Red-shifted optogenetics

The common optogenetic actuators are sensible to blue and green light but red-light activation would allow better tissue penetration and less phototoxicity. Cyp27c1 is a recently deorphanized enzyme that converts vitamin A1, the chromophore in photoreceptors, to vitamin A2 and thereby red-shifts their spectral sensitivity for near-infrared vision in some aquatic species. In this project, we investigated the ability of Cyp27c1-generated vitamin A2 to induce a shift in spectral sensitivity of the two optogenetic proteins Channelrhodopsin and its red-shifted version ReaChR by measuring photocurrents at different wavelengths with patch clamp technique in HEK293 cells. Because vitamin A2 incubation is not a realistic option for in vivo applications and expression of Cyp27c1 leads to a similar, even slightly better red-shift in spectral sensitivity, we propose co-expression of this enzyme as a novel strategy adding to red-shifted optogenetics in vivo.