mRNA mediates passive vaccination against infectious agents, toxins, and tumors

The delivery of genetic information has emerged as a valid therapeutic approach. Various reports have demonstrated that mRNA, besides its remarkable potential as vaccine, can also promote expression without inducing an adverse immune response against the encoded protein. In the current study, we set out to explore whether our technology based on chemically unmodified mRNA is suitable for passive immunization. To this end, various antibodies using different designs were expressed and characterized in vitro and in vivo in the fields of viral infections, toxin exposure, and cancer immunotherapies. Single injections of mRNA–lipid nanoparticle (LNP) were sufficient to establish rapid, strong, and long‐lasting serum antibody titers in vivo , thereby enabling both prophylactic and therapeutic protection against lethal rabies infection or botulinum intoxication. Moreover, therapeutic mRNA‐mediated antibody expression allowed mice to survive an otherwise lethal tumor challenge. In conclusion, the present study demonstrates the utility of formulated mRNA as a potent novel technology for passive immunization. Synopsis As a transient carrier of information, exogenous mRNA is considered a possibly powerful tool to instruct a body to produce its own therapeutics. Antibody‐encoding, sequence‐optimized but otherwise unmodified mRNA in LNPs empowered mice to successfully fight various biological threats. Sequence‐optimization enables efficient antibody expression from in vitro transcribed mRNA. Exogenous mRNA can instruct cells to produce various types of antibodies. Optimized mRNA in lipid nanoparticles provides efficient antibody expression in hepatocytes upon intravenous administration. mRNA‐mediated antibody expression can protect mice against toxins, viruses, and tumors. Graphical Abstract As a transient carrier of information, exogenous mRNA is considered a possibly powerful tool to instruct a body to produce its own therapeutics. Antibody‐encoding, sequence‐optimized but otherwise unmodified mRNA in LNPs empowered mice to successfully fight various biological threats.