Efficacy of a novel class of RNA interference therapeutic agents |
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Authors: | 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 |
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Institution: | BONAC Corporation, BIO Factory 4F, Aikawa, Kurume, Fukuoka, Japan. |
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Abstract: | 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. |
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