Maranga Luis, Cruz Pedro E, Aunins John G, Carrondo Manuel J T
Instituto de Biologia Experimental e Tecnológica/Instituto de Tecnologia Química e Biológica IBET/ITQB, Oeiras, Portugal.
Adv Biochem Eng Biotechnol. 2002;74:183-206. doi: 10.1007/3-540-45736-4_9.
In this paper the fundamental aspects of process development for the production of core and virus-like particles with baculovirus infected insect cells are reviewed. The issues addressed include: particle formation and monomer composition, chemical and physical conditions for optimal cell growth, baculovirus replication and product expression, multiplicity of infection strategy, and scale-up of the process. Study of the differences in the metabolic requirements of infected and non-infected cells is necessary for high cell density processes. In the bioreactor, the specific oxygen uptake rate (OURsp) plays a central role in process scale-up, leading to the specification of the bioreactor operational parameters. Shear stress can also be an important variable for bioreactor operation due to its influence on cell growth and product expression. The determination of the critical variables in process development is discussed, showing the relevance of the mathematical models that have been developed for the insect cells/baculovirus system in process implementation and control.
本文综述了利用杆状病毒感染昆虫细胞生产核心颗粒和病毒样颗粒过程开发的基本方面。所涉及的问题包括：颗粒形成和单体组成、细胞最佳生长的化学和物理条件、杆状病毒复制和产物表达、感染复数策略以及过程放大。对于高细胞密度过程，研究感染细胞和未感染细胞代谢需求的差异是必要的。在生物反应器中，比氧摄取率（OURsp）在过程放大中起着核心作用，从而确定生物反应器的操作参数。由于剪切应力对细胞生长和产物表达有影响，它也可能是生物反应器操作的一个重要变量。文中讨论了过程开发中关键变量的确定，展示了为昆虫细胞/杆状病毒系统开发的数学模型在过程实施和控制中的相关性。
