影响CHO细胞中重组治疗蛋白质质量的遗传因素
Chun-Liu Mi1,2, Shao-Lei Geng1,2, Jing-Wen Xue1,3
1International Joint Research Laboratory for Recombinant Pharmaceutical Protein Expression System of Henan, School of Basic Medicine, Xinxiang Medical University, Xinxiang 453003, Henan China.
Biomacromolecules
|December 11, 2025
概括
中国仓鼠卵巢 (CHO) 细胞中的基因工程改善了重组治疗蛋白质 (RTP) 的质量. 基因淘汰和过度表达等策略解决异质性,提高蛋白质的安全性和疾病治疗的疗效.
科学领域:
- 生物技术是生物技术.
- 生物制药制造业 生物制药制造业
- 分子生物学分子生物学
背景情况:
- 中国仓鼠卵巢 (CHO) 细胞是生产重组治疗性蛋白质 (RTP) 的主要系统.
- 确保RTP的高生产率和质量仍然是生物制药制造业的一个重大挑战.
- 关键的质量属性,如糖化,聚合,电荷变异和降解影响RTP的安全性,有效性和半衰期.
研究的目的:
- 审查影响CHO细胞RTP异质性的遗传因素.
- 讨论提高RTP质量和生产的创新策略.
- 为优化生物制药制造工艺提供见解.
主要方法:
- 对影响RTP质量属性的CHO细胞遗传修饰的分析.
- 对基因淘汰策略 (例如,FUT8,CPD,IDE) 的审查及其对特定质量属性的影响.
- 讨论基因过度表达技术 (例如,GRP78) 和宿主细胞工程方法.
主要成果:
- 基因修改可以显著改善RTP质量:FUT8淘汰会增强抗体依赖细胞细胞毒性 (ADCC),GRP78过度表达会减少聚合,CPD淘汰会提高电荷均性,IDE删除可以防止胰岛素降解.
- 定向基因工程提供了对关键质量属性的精确控制.
- 克里斯普尔/卡斯9和协同过度表达是宿主细胞工程的有希望的工具.
结论:
- 了解和操纵CHO细胞中的遗传因素对于产生高质量的RTP至关重要.
- 基因编辑和宿主细胞工程等创新策略是克服RTP异质性的关键.
- 优化的CHO细胞系将推动开发和制造更安全,更有效的生物治疗药物.
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