Journal of controlled release : official journal of the Controlled Release Society

Synthetic lipid nanoparticles that deliver mRNA specifically to immune cells in the spleen

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

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Abstract

Lipidoids engineered for selective mRNA delivery to the spleen showed strong targeting efficiency.

  • A series of 48 chemically distinct lipidoids were synthesized to enhance mRNA delivery.
  • Certain lipidoids with tails H228, H226x, H246x, and H446x exhibited exceptional spleen-targeting capabilities.
  • A secondary library of 36 lipidoids was screened to identify candidates with high potency and spleen selectivity.
  • The lead candidate, DMA4-H228, successfully delivered ovalbumin mRNA to antigen-presenting cells.
  • This delivery prompted interferon-α production and activation of antigen-presenting cells, which may inhibit tumor growth.

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