Mutant polypeptide, composition containing mutant polypeptide and application of mutant polypeptide

Abstract

Provided herein are viral particles comprising a heterologous viral glycoprotein and a targeting moiety wherein the targeting moiety comprises a polypeptide comprising the formula T-S1 wherein T is a target binding domain and Si is a stem moiety. The stem portion may comprise a variant Fc domain. The stem portion may comprise a flexible polypeptide domain. The targeting moiety comprising the formula T-S1 may be incorporated into viral particles to help target such particles to specific cell types. Also provided herein are compositions comprising the viral particles, and methods of use thereof.

Description

[0001] Related applications

[0002] This application claims the benefits of U.S. Provisional Application No. 63 / 391,930, filed July 25, 2022; U.S. Provisional Application No. 63 / 391,939, filed July 25, 2022; U.S. Provisional Application No. 63 / 503,815, filed May 23, 2023; and U.S. Provisional Application No. 63 / 507,783, filed June 13, 2023, each of which is hereby incorporated by reference in its entirety.

[0003] References to sequence listings submitted electronically

[0004] This application contains a sequence list, which has been submitted electronically in XML format and is hereby incorporated in its entirety by reference. The XML copy was created on July 20, 2023, named "INH-020WO_SL.xml", and is 114,351 bytes in size. Technical Field

[0005] The embodiments provided herein relate to viral particles comprising a heterologous viral glycoprotein and a targeting portion having the formula T-S1, wherein T is a target-binding domain and S1 is a stem portion. The stem portion may comprise a variant Fc domain. The stem portion may comprise a flexible peptide domain. The embodiments provided herein further relate to compositions comprising the viral particles provided herein and methods of using them. Background Art

[0006] Vesicular stomatitis virus (VSV) is an enveloped, negative-sense RNA virus belonging to the genus *Vesicavivirus* of the family Corynebacteridae. It is an arthropod-borne virus that infects insects, cattle, horses, and pigs. The VSV genome encodes five structural proteins, including a single transmembrane glycoprotein (G). This glycoprotein is a classic type I membrane glycoprotein, possessing an N-terminal signal peptide, an extracellular domain of approximately 450 amino acids, a single α-helix transmembrane segment, and a small intraviral C-terminal domain. The signal peptide cleaves in the lumen of the endoplasmic reticulum, and the naturally matured glycoprotein consists of an extracellular domain, a transmembrane domain, and an intraviral domain.

[0007] G plays a crucial role in the initial steps of viral infection (Albertini, AAV, Baquero, E., Ferlin, A., and Gaudin, Y. (2012). Molecular and Cellular Aspects of Rhabdovirus Entry. Viruses 4, 117-139.), which is hereby incorporated in its entirety by reference. First, it is responsible for attaching the virus to specific receptors. After binding, the viral particle enters the cell via the clathrin-mediated endocytosis pathway. In the acidic environment of the endocytic vesicles, G triggers the fusion between the viral membrane and the endosomal membrane, thereby releasing the genome into the cytosol for subsequent infection steps. The fusion was catalyzed by a low-pH-induced macrostructural transition from the prefusion to the postfusion conformation, both of which were trimers (Roche, S., Bressanelli, S., Rey, FA, and Gaudin, Y. (2006). Crystal structure of the low-pH form of the vesicular stomatitis virus glycoprotein G. Science 313, 187-191. Roche, S., Rey, FA, Gaudin, Y., and Bressanelli, S. (2007). Structure of the prefusion form of the vesicular stomatitis virus glycoprotein G. Science 315, 843-848), each of which is hereby incorporated in its entirety by reference).

[0008] The G extracellular domain polypeptide chain folds into three distinct domains: the fusion domain (FD), the pleckstrin homology domain (PHD), and the trimerization domain (TrD). During the structural transition, FD, PHD, and TrD retain their tertiary structure. However, due to a secondary change in the refolding of the hinge segments (S1 to S5) during a low-pH-induced conformational change, these domains undergo significant rearrangements in their relative orientations (Roche et al., 2006; Roche et al., 2007).

[0009] It has been shown that the low-density lipoprotein receptor (LDL-R) and other members of this receptor family act as VSV receptors (Finkelshtein, D., Werman, A., Novick, D., Barak, S., and Rubinstein, M. (2013). LDL receptor and its family members serve as the cellular receptors for vesicularstomatitis virus. Proceedings of the National Academy of Sciences of the United States of America 110, 7306-7311, which are hereby incorporated herein by reference in their entirety). VSV-G can be used for pseudotypening of other viruses, and VSV-G pseudotyped lentivirus (VSV-G-LV) exhibits the same broad tropism as VSV. However, this broad tropism can inhibit selective targeting to specific cell types. Therefore, there is a need for modified (mutated or mutant) VSV-G proteins that can be used for viral pseudotypening, thereby eliminating their binding to the LDL receptor. Embodiments of the present invention meet these and other needs. Summary of the Invention

[0010] In some embodiments, a viral particle is provided. In some embodiments, the viral particle comprises a heterologous viral glycoprotein and a targeting portion, wherein the targeting portion comprises a polypeptide having the formula T-S1, where T is a target-binding domain and S1 is a stem portion.

[0011] In some embodiments, the stem portion S1 contains a variant Fc protein. In some embodiments, the variant Fc protein contains a transmembrane domain, such as, but not limited to, a CD8 or CD28 transmembrane domain. In some embodiments, the variant Fc protein contains an effector mutation, wherein the effector mutation inhibits the interaction between the Fc protein and Fc-interacting proteins, such as FcγR, C1q, FcRβ, or FcRn.

[0012] In some implementations, the variant Fc protein is a variant IgG1 Fc protein containing one or more mutations selected from the group consisting of: L234A, L235A, N297A, P329G, I253A, H310A, and H435A.

[0013] In some embodiments, the variant IgG1 Fc protein comprises an amino acid sequence having at least 80% identity with SEQ ID NO:104, at least 85% identity with SEQ ID NO:104, at least 90% identity with SEQ ID NO:104, at least 95% identity with SEQ ID NO:104, at least 98% identity with SEQ ID NO:104, or at least 100% identity with SEQ ID NO:104.

[0014] In some implementations, the variant Fc protein is the variant IgG2 Fc protein, which contains one or more mutations selected from the group consisting of: N297A, P329G, I253A, H310A, and H435A.

[0015] In some implementations, the variant Fc protein is the variant IgG4 Fc protein, which contains one or more mutations selected from the group consisting of: S228P, L235E, N297A, P329G, I253A, H310A, and H435A.

[0016] In some embodiments, the targeting portion having formula T-S1 includes a stem portion S1 having formula L1-Fc-L2-X1, wherein L1 is a linker or is absent, Fc is a variant Fc protein, L2 is a linker or is absent, and X1 is a polypeptide containing a transmembrane domain, wherein the targeting portion having formula T-S1 has formula T-L1-Fc-L2-X1.

[0017] In some embodiments, the polypeptide (X1) containing a transmembrane domain comprises having the formula ECD-T M -ICD polypeptide, wherein ECD is an extracellular domain of a cell surface protein or a fragment thereof, or is absent; T M It is a transmembrane domain of a transmembrane protein; and ICD is an intracellular domain or protein that promotes the incorporation of the targeting portion into the viral particle envelope, or it may not exist; wherein the targeting portion having the formula T-L1-Fc-L2-X1 has the formula T-L1-Fc-L2-ECD-T M -ICD.

[0018] In some embodiments, the stem portion S1 comprises formula L3-X1, wherein L3 is a flexible peptide linker and X1 is a polypeptide containing a transmembrane domain; wherein the targeting portion having formula T-S1 has formula T-L3-X1.

[0019] In some embodiments, the polypeptide (X1) containing a transmembrane domain comprises having the formula ECD-T M -ICD polypeptide, wherein ECD is an extracellular domain of a cell surface protein or a fragment thereof, or is absent; TM It is a transmembrane domain of a transmembrane protein; and ICD is an intracellular domain or protein that promotes the incorporation of the targeting portion into the viral particle envelope, or it may not exist; wherein the targeting portion having the formula T-L3-X1 has the formula T-L3-ECD-T M -ICD.

[0020] In some embodiments, the targeting portion binds to CD7. In some embodiments, the targeting portion comprises a polypeptide having a heavy chain variable region comprising HCDR1 of SEQ ID NO:30, HCDR2 of SEQ ID NO:31, and HCDR3 of SEQ ID NO:32, or a variant thereof. In some embodiments, the targeting portion comprises a polypeptide having a light chain variable region comprising LCDR1 of SEQ ID NO:33, LCDR2 of SEQ ID NO:34, and LCDR3 of SEQ ID NO:35, or a variant thereof. In some embodiments, the heavy chain comprises a heavy chain variable region having at least 90% sequence identity with SEQ ID NO:36. In some embodiments, the light chain comprises a light chain variable region having at least 90% sequence identity with SEQ ID NO:37. In some embodiments, the targeting portion binding to CD7 comprises a polypeptide having a sequence having at least 90% sequence identity with SEQ ID NO:38. In some embodiments, the targeting portion that binds to CD7 comprises a polypeptide having a sequence having at least 90% sequence identity with SEQ ID NO:39.

[0021] In some embodiments, the targeting moiety binds to CD8. In some embodiments, the targeting moiety comprises a polypeptide having a heavy chain variable region comprising HCDR1 of SEQ ID NO:42, HCDR2 of SEQ ID NO:43, and HCDR3 of SEQ ID NO:44, or a variant of any of the foregoing. In some embodiments, the targeting moiety comprises a polypeptide having a light chain variable region comprising LCDR1 of SEQ ID NO:45, LCDR2 of SEQ ID NO:46, and LCDR3 of SEQ ID NO:47, or a variant of any of the foregoing. In some embodiments, the heavy chain comprises a heavy chain variable region having at least 90% sequence identity with SEQ ID NO:48. In some embodiments, the light chain comprises a light chain variable region having at least 90% sequence identity with SEQ ID NO:49. In some embodiments, the targeting moiety binding to CD8 comprises a polypeptide having a sequence having at least 90% sequence identity with SEQ ID NO:50. In some embodiments, the targeting portion that binds to CD8 comprises a polypeptide having a sequence having at least 90% sequence identity with SEQ ID NO:51.

[0022] In some embodiments, the heteroviral glycoprotein is the SVCV-G polypeptide as provided herein.

[0023] In some embodiments, the heteroviral glycoprotein is a VSV-G polypeptide. In some embodiments, the VSV-G polypeptide contains substitutions at positions I182, T214, and T352 of SEQ ID NO:2. In some embodiments, the substitution at position 182 is I182D or I182E. In some embodiments, the substitution at position 214 is T214N. In some embodiments, the substitution at position 352 is T352A.

[0024] 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 with SEQ ID NO:89 and a light chain variable region having at least 95% identity with SEQ ID NO:90. In some embodiments, the CAR comprises an antigen-binding domain having a heavy chain variable region having at least 95% identity with SEQ ID NO:94 and a light chain variable region having at least 95% identity with SEQ ID NO:95.

[0025] In some embodiments, the CAR includes an antigen-binding domain having an amino acid sequence having at least 95% identity with SEQ ID NO:92. In some embodiments, the CAR includes an antigen-binding domain having an amino acid sequence having at least 95% identity with SEQ ID NO:93. In some embodiments, the CAR includes an antigen-binding domain having an amino acid sequence having at least 95% identity with SEQ ID NO:96. In some embodiments, the CAR includes an antigen-binding domain having an amino acid sequence having at least 95% identity with SEQ ID NO:97.

[0026] In some embodiments, the CAR comprises an amino acid sequence having at least 85% identity with SEQ ID NO:99, at least 90% identity with SEQ ID NO:99, at least 95% identity with SEQ ID NO:99, at least 99% identity with SEQ ID NO:99, or at least 100% identity with SEQ ID NO:99.

[0027] In some embodiments, a method for infecting cells is provided. In some embodiments, the method includes contacting the cells with viral particles as provided herein.

[0028] In some embodiments, a method for infecting the cells of a subject is provided. In some embodiments, the method includes administering to the subject a pharmaceutical composition comprising viral particles as provided herein.

[0029] In some embodiments, a method is provided for delivering a heterologous molecule of interest into a cell. In some embodiments, the method includes contacting the cell with a viral particle as provided herein, wherein the viral particle contains a nucleic acid molecule encoding the heterologous molecule of interest.

[0030] In some embodiments, a method is provided for delivering a heterologous molecule of interest to the cells of a subject. In some embodiments, the method includes administering to the subject a viral particle as provided herein, wherein the viral particle contains a nucleic acid molecule encoding the heterologous molecule of interest.

[0031] In some embodiments, a method for treating a disease or condition in a subject is provided. In some embodiments, the method includes administering to the subject viral particles as provided herein, wherein the viral particles contain nucleic acid molecules encoding a heterologous molecule of interest to treat the disease or condition.

[0032] In some embodiments, a method for delivering a heterologous molecule to target cells is provided. In some embodiments, the method includes contacting the cells with viral particles as provided herein, wherein the viral particles contain a nucleic acid molecule encoding the heterologous molecule.

[0033] In some embodiments, a viral particle is provided. In some embodiments, the viral particle comprises a heterologous viral glycoprotein and a targeting portion, the targeting portion comprising a polypeptide having the formula T-S1, wherein T is a target-binding domain and S1 is a stem 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 stem portion S1 comprises a variant Fc protein, the variant Fc protein comprising a sequence that is a variant of SEQ ID NO:26, SEQ ID NO:27, or SEQ ID NO:28. In some embodiments, the variant of SEQ ID NO:26 comprises one or more mutations selected from the group consisting of: L234A, L235A, N297A, P329G, I253A, H310A, and H435A. In some embodiments, the variant of SEQ ID NO:27 comprises one or more mutations selected from the group consisting of: N297A, P329G, I253A, H310A, and H435A. In some embodiments, the variant of SEQ ID NO:28 comprises one or more mutations selected from the group consisting of: S228P, L235E, N297A, P329G, I253A, H310A, and H435A. In some embodiments, the variant Fc protein further comprises a transmembrane domain comprising a sequence selected from SEQ ID NO:61 or SEQ ID NO:62.

[0034] In some embodiments, a viral particle is provided. In some embodiments, the viral particle comprises a heterologous viral glycoprotein and a targeting portion, the targeting portion comprising a polypeptide having the formula T-S1, wherein T is a target-binding domain and S1 is a stem 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 stem portion S1 comprises the formula L1-Fc-L2-X1, wherein L1 is a linker comprising a sequence selected from SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, or SEQ ID NO:76, or is absent; Fc is a variant Fc protein comprising a sequence as a variant of SEQ ID NO:26, SEQ ID NO:27, or SEQ ID NO:28; L2 is a linker comprising a sequence selected from SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, or SEQ ID NO:76, or is absent; and X1 is a polypeptide comprising a transmembrane domain. In some embodiments, the variant of SEQ ID NO:26 contains 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 contains 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 contains one or more mutations selected from the group consisting of: S228P, L235E, N297A, P329G, I253A, H310A, and H435A. In some embodiments, the polypeptide (X1) containing a transmembrane domain has the formula ECD-T. M -ICD, wherein ECD is an extracellular domain or fragment thereof having a sequence selected from SEQ ID NO:59 or SEQ ID NO:60, or is absent; T MThe ICD is a transmembrane domain or a fragment thereof having a 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 target portion into the envelope of the viral particle, wherein the ICD contains an env incorporation motif that contains an amino acid sequence of SEQ ID NO:63 or SEQ ID NO:64, or the ICD is absent.

[0035] In some embodiments, a viral particle is provided. In some embodiments, the viral particle comprises a heterologous viral glycoprotein and a targeting portion, the targeting portion comprising a polypeptide having the formula T-S1, wherein T is a target-binding domain and S1 is a stem 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 stem portion S1 comprises the formula L1-Fc-L2-X1, wherein L1 is a linker containing the sequence of SEQ ID NO:55, or is absent; Fc is a variant Fc protein containing the sequence as a variant of SEQ ID NO:26, SEQ ID NO:27, or SEQ ID NO:28; L2 is a linker containing the sequence of SEQ ID NO:55, or is absent; 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 comprises one or more mutations selected from the group consisting of: N297A, P329G, I253A, H310A, and H435A. In some embodiments, the variant of SEQ ID NO:28 contains one or more mutations selected from the group consisting of: S228P, L235E, N297A, P329G, I253A, H310A, and H435A. In some embodiments, the polypeptide (X1) containing a transmembrane domain has the formula ECD-T. M -ICD, wherein ECD is an extracellular domain or fragment thereof having the sequence of SEQ ID NO:60, or is absent; T MThe ICD is a transmembrane domain or a fragment thereof having the sequence of SEQ ID NO:62; and the ICD is an intracellular domain or protein that facilitates the incorporation of the target portion into the envelope of the viral particle, wherein the ICD contains an env incorporation motif that contains the amino acid sequence of SEQ ID NO:63 or SEQ ID NO:64, or the ICD is absent.

[0036] In some embodiments, a viral particle is provided. In some embodiments, the viral particle comprises a heterologous viral glycoprotein and a targeting portion, the targeting portion comprising a polypeptide having the formula T-S1, wherein T is a target-binding domain and S1 is a stem portion. In some embodiments, the heterologous viral glycoprotein comprises a sequence selected from SEQ ID NO:23 or SEQ ID NO:25. In some embodiments, the target-binding domain comprises SEQ ID NO:39. In some embodiments, the stem portion S1 comprises the formula L1-Fc-L2-X1, wherein L1 is a linker comprising the sequence of SEQ ID NO:55; Fc is a variant Fc protein comprising the sequence of SEQ ID NO:104; L2 is a linker and is absent; and X1 is a polypeptide comprising a transmembrane domain. In some embodiments, the polypeptide (X1) comprising the transmembrane domain has the formula ECD-T. M -ICD, where ECD is an extracellular domain having the sequence SEQ ID NO: 60; T M It is a transmembrane domain having the sequence of SEQ ID NO:62; and the ICD is an intracellular domain or protein that facilitates the incorporation of the target portion into the envelope of the viral particle, wherein the ICD contains an env incorporation motif that contains the amino acid sequence of SEQ ID NO:63.

[0037] In some embodiments, a viral particle is provided, wherein the viral particle comprises a heterologous viral glycoprotein and a targeting portion. In some embodiments, the heterologous viral glycoprotein comprises an amino acid sequence having at least 90% identity with SEQ ID NO:23 or SEQ ID NO:25, at least 95% identity with SEQ ID NO:23 or SEQ ID NO:25, at least 99% identity with SEQ ID NO:23 or SEQ ID NO:25, or at least 100% identity with SEQ ID NO:23 or SEQ ID NO:25. In some embodiments, the targeting portion comprises an amino acid sequence having at least 90% identity with SEQ ID NO:98, at least 95% identity with SEQ ID NO:98, at least 99% identity with SEQ ID NO:98, or at least 100% identity with SEQ ID NO:98.

[0038] In some embodiments, a viral particle is provided, wherein the viral particle comprises a heterologous viral glycoprotein and a targeting portion. In some embodiments, the heterologous viral glycoprotein comprises an amino acid sequence having at least 90% identity with SEQ ID NO:52 or SEQ ID NO:53, at least 95% identity with SEQ ID NO:53, at least 99% identity with SEQ ID NO:53, or at least 100% identity with SEQ ID NO:52 or SEQ ID NO:53. In some embodiments, the targeting portion comprises an amino acid sequence having at least 90% identity with SEQ ID NO:98, at least 95% identity with SEQ ID NO:98, at least 99% identity with SEQ ID NO:98, or at least 100% identity with SEQ ID NO:98.

[0039] In some embodiments, a viral particle is provided. In some embodiments, the viral particle comprises a heterologous viral glycoprotein and a targeting portion, the targeting portion comprising a polypeptide having the formula T-S1, wherein T is a target-binding domain and S1 is a stem portion. In some embodiments, the target-binding domain comprises an amino acid sequence of SEQ ID NO:38 or SEQ ID NO:39. In some embodiments, the stem portion S1 comprises the formula L3-X1, wherein L3 is a flexible peptide linker comprising an 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 peptide linker comprising a transmembrane domain. In some embodiments, the polypeptide (X1) comprising the transmembrane domain has the formula ECD-T. M -ICD, wherein ECD is an extracellular domain or fragment thereof containing the amino acid sequence of SEQ ID NO:59 or SEQ ID NO:60, 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 target portion into the envelope of the viral particle, wherein 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 portion, the targeting portion comprising a polypeptide having the formula T-S1, wherein T is a target-binding domain and S1 is a stem portion. In some embodiments, the target-binding domain comprises an amino acid sequence of SEQ ID NO:50 or SEQ ID NO:51. In some embodiments, the stem portion S1 comprises the formula L3-X1, wherein L3 is a flexible peptide linker comprising an 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 peptide linker comprising a transmembrane domain. In some embodiments, the polypeptide (X1) comprising the transmembrane domain has the formula ECD-T. M -ICD, wherein ECD is an extracellular domain or fragment thereof containing the amino acid sequence of SEQ ID NO:59 or SEQ ID NO:60, 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 target portion into the envelope of the viral particle, wherein 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 portion, the targeting portion comprising a polypeptide having the formula T-S1, wherein T is a target-binding domain and S1 is a stem portion. In some embodiments, the heterologous viral glycoprotein comprises a 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 an 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 stem portion S1 comprises the formula L3-X1, wherein L3 is a flexible peptide linker comprising an 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 peptide linker comprising a transmembrane domain. In some embodiments, the polypeptide (X1) containing a transmembrane domain has the formula ECD-T M-ICD, wherein ECD is an extracellular domain or fragment thereof containing the amino acid sequence of SEQ ID NO:59 or SEQ ID NO:60, 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 target portion into the envelope of the viral particle, wherein 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.

[0042] In some embodiments, a viral particle is provided. In some embodiments, the viral particle comprises a heterologous viral glycoprotein and a targeting portion, the targeting portion comprising a polypeptide having the formula T-S1, wherein T is a target-binding domain and S1 is a stem portion. In some embodiments, the heterologous viral glycoprotein comprises the sequence of SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:52, or SEQ ID NO:53. In some embodiments, the target-binding domain comprises the amino acid sequence of SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:50, or SEQ ID NO:51. In some embodiments, the stem portion S1 comprises the formula L3-X1, wherein L3 is a flexible peptide linker comprising the amino acid sequence of SEQ ID NO:55, and X1 is a peptide linker comprising a transmembrane domain. In some embodiments, the polypeptide (X1) comprising the transmembrane domain has the formula ECD-T. M -ICD, wherein ECD is an extracellular domain or fragment thereof containing the amino acid sequence of SEQ ID NO:59 or SEQ ID NO:60, or is absent, T M The ICD is a transmembrane domain comprising 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 target portion into the envelope of the viral particle, wherein the ICD comprises an env incorporation motif comprising the amino acid sequence of SEQ ID NO:63 or SEQ ID NO:64, or the ICD is absent.

[0043] In some embodiments, a viral particle is provided. In some embodiments, the viral particle comprises a heterologous viral glycoprotein and a targeting portion, the targeting portion comprising a polypeptide having the formula T-S1, wherein T is a target-binding domain and S1 is a stem portion. In some embodiments, the heterologous viral glycoprotein comprises the sequence of SEQ ID NO:23 or SEQ ID NO:25. In some embodiments, the target-binding domain comprises the amino acid sequence of SEQ ID NO:39. In some embodiments, the stem portion S1 comprises the formula L3-X1, wherein L3 is a flexible peptide linker comprising the amino acid sequence of SEQ ID NO:55, and X1 is a peptide linker comprising a transmembrane domain. In some embodiments, the polypeptide (X1) comprising the transmembrane domain has the formula ECD-T. M -ICD, where ECD is an extracellular domain containing the amino acid sequence of SEQ ID NO:59, T M The ICD is a transmembrane domain comprising the amino acid sequence of SEQ ID NO:61, and the ICD is an intracellular domain or protein that facilitates the incorporation of the target portion into the envelope of the viral particle, wherein the ICD comprises an env incorporation motif comprising the amino acid sequence of SEQ ID NO:63 or SEQ ID NO:64.

[0044] In some embodiments, a viral particle is provided. In some embodiments, the viral particle comprises a heterologous viral glycoprotein and a targeting portion, the targeting portion comprising a polypeptide having the formula T-S1, wherein T is a target-binding domain and S1 is a stem portion. In some embodiments, the heterologous viral glycoprotein comprises the sequence of SEQ ID NO:52 or SEQ ID NO:53. In some embodiments, the target-binding domain comprises the amino acid sequence of SEQ ID NO:39. In some embodiments, the stem portion S1 comprises the formula L3-X1, wherein L3 is a flexible peptide linker comprising the amino acid sequence of SEQ ID NO:55, and X1 is a peptide linker comprising a transmembrane domain. In some embodiments, the polypeptide (X1) comprising the transmembrane domain has the formula ECD-T. M -ICD, where ECD is an extracellular domain containing the amino acid sequence of SEQ ID NO:59, T M The ICD is a transmembrane domain comprising the amino acid sequence of SEQ ID NO:61, and the ICD is an intracellular domain or protein that facilitates the incorporation of the target portion into the envelope of the viral particle, wherein the ICD comprises an env incorporation motif comprising the amino acid sequence of SEQ ID NO:63 or SEQ ID NO:64.

[0045] In some embodiments, the viral particles provided herein further comprise a nucleic acid molecule encoding a heterologous molecule of interest. In some embodiments, the heterologous molecule of interest is as provided herein. In some embodiments, the heterologous molecule of interest is a CAR. In some embodiments, the CAR comprises an amino acid sequence having at least 85% identity with SEQ ID NO:99, at least 90% identity with SEQ ID NO:99, at least 95% identity with SEQ ID NO:99, at least 99% identity with SEQ ID NO:99, or at least 100% identity with SEQ ID NO:99. BRIEF DESCRIPTION OF THE DRAWINGS

[0046] Figure 1A and Figure 1B Describe the crystal structure of VSV-G bound to LDL-R. Figure 1A Describe the crystal structure of VSV-G that is CR3-bound with LDL-R. Figure 1B Describe the crystal structure of VSV-G that is CR2-bound with LDL-R.

[0047] Figure 2A and Figure 2B This study explains the effect of adding negatively charged amino acids to the VSV-G:LDL-R binding interface on natural affinity and cohesion. Figure 2A This describes the titration of the VSV-G construct on SupT1 cells. Figure 2B Explanation by Figure 2A The functional valence of each construct was calculated by titration.

[0048] Figure 3 This demonstrates the comparison of the extracellular domains of different VSV-G proteins from different viral strains.

[0049] Figure 4 This study aims to explain the effects of various VSV-G mutations on the serum stability of combinations of viral constructs and CD7 binders.

[0050] Figure 5 This study aims to explain the effects of various VSV-G mutations on the serum stability of combinations of viral constructs and CD7 binders.

[0051] Figure 6 This demonstrates the ability of various rod-shaped virus G proteins, alone or in combination with CD7 binding agents, to transduce SupT1 and PBMC cells.

[0052] Figure 7A-7L Flow cytometry data of human PBMCs transduced with an exemplary vector containing a CD7 binding agent as disclosed herein are shown.

[0053] Figure 7MFlow cytometry data of human PBMCs transduced with an exemplary vector containing a CD7 binding agent as disclosed herein are shown.

[0054] Figure 8A-8L Flow cytometry data of non-human primate PBMCs transduced with an exemplary vector containing a CD7 binding agent as disclosed herein are shown.

[0055] Figure 8M Flow cytometry data of non-human primate PBMCs transduced with an exemplary vector containing a CD7 binding agent as disclosed herein are shown.

[0056] Figure 9A Flow cytometry data of human PBMCs transduced with an exemplary vector containing a CD8 binding agent as disclosed herein are shown.

[0057] Figure 9B Flow cytometry data of non-human primate PBMCs transduced with exemplary vectors containing CD8 binding agents as disclosed herein are shown.

[0058] Figure 10A This demonstrates the ability of VSV-G* pseudotyped lentivirus particles carrying CD7 binding agents with variant Fc stems to transduce SupT1 cells and human and non-human primate PBMCs. Figure 10B This demonstrates cell transduction in the absence of CD7 binding agents. Figure 10C The MOI calculated by SupT1 titration illustrates the transduction of human and non-human primate PBMCs. VSV-G* indicates VSV-G (I182E, T214N, T352A).

[0059] Figure 11A This demonstrates the ability of VSV-G* pseudotyped lentivirus particles carrying CD7 binders with flexible stems to transduce SupT1 cells and human and non-human primate PBMCs. Figure 11B This demonstrates cell transduction in the absence of CD7 binding agents. Figure 11C The MOI calculated by SupT1 titration illustrates the transduction of human and non-human primate PBMCs. VSV-G* indicates VSV-G (I182E, T214N, T352A).

[0060] Figure 12A This demonstrates the ability of viral particles carrying CD7 binders with flexible stems of varying lengths to transduce SupT1 cells, compared to other IgG-based binders. Figure 12B This demonstrates the ability of viral particles carrying CD7 binders with flexible stems of varying lengths to transduce activated PBMCs, compared to other IgG-based binders.

[0061] Figure 13A This demonstrates the ability of SVCV-G pseudotyped lentiviral particles carrying CD7 binding agents with variant Fc stems to transduce SupT1 cells and human and non-human primate PBMCs. Figure 13B This demonstrates cell transduction in the absence of CD7 binding agents. Figure 13C The MOI calculated by SupT1 titration illustrates the transduction of human and non-human primate PBMCs.

[0062] Figure 14A This demonstrates the ability of SVCV-G pseudotyped lentivirus particles carrying CD7 binders with flexible stems to transduce SupT1 cells and human and non-human primate PBMCs. Figure 14B This demonstrates cell transduction in the absence of CD7 binding agents. Figure 14C The MOI calculated by SupT1 titration illustrates the transduction of human and non-human primate PBMCs.

[0063] Figures 15A-15D Comparison of the transduction capabilities of VSV-G* pseudotyped lentiviral particles (Fig. A and Fig. B) and SVCV-G pseudotyped lentiviral particles (Fig. C and Fig. D) into SupT1 cells and human and non-human primate PBMCs. VSV-G* represents VSV-G (I182E, T214N, T352A).

[0064] Figures 16A-16D Comparison of the transduction capabilities of VSV-G* pseudotyped lentiviral particles (Fig. A and Fig. B) and SVCV-G pseudotyped lentiviral particles (Fig. C and Fig. D) into SupT1 cells and human and non-human primate PBMCs. VSV-G* represents VSV-G (I182E, T214N, T352A).

[0065] Figure 17A This demonstrates the ability of VSV-G* pseudotyped lentiviral particles to eliminate WT-VSV-G-driven GFP transduction in activated PBMCs, and that the inclusion of a CD7 binding agent restores GFP transduction. Figure 17B This describes a specific cell population transduced by VSV-G*, CD-7 binding pseudotyped lentiviral particles.

[0066] Figure 18A and Figure 18B This is a comparison of off-target transduction of GFP in a group of B cell lines compared to the control SupT1 cells. Figure 18A This describes data on VSV-G* pseudotyped lentiviral particles carrying CD7 binding agents with variant Fc stems. VSV-G* represents VSV-G (I182E, T214N, T352A). Figure 18B This describes data on SVCV-G pseudotyped lentivirus particles carrying CD7 binding agents with variant Fc stems.

[0067] Figure 19A and Figure 19B This is a comparison of off-target transduction of the CAR20-T2A-GFP construct in a group of B cell lines compared to the control SupT1 cells. Figure 19A This describes data on VSV-G* pseudotyped lentiviral particles carrying CD7 binding agents with variant Fc stems. VSV-G* represents VSV-G (I182E, T214N, T352A). Figure 19B This describes data on SVCV-G pseudotyped lentivirus particles carrying CD7 binding agents with variant Fc stems.

[0068] Figure 20A and Figure 20B This study describes the assessment of off-target transduction of VSV-G* pseudotyped lentivirus particles carrying CD7 binding agents with variant Fc stems. Figure 20A This indicates that CD7-negative B-cell tumors were not transduced by pseudolentiviral particles. Figure 20B This indicates that primary PBMCs isolated from patients with B-cell malignancies were not transduced by pseudotyped lentiviral particles.

[0069] Figure 21A and Figure 21B This is a comparison of off-target transduction of GFP in a group of B cell lines compared to the control SupT1. Figure 21A This describes data on VSV-G* pseudotyped lentivirus particles carrying CD7 binders with flexible stems. VSV-G* represents VSV-G (I182E, T214N, T352A). Figure 21B This describes data on SVCV-G pseudotyped lentivirus particles carrying CD7 binders with flexible stems.

[0070] Figure 22A and Figure 22B This is a comparison of off-target transduction of the CAR20-T2A-GFP construct in a group of B cell lines compared to the control SupT1. Figure 22A This describes data on VSV-G* pseudotyped lentivirus particles carrying CD7 binders with flexible stems. VSV-G* represents VSV-G (I182E, T214N, T352A). Figure 22B This describes data on SVCV-G pseudotyped lentivirus particles carrying CD7 binders with flexible stems.

[0071] Figures 23A-23C This demonstrates the ability of PBMCs transduced with the CD20 CAR construct provided in this paper to kill lymphoma cell lines. Figure 23A This describes the breakdown of CAR-positive PBMCs produced by VSV-G* pseudotyped lentivirus particles carrying CD7 binding agents with variant Fc stems. Figure 23B This demonstrates the ability of CAR20-positive PBMCs to kill Raji lymphoma cells. Figure 23C This demonstrates the ability of CAR20-positive PBMCs to kill Daudi lymphoma cells.

