从组学到哺乳动物细胞工厂开发中的细胞机制
From omics to Cellular mechanisms in mammalian cell factory development.
作者信息
Samoudi Mojtaba, Masson Helen O, Kuo Chih-Chung, Robinson Caressa M, Lewis Nathan E
机构信息
Department of Pediatrics, University of California, San Diego, La Jolla, California, USA.
Department of Bioengineering, University of California, San Diego, La Jolla, California, USA.
出版信息
Curr Opin Chem Eng. 2021 Jun;32. doi: 10.1016/j.coche.2021.100688. Epub 2021 May 26.
Mammalian cells have been used widely as biopharmaceutical cell factories due to their ability to make complex biotherapeutic proteins with human-compatible modifications. However, their application for some products has been hampered by low protein yields. Numerous studies have aimed to characterize cellular bottlenecks in the hope of boosting protein productivity, but the complexity of the underlying pathways and the diversity of the modifications have complicated cell engineering when relying solely on traditional methodologies. Incorporating omics-based and systems approaches into cell engineering can provide valuable insights into desirable phenotypes of cell factories. Here, we discuss cell engineering strategies for enhancing protein productivity in mammalian cell factories, particularly CHO and HEK293, and the opportunities and limitations of the genome-wide screening and multi-omics approaches for guiding cell engineering. Systems biology strategies will also be discussed to show how they refine our understanding of the cellular mechanisms which will aid in effective engineering strategies.
哺乳动物细胞因其能够产生具有与人类兼容修饰的复杂生物治疗蛋白，而被广泛用作生物制药细胞工厂。然而，它们在某些产品上的应用受到了低蛋白产量的阻碍。许多研究旨在表征细胞瓶颈，以期提高蛋白质生产力，但仅依靠传统方法时，潜在途径的复杂性和修饰的多样性使细胞工程变得复杂。将基于组学和系统的方法纳入细胞工程，可以为细胞工厂的理想表型提供有价值的见解。在这里，我们讨论提高哺乳动物细胞工厂（特别是CHO和HEK293）蛋白质生产力的细胞工程策略，以及全基因组筛选和多组学方法在指导细胞工程方面的机遇与局限。还将讨论系统生物学策略，以展示它们如何完善我们对细胞机制的理解，这将有助于制定有效的工程策略。
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