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Engineered mRNA Nanoparticles Reroute Delivery to Lymph Nodes in Mouse Study

The Penn design cuts liver exposure about tenfold to support lower-dose, better-tolerated mRNA vaccines.

Overview

  • The study, published Tuesday in the Journal of the American Chemical Society, reports a new class of aroLNPs that steers mRNA away from the liver and toward lymph nodes in mice.
  • Researchers added aromatic rings and bioreducible disulfide bonds to the ionizable lipid, then tuned tail length and regiochemistry to shift where the particles travel.
  • Top formulations delivered about ten times less mRNA to the liver than LNPs using Moderna’s ionizable lipid while keeping lymph-node delivery at similar levels.
  • In vaccine models, aroLNPs matched antibody responses from clinically used lipids and triggered only small rises in systemic inflammatory cytokines.
  • Biodistribution was tracked with luciferase mRNA to measure organ light signals, and the team says the approach could cut vaccine doses and enable immune therapies pending further testing.