Loading of Extracellular Vesicles with Hydrophobically Modified siRNAs

Marie-Cecile Didiot; Reka A Haraszti; Neil Aronin; Anastasia Khvorova

doi:10.1007/978-1-4939-7652-2_16

Loading of Extracellular Vesicles with Hydrophobically Modified siRNAs

Methods Mol Biol. 2018:1740:199-214. doi: 10.1007/978-1-4939-7652-2_16.

Authors

Marie-Cecile Didiot^{1

2}, Reka A Haraszti^{1

2}, Neil Aronin^{1

3}, Anastasia Khvorova^{4

5}

Affiliations

¹ RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, USA.
² Department of Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
³ Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
⁴ RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, USA. anastasia.khvorova@umassmed.edu.
⁵ Department of Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA. anastasia.khvorova@umassmed.edu.

PMID: 29388146
DOI: 10.1007/978-1-4939-7652-2_16

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; Hydrophobically modified siRNA; Oligonucleotide therapeutics; RNA interference.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Culture Techniques
Drug Delivery Systems
Extracellular Vesicles / chemistry*
Humans
Hydrophobic and Hydrophilic Interactions
RNA, Small Interfering / administration & dosage*
RNA, Small Interfering / chemistry

Substances

RNA, Small Interfering

Abstract

Publication types

MeSH terms

Substances

Grants and funding