Peptide-Functionalized Lipid Nanoparticles for Targeted Systemic mRNA Delivery to the Brain

Dec 17, 2024Nano letters

Peptide-Designed Lipid Nanoparticles for Targeted Delivery of mRNA to the Brain Through the Bloodstream

AI simplified

mRNA Technology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Lipid nanoparticles functionalized with the RVG29 peptide significantly improve neuronal transfection in the mouse brain.

Systemic delivery of mRNA to the brain is hindered by the blood-brain barrier and liver accumulation of delivery vehicles.
Peptide-functionalized lipid nanoparticles were designed to target receptors on brain endothelial cells and neurons.
Click chemistry was used to attach specific peptides (RVG29, T7, AP2, mApoE) to the lipid nanoparticles.
Enhanced mRNA transfection was observed in the mouse brain with RVG29-functionalized nanoparticles.
Functionalization with peptides reduced the delivery of mRNA to the liver after systemic administration.

AI simplified

Systemic delivery of large nucleic acids, such as mRNA, to the brain remains challenging in part due to the blood-brain barrier (BBB) and the tendency of delivery vehicles to accumulate in the liver. Here, we design a peptide-functionalized lipid nanoparticle (LNP) platform for targeted mRNA delivery to the brain. We utilize click chemistry to functionalize LNPs with peptides that target receptors overexpressed on brain endothelial cells and neurons, namely the RVG29, T7, AP2, and mApoE peptides. We evaluate the effect of LNP targeting on brain endothelial and neuronal cell transfection, investigating factors such as serum protein adsorption, intracellular trafficking, endothelial transcytosis, and exosome secretion. Finally, we show that LNP peptide functionalization enhances mRNA transfection in the mouse brain and reduces hepatic delivery after systemic administration. Specifically, RVG29 LNPs improved neuronal transfection, establishing its potential as a nonviral platform for delivering mRNA to the brain. in vitro in vivo

Full Text

Full text is available at the source.

View full text (PDF) ↗View full text ↗

Peptide-Functionalized Lipid Nanoparticles for Targeted Systemic mRNA Delivery to the Brain

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the mrna technology brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the mrna technology brief