Honeydew: A Fluorescent Aptamer for Low‐Cost Azo Food Dyes

Light-up RNA aptamers that bind nonfluorescent dyes and conditionally activate their fluorescence are powerful tools for RNA imaging and biomolecular sensing. A barrier to widespread adoption of this technology is a reliance on bespoke dyes prepared by labor-intensive or costly custom synthesis. Here, we demonstrate that azo dyes-abundant, ultra-low-cost (<$1/g), and low-toxicity molecules widely used in the food and textile industries-can serve as conditionally fluorescent aptamer ligands. We selected aptamers against tartrazine, a ubiquitous azo food dye, and identified a fluorescence-activating aptamer, which we term Honeydew. We show that Honeydew bound to tartrazine enables real-time sensing and imaging of model synthetic cells. Additionally, Honeydew selectively activates conditional fluorescence of several other azo dyes, underscoring the untapped potential of this broad dye class. By repurposing ubiquitous industrial dyes, Honeydew is a first-in-class fluorogenic azo dye aptamer that provides a highly accessible platform for imaging and sensing applications.