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PLoS By Category | Recent PLoS Articles
Biochemistry - Chemistry - Molecular Biology - Pharmacology - Respiratory Medicine

Efficacy of a Novel Class of RNA Interference Therapeutic Agents
Published: Wednesday, August 15, 2012
Author: Tomohiro Hamasaki et al.

by 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

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-ß1mRNA 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-ß1 in lung diseases, and suggest the potential usefulness of these novel RNAi agents for therapeutic application.
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