Long-Term PEDF Release in Rat Iris and Retinal Epithelial Cells after Sleeping Beauty Transposon-Mediated Gene Delivery - Archive ouverte HAL Access content directly
Journal Articles Molecular Therapy - Nucleic Acids Year : 2017

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

(1) , (1) , (1) , (1) , (2) , (3) , (3) , (4) , (5) , (6) , (4) , (7) , (7) , (2) , (1) , (1)
1
2
3
4
5
6
7

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.
Fichier principal
Vignette du fichier
scherman_utcbs.pdf (3.54 Mo) Télécharger le fichier

Dates and versions

hal-03292049 , version 1 (10-09-2021)

Identifiers

Cite

Laura Garcia-Garcia, Sergio Recalde, Maria Hernandez, Jaione Bezunartea, Juan Roberto Rodriguez-Madoz, et al.. Long-Term PEDF Release in Rat Iris and Retinal Epithelial Cells after Sleeping Beauty Transposon-Mediated Gene Delivery. Molecular Therapy - Nucleic Acids, 2017, 9, ⟨10.1016/j.omtn.2017.08.001⟩. ⟨hal-03292049⟩
64 View
16 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More