Synthetic biology approaches for dynamic CHO cell engineering

Fed-batch culture of Chinese hamster ovary (CHO) cells remains the most commonly used method for producing biopharmaceuticals. Static CHO cell-line engineering approaches have incrementally improved productivity, growth and product quality through permanent knockout of genes with a negative impact o...

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Bibliographic Details
Published in:Current opinion in biotechnology 2022-12, Vol.78, p.102806-102806, Article 102806
Main Authors: Donaldson, James, Kleinjan, Dirk-Jan, Rosser, Susan
Format: Article
Language:English
Subjects:
Animals
Batch Cell Culture Techniques - methods
biotherapeutics
Cell Engineering
Cell line engineering
Chinese hamster ovary cell (CHO)
CHO Cells
CHO production
Cricetinae
Cricetulus
Dynamic Engineering
Engineering Biology
Gene Circuits
lactate metabolism
quorum sensing
Recombinant Proteins - genetics
self-regulating
Synthetic Biology
synthetic promoters
synthetic receptors
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Summary:Fed-batch culture of Chinese hamster ovary (CHO) cells remains the most commonly used method for producing biopharmaceuticals. Static CHO cell-line engineering approaches have incrementally improved productivity, growth and product quality through permanent knockout of genes with a negative impact on production, or constitutive overexpression of genes with a positive impact. However, during fed-batch culture, conditions (such as nutrient availability) are continually changing. Therefore, traits that are most beneficial during early-phase culture (such as high growth rate) may be less desirable in late phase. Unlike with static approaches, dynamic cell line engineering strategies can optimise such traits by implementing synthetic sense-and-respond programmes. Here, we review emerging synthetic biology tools that can be used to build dynamic, self-regulating CHO cells, capable of detecting intra-/extracellular cues and generating user-defined responses tailored to the stage-specific needs of the production process.
ISSN:0958-1669
1879-0429
DOI:10.1016/j.copbio.2022.102806