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bioRxiv · 10.1101/2024.05.25.595884

Mapping and Engineering Antibody-Antigen Interaction Landscapes for Systematic Affinity Enhancement

Chun, C.·Sohn, B.-K.·Jo, J. H.·Lee, J.·Yu, B.·Baek, M.·Yoon, T.-Y.
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Abstract

Antibodies, crucial in adaptive immunity, recognize antigens through specific interactions facilitated by Complementarity Determining Regions (CDRs), diversified via Variable-Diversity-Joining (VDJ) recombination. Traditional antibody development, limited by the scope of animal models and phage display libraries, captures a fraction of the potential antibody-antigen interactions. This underscores a gap in understanding antibody specificity and the relationship between antibody sequence and binding affinity. Here we introduce an approach using the Single-Protein Interaction Detection (SPID) platform, repurposed to systematically map local landscapes of antibody-antigen interactions with unprecedented depth and speed, aiming to rival the precision of methods like Surface Plasmon Resonance (SPR) and Bio-Layer Interferometry (BLI) while significantly boosting throughput. By editing CDR sequences and measuring effects on dissociation constants, we elucidated pathways for optimizing antibody affinity, enhancing predictive models for interactions. Our findings demonstrate the capability of the SPID platform to characterize thousands of variants weekly, offering a deeper insight into antibody-antigen interactions and advancing antibody development with finely-tuned affinities.

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Chun, C., Sohn, B.-K., Jo, J. H., Lee, J., Yu, B., Baek, M., Yoon, T.-Y.. 2024-05-30. Mapping and Engineering Antibody-Antigen Interaction Landscapes for Systematic Affinity Enhancement. https://doi.org/10.1101/2024.05.25.595884

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