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Perfecting antibodies with language models

October 17, 2023
in Science
Perfecting antibodies with language models
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A general-purpose protein language model rapidly improves antibody properties.

Designing a therapeutic antibody is a complex puzzle. Each piece — from how well the antibody neutralizes the target to its specificity and stability — must fit together perfectly to create an equilibrated, functional medicine. Balancing these properties requires meticulous fine-tuning that often takes years of hard work. Writing in Nature Biotechnology, Hie et al.1 present a computational strategy to make this optimization process faster and cheaper. Their approach, demonstrated experimentally on seven clinical antibodies, exploits a general-purpose protein language model to propose beneficial mutations. As their data show, it holds enormous potential both for antibody therapeutics and for protein engineering more broadly.

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Fig. 1: Directed evolution with language models.

References

Hie, B. L. et al. Nat. Biotechnol. https://doi.org/10.1038/s41587-023-01763-2 (2023).

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Ferruz, N. et al. Nat. Machin. Intell. 4, 521–532 (2022).

Rives, A. et al. Proc. Natl Acad. Sci. USA 118, e2016239118 (2021).

Meier, J. et al. Adv. Neural Inf. Process. Syst. 34, 29287–29303 (2021).

Olsen, T. H. et al. Bioinform. Adv. 2, vbac046 (2022).

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Fowler, D. M. et al. Nat. Methods 11, 801–807 (2014).

Outeiral, C. & Deane, C. M. Preprint at bioRxiv https://doi.org/10.1101/2022.12.15.519894 (2022).

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Author information

Authors and Affiliations

Department of Statistics, University of Oxford, Oxford, UK

Carlos Outeiral & Charlotte M. Deane

Corresponding author

Correspondence to
Charlotte M. Deane.

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Cite this article

Outeiral, C., Deane, C.M. Perfecting antibodies with language models.
Nat Biotechnol (2023). https://doi.org/10.1038/s41587-023-01991-6

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Published: 16 October 2023

DOI: https://doi.org/10.1038/s41587-023-01991-6

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