Optimization of Cell Expression Systems to Maximize Production

While the initial goal of the discovery process is to express and purify the recombinant protein, without regard to cost and as quickly as possible, ultimately the production of a recombinant protein must be optimized to ensure that it can be produced at a reasonable cost. In most cases expression systems used to produce small quantities of recombinant protein for preliminary evaluation are not suitable to produce large quantities. Therefore, the gene inserted in the initial expression vectors must be systematically modified and recloned into vectors that can produce (1) a high yield of expressed protein, (2) stable host cell transfections, and (3) protein excretion.

Excretion of protein outside the cells allows harvesting without having to kill the cells. This process allows cells to continue to produce recombinant protein. Not all recombinant proteins can be made to be secreted from the cell. These proteins must be harvested after disruption of the cell membrane; in the process, fermentation is terminated and cells are destroyed. Isolation of proteins expressed intracellularly in cytoplasm or inclusion bodies is not only complex but also expensive. Harvesting an excreted protein from the culture medium significantly reduces the cost of making a recombinant protein. The optimization of recombinant expression systems is a continuous and important challenge in drug development and plays a key role in the profit margin of a drug company.

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