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Nanoparticle-mediated gene transfer specific to retinal pigment epithelial cells

Paper ID Volume ID Publish Year Pages File Format Full-Text
7900 568 2011 11 PDF Available
Title
Nanoparticle-mediated gene transfer specific to retinal pigment epithelial cells
Abstract

Previously, we demonstrated that CK30PEG10k-compacted DNA nanoparticles (NPs) efficiently target photoreceptor cells and improve visual function in a retinitis pigmentosa model. Here, we test the ability of these NPs in driving transgene expression in the retinal pigment epithelium (RPE), using an RPE-specific reporter vector (VMD2-eGFP). NPs, uncompacted plasmid, or saline were subretinally delivered to adult BALB/c mice. NP-based expression was specific to RPE cells and caused no deleterious effects on retinal structure and function. eGFP expression levels in NP-injected eyes peaked at post-injection day 2 (PI-2), stabilized at levels ∼3-fold higher than in naked DNA-injected eyes, and remained elevated at the latest time-point examined (PI-30). Unlike naked DNA, which only transfected cells at the site of injection, NPs were able to transfect cells throughout the RPE. Subretinal injections of rhodamine labeled NPs and naked DNA showed comparable initial uptake into RPE cells. However, at PI-7 and -30 days significantly more fluorescence was detected inside the RPE of NP-injected eyes compared to naked DNA, suggesting NPs are stable inside the cell which could possibly lead to higher and sustained expression. Overall, our results demonstrate that NPs can efficiently deliver genes to the RPE and hold great potential for the treatment of RPE-associated diseases.

Keywords
Gene therapy; Retinal pigment epithelium; DNA nanoparticle; Subretinal injection; Polyethylene glycol (PEG)
First Page Preview
Nanoparticle-mediated gene transfer specific to retinal pigment epithelial cells
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 32, Issue 35, December 2011, Pages 9483–9493
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering