Single-molecule amplification-free multiplexed detection of circulating microRNA cancer biomarkers from serum

Shenglin Cai, Thomas Pataillot-Meakin, Akifumi Shibakawa, Ren Ren, Charlotte L. Bevan (), Sylvain Ladame (), Aleksandar P. Ivanov () and Joshua B. Edel ()
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Shenglin Cai: Molecular Science Research Hub
Thomas Pataillot-Meakin: Molecular Science Research Hub
Akifumi Shibakawa: Hammersmith Hospital
Ren Ren: Molecular Science Research Hub
Charlotte L. Bevan: Hammersmith Hospital
Sylvain Ladame: Sir Michael Uren Hub
Aleksandar P. Ivanov: Molecular Science Research Hub
Joshua B. Edel: Molecular Science Research Hub

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: Abstract MicroRNAs (miRNAs) play essential roles in post-transcriptional gene expression and are also found freely circulating in bodily fluids such as blood. Dysregulated miRNA signatures have been associated with many diseases including cancer, and miRNA profiling from liquid biopsies offers a promising strategy for cancer diagnosis, prognosis and monitoring. Here, we develop size-encoded molecular probes that can be used for simultaneous electro-optical nanopore sensing of miRNAs, allowing for ultrasensitive, sequence-specific and multiplexed detection directly in unprocessed human serum, in sample volumes as small as 0.1 μl. We show that this approach allows for femtomolar sensitivity and single-base mismatch selectivity. We demonstrate the ability to simultaneously monitor miRNAs (miR-141-3p and miR-375-3p) from prostate cancer patients with active disease and in remission. This technology can pave the way for next generation of minimally invasive diagnostic and companion diagnostic tests for cancer.

Date: 2021
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DOI: 10.1038/s41467-021-23497-y

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