Viral-mediated gene transfer in the cochlea
Viral-mediated gene transfer in the cochlea
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DOI：
10.1016/s0736-5748(96)00112-8
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发表时间：
1997-07-01
影响因子：
1.8
通讯作者：
Raphael, Y
中科院分区：
文献类型：
--
作者：
Weiss, MA;Frisancho, JC;Raphael, Y
基因转移在医学治疗和科学研究中是一种令人兴奋的新工具，但直到最近才开始在听觉系统中开发。本文描述了用腺病毒载体(Ad.RSVntlacZ)，它是一种基于人腺病毒(血清型5)基因组骨架的复制缺陷病毒。体内实验表明，基因转移成功地进入了多种类型的耳蜗细胞。我们观察到了一个相对有效的转导，几周的持续转基因表达，在成年动物的螺旋神经节和耳蜗管上皮细胞中没有主要的致命性细胞毒性。体外实验采用体外转导Ad的成纤维细胞。RSVntlacZ.将成纤维细胞接种到外淋巴中2周后，我们观察到移植的成纤维细胞附着在外淋巴间隙的衬里上，并表达LacZ转基因。我们推测，由于退行性耳蜗病的遗传基础是以突变水平为特征的，转基因表达将使我们能够检验关于特定基因对耳蜗细胞生物学影响的假说。基因转移不仅可以增加我们对听力损失的病理生理学的了解，还可以为疾病提供基因治疗。(C)1997年综合业务数字网。
Gene transfer is an exciting new tool in medical therapy and scientific investigation, but only very recently has it begun to be developed in the auditory system. This paper describes in vivo and ex vivo experiments using an adenoviral vector (Ad. RSVntlacZ), which is a replication-deficient virus based on a human adenoviral (serotype 5) genomic backbone. The in vivo experiments demonstrate successful gene transfer into multiple types of cochlear cells. We observed a relatively efficient transduction, several weeks of sustained transgene expression and an absence of major lethal cytotoxicity in spiral ganglion and epithelial cells of the cochlea in adult animals. The ex vivo experiments were performed using fibroblasts transduced in vitro with Ad. RSVntlacZ. Two weeks after inoculation of the fibroblasts into the perilymph, we observed transplanted fibroblasts, which were adherent to the lining of the perilymphatic spaces, and were expressing the lacZ transgene. We speculate that, as the genetic basis of degenerative cochlear diseases is characterized on a mutational level, transgene expression will allow us to test hypotheses regarding the effects of specific genes on cochlear cell biology. Gene transfer will not only increase our understanding of the pathophysiology of hearing loss, but also may provide gene therapy for disease. (C) 1997 ISDN.