Mount Sinai Nature Biotechnology (April 29): Liver-Detargeted mRNA Vaccines Boost Cancer Immunity, Cut Lymphoma Tumor Burden by Over 50% in Mouse Models
An Icahn School of Medicine at Mount Sinai team reported in Nature Biotechnology on April 29 that hepatocytes actively dampen the immune response to standard mRNA vaccines and that engineering vaccines to avoid hepatocyte expression sharply boosts efficacy. In mice with lymphoma, an mRNA vaccine engineered to silence hepatocyte expression cut tumor burden by more than 50% versus a conventional mRNA vaccine, driven by a stronger killer T-cell response. The finding inverts a longstanding assumption that liver expression is helpful and supplies a generalizable design principle for mRNA cancer vaccines, infectious-disease vaccines, and gene-editing payloads.