遗传性听力障碍的基因治疗研究进展

令娜娜; 郭玉芬; 徐百成

doi:10.3969/j.issn.1672-4933.2023.04.015

您当前的位置：

首页 >

文章列表页 >

遗传性听力障碍的基因治疗研究进展

综述 | 更新时间：2026-07-10

- 遗传性听力障碍的基因治疗研究进展
- Recent Development of Gene Therapy for Hereditary Deafness
- 中国听力语言康复科学杂志 2023年21卷第4期页码：394-398
- 作者机构：
  
  1.兰州大学第二医院耳鼻咽喉头颈外科兰州 730000
  2.西安市人民医院（西安市第四医院）耳鼻咽喉头颈外科西安 710000
- 作者简介：
  
  令娜娜硕士研究生；研究方向：听力障碍的基础与临床
  徐百成，E-mail：xbsuc@126.com
- 基金信息：
  
  国家自然科学基金项目(31960132);甘肃省卫生行业计划项目(GSWSKY2018-40)
- DOI：10.3969/j.issn.1672-4933.2023.04.015
  中图分类号：
- 收稿：2022-04-15，
  
  纸质出版：2023-07-15
- 稿件说明：
移动端阅览
令娜娜,郭玉芬,徐百成.遗传性听力障碍的基因治疗研究进展[J].中国听力语言康复科学杂志,2023,21(04):394-398.

LING Na-na,GUO Yu-fen,XU Bai-cheng.Recent Development of Gene Therapy for Hereditary Deafness[J].Chinese Scientific Journal of Hearing and Speech Rehabilitation,2023,21(04):394-398.
令娜娜,郭玉芬,徐百成.遗传性听力障碍的基因治疗研究进展[J].中国听力语言康复科学杂志,2023,21(04):394-398. DOI： 10.3969/j.issn.1672-4933.2023.04.015.

LING Na-na,GUO Yu-fen,XU Bai-cheng.Recent Development of Gene Therapy for Hereditary Deafness[J].Chinese Scientific Journal of Hearing and Speech Rehabilitation,2023,21(04):394-398. DOI： 10.3969/j.issn.1672-4933.2023.04.015.

摘要

听力障碍是常见的感觉障碍性疾病之一，目前用于治疗遗传性听力障碍的临床选择有限，主要是通过配戴助听器或植入人工耳蜗等补偿或重建听力，并不能恢复自然听力。从病理学来说，恢复生理听觉是听力障碍治疗的必然目标，因此基因治疗才是听力障碍康复的最终方法。目前遗传性听力障碍的基因治疗还处在动物实验阶段，如何强化该基础研究并促进其向临床转化，是未来研究的重点。本文对遗传性听力障碍基因治疗的现状、发展前景和挑战等进行文献复习和发展展望。

Abstract

Deafness is one of the common sensory disorders. At present

the clinical options for the treatment of hereditary deafness are still very limited

mainly by wearing hearing aids or undergoing cochlear implant surgery to compensate the hearing. In fact

natural hearing cannot be restored. From the pathological point of view

restoring physiological hearing is the inevitable goal of deafness treatment

so in this sense

a gene therapy is the ultimate method of deafness rehabilitation. At present

the gene therapy of hereditary deafness is still in the stage of animal experiments. How to strengthen this basic research and promote its transformation into clinical are the focus of future research. This article reviews the current status

development prospects and challenges of gene therapy for hereditary deafness.

关键词

Keywords

references

Liberman MC . Noise-induced and age-related hearing loss: new perspectives and potential therapies [J ] . F1000Research , 2017 , 6 : 927 .

Ivanchenko MV , Hanlon KS , Devine MK , et al . Preclinical testing of AAV9-PHP.B for transgene expression in the non-human primate cochlea [J ] . Hearing research , 2020 , 394 : 107930 .

Lee J , Nist-Lund C , Solanes P , et al . Efficient viral transduction in mouse inner ear hair cells with utricle injection and AAV9-PHP.B [J ] . Hearing research , 2020 , 394 : 107882 .

Ponnath A , Depreux FF , Jodelka FM , et al . Rescue of Outer Hair Cells with Antisense Oligonucleotides in Usher Mice Is Dependent on Age of Treatment [J ] . Journal of the Association for Research in Otolaryngology:JARO , 2018 , 19 ( 1 ): 1 - 16 .

Fettiplace R . Hair Cell Transduction, Tuning, and Synaptic Transmission in the Mammalian Cochlea [J ] . Comprehensive Physiology , 2017 , 7 ( 4 ): 1197 - 1227 .

