The genomic sequence of the chinese hamster ovary (CHO)-K1 cell line

Xun Xu; Harish Nagarajan; Nathan E. Lewis; Shengkai Pan; Zhiming Cai; Xin Liu; Wenbin Chen; Min Xie; Wenliang Wang; Stephanie Hammond; Mikael Rørdam Andersen; Norma Neff; Benedetto Passarelli; Winston Koh; H. Chritina Fan; Jianbin Wang; Yaoting Gui; Kelvin H. Lee; Michael Betenbaugh; Stephen R. Quake; Iman Famili; Bernhard O. Palsson; Jun Wang

doi:10.1038/nbt.1932

The genomic sequence of the chinese hamster ovary (CHO)-K1 cell line

Xun Xu, Harish Nagarajan, Nathan E. Lewis, Shengkai Pan, Zhiming Cai, Xin Liu, Wenbin Chen, Min Xie, Wenliang Wang, Stephanie Hammond, Mikael Rørdam Andersen, Norma Neff, Benedetto Passarelli, Winston Koh, H. Chritina Fan, Jianbin Wang, Yaoting Gui, Kelvin H. Lee, Michael Betenbaugh, Stephen R. QuakeIman Famili, Bernhard O. Palsson, Jun Wang

Genome Research and Molecular Bio Medicine

496 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Nature Biotechnology
Volume	29
Issue number	8
Pages (from-to)	735-741
Number of pages	7
ISSN	1087-0156
DOIs	https://doi.org/10.1038/nbt.1932
Publication status	Published - Aug 2011

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10.1038/nbt.1932

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Xu, X., Nagarajan, H., Lewis, N. E., Pan, S., Cai, Z., Liu, X., Chen, W., Xie, M., Wang, W., Hammond, S., Andersen, M. R., Neff, N., Passarelli, B., Koh, W., Fan, H. C., Wang, J., Gui, Y., Lee, K. H., Betenbaugh, M., ... Wang, J. (2011). The genomic sequence of the chinese hamster ovary (CHO)-K1 cell line. Nature Biotechnology, 29(8), 735-741. https://doi.org/10.1038/nbt.1932

Xu, X, Nagarajan, H, Lewis, NE, Pan, S, Cai, Z, Liu, X, Chen, W, Xie, M, Wang, W, Hammond, S, Andersen, MR, Neff, N, Passarelli, B, Koh, W, Fan, HC, Wang, J, Gui, Y, Lee, KH, Betenbaugh, M, Quake, SR, Famili, I, Palsson, BO & Wang, J 2011, 'The genomic sequence of the chinese hamster ovary (CHO)-K1 cell line', Nature Biotechnology, vol. 29, no. 8, pp. 735-741. https://doi.org/10.1038/nbt.1932

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title = "The genomic sequence of the chinese hamster ovary (CHO)-K1 cell line",

abstract = "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.",

author = "Xun Xu and Harish Nagarajan and Lewis, {Nathan E.} and Shengkai Pan and Zhiming Cai and Xin Liu and Wenbin Chen and Min Xie and Wenliang Wang and Stephanie Hammond and Andersen, {Mikael R{\o}rdam} and Norma Neff and Benedetto Passarelli and Winston Koh and Fan, {H. Chritina} and Jianbin Wang and Yaoting Gui and Lee, {Kelvin H.} and Michael Betenbaugh and Quake, {Stephen R.} and Iman Famili and Palsson, {Bernhard O.} and Jun Wang",

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AU - Xu, Xun

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AU - Lewis, Nathan E.

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AU - Cai, Zhiming

AU - Liu, Xin

AU - Chen, Wenbin

AU - Xie, Min

AU - Wang, Wenliang

AU - Hammond, Stephanie

AU - Andersen, Mikael Rørdam

AU - Neff, Norma

AU - Passarelli, Benedetto

AU - Koh, Winston

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AU - Wang, Jianbin

AU - Gui, Yaoting

AU - Lee, Kelvin H.

AU - Betenbaugh, Michael

AU - Quake, Stephen R.

AU - Famili, Iman

AU - Palsson, Bernhard O.

AU - Wang, Jun

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AB - 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.

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