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

BMC Biotechnology

Research Article

Patrick Gammell¹  Mark W Melville²  Mark Leonard²  Padraig Doolan³  Colin Clarke³  Niall Barron³  Michael Henry³  Joanne Keenan³  Finbar O'Sullivan³  Paula Meleady³  Martin Clynes³ 

[1] Bio-Manufacturing Sciences group, Pfizer, Inc, Grange Castle International Business Park, Clondalkin, Dublin 22, Ireland;Bioprocess R&D, Pfizer Inc, 1 Burtt Rd, 01810, Andover, MA, USA;National Institute for Cellular Biotechnology, Dublin City University, Dublin 9, Ireland;

关键词: Chinese Hamster Ovary Cell;    Chinese Hamster Ovary;    Clone 3B12;    Cell Line Pair;    Cell Line Sample;   

DOI  :  10.1186/1472-6750-11-78

 received in 2011-03-30, accepted in 2011-07-24,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundThe 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.ResultsProteomic 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.ConclusionThese 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.

【 授权许可】

CC BY   
© Meleady et al; licensee BioMed Central Ltd. 2011