Staphylokinase

Staphylokinase is often compared to another fibrinolytic agent, streptokinase (SK). While SK is widely used due to its lower cost, it has several drawbacks, including significant allergenic potential, lack of fibrin selectivity, and transient hypotensive effects at high doses . In contrast, recombinant wild-type staphylokinase (wt-SAK) has shown higher fibrinolytic efficacy and lower fibrinogenolytic effects .

Recombinant staphylokinase (rSAK) is a modified version of the naturally occurring protein. The development of rSAK aims to enhance its efficacy and safety profile while maintaining a cost-effective production process. Pre-clinical data suggest that rSAK and its variants could be promising candidates for thrombolytic therapy .

One of the main challenges in developing rSAK has been the lack of an efficient expression system. Researchers have explored various methods to produce biologically active rSAK at high yields. For instance, a study described the development of an efficient fermentation process using the yeast Hansenula polymorpha. This process involved optimizing critical parameters such as temperature, pH, feeding strategy, and medium composition . The result was a high-yield production of non-glycosylated, biologically active rSAK .

Despite its potential, wt-SAK, as a heterologous (bacterial) protein, can produce immunogenic effects in animals, compromising its effectiveness upon repeated administration . To address this, researchers have investigated various rSAK variants with reduced immunogenicity. For example, a sequence-optimized SAK variant named THR174 showed improved properties in pre-clinical trials .