AAV2.7m8 is a powerful viral vector for inner ear gene therapy
AAV2.7m8 is a powerful viral vector for inner ear gene therapy
复制标题
DOI：
10.1038/s41467-018-08243-1
复制
发表时间：
2019-01-25
影响因子：
16.6
通讯作者：
Chien, Wade W.
中科院分区：
文献类型：
--
作者：
Isgrig, Kevin;McDougald, Devin S.;Chien, Wade W.
腺相关病毒（AAV）已成功地用于基因治疗，以改善遗传性听力损失小鼠模型的听觉功能。许多形式的遗传性听力损失具有影响耳蜗毛细胞的突变，耳蜗毛细胞是允许声音检测和处理的机械感觉细胞。虽然大多数传统的腺相关病毒以不同的效率感染内毛细胞（IHC），但它们感染耳蜗中较低水平的外毛细胞（OHC）和支持细胞。在这里，我们研究了两种合成的AAV（AAV2.7m8和AAV8BP2）在小鼠内耳中的感染模式。AAV2.7m8以高效率感染IHC和OHC。此外，AAV2.7m8以高效率感染内柱细胞和内趾骨细胞。结果表明，AAV2.7m8是一种以耳蜗毛细胞和支持细胞为靶点的内耳基因治疗的理想病毒载体，它将极大地拓展内耳基因治疗的应用前景。
Adeno-associated virus (AAV) has been successfully used to deliver gene therapy to improve auditory function in mouse models of hereditary hearing loss. Many forms of hereditary hearing loss have mutations which affect the cochlear hair cells, the mechanosensory cells which allow for sound detection and processing. While most conventional AAVs infect inner hair cells (IHCs) with various efficiencies, they infect outer hair cells (OHCs) and supporting cells at lower levels in the cochlea. Here we examine the infection patterns of two synthetic AAVs (AAV2.7m8 and AAV8BP2) in the mouse inner ear. AAV2.7m8 infects both IHCs and OHCs with high efficiency. In addition, AAV2.7m8 infects inner pillar cells and inner phalangeal cells with high efficiency. Our results suggest that AAV2.7m8 is an excellent viral vector for inner ear gene therapy targeting cochlear hair cells and supporting cells, and it will likely greatly expand the potential applications for inner ear gene therapy.