The present disclosure relates to an oncolytic virus and methods of using such to treat cancer. The methods may advantageously involve further treating with at least a first DNA damaging agent, such as radiation or a chemotherapeutic agent. In some embodiments, the oncolytic virus is an oncolytic herpes simplex virus (oHSV) that optionally has been engineered to expression a portion of CD44, in particular the extracellular domain of CD44.

Provided herein are oncolytic viruses including payload genes, encompassing genes that encode IL-12, FLT3L, CD40 agonists, and/or CTLA-4 antibodies. Also provided are expression cassettes, pharmaceutical compositions, and methods of treatment employing these viruses. Furthermore, expression cassettes and CD40 agonist molecules are also provided in this disclosure.

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 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 generally provides methods for producing recombinant AAV viral particles using cells grown in suspension. The invention provides recombinant AAV particles for use in methods for delivering genes encoding therapeutic proteins, and methods for using the recombinant AAV particles in gene therapy.

The disclosure encompasses recombinant nucleic acids comprising a nucleotide sequence encoding a live-attenuated chimeric Herpes Simplex Virus Type-1 (HSV-1) VC2 virus and a nucleotide sequence encoding a heterologous polypeptide operably linked to a promoter. The nucleotide sequence encoding the heterologous polypeptide can be operably linked to a promoter encoding the glycoprotein D (gD) of Equine Herpesvirus-1 (EHV-1) or a fragment thereof. Also provided is a live-attenuated recombinant Herpes Simplex Virus Type-1 (HSV-1) VC2 virus comprising a nucleotide sequence encoding a nucleotide sequence encoding a heterologous polypeptide operably linked to a promoter.

Provided herein are Vero cell lines that stably express Herpes Simplex Virus (HSV) ICP0 protein. These cells have the same morphology of Vero cells, exhibit stable expression of HSV ICP0 protein, and also efficiently complement replication of HSV ICP0 deficient virus for greater than 20, 30, or even 40 cell passages.

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.

In one example, a system electrically stimulates target cells of a living animal using an elongated structure, a modulation circuit and a light pathway such as provided by an optical fiber arrangement. The elongated structure is for insertion into a narrow passageway in the animal such that an end of the elongated structure is sufficiently near the target cells to deliver stimulation thereto. The modulation circuit is for modulating the target cells while the elongated structure is in the narrow passageway, where the modulation circuit is adapted to deliver viral vectors through the elongated structure for expressing light responsive proteins in the target cells. The light pathway is used for stimulating the target cells by delivering light to the light-responsive proteins in the target cells.

The present invention is directed to the composition and use of a modified Herpes Simplex Virus Type 2 (HSV-2) as a medicament in the treatment of cancer. The modified HSV-2 has fusogenic activity, and comprises a modified/mutated ICP10 polynucleotide encoding a polypeptide having ribonucleotide reductase activity and lacking protein kinase activity.