Luo Haiyan, Wang Shuai, Chong Collin, Wang Lile, Sun Xiaojun, Guo Qian, Zhang Sam, Chen Xiaoyue, Zhou Hang, Zhou Weichang
WuXi Biologics, Cell Line Development, Mashan, Wuxi, China.
WuXi Biologics, Protein Science, Mashan, Wuxi, China.
Biotechnol Lett. 2025 May 8;47(3):54. doi: 10.1007/s10529-025-03573-9.
To develop a scale-down clone screening platform for the intensified fed-batch (IFB) process to allow efficient identification of high expressing clones fitting the IFB culture strategy in bioreactor.
Three monoclonal antibodies (mAbs) were used in the development and validation of the IFB specific clone screening platform for CHO cells. The IFB platform significantly improved titer levels, achieving an average titer of 8 g/L and the highest titer of 9.6 g/L. With similar cell viability, lactate profile and titer levels, both the spin tube model and the AMBR250 bioreactor system were effective in screening clones suitable for IFB process. The addition of aurintricarboxylic acid (ATA) and uridine in the process optimization led to a further increase in expression levels in both systems, achieving the highest titer of 12.2 g/L.
This IFB-process specific clone screening serves as an alternative platform for industry application that can increase the effectiveness and efficiency of screening high-expressing CHO cell lines for IFB production.
开发一种用于强化补料分批培养（IFB）工艺的小型化克隆筛选平台，以便在生物反应器中高效鉴定适合IFB培养策略的高表达克隆。
三种单克隆抗体（mAb）用于CHO细胞IFB特异性克隆筛选平台的开发和验证。IFB平台显著提高了滴度水平，平均滴度达到8 g/L，最高滴度为9.6 g/L。在细胞活力、乳酸谱和滴度水平相似的情况下，旋转管模型和AMBR250生物反应器系统在筛选适合IFB工艺的克隆方面均有效。在工艺优化中添加金精三羧酸（ATA）和尿苷导致两个系统的表达水平进一步提高，最高滴度达到12.2 g/L。
这种IFB工艺特异性克隆筛选作为一种工业应用的替代平台，可以提高筛选用于IFB生产的高表达CHO细胞系的有效性和效率。
