Recombinant herpes simplex virus 2 (HSV-2) vaccine vectors, virions thereof, compositions and vaccines comprising such, and methods of use thereof are each provided.

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 invention provides an in vitro model of Alzheimer's disease (AD) comprising human induced neuronal stem cells (hiNSCs) infected with herpes simplex 1 that develop an Alzheimer's disease phenotype. The invention further provides AD model comprising genetically modified HSV infected hiNSCs. The use of these in vitro AD models for high throughput screening and phenotypic analysis are also provided.

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 present invention relates to a vaccine composition comprising an effective amount of a replication-competent controlled recombinant virus. Further encompassed are uses in immunization and methods of immunization employing compositions comprising a replication-competent controlled recombinant virus of the invention.

The present invention relates to an oncolytic virus encoding a CTLA-4 inhibitor, such as an anti-CTLA-4 antibody, or an antigen binding fragment thereof.

The present invention provides a method and a pharmaceutical composition for the treatment of the NDO comprising the viral expression vector carrying a transcription cassette that harbors transgene(s) inhibiting/silencing neurotransmission or synaptic transmission of afferent neurons.

The present disclosure relates, in part, to pharmaceutical compositions comprising one or more polynucleotides suitable for enhancing, increasing, augmenting, and/or supplementing the levels of Collagen alpha-1 (VII) chain polypeptide and/or Lysyl hydroxylase 3 polypeptide and/or Keratin type I cytoskeletal 17 polypeptide in a subject. The present disclosure also relates, in part, to pharmaceutical compositions and methods of use for providing prophylactic, palliative, or therapeutic relief of a wound, disorder, or disease of the skin in a subject, including a subject having, or at risk of developing, one or more symptoms of epidermolysis bullosa.

The invention provides a method for ameliorating chronic pain signaling involving transient receptor potential cation channel subfamily V member 1 (TRPV1) by expressing PP1 in neurons. The invention also provides HSV vectors for expressing PP1 within neurons and compositions comprising such vectors.

In one embodiment, the invention provides a herpes simplex virus (HSV) vector that does not express toxic HSV genes in non-complementing cells and which comprises a genome comprising one or more transgenes, wherein the vector is capable of expression of a transgene for at least 28 days in non-complementing cells. The invention also relates to viral stocks of the inventive vectors, compositions thereof suitable for use therapeutically or for in vitro applications, and methods relating thereto. In another aspect, the invention provides a complementing cell engineered to express ICP4 and ICP27 when the cell is infected with HSV for the production of the inventive vector.