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Determination of High-affinity Antibody-antigen Binding Kinetics Using Four Biosensor Platforms
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Optimizing Antibody-Antigen Binding Affinities with the ADAPT Platform.

Traian Sulea1, Christophe Deprez1, Christopher R Corbeil1

  • 1National Research Council Canada, Human Health Therapeutics Research Centre, Montreal, QC, Canada.

Methods in Molecular Biology (Clifton, N.J.)
|November 8, 2022
PubMed
Summary
This summary is machine-generated.

The Assisted Design of Antibody and Protein Therapeutics (ADAPT) platform optimizes biologic affinity through computational prediction and experimental validation. This iterative approach rapidly identifies high-affinity mutants, achieving significant improvements.

Keywords:
Affinity maturationAntibody designConsensus scoringProtein engineeringVirtual mutagenesisZ-score

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Area of Science:

  • Biotechnology
  • Protein Engineering
  • Immunology

Background:

  • Antibody and biologic therapeutics require precise affinity modulation for efficacy.
  • Rational design of mutants is challenging due to combinatorial complexity.
  • Existing methods may lack efficiency in identifying optimal mutations.

Purpose of the Study:

  • To introduce the ADAPT platform for guided selection of antibody and protein mutants.
  • To enhance the robustness of mutant design through integrated computational and experimental approaches.
  • To achieve significant affinity improvements in biologics.

Main Methods:

  • Utilizing a consensus z-score from three scoring functions for affinity prediction.
  • Performing an initial exhaustive virtual single-mutant scan to identify hot spots.
  • Interleaving computational predictions with experimental validation for iterative design.

Main Results:

  • Identification of key mutation 'hot spots' through virtual screening.
  • Successful design and validation of single mutants with improved affinity.
  • Achieving 10- to 100-fold affinity improvements with 30-50 designed mutants.

Conclusions:

  • The ADAPT platform enables efficient and robust design of high-affinity biologics.
  • Iterative cycles of prediction and validation overcome design challenges.
  • This approach significantly accelerates the development of improved antibody and protein therapeutics.