Compositions and methods for the treatment of immunological disorders

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 S1 is a stem moiety. As provided herein, the viral particle also comprises a nucleic acid molecule encoding a heterologous molecule of interest. As provided herein, the heterologous molecule of interest may be a CD19 CAR. Also provided herein are compositions comprising the viral particles and methods of using the viral particles.

Description

(19) State Intellectual Property Office (12) Invention Patent Application (10) Publication Number (43) Publication Date (21) Application Number 202480045904.8 (22) Application Date 2024.06.11 (30) Priority Data 63 / 507,531 2023.06.12 US 63 / 644,196 2024.05.08 US (85) PCT International Application Entering National Phase Date 2026.01.07 (86) PCT International Application Application Data PCT / US2024 / 033431 2024.06.11 (87) PCT International Application Publication Data WO2024 / 258866 EN 2024.12.19 (71) Applicant: Interus Biotherapeutics, Inc. Address: Pennsylvania, USA (72) Inventor: P.R. Johnson (74) Patent Agency: Beijing Liu Shen Law Firm, 11105 Patent Attorney: Qin Jian (51) Int.Cl. A61K 48 / 00 (2006.01) A61P 35 / 00 (2006.01) A61P 37 / 00 (2006.01) C07K 14 / 005 (2006.01) C07K 14 / 145 (2006.01) C07K 14 / 705 (2006.01) C07K 16 / 28 (2006.01) C12N 15 / 113 (2006.01) C12N 15 / 63 (2006.01) C12N 15 / 86(2006.01) C12N 7 / 01(2006.01) A61K 31 / 711(2006.01) A61K 38 / 16(2006.01) (54) Invention Title Composition and Method for Treating Immunological Disorders (57) Abstract This document provides viral particles comprising a heterologous viral glycoprotein and a targeting portion, wherein the targeting portion comprises a polypeptide containing the formula T-S1, wherein T is a target-binding domain and S1 is a stem portion. As provided herein, the viral particle also comprises a nucleic acid molecule encoding a heterologous molecule of interest. As provided herein, the heterologous molecule of interest may be a CD19 CAR. This document also provides compositions comprising the viral particle and methods of using the viral particle. Claims 6 pages Description 167 pages Sequence Listing (Electronic Publication) Figures 46 pages CN 121487755 A 2026.02.06 CN 1 21 48 77 55 A

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 stalk moiety.

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

3. The viral particle of claim 2, wherein the heterologous molecule of interest is a chimeric antigen receptor ("CAR") comprising an antigen binding domain comprising an antibody or fragment thereof, wherein the antigen binding domain of the CAR binds to CD19.

4. The viral particle of claim 3, wherein the antibody or fragment thereof is an antibody, an scFv antibody, an antigen binding domain, an ankyrin repeat, a VHH domain antibody, a nanobody, a single domain antibody, or a FN3 antibody.

5. The viral particle of claim 3, wherein the antigen binding domain of the CAR that binds to CD19 comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises the sequence of HCDR1 as set forth in SEQ ID NO: 108; HCDR2 as set forth in SEQ ID NO: 109, and HCDR3 as set forth in SEQ ID NO: 110, and wherein the light chain variable region comprises the sequence of LCDR1 as set forth in SEQ ID NO: 111; LCDR2 as set forth in SEQ ID NO: 112, and LCDR3 as set forth in SEQ ID NO:

113.

6. The viral particle of claim 3, wherein the antigen binding domain that binds to CD19 comprises a polypeptide comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 89; and wherein the light chain variable region comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 90, wherein the heavy chain variable region comprises the sequence of HCDR1 as set forth in SEQ ID NO: 108; HCDR2 as set forth in SEQ ID NO: 109, HCDR3 as set forth in SEQ ID NO: 110; and wherein the light chain variable region comprises the sequence of LCDR1 as set forth in SEQ ID NO: 111; LCDR2 as set forth in SEQ ID NO: 112, and LCDR3 as set forth in SEQ ID NO:

113.

7. The viral particle of claim 3, wherein the antigen binding domain that binds to CD 19 comprises a polypeptide comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 89; and the light chain variable region comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO:

90.

8. The viral particle of claim 3, wherein the antigen binding domain that binds to CD 19 comprises a polypeptide comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 89; and the light chain variable region comprises the amino acid sequence of SEQ ID NO:

90.

9. The viral particle of any one of claims 5-8, wherein the heavy chain variable region and the light chain variable region are directly connected to one another and are not connected by a linker.

