Pseudovirus particles containing genetically modified chimeric receptor proteins

Abstract

This specification provides a viral particle comprising a heterologous viral glycoprotein and a targeting moiety, wherein the targeting moiety comprises a polypeptide comprising the formula T-S1, where T is the target-binding domain and S1 is the stalk moiety. As provided herein, the viral particle further comprises a nucleic acid molecule encoding a heterologous molecule of interest. As provided herein, the heterologous molecule of interest may be a tandem CAR. This specification also provides a composition comprising the same and a method of using the same.

Description

[Technical Field]

[0001] (Related applications) This application claims the interests of U.S. Provisional Patent Application No. 63 / 508,169, filed on 14 June 2023, which is incorporated herein by reference in its entirety.

[0002] (Reference to electronically submitted sequence listings) This application includes a sequence listing submitted electronically in XML format, the entirety of which is incorporated herein by reference. The XML copy, created on June 6, 2024, is named "INH-028WO_SL" and has a size of 242,242 bytes.

[0003] (Field of invention) The embodiments provided herein relate to viral particles comprising a heterologous viral glycoprotein and a targeting moiety having the formula T-S1, where T is a target-binding domain and S1 is a stalk moiety. The stalk moiety may include a mutant Fc domain. The stalk moiety may include a flexible peptide domain. The embodiments provided herein further relate to compositions comprising the viral particles provided herein and methods of using the same. [Background technology]

[0004] Vesicular stomatitis virus (VSV) is an enveloped, negative-strand RNA virus belonging to the genus Becyclovirus of the family Rhabdoviridae. It is an arbovirus that can infect insects, cattle, horses, and pigs. The VSV genome encodes five structural proteins, including one transmembrane glycoprotein (G). The glycoprotein is a classic type I membrane glycoprotein with an amino-terminal signal peptide, an ectodomain of approximately 450 amino acids, a single α-helix transmembrane segment, and a small intraviral carboxy-terminal domain. The signal peptide is cleaved in the lumen of the endoplasmic reticulum, and the native glycoprotein consists of the ectodomain, transmembrane domain, and intraviral domain.

[0005] G plays a crucial role during the initial stages of viral infection (see Albertini, AAV, Baquero, E., Ferrin, A., and Gaudin, Y. (2012). Molecular and Cellular Aspects of Rhabdovirus Entry. Viruses 4, 117-139). The entire text is incorporated herein by reference. First, it is involved in viral attachment to specific receptors. After binding, the virion enters the cell via the clathrin-mediated endocytosis pathway. In the acidic environment of the endocytic vesicle, G induces fusion between the viral membrane and the endosomal membrane, which releases the genome into the cytosol for subsequent stages of infection. Fusion is catalyzed by a large structural transition from the pre-fusion conformation to the post-fusion conformation (both trimers) induced by low pH (Roche, S., Bresanelli, S., Rey, FA, and Gaudin, Y. (2006). Crystal structure of the low-pH form of the vesicular stomatitis virus glycoprotein G. Science 313, 187-191. Roche, S., Rey, FA, Gaudin, Y., and Bresanelli, S. (2007). Structure of the prefusion form of the vesicular stomatitis virus glycoprotein G. Science 315, 843-848) (each of these references is incorporated herein by reference in its entirety).

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

[0007] Low-density lipoprotein receptor (LDL-R) and other members of this receptor family have been shown to function as VSV receptors (see 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. This document is incorporated herein by reference in its entirety). VSV-G can be used to pseudotype other viruses, but VSV-G pseudotyped lentiviruses (VSV-G-LV) exhibit the same broad affinity as VSV. However, this broad affinity can inhibit selective targeting of specific cell types. Therefore, there is a need for modified (mutated or mutated) VSV-G proteins that can be used to pseudotype viruses that have lost their binding to the LDL receptor. This embodiment satisfies these needs as well as other needs. [Overview of the project]

[0008] In some embodiments, a viral particle is provided. In some embodiments, the viral particle comprises a heterologous viral glycoprotein and a targeting moiety, the targeting moiety comprising a polypeptide having the formula T-S1, where T is a target-binding domain and S1 is a stalk moiety.

[0009] In some embodiments, the stalk portion S1 comprises a mutant Fc protein. In some embodiments, the mutant Fc protein comprises a transmembrane domain, such as but not limited to a CD8 or CD28 transmembrane domain. In some embodiments, the mutant Fc protein comprises an effector mutation, which inhibits the interaction between the Fc protein and Fc-interacting proteins such as FcγR, C1q, FcRβ, or FcRn.

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

[0011] In some embodiments, the mutant IgG1 Fc protein contains 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 mutant Fc protein is a mutant IgG2 Fc protein containing one or more mutations selected from the group consisting of N297A, P329G, I253A, H310A, and H435A.

[0013] In some embodiments, the mutant Fc protein is a mutant IgG4 Fc protein containing 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 formula T-S1 includes a stalk moiety S1 having formula L1-Fc-L2-X1, where L1 is a linker or absent, Fc is a mutant Fc protein, L2 is a linker or absent, and X1 is a polypeptide containing a transmembrane domain.

[0015] In some embodiments, the polypeptide containing the transmembrane domain (X1) is ECD-T M - Contains a polypeptide having the formula ICD, where ECD is either the extracellular domain of a cell surface protein or a fragment thereof, or is absent. M ICD is the transmembrane domain of a transmembrane protein, and ICD is a protein that promotes the incorporation of the targeting portion into the intracellular domain or the envelope of a viral particle, or is absent, and the targeting portion having the formula T-L1-Fc-L2-X1 is the formula T-L1-Fc-L2-ECD-T M - Has an ICD.

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

[0017] In some embodiments, the polypeptide containing the transmembrane domain (X1) is ECD-T M - Contains a polypeptide having the formula ICD, where ECD is either the extracellular domain of a cell surface protein or a fragment thereof, or is absent. MICD is the transmembrane domain of a transmembrane protein, and ICD is a protein that promotes the incorporation of the targeting portion into the intracellular domain or the envelope of a viral particle, or is absent, and the targeting portion having the formula T-L3-X1 is the formula T-L3-ECD-T M - Has an ICD.

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

[0019] In some embodiments, the targeted moiety binds to CD8. In some embodiments, the targeted moiety includes a polypeptide having a heavy chain variable region containing HCDR1 of SEQ ID NO: 42, HCDR2 of SEQ ID NO: 43, and HCDR3 of SEQ ID NO: 44, or a variant thereof. In some embodiments, the targeted moiety includes a polypeptide having a light chain variable region containing LCDR1 of SEQ ID NO: 45, LCDR2 of SEQ ID NO: 46, and LCDR3 of SEQ ID NO: 47, or a variant thereof. In some embodiments, the heavy chain includes a heavy chain variable region having at least 90% sequence identity with SEQ ID NO: 48. In some embodiments, the light chain includes a light chain variable region having at least 90% sequence identity with SEQ ID NO: 49. In some embodiments, the targeted moiety that binds to CD8 includes a polypeptide having a sequence having at least 90% sequence identity with SEQ ID NO: 50. In some embodiments, the targeted moiety that binds to CD8 includes a polypeptide having a sequence having at least 90% sequence identity with 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 a VSV-G polypeptide. In some embodiments, the VSV-G polypeptide includes substitutions at positions I182, T214, and T352 in 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 having at least 95% identity to SEQ ID NOs: 113, 89, 94, 105, or 109, 136, 137, and a light chain variable region having at least 95% identity to SEQ ID NOs: 90, 95, 106, or 110. In some embodiments, the CAR comprises an antigen-binding domain having a heavy chain variable region having at least 95% identity to SEQ ID NOs: 94, and a light chain variable region having at least 95% identity to SEQ ID NOs: 95.

[0023] In some embodiments, the CAR includes an antigen-binding domain having an amino acid sequence that is at least 95% identical to SEQ ID NOs. 92, 96, 107, or 111. In some embodiments, the CAR includes an antigen-binding domain having an amino acid sequence that is at least 95% identical to SEQ ID NOs. 93, 97, 108, or 112.

[0024] In some embodiments, the CAR includes an antigen-binding domain having an amino acid sequence that is at least 95% identical to SEQ ID NO: 114 or 118. In some embodiments, the CAR includes an antigen-binding domain having an amino acid sequence that is at least 95% identical to SEQ ID NO: 115 or 119. In some embodiments, the CAR includes an antigen-binding domain having an amino acid sequence that is at least 95% identical to SEQ ID NO: 116, 120, 122, or 124. In some embodiments, the CAR includes an antigen-binding domain having an amino acid sequence that is at least 95% identical to SEQ ID NO: 117, 121, 123, or 125.

[0025] In some embodiments, methods for infecting cells are provided. In some embodiments, the method includes bringing cells into contact with viral particles provided herein.

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

[0027] In some embodiments, a method for delivering a target heterologous molecule to a cell is provided. In some embodiments, the method comprises contacting a cell with a viral particle provided herein, the viral particle comprising a nucleic acid molecule encoding the target heterologous molecule.

[0028] In some embodiments, methods are provided for delivering a target heterologous molecule to target cells. In some embodiments, the method comprises administering viral particles provided herein to the target, the viral particles comprising a nucleic acid molecule encoding the target heterologous molecule.

[0029] In some embodiments, methods are provided for treating a disease or disorder in a subject. In some embodiments, the method comprises administering viral particles provided herein to a subject, the viral particles comprising nucleic acid molecules encoding a target heterogeneous molecule for treating a disease or disorder.

[0030] In some embodiments, a method is provided for delivering heterologous molecules to target cells. In some embodiments, the method comprises contacting cells with viral particles provided herein, the viral particles comprising nucleic acid molecules encoding heterologous molecules.

[0031] In some embodiments, a viral particle is provided. In some embodiments, the viral particle comprises a heterologous viral glycoprotein and a targeting moiety comprising a polypeptide having the formula T-S1, where T is a target-binding domain and S1 is a stalk moiety. The compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 25. 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 target-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 moiety S1 comprises a mutant Fc protein comprising a sequence that is a mutant of SEQ ID NO: 26, SEQ ID NO: 27, or SEQ ID NO: 28. In some embodiments, the mutant 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 mutant 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 mutant 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 mutant Fc protein further includes a transmembrane domain containing a sequence selected from SEQ ID NO: 61 or SEQ ID NO: 62.

[0032] In some embodiments, a viral particle is provided. In some embodiments, the viral particle comprises a heterologous viral glycoprotein and a targeting moiety comprising a polypeptide having the formula T-S1, where T is a target-binding domain and S1 is a stalk moiety. 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 target-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, where L1 is a linker containing or absent 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; Fc is a mutant Fc protein containing a sequence that is a variant of SEQ ID NO: 26, SEQ ID NO: 27, or SEQ ID NO: 28; L2 is a linker containing or absent 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; and X1 is a polypeptide containing 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 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 polypeptide containing the transmembrane domain (X1) is ECD-T M - Having the formula ICD, where 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 portion into the envelope of the viral particle, and ICD contains an Env incorporation motif containing 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 heterologous viral glycoprotein and a targeting portion comprising 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 target 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 the sequence of SEQ ID NO: 55 or is absent; Fc is a mutant Fc protein comprising a sequence that is a mutant 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 mutant 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 mutant 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 mutant 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 ICD, where ECD is either an extracellular domain or fragment thereof having the sequence of sequence number 60, or not present; T M is a transmembrane domain or fragment thereof having the sequence of SEQ ID NO: 62; ICD is an intracellular domain or protein that facilitates the incorporation of the targeting portion into the envelope of the viral particle, and ICD contains an Env incorporation motif having the amino acid sequence of SEQ ID NO: 63 or SEQ ID NO: 64, or ICD is absent.

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

[0035] In some embodiments, a viral particle is provided, which comprises 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, at least 95% identity to SEQ ID NO: 23 or SEQ ID NO: 25, at least 99% identity to SEQ ID NO: 23 or SEQ ID NO: 25, or 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, 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.

[0036] In some embodiments, a viral particle is provided, which comprises 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, at least 95% identity to SEQ ID NO: 52 or SEQ ID NO: 53, at least 99% identity to SEQ ID NO: 52 or SEQ ID NO: 53, or 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, 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.

[0037] In some embodiments, a viral particle is provided. In some embodiments, the viral particle comprises a heterologous viral glycoprotein and a targeting moiety comprising a polypeptide having the formula T-S1, where T is a target-binding domain and S1 is a stalk moiety. 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 moiety S1 comprises the formula L3-X1, where 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 ICD, ECD is either an extracellular domain containing the amino acid sequence of SEQ ID NO: 59 or SEQ ID NO: 60, or a fragment thereof, or is absent, T M The ICD is a transmembrane domain containing the amino acid sequence of SEQ ID NO: 61 or SEQ ID NO: 62, and the ICD is an intracellular domain or protein that facilitates the incorporation of the targeting portion into the envelope of the viral particle, and the ICD contains an Env incorporation motif containing the amino acid sequence of SEQ ID NO: 63 or SEQ ID NO: 64, or the ICD is absent.

[0038] In some embodiments, a viral particle is provided. In some embodiments, the viral particle comprises a heterologous viral glycoprotein and a targeting moiety comprising a polypeptide having the formula T-S1, where T is a target-binding domain and S1 is a stalk moiety. 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 moiety S1 comprises the formula L3-X1, where 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 ICD, ECD is either an extracellular domain containing the amino acid sequence of SEQ ID NO: 59 or SEQ ID NO: 60, or a fragment thereof, or is absent, T M The ICD is a transmembrane domain containing the amino acid sequence of SEQ ID NO: 61 or SEQ ID NO: 62, and the ICD is an intracellular domain or protein that facilitates the incorporation of the targeting portion into the envelope of the viral particle, and the ICD contains an Env incorporation motif containing the amino acid sequence of SEQ ID NO: 63 or SEQ ID NO: 64, or the ICD is absent.

[0039] In some embodiments, a viral particle is provided. In some embodiments, the viral particle comprises a heterologous viral glycoprotein and a targeting moiety comprising a polypeptide having the formula T-S1, where T is a target-binding domain and S1 is a stalk moiety. 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 moiety S1 comprises the formula L3-X1, where 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 ICD, ECD is either an extracellular domain containing the amino acid sequence of SEQ ID NO: 59 or SEQ ID NO: 60, or a fragment thereof, or is absent, T M The ICD is a transmembrane domain containing the amino acid sequence of SEQ ID NO: 61 or SEQ ID NO: 62, and the ICD is an intracellular domain or protein that facilitates the incorporation of the targeting portion into the envelope of the viral particle, and the ICD contains an Env incorporation motif containing the amino acid sequence of SEQ ID NO: 63 or SEQ ID NO: 64, or the ICD is absent.

[0040] In some embodiments, a viral particle is provided. In some embodiments, the viral particle comprises a heterologous viral glycoprotein and a targeting moiety comprising a polypeptide having the formula T-S1, where T is a target-binding domain and S1 is a stalk moiety. 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 moiety S1 comprises the formula L3-X1, where 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 -Having the formula ICD, ECD is either an extracellular domain containing the amino acid sequence of SEQ ID NO: 59 or SEQ ID NO: 60, or a fragment thereof, or is absent, T M The ICD is a transmembrane domain containing the amino acid sequence of SEQ ID NO: 61 or SEQ ID NO: 62, and the ICD is an intracellular domain or protein that facilitates the incorporation of the targeting portion into the envelope of the viral particle, and the ICD contains an Env incorporation motif containing the amino acid sequence of SEQ ID NO: 63 or SEQ ID NO: 64, or the ICD is absent.

[0041] In some embodiments, a viral particle is provided. In some embodiments, the viral particle comprises a heterologous viral glycoprotein and a targeting moiety comprising a polypeptide having the formula T-S1, where T is a target-binding domain and S1 is a stalk moiety. 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 moiety S1 comprises the formula L3-X1, where 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 - It has the formula ICD, and ECD is an extracellular domain containing the amino acid sequence of SEQ ID NO: 59, T M ICD is a transmembrane domain containing the amino acid sequence of SEQ ID NO: 61, and ICD is an intracellular domain or protein that facilitates the incorporation of the targeting portion into the envelope of the viral particle, and ICD contains an Env incorporation motif containing the amino acid sequence of SEQ ID NO: 63 or SEQ ID NO: 64.

[0042] In some embodiments, a viral particle is provided. In some embodiments, the viral particle comprises a heterologous viral glycoprotein and a targeting moiety comprising a polypeptide having the formula T-S1, where T is a target-binding domain and S1 is a stalk moiety. 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 moiety S1 comprises the formula L3-X1, where 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 - It has the formula ICD, and ECD is an extracellular domain containing the amino acid sequence of SEQ ID NO: 59, T MICD is a transmembrane domain containing the amino acid sequence of SEQ ID NO: 61, and ICD is an intracellular domain or protein that facilitates the incorporation of the targeting portion into the envelope of the viral particle, and 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 that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to any one of the sequences of SEQ ID NOs. 126-135. [Brief explanation of the drawing]

[0044] [Figure 1A] The crystal structure of VSV-G bound to LDL-R is shown. Figure 1A shows the crystal structure of VSV-G bound to CR3 of LDL-R. [Figure 1B] Figure 1B shows the crystal structure of VSV-G bound to LDL-R.

[0045] [Figure 2A] The effect of adding negatively charged amino acids to VSV-G is demonstrated. LDL-R binding interacts with innate affinity and fusion properties. Figure 2A shows the titration of the VSV-G construct on SupT1 cells. [Figure 2B] The effect of adding negatively charged amino acids to VSV-G is demonstrated. The LDL-R bond interacts with innate affinity and fusion properties. Figure 2B shows the functional titer of each construct calculated from the titration in Figure 2A.

[0046] [Figure 3-1]This shows the alignment of ectodomains of different VSV-G proteins from different strains. [Figure 3-2] This shows the alignment of ectodomains of different VSV-G proteins from different strains. [Figure 3-3] This shows the alignment of ectodomains of different VSV-G proteins from different strains. [Figure 3-4] This shows the alignment of ectodomains of different VSV-G proteins from different strains.

[0047] [Figure 4] This study demonstrates the effects of various VSV-G mutations on the serum stability of viral constructs combined with CD7 conjugates.

[0048] [Figure 5] This study demonstrates the effects of various VSV-G mutations on the serum stability of viral constructs combined with CD7 conjugates.

[0049] [Figure 6] These various rhabdoviral G proteins, used alone or in combination with CD7 conjugates, demonstrate the ability to transduce SupT1 and PBMC cells.

[0050] [Figure 7A] Flow cytometry data of human PBMCs transduced with exemplary vectors containing the CD7 binder disclosed herein are shown. [Figure 7B] Flow cytometry data of human PBMCs transduced with exemplary vectors containing the CD7 binder disclosed herein are shown. [Figure 7C] Flow cytometry data of human PBMCs transduced with exemplary vectors containing the CD7 binder disclosed herein are shown. [Figure 7D] Flow cytometry data of human PBMCs transduced with exemplary vectors containing the CD7 binder disclosed herein are shown. [Figure 7E]Flow cytometry data of human PBMCs transduced with exemplary vectors containing the CD7 binder disclosed herein are shown. [Figure 7F] Flow cytometry data of human PBMCs transduced with exemplary vectors containing the CD7 binder disclosed herein are shown. [Figure 7G] Flow cytometry data of human PBMCs transduced with exemplary vectors containing the CD7 binder disclosed herein are shown. [Figure 7H] Flow cytometry data of human PBMCs transduced with exemplary vectors containing the CD7 binder disclosed herein are shown. [Figure 7I] Flow cytometry data of human PBMCs transduced with exemplary vectors containing the CD7 binder disclosed herein are shown. [Figure 7J] Flow cytometry data of human PBMCs transduced with exemplary vectors containing the CD7 binder disclosed herein are shown. [Figure 7K] Flow cytometry data of human PBMCs transduced with exemplary vectors containing the CD7 binder disclosed herein are shown. [Figure 7L] Flow cytometry data of human PBMCs transduced with exemplary vectors containing the CD7 binder disclosed herein are shown.

[0051] [Figure 7M] Flow cytometry data of human PBMCs transduced with exemplary vectors containing the CD7 binder disclosed herein are shown.

[0052] [Figure 8A] Flow cytometry data of non-human primate PBMCs transduced with exemplary vectors containing the CD7 binders disclosed herein are shown. [Figure 8B] Flow cytometry data of non-human primate PBMCs transduced with exemplary vectors containing the CD7 binders disclosed herein are shown. [Figure 8C] Flow cytometry data of non-human primate PBMCs transduced with exemplary vectors containing the CD7 binders disclosed herein are shown. [Figure 8D] Flow cytometry data of non-human primate PBMCs transduced with exemplary vectors containing the CD7 binders disclosed herein are shown. [Figure 8E] Flow cytometry data of non-human primate PBMCs transduced with exemplary vectors containing the CD7 binders disclosed herein are shown. [Figure 8F] Flow cytometry data of non-human primate PBMCs transduced with exemplary vectors containing the CD7 binders disclosed herein are shown. [Figure 8G] Flow cytometry data of non-human primate PBMCs transduced with exemplary vectors containing the CD7 binders disclosed herein are shown. [Figure 8H] Flow cytometry data of non-human primate PBMCs transduced with exemplary vectors containing the CD7 binders disclosed herein are shown. [Figure 8I] Flow cytometry data of non-human primate PBMCs transduced with exemplary vectors containing the CD7 binders disclosed herein are shown. [Figure 8J] Flow cytometry data of non-human primate PBMCs transduced with exemplary vectors containing the CD7 binders disclosed herein are shown. [Figure 8K] Flow cytometry data of non-human primate PBMCs transduced with exemplary vectors containing the CD7 binders disclosed herein are shown. [Figure 8L] Flow cytometry data of non-human primate PBMCs transduced with exemplary vectors containing the CD7 binders disclosed herein are shown.

[0053] [Figure 8M]Flow cytometry data of non-human primate PBMCs transduced with exemplary vectors containing the CD7 binders disclosed herein are shown.

[0054] [Figure 9A] Flow cytometry data of human PBMCs transduced with exemplary vectors containing the CD8 binder disclosed herein are shown.

[0055] [Figure 9B] Flow cytometry data of non-human primate PBMCs transduced with exemplary vectors containing the CD8 binder disclosed herein are shown.

[0056] [Figure 10A] This demonstrates the ability of VSV-G* pseudotyped lentivirus particles containing a mutant Fc stalk and a CD7 conjugate to transduce SupT1 cells and human and non-human primate PBMCs. [Figure 10B] This demonstrates cell transduction in the absence of a CD7 binder. [Figure 10C] The MOI calculated from SupT1 titrations shows the transduction of human and non-human primate PBMCs. VSV-G* indicates VSV-G(I182E, T214N, T352A).

[0057] [Figure 11A] This demonstrates the ability of VSV-G* pseudotyped lentivirus particles with a flexible stalk and CD7 conjugate to transduce SupT1 cells and human and non-human primate PBMCs. [Figure 11B] This demonstrates cell transduction in the absence of a CD7 binder. [Figure 11C] The MOI calculated from SupT1 titrations shows the transduction of human and non-human primate PBMCs. VSV-G* indicates VSV-G(I182E, T214N, T352A).

[0058] [Figure 12A]This study demonstrates the ability of viral particles with CD7 conjugates having flexible stalks of varying lengths to transduce SupT1 cells, compared to other IgG-based conjugates. [Figure 12B] This study demonstrates the ability of viral particles with CD7 conjugates having flexible stalks of varying lengths to transduce activated PBMC cells, compared to other IgG-based conjugates.

[0059] [Figure 13A] This demonstrates the ability of SVCV-G pseudotyped lentiviral particles with a mutant Fc stalk and CD7 conjugate to transduce SupT1 cells and human and non-human primate PBMCs. [Figure 13B] This demonstrates cell transduction in the absence of a CD7 binder. [Figure 13C] The MOI calculated from SupT1 titrations shows the transduction of human and non-human primate PBMCs.

[0060] [Figure 14A] This demonstrates the ability of SVCV-G pseudotyped lentiviral particles with a flexible stalk and CD7 conjugate to transduce SupT1 cells and human and non-human primate PBMCs. [Figure 14B] This demonstrates cell transduction in the absence of a CD7 binder. [Figure 14C] The MOI calculated from SupT1 titrations shows the transduction of human and non-human primate PBMCs.

[0061] [Figure 15A] This study compares the ability of VSV-G* pseudotyped lentiviral particles (Panels A and B) and SVCV-G pseudotyped lentiviral particles (Panels C and D) to transduce SupT1 cells and human and non-human primate PBMCs. VSV-G* refers to VSV-G(I182E, T214N, T352A). [Figure 15B]This study compares the ability of VSV-G* pseudotyped lentiviral particles (Panels A and B) and SVCV-G pseudotyped lentiviral particles (Panels C and D) to transduce SupT1 cells and human and non-human primate PBMCs. VSV-G* refers to VSV-G(I182E, T214N, T352A). [Figure 15C] This study compares the ability of VSV-G* pseudotyped lentiviral particles (Panels A and B) and SVCV-G pseudotyped lentiviral particles (Panels C and D) to transduce SupT1 cells and human and non-human primate PBMCs. VSV-G* refers to VSV-G(I182E, T214N, T352A). [Figure 15D] This study compares the ability of VSV-G* pseudotyped lentiviral particles (Panels A and B) and SVCV-G pseudotyped lentiviral particles (Panels C and D) to transduce SupT1 cells and human and non-human primate PBMCs. VSV-G* refers to VSV-G(I182E, T214N, T352A).

[0062] [Figure 16A] This study compares the ability of VSV-G* pseudotyped lentiviral particles (Panels A and B) and SVCV-G pseudotyped lentiviral particles (Panels C and D) to transduce SupT1 cells and human and non-human primate PBMCs. VSV-G* refers to VSV-G(I182E, T214N, T352A). [Figure 16B] This study compares the ability of VSV-G* pseudotyped lentiviral particles (Panels A and B) and SVCV-G pseudotyped lentiviral particles (Panels C and D) to transduce SupT1 cells and human and non-human primate PBMCs. VSV-G* refers to VSV-G(I182E, T214N, T352A). [Figure 16C] This study compares the ability of VSV-G* pseudotyped lentiviral particles (Panels A and B) and SVCV-G pseudotyped lentiviral particles (Panels C and D) to transduce SupT1 cells and human and non-human primate PBMCs. VSV-G* refers to VSV-G(I182E, T214N, T352A). [Figure 16D]This study compares the ability of VSV-G* pseudotyped lentiviral particles (Panels A and B) and SVCV-G pseudotyped lentiviral particles (Panels C and D) to transduce SupT1 cells and human and non-human primate PBMCs. VSV-G* refers to VSV-G(I182E, T214N, T352A).

[0063] [Figure 17A] This is a comparison of off-target transduction of GFP in a panel of B cell lines compared to control SupT1 cells. Figure 17A shows data for VSV-G* pseudotyped lentiviral particles with CD7 conjugates containing mutant Fc stalks. VSV-G* refers to VSV-G(I182E, T214N, T352A). [Figure 17B] This is a comparison of off-target transduction of GFP in a panel of B cell lines compared to control SupT1 cells. Figure 17B shows data for SVCV-G pseudotyped lentiviral particles with a CD7 conjugate containing mutant Fc stalk.

[0064] [Figure 18A] This is a comparison of off-target transduction of CAR20-T2A-GFP constructs in a panel of B cell lines compared to control SupT1 cells. Figure 18A shows data for VSV-G* pseudotyped lentiviral particles with a CD7 conjugate containing mutant Fc stalks. VSV-G* refers to VSV-G(I182E, T214N, T352A). [Figure 18B] This is a comparison of off-target transduction of CAR20-T2A-GFP constructs in a panel of B cell lines compared to control SupT1 cells. Figure 18B shows data for SVCV-G pseudotyped lentiviral particles with CD7 conjugate containing mutant Fc stalks.

[0065] [Figure 19A]This is a comparison of off-target transduction of GFP in a panel of B cell lines compared to the control SupT1. Figure 19A shows data for VSV-G* pseudotyped lentiviral particles with a CD7 conjugate having a flexible stalk. VSV-G* refers to VSV-G(I182E, T214N, T352A). [Figure 19B] This is a comparison of off-target transduction of GFP in a panel of B cell lines compared to the control SupT1. Figure 19B shows data for SVCV-G pseudotyped lentiviral particles with a CD7 conjugate having a flexible stalk.

[0066] [Figure 20A] This is a comparison of off-target transduction of CAR20-T2A-GFP constructs in a panel of B cell lines compared to control SupT1. Figure 20A shows data for VSV-G* pseudotyped lentiviral particles with a CD7 conjugate having a flexible stalk. VSV-G* refers to VSV-G(I182E, T214N, T352A). [Figure 20B] This is a comparison of off-target transduction of CAR20-T2A-GFP constructs in a panel of B cell lines compared to control SupT1. Figure 20B shows data for SVCV-G pseudotyped lentiviral particles with a CD7 conjugate having a flexible stalk.

[0067] [Figure 21] This specification demonstrates that PBMCs transduced with the FHVH33 BCMA CAR construct (SEQ ID NO: 126) provided herein can kill three distinct BCMA-positive multiple myeloma cell lines. The PBMCs were transduced with the viral particles provided herein.

[0068] [Figure 22A] This shows the loss of efficacy of FHVH33 BCMA CAR (SEQ ID NO: 126) PBMCs when BCMA is knocked down in the NCI-H929 multiple myeloma cell line. Figure 22A shows the relative BCMA content in WT and KD cell lines. [Figure 22B] Figure 22B shows the loss of efficacy of FHVH33 BCMA CAR (SEQ ID NO: 126) PBMCs when BCMA is knocked down in the NCI-H929 multiple myeloma cell line. Figure 22B shows the efficacy of CAR (SEQ ID NO: 126) in WT and KD cell lines.

