Sequenced defined oligophosphoester mucosal adjuvants for mRNA vaccines

Project ID: 2228cd1339 (You will need this ID for your application)

Under Offer

Research Theme: Healthcare Technologies

UCL Lead department: School of Pharmacy

Department Website

Lead Supervisor: Pratik Gurnani

Project Summary:

Why this research is important:

Vaccination through messenger RNA (mRNA) technology has now been clinically demonstrated due to its successes in the COVID-19 pandemic. Although these first-generation vaccines are effective at preventing severe disease, there are opportunities to improve protection against contracting the infection itself. One of these routes is through adjuvantation.

Adjuvants are immunostimulatory molecules included in vaccine formulations designed to enhance durability of protection by boosting immune response. Adjuvants that offer the strongest response achieve this by initialising innate cellular immunity pathways by binding to pathogen sensing receptors, such as Toll-like receptors (TLRs), mimicking the natural infection process. However, modulating the strength and quality of TLR response is imperative to balance immunogenicity and adjuvanticity without affecting translation of the delivered mRNA vaccine, however this is not easily achieved using current adjuvant technologies.

This project aims to develop a new TLR adjuvant platform for mucosally delivered mRNA vaccines based on DNA/RNA mimicking synthetic, sequence controlled, oligophosphoesters. This project will combine organic chemistry, polymer/materials chemistry, pharmaceutics and biomedical science, and in vitro and in vivo characterisation.

There are five main objectives for this research project:

  1. Computational structure/activity investigation of oligophosphoester binding to Toll-like receptors
  2. Solid phase synthesis of hit oligophosphoester sequences
  3. Formulation with mRNA into lipid nanoparticles, and in vitro testing of mRNA expression/immunogenicity
  4. Permeation through mucosal tissues
  5. In vivo immunogenicity

Who you will be working with: You will join the groups of Dr Pratik Gurnani (RNA therapeutics), Dr Sudax Murdan (vaccines), Dr Chris Serpell (oligophosphoester synthesis) and Dr Fatme Mawas (Immunology).

Who we are looking for: Looking for motivated candidate with background in chemistry/medicinal chemistry/pharmacy interested in combining synthesis with pharmaceutics research. Candidates with a biology/biomedicine background will also be considered.