Emerging applications of aptamers for anticoagulation and hemostasis

Current Opinion in Hematology
Charlene V ChabataRuwan Gunaratne

Abstract

Since the selection of the first thrombin-binding aptamer in 1992, the use of nucleic acid aptamers to target specific coagulation factors has emerged as a valuable approach for generating novel anticoagulant and procoagulant therapeutics. Herein, we highlight the most recent discoveries involving application of aptamers for those purposes. Learning from the successes and pitfalls of the FIXa-targeting aptamer pegnivacogin in preclinical and clinical studies, the latest efforts to develop antidote-controllable anticoagulation strategies for cardiopulmonary bypass that avoid unfractionated heparin involve potentiation of the exosite-binding factor X (FX)a aptamer 11F7t by combination with either a small molecule FXa catalytic site inhibitor or a thrombin aptamer. Recent work has also focused on identifying aptamer inhibitors of contact pathway factors such as FXIa and kallikrein, which may prove to be well tolerated and effective antithrombotic agents in certain clinical settings. Finally, new approaches to develop procoagulant aptamers to control bleeding associated with hemophilia and other coagulopathies involve targeting activated protein C and tissue plasminogen activator. Overall, these recent findings exemplify the versat...Continue Reading

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Citations

Jan 13, 2019·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Nils Henninger, Yunis Mayasi
Jun 4, 2019·Frontiers in Chemistry·Ting-Xuan LinChih-Ching Huang
Aug 3, 2020·Current Opinion in Hematology·Priyanka Srivastava, David Gailani
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Jan 14, 2022·Nucleic Acid Therapeutics·Charlene V ChabataBruce A Sullenger

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