Gene therapy of cancer: activation of nucleoside prodrugs with E. coli purine nucleoside phosphorylase.

Academic Article

Abstract

  • During the last few years, many gene therapy strategies have been developed for various disease targets. The development of anticancer gene therapy strategies to selectively generate cytotoxic nucleoside or nucleotide analogs is an attractive goal. One such approach involves the delivery of herpes simplex virus thymidine kinase followed by the acyclic nucleoside analog ganciclovir. We have developed another gene therapy methodology for the treatment of cancer that has several significant attributes. Specifically, our approach involves the delivery of E. coli purine nucleoside phosphorylase, followed by treatment with a relatively non-toxic nucleoside prodrug that is cleaved by the enzyme to a toxic compound. This presentation describes the concept, details our search for suitable prodrugs, and summarizes the current biological data.
  • Published In

    Keywords

  • Animals, Biotransformation, Escherichia coli, Flucytosine, Ganciclovir, Genetic Therapy, Mice, Mice, Nude, Neoplasms, Prodrugs, Purine-Nucleoside Phosphorylase, Simplexvirus, Thymidine Kinase
  • Authorlist

  • Secrist JA; Parker WB; Allan PW; Bennett LL; Waud WR; Truss JW; Fowler AT; Montgomery JA; Ealick SE; Wells AH
  • Start Page

  • 745
  • End Page

  • 757
  • Volume

  • 18
  • Issue

  • 4-5