Noninvasive in vivo delivery of transgene via adeno-associated virus into supporting cells of the neonatal mouse cochlea
Noninvasive in vivo delivery of transgene via adeno-associated virus into supporting cells of the neonatal mouse cochlea
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DOI：
10.1089/hum.2007.167
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发表时间：
2008-04-01
影响因子：
4.2
通讯作者：
Ikeda, Katsuhisa
中科院分区：
文献类型：
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作者：
Iizuka, Takashi;Kanzaki, Sho;Ikeda, Katsuhisa
有许多遗传性疾病会在生命早期影响耳蜗，这些疾病需要在早期发育阶段进行正常的基因转移以防止耳聋。研究了腺病毒（AdV）和腺相关病毒（AAV）的递送，以阐明转基因在新生小鼠耳蜗中表达的效率和细胞特异性。AdV转染的程度与成年小鼠相当。通过耳蜗造口注射入中阶后，AAV定向基因转移在支持细胞、内毛细胞（IHC）和侧壁中显示转基因表达，导致听力损失。另一方面，通过圆窗将AAV应用于鼓阶后，在Deiters细胞、IHC和外侧壁中观察到基因表达，而没有听力损失。这些发现表明，将AAV注射到新生小鼠耳蜗的鼓阶中因此具有有效且非侵入性地将转基因引入耳蜗支持细胞的潜力，并且这种方式因此被认为是预防遗传性语前聋的有希望的策略。
There are a number of genetic diseases that affect the cochlea early in life, which require normal gene transfer in the early developmental stage to prevent deafness. The delivery of adenovirus (AdV) and adeno-associated virus (AAV) was investigated to elucidate the efficiency and cellular specificity of transgene expression in the neonatal mouse cochlea. The extent of AdV transfection is comparable to that obtained with adult mice. AAV-directed gene transfer after injection into the scala media through a cochleostomy showed transgene expression in the supporting cells, inner hair cells (IHCs), and lateral wall with resulting hearing loss. On the other hand, gene expression was observed in Deiters cells, IHCs, and lateral wall without hearing loss after the application of AAV into the scala tympani through the round window. These findings indicate that injection of AAV into the scala tympani of the neonatal mouse cochlea therefore has the potential to efficiently and noninvasively introduce transgenes to the cochlear supporting cells, and this modality is thus considered to be a promising strategy to prevent hereditary prelingual deafness.