Two-step targeting of urokinase to plasma clot provides efficient fibrinolysis

Two-step targeting of urokinase to a model thrombus (human plasma clot) has been examined in vitro. To this purpose a covalent conjugate of vector antibodies to fibrinogen with monoclonal non-inhibiting antibody to urokinase was obtained using cross-linking agent disuccinimidilsuberate. After pretreatment with the conjugate clot acquired affinity for urokinase, which alters the character of fibrinolysis. Pretreatment with the conjugate resulted in at least 10-fold decrease in dose of urokinase needed for effective clot lysis (from 150 IU/ml for intact clot to 10-15 IU/ml for pretreated one). This variant of urokinase targeting provides effective clot lysis without fibrinogenolysis in plasma.