生产 SARS-CoV-2 穗状病毒蛋白的 CHO 稳定池喂料批次工艺开发:通气条件和喂料策略的影响。

IF 2.5 3区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Sebastian-Juan Reyes, Phuong Lan Pham, Yves Durocher, Olivier Henry
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引用次数: 0

摘要

技术放大和转让是生物制造工艺开发的基础和关键部分。必须根据关键性能指标 (KPI) 选择重要的生物反应器流体动力学特性,如工作容积、顶置气体流速、容积功率输入 (P/V)、叶轮类型、搅拌方案、喷射曝气策略、喷射器类型和 kLa,以确保工艺放大和转移顺利无缝。找到合适的操作设定点和制定高效的进料方案以确保工艺的有效性和一致性至关重要。在这项研究中,详细介绍了在 1.8 升台式搅拌罐生物反应器中表达三聚 SARS-CoV-2 尖峰蛋白的积乳酸诱导型中国仓鼠卵巢 (CHO) 稳定池的工艺开发。研究了各种溶解氧水平和通气气帽,以确定它们对细胞生长和新陈代谢、培养寿命和终点产品滴度的影响。水动力条件调整到最佳区域后,研究人员探索了各种进料策略,以提高培养性能。测试了动态喂料,如根据当前培养体积、存活细胞密度(VCD)、摄氧率(OUR)和生物电容信号喂料,并与标准栓剂添加进行了比较。与定期栓剂喂养相比,动态喂养策略观察到存活细胞浓度积分(IVCC)(1.25 倍)和蛋白质产量(2.52 倍)的增加,以及更长的培养寿命(延长 5 天)。我们的研究强调了围绕新陈代谢相关信号(如 OUR 和生物电容信号)设计喂养策略的益处。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
CHO stable pool fed-batch process development of SARS-CoV-2 spike protein production: Impact of aeration conditions and feeding strategies.

Technology scale-up and transfer are a fundamental and critical part of process development in biomanufacturing. Important bioreactor hydrodynamic characteristics such as working volume, overhead gas flow rate, volumetric power input (P/V), impeller type, agitation regimen, sparging aeration strategy, sparger type, and kLa must be selected based on key performance indicators (KPI) to ensure a smooth and seamless process scale-up and transfer. Finding suitable operational setpoints and developing an efficient feeding regimen to ensure process efficacy and consistency are instrumental. In this investigation, process development of a cumate inducible Chinese hamster ovary (CHO) stable pool expressing trimeric SARS-CoV-2 spike protein in 1.8 L benchtop stirred-tank bioreactors is detailed. Various dissolved oxygen levels and aeration air caps were studied to determine their impact on cell growth and metabolism, culture longevity, and endpoint product titers. Once hydrodynamic conditions were tuned to an optimal zone, various feeding strategies were explored to increase culture performance. Dynamic feedings such as feeding based on current culture volume, viable cell density (VCD), oxygen uptake rate (OUR), and bio-capacitance signals were tested and compared to standard bolus addition. Increases in integral of viable cell concentration (IVCC) (1.25-fold) and protein yield (2.52-fold), as well as greater culture longevity (extension of 5 days) were observed in dynamic feeding strategies when compared to periodic bolus feeding. Our study emphasizes the benefits of designing feeding strategies around metabolically relevant signals such as OUR and bio-capacitance signals.

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来源期刊
Biotechnology Progress
Biotechnology Progress 工程技术-生物工程与应用微生物
CiteScore
6.50
自引率
3.40%
发文量
83
审稿时长
4 months
期刊介绍: Biotechnology Progress , an official, bimonthly publication of the American Institute of Chemical Engineers and its technological community, the Society for Biological Engineering, features peer-reviewed research articles, reviews, and descriptions of emerging techniques for the development and design of new processes, products, and devices for the biotechnology, biopharmaceutical and bioprocess industries. Widespread interest includes application of biological and engineering principles in fields such as applied cellular physiology and metabolic engineering, biocatalysis and bioreactor design, bioseparations and downstream processing, cell culture and tissue engineering, biosensors and process control, bioinformatics and systems biology, biomaterials and artificial organs, stem cell biology and genetics, and plant biology and food science. Manuscripts concerning the design of related processes, products, or devices are also encouraged. Four types of manuscripts are printed in the Journal: Research Papers, Topical or Review Papers, Letters to the Editor, and R & D Notes.
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