Injecting mRNA nanoparticles into mouse fetuses improves survival in spinal muscular atrophy

One lipid nanoparticle (LNP1) efficiently delivered mRNA to specific brain cells in fetal models.

• Lipid nanoparticles are effective for delivering messenger RNA for base editing but struggle with targeting the central nervous system.
• LNP1 was identified as capable of delivering mRNA to endothelial cells, microglia, and neurons in the fetal cortex.
• Application of LNP1 in a mouse model for spinal muscular atrophy enabled base editing in the liver and cortex.
• Low levels of editing were observed in central nervous system organs, yet fetal administration led to modestly increased survival in SMA mice.
• Findings suggest that fetal biology may play a role in enhancing mRNA delivery for potential central nervous system therapies.

Simplified