Cell Culture Development, Biogen, 225 Binney Street, Cambridge, MA 02142, United States.
Cell Culture Development, Biogen, 225 Binney Street, Cambridge, MA 02142, United States.
Curr Opin Biotechnol. 2018 Oct;53:151-157. doi: 10.1016/j.copbio.2018.01.007. Epub 2018 Feb 3.
Chinese hamster ovary (CHO) cells have been extensively used for industrial production of biotherapeutics. With advances in cell line development and process optimization, production levels of therapeutic proteins using the CHO expression system have increased to beyond 10g per liter scale. These high-titer processes could challenge the secretory capacity of CHO cells, which can result in degradation and aggregation of the protein of interest. This review discusses bottlenecks in the secretory pathway of CHO cells that lead to inefficient secretion and aggregation of proteins, and summarizes current strategies to tackle these bottlenecks. In addition, emerging technologies that facilitate better understanding of cellular mechanisms in protein production could provide new avenues to improve the secretion and quality of protein therapeutics.
中国仓鼠卵巢（CHO）细胞已被广泛用于生物治疗药物的工业生产。随着细胞系开发和工艺优化的进展，使用 CHO 表达系统生产治疗蛋白的水平已提高到每升 10 克以上。这些高滴度的工艺可能会挑战 CHO 细胞的分泌能力，从而导致目标蛋白的降解和聚集。本文综述了 CHO 细胞分泌途径中的瓶颈，这些瓶颈导致蛋白质分泌和聚集效率低下，并总结了目前解决这些瓶颈的策略。此外，促进更好地了解蛋白质生产中细胞机制的新兴技术可能为改善蛋白质治疗药物的分泌和质量提供新途径。
