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8.2 Mechanism of suicidal gene therapy

Retroviruses or lentiviral vectors are designed to carry a therapeutic gene. Since the retroviruses only grow in dividing cells so they will specifically multiply in tumor cells. Retroviral vectors are designed to express the thymidine kinase gene (tk) from herpes virus.

The tk gene sensitizes the tumor cells for a prodrug ganciclovir. Herepes virus tk is a normal substrate for the ganciclovir while the host tk is not affected by the drug. Therefore host cells surrounding the tumors will not have any effect of ganciclovir.

Ganciclovir is phosphorylated by the herpes virus tk into monophosphate form; the ganciclovir is then converted into triphosphate form which inhibits the DNA synthesis in tumor cells. The tumors cells are specifically killed by this process as the host tk has little affinity with the ganciclovir.

Figure 8.1 Schematic representation of suicidal gene therapy:

Herpes simplex virus contains an enzyme called THYMIDINE KINASE which is used in targeting cancer cells for suicidal gene therapy. The Ganciclovir, an antiviral drug is used for suicidal gene therapy. The underlying mechanism behind the killing of a cancer cells is by phosphorylation of Ganciclovir.