Strategies for Glycoengineering Therapeutic Proteins

被引：32

作者：

Dammen-Brower, Kris ^{[1
,2
]}

Epler, Paige ^{[1
,2
]}

Zhu, Stanley ^{[1
,2
]}

Bernstein, Zachary J. ^{[1
,2
]}

Stabach, Paul R. ^{[3
]}

Braddock, Demetrios T. ^{[3
]}

Spangler, Jamie B. ^{[1
,2
,4
,5
,6
,7
,8
]}

Yarema, Kevin J. ^{[1
,2
]}

机构：

[1] Johns Hopkins Sch Med, Translat Tissue Engn Ctr, Baltimore, MD 21205 USA

[2] Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21218 USA

[3] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA

[4] Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD USA

[5] Johns Hopkins Sch Med, Dept Oncol, Baltimore, MD USA

[6] Johns Hopkins Sch Med, Sidney Kimmel Comprehens Canc Ctr, Bloomberg Kimmel Inst Canc Immunotherapy, Baltimore, MD USA

[7] Johns Hopkins Sch Med, Wilmer Eye Inst, Dept Ophthalmol, Baltimore, MD USA

[8] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA

来源：

FRONTIERS IN CHEMISTRY | 2022年 / 10卷

基金：

美国国家卫生研究院;

关键词：

glycoengineering; pharmacodynamics; pharmacokinetics; therapeutic; glycosylation; N-glycans; biomanufacturing; N-LINKED GLYCOSYLATION; HAMSTER OVARY CELLS; ACYL SIDE-CHAIN; SIALIC-ACID; INSECT CELLS; HUMAN CARBOXYLESTERASE-1; ANTIBODY GLYCOSYLATION; MANNOSE RECEPTOR; IMMUNOGLOBULIN-G; METABOLIC FLUX;

D O I：

10.3389/fchem.2022.863118

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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 (R), Poteligeo (R), Fasenra (TM), and Uplizna (R)). 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.

引用

页数：27

共 260 条

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