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.

AAV-WM04, an AAV vector identified through in-vivo-directed screening in the adult cochlea, enables highly efficient and selective inner hair cell transduction. Dual-AAV delivery of OTOF using AAV-WM04 restores hearing in a DFNA9 deafness mouse model at low doses, highlighting its translational potential for gene therapy.