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Therapeutic Silencing of MicroRNA-122 in Primates with Chronic Hepatitis C Virus Infection -Science Magazine article today - full text pdf attached
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Download the pdf here
Science Magazine Dec 3 2009
Robert E. Lanford,1,* Elisabeth S. Hildebrandt-Eriksen,2,* Andreas Petri,2,* Robert Persson,2 Morten Lindow,2 Martin E. Munk,2 Sakari Kauppinen,2,3,* Henrik rum2,{dagger}
The liver-expressed microRNA-122 (miR-122) is essential for hepatitis C virus (HCV) RNA accumulation in cultured liver cells, but its potential as a target for antiviral intervention has not been assessed. Here, we show that treatment of chronically infected chimpanzees with a locked nucleic acid (LNA)-modified oligonucleotide (SPC3649) complementary to miR-122 leads to long-lasting suppression of HCV viremia with no evidence for viral resistance or side effects in the treated animals. Furthermore, transcriptome and histological analyses of liver biopsies demonstrated derepression of target mRNAs with miR-122 seed sites, down-regulation of interferon-regulated genes (IRGs), and improvement of HCV-induced liver pathology. The prolonged virological response to SPC3649 treatment without HCV rebound holds promise of a new antiviral therapy with a high barrier to resistance.
1 Department of Virology and Immunology and Southwest National Primate Research Center, Southwest Foundation for Biomedical Research, San Antonio, TX 78227, USA.
2 Santaris Pharma, Kogle Alle 6, DK-2970 Hrsholm, Denmark.
3 Copenhagen Institute of Technology, Aalborg University, Lautrupvang 15, DK-2750 Ballerup, Denmark.
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