Development of a long-term RNAi based gene therapy for choroidal neovasularization

碩士 === 長庚大學 === 醫學生物技術暨檢驗學系 === 99 === Neovascularization, also called new vessel growth or angiogenesis, is the common pathway of many popular ocular diseases, including age-related macular degeneration, diabetic retinopathy, retinopathy of premature infants, and high myopia. The neovascularization...

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Bibliographic Details
Main Authors: Jyun Yue Wu, 吳俊樂
Other Authors: C. R. Shen
Format: Others
Published: 2010
Online Access:http://ndltd.ncl.edu.tw/handle/71132579158229852576
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Summary:碩士 === 長庚大學 === 醫學生物技術暨檢驗學系 === 99 === Neovascularization, also called new vessel growth or angiogenesis, is the common pathway of many popular ocular diseases, including age-related macular degeneration, diabetic retinopathy, retinopathy of premature infants, and high myopia. The neovascularization is originally physiologic and essential for organ development as well as wound healing. The over-expression of vascular endothelial growth factor (VEGF) has been recognized as the major contributor for neovascularization. A neutralizing antibody called bevacizumab (Avastin) is currently available. However, the risk of infectious endophthalmitis and the pain from frequent injections, as well as the expensive expense have blocked the patients from seeking proper therapies. In the study, we developed the efficient long-term RNA interference (RNAi) against VEGF by adeno-associated virus (AAV). In vitro transfection experiments demonstrated the specific VEGF inhibition. In vivo studies revealed the high efficiency of AAV transfection for retinochoroidal tissues and the inhibitory effects for VEGF expression. Most importantly, such inhibition demonstrated the reduction of laser-induced choroidal neovascularization. Besides, a preliminary study also revealed that such gene therapy can be applied to the retinal neovascularization lesions of oxygen-induced retinopathy. Conclusively, the use of adeno-associated virus expressing RNAi for VEGF inhibition has the potential to become a new trend of anti-angiogenesis therapy in ocular neovascularization disorders.