哺乳动物细胞单抗生产的载体策略

Vector Strategies for Mammalian Cell Monoclonal Antibody Production

抗体药物在生物医药行业所占比重持续增加,抗体高效表达需要在合适的系统中进行,载体在这一过程中尤其重要,可以参与一系列抗体生产步骤:搭配合适的元件来筛选阳性、高表达克隆,选择轻重链的最优表达比例,稳定基因转录,增强翻译效率,对抗体进行正确的翻译后修饰等。对哺乳动物细胞表达载体构建所涉及的启动子、增强子、绝缘子、支架/基质附着区、信号肽、多顺反子策略、筛选系统、加尾信号以及用于增强目的基因表达所涉及的遗传工具等研究进展进行讨论,以期全面了解哺乳动物细胞重组抗体表达所涉及关键点,克服与之相关的挑战,进而推动抗体疗法发展。

The proportion of antibody drugs in the biomedical industry continues to grow.The efficient expression of antibodies must be carried out in suitable systems.The vector is particularly important in this process.It can be involved in a number of antibody production steps:matching appropriate elements to screen positive and highly expressed clones,selecting the optimal light/heavy chain expression ratio,stabilizing gene transcription,increasing translation efficiency,and performing correct post-translational modification of antibodies.In this article,we discuss the promoters,enhancers,insulators,scaffold/matrix attachment regions,signal peptides,multi-cistron strategies,screening systems,poly(A)signals and genetic tools used to enhance the expression of target genes involved in the construction of mammalian cell expression vectors.We aim to fully understand the key issues involved in recombinant antibody expression in mammalian cells,overcome the challenges,and advance the development of antibody therapy.