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Loading of Extracellular Vesicles with Hydrophobically Modified siRNAs

  • Marie-Cecile Didiot
  • Reka A. Haraszti
  • Neil Aronin
  • Anastasia KhvorovaEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1740)

Abstract

Delivery represents a significant barrier to the clinical advancement of oligonucleotide therapeutics. Small, endogenous extracellular vesicles (EVs) have the potential to act as oligonucleotide delivery vehicles, but robust and scalable methods for loading RNA therapeutic cargo into vesicles are lacking. Here we describe the efficient loading of hydrophobically modified siRNAs (hsiRNAs) into EVs upon co-incubation, without altering vesicle size distribution or integrity. This method is expected to advance the development of EV-based therapies for the treatment of a broad range of disorders.

Keywords

Extracellular vesicles Oligonucleotide therapeutics Hydrophobically modified siRNA RNA interference 

Notes

Acknowledgments

We thank the members of the Khvorova and Aronin Laboratories, NIH Extracellular RNA Consortium and CHDI Foundation Inc. for helpful discussions. This work is supported in part NIH UH2-UH3 grant TR 000888 05 to N.A. and A.K., NIH grants RO1GM10880304, RO1NS10402201, and S10 OD020012 to A.K. and CHDI Foundation (Research Agreement A-6119, JSC A6367) to N.A. Marie-Cecile Didiot was supported by Huntington’s Disease Society of America Postdoctoral Fellowship. The authors declare no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC 2018

Authors and Affiliations

  • Marie-Cecile Didiot
    • 1
    • 2
  • Reka A. Haraszti
    • 1
    • 2
  • Neil Aronin
    • 1
    • 3
  • Anastasia Khvorova
    • 1
    • 2
    Email author
  1. 1.RNA Therapeutics InstituteUniversity of Massachusetts Medical SchoolWorcesterUSA
  2. 2.Department of Molecular MedicineUniversity of Massachusetts Medical SchoolWorcesterUSA
  3. 3.Department of MedicineUniversity of Massachusetts Medical SchoolWorcesterUSA

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