NDLI: Nanoparticle-mediated gene transfer specific to retinal pigment epithelial cells

Content Provider	PubMed Central
Author	Koirala, Adarsha Makkia, Rasha S. Cooper, Mark J. Naash, Muna I.
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.
Related Links	http://dx.doi.org/10.1016/j.biomaterials.2011.08.062
Ending Page	9493
Page Count	11
Starting Page	9483
File Format	PDF
ISSN	01429612
e-ISSN	18785905
Journal	Biomaterials
Issue Number	35
Volume Number	32
Language	English
Publisher Date	2011-12-01
Access Restriction	Open
Subject Keyword	Biophysics Mechanics of Materials Bioengineering Biomaterials Ceramics and Composites Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Ceramics and Composites Nanoscience and Nanotechnology Mechanics of Materials Biomaterials Biophysics Bioengineering

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