AAV-S9RE-HSV-TK

AAV-S9RE-HSV-TK is an experimental adeno-associated virus (AAV)-based suicide gene therapy designed to target therapy-resistant medulloblastoma, a common malignant pediatric brain tumor. The vector utilizes a SOX9-responsive element (S9RE), which consists of four copies of a minimal COL2A1 enhancer coupled to a minimal promoter, to drive the expression of the herpes simplex virus thymidine kinase (HSV-TK) gene specifically in cells with high SOX9 activity. SOX9 is a transcription factor associated with poor prognosis and therapy resistance in medulloblastoma. When combined with the prodrug ganciclovir, HSV-TK converts it into a cytotoxic metabolite that selectively induces apoptosis in mitotic SOX9-positive cancer cells. This approach aims to eradicate the resistant cell populations that often lead to tumor recurrence.