Dual-controlled optogenetic system for the rapid down-regulation of protein levels in mammalian cells.

摘要: Optogenetic switches are emerging molecular tools for studying cellular processes as they offer higher spatiotemporal and quantitative precision than classical, chemical-based switches. Light-controllable gene expression systems designed to upregulate protein levels meanwhile show performances superior their counterparts. However, reduce with similar efficiency lagging behind. Here, we present a novel two-component, blue light-responsive optogenetic OFF switch (‘Blue-OFF’), which enables rapid down-regulation of upon illumination. Blue-OFF combines the first light responsive repressor KRAB-EL222 degradation module B-LID (blue light-inducible domain) simultaneously control stability single wavelength. thus outperforms current controlling levels. The system is described by mathematical model aids in choice experimental conditions such intensity illumination regime obtain desired outcome. This approach represents an advancement dual-controlled multiple photosensory modules operate synergistically. As exemplified here apoptosis mammalian cell culture, opens up perspectives fundamental research applications tissue engineering.