In utero gene therapy rescues vision in a murine model of congenital blindness
In utero gene therapy rescues vision in a murine model of congenital blindness
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DOI：
10.1016/j.ymthe.2003.11.013
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发表时间：
2004-02-01
影响因子：
12.4
通讯作者：
Bennett, J
中科院分区：
文献类型：
--
作者：
Dejneka, NS;Surace, EM;Bennett, J
先天性视网膜盲称为Leber先天性黑蒙（LCA）可能是由RPE 65基因突变引起的。RPE 65在产生光敏色素视紫红质的视觉周期中起着关键作用。最近对LCA的人类研究表明，早期干预比晚期干预更有可能恢复视力。我们使用包装在AAV 1衣壳（AAV 2/1）内的血清型2腺相关病毒，在LCA的鼠模型（Rpe 65（-/-）小鼠）中确定子宫内递送人Rpe 65 cDNA至视网膜色素上皮细胞的影响。将AAV 2/1-CMV-hRPE 65递送至胎儿（胚胎第14天）导致视网膜色素上皮的有效转导、视觉功能的恢复和可测量的视紫红质。结果证明了AAV介导的缺陷的校正，并表明子宫内视网膜基因递送可能是治疗各种致盲性先天性视网膜疾病的有用方法。
The congenital retinal blindness known as Leber congenital amaurosis (LCA) can be caused by mutations in the RPE65 gene. RPE65 plays a critical role in the visual cycle that produces the photosensitive pigment rhodopsin. Recent evidence from human studies of LCA indicates that earlier rather than later intervention may be more likely to restore vision. We determined the impact of in utero delivery of the human RPE65 cDNA to retinal pigment epithelium cells in a murine model of LCA, the Rpe65(-/-) mouse, using a serotype 2 adeno-associated virus packaged within an AAV1 capsid (AAV2/1). Delivery of AAV2/1-CMV-hRPE65 to fetuses (embryonic day 14) resulted in efficient transduction of retinal pigment epithelium, restoration of visual function, and measurable rhodopsin. The results demonstrate AAV-mediated correction of the deficit and suggest that in utero retinal gene delivery may be a useful approach for treating a variety of blinding congenital retinal diseases.