Revolutionary RNA Biosensor Illuminates the Future of Medical Imaging
A team of researchers has achieved a significant breakthrough in biosensor technology, developing a novel RNA-based biosensor capable of detecting small inorganic molecules with unprecedented accuracy.This innovative approach, detailed in a recent publication, bypasses customary RNA engineering by focusing on modifying the fluorescent ligand molecule itself. This advancement promises to revolutionize medical imaging and diagnostics.
The foundation for this discovery rests on earlier work from 2011, where scientists engineered fluorescent RNA molecules using an RNA aptamer that binds to a hydroxybenzylidene imidazolinone (HBI) ligand. The key innovation? Neither component fluoresces independently; the glow only appears upon their binding, enabling visualization of RNA within living cells. Previous research laid the groundwork for this exciting progress.
building upon this foundation, scientists explored combining riboswitches—RNA structures that change shape when binding other molecules—with aptamers to create biosensors that fluoresce only when both an HBI and a specific biomolecule, such as S-adenosylmethionine, are present. However, creating such sensors for inorganic molecules proved challenging. As Rutgers University chemist Enver Cagri Izgu explains,“RNA has a folding problem,especially in cells. It’s really arduous to control these things and really make them useful biomedically.”
Izgu’s team ingeniously circumvented this challenge. “Why don’t we just make an organic molecule to interact with the metabolite of interest?” Izgu reasoned. Their solution, published in Angewandte Chemie, involves creating “preligands” that react to form a fluorescent HBI in the presence of specific inorganic redox-signaling molecules. These preligands act as biosensing aptamers. This research is available via DOI: 10.1002/anie.202421936.
The researchers cleverly added a “caging group” to the HBI structure. This group is sensitive to hydrogen peroxide but doesn’t react with other reactive oxygen species. crucially, the preligand remains non-fluorescent until cleaved. The team replicated this process using a functional group cleavable by hydrogen sulfide, demonstrating versatility in targeting different analytes.The result? When the preligand is introduced to bacteria expressing the aptamer, the addition of hydrogen peroxide causes the cells to visibly fluoresce.
This breakthrough has significant implications for various fields, including medical diagnostics and environmental monitoring. The ability to visualize specific molecules within living cells opens doors to improved disease detection and treatment. Izgu and his team are actively developing more HBI-derived compounds to expand the range of detectable analytes, promising even greater advancements in the future.
This research represents a significant leap forward in biosensor technology, offering a powerful new tool for researchers and clinicians alike. The potential applications are vast,and the future of medical imaging looks brighter than ever.
