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Related Concept Videos

In vitro Mutagenesis01:16

In vitro Mutagenesis

To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.

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Cell function profiling to assess clone stability.

Paul D Dobson1, Karen P Coss1, Carolanne Doherty1

  • 1Valitacell Ltd, NIBRT Foster Avenue, Mount Merrion, Blackrock, County Dublin, Ireland.

Biotechnology and Bioengineering
|March 18, 2020
PubMed
Summary
This summary is machine-generated.

Identifying stable Chinese hamster ovary (CHO) cell lines for bioproduction is challenging. A new assay, ChemStress® cell function profiling, monitors cellular pathways to find truly stable CHO clones, improving production reliability.

Keywords:
CHObioprocessingcell functionclone stabilitymonitoringphenotypingprocess

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Area of Science:

  • Biotechnology
  • Cell Line Development
  • Bioprocess Engineering

Background:

  • Identifying stable Chinese hamster ovary (CHO) cell lines is crucial for biopharmaceutical production but challenging.
  • Traditional stability trials focusing on high-level attributes can overlook underlying cellular instability, leading to the selection of suboptimal clones.
  • Assessing cellular pathway stability without increasing development costs is a significant hurdle.

Purpose of the Study:

  • To introduce and validate ChemStress® cell function profiling as a method to assess the internal stability of CHO cell clones.
  • To develop a novel stability metric for identifying genuinely stable CHO clones during stability trials.
  • To enable a deeper understanding of cell line stability beyond traditional high-level production attributes.

Main Methods:

  • ChemStress® cell function profiling, a multiwell plate-based assay, was employed using a panel of chemicals to simulate bioprocess stresses.
  • The assay challenged key cellular pathways in 131 CHO clones over 3 days of static culture.
  • Functional responses, including titer and growth, were measured, and a novel stability metric was defined.

Main Results:

  • ChemStress® profiling successfully monitored the stability of 131 CHO clones throughout real stability trials.
  • A novel stability metric was defined, enabling the identification of clones that remained unperturbed across multiple cellular functions.
  • The assay provided insights into internal cellular stability, going beyond superficial production metrics like titer.

Conclusions:

  • ChemStress® cell function profiling offers a cost-effective method to assess the underlying stability of CHO cell lines.
  • This approach allows for the selection of more robust and internally stable CHO clones for bioproduction.
  • Implementing this assay enhances the reliability of cell line development by looking beneath simple titer measurements to ensure true clone stability.