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

RPE65是一种只存在于视网膜内的基因。目前，RPE65的确切作用尚不清楚，但最近的研究表明，在许多遗传性视网膜营养不良症（这些营养不良症包括Leber先天性黑朦和常染色体隐性视网膜色素变性）中发现了RPE65基因的突变。因此，一个功能性的、非突变的RPE65基因对正常视力至关重要。一种RPE65相关视网膜营养不良的小鼠模型最近被开发出来，通过产生RPE65基因敲除的小鼠品种，其中小鼠的RPE65基因已经突变为非活性形式。对这些老鼠的研究表明，它们会患上视网膜营养不良症，这与携带RPE65基因突变的患者非常相似。我们建议使用这些RPE65基因敲除小鼠来测试治疗RPE65相关视网膜营养不良患者的潜在方法。特别是，我们将研究利用基因疗法治疗这些疾病的潜力。该项目将涉及将一个新的功能性RPE65基因植入RPE65基因敲除小鼠的视网膜。新的、功能性的RPE65基因将取代小鼠视网膜中失活的、突变的RPE65基因，我们预测这一行为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rpe65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.