Evaluation of Bovine Milk Extracellular Vesicles for the Delivery of Locked Nucleic Acid Antisense Oligonucleotides


Authors: P. Grossen, M. Portmann, E. Koller, M. Duschmalé, T. Minz, S. Sewing and M. Keller et. al.

Journal: European Journal of Pharmaceutics and Biopharmaceutics

DOI: 10.1016/j.ejpb.2020.11.012

Publication - Abstract

November 26, 2020

Abstract

The natural capacity of extracellular vesicles (EVs) to transport their payload to recipient cells has raised big interest to repurpose EVs as delivery vehicles for xenobiotics. In the present study, bovine milk-derived EVs (BMEVs) were investigated for their potential to shuttle locked nucleic acid-modified antisense oligonucleotides (LNA ASOs) into the systemic circulation after oral administration. To this end, a broad array of analytical methods including proteomics and lipidomics were used to thoroughly characterize BMEVs. We found that additional purification by density gradients efficiently reduced levels of non-EV associated proteins. The potential of BMEVs to functionally transfer LNA ASOs was tested using advanced in vitro systems (i.e. hPSC-derived neurons and primary human cells). A slight increase in cellular LNA ASO internalization and target gene reduction was observed when LNA ASOs were delivered using BMEVs. When dosed orally in mice, only a small fraction (about 1% of total administered dose) of LNA ASOs was recovered in the peripheral tissues liver and kidney, however, no significant reduction in target gene expression (i.e. functional knockdown) was observed.

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

Microsystems offer promising possibilities to produce nanoparticles which can be used as carriers for poorly water-soluble active substances. The aim of the present study was to compare the preparation of lipid nanoparticles by precipitation in different microsystems: A segmented...
Read More


Publication - Summary

Lipid Nanoparticles Containing siRNA Synthesized by Microfluidic Mixing Exhibit an Electron-Dense Nanostructured Core

A.K.K. Leung, I.M. Hafez, S. Baoukina, N.M. Belliveau, I.V. Zhigaltsev, E. Afshinmanesh, D.P. Tieleman, C.L. Hansen, M.J. Hope, and P.R. Cullis

Gene therapy can be the solution to treatment of many undruggable conditions. RNA interference (RNAi) has been identified as a powerful gene therapy tool which can regulate and improve defective biological pathways through downregulation of target ...

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.