Human promoter-driven AAV tools enable precision gene therapy targeting cochlear hair cells
Year: 2026
Type: article
Abstract: Approximately 50% of hereditary deafness cases and most age-related hearing loss result from cochlear hair cell dysfunction. Adeno-associated virus (AAV)-mediated gene therapy offers a promising strategy for hearing restoration. However, the cochlea's complex cellular composition poses a significant challenge for targeted gene delivery into hair cells. Here, we establish a cross-species screening platform for cochlear AAV tools, applicable from rodents to large animals. Using this platform, we identify human promoters that specifically target inner hair cells, outer hair cells, or all hair cells in mice. The hair cell-specific coProB2 promoter is further validated in Bama miniature pigs and cynomolgus monkeys, achieving specific transgene expression in hair cells without auditory toxicity. Importantly, coProB2-driven gene therapies in DFNB79 and DFNB9 mouse models restore auditory function to near wild-type levels. Thus, this study establishes a cross-species-compatible, hair cell-specific AAV system, providing a versatile toolbox for cochlear hair cell gene therapy.
Source: Cell Reports Medicine
Authors: Liyan Zhang, Yicheng Lu, Xianmin Wu, Jinyi Fan, Xinru Zhang, Yang Xu, Hao Wei, Qiuhan Sun, Lulu Jiang, Huawei Tuo, Nianci Li, Hua Jin, Wu Cao, Beibei Ye, Ziyu Zhang, Yunkai Zhang, Fangyi Chen, Ling Lu, Jieyu Qi, Renjie Chai, Fangzhi Tan
Institutions: Zhongda Hospital Southeast University, State Key Laboratory of Digital Medical Engineering, Inner Mongolia Medical University, Southeast University, Southern University of Science and Technology, Nanjing Drum Tower Hospital, Nanjing University, Beijing Institute of Technology, Zhuhai People's Hospital, Nantong University
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,620
Funders: Academy of Medical Sciences, National Natural Science Foundation of China, Natural Science Foundation of Jiangsu Province, Natural Science Foundation of Beijing Municipality, Natural Science Foundation of Shandong Province, Southeast University, Taishan Scholar Foundation of Shandong Province, Graduate Research and Innovation Projects of Jiangsu Province, National Key Research and Development Program of China, Shenzhen Science and Technology Innovation Program
Awards: G1083476708, G2215119364, G2318732474, G2462171634, G2562545184, G267354232, G4688080473, G4855079309, G4955491753, G5359620978, G5591760066, G6171391990, G6973767439, G7242850194, G7448286613, G7797219003, G7844431965, G8162577065, G8272360692, G8454626044, G8724284487, G8878369696, G997334894
OpenAlex ID: W7147107230