Document Detail


Suprachoroidal electrotransfer: a nonviral gene delivery method to transfect the choroid and the retina without detaching the retina.
MedLine Citation:
PMID:  22252448     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Elodie Touchard; Marianne Berdugo; Pascal Bigey; Mohamed El Sanharawi; Michèle Savoldelli; Marie-Christine Naud; Jean-Claude Jeanny; Francine Behar-Cohen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-01-17
Journal Detail:
Title:  Molecular therapy : the journal of the American Society of Gene Therapy     Volume:  20     ISSN:  1525-0024     ISO Abbreviation:  Mol. Ther.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-08-01     Completed Date:  2013-01-11     Revised Date:  2013-08-15    
Medline Journal Info:
Nlm Unique ID:  100890581     Medline TA:  Mol Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1559-70     Citation Subset:  IM    
Affiliation:
INSERM, U872 Physiopathology of Ocular Diseases: Therapeutic Innovations, Paris, France.
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MeSH Terms
Descriptor/Qualifier:
Animals
Choroid / metabolism*
Female
Gene Transfer Techniques*
Male
Rats
Retina / metabolism*
Transfection / methods*
Comments/Corrections

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