There have been a number of studies published using expression microarray and proteomic technologies to gain insights into the biology of mammalian cell lines used for biopharmaceutical production (reviewed ). If there are to be considerable improvements in increasing cellular productivity, a fundamental understanding of the biology underpinning productivity of these cells is required. However, the bottlenecks in the cellular machinery for the efficient production of recombinant proteins are poorly understood. There has been considerable success in developing high-producing CHO cell culture processes using approaches such as optimisation of media formulation, improvements in expression vector design and also improvements in the design of bioreactors. 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.Ĭhinese hamster ovary (CHO) cells are the most widely used vehicle for the production of biopharmaceuticals due to their high productivity, robust nature, track record in industry, and their safety record. These proteins may have an important role in sustaining high productivity of recombinant protein over the duration of a fed-batch bioprocess culture. 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. 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.
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.
Ivcd cell culture full#
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.