Engineering of Chinese hamster ovary cells for co-overexpressing MYC and XBP1s increased cell proliferation and recombinant EPO production.
Engineering of Chinese hamster ovary cells for co-overexpressing MYC and XBP1s increased cell proliferation and recombinant EPO production.
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DOI：
10.1038/s41598-023-28622-z
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发表时间：
2023-01-27
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
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作者：
提高中国仓鼠卵巢(CHO)细胞产生大量治疗性蛋白的细胞能力仍然是生物制药行业面临的主要挑战。在以前的研究中，我们观察到CHO细胞的表现与两种转录因子(TF)的表达密切相关，MYC和XBP1s。在这里，我们评估了过表达这两种转录因子对CHO细胞生产力的影响。为了解决这一目标，我们使用靶向整合的方法建立了一个产生EPO的细胞系(CHOEPO)，并随后对其进行了改造，使其能够同时过表达MYC和XBP1s(称为CHOCXEPO的细胞系)。过量表达MYC和XBP1s的细胞同时增加了活细胞密度和EPO产量，从而提高了培养的整体性能。这些改进是由于每种转铁蛋白对细胞行为(即MYC生长和XBP1s生产力)的单独影响。对CHOCXEPO细胞在不同环境条件(温度和葡萄糖浓度)下的评价表明，CHOCXEPO细胞在高糖浓度下提高了细胞生产率。这项研究显示了将基于转铁蛋白的细胞工程和工艺优化结合起来提高CHO细胞生产率的潜力。
Improving the cellular capacity of Chinese hamster ovary (CHO) cells to produce large amounts of therapeutic proteins remains a major challenge for the biopharmaceutical industry. In previous studies, we observed strong correlations between the performance of CHO cells and expression of two transcription factors (TFs), MYC and XBP1s. Here, we have evaluated the effective of overexpression of these two TFs on CHO cell productivity. To address this goal, we generated an EPO-producing cell line (CHOEPO) using a targeted integration approach, and subsequently engineered it to co-overexpress MYC and XBP1s (a cell line referred to as CHOCXEPO). Cells overexpressing MYC and XBP1s increased simultaneously viable cell densities and EPO production, leading to an enhanced overall performance in cultures. These improvements resulted from the individual effect of each TF in the cell behaviour (i.e., MYC-growth and XBP1s-productivity). An evaluation of the CHOCXEPO cells under different environmental conditions (temperature and media glucose concentration) indicated that CHOCXEPO cells increased cell productivity in high glucose concentration. This study showed the potential of combining TF-based cell engineering and process optimisation for increasing CHO cell productivity.
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影响因子：
2.9
作者：
Altamirano, C;Paredes, C;Gòdia, F
通讯作者：
Gòdia, F
DOI：
10.1158/1078-0432.ccr-12-3066
发表时间：
2013-04-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Cheng Z;Gong Y;Ma Y;Lu K;Lu X;Pierce LA;Thompson RC;Muller S;Knapp S;Wang J
通讯作者：
Wang J
DOI：
10.1007/978-1-4939-6972-2_9
发表时间：
2017-01-01
期刊：
HETEROLOGOUS PROTEIN PRODUCTION IN CHO CELLS: METHODS AND PROTOCOLS
影响因子：
--
作者：
Gallagher, Clair;Kelly, Paul S.
通讯作者：
Kelly, Paul S.
影响因子：
3.8
作者：
Ku, Sebastian C. Y.;Ng, Daphne T. W.;Chao, Sheng-Hao
通讯作者：
Chao, Sheng-Hao
影响因子：
3.7
作者：
Bedoya-López A;Estrada K;Sanchez-Flores A;Ramírez OT;Altamirano C;Segovia L;Miranda-Ríos J;Trujillo-Roldán MA;Valdez-Cruz NA
通讯作者：
Valdez-Cruz NA