HEK293 Cells Overexpressing Nuclear Factor E2-Related Factor-2 Improve Expression of Recombinant Coagulation Factor VII

Abstract

The mammalian expression system plays a key central role in the production of therapeutic recombinant proteins. Conspicuously, any improvements in the expression system which lead to a higher expression level would have an impact especially in bio-pharmaceutical industries. In the current study, to take steps toward the improvement of expression of recombinant protein, first, we established a stable HEK293 cell line to overexpress a well-known cytoprotective and antioxidant gene, Nrf2. Next, we transiently expressed human recombinant coagulation factor VII, as an example of human recombinant protein, in the engineered-HEK293 cell line. Our results revealed that the established cells had a higher growth rate and were able to endure to UV-induced oxidative stress. Furthermore, within our expectation, our results revealed that the expression level of recombinant FVII in Nrf2-engineered HEK293 cells (315 ng/ml) was higher than the HEK293 (198 ng/ml) cells and it was functional in a coagulation test assay. Moreover, our new cell line could be a suitable cell to express other recombinant proteins especially for large-scale production of recombinant protein under other culture condition such as lower serum and suspension culture that imposed advantages especially in terms of cost benefits in bio-pharmaceutical industries.

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