ShanghaiTech University Knowledge Management System
| Deciphering enhancers of hearing loss genes for efficient and targeted gene therapy of hereditary deafness | |
| 2025-04-21 | |
| 发表期刊 | NEURON (IF:14.7[JCR-2023],16.9[5-Year]) |
| ISSN | 0896-6273 |
| 发表状态 | 已发表 |
| DOI | 10.1016/j.neuron.2025.03.023 |
| 摘要 | Hereditary hearing loss accounts for about 60% of congenital deafness. Although adeno-associated virus (AAV)-mediated gene therapy shows substantial potential for treating genetic hearing impairments, there remain significant concerns regarding the specificity and safety of AAV vectors. The sophisticated nature of the cochlea further complicates the challenge of precisely targeting gene delivery. Here, we introduced an AAV-reporter-based in vivo transcriptional enhancer reconstruction (ARBITER) workflow, enabling efficient and reliable dissection of enhancers. With ARBITER, we successfully demonstrated that the conserved non-coding elements (CNEs) within the gene locus collaboratively regulate the expression of Slc26a5, which was further validated using knockout mouse models. We also assessed the potential of identified enhancers to treat hereditary hearing loss by conducting gene therapy in Slc26a5 mutant mice. Based on the original Slc26a5 enhancer with limited efficiency, we engineered a highly efficient and outer hair cell (OHC)-specific enhancer, B8, which successfully restored hearing of Slc26a5 knockout mice. |
| 关键词 | hereditary hearing loss gene therapy adeno-associated viruses AAVs outer hair cell OHC Slc26a5 transcriptional enhancer conserved non-coding elements CNEs |
| 学科门类 | 理学 |
| 收录类别 | SCI |
| 语种 | 英语 |
| 文献类型 | 期刊论文 |
| 条目标识符 | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/527140 |
| 专题 | iHuman研究所 生命科学与技术学院_PI研究组_林照博组 iHuman研究所_特聘教授组_Raymond Stevens组 iHuman研究所_公共科研平台_超分辨生物成像平台 iHuman研究所_PI研究组_钟桂生组 生命科学与技术学院_硕士生 生命科学与技术学院_博士生 生命科学与技术学院_本科生 生命科学与技术学院_PI研究组_马涵慧组 |
| 共同第一作者 | Qiuxiang Yang; Zehua Yu |
| 通讯作者 | Simeng Zhao; Guisheng Zhong |
| 作者单位 | 1.iHuman Institute, ShanghaiTech University, Shanghai 201210, China 2.School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China 3.State Key Laboratory of Genetic Evolution and Animal Models, Yunnan Key Laboratory of Animal Models and Human Disease Mechanisms, Yunnan Engineering Center on Brain Disease Models, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650204, China 4.Shanghai Clinical Research and Trial Center, Shanghai 201210, China 5.Shanghai Key Laboratory of High-Resolution Electron Microscopy, ShanghaiTech University, Shanghai 201210, China 6.National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), and National Resource Center for Non-Human Primates, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650107, Yunnan, China 7.Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming 650204, Yunnan, China 8.Shanghai Key Laboratory of High-Resolution Electron Microscopy, ShanghaiTech University, Shanghai 201210, China 9.Shanghai Key Laboratory of Gene Editing and Cell Therapy for Rare Diseases, Fudan University, Shanghai 20031, China |
| 第一作者单位 | iHuman研究所 |
| 通讯作者单位 | iHuman研究所; 生命科学与技术学院; 上海科技大学 |
| 第一作者的第一单位 | iHuman研究所 |
| 推荐引用方式 GB/T 7714 | Simeng Zhao,Qiuxiang Yang,Zehua Yu,et al. Deciphering enhancers of hearing loss genes for efficient and targeted gene therapy of hereditary deafness[J]. NEURON,2025. |
| APA | Simeng Zhao.,Qiuxiang Yang.,Zehua Yu.,Cenfeng Chu.,Shengqi Dai.,...&Guisheng Zhong.(2025).Deciphering enhancers of hearing loss genes for efficient and targeted gene therapy of hereditary deafness.NEURON. |
| MLA | Simeng Zhao,et al."Deciphering enhancers of hearing loss genes for efficient and targeted gene therapy of hereditary deafness".NEURON (2025). |
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