Debottlenecking protein secretion and reducing protein aggregation in the cellular host. (October 2018)

• Record Type: Journal Article
• Authors: Zhou, Yizhou; Raju, Ravali; Alves, Christina; Gilbert, Alan
• Is Part Of: Current opinion in biotechnology. Volume 53(2018)
• Page Start: 151
• Page End: 157
• Publication Date: 2018-10
• Subjects: Biotechnology -- Periodicals; 660.6
• DOI: 10.1016/j.copbio.2018.01.007
• Languages: English
• ISSNs: 0958-1669

Abstract

Highlights: The high-titer process can lead to inefficient protein secretion and aggregation. Genetic engineering has shown promise to tackle bottlenecks in secretion pathways. Media and process optimization are also effective strategies. Advances in omics and genome editing tools provide potential new avenues. Abstract : 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 10 g 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.