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A HERPES SIMPLEX VIRUS TYPE 1 (HSV-1)-DERIVED VECTOR FOR SELECTIVELY INHIBITING MALIGNANT CELLS AND METHODS FOR ITS USE TO TREAT CANCERS AND TO EXPRESS DESIRED TRAITS IN MALIGNANT AND NON-MALIGNANT MAMMALIAN CELLS
A HERPES SIMPLEX VIRUS TYPE 1 (HSV-1)-DERIVED VECTOR FOR SELECTIVELY INHIBITING MALIGNANT CELLS AND METHODS FOR ITS USE TO TREAT CANCERS AND TO EXPRESS DESIRED TRAITS IN MALIGNANT AND NON-MALIGNANT MAMMALIAN CELLS
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-gamma. Also, disclosed are kits for expressing in a mammalian cell a gene encoding a preselected protein, and mammalian cells containing the HSV-derived vectors.
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