[0069] [Figure 23A] This specification demonstrates the ability of transduced PBMCs with the FCRL5 CAR constructs (SEQ ID NOs. 129 and 130) to kill FCRL5-positive Rec-1 cells. Figure 23A shows the efficacy of the FCRL5 CAR construct (SEQ ID NOs. 129) having VL-VH scFv orientation. [Figure 23B] This specification demonstrates the ability of transduced PBMCs with the FCRL5 CAR constructs (SEQ ID NOs: 129 and 130) to kill FCRL5-positive Rec-1 cells. Figure 23B shows the efficacy of the FCRL5 CAR construct (SEQ ID NO: 130) having VH-VL scFv orientation.

[0070] [Figure 24] This study demonstrates the ability of transduced PBMCs (Primary Bacterial Microorganisms) with the FHVH33 BCMA CAR construct (SEQ ID NO: 126), FCRL5 CAR construct (SEQ ID NO: 130), BCMA-FCRL5 tandem CAR construct (SEQ ID NO: 127), or FCRL5-BCMA tandem CAR construct (SEQ ID NO: 128) to kill BCMA-positive NCI-H929 WT cells.

[0071] [Figure 25] This study demonstrates the ability of transduced PBMCs (Primary Bacterial Microorganisms) with the FHVH33 BCMA CAR construct (SEQ ID NO: 126), FCRL5 CAR construct (SEQ ID NO: 130), BCMA-FCRL5 (SEQ ID NO: 127) tandem CAR construct, or FCRL5-BCMA tandem CAR construct (SEQ ID NO: 128) to kill FCRL5-positive Rec-1 WT cells.

[0072] [Figure 26A]When testing efficacy against Raji (Figure 26A) and Daudi (Figure 26B) cells, m971 HL (SEQ ID NO: 132) is functionally preferable to m971 LH (SEQ ID NO: 133) in CD22 CARs. [Figure 26B] When testing efficacy against Raji (Figure 26A) and Daudi (Figure 26B) cells, m971 HL (SEQ ID NO: 132) is functionally preferable to m971 LH (SEQ ID NO: 133) in CD22 CARs.

[0073] [Figure 27A] This document shows TanCAR20 / 22 (SEQ ID NOs. 134 and 135) that overcome the loss of CD20 or CD22 expression in Raji cells. Figure 27A shows the results in Raji cells with CD20 knockout. [Figure 27B] This document shows TanCAR20 / 22 (SEQ ID NOs. 134 and 135) that overcome the loss of CD20 or CD22 expression in Raji cells. Figure 27B shows the results in Raji cells with CD22 knockout. [Figure 27C] This document shows TanCAR20 / 22 (SEQ ID NOs. 134 and 135) that overcome the loss of CD20 or CD22 expression in Raji cells. Figure 27A shows the results for WT Raji cells.

[0074] [Figure 28A] The dual CAR20 / 22 (SEQ ID NOs. 134 and 135) in the pSF scaffold maintains death against CD20 or CD22 single knockout clones. Figure 28A shows the results of luciferase assays in the provided cell lines. [Figure 28B] Figure 28B shows dual CAR20 / 22 (SEQ ID NOs. 134 and 135) in the pSF scaffold that maintains death against CD20 or CD22 single knockout clones. [Figure 28C]Figure 28C shows dual CAR20 / 22 (SEQ ID NOs. 134 and 135) in the pSF scaffold that maintains death against CD20 or CD22 single knockout clones. [Figure 29] This shows dual CAR20 / 22 (SEQ ID NOs. 134 and 135) in the pSF skeleton that maintains death against single CD20 or CD22 knockout clones.

[0075] [Figure 30A] The effects of CD19 CAR (SEQ ID NO: 203), CD20 CAR (SEQ ID NO: 150), or CD19 / CD20 TanCAR (SEQ ID NOs: 167 and 170) on the induction of Raji cell death when CART cells expressing the indicated CARs are incubated at a predetermined E:T ratio. Figure 30A shows the results for Raji-GFP / luciferase cells. [Figure 30B] The effects of CD19 CAR (SEQ ID NO: 203), CD20 CAR (SEQ ID NO: 150), or CD19 / CD20 TanCAR (SEQ ID NOs: 167 and 170) on inducing Raji cell death when CART cells expressing the indicated CARs are incubated at a predetermined E:T ratio. Figure 30B shows the results for Raji-GFP / luciferase cells in which both CD19 and CD20 were knocked out. [Figure 30C] The effects of CD19 CAR (SEQ ID NO: 203), CD20 CAR (SEQ ID NO: 150), or CD19 / CD20 TanCAR (SEQ ID NOs: 167 and 170) on the induction of Raji cell death when CART cells expressing the indicated CARs are incubated at a predetermined E:T ratio. Figure 30C shows the results for Raji-GFP / luciferase cells with CD19 knockout. [Figure 30D]The effects of CD19 CAR (SEQ ID NO: 203), CD20 CAR (SEQ ID NO: 150), or CD19 / CD20 TanCAR (SEQ ID NOs: 167 and 170) on the induction of Raji cell death when CART cells expressing the indicated CARs are incubated at a predetermined E:T ratio. Figure 30D shows the results for Raji-GFP / luciferase cells with CD20 knockout.

[0076] [Figure 31A] The effect of the TanCAR construct on inducing Raji cell death in a given Raji cell line when CART cells expressing the indicated CAR are incubated at a predetermined E:T ratio is shown. Figure 31A shows the results for CD19-CD20 TanCAR Sequence ID No. 167. [Figure 31B] The effect of the TanCAR construct on inducing Raji cell death in a given Raji cell line when CART cells expressing the indicated CAR are incubated at a predetermined E:T ratio is shown. Figure 31B shows the results for CD19-CD20 TanCAR Sequence ID No. 170. [Modes for carrying out the invention]

[0077] This specification describes a viral particle comprising a heterologous viral glycoprotein and a targeting moiety, wherein the targeting moiety comprises a polypeptide having the formula T-S1, where T is the target-binding domain and S1 is the stalk moiety. . A viral particle is provided. In some embodiments, S1 comprises a mutant Fc polypeptide that can be linked to, for example, a transmembrane domain provided herein. In some embodiments, S1 comprises a flexible polypeptide such as provided herein. The mutant Fc polypeptide or flexible polypeptide can be incorporated into the viral particle to help facilitate the targeting of the viral particle to a specific cell type.

[0078] Furthermore, the viral particles may contain a VSV-G protein, which can be used to pseudotype viruses, such as lentiviruses. In some embodiments, the pseudotyped virus-like particles are pseudotyped using viral glycoproteins of the New Jersey virus strain for bullous stomatitis, the Indiana virus strain for bullous stomatitis, the Aragoas virus strain for bullous stomatitis, the Maraba virus strain for bullous stomatitis, or the Karajas virus strain for bullous stomatitis. Examples of such proteins are provided herein.

[0079] Pseudotyped viruses containing a mutant VSV-G protein, such as those provided herein, can be used in conjunction with a targeting moiety to facilitate the fusion of the pseudotyped virus with a specific cell or tissue based on the expression of a target on the cell or tissue. As provided herein, the targeting moiety may be linked to an Fc protein, which may be called a stalk protein, containing a transmembrane domain to facilitate the attachment of the targeting moiety to the surface of the virus. In some embodiments, the Fc protein includes an Fc effector mutation, such as those provided herein.

[0080] Unless otherwise defined, all technical and scientific terms have the same meaning as they would be generally understood by those skilled in the art in which the disclosed embodiments belong.

[0081] As used herein, the terms "a" or "an" mean "at least one" or "one or more" unless the context clearly indicates otherwise.

[0082] Where used herein, the term “about” means that a number is an approximation and small variations will not significantly affect the implementation of the disclosed embodiment. Where numerical limitations are used, unless the context indicates otherwise, “about” means that the number may vary by ±10% and remain within the scope of the disclosed embodiment. Furthermore, where a phrase describes “about x to y,” the term “about” can be used interchangeably with the phrase “about x to y” unless the context indicates otherwise, modifying both x and y.

[0083] As used herein, the terms “individual,” “subject,” or “patient,” used interchangeably, mean any animal, including mammals such as mice, rats, other rodents, rabbits, dogs, cats, pigs, cattle, sheep, horses, or primates such as humans.

[0084] As used herein, the terms “comprising” (and any other form of “comprising,” such as “comprise,” “comprises,” and “comprised”), “having” (and any other form of “having,” such as “have,” and “has”), “including” (and any other form of “includings,” and “include”), or “containing” (and any other form of “containing,” such as “contains,” and “contain”) are inclusive or non-exclusive and do not exclude additional unlisted elements or method steps. Any step or composition using the transitional phrase “comprise” or “comprising” can be said to describe the same thing as the transitional phrase “consisting of” or “consists.”

[0085] As used herein, the term “contact” means bringing two elements together in an in vitro or in vivo setting. For example, “contact” of a virus or vector described herein with an individual, patient, or cells includes administering the virus to an individual or patient, such as a human, and introducing a compound into, for example, a sample containing cells or a purified preparation containing cells.

[0086] As used herein, the terms “fused” or “linked” when used in reference to proteins having different domains or heterogeneous sequences mean that the protein domains are part of the same peptide chain, connected to each other by either peptide bonds or other covalent bonds. Domains or sections may be directly linked or fused to each other, or another domain or peptide sequence may exist between the two domains or sequences, but such sequences are not considered to be fused or linked to each other. In some embodiments, the various domains or proteins provided herein are either directly linked or fused to each other, or a linker sequence, such as a glycine / serine sequence described herein, links the two domains together.

[0087] A "disease" is a state of animal health in which the animal is unable to maintain homeostasis, and if the disease does not improve, the animal's health continues to deteriorate. In contrast, a "disorder" in animals is a state of health in which the animal is able to maintain homeostasis, but the animal's health is less desirable than in the absence of the disorder. Leaving a disorder untreated does not necessarily lead to a further deterioration of the animal's health.

[0088] "Effective dose" or "therapeutic effective dose" is used interchangeably herein and refers to the amount of a compound, formulation, material, or composition described herein that is effective in achieving a particular biological outcome or providing a therapeutic or preventive benefit. Such an outcome may include, but is not limited to, an amount that, when administered to a mammal, elicits a detectable level of immune cell activation compared to the immune cell activation detected in the absence of the composition. The immune response can be readily assessed by many methods recognized in the art. Those skilled in the art will understand that the amount of composition administered herein may vary and can be readily determined based on several factors, such as the disease or condition being treated, the age and health and physical condition of the mammal being treated, the severity of the disease, and the particular compound being administered.

[0089] "Code" refers to the inherent properties of a particular sequence of nucleotides in a polynucleotide (e.g., a gene, cDNA, or mRNA) and the resulting biological properties, which serve as a template for the synthesis of other polymers and macromolecules in biological processes having either a defined sequence of nucleotides (i.e., rRNA, tRNA, and mRNA) or a defined sequence of amino acids. Thus, a gene codes for a protein if the transcription and translation of the mRNA corresponding to that gene produces a protein in a cell or other biological system. Both the coding strand, whose nucleotide sequence is identical to the mRNA sequence and is usually provided in a sequence listing, and the non-coding strand, which is used as a template for the transcription of a gene or cDNA, may be referred to as coding for a protein or other product of that gene or cDNA.

[0090] An "expression vector" refers to a vector containing recombinant polynucleotides that include an expression regulatory sequence operably ligated to the nucleotide sequence to be expressed. An expression vector contains sufficient cis-acting elements for expression. Other elements for expression may be supplied by the host cell or in an in vitro expression system. Expression vectors include all vectors known in the art, such as cosmids, plasmids (e.g., naked or contained in liposomes), and viruses (e.g., Sendai virus, lentivirus, retrovirus, adenovirus, and adeno-associated virus) that incorporate recombinant polynucleotides.

[0091] As used herein, the term "ex vivo" with respect to cells transfected, transfected, or transformed ex vivo means cells that are transfected, transfected, or transformed outside of the subject, i.e., the cells are removed from the subject before such cells are transfected, transfected, or transformed.

[0092] As used herein, “identity” refers to the subunit sequence identity between two polymer molecules, such as between two polynucleotide molecules or two polypeptide molecules, or between two nucleic acid molecules or two amino acid molecules. Two amino acid sequences are identical at the same position if they have the same residue at the same location, for example, if the position in each of two polypeptide molecules is occupied by arginine. The identity or degree to which two amino acids or two nucleic acid sequences have the same residue at the same position in alignment is often expressed as a percentage. The identity between two amino acid sequences or two nucleic acid sequences is a linear function of the number of matching or identical positions. For example, if half of the positions in two sequences are identical, the two sequences are 50% identical. If 90% of the positions (e.g., 9 out of 10) are matching or identical, the two amino acid sequences are 90% identical.

[0093] "Substantially identical" means a polypeptide or nucleic acid molecule that exhibits at least 50% identity with respect to a reference amino acid sequence (e.g., any one of the amino acid sequences described herein) or a reference nucleic acid sequence (e.g., any one of the nucleic acid sequences described herein). In some embodiments, such sequences are at least 60%, 80%, or 85%, or 90%, 95%, or even 99%, identical at the amino acid level or nucleic acid level to the sequence used for comparison. Other percentages of identity with respect to specific sequences are described herein.

[0094] Sequence identity can be measured / determined using sequence analysis software (e.g., BLAST, BESTFIT, GAP, or PILEUP / PRETTYBOX programs from the Sequence Analysis Software Package of the Genetics Computer Group, University of Wisconsin Biotechnology Center, 1710 University Avenue, (Madison, WI) 53705). Such software matches identical or similar sequences by assigning degrees of homology to various substitutions, deletions, and / or other modifications. Conservative substitutions typically include substitutions within the following groups: glycine, alanine; valine, isoleucine, leucine; aspartic acid, glutamic acid, asparagine, glutamine; serine, threonine; lysine, arginine; and phenylalanine, tyrosine. In an exemplary approach to determining the degree of identity, the BLAST program may be used, where probability scores between e3 and e100 indicate closely related sequences. In some embodiments, sequence identity is determined by using BLAST with default settings.

[0095] To the extent that the embodiments provided herein include compositions comprising various proteins, these proteins may, in some examples, include amino acid sequences having sequence identity with the amino acid sequences disclosed herein. Therefore, in some 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) with respect to the sequence numbers disclosed herein. In addition to these percentages, other percentages of identity are provided herein. Polypeptide identity can be determined using an affine gap search with the parameters of gap-open penalty -12 and gap-extension penalty =1, performed by the Smith-Waterman homology search algorithm in the MPSRCH program (Oxford Molecular).

[0096] These proteins may contain one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) conserved amino acid substitutions, i.e., substitutions of one amino acid with another amino acid having a corresponding side chain, compared to the disclosed proteins. Genetically encoded amino acids are generally divided into four families: (1) acidic, i.e., aspartate, glutamate; (2) basic, i.e., lysine, arginine, histidine; (3) nonpolar, i.e., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan; and (4) non-charged, i.e., glycine, asparagine, glutamine, cysteine, serine, threonine, tyrosine. Phenylalanine, tryptophan, and tyrosine are sometimes classified together as aromatic amino acids. In general, single amino acid substitutions within these families do not have a significant impact on biological activity. A protein may have one or more single amino acid deletions (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) relative to the disclosed protein sequence. A protein may also have one or more insertions (e.g., each of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) relative to the disclosed protein sequence (e.g., each of 1, 2, 3, 4, or 5 amino acids).

[0097] As used herein, the term "in vivo" with respect to cells transfected, transfected, or transformed in vivo means cells that are transfected, transfected, or transformed in a subject without the cells being removed from the subject before such cells are transfected, transfected, or transformed.

[0098] "Isolated" means that something has been altered or removed from its natural state. For example, nucleic acids or peptides that are naturally present in living animals are not "isolated," but the same nucleic acids or peptides that have been partially or completely separated from their naturally occurring coexisting substances are "isolated." Isolated nucleic acids or proteins may exist in a substantially purified form or in a non-natural environment, such as a host cell.

[0099] As used herein, "lentivirus" refers to a genus of retroviridae capable of infecting non-dividing cells. Non-exclusive examples of lentiviruses include HIV, SIV, and FIV. Lentivirus-derived vectors or virus-like particles can be used to transduce cells, deliver genes or other molecules, and express them in cells either in vitro (ex vivo) or in vivo.

[0100] As used herein, the term “modified” means an altered state or structure of a molecule or cell provided herein. Molecules can be modified in many ways, including chemical, structural, and functional ways, such as mutation, substitution, insertion, or deletion (e.g., internal deletion, cleavage). Cells can be modified by the introduction of nucleic acids or the expression of heterologous proteins.

[0101] As used herein, the term “modulate” means mediating an increase or decrease in the level of response in a subject compared to the level of response in the subject in the absence of the treatment or compound, and / or compared to the level of response in an otherwise identical but untreated subject. This term encompasses mediating a beneficial therapeutic response in a subject such as a human by disrupting and / or influencing a natural signal or response.

[0102] Unless otherwise specified, "nucleotide sequences encoding an amino acid sequence" include all nucleotide sequences that encode the same amino acid sequence, including degenerate versions of each other. The phrase "nucleotide sequence encoding a protein or RNA" can also include introns to the extent that a nucleotide sequence encoding a protein may contain introns in some version.

[0103] The term “oligonucleotide” typically refers to a short polynucleotide. When a nucleotide sequence is represented by a DNA sequence (i.e., A, T, C, G), it is understood that this also provides a corresponding RNA sequence (i.e., A, U, C, G) where “U” substitutes for “T”.

[0104] Parenteral administration of the composition includes, for example, subcutaneous (sc), intravenous (iv), intramuscular (im), or intrasternal injection, or infusion techniques.

[0105] As used herein, the term “polynucleotide” is defined as a chain of nucleotides. Furthermore, nucleic acids are polymers of nucleotides. Therefore, as used herein, the terms “nucleic acid” and “polynucleotide” are interchangeable. As used herein, polynucleotide includes, but is not limited to, all nucleic acid sequences obtained by any method available in the art, including recombinant methods, i.e., cloning of nucleic acid sequences from recombinant libraries or cell genomes using cloning techniques and PCR, etc., as well as by synthetic means.

[0106] As used herein, the terms “peptide,” “polypeptide,” and “protein” are interchangeable and refer to compounds composed of multiple amino acid residues covalently linked by peptide bonds. As used herein, this term refers to both short chains, also commonly referred to in the art as peptides, oligopeptides, and oligomers, and long chains, of which there are many types, commonly referred to in the art as proteins. “Polypeptides” include, for example, biologically active fragments, substantially homologous polypeptides, oligopeptides, homodimers, heterodimers, variants of polypeptides, modified polypeptides, derivatives, analogs, and fusion proteins. Polypeptides include native peptides, recombinant peptides, synthetic peptides, or combinations thereof.

[0107] Unless otherwise specified, the terms “heteroviral structural protein” and “heteroviral glycoprotein” as used herein are synonymous and interchangeable. Therefore, unless otherwise specified, embodiments referring to “heteroviral structural protein” are understood to refer to “heteroviral glycoprotein,” and vice versa.

[0108] As used herein, the terms “pseudotype” or “pseudotyped viral particle” refer to a viral particle having a glycoprotein derived from another enveloped virus, or a viral vector encoding an envelope glycoprotein derived from a virus different from the parent virus. Therefore, the host range of the vector particle may be expanded or modified depending on the type of cell surface receptor used by the glycoprotein. For example, a virus may be pseudotyped with a VSV-G mutant protein, such as those provided herein.

[0109] As used herein with respect to antibodies, the term “specifically binding” means an antibody that recognizes a specific antigen but substantially does not recognize or bind to other molecules in the sample. For example, an antibody that specifically binds to an antigen from one species may also bind to that antigen from one or more species. However, such interspecies reactivity does not in itself change the antibody’s classification as specific. In another example, an antibody that specifically binds to an antigen may also bind to different alleles of the antigen. However, such cross-reactivity does not in itself change the antibody’s classification as specific. In some cases, the term “specific binding” or “specifically binding” may be used in relation to the interaction of an antibody, protein, or peptide with a second chemical species, meaning that the interaction depends on the presence of a specific structure on the chemical species (e.g., an antigenic determinant or epitope). For example, an antibody recognizes and binds to a specific protein structure, rather than to the protein in general. If an antibody is specific to epitope “A”, the presence of labeled “A” and molecules containing epitope A (or free, unlabeled A) in the reactant containing the antibody will reduce the amount of labeled A bound to the antibody. In some embodiments, the targeting moieties described herein, which may be used to target viral particles containing mutant VSV-G proteins or other viral structural proteins used to pseudotype the virus, can specifically bind to those targets.

[0110] The term "subject" includes living organisms, including those capable of eliciting an immune response (e.g., mammals). As used herein, "subject" or "patient" may be human or non-human mammals. Examples of non-human mammals include livestock and pets, such as sheep, cattle, pigs, dogs, non-human primates, cats, and mouse mammals. In some embodiments, the subject is human.

[0111] As used herein, the term “therapeutic” means treatment and / or prevention. Therapeutic effects are obtained by suppression, remission, or eradication of a disease state.

[0112] As used herein, the terms “transfected,” “transformed,” or “transduced” refer to the process by which an exogenous nucleic acid is introduced into or into a cell. A “transfected,” “transformed,” or “transduced” cell refers to a cell that has been transfected, transformed, or transduced with an exogenous nucleic acid. Cells include primary target cells and their offspring. In some embodiments, transfection, transformation, or transduction is carried out or occurs in vivo.

[0113] When used herein, “to treat” a disease means to reduce the frequency or severity of at least one sign or symptom of the disease or disorder experienced by the subject.

[0114] A "vector" is a composition of substances containing isolated nucleic acids that encode proteins or peptides. Numerous vectors are known in the art and include, but are 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, and lentiviral vectors.

[0115] The "carrier" or "delivery vehicle" includes viral particles, viruses, polylysine compounds, and liposomes, which facilitate the transfer of nucleic acids into cells. Proteins or peptides can also be delivered to cells using the carrier or delivery vehicle.

[0116] Scope: Throughout this disclosure, various aspects of the embodiments may be presented in range form. It should be understood that the use of range form is merely for convenience and brevity and should not be interpreted as an inflexible limitation. Therefore, a range description should be considered to specifically disclose all possible subranges, as well as the individual numbers within that range. For example, a range description such as 1–6 should be considered to specifically disclose subranges such as 1–3, 1–4, 1–5, 2–4, 2–6, 3–6, as well as the individual numbers within that range, e.g., 1, 2, 2.7, 3, 4, 5, 5.3, and 6. This applies regardless of the width of the range. Unless otherwise explicitly stated, the disclosed range includes its endpoints.

[0117] Throughout this specification, amino acid constructs that include or do not include a leader sequence or peptide may be referred to. Certain embodiments may refer only to sequences that include or do not include a leader sequence, but it should be understood that these embodiments encompass both sequences that include a leader peptide and sequences that do not. Viral particles containing heterologous viral glycoproteins and targeting moieties

[0118] In some embodiments, a viral particle is provided comprising a heterologous viral glycoprotein and a targeting moiety. In some embodiments, the targeting moiety comprises a polypeptide having the formula T-S1, where T is a target-binding domain and S1 is a stalk moiety. In some embodiments, S1 comprises a mutant Fc protein, which comprises a transmembrane domain such as, but not limited to, a CD8 or CD28 transmembrane domain. Thus, in some embodiments, the stalk moiety S1 comprises an N-terminus to C-terminus orientation of the mutant Fc transmembrane domain. In some embodiments, the mutant Fc protein comprises an effector mutation, which inhibits the interaction between the Fc protein and Fc-interacting proteins such as FcγR, C1q, FcRβ, or FcRn.

[0119] In some embodiments, the S1 stalk portion is bound to the surface of the viral particle via a transmembrane domain. In some embodiments, the mutant Fc protein is a variant of the IgG1 Fc, IgG2 Fc, or IgG4 Fc protein. In some embodiments, the mutant 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).

[0120] In some embodiments, the mutant Fc protein is the mutant IgG1 Fc protein (SEQ ID NO: 26). In some embodiments, the mutant IgG1 Fc protein contains one or more mutations selected from the group consisting of L234A, L235A, N297A, P329G, I253A, H310A, and H435A of SEQ ID NO: 26, numbered according to Kabat's EU numbering index, which is described in Edelman, GM 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, which is incorporated herein by reference in its entirety. Any of the mutations L234A, L235A, N297A, P329G, I253A, H310A, and H435A in SEQ ID NO: 26 may or may not be present, and the mutations may be combined in any combination. In some embodiments, the mutant IgG1 Fc protein includes mutations corresponding to L234A and L235A in SEQ ID NO: 26. In some embodiments, the mutant IgG1 Fc protein includes a mutation corresponding to N297A in SEQ ID NO: 26. In some embodiments, the mutant IgG1 Fc protein includes a mutation corresponding to P329G in SEQ ID NO: 26. In some embodiments, the mutant IgG1 Fc protein includes mutations corresponding to L234A, L235A, N297A, and P329G in SEQ ID NO: 26. In some embodiments, the mutant IgG1 Fc protein includes a mutation corresponding to I253A in SEQ ID NO: 26. In some embodiments, the mutant IgG1 Fc protein includes a mutation corresponding to H310A in SEQ ID NO: 26. In some embodiments, the mutant IgG1 Fc protein contains a mutation corresponding to H435A in SEQ ID NO: 26.In some embodiments, the mutant IgG1 Fc protein includes mutations corresponding to I253A, H310A, and H435A of SEQ ID NO: 26. In some embodiments, the mutant IgG1 Fc protein includes mutations corresponding to L234A, L235A, N297A, P329G, I253A, H310A, and H435A of SEQ ID NO: 26.

[0121] In some embodiments, the mutant Fc protein containing the mutant IgG1 Fc protein includes a cleavage of the IgG1 Fc sequence. The cleavage may 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 mutant Fc protein containing the mutant IgG1 Fc protein includes a cleavage of SEQ ID NO: 26. The cleavage may include the deletion of any number of amino acids from the N-terminus, C-terminus, or both of the SEQ ID NO: 26. In some embodiments, the cleavage includes the deletion of an amino acid from the N-terminus of SEQ ID NO: 26. In some embodiments, the cleavage includes the deletion of an amino acid from the C-terminus of SEQ ID NO: 26. In some embodiments, the cleavage includes the deletion of an amino acid from both the N-terminus and C-terminus of SEQ ID NO: 26. In some embodiments, the cleavage of SEQ ID NO: 26 includes the amino acid sequence of SEQ ID NO: 103: EPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK(Sequence ID 103)

[0122] In some embodiments, the mutant IgG1 Fc protein contains one or more mutations selected from the group consisting of L19A, L20A, N82A, P114G, I38A, H95A, and H220A, compared to SEQ ID NO: 103. It should be understood that positions L19, L20, sN82, P114, I38, H95, and H220 refer only to SEQ ID NO: 103. Those skilled in the art will readily recognize that positions L234, L235, N297, P329, I253, H310, and H435, numbered according to Kabat's 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 in SEQ ID NO: 103 may or may not be present, and the mutations may be combined in any combination. In some embodiments, the mutant IgG1 Fc protein includes mutations corresponding to L19A and L20A in SEQ ID NO: 103. In some embodiments, the mutant IgG1 Fc protein includes mutations corresponding to N82A in SEQ ID NO: 103. In some embodiments, the mutant IgG1 Fc includes mutations corresponding to P114G in SEQ ID NO: 103. In some embodiments, the mutant IgG1 Fc includes mutations corresponding to L19A, L20A, N82A, and P114G in SEQ ID NO: 103. In some embodiments, the mutant IgG1 Fc protein includes mutations corresponding to I38A in SEQ ID NO: 103. In some embodiments, the mutant IgG1 Fc protein includes mutations corresponding to H95A in SEQ ID NO: 103. In some embodiments, the mutant IgG1 Fc protein includes a mutation corresponding to H220A in SEQ ID NO: 103. In some embodiments, the mutant IgG1 Fc protein includes mutations corresponding to I38A, H95A, and H220A in SEQ ID NO: 103. In some embodiments, the mutant IgG1 Fc protein includes mutations corresponding to L19A, L20A, N82A, P114G, I38A, H95A, and H220A in SEQ ID NO: 103.In some embodiments, the mutant IgG1 Fc protein contains mutations corresponding to L18A, L19A, N82A, P114G, I38A, H95A, and H220A, respectively, in SEQ ID NO: 103. Exemplary mutant IgG1 proteins containing L18A, L19A, N82A, P114G, I38A, H95A, and H220A are shown below in the amino acid sequence of SEQ ID NO: 104: EPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMASRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLAQDWLNGKEYKCKVSNKALGAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNAYTQKSLSLSPGK(Sequence ID 104)

[0123] In some embodiments, the mutant Fc protein is the mutant IgG2 Fc protein (SEQ ID NO: 27). In some embodiments, the mutant IgG2 Fc protein includes one or more mutations selected from the group consisting of N297A, P329G, I253A, H310A, and H435A, where these positions correspond to SEQ ID NO: 27 numbered according to Kabat's EU numbering index. Any of the mutations N297A, P329G, I253A, H310A, and H435A in SEQ ID NO: 27 may or may not be present, and the mutations may be combined in any combination. In some embodiments, the mutant IgG2 Fc protein includes the mutation corresponding to N297A in SEQ ID NO: 27. In some embodiments, the mutant IgG2 Fc protein includes the mutation corresponding to P329G in SEQ ID NO: 27. In some embodiments, the mutant IgG2 Fc protein includes the mutations corresponding to N297A and P329G in SEQ ID NO: 27. In some embodiments, the mutant IgG2 Fc protein includes a mutation corresponding to I253A in SEQ ID NO: 27. In some embodiments, the mutant IgG2 Fc protein includes a mutation corresponding to H310A in SEQ ID NO: 27. In some embodiments, the mutant IgG2 Fc protein includes a mutation corresponding to H435A in SEQ ID NO: 27. In some embodiments, the mutant IgG2 Fc protein includes mutations corresponding to I253A, H310A, and H435A in SEQ ID NO: 27.

