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

作者：Afonin Kirill A^*; Viard Mathias; Martins Angelica N; Lockett Stephen J; Maciag Anna E; Freed Eric O; Heldman Eliahu; Jaeger Luc; Blumenthal Robert; Shapiro Bruce A

来源：Nature Nanotechnology, 2013, 8(4): 296-304.

DOI：10.1038/NNANO.2013.44

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 %26apos;smart%26apos; nucleic acid-based nanoparticles and switches for various biomedical applications.

• 出版日期2013-4