[0072] Figure 24A and Figure 24B This demonstrates the ability to kill Daudi lymphoma cells using VSV-G* pseudotyped lentiviral particles transgenic with CD7 binding agents and CD20-CAR as described in this paper. Figure 24A ) or Raji lymphoma cells ( Figure 24B The CAR20 construct utilizes an antigen-binding domain comprising rituximab or CD20AB1 SEQ ID NO 92 or 93 as provided herein.

[0073] Figures 25A-25C This describes the results of an experiment assessing the risk of developing CAR-resistant B-cell tumors. Figure 25A Explain the experimental design. Figure 25B This demonstrates the ability of CAR20-positive PBMCs to kill B cells expressing GFP or both CAR20 and GFP. Figure 23C This describes the results of the GFP assessment of the remaining cells.

[0074] Figure 26A and Figure 26B This demonstrates the ability of VSV-G* pseudotyped lentiviral particles, transgenic with CD7 binding agents and CD20-CAR as provided in this paper, to deplete B cells in huCD34 NSG mice in vivo. The ability of CD20-CAR transgenic VSV-G* pseudotyped lentiviral particles to deplete B cells in vivo was assessed by evaluating CD20-CAR transgenic VSV-G* pseudotyped lentiviral particles. Figure 26A ) or CD19 ( Figure 26B (To detect B cells)

[0075] Figure 27A and Figure 27B This demonstrates the ability of VSV-G* pseudotyped lentiviral particles transgenic with CD7 binding agents and CD20-CAR, as provided in this paper, to deplete B cells in huCD34 NSG mice in vivo. Figure 27A This indicates that VSV-G* pseudotyped lentiviral particles can deplete CD20+B cells. Figure 27B The study demonstrated that mice injected with VSV-G* pseudotyped lentivirus particles produced CAR20+ cells, which were detectable in blood samples during the duration of the study.

[0076] Figure 28A and Figure 28B This demonstrates the ability of VSV-G* pseudolentiviral particles, which utilize CD7 binding agents and CD20-CAR transgenics as provided in this paper, to prevent tumor formation in vivo. Figure 28A Describe the experimental design. Figure 28BThis indicates that mice receiving the iv lentiviral particles described herein prior to Raji tumor infusion had significantly lower tumor burden than mice receiving the control (GFP) vector or untreated mice. Tumor burden was measured by IVIS imaging.

[0077] Figures 29A-29D This demonstrates the ability of VSV-G* pseudotyped lentiviral particles, which utilize CD7 binding agents and CD20-CAR transgenes as described herein, to eliminate established Raji tumors in vivo. Figure 29A Describe the experimental design. Figure 29B This indicates that the tumor burden in mice that received the iv lentiviral particles described in this article 6 days after Raji tumor infusion was reduced to below the detection limit. Figure 29C This illustrates the results of similar studies using different viral concentrations. Figure 29D Mice receiving the highest viral concentration produced CAR20-positive cells, which were detectable in blood samples throughout the duration of the study. Tumor burden was measured by IVIS imaging.

[0078] Figures 30A-30F This demonstrates the ability of VSV-G* pseudotyped lentiviral particles, which utilize CD7 binding agents and CD20-CAR transgenes as provided in this paper, to deplete B cells in NHP in vivo. Figure 30A Explain the data for animal 1. Figure 30B Explain the data for animal 2. Figure 30C Explain the data for animal 3. Figure 30D Explain the data for animal 4. Figure 30E Explain the data for animal 5. Figure 30F Explain the data for animal 6.

[0079] Figure 31 This describes the detection of proviral DNA in the PBMCs of NHP. Figure 31 The animal corresponds to the Figures 30A-30F The same animal.

[0080] Figures 32A-32F This demonstrates the ability of VSV-G* pseudotyped lentiviral particles, which utilize CD7 binding agents and CD20-CAR transgenes as provided in this paper, to deplete B cells in NHP in vivo. Figure 32A Explain the data for animal 1. Figure 32B Explain the data for animal 2. Figure 32C Explain the data for animal 3. Figure 32D Explain the data for animal 4. Figure 32E This indicates that only data from control animal 1 (using buffer) are accepted. Figure 32F This indicates that only data from control animal 2 (using buffer) are accepted.

[0081] Figure 33This describes the detection of proviral DNA in the PBMCs of NHP. Figure 33 The animal corresponds to the Figure 32A -D refers to the same animal.

[0082] Figures 34A-34H This demonstrates the ability of VSV-G* pseudotyped lentiviral particles, which utilize CD7 binding agents and CD20-CAR transgenes as provided in this paper, to deplete B cells in NHP in vivo. Figure 34A Explain the data for animal 1. Figure 34B Explain the data for animal 2. Figure 34C Explain the data for animal 3. Figure 34D Explain the data for animal 4. Figure 34E Explain the data for animal 5. Figure 34F Explain the data for animal 6. Figure 34G This indicates that only data from control animal 1 (using buffer) are accepted. Figure 34H This indicates that only data from control animal 2 (using buffer) are accepted.

[0083] Figure 35 This describes the detection of proviral DNA in the PBMCs of NHP. Figure 35 The animal corresponds to the Figure 34A -H refers to the same animal.

[0084] Figures 36A-36D This study describes the assessment of CD20 CAR-specific immune responses in different NHP groups that received different CD20 CAR transgenes. Figure 36A This describes the detection of anti-CD20 specific antibodies in the plasma of animals that have received a CD20 CAR molecule containing the antigen-binding domain of SEQ ID NO: 96. Figure 36B This study describes the levels of INF-γ and TNF-α in animals that received the CD20 CAR molecule with the antigen-binding domain of SEQ ID NO:96, which are indicators of T cell response. Figure 36C This describes the detection of anti-CD20 specific antibodies in the plasma of animals that have received a CD20 CAR molecule containing the antigen-binding domain of SEQ ID NO:92. Figure 36D This study describes the levels of INF-γ and TNF-α in animals that received the CD20 CAR molecule with the antigen-binding domain of SEQ ID NO:92, which are indicators of T cell response.

[0085] Figure 37 This study describes the results of a B-cell depletion study in cynomolgus monkeys. Data from three animals that did not produce an immune response to the humanized CAR transgene demonstrate that, in the absence of an immune response, VSV-G* pseudotyped lentiviral particles using CD7 binding agents and CD20-CAR transgenes, as presented herein, can stimulate sustained B-cell depletion.

[0086] Figures 38A-38D This demonstrates the ability of VSV-G* pseudotyped lentiviral particles, which utilize CD7 binding agents and CD20-CAR transgenes as provided in this paper, to deplete B cells in NHP in vivo. Figure 38A Explain the data for animal 1. Figure 38B Explain the data for animal 2. Figure 38C This indicates that only data from control animal 1 (using buffer) are accepted. Figure 38D This indicates that only data from control animal 2 (using buffer) are accepted.

[0087] Figure 39 This describes the detection of proviral DNA in the PBMCs of NHP. Figure 39 The animal corresponds to the Figure 38A -D refers to the same animal. DETAILED DESCRIPTION

[0088] This document provides viral particles comprising a heterologous viral glycoprotein and a targeting portion, wherein the targeting portion comprises a polypeptide having the formula T-S1, where T is a target-binding domain and S1 is a stem portion. In some embodiments, S1 comprises a mutant Fc polypeptide, which may, for example, be linked to a transmembrane domain as provided herein. In some embodiments, S1 comprises a flexible polypeptide as provided herein. The mutant Fc polypeptide or the flexible polypeptide may be incorporated into the viral particle to help facilitate the viral particle targeting of specific cell types.

[0089] Additionally, viral particles may contain the VSV-G protein, which can be used, for example, for pseudotypening viruses such as lentiviruses. In some embodiments, viral glycoproteins from vesicular stomatitis virus strains such as New Jersey vesicular stomatitis virus strain, Indiana vesicular stomatitis virus strain, Aragos vesicular stomatitis virus strain, Malaba vesicular stomatitis virus strain, or Kalapas vesicular stomatitis virus strain are used to pseudotype virus-like particles. Examples of such proteins are provided herein.

[0090] Pseudoviruses containing mutant VSV-G proteins (such as those provided herein) can be used in conjunction with a targeting moiety to promote fusion of the pseudovirus with a target on a specific cell or tissue. As provided herein, the targeting moiety may be linked to an Fc protein, which may be referred to as a stem protein, and contains a transmembrane domain to facilitate attachment of the targeting moiety to the viral surface. In some embodiments, the Fc protein contains Fc effector mutations, such as those provided herein.

[0091] Unless otherwise defined, all technical and scientific terms have the same meaning as commonly understood by one of ordinary skill in the art to which the disclosed embodiments pertain.

[0092] Unless the context clearly indicates otherwise, as used herein, the term "a / an" means "at least one / an" or "one / an or more / an".

[0093] As used herein, the term “about” means an index value that is approximate and that small variations will not significantly affect the practice of the disclosed embodiments. When numerical limits are used, the “about” index value may vary by ±10% and remain within the range of the disclosed embodiments unless the context otherwise indicates. Additionally, when the phrase “about x to y” is used, the term “about” modifies both x and y and may be used interchangeably with the phrase “about x to about y” unless the context otherwise specifies.

[0094] As used herein, the terms “individual” or “subject” or “patient” are used interchangeably to mean any animal, including mammals such as mice, rats, other rodents, rabbits, dogs, cats, pigs, cattle, sheep, horses, or primates (such as humans).

[0095] As used herein, the terms “comprising” (and any form of inclusion, such as “comprise / comprises / comprised”), “having” (and any form of having, such as “have / has”), “including” (and any form of including, such as “includes / include”), or “containing” (and any form of containing, such as “contains / contain”) are inclusive or open-ended and do not exclude additional undescribed elements or method steps. It is said that any step or composition using the transitional phrase “comprise / comprising” can also be described using the transitional phrase “consisting of / consists”.

[0096] As used herein, the term “contacting” means bringing together two elements in an in vitro or in vivo system. For example, bringing a virus or vector described herein into “contact” with an individual or patient or cells includes administering a virus to an individual or patient (such as a human), and, for example, introducing a compound into a sample containing a cell-containing preparation or purified preparation.

[0097] As used herein, the terms “fusion” or “linkage” when referring to proteins with different domains or heterologous sequences mean that the protein domains are portions of the same peptide chain linked together by peptide bonds or other covalent bonds. The domains or segments may be directly linked or fused together, or another domain or peptide sequence may be located between two domains or sequences, and such sequences will still be considered fused or linked together. In some embodiments, the various domains or proteins provided herein are directly linked or fused together, or a linker sequence (such as the glycine / serine sequence described herein) links two domains together.

[0098] "Disease" is a state of health in an animal in which the animal is unable to maintain homeostasis, and in which the animal's health continues to deteriorate if the disease is not treated. In contrast, an animal's "symptom" is a state of health in which the animal is able to maintain homeostasis, but in which the animal's health is not as good as it would be without the symptom. A symptom, without treatment, does not necessarily lead to a further decline in the animal's health.

[0099] The terms "effective amount" or "therapeutic effective amount" are used interchangeably herein and refer to the amount of a compound, formulation, material, or composition as described herein that effectively achieves a specific biological outcome or provides a therapeutic or preventative benefit. Such outcomes may include, but are not limited to, the amount of immune cell activation that results in a detectable level of immune cell activation when administered to a mammal compared to the activation detected in the absence of the composition. Immune responses can be readily assessed using a wide range of technically recognized methods. Those skilled in the art will understand that the amount of the composition administered herein will vary and can be readily determined based on a variety of factors, such as the disease or ailment being treated, the age and health status and physical condition of the mammal being treated, the severity of the disease, and the specific compound administered.

[0100] "Encoding" refers to the inherent characteristic of a specific nucleotide sequence in a polynucleotide (such as a gene, cDNA, or mRNA) to serve as a template for the synthesis of other polymers and macromolecules with defined nucleotide sequences (i.e., rRNA, tRNA, and mRNA) or defined amino acid sequences, and the resulting biological properties, during biological processes. Therefore, if the transcription and translation of mRNA corresponding to a gene produces a protein in a cell or other biological system, then that gene encodes that protein. Both the coding strand (whose nucleotide sequence is identical to the mRNA sequence and is usually provided in the sequence listing) and the non-coding strand (which serves as a template for gene or cDNA transcription) can be referred to as encoding that protein or other products of that gene or cDNA.

[0101] "Expression vector" refers to a vector containing a recombinant polynucleotide that includes an expression control sequence operatively linked to a nucleotide sequence to be expressed. The expression vector contains sufficient cis-acting components for expression; other components for expression may be provided by a host cell or in an in vitro expression system. Expression vectors include all those known in the art, such as clomids, plasmids (e.g., naked or contained in liposomes) and viruses (e.g., Sendai virus, lentivirus, retrovirus, adenovirus, and adeno-associated virus) incorporating the recombinant polynucleotide.

[0102] As used herein, the phrase “ex vivo” in relation to cells transduced, transfected, or transformed in vitro means that the cells are transduced, transfected, or transformed outside the subject, i.e., the cells are removed from the subject prior to transduction, transfection, or transformation.

[0103] As used herein, “identity” refers to the subunit sequence identity between two polymer molecules (such as between two nucleic acid or amino acid molecules, or between two polynucleotide or polypeptide molecules). Two amino acid sequences are identical when they have the same residue at the same position; for example, if one position in each of two polypeptide molecules is occupied by arginine, then they are identical at that position. The degree of identity or similarity between two amino acid or nucleic acid sequences in an alignment is typically expressed as a percentage. Identity between two amino acid or nucleic acid sequences is a direct function of the number of matching or identical positions; for example, if half of the positions in two sequences are identical, then the two sequences are 50% identical; if 90% of the positions (e.g., 9 out of 10) are matching or identical, then the two amino acid sequences are 90% identical.

[0104] "Substantially identical" means that the polypeptide or nucleic acid molecule exhibits at least 50% identity with a reference amino acid sequence (e.g., any of the amino acid sequences described herein) or nucleic acid sequence (e.g., any 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 to the sequences used for comparison at the amino acid level or nucleic acid level. Other percentages of identity with respect to specific sequences are described herein.

[0105] Sequence identity can be measured / determined using sequence analysis software (e.g., Sequence Analysis Software Package of the Genetics Computer Group (University of Wisconsin Biotechnology Center, 1710 University Avenue, Madison, Wis. 53705), BLAST, BESTFIT, GAP, or PILEUP / PRETTYBOX programs). Such software matches identical or similar sequences by assigning degrees of homology to various substitutions, deletions, and / or other modifications. Conserved 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 exemplary methods for determining the degree of identity, a BLAST program with a probability score between e3 and e100 can be used, indicating closely related sequences. In some embodiments, sequence identity is determined using a BLAST program with preset settings.

[0106] For the purposes of the embodiments provided herein, compositions comprising various proteins may, in some cases, contain amino acid sequences that have sequence identity with the amino acid sequences disclosed herein. Therefore, in some embodiments, the degree of sequence identity with the SEQ ID NO disclosed herein is preferably greater than 50% (e.g., 60%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more, depending on the specific sequence). Other identity percentages are also provided herein. Identity between peptides can be determined using the Smith-Waterman homology search algorithm implemented in the MPSRCH (Oxford Molecular) procedure, which uses an affine gap search with parameters: gap opening penalty – 12 and gap extension penalty = 1.

[0107] Compared to the disclosed proteins, these proteins may include one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) conserved amino acid substitutions, i.e., one amino acid is replaced by another amino acid with a related side chain. Genetically encoded amino acids are generally classified into four families: (1) acidic, i.e., aspartic acid and glutamic acid; (2) basic, i.e., lysine, arginine, and histidine; (3) nonpolar, i.e., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, and tryptophan; and (4) uncharged polar, i.e., glycine, asparagine, glutamine, cysteine, serine, threonine, and tyrosine. Phenylalanine, tryptophan, and tyrosine are sometimes collectively classified as aromatic amino acids. Generally, substitution of a single amino acid within these families does not have a significant impact on biological activity. Compared to the disclosed protein sequence, the proteins may have one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) single amino acid deletions. The protein may also contain one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) insertions (e.g., each of 1, 2, 3, 4, or 5 amino acids) relative to the disclosed protein sequence.

[0108] As used herein, the phrase “in vivo” in relation to cells transduced, transfected, or transformed in vivo means that the cells are transduced, transfected, or transformed in the subject without being removed from the subject prior to the transduction, transfection, or transformation of such cells.

[0109] "Separation" means alteration or removal from the native state. For example, nucleic acids or peptides naturally present in living organisms are not "separated," but the same nucleic acids or peptides that are partially or completely separated from their native coexisting material are "separated." Separated nucleic acids or proteins can exist in substantially purified forms or in non-native environments (such as host cells).

[0110] As used herein, “lentivirus” refers to a genus of retroviridae that can infect non-dividing cells. Non-limiting examples of lentiviruses include HIV, SIV, and FIV. Vectors or virus-like particles derived from lentiviruses can be used to transduce cells and deliver genes or other molecules, and to express them in vitro (in vitro) or in vivo cells.

[0111] As used herein, the term "modification" refers to a change in the state or structure of a molecule or cell, as described herein. Molecules can be modified in a variety of ways, including chemically, structurally, and functionally, such as through mutation, substitution, insertion, or deletion (e.g., internal deletion, truncation). Cells can be modified by introducing nucleic acids or expressing heterologous proteins.

[0112] As used herein, the term "modulation" means mediating an increase or decrease in the level of response in a subject compared to the level of response in a subject without treatment or a compound, and / or compared to the level of response in a otherwise identical but untreated subject. The term encompasses disrupting and / or influencing natural signals or responses, thereby mediating a beneficial therapeutic response in a subject (such as a human).

[0113] Unless otherwise specified, "nucleotide sequence encoding an amino acid sequence" includes all nucleotide sequences that are degenerate to each other and encode the same amino acid sequence. A nucleotide sequence encoding a protein or RNA phrase may also contain introns, to the extent that the nucleotide sequence encoding said protein may contain introns in some forms.

[0114] The term "oligonucleotide" generally refers to short polynucleotides. It should be understood that when the nucleotide sequence is represented by a DNA sequence (i.e., A, T, C, G), this also provides the corresponding RNA sequence (i.e., A, U, C, G), where "U" replaces "T".

[0115] "Parenteral" administration of the composition includes techniques such as subcutaneous (sc), intravenous (iv), intramuscular (im), or intrasternal injection or infusion.

[0116] As used herein, the term "polynucleotide" is defined as a nucleotide chain. Furthermore, nucleic acids are polymers of nucleotides. Therefore, as used herein, the terms "nucleic acid" and "polynucleotide" are interchangeable. As used herein, polynucleotides include, but are not limited to, all nucleic acid sequences obtained by any method available in the art, including but not limited to recombinant methods, i.e., cloning nucleic acid sequences from recombinant libraries or cell genomes using cloning techniques and PCR, as well as synthetic methods.

[0117] As used herein, the terms “peptide,” “polypeptide,” and “protein” are used interchangeably and refer to compounds comprising a plurality of amino acid residues covalently linked by peptide bonds. As used herein, the term refers to short chains, which are also commonly referred to in the art, for example, peptides, oligopeptides, and oligomers; and long chains, which are generally referred to in the art, for example, proteins, of which various types exist. “Polypeptide” includes, for example, biologically active fragments, substantially homologous polypeptides, oligopeptides, homodimers, heterodimers, polypeptide variants, modified polypeptides, derivatives, analogs, fusion proteins, etc. Polypeptides include natural peptides, recombinant peptides, synthetic peptides, or combinations thereof.

[0118] Unless otherwise expressly stated, the terms “heteroviral structural protein” and “heteroviral glycoprotein” are synonymous and used interchangeably as used herein. Therefore, unless otherwise expressly stated, any implementation that refers to “heteroviral structural protein” should be understood to mean “heteroviral glycoprotein”, and vice versa.

[0119] As used herein, the term "pseudotype" or "pseudotyped viral particle" refers to a viral particle carrying a glycoprotein derived from another enveloped virus or a viral vector encoding an envelope glycoprotein from a virus different from its parent virus. Therefore, the host range of vector particles can be expanded or altered depending on the type of cell surface receptor used by the glycoprotein. For example, viruses can be pseudotyped using the VSV-G mutant protein as described herein.

[0120] As used herein with respect to antibodies, the term "specific binding" means that an antibody recognizes a specific antigen but does not substantially 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 cross-species reactivity does not, in itself, change the antibody's specific classification. In another instance, an antibody that specifically binds to an antigen may also bind to different allelic forms of said antigen. However, such cross-reactivity does not, in itself, change the antibody's specific classification. In some cases, the term "specific binding" may be used with respect to the interaction of an antibody, protein, or peptide with a second chemical substance, meaning that the interaction depends on the presence of a specific structure (e.g., an antigenic determinant or epitope) on said chemical substance; for example, the antibody recognizes and binds to a specific protein structure, rather than a protein in general. If an antibody is specific for epitope "A," then in a reaction containing labeled "A" and the antibody, the presence of a molecule containing epitope A (or free, unlabeled A) will reduce the amount of labeled A that binds to the antibody. In some implementations, the targeting portion described herein can be used to specifically bind to the target of a viral particle containing a mutant VSV-G protein or other viral structural proteins used for pseudotyping the virus.

[0121] The term "subject" includes living organisms, including those in which an immune response can be elicited (e.g., mammals). As used herein, "subject" or "patient" can be human or non-human mammals. Non-human mammals include, for example, livestock and pets, such as sheep, bovines, swine, canines, non-human primates, felines, and rodents. In some embodiments, the subject is a human.

[0122] As used in this article, the term "treatment" means to cure and / or prevent disease conditions. Therapeutic effects are achieved by suppressing, alleviating, or eradicating disease states.

[0123] As used herein, the terms “transfected,” “transformed,” or “transduced” refer to the process of transferring or introducing exogenous nucleic acids into or into cells. A “transfected,” “transformed,” or “transduced” cell line is a cell that has been transfected, transformed, or transduced with exogenous nucleic acids. Cells include primary subject cells and their progeny. In some embodiments, transfection, transformation, or transduction is performed or occurs in vivo.

[0124] As used herein, the term “treatment” for a disease means reducing the frequency or severity of at least one sign or symptom of a disease or condition experienced by a subject.

[0125] A "vector" is a composition of substances containing isolated nucleic acids encoding proteins or peptides. Many vectors are known in the art, including but not limited to linear polynucleotides, plasmids, DNA, and RNA. Examples of viral vectors include, but are not limited to, Sendai virus vectors, adenovirus vectors, adeno-associated virus vectors, retroviral vectors, lentiviral vectors, etc.

[0126] "Carriers" or "delivery mediators" include viral particles, viruses, polylysine compounds, and liposomes, which facilitate the transfer of nucleic acids into cells. Carriers or delivery mediators can also be used to deliver proteins or peptides into cells.

[0127] Scope: In this disclosure, various aspects of the embodiments may be presented in a scope format. It should be understood that the scope format description is for convenience and brevity only and should not be considered a rigid limitation. Therefore, a description of a scope should be considered as specifically disclosing all possible sub-scopes and individual numerical values ​​within that scope. For example, a description of a scope (such as 1 to 6) should be considered as specifically disclosing sub-scopes such as 1 to 3, 1 to 4, 1 to 5, 2 to 4, 2 to 6, 3 to 6, etc., and individual numbers within that scope, such as 1, 2, 2.7, 3, 4, 5, 5.3, and 6. This applies regardless of the size of the scope. Unless otherwise expressly stated to the contrary, the disclosed scope also includes the endpoints of the scope.

[0128] In some embodiments, a polypeptide comprising a variant Fc polypeptide is provided. In some embodiments, the variant Fc polypeptide is an Fc polypeptide variant comprising the amino acid sequence of SEQ ID NO:26 (IgG1 Fc), SEQ ID NO:27 (IgG2 Fc), or SEQ ID NO:28 (IgG4 Fc). In some embodiments, the variant comprises an N-terminal deletion. In some embodiments, the N-terminal deletion does not comprise up to 100 amino acid residues from the N-terminus of SEQ ID NO:26, SEQ ID NO:27, or SEQ ID NO:28. In some embodiments, the N-terminal deletion does not comprise up to 98 amino acid residues as counted from the N-terminus of SEQ ID NO:26, SEQ ID NO:27, or SEQ ID NO:28. In some embodiments, the N-terminal deletion does not comprise 98 amino acid residues as counted from the N-terminus of SEQ ID NO:26. In some embodiments, the N-terminal deletion does not include 90-98 amino acid residues as counted from the N-terminus of SEQ ID NO:26, SEQ ID NO:27, or SEQ ID NO:28. In some embodiments, the N-terminal deletion does not include 75-98 amino acid residues as counted from the N-terminus of SEQ ID NO:26, SEQ ID NO:27, or SEQ ID NO:28. In some embodiments, the N-terminal deletion does not include 60-98 amino acid residues as counted from the N-terminus of SEQ ID NO:26, SEQ ID NO:27, or SEQ ID NO:28. In some embodiments, the N-terminal deletion does not include 50-98 amino acid residues as counted from the N-terminus of SEQ ID NO:26, SEQ ID NO:27, or SEQ ID NO:28. In some embodiments, the N-terminal deletion does not include 40-98 amino acid residues as counted from the N-terminus of SEQ ID NO:26, SEQ ID NO:27, or SEQ ID NO:28. In some embodiments, the N-terminal deletion does not include 30-98 amino acid residues as counted from the N-terminus of SEQ ID NO:26, SEQ ID NO:27, or SEQ ID NO:28. In some embodiments, the N-terminal deletion does not include 10-98 amino acid residues as counted from the N-terminus of SEQ ID NO:26, SEQ ID NO:27, or SEQ ID NO:28. In some embodiments, the N-terminal deletion does not include 5-98 amino acid residues as counted from the N-terminus of SEQ ID NO:26, SEQ ID NO:27, or SEQ ID NO:28.In some embodiments, the N-terminal deletion does not include 1-98 amino acid residues counted from the N-terminus of SEQ ID NO:26, SEQ ID NO:27, or SEQ ID NO:28. In some embodiments, the variant Fc polypeptide does not contain the following amino acid sequence:

[0129] ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWN SGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHK PSNTKVDKKV(SEQ ID NO:105)

[0130] In some embodiments, the variant Fc polypeptide does not contain any of the sequences in SEQ ID NO:105. In some embodiments, the variant Fc polypeptide does not contain the entire sequence of SEQ ID NO:105. As used herein, the phrase “as counted from the N-terminus” regarding the N-terminal deletion of a reference sequence means that the first residue of the reference sequence is considered residue 1, even though under a numbering scheme (such as the EU numbering scheme for Fc polypeptides), said first residue would have a different number. Thus, for example, the phrase “N-terminal deletion does not contain 3 amino acid residues as counted from the N-terminus of SEQ ID NO:26” refers to the deletion of residue “ASK”, as it is the first three residues of SEQ ID NO:26. In some embodiments, the variant Fc polypeptide, with or without the N-terminal deletion, as provided herein contains one or more mutations at positions corresponding to L234, L235, M297, P329, I253, H310, or H435. The positions refer to the EU number of the Fc polypeptide. In some embodiments, the variant Fc peptides with or without N-terminal deletions as provided herein contain mutations corresponding to L234, L235, M297, P329, I253, H310, and H435. In some embodiments, the variant Fc peptides with or without N-terminal deletions as provided herein contain mutations corresponding to L234 and L235. In some embodiments, the variant Fc peptides with or without N-terminal deletions as provided herein contain mutations corresponding to M297. In some embodiments, the variant Fc peptides with or without N-terminal deletions as provided herein contain mutations corresponding to P329. In some embodiments, the variant Fc peptides with or without N-terminal deletions as provided herein contain mutations corresponding to I253. In some embodiments, the variant Fc peptides with or without N-terminal deletions as provided herein contain mutations corresponding to H310. In some embodiments, the variant Fc peptides with or without N-terminal deletions as provided herein contain mutations corresponding to H435. In some embodiments, the variant Fc polypeptides with or without N-terminal deletions, as provided herein, comprise one or more mutations corresponding to L234A, L235A, M297A, P329G, I253A, H310A, or H435A. In some embodiments, the variant Fc polypeptides with or without N-terminal deletions, as provided herein, comprise mutations corresponding to L234A, L235A, M297A, P329G, I253A, H310A, and H435A.In some embodiments, the Fc variant polypeptide comprises an amino acid sequence that is at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:103, provided that the Fc variant does not contain the amino acid sequence of SEQ ID NO:105, and provided that the variant contains one or more mutations corresponding to L234A, L235A, M297A, P329G, I253A, H310A, or H435A. In some embodiments, the Fc variant polypeptide comprises an amino acid sequence that is at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:103, provided that the Fc variant does not contain the amino acid sequence of SEQ ID NO:105, and provided that the variant contains mutations corresponding to L234A, L235A, M297A, P329G, I253A, H310A, and H435A. In some embodiments, the Fc variant polypeptide comprises an amino acid sequence that is at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:104, provided that the Fc variant does not contain the amino acid sequence of SEQ ID NO:105. In some embodiments, the Fc variant polypeptide comprises the sequence of SEQ ID NO:104, provided that the Fc variant does not contain the amino acid sequence of SEQ ID NO:105. As used herein, positions mentioned in the Fc polypeptide refer to positions according to the EU numbering scheme, which is known in the art. For example, in the polypeptide of SEQ ID NO:104, position 234 refers to residue 19 of SEQ ID NO:104, position 235 refers to residue 20 of SEQ ID NO:104, and so on.

[0131] As provided herein, in some embodiments, the Fc variant may be fused to or linked to another protein (such as a targeting moiety). The Fc variant may also be fused to or linked to transmembrane domains and / or intracellular domains, allowing it to insert into the cell membrane or viral envelope (such as the envelope of a lentivirus). In some embodiments, the targeting moiety is linked to or fused to the N-terminus of the Fc variant peptide. In some embodiments, the Fc variant peptide is linked to a transmembrane domain at its C-terminus.

[0132] In some embodiments, viral particles are provided that contain variant Fc polypeptides provided herein, such as those described herein, including those described above and below.

[0133] Viral particles containing heterologous viral glycoproteins and targeting components

[0134] In some embodiments, a viral particle is provided comprising a heterologous viral glycoprotein and a targeting portion. In some embodiments, the targeting portion comprises a polypeptide having the formula T-S1, where T is a target-binding domain and S1 is a stem portion. In some embodiments, S1 comprises a variant Fc protein, wherein the variant Fc protein comprises a transmembrane domain, such as, but not limited to, a CD8 or CD28 transmembrane domain. Thus, in some embodiments, the stem portion S1 comprises an N-terminal to C-terminal orientation of the variant Fc transmembrane domain. In some embodiments, the variant Fc protein comprises an effector mutation, wherein the effector mutation inhibits the interaction between the Fc protein and Fc-interacting proteins, such as FcγR, C1q, FcRβ, or FcRn.

[0135] In some embodiments, the S1 stem portion is attached to the surface of the viral particle via a transmembrane domain. For example, the transmembrane domain may penetrate or insert into the envelope of an enveloped virus (e.g., the lentivirus or other virus described herein). Thus, the S1 stem portion attached to the transmembrane domain is presented on the outer surface of the enveloped virus.

[0136] In some embodiments, the variant Fc protein is a variant of the IgG1 Fc, IgG2 Fc, or IgG4 Fc protein. In some embodiments, the variant Fc protein comprises a variant of the sequence SEQ ID NO:26 (IgG1 Fc), SEQ ID NO:27 (IgG2 Fc), or SEQ ID NO:28 (IgG4 Fc).

[0137] In some embodiments, the variant Fc protein is the variant IgG1 Fc protein (SEQ ID NO:26). In some embodiments, the variant IgG1 Fc protein comprises one or more mutations corresponding to those mutations selected from the group consisting of: L234A, L235A, N297A, P329G, I253A, H310A, and H435A of SEQ ID NO:26, according to the Kabat EU number index, as 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 hereby incorporated by reference in its entirety. The mutations L234A, L235A, N297A, P329G, I253A, H310A, and H435A of SEQ ID NO:26 may be present or absent, and the mutations may be combined in any combination. In some embodiments, the variant IgG1 Fc protein contains mutations corresponding to L234A and L235A of SEQ ID NO:26. In some embodiments, the variant IgG1 Fc protein contains a mutation corresponding to N297A of SEQ ID NO:26. In some embodiments, the variant IgG1 Fc protein contains a mutation corresponding to P329G of SEQ ID NO:26. In some embodiments, the variant IgG1 Fc protein contains mutations corresponding to L234A, L235A, N297A, and P329G of SEQ ID NO:26. In some embodiments, the variant IgG1 Fc protein contains a mutation corresponding to I253A of SEQ ID NO:26. In some embodiments, the variant IgG1 Fc protein contains the mutation corresponding to H310A of SEQ ID NO:26. In some embodiments, the variant IgG1 Fc protein contains the mutation corresponding to H435A of SEQ ID NO:26. In some embodiments, the variant IgG1 Fc protein contains the mutations corresponding to I253A, H310A, and H435A of SEQ ID NO:26. In some embodiments, the variant IgG1 Fc protein contains the mutations corresponding to L234A, L235A, N297A, P329G, I253A, H310A, and H435A of SEQ ID NO:26.

