Department of Chemical Engineering, Worcester Polytechnic Institute, 100 Institute Road, Worcester, MA 01609, United States.
Department of Chemical Engineering, Worcester Polytechnic Institute, 100 Institute Road, Worcester, MA 01609, United States.
Curr Opin Biotechnol. 2018 Oct;53:191-200. doi: 10.1016/j.copbio.2018.02.001. Epub 2018 Feb 19.
Pharmaceutical production hosts may be derived from almost any organism, from Chinese Hamster Ovary (CHO) cell lines to isolated actinomycetes. Each host can be improved, historically only through adaptive evolution. Recently, the maturation of organism engineering has expanded the available models, methods, and tools for altering host phenotypes. New tools like CRISPR-associated endonucleases promise to enable precise cellular reprogramming and to access previously intractable hosts. In this review, we discuss the most recent advances in engineering several types of pharmaceutical production hosts. These include model organisms, potential platform hosts with advantageous metabolism or physiology, specialized producers capable of unique biosynthesis, and CHO, the most widely used recombinant protein production host. To realize improved engineered hosts, an increasing number of approaches involving DNA sequencing and synthesis, host rewriting technologies, computational methods, and organism engineering strategies must be used. Integrative workflows that enable application of the right combination of methods to the right production host could enable economical production solutions for emerging human health treatments.
制药生产宿主可以来源于几乎任何生物体，从中国仓鼠卵巢（CHO）细胞系到分离的放线菌。每个宿主都可以进行改良，历史上仅通过适应性进化。最近，生物体工程学的成熟扩展了改变宿主表型的可用模型、方法和工具。新工具如 CRISPR 相关内切酶有望实现精确的细胞重编程，并能够访问以前难以处理的宿主。在这篇综述中，我们讨论了工程几种类型的制药生产宿主的最新进展。这些包括模式生物、具有有利代谢或生理学的潜在平台宿主、能够进行独特生物合成的专用生产者，以及 CHO，这是最广泛使用的重组蛋白生产宿主。为了实现改良的工程化宿主，必须使用越来越多涉及 DNA 测序和合成、宿主重写技术、计算方法和生物体工程策略的方法。能够将正确的方法组合应用于正确的生产宿主的综合工作流程，可以为新兴的人类健康治疗提供经济的生产解决方案。
