RPE MEDIATED RETINAL GENE THERAPY

描述（改编自申请人摘要）：遗传性疾病 影响视网膜色素上皮（RPE）和感光层 导致人类和动物失明。该研究将解决 对潜在增殖细胞的基因治疗 人群（RPE）可以治愈遗传性疾病， 视网膜色素上皮细胞，其次是感光细胞。自体RPE细胞将 将基因产物递送到视网膜以治疗视网膜的原发性疾病， RPE。这项研究现在是可行的，因为最近开发的 提供进入视网膜下腔的手术技术，以及 因为病毒载体可用于高效基因转移， RPE细胞犬粘多糖（MPS）VII型模型提供了 用于治疗和评估的独特靶组织，其中锥 光感受器病理学是光感受器的显著改变的继发结果， IPM中的硫酸软骨素周转率。两种方法将是 使用：（1）RPE的离体校正，随后细胞 移植到对侧眼，和（2）直接原位 转导两种方法的有效性将通过以下方式进行评估： 临床、功能、生化、形态和基因表达 技术.拟议的研究将作为一个实验模型 为了发展必要的技术， 修饰的RPE以治疗感光细胞的原发性病症和/或 RPE。

DESCRIPTION (Adapted from applicant's abstract): Inherited disorders affecting the retinal pigment epithelium (RPE) and photoreceptor layers cause blindness in both humans and animals. The research will address the issue of whether gene therapy of a potentially proliferating cell population (RPE) can effect a cure for an inherited disease affecting the RPE and, secondarily, the photoreceptors. Autologous RPE cells will deliver gene products to the retina to treat primary disorders of the RPE. This research is now feasible because of recently-developed surgical techniques that provide access to the subretinal space, and because viral vectors can be used for high efficiency gene transfer to RPE cells. The canine mucopolysaccaridoses (MPS) type VII model offers a unique target tissue for therapy and evaluation, where cone photoreceptor pathology is a secondary result of marked alterations in the chondroitin sulfate turnover in the IPM. Two approaches will be used: (1) ex vivo correction of the RPE followed by cell transplantation into the fellow eye, and (2) direct in situ transduction. Both approaches will be assessed for efficacy by clinical, functional, biochemical, morphological and gene expression techniques. The proposed studies will serve as an experimental model for the development of the technology necessary to use genetically modified RPE to treat primary disorders of photoreceptor cells and/or the RPE.