生物过程
腺相关病毒
HEK 293细胞
生化工程
下游(制造业)
计算生物学
过程(计算)
重组DNA
生物技术
计算机科学
生物
工程类
细胞培养
载体(分子生物学)
遗传学
古生物学
运营管理
基因
操作系统
作者
Jordan B. Joiner,Zhuangrong Huang,Kyle P. McHugh,Matthew Stebbins,Kathryn Aron,Michael Borys,Anurag Khetan
标识
DOI:10.1016/j.coche.2022.100823
摘要
With a high required dosing and relatively low process efficiency, providing recombinant adeno-associated virus (rAAV) supply for clinical trials and commercial demand remains challenging. One of the most widely used protocols to produce rAAVs is transient transfection of HEK293 cells. Despite decades of research, there are relatively few studies that focus on key factors in rAAV manufacturing processes. Only about 5–30% of rAAV capsids produced by cells contain the therapeutic element, causing low yields and an immense burden on downstream purification. Modeling approaches are valuable tools for bioprocess understanding and optimization. This review summarizes the recent mechanistic models of HEK293 metabolism and rAAV production. We also provide an outline for future development of hybrid mechanistic and data-driven models for understanding the underlying mechanisms and identifying critically relevant process variables.
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