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相关概念视频

Bioreactor Controls-III01:22

Bioreactor Controls-III

Strain improvement is a foundational strategy in industrial microbiology aimed at maximizing microbial productivity, particularly because natural isolates typically yield commercially valuable products in very low concentrations. Although optimizing the culture medium and environmental conditions can improve yields, these adjustments are inherently limited by the organism’s genetic potential. As a result, the focus shifts toward genetic modifications to enhance biosynthetic capacity. The...
Upstream Processing01:27

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...
Production of Pharmaceuticals01:30

Production of Pharmaceuticals

Industrial insulin production uses genetically engineered E. coli expressing a proinsulin gene controlled by a tryptophan promoter and containing a methionine linker for later cleavage. The cells also carry ampicillin resistance for selective growth. Seed cultures are stored at −80 °C and production begins by thawing a small amount to inoculate starter cultures, which are progressively scaled to a 50,000-L bioreactor. In the bioreactor, E. coli grow in nutrient-rich media under sterile, tightly...
Downstream Processing01:29

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...

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A High-throughput Automated Platform for the Development of Manufacturing Cell Lines for Protein Therapeutics
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改进下游流程相关的可制造性基于蛋白质工程-一个可行性研究.

Florian Capito1, Ting Hin Wong1,2, Christine Faust3

  • 1Sanofi-Aventis Deutschland GmbH, CMC Microbial Platform Downstream Process Development Industriepark Höchst Frankfurt am Main Germany.

Engineering in life sciences
|September 5, 2024
PubMed
概括

通过调整生物治疗蛋白质的表面电荷,可以通过高效的净化来提高制造能力. 这一策略有助于去除宿主细胞蛋白 (HCP) 和病毒,降低制造成本.

关键词:
在Fc-fusion蛋白质中.离子交换色谱学 离子交换色谱学codon 的使用情况可以制造的可制造性.蛋白质表面电荷是蛋白质的表面电荷.

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科学领域:

  • 生物制药制造业 生物制药制造业
  • 蛋白质工程是指蛋白质的工程.
  • 下游加工 下游加工

背景情况:

  • 生物治疗药物的可制造性至关重要,它超越药物稳定性,包括净化效率.
  • 目前的文献往往忽视了下游工艺相关的可制造性,而是专注于配方.
  • 有效地去除与过程相关的杂质,如宿主细胞蛋白 (HCP) 和病毒,对于患者的安全至关重要.

研究的目的:

  • 研究修改生物治疗性蛋白质表面电荷的潜力,以提高下游净化.
  • 通过表面电荷适应来提高可制造性的概念证明.

主要方法:

  • 产生一种具有改变表面电荷特征的GLP1-受体-激动剂-Fc-域-FGF21融合蛋白的工程变体.
  • 使用离子交换染色学 (AEX) 评估净化效率.

主要成果:

  • 证明改变聚变蛋白的表面电荷分布可以实现高效的净化.
  • 展示了在高pH值下运行离子交换色谱的可行性,最大限度地提高了产品回收率.
  • 在净化过程中成功去除宿主细胞蛋白 (HCP) 和病毒.

结论:

  • 调整生物治疗蛋白质的表面电荷是改善可制造性的可行策略.
  • 这种方法有助于有效地去除关键杂质,如HCP和病毒.
  • 优化表面电荷可以导致更具成本效益的生物制药制造工艺.