[0124] In some embodiments, the mutant Fc protein containing the mutant IgG2 Fc protein includes a cleavage of the IgG2 Fc sequence. The cleavage may include the deletion of any number of amino acids from the N-terminus, C-terminus, or both of the IgG2 Fc sequence. In some embodiments, the mutant Fc protein containing the mutant IgG2 Fc protein includes a cleavage of SEQ ID NO: 27. The cleavage may include the deletion of any number of amino acids from the N-terminus, C-terminus, or both of the SEQ ID NO: 27. In some embodiments, the cleavage includes the deletion of an amino acid from the N-terminus of SEQ ID NO: 27. In some embodiments, the cleavage includes the deletion of an amino acid from the C-terminus of SEQ ID NO: 27. In some embodiments, the cleavage includes the deletion of amino acids from both the N-terminus and C-terminus of SEQ ID NO: 27.

[0125] In some embodiments, the mutant Fc protein is the mutant IgG4 Fc protein (SEQ ID NO: 28). In some embodiments, the mutant IgG4 Fc protein includes one or more mutations selected from the group consisting of S228P, L235E, N297A, P329G, I253A, H310A, and H435A, where these positions correspond to SEQ ID NO: 28 numbered according to Kabat's EU numbering index. Any of the mutations S228P, L235E, N297A, P329G, I253A, H310A, and H435A in SEQ ID NO: 28 may or may not be present, and the mutations may be combined in any combination. In some embodiments, the mutant IgG4 Fc protein includes the mutation corresponding to S228P in SEQ ID NO: 28. In some embodiments, the mutant IgG4 Fc protein includes the mutation corresponding to L235E in SEQ ID NO: 28. In some embodiments, the mutant IgG4 Fc protein includes a mutation corresponding to N297A in SEQ ID NO: 28. In some embodiments, the mutant IgG4 Fc protein includes a mutation corresponding to P329G in SEQ ID NO: 28. In some embodiments, the mutant IgG4 Fc protein includes mutations corresponding to S228P, L235E, N297A, and P329G in SEQ ID NO: 28. In some embodiments, the mutant IgG4 Fc protein includes a mutation corresponding to I253A in SEQ ID NO: 28. In some embodiments, the mutant IgG4 Fc protein includes a mutation corresponding to H310A in SEQ ID NO: 28. In some embodiments, the mutant IgG4 Fc protein includes a mutation corresponding to H435A in SEQ ID NO: 28. In some embodiments, the mutant IgG4 Fc protein includes mutations corresponding to I253A, H310A, and H435A in SEQ ID NO: 28.

[0126] In some embodiments, the mutant Fc protein containing the mutant IgG4 Fc protein includes a cleavage of the IgG4 Fc sequence. The cleavage may include the deletion of any number of amino acids from the N-terminus, C-terminus, or both of the IgG4 Fc sequence. In some embodiments, the mutant Fc protein containing the mutant IgG4 Fc protein includes a cleavage of SEQ ID NO: 28. The cleavage may include the deletion of any number of amino acids from the N-terminus, C-terminus, or both of the SEQ ID NO: 28. In some embodiments, the cleavage includes the deletion of an amino acid from the N-terminus of SEQ ID NO: 28. In some embodiments, the cleavage includes the deletion of an amino acid from the C-terminus of SEQ ID NO: 28. In some embodiments, the cleavage includes the deletion of an amino acid from both the N-terminus and C-terminus of SEQ ID NO: 28.

[0127] In some embodiments, the stalk moiety S1, comprising the mutant Fc protein, is given by the formula L1-Fc-L2-X1, where L1 is a linker or absent; Fc is a mutant Fc protein; L2 is a linker or absent; and X1 is a polypeptide comprising a transmembrane domain. Thus, the targeting moiety 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 mutant Fc protein; L2 is a linker or absent; and X1 is a polypeptide comprising a transmembrane domain. Therefore, it should be understood that in some embodiments, the stalk moiety S1 may be given by the formula L1-Fc-L2-X1. In some embodiments, the target-binding domain T is as disclosed herein. In some embodiments, the mutant Fc protein is as provided herein.

[0128] In some embodiments, L1 and L2 are polypeptide linkers, each independently. In some embodiments, the polypeptide linker is (GGGGA) n (Sequence No. 54), (GGGGS) n (Sequence ID 55), (EAAAK) n(Sequence ID 73), A(EAAAK) n A (Sequence ID 74), (XP) n The formula includes (SEQ ID NO: 75), where X is Ala, Lys, or Glu, GSAGSAAGSGEF (SEQ ID NO: 56), KESGSVSSEQLAQFRSLD (SEQ ID NO: 57), EGKSSGSGSESKST (SEQ ID NO: 58), AEAAAKEAAAKA (SEQ ID NO: 76), or a combination thereof, where each n is independently 1 to 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 (Sequence No. 54) or (GGGGS) n (Sequence ID 55), where each n is independently 1 to 5. In some embodiments, L1 is (GGGGA) n (Sequence No. 54) or (GGGGS) n (Sequence ID 55), where each n is independently 1. In some embodiments, L1 is (GGGGA) n (Sequence No. 54) or (GGGGS) n (Sequence ID 55), where each n is independently 2. In some embodiments, L1 is (GGGGA) n (Sequence No. 54) or (GGGGS) n (Sequence ID 55), where each n is independently 3. In some embodiments, L1 is (GGGGA) n (Sequence No. 54) or (GGGGS) n (Sequence ID 55), where each n is independently 4. In some embodiments, L1 is (GGGGA) n (Sequence No. 54) or (GGGGS) n(Sequence ID 55), where each n is independently 5. In some embodiments, L1 is (GGGGA) n (Sequence No. 54) or (GGGGS) n (Sequence ID 55) where each n is independently greater than 5. In some embodiments, L2 is absent. In some embodiments, L2 is (GGGGA) n (Sequence No. 54) or (GGGGS) n (Sequence ID 55), where each n is independently 1 to 5. In some embodiments, L2 is (GGGGA) n (Sequence No. 54) or (GGGGS) n (Sequence ID 55), where each n is independently 1. In some embodiments, L2 is (GGGGA) n (Sequence No. 54) or (GGGGS) n (Sequence ID 55), where each n is independently 2. In some embodiments, L2 is (GGGGA) n (Sequence No. 54) or (GGGGS) n (Sequence ID 55), where each n is independently 3. In some embodiments, L2 is (GGGGA) n (Sequence No. 54) or (GGGGS) n (Sequence ID 55), where each n is independently 4. In some embodiments, L2 is (GGGGA) n (Sequence No. 54 or GGGGS) n (Sequence ID 55), where each n is independently 5. In some embodiments, L2 is (GGGGA) n (Sequence No. 54) or (GGGGS) n (Sequence code 55), where each n is independently greater than 5.

[0129] In some embodiments, X1 is ECD-T M - Contains a polypeptide having the formula ICD, where ECD is either the extracellular domain or a fragment thereof of a cell surface protein, or is absent; T Mis the transmembrane domain of a transmembrane protein, and ICD is a protein that facilitates the incorporation of the targeting portion into the intracellular domain of the protein or the envelope of a viral particle, or it is absent. Therefore, in some embodiments, the targeting portion containing formula T-S1, which can also be given by formula T-L1-Fc-L2-X1, is formula T-L1-Fc-L2-ECD-T M -ICD may also be given by formula, where T is the target-binding domain; L1 is a linker or is absent; Fc is a mutant Fc protein; L2 is a linker or is absent; ECD is the extracellular domain or fragment thereof of a cell surface protein or is absent; T M ICD is the transmembrane domain of a transmembrane protein, and ICD is a protein that facilitates the incorporation of the targeting portion into the intracellular domain of the protein or the envelope of a viral particle, or it is not present. Therefore, in some embodiments, the stalk portion S1 is of the formula L1-Fc-L2-ECD-T M -Please understand that this information may be provided by an ICD.

[0130] In some embodiments, the stalk portion S1 does not include a mutated Fc region. In some embodiments, the stalk portion S1 is given by formula L3-X1, where L3 is a flexible peptide linker and X1 is a polypeptide comprising a transmembrane domain provided herein. Thus, in some embodiments, the targeting portion comprising formula T-S1 may also be given by formula T-L3-X1, where T is a target-binding domain, L3 is a flexible peptide linker, and X1 is a polypeptide comprising a transmembrane domain provided herein. Therefore, it should be understood that in some embodiments, the stalk portion S1 may be given by formula L3-X1. In some embodiments, the S1 stalk portion is bound to the surface of the viral particle via a transmembrane domain.

[0131] In some embodiments, the flexible peptide linker L3 may be any flexible peptide linker. In some embodiments, L3 is not limited to (GGGGA) n (Sequence No. 54), (GGGGS) n Selected from a group of flexible linkers including (SEQ ID NO: 55), GSAGSAAGSGEF (SEQ ID NO: 56), KESGSVSSEQLAQFRSLD (SEQ ID NO: 57), EGKSSGSGSESKST (SEQ ID NO: 58), or any combination thereof, where each n is an integer independently selected from 1 to 4. In some embodiments, each n is an integer independently 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 (Sequence ID 54), where n is 1. In some embodiments, L3 is (GGGGA) n (Sequence ID 54) where n is 2. In some embodiments, L3 is (GGGGA) n (Sequence ID 54) where n is 3. In some embodiments, L3 is (GGGGA) n (Sequence ID 54), where n is 4. In some embodiments, L3 is (GGGGA) n (Sequence ID 54), where n is 5. In some embodiments, L3 is (GGGGA) n (Sequence ID 54) where n is 6. In some embodiments, L3 is (GGGGA) n (Sequence ID 54) where n is 7. In some embodiments, L3 is (GGGGA) n(Sequence ID 54) where n is 8. In some embodiments, L3 is (GGGGA) n (Sequence ID 54) where n is 9. In some embodiments, L3 is (GGGGA) n (Sequence ID 54), where n is 10. In some embodiments, L3 is (GGGGA) n (Sequence ID 54) where n is greater than 10. In some embodiments, L3 is (GGGGS) n (Sequence ID 55), where n is 1. In some embodiments, L3 is (GGGGS) n (Sequence ID 55), where n is 2. In some embodiments, L3 is (GGGGS) n (Sequence ID 55), where n is 3. In some embodiments, L3 is (GGGGS) n (Sequence ID 55), where n is 4. In some embodiments, L3 is (GGGGS) n (Sequence ID 55), where n is 5. In some embodiments, L3 is (GGGGS) n (Sequence ID 55), where n is 6. In some embodiments, L3 is (GGGGS) n (Sequence ID 55), where n is 7. In some embodiments, L3 is (GGGGS) n (Sequence ID 55), where n is 8. In some embodiments, L3 is (GGGGS) n (Sequence ID 55), where n is 9. In some embodiments, L3 is (GGGGS) n (Sequence ID 55), where n is 10. In some embodiments, L3 is (GGGGS) n (Sequence ID 55) where n is greater than 10. In some embodiments, L3 is GSAGSAAGSGEF (Sequence ID 56). In some embodiments, L3 is KESGSVSSEQLAQFRSLD (Sequence ID 57). In some embodiments, L3 is EGKSSGSGSESKST (Sequence ID 58).

[0132] In some embodiments, the flexible peptide linker L3 can be any flexible peptide linker. In some embodiments, L3 is, but not limited to, (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 (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 (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).

[0133] In some embodiments, L3 is, but not limited to, (GGGGA)n (Sequence No. 54), (GGGGS) n A flexible linker is selected from the group including (SEQ ID NO: 55), GSAGSAAGSGEF (SEQ ID NO: 56), KESGSVSSEQLAQFRSLD (SEQ ID NO: 57), EGKSSGSGSESKST (SEQ ID NO: 58), or any combination thereof, where each n is an integer independently 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 (Sequence ID 54), where n is 1. In some embodiments, L3 is (GGGGA) n (Sequence ID 54) where n is 2. In some embodiments, L3 is (GGGGA) n (Sequence ID 54) where n is 4. In some embodiments, L3 is (GGGGS) n (Sequence ID 55), where n is 1. In some embodiments, L3 is (GGGGS) n (Sequence ID 55), where n is 2. In some embodiments, L3 is (GGGGS) n (Sequence ID 55) where n is 4. In some embodiments, L3 is GSAGSAAGSGEF (Sequence ID 56). In some embodiments, L3 is KESGSVSSEQLAQFRSLD (Sequence ID 57). In some embodiments, L3 is EGKSSGSGSESKST (Sequence ID 58).

[0134] In some embodiments, X1 is ECD-T M - Contains a polypeptide having the formula ICD, where ECD is either the extracellular domain or a fragment thereof of a cell surface protein, or is absent; T MICD is the transmembrane domain of a transmembrane protein, and ICD is a protein that facilitates the incorporation of the targeting portion into the intracellular domain of the protein or the envelope of a viral particle, or it is absent. Therefore, in some embodiments, the targeting portion containing formula T-S1, which can also be given by formula T-L3-X1, is formula T-L3-ECD-T M -Can also be given by ICD. In the formula, T is the target-binding domain, L3 is the flexible peptide linker, and ECD is either the extracellular domain of a cell surface protein or a fragment thereof, or is absent. M ICD is the transmembrane domain of a transmembrane protein, and ICD is either a protein that facilitates the incorporation of the targeting portion into the intracellular domain of the protein or the envelope of a viral particle, or it is absent. Therefore, in some embodiments, the stalk portion S1 is of formula L3-ECD-T M -Please understand that this information may be provided by an ICD.

[0135] In some embodiments, the ECD is absent. In some embodiments, the ECD may be any suitable extracellular domain or a fragment thereof. In some embodiments, the ECD may originate from a different protein compared to the transmembrane domain. The ECD domain may 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 ECD domain of CD8, or a fragment thereof. In some embodiments, the ECD domain of CD8 contains the polypeptide FVPVFLPAKPTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACD (SEQ ID NO: 59). In some embodiments, the ECD domain of CD8 consists of or is essentially derived from the polypeptide FVPVFLPAKPTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACD (SEQ ID NO: 59). In some embodiments, the ECD domain contains a polypeptide that is 25 to 45 amino acids long. 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 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 ECD domain of CD28 comprises the polypeptide KIEVMYPPPYLDNEKSNGTIIHVKGKHLCPSPLFPGPSKP (SEQ ID NO: 60). In some embodiments, the ECD domain of CD28 consists of or is essentially derived from the polypeptide KIEVMYPPPYLDNEKSNGTIIHVKGKHLCPSPLFPGPSKP (SEQ ID NO: 60). In some embodiments, the ECD domain comprises a polypeptide that is 25 to 45 amino acids long.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 KIEVMYPPPYLDNEKSNGTIIHVKGKHLCPSPLFPGPSKP (SEQ ID NO: 60).

[0136] In some embodiments, T M This can be any suitable transmembrane domain or fragment thereof. In some embodiments, T M The domain is CD8 or CD28 T M It is a domain or a fragment thereof. In some embodiments, T M The domain is CD8 T M It is a domain or a fragment thereof. In some embodiments, it is the T of CD8. M The domain contains the polypeptide IYIWAPLAGTCGVLLLSLVITLYCNHRN (SEQ ID NO: 61). In some embodiments, the T of CD8 M The domain consists of or is essentially derived from the polypeptide IYIWAPLAGTCGVLLLSLVITLYCNHRN (SEQ ID NO: 61). In some embodiments, T M This 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 The domain is CD28 T M It is a domain or a fragment thereof. In some embodiments, T of CD28 M The domain contains the polypeptide FWVLVVVGGVLACYSLLVTVAFIIFWV (SEQ ID NO: 62). In some embodiments, the T of CD28 M The domain consists of or is essentially derived from the polypeptide FWVLVVVGGVLACYSLLVTVAFIIFWV (SEQ ID NO: 62). In some embodiments, T MThis includes 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 FWVLVVVGGVLACYSLLVTVAFIIFWV (SEQ ID NO: 62).

[0137] In some embodiments, T M The domain originates from the same protein as ECD. In some embodiments, T M The domain originates from a protein different from ECD. In some embodiments, T M The domain is CD8 or CD28 T M A domain or fragment thereof, and an ECD domain is an ECD domain or fragment thereof of CD8 or CD28. 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 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 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 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 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 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 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 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 KIEVMYPPPYLDNEKSNGTIIHVKGKHLCPSPLFPGPSKP (SEQ ID NO: 60).

[0138] In some embodiments, the transmembrane domain is ligated to the intracellular domain (ICD) or a fragment thereof of a transmembrane protein. 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 includes an Env integration motif. The Env integration motif is a molecule, e.g., a polypeptide, that can help facilitate the integration of proteins into the viral envelope. A non-limiting example of an Env integration motif is a polypeptide containing the amino acid sequence NRVRQGYS (SEQ ID NO: 63). This is a non-limiting example, and other peptide sequences, e.g., GGTETSQVAPA (SEQ ID NO: 64), may be used. In some embodiments, the Env integration motif includes the amino acid sequence of SEQ ID NO: 63, SEQ ID NO: 64, or a combination thereof. In some embodiments, the Env integration motif includes the amino acid sequence of SEQ ID NO: 63. In some embodiments, the Env integration motif includes the amino acid sequence of SEQ ID NO: 64.

[0139] 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 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, or expressed on acute leukemia or lymphoma but not on hematopoietic progenitor cells. Glycosylated CD43 epitope; glycosylated CD43 epitope expressed on non-hematopoietic cancers; A kinase anchor protein 4 (AKAP-4); adrenergic receptor β3 (ADRB3); AFP; anaplastic lymphoma kinase (ALK); androgen receptor; angiopoietin-binding cell surface receptor 2 (Tie2); autoantibody against desmoglein 1 (Dsg1); autoantibody against desmoglein 3 (Dsg3); B7H3 (CD276); biotin; intermyelin Plasma cell antigen 2 (BST2); BST1 / CD157; Cancer / testicular antigen 1 (NY-ESO-1); Cancer / testicular antigen 2 (LAGE-la); Carbonic anhydrase IX (CAIX); Carcinoembryonic antigen (CEA); CCCTC binding factor (zinc finger protein)-like (brother of BORIS or imprint site regulatory factors); CCR4; CD5; CD19; CD20; CD22; CD24; CD30; CD32 (FCGR2A); CD33; CD34; CD38; CD44v6; CD 72; CD79a; CD79b; CD97; CD99; CD123; CD171; CD179a; CD179b-IGLll; CD200R; CD276 / B7H3; CD300 molecule-like family member f (CD300LF); CDH1-CD324; CDH6; CDH17; CDH19; X chromosome open reading frame 61 (CXORF61); Claudin 6 (CLDN6); Claudin 18.2 (CLD18A2 or CLDN18A.2); CMV pp65; C-MYC epitope tag; Crypto; CS1 (also known as CD2 subset 1, CRACC, SLAMF7, CD319, or 19A24);CSF2RA (GM-CSFR-α); C-type lectin domain family 12 member A (CLEC12A); C-type lectin-like molecule-1 (CLL-1 or CLECL1); Cyclin B1; Cytochrome P450 IB 1 (CYP1B 1); DLL3; EBV-EBNA3c; EGF-like module-containing mucin-like hormone receptor-like 2 (EMR2); Elongation factor 2 mutant (ELF2M); Ephrin B2; Ephrin type A receptor 2 (EphA2); Epidermal growth factor receptor (EGFR); Epidermal growth factor receptor mutant III (EGFRviii); Epithelial cell adhesion molecule (EPCAM); ERG; ETS translocation mutant gene 6 located on chromosome 12p (ETV6-AML); Fc fragment of IgA receptor (FCAR or CD89); Fc receptor-like 5 5. FCRL5); Fibroblast-activating protein α (FAP); FITC; Fms-like tyrosine kinase 3 (FLT3); Folate receptor alpha (Fra or FR1); Folate receptor beta (FRb); Follicular-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 (αNeu5Ac(2-8)αNe u5Ac(2-3)bDGalp(1-4)bDGlcp(1-1)Cer); ganglioside GM3(αNeu5Ac(2-3)bDClalp(1-4)bDGlcp(1-1)Cer); GD3; GFRalpha4; glycoprotein 100 (gp100); glypican-3 (GPC3); gonadotropin hormone receptor (CGHR or GR); GpA33; GpNMB; GPRC5D; guanylyl cyclase C (GCC); heat shock protein 70-2 mutant (mut hsp70-2); Hepatitis A virus cell receptor 1 (HAVCR1); Hexasaccharide portion of globoH glycoceramide (GloboH); High molecular weight melanoma-associated antigen (HMWMAA); HIV1 envelope glycoprotein; HLA; HLA-DOA; HLA-A; HLA-A2; HLA-B; HLA-C; HLA-DM; HLA-DOB; HLA-DP; HLA-DQ; HLA-DR; HLA-G; HTLV1-Tax; Human papillomavirus E6 (HPV E6);Human papillomavirus E7 (HPV E7); human telomerase reverse transcriptase (hTERT); IgE; IL13Ra2; Ill IRa; and immunoglobulin λ-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 α-2 (IL-13Ra2 or CD213A2); intestinal carboxylesterase; KIT (CD117); KSHV K8.1; KSHV-gH; LAMP1; legmaine; 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; K9 locus (LY6K); low-conductance chloride channel; lymphocyte antigen 6 complex; lymphocyte antigen 75 (LY75); lymphocyte-specific protein tyrosine kinase (LCK); mammary gland differentiation antigen (NY-BR-1); melanoma antigen recognized by T cell 1 (MelanA or MART1); melanoma-associated antigen 1 (MAGE-A1); melanoma carcinoma testis antigen-1 (MAD-CT-1); melanoma carcinoma testis antigen-2 (MAD-CT-2); melanoma apoptosis inhibitor (ML-IAP); mesothelin; MPL; cell surface-bound mucin 1 (MUC1); N-acetylglucosaminyltransferase V (NA17); nectin-4; nerve cell adhesion molecule (NCAM); NKG2D ;NYBR1;O-acetyl-GD2 ganglioside (OacGD2);olfactory receptor 51E2 (OR51E2);oncogene fusion protein consisting of a cleavage cluster region (BCR) and Abelson mouse leukemia virus oncogene homolog 1 (Ab1) (bcr-ab1);P53 variant;paired box protein Pax-3 (PAX3);paired box protein Pax-5 (PAX5);panexin 3 (PANX3);PDL1;P-glycoprotein;placenta-specific 1 (PLAC1);platelet-derived growth factor receptor beta (PDGFR-beta);polysialic acid;proacrosin-binding protein sp32 (OY-TES1);prostase;prostate cancer tumor antigen-1 (PCT A-1 or galectin 8);prostate stem cell antigen (PSCA);Prostate-specific membrane antigen (PSMA); prostatic acid phosphatase (PAP); prostein; protease serine 21 (testisin or PRSS21); proteasome (prosome, macropain) subunit, beta type 9 (LMP2); PTK7; Ras G12V; Ras homolog family member C (RhoC); rat sarcoma (Ras) mutant; advanced glycation end product receptor (RAGE-1); receptor tyrosine kinase-like orphan receptor 1 (ROR1); receptor tyrosine protein kinase, ERBB2 or Her-22 / neu; renal ubiquitous receptor 1 (RU1); renal ubiquitous receptor 2 (RU2); sarcoma translocation breakpoint; serine 2 (TMPRSS2) ETS fusion gene; sialyl Lewis adhesion molecule (sLe); SLAMF4; SLAMF6; Slea (CA19.9 or sialyl Lewis antigen); sperm protein 17 (SPA17); T cell Squamous cell carcinoma antigen recognized by 3 (SART3); Stage-specific embryonic antigen-4 (SSEA-4); STEAP1; Sulbibin; Synovial sarcoma X-section 2 (SSX2); TCR-γ alternative leading frame protein (TARP); TCR-beta-1 chain; TCR-beta-2 chain; TCR-delta chain; TCR-gamma chain; TCR-gamma-delta; Telomerase; TGFbetaR2; Antigen recognized by TNT antibody; Thyroid-stimulating hormone receptor (TSHR); Timl- / HVCR1; Tissue factor 1 (TF1); Tn ag; Tn antigen ((Tn Ag) or (GaINAcu-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 myeloma virus oncogene neuroblastoma-derived homolog (MYCN); Wilms tumor protein (WT1);Alternatively, a viral particle according to claim 3, which binds to member 1A (XAGE1) of the X antigen family. 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 this disclosure, it should be understood that "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 antibody fragments of any isotype, including but not limited to 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, and fusion proteins comprising the antigen-binding moiety of an antibody and a non-antibody protein. In some embodiments, the antibody is selected from the group including 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 a VHH antibody. In some embodiments, the antibody is a single-domain antibody.

[0140] In some embodiments, the viral particles provided herein are pseudotyped viral particles. In some embodiments, the viral particles are pseudotyped using viral glycoproteins of Paramyxoviridae viruses. In some embodiments, the pseudotyped virus-like particles are pseudotyped using viral glycoproteins of Morbilliviruses, such as measles virus. In some embodiments, the pseudotyped virus-like particles are pseudotyped using viral glycoproteins of Measles virus. In some embodiments, the pseudotyped virus-like particles are pseudotyped using viral glycoproteins of Henipaviruses, such as Nipah virus, Cedar virus, or Hendra virus. In some embodiments, the pseudotyped virus-like particles are pseudotyped using viral glycoproteins of Nipah virus. In some embodiments, the polypeptides or antibodies provided herein are linked to envelope glycoproteins G or H of Paramyxoviridae viruses via a linker. In some embodiments, the Paramyxoviridae viruses are Morbilliviruses, such as measles virus. In some embodiments, the Paramyxoviridae viruses are Henipaviruses, such as Nipah virus, Cedar virus, or Hendra virus.

[0141] As provided herein, viruses can be pseudotyped with the VSV-G protein (either its wild-type or mutant form). While not 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 a virus and transduce cells if the virus contains a targeting moiety. This mutation inhibits or reduces the affinity of VSV-G for its native co-receptor, LDL-R. In some embodiments, the mutant VSV-G protein provided can be used to transduce target cells and deliver heterologous molecules to the targeted cells.

[0142] In some embodiments, a VSV-G protein is provided that contains a mutation at position 198 compared to SEQ ID NO: 1, or at position 182 compared to SEQ ID NO: 2. SEQ ID NO: 1 is the full-length protein, and SEQ ID NO: 2 is the ectodomain of the VSV-G protein. The 16-mer signal peptide MKCLLYLAFLFIGVNC (SEQ ID NO: 65), as shown at the N-terminus of SEQ ID NO: 1, is cleaved, leaving the protein of SEQ ID NO: 2. Thus, the mutation may be mentioned in the context of SEQ ID NO: 2, but it should be understood that it is also made in the context of SEQ ID NO: 1, which contains the leader sequence, and is therefore 16 position numbers greater than the position enumerated for SEQ ID NO: 2. In some embodiments, the mutation inhibits or reduces the binding of the VSV-G protein to the LDL receptor (LDL-R). In some embodiments, the mutation is the I182D mutation compared to SEQ ID NO: 2. In some embodiments, the mutation is the I182E mutation compared to SEQ ID NO: 2.

[0143] In some embodiments, VSV-G proteins are provided that contain a mutation at position 198 compared to SEQ ID NO: 10, or at position 182 compared to SEQ ID NO: 11. SEQ ID NO: 10 is the full-length protein, and SEQ ID NO: 11 is the ectodomain of the VSV-G protein. The 16-mer signal peptide of MLSYLIFALVVSPILG (SEQ ID NO: 66), as shown at the N-terminus of SEQ ID NO: 10, is cleaved, leaving the protein of SEQ ID NO: 11. Thus, the mutation may be mentioned in the context of SEQ ID NO: 11, but it should be understood that it is also made in the context of SEQ ID NO: 10, which contains the leader sequence, and is therefore 16 position numbers greater than the position enumerated for SEQ ID NO: 11. In some embodiments, the mutation inhibits or reduces the binding of the VSV-G protein to the LDL receptor (LDL-R). In some embodiments, the mutation is the T182D mutation compared to SEQ ID NO: 11. In some embodiments, the mutation is the T182E mutation compared to SEQ ID NO: 11.

[0144] In some embodiments, VSV-G proteins are provided that contain a mutation at position 198 compared to SEQ ID NO: 12, or at position 182 compared to SEQ ID NO: 13. SEQ ID NO: 12 is the full-length protein, and SEQ ID NO: 13 is the ectodomain of the VSV-G protein. The 16-mer signal peptide of MLRLFLFCFLALGAHS (SEQ ID NO: 67), as shown at the N-terminus of SEQ ID NO: 12, is cleaved, leaving the protein of SEQ ID NO: 13. Thus, the mutation may be mentioned in the context of SEQ ID NO: 13, but it should be understood that it is also made in the context of SEQ ID NO: 12, which contains the leader sequence, and is therefore 16 position numbers greater than the position enumerated for SEQ ID NO: 13. In some embodiments, the mutation inhibits or reduces the binding of the VSV-G protein to the LDL receptor (LDL-R). In some embodiments, the mutation is the A182D mutation compared to SEQ ID NO: 13. In some embodiments, the mutation is the A182E mutation compared to SEQ ID NO: 13.

