Neurotology Program, National Institute on Deafness and Other Communication Disorders (NIDCD), National Institutes of Health, Bethesda, MD, 20892, USA.
Center for Advanced Retinal and Ocular Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Nat Commun. 2019 Jan 25;10(1):427. doi: 10.1038/s41467-018-08243-1.
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.
腺相关病毒 (AAV) 已成功用于基因治疗，以改善遗传性听力损失的小鼠模型中的听觉功能。许多形式的遗传性听力损失都有突变，这些突变会影响耳蜗毛细胞，即允许声音检测和处理的机械感觉细胞。虽然大多数常规 AAV 以不同的效率感染内耳毛细胞 (IHC)，但它们在耳蜗中以较低的水平感染外毛细胞 (OHC) 和支持细胞。在这里，我们研究了两种合成 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指细胞。我们的结果表明，AAV2.7m8 是一种用于针对耳蜗毛细胞和支持细胞的内耳基因治疗的优秀病毒载体，它可能极大地扩展内耳基因治疗的潜在应用。
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