Gene editing compositions of polypeptides and nucleic acids, and uses thereof

Abstract

Provided herein are viral particles comprising a heterologous viral structural protein, a targeting moiety, and at least one nucleic acid molecule encoding a gene editing system, compositions comprising these viral particles, and methods of using these viral particles.

Description

(19) State Intellectual Property Office (12) Invention Patent Application (10) Application Publication Number (43) Application Publication Date (21) Application Number 202480045905.2 (22) Application Date 2024.05.23 (30) Priority Data 63 / 504,068 2023.05.24 US (85) PCT International Application Entering National Phase Date 2026.01.07 (86) PCT International Application Application Data PCT / US2024 / 030826 2024.05.23 (87) PCT International Application Publication Data WO2024 / 243434 EN 2024.11.28 (71) Applicant Interus Biotherapeutics Company Address Pennsylvania, USA (72) Inventors P.R. Johnson S.J. Doolittle (74) Patent Agency Beijing Liu Shen Law Firm 11105 Patent Attorney Qin Jian (51) Int.Cl. C12N 15 / 86 (2006.01) C12N 9 / 22 (2006.01) (54) Invention Title Gene Editing Composition of Polypeptide and Nucleic Acid and Its Use Thereof (57) Abstract This document provides viral particles comprising a heterologous viral structural protein, a targeting portion and at least one nucleic acid molecule encoding a gene editing system, compositions comprising such viral particles and methods of using such viral particles. Claims 8 pages Description 137 pages Sequence Listing (Electronic Publication) Drawings 48 pages CN 121532516 A 2026.02.13 CN 1 21 53 25 16 A

Claims

1. A viral particle comprising: a heterologous viral glycoprotein, a targeting moiety, and at least one nucleic acid molecule encoding a gene editing system, 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 gene editing system is a CRISPR-Cas system, a zinc finger nuclease system, a TALEN, a meganuclease, or a gene product modulating nucleic acid molecule.

3. The viral particle of claim 2, wherein the nucleic acid molecule encodes a CRISPR-Cas system comprising a Cas protein and a guide RNA, a single guide RNA, or at least one nucleic acid molecule that targets the Cas protein to a target nucleic acid molecule.

4. The viral particle of claim 2, wherein the CRISPR-Cas system is a Class 1 or Class 2 CRISPR-Cas system.

5. The viral particle of claim 4, wherein the Class 2 CRISPR-Cas system comprises a Type II Cas protein.

6. The viral particle of claim 5, wherein the Type II Cas protein is a Cas9 protein.

7. The viral particle of claim 4, wherein the Class 2 CRISPR-Cas system comprises a Type V Cas protein.

8. The viral particle of claim 7, wherein the Type V Cas protein is selected from Casl2a, Casl2b, Casl2c, Casl2d, Casl2e, or Cas 14.

9. The viral particle of claim 4, wherein the Class 2 CRISPR-Cas system comprises a Type VI Cas protein.

10. The viral particle of claim 9, wherein the Type VI Cas protein is selected from Casl3a, Casl3b, Casl3c, or Casl3d.

11. The viral particle of claim 2, wherein the CRISPR-Cas system is a base editing system.

12. The viral particle of claim 11, wherein the CRISPR-Cas system comprises a dCas linked to a cytidine deaminase or an adenosine deaminase.

13. The viral particle of claim 2, wherein the CRISPR-Cas system is a prime editing system.

14. The viral particle of claim 2, wherein the CRISPR-Cas system comprises a CRISPRa, a CRISPRi, a Cas 3, or a CasMINI protein.

15. The viral particle of claim 2, wherein the gene product modulating nucleic acid molecule encodes at least one molecule selected from an siRNA, a piRNA, a miRNA, an RNAi RNA, an mRNA, an shRNA, and an antisense RNA.

16. The viral particle of claim 1, wherein the stalk moiety S1 comprises a variant Fc protein, wherein the variant Fc protein comprises a transmembrane domain, and wherein the mutant Fc protein comprises at least one effector mutation, wherein the effector mutation inhibits interaction between the Fc protein and an Fc interacting protein such as FcyR, C1q, FcRb, or FcRn.

17. The viral particle of claim 16, wherein the S1 stalk moiety is attached to the surface of the viral particle via the transmembrane domain.

18. The viral particle of claim 16, wherein the Fc protein is an IgG1 Fc, IgG2 Fc, or IgG4 Fc protein.

19. The viral particle of claim 16, wherein the variant Fc protein comprises a variant of the sequence of SEQ ID NO: 26, SEQ ID NO: 27, or SEQ ID NO:

28.

20. The viral particle of claim 16, wherein the variant Fc protein is a variant IgG1 Fc protein.

21. The viral particle of claim 20, wherein the variant IgG1 Fc protein comprises one or more of the following mutations selected from the group consisting of L234A, L235A, N297A, P329G, I253A, H310A, and H435A.

