Hypoxia-regulated transgene expression in experimental retinal and choroidal neovascularization

Gene Therapy
J W B BainbridgeR R Ali

Abstract

Recombinant AAV vectors mediate efficient and sustained transgene expression in retinal tissues and offer a powerful approach to the local, sustained delivery of angiostatic proteins for the treatment of ocular neovascular disorders. The application of such strategies may also require regulated gene expression to minimize the potential for unwanted adverse effects. In this study, we have evaluated the effect of a hypoxia-responsive element (HRE) on the kinetics of recombinant adeno-associated (rAAV)-mediated reporter gene expression in murine models of retinal and choroidal neovascularization. In murine ischaemia-induced retinal neovascularization, intravitreal delivery of rAAV.HRE.GFP results in reporter gene expression specifically at sites of vascular closure during the period of active neovascularization and not after vector delivery in normal controls. In murine laser-induced choroidal neovascularization, subretinal delivery of rAAV.HRE.GFP results in reporter gene expression at sites of active neovascularization but not elsewhere or after vector delivery in normal controls. HRE-driven gene expression offers an attractive strategy for the targeted and regulated delivery of angiostatic proteins to the retina in the manageme...Continue Reading

References

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Citations

May 26, 2006·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Jin-Shun PanBin Wang
Jul 29, 2008·Investigative Ophthalmology & Visual Science·Yuichiro TakadaPaul A Sieving
Apr 15, 2008·Expert Opinion on Biological Therapy·Joseph C Corbo
Jan 17, 2007·Expert Opinion on Biological Therapy·Mariacarmela AlloccaAlberto Auricchio
Dec 23, 2008·Trends in Molecular Medicine·Pasqualina ColellaAlberto Auricchio
Dec 24, 2014·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·M Ángeles SolinísAlicia Rodríguez-Gascón
May 4, 2004·Molecular and Cellular Neurosciences·Stefan IsenmannAlexandra Kretz
Oct 10, 2007·Vision Research·Enrico M Surace, Alberto Auricchio
Jan 18, 2006·Molecular Therapy : the Journal of the American Society of Gene Therapy·Ronald J MandelCorinna Burger
Jul 14, 2006·Gene Therapy·J W B BainbridgeR R Ali
Dec 5, 2017·Biological & Pharmaceutical Bulletin·Tsutomu NakaharaKenji Sakamoto
Aug 15, 2018·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Manas R BiswalJanet C Blanks

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