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Thromb Haemost 2000; 84(05): 841-848
DOI: 10.1055/s-0037-1614126
DOI: 10.1055/s-0037-1614126
Review Article
Blocking the Initiation of Coagulation by RNA Aptamers to Factor VIIa
We thank J. Jones and S. Daubendiek for helpful discussion, and the Duke Clinical Coagulation Lab, especially T. Ortel, A. Joyner and L. Estrada for their time, technical assistance and use of equipment and reagents. C.P.R. is a Fellow of the Jane Coffin Childs Memorial Fund for Medical Research. A. Y. was supported by a Claude E. Welch fellowship sponsored through the Department of Surgery at the Massachusetts General Hospital. J.H.L is a supported by a Clinician Scientist Award from the American Heart Association.
Weitere Informationen
Publikationsverlauf
Received
17. Februar 2000
Accepted after revision
31. Mai 2000
Publikationsdatum:
13. Dezember 2017 (online)
Summary
The tissue factor/factor VIIa complex is thought to be the primary initiator of most physiologic blood coagulation events. Because of its proximal role in this process, we sought to generate new inhibitors of tissue factor/factor VIIa activity by targeting factor VIIa. We employed a combinatorial RNA library and in vitro selection methods to isolate a high affinity, nuclease-resistant RNA ligand that binds specifically to coagulation factor VII/VIIa. This RNA inhibits the tissue factordependent activation of factor X by factor VIIa. Kinetic analyses of the mechanism of action of this RNA suggest that it antagonizes factor VIIa activity by preventing formation of a functional factor VII/tissue factor complex. Furthermore, this RNA significantly prolongs the prothrombin time of human plasma in a dose dependent manner, and has an in vitro half-life of ∼15 h in human plasma. Thus, this RNA ligand represents a novel class of anticoagulant agents directed against factor VIIa.
* C. P. R. and A. Y. contributed equally to this work
* Present address: Dr. A. Yeh, Department of Surgery, Massachusetts General Hospital, Boston, MA 02115, USA
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