Receptor activated solely by a synthetic ligand

A receptor activated solely by a synthetic ligand (RASSL) or Designer Receptor Exclusively Activated by Designer Drugs (DREADD), permits spatial and temporal control of G protein signaling in vivo. These systems utilize G protein-coupled receptors (GPCR) engineered to respond exclusively to synthetic small molecules ligands, like clozapine N-oxide (CNO), and not to their natural ligand(s). RASSL's represent a GPCR-based chemogenetic tool.

Mechanism

RASSLs and DREADDs are a family of designer G-protein-coupled receptors (GPCRs) built specifically to allow for precise spatiotemporal control of GPCR signaling in vivo. These engineered GPCRs, called RASSLs (receptors activated solely by synthetic ligands), are unresponsive to endogenous ligands but can be activated by nanomolar concentrations of pharmacologically inert, drug-like small molecules. Currently, RASSLs exist for the three major GPCR signaling pathways (Gs, Gi, Gq). A major cause for success of RASSL resources has been open exchange of DNA constructs, and RASSL related resources.