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

被引:0
作者
Afonin K.A. [1 ]
Viard M. [1 ,2 ]
Martins A.N. [3 ]
Lockett S.J. [4 ]
MacIag A.E. [2 ,5 ]
Freed E.O. [3 ]
Heldman E. [2 ,6 ]
Jaeger L. [7 ]
Blumenthal R. [1 ]
Shapiro B.A. [1 ]
机构
[1] Center for Cancer Research Nanobiology Program, NCI, Frederick
[2] Basic Science Program, SAIC-Frederick, Frederick National Laboratory for Cancer Research, Frederick
[3] HIV Drug Resistance Program, NCI, Frederick
[4] Advanced Technology Program, SAIC-Frederick, Frederick National Laboratory for Cancer Research, Frederick
[5] Chemical Biology Laboratory, NCI, Frederick
[6] Ben-Gurion University of the Negev, Beer Sheva
[7] Department of Chemistry and Biochemistry, Biomolecular Science and Engineering Program, University of California, Santa Barbara
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D O I
10.1038/nnano.2013.44
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摘要
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 protein functions and improved detection sensitivity. Here we report a similar technique based on a pair of RNA-DNA hybrids that can be used generally 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 mainly focuses on the activation of RNA interference. However, the release of other functionalities (such as resonance energy transfer and RNA aptamer) is also shown. Furthermore, in vivo studies demonstrate a significant uptake of the hybrids by tumours together with specific gene silencing. This split-functionality approach presents a new route in the development of 'smart' nucleic acid-based nanoparticles and switches for various biomedical applications. Copyright © 2013 Macmillan Publishers Limited. All rights reserved.
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页码:296 / 304
页数:8
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