title: Span poly-L-arginine nanoparticles are efficient non-viral vectors for PRPF31 gene delivery: An approach of gene therapy to treat retinitis pigmentosa.
abstract: Retinitis pigmentosa (RP) is the most common cause of inherited blindness in adults. Mutations in the PRPF31 gene produce autosomal dominant RP (adRP). To date there are no effective treatments for this disease. The purpose of this study was to design an efficient non-viral vector for human PRPF31 gene delivery as an approach to treat this form of adRP. Span based nanoparticles were developed to mediate gene transfer in the subretinal space of a mouse model of adRP carrying a point mutation (A216P) in the Prpf31 gene. Funduscopic examination, electroretinogram, optomotor test and optical coherence tomography were conducted to further in vivo evaluate the safety and efficacy of the nanosystems developed. Span-polyarginine (SP-PA) nanoparticles were able to efficiently transfect the GFP and PRPF31 plasmid in mice retinas. Statistically significant improvement in visual acuity and retinal thickness were found in Prpf31A216P/+mice treated with the SP-PA-PRPF31 nanomedicine.
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Universidade de Santiago de Compostela, Campus Vida, Santiago de Compostela, Spain.
authors.forename: Andrea
authors.initials: A
authors.lastname: Pensado
authors.affiliation: Department of Cell Therapy and Regenerative Medicine, Andalusian Molecular Biology and Regenerative Medicine Centre (CABIMER), Seville, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Diaz-Corrales
authors.affiliation: Department of Cell Therapy and Regenerative Medicine, Andalusian Molecular Biology and Regenerative Medicine Centre (CABIMER), Seville, Spain.
authors.forename: Berta
authors.initials: B
authors.lastname: De la Cerda
authors.affiliation: Department of Cell Therapy and Regenerative Medicine, Andalusian Molecular Biology and Regenerative Medicine Centre (CABIMER), Seville, Spain.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Valdés-Sánchez
authors.affiliation: Department of Cell Therapy and Regenerative Medicine, Andalusian Molecular Biology and Regenerative Medicine Centre (CABIMER), Seville, Spain.
authors.forename: Ana Aramburu
authors.initials: AA
authors.lastname: Del Boz
authors.affiliation: Department of Cell Therapy and Regenerative Medicine, Andalusian Molecular Biology and Regenerative Medicine Centre (CABIMER), Seville, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Rodriguez-Martinez
authors.affiliation: Department of Cell Therapy and Regenerative Medicine, Andalusian Molecular Biology and Regenerative Medicine Centre (CABIMER), Seville, Spain.
authors.forename: Ana B
authors.initials: AB
authors.lastname: García-Delgado
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Universidade de Santiago de Compostela, Campus Vida, Santiago de Compostela, Spain; Molecular Image Group, Health Research Institute-University Clinical Hospital of Santiago de Compostela (IDIS), Santiago de Compostela, Spain.
authors.forename: Begoña
authors.initials: B
authors.lastname: Seijo
authors.affiliation: Department of Cell Therapy and Regenerative Medicine, Andalusian Molecular Biology and Regenerative Medicine Centre (CABIMER), Seville, Spain.
authors.forename: Shomi S
authors.initials: SS
authors.lastname: Bhattacharya
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Universidade de Santiago de Compostela, Campus Vida, Santiago de Compostela, Spain; Molecular Image Group, Health Research Institute-University Clinical Hospital of Santiago de Compostela (IDIS), Santiago de Compostela, Spain. Electronic address: alejandro.sanchez@usc.es.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Sanchez
mesh_terms: D000818:Animals; D001120:Arginine; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000008:administration & dosage*; D005799:Genes, Dominant; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D051379:Mice; D009154:Mutation; D053758:Nanoparticles; D010375:Pedigree; D012174:Retinitis Pigmentosa / Q000628:therapy*
chemical_list: D005136:Eye Proteins; C454222:PRPF31 protein, human; D001120:Arginine
keywords: Gene therapy; Nanoparticle; Ophthalmology; Retinitis pigmentosa; Span