Hemophilia is a genetic bleeding disorder caused by deficiencies in coagulation factor VIII or IX. Although current therapies-including factor replacement, bispecific antibodies, and gene therapy-have improved disease management, they are limited by short half-lives, immunogenicity, complex manufacturing processes, and the need for repeated administration. Here, we report a lipid nanoparticle (LNP)- encapsulated messenger RNA (mRNA) encoding MG1113, a humanized monoclonal antibody that targets tissue factor pathway inhibitor (TFPI), enabling sustained in vivo antibody production as a factor-unrelated therapeutic strategy. The mRNA was optimized with a tailored signal peptide, regulatory UTRs, uridine depletion, and N1-methyl-pseudouridine incorporation to enhance the efficiency and stability of its translation. Systemic administration of the MG1113 mRNA-LNPs to mice and rabbits led to robust and durable antibody expression, efficient plasma TFPI suppression, and extended pharmacodynamic effects compared with direct administration of the recombinant MG1113 protein. This study explores an mRNA-LNP platform for antibody delivery in hemophilia, offering the potential for prolonged pharmacological activity, simplified manufacturing, and flexible therapeutic application. Taken together, our findings suggest that mRNA LNP systems could advance next-generation antibody-based treatment strategies for bleeding disorders and potentially other diseases.
mRNA Technology