Protein and genetic engineering for novel and biogeneric thrombolytic protein constructs with clinical potential

Abstract

Thrombosis is known to be the underlying cause of all cardiovascular diseases such as myocardial infarction and stroke, for which most common therapy used is the infusion of thrombolytic drugs. For developing more effective thrombotic agents, we designed fusion construct, EGF_SAK, by incorporation of EGF4,5,6 domains of human thrombomodulin to N-terminal of staphylokinase, a promising fibrin specific thrombolytic to address the persistant clinical problem of reocclusion. EGF_SAK expressed in Pichia pastoris was characterized thereby confirming properties of clot lysis, fibrin specificity and prevention of clot re-occlusion. Another study included development of affordable biogeneric drug tPA by expression in Pichia in high yields. Together, these studies have led to the first but vital stages of new and biogeneric technologies for thrombolytic drugs with potential societal benefits. newline