[0138] In some embodiments, the variant Fc protein comprising the variant IgG1 Fc protein comprises a truncated IgG1 Fc sequence. The truncation may comprise the deletion of any number of amino acids from the N-terminus, C-terminus, or both of the IgG1 Fc sequence. In some embodiments, the variant Fc protein comprising the variant IgG1 Fc protein comprises a truncated SEQ ID NO:26. The truncation may comprise the deletion of any number of amino acids from the N-terminus, C-terminus, or both of SEQ ID NO:26. In some embodiments, the truncation comprises the deletion of amino acids from the N-terminus of SEQ ID NO:26. In some embodiments, the truncation comprises the deletion of amino acids from the C-terminus of SEQ ID NO:26. In some embodiments, the truncation comprises the deletion of amino acids from both the N-terminus and C-terminus of SEQ ID NO:26. In some embodiments, the truncated SEQ ID NO:26 comprises the amino acid sequence of SEQ ID NO:103:

[0139] EPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE KTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK(SEQ ID NO:103)

[0140] In some embodiments, the variant IgG1 Fc protein comprises one or more mutations relative to SEQ ID NO:103, said one or more mutations being selected from the group consisting of: L19A, L20A, N82A, P114G, I38A, H95A, and H220A. It should be understood that positions L19, L20, N82, P114, I38, H95, and H220 refer only to SEQ ID NO:103. 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. The mutations L19A, L20A, N82A, P114G, I38A, H95A, and H220A of SEQ ID NO:103 may be present or absent, and the mutations may be combined in any combination. In some embodiments, the variant IgG1 Fc protein contains mutations corresponding to L19A and L20A of SEQ ID NO:103. In some embodiments, the variant IgG1 Fc protein contains a mutation corresponding to N82A of SEQ ID NO:103. In some embodiments, the variant IgG1 Fc contains a mutation corresponding to P114G of SEQ ID NO:103. In some embodiments, the variant IgG1 Fc contains mutations corresponding to L19A, L20A, N82A, and P114G of SEQ ID NO:103. In some embodiments, the variant IgG1 Fc protein contains a mutation corresponding to I38A of SEQ ID NO:103. In some embodiments, the variant IgG1 Fc protein contains a mutation corresponding to H95A of SEQ ID NO:103. In some embodiments, the variant IgG1 Fc protein contains a mutation corresponding to H220A of SEQ ID NO:103. In some embodiments, the variant IgG1 Fc protein contains mutations corresponding to I38A, H95A, and H220A of SEQ ID NO:103. In some embodiments, the variant IgG1 Fc protein contains mutations corresponding to L19A, L20AN82A, P114G, I38A, H95A, and H220A of SEQ ID NO:103. In some embodiments, the variant IgG1 Fc protein contains a mutation corresponding to each of L19A, L20AN82A, P114G, I38A, H95A, and H220A of SEQ ID NO:103.Exemplary variants of IgG1 protein comprising each of L19A, L20AN82A, P114G, I38A, H95A, and H220A are shown in the amino acid sequence of SEQ ID NO:104 as follows:

[0141] EPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMASRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLAQDWLNGKEYKCKVSNKALGAPIE KTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNAYTQKSLSLSPGK(SEQ ID NO:104)

[0142] In some embodiments, the variant Fc protein is the variant IgG2 Fc protein (SEQ ID NO:27). In some embodiments, the variant IgG2 Fc protein contains one or more mutations selected from the group consisting of N297A, P329G, I253A, H310A, and H435A, because those positions correspond to SEQ ID NO:27, according to the Kabat EU number index. Any of the mutations N297A, P329G, I253A, H310A, and H435A in SEQ ID NO:27 may be present or absent, and the mutations may be combined in any combination. In some embodiments, the variant IgG2 Fc protein contains the mutation corresponding to N297A of SEQ ID NO:27. In some embodiments, the variant IgG2 Fc protein contains the mutation corresponding to P329G of SEQ ID NO:27. In some embodiments, the variant IgG2 Fc protein contains mutations corresponding to both N297A and P329G of SEQ ID NO:27. In some embodiments, the variant IgG2 Fc protein contains the mutation corresponding to I253A of SEQ ID NO:27. In some embodiments, the variant IgG2 Fc protein contains the mutation corresponding to H310A of SEQ ID NO:27. In some embodiments, the variant IgG2 Fc protein contains the mutation corresponding to H435A of SEQ ID NO:27. In some embodiments, the variant IgG2 Fc protein contains mutations corresponding to I253A, H310A, and H435A of SEQ ID NO:27.

[0143] In some embodiments, the variant Fc protein comprising the variant IgG2 Fc protein comprises a truncated IgG2 Fc sequence. The truncation may comprise 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 variant Fc protein comprising the variant IgG2 Fc protein comprises a truncated SEQ ID NO:27. The truncation may comprise the deletion of any number of amino acids from the N-terminus, C-terminus, or both of SEQ ID NO:27. In some embodiments, the truncation comprises the deletion of amino acids from the N-terminus of SEQ ID NO:27. In some embodiments, the truncation comprises the deletion of amino acids from both the N-terminus and C-terminus of SEQ ID NO:27.

[0144] In some embodiments, the variant Fc protein is the variant IgG4 Fc protein (SEQ ID NO:28). In some embodiments, the variant IgG4 Fc protein comprises one or more mutations selected from the group consisting of: S228P, L235E, N297A, P329G, I253A, H310A, and H435A, because those positions correspond to SEQ ID NO:28, according to the Kabat EU number index. Any of the mutations S228P, L235E, N297A, P329G, I253A, H310A, and H435A in SEQ ID NO:28 may be present or absent, and the mutations may be combined in any combination. In some embodiments, the variant IgG4 Fc protein comprises the mutation corresponding to S228P of SEQ ID NO:28. In some embodiments, the variant IgG4 Fc protein comprises the mutation corresponding to L235E of SEQ ID NO:28. In some embodiments, the variant IgG4 Fc protein contains the mutation corresponding to N297A of SEQ ID NO:28. In some embodiments, the variant IgG4 Fc protein contains the mutation corresponding to P329G of SEQ ID NO:28. In some embodiments, the variant IgG4 Fc protein contains mutations corresponding to S228P, L235E, N297A, and P329G of SEQ ID NO:28. In some embodiments, the variant IgG4 Fc protein contains the mutation corresponding to I253A of SEQ ID NO:28. In some embodiments, the variant IgG4 Fc protein contains the mutation corresponding to H310A of SEQ ID NO:28. In some embodiments, the variant IgG4 Fc protein contains the mutation corresponding to H435A of SEQ ID NO:28. In some embodiments, the variant IgG4 Fc protein contains mutations corresponding to I253A, H310A, and H435A of SEQ ID NO:28.

[0145] In some embodiments, the variant Fc protein comprising the variant IgG4 Fc protein comprises a truncated IgG4 Fc sequence. The truncation may comprise 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 variant Fc protein comprising the variant IgG4 Fc protein comprises a truncated SEQ ID NO:28. The truncation may comprise the deletion of any number of amino acids from the N-terminus, C-terminus, or both of SEQ ID NO:28. In some embodiments, the truncation comprises the deletion of amino acids from the N-terminus of SEQ ID NO:28. In some embodiments, the truncation comprises the deletion of amino acids from both the N-terminus and C-terminus of SEQ ID NO:28.

[0146] In some embodiments, the stem portion S1 comprising the variant Fc protein is given by the formula L1-Fc-L2-X1, where L1 is a linker or is absent; Fc is the variant Fc protein; L2 is a linker or is absent; and X1 is a polypeptide comprising a transmembrane domain. Therefore, the targeting portion comprising the formula T-S1 can also be given by the formula T-L1-Fc-L2-X1, where: T is a target-binding domain; L1 is a linker or is absent; Fc is the variant Fc protein; L2 is a linker or is absent; and X1 is a polypeptide comprising a transmembrane domain. Therefore, it should be understood that in some embodiments, the stem portion S1 can be given by the formula L1-Fc-L2-X1. In some embodiments, the target-binding domain T is as provided herein. In some embodiments, the variant Fc protein is as provided herein.

[0147] In some embodiments, L1 and L2 are each independently a peptide linker. In some embodiments, the peptide linker comprises (GGGGA). n (SEQ ID NO:54), (GGGGS) n (SEQ ID NO:55), (EAAAK) n (SEQ ID NO:73), A(EAAAK) n A(SEQ ID NO:74), (XP) n(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), AEAAAAKEAAAKA (SEQ ID NO:76), or combinations thereof, wherein each n is independently 1-5. In some embodiments, each n is independently 1. In some embodiments, each n is independently 2. In some embodiments, each n is independently 3. In some embodiments, each n is independently 4. In some embodiments, each n is independently 5. In some embodiments, each n is independently greater than 5. In some embodiments, L1 is absent. In some embodiments, L1 is (GGGGA). n (SEQ ID NO:54) or (GGGGS) n (SEQ ID NO:55) ， Each n is independently between 1 and 5. In some implementations, L1 is (GGGGA). n (SEQ ID NO:54) or (GGGGS) n (SEQ ID NO:55) ， Each n is independently 1. In some implementations, L1 is (GGGGA). n (SEQ ID NO:54) or (GGGGS) n (SEQ ID NO:55) ， Each n is independently 2. In some implementations, L1 is (GGGGA). n (SEQ ID NO:54) or (GGGGS) n (SEQ ID NO:55) ， Each n is independently 3. In some implementations, L1 is (GGGGA). n (SEQ ID NO:54) or (GGGGS) n (SEQ ID NO:55) ， Each n is independently 4. In some implementations, L1 is (GGGGA). n (SEQ ID NO:54) or (GGGGS) n (SEQ ID NO:55) ， Each n is independently 5. In some implementations, L1 is (GGGGA). n (SEQ ID NO:54) or (GGGGS) n(SEQ ID NO:55) ， Each n is independently greater than 5. In some implementations, L2 does not exist. In some implementations, L2 is (GGGGA). n (SEQ ID NO:54) or (GGGGS) n (SEQ ID NO:55) ， Each n is independently between 1 and 5. In some implementations, L2 is (GGGGA). n (SEQ ID NO:54) or (GGGGS) n (SEQ ID NO:55) ， Each n is independently 1. In some implementations, L2 is (GGGGA). n (SEQ ID NO:54) or (GGGGS) n (SEQ IDNO:55) ， Each n is independently 2. In some implementations, L2 is (GGGGA). n (SEQ ID NO:54) or (GGGGS) n (SEQ ID NO:55) ， Each n is independently 3. In some implementations, L2 is (GGGGA). n (SEQ ID NO: 54) or (GGGGS) n (SEQ ID NO:55) ， Each n is independently 4. In some implementations, L2 is (GGGGA). n (SEQ ID NO:54) or (GGGGS) n (SEQ ID NO:55) ， Each n is independently 5. In some implementations, L2 is (GGGGA). n (SEQ ID NO:54) or (GGGGS) n (SEQ ID NO:55) ， Each n is independently greater than 5.

[0148] In some implementations, X1 includes a formula ECD-T M -ICD polypeptide, wherein ECD is the extracellular domain of a cell surface protein or a fragment thereof, or is absent; T MThe target region is a transmembrane domain of a transmembrane protein; and the ICD is an intracellular domain or protein that promotes the incorporation of the targeting portion into the envelope of the viral particle, or it may not exist. Therefore, in some embodiments, the targeting portion of formula T-S1, which may be given by formula T-L1-Fc-L2-X1, may also be given by formula T-L1-Fc-L2-ECD-T. M -ICD is given, where T is the target-binding domain; L1 is the linker or absent; Fc is the variant Fc protein; L2 is the linker or absent; ECD is the extracellular domain or fragment of a cell surface protein, or absent; T M The transmembrane domain is a transmembrane protein; and the ICD is an intracellular domain or protein that promotes the incorporation of the target portion into the envelope of the viral particle, or may not exist. Therefore, it should be understood that in some embodiments, the stem portion S1 may be derived from the formula L1-Fc-L2-ECD-T. M -ICD provides this information.

[0149] In some embodiments, the stem portion S1 does not contain a variant Fc region. In some embodiments, the stem portion S1 is given by formula L3-X1, where L3 is a flexible peptide linker and X1 is a polypeptide containing a transmembrane domain as provided herein. Therefore, in some embodiments, the targeting portion containing 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 containing a transmembrane domain as provided herein. Therefore, it should be understood that in some embodiments, the stem portion S1 may be given by formula L3-X1. In some embodiments, the S1 stem portion is attached to the surface of the viral particle via a transmembrane domain.

[0150] In some embodiments, the flexible peptide linker L3 can be any flexible peptide linker. In some embodiments, L3 is selected from the group of flexible linkers, including 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, wherein each n is independently an integer selected from 1 to 4. In some embodiments, each n is independently an integer selected from 1-4, 1-5, 1-6, 1-7, 1-8, 1-9, or 1-10. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 3. In some embodiments, n is 4. In some embodiments, n is 5. In some embodiments, n is 6. In some embodiments, n is 7. In some embodiments, n is 8. In some embodiments, n is 9. In some embodiments, n is 10. In some embodiments, each n is independently greater than 10. In some embodiments, L3 is (GGGGA). n (SEQ ID NO:54) and n is 1. In some implementations, L3 is (GGGGA). n (SEQ ID NO:54) and n is 2. In some implementations, L3 is (GGGGA). n (SEQ ID NO:54) and n is 3. In some implementations, L3 is (GGGGA). n (SEQ ID NO:54) and n is 4. In some implementations, L3 is (GGGGA). n (SEQ ID NO:54) and n is 5. In some implementations, L3 is (GGGGA). n (SEQ ID NO:54) and n is 6. In some implementations, L3 is (GGGGA). n (SEQ ID NO:54) and n is 7. In some implementations, L3 is (GGGGA). n (SEQ ID NO:54) and n is 8. In some implementations, L3 is (GGGGA). n (SEQ ID NO:54) and n is 9. In some implementations, L3 is (GGGGA). n (SEQ ID NO:54) and n is 10. In some implementations, L3 is (GGGGA). n (SEQ ID NO:54) and n is greater than 10. In some implementations, L3 is (GGGGS). n (SEQ ID NO:55) and n is 1. In some implementations, L3 is (GGGGS). n(SEQ ID NO:55) and n is 2. In some implementations, L3 is (GGGGS). n (SEQ ID NO:55) and n is 3. In some implementations, L3 is (GGGGS). n (SEQ ID NO:55) and n is 4. In some implementations, L3 is (GGGGS). n (SEQ ID NO:55) and n is 5. In some implementations, L3 is (GGGGS). n (SEQ ID NO:55) and n is 6. In some implementations, L3 is (GGGGS). n (SEQ ID NO:55) and n is 7. In some implementations, L3 is (GGGGS). n (SEQ ID NO:55) and n is 8. In some implementations, L3 is (GGGGS). n (SEQ ID NO:55) and n is 9. In some implementations, L3 is (GGGGS). n (SEQ ID NO:55) and n is 10. In some implementations, L3 is (GGGGS). n (SEQ ID NO:55) and n is greater than 10. In some embodiments, L3 is GSAGSAAGSGEF (SEQ ID NO:56). In some embodiments, L3 is KESGSVSSEQLAQFRSLD (SEQ ID NO:57). In some embodiments, L3 is EGKSSGSGSESKST (SEQ ID NO:58).

[0151] In some embodiments, the flexible peptide linker L3 can be any flexible peptide linker. In some embodiments, L3 is selected from the group of flexible linkers, including 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), EGKSSGSGSESSKST (SEQ ID NO:58), or any combination thereof, wherein 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 implementations, L3 is (GGGGA). n (SEQ ID NO:54) and n is 2. In some implementations, L3 is (GGGGA). n (SEQ ID NO:54) and n is 3. In some implementations, L3 is (GGGGA). n (SEQ ID NO:54) and n is 4. In some implementations, L3 is (GGGGS). n (SEQ ID NO:55) and n is 1. In some implementations, L3 is (GGGGS). n (SEQ ID NO:55) and n is 2. In some implementations, L3 is (GGGGS). n (SEQ ID NO:55) and n is 3. In some implementations, 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).

[0152] In some implementations, L3 is selected from the group of flexible joints, including 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), EGKSSGSGSESSKST (SEQ ID NO:58), or any combination thereof, wherein each n is independently an integer selected from 1, 2, or 4. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 4. In some embodiments, L3 is (GGGGA). n (SEQ ID NO:54) and n is 1. In some implementations, L3 is (GGGGA). n (SEQ ID NO:54) and n is 2. In some implementations, L3 is (GGGGA). n (SEQ ID NO:54) and n is 4. In some implementations, L3 is (GGGGS). n(SEQ ID NO:55) and n is 1. In some implementations, L3 is (GGGGS). n (SEQ ID NO:55) and n is 2. In some implementations, 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).

[0153] In some implementations, X1 includes a formula ECD-T M -ICD polypeptide, wherein ECD is the extracellular domain of a cell surface protein or a fragment thereof, or is absent; T M The target region is a transmembrane domain of a transmembrane protein; and the ICD is an intracellular domain or protein that promotes the incorporation of the targeting portion into the envelope of the viral particle, or it may not exist. Therefore, in some embodiments, the targeting portion comprising formula T-S1, which may be given by formula T-L3-X1, may also be given by formula T-L3-ECD-T. M -ICD is given, where T is the target-binding domain, L3 is the flexible peptide linker, and ECD is the extracellular domain of a cell surface protein or a fragment thereof, or it may not exist; T M The transmembrane domain is a transmembrane protein; and the ICD is an intracellular domain or protein that promotes the incorporation of the target portion into the envelope of the viral particle, or may not exist. Therefore, it should be understood that in some embodiments, the stem portion S1 may be derived from formula L3-ECD-T. M -ICD provides this information.

[0154] 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 originates from a different protein than the transmembrane domain. The ECD domain may be the entire ECD domain or a fragment thereof. In some embodiments, the ECD domain is a CD8 or CD28 ECD domain or a fragment thereof. In some embodiments, the ECD domain is a CD8 ECD domain or a fragment thereof. In some embodiments, the CD8 ECD domain comprises a polypeptide of FVPVFLPAKPTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACD (SEQ ID NO:59). In some embodiments, the CD8 ECD domain consists of, or is substantially composed of, the polypeptide of FVPVFLPAKPTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACD (SEQ ID NO:59). In some embodiments, the ECD domain comprises a polypeptide of 25-45 amino acids in length. In some embodiments, the ECD comprises at least or about 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the peptide of FVPVFLPAKPTTTPAPRPPTP APTIASQPLSLRPEACRPAAGGAVHTRGLDFACD (SEQ ID NO: 59). In some embodiments, the ECD domain is a CD28 ECD domain or a fragment thereof. In some embodiments, the CD28 ECD domain comprises a polypeptide of KIEVMYPPPYLDNEKSNGTIIHVKGKHLCPSPLFPGPSKP (SEQ ID NO: 60). In some embodiments, the CD28 ECD domain is composed of, or substantially composed of, the polypeptide of KIEVMYPPPYLDNEKSNGTIIHVKGKHLCPSPLFPGPSKP (SEQ ID NO: 60). In some embodiments, the ECD domain comprises a polypeptide of 25-45 amino acids in length. In some embodiments, the ECD contains at least or about 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the peptide of KIEVMYPPPYLDNEKSNGTIIHVKGKHLCPSPL FPGPSKP (SEQ ID NO:60).

[0155] In some implementations, T M It can be any suitable transmembrane domain or fragment thereof. In some embodiments, T MThe structural domain is CD8 or CD28 T M A domain or a fragment thereof. In some implementations, T M The structural domain is CD8 T M A domain or a fragment thereof. In some implementations, CD8 T M The domain contains a polypeptide of the form IYIWAPLAGTCGVLLLSLVITLY CNHRN (SEQ ID NO: 61). In some embodiments, CD8 T M The domain is composed of a polypeptide of IYIWAPLAGTCGVLLLSLVITLYCNHRN (SEQ ID NO: 61), or is substantially composed of said polypeptide. In some embodiments, T M The polypeptide comprises at least or about 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the peptide identical to that of IYIWAPLAGTCGVLLLSLVITLYCNHRN (SEQ ID NO: 61). In some embodiments, T M The structural domain is CD 28T M A domain or a fragment thereof. In some implementations, CD28 T M The domain contains a polypeptide of the form FWVLVVVGGVLACYSLLVTVAFIIFWV (SEQ ID NO:62). In some embodiments, CD28 T M The domain is composed of a polypeptide of FWVLVVVGGVLACYSLLV TVAFIIFWV (SEQ ID NO:62), or is substantially composed of said polypeptide. In some embodiments, T M A polypeptide comprising at least or about 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% of the peptide identical to FWVLVVVGGVLACYSLLVTVA FIIFWV (SEQ ID NO:62).

[0156] In some implementations, T M The domain originates from the same protein as ECD. In some implementations, T M The domain originates from a protein different from ECD. In some implementations, T M The structural domain is CD8 or CD28 T M The structural domain or a fragment thereof, and the ECD structural domain is CD8 or CD28. The ECD structural domain or a fragment thereof. In some embodiments, T MThe peptide with the structural domain is at least or about 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to that of IYIWAPLAGTCGVLLLSLVITLYCNHRN (SEQ ID NO: 61), and the ECD structural domain is at least or about 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to that of FVPVFLPAKPTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHT RGLDFACD (SEQ ID NO: 59). In some embodiments, T M The peptide with the structural domain is at least or about 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to that of IYIWAPLAGTCGVLLLSLVITLYCNHRN (SEQ ID NO: 61), and the ECD structural domain is at least or about 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to that of KIEVMYPPPYLDNEKSNGTIIHVKGKHLCPSPLFPGPSKP (SEQ ID NO: 60). In some embodiments, T M The peptide with the structural domain is at least or about 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to that of FWVLVVVGGVLACYSLLVTVAFIIFWV (SEQ ID NO: 62), and the ECD structural domain is at least or about 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to that of FVPVFLPAKPTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHT RGLDFACD (SEQ ID NO: 59). In some embodiments, T M The peptide with the structural domain is at least or about 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the peptide with the structural domain of FWVLVVVGGVLACYSLLVTVAFIIFWV (SEQ ID NO:62), and the ECD structural domain is at least or about 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the peptide with the structural domain of KIEVMYPPPYLDNEKSNGTIIHVKGKHLCPSPLFPGPSKP (SEQ ID NO:60).

[0157] In some embodiments, the transmembrane domain is linked to the intracellular domain (ICD) of a cellular transmembrane protein or a fragment thereof. In some embodiments, the ICD is absent. In some embodiments, the ICD originates from a protein that is the same as or different from the TM domain. In some embodiments, the ICD contains an Env incorporation motif. An Env incorporation motif is a molecule, such as a polypeptide, that helps facilitate protein incorporation into the viral envelope. A non-limiting example of an Env incorporation motif is a polypeptide containing the amino acid sequence NRVRQGYS (SEQ ID NO: 63). This is a non-limiting example and other peptide sequences, such as, but not limited to, GGTETSQVAPA (SEQ ID NO: 64), may be used. In some embodiments, the Env incorporation motif contains the amino acid sequence of SEQ ID NO: 63, SEQ ID NO: 64, or a combination thereof. In some embodiments, the Env incorporation motif contains the amino acid sequence of SEQ ID NO: 63. In some embodiments, the Env incorporation motif contains the amino acid sequence of SEQ ID NO: 64.

[0158] In some implementations, the target-binding domain "T" is any polypeptide or polynucleotide that can be used to bind to the desired target. In some embodiments, T represents any polypeptide, polynucleotide, or fragment thereof bound to: CD7, CD8, cKit (CD117), CD4, CD3, CD5, CD6, CD2, TCRα, TCRβ, TCRγ, TCRδ, CD10, CD34, CD110, CD33, CD14, CD68, CCR7, CD62L, CD25, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, or CXCR3; glycosylated CD43 epitopes expressed on acute leukemia or lymphoma but not on hematopoietic progenitor cells; glycosylated CD43 epitopes expressed on non-hematopoietic cancers; kinase-anchored protein 4 (AKAP-4); adrenaline receptor β3 (ADRB3); AFP; anaplastic lymphoma kinase (ALK); androgen receptor; angiopoietin-binding cell surface receptor 2 (Tie 2); Desmosome core protein 1 (Dsg1) autoantibody; Desmosome core protein 3 (Dsg3) autoantibody; B7H3 (CD276); Biotin; Bone marrow stromal cell antigen 2 (BST2); BST1 / CD157; Cancer / testis antigen 1 (NY-ESO-1); Cancer / testis antigen 2 (LAGE-la); Carbonic anhydrase IX (CA1X); Carcinoembryonic antigen (CEA); CCCTC binding factor (zinc finger protein)-like (BORIS or imprinting site regulatory factor-like protein); CCR4; CD5; CD19; CD20; CD22; CD24; CD30; CD32 (FCGR) 2A); CD33; CD34; CD38; CD44v6; CD72; CD79a; CD79b; CD97; CD99; CD123; CD171; CD179a; CD179b-IGL11; CD200R; CD276 / B7H3; CD300 molecular-like family member f (CD300LF); CDH1-CD324; CDH6; CDH17; CDH19; Chromosome X open reading frame 61 (CXORF61); Sealing protein 6 (CLDN6); Sealing protein l8.2 (CLD18A2 or CLDN18A.2); CMV pp65; C-MYC epitope tag; Cripto; CS1 (also known as CD2 subset 1 or CRACC or SLAMF7 or CD319 or 19A24); CSF2RA (GM-CSFR-α); C-type lectin domain family 12 member A (CLEC12A); C-type lectin-like molecule-1 (CLL-1 or CLECL1); Cyclin B1; Cytochrome P450 IB 1 (CYP1B 1); DLL3; EBV-EBNA3c; EGF-bke module mucin-like hormone receptor-like 2 (EMR2);Mutant elongation factor 2 (ELF2M); liver glycoside B2; liver glycoside A receptor 2 (EphA2); epidermal growth factor receptor (EGFR); epidermal growth factor receptor variant III (EGFRviii); epithelial cell adhesion molecule (EPCAM); ERG; ETS translocation variant gene 6 located on chromosome 12p (ETV6-AML); Fc fragment of IgA receptor (FCAR or CD89); Fc receptor-like 5 (FCRL5); fibroblast activating protein α (FAP); FITC; Fms-like tyrosine kinase 3 (FLT3); folate receptor α (FRa or FR1); folate receptor β (FRb); follicle-stimulating hormone receptor (FSHR); Fos-associated antigen 1; fucose-GM1; G protein-coupled Group 5 member of receptor class C D (GPRC5D); G protein-coupled receptor 20 (GPR20); GAD; ganglioside G2 (GD2); ganglioside GD3 (aNeu5Ac(2-8)aNeu5Ac(2-3)bDGalp(1-4)bDGlcp(11)Cer); ganglioside GM3 (aNeu5Ac(2-3)bDClalp(1-4)bDGlcp(11)Cer); GD3; GFRα4; glycoprotein 100 (gplOO); phosphatidylinositol proteoglycan-3 (GPC3); gonadotropin receptor (CGHR or GR); GpA33; GpNMB; GPRC5D; guanylate cyclase C (GCC); mutant heat shock protein 70-2 (mut HSP70-2); Hepatitis A virus cell receptor 1 (HAVCR1); hexasaccharide moiety of globoH glycerol ceramide (GloboH); high molecular weight melanoma-associated antigen (HMWMAA); HIV1 envelope glycoprotein; HLA; HLA-DOA; HLA-A; HLA-A2; HLA-B; HLA-C; HLA-DM; HLA-DOB; HLA-DP; HLA-DQ; HLA-DR; HLA-G; HTLV1-Tax; Human papillomavirus E6 (HPV E6); Human papillomavirus E7 (HPV E7); Human telomerase reverse transcriptase (hTERT); IgE; IL13Ra2; IL1 lRa; Immunoglobulin λ-like polypeptide 1 (IGLL1); Influenza A hemagglutinin (HA); Insulin-like growth factor 1 receptor (IGF-I receptor); Interleukin 11 receptor α (IL-11Ra); Interleukin-13 receptor subunit α-2 (IL-13Ra2 or CD213A2); Intestinal carboxyl esterase; KIT (CD117); KSHV K8.1; KSHV-gH; LAMP1; pod protein; Leukocyte immunoglobulin-like receptor subfamily A member 2 (LILRA2); Leukocyte-associated immunoglobulin-like receptor 1 (LAIR1); Luteinizing hormone receptor (LHR);Lewis (Y) antigen; Lews Ag; Livl; Locus K9 (LY6K); Low-conductivity chloride channel; Lymphocyte antigen 6 complex; Lymphocyte antigen 75 (LY75); Lymphocyte-specific protein tyrosine kinase (LCK); Breast differentiation antigen (NY-BR-1); T-cell recognized melanoma antigen 1 (MelanA or MARTI); Melanoma-associated antigen 1 (MAGE-A1); Melanoma cancer testis antigen-1 (MAD-CT-1); Melanoma cancer testis antigen-2 (MAD-CT-2); Melanoma cell apoptosis inhibitor (ML-IAP); Mesothelin; MPL; Mucin 1 cell surface associated (MUC1); N-acetylglucosamine aminotransferase V (NA17); Adhesionin-4; Neural cell adhesion molecule (NCAM); N KG2D; NYBR1; O-acetyl-GD2 ganglioside (OAcGD2); olfactory receptor 51E2 (OR51E2); oncogene fusion protein (bcr-abl) composed of breakpoint cluster region (BCR) and Abelson murine leukemia virus oncogene homolog 1 (Abl); P53 mutant; pairing box protein Pax-3 (PAX3); pairing box protein Pax-5 (PAX5); pan-connector protein 3 (PANX3); PDL1; P-glycoprotein; placenta-specific 1 (PLAC1); platelet-derived growth factor receptor β (PDGFR-β); polysialic acid; proapocrine-binding protein sp32 (OY-TES1); prostate enzyme; prostate cancer tumor antigen-1 (PCT) Al or galactose lectin 8); prostate stem cell antigen (PSCA); prostate-specific membrane antigen (PSMA); prostate acid phosphatase (PAP); prostaglandins; protease serine 21 (testin or PRSS21); proteasome macropain subunit β9 (LMP2); PTK7; Ras G12V; Ras homologous family member C (RhoC); rat sarcoma (Ras) mutant; receptor for advanced glycation end products (RAGE-1); receptor tyrosine kinase-like orphan receptor 1 (ROR1); receptor tyrosine protein kinase ERBB2 or Her-22 / neu; renal pervasive 1 (RU1); renal pervasive 2 (RU2); sarcoma translocation breakpoint; serine 2 (TMPRSS2) ETS fusion gene; sialic acid Lewis adhesion molecule (sLe); S LAMF4; SLAMF6; Slea (CA19.9 or sialic acid Lewis antigen); spermin 17 (SPA17); T cell-recognized squamous cell carcinoma antigen 3 (SART3); stage-specific embryonic antigen-4 (SSEA-4); STEAP1; susceptin; synovial sarcoma X breakpoint 2 (SSX2); TCRγ alternating reading frame protein (TARP); TCR-β1 chain; TCR-β2 chain; TCR-δ chain; TCR-γ chain;TCRγ-δ; telomerase; TGFβR2; antigen recognized by TNT antibody; thyroid-stimulating hormone receptor (TSHR); Timol / HVCR1; tissue factor 1 (TF1); Tn ag; Tn antigen ((Tn (Ag) or (GalNAca-Ser / Thr)); TNF receptor family member B cell maturation (BCMA); transglutaminase 5 (TGS5); transmembrane protease; TROP2; tumor endothelial marker 1 (TEM1 / CD248); tumor endothelial marker 7 associated (TEM7R); tumor protein p53 (p53); tumor-associated glycoprotein 72 (TAG72); tyrosinase; tyrosinase-associated protein 2 (TRP-2); plaque protein 2 (UPK2); vascular endothelial growth factor receptor 2 (VEGFR2); V-myc avian myeloma virus oncogene neuroblastoma-derived homolog (MYCN); Wilms' tumor protein (WT1); or X antigen family member 1A (XAGE1). In some embodiments, the targeting domain "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. It should be understood that, in the context of this disclosure, "antibody" refers not only to a "complete" antibody comprising two identical heavy chains, two identical light chains, and two antigen-binding fragments, but also to any isotype of antibody, antibody fragment (including but not limited to Fab, Fv, scFv, and Fd fragments), chimeric antibody, humanized antibody, single-chain antibody (scAb), single-domain antibody (dAb), single-domain heavy chain antibody, single-domain light chain antibody, bispecific antibody, multispecific antibody, and fusion protein comprising the antigen-binding portion of an antibody and a non-antibody protein. In some embodiments, the antibody is selected from the group comprising scFv, Fab, VHH, single-domain antibody, etc. In some embodiments, the antibody is scFv. In some embodiments, the antibody is Fab. In some embodiments, the antibody is VHH. In some embodiments, the antibody is a single-domain antibody.

