The secretory pathway - the key for unlocking the potential of Chinese hamster ovary cell factories for manufacturing therapeutic proteins.
The secretory pathway - the key for unlocking the potential of Chinese hamster ovary cell factories for manufacturing therapeutic proteins.
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分泌途径——释放中国仓鼠卵巢细胞工厂制造治疗性蛋白质潜力的关键。
DOI：
10.1080/07388551.2022.2047004
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发表时间：
2023
影响因子：
9
通讯作者：
Torres M
中科院分区：
文献类型：
--
作者：
Torres M
哺乳动物细胞工厂(尤其是CHO细胞系统)在生物制药的兴起中起着至关重要的作用。哺乳动物细胞已经划分了细胞器，在那里复杂的蛋白质网络在一条专门的生产管道--分泌途径--中制造高度复杂的生物药物。在生物生产方面，分泌途径的功能是细胞工厂生产这些改变生命的药物的有效性的关键。本文综述了分泌途径中涉及的分子组成和事件，并对限制治疗性蛋白产生的细胞内步骤以及工程CHO细胞分泌机制方面的成就进行了全面的总结。我们还研究了产生抗体的浆细胞(所谓的“专业”分泌细胞)，以探索其独特的分泌功能/特征的机制。这些理解为进一步加强目前用于制造下一代生物制药的CHO细胞生产平台提供了潜力。
Mammalian cell factories (in particular the CHO cell system) have been crucial in the rise of biopharmaceuticals. Mammalian cells have compartmentalized organelles where intricate networks of proteins manufacture highly sophisticated biopharmaceuticals in a specialized production pipeline – the secretory pathway. In the bioproduction context, the secretory pathway functioning is key for the effectiveness of cell factories to manufacture these life-changing medicines. This review describes the molecular components and events involved in the secretory pathway, and provides a comprehensive summary of the intracellular steps limiting the production of therapeutic proteins as well as the achievements in engineering CHO cell secretory machinery. We also consider antibody-producing plasma cells (so called “professional” secretory cells) to explore the mechanisms underpinning their unique secretory function/features. Such understandings offer the potential to further enhancement of the current CHO cell production platforms for manufacturing next generation of biopharmaceuticals.