 (Abl) (bcr-abl); P53 Mutant; Paired Box Protein Pax-3 (PAX3); Paired Box Protein Pax-5 (PAX5); Pannexin 3 (PANX3); PDL1; P-glycoprotein; Placenta-specific 1 (PLAC1); Platelet-derived Growth Factor Receptor Beta (PDGFR-beta); Polysialic Acid; Proacrosin-binding Protein sp32 (OY-TES1);Prostase; Prostate cancer tumor antigen-1 (PCT A-1 or Galectin 8); Prostate stem cell antigen (PSCA); Prostate specific membrane antigen (PSMA); Prostatic acid phosphatase (PAP); Prostein; Protease serine 21 (Testocin or PRSS21); Proteasome (Prososome macropain) subunit beta type 9 (LMP2); PTK7; Ras G12V; 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); Spermatid 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 breakpoint 2 (SSX2); TCR gamma alternative reading frame protein (TARP); TCR-beta1 chain; TCR-beta2 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 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 virus oncogene neuroblastoma derived homolog (MYCN); Wilms tumor protein (WT1);Alternatively, it binds to X antigen family member 1A (XAGE1). In some embodiments, the targeting moiety "T" binds to CD7. In some embodiments, the target binding domain "T" binds to CD8. In some embodiments, the target binding domain "T" is an antibody. In the context of the present disclosure, "antibody" refers not only to a "complete" antibody comprising two identical heavy chains, two identical light chains, and two antigen-binding fragments, but also to antibodies of any isotype, Fab, Fv, scFv, and Fd fragments, chimeric antibodies, humanized antibodies, single-chain antibodies (scAb), single-domain antibodies (dAb), single-domain heavy-chain antibodies, single-domain light-chain antibodies, bispecific antibodies, multispecific antibodies, fragments of antibodies including but not limited to these, as well as fusion proteins comprising the antigen-binding portion of an antibody and a non-antibody protein. In some embodiments, the antibody is selected from the group comprising scFv, Fab, VHH, single-domain antibodies, etc. In some embodiments, the antibody is scFv. In some embodiments, the antibody is Fab. In some embodiments, the antibody is VHH. In some embodiments, the antibody is a single-domain antibody.;

[0112] In some embodiments, the polypeptide represented by the formula T-S1 can form a dimer when present on the surface of the viral particle. The dimer can be formed, for example, by the interaction between the stalk portions of the polypeptide molecules. For example, when the stalk portion comprises the Fc domain or a variant Fc domain provided herein, the Fc domains of the polypeptide molecules interact with each other on the surface of the virus to form a dimer. Without being bound by any particular theory, in some embodiments, the dimer may also improve specificity by increasing the affinity for the target protein via the targeting binding domain (T) as compared to a polypeptide that does not form a dimer or cannot form a dimer. Thus, in some embodiments, the viral particle comprises a dimer, which can be a homodimer or a heterodimer comprising two polypeptides having the formula T-S1. In some embodiments, the homodimer refers to two polypeptides having the formula T-S1 with exactly the same amino acid sequence. The dimer can also be formed by two polypeptides having either different targeting binding domains (T) or two different S1 moieties, for example, two different Fc domains comprising variant Fc domains. A dimer formed by two polypeptides having either different targeting binding domains or different Fc domains can be referred to as a heterodimer. In some embodiments, the heterodimer is formed by a first polypeptide having the formula T-S1 and a second polypeptide having the formula T-S2, wherein the first polypeptide has a first targeting binding domain and a first S1 polypeptide, and the second polypeptide has a second targeting binding domain and an S1 polypeptide. In some embodiments, the first and second targeting binding domains are the same. In some embodiments, the first and second targeting binding domains are different. In some embodiments, the first and second targeting binding domains bind to the same target but have different epitopes. In some embodiments, the first and second S1 polypeptides are the same. In some embodiments, the first and second S1 polypeptides are different.In some embodiments, the first and second S1 polypeptides are the same except that they have different Fc domains. The Fc domains that can be used herein can also, in some embodiments, be engineered not to form dimers.

[0113] In some embodiments, the viral particles provided herein are pseudotyped viral particles. In some embodiments, the viral particles are pseudotyped using the viral glycoproteins of a Paramyxoviridae virus. In some embodiments, the pseudotyped virus-like particles are pseudotyped using the viral glycoproteins of a virus of the genus Morbillivirus, such as measles virus. In some embodiments, the pseudotyped virus-like particles are pseudotyped using the viral glycoproteins of measles virus. In some embodiments, the pseudotyped virus-like particles are pseudotyped using the 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 the 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 Paramyxoviridae virus. In some embodiments, the Paramyxoviridae virus is a virus of the genus Morbillivirus, such as measles virus. In some embodiments, the Paramyxoviridae virus is a Henipavirus, such as Nipah virus, Cedar virus, or Hendra virus.

[0114] As provided herein, a virus can be pseudotyped with a VSV-G protein that is either wild-type or a variant thereof. Without being bound by any particular theory, a mutant VSV-G protein that can be used to pseudotype a virus (e.g., a lentivirus) containing a mutation at position 182 can be used to pseudotype the virus and transduce cells when the virus contains a targeting moiety. This mutation inhibits or reduces the affinity of VSV-G for the natural co-receptor, LDL-R. The provided mutant VSV-G protein can, in some embodiments, be used to transduce target cells and deliver a heterologous molecule to the target cells.

[0115] In some embodiments, a VSV-G protein is provided that contains a mutation at position 198 compared to SEQ ID NO:1 or at position 182 compared to SEQ ID NO:2. SEQ ID NO:1 is a full-length protein and SEQ ID NO:2 is the extracellular domain of the VSV-G protein. The 16-mer signal peptide of MKCLLYLAFLFIGVNC (SEQ ID NO:65) shown at the N-terminus of SEQ ID NO:1 is cleaved, leaving the protein of SEQ ID NO:2. Thus, the mutation can be referred to in the context of SEQ ID NO:2, but is also made in the context of SEQ ID NO:1, includes the leader sequence, and it should be understood that the position number will be 16 positions more than the position number listed in SEQ ID NO:2. In some embodiments, the mutation inhibits or decreases the binding of the VSV-G protein to the LDL receptor (LDL-R). In some embodiments, the mutation is an I182D mutation compared to SEQ ID NO:2. In some embodiments, the mutation is an I182E mutation compared to SEQ ID NO:2.

[0116] In some embodiments, a VSV-G protein is provided that contains 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 extracellular domain of the VSV-G protein. The 16-mer signal peptide MLSYLIFALVVSPILG (SEQ ID NO: 66) shown at the N-terminus of SEQ ID NO: 10 is cleaved, leaving the protein of SEQ ID NO: 11. Thus, the mutation can be referred to in the context of SEQ ID NO: 11, but is also made in the context of SEQ ID NO: 10, including the leader sequence, and it should be understood that the position number will be 16 positions more than the position listed in SEQ ID NO: 11. In some embodiments, the mutation inhibits or decreases the binding of the VSV-G protein to the LDL receptor (LDL-R). In some embodiments, the mutation is a T182D mutation compared to SEQ ID NO: 11. In some embodiments, the mutation is a T182E mutation compared to SEQ ID NO: 11.

[0117] In some embodiments, a VSV-G protein is provided that contains 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 extracellular domain of the VSV-G protein. The 16-mer signal peptide MLRLFLFCFLALGAHS (SEQ ID NO: 67) shown at the N-terminus of SEQ ID NO: 12 is cleaved, leaving the protein of SEQ ID NO: 13. Thus, the mutation can be referred to in the context of SEQ ID NO: 13, but is also made in the context of SEQ ID NO: 12, including the leader sequence, and it should be understood that the position number will be 16 positions more than the position listed in SEQ ID NO: 13. In some embodiments, the mutation inhibits or decreases the binding of the VSV-G protein to the LDL receptor (LDL-R). In some embodiments, the mutation is an A182D mutation compared to SEQ ID NO: 13. In some embodiments, the mutation is an A182E mutation compared to SEQ ID NO: 13.

[0118] In some embodiments, a VSV-G protein is provided that contains a mutation at position 203 when compared to SEQ ID NO: 14, or at position 182 when compared to SEQ ID NO: 15. SEQ ID NO: 14 is the full-length protein, and SEQ ID NO: 15 is the extracellular domain of the VSV-G protein. The 21-mer signal peptide of MKMKMVIAGLILCIGILPAIG (SEQ ID NO: 68) shown at the N-terminus of SEQ ID NO: 14 is cleaved, leaving the protein of SEQ ID NO: 15. Thus, the mutation can be referred to in the context of SEQ ID NO: 15, but is also made in the context of SEQ ID NO: 14, including the leader sequence, and it should be understood that the position number will be 21 positions more than the position listed in SEQ ID NO: 15. In some embodiments, the mutation inhibits or reduces the binding of the VSV-G protein to the LDL receptor (LDL-R). In some embodiments, the mutation is a V182D mutation when compared to SEQ ID NO: 15. In some embodiments, the mutation is a V182E mutation when compared to SEQ ID NO: 15.

[0119] In some embodiments, a VSV-G protein is provided that contains a mutation at position 199 when compared to SEQ ID NO: 16, or at position 182 when compared to SEQ ID NO: 17. SEQ ID NO: 16 is the full-length protein, and SEQ ID NO: 17 is the extracellular domain of the VSV-G protein. The 17-mer signal peptide of MTPAFILCMLLAGSSWA (SEQ ID NO: 69) shown at the N-terminus of SEQ ID NO: 16 is cleaved, leaving the protein of SEQ ID NO: 17. Thus, the mutation can be referred to in the context of SEQ ID NO: 17, but is also made in the context of SEQ ID NO: 16, including the leader sequence, and it should be understood that the position number will be 17 positions more than the position listed in SEQ ID NO: 17. In some embodiments, the mutation inhibits or reduces the binding of the VSV-G protein to the LDL receptor (LDL-R). In some embodiments, the mutation is a V182D mutation when compared to SEQ ID NO: 17. In some embodiments, the mutation is a V182E mutation when compared to SEQ ID NO: 17.

[0120] In some embodiments, a VSV-G protein is provided that contains 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 extracellular domain of the VSV-G protein. The 17-mer signal peptide of MNFLLLTFIVLPLCSHA (SEQ ID NO: 70) shown at the N-terminus of SEQ ID NO: 18 is cleaved, leaving the protein of SEQ ID NO: 19. Thus, the mutation can be referred to in the context of SEQ ID NO: 19, but is also made in the context of SEQ ID NO: 18, including the leader sequence, and it should be understood that the position number will be 17 more than the position listed in SEQ ID NO: 19. In some embodiments, the mutation inhibits or decreases the binding of the VSV-G protein to the LDL receptor (LDL-R). In some embodiments, the mutation is a V182D mutation compared to SEQ ID NO: 19. In some embodiments, the mutation is a V182E mutation compared to SEQ ID NO: 19.

[0121] In some embodiments, a VSV-G protein is provided that contains 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 extracellular domain of the VSV-G protein. The 17-mer signal peptide of MLVLYLLLSLLALGAQC (SEQ ID NO: 71) shown at the N-terminus of SEQ ID NO: 20 is cleaved, leaving the protein of SEQ ID NO: 21. Thus, the mutation can be referred to in the context of SEQ ID NO: 21, but is also made in the context of SEQ ID NO: 20, including the leader sequence, and it should be understood that the position number will be 17 more than the position listed in SEQ ID NO: 21. In some embodiments, the mutation inhibits or decreases the binding of the VSV-G protein to the LDL receptor (LDL-R). In some embodiments, the mutation is an I182D mutation compared to SEQ ID NO: 21. In some embodiments, the mutation is an I182E mutation compared to SEQ ID NO: 21.

[0122] As used herein, when a polypeptide is said to have a mutation as compared to a reference sequence, such comparison is based on an alignment using, for example, BlastP or ClustalW or ClutalOmega alignment software using default parameters. For example, position 182 can be found in SEQ ID NO:2 and when compared to other strains shown in FIG. 3. FIG. 3 shows a clustal alignment of the wild-type sequences of the extracellular domains of various strains of the VSV-G protein. The residues in bold and underlined are the residues that align with position 182 of SEQ ID NO:2 for the various strains. SEQ ID NO:2 refers to the extracellular domain of the VSV-G protein of the Indiana strain. SEQ ID NO:11 refers to the extracellular domain of the VSV-G protein of the New Jersey strain. SEQ ID NO:13 refers to the extracellular domain of the VSV-G protein of the Marraba strain. SEQ ID NO:15 refers to the extracellular domain 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 extracellular domain of the VSV-G protein of the Cocal strain. SEQ ID NO:21 refers to the extracellular domain of the VSV-G protein of the Morreton strain. Thus, the residues that align with residue 182 when compared to SEQ ID NO:2 can also be mutated as provided herein.

[0123] In some embodiments, the mutation at position 182 when compared to SEQ ID NO:2 is not alanine. In some embodiments, the mutation at position 182 when compared to SEQ ID NO:2 is not valine.

[0124] In some embodiments, the mutation at position 182 compared to SEQ ID NO: 2 is I182S, I182H, I182T, I182Q, or I182N. In some embodiments, the mutation at position 182 compared to SEQ ID NO: 11 is T182S, T182H, T182Q, or T182N. In some embodiments, the mutation at position 182 compared to SEQ ID NO: 13 is A182S, A182H, A182T, A182Q, or A182N. In some embodiments, the mutation at position 182 compared to SEQ ID NO: 15 is V182S, V182H, V182T, V182Q, or V182N. In some embodiments, the mutation at position 182 compared to SEQ ID NO: 17 is V182S, V182H, V182T, V182Q, or V182N. In some embodiments, the mutation at position 182 compared to SEQ ID NO: 19 is V182S, V182H, V182T, V182Q, or V182N. In some embodiments, the mutation at position 182 compared to SEQ ID NO: 21 is I182S, I182H, I182T, I182Q, or I182N. In some embodiments, the mutation at position 182 is not a hydrophobic residue. In some embodiments, the mutation at position 182 is a charged residue. In some embodiments, the mutation at position 182 is not a negatively charged residue.

[0125] The mutations can be described with reference to SEQ ID NO: 1 or SEQ ID NO: 2, which is the VSV-G protein from the Indiana strain, but the mutations can also be used in other strains of the VSV-G protein. For example, the mutations can be made in the New Jersey strain of VSV-G, the Marraba strain of VSV-G, the Carajas strain of VSV-G, the Alagoa strain of VSV-G, the Cocal strain of VSV-G, or the Morreton strain of VSV-G. In some embodiments, each sequence is as provided herein. These examples can be found, for example, in US Patent Application Publication No. 20200216502, which is incorporated herein by reference in its entirety. For example, the wild-type full-length or extracellular domain 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 extracellular domain of the Marraba strain of VSV-G is SEQ ID NO: 12 and SEQ ID NO: 13, respectively, the wild-type full-length or extracellular domain of the Carajas strain of VSV-G is SEQ ID NO: 14 and SEQ ID NO: 15, respectively, the wild-type full-length or extracellular domain of the Alagoa strain of VSV-G is SEQ ID NO: 16 and SEQ ID NO: 17, respectively, the wild-type full-length or extracellular domain of the Cocal strain of VSV-G is SEQ ID NO: 18 and SEQ ID NO: 19, respectively, or the wild-type full-length or extracellular domain of the Morreton strain of VSV-G is SEQ ID NO: 20 and SEQ ID NO: 21, respectively.

[0126] The VSV-G protein containing a mutation at position 182 compared to SEQ ID NO: 2 can also include other mutations such as those described in US Patent Application Publication No. 20200216502, which is incorporated herein by reference in its entirety. For example, the VSV-G protein can include mutations at positions corresponding to positions 8, 47, 209, and / or 354 of SEQ ID NO: 2.

[0127] In some embodiments, the 8-position substitution is by any amino acid different from the amino acid shown at that position in the sequence of SEQ ID NO: 2, except for Y. In some embodiments, the 209-position substitution is by any amino acid different from the amino acid shown at that position in the sequence of SEQ ID NO: 2, except for H. In some embodiments, the 47-position substitution is by any amino acid different from the amino acid shown at that position in SEQ ID NO: 2, except for K or R. In some embodiments, the 354-position substitution is by any amino acid different from the amino acid shown at that position in the sequence of SEQ ID NO: 2, except for K or R.

[0128] In some embodiments, the substitution is at the 47-position or the 354-position, or both the 47-position and the 354-position, and is substituted by A, G, F, or Q. In some embodiments, the substitution is A or Q.

[0129] In some embodiments, the 8-position substitution is alanine, i.e., H8A.

[0130] In some embodiments, the 47-position substitution is Q or N, i.e., K47Q or K47N.

[0131] In some embodiments, the protein contains a mutation (substitution) at the 10-position. In some embodiments, the substitution / mutation is Q10A, Q10R, or Q10K.

[0132] In some embodiments, a protein containing a mutation at position 182 compared to SEQ ID NO: 2 contains, at position 182, 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 mutation compared to SEQ ID NO: 2 (or SEQ ID NO: 1 if using the full-length protein). In some embodiments, the polypeptide contains the mutation I182D or I182E. In some embodiments, the VSV-G protein contains the mutation I182S, I182H, I182T, I182Q, or I182N.

[0133] In some embodiments, a protein containing a mutation at position 182 compared to SEQ ID NO: 11 contains, at position 182, 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 mutation compared to SEQ ID NO: 11 (or SEQ ID NO: 10 if using the full-length protein). In some embodiments, the polypeptide contains the mutation T182D or T182E. In some embodiments, the VSV-G protein contains the mutation T182S, T182H, T182Q, or T182N.

[0134] In some embodiments, a protein comprising a mutation at position 182 as compared to SEQ ID NO: 13 comprises, at position 182, 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 mutation as compared to SEQ ID NO: 13 (or SEQ ID NO: 12 if using the full-length protein). In some embodiments, the polypeptide comprises a mutation of A182D or A182E. In some embodiments, the VSV-G protein comprises a mutation of A182S, A182H, A182T, A182Q, or A182N.

[0135] In some embodiments, a protein comprising a mutation at position 182 as compared to SEQ ID NO: 15 comprises, at position 182, 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 mutation as compared to SEQ ID NO: 15 (or SEQ ID NO: 14 if using the full-length protein). In some embodiments, the polypeptide comprises a mutation of V182D or V182E. In some embodiments, the VSV-G protein comprises a mutation of V182S, V182H, V182T, V182Q, or V182N.

[0136] In some embodiments, a protein comprising a mutation at position 182 as compared to SEQ ID NO: 17 comprises, at position 182, 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 mutation as compared to SEQ ID NO: 17 (or SEQ ID NO: 16 if using the full-length protein). In some embodiments, the polypeptide comprises a V182D or V182E mutation. In some embodiments, the VSV-G protein comprises a V182S, V182H, V182T, V182Q, or V182N mutation.

[0137] In some embodiments, a protein comprising a mutation at position 182 as compared to SEQ ID NO: 19 comprises, at position 182, 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 mutation as compared to SEQ ID NO: 19 (or SEQ ID NO: 18 if using the full-length protein). In some embodiments, the polypeptide comprises a V182D or V182E mutation. In some embodiments, the VSV-G protein comprises a V182S, V182H, V182T, V182Q, or V182N mutation.

[0138] In some embodiments, a protein containing a mutation at position 182 as compared to SEQ ID NO: 21 contains, at position 182, 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 mutation as compared to SEQ ID NO: 21 (or SEQ ID NO: 20 if using the full-length protein). In some embodiments, the polypeptide contains a mutation of I182D or I182E. In some embodiments, the VSV-G protein contains a mutation of I182S, I182H, I182T, I182Q, or I182N.

[0139] Viral glycoprotein The mutant VSV-G protein can be used, for example, but not limited to, pseudotyping of viruses such as lentiviruses. Thus, in some embodiments, virus particles comprising the mutant VSV-G protein provided herein are provided. In some embodiments, the virus particle comprises a VSV-G protein containing a mutation at position 198 as compared to SEQ ID NO: 1. In some embodiments, a protein containing a mutation at position 182 as compared to SEQ ID NO: 2 contains, at position 182, 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 mutation as compared to SEQ ID NO: 2 (or SEQ ID NO: 1 if using the full-length protein). In some embodiments, the polypeptide contains a mutation of I182D or I182E as compared to SEQ ID NO: 2. In some embodiments, the VSV-G protein contains a mutation of I182S, I182H, I182T, I182Q, or I182N.

[0140] 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, at position 182, a mutation that 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 the mutation compared to SEQ ID NO: 11 (or SEQ ID NO: 10 if the full-length protein is being 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.

[0141] 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, at position 182, a mutation that 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 the mutation compared to SEQ ID NO: 13 (or SEQ ID NO: 12 if the full-length protein is being 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.

[0142] 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, a protein comprising a mutation at position 182 compared to SEQ ID NO: 15 comprises, at position 182, 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 mutations compared to SEQ ID NO: 15 (or SEQ ID NO: 14 if using the full-length protein). In some embodiments, the polypeptide comprises a V182D or V182E mutation compared to SEQ ID NO: 15. In some embodiments, the VSV-G protein comprises a V182S, V182H, V182T, V182Q, or V182N mutation.

