LEBER HEREDITARY OPTIC NEUROPATHY: GENE THERAPY

描述(摘自申请者的摘要)：莱伯氏遗传性视神经 神经病(LHON)是一种与基因突变相关的遗传病 线粒体DNA。这种突变具有不同的外显性，但在许多情况下 导致年轻人严重的双眼失明。在这次修订中， 调查人员和他的资深合作者提议测试可行性 向线粒体递送、表达和靶向正常基因产物 其长期目标是设计线粒体疾病的治疗方法。 携带绿色荧光蛋白的重组腺相关病毒 (GFP)基因和线粒体特异性靶向/处理信号序列 将用于测试蛋白质是否可以安全、高效和 在细胞培养系统中有效地进入线粒体。这项体外分析 之后将进行体内转导实验，其中尝试将 被要求将安全剂量的野生型NADH脱氢酶 大鼠视网膜和视神经的线粒体。

DESCRIPTION (Adapted from the applicant's abstract): Leber's hereditary optic neuropathy (LHON) is a genetic disease associated with mutations in mitochondrial DNA. The mutation has variable penetrance, but in many cases leads to severe and bilateral loss of vision in young adults. In this revision, the investigator and his senior collaborators propose to test the feasibility of delivering, expressing, and targeting normal gene products to mitochondria with the long-term objective of devising therapies for mitochondrial diseases. A recombinant adeno-associated virus (AAV) bearing a green fluorescent protein (GFP) gene and mitochondrion-specific targeting/processing signal sequences will be used to test whether proteins can be delivered safely, efficiently, and effectively into mitochondria in a cell culture system. This in vitro analysis will be followed by in vivo transduction experiments in which an attempt will be made to deliver a safe dose of a wild type NADH dehydrogenase to mitochondria in the retina and optic nerve of rats.