Oxford Expression Technologies Ltd, Bioinnovation Hub, Oxford, UK.
Department of Biological Medical Sciences, Oxford Brookes University, Oxford, UK.
Curr Issues Mol Biol. 2020;34:215-230. doi: 10.21775/cimb.034.215. Epub 2019 Jun 6.
Over 35 years since it was established to make recombinant proteins, the baculovirus expression vector system continues to develop and improve. Early systems for recombinant virus selection were laborious, but better methods were rapidly devised that enabled non-virologists to use baculovirus vectors successfully in a wide range of applications. These applications include multiple gene expression for complex molecules, production of adeno-associated virus-like particles for gene therapy, the use of baculovirus budded virus for the same purpose, numerous potential human and animal vaccines, and for other therapeutic proteins. A number of products for human and veterinary use are now on the market, which attests to the utility of the systems. Despite these successes, baculovirus vectors essentially remain in a relatively primitive state of development. Many proteins, particularly membrane-bound or secreted products, continue to be difficult to produce. Various research groups are working to identify potential areas of improvement, which if combined into an ideal vector might offer considerable advances to the system. This chapter will review some of the most recent reports and highlight those that might have generic application for recombinant protein synthesis in insect cells. We also summarize parallel developments in host cells used for baculovirus expression and how culture conditions can influence protein production.
自杆状病毒表达载体系统成立以来,已有 35 年的历史,它一直在不断发展和完善。早期的重组病毒选择系统非常繁琐,但很快就设计出了更好的方法,使非病毒学家能够成功地将杆状病毒载体应用于广泛的领域。这些应用包括用于复杂分子的多种基因表达、用于基因治疗的腺相关病毒样颗粒的生产、用于相同目的的杆状病毒芽生病毒的使用、许多潜在的人类和动物疫苗以及其他治疗性蛋白质。现在有一些用于人类和兽医用途的产品在市场上,这证明了该系统的实用性。尽管取得了这些成功,但杆状病毒载体本质上仍然处于相对原始的发展阶段。许多蛋白质,特别是膜结合或分泌产物,仍然难以生产。许多研究小组正在努力寻找潜在的改进领域,如果将这些领域结合到一个理想的载体中,可能会为该系统带来重大进展。本章将回顾一些最新的报道,并重点介绍那些可能对昆虫细胞中重组蛋白合成具有普遍应用的报道。我们还总结了用于杆状病毒表达的宿主细胞的平行发展以及培养条件如何影响蛋白质生产。