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通过表观遗传转录沉默,SETDB1的淘汰促进了CHO细胞中的重组蛋白

Jiang-Tao Lu^1,2,3, Miao Zhang^1,2,3, Yan-Ping Gao^1,2,3

¹School of Pharmacy, Xinxiang Medical University, Xinxiang, 453003, Henan, China.

|July 27, 2025

概括

SET域分叉的素基甲转移酶1 (SETDB1) 调节中国仓鼠卵巢 (CHO) 细胞中复合蛋白质的产生. 抑制SETDB1增强蛋白质表达和染色体稳定性,为生物制造优化提供了战略.

科学领域:

生物技术是生物技术.
表观遗传学在表观遗传学中,表观遗传学是指表观遗传学.
哺乳动物细胞培养

背景情况:

中国仓鼠卵巢 (CHO) 细胞对于重组蛋白质生产至关重要,但面临表达不稳定性和异质性的挑战.
SET域二分化组胺氨酸甲基转移酶1 (SETDB1) 是一种表观遗传调节剂,但其在CHO细胞中的作用尚不清楚.

研究的目的:

研究SETDB1在调节CHO细胞中重组蛋白质生产中的作用.
探索SETDB1作为提高生物制造效率的目标.

主要方法:

对高产和低产CHO克隆的转录组分析.
在 CHO 细胞中进行 SETDB1 敲除 (SETDB1-KD).
用小分子SETDB1抑制剂进行治疗.
在延长培养期间评估复合抗体特异性生产力和染色体稳定性.

主要成果:

SETDB1表达与重组蛋白水平相反相关.
SETDB1-KD和SETDB1抑制剂显著提高了复合抗体特异性生产力.
通过SETDB1介导的表观遗传调节对于维持蛋白位和染色体稳定性至关重要.
SETDB1沉默诱导的转录重塑.

结论:

在CHO细胞中,SETDB1是重组蛋白生产和染色体稳定的关键调节者.
准SETDB1为优化工业生物制造中的重组蛋白质生产提供了一个有希望的策略.

关键词:

在CHO细胞中.表观遗传调节表观遗传调节基因组胺基因的修改在SETDB1中,我们可以使用SETDB1.转基因表达的表达方式

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