New RNA Origami Method Supports Faster Targeted Testing for Repeat Expansion Disorders

Repeat expansion disorders drive conditions such as myotonic dystrophy, Huntington’s disease, and amyotrophic lateral sclerosis (ALS), yet accurately sizing the mutated sequences remains difficult. These disorders affect about one in 280 people, and as many as 90% may be undiagnosed, highlighting the need for fast, affordable sizing assays. Conventional polymerase chain reaction (PCR) can distort true repeat length, and some sequencing approaches struggle in repetitive regions. A new study shows an RNA “origami” nanopore method that distinguishes disease‑associated repeat lengths using minimal RNA.

At the University of Cambridge, researchers have developed an RNA origami method that stretches RNA molecules into labeled nanostructures for analysis through tiny glass holes known as nanopores. The technique uses short pieces of DNA to stretch and label the RNA, allowing each construct to generate a distinct electrical pattern as it passes through a nanopore. This pattern reflects the RNA’s structure and reveals how many tandem repeats are present, enabling clear distinction between normal and pathogenic repeat lengths.

Image: The new RNA origami method achieved 18-nucleotide resolution, enough to distinguish healthy from disease-associated repeat sections (image credit: Adobe Stock)

Working with collaborators at the University of Belgrade in Serbia, the team achieved resolution of 18 nucleotides, sufficient to tell apart healthy and disease‑associated repeat sections. The method required extremely small amounts of RNA, an advantage when clinical material is limited. The results were published in Nature Communications on May 8, 2026.

Accurate repeat sizing is central to diagnosis because symptom severity often correlates with expansion length. In myotonic dystrophy type 1, the most common adult muscular dystrophy, around 50 repeats in the DMPK gene mark the disease threshold, with larger expansions linked to greater severity and higher transmission risk. In congenital central hypoventilation syndrome, even a difference of six repeats can separate normal respiratory control from dangerous sleep-related breathing failure.

The investigators note they have not yet tested patient samples and that scaling to many nanopores in parallel is needed for routine diagnostics. While unlikely to immediately replace PCR‑based testing, the approach could complement sequencing by providing fast, targeted sizing for families known to carry repeat‑expansion disorders or for clinicians needing quick answers. Cambridge Nucleomics, a University of Cambridge spin‑out, is developing the method into a diagnostics platform.

"RNA is incredibly informative in terms of what it can tell you about the disorders we want to study, but it's also incredibly fragile and often challenging to study. Current techniques were designed for DNA, so they often lose the information in RNA that signals disease. We wanted to fix that," said Gerardo Patiño‑Guillén, lead author, Cavendish Laboratory, University of Cambridge.

"We have a very strong molecular platform. We're confident about what it can do in controlled samples. The next challenge is proving it works just as well in clinical material," added Patiño-Guillén.

Related Links
Cavendish Laboratory, University of Cambridge
Cambridge Nucleomics