Breaking Barriers--Lipid Nanoparticles Unlock mRNA Delivery to the Brain

A groundbreaking study led by Chang Wang and colleagues, published in Nature Materials on February 17, 2025, unveils a novel approach for delivering mRNA across the blood-brain barrier (BBB) to the central nervous system (CNS). The researchers synthesized 72 lipid nanoparticles (LNPs) by conjugating BBB-crossing modules with amino lipids, aiming to facilitate mRNA delivery to the brain. Through extensive screening and optimization, they identified a lead LNP formulation that demonstrated significantly higher mRNA delivery efficiency to the brain compared to existing FDA-approved LNPs. In mouse models, these LNPs successfully transfected neurons and astrocytes throughout the brain following intravenous administration and were well-tolerated across various dosing regimens. Moreover, the LNPs effectively delivered mRNA to human brain samples ex vivo.

This advancement holds promise for treating a range of CNS diseases by enabling targeted mRNA delivery to critical brain regions.