[0145] In some embodiments, VSV-G proteins are provided that contain a mutation at position 203 compared to SEQ ID NO: 14, or at position 182 compared to SEQ ID NO: 15. SEQ ID NO: 14 is the full-length protein, and SEQ ID NO: 15 is the ectodomain of the VSV-G protein. The 21-mer signal peptide of MKMKMVIAGLILCIGILPAIG (SEQ ID NO: 68), as shown at the N-terminus of SEQ ID NO: 14, is cleaved, leaving the protein of SEQ ID NO: 15. Thus, the mutation may be mentioned in the context of SEQ ID NO: 15, but it should be understood that it is also made in the context of SEQ ID NO: 14, which contains the leader sequence, and is therefore a position number 21 more than the position enumerated for SEQ ID NO: 15. In some embodiments, the mutation inhibits or reduces the binding of the VSV-G protein to the LDL receptor (LDL-R). In some embodiments, the mutation is the V182D mutation compared to SEQ ID NO: 15. In some embodiments, the mutation is the V182E mutation compared to SEQ ID NO: 15.

[0146] In some embodiments, VSV-G proteins are provided that contain a mutation at position 199 compared to SEQ ID NO: 16, or at position 182 compared to SEQ ID NO: 17. SEQ ID NO: 16 is the full-length protein, and SEQ ID NO: 17 is the ectodomain of the VSV-G protein. The 17-mer signal peptide of MTPAFILCMLLAGSSWA (SEQ ID NO: 69), as shown at the N-terminus of SEQ ID NO: 16, is cleaved, leaving the protein of SEQ ID NO: 17. Thus, the mutation may be mentioned in the context of SEQ ID NO: 17, but it should be understood that it is also made in the context of SEQ ID NO: 16, which contains the leader sequence, and is therefore a position number 17 higher than the position enumerated for SEQ ID NO: 17. In some embodiments, the mutation inhibits or reduces the binding of the VSV-G protein to the LDL receptor (LDL-R). In some embodiments, the mutation is the V182D mutation compared to SEQ ID NO: 17. In some embodiments, the mutation is the V182E mutation compared to SEQ ID NO: 17.

[0147] In some embodiments, VSV-G proteins are provided that contain a mutation at position 199 compared to SEQ ID NO: 18, or at position 182 compared to SEQ ID NO: 19. SEQ ID NO: 18 is the full-length protein, and SEQ ID NO: 19 is the ectodomain of the VSV-G protein. The 17-mer signal peptide of MNFLLLTFIVLPLCSHA (SEQ ID NO: 70), as shown at the N-terminus of SEQ ID NO: 18, is cleaved, leaving the protein of SEQ ID NO: 19. Thus, the mutation may be mentioned in the context of SEQ ID NO: 19, but it should be understood that it is also made in the context of SEQ ID NO: 18, which contains the leader sequence, and is therefore 17 position numbers greater than the position enumerated for SEQ ID NO: 19. In some embodiments, the mutation inhibits or reduces the binding of the VSV-G protein to the LDL receptor (LDL-R). In some embodiments, the mutation is the V182D mutation compared to SEQ ID NO: 19. In some embodiments, the mutation is the V182E mutation compared to SEQ ID NO: 19.

[0148] In some embodiments, VSV-G proteins are provided that contain a mutation at position 199 compared to SEQ ID NO: 20, or at position 182 compared to SEQ ID NO: 21. SEQ ID NO: 20 is the full-length protein, and SEQ ID NO: 21 is the ectodomain of the VSV-G protein. The 17-mer signal peptide of MLVLYLLLSLLALGAQC (SEQ ID NO: 71), as shown at the N-terminus of SEQ ID NO: 20, is cleaved, leaving the protein of SEQ ID NO: 21. Thus, the mutation may be mentioned in the context of SEQ ID NO: 21, but it should be understood that it is also made in the context of SEQ ID NO: 20, which includes the leader sequence, and is therefore 17 position numbers greater than the position enumerated for SEQ ID NO: 21. In some embodiments, the mutation inhibits or reduces the binding of the VSV-G protein to the LDL receptor (LDL-R). In some embodiments, the mutation is the I182D mutation compared to SEQ ID NO: 21. In some embodiments, the mutation is the I182E mutation compared to SEQ ID NO: 21.

[0149] Where used herein, when a polypeptide is said to have mutations compared to a reference sequence, such comparison is based on alignment, such as using BlastP, ClustalW, or ClutalOmega alignment software with default parameters. For example, position 182 can be found in SEQ ID NO: 2 and can also be found when comparing with other strains, as shown in Figure 3. Figure 3 shows cluster alignments of wild-type sequences of the ectodomains of various strains of the VSV-G protein. The residues in bold and underlined are the residues that align to position 182 of SEQ ID NO: 2 in various strains. SEQ ID NO: 2 refers to the ectodomain of the VSV-G protein from the Indiana strain. SEQ ID NO: 11 refers to the ectodomain of the VSV-G protein from the New Jersey strain. SEQ ID NO: 13 refers to the ectodomain of the VSV-G protein from the Malaba strain. SEQ ID NO: 15 refers to the ectodomain of the VSV-G protein from the Karajas strain. SEQ ID NO: 17 refers to the ectodomain of the VSV-G protein from the Alagoa strain. Sequence ID 19 refers to the ectodomain of the VSV-G protein of the Cocal strain. Sequence ID 21 refers to the ectodomain of the VSV-G protein of the Moreton strain. Therefore, the residue aligned at residue 182 compared to Sequence ID 2 can also be mutated as provided herein.

[0150] In some embodiments, the mutation at position 182 compared to SEQ ID NO: 2 is not alanine. In some embodiments, the mutation at position 182 compared to SEQ ID NO: 2 is not valine.

[0151] In some embodiments, the mutation at position 182 compared to sequence number 2 is I182S, I182H, I182T, I182Q, or I182N. In some embodiments, the mutation at position 182 compared to sequence number 11 is T182S, T182H, T182Q, or T182N. In some embodiments, the mutation at position 182 compared to sequence number 13 is A182S, A182H, A182T, A182Q, or A182N. In some embodiments, the mutation at position 182 compared to sequence number 15 is V182S, V182H, V182T, V182Q, or V182N. In some embodiments, the mutation at position 182 compared to sequence number 17 is V182S, V182H, V182T, V182Q, or V182N. In some embodiments, the mutation at position 182, compared to SEQ ID NO: 19, is V182S, V182H, V182T, V182Q, or V182N. In some embodiments, the mutation at position 182, compared to SEQ ID NO: 21, is I182S, I182H, I182T, I182Q, or I182N. In some embodiments, the mutation at position 182 is not a hydrophobic residue. In some embodiments, the mutation at position 182 is a charged residue. In some embodiments, the mutation at position 182 is a negatively charged residue.

[0152] These mutations may be described with reference to SEQ ID NO: 1 or SEQ ID NO: 2, which are VSV-G proteins derived from the Indiana strain, but these mutations may also be used in other strains of the VSV-G protein. For example, the mutations can be produced in the VSV-G New Jersey strain, the VSV-G Malaba strain, the VSV-G Carajas strain, the VSV-G Alagoa strain, the VSV-G Cocal strain, or the VSV-G Moreton strain. In some embodiments, the respective sequences are as provided herein. Examples of these can be found, for example, in U.S. Patent Application Publication No. 2020 / 0216502, which is incorporated herein by reference. For example, the wild-type full-length or ectodomain of the VSV-G New Jersey strain is sequence number 10 and sequence number 11, respectively; the wild-type full-length or ectodomain of the VSV-G Malaba strain is sequence number 12 and sequence number 13, respectively; the wild-type full-length or ectodomain of the VSV-G Carajas strain is sequence number 14 and sequence number 15, respectively; the wild-type full-length or ectodomain of the VSV-G Alagoa strain is sequence number 16 and sequence number 17, respectively; the wild-type full-length or ectodomain of the VSV-G Cocal strain is sequence number 18 and sequence number 19, respectively; or the wild-type full-length or ectodomain of the VSV-G Moreton strain is sequence number 20 and sequence number 21, respectively.

[0153] VSV-G proteins containing a mutation at position 182 compared to SEQ ID NO: 2 may also contain other mutations, such as those described in U.S. Patent Application Publication No. 2020 / 0216502 (which is incorporated herein by reference in its entirety). For example, VSV-G proteins may contain mutations at positions corresponding to positions 8, 47, 209 and / or 354 of SEQ ID NO: 2.

[0154] In some embodiments, the substitution at position 8 is by any amino acid other than the amino acid shown at that position in the sequence of SEQ ID NO: 2, excluding Y. The substitution at position 209 is by any amino acid other than the amino acid shown at that position in the sequence of SEQ ID NO: 2, excluding H. In some embodiments, the substitution at position 47 is by any amino acid other than the amino acid shown at that position in the sequence of SEQ ID NO: 2, excluding K or R. In some embodiments, the substitution at position 354 is by any amino acid other than the amino acid shown at that position in the sequence of SEQ ID NO: 2, excluding K or R.

[0155] In some embodiments, the substitution is by A, G, F, or Q at position 47 or 354, or at both positions 47 and 354. In some embodiments, the substitution is A or Q.

[0156] In some embodiments, the substitution at position 8 is alanine, i.e., H8A.

[0157] In some embodiments, the substitution at position 47 is Q or N, i.e., K47Q or K47N.

[0158] In some embodiments, the protein contains a mutation (substitution) at position 10. In some embodiments, the substitution / mutation is Q10A, Q10R, or Q10K.

[0159] In some embodiments, a protein containing a mutation at position 182 compared to SEQ ID NO: 2 is at least or about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 2 (or SEQ ID NO: 1 if a full-length protein is used). In some embodiments, the polypeptide contains the I182D or I182E mutation. In some embodiments, the VSV-G protein contains the I182S, I182H, I182T, I182Q, or I182N mutation.

[0160] In some embodiments, a protein containing a mutation at position 182 compared to SEQ ID NO: 11 is at least or about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 11 (or SEQ ID NO: 10 if a full-length protein is used). In some embodiments, the polypeptide contains the T182D or T182E mutation. In some embodiments, the VSV-G protein contains the T182S, T182H, T182Q, or T182N mutation.

[0161] In some embodiments, a protein containing a mutation at position 182 compared to SEQ ID NO: 13 is at least or about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 13 (or SEQ ID NO: 12 if a full-length protein is used). In some embodiments, the polypeptide contains the A182D or A182E mutation. In some embodiments, the VSV-G protein contains the A182S, A182H, A182T, A182Q, or A182N mutation.

[0162] In some embodiments, a protein containing a mutation at position 182 compared to SEQ ID NO: 15 is at least or about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 15 (or SEQ ID NO: 14 if a full-length protein is used). In some embodiments, the polypeptide contains the V182D or V182E mutation. In some embodiments, the VSV-G protein contains the V182S, V182H, V182T, V182Q, or V182N mutation.

[0163] In some embodiments, a protein containing a mutation at position 182 compared to SEQ ID NO: 17 is at least or about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 17 (or SEQ ID NO: 16 if a full-length protein is used). In some embodiments, the polypeptide contains the V182D or V182E mutation. In some embodiments, the VSV-G protein contains the V182S, V182H, V182T, V182Q, or V182N mutation.

[0164] In some embodiments, a protein containing a mutation at position 182 compared to SEQ ID NO: 19 is at least or about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 19 (or SEQ ID NO: 189 if a full-length protein is used). In some embodiments, the polypeptide contains the V182D or V182E mutation. In some embodiments, the VSV-G protein contains the V182S, V182H, V182T, V182Q, or V182N mutation.

[0165] In some embodiments, a protein containing a mutation at position 182 compared to SEQ ID NO: 21 is at least or about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 21 (or SEQ ID NO: 20 if a full-length protein is used). In some embodiments, the polypeptide contains the I182D or I182E mutation. In some embodiments, the VSV-G protein contains the I182S, I182H, I182T, I182Q, or I182N mutation. Viral glycoproteins

[0166] The mutant VSV-G protein can be used, for example, to pseudotype a virus (e.g., a lentivirus). Thus, in some embodiments, viral particles comprising the mutant VSV-G protein provided herein are provided. In some embodiments, the viral particles comprise a VSV-G protein having a mutation at position 198 compared to SEQ ID NO: 1. In some embodiments, a protein having a mutation at position 182 compared to SEQ ID NO: 2 is at least or about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 2 (or SEQ ID NO: 1 if a full-length protein is used). In some embodiments, the polypeptide contains the I182D or I182E mutation compared to SEQ ID NO: 2. In some embodiments, the VSV-G protein contains the I182S, I182H, I182T, I182Q, or I182N mutation.

[0167] In some embodiments, the viral particle contains a VSV-G protein with a mutation at position 198 compared to SEQ ID NO: 10. In some embodiments, the protein with a mutation at position 182 compared to SEQ ID NO: 11 is at least or about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 11 (or SEQ ID NO: 10 if a full-length protein is used). In some embodiments, the polypeptide contains a T182D or T182E mutation compared to SEQ ID NO: 11. In some embodiments, the VSV-G protein includes T182S, T182H, T182Q, or T182N mutations.

[0168] In some embodiments, the viral particle contains a VSV-G protein with a mutation at position 198 compared to SEQ ID NO: 12. In some embodiments, the protein with a mutation at position 182 compared to SEQ ID NO: 13 is at least or about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 13 (or SEQ ID NO: 12 if a full-length protein is used). In some embodiments, the polypeptide contains an A182D or A182E mutation compared to SEQ ID NO: 13. In some embodiments, the VSV-G protein includes A182S, A182H, A182T, A182Q, or A182N mutations.

[0169] In some embodiments, the viral particle contains a VSV-G protein with a mutation at position 203 compared to SEQ ID NO: 14. In some embodiments, the protein with a mutation at position 182 compared to SEQ ID NO: 15 is at least or about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 15 (or SEQ ID NO: 14 if a full-length protein is used). In some embodiments, the polypeptide contains a V182D or V182E mutation compared to SEQ ID NO: 15. In some embodiments, the VSV-G protein includes V182S, V182H, V182T, V182Q, or V182N mutations.

[0170] In some embodiments, the viral particle contains a VSV-G protein with a mutation at position 199 compared to SEQ ID NO: 16. In some embodiments, the protein with a mutation at position 182 compared to SEQ ID NO: 17 is at least or about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 17 (or SEQ ID NO: 16 if a full-length protein is used). In some embodiments, the polypeptide contains a V182D or V182E mutation compared to SEQ ID NO: 17. In some embodiments, the VSV-G protein includes V182S, V182H, V182T, V182Q, or V182N mutations.

[0171] In some embodiments, the viral particle contains a VSV-G protein with a mutation at position 199 compared to SEQ ID NO: 18. In some embodiments, the protein with a mutation at position 182 compared to SEQ ID NO: 19 is at least or about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 19 (or SEQ ID NO: 18 if a full-length protein is used). In some embodiments, the polypeptide contains a V182D or V182E mutation compared to SEQ ID NO: 19. In some embodiments, the VSV-G protein includes V182S, V182H, V182T, V182Q, or V182N mutations.

[0172] In some embodiments, the viral particle contains a VSV-G protein with a mutation at position 199 compared to SEQ ID NO: 20. In some embodiments, the protein with a mutation at position 182 compared to SEQ ID NO: 21 is at least or about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 21 (or SEQ ID NO: 20 if a full-length protein is used). In some embodiments, the polypeptide contains an I182D or I182E mutation compared to SEQ ID NO: 21. In some embodiments, the VSV-G protein includes I182S, I182H, I182T, I182Q, or I182N mutations.

[0173] In some embodiments, the VSV-G protein further includes mutations at positions corresponding to positions 214 and / or 352 of SEQ ID NO: 2. In some embodiments, the residue corresponding to position 214 of SEQ ID NO: 2 is T214. In some embodiments, the residue corresponding to position 352 of SEQ ID NO: 1 is T352. In some embodiments, the VSV-G protein includes a mutation corresponding to the T214N mutation compared to SEQ ID NO: 2. In some embodiments, the VSV-G protein includes a mutation corresponding to the T352A mutation compared to SEQ ID NO: 2. In some embodiments, the VSV-G protein includes the T214N and T352A mutations compared to SEQ ID NO: 2. These mutations can be combined with any other mutations provided herein. In some embodiments, the T214N and / or T352A mutations are combined with the I182E or I182D mutation. In some embodiments, the VSV-G protein comprises the amino acid sequences of SEQ ID NOs. 22 and 23, which combine I182D or I182E with the T214N and T352A mutations, respectively. The sequences are also illustrated below along with the leader sequences that are removed during protein processing. VSV-G protein I196D, T230N, and T368A mutations (with leader sequences and adjusted numbering) MKCLLYLAFLFIGVNCKFTIVFPHNQKGNWKNVPSNYHYCPSSSDLNWHNDLIGTALQVKMPKSHKAIQADGWMCHASKWVTTCDFRWYGPKYITHSIRSFTPSVEQCKESIEQTKQGTWLNPGFPPQS CGYATVTDAEAVIVQVTPHHVLVDEYTGEWVDSQFINGKCSNYICPTVHNSTTWHSDYKVKGLCDSNLDSMDITFFSEDGELSSLGKEGTGFRSNYFAYENGGKACKMQYCKHWGVRLPSGVWFEMADKD LFAAARFPECPEGSSISAPSQTSVDVSLIQDVERILDYSLCQETWSKIRAGLPISPVDLSYLAPKNPGTGPAFTIINGTLKYFETRYIRVDIAAPILSRMVGMISGTTAERELWDDWAPYEDVEIGPNGVLRTSSGYKFPLYMIGHGMLDSDLHLSSKAQVFEHPHIQDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCIKLKHTKKRQIYTDIEMNRLGK(Sequence ID 24) VSV-G protein_I182D, T214N, and T352A mutations (no leader sequence) KFTIVFPHNQKGNWKNVPSNYHYCPSSSDLNWHNDLIGTALQVKMPKSHKAIQADGWMCHASKWVTTCDFRWYGPKYITHSIRSFTPSVEQCKESIEQTKQGTWLNPGFPPQSCGYATVTDAEAV IVQVTPHHVLVDEYTGEWVDSQFINGKCSNYICPTVHNSTTWHSDYKVKGLCDSNLDSMDITFFSEDGELSSLGKEGTGFRSNYFAYENGGKACKMQYCKHWGVRLPSGVWFEMADKDLFAAARFP ECPEGSSISAPSQTSVDVSLIQDVERILDYSLCQETWSKIRAGLPISPVDLSYLAPKNPGTGPAFTIINGTLKYFETRYIRVDIAAPILSRMVGMISGTTAERELWDDWAPYEDVEIGPNGVLRTSSGYKFPLYMIGHGMLDSDLHLSSKAQVFEHPHIQDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCIKLKHTKKRQIYTDIEMNRLGK(Sequence ID 22) VSV-G protein with I196E, T230N, and T368A mutations (with leader sequence and adjusted numbering) MKCLLYLAFLFIGVNCKFTIVFPHNQKGNWKNVPSNYHYCPSSSDLNWHNDLIGTALQVKMPKSHKAIQADGWMCHASKWVTTCDFRWYGPKYITHSIRSFTPSVEQCKESIEQTKQGTWLNPGFPPQS CGYATVTDAEAVIVQVTPHHVLVDEYTGEWVDSQFINGKCSNYICPTVHNSTTWHSDYKVKGLCDSNLESMDITFFSEDGELSSLGKEGTGFRSNYFAYENGGKACKMQYCKHWGVRLPSGVWFEMADKD LFAAARFPECPEGSSISAPSQTSVDVSLIQDVERILDYSLCQETWSKIRAGLPISPVDLSYLAPKNPGTGPAFTIINGTLKYFETRYIRVDIAAPILSRMVGMISGTTAERELWDDWAPYEDVEIGPNGVLRTSSGYKFPLYMIGHGMLDSDLHLSSKAQVFEHPHIQDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCIKLKHTKKRQIYTDIEMNRLGK(Sequence ID 25) VSV-G protein with I182E, T214N, and T352A mutations (leader sequence not included) KFTIVFPHNQKGNWKNVPSNYHYCPSSSDLNWHNDLIGTALQVKMPKSHKAIQADGWMCHASKWVTTCDFRWYGPKYITHSIRSFTPSVEQCKESIEQTKQGTWLNPGFPPQSCGYATVTDAEAV IVQVTPHHVLVDEYTGEWVDSQFINGKCSNYICPTVHNSTTWHSDYKVKGLCDSNLESMDITFFSEDGELSSLGKEGTGFRSNYFAYENGGKACKMQYCKHWGVRLPSGVWFEMADKDLFAAARFP ECPEGSSISAPSQTSVDVSLIQDVERILDYSLCQETWSKIRAGLPISPVDLSYLAPKNPGTGPAFTIINGTLKYFETRYIRVDIAAPILSRMVGMISGTTAERELWDDWAPYEDVEIGPNGVLRTSSGYKFPLYMIGHGMLDSDLHLSSKAQVFEHPHIQDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCIKLKHTKKRQIYTDIEMNRLGK(Sequence ID 23)

[0174] Other strains of the VSV-G protein described herein may also include mutations corresponding to T214N and / or T352A in SEQ ID NO: 2, and the mutations shown in SEQ ID NO: 22 and SEQ ID NO: 23.

[0175] In some embodiments, the composition includes mutations described in Hwang et al., Gene Ther 2013 Aug;20(8):807-15. (Epub 2013 Jan 31), which is incorporated herein by reference in its entirety. For example, the mutations may be at positions 230, 368, 66, and / or 162, corresponding to SEQ ID NO: 1. If the leader sequence is removed, the positions will be 16 positions fewer than those in SEQ ID NO: 2. In some embodiments, the mutations at those positions are, for example, T230N, T368A, K66T, S162T, or any combination thereof. In some embodiments, the VSV-G protein includes the T230N and T368A mutations. In some embodiments, the VSV-G polypeptide includes K66T, S162T, T230N, and T368A. These positions correspond to the positions in the full-length protein (SEQ ID NO: 1). In some embodiments, the VSV-G protein includes the T230N mutation, the T368A mutation, the K66T mutation, the S162T mutation, or any combination thereof. In some embodiments, the VSV-G protein further includes one or more mutations (e.g., the mutations described in U.S. Patent Application Publication 2020 / 0216502, which is incorporated herein by reference in its entirety) in addition to the mutation corresponding to position 182 of SEQ ID NO: 2. For example, the VSV-G protein may further include mutations at positions 8, 47, 209 and / or 354 of SEQ ID NO: 2.

[0176] In some embodiments, the substitution at position 8 is by any amino acid other than the amino acid shown at that position in the sequence of SEQ ID NO: 2, except Y. The substitution at position 209 is by any amino acid other than the amino acid shown at that position in the sequence of SEQ ID NO: 2, except H. In some embodiments, the substitution at position 47 is by any amino acid other than the amino acid shown at that position in the sequence of SEQ ID NO: 2, except K or R. In some embodiments, the substitution at position 354 is by any amino acid other than the amino acid shown at that position in the sequence of SEQ ID NO: 2, except K or R. In some embodiments, the substitution occurs at position 47 or 354, or both positions 47 and 354, and is substituted by A, G, F, or Q. In some embodiments, the substitution at position 8 is alanine, i.e., H8A. In some embodiments, the substitution at position 47 is Q or N, i.e., K47Q or K47N. In some embodiments, the protein contains a mutation (substitution) at position 10. In some embodiments, the substitution / mutation is Q10A, Q10R, or Q10K.

[0177] Furthermore, in some embodiments, the virus may be pseudotyped with other viral structural proteins instead of the VSV-G protein or its variants.

[0178] For example, a viral particle can be pseudotyped with the carp spring viremia virus G (SVCV-G) protein and transduction into a cell if the virus contains a targeting moiety. The provided carp spring viremia virus G protein can be used in some embodiments to transduction into target cells and deliver heterologous molecules to target cells. In some embodiments, the carp spring viremia 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 ectodomain of the carp spring viremia virus G protein with the N-terminal signal peptide removed. Thus, in some embodiments, the protein comprises the amino acid sequence of SEQ ID NO: 53. The carp spring viremia virus G protein can be used to pseudotype viruses such as, for example, lentiviruses, but is not limited to these. Thus, in some embodiments, viral particles comprising the carp spring viremia virus G protein provided herein are provided. In some embodiments, the virus particles include a carp spring viremia virus G protein that includes sequence number 52 or sequence number 53, or 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 the sequence of sequence number 52 or sequence number 53.

[0179] Sequence of the carp spring viremia virus-G (SEQ ID NO: 52 - with leader sequence) MSIISYIAFLLLIDSNLGIPIFVPSGRNISWQPVIQPFDYQCPIHGNLPNTMGLSATKLTIKSPSVFSTDKVSGWICHAAEWKTTCDYRWYGPQYITHSIHPISPTIDECRRIIQRIASGTDEDDLGF PPQSCGWASVTTVSNTNYRVVPHSVHLEPYGGHWIDHEFNGGECREKVCEMKGNHSIWITEETVQHECAKHIEEVEGIMYGNVPRGDVMYANNFIIDRHHRVYRFGGSCQMKFCNKDGIKFARGDWV EKTAGTLTTIHDNVPKCVDGTLVSGHRPGLDLIDTVFNLENVVEYTLCEGTKRKINKQEKLTSVDLSYLAPRIGGFGSVFRVRNGTLERGSTTYIRIEVEGPIVDSLNGTDPRTNASRVFWDDWELD GNIYQGFNGVYKGKDGKIHIPLNMIESGIIDDELQHAFQADIIPHPHYDDDEIREDDIFFDNTGENGNPVDAVVEWVSGWGTSLKFFGMTLVALILIFLLIRCCVACTYLMKRSKRPATESHEMRSLV

[0180] Sequence of the carp spring viremia virus-G (SEQ ID NO: 53 - no leader sequence): IPIFVPSGRNISWQPVIQPFDYQCPIHGNLPNTMGLSATKLTIKSPSVFSTDKVSGWICHAAEWKTTCDYRWYGPQYITHSIHPISPTIDECRRIIQRIASGTDEDLGFPPQSCGWASVTTVSNTNYRVVPHSVHLEPYGGHWIDHEFNGGECREKVCEMKGNHSIWITEETVQHECAKHIEEVEGIMYGNVPRGDVMYANNFIIDRHHRVYRFGGSCQMKFCNKDGIKFARGDWVEKTAGTLTT IHDNVPKCVDGTLVSGHRPGLDLIDTVFNLENVVEYTLCEGTKRKINKQEKLTSVDLSYLAPRIGGFGSVFRVRNGTLERGSTTYIRIEVEGPIVDSNLGTDPRTNASRVFWDDWELDGNIYQGFNGVYKGKDGKIHIPLNMIESGIIDDELQHAFQADIIPHPHYDDDEIREDDIFFDNTGENGNPVDAVVEWVSGWGTSLKFFGMTLVALILIFLLIRCCVACTYLMKRSPRATESHEMRSLV The target part

[0181] In some embodiments, the viral particle comprises a targeting moiety having the formula T-S1, where T is a target-binding domain and S1 is a stalk moiety. The targeting moiety can be used to target viral particles containing mutant VSV-G protein or SVCV-G protein to cells expressing 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 may be attached to the viral surface via a mutant Fc protein (e.g., L1-Fc-L2-X1) as provided herein, or via a flexible polypeptide (e.g., L3-X1) as provided herein. In some embodiments, the targeting moiety is bound (fused or ligated) 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 may be bound (fused or ligated) to the glycoprotein of a Rhabdoviridae virus, such as bullous stomatitis New Jersey virus, bullous stomatitis Indiana virus, bullous stomatitis Aragoas virus, bullous stomatitis Maraba virus, bullous stomatitis Karajas virus, parainfluenza virus, fall armyworm rhabdovirus isolate Sf-G, Drosophila Sigma virus 10A, Wuhan insect virus 7, perch virus, or carp spring viremia virus. In some embodiments, the VSV protein is a mutant protein, such as those provided herein. In some embodiments, the targeting moiety is bound to the glycoprotein of a filoviridae virus, such as Ebola virus, or to the glycoprotein of an Arenaviridae virus, such as Machupovirus.

[0182] In some embodiments, the target-binding domain is scFv. In some embodiments, the target-binding domain is a single-domain antibody. In some embodiments, the target-binding domain is VHH.

