A synthetic DNA template for fast manufacturing of versatile single epitope mRNA
De Mey et al. – Molecular Therapy Nucleic Acids, 2022
Research on a synthetic DNA template assembly process for cost- and time-efficient manufacturing of single neoepitope mRNA vaccines with validated T-cell activation.
Abstract
A flexible, affordable, and rapid vaccine platform is necessary to unlock the potential of personalized cancer vaccines in order to achieve full clinical efficiency. mRNA cancer vaccine manufacture relies on the rigid sequence design of multiepitope constructs produced by laborious bacterial cloning and time-consuming plasmid preparation. Here, we introduce a synthetic DNA template (SDT) assembly process, which allows cost- and time-efficient manufacturing of single (neo)epitope mRNA. We benchmarked SDT-derived mRNA against mRNA derived from a plasmid DNA template (PDT), showing that monocyte-derived dendritic cells electroporated with SDT-mRNA or PDT-mRNA equally activated T cells that were modified to express the cognate T cell receptors. Furthermore, we validated the SDT-mRNA platform for neoepitope immunogenicity screening and compared SDT-mRNA with PDT-mRNA for vaccine development purposes.
DOI: 10.1016/j.omtn.2022.08.021
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