AIEgens/Nucleic Acid Nanostructures for Bioanalytical Applications

DNA occupies significant roles in life processes, which include encoding the sequences of proteins and accurately transferring genetic information from generation to generation. Recent discoveries have demonstrated that a variety of biological functions are correlated with DNA′s conformational transitions. The non‐B form has attained great attention among the diverse forms of DNA over the past several years. The main reason for this is that a large number of studies have shown that the non‐B form of DNA is associated with gross deletions, inversions, duplications, translocations as well as simple repeating sequences, which therefore causes human diseases. Consequently, the conformational transition of DNA between the B‐form and the non‐B form is important for biology. Conventional fluorescence probes based on the conformational transitions of DNA usually need a fluorophore and a quencher group, which suffers from the complex design of the structure and tedious synthetic procedures. Moreover, conventional fluorescence probes are subject to the aggregation‐caused quenching (ACQ) effect, which limits their application toward imaging and analyte detection. Fluorogens exhibiting aggregation‐induced emission (AIE) have attracted tremendous attention over the past decade. By taking advantage of this unique behavior, plenty of fluorescent switch‐on probes without the incorporation of fluorescent quenchers/fluorophore pairs have been widely developed as biosensors for imaging a variety of analytes. Herein, the recent progress in bioanalytical applications on the basis of aggregation‐induced emission luminogens (AIEgens)/nucleic acid nanostructures are presented and discussed.     

High-Performance Nucleic Acid Sensors for Liquid Biopsy Applications

Circulating tumour nucleic acids (ctNAs) are released from tumours cells and can be detected in blood samples, providing a way to track tumors without requiring a tissue sample. This “liquid biopsy” approach has the potential to replace invasive, painful, and costly tissue biopsies in cancer diagnosis and management. However, a very sensitive and specific approach is required to detect relatively low amounts of mutant sequences linked to cancer because they are masked by the high levels of wild-type sequences. This review discusses high-performance nucleic acid biosensors for ctNA analysis in patient samples. We compare sequencing- and amplification-based methods to next-generation sensors for ctDNA and ctRNA (including microRNA) profiling, such as electrochemical methods, surface plasmon resonance, Raman spectroscopy, and microfluidics and dielectrophoresis-based assays. We present an overview of the analytical sensitivity and accuracy of these methods as well as the biological and technical challenges they present.     

Nucleic Acid/Organic Polymer Hybrid Materials: Synthesis,Superstructures, and Applications

Extensive efforts have been devoted to the development of hybrid structures consisting of biomacromolecules and organic polymers connected through covalent bonds. While the combination of proteins and peptides with synthetic macromolecules has been explored in depth, far fewer examples of nucleic acid/polymer hybrids are known. In this Review we give selected examples of this exciting class of materials which can be arranged as linear block copolymer architectures, as side‐chain polymers, or as cross‐linked networks. Emphasis is placed on the fabrication of these materials as well as on their potential applications in nanoscience, diagnostics, and biomedicine.     

发光标记分析及其在核酸检测中的应用

综述了化学发光,生物发光,电致化学发光中最重要的发光体系,增强鲁米诺体系,吖啶酯发光体系,碱性磷酸酶／1,2－二氧环乙烷体系,荧火虫荧光素／荧光素酶及联吡啶钌发光体系的原理,标记检测方法,最近的进展及在核酸领域的应用,对近年来新发展的发光标记方法作了介绍并分析了该领域今后可能的研究方向。     

Metal-Organic Frameworks Nanocarriers for Functional Nucleic Acid Delivery in Biomedical Applications

Metal−organic frameworks (MOFs), a distinctive funtionalmaterials which is constructed by various metal ions and organic molecules, have gradually attracted researchers′ attention from they were founded. In the last decade, MOFs emerge as a biomedical material with potential applications due to their unique properties. However, the MOFs performed as nanocarriers for functional nucleic acid delivery in biomedical applications rarely summarized. In this review, we introduce recent developments of MOFs for nucleic acid delivery in various biologically relevant applications, with special emphasis on cancer therapy (including siRNA, ASO, DNAzyme, miRNA and CpG oligodeoxynucleotides), bioimaging, biosensors and separation of biomolecules. We expect the accomplishment of this review could benefit certain researchers in biomedical field to develop novel sophisticated nanocarriers for functional nucleic acid delivery based on the promising material of MOFs.     

