Plug-and-play assembly of biodegradable ionizable lipids for potent mRNA delivery and gene editing in vivo

May 26, 2026Proceedings of the National Academy of Sciences of the United States of America

Easy-to-build biodegradable lipids for strong mRNA delivery and gene editing in living animals

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Abstract

Screening 500 ionizable lipids led to the identification of a potent candidate for mRNA delivery.

  • A combinatorial chemistry approach enabled the assembly of diverse biodegradable lipids for gene delivery.
  • Machine learning facilitated the understanding of structure-activity relationships for effective mRNA delivery.
  • The lead lipid candidate outperformed both literature and industry benchmark lipid nanoparticles in mice.
  • Favorable physicochemical properties of the lipid nanoparticles may enhance their delivery performance.
  • The synthetic method demonstrates potential for broad application in in vivo gene editing.

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