The present invention relates to an oncolytic virus comprising: (i) a fusogenic protein-encoding gene; and (ii) an immune stimulatory molecule-encoding gene.

Provided is a recombinant viral vector that expresses a NKG2D activating ligand, such as a UL-16 binding protein. When introduced into a cancer cell, the vector can cause expression of the NKG2D activating ligand, thereby overcoming repression of NK-mediated (or other effector cell, e.g., macrophage) cytotoxicity and causing effector cell-mediated death of the cancer cell. Expression of the NKG2D activating ligand can be controlled by a miRNA present in greater concentration in noncancerous cells than in cancer cells, which can permit selective expression of the ligand in cancer cells and reduced cytotoxicity toward noncancerous cells. The vector can cause expression of an oncolytic factor. When formulated into a pharmaceutical composition and administered to a patient, the vector can be used to treat cancer. The cancer can be a glioma, such as glioblastoma including one with an isocitrate dehydrogenase (IDH) mutation. The vector can be a herpes simplex virus vector, among others.

The invention described herein provides a recombinant replication-defective vims derived from Herpesvirales order, wherein the virus is characterized by a complete deletion of a gene encoding ICP27, or a functional equivalent gene thereof. The invention also provides production cell lines for such recombinant replication-defective vims, wherein the cell lines have a coding sequence for ICP27 or a functional equivalent thereof, and wherein the coding sequence has no or minimal sequence overlap with the virus characterized by the complete deletion of the gene encoding ICP27. Method of using such recombinant replication-defective vims and production cell lines are also provided.

Proposed are a recombinant herpes simplex virus having a modified glycoprotein gH for retargeting and the use thereof. Particularly, the recombinant herpes simplex virus is capable of infecting a target cell having a target molecule to which a cell-targeting domain specifically recognizes and binds due to the presence of the cell-targeting domain in the glycoprotein gH thereof, and is thus useful for anticancer therapy or gene therapy.

Modified and improved oncolytic viruses (and methods of use thereof) are disclosed. More particularly, modified and oncolytic human herpesviruses (and methods of use thereof) are disclosed, which include a modified amino acid sequence that includes a deletion in a region that represents the amino terminus of glycoprotein K. The modified and oncolytic human herpesviruses include a deletion of amino acid residues 31-68, relative to the wild type amino acid sequence of glycoprotein K in human herpesviruses. Isolated vector constructs that encode such oncolytic viruses are also disclosed. In addition, methods for using such oncolytic viruses to treat cancers are disclosed.

Stimulation of target cells using light, e.g., in vivo or in vitro, is implemented using a variety of methods and devices. One example involves a vector for delivering a light-activated NpHR-based molecule comprising a nucleic acid sequence that codes for light-activated NpHR-based molecule and a promoter. Either a high expression of the molecule manifests a toxicity level that is less than about 75%, or the light-activated NpHR-based proteins are expressed using at least two NpHR-based molecular variants. Each of the variants characterized in being useful for expressing a light-activated NpHR-based molecule that responds to light by producing an inhibitory current to dissuade depolarization of the neuron. Other aspects and embodiments are directed to systems, methods, kits, compositions of matter and molecules for ion pumps or for controlling inhibitory currents in a cell (e.g., in in vivo and in vitro environments).

The present invention relates to a vaccine composition comprising an effective amount of a replication-competent controlled herpesvirus expressing an antigen of a pathogen other than a herpesvirus. Encompassed are uses in immunization and methods of immunization employing the vaccine compositions, wherein transient activation of the replication of the herpesvirus at the site of vaccine administration to a subject enhances systemic immune responses to the antigen.

The present disclosure relates to polynucleotides comprising a nucleic acid sequence encoding a replication competent viral genome, wherein the polynucleotide is capable of producing a replication competent virus when introduced into a cell by a non-viral delivery vehicle. The present disclosure further relates to the encapsulation of the polynucleotides and the use of the polynucleotides and/or particles for the treatment and prevention of cancer.

Provided herein is a powder comprising a live, attenuated virus, recombinant human serum albumin (rHSA), a sugar other than lactose, a sugar alcohol, a source of phosphate, a source of chloride, wherein the composition is substantially free of lactose, gelatin, antibiotic, and free amino acids. In exemplary aspects, the powder is a lyophilizate of a liquid composition. Related liquid compositions, methods of preparing an oncolytic virus for administration and methods of treating melanoma are also provided herein.

Compositions for expressing a polypeptide within a target organ, the composition comprising a delivery particle, and at least a first mRNA sequence complexed with, encapsulated by, or otherwise associated with the delivery particle, wherein the mRNA sequence comprises at least one coding sequence which codes for at least one polypeptide, at least a first untranslated region (UTR) sequence, and at least one micro-RNA (miRNA) binding site sequence, wherein the miRNA binding site sequence is located within, immediately 5′ to, or immediately 3′ to, the first UTR sequence; and wherein the miRNA binding site sequence provides for differential expression of the coding sequence between first and second cell types comprised within the target organ.