The genomic sequence of the Chinese hamster ovary (CHO)-K1 cell line
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Open Access
- 1 August 2011
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Biotechnology
- Vol. 29 (8), 735-741
- https://doi.org/10.1038/nbt.1932
Abstract
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.Keywords
This publication has 51 references indexed in Scilit:
- Whole-genome molecular haplotyping of single cellsNature Biotechnology, 2011
- α V β 3 -integrin routes herpes simplex virus to an entry pathway dependent on cholesterol-rich lipid rafts and dynamin2Proceedings of the National Academy of Sciences of the United States of America, 2010
- Implications of the presence of N-glycolylneuraminic acid in recombinant therapeutic glycoproteinsNature Biotechnology, 2010
- Assembly algorithms for next-generation sequencing dataGenomics, 2010
- De novo assembly of human genomes with massively parallel short read sequencingGenome Research, 2009
- The growing scope of applications of genome-scale metabolic reconstructions using Escherichia coliNature Biotechnology, 2008
- The Galα1,3Galβ1,4GlcNAc-R (α-Gal) epitope: A carbohydrate of unique evolution and clinical relevanceBiochimica et Biophysica Acta (BBA) - General Subjects, 2008
- Production of recombinant protein therapeutics in cultivated mammalian cellsNature Biotechnology, 2004
- Genome sequence of the Brown Norway rat yields insights into mammalian evolutionNature, 2004
- Initial sequencing and comparative analysis of the mouse genomeNature, 2002