Title

Loading of Extracellular Vesicles with Chemically Stabilized Hydrophobic siRNAs for the Treatment of Disease in the Central Nervous System

UMMS Affiliation

RNA Therapeutics Institute; Program in Molecular Medicine; Department of Medicine

Publication Date

2017-06-20

Document Type

Article

Disciplines

Biochemistry, Biophysics, and Structural Biology | Neuroscience and Neurobiology

Abstract

Efficient delivery of oligonucleotide therapeutics, i.e., siRNAs, to the central nervous system represents a significant barrier to their clinical advancement for the treatment of neurological disorders. Small, endogenous extracellular vesicles were shown to be able to transport lipids, proteins and RNA between cells, including neurons. This natural trafficking ability gives extracellular vesicles the potential to be used as delivery vehicles for oligonucleotides, i.e., siRNAs. However, robust and scalable methods for loading of extracellular vesicles with oligonucleotide cargo are lacking. We describe a detailed protocol for the loading of hydrophobically modified siRNAs into extracellular vesicles upon simple co-incubation. We detail methods of the workflow from purification of extracellular vesicles to data analysis. This method may advance extracellular vesicles-based therapies for the treatment of a broad range of neurological disorders.

Keywords

Extracellular vesicles, hydrophobically modified siRNA, neurological disorder, RNA interference, therapy

Rights and Permissions

Copyright: © 2017 The Authors; exclusive licensee Bio-protocol LLC.

DOI of Published Version

10.21769/BioProtoc.2338

Source

Bio Protoc. 2017 Jun 20;7(20). pii: e2338. doi: 10.21769/BioProtoc.2338. Link to article on publisher's site

Journal/Book/Conference Title

Bio-protocol

Related Resources

Link to Article in PubMed

PubMed ID

28868334

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