10. The viral particle of claim 3, wherein the antigen binding domain that binds to CD 19 comprises a polypeptide comprising an amino acid sequence that is at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 92, at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 92, at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 92, or the sequence as set forth in SEQ ID NO:

92.

11. The viral particle of claim 3, wherein the antigen binding domain that binds to CD 19 comprises a polypeptide comprising an amino acid sequence that is at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 93, at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 93, at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 93, or the sequence as set forth in SEQ ID NO:

93.

12. The viral particle of claim 3, wherein the antigen binding domain of the CAR that binds to CD 19 comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises the sequence of HCDR1 as set forth in SEQ ID NO: 114; HCDR2 as set forth in SEQ ID NO: 115, and HCDR3 as set forth in SEQ ID NO: 116, and wherein the light chain variable region comprises the sequence of LCDR1 as set forth in SEQ ID NO: 117; LCDR2 as set forth in SEQ ID NO: 118, and LCDR3 as set forth in SEQ ID NO:

119.

13. The viral particle of claim 3, wherein the antigen binding domain that binds to CD 19 comprises a polypeptide comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 94; and the light chain variable region comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 95, wherein the heavy chain variable region comprises the sequence of a HCDR1 as set forth in SEQ ID NO: 114; a HCDR2 as set forth in SEQ ID NO: 115, a HCDR3 as set forth in SEQ ID NO: 116; a LCDR1 as set forth in SEQ ID NO: 117; a LCDR2 as set forth in SEQ ID NO: 118, and a LCDR3 as set forth in SEQ ID NO:

119.

14. The viral particle of claim 3, wherein the antigen binding domain that binds to CD 19 comprises a polypeptide comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 94; and the light chain variable region comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO:

95.

15. The viral particle of claim 3, wherein the antigen binding domain that binds to CD 19 comprises a polypeptide comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 94; and the light chain variable region comprises the amino acid sequence of SEQ ID NO:

95.

16. The viral particle of any one of claims 12 to 15, wherein the heavy chain variable region and the light chain variable region are connected via a polypeptide linker comprising the amino acid sequence of SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, or SEQ ID NO:

76.

17. The viral particle of claim 3, wherein the antigen binding domain that binds to CD 19 comprises a polypeptide comprising a sequence that is at least 90% sequence identical to the amino acid sequence of SEQ ID NO: 96, at least 95% sequence identical to the amino acid sequence of SEQ ID NO: 96, at least 99% sequence identical to the amino acid sequence of SEQ ID NO: 96, or the sequence as set forth in SEQ ID NO:

96.

18. The viral particle of claim 3, wherein the antigen binding domain that binds to CD19 comprises a polypeptide comprising a sequence with at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 97, at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 97, at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 97, or a sequence as set forth in SEQ ID NO:

97.

19. The viral particle of any one of claims 3-18, wherein the CAR further comprises a hinge domain, a transmembrane domain, a costimulatory domain, and a signaling domain.

20. The viral particle of claim 3, wherein the CAR comprises an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 99, at least 90% identical to the amino acid sequence of SEQ ID NO: 99, at least 95% identical to the amino acid sequence of SEQ ID NO: 99, at least 99% identical to the amino acid sequence of SEQ ID NO: 99, or at least 100% identical to the amino acid sequence of SEQ ID NO:

99.

21. The viral particle of claim 3, wherein the CAR comprises an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 105, at least 90% identical to the amino acid sequence of SEQ ID NO: 105, at least 95% identical to the amino acid sequence of SEQ ID NO: 105, at least 99% identical to the amino acid sequence of SEQ ID NO: 105, or at least 100% identical to the amino acid sequence of SEQ ID NO:

105.

22. The viral particle of claim 3, wherein the CAR comprises an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 106, at least 90% identical to the amino acid sequence of SEQ ID NO: 106, at least 95% identical to the amino acid sequence of SEQ ID NO: 106, at least 99% identical to the amino acid sequence of SEQ ID NO: 106, or at least 100% identical to the amino acid sequence of SEQ ID NO:

106.

23. The viral particle of claim 3, wherein the CAR comprises an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 107, at least 90% identical to the amino acid sequence of SEQ ID NO: 107, at least 95% identical to the amino acid sequence of SEQ ID NO: 107, at least 99% identical to the amino acid sequence of SEQ ID NO: 107, or at least 100% identical to the amino acid sequence of SEQ ID NO:

107.

