Efficient and sustained optogenetic control of nervous and cardiac systems

Optogenetic control of cells is a key life sciences method and promises novel therapies. Here we report on ChReef, an improved variant of the channelrhodopsin ChRmine, enabling efficient (nano-Joule) and sustained optogenetic stimulation of excitable cells. ChReef offers minimal photocurrent desensitization, a unitary conductance of 80 fS and closing kinetics of 30 ms, which together enable reliable optogenetic control of cardiac and nervous systems at low light levels with good temporal fidelity. We demonstrate efficient and reliable red-light pacing and depolarization block of ChReef-expressing cardiomyocyte clusters. ChReef-expression in the optic nerve restores visual function in blind mice with light sources as weak as an iPad screen. ChReef enables stimulation of the auditory nerve at up to 50-100 Hz with good temporal precision and low pulse energy threshold (170 nJ) close that of electrical stimulation (50 nJ). Thus, ChReef outperforms ChRmine and bears great potential for life sciences and clinical application. ### Competing Interest Statement TM is co-founder of the OptoGenTech Company. TM, MZ and TMa are authors on a pending patent application related to this work, filed by Universitaetsmedizin Goettingen and OptoGenTech (EPA-22155173). Remaining authors declare no conflict of interest.