Synthetic protein-binding DNA sponge as a tool to tune gene expression and mitigate protein toxicity

Joy Wan, Filipe Pinto, Luyang Yu, Baojun Wang

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Versatile tools for gene expression regulation are vital for engineering gene networks of increasing scales and complexity with bespoke responses. Here, we investigate and repurpose a ubiquitous, indirect gene regulation mechanism from nature, which uses decoy protein-binding DNA sites, named DNA sponge, to modulate target gene expression in Escherichia coli. We show that synthetic DNA sponges can be designed to reshape the response profiles of gene circuits, lending multifaceted tuning capacities including reducing basal leakage by >20-fold, increasing system output amplitude by >130-fold and dynamic range by >70-fold, and mitigating host growth inhibition by >20%. Further, multi-layer DNA sponges for decoying multiple regulatory proteins provide additive tuning effect on the responses of layered circuits compared to single-layer sponges. Our work shows synthetic DNA sponges offer a simple yet generalizable route to systematically engineer the performance of synthetic gene circuits, expanding the current toolkit for gene regulation with broad potential applications.
Original languageEnglish
Article number5961
Number of pages12
JournalNature Communications
Volume11
Issue number1
DOIs
Publication statusPublished - 24 Nov 2020

Keywords / Materials (for Non-textual outputs)

  • DNA sponge
  • decoy binding
  • transcriptional regulation
  • gene expression
  • protein toxicity
  • synthetic biology

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