AAV‐Mediated Gene Therapy Restores Hearing in Patients with DFNB9 Deafness

Mutations in OTOFERLIN (OTOF) lead to the autosomal recessive deafness 9 (DFNB9). The efficacy of adeno-associated virus (AAV)-mediated OTOF gene replacement therapy is extensively validated in Otof-deficient mice. However, the clinical safety and efficacy of AAV-OTOF is not reported. Here, AAV-OTOF is generated using good manufacturing practice and validated its efficacy and safety in mouse and non-human primates in order to determine the optimal injection dose, volume, and administration route for clinical trials. Subsequently, AAV-OTOF is delivered into one cochlea of a 5-year-old deaf patient and into the bilateral cochleae of an 8-year-old deaf patient with OTOF mutations. Obvious hearing improvement is…

• NN
  National Natural Science Foundation of China

  Awards: 82071059, 92149304, STI2030, 82030029, 2021YFA1101300, 82371162, 82330033, 82371161, 82000984, 2021K156B, KF202201
• CP
  China Postdoctoral Science Foundation

  Award: 2020M681468
• DO
  Department of Science and Technology of Sichuan Province

  Awards: 2021YFS0371, YKK19072
• NP
  National Postdoctoral Program for Innovative Talents

  Award: BX20200082
• NK
  National Key Research and Development Program of China

  Awards: 2021YFA1101800, STI2030, JCYJ20190814093401920, 2021YFA1101300, JCYJ20210324125608022, 2020YFA0112503, 2020YFA0113600, 2022ZD0205400
• FR
  Fundamental Research Funds for the Central Universities

  Awards: 2020YFA0113600, 2020YFA0112503, 2021YFA1101300, 2021YFA1101800