Inventors:
Steven L. Wechsler - Westlake Village CA, US
Anthony B. Nesburn - Malibu CA, US
John S. Yu - Los Angeles CA, US
Keith L. Black - Los Angeles CA, US
Assignee:
Cedars-Sinai Medical Center - Los Angeles CA
International Classification:
A61K 4800, C12N 1563, C12N 1587, C12N 500
US Classification:
4353201, 435325, 435455, 435456, 435 691, 514 44, 4241991
Abstract:
Disclosed is an HSV-1-derived vector containing a DNA having a functional LAT promoter, or operative fragment thereof, a deletion in both copies of the HSV-1 LAT gene, and a deletion in both copies of the HSV-1 ICP34. 5 gene. The HSV-1-derived vectors are non-neurovirulent and do not spontaneously reactivate from latency, and they optionally contain a functional HSV thymidine kinase gene, which can enhance the effectiveness against cancer of drug treatment with gancyclovir or acyclovir. Alternatively, the HSV-1-derived vectors contain at least one transcriptional unit of a LAT promoter sequence operatively linked to a nucleic acid encoding a preselected protein. In some embodiments, the preselected protein is a nucleotide sequence encoding a polypeptide toxic for cells expressing the vector, for example, human interferon-γ. Also, disclosed are kits for expressing in a mammalian cell a gene encoding a preselected protein, and mammalian cells containing the HSV-derived vectors.