Abstract

Efficacious use of therapeutic gene delivery via nanoparticles is hampered by the challenges associated with targeted delivery to tissues of interest. Systemic administration of lipid nanoparticle (LNP)-encapsulated mRNA leads to a protein expressed predominantly in the liver and spleen. Here, LNP encapsulating mRNA was covalently conjugated to an antibody, specifically binding plasmalemma vesicle-associated protein (PV₁) as a means to target lung tissue. Systemic administration of PV₁-targeted LNPs demonstrated significantly increased delivery of mRNA to the lungs and a 40-fold improvement in protein expression in the lungs, compared with control LNPs. We also investigated the effect of LNP size to determine optimal tissue distribution and transfection. Larger-size PV₁-targeted LNPs not only have the elasticity to target the PV₁ expressed in the caveolae but also enable robust mRNA expression in the lungs. Targeted delivery of mRNA to the lungs is a promising approach in the treatment of lung diseases.

Engineering Caveolae-Targeted Lipid Nanoparticles To Deliver mRNA to the Lungs

Abstract

Advanced Search

Browse by Category

related content

Combined Hybrid Structure of siRNA Tailed IVT mRNA (ChriST mRNA) for Enhancing DC Maturation and Subsequent Anticancer T Cell Immunity

Harnessing RNAi-Based Nanomedicines for Therapeutic Gene Silencing in B-cell Malignancies