ABSTRACT

Mammalian cell culture is necessary for the production of several complex biopharmaceutical products, including complex proteins such as monoclonal antibodies (MAbs), viral vaccines, and gene therapy vectors. Metabolic engineering of mammalian cells involves several unique challenges. Mammalian cells are slow growing, have complex nutritional requirements and are cumbersome to genetically engineer greatly reducing throughput. e key pathways involved in complex biopharmaceutical production-folding, glycosylation, and secretion-remain poorly characterized. Moreover, mammalian cells respond to most stresses by undergoing programmed cell death (apoptosis). Dealing with a complex system, we are nding a need for more sophisticated systems-level assessment and intervention tools to gain physiological insights into the dynamic interactions between large array of cellular components, and endeavoring to identify molecular mechanisms that confer cells with greater productivity and robustness.