[0143] 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, a protein comprising a mutation at position 182 compared to SEQ ID NO: 17 comprises, at position 182, 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 mutations compared to SEQ ID NO: 17 (or SEQ ID NO: 16 if using the full-length protein). In some embodiments, the polypeptide comprises a V182D or V182E mutation compared to SEQ ID NO: 17. In some embodiments, the VSV-G protein comprises a V182S, V182H, V182T, V182Q, or V182N mutation.

[0144] In some embodiments, the viral particle comprises a VSV-G protein that contains a mutation at position 199 compared to SEQ ID NO: 18. In some embodiments, the protein that contains a mutation at position 182 compared to SEQ ID NO: 19 contains, at position 182, 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 mutations compared to SEQ ID NO: 19 (or SEQ ID NO: 18 if the full-length protein is used). In some embodiments, the polypeptide contains a V182D or V182E mutation compared to SEQ ID NO: 19. In some embodiments, the VSV-G protein contains a V182S, V182H, V182T, V182Q, or V182N mutation.

[0145] In some embodiments, the viral particle comprises a VSV-G protein that contains a mutation at position 199 compared to SEQ ID NO: 20. In some embodiments, the protein that contains a mutation at position 182 compared to SEQ ID NO: 21 contains, at position 182, 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 mutations compared to SEQ ID NO: 21 (or SEQ ID NO: 20 if the full-length protein is used). In some embodiments, the polypeptide contains an I182D or I182E mutation compared to SEQ ID NO: 21. In some embodiments, the VSV-G protein contains an I182S, I182H, I182T, I182Q, or I182N mutation.

[0146] 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 is T214 corresponding to position 214 of SEQ ID NO: 2. In some embodiments, the residue corresponding to position 352 of the SEQ ID NO is T352. In some embodiments, the VSV-G protein comprises a mutation corresponding to the T214N mutation as compared to SEQ ID NO: 2. In some embodiments, the VSV-G protein comprises a mutation corresponding to the T352A mutation as compared to SEQ ID NO: 2. In some embodiments, the VSV-G protein comprises the T214N and T352A mutations as compared to SEQ ID NO: 2. These mutations may be combined with any other mutations provided herein. In some embodiments, the T214N and / or T352A mutations are combined with the I182E or I182D mutations. In some embodiments, the VSV-G protein comprises the amino acid sequences of SEQ ID NO: 22 and SEQ ID NO: 23, which are the combinations of I182D or I182E with the T214N and T352A mutations, respectively. This sequence is also shown below together with a leader sequence that is removed during protein processing. VSV-G protein_Mutations of I196D, T230N and T368A (including leader sequence and adjusted numbering) MKCLLYLAFLFIGVNCKFTIVFPHNQKGNWKNVPSNYHYCPSSSDLNWHNDLIGTALQVKMPKSHKAIQADGWMCHASKWVTTCDFRWYGPKYITHSIRSFTPSVEQCKESIEQTKQGTWLNPGFPPQSCGYATVTDAEAVIVQVTPHHVLVDEYTGEWVDSQFINGKCSNYICPTVHNSTTWHSDYKVKGLCDSNLDSMDITFFSEDGELSSLGKEGTGFRSNYFAYENGGKACKMQYCKHWGVRLPSGVWFEMADKDLFAAARFPECPEGSSISAPSQTSVDVSLIQDVERILDYSLCQETWSKIRAGLPISPVDLSYLAPKNPGTGPAFTIINGTLKYFETRYIRVDIAAPILSRMVGMISGTTAERELWDDWAPYEDVEIGPNGVLRTSSGYKFPLYMIGHGMLDSDLHLSSKAQVFEHPHIQDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCIKLKHTKKRQIYTDIEMNRLGK(SEQ ID NO:24) VSV-G protein_I182D, T214N and T352A mutations (without leader sequence) KFTIVFPHNQKGNWKNVPSNYHYCPSSSDLNWHNDLIGTALQVKMPKSHKAIQADGWMCHASKWVTTCDFRWYGPKYITHSIRSFTPSVEQCKESIEQTKQGTWLNPGFPPQSCGYATVTDAEAVIVQVTPHHVLVDEYTGEWVDSQFINGKCSNYICPTVHNSTTWHSDYKVKGLCDSNLDSMDITFFSEDGELSSLGKEGTGFRSNYFAYENGGKACKMQYCKHWGVRLPSGVWFEMADKDLFAAARFPECPEGSSISAPSQTSVDVSLIQDVERILDYSLCQETWSKIRAGLPISPVDLSYLAPKNPGTGPAFTIINGTLKYFETRYIRVDIAAPILSRMVGMISGTTAERELWDDWAPYEDVEIGPNGVLRTSSGYKFPLYMIGHGMLDSDLHLSSKAQVFEHPHIQDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCIKLKHTKKRQIYTDIEMNRLGK (SEQ ID NO: 22) VSV-G protein (including leader sequence and modified numbering) containing the I196D, T230N and T368A mutations MKCLLYLAFLFIGVNCKFTIVFPHNQKGNWKNVPSNYHYCPSSSDLNWHNDLIGTALQVKMPKSHKAIQADGWMCHASKWVTTCDFRWYGPKYITHSIRSFTPSVEQCKESIEQTKQGTWLNPGFPPQSCGYATVTDAEAVIVQVTPHHVLVDEYTGEWVDSQFINGKCSNYICPTVHNSTTWHSDYKVKGLCDSNLESMDITFFSEDGELSSLGKEGTGFRSNYFAYENGGKACKMQYCKHWGVRLPSGVWFEMADKDLFAAARFPECPEGSSISAPSQTSVDVSLIQDVERILDYSLCQETWSKIRAGLPISPVDLSYLAPKNPGTGPAFTIINGTLKYFETRYIRVDIAAPILSRMVGMISGTTAERELWDDWAPYEDVEIGPNGVLRTSSGYKFPLYMIGHGMLDSDLHLSSKAQVFEHPHIQDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCIKLKHTKKRQIYTDIEMNRLGK(SEQ ID NO:25) VSV-G protein (excluding the leader sequence) containing the mutations I182E, T214N and T352A KFTIVFPHNQKGNWKNVPSNYHYCPSSSDLNWHNDLIGTALQVKMPKSHKAIQADGWMCHASKWVTTCDFRWYGPKYITHSIRSFTPSVEQCKESIEQTKQGTWLNPGFPPQSCGYATVTDAEAVIVQVTPHHVLVDEYTGEWVDSQFINGKCSNYICPTVHNSTTWHSDYKVKGLCDSNLESMDITFFSEDGELSSLGKEGTGFRSNYFAYENGGKACKMQYCKHWGVRLPSGVWFEMADKDLFAAARFPECPEGSSISAPSQTSVDVSLIQDVERILDYSLCQETWSKIRAGLPISPVDLSYLAPKNPGTGPAFTIINGTLKYFETRYIRVDIAAPILSRMVGMISGTTAERELWDDWAPYEDVEIGPNGVLRTSSGYKFPLYMIGHGMLDSDLHLSSKAQVFEHPHIQDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCIKLKHTKKRQIYTDIEMNRLGK(SEQ ID NO: 23)

[0147] Other strains of the VSV-G protein described in this specification may also contain mutations corresponding to T214N and / or T352A of SEQ ID NO: 2, as well as the mutations shown in SEQ ID NO: 22 and SEQ ID NO: 23.

[0148] In some embodiments, the composition comprises the mutations described in Hwang et al., Gene Ther 2013 Aug;20(8):807-15. (Epub 2013 Jan 31), which is hereby incorporated by reference in its entirety. For example, the mutations can be at positions 230, 368, 66, and / or 162 corresponding to SEQ ID NO: 1. These positions are 16 positions less compared to 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 mutations T230N and T368A. In some embodiments, the VSV-G polypeptide comprises K66T, S162T, T230N, and T368A. These positions correspond to the positions in the full-length protein (SEQ ID NO: 1). In some embodiments, the VSV-G protein comprises the mutation T230N, the mutation T368A, the mutation K66T, the mutation S162T, or any combination thereof. In some embodiments, the VSV-G protein further comprises one or more mutations, such as those described in U.S. Patent Application Publication No. 20200216502, in addition to the mutation corresponding to position 182 of SEQ ID NO: 2, which is hereby incorporated 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.

[0149] In some embodiments, the 8-position substitution is by any amino acid different from the amino acid shown at that position in the sequence of SEQ ID NO:2, except for Y. In some embodiments, the 209-position substitution is by any amino acid different from the amino acid shown at that position in the sequence of SEQ ID NO:2, except for H. In some embodiments, the 47-position substitution is by any amino acid different from the amino acid shown at that position in the sequence of SEQ ID NO:2, except for K or R. In some embodiments, the 354-position substitution is by any amino acid different from the amino acid shown at that position in the sequence of SEQ ID NO:2, except for K or R. In some embodiments, the substitution is at the 47-position or the 354-position, or both the 47-position and the 354-position, and is substituted by A, G, F, or Q. In some embodiments, the substitution is A or Q. In some embodiments, the 8-position substitution is alanine, i.e., H8A. In some embodiments, the 47-position substitution is Q or N, i.e., K47Q or K47N. In some embodiments, the protein contains a mutation (substitution) at position 10. In some embodiments, the substitution / mutation is Q10A, Q10R, or Q10K.

[0150] Furthermore, in some embodiments, instead of the VSV-G protein or a variant thereof, the virus can be pseudotyped with other viral structural proteins.

[0151] For example, virus particles can be pseudotyped with the Spring viremia of carp virus G (SVCV-G) protein and transduce cells when the virus contains a targeting moiety. The provided Spring viremia of carp virus G protein can, in some embodiments, be used to transduce target cells and deliver heterologous molecules to the target cells. In some embodiments, a Spring viremia of carp virus G protein comprising SEQ ID NO: 52 is provided. SEQ ID NO: 52 is a full-length protein, and SEQ ID NO: 53 is the extracellular domain of the Spring viremia of carp virus G protein with the N-terminal signal peptide removed. Thus, in some embodiments, this protein comprises the amino acid sequence of SEQ ID NO: 53. The Spring viremia of carp virus G protein can be used, for example, but not limited to, in the pseudotyping of viruses such as lentiviruses. Thus, in some embodiments, virus particles comprising the Spring viremia of carp virus G protein provided herein are provided. In some embodiments, the virus particles comprise a Spring viremia of carp virus G protein comprising a 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%, or 99% identical to SEQ ID NO: 52 or SEQ ID NO: 53.

[0152] Sequence - G of Spring viremia of carp virus (including SEQ ID NO: 52 - leader sequence) MSIISYIAFLLLIDSNLGIPIFVPSGRNISWQPVIQPFDYQCPIHGNLPNTMGLSATKLTIKSPSVFSTDKVSGWICHAAEWKTTCDYRWYGPQYITHSIHPISPTIDECRRIIQRIASGTDEDLGFPPQSCGWASVTTVSNTNYRVVPHSVHLEPYGGHWIDHEFNGGECREKVCEMKGNHSIWITEETVQHECAKHIEEVEGIMYGNVPRGDVMYANNFIIDRHHRVYRFGGSCQMKFCNKDGIKFARGDWVEKTAGTLTTIHDNVPKCVDGTLVSGHRPGLDLIDTVFNLENVVEYTLCEGTKRKINKQEKLTSVDLSYLAPRIGGFGSVFRVRNGTLERGSTTYIRIEVEGPIVDSLNGTDPRTNASRVFWDDWELDGNIYQGFNGVYKGKDGKIHIPLNMIESGIIDDELQHAFQADIIPHPHYDDDEIREDDIFFDNTGENGNPVDAVVEWVSGWGTSLKFFGMTLVALILIFLLIRCCVACTYLMKRSKRPATESHEMRSLV

[0153] Sequence of Infectious Pancreatic Necrosis Virus - G (excluding the leader sequence, SEQ ID NO: 53): IPIFVPSGRNISWQPVIQPFDYQCPIHGNLPNTMGLSATKLTIKSPSVFSTDKVSGWICHAAEWKTTCDYRWYGPQYITHSIHPISPTIDECRRIIQRIASGTDEDLGFPPQSCGWASVTTVSNTNYRVVPHSVHLEPYGGHWIDHEFNGGECREKVCEMKGNHSIWITEETVQHECAKHIEEVEGIMYGNVPRGDVMYANNFIIDRHHRVYRFGGSCQMKFCNKDGIKFARGDWVEKTAGTLTTIHDNVPKCVDGTLVSGHRPGLDLIDTVFNLENVVEYTLCEGTKRKINKQEKLTSVDLSYLAPRIGGFGSVFRVRNGTLERGSTTYIRIEVEGPIVDSLNGTDPRTNASRVFWDDWELDGNIYQGFNGVYKGKDGKIHIPLNMIESGIIDDELQHAFQADIIPHPHYDDDEIREDDIFFDNTGENGNPVDAVVEWVSGWGTSLKFFGMTLVALILIFLLIRCCVACTYLMKRSKRPATESHEMRSLV

[0154] Targeted part In some embodiments, the viral particle comprises a targeting moiety having the formula T-S1, wherein T is a target binding domain and S1 is a stalk portion. The targeting moiety can be used to target a viral particle comprising a mutant VSV-G protein or an SVCV-G protein to a cell that expresses a target to which the targeting moiety binds. In some embodiments, the target binding domain is an antibody, scFv antibody, antigen binding domain, ankyrin repeat (e.g., DARPIN), VHH domain antibody, nanobody, single domain antibody, FN3 domain, or any combination thereof. The target binding domain can be attached to the viral surface via a variant Fc protein (e.g., L1-Fc-L2-X1) provided herein or via a flexible polypeptide (e.g., L3-X1) provided herein. In some embodiments, the targeting moiety is bound (fused or linked) to the envelope glycoprotein G or H of a Paramyxoviridae virus 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 can be bound (fused or linked) to the glycoprotein of a Rhabdoviridae virus such as Vesicular stomatitis New Jersey virus, Vesicular stomatitis Indiana virus, Vesicular stomatitis Araguaia 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, Partitivirus, or Spring viraemia 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 bound to the glycoprotein of a Filoviridae virus such as Ebola virus or the glycoprotein of an Arenaviridae virus such as Machupo virus.

[0155] In some embodiments, the target binding domain is an scFv. In some embodiments, the target binding domain is a single domain antibody. In some embodiments, the target binding domain is a VHH.

[0156] In some embodiments, the targeting moiety is a glycosylated CD43 epitope that is expressed in acute leukemia or lymphoma but not in hematopoietic progenitor cells, expressed in 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 (Tie 2), autoantibody to desmoglein 1 (Dsgl), autoantibody to desmoglein 3 (Dsg3), B7H3 (CD276), biotin, bone marrow stromal cell antigen 2 (BST2), BST1 / CD157, cancer / testis antigen 1 (NY-ESO-1), cancer / testis antigen 2 (LAGE-la), carbonic anhydrase IX (CA1X), carcinoembryonic antigen (CEA), CCCTC-binding factor (zinc finger protein)-like (BORIS or a homolog of the imprinting site regulator), CCR4, CD5, CD19, CD20, CD22, CD24, CD30, CD32 (FCGR2A), CD33, CD34, CD38, CD44v6, CD72, CD79a, CD79b, CD97, CD99, CD123, CD171, CD179a, CD179b-IGLll, CD200R, CD276 / B7H3, CD300 molecule-like family member f (CD300LF), CDH1-CD324, CDH6, CDH17, CDH19, chromosome X open reading frame 61 (CXORF61), claudin 6 (CLDN6), claudin 18.2 (CLD18A2 or CLDN18A. 2), CMV pp65, 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 1B1 (CYP1B1); DLL3; EBV-EBNA3c; EGF-bke module-containing mucin-like hormone receptor-like 2 (EMR2); Mutated elongation factor 2 (ELF2M); Ephrin B2; Ephrin 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); Folic acid receptor alpha (Fra or FR1); Folic acid receptor beta (FRb); Follicle-stimulating hormone receptor (FSHR); Fos-related antigen 1; Fucosyl GM1; G protein-coupled receptor class C group 5 member D (GPRC5D); G protein-coupled receptor 20 (GPR20); GAD; Ganglioside G2 (GD2); Ganglioside GD3 (aNeu5Ac(2-8)aNeu5Ac(2-3)bDGalp(1-4)bDGlcp(1-1)Cer); Ganglioside GM3 (aNeu5Ac(2-3)bDClalp(1-4)bDGlcp(1-1)Cer); GD3; GFR alpha 4; Glycoprotein 100 (gp100); Glypican-3 (GPC3); Gonadotropin hormone receptor (CGHR or GR); GpA33; GpNMB; GPRC5D; Guanylate cyclase C (GCC); Heat shock protein 70-2 mutation (mut hsp70-2); Hepatitis A virus cell receptor 1 (HAVCR1); Hexasaccharide moiety of globoH glycosphingolipid (GloboH); High molecular weight melanoma-associated antigen (HMWMAA): HIV1 envelope glycoprotein; HLA; HLA-DOA; HLA-A; HLA-A2; HLA-B; HLA-C; HLA-DM; HLA-DOB; HLA-DP; HLA-DQ; HLA-DR; HLA-G; HTLV1-Tax; Human papillomavirus E6 (HPV E6); Human papillomavirus E7 (HPV E7); Human telomerase reverse transcriptase (hTERT); IgE; IL13Ra2; IL11Ra;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 K 9 (LY6K); Low-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 recognized by T cells 1 (MelanA or MARTI); Melanoma-associated antigen 1 (MAGE-A1); Melanoma cancer testis antigen 1 (MAD-CT-1); Melanoma cancer testis antigen 2 (MAD-CT-2); Melanoma apoptosis inhibitor (ML-IAP); Mesothelin; MPL; Mucin 1 cell surface-associated (MUC1); N-acetylglucosaminyltransferase V (NA17); Necltin 4; Neural cell adhesion molecule (NCAM); NKG2D; NYBR1; O-acetyl-GD2 ganglioside (OAcGD2); Olfactory receptor 51E2 (OR51E2); Oncogene fusion protein consisting of breakpoint cluster region (BCR) and Abelson murine leukemia virus oncogene homolog 1 (Abl) (bcr-abl); P53 mutant; Paired box protein Pax-3 (PAX3); Paired box protein Pax-5 (PAX5); Pannexin 3 (PANX3); PDL1; P-glycoprotein; Placenta-specific 1 (PLAC1); Platelet-derived growth factor receptor beta (PDGFR-beta); Polysialic acid; Proacrosin-binding protein sp32 (OY-TES1); Prostate; Prostate cancer tumor antigen-1 (PCT A-1 or galectin 8); Prostate stem cell antigen (PSCA); Prostate-specific membrane antigen (PSMA); Prostate acid phosphatase (PAP); Prostain;Protease serine 21 (testisin or PRSS21); proteasome (prososome macropain) subunit beta type 9 (LMP2); PTK7; Ras G12V; 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 protein 17 (SPA17); squamous cell carcinoma antigen recognized by T cells 3 (SART3); stage-specific embryonic antigen 4 (SSEA-4); STEAP1; survivin; synovial sarcoma X breakpoint 2 (SSX2); TCR gamma alternative reading frame protein (TARP); TCR-beta1 chain; TCR-beta2 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 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 virus oncogene neuroblastoma-derived homolog (MYCN); Wilms tumor protein (WT1); or binds to X antigen family member 1A (XAGE1). In some embodiments, the targeting moiety binds to CD7. In some embodiments, the targeting moiety binds to CD8.;

[0157] 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 a T cell, B cell, NK cell, dendritic cell, neutrophil, macrophage, cancer cell, or an immune cell such as, for example, CD3+ T cell, CD4+ T cell, CD7+ T cell, CD8+ T cell, CD19+ B cell, CD19+ cancer cell, CD20+ B cell, CD20+ cancer cell, CD30+ lung epithelial cell, CD34+ hematopoietic stem cell, CD105+ endothelial cell, CD105+ hematopoietic stem cell, CD117+ hematopoietic stem cell, CD133+ cancer cell, EpCAM+ cancer cell, GluA2+ neuron, GluA4+ neuron, hematopoietic stem cell, hepatocyte, Her2 / Neu+ cancer cell, NKG2D+ natural killer cell, SLC1A3+ astrocyte, SLC7A10+ adipocyte, etc., but is not limited thereto. In some embodiments, the cell is a T cell. In some embodiments, the cell is a B cell. In some embodiments, the cell is a CD7+ T cell and / or a CD8+ T cell.

[0158] CD7-binding polypeptide In some embodiments, the targeting moiety (e.g., a polypeptide) binds to CD7.

[0159] 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: 29): MAGPPRLLLLPLLLALARGLPGALAAQEVQQSPHCTTVPVGASVNITCSTSGGLRGIYLRQLGPQPQDIIYYEDGVVPTTDRRFRGRIDFSGSQDNLTITMHRLQLSDTGTYTCQAITEVNVYGSGTLVLVTEEQSQGWHRCSDAPPRASALPAPPTGSALPDPQTASALPDPPAASALPAALAVISFLLGLGLGVACVLARTQIKKLCSWRDKNSAACVVYEDMSHSRCNTLSSPNQYQ (SEQ ID NO: 29).

