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Synthetic DNA sponges – a powerful new tool for gene circuit engineering

12/17/2020

On 24 November 2020, Prof. WANG Baojun and Prof. Yu Luyang’s team from the ZJU-UoE Joint Research Centre of Engineering Biology (the International Campus) has published their latest synthetic biology research results as an article in Nature Communications titled “Synthetic protein-binding DNA sponge as a tool to tune gene expression and mitigate protein toxicity”.


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In this work, the team investigated and repurposed a ubiquitous, indirect gene regulation mechanism from nature, which uses decoy protein-binding DNA sites named DNA sponge to modulate target gene expression. They showed that synthetic DNA sponge-mediated protein sequestration can systematically regulate gene expression within gene circuits with multifaceted quantitative tuning capacities and mitigate the burden of protein expression on host cells. This approach provides a simple yet generalizable route for addressing many commonly met issues in gene circuit design such as intolerable basal expression leakage, low output amplitude and narrow dynamic range, and cellular burden induced by protein expression toxicity.

Importantly, unlike many typical transcriptional and translational regulation methods which may increase cellular burden due to the need of expression of additional protein components, the DNA sponges used did not show any notable growth burden to the host cell. In addition, the synthetic DNA sponges have been shown to be genetically stable in their host strains.

Their work shows for the first time that synthetic DNA sponge offers a simple method to systematically engineer the performance of synthetic gene circuits, expanding the current synthetic biology toolkit for gene regulation with broad potential applications.

Article link: Wan X, Pinto F, Yu L and Wang B, “Synthetic protein-binding DNA sponge as a tool to tune gene expression and mitigate protein toxicity”, Nature Communications, 2020, 11, 5961 doi 

https://doi.org/10.1038/s41467-020-19552-9


 

(Provided by ZJU-UoE Joint Research Centre for Engineering Biology)

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