An RNA Motif That Enables Optozyme Control and Light‐Dependent Gene Expression in Bacteria and Mammalian Cells

Abstract The regulation of gene expression by light enables the versatile, spatiotemporal manipulation of biological function in bacterial and mammalian cells. Optoribogenetics extends this principle by molecular RNA devices acting on the RNA level whose functions are controlled by the photoinduced interaction of a light‐oxygen‐voltage photoreceptor with cognate RNA aptamers. Here light‐responsive ribozymes, denoted optozymes, which undergo light‐dependent self‐cleavage and thereby control gene expression are described. This approach transcends existing aptamer‐ribozyme chimera strategies that predominantly rely on aptamers binding to small molecules. The optozyme method thus stands to enable the graded, non‐invasive, and spatiotemporally resolved control of gene expression. Optozymes are found efficient in bacteria and mammalian cells and usher in hitherto inaccessible optoribogenetic modalities with broad applicability in synthetic and systems biology.