Post-transcriptional modular synthetic receptors

Abstract

Inspired by the power of transcriptional synthetic receptors and hoping to complement them to expand the toolbox for cell engineering, we establish LIDAR (Ligand-Induced Dimerization-Activating RNA editing), a modular post-transcriptional synthetic receptor platform that harnesses RNA editing by adenosine deaminases acting on RNA. LIDAR is compatible with various receptor architectures in different cellular contexts and enables the sensing of diverse ligands and the production of functional outputs. Furthermore, LIDAR can sense orthogonal signals in the same cell and produce synthetic spatial patterns, potentially enabling the programming of complex multicellular behaviors. Lastly, LIDAR is compatible with compact encoding and can be delivered as synthetic mRNA. Thus, LIDAR expands the family of synthetic receptors, holding the promise to empower basic research and therapeutic applications. Zhang, Mille-Fragoso and colleagues developed a synthetic receptor platform named LIDAR (Ligand-Induced Dimerization-Activating RNA editing), which enables ligand-responsive gene regulation without the need of DNA promoters and is, thus, compatible with mRNA delivery.