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

Abhijit Rangnekar; Alex M. Zhang; Susan Shiyuan Li; Kristin M. Bompiani; Majken Nørgaard Hansen; Kurt Vesterager Gothelf; Bruce A. Sullenger; Thomas H. Labean

doi:10.1016/j.nano.2011.08.011

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

Abhijit Rangnekar, Alex M. Zhang, Susan Shiyuan Li, Kristin M. Bompiani, Majken Nørgaard Hansen, Kurt Vesterager Gothelf, Bruce A. Sullenger, Thomas H. Labean

Department of Chemistry

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

38 Citations (Scopus)

781 Downloads (Pure)

Abstract

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 language	English
Journal	Nanomedicine: Nanotechnology, Biology and Medicine
Volume	8
Issue	5
Pages (from-to)	673-681
Number of pages	9
ISSN	1549-9634
DOIs	https://doi.org/10.1016/j.nano.2011.08.011
Publication status	Published - 2012

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10.1016/j.nano.2011.08.011

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

Cite this

@article{e394aaafa02c4a6db3d9ff14dbf40fc2,

title = "Increased anticoagulant activity of thrombin-binding DNA aptamers by nanoscale organization on DNA nanostructures",

abstract = "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.",

author = "Abhijit Rangnekar and Zhang, {Alex M.} and {Shiyuan Li}, Susan and {M. Bompiani}, Kristin and Hansen, {Majken N{\o}rgaard} and Gothelf, {Kurt Vesterager} and Sullenger, {Bruce A.} and Labean, {Thomas H.}",

year = "2012",

doi = "10.1016/j.nano.2011.08.011",

language = "English",

volume = "8",

pages = "673--681",

journal = "Nanomedicine: Nanotechnology, Biology and Medicine",

issn = "1549-9634",

publisher = "Elsevier Inc.",

number = "5",

}

Increased anticoagulant activity of thrombin-binding DNA aptamers by nanoscale organization on DNA nanostructures. / Rangnekar, Abhijit; Zhang, Alex M.; Shiyuan Li, Susan et al.
In: Nanomedicine: Nanotechnology, Biology and Medicine, Vol. 8, No. 5, 2012, p. 673-681.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Increased anticoagulant activity of thrombin-binding DNA aptamers by nanoscale organization on DNA nanostructures

AU - Rangnekar, Abhijit

AU - Zhang, Alex M.

AU - Shiyuan Li, Susan

AU - M. Bompiani, Kristin

AU - Hansen, Majken Nørgaard

AU - Gothelf, Kurt Vesterager

AU - Sullenger, Bruce A.

AU - Labean, Thomas H.

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

U2 - 10.1016/j.nano.2011.08.011

DO - 10.1016/j.nano.2011.08.011

M3 - Journal article

C2 - 21889476

SN - 1549-9634

VL - 8

SP - 673

EP - 681

JO - Nanomedicine: Nanotechnology, Biology and Medicine

JF - Nanomedicine: Nanotechnology, Biology and Medicine

IS - 5

ER -