Zhang and colleagues reveal that GPX4 serves as a critical regulator of NRF2-mediated otoprotection against aminoglycoside-induced hair cell injury. Their findings identify a GPX4-dependent antioxidant mechanism that enables therapeutic activation of NRF2 and provides new insights into strategies for preventing drug-induced hearing loss.

This study developed a multi-layer inducible RNA switch that achieves transient expression of gene-delivery vectors in hepatic and non-hepatic tissues. As an exemplary application, this RNA switch triggers pulsive expression of gene editors that reduces the off-target effects and immunotoxicity of gene editing.