Department of Chemistry, Imperial College London, Molecular Science Research Hub, London, W12 0BZ, UK.
Department of Bioengineering, Imperial College London, Sir Michael Uren Hub, London, W12 0BZ, UK.
Nat Commun. 2021 Jun 10;12(1):3515. doi: 10.1038/s41467-021-23497-y.
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.
微小 RNA（miRNAs）在后转录基因表达中发挥着重要作用，并且在血液等体液中也能自由循环。失调的 miRNA 特征与许多疾病有关，包括癌症，而液体活检中的 miRNA 分析为癌症诊断、预后和监测提供了一种很有前途的策略。在这里，我们开发了大小编码的分子探针，可用于同时进行电-光纳米孔检测 miRNA，允许在未经处理的人血清中直接进行超灵敏、序列特异性和多重检测，样品体积小至 0.1μl。我们表明，这种方法可以实现飞摩尔级的灵敏度和单碱基错配的选择性。我们证明了能够同时监测患有活动性疾病和缓解期的前列腺癌患者的 miRNA（miR-141-3p 和 miR-375-3p）。这项技术可以为下一代微创诊断和癌症伴随诊断测试铺平道路。
