Fleishman Lab

Weizmann Institute

- · Israel

ERC-funded
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ERC Advanced Grant · 2023

Computational design of synthetic antibody repertoires for accelerated therapeutic discovery

Synthetic human antibody repertoires are an important source of therapeutics; however, antibodies often exhibit undesirable developability liabilities, such as low stability, solubility, and polyreactivity, that limit their potential as drug candidates. CADABRE will design next-generation repertoires comprising billions of diverse human antibodies that exhibit excellent developability properties, with the following aims: 1. Repertoire design: We will use our newly developed combinatorial Rosetta atomistic design paradigm to select human germline genes and design H3 multipoint mutants. These will combine into billions of diverse, low-energy, and foldable full-length antibody variable domains…

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