Scientists from UNIGE have developed a tool to control the activity and location of a molecule using light, which could help target better drug treatment.
Action in the right place at the right time is the key to effective medical treatment with limited side effects, but it’s a feat that is still difficult to achieve.
Biologists and chemists from the University of Geneva (UNIGE) have succeeded in developing a tool that allows the activation site of a molecule to be controlled by a simple pulse of light lasting a few seconds.
Tested on a protein essential to cell division, this system could be applied to other molecules. The prospects are immense, both for basic research and for improving existing treatments, for example against skin cancer. These results can be found in the journal Nature Communications.
Regardless of its method of administration, a drug does not only act on the diseased organ but on the entire organism.
This imprecision is not without risk: it can miss its target and not have the expected effect or have serious consequences. Each year in Switzerland, several thousand people suffer from serious uncontrolled side effects.
The system allows the spatial and temporal control of the activity of a molecule in a living organism using light.
The solution, simple in theory but very complex in practice, would be to manage to activate drugs only where they are needed. Such a process would also make it possible to activate or deactivate a protein in a living organism to better understand its functions.
“It was from this methodological question that everything started,” recalls Monica Gotta, full professor in the Department of Cellular Physiology and Metabolism at the UNIGE Faculty of Medicine, who initiated and coordinated this research with Nicolas Winssinger, full professor in the Department of Organic Chemistry at the UNIGE Faculty of Science.
“We were then looking for a way to inhibit a protein involved in cell division, the Plk1 protein, where and when we wanted, to better understand the function of this protein in the development of an organism.”
Breaking a biological lock
By combining their expertise in chemistry and biology, the scientists were able to modify a Plk1 inhibitor molecule so that it would only activate in the presence of light.
“After a complex process, we managed to lock the active site of our inhibitor with a coumarin derivative, a compound naturally present in certain plants, which a simple pulse of light could detach,” explains Victoria von Glasenapp, a postdoctoral fellow in the laboratories of Professor Gotta at the Faculty of Medicine and Professor Winssinger at the Faculty of Science, and first author of the study.
But it was still a matter of finding a way to anchor the inhibitor to the exact location in the organism where its action was desired. “We managed to modify the inhibitor so that it was immobilized at the targeted location, by adding a molecular anchor released only by light,” explains Nicolas Winssinger.
“This therefore allowed us to activate and anchor the inhibitor with the same light pulse, and thus deactivate Plk1 and stop cell division at the exact desired location.”
Countless possible applications
The system developed by UNIGE scientists makes it possible to spatially and temporally control the activity of a molecule in a living organism using light. It can be adapted to many molecules and could enable a drug to be activated only at the desired location.
This discovery should make it possible, with a simple laser, to trigger a treatment exactly where it is needed and to preserve the surrounding healthy tissues, thus limiting undesirable side effects. “We hope that our tool will be widely used and will allow us to better understand how living things work and, in the long term, to develop more localized treatments,” Monica concludes.
REFERENCE
Spatio-temporal control of mitosis using light via a Plk1 inhibitor caged for activity and cellular permeability” by Victoria von Glasenapp, Ana C. Almeida, Dalu Chang, Ivana Gasic, Nicolas Winssinger and Monica Gotta, 19 February 2025, Nature Communications.
DOI: 10.1038/s41467-025-56746-5
