PhD Studentship: Novel Stabilisation and Delivery Materials for RNA-based Therapies

After nearly five decades of research and innovation, the first mRNA-based vaccines burst on to the world stage during the COVID-19 pandemic halting the spread of infections and heralding a new era in vaccine development and biotherapeutics. [1] In vitro transcribed (IVT) messenger (m)RNA is viewed as a paradigm shift within the pharmaceutical field; with the potential to revolutionise pharmaceutics and approaches to medicine. The idea, beautiful in its simplicity, of engineering mRNA sequences which elicit the patient’s own cells to regulate and produce therapeutic agents, verges on the apex of personalised medicines. [2]

The current gold-standard for the stabilisation and delivery of RNA-based therapies centres around the use of lipid nano-particles (LNPs). However, these come with a plethora of drawbacks including poor encapsulation efficiencies, long-term stability and concerns surrounding toxicity. [3] To unlock the full potential of RNA-based therapies, new formulations are required which not only stabilise but facilitate better delivery. At the University of Birmingham, we have demonstrated an ability to improve the stability of RNA using sugar-based polymers. Our early data demonstrates that these materials can interact with the RNA and act as scaffolds to prevent denaturation, providing new opportunities for lower cost manufacturing, improved storage and shelf-life and the ability to formulate RNA into various dosage forms (sprays, drops, hydrogels). Moreover, it offers a solution for the effective distribution of RNA medicines to developing countries, where the costs of cold chain have hindered their usage.

The vision for this multi-disciplinary research project is to build a deeper understanding of how polysaccharides can be used to stabilise and deliver RNA-based therapies, focussing specifically on:

• understanding how sugar-based polymers stabilise RNA;
• demonstrating that these new materials can be used to deliver RNA into cells; and
• formulating the materials into usable dosage formats.

The research will be conducted at the School of Chemical Engineering’s Healthcare Technologies Institute (HTI) – a multi-million-pound facility designed to accelerate new technologies to patients. It is here that you will learn a wide range of skills in Biotechnology, Engineering and Materials Science and Translational Medicine, including but not limited to the following:

• in vitro transcription of and purification of mRNA;
• gel electrophoresis-based analyses;
• biophysical characterisation (incl. zeta potential measurements; particle size analysis, CD – Circular Dichroism, DSC – Differential Scanning Calorimetry);
• cell culture and transfection assays;
• microstructural design and materials formulation;
• microstructural characterisation (incl. rheometry, microscopy, spectroscopy, SAX – Small Angle X-Ray Scattering); and
• understanding pathways to clinic.

Funding notes:

This project is part of the BBSRC-funded Midlands Integrative Biosciences Training Partnership (MIBTP) scheme. This MIBTP studentship offer a comprehensive support package, including fees (the cost of the UK fee rate), a tax-free annual stipend, a travel and conference budget, a generous consumables budget, and the use of a MacBook Pro for the duration of the programme.

For more information on the MIBTP scheme please refer to the following websites:
Main MIBTP page - https://warwick.ac.uk/fac/cross_fac/mibtp/
Birmingham MIBTP page - https://www.birmingham.ac.uk/research/activity/mibtp
University of Birmingham Press release - https://www.birmingham.ac.uk/news/2024/major-investment-in-doctoral-students-to-support-next-generation-of-researchers
UKRI press release - https://www.gov.uk/government/news/over-4700-newly-funded-post-graduate-places-in-uk-universities-to-create-new-generation-of-engineers-and-scientists

For more information on the project please contact Dr Richard Moakes: r.j.a.moakes@bham.ac.uk

References:

[1] Barbier, A.J et al (2022) Nature Biotechnology 40, 840-854.
[2] Sahin, U. et al (2014) Nature Reviews Drug Discovery 13: 759-780.
[3] Hou, X. et al (2021) Nature Reviews Materials 6: 1078-1094.

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