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Engineering protein-based therapeutics through structural and chemical design

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  • Sasha B. Ebrahimi

    (Drug Product Development—Steriles, GlaxoSmithKline)

  • Devleena Samanta

    (The University of Texas at Austin)

Abstract

Protein-based therapeutics have led to new paradigms in disease treatment. Projected to be half of the top ten selling drugs in 2023, proteins have emerged as rivaling and, in some cases, superior alternatives to historically used small molecule-based medicines. This review chronicles both well-established and emerging design strategies that have enabled this paradigm shift by transforming protein-based structures that are often prone to denaturation, degradation, and aggregation in vitro and in vivo into highly effective therapeutics. In particular, we discuss strategies for creating structures with increased affinity and targetability, enhanced in vivo stability and pharmacokinetics, improved cell permeability, and reduced amounts of undesired immunogenicity.

Suggested Citation

  • Sasha B. Ebrahimi & Devleena Samanta, 2023. "Engineering protein-based therapeutics through structural and chemical design," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38039-x
    DOI: 10.1038/s41467-023-38039-x
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    1. Lucien F. Krapp & Fernando A. Meireles & Luciano A. Abriata & Jean Devillard & Sarah Vacle & Maria J. Marcaida & Matteo Dal Peraro, 2024. "Context-aware geometric deep learning for protein sequence design," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    2. Ziying Li & Kaiyuan Song & Yu Chen & Qijing Huang & Lujia You & Li Yu & Baiyang Chen & Zihang Yuan & Yaqin Xu & Yue Su & Lintai Da & Xinyuan Zhu & Ruijiao Dong, 2024. "Sequence-encoded bioactive protein-multiblock polymer conjugates via quantitative one-pot iterative living polymerization," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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