Long-Term PEDF Release in Rat Iris and Retinal Epithelial Cells after Sleeping Beauty Transposon-Mediated Gene Delivery
| Autor: | Daniel Scherman, Sergio Recalde, Zoltán Ivics, Sandra Johnen, Sabine Diarra, Gabriele Thumann, Zsuzsanna Izsvák, Maria Hernandez, Juan R. Rodriguez-Madoz, Felipe Prosper, Corinne Marie, Martina Kropp, Jaione Bezunartea, Patricia Fernandez-Robredo, Alfredo García-Layana, Laura Garcia-Garcia |
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| Přispěvatelé: | IdiSNA, Navarra Institute for Health Research, Center for Applied Medical Research [Plamplona] (CIMA), Universidad de Navarra [Pamplona] (UNAV), Universitätsklinikum RWTH Aachen - University Hospital Aachen [Aachen, Germany] (UKA), RWTH Aachen University, Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Max Delbrück Center for Molecular Medicine [Berlin] (MDC), Helmholtz-Gemeinschaft = Helmholtz Association, Paul-Ehrlich-Institute - Federal Institute for Vaccines and Biomedicines (EPI), University of Geneva [Switzerland], Navarra Institute for Health Research / Instituto de Investigación Sanitaria de Navarra (IdiSNA), Universidad Pública de Navarra [Espagne] = Public University of Navarra (UPNA)-Universidad de Navarra [Pamplona] (UNAV)-Clínica Universidad de Navarra [Pamplona], Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Genève = University of Geneva (UNIGE), ORANGE, Colette |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
[SDV.BIO]Life Sciences [q-bio]/Biotechnology THERAPY chemistry.chemical_compound 0302 clinical medicine Drug Discovery pFAR4 miniplasmids Anatomy INDUCED CHOROIDAL NEOVASCULARIZATION 3. Good health Cell biology Vascular endothelial growth factor medicine.anatomical_structure Choroidal neovascularization [SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs INTRAVITREAL BEVACIZUMAB Molecular Medicine Original Article medicine.symptom pigment epithelium-derived factor primary pigment epithelial cells VECTOR Gene delivery Biology choroidal neovascularization TRANSGENE EXPRESSION 03 medical and health sciences Sleeping Beauty transposon system PEDF medicine Iris pigment epithelium [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs Retina lcsh:RM1-950 MACULAR DEGENERATION RANIBIZUMAB eye diseases [SDV.BIO] Life Sciences [q-bio]/Biotechnology ddc:616.8 MODEL Transplantation lcsh:Therapeutics. Pharmacology non-viral ex vivo gene therapy 030104 developmental biology chemistry Cardiovascular and Metabolic Diseases ENDOTHELIAL GROWTH-FACTOR 030221 ophthalmology & optometry sense organs SYSTEM |
| Zdroj: | Molecular Therapy-Nucleic Acids, Vol. 9 (2017) pp. 1-11 Molecular Therapy-Nucleic Acids Molecular Therapy-Nucleic Acids, Elsevier, 2017, 9, ⟨10.1016/j.omtn.2017.08.001⟩ Molecular Therapy. Nucleic Acids Molecular Therapy: Nucleic Acids, Vol 9, Iss C, Pp 1-11 (2017) Molecular Therapy / Nucleic Acids 9, 1-11 (2017). doi:10.1016/j.omtn.2017.08.001 Molecular Therapy-Nucleic Acids, 2017, 9, ⟨10.1016/j.omtn.2017.08.001⟩ |
| ISSN: | 2162-2531 |
| DOI: | 10.1016/j.omtn.2017.08.001⟩ |
| Popis: | International audience; Pigment epithelium derived factor (PEDF) is a potent antiangiogenic, neurotrophic, and neuroprotective molecule that is the endogenous inhibitor of vascular endothelial growth factor (VEGF) in the retina. An ex vivo gene therapy approach based on transgenic overexpression of PEDF in the eye is assumed to rebalance the angiogenic-antiangiogenic milieu of the retina, resulting in growth regression of choroidal blood vessels, the hallmark of neovascular age-related macular degeneration. Here, we show that rat pigment epithelial cells can be efficiently transfected with the PEDF-expressing non-viral hyperactive Sleeping Beauty transposon system delivered in a form free of antibiotic resistance marker miniplasmids. The engineered retinal and iris pigment epithelium cells secrete high (141 +/- 13 and 222 +/- 14 ng) PEDF levels in 72 hr in vitro. In vivo studies showed cell survival and insert expression during at least 4 months. Transplantation of the engineered cells to the subretinal space of a rat model of choroidal neovascularization reduces almost 50% of the development of new vessels. |
| Databáze: | OpenAIRE |
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