通过数据驱动和模型导向分析,消除瓶和重新制定料介质,以改善CHO细胞生长和标位
Seo-Young Park1, Dong-Hyuk Choi1, Jinsung Song1
1School of Chemical Engineering, Sungkyunkwan University, Suwon, Gyeonggi-do, Republic of Korea.
Biotechnology journal
|August 22, 2023
概括
优化细胞培养基对于生物制药生产至关重要. 这项研究通过识别和调整关键氨基酸来增强料介质,显著改善了中国仓鼠卵巢 (CHO) 细胞培养中的细胞生长,寿命和抗体标位.
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:
- 哺乳动物细胞培养基和养策略对于生物制药生产至关重要.
- 特定的营养需求会影响细胞生长,蛋白质生产 (如抗体) 和代谢物概况.
- 之前的工作建立了一个基于数据的框架,用于在中国仓鼠卵巢 (CHO) 细胞培养中进行基底介质设计.
研究的目的:
- 评估和优化化学定义的料介质用于CHO-K1细胞中单克隆抗体的产生.
- 通过系统的,以模型为导向的方法,识别影响细胞培养性能的代谢瓶.
- 通过向关键氨基酸来重组料介质,以增强细胞生长,活力和生产力.
主要方法:
- 在ambr15生物反应器中对两个化学定义的料介质 (A和B) 的评估,使用单克隆抗体产生CHO-K1细胞系进行.
- 对代谢瓶的系统研究,重点关注三酸循环和氨基酸转移酶反应.
- 以数据为导向的分析,以确定用于料介质再配方的关键氨基酸.
主要成果:
- 料介质显著影响了细胞生长,寿命,活力,生产力和有毒代谢物生产.
- 与料B相比,缩料A在维持培养和实现高位数方面表现不佳.
- 将谷氨酸添加到料A和阿斯巴拉金添加到料B中缓解了代谢瓶.
- 用调整的氨基酸水平重新配制料成功增强了细胞生长,寿命和/或标位.
结论:
- 向性氨基酸补充剂 (谷氨酸和氨酸) 有效地克服了CHO细胞培养中的代谢限制.
- 优化料介质配方可以显著提高生物制药生产性能.
- 系统框架为设计和改进细胞培养介质提供了一种有价值的方法,用于增强生物处理.
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