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透析滚轴式生物反应器可减少培养基使用量,延长单克隆抗体生产时间。

Dialysis rolled scaffold bioreactor allows extended production of monoclonal antibody with reduced media use.

机构信息

Division of Electrical Computer Engineering, Louisiana State University, Baton Rouge, Louisiana, USA.

出版信息

Biotechnol J. 2024 Aug;19(8):e2400249. doi: 10.1002/biot.202400249.

DOI:10.1002/biot.202400249
PMID:39212207
Abstract

Rapidly expanding biopharmaceutical market demands more cost-effective platforms to produce protein therapeutics. To this end, novel approaches, such as perfusion culture or concentrated fed-batch, have been explored for higher yields and lower manufacturing costs. Although these new approaches produced promising results, but their wide-spread use in the industry is still limited. In this study, a dialysis rolled scaffold bioreactor was presented for long-term production of monoclonal antibodies with reduced media consumption. Media dialysis can selectively remove cellular bio-wastes without losing cells or produced recombinant proteins. The dialysis process was streamlined to significantly improve its efficiency. Then, extended culture of recombinant CHO cells for 41 days was successfully demonstrated with consistent production rate and minimal media consumption. The unique configuration of the developed bioreactor allows efficient dialysis for media management, as well as rapid media exchange to harvest produced recombinant proteins before they degrade. Taken together, it was envisioned that the developed bioreactor will enable cost-effective and long-term large-scale culture of various cells for biopharmaceutical production.

摘要

快速扩张的生物制药市场需要更具成本效益的平台来生产蛋白类药物。为此,人们探索了新型方法,如灌流培养或浓缩分批补料培养,以提高产量并降低制造成本。尽管这些新方法取得了有希望的结果,但它们在工业中的广泛应用仍然受到限制。在这项研究中,提出了一种透析卷绕支架生物反应器,用于在降低培养基消耗的情况下长期生产单克隆抗体。培养基透析可以选择性地去除细胞生物废物,而不会损失细胞或产生的重组蛋白。优化了透析过程,以显著提高其效率。然后,成功地证明了重组 CHO 细胞的延长培养 41 天,具有一致的产率和最小的培养基消耗。所开发的生物反应器的独特结构允许进行有效的培养基管理透析,以及在产生的重组蛋白降解之前快速进行培养基交换以收获它们。总的来说,预计所开发的生物反应器将能够实现用于生物制药生产的各种细胞的经济高效且长期的大规模培养。

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