Combination of HSV-thymidine kinase gene (HSV tk) and ganciclovir [GCV; 9-(1, 3-dihydroxy-2-propoxymethyl) guanine] has been used to eradicate proliferating tumor cells.
Transfecting tumor cells in vivo with HSV tk gene under the control of an active promoter and after few days ganciclovir is administered.
HSV tk phosphorylates ganciclovir to form monophosphate
GCV. Triphosphate-GCV inhibits DNA polymerase and terminates DNA synthesis, causing death of tumor cell.
Triphosphate-GCV can pass unmodified cells by cell to cell contact and kill these cells as well. 1 HSV tk expressing tumor cell can kill up to 10 unmodified cells. This phenomenon is called “bystander effect”.
When gene under certain conditions causes death of its own cell –
suicide gene.
Prodrug- Inactive form of therapeutic agent that is activated biologically after it is administered as part of a treatment.