Antidote-controlled platelet inhibition targeting von Willebrand factor with aptamers.

Journal Article

Thrombus formation is initiated by platelets and leads to cardiovascular, cerebrovascular, and peripheral vascular disease, the leading causes of morbidity and mortality in the Western world. A number of antiplatelet drugs have improved clinical outcomes for thrombosis patients. However, their expanded use, especially in surgery, is limited by hemorrhage. Here, we describe an antiplatelet agent that can have its activity controlled by a matched antidote. We demonstrate that an RNA aptamer targeting von Willebrand factor (VWF) can potently inhibit VWF-mediated platelet adhesion and aggregation. By targeting this important adhesion step, we show that the aptamer molecule can inhibit platelet aggregation in PFA-100 and ristocetin-induced platelet aggregation assays. Furthermore, we show that a rationally designed antidote molecule can reverse the effects of the aptamer molecule, restoring platelet function quickly and effectively over a clinically relevant period. This aptamer-antidote pair represents a reversible antiplatelet agent inhibiting a platelet specific pathway. Furthermore, it is an important step towards creating safer drugs in clinics through the utilization of an antidote molecule.

Full Text

Duke Authors

Cited Authors

  • Oney, S; Nimjee, SM; Layzer, J; Que-Gewirth, N; Ginsburg, D; Becker, RC; Arepally, G; Sullenger, BA

Published Date

  • 2007

Published In

Volume / Issue

  • 17 / 3

Start / End Page

  • 265 - 274

PubMed ID

  • 17854267

International Standard Serial Number (ISSN)

  • 1545-4576

Digital Object Identifier (DOI)

  • 10.1089/oli.2007.0089

Language

  • eng

Conference Location

  • United States