title: Gene therapy of cancer: activation of nucleoside prodrugs with E. coli purine nucleoside phosphorylase.
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.
authors.affiliation: Southern Research Institute, Birmingham, Alabama, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Secrist
authors.forename: W B
authors.initials: WB
authors.lastname: Parker
authors.forename: P W
authors.initials: PW
authors.lastname: Allan
authors.forename: L L
authors.initials: LL
authors.lastname: Bennett
authors.forename: W R
authors.initials: WR
authors.lastname: Waud
authors.forename: J W
authors.initials: JW
authors.lastname: Truss
authors.forename: A T
authors.initials: AT
authors.lastname: Fowler
authors.forename: J A
authors.initials: JA
authors.lastname: Montgomery
authors.forename: S E
authors.initials: SE
authors.lastname: Ealick
authors.forename: A H
authors.initials: AH
authors.lastname: Wells
authors.forename: G Y
authors.initials: GY
authors.lastname: Gillespie
authors.forename: V K
authors.initials: VK
authors.lastname: Gadi
authors.forename: E J
authors.initials: EJ
authors.lastname: Sorscher
mesh_terms: D000818:Animals; D001711:Biotransformation; D004926:Escherichia coli / Q000201:enzymology*; D005437:Flucytosine / Q000493:pharmacokinetics; D015774:Ganciclovir / Q000493:pharmacokinetics; D015316:Genetic Therapy; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000628:therapy*; D011355:Prodrugs / Q000493:pharmacokinetics*; D011683:Purine-Nucleoside Phosphorylase / Q000235:genetics / Q000378:metabolism*; D018139:Simplexvirus / Q000201:enzymology; D013937:Thymidine Kinase / Q000235:genetics
chemical_list: D011355:Prodrugs; D005437:Flucytosine; D011683:Purine-Nucleoside Phosphorylase; D013937:Thymidine Kinase; D015774:Ganciclovir