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

被引：603

作者：

Xu, Xun ^{[1
]}

Nagarajan, Harish ^{[2
]}

Lewis, Nathan E. ^{[2
]}

Pan, Shengkai ^{[1
]}

Cai, Zhiming ^{[3
]}

Liu, Xin ^{[1
]}

Chen, Wenbin ^{[1
]}

Xie, Min ^{[1
]}

Wang, Wenliang ^{[1
]}

Hammond, Stephanie ^{[4
,5
]}

Andersen, Mikael R. ^{[6
]}

Neff, Norma ^{[7
,8
]}

Passarelli, Benedetto ^{[7
,8
]}

Koh, Winston ^{[7
,8
]}

Fan, H. Christina ^{[7
,8
]}

Wang, Jianbin ^{[7
,8
]}

Gui, Yaoting ^{[3
]}

Lee, Kelvin H. ^{[4
,5
]}

Betenbaugh, Michael J. ^{[9
,10
]}

Quake, Stephen R. ^{[7
,8
]}

Famili, Iman ^{[2
]}

Palsson, Bernhard O. ^{[2
,10
]}

Wang, Jun ^{[1
,11
,12
]}

机构：

[1] BGI Shenzhen, Shenzhen, Peoples R China

[2] GT Life Sci, San Diego, CA USA

[3] Peking Univ, Shenzhen PKU HKUST Med Ctr, Guangdong Key Lab Male Reprod Med & Genet, Shenzhen Hosp, Shenzhen, Peoples R China

[4] Univ Delaware, Dept Chem Engn, Newark, DE USA

[5] Univ Delaware, Delaware Biotechnol Inst, Newark, DE USA

[6] Tech Univ Denmark, Ctr Microbial Biotechnol, Dept Syst Biol, DK-2800 Lyngby, Denmark

[7] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA

[8] Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA

[9] Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD USA

[10] Tech Univ Denmark, Novo Nordisk Fdn, Ctr Biosustainabil, Horsholm, Denmark

[11] Univ Copenhagen, Novo Nordisk Fdn, Ctr Basic Metab Res, Copenhagen, Denmark

[12] Univ Copenhagen, Dept Biol, Copenhagen, Denmark

来源：

NATURE BIOTECHNOLOGY | 2011年 / 29卷 / 08期

基金：

美国国家卫生研究院;

关键词：

HERPES-SIMPLEX-VIRUS; HEPARAN-SULFATE; 6-SULFOTRANSFERASE; THERAPEUTIC ANTIBODIES; SIALIC-ACID; GLYCOSYLATION; EXPRESSION; CHO; SURFACE; PURIFICATION; RECEPTORS;

D O I：

10.1038/nbt.1932

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

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.

引用

页码：735 / U131

页数：8

共 55 条

[1] Trends in Glycosylation, Glycoanalysis and Glycoengineering of Therapeutic Antibodies and Fc-Fusion Proteins [J].