An 'omics approach towards CHO cell engineering

Abstract

Chinese hamster ovarian cells (CHO) cells have been extensively utilized for industrial production of biopharmaceutical products, such as monoclonal antibodies, human growth hormones, cytokines, and blood-products. Recent advances in recombinant DNA technology have resulted in the bioengineering of CHO cells that have robust gene amplification systems and can also be adapted to grow in suspension cultures. In parallel, recent advances in techniques and tools for decoding the CHO cell genome, transcriptome, proteome, and glycome have led to new areas of study for better understanding the metabolic pathways in CHO cells with the long-term goal of developing new biologics. This review paper discusses the recent advances in bioengineering strategies in CHO cell lines and the impact of the knowledge gained by CHO cell genomics, transcriptomics, and glycomics on the future of CHO-cell engineering.

Genomic landscapes of Chinese hamster ovary cell lines as revealed by the Cricetulus griseus draft genome

“…These resources have transformed our ability to study and modify the functions of human cells (e.g., cancer and human embryonic kidney cells) and other model organisms. Similar tools are becoming available for CHO cells 16,39,40 , but maximizing their potential requires a clear picture of the genomic landscape of CHO cells. Here, we demonstrated how the C. griseus genome can provide a sequence-level view of genomic heterogeneity between cell lines and yield a more comprehensive picture of the variants in a cell line of choice.…”

Proteomic Analysis of Bioreactor Cultures of an Antibody Expressing CHOGS Cell Line that Promotes High Productivity

“…Proteomics approaches for improving productivity in CHO cells have been used previously [28][29][30][31][32][33]; specifically, a proteomics approach was used by Yee et al [28] to study the effect of sodium butyrate on CHO cells, whereas Kaufmann et al studied the effect of lowering culture temperature on productivity [43]. While similar to these studies, there are several important features that distinguish the current study from the above published studies.…”

“…improving productivity has been embraced by a number of researchers [27,29,33]. Indeed, we have performed microarray analysis of selected myeloma production cell lines in order to determine if there is a correlation between expressions of one or more myeloma cellular genes to productivity [27].…”

“…'Global protein expression profiling using shotgun proteomics has been used in our laboratory to determine the protease profile of the CHO-GS host cell line [26] as well as gene expression profile of high producing cell lines [27]. Genome, transcriptome and proteome analysis of CHO cells have been reported multiple times [28][29][30][31][32][33]. Unfortunately, in a majority of these studies, the cells were cultured in shake-flasks prior to analysis.…”

Modulation of heparan sulfate biosynthesis by sodium butyrate in recombinant CHO cells

“…CHO cells have been extensively used in the biopharmaceutical industry for the production of glycoprotein biologics (Datta et al 2013). Hence, we hypothesized that they could also be used to produce GAG biopharmaceuticals, specifically HP.…”