细胞内膜网膜的pH值升高与CHO细胞的高生长和bisAb聚合有关
Kevin S McFarland1,2, Kaitlin Hegadorn1, Michael J Betenbaugh2
1Cell Culture and Fermentation Sciences, BioPharmaceuticals Development R&D, AstraZeneca, Gaithersburg, USA.
Biotechnology and bioengineering
|October 22, 2024
概括
中国仓鼠卵巢 (CHO) 细胞培养中的细胞内pH值显著影响治疗蛋白质质量. 这项研究揭示了生物处理过程中的内等质网膜pH (pHER) 变化,与蛋白质聚合直接相关.
科学领域:
- 生物技术是生物技术.
- 细胞生物学 细胞生物学
- 生物工艺工程 生物工艺工程
背景情况:
- 中国仓鼠卵巢 (CHO) 细胞生物过程对于治疗性蛋白质生产至关重要.
- 细胞内条件,特别是pH值,影响蛋白质质量,但很难测量.
- 了解细胞内pH动态对于优化生物过程至关重要.
研究的目的:
- 在生物处理过程中调查中国大鼠卵巢 (CHO) 细胞内质网膜pH (pHER) 的变化.
- 确定乳酸代谢对pHER,细胞氧化还原和产品质量的影响.
- 为了确定细胞内pH值和治疗性蛋白质聚合之间的相关性.
主要方法:
- 将光pH敏感生物传感器集成到产生双特异抗体 (bisAb) 的CHO细胞系中.
- 在料批量和 perfusion 生物反应器中监测pHER,细胞氧化还原和产品质量.
- 分析乳酸代谢对细胞内参数的影响.
主要成果:
- pHER在指数增长过程中增加,并在静止阶段急剧下降.
- 在静止阶段观察到细胞pH调节的丧失,独立于氧化还原概况.
- 蛋白质总量水平与pHER的相关性最强.
结论:
- 细胞内膜网膜的pH值是影响CHO生物过程中治疗性蛋白质质量的关键因素.
- pHER动态为蛋白质聚合物形成提供了新的见解.
- 监测和控制pHER可以改善生物过程优化和细胞工程策略.
关键词:
两种特定蛋白质的生产生产.高含量查的高含量查细胞内pH值生物传感器氧化应激是一种氧化应激.perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion 是一种生物工艺的生物工艺,它可以通过输入或输送液体而形成.蛋白质聚合蛋白质的聚合物相关概念视频
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