Biological Behaviour of Unnatural Nucleic Acids

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.