22. The viral particle of claim 20, wherein the variant IgG1 Fc protein comprises an amino acid sequence that is at least 80% identical to SEQ ID NO: 82, at least 85% identical to SEQ ID NO: 82, at least 90% identical to SEQ ID NO: 82, at least 95% identical to SEQ ID NO: 82, at least 98% identical to SEQ ID NO: 82, or at least 100% identical to SEQ ID NO:

82.

23. The viral particle of claim 1, 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 a transmembrane domain, wherein the targeting moiety having the formula T-S1 has the formula T-L1-Fc-L2-X1.

24. The viral particle of claim 23, 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. ECD is an extracellular domain of a cell surface protein or fragment thereof, or is absent; ​ ​ ​ ​ 25. The viral particle of claim 24, wherein X1comprises a polypeptide having the formula ECD-T M -ICD, wherein: ​ 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.

26. The viral particle of claim 25, wherein the ECD comprises the amino acid sequence of SEQ ID NO: 59 or SEQ ID NO:

60.

27. The viral particle of claim 25, wherein the T M comprises the amino acid sequence of SEQ ID NO: 61 or SEQ ID NO:

62.

28. The viral particle of claim 25, wherein the ICD comprises an Env incorporation motif comprising the amino acid sequence of SEQ ID NO: 63 or SEQ ID NO:

64.

29. The viral particle of claim 1, wherein the target-binding domain (T) binds to: CD7, CD8, cKit (CD117), CD4, CD3, CD5, CD6, CD2, TCR α, TCR β, TCR γ, TCR δ, 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, A kinase anchoring protein 4 (AKAP-4), adrenaline receptor β3 (ADRB3), AFP, anaplastic lymphoma kinase (ALK), androgen receptor, angiopoietin-binding cell surface receptor 2 (TIP). 2) Anti-desmosome 1 (Dsg1) autoantibody, anti-desmosome 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 imprinted site regulator sibling factor), CCR4, CD5, CD19, CD20, CD22, CD24, CD30, CD32 (FCG) R2A), CD33, CD34, CD38, CD44v6, CD72, CD79a, CD79b, CD97, CD99, CD123, CD171, CD179a, CD179b-IGLll, 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 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 B1, cytochrome P450 IB 1 (CYP1B)1), DLL3, EBV-EBNA3c, EGF-bike module 2 containing mucin-like hormone receptor-like (EMR2), Mutated elongation factor 2 (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, GFRa4, Glycoprotein 100 (gp100), Glypican-3 (GPC3), Gonadotropin-releasing hormone 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 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), KSHVK8.1, 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 gland differentiation antigen (NY-BR-1), Melanoma antigen recognized by T cells 1 (Melan A 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-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), Paired box protein Pax-5 (PAX5), Pannexin 3 (PANX3), PDL1, P-Glycoprotein, Placenta-specific 1 (PLAC1), Platelet-derived growth factor receptor beta (PDGFR-beta), Polysialic acid, Pre-migratory trophoblast antigen sp32 (OY-TES1), Prostase, Prostate carcinoma tumor antigen-1 (PCTA-1 or Galectin 8), Prostate stem cell antigen (PSCA), Prostate-specific membrane antigen (PSMA), Prostate acid phosphatase (PAP), Prostein, Serine protease 21 (Testisin or PRSS21), Proteasome (Prosome Macropain) subunit beta9, PTK7, Ras G12V, 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 / neu, ubiquitous 1 (RU1), ubiquitous 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), SART3, stage-specific embryonic antigens-4 (SSEA-4), STEAP1, survivin, SSX2, TCR gamma alternate 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), UPK2, VEGFR2, V-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN), Wilms tumor protein (WT1), or X antigen family member 1A (XAGE1).

30. The viral particle of claim 29, wherein the target binding domain (T) binds to CD7.

31. The viral particle of claim 30, wherein the polypeptide comprises a heavy chain and a light chain comprising: a heavy chain variable region of the heavy chain having at least 90% sequence identity to SEQ ID NO: 36, and a light chain variable region of the light chain having at least 90% sequence identity to SEQ ID NO: 37, wherein the polypeptide comprises a sequence of HCDR1 as set forth in SEQ ID NO: 30; a sequence of HCDR2 as set forth in SEQ ID NO: 31; a sequence of HCDR3 as set forth in SEQ ID NO: 32; a sequence of LCDR1 as set forth in SEQ ID NO: 33; a sequence of LCDR2 as set forth in SEQ ID NO: 34; and a sequence of LCDR3 as set forth in SEQ ID NO:

35.