24. The viral particle of claim 3, wherein the stalk moiety S1 comprises a variant Fc protein, wherein the variant Fc protein comprises a transmembrane domain and an effector mutation, wherein the effector mutation inhibits interaction between the Fc protein and an Fc interacting protein such as FcyR, Clq, FcRb, or FcRn.

25. The viral particle of claim 24, wherein the S1 stalk moiety is attached to the surface of the viral particle by the transmembrane domain.

26. The viral particle of claim 24, wherein the variant Fc protein is a variant IgGl Fc protein.

27. The viral particle of claim 26, wherein the variant IgGl Fc protein comprises one or more of the following mutations selected from the group consisting of L234A, L235A, N297A, P329G, I253A, H310A, and H435A.

28. The viral particle of claim 26, wherein the variant IgGl 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.

29. The viral particle of any one of claims 2-37, wherein the targeting moiety having the formula T-S1 comprises a stalk moiety S1 having the formula L1-Fc-L2-X1, wherein: L1 is a linker or is absent; 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.

30. The viral particle of claim 29, wherein L1 and L2 are each independently absent or a polypeptide linker comprising the amino acid sequence of SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, or SEQ ID NO:

76.

31. The viral particle of claim 29, wherein X1comprises a polypeptide having the formula ECD-T M -ICD, wherein: ECD is an extracellular domain of a cell surface protein or a fragment thereof, or is absent; T M is a transmembrane domain of a transmembrane protein; and ICD is an intracellular domain or a protein that facilitates incorporation of the targeting moiety into the envelope of the viral particle, or is absent, wherein said targeting moiety having said formula T-L1-Fc-L2-X1 has the formula T-L1-Fc-L2-ECD-T M - ICD.

32. The viral particle of claim 31, wherein the ECD comprises the amino acid sequence of SEQ ID NO: 59 or SEQ ID NO:

60.

33. The viral particle of claim 31, wherein the T M comprises the amino acid sequence of SEQ ID NO: 61 or SEQ ID NO:

62.

34. The viral particle of any one of claims 31 to 33, wherein the ICD comprises an Env incorporation motif comprising the amino acid sequence of SEQ ID NO: 63 or SEQ ID NO:

64.

