Gene Therapy Restores Balance and Auditory Functions in a Mouse Model of Usher Syndrome
Gene Therapy Restores Balance and Auditory Functions in a Mouse Model of Usher Syndrome
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DOI：
10.1016/j.ymthe.2017.01.007
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发表时间：
2017-03-01
影响因子：
12.4
通讯作者：
Chien, Wade W.
中科院分区：
文献类型：
--
作者：
Isgrig, Kevin;Shteamer, Jack W.;Chien, Wade W.
头晕和听力丧失是最常见的残疾症状。许多形式的遗传性平衡和听力障碍是由静纤毛的异常发育引起的，静纤毛是内耳毛细胞顶端表面的机械感觉细胞器。聋鼠（一种人类Usher综合征的模型，表现为听力丧失、头晕和失明）在whirlin基因上有一个隐性突变，这使得毛细胞静纤毛短小且功能失调。在这项研究中，通过将腺相关病毒2/8型（AAV8 - whirlin）注射到后半规管，将野生型whirlin基因的互补DNA输送到新生聋鼠的内耳。单侧whirlin基因治疗注射能够恢复聋鼠的平衡功能，并至少在4个月内改善其听力。我们的数据表明，基因治疗可能会成为治疗遗传性平衡和听力障碍的一种选择。
Dizziness and hearing loss are among the most common disabilities. Many forms of hereditary balance and hearing disorders are caused by abnormal development of stereocilia, mechanosensory organelles on the apical surface of hair cells in.the inner ear. The deaf whirler mouse, a model of human Usher syndrome (manifested by hearing loss, dizziness, and blindness), has a recessive mutation in the whirlin gene, which renders hair cell stereocilia short and dysfunctional. In this study, wild-type whirlin cDNA was delivered to the inner ears of neonatal whirler mice using adeno-associated virus serotype 2/8 (AAV8-whirlin) by injection into the posterior semicircular canal. Unilateral whirlin gene therapy injection was able to restore balance function as well as improve hearing in whirler mice for at least 4 months. Our data indicate that gene therapy is likely to become a treatment option for hereditary disorders of balance and hearing.