内耳
圆窗
毛细胞
腺相关病毒
转基因
耳蜗
遗传增强
生物
细胞生物学
载体(分子生物学)
病毒载体
前庭系统
基因
基因传递
转导(生物物理学)
神经科学
遗传学
重组DNA
生物物理学
作者
Lukas D. Landegger,Bifeng Pan,Charles Askew,Sarah Wassmer,Sarah D Gluck,Alice Galvin,Ruth Taylor,Andrew Forge,Konstantina M. Stanković,Jeffrey R. Holt,Luk Vandenberghe
摘要
Efficient gene transfer to the mouse inner ear is achieved with a synthetic adeno-associated viral vector. Efforts to develop gene therapies for hearing loss have been hampered by the lack of safe, efficient, and clinically relevant delivery modalities1,2. Here we demonstrate the safety and efficiency of Anc80L65, a rationally designed synthetic vector3, for transgene delivery to the mouse cochlea. Ex vivo transduction of mouse organotypic explants identified Anc80L65 from a set of other adeno-associated virus (AAV) vectors as a potent vector for the cochlear cell targets. Round window membrane injection resulted in highly efficient transduction of inner and outer hair cells in mice, a substantial improvement over conventional AAV vectors. Anc80L65 round window injection was well tolerated, as indicated by sensory cell function, hearing and vestibular function, and immunologic parameters. The ability of Anc80L65 to target outer hair cells at high rates, a requirement for restoration of complex auditory function, may enable future gene therapies for hearing and balance disorders.
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