Journal
NATURE BIOTECHNOLOGY
Volume 29, Issue 8, Pages 735-U131Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nbt.1932
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Funding
- National Natural Science Foundation (NSFC) of China [30725008]
- Shenzhen government [ZYC200903240077A]
- Guangdong Innovation Team
- National Basic Research Program of China (973 program) [2007CB815703]
- US National Institutes of Health (NIH) [2P20RR016472-10]
- National Cancer Institute [NIH R44CA139977]
- Danish Agency for Science, Technology and Innovation [07-015498]
- [CXB200903110066A]
- Novo Nordisk Fonden [NNF10CC1016517] Funding Source: researchfish
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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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