Therapeutic Silencing of MicroRNA-122 in Primates with Chronic Hepatitis C Virus Infection
Top Cited Papers
- 8 January 2010
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 327 (5962), 198-201
- https://doi.org/10.1126/science.1178178
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.Keywords
This publication has 19 references indexed in Scilit:
- Decreased levels of microRNA miR-122 in individuals with hepatitis C responding poorly to interferon therapyNature Medicine, 2009
- Interferon (IFN)–γ–Inducible Protein–10: Association with Histological Results, Viral Kinetics, and Outcome during Treatment with Pegylated IFN‐α2a and Ribavirin for Chronic Hepatitis C Virus InfectionThe Journal of Infectious Diseases, 2006
- Genomic response to interferon-α in chimpanzees: Implications of rapid downregulation for hepatitis C kineticsHepatology, 2006
- Association of pretreatment serum interferon inducible protein 10 levels with sustained virological response to peginterferon plus ribavirin therapy in genotype 1 infected patients with chronic hepatitis CGut, 2006
- Modulation of Hepatitis C Virus RNA Abundance by a Liver-Specific MicroRNAScience, 2005
- Unscrambling hepatitis C virus–host interactionsNature, 2005
- Mechanism of action of interferon and ribavirin in treatment of hepatitis CNature, 2005
- Plasma chemokine levels correlate with the outcome of antiviral therapy in patients with hepatitis CBlood, 2005
- Hepatic Gene Expression Discriminates Responders and Nonresponders in Treatment of Chronic Hepatitis C Viral InfectionGastroenterology, 2005
- Intrahepatic Gene Expression during Chronic Hepatitis C Virus Infection in ChimpanzeesJournal of Virology, 2004