抗体被广泛运用于科学研究、临床诊断和治疗的各个领域。建立在抗体展示系统（核糖体展示、噬菌体展示、酵母展示、细菌展示及哺乳动物细胞展示）基础上的抗体体外进化技术，是抗体技术领域的一次重大突破。将哺乳动物细胞抗体展示与体细胞高频突变结合，模拟哺乳动物 B 细胞内抗体亲和力成熟过程进行抗体体外进化，是极为巧妙和创新的策略。但该技术处于起步阶段，缺乏针对抗体基因库多样性产生效率的系统和深入研究。此外，哺乳动物细胞抗体进化平台一个很大优势是不仅能进行亲和力优化，还可针对抗体的其他特性如特异性，表达，热稳定性等进行优化。但这一优势还未被充分发掘。申请者所在实验室已经结合体细胞高频突变原理，建立了自己特有的哺乳动物细胞抗体人工进化平台。本项目中，我们将对此平台进行以下两方面的深入研究：1）抗体基因库多样性产生效率的研究；2）抗体亲和力和特异性同时优化的研究。以进一步完善该进化平台并拓展其应用。

Antibodies have a wide range of application in scientific research, clinical diagnosis and treatment. In vitro antibody evolution which was based on the in vitro antibody display, such as ribosome display, phage display, bacteria display, yeast display and mammal cell display, is a major breakthrough in the field of antibody technology. Coupling in vitro somatic hypermutation (SHM) with mammalian cell display, mimicking the process of antibody affinity maturation in mammalian B cells, offers an innovative technology in antibody discovery and optimization. However, this technology is at the initial stage and there is little information on the systemic study of the efficiency of the diversity generation of the antibody gene pool produced in the mammalian cells. Furthermore, as cell display technology, the mammalian cell antibody evolution platform can improve not only the affinity, but also many other properties such as specificity, mammalian cell expression level, or stability, but this advantage has not yet been fully exploited. Our lab has established the unique mammalian cell platform for antibody evolution coupling in vitro SHM with mammalian cell display. In this study, we will perform the following two in-depth study on our established platform, 1) the study on the efficiency of the diversity of the antibody gene pool produced in the mammal cells; 2) the study on the optimization of both the affinity and the specificity of the antibody using this platform. Our work will further improve this mammalian cell platform and expand its application.