The present disclosure provides recombinant nucleic acids comprising one or more polynucleotides encoding a transglutaminase (TGM) polypeptide (e.g., a Transglutaminase-1 (TGM1) polypeptide); viruses comprising the recombinant nucleic acids; compositions comprising the recombinant nucleic acids and/or viruses; methods of their use; and articles of manufacture or kits thereof.

The disclosure provides oncolytic herpes virus comprising a heterologous gene encoding E-cadherin. The disclosure further provides pharmaceutical compositions that comprise such oncolytic herpes virus, and methods of treatment using such oncolytic herpes virus.

Disclosed herein are high transducing replication defective herpes simplex virus (HSV) vectors of McKrae strain.

Recombinant oncolytic viruses that produce and secrete novel immunomodulatory fusion proteins are described. The fusion proteins encode a single chain variable fragment antibody (ScFv) that specifically binds PD-1 OR PD-L1 fused via an antibody Fc region to the ectodomain of the TGFβ receptor II (TGFβRII.sub.ecto). The immunomodulatory fusion proteins have dual function: blocking inhibitory pathways mediated by PD-1/PD-L1 and blocking the immune-dampening activity of TGFβ. In addition, dual gene oncolytic herpes simplex viruses (HSVs) are provided that include, in addition to a gene encoding an ScFv-Fc-TGFβRII.sub.ecto fusion protein, a gene encoding IL12, a T cell stimulatory factor.

Described herein are pseudotyped oncolytic viruses comprising nucleic acids encoding an engager molecule. In some embodiments, the pseudotyped oncolytic viruses comprises nucleic acids encoding an engager molecule and one or more therapeutic molecules. Pharmaceutical compositions containing the pseudotyped oncolytic virus and methods of treating cancer using the pseudotyped oncolytic viruses are further provided herein.

Nucleic acid expression systems for delivery of RNA oligonucleotides to target cells and methods of using the same are provided herein. For example, in some embodiments, a nucleic acid expression system comprises: (i) an RNA oligonucleotide comprising a payload sequence (e.g., a Myc inhibitor), and (ii) an RNA oligonucleotide comprising a sequence that encodes a US11 polypeptide. Provided herein are also pharmaceutical compositions comprising an RNA oligonucleotide comprising a payload sequence that encodes a dominant negative variant of a Myc polypeptide or portions thereof, and a pharmaceutically acceptable carrier.

The present invention provides a recombinant oncolytic Herpes Simplex Virus (oHSV) comprising a non-HSV ligand specific for a molecule (protein, lipid, or carbohydrate determinant) present on the surface of a cell (such as a cancer cell) and one or more copies of one or more microRNA target sequences inserted into one or more HSV gene loci, preferably one or more HSV gene(s) required for replication of HSV in normal (i.e., non-cancerous) cells. The invention further provides stocks and pharmaceutical compositions comprising the inventive oHSV and methods for killing tumor cells employing the inventive oHSV.

The present disclosure is in the field of genome engineering, particularly targeted integration of a functional SCID-related genes (e.g., IL2RG, RAG1 and/or RAG2 gene) into an IL2RG gene of a cell for provision of proteins lacking or deficient in SCID.

The invention concerns a modified enveloped virus wherein said virus has at least one anti-tumor, tumor-specific peptide non-genetically attached to or inserted in/through the viral envelope; a pharmaceutical composition comprising same; and a method of treating cancer using same.

Vaccines are provided comprising a recombinant virus which expresses an immunomodulatory protein and a target antigen unrelated to said recombinant virus, and a pharmaceutically acceptable excipient.