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Engineering Caveolae-Targeted Lipid Nanoparticles To Deliver mRNA to the Lungs
journal contribution
posted on 2020-03-13, 14:11 authored by Qing Li, Chingshen Chan, Norman Peterson, Richard N. Hanna, Alex Alfaro, Kevin L. Allen, Herren Wu, William F. Dall’Acqua, M. Jack Borrok, Jose Luis SantosEfficacious
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.