| First Author | Shubina-Oleinik O | Year | 2021 |
| Journal | Sci Adv | Volume | 7 |
| Issue | 51 | Pages | eabi7629 |
| PubMed ID | 34910522 | Mgi Jnum | J:335790 |
| Mgi Id | MGI:6842829 | Doi | 10.1126/sciadv.abi7629 |
| Citation | Shubina-Oleinik O, et al. (2021) Dual-vector gene therapy restores cochlear amplification and auditory sensitivity in a mouse model of DFNB16 hearing loss. Sci Adv 7(51):eabi7629 |
| abstractText | Hearing loss affects an estimated 466 million people worldwide, with a substantial fraction due to genetic causes. Approximately 16% of genetic hearing loss is caused by pathogenic mutations in STRC, a gene that encodes the protein stereocilin. To develop gene therapy strategies for patients with STRC hearing loss, we generated a mouse model with a targeted deletion in the Strc gene. We devised a novel dual-vector approach to circumvent the size limitation of AAV vectors and drive expression of full-length STRC protein. To target outer hair cells, which are difficult to transduce, we used synthetic AAV9-PHP.B vectors for efficient dual-vector transduction. We report robust recovery of exogenous STRC expression in outer hair cells of Strc-deficient mice, recovery of hair bundle morphology, substantially improved cochlear amplification, and enhanced auditory sensitivity. The data raise the prospect that our strategy could benefit ~2.3 million patients worldwide affected by STRC mutations. |
