Gene Therapy for the treatment of retinal dystrophy in the RPE65 knockout mouse using rAAV virus mediated gene therapy.

RPE 65是一种仅在视网膜内发现的基因。目前RPE 65的确切作用尚不清楚，但最近的研究表明，RPE 65基因的突变已在许多遗传性视网膜营养不良中发现（这些营养不良包括Leber先天性黑蒙和常染色体隐性视网膜色素变性）。因此，一个功能性的，非突变的RPE 65基因对正常视力是必不可少的。最近已经通过产生RPE 65敲除小鼠品种开发了RPE 65相关视网膜营养不良的小鼠模型，其中小鼠的RPE 65基因已经突变成失活形式。对这些小鼠的研究表明，它们患上的视网膜营养不良与RPE 65基因突变患者非常相似。我们建议使用这些RPE 65敲除小鼠来测试治疗患者中RPE 65相关视网膜营养不良的潜在方法。特别是，我们将研究使用基因疗法治疗这些疾病的潜力。该项目将涉及将一种新的功能性RPE 65基因输送到RPE 65敲除小鼠的视网膜。然后，新的功能性RPE 65基因将取代小鼠视网膜内失活的突变RPE 65基因，我们预测这一行动将能够阻止这些小鼠发生视网膜营养不良。进行这样的研究将使我们能够提高我们对RPE 65相关视网膜营养不良的理解，并提供是否可以用基因疗法治疗的指示。

RPE65 is a gene that is found exclusively within the retina. At the moment the exact role of RPE65 is not known, however recent research has shown that mutations in the RPE65 gene have been found in a number of inherited retinal dystrophies (these dystrophies include Leber congenital amaurosis and autosomal recessive retinitis pigmentosa). It therefore appears that a functional, non-mutated RPE65 gene is essential for normal vision. A mouse model of RPE65-related retinal dystrophies has been recently developed, by producing a RPE65 knockout mouse breed in which the mouse's RPE65 gene has been mutated into an inactive form. Research on these mice have shown that they develop retinal dystrophies very similar to those seen in patients with mutated RPE65 genes. We propose to use these RPE65 knockout mice to test potential methods for treating the RPE65-related retinal dystrophies in patients. In particular, we will study the potential of using gene therapy to treat these diseases. The project will involve delivering a new, functional RPE65 gene to the retinas of the RPE65 knockout mice. The new, functional RPE65 gene will then replace the inactive, mutated RPE65 gene within the mouse retinas, an action that we predict will be able to stop these mice developing retinal dystrophy. Performing such a study will allow us to improve our understanding of the RPE65-related retinal dystrophies, and provide an indication of whether they can be treated with gene therapy.