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Patatin-like phospholipase domain containing 3: A case in point linking genetic susceptibility for alcoholic and nonalcoholic liver disease

✍ Scribed by Devanshi Seth; Ann K. Daly; Paul S. Haber; Christopher P. Day

Publisher: John Wiley and Sons
Year: 2010
Tongue: English
Weight: 285 KB
Volume: 51
Category: Article
ISSN: 0270-9139
DOI: 10.1002/hep.23606

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✦ Synopsis

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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