Prodrugs for Gene-Directed Enzyme-Prodrug Therapy (Suicide Gene Therapy)

Show simple item record Denny, W. en 2009-06-12T00:11:32Z en 2009-06-12T00:11:32Z en 2003 en
dc.identifier.citation Journal of Biomedicine and Biotechnology 2003 (1), 48-70. 2003 en
dc.identifier.issn 1110-7243 en
dc.identifier.uri en
dc.description An open access copy of this article is available and complies with the copyright holder/publisher conditions. en
dc.description.abstract This review focuses on the prodrugs used in suicide gene therapy. These prodrugs need to satisfy a number of criteria. They must be efficient and selective substrates for the activating enzyme, and be metabolized to potent cytotoxins preferably able to kill cells at all stages of the cell cycle. Both prodrugs and their activated species should have good distributive properties, so that the resulting bystander effects can maximize the effectiveness of the therapy, since gene transduction efficiencies are generally low. A total of 42 prodrugs explored for use in suicide gene therapy with 12 different enzymes are discussed, particularly in terms of their physiocochemical properties. An important parameter in determining bystander effects generated by passive diffusion is the lipophilicity of the activated form, a property conveniently compared by diffusion coefficients (log P for nonionizable compounds and log D7 for compounds containing an ionizable centre). Many of the early antimetabolite-based prodrugs provide very polar activated forms that have limited abilities to diffuse across cell membranes, and rely on gap junctions between cells for their bystander effects. Several later studies have shown that more lipophilic, neutral compounds have superior diffusion-based bystander effects. Prodrugs of DNA alkylating agents, that are less cell cycle-specific than antimetabolites and more effective against noncycling tumor cells, appear in general to be more active prodrugs, requiring less prolonged dosing schedules to be effective. It is expected that continued studies to optimize the bystander effects and other properties of prodrugs and the activated species they generate will contribute to improvements in the effectiveness of suicide gene therapy. en
dc.publisher Hindawi Publishing Corporation en
dc.relation.ispartofseries Journal of Biomedicine and Biotechnology en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from en
dc.rights.uri en
dc.source.uri en
dc.title Prodrugs for Gene-Directed Enzyme-Prodrug Therapy (Suicide Gene Therapy) en
dc.type Journal Article en
dc.subject.marsden Fields of Research::290000 Engineering and Technology::291500 Biomedical Engineering en
dc.identifier.doi 10.1155/S1110724303209098 en
pubs.issue 1 en
pubs.begin-page 48 en
pubs.volume 2003 en
dc.description.version VoR - Version of Record en
dc.rights.holder Copyright: Hindawi Publishing Corporation en
pubs.end-page 70 en
dc.rights.accessrights en

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