Linkage Between Endosomal Escape of LNP-mRNA and Loading into EVs for Transport to Other Cells


Authors: M. Maugeri, M. Nawaz, A. Papadimitriou, A. Angerfors, A. Camponeschi, M. Na, M. Hölttä, P. Skantze, S. Johansson, M. Sundqvist, J. Lindquist, T. Kjellman, I.-L. Mårtensson, T. Jin, P. Sunnerhagen, S. Östman, L. Lindors, and H. Valadi

Journal: Nature Communications

DOI: 10.1038/s41467-019-12275-6

Publication - Abstract

September 24, 2019

Abstract

RNA-based therapeutics hold great promise for treating diseases and lipid nanoparticles (LNPs) represent the most advanced platform for RNA delivery. However, the fate of the LNP-mRNA after endosome-engulfing and escape from the autophagy-lysosomal pathway remains unclear. To investigate this, mRNA (encoding human erythropoietin) was delivered to cells using LNPs, which shows, for the first time, a link between LNP-mRNA endocytosis and its packaging into extracellular vesicles (endo-EVs: secreted after the endocytosis of LNP-mRNA). Endosomal escape of LNP-mRNA is dependent on the molar ratio between ionizable lipids and mRNA nucleotides. Our results show that fractions of ionizable lipids and mRNA (1:1 molar ratio of hEPO mRNA nucleotides:ionizable lipids) of endocytosed LNPs were detected in endo-EVs. Importantly, these EVs can protect the exogenous mRNA during in vivo delivery to produce human protein in mice, detected in plasma and organs. Compared to LNPs, endo-EVs cause lower expression of inflammatory cytokines.

Advanced Search

close
  • Publications
  • Application Notes
  • Posters
  • Workshops
  • Videos & Webinars
  • Articles
Search

Browse by Category

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


related content

Publication - Abstract

Combined hybrid of siRNA tailed mRNA (ChriST mRNA) functioned as siRNA and mRNA to simultaneous suppress and express protein.

siRNA and mRNA structures were separated from the ChriST mRNA by RNase H-mediated cleavage of RNA/DNA ...

Read More


Publication - Abstract

Microfluidic Formulation of DNA-Loaded Multicomponent Lipid Nanoparticles for Gene Delivery

E. Quagliarini, S. Renzi, L. Digiacomo, F. Giulimondi, B. Sartori, H. Amenitsch, V. Tassinari, L. Masuelli, R. Bei, L. Cui, J. Wang, A. Amici, C. Marchini, D. Pozzi, and G. Caracciolo

With recent successes reflected in literature on mRNA delivery using LNPs, scientists from the University of Rome set out to investigate whether that success can be achieved with plasmid DNA delivery using LNPs (pDNA-LNPs). Authors Quagliarini et al. 2021 synthesized pDNA-LNPs us...
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.