Enzymatic Technologies for Discovery of Improved Oligonucleotide-peptide Conjugates

About the Project

This project is co-sponsored by the EPSRC CDT in Chemical Biology and AstraZeneca.

Supervisors:

• Dr Louise Walport, Department of Chemistry, Imperial
• Professor Jason Micklefield, Department of Chemistry, Imperial
• Dr Nazila Kamaly, Department of Chemistry, Imperial
• Dr Siddique Amin, AstraZeneca
• Dr Samantha Staniland, AstraZeneca

Abstract:

Modified nucleic acids have emerged as an important class of therapeutic agents and vaccines, which are set to transform the prevention and treatment of many diseases. The three main classes of nucleic acid therapeutics (NAT) are antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs) and modified aptamers. In addition to 18 approved drugs, more than 150 different modified nucleic acid therapeutics are currently in clinical trials for the treatment of cancer, cardiovascular, neurodegenerative and various infectious diseases, as well as other ailments.

Currently two main challenges remain to be addressed around: (i) scalable synthesis of NAT; and (ii) efficient target cellular delivery. The production of modified oligonucleotides relies on solid phase chemical synthesis, which is challenging at the scale required for NAT manufacture. This is beginning to be addressed through the development of new enzymatic methods for modified oligonucleotide assembly, but this technology has a long way to go before it will be industry ready. Oligonucleotide delivery has been partially addressed through the development of lipid nanoparticles, but these lack the necessary selectivity, require relatively high doses, and thus risk off-target toxic effects. Several oligonucleotide-peptide conjugates (OPCs) show promise in clinical trials. However, the assembly of OPCs is synthetically challenging, which can limit the number of constructs/sequences available for screening.

In this project, we aim to develop new enzymatic technology that will allow vast libraries of OPCs to be assembled and then rapidly screened “direct-to-biology” for highly efficient receptor mediated, tissue specific cellular uptake, increased stability, and improved efficacy in vivo. This opportunity is ideally suited to applicants with interests in chemical biology, drug discovery, nucleic acids, and/or peptide research. Individuals who are keen to work at the chemistry–biology interface in a highly interdisciplinary environment are encouraged to apply. This project is a collaboration between researchers at Imperial College and AstraZeneca. The successful candidate will benefit from a placement period working in the AstraZeneca labs, and will receive a significantly enhanced stipend of £31,805 pa, which includes additional funding from the UK government’s TechExpert pilot scheme.

For further information contact: j.micklefield@imperial.ac.uk

Also see our websites:

• crick.ac.uk/research/labs/louise-walport
• https://profiles.imperial.ac.uk/j.micklefield
• https://profiles.imperial.ac.uk/nazila.kamaly

Eligibility:

This project is only open to applicants with Home fee status. For further information, please review our Eligibility criteria and How to apply.

Deadline:

Thursday 16th May 2026, 5pm.

This studentship opportunity was released on 1st May 2026