Researchers at the Icahn School of Medicine at Mount Sinai reported that detargeting mRNA expression away from hepatocytes can strengthen T-cell immunity in preclinical lymphoma models. Published in Nature Biotechnology, the work argues vaccine potency can depend on which cell types express the delivered mRNA, challenging a long-standing focus on dendritic-cell delivery alone. The team used microRNA-targeted approaches to silence mRNA expression in specific cell populations, including dendritic cells, hepatocytes and muscle cells. Silencing in dendritic cells did not impair T-cell priming, while silencing in muscle weakened responses and silencing in hepatocytes tripled immune activity. Lead scientists framed hepatocytes as dampeners of vaccine immunity and described the findings as a design lever for next-generation mRNA therapeutics and vaccines.