Blocking the initiation of coagulation by RNA aptamers to factor VIIa.

Journal Article

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 factor-dependent 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 approximately 15 h in human plasma. Thus, this RNA ligand represents a novel class of anticoagulant agents directed against factor VIIa.

Full Text

Duke Authors

Cited Authors

  • Rusconi, CP; Yeh, A; Lyerly, HK; Lawson, JH; Sullenger, BA

Published Date

  • November 2000

Published In

Volume / Issue

  • 84 / 5

Start / End Page

  • 841 - 848

PubMed ID

  • 11127866

International Standard Serial Number (ISSN)

  • 0340-6245

Language

  • eng

Conference Location

  • Germany