Dicker Martina, Strasser Richard
a 1 University of Natural Resources and Life Sciences , Department of Applied Genetics and Cell Biology , Muthgasse 18, Vienna, Austria.
b 2 University of Natural Resources and Life Sciences, Department of Applied Genetics and Cell Biology , Muthgasse 18, Vienna, Austria +43 1 47654 6705 ; +43 1 47654 6392 ;
Expert Opin Biol Ther. 2015;15(10):1501-16. doi: 10.1517/14712598.2015.1069271. Epub 2015 Jul 14.
Glycans are increasingly important in the development of new biopharmaceuticals with optimized efficacy, half-life, and antigenicity. Current expression platforms for recombinant glycoprotein therapeutics typically do not produce homogeneous glycans and frequently display non-human glycans which may cause unwanted side effects. To circumvent these issues, glyco-engineering has been applied to different expression systems including mammalian cells, insect cells, yeast, and plants.
This review summarizes recent developments in glyco-engineering focusing mainly on in vivo expression systems for recombinant proteins. The highlighted strategies aim at producing glycoproteins with homogeneous N- and O-linked glycans of defined composition.
Glyco-engineering of expression platforms is increasingly recognized as an important strategy to improve biopharmaceuticals. A better understanding and control of the factors leading to glycan heterogeneity will allow simplified production of recombinant glycoprotein therapeutics with less variation in terms of glycosylation. Further technological advances will have a major impact on manufacturing processes and may provide a completely new class of glycoprotein therapeutics with customized functions.
聚糖在开发具有优化疗效、半衰期和抗原性的新型生物药物中日益重要。目前用于重组糖蛋白治疗药物的表达平台通常不会产生均一的聚糖,并且经常呈现非人类聚糖,这可能会导致不良副作用。为了规避这些问题,糖基工程已应用于包括哺乳动物细胞、昆虫细胞、酵母和植物在内的不同表达系统。
本综述总结了糖基工程的最新进展,主要聚焦于重组蛋白的体内表达系统。所强调的策略旨在生产具有确定组成的均一N-连接和O-连接聚糖的糖蛋白。
表达平台的糖基工程日益被视为改善生物药物的重要策略。对导致聚糖异质性的因素有更好的理解和控制,将使重组糖蛋白治疗药物的生产更加简化,糖基化方面的变化更少。进一步的技术进步将对制造工艺产生重大影响,并可能提供一类具有定制功能的全新糖蛋白治疗药物。