ABSTRACT
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 154
Aggregation and protein misfolding are ubiquitous problems in production of protein therapeutics. Bacterial hosts are very efficient expression systems for production of recombinant protein products. However, overexpression of protein products in bacterial expression hosts generally yield large quantities of aggregated, inactive recombinant protein in the form of inclusion bodies. Other expression systems that utilize mammalian, fungal, or yeast cells may also produce either insoluble inclusion bodies, soluble aggregates, or improperly folded recombinant protein. Aggregation may also occur during processing due to filtration, agitation, or other processing steps. Aggregates are problematic because they are inactive and frequently cause immune reactions when injected into patients. Improperly folded protein, or misfolds, are usually considered impurities and must be purified from native protein, resulting in reduced process yields.
