Cidea Targeting Protects Cochlear Hair Cells and Hearing Function From Drug- and Noise-Induced Damage

Acquired sensorineural hearing loss (SNHL) is primarily caused by the damage or loss of hair cells (HCs), induced by factors such as noise exposure and ototoxic drugs. However, clinical treatments for SNHL remain limited. Here, the role of the apoptosis-inducing gene Cidea in SNHL is investigated. It is initially observed that Cidea expression is specifically increased in neomycin-damaged HCs at both the protein and mRNA levels. To further explore its role, Cidea knockout (Cidea-/-) mice are obtained, and it is found that the absence of Cidea effectively alleviates HC apoptosis caused by neomycin treatment and noise exposure in vivo. Moreover, a novel therapeutic strategy for SNHL has been developed by delivering CRISPR/SlugCas9-HF via AAV to edit Cidea, and this approach significantly reduced HC loss induced by both neomycin and noise exposure. These findings suggest that Cidea may serve as a promising target for the prevention of neomycin- and noise-induced SNHL in clinical settings.