Direct detection of C9orf72 hexanucleotide repeat expansions by nanopore biosensor

Diagnostic C9orf72 hexanucleotide repeat expansions (C9-HRE) is essential for the early and accurate diagnosis of amyotrophic lateral sclerosis (ALS) and will provide support for the prognosis and gene therapy of ALS. In the present study, by combining catalytic hairpin assembly (CHA) with Mycobacterium smegmatis porin A (MspA) nanopore, a new nanopore-based strategy for the detection of C9-HRE was reported. Less than 30 repeats of C9-HRE could be detected via this method, and the results have the potential to help distinguish between patients and healthy individuals. Moreover, the method demonstrated its great specificity for C9-HRE by identifying other repeat expansions. Given the high selectivity, this approach had been successfully used to detect C9-HRE in cell and blood samples with high accuracy. This detection strategy is user-friendly and has a strong anti -interference ability, thus providing a powerful tool for clinical diagnosis. (c) 2024 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.