Rapid Surface Display of mRNA Antigens by Bacteria‐Derived Outer Membrane Vesicles for a Personalized Tumor Vaccine

Abstract Therapeutic mRNA vaccination is an attractive approach to trigger antitumor immunity. However, the mRNA delivery technology for customized tumor vaccine is still limited. In this work, bacteria‐derived outer membrane vesicles (OMVs) are employed as an mRNA delivery platform by genetically engineering with surface decoration of RNA binding protein, L7Ae, and lysosomal escape protein, listeriolysin O (OMV‐LL). OMV‐LL can rapidly adsorb box C/D sequence‐labelled mRNA antigens through L7Ae binding (OMV‐LL‐mRNA) and deliver them into dendritic cells (DCs), following by the cross‐presentation via listeriolysin O‐mediated endosomal escape. OMV‐LL‐mRNA significantly inhibits melanoma progression and elicits 37.5% complete regression in a colon cancer model. OMV‐LL‐mRNA induces a long‐term immune memory and protects the mice from tumor challenge after 60 days. In summary, this platform provides a delivery technology distinct from lipid nanoparticles (LNPs) for personalized mRNA tumor vaccination, and with a “Plug‐and‐Display” strategy that enables its versatile application in mRNA vaccines.