title: Suppression of hepatitis C virus replicon by adenovirus vector-mediated expression of tough decoy RNA against miR-122a.
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.
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan. mizuguch@phs.osaka-u.ac.jp
authors.forename: Fuminori
authors.initials: F
authors.lastname: Sakurai
authors.forename: Norihisa
authors.initials: N
authors.lastname: Furukawa
authors.forename: Maiko
authors.initials: M
authors.lastname: Higuchi
authors.forename: Sayuri
authors.initials: S
authors.lastname: Okamoto
authors.forename: Kaori
authors.initials: K
authors.lastname: Ono
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yoshida
authors.forename: Masuo
authors.initials: M
authors.lastname: Kondoh
authors.forename: Kiyohito
authors.initials: K
authors.lastname: Yagi
authors.forename: Naoya
authors.initials: N
authors.lastname: Sakamoto
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Katayama
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mizuguchi
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D002460:Cell Line; D005822:Genetic Vectors; D016174:Hepacivirus / Q000254:growth & development / Q000502:physiology*; D022781:Hepatocytes / Q000821:virology; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000235:genetics; D014779:Virus Replication
chemical_list: C531907:MIRN122 microRNA, human; D035683:MicroRNAs