[0160] In some embodiments, the CD7 to which the polypeptide binds is expressed on the surface of the cell. In some embodiments, the cell is an immune cell. In some embodiments, the immune cell is a CD7+ T cell, CD4+ T cell, CD8+ T cell, NK cell, alpha-beta T cell, gamma-delta T cell, lymphoid progenitor cell, hematopoietic stem cell, myeloid cell, monocyte, macrophage, central memory T cell, effector memory T cell, stem cell-like memory T cell, naive T cell, activated T cell, regulatory T cell (TReg), terminally differentiated effector memory T cell (TEMRA), resident memory T cell (TRM) or CD8+ CCR7+ T cell.

[0161] In some embodiments, the antibody comprises an Fc region. The Fc region can bind 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 described herein, e.g., SEQ ID NO: 26, 27, or 28 provided herein or a variant thereof.

[0162] In some embodiments, a polypeptide (e.g., a CD7-binding polypeptide) is provided herein. In some embodiments, an antibody (e.g., an anti-CD7 antibody) is provided herein. 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 is not isolated from a human subject.

[0163] In some embodiments, an antibody or an antigen-binding fragment thereof is provided, and the antibody or antibody fragment comprises a peptide selected from the following table showing CDRs based on Kabat numbering. [Table 1]

[0164] In some embodiments, the polypeptide, antibody or an antibody-binding fragment thereof comprises the CDRs of the heavy or light chain provided by the above table. In some embodiments, the polypeptide, antibody or an antibody-binding fragment thereof comprises the CDRs of the heavy or light chain provided by the above table and binds to non-human primate CD7. In some embodiments, the polypeptide, antibody or an antibody-binding fragment thereof comprises the CDRs of the heavy or light chain provided by the above table and binds to human CD7. In some embodiments, the polypeptide, antibody or an antibody-binding fragment thereof comprises a light chain CDR having a sequence selected from SEQ ID NOs: 33-35. In some embodiments, the polypeptide, antibody or an antibody-binding fragment thereof comprises a light chain CDR having the sequence of SEQ ID NO: 33. In some embodiments, the polypeptide, antibody or an antibody-binding fragment thereof comprises a light chain CDR having the sequence of SEQ ID NO: 34. In some embodiments, the polypeptide, antibody or an antibody-binding fragment thereof comprises a light chain CDR having the sequence of SEQ ID NO: 35. In some embodiments, the polypeptide, antibody or an antibody-binding fragment thereof comprises a heavy chain CDR having a sequence selected from SEQ ID NOs: 30-32. In some embodiments, the polypeptide, antibody or an antibody-binding fragment thereof comprises a heavy chain CDR having the sequence of SEQ ID NO: 30. In some embodiments, the polypeptide, antibody or an antibody-binding fragment thereof comprises a heavy chain CDR having the sequence of SEQ ID NO: 31. In some embodiments, the polypeptide, antibody or an antibody-binding fragment thereof comprises a heavy chain CDR having the sequence of SEQ ID NO: 32. The CDRs referred to in the embodiments throughout this specification are interchangeable with CDRs characterized by different formats such as Chothia and IMGT.

[0165] In some embodiments, the polypeptide, antibody or antigen-binding fragment thereof comprises a light chain variable region having LCDR1, LCDR2 and LCDR3, wherein LCDR1 has the sequence of SEQ ID NO: 33, LCDR2 has the sequence of SEQ ID NO: 34, and LCDR3 has the sequence of SEQ ID NO: 35.

[0166] In some embodiments, the polypeptide, antibody or antigen-binding fragment thereof comprises a heavy chain variable region having HCDR1, HCDR2 and HCDR3, wherein HCDR1 has the sequence of SEQ ID NO: 30, HCDR2 has the sequence of SEQ ID NO: 31, and HCDR3 has the sequence of SEQ ID NO: 32.

[0167] In some embodiments, the polypeptide, antibody or antigen-binding fragment thereof comprises (i) a light chain having any one of the aforementioned combinations of LCDR1, LCDR2, and LCDR3 sequences; and (ii) a heavy chain having any one of the aforementioned combinations of HCDR1, HCDR2, and HCDR3 sequences.

[0168] The different CDR motifs can be combined in any combination, including those not shown in the above table. For example, the following embodiments are provided as non-limiting examples of such combinations.

[0169] 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: 33; the light chain CDR2 has the amino acid sequence of SEQ ID NO: 34; the light chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 35, 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: 30; the heavy chain CDR2 sequence has the amino acid sequence of SEQ ID NO: 31; the heavy chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 32; or a variant of any of the foregoing.

[0170] In the foregoing paragraphs, reference may be made to CDRs in the Kabat system, but equivalent CDR sequences may be used from the IMGT and Chothia notations.

[0171] In some embodiments, the light chain variable region CDR1 is replaced with any of the other light chain CDR1 sequences. In some embodiments, the light chain variable region CDR2 is replaced with any of the other light chain CDR2 sequences. In some embodiments, the light chain variable region CDR3 is replaced with any of the other light chain CDR3 sequences. In some embodiments, the heavy chain variable region CDR1 is replaced with any of the other heavy chain CDR1 sequences. In some embodiments, the heavy chain variable region CDR2 is replaced with any of the other heavy chain CDR2 sequences. In some embodiments, the heavy chain variable region CDR3 is replaced with any of the other heavy chain CDR3 sequences.

[0172] In some embodiments, the polypeptide comprises a heavy chain variable region peptide having one of the following sequences, or a variant thereof: [Table 2]

[0173] In some embodiments, the polypeptide comprises a light chain variable region peptide having one of the following sequences, or a variant thereof: [Table 3]

[0174] In some embodiments, the polypeptide, antibody, or antigen-binding fragment thereof comprises the V H peptide of SEQ ID NO: 36. In some embodiments, the polypeptide, antibody, or antigen-binding fragment thereof comprises the V L peptide of SEQ ID NO: 37. In some embodiments, the polypeptide, antibody, or antigen-binding fragment thereof comprises the V H peptide and the V L peptide, and the VH The peptide comprises the sequence of SEQ ID NO: 36 or a variant thereof; V L The peptide comprises the sequence of SEQ ID NO: 37 or a variant thereof. In some embodiments, the polypeptide, antibody or antigen-binding fragment thereof binds to non-human primate CD7. V H The peptide and V L Comprises the peptide, V H The peptide comprises the sequence of SEQ ID NO: 36 or a variant thereof; V L The peptide comprises the sequence of SEQ ID NO: 37 or a variant thereof, and the polypeptide, antibody or antigen-binding fragment thereof binds to human CD7. In some embodiments, the polypeptide, antibody, or antigen-binding fragment thereof V H The peptide and V L Comprises the peptide, V H The peptide comprises the sequence of SEQ ID NO: 36 or a variant thereof; V L The peptide comprises the sequence of SEQ ID NO: 37 or a variant thereof, and the polypeptide, antibody or antigen-binding fragment thereof binds to human CD7. In some embodiments, V H The peptide comprises the sequence of SEQ ID NO: 36; V L The peptide comprises the sequence of SEQ ID NO: 37.

[0175] V H The sequence and V L The sequence is V H The region and V L It can be any format including, but not limited to, an scFv format in which the regions are linked by a peptide linker. Examples of peptide linkers that can be used to link the various peptides provided herein are (GGGGS) n(SEQ ID NO: 55) (each n is independently 1 - 5), but is not limited thereto. 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: 36 and SEQ ID NO: 37.

[0176] As provided herein, a polypeptide, antibody or antigen - binding fragment thereof can be a variant of a sequence.

[0177] The sequence of a polypeptide or antibody can be modified to generate a human IgG antibody. The sequence conversions provided herein can be modified to generate other types of antibodies. CDRs can also be linked to other antibodies, proteins or molecules to create antibody fragments that bind to CD7.

[0178] In some embodiments, the polypeptides or antibodies provided herein are targeting moieties on the surface of modified virus particles. In some embodiments, the targeting moiety enables binding to target cells. In some embodiments, the targeting moiety is a CD7 - binding moiety such as the polypeptides or antibodies provided herein. In some embodiments, the target - binding domain (“T”) 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: 38: DILLTQSPAILSVSPGERVSFSCRASQSIGTSIHWYQQRTNDSPRLLIKYASESISGIPSRFSGSGSGTDFTLSINSVESEDIADYYCQQSNSWPTTFGGGTKLEIKRGGGGSGGGGSGGGGSGGGGSGGGGSQVQLQQPGAELVKPGASVKLSCKASGYPFTSYWIHWVKQRPGRGLEWLGRIDPNSGDTKYNEKFKNKATLTVDKSSTTAYMQLSSLTSEDSAVYYCARSPYYSNDNSMDYWGQGTSVTVSS(SEQ ID NO: 38) Or is substantially similar to SEQ ID NO: 38 or is an active fragment of SEQ ID NO: 38. In some embodiments, the target binding domain ("T") comprises a sequence that is at least 90% identical to the sequence of SEQ ID NO: 38. In some embodiments, the target binding domain ("T") comprises a sequence that is at least 95% identical to the sequence of SEQ ID NO: 38. In some embodiments, the target binding domain ("T") comprises a sequence that is at least 99% identical to the sequence of SEQ ID NO: 38. In some embodiments, the target binding domain ("T") comprises the sequence set forth in SEQ ID NO: 38. In some embodiments, the target binding domain ("T") set forth in SEQ ID NO: 38 is an antibody or an antigen-binding fragment thereof. In some embodiments, the target binding domain ("T") is an anti-CD7 antibody.

[0179] In some embodiments, the polypeptides or antibodies provided herein are targeting moieties on the surface of modified viral particles. In some embodiments, the modified viral particles are pseudotyped virus-like particles. In some embodiments, the targeting moiety enables binding to target cells. In some embodiments, the targeting moiety is a CD7 binding moiety such as the polypeptides or antibodies provided herein. In some embodiments, the target binding domain ("T") 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: 39. In some embodiments, the target binding domain ("T") comprises a sequence that is at least 90% identical to the sequence of SEQ ID NO: 39. QVQLQQPGAELVKPGASVKLSCKASGYPFTSYWIHWVKQRPGRGLEWLGRIDPNSGDTKYNEKFKNKATLTVDKSSTTAYMQLSSLTSEDSAVYYCARSPYYSNDNSMDYWGQGTSVTVSSGGGGSGGGGSGGGGSGGGGSDILLTQSPAILSVSPGERVSFSCRASQSIGTSIHWYQQRTNDSPRLLIKYASESISGIPSRFSGSGSGTDFTLSINSVESEDIADYYCQQSNSWPTTFGGGTKLEIKR (SEQ ID NO: 39) Or is substantially similar to SEQ ID NO: 39 or is an active fragment of SEQ ID NO: 39. In some embodiments, the target binding domain ("T") comprises a sequence that is at least 95% identical to the sequence of SEQ ID NO: 39. In some embodiments, the target binding domain ("T") comprises a sequence that is at least 99% identical to the sequence of SEQ ID NO: 39. In some embodiments, the target binding domain ("T") comprises the sequence set forth in SEQ ID NO: 39. In some embodiments, the target binding domain ("T") set forth in SEQ ID NO: 39 is an antibody or an antigen-binding fragment thereof. In some embodiments, the target binding domain ("T") 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.

[0180] CD8-binding polypeptide In some embodiments, the targeting moiety (e.g., a polypeptide) can bind to CD8.

[0181] 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 the CD8 heterodimer. In some embodiments, the CD8 heterodimer comprises a CD8-alpha subunit and a CD8-beta subunit. In some embodiments, the polypeptide binds to the 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: 40): MALPVTALLLPLALLLHAARPSQFRVSPLDRTWNLGETVELKCQVLLSNPTSGCSWLFQPRGAAASPTFLLYLSQNKPKAAEGLDTQRFSGKRLGDTFVLTLSDFRRENEGCYFCSALSNSIMYFSHFVPVFLPAKPTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCNHRNRRRVCKCPRPVVKSGDKPSLSARYV (SEQ ID NO: 40).

[0182] The sequence of human CD8-beta (UniProtKB Q8TD28) is as follows (SEQ ID NO: 31): MRPRLWLLLAAQLTVLHGNSVLQQTPAYIKVQTNKMVMLSCEAKISLSNMRIYWLRQRQAPSSDSHHEFLALWDSAKGTIHGEEVEQEKIAVFRDASRFILNLTSVKPEDSGIYFCMIVGSPELTFGKGTQLSVVDFLPTTAQPTKKSTLKKRVCRLPRPETQKGPLCSPITLGLLVAGVLVLLVSLGVAIHLCCRRRRARLRFMKQLYK (SEQ ID NO: 41).

[0183] In some embodiments, the CD8 to which the polypeptide binds is expressed on the surface of the cell. In some embodiments, the cell is an immune cell. In some embodiments, the immune cell is a CD7+ T cell, CD4+ T cell, CD8+ T cell, NK cell, alpha-beta T cell, gamma-delta T cell, lymphoid progenitor cell, hematopoietic stem cell, myeloid cell, monocyte, macrophage, central memory T cell, effector memory T cell, stem cell-like memory T cell, naive T cell, activated T cell, regulatory T cell (TReg), terminally differentiated effector memory T cell (TEMRA), resident memory T cell (TRM) or CD8+ CCR7+ T cell. In some embodiments, the cell is a CD8+ T cell. In some embodiments, the cell is a CD8+ cell.

[0184] In some embodiments, the antibody comprises an Fc region. The Fc region can bind 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 described herein, such as SEQ ID NO: 26, 27, or 28, or a variant thereof.

[0185] In some embodiments, a polypeptide (e.g., a CD8-binding polypeptide) is provided herein. In some embodiments, an antibody (e.g., an anti-CD8 antibody) is provided herein. 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 is not isolated from a human subject.

[0186] In some embodiments, an antibody or an antigen-binding fragment thereof is provided, and the antibody or antibody fragment comprises a peptide selected from the following table showing CDRs based on Kabat numbering.

Table 4

[0187] In some embodiments, the polypeptide, antibody or antibody-binding fragment thereof comprises the CDRs of the heavy or light chain provided by the above table. In some embodiments, the polypeptide, antibody or antibody-binding fragment thereof comprises the CDRs of the heavy or light chain provided by the above table and binds to non-human primate CD8. In some embodiments, the polypeptide, antibody or antibody-binding fragment thereof comprises the CDRs of the heavy or light chain provided by the above table 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: 45-47. In some embodiments, the polypeptide, antibody or antibody-binding fragment thereof comprises a light chain CDR having the sequence of SEQ ID NO: 45. In some embodiments, the polypeptide, antibody or antibody-binding fragment thereof comprises a light chain CDR having the sequence of SEQ ID NO: 46. In some embodiments, the polypeptide, antibody or antibody-binding fragment thereof comprises a light chain CDR having the sequence of SEQ ID NO: 47. In some embodiments, the polypeptide, antibody or antibody-binding fragment thereof comprises a heavy chain CDR having a sequence selected from SEQ ID NOs: 42-44. In some embodiments, the polypeptide, antibody or antibody-binding fragment thereof comprises a heavy chain CDR having the sequence of SEQ ID NO: 42. In some embodiments, the polypeptide, antibody or antibody-binding fragment thereof comprises a heavy chain CDR having the sequence of SEQ ID NO: 43. In some embodiments, the polypeptide, antibody or antibody-binding fragment thereof comprises a heavy chain CDR having the sequence of SEQ ID NO: 44. The CDRs referred to in the embodiments throughout this specification are interchangeable with CDRs characterized by different formats such as Chothia and IMGT.

[0188] 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: 45, LCDR2 has the sequence of SEQ ID NO: 46, and LCDR3 has the sequence of SEQ ID NO: 47.

[0189] 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: 42, HCDR2 has the sequence of SEQ ID NO: 43, and LCDR3 has the sequence of SEQ ID NO: 44.

[0190] In some embodiments, the polypeptide, antibody or antibody binding fragment thereof comprises: (i) a light chain having any one of the foregoing combinations of LCDR1, LCDR2, and LCDR3 sequences; and (ii) a heavy chain having any one of the foregoing combinations of HCDR1, HCDR2, and HCDR3 sequences.

[0191] The different CDR motifs can be combined in any combination, including those not shown in the above table. For example, the following embodiments are provided as non-limiting examples of such combinations.

[0192] 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: 45; the light chain CDR2 has the amino acid sequence of SEQ ID NO: 46; the light chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 47; 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: 42; the heavy chain CDR2 sequence has the amino acid sequence of SEQ ID NO: 43; the heavy chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 44; or comprises any variant of the foregoing.

[0193] In the foregoing paragraphs, reference may be made to CDRs in the Kabat system, but equivalent CDR sequences may be used from the IMGT and Chothia notations.

[0194] In some embodiments, the light chain variable region CDR1 is replaced with any one of other light chain CDR1 sequences. In some embodiments, the light chain variable region CDR2 is replaced with any one of other light chain CDR2 sequences. In some embodiments, the light chain variable region CDR3 is replaced with any one of other light chain CDR3 sequences. In some embodiments, the heavy chain variable region CDR1 is replaced with any one of other heavy chain CDR1 sequences. In some embodiments, the heavy chain variable region CDR2 is replaced with any one of other heavy chain CDR2 sequences. In some embodiments, the heavy chain variable region CDR3 is replaced with any one of other heavy chain CDR3 sequences.

[0195] In some embodiments, the polypeptide comprises a heavy chain variable region peptide having one of the following sequences, or a variant thereof: [Table 5]

[0196] In some embodiments, the polypeptide comprises a light chain variable region peptide having one of the following sequences, or a variant thereof: [Table 6]

[0197] In some embodiments, the polypeptide, antibody or antigen-binding fragment thereof comprises the V H peptide of SEQ ID NO: 48. In some embodiments, the polypeptide, antibody or antigen-binding fragment thereof comprises the V L peptide of SEQ ID NO: 49. In some embodiments, the polypeptide, antibody, or antigen-binding fragment thereof comprises the V H peptide and the V L peptide, wherein the V H peptide comprises the sequence of SEQ ID NO: 48, or a variant thereof; and the V L peptide comprises the sequence of SEQ ID NO: 49, or a variant thereof. In some embodiments, the polypeptide, antibody, or antigen-binding fragment thereof comprises the V HPeptide and V L Comprising a peptide and V H The peptide comprises the sequence of SEQ ID NO: 48, or a variant thereof; V L The peptide comprises the sequence of SEQ ID NO: 49, 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 is V H Peptide and V L Comprising a peptide and V H The peptide comprises the sequence of SEQ ID NO: 48, or a variant thereof; V L The peptide comprises the sequence of SEQ ID NO: 49, or a variant thereof, and the polypeptide, antibody, or antigen-binding fragment thereof binds to human CD8. In some embodiments, V H The peptide comprises the sequence of SEQ ID NO: 48; V L The peptide comprises the sequence of SEQ ID NO: 49.

[0198] V H Sequence and V L The sequence is V H Region and V L It may be any format including, but not limited to, an scFv format in which the regions are linked by a peptide linker. Examples of peptide linkers that can be used to link the various peptides provided herein include, but are not limited to, (GGGGS)n (SEQ ID NO: 55) (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 examples, the polypeptide comprises SEQ ID NO: 48 and SEQ ID NO: 49.

[0199] As provided herein, the polypeptide, antibody or antigen-binding fragment thereof may be a variant of the sequence.

[0200] The sequences of polypeptides or antibodies can be modified to generate human IgG antibodies. The sequence conversions provided herein can be modified to generate other types of antibodies. CDRs can also be linked to other antibodies, proteins or molecules to create antibody fragments that bind to CD8.

[0201] In some embodiments, the polypeptides or antibodies provided herein are targeting moieties on the surface of modified virus particles. In some embodiments, the targeting moiety enables binding to target cells. In some embodiments, the target binding domain (“T”) is a CD8 binding moiety such as the polypeptides or antibodies provided herein. In some embodiments, the target binding domain (“T”) 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: 50: NIVLTQSPASLAVSLGQRATISCRASESVDGFGNSFMNWYQQKPGQSPKLLIYLASNLESGVPARFSGSGSRTDFTLTIDPVEADDAATYYCQQNNEDPYTFGGGTKLEIKRGGGGSGGGGSGGGGSGGGGSEVQLQQSGPELVKPGASVKISCKASRYTFTDYNLHWVKLSHEKSLEWIGFIYPYNGGTGYNQKFKNKAKLTVDYSSSTAYMELRSLTSVDAAVYYCARDHRYNEGVSFDYWGQGTTLTVSS (SEQ ID NO: 50) Or is substantially similar to SEQ ID NO: 50 or is an active fragment of SEQ ID NO: 50. In some embodiments, the target binding domain (“T”) comprises a sequence that is at least 90% identical to the sequence of SEQ ID NO: 50. In some embodiments, the target binding domain (“T”) comprises a sequence that is at least 95% identical to the sequence of SEQ ID NO: 50. In some embodiments, the target binding domain (“T”) comprises a sequence that is at least 99% identical to the sequence of SEQ ID NO: 50. In some embodiments, the target binding domain (“T”) comprises the sequence set forth in SEQ ID NO: 50. In some embodiments, the target binding domain (“T”) set forth in SEQ ID NO: 50 is an antibody or an antigen-binding fragment thereof. In some embodiments, the targeting moiety is an anti-CD8 antibody.

