人們常說(shuō),，激發(fā)改變的最好的方法是從系統(tǒng)內(nèi)著手,。 現(xiàn)在，研究人員基于RNA創(chuàng)建了控制裝置,，該裝置可被用來(lái)以合成的方式重新為細(xì)胞行為排布線路,，使得這些細(xì)胞對(duì)藥物更為敏感而造成其死亡。 這一工作著重顯示了RNA作為設(shè)計(jì)合成系統(tǒng)平臺(tái)以控制基因表達(dá)及用這類技術(shù)來(lái)治療疾病的前途,，特別是用基因療法來(lái)為癌性或有病細(xì)胞設(shè)計(jì)使其走向死亡的程式的可能性,。 Stephanie Culler及其同事應(yīng)用短片段的RNA來(lái)制造可編程式的控制裝置，當(dāng)這些裝置在存在某些蛋白的時(shí)候可被激發(fā),，使得基因表達(dá)通路被重新安排并改變了人類細(xì)胞的行為,。
在該實(shí)驗(yàn)中，研究人員將某關(guān)鍵性信號(hào)轉(zhuǎn)導(dǎo)通路的刺激與某個(gè)基因表達(dá)發(fā)生關(guān)聯(lián),，而該基因的表達(dá)可使細(xì)胞對(duì)藥物甲基鳥嘌呤變得敏感,，并誘導(dǎo)程序化細(xì)胞死亡。 他們的RNA控制裝置可重新安排有關(guān)的通路并促使細(xì)胞探測(cè)到一種與癌癥有關(guān)聯(lián)的標(biāo)志并激活產(chǎn)生一種蛋白質(zhì),。該蛋白質(zhì)可令細(xì)胞對(duì)某種抗癌藥物變得敏感,。 這些結(jié)果顯示，這種RNA裝置可用來(lái)改變細(xì)胞轉(zhuǎn)導(dǎo)通路的線路并指引細(xì)胞走向某種特定的命運(yùn),。 一則相關(guān)的觀點(diǎn)欄目對(duì)這一創(chuàng)建一個(gè)單一框架結(jié)構(gòu)以建立合成基因調(diào)控系統(tǒng)的工作的可能的影響進(jìn)行了討論,。（生物谷Bioon.com）
生物谷推薦英文摘要：
Science DOI: 10.1126/science.1192128
Reprogramming Cellular Behavior with RNA Controllers Responsive to Endogenous Proteins
Stephanie J. Culler1, Kevin G. Hoff1 and Christina D. Smolke1,2,*
Synthetic genetic devices that interface with native cellular pathways can be used to change natural networks to implement new forms of control and behavior. The engineering of gene networks has been limited by an inability to interface with native components. We describe a class of RNA control devices that overcome these limitations by coupling increased abundance of particular proteins to targeted gene expression events through the regulation of alternative RNA splicing. We engineered RNA devices that detect signaling through the nuclear factor κB and Wnt signaling pathways in human cells and rewire these pathways to produce new behaviors, thereby linking disease markers to noninvasive sensing and reprogrammed cellular fates. Our work provides a genetic platform that can build programmable sensing-actuation devices enabling autonomous control over cellular behavior.
