Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Plant Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.
Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
Biotechnol Adv. 2020 May-Jun;40:107499. doi: 10.1016/j.biotechadv.2019.107499. Epub 2019 Dec 18.
Most of the recent approved therapeutic proteins are multi-subunit biologics, which need glycosylation and disulfide bridges for their correct conformation and biological functions. Currently, there exist many protein-based drugs that are mostly produced in the Chinese hamster ovary (CHO) cells. However, this expression system appears to associate with some limitations both in upstream and downstream processing steps, including low growth rate, sensitivity to different stresses and pathogens, and time-consuming purification processes. Some microalgae species offer a suitable expression system for the production of a wide range of recombinant proteins due to their key features such as fast-growing rate, having no common pathogens with the human, being used as the human food, and providing the possibility for the large-scale production in the closed/controlled bioreactors. More importantly, the protein biosynthesis machinery of some microalgae seems to be relatively similar to those of the human and animal cells. In fact, microalgae can assemble fully functional complex proteins that can be safely used in humans. In this review, we provide comprehensive insights into the currently used expression systems for the production of therapeutic proteins and discuss the essential features of the microalgae as a novel protein expression platform.
大多数最近批准的治疗性蛋白都是多亚基生物制剂,它们需要糖基化和二硫键来维持正确的构象和生物学功能。目前,有许多基于蛋白质的药物主要是在中华仓鼠卵巢 (CHO) 细胞中生产的。然而,这种表达系统似乎在上游和下游处理步骤中都存在一些限制,包括生长速度慢、对不同应激和病原体敏感以及耗时的纯化过程。由于某些微藻物种具有生长速度快、与人无共同病原体、可作为人类食物以及可在封闭/控制生物反应器中进行大规模生产等关键特征,因此为生产广泛的重组蛋白提供了合适的表达系统。更重要的是,某些微藻的蛋白质生物合成机制似乎与人类和动物细胞的机制较为相似。事实上,微藻可以组装出功能齐全的复杂蛋白,这些蛋白可以安全地用于人类。在这篇综述中,我们全面介绍了目前用于生产治疗性蛋白的表达系统,并讨论了微藻作为一种新型蛋白表达平台的重要特征。