Suprachoroidal electrotransfer: a nonviral gene delivery method to transfect the choroid and the retina without detaching the retina.

Détails

ID Serval
serval:BIB_E939AE8D7DC0
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Suprachoroidal electrotransfer: a nonviral gene delivery method to transfect the choroid and the retina without detaching the retina.
Périodique
Molecular Therapy : the Journal of the American Society of Gene Therapy
Auteur(s)
Touchard E., Berdugo M., Bigey P., El Sanharawi M., Savoldelli M., Naud M.C., Jeanny J.C., Behar-Cohen F.
ISSN
1525-0024 (Electronic)
ISSN-L
1525-0016
Statut éditorial
Publié
Date de publication
2012
Peer-reviewed
Oui
Volume
20
Numéro
8
Pages
1559-1570
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
Photoreceptors and retinal pigment epithelial cells (RPE) targeting remains challenging in ocular gene therapy. Viral gene transfer, the only method having reached clinical evaluation, still raises safety concerns when administered via subretinal injections. We have developed a novel transfection method in the adult rat, called suprachoroidal electrotransfer (ET), combining the administration of nonviral plasmid DNA into the suprachoroidal space with the application of an electrical field. Optimization of injection, electrical parameters and external electrodes geometry using a reporter plasmid, resulted in a large area of transfected tissues. Not only choroidal cells but also RPE, and potentially photoreceptors, were efficiently transduced for at least a month when using a cytomegalovirus (CMV) promoter. No ocular complications were recorded by angiographic, electroretinographic, and histological analyses, demonstrating that under selected conditions the procedure is devoid of side effects on the retina or the vasculature integrity. Moreover, a significant inhibition of laser induced-choroidal neovascularization (CNV) was achieved 15 days after transfection of a soluble vascular endothelial growth factor receptor-1 (sFlt-1)-encoding plasmid. This is the first nonviral gene transfer technique that is efficient for RPE targeting without inducing retinal detachment. This novel minimally invasive nonviral gene therapy method may open new prospects for human retinal therapies.
Mots-clé
Animals, Choroid/metabolism, Female, Gene Transfer Techniques, Male, Rats, Retina/metabolism, Transfection/methods
Pubmed
Web of science
Open Access
Oui
Création de la notice
19/08/2013 16:25
Dernière modification de la notice
20/08/2019 17:11
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