Advancing electrochemical detection of therapeutic LNA Oligonucleotides through a simple paper‑based platform

Locked nucleic acids (LNAs) are chemically modified oligonucleotides that play a central role in modern gene silencing strategies, particularly in precision oncology. However, their clinical application is limited by the absence of simple and rapid methods to monitor their concentration in biological fluids, which is essential for optimizing dosage and enabling real-time therapeutic feedback. In this study, we report the first electrochemical biosensor specifically designed for the detection of antisense LNA oligonucleotides. The platform employs a methylene blue-labelled probe that mimics the natural miRNA target, producing a clear signal-off response upon hybridization with LNA-anti-miR-155. The biosensor demonstrates excellent performance and achieves a detection limit in the picomole range, even in undiluted human plasma. Combining high sensitivity, rapid analysis, and direct operation in complex matrices, this device represents a concrete step toward point-of-care monitoring of LNA-based therapies, paving the way for truly personalized treatment regimens.