Advances towards biological hearing restoration by genetic reprogramming.

PURPOSE OF REVIEW: Advances in genetic reprogramming and groundbreaking first-in-human gene therapy trials have generated significant momentum for treating sensorineural hearing loss. This review evaluates the expanding potential of biological approaches for hearing restoration.

RECENT FINDINGS: The mammalian organ of Corti possesses limited natural regenerative capacity. Recent studies are attempting to restore hearing by genetically reprogramming supporting cells into hair cells. While merely modulating cell signaling pathways in the inner ear is currently insufficient to regenerate hair cells, expressing hair cell-specific specific transcription factors can partially activate hair cell identity. However, current attempts at reprogramming are only partially successful, yielding only immature and nonfunctional "hair cell-like cells."

SUMMARY: To develop viable gene therapies, future research must identify the molecular mechanisms that maintain supporting cell identity in the mature cochlea. Targeting and suppressing these gene networks in addition to activating hair cell gene networks is essential to improve the complete transition of supporting cells into functional hair cells, paving the way for translating these regenerative strategies into effective clinical treatments.