title: Directing membrane chromatography to manufacture α1-antitrypsin from human plasma fraction IV.
abstract: The surging demand for plasma proteins, mainly driven by the growing market and the development of new therapeutic indications, is promoting manufacturers to improve the throughput of plasma proteins. Due to the inherent convective mass transfer, membrane chromatography has been proved to be an efficient approach for extracting a small amount of target proteins from large-volume feed. In this study, α1-antitrypsin (AAT) was extracted from human plasma fraction IV by a two-step membrane chromatography. An anion-exchange membrane chromatography (AEMC) was used to capture the plasma proteins in bind/elute mode, and the obtained effluent was further polished by a hydrophobic interaction membrane chromatography (HIMC) in flow-through mode. Under optimal conditions, the recovery and purity of AAT achieved 87.0% and 0.58 AAT/protein (g/g) by AEMC, respectively. After the precise polishing by HIMC, the purity of AAT was 1.22 AAT/protein (g/g). The comparison results showed that membrane chromatography outperformed column chromatography in both steps because of its high throughput. This two-step membrane chromatography could obtain an AAT recovery of 83.3% and an activity recovery of 91.4%. The outcome of this work not only offers an alternative process for protein purification from plasma, but also provides guidelines for manufacturing product from a large-volume feed with multi-components by membrane chromatography.
authors.affiliation: State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Jinxin
authors.initials: J
authors.lastname: Fan
authors.affiliation: State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China. Electronic address: jqluo@ipe.ac.cn.
authors.forename: Jianquan
authors.initials: J
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China.
authors.forename: Weijie
authors.initials: W
authors.lastname: Song
authors.affiliation: State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China.
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China. Electronic address: yhwan@ipe.ac.cn.
authors.forename: Yinhua
authors.initials: Y
authors.lastname: Wan
mesh_terms: D001798:Blood Proteins / Q000302:isolation & purification; D002846:Chromatography, Affinity; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D000515:alpha 1-Antitrypsin / Q000302:isolation & purification*
chemical_list: D001798:Blood Proteins; D000515:alpha 1-Antitrypsin
keywords: Hydrophobic interaction; Ion-exchange; Membrane adsorber; Membrane chromatography; Plasma protein; α(1)-Antitrypsin