[0159] In some embodiments, the polypeptide represented by formula T-S1 can form a dimer when present on the surface of a viral particle. The dimer can form, for example, through interactions between the stem portions of the polypeptide molecule. For instance, when the stem portion contains an Fc domain or a variant Fc domain as provided herein, the Fc domains of the polypeptide molecule will interact with each other on the viral surface and form a dimer. Without being bound by any particular theory, in some embodiments, the dimer may also exhibit improved specificity due to increased affinity for the target protein via the target-binding domain (T) compared to polypeptides that do not form or cannot form dimers. Therefore, in some embodiments, the viral particle contains a dimer, which can be a homodimer or a heterodimer, comprising two polypeptides having the formula T-S1. In some embodiments, a homodimer refers to two polypeptides having the formula T-S1 with identical amino acid sequences. The dimer can also be formed by two polypeptides with different target-binding domains (T) or two different S1 portions (such as two different Fc domains, including variant Fc domains). A dimer formed by two polypeptides having different target-binding domains or different Fc domains can be called a heterodimer. In some embodiments, the heterodimer is formed by a first polypeptide having the formula T-S1 and a second polypeptide having the formula T-S1, wherein the first polypeptide has a first target-binding domain and a first S1 polypeptide, and the second polypeptide has a second target-binding domain and a second S1 polypeptide. In some embodiments, the first and second target-binding domains are the same. In some embodiments, the first and second target-binding domains are different. In some embodiments, the first and second target-binding domains bind to the same target but at different epitopes. In some embodiments, the first S1 polypeptide and the second S1 polypeptide are the same. In some embodiments, the first S1 polypeptide and the second S1 polypeptide are different. In some embodiments, the first S1 polypeptide and the second S1 polypeptide are the same except that they have different Fc domains. In some embodiments, the Fc domains used herein may also be engineered to prevent dimer formation.

[0160] In some embodiments, the viral particles provided herein are pseudotyped viral particles. In some embodiments, the viral particles are pseudotyped using viral glycoproteins of a paramyxoviridae virus. In some embodiments, the pseudotyped virus-like particles are pseudotyped using viral glycoproteins of measles virus (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 Hennipa virus (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, peptides or antibodies as provided herein are linked via adapters to envelope glycoproteins G or H of a paramyxoviridae virus. In some embodiments, the paramyxoviridae virus is a measles virus (such as measles virus). In some embodiments, the paramyxoviridae virus is a Hennipa virus (such as Nipah virus, cedar virus, or Hendra virus).

[0161] As provided herein, the virus can be pseudotyped using the VSV-G protein (either wild-type or mutant). Without being bound by any particular theory, the mutant VSV-G protein, which can be used to pseudotype viruses (e.g., lentiviruses) containing a mutation at position 182, can be used to pseudotype the virus and transduce cells when the virus contains a targeting region. This mutation inhibits or reduces the affinity of VSV-G for its natural co-receptor LDL-R. In some embodiments, the provided mutant VSV-G protein can be used to transduce target cells and deliver heterologous molecules to target cells.

[0162] In some embodiments, a VSV-G protein is provided comprising 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 extracellular domain of the VSV-G protein. The 16-mer signal peptide MKCLLYLAFLFIGVNC (SEQ ID NO:65) shown at the N-terminus of SEQ ID NO:1 is cleaved, leaving the protein of SEQ ID NO:2. Therefore, although the mutation may be mentioned in the context of SEQ ID NO:2, it should be understood that the mutation is also mentioned in the context of SEQ ID NO:1 containing the leader sequence, and will therefore be a position number 16 more than that described 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.

[0163] In some embodiments, a VSV-G protein is provided comprising a mutation at position 198 compared to SEQ ID NO:10 or at position 182 compared to SEQ ID NO:11. SEQ ID NO:10 is the full-length protein and SEQ ID NO:11 is the extracellular domain of the VSV-G protein. The 16-mer signal peptide 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. Therefore, although the mutation may be mentioned in the context of SEQ ID NO:11, it should be understood that the mutation is also mentioned in the context of SEQ ID NO:10 containing the leader sequence, and will therefore be a position number 16 more than that described 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 implementations, the mutation is the T182E mutation compared to SEQ ID NO:11.

[0164] In some embodiments, a VSV-G protein is provided comprising a mutation at position 198 compared to SEQ ID NO:12 or at position 182 compared to SEQ ID NO:13. SEQ ID NO:12 is the full-length protein and SEQ ID NO:13 is the extracellular domain of the VSV-G protein. The 16-mer signal peptide MLRLFLFCFLALGAHS (SEQ ID NO:67) shown at the N-terminus of SEQ ID NO:12 is cleaved, leaving the protein of SEQ ID NO:13. Therefore, although the mutation may be mentioned in the context of SEQ ID NO:13, it should be understood that the mutation is also mentioned in the context of SEQ ID NO:12 containing the leader sequence, and will therefore be a position number 16 more than that described 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 implementations, the mutation is the A182E mutation compared to SEQ ID NO:13.

[0165] In some embodiments, a VSV-G protein is provided comprising 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 extracellular domain of the VSV-G protein. The 21-mer signal peptide MKMKMVIAGLILCIGILPAIG (SEQ ID NO:68) shown at the N-terminus of SEQ ID NO:14 is cleaved, leaving the protein of SEQ ID NO:15. Therefore, although the mutation may be mentioned in the context of SEQ ID NO:15, it should be understood that the mutation is also mentioned in the context of SEQ ID NO:14 containing the leader sequence, and will therefore be a position number 21 more than that described 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 implementations, the mutation is the V182E mutation compared to SEQ ID NO:15.

[0166] In some embodiments, a VSV-G protein is provided comprising 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 extracellular domain 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. Therefore, although the mutation may be mentioned in the context of SEQ ID NO:17, it should be understood that the mutation is also mentioned in the context of SEQ ID NO:16 containing the leader sequence, and will therefore be a position number 17 more than that described 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 implementations, the mutation is the V182E mutation compared to SEQ ID NO:17.

[0167] In some embodiments, a VSV-G protein is provided comprising a mutation at position 199 compared to SEQ ID NO:18 or at position 182 compared to SEQ ID NO:19. SEQ ID NO:18 is the full-length protein and SEQ ID NO:19 is the extracellular domain of the VSV-G protein. The 17-mer signal peptide MNFLLLTFIVLPLCSHA (SEQ ID NO:70) shown at the N-terminus of SEQ ID NO:18 is cleaved, leaving the protein of SEQ ID NO:19. Therefore, although the mutation may be mentioned in the context of SEQ ID NO:19, it should be understood that the mutation is also mentioned in the context of SEQ ID NO:18 containing the leader sequence, and will therefore be a position number 17 more than that described 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 implementations, the mutation is the V182E mutation compared to SEQ ID NO:19.

[0168] In some embodiments, a VSV-G protein is provided comprising a mutation at position 199 compared to SEQ ID NO:20 or at position 182 compared to SEQ ID NO:21. SEQ ID NO:20 is the full-length protein and SEQ ID NO:21 is the extracellular domain of the VSV-G protein. The 17-mer signal peptide of MLVLYLLLSLLALGAQC (SEQ ID NO:71) as shown at the N-terminus of SEQ ID NO:20 is cleaved, leaving the protein of SEQ ID NO:21. Therefore, although the mutation may be mentioned in the context of SEQ ID NO:21, it should be understood that the mutation is also mentioned in the context of SEQ ID NO:20 containing the leader sequence, and will therefore be a position number 17 more than that described 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 implementations, the mutation is the I182E mutation compared to SEQ ID NO:21.

[0169] As used herein, when a peptide is considered to have a mutation compared to a reference sequence, such comparisons are based on alignments using software such as BlastP, ClustalW, or ClustalOmega with default parameters. For example, position 182 is found in SEQ ID NO:2 and is similar to... Figure 3 The same applies to other viral strains shown. Figure 3 Cluster alignments of wild-type sequences of the extracellular domain of the VSV-G protein from various viral strains are shown. Bold and underlined residues are those aligned to position 182 of SEQ ID NO:2 for each viral strain. SEQ ID NO:2 refers to the extracellular domain of the VSV-G protein of the Indiana virus strain. SEQ ID NO:11 refers to the extracellular domain of the VSV-G protein of the New Jersey virus strain. SEQ ID NO:13 refers to the extracellular domain of the VSV-G protein of the Malaba virus strain. SEQ ID NO:15 refers to the extracellular domain of the VSV-G protein of the Kalahari virus strain. SEQ ID NO:17 refers to the extracellular domain of the VSV-G protein of the Aragova virus strain. SEQ ID NO:19 refers to the extracellular domain of the VSV-G protein of the Cocal virus strain. SEQ ID NO:21 refers to the extracellular domain of the VSV-G protein of the Morreton virus strain. Therefore, residues aligned with residue 182 compared to SEQ ID NO:2 can also undergo mutations as provided herein.

[0170] 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.

[0171] In some embodiments, the mutation at position 182 compared to SEQ ID NO:2 is I182S, I182H, I182T, I182Q, or I182N. In some embodiments, the mutation at position 182 compared to SEQ ID NO:11 is T182S, T182H, T182Q, or T182N. In some embodiments, the mutation at position 182 compared to SEQ ID NO:13 is A182S, A182H, A182T, A182Q, or A182N. In some embodiments, the mutation at position 182 compared to SEQ ID NO:15 is V182S, V182H, V182T, V182Q, or V182N. In some embodiments, the mutation at position 182 compared to SEQ ID NO:17 is V182S, V182H, V182T, V182Q, or V182N. In some embodiments, the mutation at position 182 compared to SEQ ID NO:19 is V182S, V182H, V182T, V182Q, or V182N. In some embodiments, the mutation at position 182 compared to SEQ ID NO:21 is I182S, I182H, I182T, I182Q, or I182N. In some embodiments, the mutation at position 182 is not a hydrophobic residue. In some embodiments, the mutation at position 182 is a charged residue. In some embodiments, the mutation at position 182 is a negatively charged residue.

[0172] Although the mutation may be described with reference to SEQ ID NO:1 or SEQ ID NO:2 (which is the VSV-G protein from the Indiana virus strain), the mutation can also be used in other viral strains of the VSV-G protein. For example, the mutation can be made in the New Jersey strain of VSV-G, the Malaba virus strain of VSV-G, the Kalahari virus strain of VSV-G, the Aragonia virus strain of VSV-G, the Kocal virus strain of VSV-G, or the Moriton virus strain of VSV-G. In some embodiments, the sequence of each is as provided herein. Examples of such sequences can be found, for example, in U.S. Patent Application Publication No. 20200216502, which is hereby incorporated by reference. For example, the wild-type full-length or extracellular domains of the New Jersey strain of VSV-G are SEQ ID NO:10 and SEQ ID NO:11, respectively; the wild-type full-length or extracellular domains of the Malaba strain of VSV-G are SEQ ID NO:12 and SEQ ID NO:13, respectively; the wild-type full-length or extracellular domains of the Kalahari strain of VSV-G are SEQ ID NO:14 and SEQ ID NO:15, respectively; the wild-type full-length or extracellular domains of the Aragora strain of VSV-G are SEQ ID NO:16 and SEQ ID NO:17, respectively; the wild-type full-length or extracellular domains of the Kocal strain of VSV-G are SEQ ID NO:18 and SEQ ID NO:19, respectively; or the wild-type full-length or extracellular domains of the Moriton strain of VSV-G are SEQ ID NO:20 and SEQ ID NO:21, respectively.

[0173] The VSV-G protein containing the mutation at position 182 compared to SEQ ID NO:2 may also contain other mutations, such as those described in U.S. Patent Application Publication No. 20200216502, which is hereby incorporated herein by reference in its entirety. For example, the VSV-G protein may contain mutations at positions 8, 47, 209, and / or 354 corresponding to SEQ ID NO:2.

[0174] In some embodiments, the substitution at position 8 is replaced by any amino acid different from the amino acid indicated at that position in sequence SEQ ID NO:2, except Y. In some embodiments, the substitution at position 209 is replaced by any amino acid different from the amino acid indicated at that position in sequence SEQ ID NO:2, except H. In some embodiments, the substitution at position 47 is replaced by any amino acid different from the amino acid indicated at that position in sequence SEQ ID NO:2, except K or R. In some embodiments, the substitution at position 354 is replaced by any amino acid different from the amino acid indicated at that position in sequence SEQ ID NO:2, except K or R.

[0175] In some embodiments, the substitution is at position 47 or at position 354, or at both positions 47 and 354, by A, G, F, or Q. In some embodiments, the substitution is A or Q.

[0176] In some implementations, the substitution at position 8 is alanine, i.e., H8A.

[0177] In some implementations, position 47 is replaced by Q or N, i.e., K47Q or K47N.

[0178] In some embodiments, the protein contains a mutation (substitution) at position 10. In some embodiments, the substitution / mutation is Q10A, Q10R, or Q10K.

[0179] In some embodiments, a protein containing a mutation at position 182 compared to SEQ ID NO:2 contains a mutation at position 182 and is at least or about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO:2 (or SEQ ID NO:1, if using the full-length protein). In some embodiments, the polypeptide contains an I182D or I182E mutation. In some embodiments, the VSV-G protein contains an I182S, I182H, I182T, I182Q, or I182N mutation.

[0180] In some embodiments, a protein containing a mutation at position 182 compared to SEQ ID NO:11 contains a mutation at position 182 and is at least or about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO:11 (or SEQ ID NO:10, if full-length protein is used). In some embodiments, the polypeptide contains a T182D or T182E mutation. In some embodiments, the VSV-G protein contains a T182S, T182H, T182Q, or T182N mutation.

[0181] In some embodiments, a protein containing a mutation at position 182 compared to SEQ ID NO:13 contains a mutation at position 182 and is at least or about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO:13 (or SEQ ID NO:12, if full-length protein is used). In some embodiments, the polypeptide contains an A182D or A182E mutation. In some embodiments, the VSV-G protein contains an A182S, A182H, A182T, A182Q, or A182N mutation.

[0182] In some embodiments, a protein containing a mutation at position 182 compared to SEQ ID NO:15 contains a mutation at position 182 and is at least or about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO:15 (or SEQ ID NO:14, if full-length protein is used). In some embodiments, the polypeptide contains a V182D or V182E mutation. In some embodiments, the VSV-G protein contains a V182S, V182H, V182T, V182Q, or V182N mutation.

[0183] In some embodiments, a protein containing a mutation at position 182 compared to SEQ ID NO:17 contains a mutation at position 182 and is at least or about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO:17 (or SEQ ID NO:16, if full-length protein is used). In some embodiments, the polypeptide contains a V182D or V182E mutation. In some embodiments, the VSV-G protein contains a V182S, V182H, V182T, V182Q, or V182N mutation.

[0184] In some embodiments, a protein containing a mutation at position 182 compared to SEQ ID NO:19 contains a mutation at position 182 and is at least or about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO:19 (or SEQ ID NO:18, if full-length protein is used). In some embodiments, the polypeptide contains a V182D or V182E mutation. In some embodiments, the VSV-G protein contains a V182S, V182H, V182T, V182Q, or V182N mutation.

[0185] In some embodiments, a protein containing a mutation at position 182 compared to SEQ ID NO:21 contains a mutation at position 182 and is at least or about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO:21 (or SEQ ID NO:20, if full-length protein is used). In some embodiments, the polypeptide contains an I182D or I182E mutation. In some embodiments, the VSV-G protein contains an I182S, I182H, I182T, I182Q, or I182N mutation.

[0186] viral glycoproteins

[0187] The mutant VSV-G protein can be used, for example, for pseudotypening viruses (such as, but not limited to, lentiviruses). Therefore, in some embodiments, a viral particle comprising the mutant VSV-G protein as provided herein is provided. In some embodiments, the viral particle comprises the VSV-G protein containing a mutation at position 198 compared to SEQ ID NO:1. In some embodiments, a protein containing a mutation at position 182 compared to SEQ ID NO:2 contains a mutation at position 182 and is at least or about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO:2 (or SEQ ID NO:1, if using the full-length protein). In some embodiments, the polypeptide contains an I182D or I182E mutation compared to SEQ ID NO:2. In some implementations, the VSV-G protein contains I182S, I182H, I182T, I182Q, or I182N mutations.

[0188] In some embodiments, the viral particle comprises the VSV-G protein, which contains a mutation at position 198 compared to SEQ ID NO:10. In some embodiments, the protein containing a mutation at position 182 compared to SEQ ID NO:11 contains the mutation at position 182 and is at least or about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO:11 (or SEQ ID NO:10, if using the full-length protein). In some embodiments, the polypeptide contains a T182D or T182E mutation compared to SEQ ID NO:11. In some implementations, the VSV-G protein contains T182S, T182H, T182Q, or T182N mutations.

[0189] In some embodiments, the viral particle comprises the VSV-G protein, which contains a mutation at position 198 compared to SEQ ID NO:12. In some embodiments, the protein containing a mutation at position 182 compared to SEQ ID NO:13 contains the mutation at position 182 and is at least or about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO:13 (or SEQ ID NO:12, if using the full-length protein). In some embodiments, the polypeptide contains an A182D or A182E mutation compared to SEQ ID NO:13. In some implementations, the VSV-G protein contains mutations of A182S, A182H, A182T, A182Q, or A182N.

[0190] In some embodiments, the viral particle comprises the VSV-G protein, which contains a mutation at position 203 compared to SEQ ID NO:14. In some embodiments, the protein containing a mutation at position 182 compared to SEQ ID NO:15 contains the mutation at position 182 and is at least or about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO:15 (or SEQ ID NO:14, if full-length protein is used). In some embodiments, the polypeptide contains a V182D or V182E mutation compared to SEQ ID NO:15. In some implementations, the VSV-G protein contains mutations of V182S, V182H, V182T, V182Q, or V182N.

[0191] In some embodiments, the viral particle comprises the VSV-G protein, which contains a mutation at position 199 compared to SEQ ID NO:16. In some embodiments, the protein containing a mutation at position 182 compared to SEQ ID NO:17 contains the mutation at position 182 and is at least or about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO:17 (or SEQ ID NO:16, if full-length protein is used). In some embodiments, the polypeptide contains a V182D or V182E mutation compared to SEQ ID NO:17. In some implementations, the VSV-G protein contains mutations of V182S, V182H, V182T, V182Q, or V182N.

[0192] In some embodiments, the viral particle comprises the VSV-G protein, which contains a mutation at position 199 compared to SEQ ID NO:18. In some embodiments, the protein containing a mutation at position 182 compared to SEQ ID NO:19 contains the mutation at position 182 and is at least or about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO:19 (or SEQ ID NO:18, if full-length protein is used). In some embodiments, the polypeptide contains a V182D or V182E mutation compared to SEQ ID NO:19. In some implementations, the VSV-G protein contains mutations of V182S, V182H, V182T, V182Q, or V182N.

[0193] In some embodiments, the viral particle comprises the VSV-G protein, which contains a mutation at position 199 compared to SEQ ID NO:20. In some embodiments, the protein containing a mutation at position 182 compared to SEQ ID NO:21 contains the mutation at position 182 and is at least or about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO:21 (or SEQ ID NO:20, if full-length protein is used). In some embodiments, the polypeptide contains an I182D or I182E mutation compared to SEQ ID NO:21. In some implementations, the VSV-G protein contains I182S, I182H, I182T, I182Q, or I182N mutations.

[0194] In some embodiments, the VSV-G protein further includes mutations at positions 214 and / or 352 corresponding to SEQ ID NO:2. In some embodiments, the residue corresponding to position 214 of SEQ ID NO:2 is T214. In some embodiments, the residue corresponding to position 352 of SEQ ID NO:2 is T352. In some embodiments, the VSV-G protein includes a mutation corresponding to the T214N mutation compared to SEQ ID NO:2. In some embodiments, the VSV-G protein includes a mutation corresponding to the T352A mutation compared to SEQ ID NO:2. In some embodiments, the VSV-G protein includes both the T214N and T352A mutations compared to SEQ ID NO:2. These mutations may be combined with any other mutations as provided herein. In some embodiments, the T214N and / or T352A mutations are combined with the I182E or I182D mutation. In some embodiments, the VSV-G protein comprises the amino acid sequences of SEQ ID NO:22 and SEQ ID NO:23, which combine I182D or I182E with the T214N and T352A mutations, respectively. These sequences are also illustrated below with a leader sequence, which is removed during protein processing.

[0195] VSV-G protein mutations I196D, T230N, and T368A (with leader sequence and regulatory number)

[0196] MKCLLYLAFLFIGVNCKFTIVFPHNQKGNWKNVPSNYHYCPSSSDLNWHNDLIGTALQVKMPKSHKAIQADGWMCHASKWVTTCDFRWYGPKYITHSIRSFTPSVEQCKESIEQTKQGTWLNPGFPPQSCGYATVTDAEAVIVQVTPHHVLVDEYTGEWVDSQFINGKCSNYICPTVHNSTTWHSDYKVKGLCDSNLDSMDITFFSEDGELSSLGKEGTGFRSNYFAYENGGKACKMQYCKHWGVRLPSGVWFEMADKDLFAAARFPECPEGSSISAPSQTSVDVSLIQDVERILDYSLCQETWSKIRAGLPISPVDLSYLAPKNPGTGPAFTIINGTLKYFETRYIRVDIAAPILSRMVGMISGTTAERELWDDWAPYEDVEIGPNGVLRTSSGYKFPLYMIGHGMLDSDLHLSSKAQVFEHPHIQDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCIKLKHTKKRQIYTDIEMNRLGK(SEQ ID NO:24)

[0197] VSV-G protein_I182D, T214N and T352A mutations (without leader sequence)

[0198] KFTIVFPHNQKGNWKNVPSNYHYCPSSSDLNWHNDLIGTALQVKMPKSHKAIQADGWMCHASKWVTTCDFRWYGPKYITHSIRSFTPSVEQCKESIEQTKQGTWLNPGFPPQSCGYATVTDAEAVIVQVTPHHVLVDEYTGEWVDSQFINGKCSNYICPTVHNSTTWHSDYKVKGLCDSNLDSMDITFFSEDGELSSLGKEGTGFRSNYFAYENGGKACKMQYCKHWGVRLPSGVWFEMADKDLFAAARFPECPEGSSISAPSQTSVDVSLIQDVERILDYSLCQETWSKIRAGLPISPVDLSYLAPKNPGTGPAFTIINGTLKYFETRYIRVDIAAPILSRMVGMISGTTAERELWDDWAPYEDVEIGPNGVLRTSSGYKFPLYMIGHGMLDSDLHLSSKAQVFEHPHIQDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCIKLKHTKKRQIYTDIEMNRLGK(SEQ ID NO:22)

[0199] VSV-G protein with I196E, T230N, and T368A mutations (with leader sequence and adjusted numbering)

[0200] MKCLLYLAFLFIGVNCKFTIVFPHNQKGNWKNVPSNYHYCPSSSDLNWHNDLIGTALQVKMPKSHKAIQADGWMCHASKWVTTCDFRWYGPKYITHSIRSFTPSVEQCKESIEQTKQGTWLNPGFPPQSCGYATVTDAEAVIVQVTPHHVLVDEYTGEWVDSQFINGKCSNYICPTVHNSTTWHSDYKVKGLCDSNLESMDITFFSEDGELSSLGKEGTGFRSNYFAYENGGKACKMQYCKHWGVRLPSGVWFEMADKDLFAAARFPECPEGSSISAPSQTSVDVSLIQDVERILDYSLCQETWSKIRAGLPISPVDLSYLAPKNPGTGPAFTIINGTLKYFETRYIRVDIAAPILSRMVGMISGTTAERELWDDWAPYEDVEIGPNGVLRTSSGYKFPLYMIGHGMLDSDLHLSSKAQVFEHPHIQDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCIKLKHTKKRQIYTDIEMNRLGK(SEQ ID NO:25)

[0201] VSV-G protein (without leader sequence) with I182E, T214N, and T352A mutations

[0202] KFTIVFPHNQKGNWKNVPSNYHYCPSSSDLNWHNDLIGTALQVKMPKSHKAIQADGWMCHASKWVTTCDFRWYGPKYITHSIRSFTPSVEQCKESIEQTKQGTWLNPGFPPQSCGYATVTDAEA VIVQVTPHHVLVDEYTGEWVDSQFINGKCSNYICPTVHNSTTWHSDYKVKGLCDSNLESMDITFFSEDGELSSLGKEGTGFRSNYFAYENGGKACKMQYCKHWGVRLPSGVWFEMADKDLFAAAR FPECPEGSSISAPSQTSVDVSLIQDVERILDYSLCQETWSKIRAGLPISPVDLSYLAPKNPGTGPAFTIINGTLKYFETRYIRVDIAAPILSRMVGMISGTTAERELWDDWAPYEDVEIGPNGVL RTSSGYKFPLYMIGGHGMLDSDLHLSSKAQVFEHPHIQDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLRVGIHLCIKLKHTKKRQIYTDIEMNRLGK(SEQ ID NO:23)

[0203] Other viral strains of the VSV-G protein described herein may also contain mutations corresponding to T214N and / or T352A in SEQ ID NO:2 and as shown in SEQ ID NO:22 and SEQ ID NO:23.

[0204] In some embodiments, the composition comprises mutations as described in Hwang et al., Gene Ther, August 2013; 20(8):807-15. (Electronic publication, January 31, 2013), which are hereby incorporated in their entirety by reference. For example, mutations may be at positions 230, 368, 66, and / or 162 corresponding to SEQ ID NO:1. When the leader sequence is removed, these positions will be 16 fewer than those in SEQ ID NO:2. In some embodiments, mutations at those positions are, for example, T230N, T368A, K66T, S162T, or any combination thereof. In some embodiments, the VSV-G protein comprises the T230N and T368A mutations. In some embodiments, the VSV-G polypeptide comprises K66T, S162T, T230N, and T368A. These positions are those corresponding to the positions in the full-length protein (SEQ ID NO:1). In some embodiments, the VSV-G protein comprises the T230N mutation, the T368A mutation, the K66T mutation, the S162T mutation, or any combination thereof. In some embodiments, in addition to the mutation corresponding to position 182 of SEQ ID NO:2, the VSV-G protein further comprises one or more mutations, such as those described in U.S. Patent Application Publication No. 20200216502, which is hereby incorporated herein by reference in its entirety. For example, the VSV-G protein may further comprise mutations at positions 8, 47, 209, and / or 354 corresponding to SEQ ID NO:2.

[0205] In some embodiments, the substitution at position 8 is replaced by any amino acid different from the amino acid indicated at that position in sequence SEQ ID NO:2, except Y. In some embodiments, the substitution at position 209 is replaced by any amino acid different from the amino acid indicated at that position in sequence SEQ ID NO:2, except H. In some embodiments, the substitution at position 47 is replaced by any amino acid different from the amino acid indicated at that position in sequence SEQ ID NO:2, except K or R. In some embodiments, the substitution at position 354 is replaced by any amino acid different from the amino acid indicated at that position in sequence SEQ ID NO:2, except K or R. In some embodiments, the substitution is at position 47 or at position 354, or at both positions 47 and 354, by A, G, F, or Q. In some embodiments, the substitution is A or Q. In some embodiments, the substitution at position 8 is alanine, i.e., H8A. In some embodiments, the substitution at position 47 is Q or N, i.e., K47Q or K47N. In some embodiments, the protein contains a mutation (substitution) at position 10. In some implementations, the substitution / mutation is to Q10A, Q10R, or Q10K.

[0206] In addition, in some implementations, instead of the VSV-G protein or its mutants, the virus can be pseudotyped using other viral structural proteins.

[0207] For example, when a virus contains a targeting portion, the carp spring viremia virus G (SVCV-G) protein can be used to pseudotype viral particles and transduce cells. In some embodiments, the provided carp spring viremia virus G protein can be used to transduce target cells and deliver heterologous molecules to target cells. In some embodiments, a carp spring viremia virus G protein is provided that comprises SEQ ID NO:52. SEQ ID NO:52 is the full-length protein and SEQ ID NO:53 is the extracellular domain of the carp spring viremia virus G protein, with its 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, for example, to pseudotype viruses (such as, but not limited to, lentiviruses). Thus, in some embodiments, viral particles comprising the carp spring viremia virus G protein as provided herein are provided. In some embodiments, the virus particle comprises the G protein of carp spring viremia virus, which contains 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% of the same sequence as SEQ ID NO:52 or SEQ ID NO:53.

[0208] The sequence of carp spring viremia virus-G (SEQ ID NO:52 - with leader sequence)

[0209] MSIISYIAFLLLIDSNLGIPIFVPSGRNISWQPVIQPFDYQCPIHGNLPNTMGLSATKLTIKSPSVFSTDKVSGWICHAAEWKTTCDYRWYGPQYITHSIHPISPTIDECRRIIQRIASGTDEDLGFPPQSCGWASVTTVSNTNYRVVPHSVHLEPYGGHWIDHEFNGGECREKVCEMKGNHSIWITEETVQHECAKHIEEVEGIMYGNVPRGDVMYANNFIIDRHHRVYRFGGSCQMKFCNKDGIKFARGDWVEKTAGTLTTIHDNVPKCVDGTLVSGHRPGLDLIDTVFNLENVVEYTLCEGTKRKINKQEKLTSVDLSYLAPRIGGFGSVFRVRNGTLERGSTTYIRIEVEGPIVDSLNGTDPRTNASRVFWDDWELDGNIYQGFNGVYKGKDGKIHIPLNMIESGIIDDELQHAFQADIIPHPHYDDDEIREDDIFFDNTGENGNPVDAVVEWVSGWGTSLKFFGMTLVALILIFLLIRCCVACTYLMKRSKRPATESHEMRSLV

[0210] Sequence of Spring viremia of carp virus – G (SEQ ID NO: 53 - without leader sequence):

[0211] IPIFVPSGRNISWQPVIQPFDYQCPIHGNLPNTMGLSATKLTIKSPSVFSTDKVSGWICHAAEWKTTCDYRWYGPQYITHSIHPISPTIDECRRIIQRIASGTDEDLGFPPQSCGWASVTTVSNTNYRVVPHSVHLEPYGGHWIDHEFNGGECREKVCEMKGNHSIWITEETVQHECAKHIEEVEGIMYGNVPRGDVMYANNFIIDRHHRVYRFGGSCQMKFCNKDGIKFARGDWVEKTAGTLTT IHDNVPKCVDGTLVSGHRPGLDLIDTVFNLENVVEYTLCEGTKRKINKQEKLTSVDLSYLAPRIGGFGSVFRVRNGTLERGSTTYIRIEVEGPIVDSNLGTDPRTNASRVFWDWDWELDGNIYQGFNGVYKGKDGKIHIPLNMIESGIIDDELQHAFQADIIPHPHYDDDEIREDDIFFDNTGENGNPVDAVVEWVSGWGTSLKFFGMTLVALILIFLLIRCCVACTYLMKRSPRATESHEMRSLV

[0212] target part

[0213] In some embodiments, the viral particle includes a targeting portion having the formula T-S1, where T is a target-binding domain and S1 is a stem portion. The targeting portion can be used to target cells expressing a target that binds to the viral particle containing a mutant VSV-G protein or SVCV-G protein. In some embodiments, the target-binding domain is an antibody, scFv antibody, antigen-binding domain, an ankyrin repeat sequence (e.g., DARPIN), a VHH domain antibody, a nanobody, a single-domain antibody, an FN3 domain, or any combination thereof. The target-binding domain can be attached to the viral surface via a variant Fc protein (e.g., L1-Fc-L2-X1) as provided herein or via a flexible polypeptide (e.g., L3-X1) as provided herein. In some embodiments, the targeting portion attaches (fused to or linked) to the envelope glycoprotein G or H of a paramyxoviridae virus (such as measles virus or Hennipa virus). In some embodiments, the targeting portion may attach (fuse or link) to a glycoprotein of a rodentaviridae virus (such as vesicular stomatitis virus New Jersey virus, vesicular stomatitis virus Indiana virus, vesicular stomatitis virus Aragos virus, vesicular stomatitis virus Malaba virus, vesicular stomatitis virus Kalapas virus, parainfluenza virus, fall armyworm rodentaviridae isolate Sf G, Drosophila sigmavirus 10A, Wuhan insect virus 7, perch virus, or carp spring viremia virus). In some embodiments, the VSV protein is a mutant protein, such as those provided herein. In some embodiments, the targeting portion attaches to a glycoprotein of a filoviridae virus (such as Ebola virus) or a glycoprotein of a arenaviridae virus (such as Machupo virus).

[0214] In some implementations, the target-binding domain is scFv. In some implementations, the target-binding domain is a single-domain antibody. In some implementations, the target-binding domain is VHH.

