CADABRE
Financiado
Computational design of synthetic antibody repertoires for accelerated therapeut...
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 potent...
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 for expression in a phage-displayed repertoire. The repertoires will comprise hundreds of possible germline gene combinations, increasing the structural diversity relative to existing repertoires and the odds of obtaining diverse antibodies toward any antigen.2. Learning developability principles: High-throughput screening will identify heat-stable antibodies that are not polyreactive. Data from deep sequencing will be used to train an AI-based predictor of these properties that will be used to improve the repertoire and rank antibody candidates. We will iterate repertoire design, screening, and learning until we converge on a repertoire that exhibits excellent properties.3. Verifying relevance to therapeutic discovery: We will select antibodies that target antigens that represent relevant drug targets, verifying that the antibodies exhibit high stability, affinity, and developability.CADABRE combines the strengths of our protein-design methods (generating stable antibodies) and phage-display screening (unbiased binder selection). It will deepen our understanding of the biophysical underpinnings of antibody developability, develop new methods for ranking drug candidates, and generate new repertoires that will accelerate the discovery of life-saving therapeutic antibodies.
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Duración del proyecto: 59 meses
Fecha Inicio: 2024-08-01
Fecha Fin: 2029-07-31
Fecha Fin: 2029-07-31
Línea de financiación: concedida
El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2024-08-01
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
ERC-2023-ADG:
ERC ADVANCED GRANTS
Cerrada
hace 1 año
Presupuesto
El presupuesto total del proyecto asciende a
3M€
Líder del proyecto
WEIZMANN INSTITUTE OF SCIENCE
No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5