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

Published

Journal Article

UNLABELLED: 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. FROM THE CLINICAL EDITOR: Thrombin inhibition via DNA aptamers has recently become a possibility. In this study, thrombin-binding DNA aptamers were further optimized by nanoscale organization on DNA nanostructures. The authors have created a novel, functional DNA nanostructure, which is a multi-aptamer inhibitor with activity eightfold higher than that of free aptamer. Reversal of thrombin inhibition was also achieved by single-stranded DNA antidotes, enabling significant control over the coagulation pathway.

Full Text

Duke Authors

Cited Authors

  • Rangnekar, A; Zhang, AM; Li, SS; Bompiani, KM; Hansen, MN; Gothelf, KV; Sullenger, BA; LaBean, TH

Published Date

  • July 2012

Published In

Volume / Issue

  • 8 / 5

Start / End Page

  • 673 - 681

PubMed ID

  • 21889476

Pubmed Central ID

  • 21889476

Electronic International Standard Serial Number (EISSN)

  • 1549-9642

Digital Object Identifier (DOI)

  • 10.1016/j.nano.2011.08.011

Language

  • eng

Conference Location

  • United States