Antagonism of microRNA-122 in mice by systemically administered LNA-antimiR leads to up-regulation of a large set of predicted target mRNAs in the liver

Elmén, Joacim; Lindow, Morten; Silahtaroglu, Asli; Bak, Mads; Christensen, Mette; Lind-Thomsen, Allan; Hedtjärn, Maj; Hansen, Jens Bo; Hansen, Henrik F.; Straarup, Ellen Marie; McCullagh, K.G.; Kearney, Phil; Kauppinen, Sakari

doi:10.1093/nar/gkm1113

articleNucleic Acids ResearchDec 23, 2007GOLD OA

Antagonism of microRNA-122 in mice by systemically administered LNA-antimiR leads to up-regulation of a large set of predicted target mRNAs in the liver

JEJoacim Elmén MLMorten Lindow ASAsli Silahtaroglu MBMads Bak MCMette Christensen

University of Copenhagen · Tris Pharma (United States)

PubMed

Indexed incrossrefdoajpubmed

Abstract

MicroRNA-122 (miR-122) is an abundant liver-specific miRNA, implicated in fatty acid and cholesterol metabolism as well as hepatitis C viral replication. Here, we report that a systemically administered 16-nt, unconjugated LNA (locked nucleic acid)-antimiR oligonucleotide complementary to the 5' end of miR-122 leads to specific, dose-dependent silencing of miR-122 and shows no hepatotoxicity in mice. Antagonism of miR-122 is due to formation of stable heteroduplexes between the LNA-antimiR and miR-122 as detected by northern analysis. Fluorescence in situ hybridization demonstrated uptake of the LNA-antimiR in mouse liver cells, which was accompanied by markedly reduced hybridization signals for mature miR-122…

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Topics & keywords

Topics

Keywords

Locked nucleic acid
Biology
MiR-122
microRNA
Gene silencing
Molecular biology
Gene expression
In vivo

UN Sustainable Development Goals

Good health and well-being

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