Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection

Robert E. Lanford, Elisabeth S. Hildebrandt-Eriksen, Andreas Petri, Robert Persson, Morten Lindow, Martin E. Munk, Sakari Kauppinen, Henrik Rum

Research output: Contribution to journalArticle

1303 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)198-201
Number of pages4
JournalScience
Volume327
Issue number5962
DOIs
StatePublished - 2010
Externally publishedYes

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Chronic Hepatitis C
Virus Diseases
MicroRNAs
Hepacivirus
Primates
Liver
Antiviral Agents
Pan troglodytes
Viremia
Gene Expression Profiling
Therapeutics
Oligonucleotides
Interferons
Cultured Cells
Seeds
Down-Regulation
RNA
Pathology
Biopsy
Messenger RNA

ASJC Scopus subject areas

  • General

Cite this

Lanford, R. E., Hildebrandt-Eriksen, E. S., Petri, A., Persson, R., Lindow, M., Munk, M. E., ... Rum, H. (2010). Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection. Science, 327(5962), 198-201. https://doi.org/10.1126/science.1178178

Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection. / Lanford, Robert E.; Hildebrandt-Eriksen, Elisabeth S.; Petri, Andreas; Persson, Robert; Lindow, Morten; Munk, Martin E.; Kauppinen, Sakari; Rum, Henrik.

In: Science, Vol. 327, No. 5962, 2010, p. 198-201.

Research output: Contribution to journalArticle

Lanford, RE, Hildebrandt-Eriksen, ES, Petri, A, Persson, R, Lindow, M, Munk, ME, Kauppinen, S & Rum, H 2010, 'Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection', Science, vol. 327, no. 5962, pp. 198-201. https://doi.org/10.1126/science.1178178
Lanford RE, Hildebrandt-Eriksen ES, Petri A, Persson R, Lindow M, Munk ME et al. Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection. Science. 2010;327(5962):198-201. https://doi.org/10.1126/science.1178178
Lanford, Robert E. ; Hildebrandt-Eriksen, Elisabeth S. ; Petri, Andreas ; Persson, Robert ; Lindow, Morten ; Munk, Martin E. ; Kauppinen, Sakari ; Rum, Henrik. / Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection. In: Science. 2010 ; Vol. 327, No. 5962. pp. 198-201.
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