Control of HCV replication with iMIRs, a novel anti-RNAi agent

Saori Itami, Yutaka Eguchi, Takayuki Mizutani, Eriko Aoki, Tadaaki Ohgi, Masahiko Kuroda, Takahiro Ochiya, Nobuyuki Kato, Hiroshi I. Suzuki, Norifumi Kawada, Yoshiki Murakami

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Abstract

MicroRNAs (miRNAs) serve important roles in regulating various physiological activities through RNA interference (RNAi). miR-122 is an important mediator of RNAi that is known to control hepatitis C virus (HCV) replication and is being investigated in clinical trials as a target for anti-HCV therapy. In this study, we developed novel oligonucleotides containing non-nucleotide residues, termed iMIRs, and tested their abilities to inhibit miR-122 function. We compared the inhibitory effects of iMIRs and locked nucleic acids (LNAs) on HCV replication in OR6 cells, which contained full-length HCV (genotype 1b) and a luciferase reporter gene. We found that RNA-type iMIRs with bulge-type, imperfect complementarity with respect to miR-122 were 10-fold more effective than LNAs in inhibiting HCV replication and functioned in a dose-dependent manner. Moreover, iMIR treatment of OR6 cells reduced HCV replication without inducing interferon responses or cellular toxicity. Based on these results, we suggest that iMIRs can inhibit HCV replication more effectively than LNAs and are therefore promising as novel antiviral agents.

Original languageEnglish
Article numbere219
JournalMolecular Therapy - Nucleic Acids
Volume4
Issue number1
DOIs
Publication statusPublished - Jan 1 2015

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Keywords

  • Anti-sense oligonucleotide
  • Hepatitis C virus
  • Interferon
  • Locked nucleic acid
  • MiRNA
  • RNA interference

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Itami, S., Eguchi, Y., Mizutani, T., Aoki, E., Ohgi, T., Kuroda, M., Ochiya, T., Kato, N., Suzuki, H. I., Kawada, N., & Murakami, Y. (2015). Control of HCV replication with iMIRs, a novel anti-RNAi agent. Molecular Therapy - Nucleic Acids, 4(1), [e219]. https://doi.org/10.1038/mtna.2014.71