Engineering Therapeutic Proteins by Homology-Directed Mutagenesis and Deep Mutational Scanning - NCCR MSE

Engineering Therapeutic Proteins by Homology-Directed Mutagenesis and Deep Mutational Scanning

Protein engineering is the field of discovering novel, synthetic proteins or improving a known protein’s activity (e.g., antibody binding affinity for a particular antigen) by using either rational or directed evolution methods. A new method that combines elements of both rational design and directed evolution is deep mutational scanning, which combines high-throughput screening with next-generation DNA sequencing to assess the functional impact of mutations across the protein sequence.

This project aims to establish deep mutational scanning as a viable approach for engineering complex therapeutic proteins. As a starting point, we will use already existing therapeutic monoclonal antibodies against cancer targets, such as Herceptin, Avastin, Cetuximab, and Rituximab, and improve their binding affinity and expression stability. We will also use sequencing data and combine it with biophysical and structural modelling to determine if we can improve the functional scoring systems generated by deep mutational scanning.

Publications

D. M. Mason, S. Friedensohn, C. R. Weber, C. Jordi, B. Wagner, S. M. Meng, R. A. Ehling, L. Bonati, J. Dahinden, P. Gainza, B. CorreiaS. Reddy “Optimization of Therapeutic Antibodies by Predicting Antigen Specificity from Antibody Sequence Via Deep Learning“ Nat. Biomed. Eng. 2021. [DOI]

Project Leader

Bruno Correia
Sai Reddy

Persons involved

Pablo Gainza

Lab

Correia group @EPFL

Reddy group @D-BSSE