三种中国仓鼠卵巢（CHO）宿主细胞的比较蛋白质组学分析
Comparative Proteomic Analysis of Three Chinese Hamster Ovary (CHO) Host Cells.
作者信息
Xu Ningning, Ma Chao, Ou Jianfa, Sun Wanqi Wendy, Zhou Lufang, Hu Hui, Liu Xiaoguang Margaret
机构信息
Department of Biomedical Engineering, University of Alabama at Birmingham (UAB), 1670 University Blvd, Birmingham, AL 35233, USA.
Department of Chemical and Biological Engineering, The University of Alabama (UA), 245 7th Avenue, Tuscaloosa, AL 35401, USA.
出版信息
Biochem Eng J. 2017 Aug 15;124:122-129. doi: 10.1016/j.bej.2017.05.007. Epub 2017 May 15.
Chinese hamster ovary (CHO) cells have been widely used to express heterologous genes and produce therapeutic proteins in biopharmaceutical industry. Different CHO host cells have distinct cell growth rates and protein expression characteristics. In this study, the expression of about 1,307 host proteins in three sublines, i.e. CHO K1, CHO S and CHO/dihydrofolate reductase ( , were investigated and compared using proteomic analysis. The proteins involved in cell growth, glycolysis, tricarboxylic acid cycle, transcription, translation and glycosylation were quantitated using Liquid chromatography tandem-mass spectrometry (LC-MS/MS). The key host cell proteins that regulate the kinetics of cell growth and the magnitude of protein expression levels were identified. Furthermore, several rational cell engineering strategies on how to combine the desired features of fast cell growth and efficient production of therapeutic proteins into one new super CHO host cell have been proposed.
中国仓鼠卵巢（CHO）细胞已被广泛用于在生物制药行业中表达异源基因和生产治疗性蛋白质。不同的CHO宿主细胞具有不同的细胞生长速率和蛋白质表达特征。在本研究中，使用蛋白质组学分析研究并比较了三个亚系（即CHO K1、CHO S和CHO/二氢叶酸还原酶）中约1307种宿主蛋白的表达。使用液相色谱串联质谱（LC-MS/MS）对参与细胞生长、糖酵解、三羧酸循环、转录、翻译和糖基化的蛋白质进行定量。鉴定了调节细胞生长动力学和蛋白质表达水平大小的关键宿主细胞蛋白。此外，还提出了几种合理的细胞工程策略，即如何将快速细胞生长和高效生产治疗性蛋白质的所需特征结合到一个新的超级CHO宿主细胞中。
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