School of Biological Sciences , Indian Association for the Cultivation of Science , Jadavpur, Kolkata 700 032 , India.
Langmuir. 2019 Jul 9;35(27):8875-8888. doi: 10.1021/acs.langmuir.8b02770. Epub 2018 Nov 20.
Challenges in reliable nucleic acid detection are manifold. The major ones are related to false positive or negative signals due to a lack of target specificity in detection and to low sensitivity, especially when a plethora of background sequences are present that can mask the specific recognition signal. Utilizing designed synthetic nucleic acids that are commonly called xeno nucleic acids could offer potential routes to meeting such challenges. In this article, we present the general framework of nucleic acid detection, especially for nanoscale applications, and discuss how and why the xeno nucleic acids could be truly an alternative to the DNA probes. Two specific cases, locked nucleic acid (LNA) and peptide nucleic acid (PNA), which are nuclease-resistant and can form thermally stable duplexes with DNA, are addressed. It is shown that the relative ease of the conformationally rigid LNA probe to be oriented upright on the substrate surface and of the nonionic PNA probe to result into high probe density assists in their use in nanoscale nucleic acid recognition. It is anticipated that success with these probes may lead to important developments such as PCR-independent approaches where the major aim is to detect a small number of target sequences present in the analyte medium.
可靠的核酸检测面临诸多挑战。主要问题是由于检测缺乏目标特异性和灵敏度低而导致假阳性或假阴性信号，尤其是存在大量可能掩盖特定识别信号的背景序列时。利用通常称为异源核酸的设计合成核酸可以提供应对这些挑战的潜在途径。本文介绍了核酸检测的一般框架，特别是针对纳米级应用，并讨论了异源核酸如何以及为何可以真正替代 DNA 探针。文中还介绍了两种特定的案例，即锁核酸（LNA）和肽核酸（PNA），它们具有抗核酸酶的特性，并能与 DNA 形成热稳定的双链体。结果表明，构象刚性的 LNA 探针易于在基底表面垂直定向，以及非离子 PNA 探针易于实现高探针密度，这有助于它们在纳米级核酸识别中的应用。预计这些探针的成功可能会带来重要的发展，例如不需要 PCR 的方法，其主要目的是检测分析物中存在的少量靶序列。
