Gene therapy of cancer: Activation of nucleoside prodrugs with E-coli purine nucleoside phosphorylase

During the last few years, many gene therapy strategies have been developed for various disease targets. The development of anticancer gene therapy st rategies to selectively generate cytotoxic nucleoside or nucleotide analogs is an attractive goal. One such approach involves the delivery of herpes s implex virus thymidine kinase followed by the acyclic nucleoside analog gan ciclovir. We have developed another gene therapy methodology for the treatm ent of cancer that has several significant attributes. Specifically, our ap proach involves the delivery off. coli purine nucleoside phosphorylase, fol lowed by treatment with a relatively non-toxic nucleoside prodrug that is c leaved by the enzyme to a toxic compound. This presentation describes the c oncept, details our search for suitable prodrugs, and summarizes the curren t biological data.