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

The present disclosure relates, in part, to methods of delivering transgenes to an eye of a subject comprising the use of pharmaceutical compositions having one or more polynucleotides suitable for enhancing, increasing, augmenting, and/or supplementing the levels of transgene expression in the eye. The present disclosure also relates, in part, to methods of correcting vision loss in a subject in need thereof comprising the use of the pharmaceutical compositions described herein.

An oncolytic HSV vector comprising an NF-κB response element or an Oct-3/4-SOX2 response element in a regulatory region of a viral gene that affects viral replication efficiency.

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.

In certain aspects, the disclosure relates to a virus engineered to comprise one or more polynucleotides that promote thanotransmission by a target cell. Thanotransmission is communication between cells that is a result of activation of a cell turnover pathway in a target cell, which signals a responding cell to undergo a biological response. Methods of promoting thanotransmission by a target cell, methods of promoting an immune response in a subject, and methods of treating cancer in a subject are also disclosed.

An anterograde monosynaptic transneuronal viral tracer system for mapping the direct postsynaptic targets of neurons in a given brain nucleus comprises a tracer H129-derived recombinant HSV-1 virion; and a helper AAV2/9-derived recombinant AAV2/9 virion; wherein the tracer H129-derived recombinant HSV-1 virion comprises a recombinant HSV-1-H129 viral genome with an impaired gK gene, and a mutant gK protein that pseudotypes the tracer H129-derived recombinant HSV-1 virion; and wherein the helper AAV2/9-derived recombinant AAV2/9 virion comprises a recombinant AAV2/9 viral genome that contains an HSV-1 H129 wild-type gK encoding sequence.

Disclosed are novel modified viruses comprising recombinant PTEN-Long and methods of using the same for treating cancer.

The present disclosure provides recombinant nucleic acids comprising one or more polynucleotides encoding an immunomodulatory polypeptide (e.g., a pro-inflammatory cytokine such as a human IL-2 or IL-12 polypeptide); viruses comprising the recombinant nucleic acids; compositions and formulations comprising the recombinant nucleic acids and/or viruses; methods of their use (e.g., for the treatment of cancer, such as lung cancer); and articles of manufacture or kits thereof.

The use of iNOS inhibitors, including aurintricarboxylic acid, dexamethasone and valproic acid, to increase the yield of a variety of viruses in culture, including recombinant herpesviruses is described.

The present invention relates to an oncolytic virus which is, or is derived from, a clinical isolate which has been selected by comparing the abilities of a panel of three or more clinical isolates of the same viral species to kill tumor cells of two or more tumor cell lines in vitro and selecting a clinical isolate which is capable of killing cells of two or more tumor cell lines more rapidly and/or at a lower dose in vitro than one or more of the other clinical isolates in the panel.