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Nucleic Acid Ther. 2016 Dec;26(6):355-362. Epub 2016 Oct 13.

In Vitro Evaluation of Aptamer-Based Reversible Inhibition of Anticoagulant Activated Protein C as a Novel Supportive Hemostatic Approach.

Author information

1
1 Institute of Experimental Hematology and Transfusion Medicine, University of Bonn Medical Center , Bonn, Germany .
2
2 Pall GmbH , Dreieich, Germany .
3
3 Life and Medical Sciences Institute, University of Bonn , Bonn, Germany .

Abstract

Activated protein C (APC) is a critical regulator of thrombin formation and thereby protects against thrombosis. On the other hand, overwhelming formation of APC increases the risk of bleeding such as in trauma-induced coagulopathy. Thus, pharmacological inhibition of APC activity may improve blood clottability in certain clinical situations. In this study, we demonstrate that the DNA aptamer HS02-52G binds with fast onset (1.118 ± 0.013 × 105 M-1 s-1) to APC and possesses a long residence time of 13.5 min within the aptamer-APC complex. Functional analysis revealed HS02-52G as a highly potent and specific inhibitor of APC in plasma and whole blood with IC50 values ≤30 nM, whose activity can be readily neutralized by the short complementary DNA molecule AD22. These features qualify the novel aptamer-antidote pair as a candidate treatment option for acute APC-related bleedings.

KEYWORDS:

activated protein C (APC); antidote; aptamer; hemophilia; inhibitor; trauma-induced coagulopathy (TIC)

PMID:
27736370
DOI:
10.1089/nat.2016.0645
[Indexed for MEDLINE]

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