[0183] In some embodiments, the targeted portion is expressed on CD7, CD8, cKit(CD117), CD4, CD3, CD5, CD6, CD2, TCR alpha, TCR beta, TCR gamma, TCR delta, CD10, CD34, CD110, CD33, CD14, CD68, CCR7, CD62L, CD25, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, or CXCR3, or on acute leukemia or lymphoma, but not on hematopoietic progenitor cells. Glycosylated CD43 epitopes that are not expressed; glycosylated CD43 epitopes expressed on non-hematopoietic cancers; A kinase anchor protein 4 (AKAP-4); adrenergic receptor β3 (ADRB3); AFP; anaplastic lymphoma kinase (ALK); androgen receptor; angiopoietin-binding cell surface receptor 2 (Tie2); autoantibodies against desmoglein 1 (Dsg1); autoantibodies against desmoglein 3 (Dsg3); B7H3 (CD276); biotin; bone Medullary stromal cell antigen 2 (BST2); BST1 / CD157; Cancer / testicular antigen 1 (NY-ESO-1); Cancer / testicular antigen 2 (LAGE-la); Carbonic anhydrase IX (CAIX); Carcinoembryonic antigen (CEA); CCCTC binding factor (zinc finger protein)-like (brother of BORIS or imprint site regulatory factors); CCR4; CD5; CD19; CD20; CD22; CD24; CD30; CD32 (FCGR2A); CD33; CD34; CD38; CD44v6; C D72; CD79a; CD79b; CD97; CD99; CD123; CD171; CD179a; CD179b-IGLll; CD200R; CD276 / B7H3; CD300 molecule-like family member f (CD300LF); CDH1-CD324; CDH6; CDH17; CDH19; X chromosome open reading frame 61 (CXORF61); Claudin 6 (CLDN6); Claudin 18.2 (CLD18A2 or CLDN18A.2); CMV pp65; C-MYC epitope tag; Crypto; CS1 (also known as CD2 subset 1, CRACC, SLAMF7, CD319, or 19A24); CSF2RA (GM-CSFR-α); C-type lectin domain family 12 member A (CLEC12A); C-type lectin-like molecule-1 (CLL-1 or CLECL1);Cyclin B1; Cytochrome P450 IB 1 (CYP1B 1); DLL3; EBV-EBNA3c; EGF-like module-containing mucin-like hormone receptor 2 (EMR2); Elongation factor 2 mutant (ELF2M); Ephrin B2; Ephrin A receptor 2 (EphA2); Epidermal growth factor receptor (EGFR); Epidermal growth factor receptor mutant III (EGFRviii); Epithelial cell adhesion molecule (EPCAM); ERG; ETS translocation mutant gene 6 located on chromosome 12p (ETV6-AML); Fc fragment of IgA receptor (FCAR or CD89); Fc receptor-like 5 5. FCRL5); Fibroblast-activating protein α (FAP); FITC; Fms-like tyrosine kinase 3 (FLT3); Folate receptor alpha (Fra or FR1); Folate receptor beta (FRb); Follicular-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 (αNeu5Ac(2-8)αNe u5Ac(2-3)bDGalp(1-4)bDGlcp(1-1)Cer); ganglioside GM3(αNeu5Ac(2-3)bDClalp(1-4)bDGlcp(1-1)Cer); GD3; GFRalpha4; glycoprotein 100 (gp100); glypican-3 (GPC3); gonadotropin hormone receptor (CGHR or GR); GpA33; GpNMB; GPRC5D; guanylyl cyclase C (GCC); heat shock protein 70-2 mutant (mut hsp70-2); Hepatitis A virus cell receptor 1 (HAVCR1); Hexasaccharide portion of globoH glycoceramide (GloboH); High molecular weight melanoma-associated antigen (HMWMAA); HIV1 envelope glycoprotein; HLA; HLA-DOA; HLA-A; HLA-A2; HLA-B; HLA-C; HLA-DM; HLA-DOB; HLA-DP; HLA-DQ; HLA-DR; HLA-G; HTLV1-Tax; Human papillomavirus E6 (HPV E6); Human papillomavirus E7 (HPV E7); Human telomerase reverse transcriptase (hTERT); IgE; IL13Ra2; IllRa;Also, immunoglobulin λ-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 α-2 (IL-13Ra2 or CD213A2); intestinal carboxylesterase; KIT (CD117); KSHV K8.1; KSHV-gH; LAMP1; regmine; leukocyte immunoglobulin-like receptor subfamily A member 2 (LILRA2); leukocyte-associated immunoglobulin-like receptor 1 (LAIR1); luteinizing hormone receptor (LHR); Lewis (Y) antigen; Lewis Ag; Livl; K9 locus (LY6K); low-conductance chloride channel; lymphocyte antigen 6 complex; lymphocyte antigen 75 (LY75); lymphocyte-specific protein tyrosine kinase (LCK); mammary gland differentiation antigen (NY-BR-1); melanoma antigen recognized by T cell 1 (MelanA or MART1); melanoma-associated antigen 1 (MAGE-A1); melanoma carcinoma testis antigen-1 (MAD-CT-1); melanoma carcinoma testis antigen-2 (MAD-CT-2); melanoma apoptosis inhibitor (ML-IAP); mesothelin; MPL; cell surface-bound mucin 1 (MUC1); N-acetylglucosaminyltransferase V (NA17); nectin-4; nerve cell adhesion molecule (NCAM); NKG2D ;NYBR1;O-acetyl-GD2 ganglioside (OacGD2);olfactory receptor 51E2 (OR51E2);oncogene fusion protein consisting of cleavage cluster region (BCR) and Abelson mouse leukemia virus oncogene homolog 1 (Ab1) (bcr-ab1);P53 variant;paired box protein Pax-3 (PAX3);paired box protein Pax-5 (PAX5);panexin 3 (PANX3);PDL1;P-glycoprotein;placenta-specific 1 (PLAC1);platelet-derived growth factor receptor beta (PDGFR-beta);polysialic acid;proacrosin-binding protein sp32 (OY-TES1);prostase;prostate cancer tumor antigen-1 (PCT A-1 or galectin 8);prostate stem cell antigen (PSCA);prostate-specific membrane antigen (PSMA);prostatic acid phosphatase (PAP);prostein;protease serine 21 (testicin or PRSS21);Proteasome (prosome, macropain) subunit, beta type 9 (LMP2); PTK7; Ras G12V; Ras homolog family member C (RhoC); Rat sarcoma (Ras) mutant; Advanced glycation end product receptor (RAGE-1); Receptor tyrosine kinase-like orphan receptor 1 (ROR1); Receptor tyrosine protein kinase, ERBB2 or Her-22 / neu; Renal ubiquitous receptor 1 (RU1); Renal ubiquitous receptor 2 (RU2); Sarcoma translocation breakpoint; Serine 2 (TMPRSS2) ETS fusion gene; Sialyl Lewis adhesion molecule (sLe); SLAMF4; SLAMF6; Slea (CA19.9 or sialyl Lewis antigen); Sperm protein 17 (SPA17); T cell Squamous cell carcinoma antigen recognized by 3 (SART3); Stage-specific embryonic antigen-4 (SSEA-4); STEAP1; Sulbibin; Synovial sarcoma X-section 2 (SSX2); TCR-γ alternative leading frame protein (TARP); TCR-beta-1 chain; TCR-beta-2 chain; TCR-delta chain; TCR-gamma chain; TCR-gamma-delta; Telomerase; TGFbetaR2; Antigen recognized by TNT antibody; Thyroid-stimulating hormone receptor (TSHR); Timl- / HVCR1; Tissue factor 1 (TF1); Tn A viral particle according to claim 3, which binds to ag; Tn antigen ((Tn Ag) or (GaINAcu-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 myeloma virus oncogene neuroblastoma-derived homolog (MYCN); Wilms tumor protein (WT1); or X antigen family, member 1A (XAGE1). In some embodiments, the targeted moiety binds to CD7. In some embodiments, the targeted moiety binds to CD8.

[0184] In some embodiments, the targeting portion binds to a target present on a cell, such as an immune cell. In some embodiments, the cell is an immune cell, such as a T cell, a B cell, etc., but not limited to these; NK cells, dendritic cells, neutrophils, macrophages, cancer cells; or, for example, a 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, as described in any one of embodiments 182 to 186. In some embodiments, the cells are T cells. In some embodiments, the cells are B cells. In some embodiments, the cells are CD7+ T cells and / or CD8+ T cells. CD7-conjugated polypeptide

[0185] In some embodiments, the targeted portion (e.g., polypeptide) binds to CD7.

[0186] 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(Sequence ID 29).

[0187] In some embodiments, the CD7 to which the polypeptide binds is expressed on the surface of the cell. In some embodiments, the cells are immune cells. In some embodiments, the immune T cells are CD7+ T cells, CD4+ T cells, CD8+ T cells, NK cells, α-β T cells, γ-δ T cells, lymphoid progenitor cells, hematopoietic stem cells, myeloid cells, monocytes, macrophages, central memory T cells, effector memory T cells, stem cell-like memory T cells, naive T cells, activated T cells, regulatory T cells (TReg), terminally differentiated effector memory T cells (TEMRA), resident memory T cells (TRM), or T cells CD8+CCR7+.

[0188] In some embodiments, the antibody includes an Fc region. The Fc region may be linked to the heavy or light chain of the antibody. In some embodiments, the Fc region is IgG Fc. In some embodiments, IgG is selected from IgG1, IgG2, IgG3, or IgG4. In some embodiments, IgG Fc is IgG1 Fc. In some embodiments, the antibody includes a constant Fc region as described herein, such as SEQ ID NOs. 26, 27, or 28, or a variant thereof provided herein.

[0189] In some embodiments, polypeptides (e.g., CD7-binding polypeptides) are provided herein. In some embodiments, antibodies (e.g., anti-CD7 antibodies) are provided herein. In some embodiments, the antibody includes 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 (e.g., mouse, rat, pig, dog, non-human primate) CD7 protein. As used herein, the term “recombinant antibody” refers to an antibody that does not exist in nature. In some embodiments, the term “recombinant antibody” refers to an antibody that has not been isolated from a human subject.

[0190] In some embodiments, an antibody or an antigen-binding fragment thereof is provided, comprising a peptide selected from the following table illustrating CDRs based on Chothia numbering. TIFF2026520754000002.tif24170

[0191] In some embodiments, the polypeptide, antibody, or antibody-conjugated fragment comprises a heavy chain CDR or light chain CDR provided in the table above. In some embodiments, the polypeptide, antibody, or antibody-conjugated fragment comprises a heavy chain CDR or light chain CDR provided in the table above and binds to non-human primate CD7. In some embodiments, the polypeptide, antibody, or antibody-conjugated fragment comprises a heavy chain CDR or light chain CDR provided in the table above and binds to human CD7. In some embodiments, the polypeptide, antibody, or antibody-conjugated fragment comprises a light chain CDR having a sequence selected from SEQ ID NOs.33 to 35. In some embodiments, the polypeptide, antibody, or antibody-conjugated fragment comprises a light chain CDR having the sequence of SEQ ID NO.33. In some embodiments, the polypeptide, antibody, or antibody-conjugated fragment comprises a light chain CDR having the sequence of SEQ ID NO.34. In some embodiments, the polypeptide, antibody, or antibody-conjugated fragment comprises a light chain CDR having the sequence of SEQ ID NO.35. In some embodiments, the polypeptide, antibody, or antibody-conjugated fragment comprises a heavy chain CDR having a sequence selected from SEQ ID NOs.30 to 32. In some embodiments, the polypeptide, antibody, or antibody-conjugated fragment comprises a heavy chain CDR having the sequence of SEQ ID NO: 30. In some embodiments, the polypeptide, antibody, or antibody-conjugated fragment comprises a heavy chain CDR having the sequence of SEQ ID NO: 31. In some embodiments, the polypeptide, antibody, or antibody-conjugated fragment comprises a heavy chain CDR having the sequence of SEQ ID NO: 32. The CDRs referenced in embodiments throughout this specification can be interchanged with CDRs characterized by different formats such as Kabat and IMGT.

[0192] In some embodiments, the polypeptide, antibody, or antibody-conjugated 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.

[0193] In some embodiments, the polypeptide, antibody, or antibody-conjugated fragment thereof comprises a heavy chain variable region having HCDR1, HCDR2, and HCDR3, where 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.

[0194] In some embodiments, the polypeptide, antibody, or antibody-conjugated fragment comprises (i) a light chain having any one of the aforementioned enumerated combinations of LCDR1, LCDR2, and LCDR3 sequences; and (ii) a heavy chain having any one of the aforementioned enumerated combinations of HCDR1, HCDR2, and HCDR3 sequences.

[0195] Different CDR motifs can be combined in any combination, including those not shown in the table above. For example, the following embodiments are provided as non-limiting examples of such combinations.

[0196] In some embodiments, the polypeptide, antibody, or antigen-binding fragment thereof comprises a polypeptide comprising (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 sequence has the amino acid sequence of SEQ ID NO: 34; and 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 light chain variable region having any of the aforementioned variants, according to claim 36.

[0197] The previous paragraph may refer to CDR under the Chothia system, but equivalent CDR sequences from IMGT and Kabat specifications can be used.

[0198] In some embodiments, the light chain variable region CDR1 is replaced by any of the other light chain CDR1 sequences. In some embodiments, the light chain variable region CDR2 is replaced by any of the other light chain CDR2 sequences. In some embodiments, the light chain variable region CDR3 is replaced by any of the other light chain CDR3 sequences. In some embodiments, the heavy chain variable region CDR1 is replaced by any of the other heavy chain CDR1 sequences. In some embodiments, the heavy chain variable region CDR2 is replaced by any of the other heavy chain CDR2 sequences. In some embodiments, the heavy chain variable region CDR3 is replaced by any of the other heavy chain CDR3 sequences.

[0199] In some embodiments, the polypeptide comprises a heavy chain variable region peptide or a variant thereof having one of the following sequences: TIFF2026520754000003.tif23170

[0200] In some embodiments, the polypeptide comprises a light chain variable region peptide or a variant thereof having one of the following sequences: TIFF2026520754000004.tif19170

[0201] In some embodiments, the polypeptide, antibody, or antigen-binding fragment thereof is V of SEQ ID NO: 36 H Contains peptides. In some embodiments, polypeptides, antibodies, or antigen-binding fragments thereof are V of SEQ ID NO: 37 L Contains peptides. In some embodiments, polypeptides, antibodies, or antigen-binding fragments thereof are V H Peptides and V L Contains peptides, V H The peptide contains the sequence of SEQ ID NO: 36 or a variant thereof, V L The peptide contains the sequence of SEQ ID NO: 37 or a variant thereof. In some embodiments, the polypeptide, antibody, or antigen-binding fragment thereof is V H Peptides and V L Contains peptides, V H The peptide contains the sequence of SEQ ID NO: 36 or a variant thereof, VL 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 non-human primate CD7. In some embodiments, the polypeptide, antibody, or antigen-binding fragment thereof is V H Peptides and V L Contains peptides, V H The peptide contains 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 contains the sequence of SEQ ID NO: 36, V L The peptide contains the sequence of SEQ ID NO: 37.

[0202] V H and V L The array is V H and V L This includes, but is not limited to, the scFv format in which regions are linked by peptide linkers, and may be any other format. Examples of peptide linkers that can be used to link the various peptides provided herein include, but are not limited to, the following: (GGGGS) n (Sequence ID 55), where 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 region is not linked to the peptide linker. In some embodiments, the polypeptide includes Sequence ID 36 or Sequence ID 37.

[0203] As provided herein, polypeptides, antibodies, or antigen-binding fragments thereof may be variants of their sequences.

[0204] The sequence of a polypeptide or antibody may be modified to obtain a human IgG antibody. The sequence transformations provided herein may be modified to obtain other types of antibodies. CDRs can also be linked to other antibodies, proteins, or molecules to create antibody fragments that bind to CD7.

[0205] In some embodiments, the polypeptide or antibody provided herein is a targeting portion on the surface of a genetically engineered viral particle. In some embodiments, the targeting portion enables binding to target cells. In some embodiments, the targeting portion is a CD7 binding portion, 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: 38: DILLTQSPAILSVSPGERVSFSCRASQSIGTSIHWYQQRTNDSPRLLIKYASESISGIPSRFSGSGSGTDFTLSINSVESEDIADYYCQQSNSWPTTFGGGTKLEIKRGGGGSGGGGSGGGGSGGGGSQVQLQQPGAELVKPGASVKLSCKASGYPFTSYWIHWVKQRPGRGLEWLGRIDPNSGDTKYNEKFKNKATLTVDKSSTTAYMQLSSLTSEDSAVYYCARSPYYSNDNSMDYWGQGTSVTVSS(Sequence ID 38) Alternatively, it may be substantially the same as SEQ ID NO: 38, or an active fragment of SEQ ID NO: 38. In some embodiments, the target-binding domain ("T") includes a sequence that is at least 90% identical to the sequence of SEQ ID NO: 38. In some embodiments, the target-binding domain ("T") includes a sequence that is at least 95% identical to the sequence of SEQ ID NO: 38. In some embodiments, the target-binding domain ("T") includes a sequence that is at least 99% identical to the sequence of SEQ ID NO: 38. In some embodiments, the target-binding domain ("T") described 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.

[0206] In some embodiments, the polypeptide or antibody provided herein is a targeting moiety on the surface of a genetically engineered viral particle. In some embodiments, the engineered viral particle is a pseudotyped virus-like particle. In some embodiments, the targeting moiety enables binding to a target cell. In some embodiments, the targeting moiety is a CD7 binding moiety, such as the polypeptide or antibody provided herein. In some embodiments, the target-binding domain ("T") 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: 39. In some embodiments, the target-binding domain ("T") includes a sequence that is at least 90% identical to the sequence of SEQ ID NO: 39. QVQLQQPGAELVKPGASVKLSCKASGYPFTSYWIHWVKQRPGRGLEWLGRIDPNSGDTKYNEKFKNKATLTVDKSSTTAYMQLSSLTSEDSAVYYCARSPYYSNDNSMDYWGQGTSVTVSSGGGGSGGGGSGGGGSGGGGSDILLTQSPAILSVSPGERVSFSCRASQSIGTSIHWYQQRTNDSPRLLIKYASESISGIPSRFSGSGSGTDFTLSINSVESEDIADYYCQQSNSWPTTFGGGTKLEIKR (Sequence ID 39) Alternatively, it may be substantially similar to SEQ ID NO: 39, or an active fragment of SEQ ID NO: 39. In some embodiments, the target-binding domain ("T") includes a sequence that is at least 95% identical to the sequence of SEQ ID NO: 39. In some embodiments, the target-binding domain ("T") includes a sequence that is at least 99% identical to the sequence of SEQ ID NO: 39. In some embodiments, the target-binding domain ("T") described 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. CD8-bound polypeptide

[0207] In some embodiments, the targeting moiety (e.g., polypeptide) may bind to CD8.

[0208] In some embodiments, the polypeptide binds to CD8. In some embodiments, the polypeptide binds to CD8-alpha. In some embodiments, the polypeptide binds to CD8-beta. In some embodiments, the polypeptide binds to a CD8 heterodimer. In some embodiments, the CD8 heterodimer contains CD8-alpha and CD8-beta subunits. In some embodiments, the polypeptide binds to a CD8-alpha homodimer. In some embodiments, the polypeptide that binds to CD8 is an antibody that binds to non-human primate CD8. In some embodiments, the antibody that binds to non-human primate CD8 is an antibody that binds to non-human primate CD8-α. 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 a non-human primate CD8-α homodimer. In some embodiments, the antibody that binds to non-human primate CD8 is an antibody that binds to a 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 (Sequence ID 40): MALPVTALLLPLALLLHAARPSQFRVSPLDRTWNLGETVELKCQVLLSNPTSGCSWLFQPRGAAASPTFLLYLSQNKPKAAEGLDTQRFSGKRLGDTFVLTLSDFRRENEGCYFCSALSNSIMYFSHFVPVFLPAKPTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCNHRNRRRVCKCPRPVVKSGDKPSLSARYV (Sequence ID 40).

[0209] The sequence of human CD8-beta (UniProtKB Q8TD28) is as follows (sequence number 41): MRPRLWLLLAAQLTVLHGNSVLQQTPAYIKVQTNKMVMLSCEAKISLSNMRIYWLRQRQAPSSDSHHEFLALWDSAKGTIHGEEVEQEKIAVFRDASRFILNLTSVKPEDSGIYFCMIVGSPELTFGKGTQLSVVDFLPTTAQPTKKSTLKKRVCRLPRPETQKGPLCSPITLGLLVAGVLVLLVSLGVAIHLCCRRRRARLRFMKQLYK (Sequence ID 41).

[0210] 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 T cell is a CD7+ T cell, CD4+ T cell, CD8+ T cell, NK cell, α-β T cell, γ-δ 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 T cell CD8+CCR7+. In some embodiments, the cell is a CD8+ T cell. In some embodiments, the cell is a CD8+ cell.

[0211] In some embodiments, the antibody includes an Fc region. The Fc region may be linked to the heavy or light chain of the antibody. In some embodiments, the Fc region is IgG Fc. In some embodiments, IgG is selected from IgG1, IgG2, IgG3, or IgG4. In some embodiments, IgG Fc is IgG1 Fc. In some embodiments, the antibody includes a constant Fc region as described herein, such as SEQ ID NOs: 26, 27, or 28 or a variant thereof.

[0212] In some embodiments, polypeptides (e.g., CD8-conjugated polypeptides) are provided herein. In some embodiments, antibodies (e.g., anti-CD8 antibodies) are provided herein. In some embodiments, the antibody includes 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 (e.g., mouse, rat, pig, dog, non-human primate) CD8 protein. As used herein, the term “recombinant antibody” refers to an antibody that does not exist in nature. In some embodiments, the term “recombinant antibody” refers to an antibody that has not been isolated from a human subject.

[0213] In some embodiments, an antibody or an antigen-binding fragment thereof is provided, comprising a peptide selected from the following table illustrating CDRs based on Chothia numbering. TIFF2026520754000005.tif24170

[0214] In some embodiments, the polypeptide, antibody, or antibody-conjugated fragment comprises a heavy-chain CDR or light-chain CDR provided in the table above. In some embodiments, the polypeptide, antibody, or antibody-conjugated fragment comprises a heavy-chain CDR or light-chain CDR provided in the table above and binds to non-human primate CD8. In some embodiments, the polypeptide, antibody, or antibody-conjugated fragment comprises a heavy-chain CDR or light-chain CDR provided in the table above and binds to human CD8. In some embodiments, the polypeptide, antibody, or antibody-conjugated fragment comprises a light-chain CDR having a sequence selected from SEQ ID NOs. 45 to 47. In some embodiments, the polypeptide, antibody, or antibody-conjugated fragment comprises a light-chain CDR having the sequence of SEQ ID NO. 45. In some embodiments, the polypeptide, antibody, or antibody-conjugated fragment comprises a light-chain CDR having the sequence of SEQ ID NO. 46. In some embodiments, the polypeptide, antibody, or antibody-conjugated fragment comprises a light-chain CDR having the sequence of SEQ ID NO. 47. In some embodiments, the polypeptide, antibody, or antibody-conjugated fragment comprises a heavy-chain CDR having a sequence selected from SEQ ID NOs. 42 to 44. In some embodiments, the polypeptide, antibody, or antibody-conjugated fragment comprises a heavy chain CDR having the sequence of SEQ ID NO: 42. In some embodiments, the polypeptide, antibody, or antibody-conjugated fragment comprises a heavy chain CDR having the sequence of SEQ ID NO: 43. In some embodiments, the polypeptide, antibody, or antibody-conjugated fragment comprises a heavy chain CDR having the sequence of SEQ ID NO: 44. The CDRs referenced in embodiments throughout this specification can be interchanged with CDRs characterized by different formats such as Kabat and IMGT.

[0215] In some embodiments, the polypeptide, antibody, or antibody-conjugated 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.

[0216] In some embodiments, the polypeptide, antibody, or antibody-bound fragment thereof comprises a heavy chain variable region having HCDR1, HCDR2, and HCDR3, where HCDR1 has the sequence of SEQ ID NO: 42, HCDR2 has the sequence of SEQ ID NO: 43, and HCDR3 has the sequence of SEQ ID NO: 44.

[0217] In some embodiments, the polypeptide, antibody, or antibody-conjugated fragment comprises (i) a light chain having any one of the aforementioned enumerated combinations of LCDR1, LCDR2, and LCDR3 sequences; and (ii) a heavy chain having any one of the aforementioned enumerated combinations of HCDR1, HCDR2, and HCDR3 sequences.

[0218] Different CDR motifs can be combined in any combination, including those not shown in the table above. For example, the following embodiments are provided as non-limiting examples of such combinations.

[0219] In some embodiments, the polypeptide, antibody, or antigen-binding fragment thereof comprises a polypeptide comprising (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 sequence has the amino acid sequence of SEQ ID NO: 46; and 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 a light chain variable region having any of the aforementioned variants, according to claim 36.

[0220] The previous paragraph may refer to CDR under the Chothia system, but equivalent CDR sequences from IMGT and Kabat specifications can be used.

[0221] In some embodiments, the light chain variable region CDR1 is replaced by any of the other light chain CDR1 sequences. In some embodiments, the light chain variable region CDR2 is replaced by any of the other light chain CDR2 sequences. In some embodiments, the light chain variable region CDR3 is replaced by any of the other light chain CDR3 sequences. In some embodiments, the heavy chain variable region CDR1 is replaced by any of the other heavy chain CDR1 sequences. In some embodiments, the heavy chain variable region CDR2 is replaced by any of the other heavy chain CDR2 sequences. In some embodiments, the heavy chain variable region CDR3 is replaced by any of the other heavy chain CDR3 sequences.

[0222] In some embodiments, the polypeptide comprises a heavy chain variable region peptide or a variant thereof having one of the following sequences: TIFF2026520754000006.tif23170

[0223] In some embodiments, the polypeptide comprises a light chain variable region peptide or a variant thereof having one of the following sequences: TIFF2026520754000007.tif19170

[0224] In some embodiments, the polypeptide, antibody, or antigen-binding fragment thereof is V of SEQ ID NO: 48 H Contains peptides. In some embodiments, polypeptides, antibodies, or antigen-binding fragments thereof are V of SEQ ID NO: 49 L Contains peptides. In some embodiments, polypeptides, antibodies, or antigen-binding fragments thereof are V H Peptides and V L Contains peptides, V H The peptide contains the sequence of SEQ ID NO: 48 or a variant thereof, V L The peptide contains the sequence of SEQ ID NO: 49 or a variant thereof. In some embodiments, the polypeptide, antibody, or antigen-binding fragment thereof is V H Peptides and V L Contains peptides, V H The peptide contains the sequence of SEQ ID NO: 48 or a variant thereof, VL 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 Peptides and V L Contains peptides, V H The peptide contains 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 contains the sequence of SEQ ID NO: 48, V L The peptide contains the sequence of SEQ ID NO: 49.

[0225] V H and V L The array is V H and V L The peptide linkers may be in any form, including but not limited to the scFv form, in which regions are linked by peptide linkers. 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), where 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 region is not linked to the peptide linker. In some embodiments, the polypeptide includes SEQ ID NO: 48 or SEQ ID NO: 49.

[0226] As provided herein, polypeptides, antibodies, or antigen-binding fragments thereof may be variants of their sequences.

[0227] The sequence of a polypeptide or antibody may be modified to obtain a human IgG antibody. The sequence transformations provided herein may be modified to obtain other types of antibodies. CDRs can also be linked to other antibodies, proteins, or molecules to create antibody fragments that bind to CD8.

[0228] In some embodiments, the polypeptide or antibody provided herein is a targeting portion on the surface of a genetically engineered viral particle. In some embodiments, the targeting portion enables binding to target cells. In some embodiments, the target-binding domain ("T") is a CD8-binding portion, 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: 50 NIVLTQSPASLAVSLGQRATISCRASESVDGFGNSFMNWYQQKPGQSPKLLIYLASNLESGVPARFSGSGSRTDFTLTIDPVEADDAATYYCQQNNEDPYTFGGGTKLEIKRGGGGSGGGGSGGGGSGGGGSEVQLQQSGPELVKPGASVKISCKASRYTFTDYNLHWVKLSHEKSLEWIGFIYPYNGGTGYNQKFKNKAKLTVDYSSSTAYMELRSLTSVDAAVYYCARDHRYNEGVSFDYWGQGTTLTVSS(Sequence ID 50) Alternatively, it may be substantially the same as SEQ ID NO: 50, or an active fragment of SEQ ID NO: 50. In some embodiments, the target-binding domain ("T") includes a sequence that is at least 90% identical to the sequence of SEQ ID NO: 50. In some embodiments, the target-binding domain ("T") includes a sequence that is at least 95% identical to the sequence of SEQ ID NO: 50. In some embodiments, the target-binding domain ("T") includes a sequence that is at least 99% identical to the sequence of SEQ ID NO: 50. In some embodiments, the target-binding domain ("T") described in SEQ ID NO: 50 is an antibody or an antigen-binding fragment thereof. In some embodiments, the targeting portion is an anti-CD8 antibody.

