Activation of Different Split Functionalities on Re-Association of RNA-DNA Hybrids

Nat Nanotechnol. 2013 Apr;8(4):296-304. doi: 10.1038/nnano.2013.44. Epub 2013 Mar 31.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Aptamers, Nucleotide / metabolism
  • Cell Line, Tumor
  • DNA / metabolism*
  • Fluorescence
  • Fluorescence Resonance Energy Transfer
  • Gene Knockdown Techniques
  • Green Fluorescent Proteins / metabolism
  • HIV-1 / metabolism
  • Humans
  • Intracellular Space / metabolism
  • Kinetics
  • Mice
  • Microscopy, Confocal
  • Nucleic Acid Heteroduplexes / metabolism*
  • RNA / metabolism*
  • RNA, Small Interfering / metabolism
  • Temperature
  • Time Factors
  • Tissue Distribution
  • Transfection
  • Xenograft Model Antitumor Assays


  • Aptamers, Nucleotide
  • Nucleic Acid Heteroduplexes
  • RNA, Small Interfering
  • Green Fluorescent Proteins
  • RNA
  • DNA