Vélez-Ortega AC , Frolenkov GI . Building and repairing the stereocilia cytoskeleton in mammalian auditory hair cells [J ] . Hearing research , 2019 , 376 : 47 - 57 .

Carpena NT , Lee MY . Genetic Hearing Loss and Gene Therapy [J ] . Genomics & informatics , 2018 , 16 ( 4 ): e20 .

Chen W , Hao QQ , Ren LL , et al . Cochlear morphology in the developing inner ear of the porcine model of spontaneous deafness [J ] . BMC neuroscience , 2018 , 19 ( 1 ): 28 - 28 .

Vojdani S , Amirsalari S , Milanizadeh S , et al . Mutation Screening of KCNQ1 and KCNE1 Genes in Iranian Patients With Jervell and Lange-Nielsen Syndrome [J ] . Fetal and pediatric pathology , 2019 , 38 ( 4 ): 273 - 281 .

Chang Q , Wang J , Li Q , et al . Virally mediated Kcnq1 gene replacement therapy in the immature scala media restores hearing in a mouse model of human Jervell and Lange-Nielsen deafness syndrome [J ] . EMBO molecular medicine , 2015 , 7 ( 8 ): 1077 - 1086 .

Mammano F . Inner Ear Connexin Channels: Roles in Development and Maintenance of Cochlear Function [J ] . Cold Spring Harbor perspectives in medicine , 2019 , 9 ( 7 ) : a033233 .

Dai P , Huang LH , Wang GJ , et al . Concurrent Hearing and Genetic Screening of 180,469 Neonates with Follow-up in Beijing, China [J ] . American journal of human genetics , 2019 , 105 ( 4 ): 803 - 812 .

Yu Q , Wang Y , Chang Q , et al . Virally expressed connexin26 restores gap junction function in the cochlea of conditional Gjb2 knockout mice [J ] . Gene therapy , 2014 , 21 ( 1 ): 71 - 80 .

Carricondo F , Romero-Gómez B . The Cochlear Spiral Ganglion Neurons: The Auditory Portion of the VIII Nerve [J ] . Anatomical record , 2019 , 302 ( 3 ): 463 - 471 .

Wagner EL , Shin JB . Mechanisms of Hair Cell Damage and Repair [J ] . Trends in neurosciences , 2019 , 42 ( 6 ): 414 - 424 .

Pinyon JL , Tadros SF , Froud KE , et al . Close-field electroporation gene delivery using the cochlear implant electrode array enhances the bionic ear [J ] . Science translational medicine , 2014 , 6 ( 233 ): 233ra54 .

Devare J , Gubbels S , Raphael Y . Outlook and future of inner ear therapy [J ] . Hearing research , 2018 , 368 : 127 - 135 .

Askew C , Chien WW . Adeno-associated virus gene replacement for recessive inner ear dysfunction: Progress and challenges [J ] . Hearing research , 2020 , 394 : 107947 .

Gu X , Chai R , Guo L , et al . Transduction of Adeno-Associated Virus Vectors Targeting Hair Cells and Supporting Cells in the Neonatal Mouse Cochlea [J ] . Frontiers in cellular neuroscience , 2019 , 13 : 8 - 8 .

Kilpatrick LA , Li Q , Yang J , et al . Adeno-associated virus-mediated gene delivery into the scala media of the normal and deafened adult mouse ear [J ] . Gene therapy , 2011 , 18 ( 6 ): 569 - 578 .

Landegger LD , Pan B , Askew C , et al . A synthetic AAV vector enables safe and efficient gene transfer to the mammalian inner ear [J ] . Nature biotechnology , 2017 , 35 ( 3 ): 280 - 284 .

György B , Meijer EJ , Ivanchenko MV , et al . Gene Transfer with AAV9-PHP.B Rescues Hearing in a Mouse Model of Usher Syndrome 3A and Transduces Hair Cells in a Non-human Primate [J ] . Molecular therapy. Methods & clinical development , 2018 , 13 : 1 - 13 .

Pan B , Askew C , Galvin A , et al . Gene therapy restores auditory and vestibular function in a mouse model of Usher syndrome type 1c [J ] . Nature biotechnology , 2017 , 35 ( 3 ): 264 - 272 .

Maeda Y , Sheffield AM , Smith RJH . Therapeutic regulation of gene expression in the inner ear using RNA interference [J ] . Advances in oto-rhino-laryngology , 2009 , 66 ( 1 ): 13 - 36 .

Gao X , Tao Y , Lamas V , et al . Treatment of autosomal dominant hearing loss by in vivo delivery of genome editing agents [J ] . Nature , 2018 , 553 ( 7687 ): 217 - 221 .