[0229] In some embodiments, the polypeptide or antibody provided herein is a targeting moiety on the surface of a genetically engineered viral particle. In some embodiments, the engineered viral particle is a pseudotyped virus-like particle. In some embodiments, the targeting moiety enables binding to a target cell. In some embodiments, the 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 (Sequence ID 51) Alternatively, it may be substantially similar to SEQ ID NO: 51, or an active fragment of SEQ ID NO: 51. In some embodiments, the target-binding domain ("T") includes a sequence that is at least 90% identical to the sequence of SEQ ID NO: 51. In some embodiments, the target-binding domain ("T") includes a sequence that is at least 95% identical to the sequence of SEQ ID NO: 51. In some embodiments, the target-binding domain ("T") includes a sequence that is at least 99% identical to the sequence of SEQ ID NO: 51. In some embodiments, the target-binding domain ("T") includes the sequence described in SEQ ID NO: 51. In some embodiments, the target-binding domain ("T") described in SEQ ID NO: 51 is an antibody or an antigen-binding fragment thereof. In some embodiments, the targeting portion 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. Targeted portion including the Fc domain

[0230] In some embodiments, V H and V LThe polypeptide is linked to a stalk portion S1 containing an Fc region. In some embodiments, the Fc region is as provided herein. In some embodiments, the Fc region is a variant Fc region provided herein. Non-restrictive mutations in the Fc region are provided herein. In some embodiments, the variant 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 mutations 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 mutations selected from the group consisting of N297A, P329G, I253A, H310A, and H435A provided herein. 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 provided herein. As provided herein, the heavy chain may be linked to the Fc region. In some embodiments, the Fc region further comprises (e.g., linked to) a transmembrane domain. In some embodiments, the Fc region further comprising the transmembrane domain has the formula L1-Fc-L2-X1, where L1 is or is absent a linker provided herein, Fc is a variant Fc region provided herein, L2 is or is absent a linker provided herein, and X1 is a polypeptide comprising a transmembrane domain provided herein. As provided herein, X1 is a polypeptide of the formula ECD-T M -May contain a polypeptide having an ICD, wherein the ECD is an extracellular domain or fragment thereof provided herein, or is absent. M The transmembrane domain provided herein is the transmembrane domain, and the ICD is either an intracellular domain provided herein or absent. Examples of ECDs include, but are not limited to, the CD8 and / or CD28 extracellular domains provided herein. MExamples include, but are not limited to, the CD8 and / or CD28 transmembrane domains provided herein. In some embodiments, X1 is T M It includes, and ECD and ICD are absent. In some embodiments, X1 is ECD, T M It includes, and ICD is not present. In some embodiments, X1 is T M and includes ICD, but does not include ECD. In some embodiments, X1 is ECD, T M , and ICD. It should be understood that in any of the following embodiments, the ECD, ICD, or both may be optionally omitted. Therefore, X1 may be CD8 and / or CD28 ECD, CD8 and / or CD28 T M Embodiments including an ICD with an Env embedded motif are understood to include the following X1 members: i) CD8 and / or CD28 ECD, CD8 and / or CD28 T M , and ICDs including the Env built-in motif; ii) CD8 and / or CD28 T M iii) ICDs including an Env built-in motif, and ICDs in which an ECD does not exist; CD8 and / or CD28 ECD, and CD8 and / or CD28 T M and for which no ICD exists; and iv) CD8 and / or CD28 T M and in which neither ECD nor ICD exists. Similarly, X1 is CD8 and / or CD28 T M Embodiments including an ICD that also includes an Env incorporation motif are understood to include the following X1 members: i) CD8 and / or CD28 T M ii) ICDs that include an Env incorporation motif; and ii) CD8 and / or CD28 T for which no ICD exists. M Similarly, X1 is CD8 and / or CD28 ECD, and CD8 and / or CD28 T M Embodiments including the following X1 members are understood to include: i) CD8 and / or CD28 ECD, and CD8 and / or CD28 T Mii) CD8 and / or CD28 T where ECD does not exist M Furthermore, the above explanation is specific to ECD, T M It should be understood that this also applies to embodiments in which ICD is not described. For example, if X1 is ECD, CD8 and / or CD28 T M Embodiments including ICD are understood to include the following X1 members: i) ECD, CD8 and / or CD28 T M ii) ICD, and CD8 and / or CD28 T M Includes, and no ICD exists; iii) CD8 and / or CD28 T M , and ICDs for which ECD is absent; and iv) CD8 and / or CD28 T for which ECD and ICD are absent. M Similarly, X1 is CD8 and / or CD28 T M Embodiments including 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 for which no ICD exists. M Similarly, X1 is ECD, and CD8 and / or CD28 T M Embodiments including the following X1 members are understood to include: i) ECD, and CD8 and / or CD28 T M ii) CD8 and / or CD28 T M However, ECD does not exist. Unless otherwise explicitly stated, the above embodiments and descriptions are applicable to any of the following embodiments.

[0231] In some embodiments, X1 is CD8 and / or CD28 ECD, T M , and ICD. In some embodiments, X1 is ECD, CD8 and / or CD28 T M , and ICD. In some embodiments, X1 is CD8 and / or CD28 ECD, CD8 and / or CD28 T M , and ICD. In some embodiments, X1 is ECD, T M, and ICD, the ICD includes the Env embedded motif provided herein. In some embodiments, X1 is CD8 and / or CD28 ECD, T M , and ICD, the ICD includes the Env embedded motif provided herein. In some embodiments, X1 is ECD, CD8 and / or CD28 T M , and ICD, the ICD includes Env embedded motifs provided herein. In some embodiments, X1 is CD8 and / or CD28 ECD, CD8 and / or CD28 T M , and including ICD, the ICD includes Env embedded motifs provided herein.

[0232] In some embodiments, V provided herein H and V L The polypeptide is linked to a stalk portion (S1) containing an Fc region provided herein. In some embodiments, V provided herein H and V L The polypeptide is linked to a stalk portion (S1) which includes an Fc region containing a transmembrane domain provided herein. In some embodiments, the Fc region further containing a transmembrane domain has the formula L1-Fc-L2-X1, where L1 is a linker provided herein or is absent, Fc is a variant Fc region provided herein, L2 is a linker provided herein or is absent, and X1 is a polypeptide containing a transmembrane domain provided herein. As provided herein, X1 is a polypeptide of the formula ECD-T M -May contain a polypeptide having an ICD, wherein the ECD is an extracellular domain or fragment thereof provided herein or not provided herein, and T M is a transmembrane domain provided herein, and ICD is either an intracellular domain provided herein or absent. In some embodiments, V provided herein H and V L Polypeptides are CD8 and / or CD28 ECD, T M, and is connected to a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD. In some embodiments, V provided herein H and V L Polypeptides are ECD, CD8 and / or CD28 T M , and is connected to a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD. In some embodiments, V provided herein H and V L Polypeptides are CD8 and / or CD28 ECD, CD8 and / or CD28 T M , and is connected to a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD. In some embodiments, V provided herein H and V L Polypeptides are ECD, T M , and connected to a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD, the ICD including an Env embedded motif provided herein. In some embodiments, V provided herein H and V L Polypeptides are CD8 and / or CD28 ECD, T M , and connected to a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD, the ICD including an Env embedded motif provided herein. In some embodiments, V provided herein H and V L Polypeptides are ECD, CD8 and / or CD28 T M , and connected to a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD, the ICD including an Env embedded motif provided herein. In some embodiments, V provided herein H and V L Polypeptides are CD8 and / or CD28 ECD, CD8 and / or CD28 T M, and connected to a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD, the ICD includes an Env embedded motif provided herein. In some embodiments, the ECD, T M , and V provided herein, connected to the stalk portion (S1) including the Fc region, including the ICD H and V L Polypeptide L1-Fc-L2-X1) is immobilized on the surface of viral particles, such as those provided herein. In some embodiments, L1, Fc, L2, ECD, T M The identity of the ICD is provided herein. In some embodiments, V H and V L Polypeptides bind to immune cells, such as those provided herein.

[0233] In some embodiments, V has the sequence described in Sequence ID No. 36. H Peptide and V having the sequence described in SEQ ID NO: 37 L Peptides are ECD, T M , and are connected to a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD. In some embodiments, V has the sequence described in sequence number 36. H Peptide and V having the sequence described in SEQ ID NO: 37 L The peptide is CD8 and / or CD28 ECD, T M , and are connected to a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD. In some embodiments, V has the sequence described in sequence number 36. H Peptide and V having the sequence described in SEQ ID NO: 37 L The peptides are ECD, CD8 and / or CD28 T M , and is connected to a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) containing the ICD. In some embodiments, V has the sequence described in sequence number 36. H Peptide and V having the sequence described in SEQ ID NO: 37 L The peptides are CD8 and / or CD28 ECD, CD8 and / or CD28 TM , and is connected to a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) which includes an ICD. In some embodiments, V has the sequence described in sequence number 36. H Peptide and V having the sequence described in SEQ ID NO: 37 L Peptides are ECD, T M , and coupled to a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD, the ICD includes an Env embedded motif provided herein. In some embodiments, V has the sequence described in Sequence ID No. 36. H Peptide and V having the sequence described in SEQ ID NO: 37 L The peptide is CD8 and / or CD28 ECD, T M , and coupled to a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD, the ICD includes an Env embedded motif provided herein. In some embodiments, V has the sequence described in Sequence ID No. 36. H Peptide and V having the sequence described in SEQ ID NO: 37 L The peptides are ECD, CD8 and / or CD28 T M , and coupled to a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD, the ICD includes an Env embedded motif provided herein. In some embodiments, V has the sequence described in Sequence ID No. 36. H Peptide and V having the sequence described in SEQ ID NO: 37 L The peptides are CD8 and / or CD28 ECD, CD8 and / or CD28 T M , and connected to a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD, the ICD includes an Env embedded motif provided herein. In some embodiments, the ECD, T M , and V having the sequence described in Sequence ID 36, which is linked to the stalk portion (S1) including the Fc region, including the ICD. H Peptide and V having the sequence described in SEQ ID NO: 37 LThe peptide (L1-Fc-L2-X1) is immobilized on the surface of a viral particle, such as those provided herein. In some embodiments, L1, Fc, L2, ECD, T M The identity of the ICD is provided herein. In some embodiments, V H and V L Polypeptides bind to immune cells, such as those provided herein.

[0234] In some embodiments, V 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 sequence number 36. H Peptide; and V containing 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 ligated to a stalk moiety (S1) containing an Fc region provided herein. In some embodiments, the V contains 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 V containing 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 a stalk moiety (S1) containing an Fc region, which includes a transmembrane domain provided herein. In some embodiments, the Fc region further containing a transmembrane domain has the formula L1-Fc-L2-X1, where L1 is either a linker provided herein or Fc, Fc is a variant Fc region provided herein, L2 is either a linker provided herein or absent, and X1 is a polypeptide containing a transmembrane domain provided herein. As provided herein, X1 is of the formula ECD-T M-May contain a polypeptide having an ICD, wherein the ECD is an extracellular domain or fragment thereof provided herein or not provided herein, and T M V is a transmembrane domain provided herein, and ICD is an intracellular domain provided herein, or is absent. In some embodiments, V 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: 36. H V containing a peptide and 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 Peptides are ECD, T M , and are linked to a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including ICD. In some embodiments, V 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 sequence number 36. H V containing a peptide and 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 CD8 and / or CD28 ECD, T M , and are coupled to a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including the ICD. In some embodiments, V 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 sequence number 36. H V containing a peptide and 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 peptides are ECD, CD8 and / or CD28 TM , and are coupled to a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including the ICD. In some embodiments, V 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 sequence number 36. H Peptide; and V containing 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 peptides are CD8 and / or CD28 ECD, CD8 and / or CD28 T M , and are coupled to a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including the ICD. In some embodiments, V 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 sequence number 36. H Peptide; and V containing 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 Peptides are ECD, T M , and linked to a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD, the ICD including an Env embedded motif provided herein. In some embodiments, V 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 sequence number 36. H Peptide; and V containing 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 CD8 and / or CD28 ECD, T M, and coupled to a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD, the ICD includes an Env embedded motif provided herein. In some embodiments, V 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 sequence number 36. H Peptide; and V containing 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 peptides are ECD, CD8 and / or CD28 T M , and coupled to a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD, the ICD includes an Env embedded motif provided herein. In some embodiments, V 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 sequence number 36. H Peptide; and V containing 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 peptides are CD8 and / or CD28 ECD, CD8 and / or CD28 T M , and connected to a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD, the ICD includes an Env embedded motif provided herein. In some embodiments, the ECD, T M , and connected to the stalk portion (S1) including the Fc region (L1-Fc-L2-X1), V H Peptides containing 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 V LPeptides containing sequences that are at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of Sequence ID No. 37 are immobilized on the surface of viral particles such as those provided herein. In some embodiments, L1, Fc, L2, ECD, T M The identity of the ICD is provided herein. In some embodiments, V H and V L Polypeptides bind to immune cells, such as those provided herein.

[0235] In some embodiments, V H Peptides and V L A polypeptide containing a peptide, V H The peptide contains 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 A polypeptide is provided, comprising a peptide whose sequence 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.

[0236] In some embodiments, the polypeptide is V H Peptides and V L Contains peptides, V H The peptide contains 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 contains 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; however, V H Peptides and V LThe peptide comprises a light chain CDR having the sequence of SEQ ID NOs. 33-35; and / or a heavy chain CDR having the sequence of SEQ ID NOs. 30-32. In some embodiments, the polypeptide is V H Peptides and V L Contains peptides, V H The peptide contains 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 contains 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; however, V H Peptides 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 CDR in the chain is as described in the combinations provided herein.

[0237] In some embodiments, the polypeptide is V H Peptides and V L Contains peptides, V H The peptide contains 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 contains 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; however, V LThe 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. H The peptides include 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.

[0238] In some embodiments, the polypeptide is V H Peptides and V L Contains peptides, V H The peptide contains 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 contains 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; however, V L The peptide comprises LCDR1 having the sequence of SEQ ID NO: 33 and containing at most one conservative amino acid substitution, LCDR2 having the sequence of SEQ ID NO: 34 and containing at most one conservative amino acid substitution, and LCDR3 having the sequence of SEQ ID NO: 35 and containing at most one conservative amino acid substitution. H The peptide comprises HCDR1 having the sequence of SEQ ID NO: 30 and containing at most one conservative amino acid substitution, HCDR2 having the sequence of SEQ ID NO: 31 and containing at most one conservative amino acid substitution, and HCDR3 having the sequence of SEQ ID NO: 32 and containing at most one conservative amino acid substitution.

[0239] In some embodiments, the polypeptide is V H Peptides and V L Contains peptides, V H The peptide contains the sequence of SEQ ID NO: 36, V L The peptide contains the sequence of SEQ ID NO: 37.

[0240] In some embodiments, the polypeptides provided herein bind to non-human primate CD7. In some embodiments, the polypeptides provided herein bind to human CD7.

[0241] As provided herein, different polypeptides (V H or V L ) may be linked to a peptide linker, or it may not be linked to a peptide linker and instead be a continuous sequence. In some embodiments, the peptide linker is (GGGGS) n The sequence (SEQ ID NO: 55) is included, where each n is independently 1 to 5. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 3. In some embodiments, n is 4. In some embodiments, n is 5. The linked peptide format is V H -ZV L or V L -ZV H It can be expressed by the formula, where Z is a peptide linker. In some embodiments, Z is (GGGGS) n (Sequence ID 55) where 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.

[0242] In some embodiments, formula V L -ZV H A polypeptide comprising the linked peptide represented by includes the heavy chain variable region described in SEQ ID NO: 36, linked to the light chain variable region described in SEQ ID NO: 37 via the linker sequence GGGGSGGGGSGGGGSGGGGS (SEQ ID NO: 72). In some embodiments, via the peptide linker V H V connected to L The polypeptide containing has the sequence described below. DILLTQSPAILSVSPGERVSFSCRASQSIGTSIHWYQQRTNDSPRLLIKYASESISGIPSRFSGSGSGTDFTLSINSVESEDIADYYCQQSNSWPTTFGGGTKLEIKRGGGGSGGGGSGGGGSGGGGSQVQLQQPGAELVKPGASVKLSCKASGYPFTSYWIHWVKQRPGRGLEWLGRIDPNSGDTKYNEKFKNKATLTVDKSSTTAYMQLSSLTSEDSAVYYCARSPYYSNDNSMDYWGQGTSVTVSS (Sequence ID 38).

[0243] In some embodiments, the polypeptide contains 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 contains a sequence that is at least 90% identical to the sequence of SEQ ID NO: 38. In some embodiments, the polypeptide contains a sequence that is at least 95% identical to the sequence of SEQ ID NO: 38. In some embodiments, the polypeptide contains a sequence that is at least 99% identical to the sequence of SEQ ID NO: 38. In some embodiments, the polypeptide contains the sequence described in SEQ ID NO: 38. In some embodiments, the polypeptide described in SEQ ID NO: 38 is an antibody or its antigen-binding fragment. 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.

[0244] In some embodiments, formula V H -ZV L A polypeptide comprising the linked peptide represented by includes a light chain variable region described in SEQ ID NO: 37 linked to the heavy chain variable region described in SEQ ID NO: 36 via the linker sequence GGGGSGGGGSGGGGSGGGGS (SEQ ID NO: 72). In some embodiments, via the peptide linker V L V connected to HThe polypeptide containing has the sequence described below. QVQLQQPGAELVKPGASVKLSCKASGYPFTSYWIHWVKQRPGRGLEWLGRIDPNSGDTKYNEKFKNKATLTVDKSSTTAYMQLSSLTSEDSAVYYCARSPYYSNDNSMDYWGQGTSVTVSSGGGGSGGGGSGGGGSGGGGSDILLTQSPAILSVSPGERVSFSCRASQSIGTSIHWYQQRTNDSPRLLIKYASESISGIPSRFSGSGSGTDFTLSINSVESEDIADYYCQQSNSWPTTFGGGTKLEIKR (Sequence ID 39).

[0245] In some embodiments, the polypeptide contains 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 contains a sequence that is at least 90% identical to the sequence of SEQ ID NO: 39. In some embodiments, the polypeptide contains a sequence that is at least 95% identical to the sequence of SEQ ID NO: 39. In some embodiments, the polypeptide contains a sequence that is at least 99% identical to the sequence of SEQ ID NO: 39. In some embodiments, the polypeptide contains the sequence described in SEQ ID NO: 39. In some embodiments, the polypeptide described in SEQ ID NO: 39 is an antibody or its antigen-binding fragment. 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.

[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: 38, and comprises a stalk portion (S1) that includes an Fc region, such as those 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 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 is a polypeptide of the formula ECD-T M -May contain a polypeptide having an ICD, wherein the ECD is an extracellular domain or fragment thereof provided herein, or is absent. 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 includes ECD, T M , and a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including 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: 38, and includes CD8 and / or CD28 ECD, T M, and a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including 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: 38, and includes ECD, CD8 and / or CD28 T M , and a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including 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: 38, and includes CD8 and / or CD28 ECD, CD8 and / or CD28 T M , and also includes a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including 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: 38, and includes ECD, T M , and a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD, the ICD including an Env embedded 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: 38, and includes CD8 and / or CD28 ECD, T M , and a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD, the ICD including an Env embedded 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: 38, and includes an ECD, CD8 and / or CD28 T M, and a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD, the ICD including an Env embedded 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: 38, and includes CD8 and / or CD28 ECD, CD8 and / or CD28 T M , and also include a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD, the ICD including an Env embedded motif provided herein. In some embodiments, the sequence includes an ECD, T which is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of sequence number 38. M A polypeptide comprising a stalk portion (S1) including an Fc region (L1-Fc-L2-X1), including ICD, is immobilized on the surface of a viral particle, such as those provided herein. In some embodiments, L1, Fc, L2, ECD, T M 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 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) that includes an Fc region, such as those 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 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 is a polypeptide of the formula ECD-T M -May contain a polypeptide having an ICD, wherein the ECD is an extracellular domain or fragment thereof provided herein or not provided herein, 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 ECD, T M , and a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including 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: 39, and includes CD8 and / or CD28 ECD, T M, and a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including 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: 39, and includes ECD, CD8 and / or CD28 T M , and a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including 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: 39, and includes CD8 and / or CD28 ECD, CD8 and / or CD28 T M , and also include a stalk portion (S1) containing an Fc region (L1-Fc-L2-X1) including 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: 39, and includes ECD, T M , and a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD, the ICD including an Env embedded 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: 39, and includes CD8 and / or CD28 ECD, T M , and a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD, wherein the ICD includes an Env embedded 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: 39, and includes an ECD, CD8 and / or CD28 T M, and a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD, the ICD including an Env embedded 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: 39, and includes CD8 and / or CD28 ECD, CD8 and / or CD28 T M , and also include a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD, the ICD including an Env embedded motif provided herein. In some embodiments, the sequence includes an ECD, T which is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of sequence number 39. M A polypeptide comprising a stalk portion (S1) including an Fc region (L1-Fc-L2-X1), including ICD, is immobilized on the surface of a viral particle, such as those provided herein. In some embodiments, L1, Fc, L2, ECD, T M The identity of the ICD is as provided herein. In some embodiments, the polypeptide binds to immune cells such as those provided herein.

[0248] In some embodiments, the polypeptide comprises a sequence having the sequence described in SEQ ID NO: 38 and includes a stalk portion (S1) including an Fc region, such as those provided herein. In some embodiments, the polypeptide comprises a sequence having the sequence described in SEQ ID NO: 38 and includes a stalk portion (S1) including an Fc region, the Fc region further includes a transmembrane domain, such as those provided herein. In some embodiments, the Fc region further including a transmembrane domain has the formula L1-Fc-L2-X1, where L1 is a linker provided herein or absent, Fc is a variant Fc region provided herein, L2 is a linker provided herein or absent, and X1 is a polypeptide including a transmembrane domain provided herein. As provided herein, X1 is of the formula ECD-T M -May contain a polypeptide having an ICD, wherein the ECD is an extracellular domain or fragment thereof provided herein, or is absent. 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 described in SEQ ID NO: 38, ECD, T M , and a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including ICD. In some embodiments, the polypeptide includes a sequence having the sequence described in Sequence ID No. 38, CD8 and / or CD28 ECD, T M , and also includes a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including ICD. In some embodiments, the polypeptide includes a sequence having the sequence described in SEQ ID NO: 38, ECD, CD8 and / or CD28 T M , and also includes a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including ICD. In some embodiments, the polypeptide includes a sequence having the sequence described in Sequence ID No. 38, CD8 and / or CD28 ECD, CD8 and / or CD28 T M, and also includes a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including ICD. In some embodiments, the polypeptide includes a sequence having the sequence described in SEQ ID NO: 38, ECD, T M , and a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD, wherein the ICD includes an Env embedded motif provided herein. In some embodiments, the polypeptide includes a sequence having the sequence described in Sequence ID No. 38, CD8 and / or CD28 ECD, T M , and a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD, wherein the ICD includes an Env embedded motif provided herein. In some embodiments, the polypeptide includes a sequence having the sequence described in SEQ ID NO: 38, ECD, CD8 and / or CD28 T M , and a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD, wherein the ICD includes an Env embedded motif provided herein. In some embodiments, the polypeptide includes a sequence having the sequence described in Sequence ID No. 38, CD8 and / or CD28 ECD, CD8 and / or CD28 T M , and also include a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD, the ICD including an Env embedded motif provided herein. In some embodiments, the sequence includes the sequence described in Sequence ID No. 38, the ECD, T M A polypeptide comprising a stalk portion (S1) including an Fc region (L1-Fc-L2-X1), including ICD, is immobilized on the surface of a viral particle, such as those provided herein. In some embodiments, L1, Fc, L2, ECD, T M The identity of the ICD is as provided herein. In some embodiments, the polypeptide binds to immune cells such as those provided herein.

[0249] In some embodiments, the polypeptide comprises a sequence having the sequence described in SEQ ID NO: 39 and includes a stalk portion (S1) including an Fc region, such as those provided herein. In some embodiments, the polypeptide comprises a sequence having the sequence described in SEQ ID NO: 39 and includes a stalk portion (S1) including an Fc region, the Fc region further includes a transmembrane domain, such as those provided herein. In some embodiments, the Fc region further including a transmembrane domain has the formula L1-Fc-L2-X1, where L1 is a linker provided herein or is absent, Fc is a variant Fc region provided herein, L2 is a linker provided herein or is absent, and X1 is a polypeptide including a transmembrane domain provided herein. As provided herein, X1 is a polypeptide of the formula ECD-T M -May contain a polypeptide having an ICD, wherein the ECD is an extracellular domain or fragment thereof provided herein or not provided herein, 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 described in SEQ ID NO: 39, ECD, T M , and a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including ICD. In some embodiments, the polypeptide includes a sequence having the sequence described in Sequence ID No. 39, CD8 and / or CD28 ECD, T M , and also includes a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including ICD. In some embodiments, the polypeptide includes a sequence having the sequence described in SEQ ID NO: 39, ECD, CD8 and / or CD28 T M , and also includes a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including ICD. In some embodiments, the polypeptide includes a sequence having the sequence described in Sequence ID No. 39, CD8 and / or CD28 ECD, CD8 and / or CD28 T M, and also includes a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including ICD. In some embodiments, the polypeptide includes a sequence having the sequence described in SEQ ID NO: 39, ECD, T M , and a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD, wherein the ICD includes an Env embedded motif provided herein. In some embodiments, the polypeptide includes a sequence having the sequence described in Sequence ID No. 39, CD8 and / or CD28 ECD, T M , and a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD, wherein the ICD includes an Env embedded motif provided herein. In some embodiments, the polypeptide includes a sequence having the sequence described in SEQ ID NO: 39, ECD, CD8 and / or CD28 T M , and a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD, wherein the ICD includes an Env embedded motif provided herein. In some embodiments, the polypeptide includes a sequence having the sequence described in Sequence ID No. 39, CD8 and / or CD28 ECD, CD8 and / or CD28 T M , and also include a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD, the ICD including an Env embedded motif provided herein. In some embodiments, the sequence includes the sequence described in Sequence ID No. 39, the ECD, T M A polypeptide comprising a stalk portion (S1) including an Fc region (L1-Fc-L2-X1), including ICD, is immobilized on the surface of a viral particle, such as those provided herein. In some embodiments, L1, Fc, L2, ECD, T M The identity of the ICD is as provided herein. In some embodiments, the polypeptide binds to immune cells such as those provided herein.

[0250] In some embodiments, a polypeptide provided herein comprising the formula T-S1, wherein T is a target-binding domain and S1 is a stalk moiety, 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. (Sequence ID 98) Alternatively, it may be substantially similar to or an active fragment of SEQ ID NO: 98. In some embodiments, the polypeptide provided herein, comprising the formula T-S1, comprises an amino acid sequence that is at least 90% identical to the sequence of SEQ ID NO: 98. In some embodiments, the polypeptide provided herein, comprising the formula T-S1, comprises an amino acid sequence that is at least 95% identical to the sequence of SEQ ID NO: 98. In some embodiments, the polypeptide provided herein, comprising the formula T-S1, comprises an amino acid sequence that is at least 98% identical to the sequence of SEQ ID NO: 98. In some embodiments, the polypeptide provided herein, comprising the formula T-S1, comprises the amino acid sequence of SEQ ID NO: 98.

[0251] In some embodiments, a polypeptide provided herein comprising the formula T-S1, where T is a target-binding domain and S1 is a stalk moiety, 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: 143. (Sequence ID 143) Alternatively, it may be substantially similar to or an active fragment of SEQ ID NO: 143. In some embodiments, the polypeptide provided herein, comprising the formula T-S1, comprises an amino acid sequence that is at least 90% identical to the sequence of SEQ ID NO: 143. In some embodiments, the polypeptide provided herein, comprising the formula T-S1, comprises an amino acid sequence that is at least 95% identical to the sequence of SEQ ID NO: 143. In some embodiments, the polypeptide provided herein, comprising the formula T-S1, comprises an amino acid sequence that is at least 98% identical to the sequence of SEQ ID NO: 143. In some embodiments, the polypeptide provided herein, comprising the formula T-S1, comprises the amino acid sequence of SEQ ID NO: 143.

[0252] In some embodiments, a polypeptide provided herein comprising the formula T-S1, where T is a target-binding domain and S1 is a stalk moiety, 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: 144. (Sequence ID 144) Alternatively, it may be substantially similar to or an active fragment of SEQ ID NO: 144. In some embodiments, the polypeptide provided herein, comprising the formula T-S1, comprises an amino acid sequence that is at least 90% identical to the sequence of SEQ ID NO: 144. In some embodiments, the polypeptide provided herein, comprising the formula T-S1, comprises an amino acid sequence that is at least 95% identical to the sequence of SEQ ID NO: 144. In some embodiments, the polypeptide provided herein, comprising the formula T-S1, comprises an amino acid sequence that is at least 98% identical to the sequence of SEQ ID NO: 144. In some embodiments, the polypeptide provided herein, comprising the formula T-S1, comprises the amino acid sequence of SEQ ID NO: 144.

[0253] In some embodiments, a polypeptide provided herein, comprising the formula T-S1, wherein T is a target-binding domain and S1 is a stalk portion, 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, wherein 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 polypeptide provided herein, comprising the formula T-S1, comprises an amino acid sequence that is at least 95% 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, and the stalk portion "S1" of the polypeptide corresponds to amino acids 284-634 of SEQ ID NO: 98. In some embodiments, the polypeptide provided herein, comprising the formula T-S1, comprises an amino acid sequence that is at least 98% 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, and the stalk portion "S1" of the polypeptide corresponds to amino acids 284-634 of SEQ ID NO: 98. In some embodiments, the polypeptide provided herein, comprising the formula T-S1, comprises the amino acid 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, and the stalk portion "S1" of the polypeptide corresponds to amino acids 284-634 of SEQ ID NO: 98.

[0254] In some embodiments, the polypeptide provided herein comprises the formula T-S1, wherein T is V H and V LThe target-binding domain, which includes S1, is a polypeptide whose stalk portion 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 the target-binding domain is V H This corresponds to amino acids 25-150 of sequence number 98, and is the V of the target-binding domain. L The stalk portion "S1" of the polypeptide 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 polypeptide provided herein comprising formula T-S1 comprises an amino acid sequence that is at least 90% identical to the sequence of SEQ ID NO: 98, and the target binding domain V H This corresponds to amino acids 25-150 of sequence number 98, and is the V of the target-binding domain. L The amino acids 172-283 of SEQ ID NO: 98 correspond to amino acids 284-634 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 polypeptide provided herein comprising formula T-S1 comprises an amino acid sequence that is at least 95% identical to the sequence of SEQ ID NO: 98, and the target binding domain V H This corresponds to amino acids 25-150 of sequence number 98, and is the V of the target-binding domain. L The stalk portion "S1" of the polypeptide 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 polypeptide provided herein comprising formula T-S1 comprises an amino acid sequence that is at least 98% identical to the sequence of SEQ ID NO: 98, and the target binding domain V H This corresponds to amino acids 25-150 of sequence number 98, and is the V of the target-binding domain. L The T-S1 portion 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 polypeptide provided herein, which includes the formula T-S1, includes the amino acid sequence of SEQ ID NO: 98, and the V portion of the target-binding domain HThis corresponds to amino acids 25-150 of sequence number 98, and is the V of the target-binding domain. L This 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.

[0255] In some embodiments, a polypeptide provided herein comprising the formula T-L1-Fc-L2-X1, wherein T is a target-binding domain, L1 is a polypeptide linker or absent, Fc is a mutant Fc domain provided herein, L2 is a polypeptide linker or absent, and X1 is a transmembrane domain, 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, 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, and X1 corresponds to amino acids 543-634 of SEQ ID NO: 98. In some embodiments, the polypeptides provided herein comprising the formula T-L1-Fc-L2-X1 comprises 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 comprises amino acids 284-301 of SEQ ID NO: 98, Fc comprises 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 comprising the formula T-L1-Fc-L2-X1 comprises 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 comprises amino acids 284-301 of SEQ ID NO: 98, Fc comprises 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, comprising the formula T-L1-Fc-L2-X1, comprises 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, Fc comprises 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.

