Optogenetics is a groundbreaking technology that uses light-sensitive proteins, known as channelrhodopsins, to specifically control the activity of nerve and muscle cells. The blueprints for these ‘molecular light switches’ are introduced into the relevant cells using special viruses. Cell activity can then be precisely switched on and off using targeted light pulses. The field of optogenetics has opened up new possibilities worldwide in basic research, but also for the treatment of diseases. In order for this technology to be used to develop new treatments for people with heart disease, severe hearing loss and blindness, for example, both the light-sensitive proteins and the viruses must be optimally adapted to ensure maximum benefit and the necessary safety for use in humans.
Scientists from the Multiscale Bioimaging (MBExC) Cluster of Excellence in Göttingen and the Else Kröner Fresenius Centre for Optogenetic Therapies (EKFZ OT) have now described the development and application of a new, particularly promising light-sensitive protein. This new channelrhodopsin, developed by Dr Thomas Mager, group leader at the Institute of Auditory Neuroscience at the University Medical Centre Göttingen (UMG), and his colleagues, is called ‘ChReef’. ‘By specifically modifying the blueprint of this light-activated protein and using partly robot-based analysis methods, we have succeeded in significantly increasing the efficiency of optogenetic stimulation,’ explains Dr. Mager. ‘This brings us a whole step closer to applicability in humans for restoring vision and hearing and regulating the heartbeat,’ says Prof. Dr. Tobias Moser, Director of the Institute of Auditory Neuroscience at UMG and MBExC and EKFZ OT spokesperson.
Promising therapeutic applications of ChReef
In a comprehensive study, scientists from MBExC and EKFZ OT tested the efficiency of the new channelrhodopsin and provided evidence of ChReef's great potential for life sciences and clinical applications.
Researchers led by Prof. Dr. Dr. Tobias Brügmann (DZHK scientist), head of the working group at the Institute for Cardiovascular Physiology at UMG, MBExC member and deputy EKFZ OT spokesperson, were able to show, for example, that the new ‘tool’ can restore irregularly beating heart muscle cells to their correct rhythm with very little energy expenditure.
In another study led by MBExC member and deputy EKFZ OT spokesperson Prof. Dr. Emilie Macé, Professor of ‘Dynamics of Excitable Cell Networks’ at the UMG Department of Ophthalmology, the new tool was introduced into the eyes of blind mice in the form of gene therapy. A subsequent behavioural test showed that the mice were able to detect differences in brightness on an iPad screen. This type of vision restoration has already been tested in other studies on humans, but the channelrhodopsins used to date required very strong light sources.
The researchers see another possible application for ChReef in the optogenetic restoration of hearing using the optogenetic cochlear implant (oCI). This promises better resolution of different pitches compared to the electrical cochlear implant currently used worldwide for hearing rehabilitation. In the recently published study, the researchers required impressively low amounts of light for ‘hearing with light’. ‘With the development of ChReef, we have taken a major step towards the clinical application of the optogenetic cochlear implant, as significantly less energy is now required for “hearing with light”,’ explains Prof. Moser. ‘On the one hand, this reduces damage to cells caused by light, and on the other hand, the batteries last longer.’ Another relevant factor for human application is that restoring hearing with light is also possible in primate models, as scientists led by Prof. Dr. Marcus Jeschke, head of the ‘Cognitive Hearing in Primates’ research group at the German Primate Centre – Leibniz Institute for Primate Research (DPZ) in Göttingen, were able to demonstrate for the first time. ‘ChReef represents a significant advance in optogenetics and offers great potential for basic research as well as for therapeutic applications, such as in cardiac arrhythmias or the restoration of hearing and vision,’ adds Dr. Bettina Wolf, postdoctoral researcher at the Institute of Auditory Neuroscience and co-author of the study.
This research was funded by the Göttingen Cluster of Excellence ‘Multiscale Bioimaging: From Molecular Machines to Networks of Excitable Cells’ (MBExC) and the Else Kröner Fresenius Centre for Optogenetic Therapies (EKFZ OT), which has been under construction since 2024 and is promoting the transfer of optogenetic therapies into clinical application. ‘Here in Göttingen, the development of new methods is closely linked to scientific and planned medical applications. We learn from each other and can thus make particularly efficient progress in the development of optogenetic therapies,’ says Prof. Moser, highlighting the potential of the synergistic collaboration between MBExC and EKFZ OT in Göttingen.
Original publication:
Alekseev, A et al., Efficient and sustained optogenetic control of sensory and cardiac systems, Nature Biomedical Engineering, July 2025
Source: Press release Göttingen University Medical Centre
