Chemical Engineering and Delaware Biotechnology Institute, University of Delaware, 15 Innovation Way, Newark, DE 19711, USA.
Biotechnol Adv. 2012 May-Jun;30(3):629-38. doi: 10.1016/j.biotechadv.2011.10.010. Epub 2011 Nov 4.
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.
明确鉴定宿主生物的基因组,包括测序、图谱绘制和注释其遗传密码,已成为生物技术领域的一个重点,旨在提高细胞培养生物加工的效率和理解。重组蛋白治疗药物主要在哺乳动物细胞中生产,构成了 1080 亿美元的全球市场。在生物生产过程中最常用的哺乳动物细胞系是中国仓鼠卵巢(CHO)细胞系,尽管在过去 25 年中产量有了很大提高,但对其潜在的分子和生理因素仍了解甚少。如果对 CHO 生物加工要素(例如细胞系选择、蛋白质生产以及工艺性能和产品规格的重现性)有充分的了解,将极大地提高对 CHO 生物加工的理解。本文综述了哺乳动物细胞培养在生物加工中的应用,获得 CHO 细胞系遗传序列的重要性,以及测序工作的现状。此外,还介绍了转录组学技术和基因表达工具,并探讨了旨在提高哺乳动物生物加工性能的基因组技术和应用的案例研究。最后,对基因组技术进步的未来影响进行了推测。