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Related Concept Videos

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Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
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A High-throughput Automated Platform for the Development of Manufacturing Cell Lines for Protein Therapeutics
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Synthetic biology approaches for dynamic CHO cell engineering.

James Donaldson1, Dirk-Jan Kleinjan1, Susan Rosser1

  • 1UK Centre for Mammalian Synthetic Biology at the Institute of Quantitative Biology, Biochemistry, and Biotechnology, School of Biological Sciences, University of Edinburgh, Edinburgh, UK.

Current Opinion in Biotechnology
|October 4, 2022
PubMed
Summary

Dynamic engineering of Chinese hamster ovary (CHO) cells using synthetic biology offers a novel approach to biopharmaceutical production. These self-regulating cells can adapt to changing culture conditions, optimizing productivity throughout the fed-batch process.

Keywords:
CHO productionCell line engineeringChinese hamster ovary cell (CHO)Dynamic EngineeringEngineering BiologyGene CircuitsSynthetic Biologybiotherapeuticslactate metabolismquorum sensingself-regulatingsynthetic promoterssynthetic receptors

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Area of Science:

  • Biotechnology
  • Synthetic Biology
  • Cell Line Engineering

Background:

  • Fed-batch culture of Chinese hamster ovary (CHO) cells is standard for biopharmaceutical manufacturing.
  • Current static cell line engineering methods offer limited adaptability to dynamic culture environments.
  • Changing conditions during fed-batch culture necessitate dynamic cellular responses.

Purpose of the Study:

  • To review emerging synthetic biology tools for dynamic CHO cell engineering.
  • To enable self-regulating CHO cells that respond to intracellular and extracellular cues.
  • To tailor cellular traits to specific production phases for improved biomanufacturing.

Main Methods:

  • Review of current synthetic biology tools and strategies.
  • Exploration of sense-and-respond programs for cell line engineering.
  • Focus on dynamic, self-regulating cell line development.

Main Results:

  • Identification of synthetic biology tools for dynamic CHO cell engineering.
  • Conceptual framework for self-regulating cells adapting to process needs.
  • Potential for enhanced productivity and product quality through dynamic control.

Conclusions:

  • Dynamic cell line engineering using synthetic biology presents a promising advancement for biopharmaceutical production.
  • Self-regulating CHO cells can optimize performance by responding to real-time environmental cues.
  • This approach moves beyond static engineering to achieve stage-specific optimization in fed-batch cultures.