title: Cell-Specific Promoters Enable Lipid-Based Nanoparticles to Deliver Genes to Specific Cells of the Retina In Vivo.
abstract: Non-viral vectors, such as lipid-based nanoparticles (liposome-protamine-DNA complex [LPD]), could be used to deliver a functional gene to the retina to correct visual function and treat blindness. However, one of the limitations of LPD is the lack of cell specificity, as the retina is composed of seven types of cells. If the same gene is expressed in multiple cell types or is absent from one desired cell type, LPD-mediated gene delivery to every cell may have off-target effects. To circumvent this problem, we have tested LPD-mediated gene delivery using various generalized, modified, and retinal cell-specific promoters. We achieved retinal pigment epithelium cell specificity with vitelliform macular dystrophy (VMD2), rod cell specificity with mouse rhodopsin, cone cell specificity with red/green opsin, and ganglion cell specificity with thymocyte antigen promoters. Here we show for the first time that cell-specific promoters enable lipid-based nanoparticles to deliver genes to specific cells of the retina in vivo. This work will inspire investigators in the field of lipid nanotechnology to couple cell-specific promoters to drive expression in a cell- and tissue-specific manner.
authors.affiliation: 1. Departments of Ophthalmology, University of Oklahoma Health Sciences Center;; 4. Dean McGee Eye Institute, Oklahoma City, OK 73104, USA;
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 1. Departments of Ophthalmology, University of Oklahoma Health Sciences Center;; 4. Dean McGee Eye Institute, Oklahoma City, OK 73104, USA;
authors.forename: Ammaji
authors.initials: A
authors.lastname: Rajala
authors.affiliation: 5. Department of Chemistry and Biochemistry, University of Oklahoma, Stephenson Life Science Research Center, Norman, OK 73019, USA;
authors.forename: Binrui
authors.initials: B
authors.lastname: Cao
authors.affiliation: 1. Departments of Ophthalmology, University of Oklahoma Health Sciences Center;; 4. Dean McGee Eye Institute, Oklahoma City, OK 73104, USA;
authors.forename: Michelle
authors.initials: M
authors.lastname: Ranjo-Bishop
authors.affiliation: 1. Departments of Ophthalmology, University of Oklahoma Health Sciences Center;; 4. Dean McGee Eye Institute, Oklahoma City, OK 73104, USA;
authors.forename: Martin-Paul
authors.initials: MP
authors.lastname: Agbaga
authors.affiliation: 5. Department of Chemistry and Biochemistry, University of Oklahoma, Stephenson Life Science Research Center, Norman, OK 73019, USA;; 6. School of Materials Science and Engineering, Zhejiang University, Hangzhou, Zhejiang 310027, China.
authors.forename: Chuanbin
authors.initials: C
authors.lastname: Mao
authors.affiliation: 1. Departments of Ophthalmology, University of Oklahoma Health Sciences Center;; 2. Departments of Physiology, University of Oklahoma Health Sciences Center;; 3. Departments of Cell Biology, University of Oklahoma Health Sciences Center;; 4. Dean McGee Eye Institute, Oklahoma City, OK 73104, USA;
authors.forename: Raju V S
authors.initials: RV
authors.lastname: Rajala
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004337:Drug Carriers / Q000008:administration & dosage* / Q000493:pharmacokinetics; D015316:Genetic Therapy / Q000379:methods*; D058449:Intravitreal Injections; D008081:Liposomes / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051379:Mice; D011401:Promoter Regions, Genetic; D051381:Rats; D012160:Retina / Q000166:cytology / Q000187:drug effects*; D017949:Retinal Cone Photoreceptor Cells / Q000187:drug effects; D012165:Retinal Ganglion Cells / Q000187:drug effects; D055213:Retinal Pigment Epithelium / Q000187:drug effects; D017948:Retinal Rod Photoreceptor Cells / Q000187:drug effects; D012680:Sensitivity and Specificity; D000068936:Theranostic Nanomedicine / Q000379:methods*; D060168:Thymocytes / Q000187:drug effects
chemical_list: D004337:Drug Carriers; D008081:Liposomes
keywords: Cell-specific promoters.; Ganglion cells; Gene therapy; Lipid nanoparticles; Retina; Retinal pigment epithelium