Development of gene therapy for a severe form of inherited retinal degeneration due to defects in AIPL1

Leber的先天性黑色素沉着症(LCA)是一个术语，用来描述一组影响儿童的遗传性视网膜退行性变。一种形式是由光感受器中表达的一种名为AIPL1的基因突变引起的。与AIPL1突变相关的视网膜疾病是进行性的，受影响的儿童在达到学龄时会出现严重的视力障碍。目前还没有有效的治疗方法。这项研究项目的目的是利用这种情况的小鼠模型来开发一种适用于人类的有效的基因治疗方案。通过引入有缺陷的AIPL1基因的正常拷贝，我们希望延缓或阻止光感受器的死亡，并保护视力。为了做到这一点，我们将设计病毒载体，将基因的正常拷贝携带到光感受器细胞，并将这些基因注射到小鼠的眼睛中。我们将研究影响基因传递效率的因素，并通过检查视网膜结构和进行视觉功能的电测试来评估结果。该项目将帮助我们优化眼睛基因治疗方案，并应促进临床试验的发展。我们还将确定和描述可能从治疗中受益的患者。

Leber‘s Congenital Amaurosis (LCA) is a term used to decribe a heterogeneous group of inherited retinal degenerations that affect children. One form is cause by mutations in a gene called AIPL1 that is expressed in photoreceptors. The retinal disease associated with AIPL1 mutations is progressive and affected children have severe visual impairment when they reach school age. There is currently no effective treatment. The aim of this research project is to use a mouse model of this condition to develop an effective gene therapy protocol that would be applicable to man. By introducing a normal copy of the defective AIPL1 gene we hope to delay or halt the death of photoreceptors and preserve vision. In order to do this we will engineer viral vectors to carry normal copies of the gene to the photoreceptor cells and injecting these into the mouse eye. We shall investigate the factors influencing the efficiency of the gene delivery and assess the outcome by examining the structure of the retina and performing electrical tests of visual function. This project will help us to optimise ocular gene therapy protocols and should facilitate the development of clinical trials. We shall also identify and characterise patients that might benefit from treatment.