Akil, O. et al. PNAS 116, 4496–4501 (2019)

Autosomal recessive genetic forms (DFNB) account for 80% cases of profound congenital deafness. In humans, DFNB is diagnosed in the neonatal period, long after the inner ear is developed. Efforts are therefore underway to identify therapies that can reverse deafness after hearing onset. A study describes a new adeno-associated virus (AAV)-based gene therapy delivered to the mature cochlea that reversed hearing loss in mice with DFNB9, a condition caused by mutations in the OTOF gene. A dual AAV approach was used, in which the two halves of the large Otof cDNA were contained in two separate vectors. Delivery of the vectors in Otof−/− mice resulted in expression of full-length otoferlin protein via DNA recombination, and a reversal of the deafness phenotype, raising hope for patients with DFNB9.