The emerging role of systems biology for engineering protein production in CHO cells.

The emerging role of systems biology for engineering protein production in CHO cells.
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DOI:
10.1016/j.copbio.2017.11.015
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发表时间:
2018-06
影响因子:
7.7
通讯作者:
Lewis NE
Lewis NE
中科院分区:
工程技术1区
文献类型:
--
作者:
Kuo CC;Chiang AW;Shamie I;Samoudi M;Gutierrez JM;Lewis NE

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为了满足对有效、安全和负担得起的蛋白质治疗剂不断增长的需求,数十年的努力旨在最大限度地提高CHO细胞中产生的重组蛋白质的数量和质量。生物加工创新和细胞工程努力提高了产品滴度;然而,未表征的细胞过程和基因调控机制仍然阻碍细胞生长,比生产率和蛋白质质量。在此,我们总结了系统生物学和数据驱动方法的最新进展,旨在揭示分子途径,细胞过程和外在因素(例如培养基补充)如何影响重组蛋白生产。特别是,随着CHO细胞的可用组学数据不断增长,预测模型和筛选将越来越多地用于揭示蛋白质生产的生物驱动因素,这些生物驱动因素可与新兴的基因组编辑技术一起使用,以合理地改造细胞,进一步控制许多生物药物的数量,质量和可负担性。
To meet the ever-growing demand for effective, safe, and affordable protein therapeutics, decades of intense efforts have aimed to maximize the quantity and quality of recombinant proteins produced in CHO cells. Bioprocessing innovations and cell engineering efforts have improved product titer; however, uncharacterized cellular processes and gene regulatory mechanisms still hinder cell growth, specific productivity, and protein quality. Herein we summarize recent advances in systems biology and data-driven approaches aiming to unravel how molecular pathways, cellular processes, and extrinsic factors (e.g. media supplementation) influence recombinant protein production. In particular, as the available omics data for CHO cells continue to grow, predictive models and screens will be increasingly used to unravel the biological drivers of protein production, which can be used with emerging genome editing technologies to rationally engineer cells to further control the quantity, quality and affordability of many biologic drugs.
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