Nanopore Method Enables Single-Molecule Quantification of RNA Tandem Repeats

A single-molecule nanopore-based strategy enables direct quantification of tandem repeats in native RNA, overcoming limitations of conventional amplification-based methods that fail to resolve repeat length accurately due to amplification bias and sequence homogeneity.

Short tandem repeat expansions underlie a class of neurological and neuromuscular diseases known as repeat expansion disorders. By assembling RNA:DNA nanostructures that encode specific repeat number, the method achieved repeat size discrimination with a resolution of 18 nucleotides.

The approach successfully detected and discriminated disease-relevant repeat lengths associated with myotonic dystrophy type 1 (DM1). It likewise distinguished those linked to myotonic dystrophy type 2 (DM2) and congenital central hypoventilation syndrome-1. Researchers then applied the method to total RNA extracted from a DM1 human cell line model.

The technique is compatible with complex biological samples. com reported that the approach offers a platform for studying repeat expansion biology at the single-molecule level. The work carries broad implications for diagnostics, clinical research and multiplexed repeat profiling.

Gerardo Patiño-Guillén, Max Earle, Sergiu Petrușca, Ulrich F. Keyser and Filip Bošković conducted the research while affiliated with the Cavendish Laboratory, University of Cambridge. Jovan Pešović, Anastasija Ninković and Dušanka Savić-Pavićević are affiliated with the University of Belgrade—Faculty of Biology, Centre for Human Molecular Genetics, while Marko Panić is affiliated with the Institute of Virology, Vaccines and Sera “Torlak”, Belgrade.

The paper was received on 16 June 2025, accepted on 24 April 2026 and published on 08 May 2026. 1038/s41467-026-72819-5. -G. received funding from the EPSRC CDT MRes/PhD Studentship in Nanoscience and Nanotechnology (NanoDTC Cambridge EP/S022953/1) and the Trinity-Henry Barlow Scholarship.

U.K. received funding from UKRI under Horizon Europe guarantee EP/X023311/1, the ERC consolidator grant DesignerPores no. 647144, the ERC-2019-PoC grant PoreDetect no. 899538, and Horizon 2020 FET-Open DNA-FAIRYLIGHTS Grant Agreement No.

964995. B. received funding from the George and Lilian Schiff Foundation Studentship, the Winton Program for the Physics of Sustainability PhD Scholarship, and St John’s College Benefactors’ Scholarship.

-P. acknowledge support by grants from the Science Fund of the Republic of Serbia (Grant No. 7754217, READ-DM1). E. P.

964995. B. K. are inventors of two patents related to RNA characterisation with nanopores (UK patent application no. 7; UK Patent application nos. 6 and PCT/GB2022/052171) submitted by Cambridge Enterprise.

U.K. is a co-founder of Cambridge Nucleomics.