Strategies for Glycoengineering Therapeutic Proteins
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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Chemistry |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fchem.2022.863118/full |
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| author | Kris Dammen-Brower Kris Dammen-Brower Paige Epler Paige Epler Stanley Zhu Stanley Zhu Zachary J. Bernstein Zachary J. Bernstein Paul R. Stabach Demetrios T. Braddock Jamie B. Spangler Jamie B. Spangler Jamie B. Spangler Jamie B. Spangler Jamie B. Spangler Jamie B. Spangler Jamie B. Spangler Kevin J. Yarema Kevin J. Yarema |
| author_facet | Kris Dammen-Brower Kris Dammen-Brower Paige Epler Paige Epler Stanley Zhu Stanley Zhu Zachary J. Bernstein Zachary J. Bernstein Paul R. Stabach Demetrios T. Braddock Jamie B. Spangler Jamie B. Spangler Jamie B. Spangler Jamie B. Spangler Jamie B. Spangler Jamie B. Spangler Jamie B. Spangler Kevin J. Yarema Kevin J. Yarema |
| author_sort | Kris Dammen-Brower |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T21:43:10Z |
| format | Article |
| id | doaj.art-3775269b6eef48569bd03841192d16ba |
| institution | Directory Open Access Journal |
| issn | 2296-2646 |
| language | English |
| last_indexed | 2024-12-12T21:43:10Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Chemistry |
| spelling | doaj.art-3775269b6eef48569bd03841192d16ba2022-12-22T00:11:00ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462022-04-011010.3389/fchem.2022.863118863118Strategies for Glycoengineering Therapeutic ProteinsKris Dammen-Brower0Kris Dammen-Brower1Paige Epler2Paige Epler3Stanley Zhu4Stanley Zhu5Zachary J. Bernstein6Zachary J. Bernstein7Paul R. Stabach8Demetrios T. Braddock9Jamie B. Spangler10Jamie B. Spangler11Jamie B. Spangler12Jamie B. Spangler13Jamie B. Spangler14Jamie B. Spangler15Jamie B. Spangler16Kevin J. Yarema17Kevin J. Yarema18Translational Tissue Engineering Center, Johns Hopkins School of Medicine, Baltimore, MD, United StatesDepartment of Biomedical Engineering, The Johns Hopkins University, Baltimore, MD, United StatesTranslational Tissue Engineering Center, Johns Hopkins School of Medicine, Baltimore, MD, United StatesDepartment of Biomedical Engineering, The Johns Hopkins University, Baltimore, MD, United StatesTranslational Tissue Engineering Center, Johns Hopkins School of Medicine, Baltimore, MD, United StatesDepartment of Biomedical Engineering, The Johns Hopkins University, Baltimore, MD, United StatesTranslational Tissue Engineering Center, Johns Hopkins School of Medicine, Baltimore, MD, United StatesDepartment of Biomedical Engineering, The Johns Hopkins University, Baltimore, MD, United StatesDepartment of Pathology, Yale University School of Medicine, New Haven, CT, United StatesDepartment of Pathology, Yale University School of Medicine, New Haven, CT, United StatesTranslational Tissue Engineering Center, Johns Hopkins School of Medicine, Baltimore, MD, United StatesDepartment of Biomedical Engineering, The Johns Hopkins University, Baltimore, MD, United StatesDepartment of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD, United StatesDepartment of Oncology, Johns Hopkins School of Medicine, Baltimore, MD, United StatesBloomberg-Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, United StatesDepartment of Ophthalmology, Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD, United StatesDepartment of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United StatesTranslational Tissue Engineering Center, Johns Hopkins School of Medicine, Baltimore, MD, United StatesDepartment of Biomedical Engineering, The Johns Hopkins University, Baltimore, MD, United StatesAlmost 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.https://www.frontiersin.org/articles/10.3389/fchem.2022.863118/fullglycoengineeringpharmacodynamicspharmacokineticstherapeuticglycosylationN-glycans |
| spellingShingle | Kris Dammen-Brower Kris Dammen-Brower Paige Epler Paige Epler Stanley Zhu Stanley Zhu Zachary J. Bernstein Zachary J. Bernstein Paul R. Stabach Demetrios T. Braddock Jamie B. Spangler Jamie B. Spangler Jamie B. Spangler Jamie B. Spangler Jamie B. Spangler Jamie B. Spangler Jamie B. Spangler Kevin J. Yarema Kevin J. Yarema Strategies for Glycoengineering Therapeutic Proteins Frontiers in Chemistry glycoengineering pharmacodynamics pharmacokinetics therapeutic glycosylation N-glycans |
| title | Strategies for Glycoengineering Therapeutic Proteins |
| title_full | Strategies for Glycoengineering Therapeutic Proteins |
| title_fullStr | Strategies for Glycoengineering Therapeutic Proteins |
| title_full_unstemmed | Strategies for Glycoengineering Therapeutic Proteins |
| title_short | Strategies for Glycoengineering Therapeutic Proteins |
| title_sort | strategies for glycoengineering therapeutic proteins |
| topic | glycoengineering pharmacodynamics pharmacokinetics therapeutic glycosylation N-glycans |
| url | https://www.frontiersin.org/articles/10.3389/fchem.2022.863118/full |
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