Activation of different split functionalities on re-association of RNA-DNA hybrids.

Activation of different split functionalities on re-association of RNA-DNA hybrids.
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DOI:
10.1038/nnano.2013.44
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发表时间:
2013-04
影响因子:
38.3
通讯作者:
--
中科院分区:
材料科学1区
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--
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分裂蛋白系统是一种依赖于蛋白质的裂解及其进一步的条件重新结合来形成功能复合体的方法,越来越多地被用于各种生物医学应用。这种方法提供了对蛋白质功能的严格控制和提高的检测灵敏度。在这里,我们展示了一种基于一对RNA-DNA杂交体的类似技术,这种杂交体通常可以用于触发不同的分裂功能。就个体而言,每个杂交都是不活跃的,但当两个同源杂交重新关联时,哺乳动物细胞内就会触发不同的功能。作为概念的证明,这项工作主要集中在RNA干扰的激活上,但也展示了其他功能(共振、能量转移和RNA适配子)的释放。此外,体内研究表明,肿瘤可以显著地摄取杂交体,并伴随着特定的基因沉默。这种功能分裂的方法为开发用于各种生物医学应用的基于“智能”核酸的纳米粒子和开关提供了一条新的途径。
Split-protein systems, an approach that relies on fragmentation of proteins with their further conditional re-association to form functional complexes, are increasingly used for various biomedical applications. This approach offers tight control of the protein functions and improved detection sensitivity. Here we show a similar technique based on a pair of RNA-DNA hybrids that can be generally used for triggering different split functionalities. Individually, each hybrid is inactive but when two cognate hybrids re-associate, different functionalities are triggered inside mammalian cells. As a proof of concept this work is mainly focused on activation of RNA interference; however the release of other functionalities (resonance energy transfer and RNA aptamer) is also shown. Furthermore, in vivo studies demonstrate a significant uptake of the hybrids by tumors together with specific gene silencing. This split-functionality approach presents a new route in the development of “smart” nucleic acids based nanoparticles and switches for various biomedical applications.
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