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Finite Element Modelling of a Cellular Electric Microenvironment
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Published on: May 18, 2021

Dynamic model for CHO cell engineering.

Ryan P Nolan1, Kyongbum Lee

  • 1Department of Chemical & Biological Engineering, Tufts University, 4 Colby Street, Medford, MA 02155, USA.

Journal of Biotechnology
|January 31, 2012
PubMed
Summary
This summary is machine-generated.

Optimizing Chinese hamster ovary (CHO) cell fed-batch processes requires balancing cell line modifications and process parameters. Dynamic modeling identified that targeting lactate-producing enzymes, alongside process adjustments, can significantly enhance antibody production.

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Area of Science:

  • Biotechnology
  • Metabolic Engineering
  • Bioprocess Engineering

Background:

  • Industrial Chinese hamster ovary (CHO) cell fed-batch processes achieve gram-per-liter recombinant protein titers.
  • Improvements stem from separate advances in process and cell line development.
  • Dynamic nature of fed-batch processes complicates model-based metabolic engineering.

Purpose of the Study:

  • To develop a dynamic model for CHO cell metabolism.
  • To simultaneously identify process and cell modifications for improved antibody production.
  • To explore the interplay between metabolic engineering targets and process parameters.

Main Methods:

  • Utilized a dynamic model of CHO cell metabolism.
  • Simulated approximately 9200 combinations of process variables (temperature shift, shift day, seed density, harvest day) and gene knockdowns (8 metabolic enzymes).
  • Analyzed the solution space to identify optimal strategies.

Main Results:

  • Optimal gene knockdown strategies are dependent on process parameters like temperature shift day, shift temperature, and seed density.
  • Knockdown of enzymes involved in lactate production showed the most significant benefits.
  • Modulating these enzymes resulted in productivity improvements ranging from no change to over a 2-fold increase, contingent on process conditions.

Conclusions:

  • Dynamic modeling is crucial for optimizing complex bioprocesses.
  • Integrated approaches considering both cell engineering and process parameters are essential for maximizing antibody production in CHO cells.
  • Targeting lactate metabolism offers a promising avenue for enhancing recombinant protein yields.