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Open Access Research article

Sustained productivity in recombinant Chinese Hamster Ovary (CHO) cell lines: proteome analysis of the molecular basis for a process-related phenotype

Paula Meleady1*, Padraig Doolan1, Michael Henry1, Niall Barron1, Joanne Keenan1, Finbar O'Sullivan1, Colin Clarke1, Patrick Gammell2, Mark W Melville3, Mark Leonard3 and Martin Clynes1

Author Affiliations

1 National Institute for Cellular Biotechnology, Dublin City University, Dublin 9, Ireland

2 Bio-Manufacturing Sciences group, Pfizer, Inc., Grange Castle International Business Park, Clondalkin, Dublin 22, Ireland

3 Bioprocess R&D, Pfizer Inc., 1 Burtt Rd, Andover, MA 01810, USA

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BMC Biotechnology 2011, 11:78  doi:10.1186/1472-6750-11-78

Published: 24 July 2011

Abstract

Background

The ability of mammalian cell lines to sustain cell specific productivity (Qp) over the full duration of bioprocess culture is a highly desirable phenotype, but the molecular basis for sustainable productivity has not been previously investigated in detail. In order to identify proteins that may be associated with a sustained productivity phenotype, we have conducted a proteomic profiling analysis of two matched pairs of monoclonal antibody-producing Chinese hamster ovary (CHO) cell lines that differ in their ability to sustain productivity over a 10 day fed-batch culture.

Results

Proteomic profiling of inherent differences between the two sets of comparators using 2D-DIGE (Difference Gel Electrophoresis) and LC-MS/MS resulted in the identification of 89 distinct differentially expressed proteins. Overlap comparisons between the two sets of cell line pairs identified 12 proteins (AKRIB8, ANXA1, ANXA4, EIF3I, G6PD, HSPA8, HSP90B1, HSPD1, NUDC, PGAM1, RUVBL1 and CNN3) that were differentially expressed in the same direction.

Conclusion

These proteins may have an important role in sustaining high productivity of recombinant protein over the duration of a fed-batch bioprocess culture. It is possible that many of these proteins could be useful for future approaches to successfully manipulate or engineer CHO cells in order to sustain productivity of recombinant protein.