Advances in animal cell recombinant protein production: GS-NS0 expression system

Abstract

The production of recombinant proteins using mammalian cell expression systems is of growing importance within biotechnology, largely due to the ability of specific mammalian cells to carry out post-translational modifications of the correct fidelity. The Glutamine Synthetase-NS0 system is now one such industrially important expression system. Glutamine synthetase catalyses the formation of glutamine from glutamate and ammonia. NS0 cells contain extremely low levels of endogenous glutamine synthetase activity, therefore exogenous glutamine synthetase can be used efficiently as a selectable marker to identify successful transfectants in the absence of glutamine in the media. In addition, the inclusion of methionine sulphoximine, an inhibitor of glutamine synthetase activity, enables further selection of those clones producing relatively high levels of transfected glutamine synthetase and hence any heterologous gene which is coupled to it. The glutamine synthetase system technology has been used for research and development purposes during this decade and its importance is clearly demonstrated now that two therapeutic products produced using this system have reached the market place.