High-Throughput in vivo and in vitro screening of lipid nanoparticles for nucleic acid delivery to the brain

DOPE-based lipid nanoparticles delivered nucleic acids to the brain with higher efficiency than other formulations.

• A library of lipid nanoparticles (LNPs) was screened for their ability to deliver nucleic acids to neurons and brain tissue.
• The top-performing LNPs were identified based on their higher delivery rates of unique barcode DNA to the brain.
• Altering the ionizable lipid in the most effective formulation to FDA-approved options did not enhance neuronal transfection efficiency.
• The top-performing LNP4 successfully induced luciferase expression in the brain following intravenous administration.
• No neurological damage, inflammation, or behavioral impairments were observed in the tested mice.

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