Oncolytic HSV vector
AssigneeUniversity of Pittsburgh—Of the Commonwealth System of Higher Education
InventorsHiroaki Uchida, Justus B. Cohen, Joseph C. Glorioso, III, Paola Grandi
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Abstract
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.
Claims49
A recombinant herpes simplex virus (HSV), comprising:
- (a) a mutation of glycoprotein B (gB) at position 285 or 549;
- and
- (b) a plurality of copies of one or more microRNA target sequences inserted into a locus of one or more HSV genes required for HSV replication,
- wherein expression of one or more genes in the internal repeat (joint) region in the HSV genome is silenced, and
- wherein the internal repeat (joint) region comprises one copy of the ICP0, ICP34.5, LAT, and ICP4 genes and the promoter of the ICP47 gene.
A recombinant Herpes Simplex Virus (HSV), comprising:
- (a) a non-HSV ligand displayed on the surface of the HSV envelope, which is specific for a molecule present on the surface of a cancer cell;
- and
- (b) a plurality of copies of one or more microRNA target sequences inserted into a locus of one or more HSV genes required for HSV replication,
- wherein the expression of one or more genes in the internal repeat (joint) region in the HSV genome is silenced, and wherein the internal repeat (joint) region comprises one copy of the ICP0, ICP34.5, LAT, and ICP4 genes and the promoter of the ICP47 gene.
Dependencies are inferred from the claim text.