[0202] In some embodiments, the polypeptide or antibody provided herein is a targeting moiety on the surface of a modified viral particle. In some embodiments, the modified viral particle is a pseudotyped virus-like particle. In some embodiments, the targeting moiety enables binding to a target cell. In some embodiments, the target binding domain (“T”) is a CD8-binding moiety such as the polypeptide or antibody provided herein. In some embodiments, the target binding domain (“T”) 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: EVQLQQSGPELVKPGASVKISCKASRYTFTDYNLHWVKLSHEKSLEWIGFIYPYNGGTGYNQKFKNKAKLTVDYSSSTAYMELRSLTSVDAAVYYCARDHRYNEGVSFDYWGQGTTLTVSSGGGGSGGGGSGGGGSGGGGSNIVLTQSPASLAVSLGQRATISCRASESVDGFGNSFMNWYQQKPGQSPKLLIYLASNLESGVPARFSGSGSRTDFTLTIDPVEADDAATYYCQQNNEDPYTFGGGTKLEIKR (SEQ ID NO: 51) Or is substantially similar to SEQ ID NO: 51 or is an active fragment of SEQ ID NO: 51. In some embodiments, the target binding domain ("T") comprises a sequence that is at least 90% identical to the sequence of SEQ ID NO: 51. In some embodiments, the target binding domain ("T") comprises a sequence that is at least 95% identical to the sequence of SEQ ID NO: 51. In some embodiments, the target binding domain ("T") comprises a sequence that is at least 99% identical to the sequence of SEQ ID NO: 51. In some embodiments, the target binding domain ("T") comprises the sequence set forth in SEQ ID NO: 51. In some embodiments, the target binding domain ("T") 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-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.

[0203] Targeting moiety comprising an Fc domain In some examples, V H and V LThe polypeptide binds to the stalk portion S1 that includes the Fc region. In some embodiments, the Fc region is as provided herein. In some embodiments, the Fc region is a mutant Fc region provided herein. Non-limiting mutations in the Fc region are provided herein. In some embodiments, the mutant Fc region includes a sequence that is a variant of SEQ ID NO: 26, SEQ ID NO: 27, or SEQ ID NO: 28 provided herein. In some embodiments, the variant of SEQ ID NO: 26 includes one or more variants selected from the group consisting of L234A, L235A, N297A, P329G, I253A, H310A, and H435A provided herein. In some embodiments, the variant of SEQ ID NO: 27 includes one or more variants selected from the group consisting of N297A, P329G, I253A, H310A, and H435A provided herein. In some embodiments, the variant of SEQ ID NO: 28 includes one or more variants selected from the group consisting of S228P, L235E, N297A, P329G, I253A, H310A, and H435A provided herein. As provided herein, the heavy chain can be linked to the Fc region. In some embodiments, the Fc region further includes (e.g., is linked to) a transmembrane domain. In some embodiments, the Fc region that further includes a transmembrane domain has the formula L1-Fc-L2-X1, wherein L1 is a linker provided herein or is absent, Fc is a mutant Fc region provided herein, L2 is a linker provided herein or is absent, and X1 is a polypeptide that includes a transmembrane domain provided herein. As provided herein, X1 has the formula ECD-T M -ICD and can include a polypeptide, wherein ECD is an extracellular domain or a fragment thereof provided herein or is absent, and T Mis a transmembrane domain provided by the present specification, and ICD is an intracellular domain provided by the present specification or does not exist. Examples of ECD include, but are not limited to, the extracellular domains of CD8 and / or CD28 provided by the present specification. T M Examples include, but are not limited to, the CD8 and / or CD28 transmembrane domains provided by the present specification. In some embodiments, X1 is T M and includes no ECD and ICD. In some embodiments, X1 includes ECD, T M and includes no ICD. In some embodiments, X1 is T M and ICD and includes no ECD. In some embodiments, X1 includes ECD, T M , and ICD. It should be understood that in any of the following embodiments, ECD, ICD, or both may optionally be absent. Thus, embodiments in which X1 includes CD8 and / or CD28 ECD, CD8 and / or CD28 T M , and an ICD including an Env integration motif are understood to encompass the following X1 members: i) CD8 and / or CD28 ECD, CD8 and / or CD28 T M , and an ICD including an Env integration motif; ii) CD8 and / or CD28 T M , and an ICD including an Env integration motif with no ECD; iii) CD8 and / or CD28 ECD with no ICD, and CD8 and / or CD28 T M ; and iv) CD8 and / or CD28 T M with no ECD and no ICD. Similarly, embodiments in which X1 includes CD8 and / or CD28 T M and an ICD including an Env integration motif are understood to encompass the following X1 members: i) CD8 and / or CD28 T M and an ICD including an Env integration motif, and ii) CD8 and / or CD28 TM 。Similarly, embodiments in which X1 is CD8 and / or CD28 ECD and CD8 and / or CD28 T M are understood to include the following X1 members: i) CD8 and / or CD28 ECD and CD8 and / or CD28 T M ; and ii) CD8 and / or CD28 T in which no ECD is present M 。The foregoing description will be further understood to apply also to embodiments in which specific ECDs, Ts M , or ICDs are not enumerated. For example, embodiments in which X1 is ECD, CD8 and / or CD28 T M , and ICD are understood to include the following X1 members: i) ECD, CD8 and / or CD28 T M , and ICD; ii) ECD, and CD8 and / or CD28 T in which no ICD is present M ; iii) CD8 and / or CD28T M , and ICD in which no ECD is present; and iv) CD8 and / or CD28 T in which neither ECD nor ICD is present M 。Similarly, embodiments in which X1 is CD8 and / or CD28 T M and ICD are understood to include the following X1 members: i) CD8 and / or CD28 T M and ICD; and ii) CD8 and / or CD28 T in which no ICD is present M 。Similarly, embodiments in which X1 is ECD and CD8 and / or CD28 T M are understood to include the following X1 members: i) ECD and CD8 and / or CD28 T M ; and ii) CD8 and / or CD28 T in which no ECD is present M 。Unless explicitly stated otherwise, the foregoing examples and description apply to any and all embodiments below.

[0204] In some embodiments, X1 is CD8 and / or CD28 ECD, T M, and includes an ICD. In some embodiments, X1 is ECD, CD8 and / or CD28 T M , and includes an ICD. In some embodiments, X1 is CD8 and / or CD28 ECD, CD8 and / or CD28 T M , and includes an ICD. In some embodiments, X1 is ECD, T M , and includes an ICD, where the ICD includes the env integration motif provided herein. In some embodiments, X1 is CD8 and / or CD28 ECD, T M , and includes an ICD, where the ICD includes the env integration motif provided herein. In some embodiments, X1 is ECD, CD8 and / or CD28 T M , and includes an ICD, where the ICD includes the env integration motif provided herein. In some embodiments, X1 is CD8 and / or CD28 ECD, CD8 and / or CD28 T M , and includes an ICD, where the ICD includes the env integration motif provided herein.

[0205] In some embodiments, the V H and V L polypeptides are linked to a stalk portion (S1) comprising the Fc region provided herein. In some embodiments, the V H and V L polypeptides are linked to a stalk portion (S1) comprising an Fc region comprising a transmembrane domain provided herein. In some embodiments, the Fc region further comprising a transmembrane domain has the formula L1-Fc-L2-X1, where L1 is a linker provided herein or is absent, Fc is a mutant Fc region provided herein, L2 is a linker provided herein or is absent, and X1 is a polypeptide comprising a transmembrane domain provided herein. As provided herein, X1 has the formula ECD-T M-It may contain a polypeptide having an ICD, wherein ECD is an extracellular domain, or a fragment thereof provided herein, or is absent, and T M is a transmembrane domain provided herein, and ICD is an intracellular domain provided herein or is absent. In some embodiments, the V provided herein H and V L polypeptide is linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) containing CD8 and / or CD28 ECD, T M , and ICD. In some embodiments, the V provided herein H and V L polypeptide is linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) containing ECD, CD8 and / or CD28 T M , and ICD. In some embodiments, the V provided herein H and V L polypeptide is linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) containing CD8 and / or CD28 ECD, CD8 and / or CD28 T M , and ICD. In some embodiments, the V provided herein H and V L polypeptide is linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) containing ECD, T M , and ICD, wherein ICD contains an env integration motif provided herein. In some embodiments, the V provided herein H and V L polypeptide is linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) containing CD8 and / or CD28 ECD, T M , and ICD, wherein ICD contains an env integration motif provided herein. In some embodiments, the V provided herein H and V L polypeptide is linked to a stalk portion (S1) containing ECD, CD8 and / or CD28 TM and linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) including an ICD, wherein the ICD comprises an env integration motif provided herein. In some embodiments, the V provided herein H and V L polypeptides are CD8 and / or CD28 ECD, CD8 and / or CD28 T M and linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) including an ICD, wherein the ICD comprises an env integration motif provided herein. In some embodiments, the V provided herein H and V L polypeptides are ECDs immobilized on the surface of virus particles such as those provided herein, T M and linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) including an ICD. In some embodiments, the identity of L1, Fc, L2, ECD, T M and ICD is as provided herein. In some embodiments, V H and V L polypeptides bind to immune cells such as those provided herein.

[0206] In some embodiments, the V peptide having the sequence set forth in SEQ ID NO: 36 H and the V peptide having the sequence set forth in SEQ ID NO: 37 L are linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) including an ICD. In some embodiments, the V peptide having the sequence set forth in SEQ ID NO: 36 M and the V peptide having the sequence set forth in SEQ ID NO: 37 H are CD8 and / or CD28 ECD, T L and linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) including an ICD. In some embodiments, the V peptide having the sequence set forth in SEQ ID NO: 36 M and the V peptide having the sequence set forth in SEQ ID NO: 37 HA peptide and a V having the sequence set forth in SEQ ID NO: 37 L The peptide is linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) containing ECD, CD8 and / or CD28 T M . In some embodiments, a V having the sequence set forth in SEQ ID NO: 36 H A peptide and a V having the sequence set forth in SEQ ID NO: 37 L The peptide is linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) containing CD8 and / or CD28 ECD, CD8 and / or CD28 T M . In some embodiments, a V having the sequence set forth in SEQ ID NO: 36 H A peptide and a V having the sequence set forth in SEQ ID NO: 37 L The peptide is linked to a stalk portion (S1) comprising ECD, T M and an Fc region (L1-Fc-L2-X1) containing ICD, where ICD comprises an env integration motif provided herein. In some embodiments, a V having the sequence set forth in SEQ ID NO: 36 H A peptide and a V having the sequence set forth in SEQ ID NO: 37 L The peptide is linked to a stalk portion (S1) comprising CD8 and / or CD28 ECD, T M and an Fc region (L1-Fc-L2-X1) containing ICD, where ICD comprises an env integration motif provided herein. In some embodiments, a V having the sequence set forth in SEQ ID NO: 36 H A peptide and a V having the sequence set forth in SEQ ID NO: 37 L The peptide is linked to a stalk portion (S1) comprising ECD, CD8 and / or CD28 T M and an Fc region (L1-Fc-L2-X1) containing ICD, where ICD comprises an env integration motif provided herein. In some embodiments, a V having the sequence set forth in SEQ ID NO: 36 H A peptide and a V having the sequence set forth in SEQ ID NO: 37 LThe peptide is linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) containing CD8 and / or CD28 ECD, CD8 and / or CD28 T M , and ICD, wherein the ICD comprises an env integration motif provided herein. In some embodiments, a V having the sequence set forth in SEQ ID NO: 36 H peptide and a V having the sequence set forth in SEQ ID NO: 37 L peptide are immobilized on the surface of a viral particle such as those provided herein, ECD, T M , and linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) containing ICD. In some embodiments, L1, Fc, L2, ECD, T M , and the identity of ICD is as provided herein. In some embodiments, V H and V L polypeptides bind to immune cells such as those provided herein.

[0207] In some embodiments, a V peptide 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: 36; and a V H peptide 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: 37 are linked to a stalk portion (S1) comprising the Fc region provided herein. In some embodiments, a V peptide 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: 36; and a V L peptide 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: 37 are linked to a stalk portion (S1) comprising the Fc region provided herein. H peptide; and a V peptide 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: 37 LThe peptide is linked to a stalk portion (S1) comprising an Fc region that includes a transmembrane domain provided herein. In some embodiments, the Fc region further comprising a transmembrane domain has the formula L1-Fc-L2-X1, wherein L1 is a linker provided herein, or Fc is a variant Fc region provided herein, L2 is a linker provided herein or is absent, and X1 is a polypeptide comprising a transmembrane domain provided herein. As provided herein, X1 has the formula ECD-T M -ICD and may include a polypeptide, wherein ECD is an extracellular domain or a fragment thereof provided herein or is absent, and T M is a transmembrane domain provided herein, and ICD is an intracellular domain provided herein or is absent. In some embodiments, a V H peptide 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: 36; and a V L peptide 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: 37 are linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) that includes ECD, T M , and ICD. In some embodiments, a V H peptide 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: 36; and a V L peptide 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: 37 are CD8 and / or CD28 ECD, T Mand is linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) containing an ICD. In some embodiments, a 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: 36 H peptide; and a 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: 37 L peptide is the ECD, CD8 and / or CD28 T M and is linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) containing an ICD. In some embodiments, a 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: 36 H peptide; and a 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: 37 L peptide is the CD8 and / or CD28 ECD, CD8 and / or CD28 T M and is linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) containing an ICD. In some embodiments, a 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: 36 H peptide; and a 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: 37 L peptide is the ECD, T M and an Fc region (L1-Fc-L 2-linked to a stalk portion (S1) comprising X1), where the ICD comprises an env integration motif provided herein. In some embodiments, a 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: 36 H peptide; and a 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: 37 L peptide comprises CD8 and / or CD28 ECD, T M linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) containing the ICD, where the ICD comprises an env integration motif provided herein. In some embodiments, a 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: 36 H peptide; and a 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: 37 L peptide comprises ECD, CD8 and / or CD28 T M linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) containing the ICD, where the ICD comprises an env integration motif provided herein. In some embodiments, a 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: 36 H peptide; and a 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: 37 LThe peptide is linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) containing CD8 and / or CD28 ECD, CD8 and / or CD28 T M , and an ICD, wherein the ICD comprises an env integration motif provided herein. In some embodiments, a 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: 36 H peptide; and a 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: 37 L The peptide is linked to an ECD fixed to the surface of virus particles such as those provided herein, T M , and a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) containing an ICD. In some embodiments, L1, Fc, L2, ECD, T M , and the identity of the ICD is as provided herein. In some embodiments, V H and V L polypeptides bind to immune cells such as those provided herein.

[0208] In some embodiments, V H peptide and V L polypeptides comprising the peptide are provided, V H 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: 36; V L 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: 37.

[0209] In some embodiments, the polypeptide is VH Peptide and V L Contains a peptide and 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: 36; V 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: 37; provided that V H Peptide and V L The peptide comprises a light chain CDR having the sequences of SEQ ID NOs: 33 - 35; and / or a heavy chain CDR having the sequences of SEQ ID NOs: 30 - 32. In some embodiments, the polypeptide is V H Peptide and V L Contains a peptide and 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: 36; V 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: 37; provided that V H Peptide and V L The peptide comprises a light chain CDR1 having the sequence of SEQ ID NO: 33; a light chain CDR2 having the sequence of SEQ ID NO: 34; a light chain CDR3 having the sequence of SEQ ID NO: 35; and / or a heavy chain CDR1 having the sequence of SEQ ID NO: 30; a heavy chain CDR2 having the sequence of SEQ ID NO: 31; and a heavy chain CDR3 having the sequence of SEQ ID NO: 32. In some embodiments, V H Or V L The CDRs of the chains are as described in the combinations provided herein.

[0210] In some embodiments, the polypeptide is V H Peptide and V L Contains a peptide and VH 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: 36; V 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: 37; provided that V L The peptide comprises LCDR1 having the sequence of SEQ ID NO: 33; LCDR2 having the sequence of SEQ ID NO: 34; and LCDR3 having the sequence of SEQ ID NO: 35; V H The peptide comprises HCDR1 having the sequence of SEQ ID NO: 30; HCDR2 having the sequence of SEQ ID NO: 31; and HCDR3 having the sequence of SEQ ID NO: 32.

[0211] In some embodiments, the polypeptide is V H the peptide and V L the peptide, and 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: 36; V 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: 37; provided that V L The peptide comprises LCDR1 having the sequence of SEQ ID NO: 33 (where LCDR1 contains at most one conservative amino acid substitution), LCDR2 having the sequence of SEQ ID NO: 34 (where LCDR2 contains at most one conservative amino acid substitution), and LCDR3 having the sequence of SEQ ID NO: 35 (where LCDR3 contains at most one conservative amino acid substitution); V HThe peptide comprises an HCDR1 having the sequence of SEQ ID NO: 30 (where HCDR1 includes at most one conservative amino acid substitution), an HCDR2 having the sequence of SEQ ID NO: 31 (where HCDR2 includes at most one conservative amino acid substitution), and an HCDR3 having the sequence of SEQ ID NO: 32 (where HCDR3 includes at most one conservative amino acid substitution).

[0212] In some embodiments, the polypeptide is V H peptide and V L peptide, and V H peptide comprises the sequence of SEQ ID NO: 36, and V L peptide comprises the sequence of SEQ ID NO: 37.

[0213] In some embodiments, the polypeptides provided herein bind to non-human primate CD7. In some embodiments, the polypeptides provided herein bind to human CD7.

[0214] As provided herein, the different polypeptides (V H or V L ) described herein can be linked with a peptide linker or linked in a continuous sequence without a peptide linker. In some embodiments, the peptide linker comprises the sequence of (GGGGS) n (SEQ ID NO: 55), and each n is independently from 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 binding peptide format can be represented by the formula of V H -Z-V L or V L -Z-V H , wherein Z is a peptide linker. In some embodiments, Z is (GGGGS) n(SEQ ID NO: 55), and 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.

[0215] In some embodiments, V L -Z-V H A polypeptide comprising a linking peptide represented by the formula of is linked to the light chain variable region described in SEQ ID NO: 37 via a linker sequence GGGGSGGGGSGGGGSGGGGS (SEQ ID NO: 72) and comprises the heavy chain variable region described in SEQ ID NO: 36. In some embodiments, V is linked via a peptide linker H linked to V L A polypeptide comprising has the sequence described below DILLTQSPAILSVSPGERVSFSCRASQSIGTSIHWYQQRTNDSPRLLIKYASESISGIPSRFSGSGSGTDFTLSINSVESEDIADYYCQQSNSWPTTFGGGTKLEIKRGGGGSGGGGSGGGGSGGGGSQVQLQQPGAELVKPGASVKLSCKASGYPFTSYWIHWVKQRPGRGLEWLGRIDPNSGDTKYNEKFKNKATLTVDKSSTTAYMQLSSLTSEDSAVYYCARSPYYSNDNSMDYWGQGTSVTVSS (SEQ ID NO: 38).

[0216] 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: 38. In some embodiments, the polypeptide comprises a sequence that is at least 90% identical to the sequence of SEQ ID NO: 38. In some embodiments, the polypeptide comprises a sequence that is at least 95% identical to the sequence of SEQ ID NO: 38. In some embodiments, the polypeptide comprises a sequence that is at least 99% identical to the sequence of SEQ ID NO: 38. In some embodiments, the polypeptide comprises the sequence set forth in SEQ ID NO: 38. In some embodiments, the polypeptide set forth in SEQ ID NO: 38 is an antibody, or an 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.

[0217] In some embodiments, V H -Z-V L A polypeptide comprising a linking peptide represented by the formula of is linked to the heavy chain variable region set forth in SEQ ID NO: 36 via a linker sequence GGGGSGGGGSGGGGSGGGGS (SEQ ID NO: 72) and comprises the light chain variable region set forth in SEQ ID NO: 37. In some embodiments, V linked via a peptide linker L to V H The polypeptide comprising has the sequence set forth below, QVQLQQPGAELVKPGASVKLSCKASGYPFTSYWIHWVKQRPGRGLEWLGRIDPNSGDTKYNEKFKNKATLTVDKSSTTAYMQLSSLTSEDSAVYYCARSPYYSNDNSMDYWGQGTSVTVSSGGGGSGGGGSGGGGSGGGGSDILLTQSPAILSVSPGERVSFSCRASQSIGTSIHWYQQRTNDSPRLLIKYASESISGIPSRFSGSGSGTDFTLSINSVESEDIADYYCQQSNSWPTTFGGGTKLEIKR (SEQ ID NO: 39).

[0218] 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: 39. In some embodiments, the polypeptide comprises a sequence that is at least 90% identical to the sequence of SEQ ID NO: 39. In some embodiments, the polypeptide comprises a sequence that is at least 95% identical to the sequence of SEQ ID NO: 39. In some embodiments, the polypeptide comprises a sequence that is at least 99% identical to the sequence of SEQ ID NO: 39. In some embodiments, the polypeptide comprises the sequence set forth in SEQ ID NO: 39. In some embodiments, the polypeptide set forth in SEQ ID NO: 39 is an antibody, or an 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.

