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Systems biotechnology of mammalian cell factories

机译：哺乳动物细胞工厂的系统生物技术

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The increasing demand for recombinant therapeutic proteins has placed significant pressure on the biopharmaceutical industry to develop high-yielding, mammalian cell-based production systems. Current efforts to increase the production of recombinant proteins by mammalian host cells largely proceed by the lengthy screening of clonal derivatives rather than by directed genetic or metabolic engineering. However, the advent of systems biology has created a new set of tools that will ensure that future engineering strategies will be informed by an understanding of the genetic/regulatory and metabolic networks that determine the functional competence of mammalian cell factories in vitro. In this review we summarize recent systems-level studies that utilize genome-scale analytical tools to analyse the functional basis for key production process characteristics such as high cell-specific productivity, correct product processing and rapid cell proliferation in the in vitro environment. We also describe the use of high-throughput -omic technologies to investigate how mammalian cell factories respond to environmental and metabolic perturbation.
机译：对重组治疗性蛋白质的日益增长的需求已给生物制药行业带来巨大压力，以开发高产量，基于哺乳动物细胞的生产系统。当前增加哺乳动物宿主细胞产生重组蛋白产量的努力主要是通过冗长的克隆衍生物筛选而不是通过定向遗传或代谢工程进行的。但是，系统生物学的出现创造了一套新的工具，这些工具将确保对遗传/调控和代谢网络的了解，从而决定未来的工程策略，而遗传/调控和代谢网络将决定哺乳动物细胞工厂的体外功能能力。在这篇综述中，我们总结了最近的系统级研究，这些研究利用基因组规模的分析工具来分析关键生产过程特征的功能基础，例如在体外环境中的高细胞比生产率，正确的产品加工和快速细胞增殖。我们还描述了使用高通量组学技术研究哺乳动物细胞工厂如何应对环境和代谢扰动。

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