期刊
PROTEIN ENGINEERING DESIGN & SELECTION
卷 26, 期 2, 页码 151-163出版社
OXFORD UNIV PRESS
DOI: 10.1093/protein/gzs090
关键词
affinity maturation; antibody engineering; mammalian display; thermal stability
资金
- DARPA
Antibodies are important tools for a broad range of applications due to their high specificity and ability to recognize virtually any target molecule. However, in order to be practically useful, antibodies must be highly stable and bind their target antigens with high affinity. We present a combinatorial approach to generate high-affinity, highly stable antibodies through the design of stable frameworks, specificity grafting and maturation via somatic hypermutation in vitro. By collectively employing these methods, we have engineered a highly stable, high-affinity, full-length antibody with a T-m over 90C that retains significant activity after heating to 90C for 1 h, and has approximate to 95-fold improved antigen-binding affinity. The stabilized IgG framework is compatible with affinity maturation, and should provide a broadly useful scaffold for grafting a variety of complementarity-determining region loops for the development of stable antibodies with desired specificities.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据