Next generation nucleic acid drugs with enhanced delivery and efficacy

Nucleic acid drugs (NAD) uniquely target mRNA, especially for cases unaddressable by conventional drugs. This project aims to chemically modify NADs to improve their cellular delivery and safety, focusing on efficient delivery and reduced toxicity. We will synthesize novel chemical modifications for targeted delivery to heart and brain tissues, addressing the challenges of delivery and efficacy that hinder NAD clinical success. You will join a vibrant research group at the School of Chemistry in Southampton, synthesizing modified phosphoramidite monomers and incorporating them into therapeutic oligonucleotides. You will investigate their biophysical and biological properties using techniques such as solid phase synthesis, UV, fluorescence, cell biology assays, and machine learning. Training in structural techniques like X-ray crystallography is provided. The project involves collaborative work with labs in Southampton and Oxford and offers opportunities for industrial training through partner companies. The project will deliver new NAD chemical modifications enabling efficient, targeted delivery to heart and brain cells while ensuring safety and high efficacy. You will gain expertise in synthetic chemistry, biophysical and biochemical assays, and structural analysis, contributing to advancing therapeutic oligonucleotide development. This research tackles critical barriers in NAD therapy, enhancing drug delivery and safety to unlock their full therapeutic potential. Success will accelerate development of precise molecular medicines, meeting unmet clinical needs and transforming treatment options for many diseases.

You must have a UK 2:1 honours degree or its international equivalent. Essential: experimental skills and knowledge in synthetic organic chemistry. Knowledge in solid phase oligonucleotides synthesis, biophysical and biochemical assays (e.g., UV, fluorescence, cell biology, machine learning), and structural techniques (e.g., X-ray crystallography) is beneficial but not essential.

Apply by choosing programme type Research, 2026/27, Faculty of Engineering and Physical Sciences; select Full time or Part time; search programme PhD Chemistry (7189); add supervisor name in application section 2. Include CV, 2 academic references, degree transcripts and certificates, and English language qualification if applicable. Contact feps-pgr-apply@soton.ac.uk for general questions or ahes@soton.ac.uk for project inquiries.