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An international research team led by TU Darmstadt Professor Beatrix Suss, working in close collaboration with partners in Germany and Denmark, has elucidated how an RNA switch newly developed at TU Darmstadt recognises the antibiotic doxycycline and thereby selectively activates or deactivates gene expression. This makes doxycycline a promising basis for synthetic biology and, potentially, for gene therapies as well. The findings were recently published in Nature Communications. Oct 13, 2026, 3:49:03 PM Bettina Bastian , Technische Universitat Darmstadt Doxycycline has been used for decades to treat bacterial infections; it is well tolerated and easily penetrates cells. This is precisely what makes it an ideal signalling molecule: by introducing it into a cell, one can control a specific RNA switch (riboswitch) from the outside. The switch, known simply as G12, is small, was developed in the laboratory and functions reliably in both yeast and human cells. The study demonstrates for the first time why it works so well - thereby establishing it as a promising foundation for synthetic biology and, potentially, for gene therapies.How do RNA switches regulate gene expression?RNA is primarily known for carrying genetic information - but it can do much more. By folding into complex three-dimensional structures, RNA molecules can also act as sensors and regulators within the cell. Riboswitches have been found for billions of years, primarily in bacteria and other microorganisms, where they help cells adapt their metabolism to a changing environment. A natural riboswitch typically recognises a specific metabolic product. When this molecule binds, the RNA changes its shape, thereby influencing whether a genetic message is translated into a protein - and thus, in most cases, into a function or property. In this way, a riboswitch acts like a molecular switch that adjusts gene expression in response to a chemical signal. Artificially produced riboswitches apply the same principle to substances that researchers can freely select. Doxycycline has been used as an antibiotic for decades. In the study now published in *Nature Communications*, however, it takes on a second role: it serves as a chemical trigger that activates the artificial RNA switch G12.From tetracycline to doxycycline: a new star among riboswitchesMany RNA molecules can bind to small compounds, but only a few can be converted into effective riboswitches. This is because binding alone is not enough: the RNA must also translate molecular recognition into a structural change that is strong enough to influence gene expression. Finding such rare candidates therefore requires extensive screening of large RNA libraries, extremely extensive sequencing and, above all, functional tests in living cells. As early as 2003, Suss and her colleagues demonstrated that aptamers - short RNA fragments that recognise a specific substance with pinpoint accuracy - could be applied to the antibiotic tetracycline and used to conditionally regulate protein production in yeast. This work, published in *Nucleic Acids Research*, established one of the pioneering platforms for synthetic RNA switches. The new study builds on this and adds another high-performance regulator to the molecular toolbox - now using doxycycline as the trigger and proving more effective than the tetracycline-based switch.Beyond the switch: where G12 might leadThe research team is currently investigating the three-dimensional structure of G12 in greater detail to better understand how it works. These findings could help in the targeted design of future RNA switches. Together with partners from academia and industry, the team is also exploring how G12 can be adapted for broader applications in synthetic biology - including the controlled expression of selected genes in plants.Another promising avenue is the combination of G12 with self-cleaving RNA enzymes, known as ribozymes. Such hybrid constructs, often referred to as aptazymes, could be designed so that doxycycline determines whether a messenger RNA (mRNA) remains intact or is cleaved and subsequently degraded. In the long term, this principle could provide an additional level of control and safety for mRNA-based medicines - including vaccines - as well as for gene therapies. Such an RNA-based emergency brake could one day make it possible to slow down or halt the production of a therapeutic protein should any undesirable effects arise. Although these applications are still in the early stages of development, the team is convinced that G12 can pave the way for the development of such protective mechanisms in the near future. Contact for scientific information: Professor Beatrix Suessbeatrix.suess@tu-darmstadt.de+49 6151/16-22000 Original Publication: https://www.nature.com/articles/s41467-026-76256-2 Source: https://idw-online.de/de/news879065
