Open AccessTherapeutic Silencing of MicroRNA-122 in Primates with Chronic Hepatitis C Virus Infection
Author(s) -
Robert E. Lanford,
Elisabeth S. Hildebrandt-Eriksen,
Andreas Petri,
Robert Persson,
Morten Lindow,
Martin E. Munk,
Sakari Kauppinen,
Henrik Ørum
Publication year - 2009
Publication title -
science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 12.556
H-Index - 1186
eISSN - 1095-9203
pISSN - 0036-8075
DOI - 10.1126/science.1178178
Subject(s) - microrna , gene silencing , virology , virus , hepatitis c virus , locked nucleic acid , biology , mir 122 , nucleic acid , rna interference , disease , oligonucleotide , immunology , rna , medicine , gene , genetics , pathology
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. We found 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 of 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, 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.
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