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Jasmina Cehajic-Kapetanovic, Annette Allen, Paul Bishop, Robert Lucas; Glycosidic Enzymes Enhance Retinal Transduction Following Intravitreal Delivery of AAV2. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2736.
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At present only limited retinal transduction can be achieved following intravitreal delivery of unmutated AAV vectors. We hypothesized that the inner limiting membrane and extracellular matrix proteoglycans act as a barrier to AAV vector entry into and movement across the retina. In this study we investigated the effects of enzymatic digestion of these barriers on the depth of vector penetration into the retina.
The green fluorescent protein (GFP)-expressing AAV2 vector was co-injected intravitreally into adult mice with various glycosidic enzymes and their combinations. The efficacy of the virus transduction was evaluated by quantitative analysis of GFP positive cells in histological cross-sections, using fluorescent microscopy. We also analyzed safety of these treatments and retinal function using electroretinography.
Glycosidic enzymes namely Chondroitin ABC lyase, Heparinase III and Hyaluronan lyase, both singly and in combinations, led to a significant improvement in retinal transduction following intravitreal delivery. Electroretinograms survived at much higher doses of enzymes than were needed for optimal retinal transduction.
AAV2-mediated retinal transduction is improved by co-injection of glycosidic enzymes into the vitreous. This approach may allow intravitreal injection to become the preferred route for delivering gene therapy to the retina in both preclinical and clinical settings.
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