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AssigneeUniversity of Pittsburgh—Of the Commonwealth System of Higher Education
InventorsJoseph C. Glorioso, III, Justus Cohen, Yoshitaka Miyagawa, David Krisky, James Wechuck, Darren Wolfe
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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 disclosed vectors include vectors having deletions in the genes ICP0, ICP4, TCP22, TCP27 and TCP47, or alternative inactivating mutations, or vectors which express one or more of these genes with modified kinetics. 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, in particular a U20S cell, engineered to express ICP4 and ICP27 when the cell is infected with HSV for the production of the inventive vector. Said cells are disclosed as naturally complementing ICP0.
A cell for the production of a herpes simplex virus (HSV) vector, wherein the cell is a U2OS cell that comprises an expression cassette comprising the HSV ICP4 gene and an expression cassette comprising the HSV ICP27 gene, wherein the cell supports the production of infectious viral particles upon infection with an HSV that comprises an inactivating mutation in the HSV ICP0 gene, the HSV ICP4 gene, and the HSV ICP27 gene or the promoters thereof.
Dependencies are inferred from the claim text.