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Long-term PEDF release in rat iris and retinal epithelial cells after Sleeping Beauty transposon-mediated gene delivery

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Item Type:Article
Title:Long-term PEDF release in rat iris and retinal epithelial cells after Sleeping Beauty transposon-mediated gene delivery
Creators Name:Garcia-Garcia, L., Recalde, S., Hernandez, M., Bezunartea, J., Rodriguez-Madoz, J.R., Johnen, S., Diarra, S., Marie, C., Izsvák, Z., Ivics, Z., Scherman, D., Kropp, M., Thumann, G., Prosper, F., Fernandez-Robredo, P. and Garcia-Layana, A.
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.
Keywords:Choroidal Neovascularization, Non-Viral Ex Vivo Gene Therapy, pFAR4 Miniplasmids, Pigment Epithelium-Derived Factor, Primary Pigment Epithelial Cells, Sleeping Beauty Transposon System, Animals, Rats
Source:Molecular Therapy - Nucleic Acids
Publisher:Nature Publishing Group
Page Range:1-11
Date:15 December 2017
Official Publication:https://doi.org/10.1016/j.omtn.2017.08.001
PubMed:View item in PubMed

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