Resource-aware construct design in mammalian cells

Roberto Di Blasi, Mara Pisani, Fabiana Tedeschi, Masue M. Marbiah, Karen Polizzi, Simone Furini, Velia Siciliano and Francesca Ceroni ()
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Roberto Di Blasi: Imperial College London, South Kensington Campus
Mara Pisani: Instituto Italiano di Tecnologia-IIT, Largo Barsanti e Matteucci
Fabiana Tedeschi: Instituto Italiano di Tecnologia-IIT, Largo Barsanti e Matteucci
Masue M. Marbiah: Imperial College London, South Kensington Campus
Karen Polizzi: Imperial College London, South Kensington Campus
Simone Furini: University of Bologna
Velia Siciliano: Instituto Italiano di Tecnologia-IIT, Largo Barsanti e Matteucci
Francesca Ceroni: Imperial College London, South Kensington Campus

Nature Communications, 2023, vol. 14, issue 1, 1-10

Abstract: Abstract Resource competition can be the cause of unintended coupling between co-expressed genetic constructs. Here we report the quantification of the resource load imposed by different mammalian genetic components and identify construct designs with increased performance and reduced resource footprint. We use these to generate improved synthetic circuits and optimise the co-expression of transfected cassettes, shedding light on how this can be useful for bioproduction and biotherapeutic applications. This work provides the scientific community with a framework to consider resource demand when designing mammalian constructs to achieve robust and optimised gene expression.

Date: 2023
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DOI: 10.1038/s41467-023-39252-4

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