Scientific publications

Long-Term PEDF Release in Rat Iris and Retinal Epithelial Cells after Sleeping Beauty Transposon-Mediated Gene Delivery

Garcia-Garcia L (1), Recalde S (1), Hernandez M (1), Bezunartea J (1), Rodriguez-Madoz JR (2), Johnen S (3), Diarra S (3), Marie C (4), Izsvák Z (5), Ivics Z (6), Scherman D (4), Kropp M (7), Thumann G (7), Prosper F (8), Fernandez-Robredo P (9), Garcia-Layana A (10)

(1) Experimental Ophthalmology Laboratory, University of Navarra, Navarra Institute for Health Research, IdiSNA, 31008 Pamplona, Spain.
(2) Cell Therapy Program, Center for Applied Medical Research (CIMA), University of Navarra, Navarra Institute for Health Research, IdiSNA, 31008 Pamplona, Spain.
(3) Department of Ophthalmology, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074 Aachen, Germany.
(4) CNRS, Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS) UMR 8258, 75006 Paris, France; Université Paris Descartes, Sorbonne-Paris-Cité, UTCBS, 75006 Paris, France; Chimie ParisTech, PSL Research University, UTCBS, 75005 Paris, France; INSERM, UTCBS U 1022, 75006 Paris, France.
(5) Max Delbrück Center for Molecular Medicine in the Helmholtz Society, 13125 Berlin, Germany.
(6) Division of Medical Biotechnology, Paul Ehrlich Institute, 63225 Langen, Germany.
(7) Experimental Ophthalmology, University of Geneva, 1205 Geneva, Switzerland; Department of Ophthalmology, University Hospitals and School of Medicine, 22 Rue Alcide-Jentzer, Geneva 1205, Switzerland.
(8) Cell Therapy Program, Center for Applied Medical Research (CIMA), University of Navarra, Navarra Institute for Health Research, IdiSNA, 31008 Pamplona, Spain; Area of Cell Therapy, Clínica Universidad de Navarra, University of Navarra, Navarra Institute for Health Research, IdiSNA, 31008 Pamplona, Spain.
(9) Experimental Ophthalmology Laboratory, University of Navarra, Navarra Institute for Health Research, IdiSNA, 31008 Pamplona, Spain.
(10) Experimental Ophthalmology Laboratory, University of Navarra, Navarra Institute for Health Research, IdiSNA, 31008 Pamplona, Spain; Ophthalmology Department, Clínica Universidad de Navarra, 31008 Pamplona, Spain.

Magazine: Molecular Therapy. Nucleic Acids

Date: Dec 15, 2017

Cell Therapy Area [SP] Ophthalmology

ABSTRACT

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.

CITATION  Mol Ther Nucleic Acids. 2017 Dec 15;9:1-11. doi: 10.1016/j.omtn.2017.08.001. Epub 2017 Aug 12

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