Efficacy of a novel class of RNA interference therapeutic agents.
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.
BONAC Corporation, BIO Factory 4F, Aikawa, Kurume, Fukuoka, Japan.
Tomohiro
T
Hamasaki
Hiroshi
H
Suzuki
Hisao
H
Shirohzu
Takahiro
T
Matsumoto
Corina N
CN
D'Alessandro-Gabazza
Paloma
P
Gil-Bernabe
Daniel
D
Boveda-Ruiz
Masahiro
M
Naito
Tetsu
T
Kobayashi
Masaaki
M
Toda
Takayuki
T
Mizutani
Osamu
O
Taguchi
John
J
Morser
Yutaka
Y
Eguchi
Masahiko
M
Kuroda
Takahiro
T
Ochiya
Hirotake
H
Hayashi
Esteban C
EC
Gabazza
Tadaaki
T
Ohgi
D055371:Acute Lung Injury / Q000628:therapy*; D000818:Animals; D001483:Base Sequence; D001992:Bronchoalveolar Lavage Fluid; D004195:Disease Models, Animal; D051379:Mice; D011658:Pulmonary Fibrosis / Q000628:therapy*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering; D053773:Transforming Growth Factor beta1 / Q000235:genetics
D012333:RNA, Messenger; D034741:RNA, Small Interfering; D053773:Transforming Growth Factor beta1