LAUSR

Significance Current messenger RNA (mRNA) vaccines in the clinic were reported to induce side effects in the liver, such as reversible hepatic damages and T cell–dominant immune-mediated hepatitis, which might be caused by the undesired expression of antigens in the liver. Therefore, exploring a lymphoid-organ–specific mRNA vaccine could be a promising strategy for developing next-generation mRNA vaccines. Herein, we reported a lymph-node–targeting mRNA vaccine based on lipid nanoparticles named 113-O12B for cancer immunotherapy. The targeted delivery of the mRNA vaccine elicits robust CD8+ T cell responses, exhibiting excellent protective and therapeutic effects on B16F10 melanoma. Notably, 113-O12B can efficiently deliver both a full-length protein and a short-peptide–based, antigens-encoded mRNA, thus providing a universal platform for mRNA vaccines.