Efficacy of a novel class of RNA interference therapeutic agents.
oleh: 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
| Format: | Article |
|---|---|
| Diterbitkan: | Public Library of Science (PLoS) 2012-01-01 |
Deskripsi
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.