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Increased anticoagulant activity of thrombin-binding DNA aptamers by nanoscale organization on DNA nanostructures

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  • Abhijit Rangnekar, Danmark
  • Alex M. Zhang, Duke University, USA
  • Susan Shiyuan Li, Davidson College, USA
  • Kristin M. Bompiani, Duke University, USA
  • Majken Nørgaard Hansen, Danmark
  • Kurt Vesterager Gothelf
  • Bruce A. Sullenger, Duke University, USA
  • Thomas H. Labean, Duke University, USA
Control over thrombin activity is much desired to regulate blood clotting in surgical and therapeutic situations. Thrombin-binding RNA and DNA aptamers have been used to inhibit thrombin activity and thus the coagulation cascade. Soluble DNA aptamers, as well as two different aptamers tethered by a flexible single-strand linker, have been shown to possess anticoagulant activity. Here, we link multiple aptamers at programmed positions on DNA nanostructures to optimize spacing and orientation of the aptamers and thereby to maximize anticoagulant activity in functional assays. By judicious engineering of the DNA nanostructures, we have created a novel, functional DNA nanostructure, which is a multi-aptamer inhibitor with activity eightfold higher than free aptamer. Reversal of the thrombin inhibition was also achieved by the use of single-stranded DNA antidotes, thus enabling significant control over blood coagulation.
OriginalsprogEngelsk
TidsskriftNanomedicine: Nanotechnology, Biology and Medicine
Vol/bind8
Nummer5
Sider (fra-til)673-681
Antal sider9
ISSN1549-9634
DOI
StatusUdgivet - 2012

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