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Gene Therapy for Retinal Degeneration using Home-grown Gene Transfer Vectors-Aim for Clinical Trial-

使用国产基因转移载体进行视网膜变性的基因治疗-旨在进行临床试验-

基本信息

批准号：
15209057
负责人：
ISHIBASHI Tatsuro
金额：
$ 29.79万
依托单位：
KYUSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15209057/
关键词：
Gene therapy Retinal degeneration Neural progenitor cells SIV vector PEDF FGF-2 Age-related macular degeneration hFGF-2 RCSラット rdsマウス PEDF

项目摘要

1. The assessment of the efficacy of gene therapy for the animal models of retinal degeneration1) Development of new gene therapy technologyWe developed the new SIV (simian immunodeficiency virus) vectors carrying hFGF-2 or both hPEDF and hFGF-2 (SIV-FGF-2 or SIV-dual). Moreover, we developed the system for large-scale production of SIV-hPEDF with the aim of the clinical trail.2) We showed the synergistic therapeutic effect using SIV-hPEDF and SIV-hFGF-2 for two animal models of retinal degeneration (RCS rats and rds mice)2. The establishment of new gene therapy strategy by use of neural progenitor cells1) Development of the culture method to isolate neural progenitor cells from ciliary body of the eyeWe identified a new and divergent mechanism (a reprogramming system) underlying the neural differentiation of ciliary body-derived cells via sphere formation. The nestin-negative epithelial-like cells from ciliary body came to express nestin.2) We demonstrated the efficient gene transfer to neural progenitor cells from ciliary body of the eye via SIV vector3. Remains1) We evaluated the ability of our 3rd generation SIV vectors to transfer genes into nonhuman primate retinas.2) We suggested the possibility that VEGF-C and VEGF-D expression in RPE modify the ocular angiogenesis, such as age-related macular degeneration (AMD) as angiogenic stimulators.

1.基因治疗对视网膜变性动物模型的疗效评估1）新基因治疗技术的开发我们开发了携带hFGF-2或同时携带hPEDF和hFGF-2的新型SIV（猿猴免疫缺陷病毒）载体（SIV-FGF-2或SIV-dual）。此外，我们还开发了大规模生产SIV-hPEDF的系统，以进行临床试验。2)我们展示了SIV-hPEDF和SIV-hFGF-2对两种视网膜变性动物模型（RCS大鼠和rds小鼠）的协同治疗作用2。利用神经祖细胞建立新的基因治疗策略1）开发从眼睛睫状体中分离神经祖细胞的培养方法我们发现了一种新的、不同的机制（重编程系统），该机制是睫状体来源的细胞通过球体形成进行神经分化的基础。来自睫状体的巢蛋白阴性上皮样细胞开始表达巢蛋白。2)我们证明了通过SIV载体可以将基因有效地从眼睛睫状体转移到神经祖细胞3。仍然是1)我们评估了我们的第三代SIV载体将基因转移到非人灵长类动物视网膜中的能力。2)我们提出了RPE中VEGF-C和VEGF-D表达改变眼部血管生成的可能性，例如作为血管生成刺激剂的年龄相关性黄斑变性(AMD)。