Centre d'Immunologie Pierre Fabre, 5 Avenue Napoléon III, F74160, Saint-Julien-en-Genevois, France + 33 4 50 35 35 55 ; + 33 4 50 35 35 90 ;
Expert Opin Drug Discov. 2010 Jan;5(1):95-111. doi: 10.1517/17460440903413504. Epub 2009 Dec 1.
Therapeutic properties of many glycoproteins strongly depend on the composition of their glycans. Most of the current approved glycoproteins are produced in mammalian cell lines, which yield mixture of different glycoforms close to the human one but not fully identical. Glyco-engineering is being developed as a method to control the composition of carbohydrates. Many alternative glycoprotein productions systems are actively investigated including new-engineered yeast strains, as developed by GlycoFi, a biotech company fully owned by Merck & Co. since 2006.
The objectives of this opinion paper is to present a comprehensive overview of the technological breakthrough developed by GlycoFi to produce recombinant human proteins with controlled glycosylation patterns in yeast, in comparison to other glyco-engineering technologies and to discuss the application to large-scale manufacturing of biologicals.
Research papers and recent review articles on protein glycosylation and glyco-engineering, and in-depth search of the bibliography by the GlycoFi's research team, summary of recent meetings discussing the biosimilar topic were analyzed by the authors and will help the reader to gain insight in the field.
The glyco-engineering technology of the Pichia pastoris N-glycosylation pathway developed by GlycoFi allows producing human proteins with complex N-glycosylation modifications, which are similar to the ones performed in human. Moreover, more homogeneous glycosylation patterns are observed, as opposed to the large heterogeneity of glycan moieties that are found naturally in mammals or in other production systems such as Chinese hamster ovary and NS0 cell lines. These properties associated with the perspective to industrialize the manufacturing process of Pichia makes it a very promising expression system to produce large-scale batches of therapeutics at a lower cost.
许多糖蛋白的治疗特性强烈依赖于其聚糖的组成。目前大多数获得批准的糖蛋白都是在哺乳动物细胞系中生产的，这些细胞系产生的糖型混合物接近人类，但不完全相同。糖工程正在被开发为一种控制碳水化合物组成的方法。许多替代糖蛋白生产系统正在被积极研究，包括由 GlycoFi 开发的新型酵母菌株，GlycoFi 是一家生物技术公司，自 2006 年以来完全归 Merck & Co. 所有。
本观点文件的目的是全面概述 GlycoFi 开发的技术突破，即在酵母中生产具有控制糖基化模式的重组人蛋白，与其他糖工程技术进行比较，并讨论其在生物制品大规模生产中的应用。
作者分析了关于蛋白质糖基化和糖工程的研究论文和最新综述文章，以及 GlycoFi 研究团队对文献的深入搜索，总结了最近讨论生物类似物话题的会议，这将帮助读者深入了解该领域。
GlycoFi 开发的毕赤酵母 N-糖基化途径的糖工程技术允许生产具有复杂 N-糖基化修饰的人蛋白，这些修饰与人的相似。此外，观察到更均匀的糖型模式，而不是在哺乳动物或其他生产系统（如中国仓鼠卵巢和 NS0 细胞系）中自然发现的糖基部分的大异质性。与将毕赤酵母的制造工艺产业化的前景相关的这些特性使其成为一种非常有前途的表达系统，可以以更低的成本大规模生产治疗药物。
