Table 2.

Summary of strategies used for SK modifications.

Modifications	Type	Examples	Mode of Action	References
Structural	Deletion	SK60-386 and SK143-386	Fibrin-specific activity, lower immunogenicity	[151]
	Substitution	Lys59 and Lys386 for glutamine	Increases half-life	[152]
Chemical	PEGylation	cysteine-specific thiol-mediated	Increases half-life and stability	[125]
	Acylation	Human plasminogen-bacterial streptokinase complex	Enhances specificity	[153]
Delivery system	Liposomal entrapment or encapsulation	PEG or chitosan nanoparticles, platelet directed liposomes	Increases half-life and stability, reduced immunogenicity, improved clot penetration properties	[154,155,156]
Domain fusion	Chimeric and conjugated protein	Fusion with epidermal growth factor 4, 5, and 6 domains of human thrombomodulin	Reduced risk of re-occlusion and hemorrhage	[157]