Nanoparticle-Assisted Targeted Delivery of Eye-Specific Genes to Eyes Significantly Improves the Vision of Blind Mice In Vivo
Year: 2014
Type: article
Abstract: Application of viruses as a carrier, though not safe, to deliver genes to eye tissue was successful. However, a safer, nonviral, biocompatible lipid-based nanoparticle has never been tested to treat blinding eye diseases. We created an artificial virus using a nanoparticle, liposome-protamine-DNA complex (LPD), modified with a cell permeable peptide and a nuclear localization signaling (NLS) peptide, to deliver a functional gene for eye disease treatment. In the eye, a photochemical, 11-cis-retinal, allows the visual pigment rhodopsin to absorb light in the visible range. Without the photochemical, we lose the ability to see light. Retinal pigment epithelium protein 65 (Rpe65) is the key enzyme in regulating the availability of photochemical; deficiency of this gene results in a blinding eye disease. Here we show for the first time that LPD promotes efficient delivery in a cell specific-manner, and a long-term expression of Rpe65 gene to mice lacking Rpe65 gene, leading to in vivo correction of blindness. Thus, LPD nanoparticles could provide a promising, efficient, nonviral method of gene delivery with clinical applications in eye disease treatment.
Source: Nano Letters
DOI: 10.1021/nl502275s
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
Funders: Oklahoma Center for Adult Stem Cell Research, U.S. Department of Defense, Research to Prevent Blindness, Oklahoma Center for the Advancement of Science and Technology, National Institutes of Health, National Heart, Lung, and Blood Institute, National Eye Institute, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute of Biomedical Imaging and Bioengineering, Division of Materials Research, Division of Chemical, Bioengineering, Environmental, and Transport Systems, Division of Civil, Mechanical and Manufacturing Innovation
Awards: G1148302489, G1346719994, Tubulin-Binding Upconversion Nanoparticles for Breast-Cancer Imaging and Therapy, ANTI-COCAINE BRAIN-HOMING VIRUS-LIKE NANOPARTICLES, G1994177349, G2080493994, G2360531407, G3031744635, G3033785425, G4000299171, G4213481227, G5508127933, G6490638229, G7056200903, G7332541666, G7872538157, G8704883479, P30 Center Core Grant for Vision Research, G965363635
OpenAlex ID: W1965542035