10067131Process Development and Stability of the RALA Peptide for mRNA VaccinesClosedCollaborative R&DInnovate UKmRNA vaccines have the potential to transform healthcare interventions as evidenced by the approval of 2 products in the last 2 years for Covid-19\. The mRNA codes for an antigen for a disease that can either be administered to healthy patients to prevent infective diseases or can treat diseases such as cancer. Vaccines that prevent disease are typically administered via intramuscular or intradermal routes and those that treat disease are delivered intravenously. According to Clinical Trials.gov there are currently 287 ongoing mRNA vaccine clinical trials. However, the key to a successful vaccine is the delivery inside the cell and for this a 'trojan horse' is required. For the approved vaccines, lipid nanoparticles (LNPs) have been used but the cells recognise the LNPs as foreign which provokes an immune response that is unrelated to the mRNA. Additionally, LNPs require cold chain storage, are solvent based, are restricted by the size of mRNA they can deliver with suboptimal endosomal escape. pHion (Belfast SME) have developed a solution for mRNA delivery that is safe, does not further exacerbate the immune system, and readily enters antigen presenting cells with full escape of the mRNA to the cytoplasm of the cell. The innovation centres around the use of a peptide termed RALA that is designed to condense mRNA into nanoparticles (NPs) irrespective of size or number. The NPs have the properties necessary to enter cells, escape endosomes and deliver the cargo to the cytoplasm with high efficiency. pHion has shown that these vaccines are highly efficient in vivo because of this intracellular entry. However, as a platform technology, we need to address some key questions to realise the potential for global manufacture. With clear alignment to the theme of this call, the aim is to develop both a liquid and powdered formulation of the RALA/mRNA vaccine platform that can be given either intravenously for therapeutic vaccines and intramuscularly or intradermally for prophylactic vaccines. Specific goals are to understand i) where the mRNA goes following injection via these routes; ii) how to formulate a stable liquid formulation; iii) how to freeze-dry large enough RALA/mRNA batches that can be scaled up; iv) how to ensure we make the NPs on multiple different types of microfluidics machines; v) how to produce a full package of critical key quality attributes and vi) an analysis of the cost of goods. This will make us and the UK future ready.