Quanterix, Partners Develop PCR-Free miRNA Detection Method for Liver Toxicity Testing

GenomeWeb| July 18, 2017

NEW YORK (GenomeWeb) – A team of investigators from Quanterix, Destina Genomics, and the University of Edinburgh have developed a new approach for the amplification-free detection of microRNA-122, a biomarker used for diagnosing liver toxicity.

The success of the method, described this month in the journal PLoS ONE, has multiple ramifications for the parties involved. For Lexington, Massachusetts-based Quanterix, which to date has deployed assays for protein analysis on its Single Molecule Array, or Simoa, platform, the approach demonstrates the applicability of its technology in nucleic acid detection, and miRNA detection in particular, as it prepares to launch a new system.

For Edinburgh, UK-based Destina Genomics, meantime, the study showcases the use of its chemistry for the PCR-free detection of miRNA on a commercial system. And for scientists at the University of Edinburgh, it offers the hope of introducing miRNA testing that is faster than PCR and less expensive than next-generation sequencing.

"What we are measuring is PCR, which is fine, but it's time consuming," said James Dear, a reader in pharmacology at the University of Edinburgh and paper coauthor, whose work is related to investigating the use of miRNA biomarkers, such as miRNA-122, that are associated with liver toxicity, particularly those resulting from the overuse of acetaminophen. Roughly 100,000 people are admitted to emergency departments in the UK annually, he said, and obtaining information about liver toxicity is crucial to prescribing treatment that can quickly mediate the drug's effects.

Clinicians currently rely on another PCR-based test for the alanine transaminase (ALT) enzyme to diagnose liver toxicity, noted Dear. Yet miRNA-122 is seen by some as a more sensitive biomarker that has not yet progressed in clinical research due to the challenges associated with detecting it using conventional PCR-based assays.

"That's the main driver of this work with Quanterix," said Dear. "PCR takes time, so if we take a sample, it will take most of the day to get the result." By partnering with Quanterix and Destina, Dear and his colleagues aimed to produce an assay for miRNA-122 that has the potential to give a more rapid result.

"This system, because it is amplification free, can give a result very quickly, which can inform whether someone is treatable or not, and can inform drug development," said Dear.

Founded by University of Edinburgh researchers in 2010, Destina's core technology is based on pairing its aldehyde-modified Smart Nucleobases with peptide nucleic acid capture probes containing an abasic position that can be made to complement any nucleic acid system. The result is a dynamic chemistry approach that relies on a chemical, rather than enzymatic, method for nucleic acid testing.

According to Juan Diaz Mochon, cofounder and CSO of Destina, the company evaluated several platforms for Dear's project, looking at alternatives to "time-consuming PCR," and ultimately decided on using the Quanterix platform, given the ability of the Simoa system to provide digital results at single-molecule resolution without a need for amplification.

"It's very disruptive from our view because if we can do direct detection with single-molecule resolution, this opens up option of doing microRNAs, which is the obvious choice," said Diaz Mochon.

As detailed in the new paper, by pairing the Destina chemistry with Quanterix's platform, the investigators were able to develop a single-probe method for detecting miRNA from human serum using Quanterix's single-molecule arrays, which had the advantages of reading sequence specificity down to a single base without the need for amplification.

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