在CHO细胞中通过MAR增强的转位子载体与布拉斯蒂奇丁选择相结合,有效地产生复合mAbs
Xiaoyin Wang1,2, Xuelian Han1, Ting Liu1
1School of Basic Medical Sciences, Henan Medical University, Xinxiang 453003, China.
Acta biochimica et biophysica Sinica
|February 13, 2026
概括
一种基于MAR的新型piggyBac转位子系统显著增强了CHO细胞中复合抗体的产生. 这种方法提高了克隆选择效率,从而提高了治疗性抗体制造的产量和长期表达稳定性.
科学领域:
- 生物技术和生物加工
- 分子生物学分子生物学
- 细胞线工程 细胞线工程
背景情况:
- 再组合抗体是关键的治疗药物,其中中国子卵巢 (CHO) 细胞是主要的生产系统.
- 稳定,高表达性克隆的有效查对于工业抗体制造至关重要.
- 对于克隆选择的传统随机整合方法往往是低效和劳动密集的.
研究的目的:
- 开发一种新的,高效的策略,用于产生稳定,高产的CHO细胞克隆,用于重组抗体生产.
- 为了评估基于MAR的piggyBac (PB) 转位子系统与布拉斯蒂奇丁 (BSD) 选择相结合的疗效.
主要方法:
- 基于MAR的PB转位子系统与BSD选择用于CHO细胞系发展的整合.
- 将MAR-PB系统与随机集成向量和PB-only向量的比较.
- 评估抗体标位,特定蛋白质生产率 (Qp),mRNA表达,克隆比例和长期表达稳定性.
主要成果:
- 与随机整合相比,MAR-PB系统显著增加了抗体标位 (3.95至5.61倍) 和Qp (4.28至6.07倍).
- 与只有PB的载体相比,观察到增强的标位 (高达2.50倍) 和Qp (1.96至2.77倍).
- 该系统提高了高表达克隆的10倍以上,提高了体积产量,并确保了60多代的稳定表达.
结论:
- 基于MAR的PB转位子系统与BSD选择相结合,为产生高产和稳定的CHO细胞克隆提供了一种卓越的方法.
- 这种方法简化了重组抗体的生产,为生物制药行业提供了有价值的工具.
- 该系统对基因表达的影响表明DNA结合和转录调节通路的调节.
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