ABSTRACT
A DNA aptamer to the von Willebrand factor (VWF) A1 domain, TAGX-0004, inhibits the binding of VWF to platelets. Nucleic acid aptamers are single-stranded DNA or RNA molecule forming three-dimensional structures that are capable of specifically binding to proteins and are expected to contribute to alternative medicine. ARC1779, an aptamer targeting the VWF A1 domain, had been evaluated in a phase II clinical trial of patients with acquired thrombotic thrombocytopenic purpura (aTTP); however, its development was terminated. Caplacizumab, an anti-VWF A1 domain nanobody, is now increasingly employed as first-line therapy for the treatment of aTTP in Western countries. However, there have been reports regarding adverse bleeding events and the high cost of the treatment. In this study, the inhibitory effects of TAGX-0004 were compared with those of ARC1779 and caplacizumab on in vitro platelet aggregation and thrombus formation. TAGX-0004 had an excellent high affinity to the VWF A1 domain and superior efficacy, such as its potent inhibitory activity in in vitro platelet aggregation and thrombus formation. Therefore, it can potentially overcome the problems associated with caplacizumab and can be developed as a promising drug not only for aTTP treatment but also for the treatment of the various VWF-mediated thrombotic disorders.