[0219] 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: 38, and comprises a stalk portion (S1) that includes 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: 38, and comprises a stalk portion (S1) that includes an Fc region, wherein the Fc region further comprises a transmembrane domain, such as those provided herein. In some embodiments, the Fc region that further comprises a transmembrane domain has the formula L1-Fc-L2-X1, wherein L1 is a linker provided herein or is absent, Fc is a mutant Fc region provided herein, L2 is a linker provided herein or is absent, and X1 is a polypeptide that includes a transmembrane domain provided herein. As provided herein, X1 has the formula ECD-T M -ICD and may comprise a polypeptide, wherein ECD is an extracellular domain or a fragment thereof provided herein or is absent, and T M is a transmembrane domain provided herein, and ICD is an intracellular domain provided herein or is absent. 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: 38, and comprises a stalk portion (S1) that includes an Fc region (L1-Fc-L2-X1) that includes ECD, T M , and ICD. 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: 38, and comprises a stalk portion (S1) that includes CD8 and / or CD28 ECD, T Mand a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) that includes an ICD. 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: 38, and an ECD, CD8 and / or CD28 T M and a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) that includes an ICD. 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: 38, and a CD8 and / or CD28 ECD, CD8 and / or CD28 T M and a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) that includes an ICD. 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: 38, and an ECD, T M and a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) that includes an ICD, where the ICD comprises an env integration motif 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: 38, and a CD8 and / or CD28 ECD, T M and a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) that includes an ICD, where the ICD comprises an env integration motif 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: 38, and an ECD, CD8 and / or CD28 TM and a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) containing an ICD, where the ICD contains the env integration motif 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: 38, and CD8 and / or CD28 ECD, CD8 and / or CD28 T M and a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) containing an ICD, where the ICD contains the env integration motif 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: 38, and an ECD fixed to the surface of a viral particle such as that provided herein, T M and a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) containing an ICD. In some embodiments, L1, Fc, L2, ECD, T M and the identity of the ICD is as provided herein. In some embodiments, the polypeptide binds to immune cells such as those provided herein.

[0220] 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: 39 and comprises a stalk portion (S1) comprising 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: 39 and comprises a stalk portion (S1) comprising an Fc region, wherein the Fc region further comprises a transmembrane domain such as those provided herein. In some embodiments, the Fc region further comprising a transmembrane domain has the formula L1-Fc-L2-X1, wherein L1 is a linker provided herein or is absent, Fc is a mutant Fc region provided herein, L2 is a linker provided herein or is absent, and X1 is a polypeptide comprising a transmembrane domain provided herein. As provided herein, X1 has the formula ECD-T M -ICD and may comprise a polypeptide, wherein ECD is an extracellular domain or a fragment thereof provided herein or is absent, and T M is a transmembrane domain provided herein, and ICD is an intracellular domain provided herein or is absent. 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: 39 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising ECD, T M , and ICD. 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: 39 and comprises CD8 and / or CD28 ECD, T Mand a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) containing an ICD. 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: 39, ECD, CD8 and / or CD28 T M and a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) containing an ICD. 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: 39, CD8 and / or CD28 ECD, CD8 and / or CD28 T M and a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) containing an ICD. 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: 39, ECD, T M and a stalk portion (S1) comprising an Fc region (L1-Fc-L 2- X1) containing an ICD, wherein the ICD comprises an env integration motif 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: 39, CD8 and / or CD28 ECD, T Mand a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) containing an ICD, where the ICD comprises an env integration motif 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: 39, and the ECD, CD8 and / or CD28 T M and a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) containing an ICD, where the ICD comprises an env integration motif 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: 39, and the CD8 and / or CD28 ECD, CD8 and / or CD28 T M and a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) containing an ICD, where the ICD comprises an env integration motif 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: 39, and the ECD fixed to the surface of virus particles such as those provided herein, T M and a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) containing an ICD. In some embodiments, L1, Fc, L2, ECD, T M and the identity of the ICD is as provided herein. In some embodiments, the polypeptide binds to immune cells such as those provided herein.

[0221] In some embodiments, the polypeptide comprises an array having the sequence set forth in SEQ ID NO: 38 and comprises a stalk portion (S1) comprising an Fc region, such as those provided herein. In some embodiments, the polypeptide comprises an array having the sequence set forth in SEQ ID NO: 38 and comprises a stalk portion (S1) comprising an Fc region, and the Fc region further comprises a transmembrane domain, such as those provided herein. In some embodiments, the Fc region further comprising a transmembrane domain has the formula L1-Fc-L2-X1, wherein L1 is a linker provided herein or is absent, Fc is a mutant Fc region provided herein, L2 is a linker provided herein or is absent, and X1 is a polypeptide comprising a transmembrane domain provided herein. As provided herein, X1 has the formula ECD-T M -ICD and may comprise a polypeptide, wherein ECD is an extracellular domain or a fragment thereof provided herein or is absent, and T M is a transmembrane domain provided herein and ICD is an intracellular domain provided herein or is absent. In some embodiments, the polypeptide comprises an array having the sequence set forth in SEQ ID NO: 38 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising ECD, T M , and ICD. In some embodiments, the polypeptide comprises an array having the sequence set forth in SEQ ID NO: 38 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising CD8 and / or CD28 ECD, T M , and ICD. In some embodiments, the polypeptide comprises an array having the sequence set forth in SEQ ID NO: 38 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising ECD, CD8 and / or CD28 T M , and ICD. In some embodiments, the polypeptide comprises an array having the sequence set forth in SEQ ID NO: 38 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising CD8 and / or CD28 ECD, CD8 and / or CD28 T Mand a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) including an ICD. In some embodiments, the polypeptide comprises a sequence having the sequence set forth in SEQ ID NO: 38, an ECD, T M and a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) including an ICD, wherein the ICD comprises an env integration motif provided herein. In some embodiments, the polypeptide comprises a sequence having the sequence set forth in SEQ ID NO: 38, a CD8 and / or CD28 ECD, T M and a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) including an ICD, wherein the ICD comprises an env integration motif provided herein. In some embodiments, the polypeptide comprises a sequence having the sequence set forth in SEQ ID NO: 38, an ECD, a CD8 and / or CD28 T M and a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) including an ICD, wherein the ICD comprises an env integration motif provided herein. In some embodiments, the polypeptide comprises a sequence having the sequence set forth in SEQ ID NO: 38, a CD8 and / or CD28 ECD, a CD8 and / or CD28 T M and a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) including an ICD, wherein the ICD comprises an env integration motif provided herein. In some embodiments, the polypeptide comprises a sequence having the sequence set forth in SEQ ID NO: 38, an ECD immobilized on the surface of a viral particle such as those provided herein, T M and a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) including an ICD. In some embodiments, L1, Fc, L2, ECD, T M and the identity of the ICD is as provided herein. In some embodiments, the polypeptide binds to immune cells such as those provided herein.

[0222] In some embodiments, the polypeptide comprises an array having the sequence set forth in SEQ ID NO: 39 and comprises a stalk portion (S1) comprising an Fc region such as those provided herein. In some embodiments, the polypeptide comprises an array having the sequence set forth in SEQ ID NO: 39 and comprises a stalk portion (S1) comprising an Fc region, and the Fc region further comprises a transmembrane domain such as those provided herein. In some embodiments, the Fc region further comprising a transmembrane domain has the formula L1-Fc-L2-X1, wherein L1 is a linker provided herein or is absent, Fc is a mutant Fc region provided herein, L2 is a linker provided herein or is absent, and X1 is a polypeptide comprising a transmembrane domain provided herein. As provided herein, X1 has the formula ECD-T M -ICD and may comprise a polypeptide, wherein ECD is an extracellular domain or a fragment thereof provided herein or is absent, and T M is a transmembrane domain provided herein, and ICD is an intracellular domain provided herein or is absent. In some embodiments, the polypeptide comprises an array having the sequence set forth in SEQ ID NO: 39 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising ECD, T M , and ICD. In some embodiments, the polypeptide comprises an array having the sequence set forth in SEQ ID NO: 39 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising CD8 and / or CD28 ECD, T M , and ICD. In some embodiments, the polypeptide comprises an array having the sequence set forth in SEQ ID NO: 39 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising ECD, CD8 and / or CD28 T M , and ICD. In some embodiments, the polypeptide comprises an array having the sequence set forth in SEQ ID NO: 39 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising CD8 and / or CD28 ECD, CD8 and / or CD28 T Mand a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) including an ICD. In some embodiments, the polypeptide comprises a sequence having the sequence set forth in SEQ ID NO: 39, an ECD, T M and a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) including an ICD, wherein the ICD comprises an env integration motif provided herein. In some embodiments, the polypeptide comprises a sequence having the sequence set forth in SEQ ID NO: 39, a CD8 and / or CD28 ECD, T M and a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) including an ICD, wherein the ICD comprises an env integration motif provided herein. In some embodiments, the polypeptide comprises a sequence having the sequence set forth in SEQ ID NO: 39, an ECD, a CD8 and / or CD28 T M and a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) including an ICD, wherein the ICD comprises an env integration motif provided herein. In some embodiments, the polypeptide comprises a sequence having the sequence set forth in SEQ ID NO: 39, a CD8 and / or CD28 ECD, a CD8 and / or CD28 T M and a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) including an ICD, wherein the ICD comprises an env integration motif provided herein. In some embodiments, it comprises a sequence having the sequence set forth in SEQ ID NO: 39, an ECD fixed to the surface of virus particles such as those provided herein, T M and a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) including an ICD. In some embodiments, L1, Fc, L2, ECD, T M and the identity of the ICD is as provided herein. In some embodiments, the polypeptide binds to immune cells such as those provided herein.

[0223] In some embodiments, the polypeptides provided herein include the formula of T-S1, where T is a target binding domain and S1 is a stalk portion, and include an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the sequence of SEQ ID NO: 98: METDTLLLWVLLLWVPGSTGDSAQVQLQQPGAELVKPGASVKLSCKASGYPFTSYWIHWVKQRPGRGLEWLGRIDPNSGDTKYNEKFKNKATLTVDKSSTTAYMQLSSLTSEDSAVYYCARSPYYSNDNSMDYWGQGTSVTVSSGGGGSGGGGSGGGGSGGGGSDILLTQSPAILSVSPGERVSFSCRASQSIGTSIHWYQQRTNDSPRLLIKYASESISGIPSRFSGSGSGTDFTLSINSVESEDIADYYCQQSNSWPTTFGGGTKLEIKRASGGGGSGGGGSGGGGSEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMASRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLAQDWLNGKEYKCKVSNKALGAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNAYTQKSLSLSPGKKIEVMYPPPYLDNEKSNGTIIHVKGKHLCPSPLFPGPSKPFWVLVVVGGVLACYSLLVTVAFIIFWVRSKRSRLLHSDYMNRVRQGYS (SEQ ID NO: 98) Or is substantially similar to SEQ ID NO: 98 or is an active fragment of SEQ ID NO: 98. In some embodiments, the polypeptides provided herein that include the formula of T-S1 include an amino acid sequence that is at least 90% identical to the sequence of SEQ ID NO: 98. In some embodiments, the polypeptides provided herein that include the formula of T-S1 include an amino acid sequence that is at least 95% identical to the sequence of SEQ ID NO: 98. In some embodiments, the polypeptides provided herein that include the formula of T-S1 include an amino acid sequence that is at least 98% identical to the sequence of SEQ ID NO: 98. In some embodiments, the polypeptides provided herein that include the formula of T-S1 include the amino acid sequence of SEQ ID NO: 98.

[0224] In some embodiments, the polypeptides provided herein include the formula T-S1, where T is a target binding domain and S1 is a stalk portion, and include an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the sequence of SEQ ID NO: 98, where the target binding domain "T" of the polypeptide corresponds to amino acids 25-283 of SEQ ID NO: 98 and the stalk portion "S1" of the polypeptide corresponds to amino acids 284-634 of SEQ ID NO: 98. In some embodiments, the polypeptides provided herein that include the formula T-S1 include an amino acid sequence that is at least 90% identical to the sequence of SEQ ID NO: 98, where the target binding domain "T" of the polypeptide corresponds to amino acids 25-283 of SEQ ID NO: 98 and the stalk portion "S1" of the polypeptide corresponds to amino acids 284-634 of SEQ ID NO: 98. In some embodiments, the polypeptides provided herein that include the formula T-S1 include an amino acid sequence that is at least 95% identical to the sequence of SEQ ID NO: 98, where the target binding domain "T" of the polypeptide corresponds to amino acids 25-283 of SEQ ID NO: 98 and the stalk portion "S1" of the polypeptide corresponds to amino acids 284-634 of SEQ ID NO: 98. In some embodiments, the polypeptides provided herein that include the formula T-S1 include an amino acid sequence that is at least 98% identical to the sequence of SEQ ID NO: 98, where the target binding domain "T" of the polypeptide corresponds to amino acids 25-283 of SEQ ID NO: 98 and the stalk portion "S1" of the polypeptide corresponds to amino acids 284-634 of SEQ ID NO: 98. In some embodiments, the polypeptides provided herein that include the formula T-S1 include the amino acid sequence of SEQ ID NO: 98, where the target binding domain "T" of the polypeptide corresponds to amino acids 25-283 of SEQ ID NO: 98 and the stalk portion "S1" of the polypeptide corresponds to amino acids 284-634 of SEQ ID NO: 98.

[0225] In some embodiments, the polypeptides provided herein include the formula T-SV, where T is a target binding domain and V Hand V L comprising, wherein S1 is the stalk portion and comprises an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the sequence of SEQ ID NO: 98, and V of the target binding domain H corresponds to amino acids 25-150 of SEQ ID NO: 98, and V of the target binding domain L corresponds to amino acids 172-283 of SEQ ID NO: 98, and the stalk portion "S1" of the polypeptide corresponds to amino acids 284-634 of SEQ ID NO: 98. In some embodiments, the polypeptides provided herein that include the formula T-S1 comprise an amino acid sequence that is at least 90% identical to the sequence of SEQ ID NO: 98, wherein V of the target binding domain H corresponds to amino acids 25-150 of SEQ ID NO: 98, and V of the target binding domain L corresponds to amino acids 172-283 of SEQ ID NO: 98, and the stalk portion "S1" of the polypeptide corresponds to amino acids 284-634 of SEQ ID NO: 98. In some embodiments, the polypeptides provided herein that include the formula T-S1 comprise an amino acid sequence that is at least 95% identical to the sequence of SEQ ID NO: 98, wherein V of the target binding domain H corresponds to amino acids 25-150 of SEQ ID NO: 98, and V of the target binding domain L corresponds to amino acids 172-283 of SEQ ID NO: 98, and the stalk portion "S1" of the polypeptide corresponds to amino acids 284-634 of SEQ ID NO: 98. In some embodiments, the polypeptides provided herein that include the formula T-S1 comprise an amino acid sequence that is at least 98% identical to the sequence of SEQ ID NO: 98, wherein V of the target binding domain H corresponds to amino acids 25-150 of SEQ ID NO: 98, and V of the target binding domain L corresponds to amino acids 172-283 of SEQ ID NO: 98, and the stalk portion "S1" of the polypeptide corresponds to amino acids 284-634 of SEQ ID NO: 98. In some embodiments, the polypeptides provided herein that include the formula T-S1 comprise the amino acid sequence of SEQ ID NO: 98, wherein V of the target binding domainH corresponds to amino acids 25 to 150 of SEQ ID NO: 98 and is the V of the target binding domain L corresponds to amino acids 172 to 283 of SEQ ID NO: 98, and the stalk portion "S1" of the polypeptide corresponds to amino acids 284 to 634 of SEQ ID NO: 98.

[0226] In some embodiments, it is a polypeptide provided herein that includes the formula T-L1-Fc-L2-X1, wherein T is a target binding domain, L1 is a polypeptide linker or is absent, Fc is a variant Fc domain provided herein, L2 is a polypeptide linker or is absent, X1 is a polypeptide that includes a transmembrane domain, and includes an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the sequence of SEQ ID NO: 98. The target binding domain "T" of the polypeptide corresponds to amino acids 25 to 283 of SEQ ID NO: 98, L1contains amino acids 284-301 of SEQ ID NO: 98, Fc contains amino acids 302-542 of SEQ ID NO: 98, L2 is absent, and X1 corresponds to amino acids 543-634 of SEQ ID NO: 98. In some embodiments, the polypeptide provided herein, which contains the formula T-L1-Fc-L2-X1, contains an amino acid sequence that is at least 90% identical to the sequence of SEQ ID NO: 98, wherein the target binding domain "T" of the polypeptide corresponds to amino acids 25-283 of SEQ ID NO: 98, L1 contains amino acids 284-301 of SEQ ID NO: 98, Fc contains amino acids 302-542 of SEQ ID NO: 98, L2 is absent, and X1 corresponds to amino acids 543-634 of SEQ ID NO: 98. In some embodiments, the polypeptide provided herein, which contains the formula T-L1-Fc-L2-X1, contains an amino acid sequence that is at least 95% identical to the sequence of SEQ ID NO: 98, wherein the target binding domain "T" of the polypeptide corresponds to amino acids 25-283 of SEQ ID NO: 98, L1 contains amino acids 284-301 of SEQ ID NO: 98, Fc contains amino acids 302-542 of SEQ ID NO: 98, L2 is absent, and X1 corresponds to amino acids 543-634 of SEQ ID NO: 98. In some embodiments, the polypeptide provided herein, which contains the formula T-L1-Fc-L2-X1, contains an amino acid sequence that is at least 98% identical to the sequence of SEQ ID NO: 98, wherein the target binding domain "T" of the polypeptide corresponds to amino acids 25-283 of SEQ ID NO: 98, L1 contains amino acids 284-301 of SEQ ID NO: 98, Fc contains amino acids 302-542 of SEQ ID NO: 98, L2 is absent, and X1 corresponds to amino acids 543-634 of SEQ ID NO: 98. In some embodiments, the polypeptide provided herein, which contains the formula T-L1-Fc-L2-X1, contains the amino acid sequence of SEQ ID NO: 98, wherein the target binding domain "T" of the polypeptide corresponds to amino acids 25-283 of SEQ ID NO: 98, L1 contains amino acids 284-301 of SEQ ID NO: 98, Fc contains amino acids 302-542 of SEQ ID NO: 98, L2 is absent, and X1 corresponds to amino acids 543-634 of SEQ ID NO: 98.

[0227] In some embodiments, it is a polypeptide provided herein that includes the formula T-L1-Fc-L2-X1, where T is V H and V L is a target binding domain that includes, Fc is a variant Fc domain provided herein, L2 is a polypeptide linker or is absent, X1 is a polypeptide that includes a transmembrane domain, and has an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the sequence of SEQ ID NO: 98. V H of the target binding domain corresponds to amino acids 25-150 of SEQ ID NO: 98, V L of the target binding domain corresponds to amino acids 172-283 of SEQ ID NO: 98, L1 includes amino acids 284-301 of SEQ ID NO: 98, Fc includes amino acids 302-542 of SEQ ID NO: 98, L2 is absent, and X1 corresponds to amino acids 543-634 of SEQ ID NO: 98. In some embodiments, the polypeptide provided herein that includes the formula T-L1-Fc-L2-X1 includes an amino acid sequence that is at least 90% identical to the sequence of SEQ ID NO: 98, where V H of the target binding domain corresponds to amino acids 25-150 of SEQ ID NO: 98, V L of the target binding domain corresponds to amino acids 172-283 of SEQ ID NO: 98, L1 includes amino acids 284-301 of SEQ ID NO: 98, Fc includes amino acids 302-542 of SEQ ID NO: 98, L2 is absent, and X1 corresponds to amino acids 543-634 of SEQ ID NO: 98. In some embodiments, the polypeptide provided herein that includes the formula T-L1-Fc-L2-X1 includes an amino acid sequence that is at least 95% identical to the sequence of SEQ ID NO: 98, where V H of the target binding domain corresponds to amino acids 25-150 of SEQ ID NO: 98, V Lcorresponds to amino acids 172 - 283 of SEQ ID NO: 98, L1 contains amino acids 284 - 301 of SEQ ID NO: 98, Fc contains amino acids 302 - 542 of SEQ ID NO: 98, L2 is absent, and X1 corresponds to amino acids 543 - 634 of SEQ ID NO: 98. In some embodiments, the polypeptides provided herein, which include the formula T - L1 - Fc - L2 - X1, include an amino acid sequence that is at least 98% identical to the sequence of SEQ ID NO: 98, wherein V of the target binding domain H corresponds to amino acids 25 - 150 of SEQ ID NO: 98, and V of the target binding domain L corresponds to amino acids 172 - 283 of SEQ ID NO: 98, L1 contains amino acids 284 - 301 of SEQ ID NO: 98, Fc contains amino acids 302 - 542 of SEQ ID NO: 98, L2 is absent, and X1 corresponds to amino acids 543 - 634 of SEQ ID NO: 98. In some embodiments, the polypeptides provided herein, which include the formula T - L1 - Fc - L2 - X1, include the amino acid sequence of SEQ ID NO: 98, wherein V of the target binding domain H corresponds to amino acids 25 - 150 of SEQ ID NO: 98, and V of the target binding domain L corresponds to amino acids 172 - 283 of SEQ ID NO: 98, L1 contains amino acids 284 - 301 of SEQ ID NO: 98, Fc contains amino acids 302 - 542 of SEQ ID NO: 98, L2 is absent, and X1 corresponds to amino acids 543 - 634 of SEQ ID NO: 98.

