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Y. Murakami, Y. Ikeda, Y. Yonemitsu, M. Miyazaki, M. Hasegawa, T. Ishibashi; Rapid Retinal Gene Transfer by Lentivirus Vectors Psuedotyped With Sendai Virus Envelope Proteins: Safe and Effective Inhibition of Choroidal Neovascularization by Long-Term Overexpressoin of PEDF but Not of Soluble VEGF Receptor. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3028.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the potential advantages using novel simian immunodeficienty virus vector pseudotyped with Sendai virus F and HN proteins (SeV-F/HN-SIV vector) for retinal gene therapy in a mouse model of choroidal neovascularization (CNV).
SeV-F/HN-SIV vector or conventional VSV-G-pseudotyped SIV (VSV-G-SIV) vector was injected into subretinal space of adult C57BL/6 mice, and the transgene expression was compared between the groups with simple injection and removal 5 minutes after injection. CNV was induced by laser photocoagulation in the eyes treated with SeV-F/HN-SIV vector encoding pigment epithelium-derived factor (PEDF) or soluble fms-like tyrosine kinase-1 (sFlt-1). The CNV area was measured by image analysis at 2 weeks after laser injury. The effect of PEDF and sFlt-1 on normal retina was assessed by histological examination.
Only 5 minutes of retinal detachment (RD) following SeV-F/HN-SIV vector injection resulted in high-level gene transfer to retinal pigment epithelium, while over several hours of RD was required in use of VSV-G-SIV vector. The transgene expression was maintained over a 1-year period. SeV-F/HN-SIV-mediated retinal delivery of PEDF or sFlt-1 significantly suppressed laser-induced CNV. Long-term expression of PEDF for 6 months showed no apparent change in retinal structure; however that of sFlt-1 resulted in photoreceptor degeneration.
SeV-F/HN-SIV vector enables effective retinal gene transfer by brief exposure. SeV-F/HN-SIV-mediated retinal delivery of PEDF may be an effective approach to the treatment of CNV with broader safety range.
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