Suppression of hepatitis C virus replicon by adenovirus vector-mediated expression of tough decoy RNA against miR-122a

Virus Research
Fuminori SakuraiHiroyuki Mizuguchi

Abstract

Recent studies have demonstrated that the liver-specific microRNA (miRNA) miR-122a plays an important role in the replication of hepatitis C virus (HCV). Antisense nucleotides against miR-122a, including locked nucleic acid (LNA), have shown promising results for suppression of HCV replication; however, a liver-specific delivery system of antisense nucleotides has not been fully developed. In this study, an adenovirus (Ad) vector that expresses tough decoy (TuD)-RNA against miR-122a (TuD-122a) was developed to suppress the HCV replication in the liver hepatocytes. Ad vectors have been well established to exhibit a marked hepatotropism following systemic administration. An in vitro reporter gene expression assay demonstrated that Ad vector-mediated expression of TuD-122a efficiently blocked the miR-122a in Huh-7 cells. Furthermore, transduction with the Ad vector expressing TuD-122a in HCV replicon-expressing cells resulted in significant reduction in the HCV replicon levels. These results indicate that Ad vector-mediated expression of TuD-122a would be a promising tool for treatment of HCV infection.

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Citations

Apr 18, 2013·Japanese Journal of Clinical Oncology·Keita UchinoFumitaka Takeshita
Jun 12, 2013·Molecular Therapy : the Journal of the American Society of Gene Therapy·Rasmus O BakJacob Giehm Mikkelsen
Jul 16, 2014·Critical Reviews in Biotechnology·Jeong-Hun KangMasaharu Murata
Jan 1, 2014·Wiley Interdisciplinary Reviews. RNA·Rasmus O Bak, Jacob Giehm Mikkelsen
Jul 18, 2017·Human Gene Therapy Methods·Elena Herrera-CarrilloBen Berkhout
May 11, 2017·RNA·Anne Kruse HollensenJacob Giehm Mikkelsen
May 15, 2021·Drug Delivery and Translational Research·Fahima Danesh PouyaMohadeseh Nemati
Dec 20, 2012·RNA·Rasmus O BakJacob Giehm Mikkelsen

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