据最新一期《Nature Chemistry》杂志报道，加拿大研究人员发现了一种检测人体血液中癌症生物标记物的新方法：利用肽核酸钳及纳米微电子芯片检测游离核酸。

核酸可分为DNA（脱氧核糖核酸）和RNA（核糖核酸），通常位于细胞内，但有时也能在循环血液中找到。癌症患者的血液中往往有更多的这种脱离细胞的核酸，其中一小部分游离核酸中就包含着与某些癌症相关的突变。

研究游离核酸的常用方法包括DNA测序和聚合酶链式反应（PCR），但两种方法都有一定缺陷。DNA测序成本高，患者往往要等待几周才能获得结果；PCR则需要准备大量样本进行修改，才能使其对基因点突变具有充分选择性。

许多遗传癌症标记会在一个特定基因中包含一个点突变。点突变是很难发现的，因为与正常游离核酸或野生型核酸相比，其在血液中的含量要小得多。科学家提高PCR灵敏度的方法之一是使用称为肽核酸的基因“钳”，这些具有互补核苷酸序列的链与野生型序列绑定后可放大目标序列。

多伦多大学和蒙特利尔儿童医院的研究人员开发出的新方法，可在无需样本或仅需少量样本的情况下对肺癌和皮肤癌中的基因突变进行选择性识别。

研究人员将肽核酸钳技术与电化学探针技术相结合，制作出一种快速、具有选择性的传感器。他们设计的钳测定技术可在KRAS基因中选择出特定的突变，KRAS基因中有7个突变与肺癌相关。

实验证明，这种利用肽核酸钳及纳米微电子芯片检测游离核酸的新方法，对检测患者血液中的癌症标记物具有足够的灵敏度和选择性。与其他方法相比，该方法具有成本低、侵入性小、几乎不用准备样本等诸多优点。（来源：科技日报）

An electrochemical clamp assay for direct, rapid analysis of circulating nucleic acids in serum

Abstract  The analysis of cell-free nucleic acids (cfNAs), which are present at significant levels in the blood of cancer patients, can reveal the mutational spectrum of a tumour without the need for invasive sampling of the tissue. However, this requires differentiation between the nucleic acids that originate from healthy cells and the mutated sequences shed by tumour cells. Here we report an electrochemical clamp assay that directly detects mutated sequences in patient serum. This is the first successful detection of cfNAs without the need for enzymatic amplification, a step that normally requires extensive sample processing and is prone to interference. The new chip-based assay reads out the presence of mutations within 15 minutes using a collection of oligonucleotides that sequester closely related sequences in solution, and thus allow only the mutated sequence to bind to a chip-based sensor. We demonstrate excellent levels of sensitivity and specificity and show that the clamp assay accurately detects mutated sequences in a collection of samples taken from lung cancer and melanoma patients.

原文链接：http://www.nature.com/nchem/journal/vaop/ncurrent/full/nchem.2270.html#affil-auth