DNA-Based Smart Reagent for Detecting Alzheimer's Associated MicroRNAs.
DNA-Based Smart Reagent for Detecting Alzheimer's Associated MicroRNAs.
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DOI：
10.1021/acssensors.1c01567
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发表时间：
2021-09-24
期刊：
影响因子：
8.9
通讯作者：
Halvorsen, Ken
中科院分区：
文献类型：
--
作者：
Chandrasekaran, Arun Richard;Halvorsen, Ken
关键词：
阿尔茨海默病（Alzheimer's disease， AD）是最常见的神经退行性疾病，研究人员致力于寻找新的生物标志物用于临床诊断和治疗。microrna已经成为AD的可能的疾病调节因子和生物标志物，现在被认为在与疾病进展相关的几个生物学过程中发挥作用。在这项工作中，我们使用miracsassay （microRNA激活的工程开关条件环）单步检测ad相关的microRNA。该技术基于构象响应的DNA纳米开关，该开关在识别目标microRNA时循环，并通过电泳读出报告其开/关状态。与许多方法不同，我们的方法直接检测天然microrna，无需扩增或标记，无需昂贵的酶，试剂和设备。对于已知的ad相关microRNA miR-107，我们证明了~ 8fm的敏感性，在同一家族的四个类似microRNA之间具有特异性，并且同时多重检测这四个microRNA靶点。为了临床应用，我们筛选了56个AD相关的microrna，发现其中4个在人类健康和AD大脑样本中提取的总RNA提取物之间存在可检测的差异。在阿尔茨海默病的背景下，这种“智能试剂”可以促进生物标志物的发现，加快人们对microrna在阿尔茨海默病中的作用的了解，并具有作为有效生物标志物的诊断或监测工具的临床潜力。
Alzheimer's disease (AD) is the most common neurodegenerative disorder, with significant research efforts devoted to identifying new biomarkers for clinical diagnosis and treatment. MicroRNAs have emerged as likely disease regulators and biomarkers for AD, now implicated as having roles in several biological processes related to progression of the disease. In this work, we use the miRacles assay (microRNA activated conditional looping of engineered switches) for single-step detection of AD-related microRNAs. The technology is based on conformationally responsive DNA nanoswitches that loop upon recognition of a target microRNA and report their on/off status through an electrophoretic readout. Unlike many methods, our approach directly detects native microRNAs without amplification or labeling, eliminating the need for expensive enzymes, reagents, and equipment. For known AD-related microRNA miR-107, we demonstrated sensitivity of ~8 fM, specificity among four similar microRNAs of the same family, and simultaneous multiplexed detection of those four microRNA targets. Toward clinical use, we screened 56 AD-related microRNAs and found four that showed detectable differences between total RNA extracts derived from human healthy and AD brain samples. In the context of AD, this "smart reagent" could facilitate biomarker discovery, accelerate efforts to understand the role of microRNAs in AD, and have clinical potential as a diagnostic or monitoring tool for validated biomarkers.
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影响因子：
11
作者：
Chopra N;Wang R;Maloney B;Nho K;Beck JS;Pourshafie N;Niculescu A;Saykin AJ;Rinaldi C;Counts SE;Lahiri DK
通讯作者：
Lahiri DK
DOI：
10.1073/pnas.0710263105
发表时间：
2008-04-29
影响因子：
11.1
作者：
Hebert, Sebastien S.;Horre, Katrien;De Strooper, Bart
通讯作者：
De Strooper, Bart
DOI：
10.1523/jneurosci.3883-11.2011
发表时间：
2011-10-12
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Geekiyanage H;Chan C
通讯作者：
Chan C
影响因子：
14.9
作者：
Chandrasekaran AR;Levchenko O;Patel DS;MacIsaac M;Halvorsen K
通讯作者：
Halvorsen K
影响因子：
5.3
作者：
Acharya, U. Rajendra;Fernandes, Steven Lawrence;Yeong, Chai Hong
通讯作者：
Yeong, Chai Hong