35. The viral particle of claim 3, wherein the target binding domain (T) binds to: CD7, CD8, cKit (CD117), CD4, CD3, CD5, CD6, CD2, TCRa, TCRp, TCRy, TCRd, CD10, CD34, CD110, CD33, CD14, CD68, CCR7, CD62L, CD25, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, or CXCR3, a glycosylated CD43 epitope expressed on acute leukemias or lymphoid cancers but not on hematopoietic progenitor cells; a glycosylated CD43 epitope expressed on non-hematopoietic cancers; A kinase anchor protein 4 (AKAP-4); adrenergic receptor beta 3 (ADRB3); AFP; anaplastic lymphoma kinase (ALK); androgen receptor; angiopoietin-binding cell surface receptor 2 (Tie 2); anti-desmoglein 1 (Dsgl) autoantibody; anti-desmoglein 3 (Dsg3) autoantibody; B7H3 (CD276); biotin; bone marrow stromal cell antigen 2 (BST2); BST1 / CD157; cancer / testis antigen 1 (NY-ESO-1); cancer / testis antigen 2 (LAGE-la); carbonic anhydrase IX (CAIX); carcinoembryonic antigen (CEA); CCCTC-binding factor (Zinc Finger Protein)-like (BORIS or Brother of the Regulator of Imprinted Site); CCR4; CD5; CD19; CD20; CD22; CD24; CD30; CD32 (FCGR2A); CD33; CD34; CD38; CD44v6; CD72; CD79a; CD79b; CD97; CD99; CD123; CD171; CD179a; CD179b-IGLll; CD200R; CD276 / B7H3; CD300 molecule-like family member f (CD300LF); CDH1-CD324; CDH6; CDH17; CDH19; Chromosome X Open Reading Frame 61 (CXORF61); Claudin 6 (CLDN6); Claudin 18 8.2 (CLD18A2 or CLDN18A.2); CMV pp65; C-MYC epitope tag; Cripto; CS1 (also known as CD2 subset 1 or CRACC or SLAMF7 or CD319 or 19A24); CSF2RA (GM-CSFR-alpha); C-type lectin domain family 12 member A (CLEC12A); C-type lectin-like molecule-1 (CLL-1 or CLECL1); Cyclin Bl; Cytochrome P450 IB 1 (CYP1B 1); DLL3; EBV-EBNA3c; EGF-bike module 2 containing mucin-like hormone receptor-like (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 6 located on chromosome 12p (ETV6-AML); Fc fragment of IgA receptor (FCAR or CD89); Fc receptor like 5 (FCRL5); Fibroblast activation protein alpha (FAP); FITC; Fms-like tyrosine kinase 3 (FLT3); Folate receptor alpha (Fra or FR1); Folate receptor beta (FRb); Follicle-stimulating hormone receptor (FSHR); Fos-related antigen 1; Fucosyl-GMl; G protein-coupled receptor class C group 5 member D (GPRC5D); G protein-coupled receptor 20 (GPR20); GAD; Ganglioside G2 (GD2); Ganglioside GD3 (aNeu5Ac(2-8)aNeu5Ac(2-3)bDGalp(l-4)bDGlcp(l-l)Cer); Ganglioside GM3 (aNeu5Ac(2-3)bDClalp(l-4)bDGlcp(l-l)Cer); GD3; GFRalpha4; Glycoprotein 100 (gplOO); Glypican-3 (GPC3); Gonadotropin receptor (CGHR or GR); GpA33; GpNMB; GPRC5D; Guanylate cyclase C (GCC); Mutated heat shock protein 70-2 (mut hsp70-2); Hepatitis A virus cellular receptor 1 (HAVCR1); Hexose portion of globoH glycosphingolipid (GloboH); High molecular weight-melanoma-associated antigen (HMWMAA); HIV1 envelope glycoprotein; HLA; HLA-DOA; HLA-A; HLA-A2; HLA-B; HLA-C; HLA-DM; HLA-DOB; HLA-DP; HLA-DQ; HLA-DR; HLA-G;. HTLVl-Tax; human papilloma virus E6 (HPV E6); human papilloma virus 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 carboxyl esterase; KIT (CD117); KSHV K8.1; KSHV-gH; LAMP1; legumain; leukocyte immunoglobulin-like receptor subfamily A member 2 (LILRA2); leukocyte-associated immunoglobulin-like receptor 1 (LAIR1); luteinizing hormone receptor (LHR); Lewis (Y) antigen; Lews Ag; Livl; locus K 9 (LY6K); low conductance chloride ion channel; lymphocyte antigen 6 complex; lymphocyte antigen 75 (LY75); lymphocyte-specific protein tyrosine kinase (LCK); mammary differentiation antigen (NY-BR-1); melanoma antigen recognized by T cells 1 (MelanA or MARTI); melanoma-associated antigen 1 (MAGE-A1); melanoma cancer testis antigen-1 (MAD-CT-1); melanoma cancer testis antigen-2 (MAD-CT-2); melanoma cell apoptosis inhibitor (ML-IAP); mesothelin; MPL; cell surface-associated mucin 1 (MUC1); N-acetylglucosaminyltransferase V (NA17); Nectin-4; neural cell adhesion molecule (NCAM); NKG2D; NYBR1; o-acetyl-GD2 ganglioside (OacGD2); olfactory receptor 51E2 (OR51E2); oncogenic fusion protein consisting of breakpoint cluster region (BCR) and Abelson murine leukemia viral oncogene homolog 1 (Abl) (bcr-abl); P53 mutant; paired box protein Pax-3 (PAX3); Pax-box protein Pax-5 (PAX5); pan adaptor protein 3 (PANX3); PDL1; P-glycoprotein; placenta-specific 1 (PLAC1); platelet-derived growth factor receptor beta (PDGFR-beta); polysialic acid; proacrosomal antigen sp32 (OY-TES1); prostein; prostate carcinoma tumor antigen-1 (PCTA-1 or galectin 8); prostate stem cell antigen (PSCA); prostate-specific membrane antigen (PSMA); prostatic acid phosphatase (PAP); prostein; serine protease 21 (Testisin or PRSS21); proteasome (Prosome Macropain) subunit beta type 9 (LMP2); PTK7; Ras G12V; Ras homolog family member C (RhoC); rat sarcoma (Ras) mutant; receptor for advanced glycation end products (RAGE-1); receptor tyrosine kinase-like orphan receptor 1 (ROR1); receptor tyrosine-protein kinase ERBB2 or Her-2 2 / neu; renal ubiquitous protein 1 (RU1); renal ubiquitous protein 2 (RU2); sarcoma translocation breakpoints; serine 2 (TMPRSS2) ETS fusion gene; sialyl Lewis adhesion molecule (sLe); SLAMF4; SLAMF6; Slea (CA19.9 or sialyl Lewis antigen); sperm protein 17 (SPA17); squamous cell carcinoma antigen recognized by T cells 3 (SART3); stage-specific embryonic antigen-4 (SSEA-4); STEAP1; survivin; synovial sarcoma X breakpoint 2 (SSX2); TCR gamma alternative reading frame protein (TARP); TCR-beta 1 chain; TCR-beta 2 chain; TCR-delta chain; TCR-gamma chain; TCR gamma-delta; telomerase; TGF beta R2; TNT antibody-recognized antigen; 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); urolipin 2 (UPK2); vascular endothelial growth factor receptor 2 (VEGFR2); V-myc avian myelocytomatosis viral oncogene neuroblastoma-derived homolog (MYCN); Wilms tumor protein (WT1); or X antigen family member 1A (XAGE1).

