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Various secretory proteins are synthesized as precursors with additional N-terminal signal peptide. The signal peptide is cleaved off by signal peptidase once it has served its purpose of targeting the protein to, and importing it into, the ER. Recently, recombinant DNA research was used to study signal peptide and made it possible to show the efficient activity of a proposed signal peptide by fusing it to another protein. For this purpose, signal peptide of human erythropoietin was replaced with the signal peptide of human IL-2, then the hydrophobic domain of the signal peptide was modified. The nucleotide sequence of modified signal peptide was inserted directly upstream of the 5' end of the human erythropoietin gene by performing two rounds of amplification with pfu DNA polymerase. After transfection of HEK293 cells with these modified signal peptides, erythropoietin levels in medium were measured. As a result, extracellular levels of erythropoietin mediated by modified signal peptide were approximatly 2.6-fold higher than erythropoietin levels mediated by native erythropoietin signal peptide. And, we also could observe significantly increased protein secretion up to 5 times high by modifying the wild-type IL-2 signal peptide, in particular the hydrophobic domain. These findings indicate that increased hydrophobicity in their respective domain augments productivity of recombinant therapeutic proteins.