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affinity maturation  affinity  antibody  form  full length  full  igg form  igg  improved affinity  length igg  length  potency  yeast display 
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Preview: Protein Engineering Design and Selection - Advance Access

Protein Engineering, Design and Selection Advance Access





Published: Wed, 21 Feb 2018 00:00:00 GMT

Last Build Date: Wed, 21 Feb 2018 06:47:15 GMT

 



Affinity maturation of an TpoR targeting antibody in full-length IgG form for enhanced agonist activity

Wed, 21 Feb 2018 00:00:00 GMT

Abstract
It has been observed that converting scFv formatted antibodies to full-length IgG often associates with loss of affinity. We aim to address this issue in this paper by establishing an integrated affinity maturation method applying yeast display technology platform. To demonstrate that, we employed a human thrombopoietin receptor targeting antibody named 3D9 which was identified previously from a combinational antibody library in scFv-Fc fusion protein form. We have observed that significant potency loss happened when 3D9 was transformed to full-length IgG form. In this study, we tested whether the potency of the full-length IgG can be improved by affinity maturation of 3D9 using a modified Fab yeast display platform. An efficient CDR3 targeted mutagenesis strategy was designed for Fab library with pre-designed CDR diversity. Next generation sequencing was also used for evaluation of the enrichment process and investigation of sequence-function relationship of the antibody. A variant with improved affinity and higher potency was identified. The study demonstrates that the strategy we used here are efficient for optimizing affinity and activity of full-length IgGs.