Caffeine as a molecular switch
2026/08/07
Caffeine is found in coffee, energy drinks and medicines. But what if we could not only consume caffeine, but also use it as a molecular switch? This is precisely what an international research team from TU Darmstadt and the University of Edinburgh has achieved. In a recent study published in “Nucleic Acids Research”, they present a new RNA aptamer – a molecule that reacts specifically to caffeine and can be used in various synthetic RNA tools.
Ribonucleic acid (RNA) is a molecule that transmits genetic information and performs a wide range of tasks within cells. RNA aptamers are short RNA sequences that form complex three-dimensional structures, enabling them to bind specifically to molecules such as caffeine. Some aptamers change their structure in the process – a property that can be utilised in synthetic biology to develop controllable RNA tools.
The challenge was that, until now, only a few RNA aptamers alter their structure after binding to a molecule in such a way that they are suitable as building blocks – for example, for riboswitches (elements that switch genes on or off), for aptazymes (self-cleaving RNA molecules) or as biosensors for detecting specific substances.
Traditional selection methods have focused primarily on finding aptamers with high binding affinity. Whether they could also alter their spatial structure in the process, however, was of little consequence. Yet it is precisely this property that is crucial for the targeted control of RNA tools. This is where the new study comes in: the authors developed a method with which they identified a caffeine aptamer that not only binds caffeine but also specifically triggers changes in the RNA structure in the process.
A modular aptamer for a wide range of applications
Using a newly developed screening method, the lead authors Leon Kraus and Vincent Gunawan from the Department of Biology at TU Darmstadt identified an aptamer from a library of different RNA sequences that reacts specifically to caffeine. The aptamer proved to be highly versatile: it can regulate gene activity in yeast and mammalian cells and serves as the basis for a biosensor capable of detecting caffeine even at low concentrations.
Sorting with light: high-throughput screening on optofluidic chips
To search for particularly potent aptazymes, the team utilised the Beacon® optofluidics platform at the University of Edinburgh. This technology allows thousands of individual cells to be examined simultaneously and selectively identified. This enabled the researchers to rapidly compare numerous variants and identify 20 promising aptazymes, 14 of which could be clearly controlled by caffeine.
Dynamic RNA structures with great potential
The new RNA tools open up a wide range of potential applications. In medicine, they could in future help to selectively switch genes on or off – for example, in cancer research or in the treatment of metabolic disorders. The biosensor developed can be used to detect caffeine in water samples, which is relevant for monitoring wastewater or drinking water quality.
The study also demonstrates that caffeine is suitable as a control molecule for RNA tools. It thus opens up new possibilities for developing RNA tools that can be controlled by other molecules in the future. Mikosch-Wersching/cst
Further information
Original publication: Kraus, L. et al. (2026). *Exploiting conformational changes in a caffeine aptamer to engineer synthetic RNA devices*. Nucleic Acids Research. DOI: 10.1093/nar/gkag584
Funding: German Research Foundation (DFG), UK Research and Innovation (UKRI)
About Leon Kraus
Leon Kraus is a early-career researcher at the Technical University of Darmstadt, specialising in synthetic RNA biology. He is investigating how RNA aptamers can be selected and utilised more efficiently, including for the regulation of microorganisms and in rapid diagnostic tests.
After completing his PhD in Prof. Beatrix Suess’s research group in Darmstadt, he took up a postdoctoral position at the University of Missouri and is now working towards his habilitation. His fascination with synthetic biology began whilst he was a student participating in the international iGEM competitions and has since developed into a passion for synthetic RNA systems.
