Human promoter-driven AAV tools enable precision gene therapy targeting cochlear hair cells - PubMed
5 hours ago
- #hearing loss
- #cochlear hair cells
- #AAV gene therapy
- Approximately 50% of hereditary deafness and most age-related hearing loss stem from cochlear hair cell dysfunction.
- AAV-mediated gene therapy is promising for hearing restoration, but targeting cochlear hair cells is challenging due to complex cellular composition.
- A cross-species screening platform was developed for cochlear AAV tools, applicable from rodents to large animals.
- Human promoters were identified that specifically target inner hair cells, outer hair cells, or all hair cells in mice.
- The coProB2 promoter was validated in pigs and monkeys, showing specific transgene expression in hair cells without auditory toxicity.
- coProB2-driven gene therapies restored auditory function to near wild-type levels in mouse models of DFNB79 and DFNB9 deafness.
- The study establishes a cross-species-compatible, hair cell-specific AAV system for precision gene therapy targeting cochlear hair cells.