Project R-16947

REcognition by SEquential Tagging (RESET). (Research)

Cancer is characterized by genetic mutations that serve as critical biomarkers for diagnosis and treatment. While traditional tissue biopsy is the standard for tumor profiling, liquid biopsy of circulating free DNA (cfDNA) in body fluids offers a dynamic, minimally invasive alternative that better captures tumor heterogeneity. However, detecting circulating tumor DNA (ctDNA) remains a major challenge because these rare mutations exist at extremely low levels (<0.1%) among a vast excess of non-mutated DNA. Existing technologies struggle to reach the necessary selectivity due to fundamental error limits. To overcome these boundaries, this project introduces a novel concept that drastically enhances the selectivity of single-point mutation detection through a multi-step labeling process. Driven by a close physicochemical collaboration that combines theoretical modeling with experimental validation, the project leverages kinetic proofreading principles within a single-reaction workflow. The resulting completed tags can be seamlessly integrated into downstream detection and purification pipelines. Beyond transforming ctDNA analysis, this high-selectivity approach is highly relevant for any domain where suppressing molecular errors is crucial.

10 October 2026 - 09 October 2031