氧化应激调控在CHO细胞培养中的应用

Applications of Oxidative Stress Regulation in CHO Cell Culture

抗体,作为应用广泛的一类蛋白质药物,主要通过大规模培养中国仓鼠卵巢(Chinese hamster ovary,CHO)细胞生产。但在CHO细胞培养过程中,细胞高水平代谢伴随着大量活性氧(Reactive Oxygen Species,ROS)生成,环境压力也可促进ROS产生。当抗氧化防御系统难以与其抗衡时将出现氧化应激,不利于细胞生长代谢和生产。本文综述了CHO细胞培养中氧化应激调控的三类工程学方法,即基因工程、抗氧化型添加剂和培养过程控制的应用,旨在为细胞培养时调控氧化还原平衡提供思路。

As a widely used therapeutic protein drugs,antibodies are mainly produced by Chinese hamster ovary(CHO)cell culture in large scales.In culture process,elevated reactive oxygen species(ROS)are produced along with enhanced cell metabolism.Besides,intracellular ROS will be formed under some stress conditions.The imbalance between intracellular ROS and antioxidant defense system will impose oxidative stress and be harmful to cell growth and productivity.Herein,three major engineering methods to alleviate oxidative stress in CHO cell culture,including cell engineering,antioxidants addition and culture process control,will be reviewed,aiming to provide strategies to regulate redox homeostasis during cell culture.