高通量DNA测序技术在抗体新药研发中的应用  

Current applications of high-throughput DNA sequencing technology in antibody drug research

作　　者：余馨[1] 刘启刚[2] 王明蓉[2] 

机构地区：[1]中山大学药学院,广东广州510006 [2]中国医药集团总公司成都生物制品研究所有限责任公司,四川成都610023

出　　处：《药学学报》2012年第3期322-331,258,共10页Acta Pharmaceutica Sinica

基　　金：十二五重大新药创制项目(2011ZX09506-007);中国医药集团新产品基金资助项目(2011SW12-3)

摘　　要：自2005年首次报道了一种基于微乳液PCR技术的高通量DNA测序技术(high-throughput DNA se-quencing technology)以来,高通量DNA测序平台已经发展为基因组和各种基因文库序列检测的强大工具。大容量的抗体基因库是目前获得抗体新药的基础,高通量DNA测序技术为从海量的抗体基因库中快速发现功能抗体分子提供了可能。本文就近几年高通量DNA测序技术在抗体基因库的多样性分析,抗体CDR3区的高通量测序、频率分析、功能基因发现及各种展示技术与高通量DNA测序技术的对接应用等方面进行了综述,以期为抗体新药的研发提供一条新的技术路线。Since the publication of a high-throughput DNA sequencing technology based on PCR reaction was carried out in oil emulsions in 2005,high-throughput DNA sequencing platforms have been evolved to a robust technology in sequencing genomes and diverse DNA libraries.Antibody libraries with vast numbers of members currently serve as a foundation of discovering novel antibody drugs,and high-throughput DNA sequencing technology makes it possible to rapidly identify functional antibody variants with desired properties.Herein we present a review of current applications of high-throughput DNA sequencing technology in the analysis of antibody library diversity,sequencing of CDR3 regions,identification of potent antibodies based on sequence frequency,discovery of functional genes,and combination with various display technologies,so as to provide an alternative approach of discovery and development of antibody drugs.

关 键 词：高通量DNA测序技术 单链抗体库 抗体多样性 抗体CDR区 抗体新药 

分 类 号：Q755[生物学—分子生物学] R943[医药卫生—药剂学]