Advancing mucoadhesive oral patches for mRNA vaccine delivery

Supervisor(s): Professor Helen Colley, Professor Steve Armes, Dr Jake Edmans, Dr Zoltan Kis

Immunisation is a cornerstone of global healthcare, preventing millions of deaths per year worldwide. The SARS-CoV-2 pandemic catalysed rapid vaccine development, with messenger RNA (mRNA)-based vaccines at the forefront of strategies to combat COVID-19. This technology has created the opportunity to expand vaccine coverage to many other diseases not previously possible. However, mRNA vaccines are not problem-free. mRNA and their carrier, lipid nanoparticles (LNP), are sensitive to heat and require strict cold-chain storage, causing logistical and quality control challenges. They are administered by injection, which requires access to sterilised equipment and trained healthcare professionals. Such facilities are not always available in parts of the world where vaccines are most needed. A self-administered, needle-free delivery system would also enable vaccination of people who suffer from needle-phobia. 

This PhD project aligns with a UKRI Engineering Biology Mission Award where we aim to resolve these problems and transform vaccine delivery by developing a mRNA vaccine-containing mucoadhesive patch to deliver mRNA directly to immune cells within the oral epithelium to initiate a protective immune response. More specifically, the PhD student will:

(i)    Synthesise and characterise new stimulus-responsive block copolymer vesicles and examine how these vesicles can be used to encapsulate mRNA for vaccine delivery.

(ii)   Optimise the mRNA loading capacity of these vesicles and compare their long-term stability, drug retention and controlled drug release to that of current LNP mRNA vaccine formulations.

(iii) Compare the release of mRNA-loaded vesicles from a mucoadhesive patch into both oral mucosal epithelium and immune cells over time to that of release from microneedles.

(iv) Study mRNA translation into a protein within these cells to generate an immune response.

This is an exciting opportunity to join a multidisciplinary research team working at the engineering and physical/life science interface and to contribute to a broader Mission Award research programme. You will contribute to the development of a novel self-administered, needle-free delivery platform for mRNA vaccines under the supervision of Professor Helen Colley (Professor of Tissue Engineering) and Professor Steve Armes FRS (Professor of Polymer and Colloid Chemistry, Department of Chemistry). 

We seek a talented and highly motivated student with a background in chemistry or material science. In this project, you will combine cutting-edge polymer chemistry and material science techniques (electrospinning/microneedle formulation) to develop next-generation mucoadhesive matrix technologies for the rapid release of mRNA-loaded stimulus-responsive block copolymer vesicles.

You will be trained in modern synthetic polymer chemistry and cell biology and use sophisticated analytical techniques such as NMR, dynamic light scattering, aqueous electrophoresis, electron microscopy, confocal fluorescence microscopy, NanoFM, flow cytometry etc. to demonstrate patch-mediated mRNA delivery into cells for translation and plasma membrane protein presentation. This PhD project is expected to lead to the development of a truly paradigm-shifting technology for vaccine delivery.

Entry Requirements:

Candidates must have a first class or upper second-class honours degree, preferably with research experience.

How to apply:

Please complete a University Postgraduate Research Application form available here: www.shef.ac.uk/postgraduate/research/apply

Please clearly state the prospective main supervisors in the respective box and select (School of Clinical Dentistry) as the department.

Enquiries:

Interested candidates should in the first instance contact Professor Helen Colley ([email protected]) or Professor Steve Armes ([email protected]).