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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...
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Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...
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Using Human Differentially Expressed Gene Lists to Perform Downstream Pathway Enrichment Analysis and Target Prioritization
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CHO gene expression profiling in biopharmaceutical process analysis and design.

Jochen Schaub1, Christoph Clemens, Peter Schorn

  • 1Department of Biopharmaceutical Process Science, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany. jochen.schaub@boehringer-ingelheim.com

Biotechnology and Bioengineering
|September 25, 2009
PubMed
Summary

Gene expression profiling reveals significant differences between high and low titer biopharmaceutical production processes. This systems-level analysis enables knowledge-based optimization, such as improving lipid metabolism for increased product yields.

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Process Optimization using High Throughput Automated Micro-Bioreactors in Chinese Hamster Ovary Cell Cultivation
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Process Optimization using High Throughput Automated Micro-Bioreactors in Chinese Hamster Ovary Cell Cultivation

Published on: May 18, 2020

Area of Science:

  • Biotechnology
  • Molecular Biology
  • Bioprocess Engineering

Background:

  • Biopharmaceutical production relies on advancements in cell line development, media, and process optimization.
  • Genome-scale technologies offer system-level analysis for deeper understanding of protein production in mammalian cells.
  • This enables knowledge-based approaches for enhanced bioprocess optimization.

Purpose of the Study:

  • To investigate the utility of gene expression profiling for analyzing low titer (LT) versus high titer (HT) fed-batch processes.
  • To elucidate the biomolecular differences impacting recombinant protein production in Chinese Hamster Ovary (CHO) cells.
  • To explore the application of transcriptomics for rational bioprocess and media design.

Main Methods:

  • Utilized gene expression profiling (transcriptomics) to compare LT and HT fed-batch processes.
  • Analyzed IgG-producing CHO cell lines under different process conditions.
  • Performed detailed metabolic pathway analysis and functional enrichment analysis.

Main Results:

  • Significant differences in gene expression were observed between HT and LT processes, attributed to distinct chemically defined, serum-free media.
  • Gene expression patterns evolved over the time course of the fed-batch cultures.
  • Metabolic pathways and 14 biological functions, including cellular growth and death, were significantly affected.
  • Transcriptomic analysis informed rational media design, leading to a ~20% increase in product titer through lipid metabolism modification.

Conclusions:

  • Gene expression profiling is a valuable tool for analyzing mammalian cell biopharmaceutical processes.
  • Transcriptomics provides insights into metabolic and functional differences between varying production titers.
  • This approach facilitates knowledge-driven optimization strategies, including rational media design for improved product yields.