没有痕迹:多次淘汰CHO宿主细胞水解酶,以防止生物制品中的聚酸盐降解
Linus Weiß1, Nikolas Zeh2, Melanie Maier3
1Biberach University of Applied Sciences, Biberach, Germany; Cell Line Development, Boehringer Ingelheim Pharma GmbH & Co.KG, Biberach, Germany.
Trends in biotechnology
|May 29, 2025
概括
宿主细胞工程在中国仓鼠卵巢 (CHO) 细胞中去除了9个水解酶,显著减少了聚酸盐 (PS) 降解. 这一进步为更稳定的生物药物配方提供了一条道路,具有更长的保质期.
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:
- 聚酸盐 (PS) 通过宿主细胞蛋白 (HCP) 的酶降解是生物制药配方的一个关键问题,导致颗粒形成和产品保质期缩短.
- 中国仓鼠卵巢 (CHO) 细胞中的水解性HCP是PS降解的主要罪祸首.
研究的目的:
- 为了设计一种具有显著降低多酸盐降解活性的CHO宿主细胞系.
- 开发一种新的宿主细胞系,用于制造稳定的生物治疗药物.
主要方法:
- 已知降解PS的九种特定的CHO宿主细胞水解酶的基因组淘汰 (KO).
- 序列KO策略,包括删除两个大型基因集群.
- 通过KO进一步优化Bax和Bak1的亲细胞遗传基因.
主要成果:
- 生产可行的CHO宿主细胞系变体,具有多个酶KOs.
- 极大减少聚酸盐降解和整体水解活性.
- 已证明工程细胞系适用于重组治疗性葡萄糖蛋白的生产.
结论:
- 一个多酶KO CHO宿主细胞系有效地减少了多酸盐降解.
- 这种工程细胞系为开发稳定,寿命长的生物药物提供了有前途的战略.
- 为未来无需聚酸盐降解的生物制造工艺铺平了道路.
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