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


Authors: Q. Li, C. Chan, N. Peterson, R.N. Hanna, A. Alfaro, K.L. Allen, H. Wu, W.F. Dall'Acqua, M.J. Borrok and J.L. Santos

Journal: ACS Chemical Biology

DOI: 10.1021/acschembio.0c00003

Publication - Abstract

March 10, 2020

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.

Advanced Search

close
  • Publications
  • Application Notes
  • Posters
  • Workshops
  • Videos & Webinars
  • Blog Posts
Search

Browse by Category

  • Application
    • Diagnostic and Imaging
    • Genetic Medicine
    • Hematology
    • Metabolic Disorders
    • Neuroscience
    • Oncology
    • Skeletal Disorders
    • Targeted Drug Delivery
    • Vaccines
    • Other Applications
  • Formulation
    • Liposomes
    • Nucleic Acid Lipid Nanoparticles
    • Polymeric Nanoparticles
    • Other Formulations
  • Payload
    • DNA
    • microRNA
    • mRNA
    • siRNA
    • Small Molecule Drugs
    • Other Payloads


related content

Publication - Summary

Vaccine Mediated Protection Against Zika Virus-Induced Congenital Disease

J.M. Richner, B.W. Jagger, C. Shan, C.R. Fontes, K.A. Dowd, B. Cao, S. Himansu, E.A. Caine, B.T. Nunes, D.B. Medeiros and A.E. Muruato

Lately there has been intense effort to develop vaccines for Zika virus, in part due to the recently established link between Zika infection and congenital birth defects such as microcephaly and the rapid spread of Zika in Oceania and the Americas ...

Read More


Publication - Abstract

New synthetic aminoxy lipids are designed and synthesized as building blocks for the formulation of functionalized nanoliposomes by microfluidization using a NanoAssemblr. Orthogonal binding of hyaluronic acid onto the outer surface of functionalized nanoliposomes via aminoxy cou...
Read More


Sign Up and Stay Informed
Sign up today to automatically receive new Precision NanoSystems application notes, conference posters, relevant science publications, and webinar invites.