Show simple item record

dc.contributor.authorO’Donnell, J. Michael
dc.contributor.authorKalichira, Asha
dc.contributor.authorBi, Jian
dc.contributor.authorLewandowski, E. Douglas
dc.date.accessioned2014-01-09T20:24:15Z
dc.date.available2014-01-09T20:24:15Z
dc.date.issued2012-12
dc.identifier.bibliographicCitationO'Donnell JM, Kalichira A, Bi J, Lewandowski ED. In Vivo, Cardiac-Specific Knockdown of a Target Protein, Malic Enzyme-1, in Rat via Adenoviral Delivery of DNA for Non-Native miRNA. Current Gene Therapy. Dec 2012;12(6):454-462.en_US
dc.identifier.issn1566-5232
dc.identifier.urihttp://hdl.handle.net/10027/11047
dc.descriptionThis is a copy of an article published in the Current Gene Therapy © 2012 Bentham Science Publishers. The final publication is available at http://www.benthamscience.com/cgt/index.htmen_US
dc.description.abstractThis study examines the feasibility of using the adenoviral delivery of DNA for a non-native microRNA to suppress expression of a target protein (cytosolic NADP+-dependent malic-enzyme 1, ME1) in whole heart in vivo, via an isolated-heart coronary perfusion approach. Complementary DNA constructs for ME1 microRNA were inserted into adenoviral vectors. Viral gene transfer to neonatal rat cardiomyocytes yielded 65% suppression of ME1 protein. This viral package was delivered to rat hearts in vivo (Adv.miR_ME1, 1013 vp/ml PBS) via coronary perfusion, using a cardiac-specific isolation technique. ME1 mRNA was reduced by 73% at 2-6 days post-surgery in heart receiving the Adv.miR_ME1. Importantly, ME1 protein was reduced by 66% (p<0.0002) at 5-6 days relative to sham-operated control hearts. Non-target protein expression for GAPDH, calsequestrin, and mitochondrial malic enzyme, ME3, were all unchanged. The non-target isoform, ME2, was unchanged at 2-5 days and reduced at day 6. This new approach demonstrates for the first time significant and acute silencing of target RNA translation and protein content in whole heart, in vivo, via non-native microRNA expression.en_US
dc.description.sponsorshipNIH grants: R37 HL49244 (Lewandowski MERIT), R01 HL62702.en_US
dc.language.isoen_USen_US
dc.publisherBentham Science Publishersen_US
dc.subjecthearten_US
dc.subjectRNA interferenceen_US
dc.subjectgene therapyen_US
dc.subjectmicroRNAen_US
dc.titleIn vivo, cardiac-specific knockdown of target protein, Malic Enzyme-1, in rat via adenoviral delivery of DNA for non-native miRNAen_US
dc.typeArticleen_US


Files in this item

Thumbnail
Thumbnail

This item appears in the following Collection(s)

Show simple item record