[0228] In some embodiments, a polypeptide provided herein that includes the formula T - L1 - Fc - L2 - ECD - T M - ICD, wherein T is a target binding domain, L1 is a polypeptide linker or is absent, Fc is a variant Fc domain provided herein, L2 is a polypeptide linker or is absent, ECD is an extracellular domain, and T Mis a transmembrane domain, ICD is an intracellular domain containing an env integration motif, and contains an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the sequence of SEQ ID NO: 98. The target binding domain "T" of the polypeptide corresponds to amino acids 25-283 of SEQ ID NO: 98, L1 contains amino acids 284-301 of SEQ ID NO: 98, Fc contains amino acids 302-542 of SEQ ID NO: 98, L2 does not exist, ECD contains amino acids 543-584 of SEQ ID NO: 98, and T M contains amino acids 585-612 of SEQ ID NO: 98, ICD contains amino acids 613-634 of SEQ ID NO: 98, where the env integration motif contains amino acids 627-634 of SEQ ID NO: 98. In some embodiments, T-L1-Fc-L2-ECD-T M -ICD, the polypeptide provided herein contains an amino acid sequence that is at least 90% identical to the sequence of SEQ ID NO: 98. In the formula, the target binding domain "T" of the polypeptide corresponds to amino acids 25-283 of SEQ ID NO: 98, L1 contains amino acids 284-301 of SEQ ID NO: 98, Fc contains amino acids 302-542 of SEQ ID NO: 98, L2 does not exist, ECD contains amino acids 543-584 of SEQ ID NO: 98, and T M contains amino acids 585-612 of SEQ ID NO: 98, ICD contains amino acids 613-634 of SEQ ID NO: 98, where the env integration motif contains amino acids 627-634 of SEQ ID NO: 98. In some embodiments, T-L1-Fc-L2-ECD-T M -ICD, the polypeptide provided herein contains an amino acid sequence that is at least 95% identical to the sequence of SEQ ID NO: 98. In the formula, the target binding domain "T" of the polypeptide corresponds to amino acids 25-283 of SEQ ID NO: 98, L1 contains amino acids 284-301 of SEQ ID NO: 98, Fc contains amino acids 302-542 of SEQ ID NO: 98, L2 does not exist, ECD contains amino acids 543-584 of SEQ ID NO: 98, and T Mcomprises amino acids 585-612 of SEQ ID NO: 98, ICD comprises amino acids 613-634 of SEQ ID NO: 98, wherein the env integration motif comprises amino acids 627-634 of SEQ ID NO: 98. In some embodiments, T-L1-Fc-L2-ECD-T M -ICD, the polypeptides provided herein comprising an amino acid sequence that is at least 98% identical to the sequence of SEQ ID NO: 98, wherein the target binding domain "T" of the polypeptide corresponds to amino acids 25-283 of SEQ ID NO: 98, L1 comprises amino acids 284-301 of SEQ ID NO: 98, L2 is absent, ECD comprises amino acids 543-584 of SEQ ID NO: 98, T M comprises amino acids 585-612 of SEQ ID NO: 98, ICD comprises amino acids 613-634 of SEQ ID NO: 98, wherein the env integration motif comprises amino acids 627-634 of SEQ ID NO: 98. In some embodiments, T-L1-Fc-L2-ECD-T M -ICD, the polypeptides provided herein comprising the amino acid sequence of SEQ ID NO: 98, wherein the target binding domain "T" of the polypeptide corresponds to amino acids 25-283 of SEQ ID NO: 98, L1 comprises amino acids 284-301 of SEQ ID NO: 98, Fc comprises amino acids 302-542 of SEQ ID NO: 98, L2 is absent, ECD comprises amino acids 543-584 of SEQ ID NO: 98, T M comprises amino acids 585-612 of SEQ ID NO: 98, ICD comprises amino acids 613-634 of SEQ ID NO: 98, wherein the env integration motif comprises amino acids 627-634 of SEQ ID NO: 98.

[0229] In some embodiments, T-L1-Fc-L2-ECD-T M -ICD, a polypeptide provided herein, wherein in the formula, T is V H and V L is a target binding domain comprising, L1 is a polypeptide linker or is absent, Fc is a variant Fc domain provided herein, L2 is a polypeptide linker or is absent, ECD is an extracellular domain, T Mis a transmembrane domain, ICD is an intracellular domain containing an env integration motif, and contains an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the sequence of SEQ ID NO: 98, and V of the target binding domain H corresponds to amino acids 25-150 of SEQ ID NO: 98, and V of the target binding domain L corresponds to amino acids 172-283 of SEQ ID NO: 98, L1 contains amino acids 284-301 of SEQ ID NO: 98, Fc contains amino acids 302-542 of SEQ ID NO: 98, L2 does not exist, ECD contains amino acids 543-584 of SEQ ID NO: 98, and T M contains amino acids 585-612 of SEQ ID NO: 98, ICD contains amino acids 613-634 of SEQ ID NO: 98, where the env integration motif contains amino acids 627-634 of SEQ ID NO: 98. In some embodiments, T-L1-Fc-L2-ECD-T M -ICD, the polypeptide provided herein contains an amino acid sequence that is at least 90% identical to the sequence of SEQ ID NO: 98, wherein V of the target binding domain H corresponds to amino acids 25-150 of SEQ ID NO: 98, and V of the target binding domain L contains amino acids 172-283 of SEQ ID NO: 98, L1 contains amino acids 284-301 of SEQ ID NO: 98, Fc contains amino acids 302-542 of SEQ ID NO: 98, L2 does not exist, ECD contains amino acids 543-584 of SEQ ID NO: 98, and T M contains amino acids 585-612 of SEQ ID NO: 98, ICD contains amino acids 613-634 of SEQ ID NO: 98, where the env integration motif contains amino acids 627-634 of SEQ ID NO: 98. In some embodiments, T-L1-Fc-L2-ECD-T M -ICD, the polypeptide provided herein contains an amino acid sequence that is at least 95% identical to the sequence of SEQ ID NO: 98, wherein V of the target binding domain H corresponds to amino acids 25-150 of SEQ ID NO: 98, and V of the target binding domain Lcorresponds to amino acids 172 - 283 of SEQ ID NO: 98, L1 contains amino acids 284 - 301 of SEQ ID NO: 98, Fc contains amino acids 302 - 542 of SEQ ID NO: 98, L2 is absent, ECD contains amino acids 543 - 584 of SEQ ID NO: 98, T M contains amino acids 585 - 612 of SEQ ID NO: 98, ICD contains amino acids 613 - 634 of SEQ ID NO: 98, where the env integration motif contains amino acids 627 - 634 of SEQ ID NO: 98. In some embodiments, T - L1 - Fc - L2 - ECD - T M - ICD, the polypeptides provided herein include an amino acid sequence that is at least 98% identical to the sequence of SEQ ID NO: 98, wherein V of the target binding domain H corresponds to amino acids 25 - 150 of SEQ ID NO: 98, and V of the target binding domain L contains amino acids 172 - 283 of SEQ ID NO: 98, L1 contains amino acids 284 - 301 of SEQ ID NO: 98, Fc contains amino acids 302 - 542 of SEQ ID NO: 98, L2 is absent, ECD contains amino acids 543 - 584 of SEQ ID NO: 98, T M contains amino acids 585 - 612 of SEQ ID NO: 98, ICD contains amino acids 613 - 634 of SEQ ID NO: 98, where the env integration motif contains amino acids 627 - 634 of SEQ ID NO: 98. In some embodiments, T - L1 - Fc - L2 - ECD - T M - ICD, the polypeptides provided herein contain amino acids of the sequence of SEQ ID NO: 98, wherein V of the target binding domain H corresponds to amino acids 25 - 150 of SEQ ID NO: 98, and V of the target binding domain L corresponds to amino acids 172 - 283 of SEQ ID NO: 98, L1 contains amino acids 284 - 301 of SEQ ID NO: 98, Fc contains amino acids 302 - 542 of SEQ ID NO: 98, L2 is absent, ECD contains amino acids 543 - 584 of SEQ ID NO: 98, T M contains amino acids 585 - 612 of SEQ ID NO: 98, ICD contains amino acids 613 - 634 of SEQ ID NO: 98, where the env integration motif contains amino acids 627 - 634 of SEQ ID NO: 98.

[0230] In some embodiments, T-L1-Fc-L2-ECD-T M -ICD, a polypeptide provided herein, wherein T is a target binding domain, L1 is a polypeptide linker or absent, Fc is a variant Fc domain provided herein, L2 is a polypeptide linker or absent, ECD is an extracellular domain, T M is a transmembrane domain, ICD is an intracellular domain containing an env integration motif, and contains an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the sequence of SEQ ID NO: 98. The target binding domain "T" of the polypeptide contains the amino acid sequence of SEQ ID NO: 39, corresponding to amino acids 25-283 of SEQ ID NO: 98. L1 contains the amino acid sequence of SEQ ID NO: 72, corresponding to amino acids 284-301 of SEQ ID NO: 98. Fc contains the amino acids of SEQ ID NO: 104, corresponding to amino acids 302-542 of SEQ ID NO: 98. L2 is absent. ECD contains the amino acid sequence of SEQ ID NO: 60, corresponding to amino acids 543-584 of SEQ ID NO: 98. T M contains the amino acid sequence of SEQ ID NO: 62, corresponding to amino acids 585-612 of SEQ ID NO: 98. ICD contains amino acids 613-634 of SEQ ID NO: 98, where the env integration motif contains the amino acid sequence of SEQ ID NO: 63, corresponding to amino acids 627-634 of SEQ ID NO: 98. In some embodiments, T-L1-Fc-L2-ECD-T M- The polypeptides provided herein that include the formula of the ICD comprise an amino acid sequence that is at least 90% identical to the sequence of SEQ ID NO: 98, wherein the target binding domain "T" of the polypeptide comprises the amino acid sequence of SEQ ID NO: 39, corresponding to amino acids 25 - 283 of SEQ ID NO: 98, L1 comprises the amino acid sequence of SEQ ID NO: 72, corresponding to amino acids 284 - 301 of SEQ ID NO: 98, Fc comprises the amino acid sequence of SEQ ID NO: 104, corresponding to amino acids 302 - 542 of SEQ ID NO: 98, L2 is absent, ECD comprises the amino acid sequence of SEQ ID NO: 60, corresponding to amino acids 543 - 584 of SEQ ID NO: 98, and T M comprises the amino acid sequence of SEQ ID NO: 62, corresponding to amino acids 585 - 612 of SEQ ID NO: 98, ICD comprises amino acids 613 - 634 of SEQ ID NO: 98, where the env integration motif comprises the amino acid sequence of SEQ ID NO: 63, corresponding to amino acids 627 - 634 of SEQ ID NO: 98. In some embodiments, T-L1-Fc-L2-ECD-T M - The polypeptides provided herein that include the formula of the ICD comprise an amino acid sequence that is at least 95% identical to the sequence of SEQ ID NO: 98, wherein the target binding domain "T" of the polypeptide comprises the amino acid sequence of SEQ ID NO: 39, corresponding to amino acids 25 - 283 of SEQ ID NO: 98, L1 comprises the amino acid sequence of SEQ ID NO: 72, corresponding to amino acids 284 - 301 of SEQ ID NO: 98, Fc comprises the amino acid sequence of SEQ ID NO: 104, corresponding to amino acids 302 - 542 of SEQ ID NO: 98, L2 is absent, ECD comprises the amino acid sequence of SEQ ID NO: 60, corresponding to amino acids 543 - 584 of SEQ ID NO: 98, and T M comprises the amino acid sequence of SEQ ID NO: 62, corresponding to amino acids 585 - 612 of SEQ ID NO: 98, ICD comprises amino acids 613 - 634 of SEQ ID NO: 98, where the env integration motif comprises the amino acid sequence of SEQ ID NO: 63, corresponding to amino acids 627 - 634 of SEQ ID NO: 98. In some embodiments, T-L1-Fc-L2-ECD-T M- The polypeptides provided herein that include the formula of the ICD include an amino acid sequence that is at least 98% identical to the sequence of SEQ ID NO: 98, wherein the target binding domain "T" of the polypeptide includes the amino acid sequence of SEQ ID NO: 39, corresponding to amino acids 25 to 283 of SEQ ID NO: 98, L1 includes the amino acid sequence of SEQ ID NO: 72, corresponding to amino acids 284 to 301 of SEQ ID NO: 98, Fc includes the amino acid sequence of SEQ ID NO: 104, corresponding to amino acids 302 to 542 of SEQ ID NO: 98, L2 is absent, ECD includes the amino acid sequence of SEQ ID NO: 60, corresponding to amino acids 543 to 584 of SEQ ID NO: 98, T M includes the amino acid sequence of SEQ ID NO: 62, corresponding to amino acids 585 to 612 of SEQ ID NO: 98, ICD includes amino acids 613 to 634 of SEQ ID NO: 98, wherein the env integration motif includes the amino acid sequence of SEQ ID NO: 63, corresponding to amino acids 627 to 634 of SEQ ID NO: 98. In some embodiments, T-L1-Fc-L2-ECD-T M - The polypeptides provided herein that include the formula of the ICD include the amino acid sequence of SEQ ID NO: 98, wherein the target binding domain "T" of the polypeptide includes the amino acid sequence of column number 39, corresponding to amino acids 25 to 283 of SEQ ID NO: 98, L1 includes the amino acid sequence of SEQ ID NO: 72, corresponding to amino acids 284 to 301 of SEQ ID NO: 98, Fc includes the amino acid sequence of SEQ ID NO: 104, corresponding to amino acids 302 to 542 of SEQ ID NO: 98, L2 is absent, ECD includes the amino acid sequence of SEQ ID NO: 60, corresponding to amino acids 543 to 584 of SEQ ID NO: 98, T M includes the amino acid sequence of SEQ ID NO: 62, corresponding to amino acids 585 to 612 of SEQ ID NO: 98, ICD includes amino acids 613 to 634 of SEQ ID NO: 98, wherein the env integration motif includes the amino acid sequence of SEQ ID NO: 63, corresponding to amino acids 627 to 634 of SEQ ID NO: 98.

[0231] In some embodiments, T-L1-Fc-L2-ECD-T M - A polypeptide provided herein that includes the formula of the ICD, wherein T is V H and V Lis a target-binding domain, L1 is a polypeptide linker or absent, Fc is a variant Fc domain provided herein, L2 is a polypeptide linker or absent, ECD is an extracellular domain, T M is a transmembrane domain, ICD is an intracellular domain containing an env integration motif, and contains an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the sequence of SEQ ID NO: 98, and V of the target-binding domain H contains the amino acid sequence of SEQ ID NO: 36, corresponding to amino acids 25-150 of SEQ ID NO: 98, and V of the target-binding domain L contains the amino acid sequence of SEQ ID NO: 37, corresponding to amino acids 172-283 of SEQ ID NO: 98, L1 contains the amino acid sequence of SEQ ID NO: 72, corresponding to amino acids 284-301 of SEQ ID NO: 98, Fc contains the amino acid sequence of SEQ ID NO: 104, corresponding to amino acids 302-542 of SEQ ID NO: 98, L2 is absent, ECD contains the amino acid sequence of SEQ ID NO: 60, corresponding to amino acids 543-584 of SEQ ID NO: 98, T M contains the amino acid sequence of SEQ ID NO: 62, corresponding to amino acids 585-612 of SEQ ID NO: 98, ICD contains amino acids 613-634 of SEQ ID NO: 98, where the env integration motif contains the amino acid sequence of SEQ ID NO: 63, corresponding to amino acids 627-634 of SEQ ID NO: 98. In some embodiments, the polypeptide provided herein containing the formula T-L1-Fc-L2-ECD-T M -ICD contains an amino acid sequence that is at least 90% identical to the sequence of SEQ ID NO: 98, wherein V of the target-binding domain H contains the amino acid sequence of SEQ ID NO: 36, corresponding to amino acids 25-150 of SEQ ID NO: 98, and V of the target-binding domain Lcontains the amino acid sequence of SEQ ID NO: 37, corresponding to amino acids 172-283 of SEQ ID NO: 98, L1 contains the amino acid sequence of SEQ ID NO: 72, corresponding to amino acids 284-301 of SEQ ID NO: 98, Fc contains the amino acid sequence of SEQ ID NO: 104, corresponding to amino acids 302-542 of SEQ ID NO: 98, L2 does not exist, ECD contains the amino acid sequence of SEQ ID NO: 60, corresponding to amino acids 543-584 of SEQ ID NO: 98, T M contains the amino acid sequence of SEQ ID NO: 62, corresponding to amino acids 585-612 of SEQ ID NO: 98, ICD contains amino acids 613-634 of SEQ ID NO: 98, where the env integration motif contains the amino acid sequence of SEQ ID NO: 63, corresponding to amino acids 627-634 of SEQ ID NO: 98. In some embodiments, T-L1-Fc-L2-ECD-T M -ICD, the polypeptides provided herein that contain the formula contain an amino acid sequence that is at least 95% identical to the sequence of SEQ ID NO: 98, wherein the V of the target binding domain H contains the amino acid sequence of SEQ ID NO: 36, corresponding to amino acids 25-150 of SEQ ID NO: 98, the V of the target binding domain L contains the amino acid sequence of SEQ ID NO: 37, corresponding to amino acids 172-283 of SEQ ID NO: 98, L1 contains the amino acid sequence of SEQ ID NO: 72, corresponding to amino acids 284-301 of SEQ ID NO: 98, Fc contains the amino acid sequence of SEQ ID NO: 104, corresponding to amino acids 302-542 of SEQ ID NO: 98, L2 does not exist, ECD contains the amino acid sequence of SEQ ID NO: 60, corresponding to amino acids 543-584 of SEQ ID NO: 98, T M contains the amino acid sequence of SEQ ID NO: 62, corresponding to amino acids 585-612 of SEQ ID NO: 98, ICD contains amino acids 613-634 of SEQ ID NO: 98, where the env integration motif contains the amino acid sequence of SEQ ID NO: 63, corresponding to amino acids 627-634 of SEQ ID NO: 98. In some embodiments, T-L1-Fc-L2-ECD-T M -ICD, the polypeptides provided herein that contain the formula contain an amino acid sequence that is at least 98% identical to the sequence of SEQ ID NO: 98, wherein the V of the target binding domain Hcontains the amino acid sequence of SEQ ID NO: 36, corresponds to amino acids 25-150 of SEQ ID NO: 98, and is the V of the target binding domain L contains the amino acid sequence of SEQ ID NO: 37, corresponds to amino acids 172-283 of SEQ ID NO: 98, L1 contains the amino acid sequence of SEQ ID NO: 72, corresponds to amino acids 284-301 of SEQ ID NO: 98, Fc contains the amino acid sequence of SEQ ID NO: 104, corresponds to amino acids 302-542 of SEQ ID NO: 98, L2 does not exist, ECD contains the amino acid sequence of SEQ ID NO: 60, corresponds to amino acids 543-584 of SEQ ID NO: 98, T M contains the amino acid sequence of SEQ ID NO: 62, corresponds to amino acids 585-612 of SEQ ID NO: 98, ICD contains amino acids 613-634 of SEQ ID NO: 98, where the env integration motif contains the amino acid sequence of SEQ ID NO: 63 and corresponds to amino acids 627-634 of SEQ ID NO: 98. In some embodiments, T-L1-Fc-L2-ECD-T M -ICD, the polypeptide provided herein, contains the amino acid sequence of SEQ ID NO: 98, wherein the V of the target binding domain H contains the amino acid sequence of SEQ ID NO: 36, corresponds to amino acids 25-150 of SEQ ID NO: 98, and is the V of the target binding domain L contains the amino acid sequence of SEQ ID NO: 37, corresponds to amino acids 172-283 of SEQ ID NO: 98, L1 contains the amino acid sequence of SEQ ID NO: 72, corresponds to amino acids 284-301 of SEQ ID NO: 98, Fc contains the amino acid sequence of SEQ ID NO: 104, corresponds to amino acids 302-542 of SEQ ID NO: 98, L2 does not exist, ECD contains the amino acid sequence of SEQ ID NO: 60, corresponds to amino acids 543-584 of SEQ ID NO: 98, T M contains the amino acid sequence of SEQ ID NO: 62, corresponds to amino acids 585-612 of SEQ ID NO: 98, ICD contains amino acids 613-634 of SEQ ID NO: 98, where the env integration motif contains the amino acid sequence of SEQ ID NO: 63 and corresponds to amino acids 627-634 of SEQ ID NO: 98.