32. The viral particle of claim 30, 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 or SEQ ID NO: 39, at least 95% sequence identity to SEQ ID NO: 38 or SEQ ID NO: 39, at least 99% sequence identity to 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.

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

34. The viral particle of claim 33, 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.

35. The viral particle of claims 1- wherein the viral particle further comprises a nucleic acid molecule encoding a heterologous molecule of interest, wherein the heterologous molecule of interest is an siRNA, shRNA, non-coding RNA (e.g., a guide RNA for a CRISPR system), a peptide, a polypeptide, a protein, a viral payload, a viral genome, or a combination thereof.

36. A method of infecting a cell, the method comprising contacting the cell with a viral particle according to any one of claims 1 to 35.

37. A method of infecting a cell of a subject, the method comprising administering to the subject a pharmaceutical composition comprising a viral particle according to any one of claims 1 to 35.

38. A method of editing a target nucleic acid molecule in a cell, the method comprising contacting the cell with a viral particle according to any one of claims 1 to 35, wherein the nucleic acid molecule encoding a gene editing system is expressed in the cell and edits the target nucleic acid molecule in the cell.

39. The method of claim 38, wherein the nucleic acid molecule encoding the gene editing system encodes a CRISPR / CAS gene editing system comprising a CAS nuclease and a gRNA that targets the CAS nuclease to the target nucleic acid molecule.

40. The method of claim 38 or 39, wherein the edited target nucleic acid molecule is an endogenous gene.

41. The method of any one of claims 36 to 40, wherein the cell is a T cell, a B cell, a NK cell, a dendritic cell, a neutrophil, a macrophage, or a cancer cell.

42. A method of treating a disease or condition in a subject in need thereof, the method comprising administering to the subject a viral particle according to any one of claims 1 to 35, wherein the nucleic acid molecule encoding the gene editing system is expressed in the subject and treats the disease or condition in the subject.

43. A method of editing a target nucleic acid molecule in a cell, the method comprising contacting the cell with a viral particle comprising: (a) a VSV-G polypeptide comprising an amino acid sequence that is at least 70% identical to SEQ ID NO: 2 and comprising a mutation at position 182 compared to SEQ ID NO: 2; (b) a nucleic acid molecule encoding a gene editing system, wherein the gene editing system is a CRISPR-Cas system comprising a Cas9 protein and a guide RNA, a single guide RNA, or at least one nucleic acid molecule that targets the Cas protein to a target nucleic acid molecule; (c) optionally; a nucleic acid molecule encoding a heterologous molecule of interest; and (d) a targeting moiety that binds to a T cell, a CD3+ T cell, a CD4+ T cell, a CD7+ T cell, or a CD8+ T cell; wherein the nucleic acid molecule encoding the gene editing system is expressed in the cell and edits the target nucleic acid molecule in the cell.

44. The method of claim 43, wherein the cell is a T cell, a CD3+ T cell, a CD4+ T cell, a CD7+ T cell, a CD8+ T cell, or a CD7+ NK cell.

45. A viral particle comprising a heterologous viral glycoprotein, a targeting moiety, and at least one nucleic acid molecule encoding a gene editing system, wherein the heterologous viral glycoprotein comprises a sequence selected from the group consisting of SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 52, and SEQ ID NO: 53; 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; wherein the target binding domain comprises a sequence selected from the group consisting of SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 50, and SEQ ID NO: 51; wherein the stalk moiety S1 comprises a variant Fc protein comprising a sequence that is a variant of SEQ ID NO: 26, SEQ ID NO: 27, or SEQ ID NO: 28; wherein 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; wherein the variant of SEQ ID NO: 27 comprises one or more mutations selected from the group consisting of N297A, P329G, I253A, H310A, and H435A; wherein 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; and wherein the variant Fc protein further comprises a transmembrane domain comprising a sequence selected from the group consisting of SEQ ID NO: 61 and SEQ ID NO: 62; and wherein the nucleic acid molecule encoding a gene editing system encodes a CRISPR-Cas system comprising a Cas9 protein and a guide RNA, a single guide RNA, or at least one nucleic acid molecule that targets the Cas protein to a target nucleic acid molecule.

