The PAEDNEOVAX trial is a personalised Phase I/II mRNA vaccine trial designed to test the safety and efficacy of an mRNALNP approach in dismal outcome pediatric brain cancers. There are many moving parts in such a trial and the design and synthesis of mRNA vaccines is evolving rapidly. Here we shall present our broad design principles, in vivo and in vitro validation of these designs, and also present technology which may be implemented in the next generation of trials.