Sserwadda, H.; Park, K.; Kim, Y.-H.; Kim, H. J.; Park, C.-G.

Background: Engineered synthetic RNAs enable cellular control by sensing and responding to intracellular biomolecules. Recently developed sense-edit-switch RNAs (sesRNAs) based on Adenosine Deaminase Acting on RNA (ADAR)--which edits a stop codon to switch on custom payload translation in the presence of a target RNA--are consistently functional across different species. The ability of sesRNAs to couple bespoke payload translation to the presence of cell type-specific transcripts will usher in an era of precise cell-targeted biotechnological interventions. Results: To expedite the generation of sesRNAs, we develop ADAR-Sense--a universal web tool for automated sensor design based on user-defined sensor length, sensor-target RNA mismatch number, mismatch proximity to the ADAR-editable stop codon, and targeted custom element inclusion for improved ADAR recruitment and subsequent payload induction. Conclusions: Compared to current tools, the simplicity and flexibility of ADAR-Sense will streamline the design and screening of sesRNAs in new cell types and conditions, supporting the swift adoption of this sensing platform in both basic and translational research.