DNA芯片技术与脱氧核糖核酸序列分析

人类基因组计划的实施,有力地促进了ＤＮＡ序列分析技术的发展。ＤＮＡ芯片综合运用了固相合成化学、照相平版印制技术以及激光共聚焦扫描等技术,能够同时扫描分析多基因乃至基因组,可广泛应用于基因的多态性分析、基因定位、表达水平的监测以及遗传病的诊断等领域,是对传统的ＤＮＡ分析技术的一次重大突破。本文介绍了ＤＮＡ芯片技术的基本原理并对其应用作一简要综述。     

High‐Performance Nucleic Acid Sensors for Liquid Biopsy Applications

Circulating tumour nucleic acids (ctNAs) are released from tumours cells and can be detected in blood samples, providing a way to track tumors without requiring a tissue sample. This “liquid biopsy” approach has the potential to replace invasive, painful, and costly tissue biopsies in cancer diagnosis and management. However, a very sensitive and specific approach is required to detect relatively low amounts of mutant sequences linked to cancer because they are masked by the high levels of wild‐type sequences. This review discusses high‐performance nucleic acid biosensors for ctNA analysis in patient samples. We compare sequencing‐ and amplification‐based methods to next‐generation sensors for ctDNA and ctRNA (including microRNA) profiling, such as electrochemical methods, surface plasmon resonance, Raman spectroscopy, and microfluidics and dielectrophoresis‐based assays. We present an overview of the analytical sensitivity and accuracy of these methods as well as the biological and technical challenges they present.     

卤素对核酸类药物的修饰与影响研究进展

药物分子中引入卤素具有改善药物脂溶性、影响药物分子的电荷分布及影响药物的作用时间等特点,故被广泛应用。 作为抗病毒、抗肿瘤、干扰素诱导和免疫增强的、具有特定碱基序列的核酸药物也不例外。 本文综述了卤素对核酸结构中的嘧啶类、嘌呤类和核糖结构修饰后的核酸类药物生物活性产生的影响,以期为核酸及核酸类似物的药物研发提供新的思路。     

锁核酸分子信标在分子识别与生物分析中的应用

分子信标是一种荧光探针,闭合时呈发夹结构。其5'末端修饰荧光基团,3'末端修饰猝灭基团。当目标存在时,环部与目标结合,发夹打开,发出荧光。锁核酸是一类双环状寡核苷酸衍生物,能够遵循碱基互补配对原则与核酸结合。锁核酸分子信标技术,结合了分子信标无需分离未结合探针而直接检测的优势和锁核酸亲合力强、热稳定性好、抗酶切以及体内无毒等特点,在核酸检测方面具有灵敏度高、特异性好的独特优势,近年来得到广泛关注。本文介绍了锁核酸修饰分子信标的结构、功能、设计要点,及其研究现状和一些重要进展,并讨论了目前锁核酸分子信标在分子识别及生物分析中的应用及存在的问题和发展前景。     

离子液与蛋白质和核酸相互作用的研究

离子液因其具有良好的生物兼容性和独特的理化性质,近年来在生物催化和生物大分子蛋白质与核酸的分离分析领域得到广泛应用。离子液与生物大分子相互作用的研究是离子液相关理论与应用研究的基础,有关离子液与蛋白质和核酸相互作用的机理研究受到关注。本文简要介绍了常用离子液的分类,离子液与蛋白质分子作用的机理,离子液与核酸分子作用的机理,以及离子液在酶催化反应、生物分子分离、生物分子电化学分析和毛细管电泳分析中的应用,并主要综述了近年的相关研究和应用进展。     

Electrostatic Complementarity Drives Amyloid/Nucleic Acid Co-Assembly

Proteinaceous plaques associated with neurodegenerative diseases contain many biopolymers including the polyanions glycosaminoglycans and nucleic acids. Polyanion-induced amyloid fibrillation has been implicated in disease etiology, but structural models for amyloid/nucleic acid co-assemblies remain limited. Here we constrain nucleic acid/peptide interactions with model peptides that exploit electrostatic complementarity and define a novel amyloid/nucleic acid co-assembly. The structure provides a model for nucleic acid/amyloid co-assembly as well as insight into the energetic determinants involved in templating amyloid assembly.     

