LEBER HEREDITARY OPTIC NEUROPATHY: GENE THERAPY

描述（改编自申请人摘要）：Leber遗传性视神经病变 神经病（LHON）是一种与以下基因突变相关的遗传性疾病： 线粒体DNA这种突变具有可变的突变率，但在许多情况下， 导致年轻人严重的双侧视力丧失。在这次修订中， 研究人员和他的高级合作者建议测试可行性， 将正常基因产物递送、表达并靶向线粒体 其长期目标是为线粒体疾病设计治疗方法。 携带绿色荧光蛋白的重组腺相关病毒（AAV） (GFP)基因和外显子特异性靶向/加工信号序列 将用于测试蛋白质是否可以安全，有效地输送， 在细胞培养系统中有效地转化为线粒体。这种体外分析 随后将进行体内转导实验， 将安全剂量的野生型NADH脱氢酶递送至 大鼠视网膜和视神经中的线粒体。

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.