Therapeutic Silencing of MicroRNA-122 in Primates with Chronic Hepatitis C Virus Infection

被引：1308

作者：

Lanford, Robert E. ^{[2
,3
]}

Hildebrandt-Eriksen, Elisabeth S. ^{[1
]}

Petri, Andreas ^{[1
]}

Persson, Robert ^{[1
]}

Lindow, Morten ^{[1
]}

Munk, Martin E. ^{[1
]}

Kauppinen, Sakari ^{[1
,4
]}

Orum, Henrik ^{[1
]}

机构：

[1] Santaris Pharma, DK-2970 Horsholm, Denmark

[2] SW Fdn Biomed Res, Dept Virol & Immunol, San Antonio, TX 78227 USA

[3] SW Fdn Biomed Res, SW Natl Primate Res Ctr, San Antonio, TX 78227 USA

[4] Univ Aalborg, Copenhagen Inst Technol, DK-2750 Ballerup, Denmark

来源：

SCIENCE | 2010年 / 327卷 / 5962期

关键词：

GENE-EXPRESSION; INTERFERON-ALPHA; CHIMPANZEES; RIBAVIRIN; LIVER; KINETICS;

D O I：

10.1126/science.1178178

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：198 / 201

页数：4

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