[0232] In some embodiments, V having the sequence set forth in SEQ ID NO: 48 H peptide and V having the sequence set forth in SEQ ID NO: 49L The peptide is linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) containing an ECD, T M , and an ICD. In some embodiments, a V H peptide having the sequence set forth in SEQ ID NO: 48 and a V L peptide having the sequence set forth in SEQ ID NO: 49 are linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) containing a CD8 and / or CD28 ECD, T M , and an ICD. In some embodiments, a V H peptide having the sequence set forth in SEQ ID NO: 48 and a V L peptide having the sequence set forth in SEQ ID NO: 49 are linked to a stalk portion (S1) comprising an ECD, CD8 and / or CD28 T M , and an ICD. In some embodiments, a V H peptide having the sequence set forth in SEQ ID NO: 48 and a V L peptide having the sequence set forth in SEQ ID NO: 49 are linked to a stalk portion (S1) comprising a CD8 and / or CD28 ECD, CD8 and / or CD28 T M , and an ICD. In some embodiments, a V H peptide having the sequence set forth in SEQ ID NO: 48 and a V L peptide having the sequence set forth in SEQ ID NO: 49 are linked to a stalk portion (S1) comprising an ECD, T M , and an ICD, where the ICD comprises an env integration motif provided herein. In some embodiments, a V H peptide having the sequence set forth in SEQ ID NO: 48 and a V L peptide having the sequence set forth in SEQ ID NO: 49 are linked to a stalk portion (S1) comprising a CD8 and / or CD28 ECD, T Mand linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) including an ICD, wherein the ICD comprises an env integration motif provided herein. In some embodiments, a V having the sequence set forth in SEQ ID NO: 48 H peptide and a V having the sequence set forth in SEQ ID NO: 49 L peptide are ECD, CD8 and / or CD28 T M and linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) including an ICD, wherein the ICD comprises an env integration motif provided herein. In some embodiments, a V having the sequence set forth in SEQ ID NO: 48 H peptide and a V having the sequence set forth in SEQ ID NO: 49 L peptide are CD8 and / or CD28 ECD, CD8 and / or CD28 T M and linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) including an ICD, wherein the ICD comprises an env integration motif provided herein. In some embodiments, a V having the sequence set forth in SEQ ID NO: 48 H peptide and a V having the sequence set forth in SEQ ID NO: 49 L peptide is an ECD, T fixed to the surface of a virus particle such as those provided herein M and linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) including an ICD. In some embodiments, L1, Fc, L2, ECD, T M and the identity of the ICD is as provided herein. In some embodiments, V H and V L polypeptides bind to immune cells such as those provided herein.

[0233] In some embodiments, a 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 HPeptide; 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: 49 L The peptide is linked to a stalk portion (S1) comprising an Fc region provided herein. In some embodiments, 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: 48 H Peptide; 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: 49 L The peptide further comprises a transmembrane domain and is linked to a stalk portion (S 1) comprising an Fc region. In some embodiments, the Fc region further comprising a transmembrane domain has the formula L1-Fc-L2-X1, wherein L1 is a linker provided herein or is absent, Fc is a mutant Fc region provided herein, L2 is a linker provided herein or is absent, and X1 is a polypeptide comprising a transmembrane domain provided herein. As provided herein, X1 can comprise a polypeptide having the formula ECD-T M -ICD, wherein ECD is an extracellular domain or a fragment thereof provided herein or is absent, TM is a transmembrane domain provided herein, and ICD is an intracellular domain provided herein or is absent. In some embodiments, 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: 48 H Peptide; 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: 49L The peptide is linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) containing an ECD, T M , and an ICD. In some embodiments, a V H peptide 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; a V L peptide is linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) containing a CD8 and / or CD28 ECD, T M , and an ICD. In some embodiments, a V H peptide 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; a V L peptide is linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) containing an ECD, CD8 and / or CD28 T M , and an ICD. In some embodiments, a V 2- peptide 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; a V H peptide 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: 49; a V L peptide is linked to a stalk portion (S1) comprising a CD8 and / or CD28 ECD, CD8 and / or CD28 T Mand is linked to a stalk portion (S1) that includes an Fc region (L1-Fc-L2-X1) containing an ICD. In some embodiments, a V that includes 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 H peptide; a V that includes 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: 49 L peptide is an ECD, T M and is linked to a stalk portion (S1) that includes an Fc region (L1-Fc-L2-X1) containing an ICD, where the ICD includes an env integration motif provided herein. In some embodiments, a V that includes 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 H peptide; a V that includes 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: 49 L peptide is a CD8 and / or CD28 ECD, T M and is linked to a stalk portion (S1) that includes an Fc region (L1-Fc-L2-X1) containing an ICD, where the ICD includes an env integration motif provided herein. In some embodiments, a V that includes 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 H peptide; a V that includes 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: 49 L peptide is an ECD, CD8 and / or CD28 T Mand linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) including an ICD, where the ICD comprises an env integration motif provided herein. In some embodiments, a 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 H peptide; a 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: 49 L peptide is linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) including an ICD, where the ICD comprises an env integration motif provided herein. In some embodiments, a 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 M peptide; and a 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: 49 H peptide is linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) including an ICD, where the ICD comprises an env integration motif provided herein. In some embodiments, a 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 peptide; and a 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: 49 M peptide is linked to a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) including an ICD, where the ICD comprises an env integration motif provided herein. In some embodiments, L1, Fc, L2, ECD, T M and the identity of the ICD is as provided herein. In some embodiments, V H and V L polypeptide binds to immune cells such as those provided herein.

[0234] In some embodiments, V H peptide and VL Polypeptides comprising the peptide V are provided. 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: 48; 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:49.

[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: 48; 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: 49; H Peptides and V L The peptide comprises a light chain CDR having the sequence of SEQ ID NO: 45-47 and / or a heavy chain CDR having the sequence of SEQ ID NO: 42-47. 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: 48; 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: 49; H Peptides and V LThe peptide comprises a light chain CDR1 having the sequence of SEQ ID NO: 45; a light chain CDR2 having the sequence of SEQ ID NO: 46; a light chain CDR3 having the sequence of SEQ ID NO: 47; and / or a heavy chain CDR1 having the sequence of SEQ ID NO: 42; a heavy chain CDR2 having the sequence of SEQ ID NO: 43; and a heavy chain CDR3 having the sequence of SEQ ID NO: 44. In some embodiments, V H or V L The CDRs of the chain are as described in the combinations provided herein.

[0236] In some embodiments, the polypeptide comprises a V H peptide and a V L peptide, and the V H 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; V L the V L 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: 49; provided that the V H peptide comprises an LCDR1 having the sequence of SEQ ID NO: 45; an LCDR2 having the sequence of SEQ ID NO: 46; and an LCDR3 having the sequence of SEQ ID NO: 47; V

[0237] In some embodiments, the polypeptide comprises a V H peptide and a V L peptide, and the V H 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; V 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: 49; provided that V L The peptide comprises an LCDR1 having the sequence of SEQ ID NO: 45 (wherein the LCDR1 comprises at most one conservative amino acid substitution), an LCDR2 having the sequence of SEQ ID NO: 46 (wherein the LCDR2 comprises at most one conservative amino acid substitution), and an LCDR3 having the sequence of SEQ ID NO: 47 (wherein the LCDR3 comprises at most one conservative amino acid substitution); V H The peptide comprises an HCDR1 having the sequence of SEQ ID NO: 42 (wherein the HCDR1 comprises at most one conservative amino acid substitution), an HCDR2 having the sequence of SEQ ID NO: 43 (wherein the HCDR2 comprises at most one conservative amino acid substitution), and an HCDR3 having the sequence of SEQ ID NO: 44 (wherein the HCDR3 comprises at most one conservative amino acid substitution).

[0238] In some embodiments, the polypeptide is V H the peptide and V L the peptide, and V H the peptide comprises the sequence of SEQ ID NO: 48, and V L the peptide comprises the sequence of SEQ ID NO: 49.

[0239] In some embodiments, the polypeptides provided herein bind to non-human primate CD8. In some embodiments, the polypeptides provided herein bind to human CD8.

[0240] As provided herein, the different polypeptides (V H or V L ) described herein can be linked with a peptide linker or linked in a continuous sequence without a peptide linker. In some embodiments, the peptide linker is (GGGGS) nIt includes the array of (Sequence Number 55), and 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 conjugated peptide format is V H -Z-V L or V L -Z-V H and can be represented by the formula, where Z is a peptide linker. In some embodiments, Z is (GGGGS) n (Sequence Number 55), and 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.

[0241] In some embodiments, the polypeptide containing the conjugated peptide represented by the formula V L -Z-V H includes the heavy chain variable region described in Sequence Number 48, which is conjugated to the light chain variable region described in Sequence Number 49 via the linker sequence GGGGSGGGGSGGGGSGGGGS (Sequence Number 72). In some embodiments, V H conjugated to V L via a peptide linker has the following sequence: NIVLTQSPASLAVSLGQRATISCRASESVDGFGNSFMNWYQQKPGQSPKLLIYLASNLESGVPARFSGSGSRTDFTLTIDPVEADDAATYYCQQNNEDPYTFGGGTKLEIKRGGGGSGGGGSGGGGSGGGGSEVQLQQSGPELVKPGASVKISCKASRYTFTDYNLHWVKLSHEKSLEWIGFIYPYNGGTGYNQKFKNKAKLTVDYSSSTAYMELRSLTSVDAAVYYCARDHRYNEGVSFDYWGQGTTLTVSS (Sequence Number 50).

[0242] 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: 50. In some embodiments, the polypeptide comprises a sequence that is at least 90% identical to the sequence of SEQ ID NO: 50. In some embodiments, the polypeptide comprises a sequence that is at least 95% identical to the sequence of SEQ ID NO: 50. In some embodiments, the polypeptide comprises a sequence that is at least 99% identical to the sequence of SEQ ID NO: 50. In some embodiments, the polypeptide comprises the sequence set forth in SEQ ID NO: 50. In some embodiments, the polypeptide of SEQ ID NO: 50 is an antibody or an 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.

[0243] In some embodiments, V H -Z-V L The polypeptide comprising the linker peptide represented by the formula of is linked to the heavy chain variable region set forth in SEQ ID NO: 48 via the linker sequence GGGGSGGGGSGGGGSGGGGS (SEQ ID NO: 72) and comprises the light chain variable region set forth in SEQ ID NO: 49. In some embodiments, V linked via a peptide linker L to V H The polypeptide comprising has the sequence described below, EVQLQQSGPELVKPGASVKISCKASRYTFTDYNLHWVKLSHEKSLEWIGFIYPYNGGTGYNQKFKNKAKLTVDYSSSTAYMELRSLTSVDAAVYYCARDHRYNEGVSFDYWGQGTTLTVSSGGGGSGGGGSGGGGSGGGGSNIVLTQSPASLAVSLGQRATISCRASESVDGFGNSFMNWYQQKPGQSPKLLIYLASNLESGVPARFSGSGSRTDFTLTIDPVEADDAATYYCQQNNEDPYTFGGGTKLEIKR (SEQ ID NO: 51).

[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: 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 an 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.

[0245] 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: 50, and comprises a stalk portion (S1) comprising 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: 50, and comprises a stalk portion (S1) comprising an Fc region, wherein the Fc region further comprises a transmembrane domain such as those provided herein. In some embodiments, the Fc region further comprising a transmembrane domain has the formula L1-Fc-L2-X1, wherein L1 is a linker provided herein or is absent, Fc is a mutant Fc region provided herein, L2 is a linker provided herein or is absent, and X1 is a polypeptide comprising a transmembrane domain provided herein. As provided herein, X1 has the formula ECD-T M -ICD and may comprise a polypeptide, wherein ECD is an extracellular domain or a fragment thereof provided herein or is absent, and T M is a transmembrane domain provided herein, and ICD is an intracellular domain provided herein or is absent. 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: 50, and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising ECD, T M , and ICD. 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: 50, and comprises CD8 and / or CD28 ECD, TM and a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) containing an ICD. 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: 50, and an ECD, CD8 and / or CD28 T M and a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) containing an ICD. In some embodiments, the polypeptide 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: 50, and a CD8 and / or CD28 ECD, CD8 and / or CD28 T M and a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) containing an ICD. 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: 50, and an ECD, T M and a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) containing an ICD, wherein the ICD comprises an env integration motif 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: 50, and a CD8 and / or CD28 ECD, T Mand a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) containing an ICD, where the ICD comprises an env integration motif 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: 50, ECD, CD8 and / or CD28 T M and a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) containing an ICD, where the ICD comprises an env integration motif 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: 50, CD8 and / or CD28 ECD, CD8 and / or CD28 T M and a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) containing an ICD, where the ICD comprises an env integration motif 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: 50, ECD fixed to the surface of virus particles such as those provided herein, T M and a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) containing an ICD. In some embodiments, L1, Fc, L2, ECD, T M and the identity of the ICD is as provided herein. In some embodiments, the polypeptide binds to immune cells such as those provided herein.

[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: 51, and comprises a stalk portion (S1) that includes 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 a stalk portion (S1) that includes an Fc region, and the Fc region further comprises a transmembrane domain, such as those provided herein. In some embodiments, the Fc region further comprising a transmembrane domain has the formula L1-Fc-L2-X1, wherein L1 is a linker provided herein or is absent, Fc is a mutant Fc region provided herein, L2 is a linker provided herein or is absent, and X1 is a polypeptide comprising a transmembrane domain provided herein. As provided herein, X1 has the formula ECD-T M -ICD and may comprise a polypeptide, wherein ECD is an extracellular domain or a fragment thereof provided herein or is absent, and T M is a transmembrane domain provided herein, and ICD is an intracellular domain provided herein or is absent. 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 a stalk portion (S1) that includes an Fc region (L1-Fc-L2-X1) comprising ECD, TM, and ICD. 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 CD8 and / or CD28 ECD, T M, and includes a stalk portion (S1) that includes an Fc region (L1-Fc-L2-X1) containing an ICD. In some embodiments, the polypeptide includes 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 an ECD, CD8 and / or CD28 T M , and includes a stalk portion (S1) that includes an Fc region (L1-Fc-L2-X1) containing an ICD. In some embodiments, the polypeptide includes 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 a CD8 and / or CD28 ECD, CD8 and / or CD28 T M , and includes a stalk portion (S1) that includes an Fc region (L1-Fc-L2-X1) containing an ICD. In some embodiments, the polypeptide includes 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 an ECD, T M , and includes a stalk portion (S1) that includes an Fc region (L1-Fc-L2-X1) containing an ICD, where the ICD includes an env integration motif provided herein. In some embodiments, the polypeptide includes 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 a CD8 and / or CD28 ECD, T Mand a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) containing an ICD, where the ICD contains an env integration motif 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 the ECD, CD8 and / or CD28 T M and a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) containing an ICD, where the ICD contains an env integration motif 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 the CD8 and / or CD28 ECD, CD8 and / or CD28 T M and a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) containing an ICD, where the ICD contains an env integration motif 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 the ECD, fixed to the surface of virus particles such as those provided herein, T M and a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) containing an ICD. In some embodiments, L1, Fc, L2, ECD, T M and the identity of the ICD is as provided herein. In some embodiments, the polypeptide binds to immune cells such as those provided herein.

[0247] In some embodiments, the polypeptide comprises a sequence having the sequence set forth in SEQ ID NO: 50 and comprises a stalk portion (S1) comprising 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: 50 and comprises a stalk portion (S1) comprising an Fc region, and the Fc region further comprises a transmembrane domain, such as those provided herein. In some embodiments, the Fc region further comprising a transmembrane domain has the formula L1-Fc-L2-X1, wherein L1 is a linker provided herein or is absent, Fc is a mutant Fc region provided herein, L2 is a linker provided herein or is absent, and X1 is a polypeptide comprising a transmembrane domain provided herein. As provided herein, X1 has the formula ECD-T M -ICD and may comprise a polypeptide, wherein ECD is an extracellular domain or a fragment thereof provided herein or is absent, and T M is a transmembrane domain provided herein, and ICD is an intracellular domain provided herein or is absent. In some embodiments, the polypeptide comprises a sequence having the sequence set forth in SEQ ID NO: 50 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising ECD, T M , and ICD. In some embodiments, the polypeptide comprises a sequence having the sequence set forth in SEQ ID NO: 50 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising CD8 and / or CD28 ECD, T M , and ICD. In some embodiments, the polypeptide comprises a sequence having the sequence set forth in SEQ ID NO: 50 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising ECD, CD8 and / or CD28 T M , and ICD. In some embodiments, the polypeptide comprises a sequence having the sequence set forth in SEQ ID NO: 50 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising CD8 and / or CD28 ECD, CD8 and / or CD28 T Mand a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) including an ICD. In some embodiments, the polypeptide comprises a sequence having the sequence set forth in SEQ ID NO: 50, an ECD, T M and a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) including an ICD, wherein the ICD comprises an env integration motif provided herein. In some embodiments, the polypeptide comprises a sequence having the sequence set forth in SEQ ID NO: 50, a CD8 and / or CD28 ECD, T M and a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) including an ICD, wherein the ICD comprises an env integration motif provided herein. In some embodiments, the polypeptide comprises a sequence having the sequence set forth in SEQ ID NO: 50, an ECD, a CD8 and / or CD28 T M and a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) including an ICD, wherein the ICD comprises an env integration motif provided herein. In some embodiments, the polypeptide comprises a sequence having the sequence set forth in SEQ ID NO: 50, a CD8 and / or CD28 ECD, a CD8 and / or CD28 T M and a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) including an ICD, wherein the ICD comprises an env integration motif provided herein. In some embodiments, the polypeptide comprises a sequence having the sequence set forth in SEQ ID NO: 50, an ECD fixed to the surface of a viral particle such as those provided herein, T M and a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) including an ICD. In some embodiments, L1, Fc, L2, ECD, T M and the identity of the ICD is as provided herein. In some embodiments, the polypeptide binds to an immune cell such as those provided herein.

[0248] In some embodiments, the polypeptide comprises a sequence having the sequence set forth in SEQ ID NO: 51 and comprises a stalk portion (S1) comprising 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 a stalk portion (S1) comprising an Fc region, and the Fc region further comprises a transmembrane domain, such as those provided herein. In some embodiments, the Fc region further comprising a transmembrane domain has the formula L1-Fc-L2-X1, wherein L1 is a linker provided herein or is absent, Fc is a mutant Fc region provided herein, L2 is a linker provided herein or is absent, and X1 is a polypeptide comprising a transmembrane domain provided herein. As provided herein, X1 has the formula ECD-T M -ICD and may comprise a polypeptide, wherein ECD is an extracellular domain or a fragment thereof provided herein or is absent, and T M is a transmembrane domain provided herein, and ICD is an intracellular domain provided herein or is absent. In some embodiments, the polypeptide comprises a sequence having the sequence set forth in SEQ ID NO: 51 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising ECD, T M , and ICD. In some embodiments, the polypeptide comprises a sequence having the sequence set forth in SEQ ID NO: 51 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising CD8 and / or CD28 ECD, T M , and ICD. In some embodiments, the polypeptide comprises a sequence having the sequence set forth in SEQ ID NO: 51 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising ECD, CD8 and / or CD28 T M , and ICD. In some embodiments, the polypeptide comprises a sequence having the sequence set forth in SEQ ID NO: 51 and comprises a stalk portion (S1) comprising an Fc region (L1-Fc-L2-X1) comprising CD8 and / or CD28 ECD, CD8 and / or CD28 T M, and includes a stalk portion (S1) that includes an Fc region (L1-Fc-L2-X1) containing an ICD. In some embodiments, the polypeptide includes a sequence having the sequence set forth in SEQ ID NO: 51, an ECD, T M , and includes a stalk portion (S1) that includes an Fc region (L1-Fc-L2-X1) containing an ICD, where the ICD includes an env integration motif provided herein. In some embodiments, the polypeptide includes a sequence having the sequence set forth in SEQ ID NO: 51, a CD8 and / or CD28 ECD, T M , and includes a stalk portion (S1) that includes an Fc region (L1-Fc-L2-X1) containing an ICD, where the ICD includes an env integration motif provided herein. In some embodiments, the polypeptide includes a sequence having the sequence set forth in SEQ ID NO: 51, an ECD, a CD8 and / or CD28 T M , and includes a stalk portion (S1) that includes an Fc region (L1-Fc-L2-X1) containing an ICD, where the ICD includes an env integration motif provided herein. In some embodiments, the polypeptide includes a sequence having the sequence set forth in SEQ ID NO: 51, a CD8 and / or CD28 ECD, a CD8 and / or CD28 T M , and includes a stalk portion (S1) that includes an Fc region (L1-Fc-L2-X1) containing an ICD, where the ICD includes an env integration motif provided herein. In some embodiments, the polypeptide includes a sequence having the sequence set forth in SEQ ID NO: 51, an ECD fixed to the surface of a viral particle such as those provided herein, T M , and includes a stalk portion (S1) that includes an Fc region (L1-Fc-L2-X1) containing an ICD. In some embodiments, L1, Fc, L2, ECD, T M , and the identity of the ICD is as provided herein. In some embodiments, the polypeptide binds to an immune cell such as those provided herein.

