期刊
BIOTECHNOLOGY AND BIOENGINEERING
卷 118, 期 11, 页码 4305-4316出版社
WILEY
DOI: 10.1002/bit.27899
关键词
aggregation; charge variants; CHO cells; mAb quality attributes; multi-omics analysis; N-glycosylation; pH; systems biology
资金
- Merck Co. Inc.
- Biomedical Research Council of Agency of Science, Technology and Research (A*STAR), Singapore
This study investigated the impact of different pH set points on mAb production using longitudinal multi-omics profiling, revealing differential regulation of intracellular pathways, resulting in variations in productivity, titer, and quality profiles. Additionally, a time-dependent change in mAb N-glycosylation profiles, independent of pH, was identified due to protein accumulation in the endoplasmic reticulum disrupting cellular homeostasis over time. The findings provide a deeper understanding of intracellular processes in mAb-producing CHO cell line and can serve as a baseline for quality optimization and control in mAb production.
A robust monoclonal antibody (mAb) bioprocess requires physiological parameters such as temperature, pH, or dissolved oxygen to be well-controlled as even small variations in them could potentially impact the final product quality. For instance, pH substantially affects N-glycosylation, protein aggregation, and charge variant profiles, as well as mAb productivity. However, relatively less is known about how pH jointly influences product quality and titer. In this study, we investigated the effect of pH on culture performance, product titer, and quality profiles by applying longitudinal multi-omics profiling, including transcriptomics, proteomics, metabolomics, and glycomics, at three different culture pH set points. The subsequent systematic analysis of multi-omics data showed that pH set points differentially regulated various intracellular pathways including intracellular vesicular trafficking, cell cycle, and apoptosis, thereby resulting in differences in specific productivity, product titer, and quality profiles. In addition, a time-dependent variation in mAb N-glycosylation profiles, independent of pH, was identified to be mainly due to the accumulation of mAb proteins in the endoplasmic reticulum disrupting cellular homeostasis over culture time. Overall, this multi-omics-based study provides an in-depth understanding of the intracellular processes in mAb-producing CHO cell line under varied pH conditions, and could serve as a baseline for enabling the quality optimization and control of mAb production.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据