Improving natural principles with genetic engineering: TNK-tissue plasminogen activator.
The fibrinolytic system plays an important role in the physiological maintenance of blood flow and the dissolution of thrombi. Administration of fibrinolytic agents in indications such as myocardial infarction, pulmonary embolism, deep vein thrombosis or stroke, therefore, offers a rational means to dissolve pathological thrombi and restore vascular patency. The functional domains of the physiological tissue plasminogen activator (t-PA) provide fibrin specificity and serine protease activity for plasminogen cleavage and binding to liver receptors which gives the molecule a short half-life. In order to combat acute thromboembolic events such as myocardial infarction, the structure of the natural t-PA molecule was genetically modified to prolong its half-life, to increase its fibrin-specificity and to improve its resistance to plasminogen activator inhibitor. These features of TNK-t-PA allow bolus administration in emergency situations, early reperfusion of the blood vessel and a low rate of bleeding complications, thus improving the overall benefit to patients.
Werner
R G
RG
Boehringer Ingelheim GmbH, Corporate Division Biopharmaceuticals, Ingelheim/Rhein, Germany.
D000595:Amino Acid Sequence; D002986:Clinical Trials as Topic; D006801:Humans; D008969:Molecular Sequence Data; D010960:Plasminogen Activators / Q000235:genetics*; D015202:Protein Engineering; D010959:Tissue Plasminogen Activator / Q000235:genetics*
D010960:Plasminogen Activators; C104096:TNK-tissue plasminogen activator; D010959:Tissue Plasminogen Activator