Efficacy of a novel class of RNA interference therapeutic agents.
Efficacy of a novel class of RNA interference therapeutic agents.
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DOI：
10.1371/journal.pone.0042655
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Ohgi T
中科院分区：
文献类型：
--
作者：
Hamasaki T;Suzuki H;Shirohzu H;Matsumoto T;D'Alessandro-Gabazza CN;Gil-Bernabe P;Boveda-Ruiz D;Naito M;Kobayashi T;Toda M;Mizutani T;Taguchi O;Morser J;Eguchi Y;Kuroda M;Ochiya T;Hayashi H;Gabazza EC;Ohgi T
RNA干扰（RNAi）广泛应用于功能基因研究，是药物发现的重要工具。然而，典型的双链短干扰RNA不稳定并会引起不良反应，因此目前临床上还没有基于RNAi的治疗方法。我们开发了一类新型 RNAi 药物，并在体外和急性肺损伤 (ALI) 和肺纤维化小鼠模型中评估了它们的有效性。新型 RNAi 试剂（nkRNA®、PnkRNA™）是在固相上以单链 RNA 形式合成的，合成后，自身退火成包含中心茎和两个环的独特螺旋结构。它们能够抵抗降解并抑制其靶基因。针对 TGF-β1mRNA 的 nkRNA 和 PnkRNA 可改善三种肺病动物模型的结果，并且不会引起脱靶效应。这项研究的结果支持了 TGF-β1 在肺部疾病中的病理相关性，并表明这些新型 RNAi 药物在治疗应用中的潜在用途。
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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影响因子：
46.9
作者：
Judge, AD;Sood, V;MacLachlan, I
通讯作者：
MacLachlan, I
DOI：
10.1093/nass/nrp033
发表时间：
2009-01-01
期刊：
Nucleic acids symposium series (2004)
影响因子：
--
作者：
Abe, Hiroshi;Abe, Naoko;Ito, Yoshihiro
通讯作者：
Ito, Yoshihiro
影响因子：
4.5
作者：
Reynolds, Angela;Anderson, Emily M.;Khvorova, Anastasia
通讯作者：
Khvorova, Anastasia
影响因子：
15.9
作者：
Pittet, JF;Griffiths, MJD;Sheppard, D
通讯作者：
Sheppard, D
DOI：
10.1152/ajplung.00379.2002
发表时间：
2003-12-01
影响因子：
4.9
作者：
Willis, BC;Kim, KJ;Borok, Z
通讯作者：
Borok, Z