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Briefings in Functional Genomics and Proteomics Advance Access originally published online on March 7, 2008
Briefings in Functional Genomics and Proteomics 2008 7(2):95-110; doi:10.1093/bfgp/eln012
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© The Author 2008. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

Special Issue Papers

Systems biotechnology of mammalian cell factories

Peter M. O'Callaghan and David C. James

Corresponding author. David C. James, Department of Chemical and Process Engineering, University of Sheffield, Mappin St., Sheffield S1 3JD, UK. Tel: +44 0114 222 7594; E-mail: d.c.james{at}sheffield.ac.uk

The increasing demand for recombinant therapeutic proteins has placed significant pressure on the biopharmaceutical industry to develop high-yielding, mammalian cell-based production systems. Current efforts to increase the production of recombinant proteins by mammalian host cells largely proceed by the lengthy screening of clonal derivatives rather than by directed genetic or metabolic engineering. However, the advent of systems biology has created a new set of tools that will ensure that future engineering strategies will be informed by an understanding of the genetic/regulatory and metabolic networks that determine the functional competence of mammalian cell factories in vitro. In this review we summarize recent systems-level studies that utilize genome-scale analytical tools to analyse the functional basis for key production process characteristics such as high cell-specific productivity, correct product processing and rapid cell proliferation in the in vitro environment. We also describe the use of high-throughput -omic technologies to investigate how mammalian cell factories respond to environmental and metabolic perturbation.

Keywords: systems biotechnology, mammalian cell culture, Chinese hamster ovary cells, cell engineering, recombinant protein, monoclonal antibody


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