Applications

As a potent inhibitor of glutamine sythetase activity, this reagent has widely been used as a selection agent for plasmid integration in Chinese hamster ovary (CHO) and other mammalian cell lines. The growing demand for high yield cell banks for production of recombinant proteins for therapeutics has resulted in two major systems for selection of stable and active clones, Methotrexate selection of dihydrofolate reductase (DHFR) overexpressing cells and MSX selection of glutamine synthetase overexpressing cells. Cells are grown in the absence of glutamine in the media and inhibition of the endogenous activity of glutamine synthease results in cell death for cells lacking overexpression. The MSX-glutamine synthase selection mechanism provides benefits over that of the Methotrexate-DHFR system in that it typically requires a single amplification step and results in significant reduction of time to produce high stability, highly amplified clones.