PNAS 115, E6722–E6730 (2018)

While CRISPR is the tool of choice for genome editing, it also has off-label applications. In recent years, biologists modified the targetable nuclease to regulate endogenous and exogenous gene expression by coupling it to transcriptional activators, with the complex controlled by illumination. By requiring irradiation, scientists can control spatial and temporal regulation. Most prior studies employed blue light actuation, but this approach suffers from phototoxicity issues. Authors in a current report put a twist on this by engineering a far-red light stimulated CRISPR-dCas9 effector (FACE) system. Using the longer wavelength technique, investigators showed in vivo upregulation of target genes in mouse muscle that significantly exceeded that of blue light activation, with no deleterious effects. As a further demonstration of its utility, FACE allowed illumination-dependent conversion of murine iPSCs to neurons via stimulation of a neuronal transcription factor.