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

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Abhijit Rangnekar, Denmark
  • Alex M. Zhang, Duke University, United States
  • Susan Shiyuan Li, Davidson College, United States
  • Kristin M. Bompiani, Duke University, United States
  • Majken Nørgaard Hansen, Denmark
  • Kurt Vesterager Gothelf
  • Bruce A. Sullenger, Duke University, United States
  • Thomas H. Labean, Duke University, United States
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.
Original languageEnglish
JournalNanomedicine: Nanotechnology, Biology and Medicine
Volume8
Issue5
Pages (from-to)673-681
Number of pages9
ISSN1549-9634
DOIs
Publication statusPublished - 2012

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