Unlocking the Brain

Penn Engineers have modified lipid nanoparticles (LNPs) — the revolutionary technology behind the COVID-19 mRNA vaccines — to not only cross the blood-brain barrier (BBB) but also to target specific types of cells, including neurons. This breakthrough marks a significant step toward potential next-generation treatments for neurological diseases like Alzheimer’s and Parkinson’s.

In a new paper in Nano Letters, the researchers demonstrate how peptides — short strings of amino acids — can serve as precise targeting molecules, enabling LNPs to deliver mRNA specifically to the endothelial cells that line the blood vessels of the brain, as well as neurons.

This represents an important advance in delivering mRNA to the cell types that would be key in treating neurodegenerative diseases; any such treatments will need to ensure that mRNA arrives at the correct location. Previous work by the same researchers proved that LNPs can cross the BBB and deliver mRNA to the brain, but did not attempt to control which cells the LNPs targeted.

“Our first paper was a proof-of-concept lipid nanoparticle design,” says Michael J. Mitchell, Associate Professor in Bioengineering (BE) and the paper’s senior author. “It was like showing we could send a package from Pennsylvania to California, but we had no idea where in California it would end up. Now, with peptides, we can address the package to specific destinations with shared features, like every house with a red mailbox.”

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