46. A viral particle comprising a heterologous viral glycoprotein, a targeting moiety, and at least one nucleic acid molecule encoding a gene editing system; wherein the heterologous viral glycoprotein comprises a sequence selected from the group consisting of SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 52, and SEQ ID NO: 53; 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; wherein the target binding domain comprises a sequence selected from the group consisting of SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 50, and SEQ ID NO: 51; wherein the stalk moiety S1 comprises the formula L1-Fc-L2-X1, wherein: L1 is a linker comprising a sequence selected from SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, or SEQ ID NO: 76 or is absent; Fc is a variant Fc protein comprising a sequence that is a variant of SEQ ID NO: 26, SEQ ID NO: 27, or SEQ ID NO: 28; wherein 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; wherein the variant of SEQ ID NO: 27 comprises one or more mutations selected from the group consisting of N297A, P329G, I253A, H310A, and H435A; wherein 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; 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 X1is a polypeptide having the formula ECD-T M - a polypeptide of the ICD comprising a transmembrane domain, wherein: ECD is an extracellular domain having a sequence selected from SEQ ID NO: 59 or SEQ ID NO: 60 or a fragment thereof or is absent; T M is a transmembrane domain having the sequence of SEQ ID NO: 61 or SEQ ID NO: 62, or a fragment thereof; and ICD is an intracellular domain or a protein that facilitates incorporation of the targeting moiety into the envelope of the viral particle, wherein the ICD comprises an env incorporation motif comprising an amino acid sequence of SEQ ID NO: 63 or SEQ ID NO: 64 or ICD is absent; and wherein the nucleic acid molecule encoding a gene editing system encodes a CRISPR-Cas system comprising a Cas9 protein and a guide RNA, a single guide RNA, or at least one nucleic acid molecule that targets the Cas protein to a target nucleic acid molecule.

47. A viral particle comprising a heterologous viral glycoprotein, a targeting moiety, and at least one nucleic acid molecule encoding a gene editing system; wherein 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; 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; wherein 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 ; wherein the stalk moiety S1 comprises the formula L1-Fc-L2-X1, wherein: L1 is a linker comprising the sequence of SEQ ID NO: 55 or is absent; Fc is a variant Fc protein comprising a sequence that is a variant of SEQ ID NO: 26, SEQ ID NO: 27, or SEQ ID NO: 28; wherein 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; wherein the variant of SEQ ID NO: 27 comprises one or more mutations selected from the group consisting of N297A, P329G, I253A, H310A, and H435A; wherein 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; L2 is a linker comprising the sequence of SEQ ID NO: 55 or is absent; and X1is a polypeptide having the formula ECD-T M - a polypeptide of the ICD comprising a transmembrane domain, wherein: ECD is an extracellular domain having the sequence of SEQ ID NO: 60 or a fragment thereof or is absent; T M is a transmembrane domain having the sequence of SEQ ID NO: 62 or a fragment thereof; and ICD is an intracellular domain or a protein that facilitates incorporation of the targeting moiety into the envelope of the viral particle, wherein the ICD comprises an env incorporation motif comprising the amino acid sequence of SEQ ID NO: 63 or SEQ ID NO: 64 or ICD is absent; and wherein the nucleic acid molecule encoding a gene editing system encodes a CRISPR-Cas system comprising a Cas9 protein and a guide RNA, a single guide RNA, or at least one nucleic acid molecule that targets the Cas protein to a target nucleic acid molecule.

48. A viral particle comprising a heterologous viral glycoprotein, a targeting moiety, and at least one nucleic acid molecule encoding a gene editing system; wherein the heterologous viral glycoprotein comprises the sequence of SEQ ID NO: 23 or SEQ ID NO: 25; 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; wherein the target binding domain comprises the sequence of SEQ ID NO: 39; wherein the stalk moiety 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: 82; L2 is a linker and is absent; X1is a polypeptide having the formula ECD-T M - a polypeptide of the ICD comprising a transmembrane domain, wherein: ECD is an extracellular domain having the sequence of SEQ ID NO: 60; T M is a transmembrane domain having the sequence of SEQ ID NO: 62; ICD is a cell internalization domain or a protein that facilitates 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; and wherein the nucleic acid molecule encoding a gene editing system encodes a CRISPR-Cas system comprising a Cas9 protein and a guide RNA, a single guide RNA, or at least one nucleic acid molecule that targets the Cas protein to a target nucleic acid molecule.

49. A viral particle comprising a heterologous viral glycoprotein, a targeting moiety, and at least one nucleic acid molecule encoding a gene editing system, 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: 83, at least 95% identical to SEQ ID NO: 83, at least 99% identical to SEQ ID NO: 83, or at least 100% identical to SEQ ID NO: 83; and the nucleic acid molecule encoding a gene editing system encodes a CRISPR-Cas system comprising a Cas9 protein and a guide RNA, a single guide RNA, or at least one nucleic acid molecule that targets the Cas protein to a target nucleic acid molecule. 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: 83, at least 95% identical to SEQ ID NO: 83, at least 99% identical to SEQ ID NO: 83, or at least 100% identical to SEQ ID NO: 83; and the nucleic acid molecule encoding a gene editing system encodes a CRISPR-Cas system comprising a Cas9 protein and a guide RNA, a single guide RNA, or at least one nucleic acid molecule that targets the Cas protein to a target nucleic acid molecule.