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DNA sponges - new tool for fine tuning cell engineering

Protein-binding DNA could be used to mop up proteins and fine-tune the control of gene expression, according to research carried out in the lab of Dr Baojun Wang, published recently in Nature Communications.

DNA Sponge - image from Nature Paper

Over expression of synthetic genes (e.g. for those used to build biologics or enzymes involved in producing novel chemicals) confounds efforts to engineer new functions in cells and can put cells under great strain. Dr Wang’s team investigated and repurposed a very common mechanism used by nature to mop up proteins that are gene expression controllers. These are short pieces of DNA that bind to target regulatory proteins specifically – so aptly called ‘DNA sponges’.

The team showed that synthetic DNA sponges could sequester proteins and fine tune gene expression within synthetic gene circuits. The sponges increased the amplitude of gene expression by >130 fold, reduced background ‘leak’ more than 20 fold, and overall created >70 fold increase in induction.

The synthetic DNA sponge can also alleviate the burden of an excess of proteins on the health of cells and their ability to grow. The sponges improved host cell growth by >20% in cells expressing sensitive transcription factors that tend to be toxic at higher expression levels.

Furthermore, adding in multiple layers of DNA sponges creates additional levels of control and allowing genetic engineers to add in even more sophisticated ‘gears’ into cell factories.

The study show that synthetic DNA sponges could be a simple method to systematically improve the performance of a wide variety of synthetic gene circuits, expanding the current synthetic biology toolkit for a wide range of applications.

 

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  

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

Dr  Xinyi Wan has written a blog for the Nature Bioengineering online community which tells the story behind about what brought them to the DNA sponge work.

Blog link: https://go.nature.com/39fHj6C