Aptamers: the emerging class of future anticoagulation for vascular disease

Wiktor Kuliczkowskia, James Floydb, Alex Malininb & Victor Serebruany*ca Silesian Center for Heart Diseases, Zabrze, Polandb HeartDrug™ Research Laboratories, Johns Hopkins University Baltimore, Osler Medical Center, 7600 Osler Drive, Ste 307, Towson, MD 21204, USAc HeartDrug™ Research Laboratories, Johns Hopkins University Baltimore, Osler Medical Center, 7600 Osler Drive, Ste 307, Towson, MD 21204, USA. † Author for correspondenceAnticoagulation is an important therapeutic strategy to treat and prevent recurrent thrombotic events in patients after acute myocardial infarction and ischemic stroke. However, available anticoagulants have numerous shortcomings including hemorrhage risks, limited clinical application including heparin-induced thrombocytopenia and modest therapeutic benefit. Each component of the coagulation cascade is a potential target for new drug developments. Representing an attractive new therapeutic class, aptamers are nucleic acid ligand with a high affinity and specificity for proteins involved in the clot growth. Potential antidote control of aptamer activity offers an important advance in anticoagulant safety. Aptamers are a promising class of compounds, both for target validation and therapy. As designer drugs, they exhibit high specificity, high affinity and modifiable bioavailability. The ability to generate inhibitors with such properties against a variety of target proteins will be valuable as the human genome and proteome are deciphered. This article summarizes current knowledge of aptamers developed against coagulation proteins, focusing on the biology, pharmacology, preclinical and early clinical experience with this novel class of anticoagulants.