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

Publication ,  Journal Article
Rangnekar, A; Zhang, AM; Li, SS; Bompiani, KM; Hansen, MN; Gothelf, KV; Sullenger, BA; LaBean, TH
Published in: Nanomedicine
July 2012

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.

Duke Scholars

Published In

Nanomedicine

DOI

EISSN

1549-9642

Publication Date

July 2012

Volume

8

Issue

5

Start / End Page

673 / 681

Location

United States

Related Subject Headings

  • Thrombin
  • Plasma
  • Nanostructures
  • Nanoscience & Nanotechnology
  • Humans
  • DNA
  • Blood Coagulation
  • Aptamers, Nucleotide
  • Anticoagulants
  • 34 Chemical sciences
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Rangnekar, A., Zhang, A. M., Li, S. S., Bompiani, K. M., Hansen, M. N., Gothelf, K. V., … LaBean, T. H. (2012). Increased anticoagulant activity of thrombin-binding DNA aptamers by nanoscale organization on DNA nanostructures. Nanomedicine, 8(5), 673–681. https://doi.org/10.1016/j.nano.2011.08.011
Rangnekar, Abhijit, Alex M. Zhang, Susan Shiyuan Li, Kristin M. Bompiani, Majken N. Hansen, Kurt V. Gothelf, Bruce A. Sullenger, and Thomas H. LaBean. “Increased anticoagulant activity of thrombin-binding DNA aptamers by nanoscale organization on DNA nanostructures.Nanomedicine 8, no. 5 (July 2012): 673–81. https://doi.org/10.1016/j.nano.2011.08.011.
Rangnekar A, Zhang AM, Li SS, Bompiani KM, Hansen MN, Gothelf KV, et al. Increased anticoagulant activity of thrombin-binding DNA aptamers by nanoscale organization on DNA nanostructures. Nanomedicine. 2012 Jul;8(5):673–81.
Rangnekar, Abhijit, et al. “Increased anticoagulant activity of thrombin-binding DNA aptamers by nanoscale organization on DNA nanostructures.Nanomedicine, vol. 8, no. 5, July 2012, pp. 673–81. Pubmed, doi:10.1016/j.nano.2011.08.011.
Rangnekar A, Zhang AM, Li SS, Bompiani KM, Hansen MN, Gothelf KV, Sullenger BA, LaBean TH. Increased anticoagulant activity of thrombin-binding DNA aptamers by nanoscale organization on DNA nanostructures. Nanomedicine. 2012 Jul;8(5):673–681.
Journal cover image

Published In

Nanomedicine

DOI

EISSN

1549-9642

Publication Date

July 2012

Volume

8

Issue

5

Start / End Page

673 / 681

Location

United States

Related Subject Headings

  • Thrombin
  • Plasma
  • Nanostructures
  • Nanoscience & Nanotechnology
  • Humans
  • DNA
  • Blood Coagulation
  • Aptamers, Nucleotide
  • Anticoagulants
  • 34 Chemical sciences