Blood–brain-barrier-crossing lipid nanoparticles for mRNA delivery to the central nervous system

Feb 17, 2025Nature materials

Lipid nanoparticles that cross the blood-brain barrier to deliver mRNA to the brain and spinal cord

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Abstract

The lead formulation of BBB-crossing lipid nanoparticles demonstrates substantially higher mRNA delivery efficiency into the brain than FDA-approved lipid nanoparticles.

  • A total of 72 BBB-crossing lipids were designed and synthesized to enhance mRNA delivery to the brain.
  • The novel lipid nanoparticles successfully transfect neurons and astrocytes across the entire brain in mouse models after intravenous injections.
  • These nanoparticles are well tolerated across several dosage regimens.
  • The ability to deliver mRNA to human brain samples was confirmed through ex vivo studies.
  • This approach may provide a new platform for treating a variety of central nervous system diseases.

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