基于AAV的遗传性耳聋基因治疗的基础和临床研究进展  

Basic and clinical research progress of AAV-based gene therapy for hereditary deafness

作　　者：周吟毅 杨雪寒 陆宜成 王晓涵 陈相琰 范瑾怡 张心茹 伍贤敏 张李燕 谈方志 齐洁玉 柴人杰 ZHOU Yinyi;YANG Xuehan;LU Yicheng;WANG Xiaohan;CHEN Xiangyan;FAN Jinyi;ZHANG Xinru;WU Xianmin;ZHANG Liyan;TAN Fangzhi;QI Jieyu;CHAI Renjie(State Key Laboratory of Digital Medical Engineering,Department of Otolaryngology Head and Neck Surgery,Zhongda Hospital,School of Life Sciences and Technology,School of Medicine,Advanced Institute for Life and Health,Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research,Southeast University,Nanjing 210096,China;Co-Innovation Center of Neuroregeneration,Nantong University,Nantong 226001,China;State Key Laboratory of Hearing and Balance Science,Department of Neurology,Aerospace Center Hospital,School of Life Science,Beijing Institute of Technology,Beijing 100081,China;Department of Otolaryngology-Head and Neck Surgery,Sichuan Provincial People’s Hospital,University of Electronic Science and Technology of China,Chengdu,610072,China;Southeast University Shenzhen Research Institute,Shenzhen 518063,China)

机构地区：[1]东南大学数字医学工程全国重点实验室,附属中大医院耳鼻咽喉头颈外科,生命科学与技术学院,生命健康高等研究院,江苏省生物医学高新技术研究重点实验室,南京210096 [2]南通大学神经再生联合创新中心,南通226001 [3]北京理工大学生命科学学院航天中心医院神经内科,听力与平衡科学国家重点实验室,北京100081 [4]四川省医学科学院,四川省人民医院/电子科技大学附属医院耳鼻咽喉头颈外科,成都610072 [5]东南大学深圳研究院,深圳518063

出　　处：《中国科学:生命科学》2025年第4期697-710,共14页Scientia Sinica(Vitae)

基　　金：国家重点研发计划(批准号:2021YFA1101300,2021YFA1101800,2020YFA0113600,2020YFA0112503);国家自然科学基金(批准号:82330033,82030029,92149304,82000984,82371162,82371161);江苏省自然科学基金基础研究计划(批准号:BK20232007);四川省科技计划重点研发项目(批准号:2021YFS0371);深圳市科技计划(批准号:JCYJ20190814093401920,JCYJ20210324125608022);广东省医学科学院2022年度开放课题(批准号:YKY-KF202201)资助。

摘　　要：听力障碍作为发病率极高的社会健康问题受到广泛关注.约60%的感音神经性耳聋由遗传物质突变引起.遗传性聋的临床治疗主要依赖人工耳蜗和助听器,更为有效全面的生物学治疗手段的开发迫在眉睫.修复受损的基因,是从根本上治疗遗传性耳聋的有效手段.多个研究已表明,替代或修复遗传性聋小鼠模型中的突变基因,可有效恢复小鼠受损的听力.目前,基因治疗已成功恢复携带OTOF突变的遗传性耳聋患者听力.包括OTOF在内的耳聋基因有200多种,作为一种精准疗法,基因治疗在遗传性耳聋中的应用尚有诸多问题需要解决.本文首先概述了遗传性耳聋的发生发展,随后深入探讨了目前基因治疗应用于遗传性耳聋临床治疗的研究进展,并提出了耳聋基因治疗现阶段面临的困境与挑战.Hearing impairment has been widely concerned as a social health problem with high incidence.About 60%of cases of sensorineural hearing loss are caused by mutations in genetic material.The clinical treatment of hereditary deafness mainly relies on cochlear implants and hearing AIDS,and the development of more effective and comprehensive biological treatment methods is imminent.Repairing the damaged genes is an effective way to fundamentally treat hereditary deafness.Several studies have shown that the replacement or repair of mutant genes in inherited deafness mouse models can effectively restore the impaired hearing in mice.At present,gene therapy has successfully restored hearing in patients with hereditary deafness carrying OTOF mutations.There are more than 200 deafness genes including OTOF.As a precision therapy,there are still many problems need to be solved in the application of gene therapy in hereditary deafness.In this paper,the occurrence and development of hereditary deafness are summarized,and then the current research progress of gene therapy applied to the clinical treatment of hereditary deafness is deeply discussed,and the dilemma and challenge of gene therapy for deafness at this stage are put forward.

关 键 词：听力损失 基因治疗 遗传性耳聋 耳蜗 

分 类 号：R764.43[医药卫生—耳鼻咽喉科]