增加CHO细胞中治疗性蛋白质的产生:一种基于proline的选择策略,以提高生产力和产品质量
Bin Zhao1, Boya Zhang1, Yanshen Kang2
1Biologics Technical Development, Global Technical Operations & Manufacturing, BeOne Medicines (Shanghai) Co. Ltd, Shanghai, China.
Biotechnology progress
|November 17, 2025
概括
使用酵母PRO1和PRO2基因的新型普罗林选择系统增强了中国仓鼠卵巢 (CHO) 细胞系的发育,用于产生治疗性蛋白质,如单克隆抗体 (mAbs) 和双特异性抗体 (bsAbs). 这种方法有效地补充了现有的谷氨酸合成酶 (GS) 选择策略.
科学领域:
- 生物技术是生物技术.
- 细胞线发展发展 细胞线发展
- 蛋白质生产 蛋白质生产
背景情况:
- 中国仓鼠卵巢 (CHO) 细胞是生产治疗性重组蛋白质的主要宿主.
- 高效的细胞系开发对于满足生物制剂需求和降低制造成本至关重要.
- 传统的选择标记物,如DHFR,GS和抗生素耐药性基因被广泛使用.
研究的目的:
- 引入和评估一种普林选择系统,作为CHO细胞系发育的替代代代谢策略.
- 优化CHO细胞系开发平台,提高单克隆抗体 (mAbs) 和双特异性抗体 (bsAbs) 的产生.
- 为了研究林选择与谷氨胺合成酶 (GS) 选择的协同效应.
主要方法:
- 利用酵母PRO1和PRO2基因作为在proline选择系统中的选择标记.
- 集成PRO1和PRO2基因与GS基因在单个等离子体上进行组合选择.
- 优化了等离子体链的配置,并探索了调节蛋白的过度表达.
主要成果:
- 林选择有效地补充了GS选择,为mAbs和bsAbs建立高产CHO细胞系.
- 同时整合PRO1,PRO2和GS基因显著提高了不对称分子的生产力.
- 优化的等离子体配置和调节蛋白过度表达进一步提高了蛋白质产量和质量.
结论:
- 林选择系统为CHO细胞系的发展提供了一个高效和精简的策略.
- 结合普罗林和GS选择,为高质量的生物制品生产提供了一种一致的方法.
- 这一综合战略解决了制药行业对治疗性蛋白质日益增长的需求.
相关概念视频
01:22Bioreactor Controls-III
Strain improvement is a foundational strategy in industrial microbiology aimed at maximizing microbial productivity, particularly because natural isolates typically yield commercially valuable products in very low concentrations. Although optimizing the culture medium and environmental conditions can improve yields, these adjustments are inherently limited by the organism’s genetic potential. As a result, the focus shifts toward genetic modifications to enhance biosynthetic capacity. The...
01:27Upstream Processing
Upstream processing represents a critical phase in biomanufacturing, wherein biological systems such as microorganisms, mammalian cells, or insect cells are cultivated to produce therapeutic proteins, vaccines, enzymes, or other biologically derived products. This phase encompasses all steps from the selection and genetic manipulation of the production organism to the cultivation of cells in bioreactors under tightly controlled environmental conditions.Host Selection and Genetic OptimizationThe...
01:30Production of Pharmaceuticals
Industrial insulin production uses genetically engineered E. coli expressing a proinsulin gene controlled by a tryptophan promoter and containing a methionine linker for later cleavage. The cells also carry ampicillin resistance for selective growth. Seed cultures are stored at −80 °C and production begins by thawing a small amount to inoculate starter cultures, which are progressively scaled to a 50,000-L bioreactor. In the bioreactor, E. coli grow in nutrient-rich media under sterile, tightly...