[0215] In some embodiments, the targeting portion binds to CD7, CD8, cKit (CD117), CD4, CD3, CD5, CD6, CD2, TCRα, TCRβ, TCRγ, TCRδ, CD10, CD34, CD110, CD33, CD14, CD68, CCR7, CD62L, CD25, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, or CXCR3; glycosylated CD43 epitopes expressed on acute leukemia or lymphoma but not on hematopoietic progenitor cells; glycosylated CD43 epitopes expressed on non-hematopoietic cancers; kinase-anchored protein 4 (AKAP-4); adrenaline receptor β3 (ADRB3); AFP; anaplastic lymphoma kinase (ALK); androgen receptor; angiopoietin-binding cell surface receptor 2 (Tie 2); Desmosome core protein 1 (Dsg1) autoantibody; Desmosome core protein 3 (Dsg3) autoantibody; B7H3 (CD276); Biotin; Bone marrow stromal cell antigen 2 (BST2); BST1 / CD157; Cancer / testis antigen 1 (NY-ESO-1); Cancer / testis antigen 2 (LAGE-la); Carbonic anhydrase IX (CA1X); Carcinoembryonic antigen (CEA); CCCTC binding factor (zinc finger protein)-like (BORIS or imprinting site regulatory factor-like protein); CCR4; CD5; CD19; CD20; CD22; CD24; CD30; CD32 (FCGR) 2A); CD33; CD34; CD38; CD44v6; CD72; CD79a; CD79b; CD97; CD99; CD123; CD171; CD179a; CD179b-IGL11; CD200R; CD276 / B7H3; CD300 molecular-like family member f (CD300LF); CDH1-CD324; CDH6; CDH17; CDH19; Chromosome X open reading frame 61 (CXORF61); Sealing protein 6 (CLDN6); Sealing protein l8.2 (CLD18A2 or CLDN18A.2); CMV pp65; C-MYC epitope tag; Cripto; CS1 (also known as CD2 subset 1 or CRACC or SLAMF7 or CD319 or 19A24); CSF2RA (GM-CSFR-α); C-type lectin domain family 12 member A (CLEC12A); C-type lectin-like molecule-1 (CLL-1 or CLECL1); Cyclin B1; Cytochrome P450 IB 1 (CYP1B 1); DLL3; EBV-EBNA3c; EGF-bke module mucin-like hormone receptor-like 2 (EMR2); Mutant elongation factor 2 (ELF2M); Hepatin B2; Hepatin A receptor 2 (EphA2); Epidermal growth factor receptor (EGFR);Epidermal growth factor receptor variant III (EGFRviii); Epithelial cell adhesion molecule (EPCAM); ERG; ETS translocation variant 6 located on chromosome 12p (ETV6-AML); Fc fragment of IgA receptor (FCAR or CD89); Fc receptor-like 5 (FCRL5); Fibroblast activation protein α (FAP); FITC; Fms-like tyrosine kinase 3 (FLT3); Folate receptor α (FRa or FR1); Folate receptor β (FRb); Follicle-stimulating hormone receptor (FSHR); Fos-associated antigen 1; Fucosylated GMO-GM1; G protein-coupled receptor class C group 5 member D (GPRC5D); G protein-coupled receptor 2 0 (GPR20); GAD; Ganglioside G2 (GD2); Ganglioside GD3 (aNeu5Ac(2-8)aNeu5Ac(2-3)bDGalp(l-4)bDGlcp(ll)Cer); Ganglioside GM3 (aNeu5Ac(2-3)bDClalp(l-4)bDGlcp(ll)Cer); GD3; GFRα4; Glycoprotein 100 (gplOO); Phosphatidylinositol proteoglycan-3 (GPC3); Gonadotropin receptor (CGHR or GR); GpA33; GpNMB; GPRC5D; Guanylate cyclase C (GCC); Mutant heat shock protein 70-2 (mut HSP70-2); Hepatitis A virus cell receptor 1 (HAVCR1); hexasaccharide moiety of globoH glycerol ceramide (GloboH); high molecular weight melanoma-associated antigen (HMWMAA); HIV1 envelope glycoprotein; HLA; HLA-DOA; HLA-A; HLA-A2; HLA-B; HLA-C; HLA-DM; HLA-DOB; HLA-DP; HLA-DQ; HLA-DR; HLA-G; HTLV1-Tax; Human papillomavirus E6 (HPV E6); Human papillomavirus E7 (HPV E7); Human telomerase reverse transcriptase (hTERT); IgE; IL13Ra2; IL1 lRa; Immunoglobulin λ-like polypeptide 1 (IGLL1); Influenza A hemagglutinin (HA); Insulin-like growth factor 1 receptor (IGF-I receptor); Interleukin 11 receptor α (IL-11Ra); Interleukin-13 receptor subunit α-2 (IL-13Ra2 or CD213A2); Intestinal carboxyl esterase; KIT (CD117); KSHV K8.1; KSHV-gH; LAMP1; pod protein; Leukocyte immunoglobulin-like receptor subfamily A member 2 (LILRA2); Leukocyte-associated immunoglobulin-like receptor 1 (LAIR1); Luteinizing hormone receptor (LHR); Lewis (Y) antigen; Lews Ag; Livl; Locus K9 (LY6K); Low-conductivity chloride channel; Lymphocyte antigen 6 complex;Lymphocyte antigen 75 (LY75); Lymphocyte-specific protein tyrosine kinase (LCK); Breast differentiation antigen (NY-BR-1); T-cell recognized melanoma antigen 1 (MelanA or MARTI); Melanoma-associated antigen 1 (MAGE-A1); Melanoma cancer testis antigen-1 (MAD-CT-1); Melanoma cancer testis antigen-2 (MAD-CT-2); Melanoma cell apoptosis inhibitor (ML-IAP); Mesothelin; MPL; Mucin 1 cell surface associated (MUC1); N-acetylglucosamine aminotransferase V (NA17); Adhesionin-4; Neural cell adhesion molecule (NCAM); NKG2D; NYBR1; O-acetyl... Acyl-GD2 ganglioside (OAcGD2); olfactory receptor 51E2 (OR51E2); oncogene fusion protein (bcr-abl) composed of breakpoint cluster region (BCR) and Abelson murine leukemia virus oncogene homolog 1 (Abl); P53 mutant; pairing box protein Pax-3 (PAX3); pairing box protein Pax-5 (PAX5); pan-connector protein 3 (PANX3); PDL1; P-glycoprotein; placenta-specific 1 (PLAC1); platelet-derived growth factor receptor β (PDGFR-β); polysialic acid; proapocrine-binding protein sp32 (OY-TES1); prostate enzyme; prostate cancer tumor antigen-1 (PCT) Al or galactose lectin 8); prostate stem cell antigen (PSCA); prostate-specific membrane antigen (PSMA); prostate acid phosphatase (PAP); prostaglandins; protease serine 21 (testin or PRSS21); proteasome macropain subunit β9 (LMP2); PTK7; Ras G12V; Ras homologous family member C (RhoC); rat sarcoma (Ras) mutant; receptor for advanced glycation end products (RAGE-1); receptor tyrosine kinase-like orphan receptor 1 (ROR1); receptor tyrosine protein kinase ERBB2 or Her-22 / neu; renal pervasive 1 (RU1); renal pervasive 2 (RU2); sarcoma translocation breakpoint; serine 2 (TMPRSS2) ETS fusion gene; sialic acid Lewis adhesion molecule (sLe); SLAMF4; SLAMF6; Slea (CA19) .9 or sialic acid Lewis antigen); spermin 17 (SPA17); T cell-recognized squamous cell carcinoma antigen 3 (SART3); stage-specific embryonic antigen-4 (SSEA-4); STEAP1; susceptin; synovial sarcoma X breakpoint 2 (SSX2); TCRγ alternating reading frame protein (TARP); TCR-β1 chain; TCR-β2 chain; TCR-δ chain; TCR-γ chain; TCRγ-δ; telomerase; TGFβR2; antigen recognized by TNT antibody; thyroid-stimulating hormone receptor (TSHR);Timl- / HVCR1; Tissue factor 1 (TF1); Tn ag; Tn antigen ((Tn Ag) or (GalNAca-Ser / Thr)); TNF receptor family member B cell maturation (BCMA); transglutaminase 5 (TGS5); transmembrane protease; TROP2; tumor endothelial marker 1 (TEM1 / CD248); tumor endothelial marker 7 associated (TEM7R); tumor protein p53 (p53); tumor-associated glycoprotein 72 (TAG72); tyrosinase; tyrosinase-associated protein 2 (TRP-2); plaque protein 2 (UPK2); vascular endothelial growth factor receptor 2 (VEGFR2); V-myc avian myeloma virus oncogene neuroblastoma-derived homolog (MYCN); Wilms' tumor protein (WT1); or X antigen family member 1A (XAGE1). In some embodiments, the targeting moiety binds to CD7. In some embodiments, the targeting moiety binds to CD8.

[0216] In some embodiments, the targeting portion binds to a target present on cells (such as immune cells). In some embodiments, the cells are immune cells, such as, but not limited to, T cells, B cells; NK cells, dendritic cells, neutrophils, macrophages, cancer cells; or, for example, CD3+ T cells; CD4+ T cells; CD7+ T cells, CD8+ T cells; CD19+ B cells; CD19+ cancer cells; CD20+ B cells; CD20+ cancer cells; CD30+ lung epithelial cells; CD34+ hematopoietic stem cells; CD105+ endothelial cells; CD105+ hematopoietic stem cells; CD117+ hematopoietic stem cells; CD133+ cancer cells; EpCAM+ cancer cells; GluA2+ neurons; GluA4+ neurons; hematopoietic stem cells; hepatocytes; Her2 / Neu+ cancer cells; NKG2D+ natural killer cells; SLC1A3+ astrocytes; SLC7A10+ adipocytes. In some embodiments, the cells are T cells. In some embodiments, the cells are B cells. In some implementations, the cells are CD7+ T cells and / or CD8+ T cells.

[0217] CD7-binding peptide

[0218] In some implementations, the targeting portion (e.g., a peptide) binds to CD7.

[0219] In some embodiments, the peptide binding to CD7 is an antibody binding to non-human primate CD7. In some embodiments, the peptide binding to CD7 is an antibody binding to human CD7. The sequence of human CD7 (UniProtKB P09564) is as follows (SEQ ID NO:29):

[0220] MAGPPRLLLLPLLLALARGLPGALAAQEVQQSPHCTTVPVGASVNITCSTSGGLRGIYLRQLGPQPQDIIYYEDGVVPTTDRRFRGRIDFSGSQDNLTITMHRLQLSDTGTYTCQAITEVNV YGSGTLVLVTEEQSQGWHRCSDAPPRASALPAPPTGSALPDPQTASALPDPPAASALPAALAVISFLLGLGVACVLARTQIKKLCSWRDKNSAACVVYEDMSHSRCNTLSSPNQYQ(SEQ ID NO:29).

[0221] In some embodiments, the CD7 bound by the peptide is expressed on the cell surface. In some embodiments, the cells are immune cells. In some embodiments, the immune 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, bone marrow cells, monocytes, macrophages, central memory T cells, effector memory T cells, stem cell-like memory T cells, native 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+.

[0222] In some embodiments, the antibody includes an Fc region. The Fc region may be linked to either the heavy or light chain of the antibody. In some embodiments, the Fc region is an IgG Fc. In some embodiments, the IgG is selected from IgG1, IgG2, IgG3, or IgG4. In some embodiments, the IgG fc is an IgG1 Fc. In some embodiments, the antibody includes a constant Fc region as described herein, such as SEQ ID NO:26, 27, or 28 or mutants thereof provided herein.

[0223] In some embodiments, this document provides a peptide (e.g., a CD7-binding peptide). In some embodiments, this document provides an antibody (e.g., an anti-CD7 antibody). In some embodiments, the antibody is a recombinant antibody that binds to CD7. In some embodiments, the CD7 protein is the human CD7 protein. In some embodiments, the CD7 protein is a non-human CD7 protein (e.g., mouse, rat, pig, dog, non-human primate). As used herein, the term "recombinant antibody" refers to an antibody that is not naturally occurring. In some embodiments, the term "recombinant antibody" refers to an antibody that has not been isolated from a human subject.

[0224] In some embodiments, an antibody or antigen-binding fragment thereof is provided, wherein the antibody or antibody fragment comprises a peptide selected from the table below, which clarifies a CDR based on Kabat numbering.

[0225]

[0226]

[0227] In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises a heavy chain or light chain CDR as provided in the table above. In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises a heavy chain or light chain CDR as provided in the table above and binds to non-human primate CD7. In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises a heavy chain or light chain CDR as provided in the table above and binds to human CD7. In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises a light chain CDR having a sequence selected from SEQ ID NO:33-35. In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises a light chain CDR having a sequence selected from SEQ ID NO:33. In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises a light chain CDR having a sequence selected from SEQ ID NO:34. In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises a light chain CDR having a sequence selected from SEQ ID NO:35. In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises a heavy chain CDR having a sequence selected from SEQ ID NO:30-32. In some embodiments, the peptide, antibody, or antibody-binding fragment thereof comprises a heavy chain CDR having the sequence of SEQ ID NO:30. In some embodiments, the peptide, antibody, or antibody-binding fragment thereof comprises a heavy chain CDR having the sequence of SEQ ID NO:31. In some embodiments, the peptide, antibody, or antibody-binding fragment thereof comprises a heavy chain CDR having the sequence of SEQ ID NO:32. The CDRs mentioned throughout the embodiments of this specification are interchangeable with CDRs characterized by different forms (such as Chothia and IMGT).

[0228] In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises a light chain variable region having LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the sequence of SEQ ID NO:33, LCDR2 has the sequence of SEQ ID NO:34, and LCDR3 has the sequence of SEQ ID NO:35.

[0229] In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises a heavy chain variable region having HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the sequence of SEQ ID NO:30, HCDR2 has the sequence of SEQ ID NO:31, and HCDR3 has the sequence of SEQ ID NO:32.

[0230] In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises: (i) a light chain having any of the aforementioned combinations of LCDR1, LCDR2, and LCDR3 sequences; and (ii) a heavy chain having any of the aforementioned combinations of HCDR1, HCDR2, and HCDR3 sequences.

[0231] Different CDR motifs can be combined in any combination, including those not depicted in the table above. For example, the following embodiments are provided as non-limiting examples of such combinations.

[0232] In some embodiments, the polypeptide, antibody, or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence of SEQ ID NO:33; the light chain CDR2 has the amino acid sequence of SEQ ID NO:34; 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; and the heavy chain CDR3 sequence has the amino acid sequence of SEQ ID NO:32; or a variation thereof.

[0233] Although the preceding paragraphs may refer to the CDR according to the Kabat system, equivalent CDR sequences from the names IMGT and CHOTHIA can be used.

[0234] In some embodiments, the light chain variable region CDR1 is replaced by any other light chain CDR1 sequence. In some embodiments, the light chain variable region CDR2 is replaced by any other light chain CDR2 sequence. In some embodiments, the light chain variable region CDR3 is replaced by any other light chain CDR3 sequence. In some embodiments, the heavy chain variable region CDR1 is replaced by any other heavy chain CDR1 sequence. In some embodiments, the heavy chain variable region CDR2 is replaced by any other heavy chain CDR2 sequence. In some embodiments, the heavy chain variable region CDR3 is replaced by any other heavy chain CDR3 sequence.

[0235] In some embodiments, the polypeptide comprises a heavy chain variable region peptide or a variant thereof having one of the following sequences:

[0236]

[0237] In some embodiments, the polypeptide comprises a light chain variable region peptide or a variant thereof having one of the following sequences:

[0238]

[0239] In some embodiments, the polypeptide, antibody, or antigen-binding fragment thereof comprises V of SEQ ID NO:36. H Peptide. In some embodiments, the polypeptide, antibody, or antigen-binding fragment thereof comprises V of SEQ ID NO:37. L Peptide. In some embodiments, the polypeptide, antibody, or antigen-binding fragment thereof contains V. H Peptides and Vitamins L peptide, wherein the V H The peptide contains the sequence of SEQ ID NO:36 or a variant thereof; and the 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 contains V H Peptides and Vitamins L peptide, wherein the V H The peptide contains the sequence of SEQ ID NO:36 or a variant thereof; and the 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 non-human primate CD7. In some embodiments, the polypeptide, antibody, or antigen-binding fragment thereof comprises V H Peptides and Vitamins L peptide, wherein the V H The peptide contains the sequence of SEQ ID NO:36 or a variant thereof; and the V L The peptide comprises the sequence of SEQ ID NO:37 or a variant thereof, and the polypeptide, antibody, or antigen-binding fragment thereof binds to human CD7. In some embodiments, the V H The peptide contains the sequence of SEQ ID NO:36; and the V L The peptide contains the sequence of SEQ ID NO:37.

[0240] V H and V L The sequence can be in any form, including but not limited to the scFv form, where V H and V LThe regions are linked using peptide linkers. Examples of peptide linkers that can be used to link the various peptides described herein include, but are not limited to: (GGGGS) n (SEQ ID NO:55), where each n is independently 1-5. 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 with a peptide linker. In some embodiments, the polypeptide comprises SEQ ID NO:36 and SEQ ID NO:37.

[0241] As provided herein, peptides, antibodies, or antigen-binding fragments thereof may be variants of the sequences described.

[0242] The sequence of a peptide or antibody can be modified to generate human IgG antibodies. Transformations of the sequences provided herein can be modified to generate other types of antibodies. The CDR can also be linked to other antibodies, proteins, or molecules to produce antibody fragments that bind to CD7.

[0243] In some embodiments, the peptides or antibodies provided herein are targeting portions on the surface of engineered viral particles. In some embodiments, the targeting portion allows binding to target cells. In some embodiments, the targeting portion is a CD7 binding portion, such as the peptides or antibodies provided herein. In some embodiments, the target-binding domain (“T”) comprises the sequence of SEQ ID NO:38:

[0244] DILLTQSPAILSVSPGERVSFSCRASQSIGTSIHWYQQRTNDSPRLLIKYASESISGIPSRFSGSGSGTDFTLSINSVESEDIADYYCQQSNSWPTTFGGGTKLEIKRGGGGSGGGGSGGGGSGGG GSQVQLQQPGAELVKPGASVKLSCKASGYPFTSYWIHWVKQRPGRGLEWLGRIDPNSGDTKYNEKFKNKATLTVDKSSTTAYMQLSSLTSEDSAVYYCARSPYYSNDNSMDYWGQGTSVTVSS(SEQ ID NO:38)

[0245] At least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence is identical to or substantially similar to or is the active fragment of SEQ ID NO:38. In some embodiments, the target-binding domain (“T”) comprises a sequence that is at least 90% identical to the sequence of SEQ ID NO:38. In some embodiments, the target-binding domain (“T”) comprises a sequence that is at least 95% identical to the sequence of SEQ ID NO:38. In some embodiments, the target-binding domain (“T”) comprises a sequence that is at least 99% identical to the sequence of SEQ ID NO:38. In some embodiments, the target-binding domain (“T”) comprises the sequence as described in SEQ ID NO:38. In some embodiments, the target-binding domain (“T”) as described in SEQ ID NO:38 is an antibody or its antigen-binding fragment. In some implementations, the target-binding domain (“T”) is an anti-CD7 antibody.

[0246] In some embodiments, the peptides or antibodies provided herein are targeting portions on the surface of engineered viral particles. In some embodiments, the engineered viral particles are pseudovirus-like particles. In some embodiments, the targeting portion allows binding to target cells. In some embodiments, the targeting portion is a CD7 binding portion, such as the peptides or antibodies provided herein. In some embodiments, the target-binding domain (“T”) comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO:39. In some embodiments, the target-binding domain (“T”) comprises a sequence identical to the sequence of SEQ ID NO:39.

[0247] QVQLQQPGAELVKPGASVKLSCKASGYPFTSYWIHWVKQRPGRGLEWLGRIDPNSGDTKYNEKFKNKATLTVDKSSTTAYMQLSSLTSEDSAVYYCARSPYYSNDNSMDYWGQGTSVTVSSGGGGS GGGGSGGGGSGGGGSDILLTQSPAILSVSPGERVSFSCRASQSIGTSIHWYQQRTNDSPRLLIKYASESISGIPSRFSGSGSGTDFTLSINSVESEDIADYYCQQSNSWPTTFGGGTKLEIKR(SEQ ID NO:39)

[0248] The sequence is at least 90% identical to or substantially similar to or a fragment of the active fragment of SEQ ID NO:39. In some embodiments, the target-binding domain (“T”) comprises a sequence at least 95% identical to the sequence of SEQ ID NO:39. In some embodiments, the target-binding domain (“T”) comprises a sequence at least 99% identical to the sequence of SEQ ID NO:39. In some embodiments, the target-binding domain (“T”) comprises the sequence as described in SEQ ID NO:39. In some embodiments, the target-binding domain (“T”) as 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.

[0249] CD8-binding peptide

[0250] In some implementations, the targeting portion (e.g., a peptide) may bind to CD8.

[0251] In some embodiments, the polypeptide binds to CD8. In some embodiments, the polypeptide binds to CD8-α. In some embodiments, the polypeptide binds to CD8-β. In some embodiments, the polypeptide binds to a CD8 heterodimer. In some embodiments, the CD8 heterodimer comprises CD8-α and CD8-β subunits. In some embodiments, the polypeptide binds to a CD8-α homodimer. In some embodiments, the polypeptide binding to CD8 is an antibody binding to non-human primate CD8. In some embodiments, the antibody binding to non-human primate CD8 is an antibody binding to non-human primate CD8-α. In some embodiments, the antibody binding to non-human primate CD8 is an antibody binding to non-human primate CD8-β. In some embodiments, the antibody binding to non-human primate CD8 is an antibody binding to non-human primate CD8-α homodimer. In some embodiments, the antibody binding to non-human primate CD8 is an antibody binding to a non-human primate CD8 heterodimer. In some embodiments, the peptide binding to CD8 is an antibody binding to human CD8. In some embodiments, the antibody binding to human CD8 is an antibody binding to human CD8-α. In some embodiments, the antibody binding to human CD8 is an antibody binding to human CD8-β. In some embodiments, the antibody binding to human CD8 is an antibody binding to a human CD8-α homodimer. In some embodiments, the antibody binding to human CD8 is an antibody binding to a human CD8 heterodimer. The sequence of human CD8-α (UniProtKB Q8TAW8) is as follows (SEQ ID NO:40):

[0252] MALPPVTALLLPLALLLHAARPSQFRVSPLDRTWNLGETVELKCQVLLSNPTSGCSWLFQPRGAAASPTFLLYLSQNKPKAAEGLDTQRFSGKRLGDTFVLTLSDFRRENEGCYFCSALS NSIMYFSHFVPVFLPAKPTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCNHRNRRRVCKCPRPVVKSGDKPSLSARYV(SEQ ID NO:40).

[0253] The sequence of human CD8-β (UniProtKB Q8TD28) is as follows (SEQ ID NO:41):

[0254] MRPRLWLLLAAQLTVLHGNSVLQQTPAYIKVQTNKMVMLSCEAKISLSNMRIYWLRQRQAPSSDSHHEFLALWDSAKGTIHGEEVEQEKIAVFRDASRFILNLTSVK PEDSGIYFCMIVGSPELTFGKGTQLSVVDFLPTTAQPTKKSTLKKRVCRLPRPETQKGPLCSPITLGLLVAGVLVLLVSLGVAIHLCCRRRRARLRFMKQLYK(SEQ ID NO:41).

[0255] In some embodiments, the CD8 bound by the peptide is expressed on the cell surface. In some embodiments, the cells are immune cells. In some embodiments, the immune 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, bone marrow cells, monocytes, macrophages, central memory T cells, effector memory T cells, stem cell-like memory T cells, native 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+. In some embodiments, the cells are CD8+ T cells. In some embodiments, the cells are CD8+ cells.

[0256] In some embodiments, the antibody includes an Fc region. The Fc region may be linked to either the heavy or light chain of the antibody. In some embodiments, the Fc region is an IgG Fc. In some embodiments, the IgG is selected from IgG1, IgG2, IgG3, or IgG4. In some embodiments, the IgG Fc is an IgG1 Fc. In some embodiments, the antibody includes a constant Fc region as described herein, such as SEQ ID NO: 26, 27, or 28, or a mutant thereof.

[0257] In some embodiments, this document provides a peptide (e.g., a CD8-binding peptide). In some embodiments, this document provides an antibody (e.g., an anti-CD8 antibody). In some embodiments, the antibody is a recombinant antibody that binds to CD8. In some embodiments, the CD8 protein is a human CD8 protein. In some embodiments, the CD8 protein is a non-human CD8 protein (e.g., mouse, rat, pig, dog, non-human primate). As used herein, the term "recombinant antibody" refers to an antibody that is not naturally occurring. In some embodiments, the term "recombinant antibody" refers to an antibody that has not been isolated from a human subject.

[0258] In some embodiments, an antibody or antigen-binding fragment thereof is provided, wherein the antibody or antibody fragment comprises a peptide selected from the table below, which clarifies a CDR based on Kabat numbering.

[0259]

[0260] In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises a heavy chain or light chain CDR as provided in the table above. In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises a heavy chain or light chain CDR as provided in the table above and binds to non-human primate CD8. In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises a heavy chain or light chain CDR as provided in the table above and binds to human CD8. In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises a light chain CDR having a sequence selected from SEQ ID NO:45-47. In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises a light chain CDR having a sequence selected from SEQ ID NO:45. In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises a light chain CDR having a sequence selected from SEQ ID NO:46. In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises a light chain CDR having a sequence selected from SEQ ID NO:47. In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises a heavy chain CDR having a sequence selected from SEQ ID NO:42-44. In some embodiments, the peptide, antibody, or antibody-binding fragment thereof comprises a heavy chain CDR having the sequence of SEQ ID NO:42. In some embodiments, the peptide, antibody, or antibody-binding fragment thereof comprises a heavy chain CDR having the sequence of SEQ ID NO:43. In some embodiments, the peptide, antibody, or antibody-binding fragment thereof comprises a heavy chain CDR having the sequence of SEQ ID NO:44. The CDRs mentioned throughout the embodiments of this specification are interchangeable with CDRs characterized by different forms (such as Chothia and IMGT).

[0261] In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises a light chain variable region having LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the sequence of SEQ ID NO:45, LCDR2 has the sequence of SEQ ID NO:46, and LCDR3 has the sequence of SEQ ID NO:47.

[0262] In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises a heavy chain variable region having HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the sequence of SEQ ID NO:42, HCDR2 has the sequence of SEQ ID NO:43, and HCDR3 has the sequence of SEQ ID NO:44.

[0263] In some embodiments, the polypeptide, antibody, or antibody-binding fragment thereof comprises: (i) a light chain having any of the aforementioned combinations of LCDR1, LCDR2, and LCDR3 sequences; and (ii) a heavy chain having any of the aforementioned combinations of HCDR1, HCDR2, and HCDR3 sequences.

[0264] Different CDR motifs can be combined in any combination, including those not depicted in the table above. For example, the following embodiments are provided as non-limiting examples of such combinations.

[0265] In some embodiments, the polypeptide, antibody, or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence of SEQ ID NO:45; the light chain CDR2 has the amino acid sequence of SEQ ID NO:46; 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; and the heavy chain CDR3 sequence has the amino acid sequence of SEQ ID NO:44; or variations thereof.

[0266] Although the preceding paragraphs may refer to the CDR according to the Kabat system, equivalent CDR sequences from the names IMGT and CHOTHIA can be used.

[0267] In some embodiments, the light chain variable region CDR1 is replaced by any other light chain CDR1 sequence. In some embodiments, the light chain variable region CDR2 is replaced by any other light chain CDR2 sequence. In some embodiments, the light chain variable region CDR3 is replaced by any other light chain CDR3 sequence. In some embodiments, the heavy chain variable region CDR1 is replaced by any other heavy chain CDR1 sequence. In some embodiments, the heavy chain variable region CDR2 is replaced by any other heavy chain CDR2 sequence. In some embodiments, the heavy chain variable region CDR3 is replaced by any other heavy chain CDR3 sequence.

[0268] In some embodiments, the polypeptide comprises a heavy chain variable region peptide or a variant thereof having one of the following sequences:

[0269]

[0270] In some embodiments, the polypeptide comprises a light chain variable region peptide or a variant thereof having one of the following sequences:

[0271]

[0272] In some embodiments, the polypeptide, antibody, or antigen-binding fragment thereof comprises V of SEQ ID NO:48. H Peptide. In some embodiments, the polypeptide, antibody, or antigen-binding fragment thereof comprises V of SEQ ID NO:49. L Peptide. In some embodiments, the polypeptide, antibody, or antigen-binding fragment thereof contains V. H Peptides and Vitamins L peptide, wherein the V H The peptide contains the sequence of SEQ ID NO:48 or a variant thereof; and the 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 contains V H Peptides and Vitamins L peptide, wherein the V H The peptide contains the sequence of SEQ ID NO:48 or a variant thereof; and the V L The peptide comprises the sequence of SEQ ID NO:49 or a variant thereof, and the polypeptide, antibody, or antigen-binding fragment thereof binds to non-human primate CD8. In some embodiments, the polypeptide, antibody, or antigen-binding fragment thereof comprises V H Peptides and Vitamins L peptide, wherein the V H The peptide contains the sequence of SEQ ID NO:48 or a variant thereof; and the 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, the V H The peptide contains the sequence of SEQ ID NO:48; and the V L The peptide contains the sequence of SEQ ID NO:49.

[0273] V H and V L The sequence can be in any form, including but not limited to the scFv form, where V H and V LThe 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 1-5. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 3. In some embodiments, n is 4. In some embodiments, n is 5. In some embodiments, the variable regions are not linked by peptide linkers. In some embodiments, the polypeptide comprises SEQ ID NO:48 and SEQ ID NO:49.

[0274] As provided herein, peptides, antibodies, or antigen-binding fragments thereof may be variants of the sequences described.

[0275] The sequence of a peptide or antibody can be modified to generate human IgG antibodies. Transformations of the sequences provided herein can be modified to generate other types of antibodies. The CDR can also be linked to other antibodies, proteins, or molecules to produce antibody fragments that bind to CD8.

[0276] In some embodiments, the peptide or antibody provided herein is a targeting portion on the surface of an engineered viral particle. In some embodiments, the targeting portion allows binding to target cells. In some embodiments, the target-binding domain (“T”) is a CD8 binding portion, such as the peptide or antibody provided herein. In some embodiments, the target-binding domain (“T”) comprises the sequence of SEQ ID NO:50:

[0277] NIVLTQSPASLAVSLGQRATISCRASESVDGFGNSFMNWYQQKPGQSPKLLIYLASNLESGVPARFSGSGSRTDFTLTIDPVEADDAATYYCQQNNEDPYTFGGGTKLEIKRGGGGSGGGGSGGGGSG GGGSEVQLQQSGPELVKPGASVKISCKASRYTFTDYNLHWVKLSHEKSLEWIGFIYPYNGGTGYNQKFKNKAKLTVDYSSSTAYMELRSLTSVDAAVYYCARDHRYNEGVSFDYWGQGTTLTVSS(SEQ ID NO:50)

[0278] At least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence is identical to or substantially similar to or is the active fragment of SEQ ID NO:50. In some embodiments, the target-binding domain (“T”) comprises a sequence that is at least 90% identical to the sequence of SEQ ID NO:50. In some embodiments, the target-binding domain (“T”) comprises a sequence that is at least 95% identical to the sequence of SEQ ID NO:50. In some embodiments, the target-binding domain (“T”) comprises a sequence that is at least 99% identical to the sequence of SEQ ID NO:50. In some embodiments, the target-binding domain (“T”) comprises the sequence as described in SEQ ID NO:50. In some embodiments, the target-binding domain (“T”) as described in SEQ ID NO:50 is an antibody or its antigen-binding fragment. In some implementations, the targeting portion is an anti-CD8 antibody.

[0279] In some embodiments, the peptide or antibody provided herein is a targeting portion on the surface of an engineered viral particle. In some embodiments, the engineered viral particle is a pseudovirus-like particle. In some embodiments, the targeting portion allows binding to target cells. In some embodiments, the target-binding domain (“T”) is a CD8 binding portion, such as the peptide or antibody provided herein. In some embodiments, the target-binding domain (“T”) comprises the sequence of SEQ ID NO:51:

[0280] EVQLQQSGPELVKPGASVKISCKASRYTFTDYNLHWVKLSHEKSLEWIGFIYPYNGGTGYNQKFKNKAKLTVDYSSSTAYMELRSLTSVDAAVYYCARDHRYNEGVSFDYWGQGTTLTVSSGGGGSGG GGSGGGGSGGGGSNIVLTQSPASLAVSLGQRATISCRASESVDGFGNSFMNWYQQKPGQSPKLLIYLASNLESGVPARFSGSGSRTDFTLTIDPVEADDAATYYCQQNNEDPYTFGGGTKLEIKR(SEQ ID NO:51)

[0281] At least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence is identical to or substantially similar to or is the active fragment of SEQ ID NO:51. In some embodiments, the target-binding domain (“T”) comprises a sequence that is at least 90% identical to the sequence of SEQ ID NO:51. In some embodiments, the target-binding domain (“T”) comprises a sequence that is at least 95% identical to the sequence of SEQ ID NO:51. In some embodiments, the target-binding domain (“T”) comprises a sequence that is at least 99% identical to the sequence of SEQ ID NO:51. In some embodiments, the target-binding domain (“T”) comprises the sequence as described in SEQ ID NO:51. In some embodiments, the target-binding domain (“T”) as described in SEQ ID NO:51 is an antibody or its antigen-binding fragment. 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.

