In pursuit of a super producer—alternative paths to high producing recombinant mammalian cells

Seth, Gargi; Charaniya, Salim; Wlaschin, Katie F.; Hu, Wei Shou

doi:10.1016/j.copbio.2007.10.012

Cited by 59 publications

(42 citation statements)

References 54 publications

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“…The desire to better understand the complex trait of hyper productivity has led to a number of studies comparing the transcriptome (Khoo et al, 2007;Seth et al, 2007b) or proteome (Alete et al, 2005;Dinnis et al, 2006;Seth et al, 2007b;Smales et al, 2004) of cell lines with varying productivities. With their large-scale surveying power, transcriptome and proteome analyses certainly hold promise for discerning the genotypic characteristics of hyper productivity (for review, see Gupta and Lee, 2007;Seth et al, 2007a).…”

Section: Introductionmentioning

confidence: 99%

Mining transcriptome data for function–trait relationship of hyper productivity of recombinant antibody

Charaniya

Karypis²,

2009

Biotech & Bioengineering

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In the past decade we have witnessed a drastic increase in the productivity of mammalian cell culture-based processes. High-producing cell lines that synthesize and secrete these therapeutics have contributed largely to the advances in process development. To elucidate the productivity trait in the context of physiological functions, the transcriptomes of several NS0 cell lines with a wide range of antibody productivity were compared. Gene set testing (GST) analysis was used to identify pathways and biological functions that are altered in high producers. Three complementary tools for GST-gene set enrichment analysis (GSEA), gene set analysis (GSA), and MAPPFinder, were used to identify groups of functionally coherent genes that are up- or downregulated in high producers. Major functional classes identified include those involved in protein processing and transport, such as protein modification, vesicle trafficking, and protein turnover. A significant proportion of genes involved in mitochondrial ribosomal function, cell cycle regulation, cytoskeleton-related elements are also differentially altered in high producers. The observed correlation of these functional classes with productivity suggests that simultaneous modulation of several physiological functions is a potential route to high productivity.

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Section: Introductionmentioning

confidence: 99%

Mining transcriptome data for function–trait relationship of hyper productivity of recombinant antibody

Charaniya

Karypis²,

2009

Biotech & Bioengineering

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“…At this, the main challenge is given by the fact that the flow of biological information and material flux in a cell occurs at many different levels and follows complex control mechanisms. Also, the genetic and physiological properties that make a certain cell a high producer cell are complex and not yet fully understood (Seth et al, 2007a).…”

Section: Introductionmentioning

confidence: 99%

CHO gene expression profiling in biopharmaceutical process analysis and design

Schaub¹,

Clemens²,

Schorn³

et al. 2009

Biotech & Bioengineering

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Increase in both productivity and product yields in biopharmaceutical process development with recombinant protein producing mammalian cells can be mainly attributed to the advancements in cell line development, media, and process optimization. Only recently, genome-scale technologies enable a system-level analysis to elucidate the complex biomolecular basis of protein production in mammalian cells promising an increased process understanding and the deduction of knowledge-based approaches for further process optimization. Here, the use of gene expression profiling for the analysis of a low titer (LT) and high titer (HT) fed batch process using the same IgG producing CHO cell line was investigated. We found that gene expression (i) significantly differed in HT versus LT process conditions due to differences in applied chemically defined, serum-free media, (ii) changed over the time course of the fed batch processes, and that (iii) both metabolic pathways and 14 biological functions such as cellular growth or cell death were affected. Furthermore, detailed analysis of metabolism in a standard process format revealed the potential use of transcriptomics for rational media design as is shown for the case of lipid metabolism where the product titer could be increased by about 20% based on a lipid modified basal medium. The results demonstrate that gene expression profiling can be an important tool for mammalian biopharmaceutical process analysis and optimization.

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“…Although single general effector genes seem to be part of the answer, multiple (general) effector genes are likely a more coherent and robust solution for increasing the secretory capacity (Harreither et al, 2015;Seth et al, 2007). In fact, multiple reactions within the biosynthetic pathway of MAb seem amenable for improvement (O'Callaghan et al, 2010).…”

Section: Concluding Remarks and Future Directionsmentioning

confidence: 99%

Improving the secretory capacity of Chinese hamster ovary cells by ectopic expression of effector genes: Lessons learned and future directions

Hansen

Pristovšek

Kildegaard

et al. 2017

Biotechnology Advances

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In pursuit of a super producer—alternative paths to high producing recombinant mammalian cells

Cited by 59 publications

References 54 publications

Mining transcriptome data for function–trait relationship of hyper productivity of recombinant antibody

Mining transcriptome data for function–trait relationship of hyper productivity of recombinant antibody

CHO gene expression profiling in biopharmaceutical process analysis and design

Improving the secretory capacity of Chinese hamster ovary cells by ectopic expression of effector genes: Lessons learned and future directions

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