Structure-guided design combined with protein language model-guided engineering and sgRNA optimization enables the development of a compact and highly efficient CRISPR–Cas12f genome editor. This integrated strategy substantially improves genome-editing activity while preserving high specificity, expanding the therapeutic potential of compact CRISPR systems.

Ouabain triggers cochlear spiral ganglion neuron (SGN) ferroptosis and hearing loss via SCD1 downregulation. MITF directly activates Scd1 transcription, and the MITF–SCD1 axis mitigates SGN ferroptosis and hearing impairment in ototoxic ouabain and cisplatin models, revealing a lipid metabolic vulnerability and therapeutic target for sensorineural hearing loss.

This study identifies AAV2.7m8-Myo15 as a safe and efficient vector for transducing cochlear outer hair cells in adult mice via posterior semicircular canal injection. These insights overcome age-related transduction barriers and suggest potential gene therapy strategies for sensorineural hearing loss.