About the project
This is a PhD Studentship in organic synthesis and chemical biology. This project focuses on developing novel backbone-modified therapeutic oligonucleotides (ONs) to improve stability, uptake, and affinity.
Therapeutic oligonucleotides (ONs) are an emerging class of drugs that modulate gene expression by binding RNA. Chemical modifications, particularly backbone alterations, can significantly improve stability, uptake, and affinity, properties that currently limit the broader therapeutic application of oligonucleotides. This project will develop novel backbone modifications to enhance ON performance.
Using advanced organic synthesis, you will design and synthesise modified ONs, characterising their biophysical properties and biological activity. You will receive training in organic chemistry, nucleic acid synthesis, biophysical analysis, and cell-based assays.
Multi-step organic synthesis will be employed to prepare the required building blocks, followed by solid-phase synthesis for the construction of ONs. This project also involves biophysical characterisation of modified ONs and assessment of their biological activity in cell-based assays.
The project builds on out recent work published in Nature Communications which explores the potential of backbone-modified nucleosides for improving oligonucleotide stability and efficacy.
You will receive extensive training in:
- synthetic organic chemistry
- solid-phase and solution-phase synthesis of nucleic acids (DNA, RNA and ONs)
- biophysical characterisation (e.g. UV-Vis, thermal melting analysis)
- cell-based assays for evaluating biological activity
The research environment includes advanced facilities such as automated DNA/RNA synthesisers, High-Performance Liquid Chromatography (HPLC), and mass spectrometry. You will work closely with experts in the therapeutic oligonucleotide field at Grünenthal, our industrial partner and a leading global pharmaceutical company. You will have the opportunity to undertake a research placement at its Aachen site in Germany.
In addition to the supervisory team at the University of Southampton, this project also has the following external supervisors:
- Dr Clemens Dialer (Grünenthal)
- Dr Keith Phillips (Grünenthal)
