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制造具有人类相容性修饰的复杂生物治疗蛋白质而被广泛用作生物制药细胞工厂。然而，它们在某些产品中的应用因蛋白质产量低而受到阻碍。许多研究旨在表征细胞瓶颈，以期提高蛋白质生产率，但当仅依靠传统方法时，潜在途径的复杂性和修饰的多样性使细胞工程变得复杂。将基于组学的系统方法纳入细胞工程中可以为细胞工厂的理想表型提供有价值的见解。在这里，我们讨论了提高哺乳动物细胞工厂蛋白质生产力的细胞工程策略，特别是 CHO 和 HEK293，以及用于指导细胞工程的全基因组筛选和多组学方法的机会和局限性。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，这将有助于有效的工程策略。