Engineering Caveolae-Targeted Lipid Nanoparticles To Deliver mRNA to the Lungs
| Autor: | Qing Li, William Dall'acqua, Chingshen Chan, Richard N. Hanna, Norman C. Peterson, Alex Alfaro, José Luís Guedes dos Santos, Kevin L Allen, M. Jack Borrok, Herren Wu |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Spleen Gene delivery Caveolae 01 natural sciences Biochemistry 03 medical and health sciences medicine Animals RNA Messenger Lung Messenger RNA Drug Carriers Mice Inbred BALB C biology 010405 organic chemistry Chemistry Gene Transfer Techniques Membrane Proteins General Medicine Transfection Lipids 0104 chemical sciences Cell biology 030104 developmental biology medicine.anatomical_structure Systemic administration biology.protein Molecular Medicine Nanoparticles Female Antibody Antibodies Immobilized |
| Zdroj: | ACS chemical biology. 15(4) |
| ISSN: | 1554-8937 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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