Engineered super-enhancers enable targeted viral immunotherapy in glioblastoma

A team created synthetic super-enhancers by assembling natural enhancer fragments bound by SOX2 and SOX9 in glioblastoma stem cells to achieve high, selective transgene expression. They packaged these SSEs into AAV vectors to drive a dual payload (HSV-TK/GCV cytotoxic system and IL-12) in a mouse glioblastoma model, achieving tumor clearance and immunological memory; SSE activity was validated in primary human GSCs and brain tissue slices, suggesting SSEs could enable cell-state-specific, potent gene therapy with broad applicability.