Otoferlin (OTOF) messenger RNA (OTOF mRNA)

Mutant OTOF mRNA refers to the transcript of the OTOF gene containing pathogenic mutations that lead to a deficiency of functional otoferlin protein in the inner hair cells of the cochlea. Otoferlin is a large transmembrane protein that acts as a critical calcium sensor, facilitating the rapid fusion of synaptic vesicles with the plasma membrane to release glutamate onto auditory nerve fibers (UniProt: O88430). Mutations in this transcript are the primary cause of Autosomal Recessive Deafness 9 (DFNB9), a form of prelingual non-syndromic hearing loss characterized by auditory neuropathy, where the ear detects sound but fails to transmit the signal to the brain (NIH: GARD). Because the OTOF coding sequence exceeds the packaging capacity of standard viral vectors, therapeutic strategies utilize dual adeno-associated virus (AAV) systems to deliver a functional cDNA that produces wild-type mRNA and protein (PubMed: 38266547). Recent clinical trials have demonstrated that this gene replacement approach can successfully restore hearing thresholds and speech perception in pediatric patients, making it a high-priority target for genetic medicine in otology (Lilly/Akouos, 2024).

Other names

OTOF transcriptOtoferlin mRNADFNB9-associated mRNAOtoferlin messenger RNA

Dual-AAV vector-mediated gene replacement therapy designed to deliver a functional OTOF gene to inner hair cells, resulting in the production of wild-type OTOF mRNA and protein to restore synaptic transmission.