Biological Behaviour of Unnatural Nucleic Acids

核酸是生命的基本成分。近年来，修饰核酸-也称为异种核酸(XNAs)-的发展扩大了核酸文库，用于从治疗到生物技术的各种应用。XNAs的一个例子是二茂铁核酸(FcNAs)，它用二茂铁单位取代DNA的糖磷酸骨架，使非天然的DNA氧化还原活跃。这个项目的目的是通过探索非自然核酸的电化学和酶行为，并将其与天然核酸进行比较，进一步了解非自然核酸，如XNAs。这首先利用二茂铁和环状铜的双标记探针系统来电化学检测单核苷酸多态(SNPs)。探针通过硫醇化学连接到金表面，形成自组装单分子膜(SAM)，在溶液中与目标DNA链形成互补碱基配对。此外，还对修饰DNA的方波伏安法(SWV)和循环伏安法(CV)进行了探索，为电化学传感工作奠定了基础。最后，酶的工作将着眼于研究天然和修饰DNA的逆转录和聚合酶链式反应(PCR)行为。该项目将寻求在癌症和SARS-CoV-2变种的早期诊断中提供可能的应用，并解决核酸疗法的局限性。

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.