[0249] A targeting moiety comprising a flexible polypeptide In some embodiments, V H and V L polypeptides are linked to a stalk portion (S1) that includes a flexible polypeptide (L3) provided herein. In some embodiments, V H and V L polypeptides are linked to a stalk portion (S1) that includes a flexible polypeptide that further includes a polypeptide having a transmembrane domain provided herein. In some embodiments, the flexible polypeptide that further includes a polypeptide having a transmembrane domain is represented by the formula L3-X1, where L3 is the flexible polypeptide provided herein and X1 is as provided herein. As provided herein, X1 can include a polypeptide having the formula ECD-T M -ICD, where ECD is an extracellular domain, or a fragment thereof provided herein, or is absent, T M is the transmembrane domain provided herein, and ICD is an intracellular domain provided herein or is absent. Examples of ECD include, but are not limited to, the extracellular domains of CD8 and / or CD28 ECD provided herein. Examples of T M include, but are not limited to, the CD8 and / or CD28 transmembrane domains provided herein. It should be understood that in any of the following embodiments, ECD, ICD, or both may optionally be absent. Thus, embodiments where X1 includes CD8 and / or CD28 ECD, CD8 and / or CD28 T M , and an ICD that includes an Env integration motif are understood to encompass the following X1 members: i) CD8 and / or CD28 ECD, CD8 and / or CD28 T M , and an ICD that includes an Env integration motif; ii) CD8 and / or CD28 T M , and an ICD that includes an Env integration motif and where ECD is absent; iii) CD8 and / or CD28 ECD and CD8 and / or CD28 T where ICD is absentM ; and iv) CD8 and / or CD28 T cells in which neither ECD nor ICD is present M . Similarly, embodiments in which X1 is CD8 and / or CD28 T cells M and includes an ICD containing an Env integration motif are understood to include the following X1 members: i) CD8 and / or CD28 T cells M and an ICD containing an Env integration motif, and ii) CD8 and / or CD28 T cells in which no ICD is present M . Similarly, embodiments in which X1 is CD8 and / or CD28 ECD as well as CD8 and / or CD28 T cells M are understood to include the following X1 members: i) CD8 and / or CD28 ECD as well as CD8 and / or CD28 T cells M ; and ii) CD8 and / or CD28 T cells in which no ECD is present M . It will be further understood that the foregoing description also applies to embodiments in which a specific ECD, T cell M , or ICD is not listed. For example, embodiments i...

Claims

1. A virus particle comprising a heterologous viral glycoprotein and a targeting moiety, wherein the targeting moiety comprises a polypeptide having the formula T-S １ wherein T is a target binding domain and S １ is a stalk portion, and the stalk portion S １ comprises a variant Fc protein, wherein the variant Fc protein comprises a transmembrane domain and an effector mutation that inhibits the interaction of the Fc protein with an Fc-interacting protein, and optionally, the Fc-interacting protein is one of FcγR, C1q, FcRβ, or FcRn, and the S １ stalk portion is bound to the surface of the virus particle via the transmembrane domain, the virus particle.

2. The viral particle according to claim 1, wherein the variant Fc protein comprises a variant of the amino acid sequence of SEQ ID NO: 26, SEQ ID NO: 27, or SEQ ID NO:

28.

3. The viral particle according to claim 1, wherein the variant Fc protein is a variant IgG1 Fc protein comprising one or more mutations selected from the group consisting of L234A, L235A, N297A, P329G, I253A, H310A, and H435A.

4. The viral particle according to claim 3, wherein the variant IgG1 Fc protein comprises an amino acid sequence having at least 70% identity to SEQ ID NO: 103 and comprises one or more mutations corresponding to L19A, L20A, N82A, P114G, I38A, H95A, and / or H220A of SEQ ID NO:

103.

5. The viral particle according to claim 4, wherein the variant IgG1 Fc protein comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 104, at least 85% identity to SEQ ID NO: 104, at least 90% identity to SEQ ID NO: 104, at least 95% identity to SEQ ID NO: 104, at least 98% identity to SEQ ID NO: 104, or at least 100% identity to SEQ ID NO:

104.

6. Said targeting moiety having the formula T-S １ comprises a stalk portion S １ having the formula L-Fc-L ２ -X １ wherein the stalk portion S １ is as defined in the formula, L １ is either a linker or does not exist; Fc is a variant Fc protein; L ２ is either a linker or absent; X １ is a polypeptide containing the transmembrane domain, the formula T-S １ wherein the targeting moiety having １ is T-L ２ -Fc-L １ -X, the virus particle according to claim 1 having the formula

7. L １ or L ２ is, independently of each other, (GGGGG A) ｎ (SEQ ID NO: 54), (GGGGG S) ｎ (SEQ ID NO: 55), (EAAA K) ｎ (SEQ ID NO: 73), A(EAAA K) ｎ A(SEQ ID NO: 74), (XP) ｎ (SEQ ID NO: 75), wherein X is a polypeptide linker comprising one of Ala, Lys, or Glu, GSAGSAAGSGEF (SEQ ID NO: 56), KESGSVSSQLAQFRSLD (SEQ ID NO: 57), EGKSGSGSKSKESKST (SEQ ID NO: 58), AEAAAK EAAAKA (SEQ ID NO: 76), or a combination thereof, and each n is independently 1 to 5, the virus particle according to claim 6.

8. L １ is (GGGGG A) ｎ (SEQ ID NO: 54) or (GGGGG S) ｎ (SEQ ID NO: 55), and The viral particle according to claim 6, wherein each n is independently 1 to 5.

9. X １ comprises a polypeptide having the formula of ECD-T Ｍ -ICD, wherein ECD is the extracellular domain of a cell surface protein, or a fragment thereof, or is absent; T Ｍ is a transmembrane domain of a transmembrane protein; ICD is the intracellular domain, or a protein that facilitates the incorporation of the targeting moiety into the envelope of the viral particle, or is absent, The aforementioned T-L １ -Fc-L ２ -X １ The aforementioned targeting moiety having the formula of is T-L １ -Fc-L ２ -ECD-T Ｍ -ICD, the virus particle according to claim 6.

10. The viral particle according to claim 9, wherein the ECD comprises the amino acid sequence of SEQ ID NO: 59 or SEQ ID NO:

60.

11. The above-mentioned T Ｍ The viral particle according to claim 9, wherein T comprises the amino acid sequence of SEQ ID NO: 61 or SEQ ID NO:

62.

12. The viral particle according to claim 9, wherein the ICD comprises an Env integration motif, and the Env integration motif comprises the amino acid sequence of SEQ ID NO: 63 or SEQ ID NO:

64.

13. The target binding domain (T) binds to immune cells, where the immune cells are 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; 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; SLC7A10+ adipocytes, the virus particle according to claim 1.

14. The target binding domain (T) is a glycosylated CD43 epitope that is expressed in acute leukemia or lymphoma, but not in hematopoietic progenitor cells, among 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 that is expressed in non-hematopoietic cancer; kinase anchor protein 4 (AKAP-4); adrenergic receptor beta 3 (ADRB3); AFP; anaplastic lymphoma kinase (ALK); androgen receptor; angiopoietin-binding cell surface receptor 2 (Tie 2); autoantibody against desmoglein 1 (Dsg1); autoantibody against 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); CCTC-binding factor (zinc finger protein)-like (BORIS or homolog of imprinting site regulator); CCR4; CD5; CD19; CD20; CD22; CD24; CD30; CD32 (FCGR2A); CD33; CD34; CD38; CD44v6; CD72; CD79a; CD79b; CD97; CD99; CD123; CD171; CD179a; CD179b-IGLll; CD200R; CD276 / B7H3; CD300 molecule-like family member f (CD300LF); CDH1-CD324; CDH6; CDH17; CDH19; chromosome X open reading frame 61 (CXORF61); claudin 6 (CLDN6); claudin 18.2 (CLD18A2 or CLDN18A.2); CMV pp65; 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 Bl; Cytochrome P450 IB1 (CYP1B1); DLL3; EBV-EBNA3c; EGF-bke module-containing mucin-like hormone receptor-like 2 (EMR2); Mutant elongation factor 2 (ELF2M); Ephrin B2; Ephrin A-type 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); Folic acid receptor alpha (Fra or FR1); Folic acid receptor beta (FRb); Follicle-stimulating hormone receptor (FSHR); Fos-related antigen 1; Fucosyl GM1; G protein-coupled receptor class C group 5 member D (GPRC5D); G protein-coupled receptor 20 (GPR20); GAD; Ganglioside G2 (GD2); Ganglioside GD3 (aNeu5Ac(2-8)aNeu5Ac(2-3)bDGalp(1-4)bDGlc(1-1)Cer); Ganglioside GM3 (aNeu5Ac(2-3)bDGalp(1-4)bDGlc(1-1)Cer); GD3; GFR alpha 4; Glycoprotein 100 (gp100); Glypican-3 (GPC3); Gonadotropin hormone receptor (CGHR or GR); GpA33; GpNMB; GPRC5D; Guanylate cyclase C (GCC); Heat shock protein 70-2 mutant (mut hsp70-2); Hepatitis A virus cell receptor 1 (HAVCR1); Hexasaccharide moiety of globoH glycosphingolipid (GloboH); High molecular weight melanoma-associated antigen (HMWMAA); HIV1 envelope glycoprotein; HLA; HLA-DOA; HLA-A; HLA-A2; HLA-B; HLA-C; HLA-DM; HLA-DOB; HLA-DP; HLA-DQ; HLA-DR; HLA-G; HTLV1-Tax; Human papillomavirus E6 (HPV E6); Human papillomavirus E7 (HPV E7); Human telomerase reverse transcriptase (hTERT); IgE; IL13Ra2; Ill lRa; Immunoglobulin lambda-like polypeptide 1 (IGLL1);Influenza A hemagglutinin (HA); Insulin-like growth factor 1 receptor (IGF-I receptor); Interleukin 11 receptor alpha (IL-11Ra); 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; Liv1; Locus K 9 (LY6K); Low-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 recognized by T cells 1 (MelanA or MART1); Melanoma-associated antigen 1 (MAGE-A1); Melanoma cancer testis antigen 1 (MAD-CT-1); Melanoma cancer testis antigen 2 (MAD-CT-2); Melanoma apoptosis inhibitor (ML-IAP); Mesothelin; MPL; Mucin 1 cell surface-associated (MUC1); N-acetylglucosaminyltransferase V (NA17); Necltin 4; Neural cell adhesion molecule (NCAM); NKG2D; NYBR1; O-acetyl-GD2 ganglioside (OAcGD2); Olfactory receptor 51E2 (OR51E2); Oncogene fusion protein consisting of breakpoint cluster region (BCR) and Abelson murine leukemia virus oncogene homolog 1 (Abl) (bcr-abl); P53 mutant; Paired box protein Pax-3 (PAX3); Paired box protein Pax-5 (PAX5); Pannexin 3 (PANX3); PDL1; P-glycoprotein; Placenta-specific 1 (PLAC1); Platelet-derived growth factor receptor beta (PDGFR-beta); Polysialic acid; Proacrosin-binding protein sp32 (OY-TES1); Prostase; Prostate cancer tumor antigen-1 (PCT A-1 or galectin 8); Prostate stem cell antigen (PSCA); Prostate-specific membrane antigen (PSMA); Prostate acid phosphatase (PAP); Prostain; Protease serine 21 (testisin or PRSS21);Proteasome (prososome macropain) subunit beta type 9 (LMP2); PTK7; Ras G12V; 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 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 breakpoint 2 (SSX2); TCR gamma alternative reading frame protein (TARP); TCR-beta1 chain; TCR-beta2 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 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 virus oncogene neuroblastoma-derived homolog (MYCN); Wilms tumor protein (WT1); or the virus particle according to claim 1, which binds to X antigen family member 1A (XAGE1).;

15. The target binding domain (T) binds to CD7, the virus particle according to claim 14.

16. The target binding domain (T) includes a heavy chain variable region of a heavy chain having at least 90% sequence identity to SEQ ID NO: 36 and a light chain variable region of a light chain having at least 90% sequence identity to SEQ ID NO: 37, and includes a polypeptide comprising the heavy chain and the light chain, where the polypeptide includes the sequences of HCDR1 set forth in SEQ ID NO: 30; HCDR2 set forth in SEQ ID NO: 31; HCDR3 set forth in SEQ ID NO: 32; LCDR1 set forth in SEQ ID NO: 33; LCDR2 set forth in SEQ ID NO: 34; and LCDR3 set forth in SEQ ID NO: 35, the virus particle according to claim 15.

17. The heavy chain includes a heavy chain variable region of the heavy chain having at least 90% sequence identity, at least 95% sequence identity, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 36; the light chain includes a light chain variable region of the light chain having at least 90% sequence identity, at least 95% sequence identity, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 37 or includes the amino acid sequence of SEQ ID NO: 37, the virus particle according to claim 16.

18. The target binding domain (T) that binds to CD7 comprises a polypeptide having a sequence with at least 90% sequence identity to SEQ ID NO: 38, at least 95% sequence identity to SEQ ID NO: 38, at least 99% sequence identity to SEQ ID NO: 38, or a sequence comprising the sequence set forth in SEQ ID NO: 38, the virus particle according to claim 15.

19. The target binding domain (T) that binds to CD7 comprises a polypeptide having a sequence with at least 90% sequence identity to SEQ ID NO: 39, at least 95% sequence identity to SEQ ID NO: 39, at least 99% sequence identity to SEQ ID NO: 39, or a sequence comprising the sequence set forth in SEQ ID NO: 39, the virus particle according to claim 15.

20. The virus particle according to claim 1, wherein the heterologous viral glycoprotein is a VSV-G polypeptide.

21. The virus particle according to claim 20, wherein the VSV-G polypeptide has at least 70% identity to SEQ ID NO: 2 and comprises an amino acid sequence containing a mutation at position 182 as compared to SEQ ID NO:

2.

22. The virus particle according to claim 20, wherein the VSV-G polypeptide contains a mutation of I182E or I182D as compared to SEQ ID NO:

2.

23. The virus particle according to claim 20, wherein the VSV-G polypeptide comprises a sequence of 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% to the sequence of SEQ ID NO:

4.

24. The virus particle according to claim 20, wherein the VSV-G polypeptide comprises a sequence of 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% to the sequence of SEQ ID NO:

5.

25. The virus particle according to claim 21, wherein the VSV-G protein further contains a mutation at position 214 and / or 352 of SEQ ID NO:

2.

26. The viral particle according to claim 25, wherein the mutation at position 182 is I182D or I182E, the mutation at position 214 is T214N, and the mutation at position 352 is T352A.

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

25.

28. The viral particle according to claim 1, wherein the viral particle further comprises a nucleic acid molecule encoding a heterologous molecule of interest.

29. The viral particle according to claim 28, wherein the heterologous molecule of interest is a chimeric antigen receptor ("CAR").

30. The viral particle according to claim 29, wherein the CAR comprises an antigen-binding domain comprising an antibody or a fragment thereof, and the antibody or the fragment thereof is an antibody, scFv antibody, antigen-binding domain, ankyrin repeat, VHH domain antibody, nanobody, single-domain antibody, or FN3 antibody.

31. The viral particle according to claim 30, wherein the antigen-binding domain of the CAR binds to CD20.

32. The viral particle according to claim 31, comprising a polypeptide comprising a heavy chain variable region of the heavy chain having at least 90% identity to the amino acid sequence of SEQ ID NO: 89, at least 95% identity to the amino acid sequence of SEQ ID NO: 89, or at least 99% identity to the amino acid sequence of SEQ ID NO: 89, or comprising the amino acid sequence of SEQ ID NO: 89; and a light chain variable region of the light chain having at least 90% identity to the amino acid sequence of SEQ ID NO: 90, at least 95% identity to the amino acid sequence of SEQ ID NO: 90, or at least 99% identity to the amino acid sequence of SEQ ID NO: 90, or comprising the amino acid sequence of SEQ ID NO:

90.

33. The viral particle according to claim 31, comprising a polypeptide having at least 90% sequence identity to SEQ ID NO: 92, at least 95% sequence identity to SEQ ID NO: 92, at least 99% sequence identity to SEQ ID NO: 92, or comprising the sequence set forth in SEQ ID NO: 92, wherein the antigen-binding domain binds to CD20.

34. The viral particle according to claim 31, wherein the antigen-binding domain that binds to CD20 comprises a polypeptide having a sequence with at least 90% sequence identity to SEQ ID NO: 93, at least 95% sequence identity to SEQ ID NO: 93, at least 99% sequence identity to SEQ ID NO: 93, or a polypeptide comprising the sequence set forth in SEQ ID NO:

93.

35. The viral particle according to claim 31, wherein the antigen-binding domain that binds to CD20 comprises a heavy chain variable region of a heavy chain having at least 90% identity to the amino acid sequence of SEQ ID NO: 94, at least 95% identity to the amino acid sequence of SEQ ID NO: 94, or at least 99% identity to the amino acid sequence of SEQ ID NO: 94, or comprising the amino acid sequence of SEQ ID NO: 94; and a light chain variable region of a light chain having at least 90% identity to the amino acid sequence of SEQ ID NO: 95, at least 95% identity to the amino acid sequence of SEQ ID NO: 95, or at least 99% identity to the amino acid sequence of SEQ ID NO: 95, or comprising the amino acid sequence of SEQ ID NO: 95, and comprises a polypeptide comprising the light chain and the heavy chain.

36. The viral particle according to claim 35, wherein the antigen-binding domain that binds to CD20 comprises a polypeptide having a sequence with at least 90% sequence identity to SEQ ID NO: 96, at least 95% sequence identity to SEQ ID NO: 96, at least 99% sequence identity to SEQ ID NO: 96, or a polypeptide comprising the sequence set forth in SEQ ID NO:

96.

37. The viral particle according to claim 35, wherein the antigen-binding domain that binds to CD20 comprises a polypeptide having a sequence with at least 90% sequence identity to SEQ ID NO: 97, at least 95% sequence identity to SEQ ID NO: 97, at least 99% sequence identity to SEQ ID NO: 97, or a polypeptide comprising the sequence set forth in SEQ ID NO:

97.

38. The viral particle according to claim 29, wherein the CAR further comprises a hinge domain, a transmembrane domain, a co-stimulatory domain, and a signaling domain.

39. The viral particle according to claim 31, wherein the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 99, at least 90% identity to SEQ ID NO: 99, at least 95% identity to SEQ ID NO: 99, at least 99% identity to SEQ ID NO: 99, or at least 100% identity to SEQ ID NO:

99.

40. A method of infecting a cell, the method comprising contacting the cell with the viral particle according to any one of claims 1 to 39.

41. A method of infecting a cell in a subject, the method comprising administering to the subject a pharmaceutical composition comprising the viral particle according to claim 1.

42. A method of delivering a heterologous molecule of interest to a cell, the method comprising contacting the cell with the viral particle according to claim 1, wherein the viral particle comprises a nucleic acid molecule encoding the heterologous molecule of interest.

43. A method of delivering a heterologous molecule of interest to a cell of a subject, the method comprising administering to the subject the viral particle according to claim 1, wherein the viral particle comprises a nucleic acid molecule encoding the heterologous molecule of interest.

44. The method according to any one of claims 40 to 43, wherein the cell is an immune cell.

45. The method according to any one of claims 40 to 43, wherein the cell is 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; an SLC7A10+ adipocyte.

46. A method of treating a disease or disorder of a subject, the method comprising administering to the subject the viral particle according to claim 1, wherein the viral particle comprises a nucleic acid molecule encoding a heterologous molecule of interest for treating the disease or disorder.

47. 47. The method of claim 46, wherein the disease or disorder is cancer (such as a T-cell or B-cell disorder or other type of cancer described herein), an immune disorder, an autoimmune disorder, a metabolic disorder, or the like.

48. A heterologous viral glycoprotein and a targeting moiety comprising a polypeptide having the formula T-S １ A viral particle comprising, wherein, T is a target binding domain, and S １ is a stalk portion, the heterologous viral glycoprotein comprises the sequence of SEQ ID NO: 23 or SEQ ID NO: 25; the target binding domain comprises the sequence of SEQ ID NO: 39; The said stalk portion S １ is L １ -Fc-L ２ -X １ and includes the formula of, where in the formula L １ is a linker containing the sequence of SEQ ID NO: 55; Fc is a variant Fc protein comprising the sequence of SEQ ID NO: 104; L ２ is a linker and does not exist; X １ is a polypeptide comprising a transmembrane domain having the formula of ECD-T Ｍ -ICD, wherein ECD is the extracellular domain having the sequence of SEQ ID NO: 60; T Ｍ is a transmembrane domain having the sequence of SEQ ID NO: 62; The viral particle, wherein the ICD is an intracellular domain or protein that facilitates incorporation of the targeting moiety into the envelope of the viral particle, and wherein the ICD comprises an env integration motif comprising the amino acid sequence of SEQ ID NO:

63.

49. 1. A viral particle comprising a heterologous viral glycoprotein and a targeting moiety, the heterologous viral glycoprotein comprises an amino acid sequence having at least 90% identity to SEQ ID NO:23 or SEQ ID NO:25, having 95% identity to SEQ ID NO:23 or SEQ ID NO:25, having at least 99% identity to SEQ ID NO:23 or SEQ ID NO:25, or having at least 100% identity to SEQ ID NO:23 or SEQ ID NO:25; The viral particle, wherein the targeting moiety comprises an amino acid sequence having at least 90% identity to SEQ ID NO:98, at least 95% identity to SEQ ID NO:98, at least 99% identity to SEQ ID NO:98, or at least 100% identity to SEQ ID NO:

98.

50. 50. The viral particle of claim 48 or claim 49, wherein the viral particle further comprises a nucleic acid molecule encoding a CAR, wherein the CAR comprises an amino acid sequence having at least 85% identity to SEQ ID NO:99, at least 90% identity to SEQ ID NO:99, at least 95% identity to SEQ ID NO:99, at least 99% identity to SEQ ID NO:99, or at least 100% identity to SEQ ID NO:99.

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