Journal
NANO LETTERS
Volume 14, Issue 9, Pages 5257-5263Publisher
AMER CHEMICAL SOC
DOI: 10.1021/nl502275s
Keywords
Lipid nanoparticles; eyes; gene therapy; nonviral vector; retina; retinal pigment epithelium
Categories
Funding
- National Institutes of Health [EY016507, EY00871, EY021725, EB015190, AR056848, HL092526]
- Research to Prevent Blindness, Inc.
- National Science Foundation [CMMI-1234957, CBET-0854465, DMR-0847758]
- Department of Defense Peer Reviewed Medical Research Program [W81XWH-12-1-0384]
- OCAST [HR11-006]
- OCASCR [434003]
- Direct For Mathematical & Physical Scien
- Division Of Materials Research [847758] Funding Source: National Science Foundation
- Div Of Civil, Mechanical, & Manufact Inn
- Directorate For Engineering [1234957] Funding Source: National Science Foundation
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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.
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