Development and characterization of a Chinese hamster ovary cell-specific oligonucleotide microarray

Melville, Mark; Doolan, Padraig; Mounts, William; Barron, Niall; Hann, L E; Leonard, Mark; Clynes, Martin; Charlebois, Tim

doi:10.1007/s10529-011-0628-2

Cited by 18 publications

(7 citation statements)

References 15 publications

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“…With this information, the use of comparative transcriptome analysis using completed CHO cell DNA microarray is facilitated, whereas research had been performed using incomplete CHO cell microarray [120,121] or non CHO derived DNA arrays [122,123] prior to the availability of CHO genomic information. In a recent study, data from large scale proteomic analysis was complemented by the genome data of CHO cells to discover a total of 6164 grouped proteins, which is an 8 fold increase over the identified proteins in the CHO cells proteome.…”

Section: Discussionmentioning

confidence: 99%

Advances in Mammalian Cell Line Development Technologies for Recombinant Protein Production

2013

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From 2006 to 2011, an average of 15 novel recombinant protein therapeutics have been approved by US Food and Drug Administration (FDA) annually. In addition, the expiration of blockbuster biologics has also spurred the emergence of biosimilars. The increasing numbers of innovator biologic products and biosimilars have thus fuelled the demand of production cell lines with high productivity. Currently, mammalian cell line development technologies used by most biopharmaceutical companies are based on either the methotrexate (MTX) amplification technology or the glutamine synthetase (GS) system. With both systems, the cell clones obtained are highly heterogeneous, as a result of random genome integration by the gene of interest and the gene amplification process. Consequently, large numbers of cell clones have to be screened to identify rare stable high producer cell clones. As such, the cell line development process typically requires 6 to 12 months and is a time, capital and labour intensive process. This article reviews established advances in protein expression and clone screening which are the core technologies in mammalian cell line development. Advancements in these component technologies are vital to improve the speed and efficiency of generating robust and highly productive cell line for large scale production of protein therapeutics.

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Section: Discussionmentioning

confidence: 99%

Advances in Mammalian Cell Line Development Technologies for Recombinant Protein Production

2013

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“…All cell lines were fed‐batch CHO K1, MAb‐producers and were sampled at days 3, 7, and 10 of culture. A total of 36 cell line samples, incorporating three replicates per experimental condition (four cell lines, three timepoints) were collected for transcriptional profiling using a proprietary (Wye2aHamster) CHO‐specific Affymetrix microarray [21]. All cultures were grown in proprietary serum‐free bioreactor suspension culture at 37°C on day 3 and thereafter temperature‐shifted to 31°C for the remaining two timepoints (days 7 and 10).…”

Section: Methodsmentioning

confidence: 99%

Microarray expression profiling identifies genes regulating sustained cell specific productivity (S‐Qp) in CHO K1 production cell lines

Doolan

Barron

Kinsella

et al. 2012

Biotechnology Journal

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Fed batch culture processes are often characterized by decreasing cell culture performance as the process continues, presumably through the depletion of vital nutrients and the accumulation of toxic byproducts. We have similarly observed that cellular productivity (Qp) often declines during the course of a fed batch process; however, it is not clear why some cell lines elicit this behavior, while others do not. We here present a transcriptomic profiling analysis of a phenotype of sustained Qp (S-Qp) in production Chinese hamster ovary (CHO) culture, in which a marked drop in Qp levels ("non-sustained" (NS) phenotype) in two cell lines irrespective of viability levels was compared to two cell lines that consistently displayed high Qp throughout the culture ("sustained" (S) phenotype). Statistical analysis of the microarray data resulted in the identification of 22 gene transcripts whose expression patterns were either significantly negatively or positively correlated with long-term maintenance of Qp over the culture lifespan. qPCR analysis of four of these genes on one of each (NS2, S2) of the cell lines examined by microarray analysis confirmed that two genes (CRYAB and MGST1) both replicated the microarray results and were differentially regulated between the NS and S phenotypes.

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“…Many of these techniques rely on the availability of known DNA sequences. Until the recent the genome sequencing of CHO cells, research was limited to incomplete CHO cell microarrays (Doolan et al, 2012; Melville et al, 2011; Wlaschin et al, 2005) and studies relying on murine DNA sequences (Yee et al, 2008b). Despite these limitations, a number of studies have been published profiling the transcriptional responses of CHO cells to different cell culture conditions (Baik et al, 2006; Clarke et al, 2011; Jing et al, 2012b; Kantardjieff et al, 2010; Kim et al, 2012a; Klausing et al, 2011; Nissom et al, 2006; Shen et al, 2010; Szperalski et al, 2011; Yee et al, 2008a).…”

Section: 'Omics Approaches Towards Cho Cell Engineeringmentioning

confidence: 99%

An 'omics approach towards CHO cell engineering

Datta

Linhardt

Sharfstein

2013

Biotech & Bioengineering

115

110

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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.

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Development and characterization of a Chinese hamster ovary cell-specific oligonucleotide microarray

Cited by 18 publications

References 15 publications

Advances in Mammalian Cell Line Development Technologies for Recombinant Protein Production

Advances in Mammalian Cell Line Development Technologies for Recombinant Protein Production

Microarray expression profiling identifies genes regulating sustained cell specific productivity (S‐Qp) in CHO K1 production cell lines

An 'omics approach towards CHO cell engineering

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