Strategies for Glycoengineering Therapeutic Proteins

Kris Dammen-Brower; Paige Epler; Stanley Zhu; Zachary J Bernstein; Paul R Stabach; Demetrios T Braddock; Jamie B Spangler; Kevin J Yarema

doi:10.3389/fchem.2022.863118

Strategies for Glycoengineering Therapeutic Proteins

Front Chem. 2022 Apr 13:10:863118. doi: 10.3389/fchem.2022.863118. eCollection 2022.

Authors

Kris Dammen-Brower^{1

2}, Paige Epler^{1

2}, Stanley Zhu^{1

2}, Zachary J Bernstein^{1

2}, Paul R Stabach³, Demetrios T Braddock³, Jamie B Spangler^{1

2

4

5

6

7

8}, Kevin J Yarema^{1

2}

Affiliations

¹ Translational Tissue Engineering Center, Johns Hopkins School of Medicine, Baltimore, MD, United States.
² Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, MD, United States.
³ Department of Pathology, Yale University School of Medicine, New Haven, CT, United States.
⁴ Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD, United States.
⁵ Department of Oncology, Johns Hopkins School of Medicine, Baltimore, MD, United States.
⁶ Bloomberg-Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, United States.
⁷ Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD, United States.
⁸ Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States.

Abstract

Almost all therapeutic proteins are glycosylated, with the carbohydrate component playing a long-established, substantial role in the safety and pharmacokinetic properties of this dominant category of drugs. In the past few years and moving forward, glycosylation is increasingly being implicated in the pharmacodynamics and therapeutic efficacy of therapeutic proteins. This article provides illustrative examples of drugs that have already been improved through glycoengineering including cytokines exemplified by erythropoietin (EPO), enzymes (ectonucleotide pyrophosphatase 1, ENPP1), and IgG antibodies (e.g., afucosylated Gazyva^®, Poteligeo^®, Fasenra™, and Uplizna^®). In the future, the deliberate modification of therapeutic protein glycosylation will become more prevalent as glycoengineering strategies, including sophisticated computer-aided tools for "building in" glycans sites, acceptance of a broad range of production systems with various glycosylation capabilities, and supplementation methods for introducing non-natural metabolites into glycosylation pathways further develop and become more accessible.

Keywords: N-glycans; biomanufacturing; glycoengineering; glycosylation; pharmacodynamics; pharmacokinetics; therapeutic.

Publication types

Review

Abstract

Publication types

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