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一个工作流程,用于开发模板辅助膜结晶的下游加工,用于单克隆抗体净化
Nazer Rajoub1, Charline J J Gerard1, Elvira Pantuso2
1CMAC Future Manufacturing Research Hub, c/o Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Technology and Innovation Centre, Glasgow, UK.
Nature protocols
|September 11, 2023
概括
模板辅助膜结晶为单克隆抗体 (mAb) 净化提供了可持续的,低成本的替代传统蛋白质A染色学. 这种新的方法使得在连续流程中实现了克尺度的生产,减少了对环境的影响和运营费用.
科学领域:
- 生物技术和生物加工
- 蛋白质结晶化 蛋白质结晶化
- 制药制造业 制药制造业 制药制造业
背景情况:
- 单克隆抗体 (mAbs) 是由中国大鼠卵巢 (CHO) 细胞系产生的关键生物制药.
- 传统的mAb净化依赖于昂贵的批量模式蛋白质A染色学,具有显著的化学和环境成本.
- 蛋白质A树脂再生需要大量使用化学物质,导致高运营费用和环境负担.
研究的目的:
- 开发一个系统和灵活的协议,用于一个强大的,经济的和可持续的mAb净化平台.
- 在传统的净化工艺中取代蛋白A亲和染色学阶段.
- 为了使毫克尺度的mAb生产在一个连续流系统.
主要方法:
- 使用模板辅助膜结晶作为蛋白质A染色体的替代品.
- 在膜内嵌入的结晶模板 (例如,聚乙烯化物与聚乙醇).
- 研究了最佳结晶条件,模板选择和mAb分离的膜选择.
主要成果:
- 证明单个结晶步骤可以取代传统的蛋白质A染色谱.
- 通过使用开发的膜结晶工艺,实现了在连续流中克尺度的mAb生产.
- 建立了一个系统的方法来优化mAb结晶参数.
结论:
- 模板辅助膜结晶为mAb净化提供了一种可行的,可持续的,经济高效的替代蛋白A染色学.
- 该协议促进了经济和环保的mAb净化平台的设计.
- 这种方法为生产单克隆抗体提供了可扩展的解决方案.
相关概念视频
Upstream Processing
Upstream processing represents a critical phase in biomanufacturing, wherein biological systems such as microorganisms, mammalian cells, or insect cells are cultivated to produce therapeutic proteins, vaccines, enzymes, or other biologically derived products. This phase encompasses all steps from the selection and genetic manipulation of the production organism to the cultivation of cells in bioreactors under tightly controlled environmental conditions.Host Selection and Genetic OptimizationThe...
Downstream Processing
Downstream processing begins once fermentation is complete and involves a series of steps to recover and purify products such as acids, vitamins, antibiotics, or proteins.Cell HarvestingFor example, for intracellular protein-based products, the first step is harvesting the cells. This is typically achieved using centrifugation or filtration to separate the cells from the liquid phase.Cell Disruption for Intracellular ProductsIf the target product is intracellular, the harvested cells must be...

