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

Kirill A. Afonin, Mathias Viard, Angelica N. Martins, Stephen J. Lockett, Anna E. MacIag, Eric O. Freed, Eliahu Heldman, Luc Jaeger, Robert Blumenthal, Bruce A. Shapiro

    Research output: Contribution to journalArticlepeer-review

    91 Scopus citations


    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.

    Original languageEnglish
    Pages (from-to)296-304
    Number of pages9
    JournalNature Nanotechnology
    Issue number4
    StatePublished - 1 Jan 2013

    ASJC Scopus subject areas

    • Bioengineering
    • Atomic and Molecular Physics, and Optics
    • Biomedical Engineering
    • General Materials Science
    • Condensed Matter Physics
    • Electrical and Electronic Engineering


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