[0282] Target portion containing Fc domain

[0283] In some implementation schemes, V H and V LThe polypeptide is linked to a stem 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 as provided herein. Non-restrictive mutations of the Fc region are provided herein. In some embodiments, the variant Fc region comprises a sequence as a variant of SEQ ID NO:26, SEQ ID NO:27, or SEQ ID NO:28 as provided herein. 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 as provided herein. In some embodiments, the variant of SEQ ID NO:27 comprises one or more mutations selected from the group consisting of N297A, P329G, I253A, H310A, and H435A as 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 as 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 a linker as provided herein or is absent, Fc is a variant Fc region as provided herein, L2 is a linker as provided herein or is absent, and X1 is a polypeptide comprising the transmembrane domain as provided herein. As provided herein, X1 may comprise a peptide having the formula ECD-T M -ICD polypeptides, wherein ECD is an extracellular domain or fragment thereof as provided herein, or is absent, T M The transmembrane domain is as described herein, and the ICD is an intracellular domain as described herein or is absent. Examples of ECDs include, but are not limited to, the CD8 and / or CD28 extracellular domains as described herein. M Examples include, but are not limited to, CD8 and / or CD28 transmembrane domains as provided herein. In some embodiments, X1 includes T M Furthermore, ECD and ICD are not present. In some implementations, X1 includes ECD and T. M And ICD does not exist. In some implementations, X1 includes T. M And ICD but ECD is not present. In some implementations, X1 includes ECD, T MAnd ICD. In any of the following embodiments, it should be understood that ECD, ICD, or both may optionally be absent. Thus, X1 comprises CD8 and / or CD28 ECD, CD8 and / or CD28 T. M And implementations of ICDs containing Env-doped motifs should be understood to cover the following X1 members: i) CD8 and / or CD28 ECD, CD8 and / or CD28 T M and ICDs containing Env-doped motifs; ii) CD8 and / or CD28 T M and ICDs containing Env-doped motifs, wherein ECDs are absent; iii) CD8 and / or CD28 ECDs and CD8 and / or CD28 TCDs. M Where ICD is absent; and iv) CD8 and / or CD28 T M In this case, neither ECD nor ICD exists. Similarly, X1 contains CD8 and / or CD28 T. M Implementations of ICDs containing Env-doped motifs should be understood to encompass the following X1 members: i) CD8 and / or CD28 T M and ICDs containing Env-doped motifs; and ii) CD8 and / or CD28T M Where ICD is absent. Similarly, where X1 contains CD8 and / or CD28 ECD and CD8 and / or CD28 T. M The implementation scheme should be understood to cover the following X1 members: i) CD8 and / or CD28 ECD and CD8 and / or CD28 T M ; and ii) CD8 and / or CD28T M The ECD is not present. It should be further understood that the previous explanation did not describe a specific ECD or T. M The implementation scheme of the ICD is also correct. For example, where X1 includes an ECD, CD8, and / or CD28 T. M The implementation scheme of ICD should be understood to cover the following X1 members: i) ECD, CD8 and / or CD28 T M and ICD; ii) ECD, CD8 and / or CD28 T M iii) CD8 and / or CD28 T M And ICD, where ECD is absent; and iv) CD8 and / or CD28 T M In this case, neither ECD nor ICD exists. Similarly, X1 contains CD8 and / or CD28 T. M The implementation scheme of ICD should be understood to cover the following X1 members: i) CD8 and / or CD28T Mand ICD; ii) CD8 and / or CD28T M Where ICD is absent. Similarly, where X1 contains ECD as well as CD8 and / or CD28T. M The implementation scheme should be understood to cover the following X1 members: i) ECD and CD8 and / or CD28 T M ; and ii) CD8 and / or CD28T M Where ECD does not exist. Unless otherwise stated, the previous examples and explanations are applicable to any of the following implementations.

[0284] In some implementations, X1 includes CD8 and / or CD28 ECD, T M And ICD. In some implementations, X1 includes an ECD, CD8, and / or CD28 T. M And an ICD. In some implementations, X1 includes a CD8 and / or CD28 ECD, a CD8 and / or CD28 TCD. M And ICD. In some implementations, X1 includes ECD, T M and ICD, wherein the ICD contains env-incorporated motifs as provided herein. In some embodiments, X1 contains CD8 and / or CD28 ECD, T M And an ICD, wherein the ICD contains an env-incorporated motif as provided herein. In some embodiments, X1 comprises an ECD, CD8, and / or CD28 T. M And an ICD, wherein the ICD contains an env-incorporated motif as provided herein. In some embodiments, X1 comprises CD8 and / or CD28 ECD, CD8 and / or CD28 TCD. M And ICD, where ICD contains env-incorporated motifs as provided in this paper.

[0285] In some implementations, the V provided herein H and V L The polypeptide is linked to a stem portion (S1) containing the Fc region as described herein. In some embodiments, the V... H and V L A polypeptide is linked to a stem portion (S1) containing an Fc region comprising a transmembrane domain as 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 as provided herein or is absent, Fc is a variant Fc region as provided herein, L2 is a linker as provided herein or is absent, and X1 is a polypeptide comprising a transmembrane domain as provided herein. As provided herein, X1 may comprise a peptide having the formula ECD-T M-ICD polypeptides, wherein ECD is an extracellular domain or fragment thereof as provided herein, or is absent, T M The ICD is a transmembrane domain as described herein, and the intracellular domain as described herein or is absent. In some embodiments, the V provided herein... H and V L The polypeptide is linked to a stem portion (S1) containing an Fc region (L1-Fc-L2-X1), the Fc region comprising CD8 and / or CD28 ECD, T M And ICD. In some implementations, the V provided herein H and V L The polypeptide is linked to a stem portion (S1) containing an Fc region (L1-Fc-L2-X1), the Fc region comprising ECD, CD8, and / or CD28 T. M And ICD. In some implementations, the V provided herein H and V L The polypeptide is linked to a stem portion (S1) containing an Fc region (L1-Fc-L2-X1), the Fc region comprising CD8 and / or CD28 ECD, CD8 and / or CD28 T. M And ICD. In some implementations, the V provided herein H and V L The polypeptide is linked to a stem portion (S1) containing an Fc region (L1-Fc-L2-X1), the Fc region comprising ECD, T... M and ICD, wherein the ICD contains env-incorporated motifs as provided herein. In some embodiments, the V provided herein H and V L The polypeptide is linked to a stem portion (S1) containing an Fc region (L1-Fc-L2-X1), the Fc region comprising CD8 and / or CD28 ECD, T M And an ICD, wherein the ICD contains an env-incorporated motif as provided herein. In some embodiments, the V provided herein... H and V L The polypeptide is linked to a stem portion (S1) containing an Fc region (L1-Fc-L2-X1), the Fc region comprising ECD, CD8, and / or CD28 T. M And an ICD, wherein the ICD contains an env-incorporated motif as provided herein. In some embodiments, the V provided herein... H and V L The polypeptide is linked to a stem portion (S1) containing an Fc region (L1-Fc-L2-X1), the Fc region comprising CD8 and / or CD28 ECD, CD8 and / or CD28 T. MAnd an ICD, wherein the ICD contains an env-incorporated motif as provided herein. In some embodiments, the V provided herein... H and V L The polypeptide is linked to a stem portion (S1) containing an Fc region (L1-Fc-L2-X1), the Fc region comprising ECD, T... M And ICD, the polypeptide is anchored to 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 as provided herein. In some implementations, the V... H and V L Peptides bind to immune cells, such as those described in this article.

[0286] In some implementations, V having a sequence such as SEQ ID NO:36 H peptides and V having the sequence shown in SEQ ID NO:37 L The peptide is linked to a stem portion (S1) containing an Fc region (L1-Fc-L2-X1), the Fc region comprising ECD, T... M and ICD. In some embodiments, V having a sequence such as SEQ ID NO:36 H peptides and V having the sequence shown in SEQ ID NO:37 L The peptide is linked to a stem portion (S1) containing an Fc region (L1-Fc-L2-X1), the Fc region comprising CD8 and / or CD28ECD, T M And ICD. In some embodiments, V having a sequence such as SEQ ID NO:36 H peptides and V having the sequence shown in SEQ ID NO:37 L The peptide is linked to a stem portion (S1) containing an Fc region (L1-Fc-L2-X1), the Fc region comprising ECD, CD8, and / or CD28 T. M And ICD. In some embodiments, V having a sequence such as SEQ ID NO:36 H peptides and V having the sequence shown in SEQ ID NO:37 L The peptide is linked to a stem portion (S1) containing an Fc region (L1-Fc-L2-X1), the Fc region comprising CD8 and / or CD28 ECD, CD8 and / or CD28 T. M And ICD. In some embodiments, V having a sequence as shown in SEQ ID NO:36 H peptides and V having the sequence shown in SEQ ID NO:37 LThe peptide is linked to a stem portion (S1) containing an Fc region (L1-Fc-L2-X1), the Fc region comprising ECD, T... M and ICD, wherein the ICD contains an env-incorporated motif as provided herein. In some embodiments, V having a sequence as shown in SEQ ID NO:36 H peptides and V having the sequence shown in SEQ ID NO:37 L The peptide is linked to a stem portion (S1) containing an Fc region (L1-Fc-L2-X1), the Fc region comprising CD8 and / or CD28 ECD, T M And an ICD, wherein the ICD contains an env-incorporated motif as provided herein. In some embodiments, a V having a sequence as shown in SEQ ID NO:36 H peptides and V having the sequence shown in SEQ ID NO:37 L The peptide is linked to a stem portion (S1) containing an Fc region (L1-Fc-L2-X1), the Fc region comprising ECD, CD8, and / or CD28 T. M And an ICD, wherein the ICD contains an env-incorporated motif as provided herein. In some embodiments, a V having a sequence as shown in SEQ ID NO:36 H peptides and V having the sequence shown in SEQ ID NO:37 L The peptide is linked to a stem portion (S1) containing an Fc region (L1-Fc-L2-X1), the Fc region comprising CD8 and / or CD28 ECD, CD8 and / or CD28 T. M And an ICD, wherein the ICD contains an env-incorporated motif as provided herein. In some embodiments, a V having a sequence as shown in SEQ ID NO:36 H peptides and V having the sequence shown in SEQ ID NO:37 L The peptide is linked to a stem portion (S1) containing an Fc region (L1-Fc-L2-X1), the Fc region comprising ECD, T... M And ICD, the peptide is anchored to 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 as provided herein. In some implementations, the V... H and V L Peptides bind to immune cells, such as those described in this article.

[0287] 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 at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence identical to the sequence of SEQ ID NO:37. L The peptide is linked to a stem portion (S1) comprising the Fc region as provided herein. In some embodiments, the V contains at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence identical to that of SEQ ID NO:36. H Peptide; and V containing at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence identical to the sequence of SEQ ID NO:37. L A peptide is linked to a stem portion (S1) containing an Fc region comprising a transmembrane domain as described herein. In some embodiments, the Fc region further comprising a transmembrane domain has the formula L1-Fc-L2-X1, wherein L1 is a linker as described herein or Fc is a variant Fc region as described herein, L2 is a linker as described herein or is absent, and X1 is a polypeptide comprising a transmembrane domain as described herein. As provided herein, X1 may comprise a peptide having the formula ECD-T M -ICD polypeptides, wherein ECD is an extracellular domain or fragment thereof as provided herein, or is absent, T M The transmembrane domain is as described herein, and the ICD is an intracellular domain as described herein or is absent. In some embodiments, V comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO:36. H Peptide; and V containing at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence identical to the sequence of SEQ ID NO: 37. L The peptide is linked to a stem portion (S1) containing an Fc region (L1-Fc-L2-X1), the Fc region comprising ECD, T... MAnd 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 SEQ ID NO:36. H Peptide; and V containing at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence identical to the sequence of SEQ ID NO:37. L The peptide is linked to a stem portion (S1) containing an Fc region (L1-Fc-L2-X1), the Fc region comprising CD8 and / or CD28 ECD, T M And 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 SEQ ID NO: 36. H Peptide; and V containing at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence identical to the sequence of SEQ ID NO:37. L The peptide is linked to a stem portion (S1) containing an Fc region (L1-Fc-L2-X1), the Fc region comprising ECD, CD8, and / or CD28 T. M And 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 SEQ ID NO:36. H Peptide; and V containing at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence identical to the sequence of SEQ ID NO: 37. L The peptide is linked to a stem portion (S1) containing an Fc region (L1-Fc-L2-X1), the Fc region comprising CD8 and / or CD28 ECD, CD8 and / or CD28 T. M And 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 SEQ ID NO:36. HPeptide; and V containing at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence identical to the sequence of SEQ ID NO:37. L The peptide is linked to a stem portion (S1) containing an Fc region (L1-Fc-L2-X1), the Fc region comprising ECD, T... M And an ICD, wherein the ICD contains an env-incorporated motif as provided herein. In some embodiments, the V comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO:36. H Peptide; and V containing at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence identical to the sequence of SEQ ID NO:37. L The peptide is linked to a stem portion (S1) containing an Fc region (L1-Fc-L2-X1), the Fc region comprising CD8 and / or CD28 ECD, T M And an ICD, wherein the ICD contains an env-incorporated motif as 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 SEQ ID NO:36. H Peptide; and V containing at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence identical to the sequence of SEQ ID NO:37. L The peptide is linked to a stem portion (S1) containing an Fc region (L1-Fc-L2-X1), the Fc region comprising ECD, CD8, and / or CD28 T. M And an ICD, wherein the ICD contains an env-incorporated motif as 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 SEQ ID NO:36. H Peptide; and V containing at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence identical to the sequence of SEQ ID NO: 37.L The peptide is linked to a stem portion (S1) containing an Fc region (L1-Fc-L2-X1), the Fc region comprising CD8 and / or CD28 ECD, CD8 and / or CD28 T. M And an ICD, wherein the ICD contains an env-incorporated motif as 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 SEQ ID NO:36. H Peptide; and V containing at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence identical to the sequence of SEQ ID NO:37. L The peptide is linked to a stem portion (S1) containing an Fc region (L1-Fc-L2-X1), the Fc region comprising ECD, T... M And ICD, the peptide is anchored to 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 as provided herein. In some implementations, the V... H and V L Peptides bind to immune cells, such as those described in this article.

[0288] In some implementations, V is provided H Peptides and Vitamins L peptides, wherein the V H The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO:36; and the V L The peptide contains at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence of SEQ ID NO:37.

[0289] In some embodiments, the polypeptide comprises V H Peptides and Vitamins L peptide, wherein the V H The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO:36; and the V LThe peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO:37; the limitation is that V H Peptides and Vitamins L The peptide comprises a light chain CDR having the sequences of SEQ ID NO:33-35; and / or a heavy chain CDR having the sequences of SEQ ID NO:30-32. In some embodiments, the polypeptide comprises V H Peptides and Vitamins L peptide, wherein the V H The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO:36; and the V L The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO:37; the limitation is that V H Peptides and Vitamins L The peptide comprises a light chain CDR1 having the sequence of SEQ ID NO:33; a light chain CDR2 having the sequence of SEQ ID NO:34; a light chain CDR3 having the sequence of SEQ ID NO:35; and / or a heavy chain CDR1 having the sequence of SEQ ID NO:30; a heavy chain CDR2 having the sequence of SEQ ID NO:31; and a heavy chain CDR3 having the sequence of SEQ ID NO:32. In some embodiments, V H or V L The CDRs in the chain are shown in the combinations provided in this article.

[0290] In some embodiments, the polypeptide comprises V H Peptides and Vitamins L peptide, wherein the V H The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO:36; and the V L The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO:37; the limitation is that 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; and V H The peptide comprises HCDR1 having the sequence of SEQ ID NO:30; HCDR2 having the sequence of SEQ ID NO:31; and HCDR3 having the sequence of SEQ ID NO:32.

[0291] In some embodiments, the polypeptide comprises V H Peptides and Vitamins L peptide, wherein the V H The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO:36; and the V L The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO:37; the limitation is that V L The peptide comprises LCDR1 having the sequence of SEQ ID NO:33, wherein the LCDR1 contains at most one conserved amino acid substitution; LCDR2 having the sequence of SEQ ID NO:34, wherein the LCDR2 contains at most one conserved amino acid substitution; and LCDR3 having the sequence of SEQ ID NO:35, wherein the LCDR3 contains at most one conserved amino acid substitution; and V H The peptide comprises HCDR1 having the sequence of SEQ ID NO:30, wherein HCDR1 comprises at most one conserved amino acid substitution; HCDR2 having the sequence of SEQ ID NO:31, wherein HCDR2 comprises at most one conserved amino acid substitution; and HCDR3 having the sequence of SEQ ID NO:32, wherein HCDR3 comprises at most one conserved amino acid substitution.

[0292] In some embodiments, the polypeptide comprises V H Peptides and Vitamins L peptides, of which V H The peptide contains the sequence of SEQ ID NO:36 and V L The peptide contains the sequence of SEQ ID NO:37.

[0293] In some embodiments, the peptides provided herein bind to CD7 in non-human primates. In some embodiments, the peptides provided herein bind to human CD7.

[0294] As provided in this article, the different polypeptides (V) described herein H or V L This may or may not be linked to a peptide linker, instead remaining a continuous sequence. In some embodiments, the peptide linker comprises (GGGGS). n The sequence (SEQ ID NO:55), wherein each n independently is 1-5. 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 form may be derived from formula V. H -ZV L or V L -ZV H This indicates that Z represents a peptide linker. In some embodiments, Z stands for (GGGGS). n (SEQ ID NO:55), where each n is independently 1-5. 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.

[0295] In some implementations, it includes formula V L -ZV H The polypeptide represented by the linked peptide includes a heavy chain variable region as shown in SEQ ID NO:36, which is linked to a light chain variable region as shown in SEQ ID NO:37 via a linker sequence GGGGSGGGGSGGGGSGGGGS (SEQ ID NO:72). In some embodiments, it includes a peptide linker to V H V L The polypeptide has the sequence shown below.

[0296] DILLTQSPAILSVSPGERVSFSCRASQSIGTSIHWYQQRTNDSPRLLIKYASESISGIPSRFSGSGSGTDFTLSINSVESEDIADYYCQQSNSWPTTFGGGTKLEIKRGGGGSGGGGSGGGGSGGG GSQVQLQQPGAELVKPGASVKLSCKASGYPFTSYWIHWVKQRPGRGLEWLGRIDPNSGDTKYNEKFKNKATLTVDKSSTTAYMQLSSLTSEDSAVYYCARSPYYSNDNSMDYWGQGTSVTVSS(SEQ ID NO:38).

[0297] In some embodiments, the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO:38. In some embodiments, the polypeptide comprises a sequence that is at least 90% identical to the sequence of SEQ ID NO:38. In some embodiments, the polypeptide comprises a sequence that is at least 95% identical to the sequence of SEQ ID NO:38. In some embodiments, the polypeptide comprises a sequence that is at least 99% identical to the sequence of SEQ ID NO:38. In some embodiments, the polypeptide comprises the sequence shown in SEQ ID NO:38. In some embodiments, the polypeptide shown in SEQ ID NO:38 is an antibody or an antigen-binding fragment thereof. In some embodiments, the antibody is an anti-CD7 antibody. In some embodiments, the anti-CD7 antibody binds to non-human primate CD7. In some embodiments, the anti-CD7 antibody binds to human CD7.

[0298] In some implementations, it includes formula V H -ZV L The polypeptide represented by the linked peptide includes a light chain variable region as shown in SEQ ID NO:37, which is linked to a heavy chain variable region as shown in SEQ ID NO:36 via a linker sequence GGGGSGGGGSGGGGSGGGGS (SEQ ID NO:72). In some embodiments, it includes a peptide linker to V L V H The polypeptide has the sequence shown below.

[0299] QVQLQQPGAELVKPGASVKLSCKASGYPFTSYWIHWVKQRPGRGLEWLGRIDPNSGDTKYNEKFKNKATLTVDKSSTTAYMQLSSLTSEDSAVYYCARSPYYSNDNSMDYWGQGTSVTVSSGGGGS GGGGSGGGGSGGGGSDILLTQSPAILSVSPGERVSFSCRASQSIGTSIHWYQQRTNDSPRLLIKYASESISGIPSRFSGSGSGTDFTLSINSVESEDIADYYCQQSNSWPTTFGGGTKLEIKR(SEQ ID NO:39).

[0300] In some embodiments, the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO:39. In some embodiments, the polypeptide comprises a sequence that is at least 90% identical to the sequence of SEQ ID NO:39. In some embodiments, the polypeptide comprises a sequence that is at least 95% identical to the sequence of SEQ ID NO:39. In some embodiments, the polypeptide comprises a sequence that is at least 99% identical to the sequence of SEQ ID NO:39. In some embodiments, the polypeptide comprises the sequence shown in SEQ ID NO:39. In some embodiments, the polypeptide shown in SEQ ID NO:39 is an antibody or an antigen-binding fragment thereof. In some embodiments, the antibody is an anti-CD7 antibody. In some embodiments, the anti-CD7 antibody binds to non-human primate CD7. In some embodiments, the anti-CD7 antibody binds to human CD7.

[0301] In some embodiments, the polypeptide comprises at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence of SEQ ID NO:38 and comprises a stem portion (S1) containing an Fc region, such as those provided herein. In some embodiments, the polypeptide comprises at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence of SEQ ID NO:38 and comprises a stem portion (S1) containing an Fc region, the Fc region further comprising a transmembrane domain, such as those provided herein. In some embodiments, the Fc region further comprising a transmembrane domain has the formula L1-Fc-L2-X1, wherein L1 is a linker as provided herein or is absent, Fc is a variant Fc region as provided herein, L2 is a linker as provided herein or is absent, and X1 is a polypeptide comprising a transmembrane domain as provided herein. As provided herein, X1 may comprise a peptide having the formula ECD-T M -ICD polypeptides, wherein ECD is an extracellular domain or fragment thereof as provided herein, or is absent, T M The transmembrane domain is as described herein, and the ICD is an intracellular domain as described herein or is absent. In some embodiments, the polypeptide comprises at least 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 stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing an ECD and a T M And ICD. In some embodiments, the polypeptide comprises at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence of SEQ ID NO:38 and comprises a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing CD8 and / or CD28 ECD, T MAnd ICD. In some embodiments, the polypeptide comprises at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence of SEQ ID NO:38 and comprises a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing ECD, CD8, and / or CD28T. M And ICD. In some embodiments, the polypeptide comprises at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence of SEQ ID NO:38 and comprises a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing CD8 and / or CD28ECD, CD8 and / or CD28 T M And ICD. In some embodiments, the polypeptide comprises at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence of SEQ ID NO:38 and comprises a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing ECD, T M And ICD, wherein the ICD contains an env incorporation motif as provided herein. In some embodiments, the polypeptide comprises at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence of SEQ ID NO:38 and comprises a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing CD8 and / or CD28 ECD, T M And an ICD, wherein the ICD contains an env incorporation motif as provided herein. In some embodiments, the polypeptide comprises at least 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 stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing an ECD, CD8, and / or CD28T. MAnd an ICD, wherein the ICD contains an env incorporation motif as provided herein. In some embodiments, the polypeptide comprises at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence of SEQ ID NO:38 and comprises a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing CD8 and / or CD28 ECD, CD8 and / or CD28 T. M And an ICD, wherein the ICD contains an env incorporation motif as provided herein. In some embodiments, the polypeptide comprises at least 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 stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing an ECD, T M And ICD, the polypeptide is anchored to 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 as provided herein. In some embodiments, the polypeptide binds to immune cells, such as those provided herein.

[0302] In some embodiments, the polypeptide comprises at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence of SEQ ID NO:39 and comprises a stem portion (S1) containing an Fc region, such as those provided herein. In some embodiments, the polypeptide comprises at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence of SEQ ID NO:39 and comprises a stem portion (S1) containing an Fc region, the Fc region further comprising a transmembrane domain, such as those provided herein. In some embodiments, the Fc region further comprising a transmembrane domain has the formula L1-Fc-L2-X1, wherein L1 is a linker as provided herein or is absent, Fc is a variant Fc region as provided herein, L2 is a linker as provided herein or is absent, and X1 is a polypeptide comprising a transmembrane domain as provided herein. As provided herein, X1 may comprise a peptide having the formula ECD-T M -ICD polypeptides, wherein ECD is an extracellular domain or fragment thereof as provided herein, or is absent, TM The transmembrane domain is as described herein, and the ICD is an intracellular domain as described herein or is absent. In some embodiments, the polypeptide comprises at least 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 stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing an ECD and a T M And ICD. In some embodiments, the polypeptide comprises at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence of SEQ ID NO:39 and comprises a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing CD8 and / or CD28 ECD, T M And ICD. In some embodiments, the polypeptide comprises at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence of SEQ ID NO:39 and comprises a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing ECD, CD8, and / or CD28T. M And ICD. In some embodiments, the polypeptide comprises at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence of SEQ ID NO:39 and comprises a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing CD8 and / or CD28ECD, CD8 and / or CD28 T M And ICD. In some embodiments, the polypeptide comprises at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence of SEQ ID NO:39 and comprises a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing ECD, T MAnd ICD, wherein the ICD contains an env incorporation motif as provided herein. In some embodiments, the polypeptide comprises at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence of SEQ ID NO:39 and comprises a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing CD8 and / or CD28 ECD, T M And an ICD, wherein the ICD contains an env incorporation motif as provided herein. In some embodiments, the polypeptide comprises at least 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 stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing an ECD, CD8, and / or CD28T. M And an ICD, wherein the ICD contains an env incorporation motif as provided herein. In some embodiments, the polypeptide comprises at least 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 stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing CD8 and / or CD28 ECD, CD8 and / or CD28 T. M And an ICD, wherein the ICD contains an env incorporation motif as provided herein. In some embodiments, the polypeptide comprises at least 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 stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing an ECD, T M And ICD, the polypeptide is anchored to 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 as provided herein. In some embodiments, the polypeptide binds to immune cells, such as those provided herein.

[0303] In some embodiments, the polypeptide comprises a sequence having the sequence shown in SEQ ID NO:38 and includes a stem portion (S1) containing an Fc region, such as those provided herein. In some embodiments, the polypeptide comprises a sequence having the sequence shown in SEQ ID NO:38 and includes a stem portion (S1) containing an Fc region, the Fc region further containing a transmembrane domain, such as those 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 as provided herein or is absent, Fc is a variant Fc region as provided herein, L2 is a linker as provided herein or is absent, and X1 is a polypeptide containing a transmembrane domain as provided herein. As provided herein, X1 may contain a peptide having the formula ECD-T M -ICD polypeptides, wherein ECD is an extracellular domain or fragment thereof as provided herein, or is absent, T M The transmembrane domain is as described herein, and the ICD is an intracellular domain as described herein or is absent. In some embodiments, the polypeptide comprises a sequence having the sequence shown in SEQ ID NO:38 and includes a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing an ECD, T M And ICD. In some embodiments, the polypeptide comprises a sequence having the sequence shown in SEQ ID NO:38 and includes a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing CD8 and / or CD28 ECD, T M And ICD. In some embodiments, the polypeptide comprises a sequence having the sequence shown in SEQ ID NO:38 and includes a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing ECD, CD8 and / or CD28 T. M And ICD. In some embodiments, the polypeptide comprises a sequence having the sequence shown in SEQ ID NO:38 and includes a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing CD8 and / or CD28 ECD, CD8 and / or CD28 T. M And ICD. In some embodiments, the polypeptide comprises a sequence having the sequence shown in SEQ ID NO:38 and includes a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing an ECD, T MAnd ICD, wherein the ICD contains an env incorporation motif as provided herein. In some embodiments, the polypeptide comprises a sequence having the sequence shown in SEQ ID NO:38 and includes a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing CD8 and / or CD28ECD, T M And an ICD, wherein the ICD contains an env incorporation motif as provided herein. In some embodiments, the polypeptide comprises a sequence having the sequence shown in SEQ ID NO:38 and includes a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing an ECD, CD8, and / or CD28T. M And an ICD, wherein the ICD contains an env incorporation motif as provided herein. In some embodiments, the polypeptide comprises a sequence having the sequence shown in SEQ ID NO:38 and includes a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing CD8 and / or CD28 ECD, CD8 and / or CD28 T. M And an ICD, wherein the ICD contains an env incorporation motif as provided herein. In some embodiments, the polypeptide comprises a sequence having the sequence shown in SEQ ID NO:38 and includes a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing an ECD, T M And ICD, the polypeptide is anchored to 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 as provided herein. In some embodiments, the polypeptide binds to immune cells, such as those provided herein.

[0304] In some embodiments, the polypeptide comprises a sequence having the sequence shown in SEQ ID NO:39 and includes a stem portion (S1) containing an Fc region, such as those provided herein. In some embodiments, the polypeptide comprises a sequence having the sequence shown in SEQ ID NO:39 and includes a stem portion (S1) containing an Fc region, the Fc region further containing a transmembrane domain, such as those 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 as provided herein or is absent, Fc is a variant Fc region as provided herein, L2 is a linker as provided herein or is absent, and X1 is a polypeptide containing a transmembrane domain as provided herein. As provided herein, X1 may contain a peptide having the formula ECD-T M-ICD polypeptides, wherein ECD is an extracellular domain or fragment thereof as provided herein, or is absent, T M The transmembrane domain is as described herein, and the ICD is an intracellular domain as described herein or is absent. In some embodiments, the polypeptide comprises a sequence having the sequence shown in SEQ ID NO:39 and includes a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing an ECD, T M And ICD. In some embodiments, the polypeptide comprises a sequence having the sequence shown in SEQ ID NO:39 and includes a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing CD8 and / or CD28 ECD, T M And ICD. In some embodiments, the polypeptide comprises a sequence having the sequence shown in SEQ ID NO:39 and includes a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing ECD, CD8 and / or CD28 T. M And ICD. In some embodiments, the polypeptide comprises a sequence having the sequence shown in SEQ ID NO:39 and includes a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing CD8 and / or CD28 ECD, CD8 and / or CD28 T. M And ICD. In some embodiments, the polypeptide comprises a sequence having the sequence shown in SEQ ID NO:39 and includes a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing an ECD, T M And ICD, wherein the ICD contains an env incorporation motif as provided herein. In some embodiments, the polypeptide comprises a sequence having the sequence shown in SEQ ID NO:39 and includes a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing CD8 and / or CD28ECD, T M And an ICD, wherein the ICD contains an env incorporation motif as provided herein. In some embodiments, the polypeptide comprises a sequence having the sequence shown in SEQ ID NO:39 and includes a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing an ECD, CD8, and / or CD28T. MAnd an ICD, wherein the ICD contains an env incorporation motif as provided herein. In some embodiments, the polypeptide comprises a sequence having the sequence shown in SEQ ID NO:39 and includes a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing CD8 and / or CD28 ECD, CD8 and / or CD28 T. M And an ICD, wherein the ICD contains an env incorporation motif as provided herein. In some embodiments, the polypeptide comprises a sequence having the sequence shown in SEQ ID NO:39 and includes a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing an ECD, T M And ICD, the polypeptide is anchored to 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 as provided herein. In some embodiments, the polypeptide binds to immune cells, such as those provided herein.

[0305] In some embodiments, the polypeptide provided herein comprises the formula T-S1, where T is a target-binding domain and S1 is a stem portion, the polypeptide comprising the sequence of SEQ ID NO:98:

[0306] (SEQ ID NO:98)

[0307] The amino acid sequence is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to or substantially similar to or the active fragment of SEQ ID NO:98. In some embodiments, the polypeptide provided herein comprises formula T-S1, the polypeptide comprising an amino acid sequence at least 90% identical to the sequence of SEQ ID NO:98. In some embodiments, the polypeptide provided herein comprises formula T-S1, the polypeptide comprising an amino acid sequence at least 95% identical to the sequence of SEQ ID NO:98. In some embodiments, the polypeptide provided herein comprises formula T-S1, the polypeptide comprising an amino acid sequence at least 98% identical to the sequence of SEQ ID NO:98. In some embodiments, the polypeptide provided herein comprises formula T-S1, the polypeptide comprising the amino acid sequence of SEQ ID NO:98.

[0308] In some embodiments, the polypeptide provided herein comprises the formula T-S1, wherein T is a target-binding domain and S1 is a stem portion, said polypeptide comprising at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% of the amino acid sequence identical to the sequence of SEQ ID NO:98, wherein the target-binding domain “T” of said polypeptide corresponds to amino acids 25-283 of SEQ ID NO:98, and wherein the stem portion “S1” of said polypeptide corresponds to amino acids 284-634 of SEQ ID NO:98. In some embodiments, the polypeptide provided herein comprises formula T-S1, the polypeptide comprising 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, and wherein the stem portion "S1" of the polypeptide corresponds to amino acids 284-634 of SEQ ID NO:98. In some embodiments, the polypeptide provided herein comprises formula T-S1, the polypeptide comprising 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, and wherein the stem portion "S1" of the polypeptide corresponds to amino acids 284-634 of SEQ ID NO:98. In some embodiments, the polypeptide provided herein comprises formula T-S1, the polypeptide comprising an amino acid sequence 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, and wherein the stem portion "S1" of the polypeptide corresponds to amino acids 284-634 of SEQ ID NO:98. In some embodiments, the polypeptide provided herein comprises formula T-S1, the polypeptide comprising the amino acid sequence of SEQ ID NO:98, wherein the target-binding domain "T" of the polypeptide corresponds to amino acids 25-283 of SEQ ID NO:98, and wherein the stem portion "S1" of the polypeptide corresponds to amino acids 284-634 of SEQ ID NO:98.

