HSV1-TK + shTERT

HSV1-TK + shTERT is an experimental **combination gene therapy** that utilizes retroviral delivery of two distinct transgenes: (1) **herpes simplex virus type-1 thymidine kinase** (HSV1-TK), a suicide gene, and (2) a **short hairpin RNA targeting human telomerase reverse transcriptase** (shTERT). HSV1-TK confers sensitivity to the nucleoside analog ganciclovir, leading to selective killing of transduced cells via DNA chain termination and apoptosis. Concurrently, shTERT silences hTERT, inhibiting telomerase activity and reducing tumor cell proliferation. The combination, expressed from the pLXSN-TK-U6-shTERT retroviral vector, has shown tumor growth inhibition and enhanced tumor-specific cytotoxicity in hepatocellular carcinoma (HCC) in vitro and in mouse xenograft models, with minimal toxicity to normal cells. This combinatorial approach attempts to maximize therapeutic efficacy by simultaneously blocking telomerase-driven immortality and enabling suicide gene-mediated ablation upon prodrug (ganciclovir) administration.

Other names

HSV-TK + shTERThTERT shRNA/HSV1-TK