小的基于RNA的核酸類藥物代表一種有前景的新一類治療性制劑,，此類制劑沉默異?；蜻^度活躍的致性基因，研究人員已發(fā)現(xiàn)了新機(jī)制,，通過這種機(jī)制RNA藥物能控制基因活性,。Nucleic Acid Therapeutics上的一篇綜合性綜述文章詳細(xì)描述了這些進(jìn)展，這種期刊是由Mary Ann Liebert公司出版的同行評(píng)審期刊,。
短鏈核酸,，也稱為小RNA，可被用于靶基因的沉默,，使它們成為吸引人的藥物代表,。這些小RNA通過多種RNA干擾通路阻斷基因表達(dá)，這些通路包括2個(gè)新發(fā)現(xiàn)的通路,，在這2個(gè)通路中小RNA結(jié)合到存在于細(xì)胞核內(nèi)的Argonaute蛋白或RNA的其他形式,，例如長(zhǎng)非編碼RNA和前mRNA。
德克薩斯大學(xué)西南醫(yī)學(xué)中心的Keith T. Gagnon,博士和 David R. Corey博士詳細(xì)地綜述了由控制基因表達(dá)的RNAi通路所共享的一般特性,，重點(diǎn)綜述了Argonaute-RNA復(fù)合物在基因調(diào)控中的潛力和其他靶向非編碼RNA和前mRNA的出現(xiàn)形式的令人興奮的新選項(xiàng),，綜述的標(biāo)題是"Argonaute and the Nuclear RNAs: New Pathways for RNA Mediated Control of Gene Expression"。
"RNA介導(dǎo)的控制基因表達(dá)的領(lǐng)域正在迅速展開,，Gagnon 和 Corey寫的文章提供了一篇生物醫(yī)學(xué)研究令人興奮并經(jīng)常令人吃驚領(lǐng)域的高度信息化與時(shí)新的綜述,。我們很欣喜地發(fā)表這篇此領(lǐng)域的重要綜述",， 北卡羅萊納達(dá)勒姆杜克大學(xué)醫(yī)學(xué)中心杜克翻譯研究院的主要主編Bruce A. Sullenger博士這樣說。（生物谷bioon.com）
doi:10.1089/nat.2011.0330
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Argonaute and the Nuclear RNAs: New Pathways for RNA-Mediated Control of Gene Expression
Keith T. Gagnon and David R. Corey
Abstract Small RNAs are a commonly used tool for gene silencing and a promising platform for nucleic acid drug development. They are almost exclusively used to silence gene expression post-transcriptionally through degradation of mRNA. Small RNAs, however, can have a broader range of function by binding to Argonaute proteins and associating with complementary RNA targets in the nucleus, including long noncoding RNAs (lncRNAs) and pre-mRNA. Argonaute-RNA complexes can regulate nuclear events like transcription, genome maintenance, and splicing. Thousands of lncRNAs and alternatively spliced pre-mRNA isoforms exist in humans, and these RNAs may serve as natural targets for regulation and therapeutic intervention. This review describes nuclear mechanisms for Argonaute proteins and small RNAs, new pathways for sequence-specific targeting, and the potential for therapeutic development of small RNAs with nuclear targets.