Dai J , Long W , Liang Z , et al . A novel vehicle for local protein delivery to the inner ear: injectable and biodegradable thermosensitive hydrogel loaded with PLGA nanoparticles [J ] . Drug development and industrial pharmacy , 2018 , 44 ( 1 ): 89 - 98 .

Zou J , Pyykkö I , Hyttinen J . Inner ear barriers to nanomedicine-augmented drug delivery and imaging [J ] . Journal of otology , 2016 , 11 ( 4 ): 165 - 177 .

Tan BT , Foong KH , Lee MM , et al . Polyethylenimine-mediated cochlear gene transfer in guinea pigs [J ] . Archives of otolaryngology-head & neck surgery , 2008 , 134 ( 8 ): 884 - 891 .

Belyantseva IA , Boger ET , Friedman TB . Myosin XVa localizes to the tips of inner ear sensory cell stereocilia and is essential for staircase formation of the hair bundle [J ] . Proceedings of the National Academy of Sciences of the United States of America , 2003 , 100 ( 24 ): 13958 - 13963 .

Li S , Qian W , Jiang G , et al . Transcription factors in the development of inner ear hair cells [J ] . Frontiers in bioscience (Landmark edition) , 2016 , 21 ( 6 ): 1118 - 1125 .

Packard AI , Lin B , Schwob JE . Sox2 and Pax6 Play Counteracting Roles in Regulating Neurogenesis within the Murine Olfactory Epithelium [J ] . PLoS One , 2016 , 11 ( 5 ): e0155167 .

Shibata SB , Yoshimura H , Ranum PT , et al . Intravenous rAAV2/9 injection for murine cochlear gene delivery [J ] . Scientific reports , 2017 , 7 ( 1 ): 9609 .

Shibata SB , Ranum PT , Moteki H , et al . RNA Interference Prevents Autosomal-Dominant Hearing Loss [J ] . American journal of human genetics , 2016 , 98 ( 6 ): 1101 - 1113 .

Yoshimura H , Shibata SB , Ranum PT , et al . Enhanced viral-mediated cochlear gene delivery in adult mice by combining canal fenestration with round window membrane inoculation [J ] . Scientific reports , 2018 , 8 ( 1 ): 2980 - 2980 .

Emptoz A , Michel V , Lelli A , et al . Local gene therapy durably restores vestibular function in a mouse model of Usher syndrome type 1G [J ] . Proceedings of the National Academy of Sciences of the United States of America , 2017 , 114 ( 36 ): 9695 - 9700 .

Lentz JJ , Jodelka FM , Hinrich AJ , et al . Rescue of hearing and vestibular function by antisense oligonucleotides in a mouse model of human deafness [J ] . Nature medicine , 2013 , 19 ( 3 ): 345 - 350 .

Pipe SW . Gene therapy for hemophilia [J ] . Pediatric blood & cancer , 2018 , 65 ( 2 ): e26865 .

Akil O , Seal RP , Burke K , et al . Restoration of hearing in the VGLUT3 knockout mouse using virally mediated gene therapy [J ] . Neuron , 2012 , 75 ( 2 ): 283 - 293 .

Mathur P , Yang J . Usher syndrome: Hearing loss, retinal degeneration and associated abnormalities [J ] . Biochimica et biophysica acta , 2015 , 1852 ( 3 ): 406 - 420 .

Luo H , Schmidt JA , Lee YS , et al . Targeted epigenetic repression of a lymphoma oncogene by sequence-specific histone modifiers induces apoptosis in DLBCL [J ] . Leukemia & lymphoma , 2017 , 58 ( 2 ): 445 - 456 .

Abedini F , Ebrahimi M , Hosseinkhani H . Technology of RNA Interference in Advanced Medicine [J ] . MicroRNA (Shariqah, United Arab Emirates) , 2018 , 7 ( 2 ): 74 - 84 .

György B , Nist-Lund C , Pan B , et al . Allele-specific gene editing prevents deafness in a model of dominant progressive hearing loss [J ] . Nature medicine , 2019 , 25 ( 7 ): 1123 - 1130 .

浏览量

324

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

上海地区人工耳蜗植入儿童生活质量评估：基于Nijmegen量表的回顾性分析

《儿童助听器验配服务指南》团体标准解读

大龄语前聋患者双侧人工耳蜗植入与双模式干预效果分析

飞行人员感音神经性聋特许飞行医学鉴定指南

良性阵发性位置性眩晕复位后残余头晕影响因素meta分析