PLoS ONE (Jan 2012)

Efficacy of a novel class of RNA interference therapeutic agents.

  • Tomohiro Hamasaki,
  • Hiroshi Suzuki,
  • Hisao Shirohzu,
  • Takahiro Matsumoto,
  • Corina N D'Alessandro-Gabazza,
  • Paloma Gil-Bernabe,
  • Daniel Boveda-Ruiz,
  • Masahiro Naito,
  • Tetsu Kobayashi,
  • Masaaki Toda,
  • Takayuki Mizutani,
  • Osamu Taguchi,
  • John Morser,
  • Yutaka Eguchi,
  • Masahiko Kuroda,
  • Takahiro Ochiya,
  • Hirotake Hayashi,
  • Esteban C Gabazza,
  • Tadaaki Ohgi

DOI
https://doi.org/10.1371/journal.pone.0042655
Journal volume & issue
Vol. 7, no. 8
p. e42655

Abstract

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RNA interference (RNAi) is being widely used in functional gene research and is an important tool for drug discovery. However, canonical double-stranded short interfering RNAs are unstable and induce undesirable adverse effects, and thus there is no currently RNAi-based therapy in the clinic. We have developed a novel class of RNAi agents, and evaluated their effectiveness in vitro and in mouse models of acute lung injury (ALI) and pulmonary fibrosis. The novel class of RNAi agents (nkRNA®, PnkRNA™) were synthesized on solid phase as single-stranded RNAs that, following synthesis, self-anneal into a unique helical structure containing a central stem and two loops. They are resistant to degradation and suppress their target genes. nkRNA and PnkRNA directed against TGF-β1mRNA ameliorate outcomes and induce no off-target effects in three animal models of lung disease. The results of this study support the pathological relevance of TGF-β1 in lung diseases, and suggest the potential usefulness of these novel RNAi agents for therapeutic application.