Anticancer LNA Oligonucleotides Detection through a Simple Paper-Based Platform

Locked nucleic acids (LNAs) are chemically modified oligonucleotides widely used in gene silencing and precision oncology, yet their clinical translation is limited by the absence of simple, rapid assays to quantify them directly in biological fluids for dose optimization and timely therapeutic feedback. Here, we report a paper-based electrochemical biosensor for the direct detection of antisense LNA oligonucleotides using LNA-anti-miR-155 as a clinically relevant model. The platform employs a methylene blue-labeled RNA probe that mimics the native miRNA target and yield a signal-off voltammetric response upon hybridization. The disposable, gold nanoparticle-modified paper electrodes support picomolar detection limits, high reproducibility, and reliable performance in undiluted human plasma without sample pretreatment. By combining portability, low cost, and rapid analysis in a single-use format, this biosensor advances point-of-care monitoring of LNA-based therapeutics and provides a versatile blueprint for future personalized treatment platforms targeting antisense oligonucleotides.