TY - JOUR
T1 - Natural or Synthetic RNA Delivery
T2 - A Stoichiometric Comparison of Extracellular Vesicles and Synthetic Nanoparticles
AU - Murphy, Daniel E
AU - de Jong, Olivier G
AU - Evers, Martijn J W
AU - Nurazizah, Maratussholikhah
AU - Schiffelers, Raymond M
AU - Vader, Pieter
N1 - Funding Information:
We thank Dr. Emilia Nagyova, Jerney Gitz Francois, and Omnia M. Elsharkasy for their technical assistance. In addition, we thank Dr. Maria Laura Tognoli for her critical reading of the manuscript and Dr. Sander van der Laan for his assistance with statistical analysis. The work of D.E.M., M.J.W.E., R.M.S., and P.V. is supported by the European Union’s Horizon 2020 Research and Innovation program in the project B-SMART (to P.V. and R.M.S.) under grant agreement No. 721058. O.G.d.J. is supported by a VENI Fellowship (VI.Veni.192.174) from the Dutch Research Council (NWO).
Publisher Copyright:
© 2021 The Authors. Published by American Chemical Society
PY - 2021/2/24
Y1 - 2021/2/24
N2 - 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.
AB - 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.
KW - Exosomes
KW - Extracellular vesicles
KW - LNP
KW - Nanomedicine
KW - RNA therapeutics
UR - http://www.scopus.com/inward/record.url?scp=85101600155&partnerID=8YFLogxK
U2 - 10.1021/acs.nanolett.1c00094
DO - 10.1021/acs.nanolett.1c00094
M3 - Article
C2 - 33570966
SN - 1530-6984
VL - 21
SP - 1888
EP - 1895
JO - Nano letters
JF - Nano letters
IS - 4
ER -