Journal
NANOMEDICINE
Volume 7, Issue 4, Pages 521-539Publisher
FUTURE MEDICINE LTD
DOI: 10.2217/NNM.11.158
Keywords
enhanced green fluorescent protein; gene transfer; nanoparticle; nonviral; repeat delivery; retinal pigment epithelial cell; subretinal injection; toxicity
Funding
- National Eye Institute [EY10609, EY018656]
- Foundation Fighting Blindness
- Oklahoma Center forthe Advancement of Science and Technology
- Ohio Third Frontier BRCP [BRCP 08-055]
- William W Talley II Research Award
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Aim: To evaluate the safety of compacted DNA nanoparticles (NPs) in retinal pigment epithelial (RPE) cells. Materials & methods: Enhanced GFP expression cassettes controlled by the RPE-specific vitelloform macular dystrophy promoter were constructed with and without a bacterial backbone and compacted into NPs formulated with polyethylene glycol-substituted lysine 30-mers. Single or double subretinal injections were administered in adult BALB/c mice. Expression levels of enhanced GFP, proinflammatory cytokines and neutrophil/macrophage mediators, and retinal function by electroretinogram were evaluated at different time-points postinjection. Results: Immunohistochemistry and real-time PCR demonstrated that NPs specifically transfect RPE cells at a higher efficiency than naked DNA and similar results were observed after the second injection. At 6 h postinjections, a transient inflammatory response was observed in all cohorts, including saline, indicating an adverse effect to the injection procedure. Subsequently, no inflammation was detected in all experimental groups. Conclusion: This study demonstrates the safety and efficacy of NP-mediated RPE gene transfer therapy following multiple subretinal administrations.
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