Journal of Biomedicine and Biotechnology
Volume 2003 (2003), Issue 1, Pages 48-70
http://dx.doi.org/10.1155/S1110724303209098
Prodrugs for Gene-Directed Enzyme-Prodrug Therapy (Suicide Gene Therapy)
Auckland Cancer Society Research Centre, School of Medical & Health Sciences, The University of Auckland, Private Bag 92019, Auckland 1000, New Zealand
Received 17 June 2002; Accepted 19 July 2002
Copyright © 2003 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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 (