Journal
BIOMATERIALS
Volume 32, Issue 35, Pages 9483-9493Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2011.08.062
Keywords
Gene therapy; Retinal pigment epithelium; DNA nanoparticle; Subretinal injection; Polyethylene glycol (PEG)
Funding
- NIH [EY010609, EY018656]
- Foundation Fighting Blindness, Baltimore, MD
- Oklahoma Center for the Advancement of Science and Technology (OCAST) Oklahoma City, OK
- State of Ohio Biomedical Research Commercialization Program
- Research to Prevent Blindness James S. Adams Scholar Award
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Previously, we demonstrated that CK3OPEG10k-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 similar to 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. Published by Elsevier Ltd.
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