[0309] In some embodiments, the polypeptide provided herein contains the formula T-S1, where T represents the number of peptides containing V. H and V LThe target-binding domain and S1 is a stem portion, the polypeptide comprising 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 V of the target-binding domain H The V of the target-binding domain, corresponding to amino acids 25-150 of SEQ ID NO:98. L The amino acids 172-283 correspond to SEQ ID NO:98, and the stem portion “S1” of the polypeptide corresponds to amino acids 284-634 of SEQ ID NO:98. In some embodiments, the polypeptide provided herein comprises formula T-S1, the polypeptide comprising an amino acid sequence that is at least 90% identical to the sequence of SEQ ID NO:98, wherein the V of the target-binding domain... H The V of the target-binding domain, corresponding to amino acids 25-150 of SEQ ID NO:98. L The amino acids 172-283 correspond to SEQ ID NO:98, and the stem portion “S1” of the polypeptide corresponds to amino acids 284-634 of SEQ ID NO:98. In some embodiments, the polypeptide provided herein comprises formula T-S1, the polypeptide comprising an amino acid sequence that is at least 95% identical to the sequence of SEQ ID NO:98, wherein the V of the target-binding domain... H The V of the target-binding domain, corresponding to amino acids 25-150 of SEQ ID NO:98. L The amino acids 172-283 correspond to SEQ ID NO:98, and the stem portion “S1” of the polypeptide corresponds to amino acids 284-634 of SEQ ID NO:98. In some embodiments, the polypeptide provided herein comprises formula T-S1, the polypeptide comprising an amino acid sequence that is at least 98% identical to the sequence of SEQ ID NO:98, wherein the V of the target-binding domain... H The V of the target-binding domain, corresponding to amino acids 25-150 of SEQ ID NO:98. L The amino acids 172-283 correspond to SEQ ID NO:98, and the stem portion “S1” of the polypeptide corresponds to amino acids 284-634 of SEQ ID NO:98. In some embodiments, the polypeptide provided herein comprises formula T-S1, the polypeptide comprising the amino acid sequence of SEQ ID NO:98, wherein the V of the target-binding domain... H The V of the target-binding domain, corresponding to amino acids 25-150 of SEQ ID NO:98.L The amino acids 172-283 correspond to SEQ ID NO:98, and the stem portion “S1” of the polypeptide corresponds to amino acids 284-634 of SEQ ID NO:98.

[0310] In some embodiments, the polypeptide provided herein comprises the formula T-L1-Fc-L2-X1, wherein T is a target-binding domain, L1 is a polypeptide linker or is absent, Fc is a variant Fc domain as provided herein, L2 is a polypeptide linker or is absent, and X1 is a polypeptide comprising a transmembrane domain, said polypeptide comprising at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% of the sequence of SEQ ID NO:98, wherein the target-binding domain “T” of said 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 comprises the formula T-L1-Fc-L2-X1, wherein the polypeptide 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 polypeptide provided herein comprises the formula T-L1-Fc-L2-X1, wherein the polypeptide 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 comprises the formula T-L1-Fc-L2-X1, wherein the polypeptide 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.In some embodiments, the polypeptide provided herein comprises the formula T-L1-Fc-L2-X1, wherein the polypeptide comprises the amino acid sequence of SEQ ID NO:98, wherein the target-binding domain "T" of the polypeptide corresponds to amino acids 25-283 of SEQ ID NO:98, L1 comprises amino acids 284-301 of SEQ ID NO:98, Fc comprises amino acids 302-542 of SEQ ID NO:98, L2 is absent, and X1 corresponds to amino acids 543-634 of SEQ ID NO:98.

[0311] In some embodiments, the polypeptide provided herein contains the formula T-L1-Fc-L2-X1, where T represents the number of peptides containing V. H and V L The target-binding domain, L1 is a peptide linker or is absent, Fc is a variant Fc domain as provided herein, L2 is a peptide linker or is absent, and X1 is a peptide containing a transmembrane domain, the peptide comprising 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 V of the target-binding domain H The V of the target-binding domain, corresponding to amino acids 25-150 of SEQ ID NO:98. L Corresponding 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 comprises the formula T-L1-Fc-L2-X1, the polypeptide comprising an amino acid sequence that is at least 90% identical to the sequence of SEQ ID NO:98, wherein the V of the target-binding domain... H The V of the target-binding domain, corresponding to amino acids 25-150 of SEQ ID NO:98. L Corresponding 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 comprises the formula T-L1-Fc-L2-X1, the polypeptide comprising an amino acid sequence that is at least 95% identical to the sequence of SEQ ID NO:98, wherein the V of the target-binding domain...H The V of the target-binding domain, corresponding to amino acids 25-150 of SEQ ID NO:98. L Corresponding 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 comprises the formula T-L1-Fc-L2-X1, the polypeptide comprising an amino acid sequence that is at least 98% identical to the sequence of SEQ ID NO:98, wherein the V of the target-binding domain... H The V of the target-binding domain, corresponding to amino acids 25-150 of SEQ ID NO:98. L Corresponding 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 comprises the formula T-L1-Fc-L2-X1, the polypeptide comprising the amino acid sequence of SEQ ID NO:98, wherein the V of the target-binding domain... H The V of the target-binding domain, corresponding to amino acids 25-150 of SEQ ID NO:98. L The amino acids 172-283 corresponding to 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.

[0312] In some embodiments, the peptide provided herein contains the formula T-L1-Fc-L2-ECD-T M -ICD, where T is the target-binding domain, L1 is the peptide linker or absent, Fc is the variant Fc domain as provided in this paper, L2 is the peptide linker or absent, ECD is the extracellular domain, T MThe polypeptide is a transmembrane domain, and the ICD is an intracellular domain containing an env-incorporated motif. The polypeptide 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. 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 the ECD comprises amino acids 543-584 of SEQ ID NO:98. M The peptide comprises amino acids 585-612 of SEQ ID NO:98, and the ICD comprises amino acids 613-634 of SEQ ID NO:98, wherein the env-incorporated motif comprises amino acids 627-634 of SEQ ID NO:98. In some embodiments, the peptide provided herein comprises the formula T-L1-Fc-L2-ECD-T M -ICD, the polypeptide 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, ECD comprises amino acids 543-584 of SEQ ID NO:98, T M The peptide comprises amino acids 585-612 of SEQ ID NO:98, and the ICD comprises amino acids 613-634 of SEQ ID NO:98, wherein the env-incorporated motif comprises amino acids 627-634 of SEQ ID NO:98. In some embodiments, the peptide provided herein comprises the formula T-L1-Fc-L2-ECD-T M -ICD, the polypeptide 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, ECD comprises amino acids 543-584 of SEQ ID NO:98, T MThe peptide comprises amino acids 585-612 of SEQ ID NO:98, and the ICD comprises amino acids 613-634 of SEQ ID NO:98, wherein the env-incorporated motif comprises amino acids 627-634 of SEQ ID NO:98. In some embodiments, the peptide provided herein comprises the formula T-L1-Fc-L2-ECD-T M -ICD, the polypeptide 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, ECD comprises amino acids 543-584 of SEQ ID NO:98, T M The peptide comprises amino acids 585-612 of SEQ ID NO:98, and the ICD comprises amino acids 613-634 of SEQ ID NO:98, wherein the env-incorporated motif comprises amino acids 627-634 of SEQ ID NO:98. In some embodiments, the peptide provided herein comprises the formula T-L1-Fc-L2-ECD-T M -ICD, the polypeptide comprises the amino acid sequence of SEQ ID NO:98, wherein the target-binding domain "T" of the polypeptide corresponds to amino acids 25-283 of SEQ ID NO:98, L1 comprises amino acids 284-301 of SEQ ID NO:98, Fc comprises amino acids 302-542 of SEQ ID NO:98, L2 is absent, ECD comprises amino acids 543-584 of SEQ ID NO:98, T M The env-incorporated motif comprises amino acids 585-612 of SEQ ID NO:98, and the ICD comprises amino acids 613-634 of SEQ ID NO:98, wherein the env-incorporated motif comprises amino acids 627-634 of SEQ ID NO:98.

[0313] In some embodiments, the peptide provided herein contains the formula T-L1-Fc-L2-ECD-T M -ICD, where T is the number of elements containing V H and V L The target-binding domain, L1 is the peptide linker or absent, Fc is the variant Fc domain as provided in this paper, L2 is the peptide linker or absent, ECD is the extracellular domain, T MThe peptide is a transmembrane domain, and the ICD is an intracellular domain containing an env-incorporated motif. The peptide 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 V of the target-binding domain... H The V of the target-binding domain, corresponding to amino acids 25-150 of SEQ ID NO:98. L Amino acids 172-283 corresponding to 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 peptide comprises amino acids 585-612 of SEQ ID NO:98, and the ICD comprises amino acids 613-634 of SEQ ID NO:98, wherein the env-incorporated motif comprises amino acids 627-634 of SEQ ID NO:98. In some embodiments, the peptide provided herein comprises the formula T-L1-Fc-L2-ECD-T M -ICD, the polypeptide contains an amino acid sequence that is at least 90% identical to the sequence of SEQ ID NO:98, wherein the V of the target-binding domain H The V of the target-binding domain, corresponding to amino acids 25-150 of SEQ ID NO:98. L Amino acids 172-283 corresponding to 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 peptide comprises amino acids 585-612 of SEQ ID NO:98, and the ICD comprises amino acids 613-634 of SEQ ID NO:98, wherein the env-incorporated motif comprises amino acids 627-634 of SEQ ID NO:98. In some embodiments, the peptide provided herein comprises the formula T-L1-Fc-L2-ECD-T M -ICD, the polypeptide contains an amino acid sequence that is at least 95% identical to the sequence of SEQ ID NO:98, wherein the V of the target-binding domain H The V of the target-binding domain, corresponding to amino acids 25-150 of SEQ ID NO:98. LAmino acids 172-283 corresponding to 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 peptide comprises amino acids 585-612 of SEQ ID NO:98, and the ICD comprises amino acids 613-634 of SEQ ID NO:98, wherein the env-incorporated motif comprises amino acids 627-634 of SEQ ID NO:98. In some embodiments, the peptide provided herein comprises the formula T-L1-Fc-L2-ECD-T M -ICD, the polypeptide contains an amino acid sequence that is at least 98% identical to the sequence of SEQ ID NO:98, wherein the V of the target-binding domain H The V of the target-binding domain, corresponding to amino acids 25-150 of SEQ ID NO:98. L Amino acids 172-283 corresponding to 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 peptide comprises amino acids 585-612 of SEQ ID NO:98, and the ICD comprises amino acids 613-634 of SEQ ID NO:98, wherein the env-incorporated motif comprises amino acids 627-634 of SEQ ID NO:98. In some embodiments, the peptide provided herein comprises the formula T-L1-Fc-L2-ECD-T M -ICD, the polypeptide comprises the amino acid sequence of SEQ ID NO:98, wherein the V of the target-binding domain H The V of the target-binding domain, corresponding to amino acids 25-150 of SEQ ID NO:98. L Amino acids 172-283 corresponding to 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 env-incorporated motif comprises amino acids 585-612 of SEQ ID NO:98, and the ICD comprises amino acids 613-634 of SEQ ID NO:98, wherein the env-incorporated motif comprises amino acids 627-634 of SEQ ID NO:98.

[0314] In some embodiments, the peptide provided herein contains the formula T-L1-Fc-L2-ECD-T M -ICD, where T is the target-binding domain, L1 is the peptide linker or absent, Fc is the variant Fc domain as provided in this paper, L2 is the peptide linker or absent, ECD is the extracellular domain, T M The polypeptide comprises a transmembrane domain and an intracellular domain containing an env-incorporated motif, wherein the polypeptide 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 comprises the amino acid sequence SEQ ID NO:39 and corresponds to amino acids 25-283 of SEQ ID NO:98, L1 comprises the amino acid sequence of SEQ ID NO:72 and corresponds to amino acids 284-301 of SEQ ID NO:98, Fc comprises 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 comprises the amino acid sequence of SEQ ID NO:60 and corresponds to amino acids 543-584 of SEQ ID NO:98, and T M The peptide comprises the amino acid sequence of SEQ ID NO:62 and corresponds to amino acids 585-612 of SEQ ID NO:98, and the ICD comprises amino acids 613-634 of SEQ ID NO:98, wherein the env-incorporated motif comprises the amino acid sequence of SEQ ID NO:63 and corresponds to amino acids 627-634 of SEQ ID NO:98. In some embodiments, the peptide provided herein comprises the formula T-L1-Fc-L2-ECD-T M -ICD, the polypeptide 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 comprises the amino acid sequence SEQ ID NO:39 and corresponds to amino acids 25-283 of SEQ ID NO:98, L1 comprises the amino acid sequence of SEQ ID NO:72 and corresponds to amino acids 284-301 of SEQ ID NO:98, Fc comprises 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 comprises the amino acid sequence of SEQ ID NO:60 and corresponds to amino acids 543-584 of SEQ ID NO:98, T MThe peptide comprises the amino acid sequence of SEQ ID NO:62 and corresponds to amino acids 585-612 of SEQ ID NO:98, and the ICD comprises amino acids 613-634 of SEQ ID NO:98, wherein the env-incorporated motif comprises the amino acid sequence of SEQ ID NO:63 and corresponds to amino acids 627-634 of SEQ ID NO:98. In some embodiments, the peptide provided herein comprises the formula T-L1-Fc-L2-ECD-T M -ICD, the polypeptide 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 comprises the amino acid sequence SEQ ID NO:39 and corresponds to amino acids 25-283 of SEQ ID NO:98, L1 comprises the amino acid sequence of SEQ ID NO:72 and corresponds to amino acids 284-301 of SEQ ID NO:98, Fc comprises 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 comprises the amino acid sequence of SEQ ID NO:60 and corresponds to amino acids 543-584 of SEQ ID NO:98, T M The peptide comprises the amino acid sequence of SEQ ID NO:62 and corresponds to amino acids 585-612 of SEQ ID NO:98, and the ICD comprises amino acids 613-634 of SEQ ID NO:98, wherein the env-incorporated motif comprises the amino acid sequence of SEQ ID NO:63 and corresponds to amino acids 627-634 of SEQ ID NO:98. In some embodiments, the peptide provided herein comprises the formula T-L1-Fc-L2-ECD-T M -ICD, the polypeptide 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 comprises the amino acid sequence SEQ ID NO:39 and corresponds to amino acids 25-283 of SEQ ID NO:98, L1 comprises the amino acid sequence of SEQ ID NO:72 and corresponds to amino acids 284-301 of SEQ ID NO:98, Fc comprises 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 comprises the amino acid sequence of SEQ ID NO:60 and corresponds to amino acids 543-584 of SEQ ID NO:98, T MThe peptide comprises the amino acid sequence of SEQ ID NO:62 and corresponds to amino acids 585-612 of SEQ ID NO:98, and the ICD comprises amino acids 613-634 of SEQ ID NO:98, wherein the env-incorporated motif comprises the amino acid sequence of SEQ ID NO:63 and corresponds to amino acids 627-634 of SEQ ID NO:98. In some embodiments, the peptide provided herein comprises the formula T-L1-Fc-L2-ECD-T M -ICD, the polypeptide comprises the amino acid sequence of SEQ ID NO:98, wherein the target-binding domain "T" of the polypeptide comprises the amino acid sequence SEQ ID NO:39 and corresponds to amino acids 25-283 of SEQ ID NO:98, L1 comprises the amino acid sequence of SEQ ID NO:72 and corresponds to amino acids 284-301 of SEQ ID NO:98, Fc comprises 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 comprises the amino acid sequence of SEQ ID NO:60 and corresponds to amino acids 543-584 of SEQ ID NO:98, T M The env-incorporated motif contains the amino acid sequence of SEQ ID NO:62 and corresponds to amino acids 585-612 of SEQ ID NO:98, and the ICD contains amino acids 613-634 of SEQ ID NO:98, wherein the env-incorporated motif contains the amino acid sequence of SEQ ID NO:63 and corresponds to amino acids 627-634 of SEQ ID NO:98.

[0315] In some embodiments, the peptide provided herein contains the formula T-L1-Fc-L2-ECD-T M -ICD, where T is the number of elements containing V H and V L The target-binding domain, L1 is the peptide linker or absent, Fc is the variant Fc domain as provided in this paper, L2 is the peptide linker or absent, ECD is the extracellular domain, T M The peptide is a transmembrane domain, and the ICD is an intracellular domain containing an env-incorporated motif. The peptide 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 V of the target-binding domain... H The amino acid sequence comprising SEQ ID NO:36 and corresponding to amino acids 25-150 of SEQ ID NO:98, wherein the target-binding domain VL The amino acid sequence containing SEQ ID NO:37 and corresponding to amino acids 172-283 of SEQ ID NO:98, L1 containing the amino acid sequence containing SEQ ID NO:72 and corresponding to amino acids 284-301 of SEQ ID NO:98, Fc containing the amino acid sequence containing SEQ ID NO:104 and corresponding to amino acids 302-542 of SEQ ID NO:98, L2 is absent, ECD containing the amino acid sequence containing SEQ ID NO:60 and corresponding to amino acids 543-584 of SEQ ID NO:98, T M The peptide comprises the amino acid sequence of SEQ ID NO:62 and corresponds to amino acids 585-612 of SEQ ID NO:98, and the ICD comprises amino acids 613-634 of SEQ ID NO:98, wherein the env-incorporated motif comprises the amino acid sequence of SEQ ID NO:63 and corresponds to amino acids 627-634 of SEQ ID NO:98. In some embodiments, the peptide provided herein comprises the formula T-L1-Fc-L2-ECD-T M -ICD, the polypeptide contains an amino acid sequence that is at least 90% identical to the sequence of SEQ ID NO:98, wherein the V of the target-binding domain H The amino acid sequence comprising SEQ ID NO:36 and corresponding to amino acids 25-150 of SEQ ID NO:98, wherein the target-binding domain V L The amino acid sequence containing SEQ ID NO:37 and corresponding to amino acids 172-283 of SEQ ID NO:98, L1 containing the amino acid sequence containing SEQ ID NO:72 and corresponding to amino acids 284-301 of SEQ ID NO:98, Fc containing the amino acid sequence containing SEQ ID NO:104 and corresponding to amino acids 302-542 of SEQ ID NO:98, L2 is absent, ECD containing the amino acid sequence containing SEQ ID NO:60 and corresponding to amino acids 543-584 of SEQ ID NO:98, T M The peptide comprises the amino acid sequence of SEQ ID NO:62 and corresponds to amino acids 585-612 of SEQ ID NO:98, and the ICD comprises amino acids 613-634 of SEQ ID NO:98, wherein the env-incorporated motif comprises the amino acid sequence of SEQ ID NO:63 and corresponds to amino acids 627-634 of SEQ ID NO:98. In some embodiments, the peptide provided herein comprises the formula T-L1-Fc-L2-ECD-T M-ICD, the polypeptide contains an amino acid sequence that is at least 95% identical to the sequence of SEQ ID NO:98, wherein the V of the target-binding domain H The amino acid sequence comprising SEQ ID NO:36 and corresponding to amino acids 25-150 of SEQ ID NO:98, wherein the target-binding domain V L The amino acid sequence containing SEQ ID NO:37 and corresponding to amino acids 172-283 of SEQ ID NO:98, L1 containing the amino acid sequence containing SEQ ID NO:72 and corresponding to amino acids 284-301 of SEQ ID NO:98, Fc containing the amino acid sequence containing SEQ ID NO:104 and corresponding to amino acids 302-542 of SEQ ID NO:98, L2 is absent, ECD containing the amino acid sequence containing SEQ ID NO:60 and corresponding to amino acids 543-584 of SEQ ID NO:98, T M The peptide comprises the amino acid sequence of SEQ ID NO:62 and corresponds to amino acids 585-612 of SEQ ID NO:98, and the ICD comprises amino acids 613-634 of SEQ ID NO:98, wherein the env-incorporated motif comprises the amino acid sequence of SEQ ID NO:63 and corresponds to amino acids 627-634 of SEQ ID NO:98. In some embodiments, the peptide provided herein comprises the formula T-L1-Fc-L2-ECD-T M -ICD, the polypeptide contains an amino acid sequence that is at least 98% identical to the sequence of SEQ ID NO:98, wherein the V of the target-binding domain H The amino acid sequence comprising SEQ ID NO:36 and corresponding to amino acids 25-150 of SEQ ID NO:98, wherein the target-binding domain V L The amino acid sequence containing SEQ ID NO:37 and corresponding to amino acids 172-283 of SEQ ID NO:98, L1 containing the amino acid sequence containing SEQ ID NO:72 and corresponding to amino acids 284-301 of SEQ ID NO:98, Fc containing the amino acid sequence containing SEQ ID NO:104 and corresponding to amino acids 302-542 of SEQ ID NO:98, L2 is absent, ECD containing the amino acid sequence containing SEQ ID NO:60 and corresponding to amino acids 543-584 of SEQ ID NO:98, T MThe peptide comprises the amino acid sequence of SEQ ID NO:62 and corresponds to amino acids 585-612 of SEQ ID NO:98, and the ICD comprises amino acids 613-634 of SEQ ID NO:98, wherein the env-incorporated motif comprises the amino acid sequence of SEQ ID NO:63 and corresponds to amino acids 627-634 of SEQ ID NO:98. In some embodiments, the peptide provided herein comprises the formula T-L1-Fc-L2-ECD-T M -ICD, the polypeptide comprises the amino acid sequence of SEQ ID NO:98, wherein the V of the target-binding domain H The amino acid sequence comprising SEQ ID NO:36 and corresponding to amino acids 25-150 of SEQ ID NO:98, wherein the target-binding domain V L The amino acid sequence containing SEQ ID NO:37 and corresponding to amino acids 172-283 of SEQ ID NO:98, L1 containing the amino acid sequence containing SEQ ID NO:72 and corresponding to amino acids 284-301 of SEQ ID NO:98, Fc containing the amino acid sequence containing SEQ ID NO:104 and corresponding to amino acids 302-542 of SEQ ID NO:98, L2 is absent, ECD containing the amino acid sequence containing SEQ ID NO:60 and corresponding to amino acids 543-584 of SEQ ID NO:98, T M The env-incorporated motif contains the amino acid sequence of SEQ ID NO:62 and corresponds to amino acids 585-612 of SEQ ID NO:98, and the ICD contains amino acids 613-634 of SEQ ID NO:98, wherein the env-incorporated motif contains the amino acid sequence of SEQ ID NO:63 and corresponds to amino acids 627-634 of SEQ ID NO:98.

[0316] In some embodiments, V having a sequence as shown in SEQ ID NO:48 H peptides and V having the sequence shown in SEQ ID NO:49 L The peptide is linked to a stem portion (S1) containing an Fc region (L1-Fc-L2-X1), the Fc region comprising ECD, T... M and ICD. In some embodiments, V having a sequence such as SEQ ID NO:48 H peptides and V having the sequence shown in SEQ ID NO:49 L The peptide is linked to a stem portion (S1) containing an Fc region (L1-Fc-L2-X1), the Fc region comprising CD8 and / or CD28ECD, T MAnd ICD. In some embodiments, V having a sequence such as SEQ ID NO:48 H peptides and V having the sequence shown in SEQ ID NO:49 L The peptide is linked to a stem portion (S1) containing an Fc region (L1-Fc-L2-X1), the Fc region comprising ECD, CD8, and / or CD28 T. M And ICD. In some embodiments, V having a sequence such as SEQ ID NO:48 H peptides and V having the sequence shown in SEQ ID NO:49 L The peptide is linked to a stem portion (S1) containing an Fc region (L1-Fc-L2-X1), the Fc region comprising CD8 and / or CD28 ECD, CD8 and / or CD28 T. M And ICD. In some embodiments, V having a sequence as shown in SEQ ID NO:48 H peptides and V having the sequence shown in SEQ ID NO:49 L The peptide is linked to a stem portion (S1) containing an Fc region (L1-Fc-L2-X1), the Fc region comprising ECD, T... M and ICD, wherein the ICD contains an env-incorporated motif as provided herein. In some embodiments, V having a sequence as shown in SEQ ID NO:48 H peptides and V having the sequence shown in SEQ ID NO:49 L The peptide is linked to a stem portion (S1) containing an Fc region (L1-Fc-L2-X1), the Fc region comprising CD8 and / or CD28 ECD, T M And an ICD, wherein the ICD contains an env-incorporated motif as provided herein. In some embodiments, a V having a sequence as shown in SEQ ID NO:48 H peptides and V having the sequence shown in SEQ ID NO:49 L The peptide is linked to a stem portion (S1) containing an Fc region (L1-Fc-L2-X1), the Fc region comprising ECD, CD8, and / or CD28 T. M And an ICD, wherein the ICD contains an env-incorporated motif as provided herein. In some embodiments, a V having a sequence as shown in SEQ ID NO:48 H peptides and V having the sequence shown in SEQ ID NO:49 L The peptide is linked to a stem portion (S1) containing an Fc region (L1-Fc-L2-X1), the Fc region comprising CD8 and / or CD28 ECD, CD8 and / or CD28 T. MAnd an ICD, wherein the ICD contains an env-incorporated motif as provided herein. In some embodiments, a V having a sequence as shown in SEQ ID NO:48 H peptides and V having the sequence shown in SEQ ID NO:49 L The peptide is linked to a stem portion (S1) containing an Fc region (L1-Fc-L2-X1), the Fc region comprising ECD, T... M And ICD, the peptide is anchored to 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 as provided herein. In some implementations, the V... H and V L Peptides bind to immune cells, such as those described in this article.

[0317] 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 Peptide; and V containing at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence identical to the sequence of SEQ ID NO:49. L The peptide is linked to a stem portion (S1) comprising the Fc region as provided herein. In some embodiments, a V-shaped portion comprises a sequence identical to at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence of SEQ ID NO:48. H Peptide; and V containing at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence identical to the sequence of SEQ ID NO:49. L The peptide is linked to a stem portion (S1) containing an Fc region, which further includes a transmembrane domain. In some embodiments, the Fc region further including the transmembrane domain has the formula L1-Fc-L2-X1, where L1 is a linker as provided herein or is absent, Fc is a variant Fc region as provided herein, L2 is a linker as provided herein or is absent, and X1 is a polypeptide containing the transmembrane domain as provided herein. As provided herein, X1 may contain a peptide having the formula ECD-T MA polypeptide containing -ICD, wherein ECD is an extracellular domain or a fragment thereof as provided herein, or is absent; TM is a transmembrane domain as provided herein; and ICD is an intracellular domain as provided herein, or is absent. In some embodiments, V comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO:48. H Peptide; and V containing at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence identical to the sequence of SEQ ID NO:49. L The peptide is linked to a stem portion (S1) containing an Fc region (L1-Fc-L2-X1), the Fc region comprising ECD, T... M And 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 SEQ ID NO:48. H Peptide; and V containing at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence identical to the sequence of SEQ ID NO:49. L The peptide is linked to a stem portion (S1) containing an Fc region (L1-Fc-L2-X1), the Fc region comprising CD8 and / or CD28 ECD, T M And 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 SEQ ID NO:48. H Peptide; and V containing at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence identical to the sequence of SEQ ID NO:49. L The peptide is linked to a stem portion (S1) containing an Fc region (L1-Fc-L2-X1), the Fc region comprising ECD, CD8, and / or CD28 T. MAnd 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 SEQ ID NO:48. H Peptide; and V containing at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence identical to the sequence of SEQ ID NO:49. L The peptide is linked to a stem portion (S1) containing an Fc region (L1-Fc-L2-X1), the Fc region comprising CD8 and / or CD28 ECD, CD8 and / or CD28 T. M And 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 SEQ ID NO:48. H Peptide; and V containing at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence identical to the sequence of SEQ ID NO:49. L The peptide is linked to a stem portion (S1) containing an Fc region (L1-Fc-L2-X1), the Fc region comprising ECD, T... M And an ICD, wherein the ICD contains an env-incorporated motif as provided herein. In some embodiments, the V comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO:48. H Peptide; and V containing at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence identical to the sequence of SEQ ID NO:49. L The peptide is linked to a stem portion (S1) containing an Fc region (L1-Fc-L2-X1), the Fc region comprising CD8 and / or CD28 ECD, T M And an ICD, wherein the ICD contains an env-incorporated motif as 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 SEQ ID NO:48.H Peptide; and V containing at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence identical to the sequence of SEQ ID NO:49. L The peptide is linked to a stem portion (S1) containing an Fc region (L1-Fc-L2-X1), the Fc region comprising ECD, CD8, and / or CD28 T. M And an ICD, wherein the ICD contains an env-incorporated motif as 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 SEQ ID NO:48. H Peptide; and V containing at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence identical to the sequence of SEQ ID NO:49. L The peptide is linked to a stem portion (S1) containing an Fc region (L1-Fc-L2-X1), the Fc region comprising CD8 and / or CD28 ECD, CD8 and / or CD28 T. M And an ICD, wherein the ICD contains an env-incorporated motif as 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 SEQ ID NO:48. H Peptide; and V containing at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence identical to the sequence of SEQ ID NO:49. L The peptide is anchored to the surface of viral particles (such as those provided herein), and the peptide is linked to a stem portion (S1) containing an Fc region (L1-Fc-L2-X1), the Fc region containing ECD, T... M and ICD. In some implementations, L1, Fc, L2, ECD, T M The identity of the ICD is as provided herein. In some implementations, the V... H and V L Peptides bind to immune cells, such as those described in this article.

[0318] In some implementations, V is provided H Peptides and Vitamins Lpeptides, wherein the V H The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO:48; and the V L The peptide contains at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence of SEQ ID NO:49.

[0319] In some embodiments, the polypeptide comprises V H Peptides and Vitamins L peptide, wherein the V H The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO:48; and the V L The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO:49; the limitation is that V H Peptides and Vitamins L The peptide comprises a light chain CDR having the sequence of SEQ ID NO:45-47; and / or a heavy chain CDR having the sequence of SEQ ID NO:42-44. In some embodiments, the polypeptide comprises V H Peptides and Vitamins L peptide, wherein the V H The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO:48; and the V L The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO:49; the limitation is that V H Peptides and Vitamins LThe peptide comprises a light chain CDR1 having the sequence of SEQ ID NO:45; a light chain CDR2 having the sequence of SEQ ID NO:46; a light chain CDR3 having the sequence of SEQ ID NO:47; and / or a heavy chain CDR1 having the sequence of SEQ ID NO:42; a heavy chain CDR2 having the sequence of SEQ ID NO:43; and a heavy chain CDR3 having the sequence of SEQ ID NO:44. In some embodiments, V H or V L The CDRs in the chain are shown in the combinations provided in this article.

[0320] In some embodiments, the polypeptide comprises V H Peptides and Vitamins L peptide, wherein the V H The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO:48; and the V L The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO:49; the limitation is that V L The 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; and V H The peptide comprises 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.

[0321] In some embodiments, the polypeptide comprises V H Peptides and Vitamins L peptide, wherein the V H The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO:48; and the V L The peptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO:49; the limitation is that V LThe peptide comprises LCDR1 having the sequence of SEQ ID NO:45, wherein the LCDR1 contains at most one conserved amino acid substitution; LCDR2 having the sequence of SEQ ID NO:46, wherein the LCDR2 contains at most one conserved amino acid substitution; and LCDR3 having the sequence of SEQ ID NO:47, wherein the LCDR3 contains at most one conserved amino acid substitution; and V H The peptide comprises HCDR1 having the sequence of SEQ ID NO:42, wherein HCDR1 comprises at most one conserved amino acid substitution; HCDR2 having the sequence of SEQ ID NO:43, wherein HCDR2 comprises at most one conserved amino acid substitution; and HCDR3 having the sequence of SEQ ID NO:44, wherein HCDR3 comprises at most one conserved amino acid substitution.

[0322] In some embodiments, the polypeptide comprises V H Peptides and Vitamins L peptides, of which V H The peptide contains the sequence of SEQ ID NO:48 and V L The peptide contains the sequence of SEQ ID NO:49.

[0323] In some embodiments, the peptides provided herein bind to non-human primate CD8. In some embodiments, the peptides provided herein bind to human CD8.

[0324] As provided in this article, the different polypeptides (V) described herein H or V L This may or may not be linked to a peptide linker, instead remaining a continuous sequence. In some embodiments, the peptide linker comprises (GGGGS). n The sequence (SEQ ID NO:55), wherein each n independently is 1-5. 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 form may be derived from formula V. H -ZV L or V L -ZV H This indicates that Z represents a peptide linker. In some embodiments, Z stands for (GGGGS). n (SEQ ID NO:55), where each n is independently 1-5. 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.

[0325] In some implementations, it includes formula V L -ZV H The polypeptide represented by the linked peptide includes a heavy chain variable region as shown in SEQ ID NO:48, which is linked to a light chain variable region as shown in SEQ ID NO:49 via a linker sequence GGGGSGGGGSGGGGSGGGGS (SEQ ID NO:72). In some embodiments, it includes a peptide linker to V H V L The polypeptide has the sequence shown below.

[0326] NIVLTQSPASLAVSLGQRATISCRASESVDGFGNSFMNWYQQKPGQSPKLLIYLASNLESGVPARFSGSGSRTDFTLTIDPVEADDAATYYCQQNNEDPYTFGGGTKLEIKRGGGGSGGGGSGGGGSG GGGSEVQLQQSGPELVKPGASVKISCKASRYTFTDYNLHWVKLSHEKSLEWIGFIYPYNGGTGYNQKFKNKAKLTVDYSSSTAYMELRSLTSVDAAVYYCARDHRYNEGVSFDYWGQGTTLTVSS(SEQ ID NO:50).

[0327] In some embodiments, the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO:50. In some embodiments, the polypeptide comprises a sequence that is at least 90% identical to the sequence of SEQ ID NO:50. In some embodiments, the polypeptide comprises a sequence that is at least 95% identical to the sequence of SEQ ID NO:50. In some embodiments, the polypeptide comprises a sequence that is at least 99% identical to the sequence of SEQ ID NO:50. In some embodiments, the polypeptide comprises the sequence shown in SEQ ID NO:50. In some embodiments, the polypeptide shown in SEQ ID NO:50 is an antibody or an antigen-binding fragment thereof. In some embodiments, the antibody is an anti-CD8 antibody. In some embodiments, the anti-CD8 antibody binds to non-human primate CD8. In some embodiments, the anti-CD8 antibody binds to human CD8.

[0328] In some implementations, it includes formula V H -ZV LThe polypeptide represented by the linked peptide includes a light chain variable region as shown in SEQ ID NO:49, which is linked to a heavy chain variable region as shown in SEQ ID NO:48 via a linker sequence GGGGSGGGGSGGGGSGGGGS (SEQ ID NO:72). In some embodiments, it includes a peptide linker to V L V H The polypeptide has the sequence shown below.

[0329] EVQLQQSGPELVKPGASVKISCKASRYTFTDYNLHWVKLSHEKSLEWIGFIYPYNGGTGYNQKFKNKAKLTVDYSSSTAYMELRSLTSVDAAVYYCARDHRYNEGVSFDYWGQGTTLTVSSGGGGSGG GGSGGGGSGGGGSNIVLTQSPASLAVSLGQRATISCRASESVDGFGNSFMNWYQQKPGQSPKLLIYLASNLESGVPARFSGSGSRTDFTLTIDPVEADDAATYYCQQNNEDPYTFGGGTKLEIKR(SEQ ID NO:51).

[0330] In some embodiments, the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO:51. In some embodiments, the polypeptide comprises a sequence that is at least 90% identical to the sequence of SEQ ID NO:51. In some embodiments, the polypeptide comprises a sequence that is at least 95% identical to the sequence of SEQ ID NO:51. In some embodiments, the polypeptide comprises a sequence that is at least 99% identical to the sequence of SEQ ID NO:51. In some embodiments, the polypeptide comprises the sequence shown in SEQ ID NO:51. In some embodiments, the polypeptide shown in SEQ ID NO:51 is an antibody or an antigen-binding fragment thereof. In some embodiments, the antibody is an anti-CD8 antibody. In some embodiments, the anti-CD8 antibody binds to non-human primate CD8. In some embodiments, the anti-CD8 antibody binds to human CD8.

[0331] In some embodiments, the polypeptide comprises at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence of SEQ ID NO:50 and comprises a stem portion (S1) containing an Fc region, such as those provided herein. In some embodiments, the polypeptide comprises at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence of SEQ ID NO:50 and comprises a stem portion (S1) containing an Fc region, the Fc region further comprising a transmembrane domain, such as those provided herein. In some embodiments, the Fc region further comprising a transmembrane domain has the formula L1-Fc-L2-X1, wherein L1 is a linker as provided herein or is absent, Fc is a variant Fc region as provided herein, L2 is a linker as provided herein or is absent, and X1 is a polypeptide comprising a transmembrane domain as provided herein. As provided herein, X1 may comprise a peptide having the formula ECD-T M -ICD polypeptides, wherein ECD is an extracellular domain or fragment thereof as provided herein, or is absent, T M The transmembrane domain is as described herein, and the ICD is an intracellular domain as described herein or is absent. In some embodiments, the polypeptide comprises at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence of SEQ ID NO:50 and comprises a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing an ECD and a T M And ICD. In some embodiments, the polypeptide comprises at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence of SEQ ID NO:50 and comprises a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing CD8 and / or CD28 ECD, T MAnd ICD. In some embodiments, the polypeptide comprises at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence of SEQ ID NO:50 and comprises a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing ECD, CD8, and / or CD28T. M In some embodiments, the polypeptide comprises a sequence identical to at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence of SEQ ID NO:50 and comprises a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing CD8 and / or CD28ECD, CD8 and / or CD28 T. M And ICD. In some embodiments, the polypeptide comprises at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence of SEQ ID NO:50 and comprises a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing ECD, T M And ICD, wherein the ICD contains an env incorporation motif as provided herein. In some embodiments, the polypeptide comprises at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence of SEQ ID NO:50 and comprises a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing CD8 and / or CD28 ECD, T M And an ICD, wherein the ICD contains an env incorporation motif as provided herein. In some embodiments, the polypeptide comprises at least 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 stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing an ECD, CD8, and / or CD28T. MAnd an ICD, wherein the ICD contains an env incorporation motif as provided herein. In some embodiments, the polypeptide comprises at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence of SEQ ID NO:50 and comprises a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing CD8 and / or CD28 ECD, CD8 and / or CD28 T. M And an ICD, wherein the ICD contains an env incorporation motif as provided herein. In some embodiments, the polypeptide comprises at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence of SEQ ID NO:50 and comprises a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing an ECD, T M And ICD, the polypeptide is anchored to 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 as provided herein. In some embodiments, the polypeptide binds to immune cells, such as those provided herein.

[0332] In some embodiments, the polypeptide comprises at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence of SEQ ID NO:51 and comprises a stem portion (S1) containing an Fc region, such as those provided herein. In some embodiments, the polypeptide comprises at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence of SEQ ID NO:51 and comprises a stem portion (S1) containing an Fc region, the Fc region further comprising transmembrane domains, such as those provided herein. In some embodiments, the Fc region further comprising a transmembrane domain has the formula L1-Fc-L2-X1, wherein L1 is a linker as provided herein or is absent, Fc is a variant Fc region as provided herein, L2 is a linker as provided herein or is absent, and X1 is a polypeptide comprising a transmembrane domain as provided herein. As provided herein, X1 may comprise a peptide having the formula ECD-T M -ICD polypeptides, wherein ECD is an extracellular domain or fragment thereof as provided herein, or is absent, TM The transmembrane domain is as provided herein, and the ICD is an intracellular domain as provided herein or is absent. In some embodiments, the polypeptide comprises at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence of SEQ ID NO:51 and comprises a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing an ECD, a TM, and an ICD. In some embodiments, the polypeptide comprises a sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of SEQ ID NO:51 and comprises a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing CD8 and / or CD28 ECD, T M And ICD. In some embodiments, the polypeptide comprises at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence of SEQ ID NO:51 and comprises a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing ECD, CD8, and / or CD28 T. M In some embodiments, the polypeptide comprises a sequence identical to at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence of SEQ ID NO:51 and comprises a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing CD8 and / or CD28 ECD, CD8 and / or CD28 T. M And ICD. In some embodiments, the polypeptide comprises at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence of SEQ ID NO:51 and comprises a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing ECD, T MAnd ICD, wherein the ICD contains an env incorporation motif as provided herein. In some embodiments, the polypeptide comprises at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the sequence of SEQ ID NO:51 and comprises a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing CD8 and / or CD28 ECD, T M And an ICD, wherein the ICD contains an env incorporation motif as provided herein. In some embodiments, the polypeptide comprises at least 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 stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing an ECD, CD8, and / or CD28T. M And an ICD, wherein the ICD contains an env incorporation motif as provided herein. In some embodiments, the polypeptide comprises at least 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 stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing CD8 and / or CD28 ECD, CD8 and / or CD28 T. M And an ICD, wherein the ICD contains an env incorporation motif as provided herein. In some embodiments, the polypeptide comprises at least 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 stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing an ECD, T M And ICD, the polypeptide is anchored to 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 as provided herein. In some embodiments, the polypeptide binds to immune cells, such as those provided herein.

[0333] In some embodiments, the polypeptide comprises a sequence having the sequence shown in SEQ ID NO:50 and includes a stem portion (S1) containing an Fc region, such as those provided herein. In some embodiments, the polypeptide comprises a sequence having the sequence shown in SEQ ID NO:50 and includes a stem portion (S1) containing an Fc region, the Fc region further containing a transmembrane domain, such as those provided herein. In some embodiments, the Fc region further containing a transmembrane domain has the formula L1-Fc-L2-X1, wherein L1 is a linker as provided herein or is absent, Fc is a variant Fc region as provided herein, L2 is a linker as provided herein or is absent, and X1 is a polypeptide containing a transmembrane domain as provided herein. As provided herein, X1 may contain a peptide having the formula ECD-T M -ICD polypeptides, wherein ECD is an extracellular domain or fragment thereof as provided herein, or is absent, T M The transmembrane domain is as described herein, and the ICD is an intracellular domain as described herein or is absent. In some embodiments, the polypeptide comprises a sequence having the sequence shown in SEQ ID NO: 50 and includes a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing an ECD, T M And ICD. In some embodiments, the polypeptide comprises a sequence having the sequence shown in SEQ ID NO:50 and includes a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing CD8 and / or CD28 ECD, T M And ICD. In some embodiments, the polypeptide comprises a sequence having the sequence shown in SEQ ID NO:50 and includes a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing ECD, CD8 and / or CD28 T. M And ICD. In some embodiments, the polypeptide comprises a sequence having the sequence shown in SEQ ID NO:50 and includes a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing CD8 and / or CD28 ECD, CD8 and / or CD28 T. M And ICD. In some embodiments, the polypeptide comprises a sequence having the sequence shown in SEQ ID NO:50 and includes a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing an ECD, T MAnd ICD, wherein the ICD contains an env incorporation motif as provided herein. In some embodiments, the polypeptide comprises a sequence having the sequence shown in SEQ ID NO:50 and includes a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing CD8 and / or CD28ECD, T M And an ICD, wherein the ICD contains an env incorporation motif as provided herein. In some embodiments, the polypeptide comprises a sequence having the sequence shown in SEQ ID NO:50 and includes a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing an ECD, CD8, and / or CD28T. M And an ICD, wherein the ICD contains an env incorporation motif as provided herein. In some embodiments, the polypeptide comprises a sequence having the sequence shown in SEQ ID NO:50 and includes a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing CD8 and / or CD28 ECD, CD8 and / or CD28 T. M And an ICD, wherein the ICD contains an env incorporation motif as provided herein. In some embodiments, the polypeptide comprises a sequence having the sequence shown in SEQ ID NO:50 and includes a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing an ECD, T M And ICD, the polypeptide is anchored to 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 as provided herein. In some embodiments, the polypeptide binds to immune cells, such as those provided herein.

[0334] In some embodiments, the polypeptide comprises a sequence having the sequence shown in SEQ ID NO:51 and includes a stem portion (S1) containing an Fc region, such as those provided herein. In some embodiments, the polypeptide comprises a sequence having the sequence shown in SEQ ID NO:51 and includes a stem portion (S1) containing an Fc region, the Fc region further containing a transmembrane domain, such as those 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 as provided herein or is absent, Fc is a variant Fc region as provided herein, L2 is a linker as provided herein or is absent, and X1 is a polypeptide containing a transmembrane domain as provided herein. As provided herein, X1 may contain a peptide having the formula ECD-T M-ICD polypeptides, wherein ECD is an extracellular domain or fragment thereof as provided herein, or is absent, T M The transmembrane domain is as described herein, and the ICD is an intracellular domain as described herein or is absent. In some embodiments, the polypeptide comprises a sequence having the sequence shown in SEQ ID NO: 51 and includes a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing an ECD, T M And ICD. In some embodiments, the polypeptide comprises a sequence having the sequence shown in SEQ ID NO:51 and includes a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing CD8 and / or CD28 ECD, T M And ICD. In some embodiments, the polypeptide comprises a sequence having the sequence shown in SEQ ID NO:51 and includes a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing ECD, CD8 and / or CD28 T. M And ICD. In some embodiments, the polypeptide comprises a sequence having the sequence shown in SEQ ID NO:51 and includes a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing CD8 and / or CD28 ECD, CD8 and / or CD28 T. M And ICD. In some embodiments, the polypeptide comprises a sequence having the sequence shown in SEQ ID NO:51 and includes a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing an ECD, T M And ICD, wherein the ICD contains an env incorporation motif as provided herein. In some embodiments, the polypeptide comprises a sequence having the sequence shown in SEQ ID NO:51 and includes a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing CD8 and / or CD28ECD, T M And an ICD, wherein the ICD contains an env incorporation motif as provided herein. In some embodiments, the polypeptide comprises a sequence having the sequence shown in SEQ ID NO:51 and includes a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing an ECD, CD8, and / or CD28T. MAnd an ICD, wherein the ICD contains an env incorporation motif as provided herein. In some embodiments, the polypeptide comprises a sequence having the sequence shown in SEQ ID NO:51 and includes a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing CD8 and / or CD28 ECD, CD8 and / or CD28 T. M And an ICD, wherein the ICD contains an env incorporation motif as provided herein. In some embodiments, the polypeptide comprises a sequence having the sequence shown in SEQ ID NO:51 and includes a stem portion (S1) containing an Fc region (L1-Fc-L2-X1) containing an ECD, T M And ICD, the polypeptide is anchored to 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 as provided herein. In some embodiments, the polypeptide binds to immune cells, such as those provided herein.

[0335] Targeting portion containing flexible peptides

[0336] In some implementations, the V H and V L The polypeptide is linked to a stem portion (S1) comprising a flexible polypeptide (L3) as provided herein. In some embodiments, the V H and V L The polypeptide is linked to a stem portion (S1) comprising a flexible polypeptide, said flexible polypeptide further comprising a polypeptide comprising a transmembrane domain as provided herein. In some embodiments, the flexible polypeptide further comprising a polypeptide comprising a transmembrane domain is represented by formula L3-X1, wherein L3 is a flexible polypeptide as provided herein and X1 is as provided herein. As provided herein, X1 may comprise having formula ECD-T M -ICD polypeptides, wherein ECD is an extracellular domain or fragment thereof as provided herein, or is absent, T M The transmembrane domain is as described herein, and the ICD is an intracellular domain as described herein or is absent. Examples of ECDs include, but are not limited to, CD8 and / or CD28 ECDs as described herein. M Examples include, but are not limited to, CD8 and / or CD28 transmembrane domains as provided herein. In any of the following embodiments, it should be understood that ECD, ICD, or both may optionally be absent. Thus, X1 comprises CD8 and / or CD28 ECD, CD8 and / or CD28 T... MImplementations of ICDs containing Env-doped motifs should be understood to encompass the following X1 members: i) CD8 and / or CD28 ECDs, CD8 and / or CD28 T M and ICDs containing Env-doped motifs; ii) CD8 and / or CD28 T M and ICDs containing Env-doped motifs, wherein ECDs are absent; iii) CD8 and / or CD28 ECDs and CD8 and / or CD28 TCDs. M Where ICD is absent; and iv) CD8 and / or CD28 T M In this case, neither ECD nor ICD exists. Similarly, X1 contains CD8 and / or CD28 T. M Implementations of ICDs containing Env-doped motifs should be understood to encompass the following X1 members: i) CD8 and / or CD28T M And ICDs containing Env-doped motifs; and ii) CD8 and / or CD28 T M Where ICD is absent. Similarly, where X1 contains CD8 and / or CD28 ECD and CD8 and / or CD28 T. M The implementation scheme should be understood to cover the following X1 members: i) CD8 and / or CD28 ECD and CD8 and / or CD28 T M ; and ii) CD8 and / or CD28 T M The ECD is not present. It should be further understood that the previous explanation did not describe a specific ECD or T. M The implementation scheme of the ICD is also correct. For example, where X1 includes an ECD, CD8, and / or CD28 T. M T...

Claims

1. A viral particle comprising a heterologous viral glycoprotein and a targeting moiety, wherein the targeting moiety comprises a polypeptide having the formula T-S1, wherein T is a target binding domain and S1 is a stem portion, wherein the stem portion S1 comprises a variant Fc protein, wherein the variant Fc protein comprises a transmembrane domain and an effector mutation, wherein the effector mutation inhibits the interaction between the Fc protein and an Fc interacting protein, optionally wherein the Fc interacting protein is one of FcγR, C1q, FcRβ or FcRn, and wherein the S1 stem portion is attached to the surface of the viral particle through the transmembrane domain.

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

28.

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

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

103.

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

104.

6. The viral particle of claim 1, wherein the targeting moiety having the formula T-S1 comprises a stem portion S1 having the formula L1-Fc-L2-X1, wherein: L1 is a linker or does not exist; Fc is a variant Fc protein; L2 is a linker or is absent; and X1 is a polypeptide comprising the transmembrane domain, wherein the targeting moiety having the formula T-S1 has the formula T-L1-Fc-L2-X1.

7. The viral particle of claim 6, wherein L1 or L2 is each independently a polypeptide linker, wherein the polypeptide linker comprises one of the following: (GGGGA) n (SEQ ID NO:54), (GGGGS) n (SEQ ID NO:55), (EAAAK) n (SEQ ID NO:73), A(EAAAK) n A (SEQ ID NO: 74), (XP) n (SEQ ID NO:75) (wherein 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, wherein each n is independently 1-5.

8. The viral particle of claim 6, wherein L1 is (GGGGA) n (SEQ ID NO:54) or (GGGGS) n (SEQ ID NO: 55), and wherein each n is independently 1-5.

9. The viral particle of claim 6, wherein X1 comprises a virus having the formula ECD-T M -ICD polypeptide, wherein: The ECD is the extracellular domain of a cell surface protein or a fragment thereof, or is absent; T M is a transmembrane domain of a transmembrane protein; and ICD is an intracellular domain or protein that facilitates incorporation of the targeting moiety into the envelope of the viral particle, or is absent, wherein the targeting moiety having the formula T-L1-Fc-L2-X1 has the formula T-L1-Fc-L2-ECD-T M -ICD.

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

60.

11. The viral particle of claim 9, wherein the T M Comprising the amino acid sequence of SEQ ID NO:61 or SEQ ID NO:

62.

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

64.

13. A viral particle as described in claim 1, wherein the target binding domain (T) binds to an immune cell, wherein the immune cell is any one of the following: T cell, B cell; NK cell, dendritic cell, neutrophil, macrophage, cancer cell; or, for example, CD3+T cell; CD4+T cell; CD7+T cell, CD8+T cell; CD19+B cell; CD19+ cancer cell; CD20+B cell; CD20+ cancer cell, CD30+ lung epithelial cell; CD34+ hematopoietic stem cell; CD105+ endothelial cell; CD105+ hematopoietic stem cell; CD117+ hematopoietic stem cell; CD133+ cancer cell; EpCAM+ cancer cell; GluA2+ neuron; GluA4+ neuron; hematopoietic stem cell; hepatocyte; Her2 / Neu+ cancer cell; NKG2D+ natural killer cell; SLC1A3+ astrocyte; SLC7A10+ adipocyte.

14. The viral particle of claim 1, wherein the target binding domain (T) binds to CD7, CD8, cKit (CD117), CD4, CD3, CD5, CD6, CD2, TCRα, TCRβ, TCRγ, TCRδ, CD10, CD34, CD110, CD33, CD14, CD68, CCR7, CD62L, CD25, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7 or CXCR3; a glycosylated CD43 epitope expressed on acute leukemia or lymphoma but not on hematopoietic progenitor cells; a glycosylated CD43 epitope expressed on non-hematopoietic cancers; kinase anchoring protein 4 (AKAP-4); adrenergic receptor β3 (ADRB3); AFP; anaplastic lymphoma kinase (ALK); androgen receptor; angiopoietin binding cell surface receptor 2 (Tie 2); autoantibodies to desmoglein 1 (Dsgl); autoantibodies to desmoglein 3 (Dsg3); B7H3 (CD276); biotin; bone marrow stromal cell antigen 2 (BST2); BST1 / CD157; cancer / testis antigen 1 (NY-ESO-1); cancer / testis antigen 2 (LAGE-la); carbonic anhydrase IX (CA1X); carcinoembryonic antigen (CEA); CCCTC-binding factor (zinc finger protein)-like (BORIS or imprinting site regulator-like protein); CCR4; CD5; CD19; CD20; CD22; CD24; CD30; CD32 (F CGR2A); CD33; CD34; CD38; CD44v6; CD72; CD79a; CD79b; CD97; CD99; CD123; CD171; CD179a; CD179b-IGLll; CD200R; CD276 / B7H3; CD300 molecule-like family member f (CD300LF); CDH1-CD324; CDH6; CDH17; CDH19; chromosome X open reading frame 61 (CXORF61); claudin 6 (CLDN6); claudin 18.2 (CLD18A2 or CLDN18A.2); CMV pp65; C-MYC epitope tag; Cripto; CS1 (also known as CD2 subset 1 or CRACC or SLAMF7 or CD319 or 19A24); CSF2RA (GM-CSFR-α); C-type lectin domain family 12 member A (CLEC12A); C-type lectin-like molecule-1 (CLL-1 or CLECL1); cyclin Bl; cytochrome P450 IB 1 (CYP1B 1); DLL3; EBV-EBNA3c; EGF-bke module-containing mucin-like hormone receptor-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 variant III (EGFRviii); epithelial cell adhesion molecule (EPCAM); ERG; ETS translocation variant gene located on chromosome 12p 6 (ETV6-AML); Fc fragment of IgA receptor (FCAR or CD89); Fc receptor-like 5 (FCRL5); fibroblast activation protein alpha (FAP); FITC; Fms-like tyrosine kinase 3 (FLT3); folate receptor alpha (FRa or FR1); folate receptor beta (F Rb); follicle stimulating hormone receptor (FSHR); Fos-related antigen 1; fucosyl-GM1; G protein-coupled receptor class C group 5 member D (GPRC5D); G protein-coupled receptor 20 (GPR20); GAD; ganglioside G2 (GD2); ganglioside GD3 (aNeu5Ac(2-8)aNeu5Ac(2-3)bDGalp(l-4)bDGlcp(ll)Cer); ganglioside GM3 (aNeu5Ac(2-3)bDClalp(l-4)bDGlcp(ll)Cer); GD3; GFRα4; glycoprotein 100 (gplOO); glypican-3 (GPC3); gonadotropin receptor (CGHR or GR); GpA33; GpNMB;. GPRC5D; guanylate cyclase C (GCC); mutant heat shock protein 70-2 (mut hsp70-2); hepatitis A virus cellular receptor 1 (HAVCR1); the hexasaccharide portion of globoH glycerol ceramide (GloboH); high molecular weight melanoma associated antigen (HMWMAA); HIV1 envelope glycoprotein; HLA; HLA-DOA; HLA-A; HLA-A2; HLA-B; HLA-C; HLA-DM; HLA-DOB; HLA-DP; HLA-DQ; HLA-DR; HLA-G; HTLVl-Tax; human papillomavirus E6 (HPV E6); human papillomavirus E7 (HPV E7); human telomerase reverse transcriptase (hTERT); IgE; IL13Ra2; Ill lRa; immunoglobulin lambda-like polypeptide 1 (IGLL1); influenza A hemagglutinin (HA); insulin-like growth factor 1 receptor (IGF-I receptor); interleukin-11 receptor alpha (IL-llRa); interleukin-13 receptor subunit alpha-2 (IL-13Ra2 or CD213A2); intestinal carboxylesterase; KIT (CD117); KSHV K8.1; KSHV-gH; LAMP1; legumin; leukocyte immunoglobulin-like receptor subfamily A member 2 (LILRA2); leukocyte-associated immunoglobulin-like receptor 1 (LAIR1); luteinizing hormone receptor (LHR); Lewis (Y) antigen; Lewis Ag; Livl; locus K 9 (LY6K); low conductance chloride channel; lymphocyte antigen 6 complex; lymphocyte antigen 75 (LY75); lymphocyte-specific protein tyrosine kinase (LCK); mammary gland differentiation antigen (NY-BR-1); melanoma antigen recognized by T cells 1 (MelanA or MARTI); melanoma associated antigen 1 (MAGE-A1); melanoma cancer testis antigen-1 (MAD-CT-1); melanoma cancer testis antigen 2 (MAD-CT-2); melanoma inhibitor of apoptosis (ML-IAP ); mesothelin; MPL; mucin 1 cell surface associated (MUC1); N-acetylglucosaminyltransferase V (NA17); fibronectin-4; neural cell adhesion molecule (NCAM); NKG2D; NYBR1; O-acetyl-GD2 ganglioside (OacGD2); olfactory receptor 51E2 (OR51E2); oncogene fusion protein composed of breakpoint cluster region (BCR) and Abelson murine leukemia virus oncogene homolog 1 (Abl) (bcr-abl); p53 mutant; paired box protein Pax-3 (PAX3); Paired box protein Pax-5 (PAX5); pan-linked protein 3 (PANX3); PDL1; P-glycoprotein; placenta-specific 1 (PLAC1); platelet-derived growth factor receptor β (PDGFR-β); polysialic acid; pre-acrosome binding protein sp32 (OY-TES1); prostate enzyme; prostate cancer tumor antigen-1 (PCT A1 or galectin 8); prostate stem cell antigen (PSCA); prostate-specific membrane antigen (PSMA); prostatic acid phosphatase (PAP); prostaglandins; protease serine 21 (testin or PRSS21); proteasome (Prosome Macropain) subunit β9 type (LMP2); PTK7; Ras G12V; Ras homology family member C (RhoC); Rat sarcoma (Ras) mutant; Receptor for advanced glycation end products (RAGE-1); Receptor tyrosine kinase-like orphan receptor 1 (ROR1); Receptor tyrosine protein kinase ERBB2 or Her-22 / neu; Renal ubiquitination 1 (RU1); Renal ubiquitination 2 (RU2); Sarcoma translocation breakpoints; ETS fusion gene at serine 2 (TMPRSS2); Sialyl Lewis adhesion molecule (sLe); SLAMF4; SLAMF6; Slea (CA19.9 or sialyl Lewis antigen) ; sperm protein 17 (SPA17); squamous cell carcinoma antigen recognized by T cells 3 (SART3); stage-specific embryonic antigen-4 (SSEA-4); STEAP1; survivin; synovial sarcoma X breakpoint 2 (SSX2); TCRγ alternate reading frame protein (TARP); TCR-β1 chain; TCR-β2 chain; TCR-δ chain; TCR-γ chain; TCRγ-δ; telomerase; TGFβR2; antigen recognized by TNT antibody; thyroid stimulating hormone receptor (TSHR); Timl- / HVCR1; tissue factor 1 (TF1); Tn ag; Tn antigen ((Tn Ag) or (GalNAca-Ser / Thr)); TNF receptor family member B cell maturation (BCMA); transglutaminase 5 (TGS5); transmembrane protease; TROP2; tumor endothelial marker 1 (TEM1 / CD248); tumor endothelial marker 7 related (TEM7R); tumor protein p53 (p53); tumor-associated glycoprotein 72 (TAG72); tyrosinase; tyrosinase-related protein 2 (TRP-2); uroplaque protein 2 (UPK2); vascular endothelial growth factor receptor 2 (VEGFR2); V-myc avian myelocytomas viral oncogene neuroblastoma-derived homolog (MYCN); Wilms' tumor protein (WT1); or X antigen family member 1A (XAGE1).

15. The viral particle of claim 14, wherein the target binding domain (T) binds to CD7.

16. A viral particle as described in claim 15, wherein the target binding domain (T) comprises a polypeptide, the polypeptide comprising a heavy chain and a light chain, which comprises: a heavy chain variable region in the heavy chain having at least 90% sequence identity with SEQ ID NO:36, and a light chain variable region in the light chain having at least 90% sequence identity with SEQ ID NO:37, wherein the polypeptide comprises the sequence of HCDR1 as shown in SEQ ID NO:30; HCDR2 as shown in SEQ ID NO:31; HCDR3 as shown in SEQ ID NO:32; LCDR1 as shown in SEQ ID NO:33; LCDR2 as shown in SEQ ID NO:34; and LCDR3 as shown in SEQ ID NO:

35.

17. The viral particle of claim 16, wherein the heavy chain comprises: a heavy chain variable region in the heavy chain that has at least 90% sequence identity, at least 95% identity, or at least 99% identity to SEQ ID NO: 36, or comprises the amino acid sequence of SEQ ID NO: 36; and the light chain comprises a light chain variable region in the light chain that has at least 90% sequence identity, at least 95% identity, or at least 99% identity to SEQ ID NO: 37, or comprises the amino acid sequence of SEQ ID NO:

37.

18. The viral particle of claim 15, wherein the target binding domain (T) that binds to CD7 comprises a polypeptide comprising a sequence having at least 90% sequence identity to SEQ ID NO: 38, at least 95% sequence identity to SEQ ID NO: 38, at least 99% sequence identity to SEQ ID NO: 38, or a sequence as shown in SEQ ID NO:

38.

19. The viral particle of claim 15, wherein the target binding domain (T) that binds to CD7 comprises a polypeptide comprising a sequence having at least 90% sequence identity to SEQ ID NO: 39, at least 95% sequence identity to SEQ ID NO: 39, at least 99% sequence identity to SEQ ID NO: 39, or a sequence as shown in SEQ ID NO:

39.

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

21. The viral particle of claim 20, wherein the VSV-G polypeptide comprises an amino acid sequence having at least 70% identity to SEQ ID NO:2 and comprising a mutation at position 182 compared to SEQ ID NO:

2.

22. The viral particle of claim 20, wherein the VSV-G polypeptide comprises an I182E or I182D mutation compared to SEQ ID NO:

2.

23. The viral particle of claim 20, wherein the VSV-G polypeptide comprises 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%, 99% or 100% identical to the sequence of SEQ ID NO:

4.

24. The viral particle of claim 20, wherein the VSV-G polypeptide comprises 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%, 99% or 100% identical to the sequence of SEQ ID NO:

5.

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

2.

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

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

25.

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

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

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

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

32. The viral particle of claim 31 , wherein the antigen binding domain that binds to CD20 comprises a polypeptide comprising a light chain and a heavy chain, comprising: a heavy chain variable region in the heavy chain that is at least 90% identical to the amino acid sequence of SEQ ID NO: 89, at least 95% identical to the amino acid sequence of SEQ ID NO: 89, or at least 99% identical to the amino acid sequence of SEQ ID NO: 89, or comprises the amino acid sequence of SEQ ID NO: 89; and a light chain variable region in the light chain that is at least 90% identical to the amino acid sequence of SEQ ID NO: 90, at least 95% identical to the amino acid sequence of SEQ ID NO: 90, or at least 99% identical to the amino acid sequence of SEQ ID NO: 90, or comprises the amino acid sequence of SEQ ID NO:

90.

33. The viral particle of claim 31, wherein the antigen binding domain that binds to CD20 comprises a polypeptide comprising a sequence having at least 90% sequence identity to SEQ ID NO:92, at least 95% sequence identity to SEQ ID NO:92, at least 99% sequence identity to SEQ ID NO:92, or a sequence as shown in SEQ ID NO:

92.

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

93.

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

95.

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

96.

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

97.

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

39. A viral particle as described in claim 31, wherein the CAR comprises an amino acid sequence that is at least 85% identical to SEQ ID NO:99, at least 90% identical to SEQ ID NO:99, at least 95% identical to SEQ ID NO:99, at least 99% identical to SEQ ID NO:99, or at least 100% identical to SEQ ID NO:

99.

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

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

42. A method of delivering a heterologous molecule of interest to a cell, the method comprising contacting the cell with a viral particle as described in any one of claims 1 to 39, wherein the viral particle comprises a nucleic acid molecule encoding the heterologous molecule of interest.

43. A method of delivering a heterologous molecule of interest to a cell of a subject, the method comprising administering to the subject a viral particle as described in any one of claims 1 to 39, wherein the viral particle comprises a nucleic acid molecule encoding the heterologous molecule of interest.

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

45. A method as described in any one of claims 40 to 43, wherein the cell is a T cell, a B cell; a NK cell, a dendritic cell, a neutrophil, a macrophage, a cancer cell; or, for example, a CD3+T cell; a CD4+T cell; a CD7+T cell, a CD8+T cell; a CD19+B cell; a CD19+ cancer cell; a CD20+B cell; a CD20+ cancer cell, a CD30+ lung epithelial cell; a CD34+ hematopoietic stem cell; a CD105+ endothelial cell; a CD105+ hematopoietic stem cell; a CD117+ hematopoietic stem cell; a CD133+ cancer cell; an EpCAM+ cancer cell; a GluA2+ neuron; a GluA4+ neuron; a hematopoietic stem cell; a hepatocyte; a Her2 / Neu+ cancer cell; a NKG2D+ natural killer cell; a SLC1A3+ astrocyte; a SLC7A10+ adipocyte.

46. ​​A method of treating a disease or condition in a subject, the method comprising administering to the subject a viral particle as described in any one of claims 1 to 39, wherein the viral particle comprises a nucleic acid molecule encoding the heterologous molecule of interest, to treat the disease or condition.

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

48. A viral particle comprising a heterologous viral glycoprotein and a targeting moiety, wherein the targeting moiety comprises a polypeptide having the formula T-S1, Wherein T is the target binding domain and S1 is the stem portion, wherein the heterologous viral glycoprotein comprises the sequence of SEQ ID NO:23 or SEQ ID NO:25; wherein the target binding domain comprises the sequence of SEQ ID NO: 39; The stem portion S1 comprises the formula L1-Fc-L2-X1, wherein: L1 is a linker comprising the sequence of SEQ ID NO: 55; Fc is a variant Fc protein comprising the sequence of SEQ ID NO: 104; L2 is the linker and is absent; X1 is a polypeptide comprising a transmembrane domain having the formula ECD-T M -ICD, where: ECD is the extracellular domain having the sequence of SEQ ID NO: 60; T M is a transmembrane domain having the sequence of SEQ ID NO: 62; and ICD is an intracellular domain or protein that facilitates the incorporation of the targeting moiety into the envelope of the viral particle, wherein the ICD comprises an env incorporation motif comprising the amino acid sequence of SEQ ID NO:

63.

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

98.

50. A viral particle as described in claim 48 or claim 49, wherein the viral particle further comprises a nucleic acid molecule encoding a CAR, wherein the CAR comprises an amino acid sequence that is at least 85% identical to SEQ ID NO:99, at least 90% identical to SEQ ID NO:99, at least 95% identical to SEQ ID NO:99, at least 99% identical to SEQ ID NO:99, or at least 100% identical to SEQ ID NO:99.

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