Modification of Nucleic Acids by Azobenzene Derivatives and Their Applications in Biotechnology and Nanotechnology

Azobenzene has been widely used as a photoregulator due to its reversible photoisomerization, large structural change between E and Z isomers, high photoisomerization yield, and high chemical stability. On the other hand, some azobenzene derivatives can be used as universal quenchers for many fluorophores. Nucleic acid is a good candidate to be modified because it is not only the template of gene expression but also widely used for building well‐organized nanostructures and nanodevices. Because the size and polarity distribution of the azobenzene molecule is similar to a nucleobase pair, the introduction of azobenzene into nucleic acids has been shown to be an ingenious molecular design for constructing light‐switching biosystems or light‐driven nanomachines. Here we review recent advances in azobenzene‐modified nucleic acids and their applications for artificial regulation of gene expression and enzymatic reactions, construction of photoresponsive nanostructures and nanodevices, molecular beacons, as well as obtaining structural information using the introduced azobenzene as an internal probe. In particular, nucleic acids bearing multiple azobenzenes can be used as a novel artificial nanomaterial with merits of high sequence specificity, regular duplex structure, and high photoregulation efficiency. The combination of functional groups with biomolecules may further advance the development of chemical biotechnology and biomolecular engineering.     

核酸探针技术

本文对核酸探针技术进行了较全面的综述，介绍了核探针的制备及非放射性标记方法，并对核酸的Ｓｏｕｔｈｅｒｎ转印杂交，Ｎｏｒｔｈｅｒｎ转印杂交，ＩｎＳｉｔｕ转印杂交及斑点杂交法的原理及应用进行了简明的评述。     

基于SERS技术的核酸检测

表面增强拉曼散射（SERS）技术因其具有超灵敏和非破坏性的检测能力,在生命科学领域已经显示出巨大的应用潜力和研究价值。本文综述了SERS技术在核酸检测方面的最新研究进展,重点介绍了基于SERS技术的非标记型、标记型以及其他一些检测方法的原理及研究成果,并讨论了基于SERS的核酸检测技术有待进一步解决的关键问题。     

核酸/高分子复合体系的制备与性能

综述了近年来核酸/高分子复合体系在设计、合成、性能研究以及应用等方面的最新研究进展,主要阐述了不同种类以及不同结构核酸/高分子体系的制备方法以及其在核酸检测、生物医药以及纳米等领域的应用,并对其未来的研究方向作了展望.     

核苷羧酸酯类化合物的酶法合成及其应用

核苷羧酸酯是一类在有机合成、核苷化学以及医药等领域具有重要应用价值的化合物. 近年来, 该类化合物的酶法合成以其绿色、高效、高选择性等优点而成为新的研究热点. 综述了近年来该领域的研究进展.     

CRISPR/Cas技术在核酸检测中的应用进展

CRISPR/Cas是大多数细菌及古细菌基于RNA的后天免疫系统。由CRISPR/Cas系统改造而成的CRISPR/Cas技术已成为一种强大的基因编辑工具,广泛应用于基因功能研究和基因修饰与治疗。除了作为基因编辑工具,Ⅱ类Cas蛋白具有的"附属切割"特性,已被开发成一种快速、低成本且高灵敏的核酸检测工具,在核酸分子诊断领域具有重要的应用潜力。该文总结了3种Ⅱ类Cas蛋白在核酸检测领域的代表性研究进展,并对CRISPR/Cas系统在该领域的应用前景进行了展望。