Enhancement of Suicide Gene Prodrug Activation by Random Mutagenesis

Suicide gene therapy provides a mechanism for sensitizing cells to normally non-toxic compounds or prodrugs. Genes are introduced into cancer cells thereby rendering them sensitive to prodrugs by virtue of the activity of the suicide gene product toward the prodrugs. The most widely investigated suicide genes and their respective prodrugs are the herpes simplex virus type I (HSV-1)-thymidine kinase (TK) with ganciclovir (GCV) and the Escherichia coli cytosine deaminase with 5-fluorocytosine (5-FC). Unfortunately, attempts to achieve high levels of antitumor activity with these systems have not been fully successful.