Publication Date:
2009-12-08
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3436126/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3436126/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lanford, Robert E -- Hildebrandt-Eriksen, Elisabeth S -- Petri, Andreas -- Persson, Robert -- Lindow, Morten -- Munk, Martin E -- Kauppinen, Sakari -- Orum, Henrik -- C06 RR 12087/RR/NCRR NIH HHS/ -- C06 RR012087/RR/NCRR NIH HHS/ -- C06 RR012087-01/RR/NCRR NIH HHS/ -- P51 RR013986/RR/NCRR NIH HHS/ -- P51 RR13986/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2010 Jan 8;327(5962):198-201. doi: 10.1126/science.1178178. Epub 2009 Dec 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Virology and Immunology and Southwest National Primate Research Center, Southwest Foundation for Biomedical Research, San Antonio, TX 78227, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965718" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Antiviral Agents/adverse effects/blood/*therapeutic use
;
Chemokine CXCL10/blood
;
Cholesterol/blood
;
Disease Models, Animal
;
Drug Evaluation, Preclinical
;
Drug Resistance, Viral
;
Female
;
Gene Expression Profiling
;
Gene Expression Regulation
;
Hepacivirus/drug effects/genetics/isolation & purification/physiology
;
Hepatitis C, Chronic/*drug therapy/genetics/virology
;
Interferons/metabolism
;
Liver/metabolism/virology
;
Male
;
MicroRNAs/*antagonists & inhibitors/genetics/metabolism
;
*Pan troglodytes
;
Phosphorothioate Oligonucleotides/adverse effects/blood/*therapeutic use
;
RNA, Messenger/genetics/metabolism
;
RNA, Viral/metabolism
;
Viral Load
;
Viremia/drug therapy
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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