Genomics in mammalian cell culture bioprocessing

被引:43
作者
Wuest, Diane M. [1 ]
Harcum, Sarah W. [2 ]
Lee, Kelvin H. [1 ]
机构
[1] Univ Delaware, Delaware Biotechnol Inst, Newark, DE 19711 USA
[2] Clemson Univ, Clemson, SC 29634 USA
基金
美国国家科学基金会;
关键词
Biologics; Genomics; Mammalian cell culture bioprocessing; Next-generation genomic sequencing; Proteomics; Recombinant DNA technology; Recombinant protein production; Transcriptomics; HAMSTER OVARY CELLS; GLYCOSYLATION GENE-EXPRESSION; ZINC-FINGER NUCLEASES; CHO-CELLS; RNA-SEQ; DIFFERENTIAL DISPLAY; SODIUM-BUTYRATE; TRANSCRIPTIONAL ANALYSIS; HYPEROSMOTIC PRESSURE; SEQUENCING TECHNOLOGY;
D O I
10.1016/j.biotechadv.2011.10.010
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
Explicitly identifying the genome of a host organism including sequencing, mapping, and annotating its genetic code has become a priority in the field of biotechnology with aims at improving the efficiency and understanding of cell culture bioprocessing. Recombinant protein therapeutics, primarily produced in mammalian cells, constitute a $108 billion global market. The most common mammalian cell line used in biologic production processes is the Chinese hamster ovary (CHO) cell line, and although great improvements have been made in titer production over the past 25 years, the underlying molecular and physiological factors are not well understood. Confident understanding of CHO bioprocessing elements (e.g. cell line selection, protein production, and reproducibility of process performance and product specifications) would significantly improve with a well understood genome. This review describes mammalian cell culture use in bioprocessing, the importance of obtaining CHO cell line genetic sequences, and the current status of sequencing efforts. Furthermore, transcriptomic techniques and gene expression tools are presented, and case studies exploring genomic techniques and applications aimed to improve mammalian bioprocess performance are reviewed. Finally, future implications of genomic advances are surmised. (C) 2011 Elsevier Inc. All rights reserved.
引用
收藏
页码:629 / 638
页数:10
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