The genomic sequence of the Chinese hamster ovary (CHO)-K1 cell line
Геномная последовательность клеточной линии яичника китайского хомячка (CHO)-K1
2011-07-31
SCID: 54.1/xdm9m82m
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CHO-K1 genome sequenceChinese hamster ovary cellsbiopharmaceutical protein productionglycosylation-associated genesviral susceptibility genes
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Abstract (AI)
Since 1987, immortalized cells from the ovary of a Chinese hamster have been the workhorse for producing recombinant therapeutics, including monoclonal antibodies, blood factors, hormones, growth factors and enzymes. Xu et al. provide the genome sequence of the ancestral CHO-K1 cell line, which should aid in the optimization of current production cell lines. Chinese hamster ovary (CHO)–derived cell lines are the preferred host cells for the production of therapeutic proteins. Here we present a draft genomic sequence of the CHO-K1 ancestral cell line. The assembly comprises 2.45 Gb of genomic sequence, with 24,383 predicted genes. We associate most of the assembled scaffolds with 21 chromosomes isolated by microfluidics to identify chromosomal locations of genes. Furthermore, we investigate genes involved in glycosylation, which affect therapeutic protein quality, and viral susceptibility genes, which are relevant to cell engineering and regulatory concerns. Homologs of most human glycosylation-associated genes are present in the CHO-K1 genome, although 141 of these homologs are not expressed under exponential growth conditions. Many important viral entry genes are also present in the genome but not expressed, which may explain the unusual viral resistance property of CHO cell lines. We discuss how the availability of this genome sequence may facilitate genome-scale science for the optimization of biopharmaceutical protein production.
Key Findings
1
A draft 2.45-Gb genomic sequence of the ancestral CHO-K1 cell line was assembled, containing 24,383 predicted genes.
2
Many important viral entry genes are present but unexpressed, potentially contributing to the unusual viral resistance of CHO cell lines.
3
Most assembled scaffolds were associated with 21 chromosomes using microfluidically isolated chromosomes, enabling chromosomal localization of genes.
4
Most human glycosylation-associated gene homologs are present in CHO-K1, but 141 are not expressed during exponential growth.
5
The genome sequence provides a foundation for genome-scale engineering and optimization of therapeutic protein production in CHO cells.
Research Object
the ancestral Chinese hamster ovary (CHO)-K1 cell line and its genome
Research Subject
the genomic organization, expression of glycosylation-associated and viral susceptibility genes, and implications for optimizing therapeutic protein production
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2011-07-31
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