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Improving gene circuit design by considering host-circuit interactions

Although synthetic network design mostly deals with DNA components alone (e.g. promoters, genes, terminators…), the genetic background-the context-in which they perform is of vital importance to predict their behaviour. The predictability of these networks, or circuits, is one of the most pressing challenges for synthetic biology. However, the links between genetic circuits and their context are often ignored, hence their function difficult to be fully characterized based on DNA alone. Here we use a library of 20 genetic inverters to rationally design different contextual features. As a result, the 20 inverters give 135 functions (instead of 20) by just changing these contextual dependencies and leaving the same DNA sequence. This implies that circuit design does not necessarily need to be focussed on genetic components, but the adoption of a whole-cell approach may improve the field substantially. We show this advantage by calculating the complementarity and modularity of genetic components-a feature greatly improved by contextual design.

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Original Paper:

Tas, H., Grozinger, L., Stoof, R., de Lorenzo, V., Goñi-Moreno, Á. 2021. Contextual dependencies expand the re-usability of genetic inverters. Nature Communications 12, 355. DOI: 10.1038/s41467-020-20656-5

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