Increasing stability of antibody via antibody engineering Stability engineering on an anti-hVEGF
Antibody stability is very important for expression, activity, specificity and storage.The present knowledge of antibody structure has made it possible for a computer-aided molecule design to be used to optimize and increase antibody stability.Many computational methods have been built based on knowledge or structure, however, there hasn”t been a good integrated engineering system developed that combines these methods.In the current study, we designed an integrated computer-aided engineering protocol, which included several successful methods.Mutants were designed from different angles that affected stability and multiwall filters screening was used to improve the design accuracy.Using this protocol, the thermo-stability of an anti-hVEGF antibody was significantly improved.Nearly 40% of the single-point mutants proved to be more stable than the parent antibody and most of the mutations could be stacked effectively.The T50 also improved about 7 ℃ by combinational mutation of 7 sites in light chain and 3 sites in heavy chain.Our results indicate that this protocol is a very effective method for optimization of antibody structure, especially for improving thermo-stability.This protocol could also be used to enhance the stability of other antibodies.
computer-aided molecule design thermo-stability structure optimization mutant
Ming Liu
Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050
国内会议
苏州
英文
229-247
2014-10-26（万方平台首次上网日期，不代表论文的发表时间）