Authors
Alekseev A, Hunniford V, Zerche M, Jeschke, M, El May F, Vavakou A, Siegenthaler D, Hueser MA, Kiehn SM, Garrido-Charles A, Meyer A, Rambousky A, Alvanos T, Witzke I, Rojas-Garcia KD, Draband M, Cyganek L, Klein E, Ruther P, Huet A, Trenholm S, Macé E, Kusch K, Bruegmann T, Wolf BJ, Mager T, Moser T
Journal
Nature Biomedical Engineering
Citation
Nat Biomed Eng. 2024. accepted manuscript.
Abstract
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. ChReef offers minimal photocurrent desensitization, a unitary conductance of 80 fS and closing kinetics of 30 ms, which together enable reliable optogenetic control of cells at low light levels (nano-Joule) with good temporal fidelity and allows sustained stimulation. We demonstrate efficient and reliable red-light pacing and depolarization block of ChReef-expressing cardiomyocyte clusters. Towards clinical application we used AAV-based gene transfer to express ChReef in retinal ganglion cells where it restores visual function in blind mice with light sources as weak as an iPad screen. Toward optogenetic hearing restoration, ChReef enables stimulation of the auditory pathway in rodents and non-human primates with nano-Joule threshold enabling efficient and frequency-specific stimulation by LED-based optical cochlear implants. Thus, ChReef bears great potential for life sciences and clinical application.
