Cytosine deaminase and Herpes simplex virus type 1 thymidine kinase (CD/HSV-1 TK)

This target represents a dual suicide gene therapy system delivered via a retroviral replicating vector (RRV) into tumor cells. The system utilizes two distinct enzymes: cytosine deaminase (CD), which converts the prodrug 5-fluorocytosine (5-FC) into the cytotoxic metabolite 5-fluorouracil (5-FU), and Herpes simplex virus type 1 thymidine kinase (HSV-1 TK), which activates the prodrug ganciclovir (GCV) into a DNA polymerase inhibitor (Tai & Kasahara, 2008, PMID: 17981778). The use of a semi-replicating retroviral vector allows for the selective infection of actively dividing cancer cells, facilitating the spread of the therapeutic genes throughout the tumor mass (Ostertag et al., 2012, PMID: 22234452). Once the enzymes are expressed, the administration of prodrugs leads to the localized production of toxins, inducing cell death through DNA damage and inhibition of nucleic acid synthesis (Fillat et al., 2003, PMID: 12769611). This approach also benefits from a "bystander effect," where the toxic metabolites diffuse to adjacent non-transduced tumor cells, enhancing the overall anti-tumor efficacy. Clinical applications have primarily focused on high-grade gliomas, where local control is critical and systemic chemotherapy is often limited by the blood-brain barrier.

Other names

Suicide gene therapy systemRRV-CD-TKRetroviral replicating vector-mediated gene therapyCD/TK dual gene system

Conversion of non-toxic prodrugs into cytotoxic metabolites (5-fluorouracil and ganciclovir triphosphate) within transduced tumor cells, leading to inhibition of DNA synthesis and induction of apoptosis.