AAV-ie-CAG-GFP

Hearing loss (HL) is a common health problem that affects more than 5% of the world’s population, or approximately 430 million people. It is predicted that by 2050, more than 700 million people, or 1 in 10 people, will suffer from disabling HL. HL is generally divided into two categories: conductive HL, which stems from problems with the ear canal, eardrum, or middle ear and its tiny bones; and sensorineural HL (SNHL), which stems from damage to the cochlear cells or auditory nerve itself. Adeno-associated virus (AAV)-mediated gene therapy represents a new frontier in the treatment of SNHL. This approach differs from traditional hearing aids and cochlear implants, which enhance auditory perception by amplifying or directly stimulating the auditory nerve. AAV-mediated gene therapy uses AAV vectors to introduce therapeutic drugs into the inner ear, thereby addressing the genetic basis of HL. AAV-ie has a transduction rate of more than 90% for both outer hair cells (OHCs) and inner hair cells (IHCs). At equivalent doses, Anc80L65 and AAV-DJ had transduction efficiencies in SCs below 55%, whereas AAV-ie was significantly more efficient, with a transduction rate of approximately 77% in SCs. Notably, AAV-ie transduction of SCs was dose-dependent. At higher doses, AAV-ie effectively targeted all SC subtypes, including Hensen cells, Deiters cells, pillar cells, inner phalanx cells, and inner border cells, with an overall efficiency exceeding 80%. In addition, delivery of the Atoh1 gene to the mouse cochlea by AAV-ie generated a large number of new HC-like cells. These studies suggest that AAV is a promising vector for repairing HL caused by genetic dysfunction and for rescuing HL caused by noise damage, ototoxic drugs, or aging through hair cell regeneration.