Natural or Synthetic RNA Delivery: A Stoichiometric Comparison of Extracellular Vesicles and Synthetic Nanoparticles


Authors: D.E. Murphy, O.G. de Jong, M.J.W. Evers, M. Nurazizah, Y.M. Schiffelers and P. Vader

Journal: Nano Letters

DOI: 10.1021/acs.nanolett.1c00094

Publication - Abstract

February 11, 2021

Abstract

RNA therapeutics have high potential that is yet to be fully realized, largely due to challenges involved in the appropriate delivery to target cells. Extracellular vesicles (EVs) are lipid bound nanoparticles released by cells of all types and possess numerous features that may help overcome this hurdle and have emerged as a promising RNA delivery vehicle candidate. Despite extensive research into the engineering of EVs for RNA delivery, it remains unclear how the intrinsic RNA delivery efficiency of EVs compares to currently used synthetic RNA delivery vehicles. Using a novel CRISPR/Cas9-based RNA transfer reporter system, we compared the delivery efficiency of EVs to clinically approved state-of-the-art DLin-MC3-DMA lipid nanoparticles and several in vitro transfection reagents. We found that EVs delivered RNA several orders of magnitude more efficiently than these synthetic systems. This finding supports the continued research into EVs as potential RNA delivery vehicles.

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