36. The viral particle of claim 35, wherein the target binding domain (T) binds to CD7.

37. The viral particle of claim 36, wherein the target binding domain (T) comprises a polypeptide comprising: (i) a heavy chain variable region comprising heavy chain CDRl, CDR2, and CDR3 sequences, wherein the heavy chain CDRl sequence has the amino acid sequence of SEQ ID NO: 30; the heavy chain CDR2 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 variant of any of the foregoing; and (ii) a light chain variable region comprising light chain CDRl, CDR2, and CDR3 sequences, wherein the light chain CDRl sequence has the amino acid sequence of SEQ ID NO: 33; the light chain CDR2 sequence has the amino acid sequence of SEQ ID NO: 34; and the light chain CDR3 sequence has the amino acid sequence of SEQ ID NO: 35; or a variant of any of the foregoing.

38. The viral particle of claim 36 or 37, wherein the target binding domain (T) comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 36 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:

37.

39. The viral particle of any one of claims 36 to 38, wherein the target binding domain (T) that binds to CD7 comprises a polypeptide comprising a sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 38 or SEQ ID NO: 39, at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 38 or SEQ ID NO: 39, at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 38 or SEQ ID NO: 39, or a sequence as set forth in SEQ ID NO: 38 or SEQ ID NO:

39.

40. The viral particle of any one of claims 1 to 39, wherein the target binding domain (T) is an antibody or antigen-binding fragment thereof, such as an scFv antibody.

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

42. The viral particle of claim 41, 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.

43. A method of infecting a cell, the method comprising contacting the cell with a viral particle of any one of claims 1 to 42.

44. A method of infecting a cell of a subject, the method comprising administering to the subject a pharmaceutical composition comprising a viral particle of any one of claims 1 to 42.

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

46. 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 according to any one of claims 1 to 42, wherein the viral particle comprises a nucleic acid molecule encoding the heterologous molecule of interest.

47. A method of treating a disease or disorder in a subject, the method comprising administering to the subject a viral particle according to any one of claims 1 to 42, wherein the viral particle comprises a nucleic acid molecule encoding the heterologous molecule of interest for treating the disease or disorder.

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

49. The method of claim 48, wherein the immune disorder is multiple sclerosis (MS), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), lupus nephritis (LN), warm autoantibody hemolytic anemia (WAHA), primary sclerosing cholangitis (PSC), IgG4-related disease (IGG4-RD), acute disseminated encephalomyelitis (ADEM), Evan's syndrome (ES), focal segmental glomerulosclerosis (FSGS), mixed connective tissue disease (MCTD), Mooren's ulcer (MU), chronic inflammatory demyelinating polyneuropathy (CIDP), membranous nephropathy (MN), or thyroid eye disease (TED).

50. A viral particle comprising a heterologous viral glycoprotein, a targeting moiety, and a nucleic acid molecule encoding a heterologous molecule of interest, 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; 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; and the nucleic acid molecule encoding the heterologous molecule of interest 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. The heterologous molecule of interest is a chimeric antigen receptor ("CAR") comprising an antigen binding domain that binds to CD19, wherein the antigen binding domain comprises an amino acid sequence that is at least 85%, 90%, 95%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 99, SEQ ID NO: 105, SEQ ID NO: 106, or SEQ ID NO:

107. The heterologous molecule of interest is a chimeric antigen receptor ("CAR") comprising an antigen binding domain that binds to CD19, wherein the antigen binding domain comprises an amino acid sequence that is at least 85%, 90%, 95%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 99, SEQ ID NO: 105, SEQ ID NO: 106, or SEQ ID NO:

107. The heterologous molecule of interest is a chimeric antigen receptor ("CAR") comprising an antigen binding domain

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