[0256] In some embodiments, the polypeptide provided herein comprises the formula T-L1-Fc-L2-X1, where T is V H and V L The target-binding domain includes L1, which is either a polypeptide linker or absent, Fc is a variant Fc domain provided herein, L2 is a polypeptide linker or absent, and X1 is a polypeptide containing a transmembrane domain, the polypeptide having 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 the target-binding domain V H This corresponds to amino acids 25-150 of sequence number 98, and is the V of the target-binding domain. LL1 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 polypeptide provided herein comprising the formula T-L1-Fc-L2-X1 comprises an amino acid sequence that is at least 90% identical to the sequence of SEQ ID NO: 98, and the target binding domain V H This corresponds to amino acids 25-150 of sequence number 98, and is the V of the target-binding domain. L L1 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 polypeptide provided herein comprising 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, and the target binding domain V H This corresponds to amino acids 25-150 of sequence number 98, and is the V of the target-binding domain. L L1 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 polypeptide provided herein comprising 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, and the target binding domain V H This corresponds to amino acids 25-150 of sequence number 98, and is the V of the target-binding domain. L L1 corresponds to amino acids 172-283 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, and X1 corresponds to amino acids 543-634 of SEQ ID NO: 98. In some embodiments, the polypeptide provided herein comprising the formula T-L1-Fc-L2-X1 comprises the amino acid sequence of SEQ ID NO: 98, and the target-binding domain V HThis corresponds to amino acids 25-150 of sequence number 98, and is the V of the target-binding domain. L L1 corresponds to amino acids 172-283 of sequence number 98, L1 contains amino acids 284-301 of sequence number 98, Fc contains amino acids 302-542 of sequence number 98, L2 is absent, and X1 corresponds to amino acids 543-634 of sequence number 98.

[0257] In some embodiments, T-L1-Fc-L2-ECD-T M A polypeptide provided herein comprising the formula -ICD, wherein T is a target-binding domain, L1 is a polypeptide linker or is absent, Fc is a mutant Fc domain provided herein, L2 is a polypeptide linker or is absent, ECD is an extracellular domain, and T M The polypeptide is a transmembrane domain, and ICD is an intracellular domain containing the Env embedded motif. The polypeptide 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 is absent, ECD contains amino acids 543-584 of SEQ ID NO: 98, and T M The formula T-L1-Fc-L2-ECD-T includes amino acids 585-612 of SEQ ID NO: 98, the ICD includes amino acids 613-634 of SEQ ID NO: 98, and the Env embedded motif includes amino acids 627-634 of SEQ ID NO: 98. In some embodiments, the formula T-L1-Fc-L2-ECD-T M - The polypeptides provided herein, including ICD, contain 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, ECD contains amino acids 543-584 of SEQ ID NO: 98, and TM The formula T-L1-Fc-L2-ECD-T includes amino acids 585-612 of SEQ ID NO: 98, the ICD includes amino acids 613-634 of SEQ ID NO: 98, and the Env embedded motif includes amino acids 627-634 of SEQ ID NO: 98. In some embodiments, the formula T-L1-Fc-L2-ECD-T M - The polypeptides provided herein, including ICD, contain 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, ECD contains amino acids 543-584 of SEQ ID NO: 98, and T M The formula T-L1-Fc-L2-ECD-T includes amino acids 585-612 of SEQ ID NO: 98, the ICD includes amino acids 613-634 of SEQ ID NO: 98, and the Env embedded motif includes amino acids 627-634 of SEQ ID NO: 98. In some embodiments, the formula T-L1-Fc-L2-ECD-T M - The polypeptides provided herein, including ICD, contain 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, ECD contains amino acids 543-584 of SEQ ID NO: 98, and T M The component contains amino acids 585-612 of SEQ ID NO: 98, the ICD contains amino acids 613-634 of SEQ ID NO: 98, and the Env embedded motif contains amino acids 627-634 of SEQ ID NO: 98. In some embodiments, T-L1-Fc-L2-ECD-T M - The polypeptides provided herein, including the formula ICD, comprise the amino acid 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 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 MThe first component contains amino acids 585-612 of SEQ ID NO: 98, the second component contains amino acids 613-634 of SEQ ID NO: 98, and the third component contains amino acids 627-634 of SEQ ID NO: 98.

[0258] In some embodiments, T-L1-Fc-L2-ECD-T M A polypeptide provided herein comprising the formula -ICD, wherein T is V H and V L A target-binding domain comprising, where L1 is a polypeptide linker or is absent, Fc is a mutant Fc domain provided herein, L2 is a polypeptide linker or is absent, ECD is an extracellular domain, T M The ICD is a transmembrane domain, and the ICD is an intracellular domain containing the Env embedded motif. The polypeptide 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 the V of the target-binding domain H This corresponds to amino acids 25-150 of sequence number 98, and is the V of the target-binding domain. L L1 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 The component contains amino acids 585-612 of SEQ ID NO: 98, the ICD contains amino acids 613-634 of SEQ ID NO: 98, and the Env embedded motif contains amino acids 627-634 of SEQ ID NO: 98. In some embodiments, T-L1-Fc-L2-ECD-T M - The polypeptides provided herein, including the formula ICD, have an amino acid sequence that is at least 90% identical to the sequence of SEQ ID NO: 98, and the target binding domain V H This corresponds to amino acids 25-150 of sequence number 98, and is the V of the target-binding domain. LL1 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 The component contains amino acids 585-612 of SEQ ID NO: 98, the ICD contains amino acids 613-634 of SEQ ID NO: 98, and the Env embedded motif contains amino acids 627-634 of SEQ ID NO: 98. In some embodiments, T-L1-Fc-L2-ECD-T M - The polypeptides provided herein, including the formula ICD, have an amino acid sequence that is at least 95% identical to the sequence of SEQ ID NO: 98, and the target binding domain V H This corresponds to amino acids 25-150 of sequence number 98, and is the V of the target-binding domain. L L1 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 The component contains amino acids 585-612 of SEQ ID NO: 98, the ICD contains amino acids 613-634 of SEQ ID NO: 98, and the Env embedded motif contains amino acids 627-634 of SEQ ID NO: 98. In some embodiments, T-L1-Fc-L2-ECD-T M - The polypeptides provided herein, including the formula ICD, comprise an amino acid sequence that is at least 98% identical to the sequence of SEQ ID NO: 98, and the target binding domain V H This corresponds to amino acids 25-150 of sequence number 98, and is the V of the target-binding domain. L L1 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 MThe component contains amino acids 585-612 of SEQ ID NO: 98, the ICD contains amino acids 613-634 of SEQ ID NO: 98, and the Env embedded motif contains amino acids 627-634 of SEQ ID NO: 98. In some embodiments, T-L1-Fc-L2-ECD-T M - The polypeptide provided herein, comprising the formula ICD, comprises the amino acids of SEQ ID NO: 98, and the target-binding domain V H This corresponds to amino acids 25-150 of sequence number 98, and is the V of the target-binding domain. L L1 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 The first component contains amino acids 585-612 of SEQ ID NO: 98, the second component contains amino acids 613-634 of SEQ ID NO: 98, and the third component contains amino acids 627-634 of SEQ ID NO: 98.

[0259] In some embodiments, the formula T-L1-Fc-L2-ECD-T M - A polypeptide provided herein comprising ICD, wherein T is a target-binding domain, L1 is a polypeptide linker or is absent, Fc is a mutant Fc domain provided herein, L2 is a polypeptide linker or is absent, ECD is an extracellular domain, T ML1 is a transmembrane domain, and ICD is an intracellular domain containing the Env embedded motif. The polypeptide 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 and corresponds to amino acids 25-283 of SEQ ID NO: 98, L1 contains the amino acid sequence of SEQ ID NO: 72 and corresponds to amino acids 284-301 of SEQ ID NO: 98, Fc contains the amino acid sequence of SEQ ID NO: 104 and corresponds to amino acids 302-542 of SEQ ID NO: 98, L2 is absent, ECD contains the amino acid sequence of SEQ ID NO: 60 and corresponds to amino acids 543-584 of SEQ ID NO: 98, T M The amino acid sequence of SEQ ID NO: 62 corresponds to amino acids 585-612 of SEQ ID NO: 98, the ICD contains amino acids 613-634 of SEQ ID NO: 98, and the Env embedded motif contains the amino acid sequence of SEQ ID NO: 63 corresponds to amino acids 627-634 of SEQ ID NO: 98. In some embodiments, T-L1-Fc-L2-ECD-T M - The polypeptides provided herein, including the formula ICD, contain an amino acid sequence that is at least 90% 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 and corresponds to amino acids 25-283 of SEQ ID NO: 98, L1 contains the amino acid sequence of SEQ ID NO: 72 and corresponds to amino acids 284-301 of SEQ ID NO: 98, Fc contains the amino acid sequence of SEQ ID NO: 104 and corresponds to amino acids 302-542 of SEQ ID NO: 98, L2 is absent, ECD contains the amino acid sequence of SEQ ID NO: 60 and corresponds to amino acids 543-584 of SEQ ID NO: 98, T M The amino acid sequence of SEQ ID NO: 62 corresponds to amino acids 585-612 of SEQ ID NO: 98, the ICD contains amino acids 613-634 of SEQ ID NO: 98, and the Env embedded motif contains the amino acid sequence of SEQ ID NO: 63 corresponds to amino acids 627-634 of SEQ ID NO: 98. In some embodiments, T-L1-Fc-L2-ECD-T M- The polypeptides provided herein, including the formula ICD, contain an amino acid sequence that is at least 95% 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 and corresponds to amino acids 25-283 of SEQ ID NO: 98, L1 contains the amino acid sequence of SEQ ID NO: 72 and corresponds to amino acids 284-301 of SEQ ID NO: 98, Fc contains the amino acid sequence of SEQ ID NO: 104 and corresponds to amino acids 302-542 of SEQ ID NO: 98, L2 is absent, ECD contains the amino acid sequence of SEQ ID NO: 60 and corresponds to amino acids 543-584 of SEQ ID NO: 98, T M The amino acid sequence of SEQ ID NO: 62 corresponds to amino acids 585-612 of SEQ ID NO: 98, the ICD contains amino acids 613-634 of SEQ ID NO: 98, and the Env embedded motif contains the amino acid sequence of SEQ ID NO: 63 corresponds to amino acids 627-634 of SEQ ID NO: 98. In some embodiments, T-L1-Fc-L2-ECD-T M - The polypeptides provided herein, including the formula ICD, comprise an amino acid sequence that is at least 98% identical to the sequence of SEQ ID NO: 98, the target-binding domain "T" of the polypeptide comprises the amino acid sequence 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, T M The amino acid sequence of SEQ ID NO: 62 corresponds to amino acids 585-612 of SEQ ID NO: 98, the ICD contains amino acids 613-634 of SEQ ID NO: 98, and the Env embedded motif contains the amino acid sequence of SEQ ID NO: 63 corresponds to amino acids 627-634 of SEQ ID NO: 98. In some embodiments, T-L1-Fc-L2-ECD-T M- The polypeptide provided herein, including the formula ICD, comprises the amino acid sequence of SEQ ID NO: 98, 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, T M The sequence contains the amino acid sequence of SEQ ID NO: 62 and corresponds to amino acids 585-612 of SEQ ID NO: 98; the ICD contains amino acids 613-634 of SEQ ID NO: 98; and the Env embedded motif contains the amino acid sequence of SEQ ID NO: 63 and corresponds to amino acids 627-634 of SEQ ID NO: 98.

[0260] In some embodiments, T-L1-Fc-L2-ECD-T M A polypeptide provided herein comprising the formula -ICD, wherein T is V H and V L A target-binding domain comprising, where L1 is a polypeptide linker or is absent, Fc is a mutant Fc domain provided herein, L2 is a polypeptide linker or is absent, ECD is an extracellular domain, T M The ICD is a transmembrane domain, and the ICD is an intracellular domain containing the Env embedded motif. The polypeptide 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 the V of the target-binding domain H This contains the amino acid sequence of SEQ ID NO: 36, corresponding to amino acids 25-150 of SEQ ID NO: 98, and the target binding domain V LL1 contains the amino acid sequence of SEQ ID NO: 37 and corresponds to amino acids 172-283 of SEQ ID NO: 98; L1 contains the amino acid sequence of SEQ ID NO: 72 and corresponds to amino acids 284-301 of SEQ ID NO: 98; Fc contains the amino acid sequence of SEQ ID NO: 104 and corresponds to amino acids 302-542 of SEQ ID NO: 98; L2 is absent; ECD contains the amino acid sequence of SEQ ID NO: 60 and corresponds to amino acids 543-584 of SEQ ID NO: 98; T M The amino acid sequence of SEQ ID NO: 62 corresponds to amino acids 585-612 of SEQ ID NO: 98, the ICD contains amino acids 613-634 of SEQ ID NO: 98, and the Env embedded motif contains the amino acid sequence of SEQ ID NO: 63 corresponds to amino acids 627-634 of SEQ ID NO: 98. In some embodiments, T-L1-Fc-L2-ECD-T M - The polypeptides provided herein, including the formula ICD, have an amino acid sequence that is at least 90% identical to the sequence of SEQ ID NO: 98, and the target binding domain V H This contains the amino acid sequence of SEQ ID NO: 36, corresponding to amino acids 25-150 of SEQ ID NO: 98, and the target binding domain V L L1 contains the amino acid sequence of SEQ ID NO: 37 and corresponds to amino acids 172-283 of SEQ ID NO: 98; L1 contains the amino acid sequence of SEQ ID NO: 72 and corresponds to amino acids 284-301 of SEQ ID NO: 98; Fc contains the amino acid sequence of SEQ ID NO: 104 and corresponds to amino acids 302-542 of SEQ ID NO: 98; L2 is absent; ECD contains the amino acid sequence of SEQ ID NO: 60 and corresponds to amino acids 543-584 of SEQ ID NO: 98; T M The amino acid sequence of SEQ ID NO: 62 corresponds to amino acids 585-612 of SEQ ID NO: 98, the ICD contains amino acids 613-634 of SEQ ID NO: 98, and the Env embedded motif contains the amino acid sequence of SEQ ID NO: 63 corresponds to amino acids 627-634 of SEQ ID NO: 98. In some embodiments, T-L1-Fc-L2-ECD-T M - The polypeptides provided herein, including the formula ICD, have an amino acid sequence that is at least 95% identical to the sequence of SEQ ID NO: 98, and the target binding domain V HThis contains the amino acid sequence of SEQ ID NO: 36, corresponding to amino acids 25-150 of SEQ ID NO: 98, and the target binding domain V L L1 contains the amino acid sequence of SEQ ID NO: 37 and corresponds to amino acids 172-283 of SEQ ID NO: 98; L1 contains the amino acid sequence of SEQ ID NO: 72 and corresponds to amino acids 284-301 of SEQ ID NO: 98; Fc contains the amino acid sequence of SEQ ID NO: 104 and corresponds to amino acids 302-542 of SEQ ID NO: 98; L2 is absent; ECD contains the amino acid sequence of SEQ ID NO: 60 and corresponds to amino acids 543-584 of SEQ ID NO: 98; T M The amino acid sequence of SEQ ID NO: 62 corresponds to amino acids 585-612 of SEQ ID NO: 98, the ICD contains amino acids 613-634 of SEQ ID NO: 98, and the Env embedded motif contains the amino acid sequence of SEQ ID NO: 63 corresponds to amino acids 627-634 of SEQ ID NO: 98. In some embodiments, T-L1-Fc-L2-ECD-T M - The polypeptides provided herein, including the formula ICD, comprise an amino acid sequence that is at least 98% identical to the sequence of SEQ ID NO: 98, and the target binding domain V H This contains the amino acid sequence of SEQ ID NO: 36, corresponding to amino acids 25-150 of SEQ ID NO: 98, and the target binding domain V L L1 contains the amino acid sequence of SEQ ID NO: 37 and corresponds to amino acids 172-283 of SEQ ID NO: 98; L1 contains the amino acid sequence of SEQ ID NO: 72 and corresponds to amino acids 284-301 of SEQ ID NO: 98; Fc contains the amino acid sequence of SEQ ID NO: 104 and corresponds to amino acids 302-542 of SEQ ID NO: 98; L2 is absent; ECD contains the amino acid sequence of SEQ ID NO: 60 and corresponds to amino acids 543-584 of SEQ ID NO: 98; T M The amino acid sequence of SEQ ID NO: 62 corresponds to amino acids 585-612 of SEQ ID NO: 98, the ICD contains amino acids 613-634 of SEQ ID NO: 98, and the Env embedded motif contains the amino acid sequence of SEQ ID NO: 63 corresponds to amino acids 627-634 of SEQ ID NO: 98. In some embodiments, T-L1-Fc-L2-ECD-T M - The polypeptide provided herein, which includes the formula ICD, comprises the amino acid sequence of SEQ ID NO: 98, and the target binding domain VH This contains the amino acid sequence of SEQ ID NO: 36, corresponding to amino acids 25-150 of SEQ ID NO: 98, and the target binding domain V L L1 contains the amino acid sequence of SEQ ID NO: 37 and corresponds to amino acids 172-283 of SEQ ID NO: 98; L1 contains the amino acid sequence of SEQ ID NO: 72 and corresponds to amino acids 284-301 of SEQ ID NO: 98; Fc contains the amino acid sequence of SEQ ID NO: 104 and corresponds to amino acids 302-542 of SEQ ID NO: 98; L2 is absent; ECD contains the amino acid sequence of SEQ ID NO: 60 and corresponds to amino acids 543-584 of SEQ ID NO: 98; T M The sequence contains the amino acid sequence of SEQ ID NO: 62 and corresponds to amino acids 585-612 of SEQ ID NO: 98; the ICD contains amino acids 613-634 of SEQ ID NO: 98; and the Env embedded motif contains the amino acid sequence of SEQ ID NO: 63 and corresponds to amino acids 627-634 of SEQ ID NO: 98.

[0261] In some embodiments, V has the sequence described in Sequence ID 48. H Peptide and V having the sequence described in SEQ ID NO: 49 L Peptides are ECD, T M , and are connected to a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD. In some embodiments, V has the sequence described in sequence number 48. H Peptide and V having the sequence described in SEQ ID NO: 49 L The peptide is CD8 and / or CD28 ECD, T M , and are connected to a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD. In some embodiments, V has the sequence described in sequence number 48. H Peptide and V having the sequence described in SEQ ID NO: 49 L The peptides are ECD, CD8 and / or CD28 T M , and is connected to a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) containing the ICD. In some embodiments, V has the sequence described in sequence number 48. H Peptide and V having the sequence described in SEQ ID NO: 49 LThe peptides are CD8 and / or CD28 ECD, CD8 and / or CD28 T M , and is coupled to a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) which includes an ICD. In some embodiments, V has the sequence described in sequence number 48. H Peptide and V having the sequence described in SEQ ID NO: 49 L Peptides are ECD, T M , and connected to a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD, the ICD includes an Env embedded motif provided herein. In some embodiments, V has the sequence described in Sequence ID No. 48. H Peptide and V having the sequence described in SEQ ID NO: 49 L The peptide is CD8 and / or CD28 ECD, T M , and coupled to a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD, the ICD includes an Env embedded motif provided herein. In some embodiments, V has the sequence described in Sequence ID No. 48. H Peptide and V having the sequence described in SEQ ID NO: 49 L The peptides are ECD, CD8 and / or CD28 T M , and coupled to a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD, the ICD includes an Env embedded motif provided herein. In some embodiments, V has the sequence described in Sequence ID No. 48. H Peptide and V having the sequence described in SEQ ID NO: 49 L The peptides are CD8 and / or CD28 ECD, CD8 and / or CD28 T M , and connected to a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD, the ICD includes an Env embedded motif provided herein. In some embodiments, the ECD, T M , and V having the sequence described in Sequence ID 48, which is linked to the stalk portion (S1) including the Fc region, including the ICD. H Peptide and V having the sequence described in SEQ ID NO: 49 LThe peptide (L1-Fc-L2-X1) is immobilized on the surface of a viral particle, such as those provided herein. In some embodiments, L1, Fc, L2, ECD, T M The identity of the ICD is provided herein. In some embodiments, V H and V L The peptides bind to immune cells, such as those provided herein.

[0262] In some embodiments, V 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 sequence number 48. H Peptide; and V containing 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 ligated to a stalk moiety (S1) containing an Fc region provided herein. In some embodiments, the V contains 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; and V containing 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 moiety (S1) which includes an Fc region further comprising a transmembrane domain. 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 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 is a polypeptide of the formula ECD-T M-May contain a polypeptide having an ICD, wherein the ECD is an extracellular domain or fragment thereof provided herein, or is absent. M V is a transmembrane domain provided herein, and ICD is an intracellular domain provided herein, or is absent. In some embodiments, V 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 V containing a peptide and 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 Peptides are ECD, T M , and are linked to a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including ICD. In some embodiments, V 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 sequence number 48. H V containing a peptide and 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 CD8 and / or CD28 ECD, T M , and are coupled to a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including the ICD. In some embodiments, V 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 sequence number 48. H V containing a peptide and 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 peptides are ECD, CD8 and / or CD28 TM , and are coupled to a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including the ICD. In some embodiments, V 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 sequence number 48. H Peptide; and V containing 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 peptides are CD8 and / or CD28 ECD, CD8 and / or CD28 T M , and are coupled to a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including the ICD. In some embodiments, V 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 sequence number 48. H Peptide; and V containing 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 Peptides are ECD, T M , and linked to a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD, the ICD including an Env embedded motif provided herein. In some embodiments, the V 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 sequence number 48. H Peptide; and V containing 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 CD8 and / or CD28 ECD, T M, and coupled to a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD, the ICD includes an Env embedded motif provided herein. In some embodiments, V 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 sequence number 48. H Peptide; and V containing 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 peptides are ECD, CD8 and / or CD28 T M , and coupled to a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD, the ICD includes an Env embedded motif provided herein. In some embodiments, V 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 sequence number 48. H Peptide; and V containing 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 peptides are CD8 and / or CD28 ECD, CD8 and / or CD28 T M , and connected to a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD, the ICD includes an Env embedded motif provided herein. In some embodiments, the ECD, T M , and connected to the stalk portion (S1) including the Fc region (L1-Fc-L2-X1), V H Peptides containing sequences that are at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of sequence number 48; and V LPeptides containing sequences that are 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 are immobilized on the surface of viral particles, such as those provided herein. In some embodiments, L1, Fc, L2, ECD, T M The identity of the ICD is provided herein. In some embodiments, V H and V L The peptides bind to immune cells, such as those provided herein.

[0263] In some embodiments, V H Peptides and V L A polypeptide containing a peptide, V H The peptide contains 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 A polypeptide is provided, comprising a peptide whose sequence 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.

[0264] In some embodiments, the polypeptide is V H Peptides and V L Contains peptides, V H The peptide contains 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 peptide contains 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; however, V H Peptides and V LThe peptide comprises a light chain CDR having the sequence of SEQ ID NOs. 45-47; and / or a heavy chain CDR having the sequence of SEQ ID NOs. 42-44. In some embodiments, the polypeptide is V H Peptides and V L Contains peptides, V H The peptide contains 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 peptide contains 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; however, V H Peptides and V L The 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 CDR in the chain is as described in the combinations provided herein.

[0265] In some embodiments, the polypeptide is V H Peptides and V L Contains peptides, V H The peptide contains 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 peptide contains 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; however, V LThe peptide comprises LCDR1 having the sequence of SEQ ID NO: 45; LCDR2 having the sequence of SEQ ID NO: 46; and LCDR3 having the sequence of SEQ ID NO: 47. H The peptides include HCDR1 having the sequence of SEQ ID NO: 42; HCDR2 having the sequence of SEQ ID NO: 43; and HCDR3 having the sequence of SEQ ID NO: 44.

[0266] In some embodiments, the polypeptide is V H Peptides and V L Contains peptides, V H The peptide contains 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 peptide contains 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; however, V L The peptide comprises LCDR1 having the sequence of SEQ ID NO: 45 and containing at most one conservative amino acid substitution, LCDR2 having the sequence of SEQ ID NO: 46 and containing at most one conservative amino acid substitution, and LCDR3 having the sequence of SEQ ID NO: 47 and containing at most one conservative amino acid substitution. H The peptide comprises HCDR1 having the sequence of SEQ ID NO: 42 and containing at most one conservative amino acid substitution, HCDR2 having the sequence of SEQ ID NO: 43 and containing at most one conservative amino acid substitution, and HCDR3 having the sequence of SEQ ID NO: 44 and containing at most one conservative amino acid substitution.

[0267] In some embodiments, the polypeptide is V H Peptides and V L Contains peptides, V H The peptide contains the sequence of SEQ ID NO: 48, V L The peptide contains the sequence of SEQ ID NO: 49.

[0268] In some embodiments, the polypeptides provided herein bind to non-human primate CD8. In some embodiments, the polypeptides provided herein bind to human CD8.

[0269] As provided herein, different polypeptides (V H or V L ) may be linked to a peptide linker, or it may not be linked to a peptide linker and instead be a continuous sequence. In some embodiments, the peptide linker is (GGGGS) n The sequence (SEQ ID NO: 55) is included, where each n is independently 1 to 5. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 3. In some embodiments, n is 4. In some embodiments, n is 5. The linked peptide format is V H -ZV L or V L -ZV H It can be expressed by the formula, where Z is a peptide linker. In some embodiments, Z is (GGGGS) n (Sequence ID 55) where 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.

[0270] In some embodiments, formula V L -ZV H A polypeptide comprising the linked peptide represented by includes the heavy chain variable region described in SEQ ID NO: 48, linked to the light chain variable region described in SEQ ID NO: 49 via the linker sequence GGGGSGGGGSGGGGSGGGGS (SEQ ID NO: 72). In some embodiments, via the peptide linker V H V connected to L The polypeptide containing has the sequence described below. NIVLTQSPASLAVSLGQRATISCRASESVDGFGNSFMNWYQQKPGQSPKLLIYLASNLESGVPARFSGSGSRTDFTLTIDPVEADDAATYYCQQNNEDPYTFGGGTKLEIKRGGGGSGGGGSGGGGSGGGGSEVQLQQSGPELVKPGASVKISCKASRYTFTDYNLHWVKLSHEKSLEWIGFIYPYNGGTGYNQKFKNKAKLTVDYSSSTAYMELRSLTSVDAAVYYCARDHRYNEGVSFDYWGQGTTLTVSS(Sequence No. 50).

[0271] In some embodiments, the polypeptide contains 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 contains a sequence that is at least 90% identical to the sequence of SEQ ID NO: 50. In some embodiments, the polypeptide contains a sequence that is at least 95% identical to the sequence of SEQ ID NO: 50. In some embodiments, the polypeptide contains a sequence that is at least 99% identical to the sequence of SEQ ID NO: 50. In some embodiments, the polypeptide contains the sequence described in SEQ ID NO: 50. In some embodiments, the polypeptide described in SEQ ID NO: 50 is an antibody or its antigen-binding fragment. 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.

[0272] In some embodiments, formula V H -ZV L A polypeptide comprising the linked peptide represented by includes a light chain variable region described in SEQ ID NO: 49 linked to the heavy chain variable region described in SEQ ID NO: 48 via the linker sequence GGGGSGGGGSGGGGSGGGGS (SEQ ID NO: 72). In some embodiments, via the peptide linker V L V connected to HThe polypeptide containing has the sequence described below. EVQLQQSGPELVKPGASVKISCKASRYTFTDYNLHWVKLSHEKSLEWIGFIYPYNGGTGYNQKFKNKAKLTVDYSSSTAYMELRSLTSVDAAVYYCARDHRYNEGVSFDYWGQGTTLTVSSGGGGSGGGGSGGGGSGGGGSNIVLTQSPASLAVSLGQRATISCRASESVDGFGNSFMNWYQQKPGQSPKLLIYLASNLESGVPARFSGSGSRTDFTLTIDPVEADDAATYYCQQNNEDPYTFGGGTKLEIKR (Sequence ID 51).

[0273] In some embodiments, the polypeptide contains 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 contains a sequence that is at least 90% identical to the sequence of SEQ ID NO: 51. In some embodiments, the polypeptide contains a sequence that is at least 95% identical to the sequence of SEQ ID NO: 51. In some embodiments, the polypeptide contains a sequence that is at least 99% identical to the sequence of SEQ ID NO: 51. In some embodiments, the polypeptide contains the sequence described in SEQ ID NO: 51. In some embodiments, the polypeptide described in SEQ ID NO: 51 is an antibody or its antigen-binding fragment. 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.

[0274] 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) that includes an Fc region, such as those 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 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 is a polypeptide of the formula ECD-T M -May contain a polypeptide having an ICD, wherein the ECD is an extracellular domain or fragment thereof provided herein, or is absent. 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 ECD, T M , and a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including 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: 50, and includes CD8 and / or CD28 ECD, T M, and a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including 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: 50, and includes ECD, CD8 and / or CD28 T M , and a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including 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: 50, and includes CD8 and / or CD28 ECD, CD8 and / or CD28 T M , and also include a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including 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: 50, and includes ECD, T M , and a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD, the ICD including an Env embedded 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: 50, and CD8 and / or CD28 ECD, T M , and a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD, wherein the ICD includes an Env embedded 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: 50, and includes an ECD, CD8 and / or CD28 T M, and a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD, the ICD including an Env embedded 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: 50, and includes CD8 and / or CD28 ECD, CD8 and / or CD28 T M , and also include a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD, the ICD including an Env embedded motif provided herein. In some embodiments, the sequence includes an ECD, T which is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of sequence number 50. M A polypeptide comprising a stalk portion (S1) including an Fc region (L1-Fc-L2-X1), including ICD, is immobilized on the surface of a viral particle, such as those provided herein. In some embodiments, L1, Fc, L2, ECD, T M The identity of the ICD is as provided herein. In some embodiments, the polypeptide binds to immune cells such as those provided herein.

