Drug intelligence / Profile preview

HSV-TK + ganciclovir

Development stage
Preclinical
Lead developer
Premier Biotech
Modality
Small Molecules, Gene Therapies
Administration
Intravenous, Local (e.g., Intratumoral For Gene Therapy), Intrathecal (in Select Trials)
01

Overview

**HSV-TK + ganciclovir** is a combination of **gene therapy** and **antiviral prodrug therapy** used primarily in experimental and investigational settings, most often as a form of suicide gene therapy for cancer and cell ablation. The therapy involves the introduction (typically via viral or other vectors) of the gene encoding herpes simplex virus thymidine kinase (HSV-TK) into target cells. HSV-TK is a viral enzyme that phosphorylates the nucleoside analogue ganciclovir (GCV), converting it into a monophosphate and subsequently, via cellular enzymes, into a cytotoxic triphosphate form. This triphosphate is then incorporated into cellular DNA, leading to chain termination and selective cell death. Because mammalian thymidine kinase does not efficiently phosphorylate GCV, only HSV-TK-expressing cells are sensitized to ganciclovir, enabling targeted ablation (the so-called "suicide effect"). The HSV-TK + ganciclovir system is also notable for the "bystander effect," whereby neighboring non-transduced cells may also be killed due to transfer of toxic metabolites, enhancing therapeutic efficacy[2][3][4][9][10].

Other names
herpes simplex virus thymidine kinase + ganciclovirHSV-TK/GCV
02

Targets

POLA1 (DNA polymerase alpha)HSV-TK (Herpes simplex virus type 1 thymidine kinase (HSV1-TK))

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