Adavanced Biotech Lab, Ipca Laboratories Ltd., Kandivali (West), Mumbai, India.
Enzyme Technology and Protein Bioinformatics Laboratory, Dept. of Microbiology, Maharshi Dayanand University, Rohtak, Haryana, India.
Appl Microbiol Biotechnol. 2018 Dec;102(24):10457-10468. doi: 10.1007/s00253-018-9430-6. Epub 2018 Oct 17.
Protein glycosylation is a very important quality attribute of any biopharmaceutical product as it affects the efficacy, serum half-life, and antigenicity of a molecule. The present expression hosts commercially utilized for a recombinant glycoprotein production generally cannot produce a desired and uniform glycan composition and generally exhibit non-human glycans that can lead to unwanted side effects. The authors provide a comprehensive review of various approaches which can be implemented to minimize the glycan heterogeneity for the production of the desired protein with improved glycoforms. The authors also describe that the industry standard expression systems such as mammalian, insect, and yeast are glycoengineered to produce human-like glycan composition of a recombinant product. This review summarizes the recent technologies used for the improvement of the glycan composition of the biotherapeutics, focusing largely on the selection of an appropriate expression host, glycoengineering, and upstream process optimization to control protein glycosylation and thus enhanced biological activity with fewer side effects. Here, we also suggest various approaches such as host and clone selection to achieve expected glycosylation in a recombinant protein. The cell culture, biochemical, and physical process parameters play a key role in the manufacturing of the desired glycoform of a therapeutic protein. Hence, these components are to be considered very carefully while developing such glycoproteins. Also, glycoengineering of production host to modulate the protein glycosylation is also recommended in the present review.
蛋白质糖基化是任何生物制药产品的一个非常重要的质量属性，因为它会影响分子的疗效、血清半衰期和抗原性。目前用于重组糖蛋白生产的商业表达宿主通常不能产生所需的和均匀的聚糖组成，并且通常表现出非人类聚糖，这可能导致不需要的副作用。作者全面回顾了各种可以用来最小化糖基化异质性的方法，以生产具有改善的糖型的所需蛋白质。作者还描述了行业标准的表达系统，如哺乳动物、昆虫和酵母，被糖基化工程化以产生重组产品的类似人类的聚糖组成。本综述总结了用于改善生物治疗剂糖基化组成的最新技术，主要侧重于选择合适的表达宿主、糖基化工程和上游工艺优化，以控制蛋白质糖基化，从而提高生物活性，减少副作用。在这里，我们还提出了各种方法，如宿主和克隆选择，以在重组蛋白中实现预期的糖基化。细胞培养、生化和物理过程参数在治疗性蛋白所需糖型的制造中起着关键作用。因此，在开发此类糖蛋白时，需要非常仔细地考虑这些因素。此外，本综述还建议对生产宿主进行糖基化工程以调节蛋白质糖基化。
