A modified protease that comprises a mutation at an amino acid position of 99, 171, 174, 180, 189, 190, 191, 215, 218 and 226 by chymotrypsin numbering in the wildtype protease scaffold. The protease scaffold can be u-PA or chymase. The protease target protein can be a cytokine, receptor, fusion protein, kinase or G protein coupled receptor. The modified protease can be used in treating a disease that respond to cleavage of the target protein selected from rheumatoid arthritis, sepsis, cancer, AIDS, respiratory tract infection, influenza, cardiovascular disease, inflammation, asthma, neurodegenerative disease, ischemic and reperfusion cell death, degenerative disorders, acute ischemic injury, infection by HIV, RSV or influenza.
