Self-deleting suicide vectors (SDSV): Selective killing of p53-deficient cancer cells

A self-deleting retrovirus vector carrying a herpes simplex virus (HSV)thym idine kinase suicide gene has been developed to selectively kill cancer cel ls expressing a dysfunctional p53 tumor suppressor protein. When cells cont aining functional p53 are infected with the virus, the integrated provirus and the HSV-thyrnidine kinase gene are deleted from the genome by site-spec ific recombination (Cre/loxP). In contrast, cells without p53 or cells expr essing a DNA-binding mutant of p53 retain the provirus and become susceptib le to killing by ganciclovir. This strategy provides a new concept for the selective killing of cancer cells that can be adapted to any other dysfunct ional transcription factor expressed by different tumors.