title: Nanoparticle-assisted targeted delivery of eye-specific genes to eyes significantly improves the vision of blind mice in vivo.
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.
authors.affiliation: Department of Ophthalmology, ‡Department of Physiology, §Department of Cell Biology, and ∥Dean A. McGee Eye Institute, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma 73104, United States.
authors.forename: Ammaji
authors.initials: A
authors.lastname: Rajala
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Wang
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhu
authors.forename: Michelle
authors.initials: M
authors.lastname: Ranjo-Bishop
authors.forename: Jian-Xing
authors.initials: JX
authors.lastname: Ma
authors.forename: Chuanbin
authors.initials: C
authors.lastname: Mao
authors.forename: Raju V S
authors.initials: RV
authors.lastname: Rajala
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D001766:Blindness / Q000628:therapy*; D004247:DNA / Q000737:chemistry; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008055:Lipids / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D050997:Nanomedicine / Q000379:methods*; D053758:Nanoparticles / Q000737:chemistry*; D019913:Nuclear Localization Signals; D010455:Peptides / Q000737:chemistry; D010777:Photochemistry; D011479:Protamines / Q000737:chemistry; D012160:Retina / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000378:metabolism; D014785:Vision, Ocular / Q000502:physiology*; D019745:cis-trans-Isomerases / Q000235:genetics*; D000099178:Retinoid Isomerohydrolase
chemical_list: D001672:Biocompatible Materials; D004247:DNA; D049452:Green Fluorescent Proteins; D008055:Lipids; D008081:Liposomes; D019913:Nuclear Localization Signals; D010455:Peptides; D011479:Protamines; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase
keywords: Lipid nanoparticles; eyes; gene therapy; nonviral vector; retina; retinal pigment epithelium