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恢复听力的CRISPR方式
A CRISPR Way to Restore Hearing


Wade W. Chien ... 其他 • 2018.03.29
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• 修复人类生殖细胞系的有力理由

遗传性听力损失是新生儿最常见的残疾之一,每1,000名活产婴儿中约有1名受累。大多数遗传性听力损失的类型是非综合征性的;80%受累新生儿的听力损失是以常染色体隐性的方式遗传,其余20%则以显性方式遗传1

许多类型的遗传性听力损失是由影响耳蜗毛细胞形成和功能的基因突变引起的,耳蜗毛细胞是高度特化的感觉细胞,在声音的探测和处理中发挥重要作用1。毛细胞的顶端表面上有类似头发的束状突起,称为静纤毛(图1)。这些纤毛在声音的作用下偏转使机械转导离子通道(位于静纤毛的尖端)开放,并因此导致毛细胞膜去极化。跨膜离子通道样蛋白1(protein transmembrane channel-like 1,TMC1)是机械转导复合体的一个组成部分,影响该蛋白的突变会导致常染色体显性和隐性遗传的听力损失2。最近Gao及其同事报道在小鼠Tmc1模型(称为“贝多芬”小鼠模型)中矫正了显性遗传的听力损失3





作者信息

Wade W. Chien, M.D.
From the Surgeon-Scientist Program, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, and the Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore - both in Maryland.

 

参考文献

1. Chien WW, Monzack EL, McDougald DS, Cunningham LL. Gene therapy for sensorineural hearing loss. Ear Hear 2015;36:1-7.

2. Pan B, Géléoc GS, Asai Y, et al. TMC1 and TMC2 are components of the mechanotransduction channel in hair cells of the mammalian inner ear. Neuron 2013;79:504-515.

3. Gao X, Tao Y, Lamas V, et al. Treatment of autosomal dominant hearing loss by in vivo delivery of genome editing agents. Nature 2018;553:217-221.

4. Shibata SB, Ranum PT, Moteki H, et al. RNA interference prevents autosomal-dominant hearing loss. Am J Hum Genet 2016;98:1101-1113.

5. Zhao Y, Wang D, Zong L, et al. A novel DFNA36 mutation in TMC1 orthologous to the Beethoven (Bth) mouse associated with autosomal dominant hearing loss in a Chinese family. PLoS One 2014;9(5):e97064-e97064.

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