[0275] 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 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 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 is a polypeptide of the formula ECD-T M -May contain a polypeptide having an ICD, wherein the ECD is an extracellular domain or fragment thereof provided herein, or is absent. M is a transmembrane domain provided herein, and ICD is an intracellular domain provided herein, or is absent. In some embodiments, the polypeptide includes a stalk portion (S1) containing an Fc region (L1-Fc-L2-X1) which 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 includes CD8 and / or CD28 ECD, T M, and a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including 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 includes ECD, CD8 and / or CD28 T M , and a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including 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 includes CD8 and / or CD28 ECD, CD8 and / or CD28 T M , and also include a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including 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 includes ECD, T M , and a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD, the ICD including an Env embedded 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 includes CD8 and / or CD28 ECD, T M , and a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD, wherein the ICD includes an Env embedded 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 includes an ECD, CD8 and / or CD28 T M, and a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD, the ICD including an Env embedded 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 includes CD8 and / or CD28 ECD, CD8 and / or CD28 T M , and also include a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD, the ICD including an Env embedded motif provided herein. In some embodiments, the sequence includes an ECD, T which is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of sequence number 51. M A polypeptide comprising a stalk portion (S1) including an Fc region (L1-Fc-L2-X1), including ICD, is immobilized on the surface of a viral particle, such as those provided herein. In some embodiments, L1, Fc, L2, ECD, T M The identity of the ICD is as provided herein. In some embodiments, the polypeptide binds to immune cells such as those provided herein.

[0276] In some embodiments, the polypeptide comprises a sequence having the sequence described in SEQ ID NO: 50 and includes a stalk portion (S1) including an Fc region, such as those provided herein. In some embodiments, the polypeptide comprises a sequence having the sequence described in SEQ ID NO: 50 and includes a stalk portion (S1) including an Fc region, the Fc region further includes a transmembrane domain, such as those provided herein. In some embodiments, the Fc region further including a transmembrane domain has the formula L1-Fc-L2-X1, where L1 is a linker provided herein or is absent, Fc is a variant Fc region provided herein, L2 is a linker provided herein or is absent, and X1 is a polypeptide including a transmembrane domain provided herein. As provided herein, X1 is a polypeptide of the formula ECD-T M -May contain a polypeptide having an ICD, wherein the ECD is an extracellular domain or fragment thereof provided herein, or is absent. 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 described in SEQ ID NO: 50, ECD, T M , and a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including ICD. In some embodiments, the polypeptide includes a sequence having the sequence described in SEQ ID NO: 50, CD8 and / or CD28 ECD, T M , and also includes a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including ICD. In some embodiments, the polypeptide includes a sequence having the sequence described in SEQ ID NO: 50, ECD, CD8 and / or CD28 T M , and also includes a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including ICD. In some embodiments, the polypeptide includes a sequence having the sequence described in SEQ ID NO: 50, and CD8 and / or CD28 ECD, CD8 and / or CD28 T M, and also includes a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including ICD. In some embodiments, the polypeptide includes a sequence having the sequence described in SEQ ID NO: 50, ECD, T M , and a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD, wherein the ICD includes an Env embedded motif provided herein. In some embodiments, the polypeptide includes a sequence having the sequence described in SEQ ID NO: 50, CD8 and / or CD28 ECD, T M , and a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD, wherein the ICD includes an Env embedded motif provided herein. In some embodiments, the polypeptide includes a sequence having the sequence described in SEQ ID NO: 50, ECD, CD8 and / or CD28 T M , and a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD, the ICD including an Env embedded motif provided herein. In some embodiments, the polypeptide includes a sequence having the sequence described in Sequence ID No. 50, CD8 and / or CD28 ECD, CD8 and / or CD28 T M , and also includes a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD, the ICD including an Env embedded motif provided herein. In some embodiments, the sequence includes the sequence described in Sequence ID No. 50, the ECD, T M A polypeptide comprising a stalk portion (S1) including an Fc region (L1-Fc-L2-X1), including ICD, is immobilized on the surface of a viral particle, such as those provided herein. In some embodiments, L1, Fc, L2, ECD, T M The identity of the ICD is as provided herein. In some embodiments, the polypeptide binds to immune cells such as those provided herein.

[0277] In some embodiments, the polypeptide comprises a sequence having the sequence described in SEQ ID NO: 51 and includes a stalk portion (S1) including an Fc region, such as those provided herein. In some embodiments, the polypeptide comprises a sequence having the sequence described in SEQ ID NO: 51 and includes a stalk portion (S1) including an Fc region, the Fc region further includes a transmembrane domain, such as those provided herein. In some embodiments, the Fc region further including a transmembrane domain has the formula L1-Fc-L2-X1, where L1 is a linker provided herein or is absent, Fc is a variant Fc region provided herein, L2 is a linker provided herein or is absent, and X1 is a polypeptide including a transmembrane domain provided herein. As provided herein, X1 is of the formula ECD-T M -May contain a polypeptide having an ICD, wherein the ECD is an extracellular domain or fragment thereof provided herein, or is absent. 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 described in SEQ ID NO: 51, ECD, T M , and a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including ICD. In some embodiments, the polypeptide includes a sequence having the sequence described in SEQ ID NO: 51, CD8 and / or CD28 ECD, T M , and also includes a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including ICD. In some embodiments, the polypeptide includes a sequence having the sequence described in SEQ ID NO: 51, ECD, CD8 and / or CD28 T M , and also includes a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including ICD. In some embodiments, the polypeptide includes a sequence having the sequence described in Sequence ID No. 51, CD8 and / or CD28 ECD, CD8 and / or CD28 T M, and also includes a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including ICD. In some embodiments, the polypeptide includes a sequence having the sequence described in SEQ ID NO: 51, ECD, T M , and a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD, wherein the ICD includes an Env embedded motif provided herein. In some embodiments, the polypeptide includes a sequence having the sequence described in SEQ ID NO: 51, CD8 and / or CD28 ECD, T M , and a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD, wherein the ICD includes an Env embedded motif provided herein. In some embodiments, the polypeptide includes a sequence having the sequence described in SEQ ID NO: 51, ECD, CD8 and / or CD28 T M , and a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD, wherein the ICD includes an Env embedded motif provided herein. In some embodiments, the polypeptide includes a sequence having the sequence described in SEQ ID NO: 51, CD8 and / or CD28 ECD, CD8 and / or CD28 T M , and also includes a stalk portion (S1) including an Fc region (L1-Fc-L2-X1) including an ICD, the ICD including an Env embedded motif provided herein. In some embodiments, the sequence includes the sequence described in Sequence ID No. 51, the ECD, T M A polypeptide comprising a stalk portion (S1) including an Fc region (L1-Fc-L2-X1), including ICD, is immobilized on the surface of a viral particle, such as those provided herein. In some embodiments, L1, Fc, L2, ECD, T M The identity of the ICD is as provided herein. In some embodiments, the polypeptide binds to immune cells such as those provided herein. Targeted portion including flexible polypeptide

[0278] In some embodiments, V H and V LThe polypeptide is linked to a stalk portion (S1) which includes a flexible polypeptide (L3) as provided herein. In some embodiments, V H and V L The polypeptide is linked to a stalk moiety (S1) comprising a flexible polypeptide, further comprising a polypeptide comprising a transmembrane domain provided herein. In some embodiments, the flexible polypeptide further comprising a polypeptide comprising a transmembrane domain is represented by formula L3-X1, where L3 is the flexible polypeptide provided herein and X1 is as provided herein. As provided herein, X1 is ECD-T M -May include a polypeptide having the formula ICD, where ECD is an extracellular domain or fragment thereof provided herein, or is absent. M The transmembrane domain provided herein is the transmembrane domain, and the ICD is either an intracellular domain provided herein or absent. Examples of ECDs include, but are not limited to, the CD8 and / or CD28 ECDs provided herein. M Examples 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, the ECD, ICD, or both may be optionally absent. Therefore, X1 may be a CD8 and / or CD28 ECD, CD8 and / or CD28 T M Embodiments including an ICD with an Env embedded motif are understood to include the following X1 members: i) CD8 and / or CD28 ECD, CD8 and / or CD28 T M , and ICDs including the Env built-in motif; ii) CD8 and / or CD28 T M iii) ICDs including an Env built-in motif, and ICDs in which an ECD does not exist; CD8 and / or CD28 ECD, and CD8 and / or CD28 T M and for which no ICD exists; and iv) CD8 and / or CD28 T Mand in which neither ECD nor ICD exists. Similarly, X1 is CD8 and / or CD28 T M Embodiments including an ICD that also includes an Env incorporation motif are understood to include the following X1 members: i) CD8 and / or CD28 T M ii) ICDs that include an Env incorporation motif; and ii) CD8 and / or CD28 T for which no ICD exists. M Similarly, X1 is CD8 and / or CD28 ECD, and CD8 and / or CD28 T M Embodiments including the following X1 members are understood to include: i) CD8 and / or CD28 ECD, and CD8 and / or CD28 T M ii) CD8 and / or CD28 T where ECD does not exist M Furthermore, the above explanation is specific to ECD, T M It should be understood that this also applies to embodiments in which ICD is not described. For example, if X1 is ECD, CD8 and / or CD28 T M Embodiments including ICD are understood to include the following X1 members: i) ECD, CD8 and / or CD28 T M ii) ICD, and CD8 and / or CD28 T M Includes, and no ICD exists; iii) CD8 and / or CD28 T M , and ICDs for which ECD is absent; and iv) CD8 and / or CD28 T for which ECD and ICD are absent. M Similarly, X1 is CD8 and / or CD28 T M Embodiments including 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 for which no ICD exists. M Similarly, X1 is ECD, and CD8 and / or CD28 T M Embodiments including the following X1 members are understood to include: i) ECD, and CD8 and / or CD28 T M ii) CD8 and / or CD28 TM However, ECD does not exist. Unless otherwise explicitly stated, the above embodiments and descriptions are applicable to any of the following embodiments.

[0279] In some embodiments, X1 is CD8 and / or CD28 ECD, T M , and ICD. In some embodiments, X1 is ECD, CD8 and / or CD28 T M , and ICD. In some embodiments, X1 is CD8 and / or CD28 ECD, CD8 and / or CD28 T M , and ICD. In some embodiments, X1 is ECD, T M , and ICD, the ICD includes the Env embedded motif provided herein. In some embodiments, X1 is CD8 and / or CD28 ECD, T M , and ICD, the ICD includes the Env embedded motif provided herein. In some embodiments, X1 is ECD, CD8 and / or CD28 T M , and ICD, the ICD includes Env embedded motifs provided herein. In some embodiments, X1 is CD8 and / or CD28 ECD, CD8 and / or CD28 T M , and including ICD, the ICD includes Env embedded motifs provided herein.

[0280] In some embodiments, V provided herein H and V L The polypeptide is linked to a stalk portion (S1) which includes a flexible polypeptide (L3) as provided herein. In some embodiments, V provided herein H and V LThe polypeptide is linked to a stalk moiety (S1) comprising a flexible polypeptide (L3) further comprising a polypeptide comprising a transmembrane domain provided herein. In some embodiments, the flexible polypeptide (L3) further comprising a polypeptide comprising a transmembrane domain is represented by the formula L3-X1, where L3 is the flexible polypeptide provided herein and X1 is the polypeptide comprising a transmembrane domain provided herein. As provided herein, X1 is ECD-T M -May contain polypeptides having the formula ICD, wherein ECD is an extracellular domain or fragment thereof as provided herein, or is absent; M V is a transmembrane domain provided herein, and ICD is an intracellular domain provided herein. In some embodiments, V provided herein H and V L Polypeptides are CD8 and / or CD28 ECD, T M , and are coupled to a stalk portion (S1) containing a flexible polypeptide (L3-X1) including an ICD. In some embodiments, V provided herein H and V L Polypeptides are ECD, CD8 and / or CD28 T M , and are coupled to a stalk portion (S1) containing a flexible polypeptide (L3-X1) including an ICD. In some embodiments, V provided herein H and V L Polypeptides are CD8 and / or CD28 ECD, CD8 and / or CD28 T M , and are coupled to a stalk portion (S1) containing a flexible polypeptide (L3-X1) including an ICD. In some embodiments, V provided herein H and V L Polypeptides are ECD, T M , and linked to a stalk portion (S1) comprising a flexible polypeptide (L3-X1) including an ICD, the ICD including an Env embedded motif provided herein. In some embodiments, V provided herein Hand V L Polypeptides are CD8 and / or CD28 ECD, T M , and linked to a stalk portion (S1) comprising a flexible polypeptide (L3-X1) including an ICD, the ICD including an Env embedded motif provided herein. In some embodiments, V provided herein H and V L Polypeptides are ECD, CD8 and / or CD28 T M , and linked to a stalk portion (S1) comprising a flexible polypeptide (L3-X1) including an ICD, the ICD including an Env embedded motif provided herein. In some embodiments, 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 a flexible polypeptide (L3-X1) including an ICD, the ICD including an Env embedded motif provided herein. In some embodiments, the ECD, T M , and V provided herein, linked to a stalk portion (S1) containing a flexible polypeptide (L3-X1) including an ICD H and V L Polypeptides are immobilized on the surface of viral particles, such as those provided herein. In some embodiments, L3, X1, ECD, T M The identity of the ICD is provided herein. In some embodiments, V H and V L Polypeptides bind to immune cells, such as those provided herein.

[0281] In some embodiments, V has the sequence described in Sequence ID No. 36. H Peptide and V having the sequence described in SEQ ID NO: 37 L Peptides are ECD, T M, and are linked to a stalk portion (S1) containing a flexible polypeptide (L3-X1) including an ICD. In some embodiments, V has the sequence described in sequence number 36. H Peptide and V having the sequence described in SEQ ID NO: 37 L The peptide is CD8 and / or CD28 ECD, T M , and is linked to a stalk portion (S1) containing a flexible polypeptide (L3-X1) including an ICD. In some embodiments, V has the sequence described in sequence number 36. H Peptide and V having the sequence described in SEQ ID NO: 37 L The peptides are ECD, CD8 and / or CD28 T M , and is linked to a stalk portion (S1) containing a flexible polypeptide (L3-X1) including an ICD. In some embodiments, V has the sequence described in sequence number 36. H Peptide and V having the sequence described in SEQ ID NO: 37 L The peptides are CD8 and / or CD28 ECD, CD8 and / or CD28 T M , and is linked to a stalk portion (S1) containing a flexible polypeptide (L3-X1) including an ICD. In some embodiments, V has the sequence described in sequence number 36. H Peptide and V having the sequence described in SEQ ID NO: 37 L Peptides are ECD, T M , and linked to a stalk portion (S1) comprising a flexible polypeptide (L3-X1) including an ICD, the ICD comprising an Env embedded motif provided herein. In some embodiments, V has the sequence described in Sequence ID No. 36. H Peptide and V having the sequence described in SEQ ID NO: 37 L The peptide is CD8 and / or CD28 ECD, T M , and linked to a stalk portion (S1) comprising a flexible polypeptide (L3-X1) including an ICD, the ICD comprising an Env embedded motif provided herein. In some embodiments, V having the sequence described in Sequence ID No. 36 H Peptide and V having the sequence described in SEQ ID NO: 37L The peptides are ECD, CD8 and / or CD28 T M , and linked to a stalk portion (S1) comprising a flexible polypeptide (L3-X1) including an ICD, the ICD comprising an Env embedded motif provided herein. In some embodiments, V having the sequence described in Sequence ID No. 36 H Peptide and V having the sequence described in SEQ ID NO: 37 L The peptides are CD8 and / or CD28 ECD, CD8 and / or CD28 T M , and linked to a stalk portion (S1) comprising a flexible polypeptide (L3-X1) including an ICD, the ICD including an Env embedded motif provided herein. In some embodiments, the ECD, T M V having the sequence described in Sequence ID No. 36, linked to a stalk portion (S1) containing a flexible polypeptide (L3-X1) including ICD. H Peptide and V having the sequence described in SEQ ID NO: 37 L The peptide is immobilized on the surface of viral particles, such as those provided herein. In some embodiments, L3, X1, ECD, T M The identity of the ICD is provided herein. In some embodiments, V H and V L The peptides bind to immune cells, such as those provided herein.

[0282] In some embodiments, V 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 sequence number 36. H Peptide; and V containing 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 moiety (S1) containing a flexible polypeptide (L3) as provided herein. In some embodiments, the V contains 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 V containing 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 a stalk moiety (S1) comprising a flexible polypeptide (L3) further comprising a polypeptide comprising a transmembrane domain provided herein. In some embodiments, the flexible polypeptide further comprising a polypeptide comprising a transmembrane domain is represented by the formula L3-X1, where L3 is the flexible polypeptide provided herein and X1 is the polypeptide comprising a transmembrane domain provided herein. As provided herein, X1 is ECD-T M -May contain polypeptides having the formula ICD, wherein ECD is an extracellular domain or fragment thereof as provided herein, or is absent; M V is a transmembrane domain provided herein, and ICD is an intracellular domain provided herein, or is absent. In some embodiments, V 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: 36. H Peptide; and V containing a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%,...

Claims

1. A virus particle comprising one or more nucleic acid molecules, a heterologous viral glycoprotein, and a targeting moiety, wherein the targeting moiety is of formula T-S １ The polypeptide comprises a polypeptide having the formula where T is a target-binding domain and S １ The stalk portion is a virus particle in which one or more nucleic acid molecules encode i) a tandem chimeric antigen receptor comprising a first antigen-binding domain and a second antigen-binding domain, or ii) a first chimeric antigen receptor (first CAR) having an antigen-binding domain and a second chimeric antigen receptor (second CAR) having an antigen-binding domain.

2. The first antigen-binding domain and the second antigen-binding domain of the tandem CAR are, each, an antibody or a fragment thereof, for example, scFv, or The virus particle according to claim 1, wherein the antigen-binding domain of the first CAR and the antigen-binding domain of the second CAR are each independently an antibody or a fragment thereof, such as scFv.

3. The first antigen-binding domain and the second antigen-binding domain of the tandem CAR bind to different antigens or different epitopes on the same antigen, or The virus particle according to claim 1, wherein the antigen-binding domain of the first CAR and the antigen-binding domain of the second CAR bind to different antigens or different epitopes on the same antigen.

4. The first antigen-binding domain and the second antigen-binding domain of the tandem CAR bind to BCMA or FCRL5, CD19 or CD20, or CD20 and / or CD22, provided that the first antigen-binding domain and the second antigen-binding domain do not bind to the same antigen, or The antigen-binding domains of the first CAR and the second CAR bind to BCMA or FCRL5, CD19 or CD20, or CD20 and / or CD22, provided that the antigen-binding domains of the first CAR and the second CAR do not bind to the same antigen, as described in claim 2.

5. The virus particle according to claim 4, wherein the antigen-binding domain that binds to BCMA comprises a polypeptide comprising a light chain and a heavy chain, the light chain and the heavy chain each comprising a heavy chain variable region of the heavy chain having at least 95% identity with respect to one of the amino acid sequences of SEQ ID NOs: 89 and 94, and a light chain variable region of the light chain having at least 95% identity with respect to the amino acid sequence of SEQ ID NO:

90.

6. The virus particle according to claim 4, wherein the antigen-binding domain that binds to BCMA and / or FCRL5 comprises a polypeptide comprising a light chain and a heavy chain, the light chain and the heavy chain comprising a heavy chain variable region of the heavy chain having one of the amino acid sequences of SEQ ID NO: 89 or 94 and a light chain variable region of the light chain having SEQ ID NO:

90.

7. The virus particle according to claim 6 or 7, wherein the antigen-binding domain that binds to BCMA and / or FCRL5 comprises a polypeptide having at least 95% sequence identity with SEQ ID NOs: 92, 96, 107, or 111.

8. The virus particle according to claim 6 or 7, wherein the antigen-binding domain that binds to BCMA and / or FCRL5 comprises a polypeptide having at least 95% sequence identity with SEQ ID NOs: 93, 97, 108, or 112.

9. The virus particle according to claim 5, wherein the antigen-binding domain that binds to CD19 and / or CD20 comprises a polypeptide comprising a light chain and a heavy chain, the light chain and the heavy chain comprising a heavy chain variable region of the heavy chain having at least 95% sequence identity with respect to one of the amino acid sequences of SEQ ID NO: 114 or 138, and a light chain variable region of the light chain having at least 95% sequence identity with respect to the amino acid sequence of SEQ ID NO: 115 or 139.

10. The virus particle according to claim 5, wherein the antigen-binding domain that binds to CD19 and / or CD20 comprises a polypeptide comprising a light chain and a heavy chain, the light chain and the heavy chain comprising a heavy chain variable region of the heavy chain comprising the amino acid sequence of SEQ ID NO: 114 or 138 and a light chain variable region of the light chain comprising the amino acid sequence of SEQ ID NO: 115 or 139.

11. The virus particle according to claim 5, wherein the antigen-binding domain that binds to CD20 and / or CD22 comprises a polypeptide comprising a light chain and a heavy chain, the light chain and the heavy chain comprising a heavy chain variable region of the heavy chain having at least 95% sequence identity with respect to one of the amino acid sequences of SEQ ID NO: 114 or 118, and a light chain variable region of the light chain having at least 95% sequence identity with respect to one of the amino acid sequences of SEQ ID NO: 115 or 119.

12. The virus particle according to claim 5, wherein the antigen-binding domain that binds to CD20 and / or CD22 comprises a polypeptide comprising a light chain and a heavy chain, the light chain and the heavy chain comprising a heavy chain variable region of the heavy chain comprising the amino acid sequence of SEQ ID NO: 114 or 118 and a light chain variable region of the light chain comprising the amino acid sequence of SEQ ID NO: 115 or 119.

13. The virus particle according to claim 5, wherein the antigen-binding domain that binds to CD20 and / or CD22 comprises a polypeptide having at least 95% sequence identity with any one of the amino acid sequences described in SEQ ID NO: 116, 120, 122, or 124, or the sequence of SEQ ID NO: 116, 120, 122, or 124.

14. The virus particle according to claim 5, wherein the antigen-binding domain that binds to CD20 and / or CD22 comprises a polypeptide having at least 95% sequence identity with any one of the amino acid sequences described in SEQ ID NO: 117, 121, 123, or 125, or the sequence of SEQ ID NO: 117, 121, 123, or 125.

15. The viral particle according to any one of claims 3 to 14, wherein the CAR further comprises a hinge domain, a transmembrane domain, a co-stimulatory domain, and a signal transduction domain.

16. The virus particle according to claim 15, wherein the hinge domain comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with the amino acid sequence of Sequence ID No.

59.

17. The virus particle according to claim 15 or 16, wherein the transmembrane domain comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with the amino acid sequence of SEQ ID NO:

61.

18. The virus particle according to any one of claims 15 to 17, wherein the co-stimulatory domain comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with the amino acid sequence of SEQ ID NO:

101.

19. The viral particle according to any one of claims 15 to 18, wherein the signal transduction domain comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with the amino acid sequence of SEQ ID NO:

102.

20. The virus particle according to claim 5, wherein the CAR or tandem CAR includes an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with any one of the amino acid sequences of SEQ ID NOs. 126-135, 138-142, and 145-207.

21. The virus particle according to claim 5, wherein the CAR or tandem CAR contains an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with any one of the sequences of sequence numbers 126-135, 142, 145-164, and 203-207.

22. The virus particle according to claim 5, wherein the CAR or tandem CAR comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with any one of the sequences of sequence numbers 150, 167, 170, or 203.

23. The virus particle according to claim 5, wherein the CAR or tandem CAR comprises the amino acid sequence of SEQ ID NO:

150.

24. The virus particle according to claim 5, wherein the CAR or tandem CAR comprises the amino acid sequence of SEQ ID NO:

167.

25. The virus particle according to claim 5, wherein the CAR or tandem CAR comprises the amino acid sequence of SEQ ID NO:

170.

26. The virus particle according to claim 5, wherein the CAR or tandem CAR comprises the amino acid sequence of SEQ ID NO:

203.

27. The aforementioned S １ The virus particle according to any one of claims 1 to 26, wherein the stalk portion contains a mutant Fc protein and is bound to the surface of the virus particle via a transmembrane domain.

28. The method according to claim 27, wherein the mutant Fc protein is IgG1, IgG2, or IgG4.

29. The viral particle according to Embodiment 28, wherein the mutant Fc protein includes a mutant of the sequence of SEQ ID NO: 26, SEQ ID NO: 27, or SEQ ID NO:

28.

30. The viral particle according to claim 28, wherein the mutant Fc protein is a mutant IgG1 Fc protein.

31. The viral particle according to claim 30, wherein the mutant IgG1 Fc protein contains one or more mutations selected from the group consisting of L234A, L235A, N297A, P329G, I253A, H310A, and H435A.

32. The above formula T-S １ The targeting portion having formula L １ -Fc-L ２ -X １ Stork portion S １ Including, in the formula, L １ is a linker or does not exist; Fc is a mutant Fc protein; L ２ It is either a linker or does not exist; X １ This is a polypeptide containing the transmembrane domain, The above formula T-S １ The targeting portion having formula T-L １ -Fc-L ２ -X １ A virus particle according to any one of claims 1 to 31, having the characteristics of a virus particle.

33. L １ and L ２ The virus particle according to claim 32, wherein each is independently a polypeptide linker.

34. The polypeptide linker is (GGGGGA) ｎ (Sequence ID 54), (GGGGS) ｎ (Sequence ID 55), (EAAAK) ｎ (Sequence ID 73), A(EAAAK) ｎ A (Sequence ID 74), (XP) ｎ The virus particle according to claim 33, comprising (SEQ ID NO: 75), wherein X is Ala, Lys, or Glu, GSAGSAAGSGEF (SEQ ID NO: 56), KESGSVSSECEQLAQFRSLD (SEQ ID NO: 57), EGKSGSGSESKST (SEQ ID NO: 58), AEAAAAKEAAAAKA (SEQ ID NO: 76), or a combination thereof, where each n is independently 1 to 5.

35. X １ ECD-T Ｍ - Containing a polypeptide having the formula ICD, in the formula, ECD is either the extracellular domain or fragment thereof of a cell surface protein, or it is absent; T Ｍ This is the transmembrane domain of a transmembrane protein, ICD is either an intracellular domain or protein that facilitates the incorporation of the targeting portion into the envelope of the viral particle, or it is not present. The above formula TL １ -Fc-L ２ -X １ The targeting portion having formula T-L １ -Fc-L ２ -ECD-T Ｍ - A virus particle according to any one of claims 32 to 34, having an ICD.

36. The virus particle according to claim 35, wherein the ECD comprises the amino acid sequence of SEQ ID NO: 59 or SEQ ID NO:

60.

37. Said T Ｍ The virus particle according to claim 35, comprising the amino acid sequence of SEQ ID NO: 61 or SEQ ID NO:

62.

38. The ICD is a virus particle according to any one of claims 35 to 37, comprising an Env embedded motif.

39. The virus particle according to claim 38, wherein the Env embedded motif comprises the amino acid sequence of SEQ ID NO: 63 or SEQ ID NO:

64.

40. The target-binding domain (T) binds to CD7, as described in any one of claims 1 to 39.

41. The target-binding domain (T) binds to CD8, as described in any one of claims 1 to 39.

42. The virus particle according to any one of claims 1 to 41, wherein the heterologous viral glycoprotein is a VSV-G polypeptide.

43. The virus particle according to claim 42, wherein the VSV-G polypeptide comprises the polypeptide of Sequence ID No. 2, which includes a mutation corresponding to the mutation at position 182 of Sequence ID No.

2.

44. The virus particle according to claim 43, wherein the VSV-G polypeptide comprises the I182E or I182D mutation compared to SEQ ID NO:

2.

45. A method for infecting cells, comprising contacting the cells with a virus particle described in any one of claims 1 to 44.

46. A method for treating a disease or disorder in a subject, comprising administering a virus particle described in any one of claims 1 to 44 to the subject.

47. The method according to claim 46, wherein the disease or disorder is cancer (e.g., T-cell or B-cell disorder or other types of cancer as described herein), an immune disorder, an autoimmune disorder, a metabolic disorder, etc.

48. A viral particle comprising a heterologous viral glycoprotein, a targeting moiety, and a nucleic acid molecule encoding the target heterologous molecule, The heterologous viral glycoprotein contains an amino acid sequence that has at least 90% identity with 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, at least 95% identity with 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, at least 99% identity with 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, or at least 100% identity with 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, The targeted portion includes an amino acid sequence having at least 90% identity with SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 50, or SEQ ID NO: 51, at least 95% identity with SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 50, or SEQ ID NO: 51, at least 99% identity with SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 50, or SEQ ID NO: 51, or at least 100% identity with SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 50, or SEQ ID NO:

51. The aforementioned heterologous molecule is a virus particle comprising a chimeric antigen receptor (CAR), a dual CAR, or a tandem CAR that binds to BCMA and / or FCRL5, CD19 and / or CD20, or CD20 and / or CD22, wherein the CAR, the dual CAR, or the tandem CAR contains an amino acid sequence having at least 85%, 90%, 95%, 99%, or 100% identity with any one of the sequences of SEQ ID NOs: 126-135, 138-142, and 145-207.

49. The virus particle according to claim 48, wherein the CAR, the dual CAR, or the tandem CAR comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with any one of the sequences of sequence numbers 150, 167, 170, or 203.

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