Biological Behaviour of Unnatural Nucleic Acids

核酸是生命的基本组成部分。近年来，修饰核酸——也称为xeno核酸（XNAs）——的发展扩大了从治疗学到生物技术的各种应用的核酸库。XNAs的一个例子是二茂铁核酸（FcNAs），它用二茂铁单元取代DNA的糖磷酸主链，使非天然DNA具有氧化还原活性。二茂铁也可以作为一种标签并入DNA。该项目的目的是进一步了解非天然的核酸，如XNAs，通过探索其电化学和酶的行为，将其与天然的对偶物进行比较。首先利用二茂铁和环二铜的双标记探针系统进行单核苷酸多态性（snp）的电化学传感。探针通过硫醇化学连接到金表面，形成自组装单层（sam），与溶液中的目标DNA链形成互补的碱基配对。除此之外，还探索了修饰DNA的方波伏安法（SWV）和循环伏安法（CV），这将有助于电化学传感工作。最后，酶的工作将着眼于研究自然和修饰DNA的逆转录和聚合酶链反应（PCR）行为。该项目将寻求在癌症和SARS-CoV-2变体的早期诊断中提供可能的应用，并解决核酸治疗的局限性。

Nucleic acids are fundamental components for life. Recent years has seen the development of modified nucleic acids - also known as xeno nucleic acids (XNAs) - to expand the nucleic acid library for various applications from therapeutics to biotechnology. An example of XNAs are ferrocene nucleic acids (FcNAs) which replaces the sugar phosphate backbone of DNA with ferrocene units, rendering the unnatural DNA redox active. Ferrocene can also be incorporated into DNA as a tag.The aim of this project is to further understand unnatural nucleic acids, such as XNAs, by exploring their electrochemical and enzymatic behaviours which will be compared to their natural counterparts. This begins with utilising a dual tagged probe system of ferrocene and copper cyclidene for electrochemical sensing of single nucleotide polymorphisms (SNPs). Probes are attached to a gold surface, via thiol chemistry, to form self-assembled monolayers (SAMs) which form complementary base pairing with target DNA strands in solution. In addition to this, square wave voltammetry (SWV) and cyclic voltammetry (CV) of modified DNA is also explored which will assist the electrochemical sensing work. Finally, enzymatic work will look to investigate reverse transcription and polymerase chain reaction (PCR) behaviours of natural and modified DNA. The project will look to provide possible application in early stage diagnostics of cancer and SARS-CoV-2 variants and address limitations in nucleic acid therapeutics.