RNA Therapeutics Institute Publications

UMMS Affiliation

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

Publication Date


Document Type



Biochemistry, Biophysics, and Structural Biology | Cell and Developmental Biology | Genetics and Genomics | Molecular Biology | Neuroscience and Neurobiology | Therapeutics


Delivery represents a significant barrier to the clinical advancement of oligonucleotide therapeutics for the treatment of neurological disorders, such as Huntington's disease. Small, endogenous vesicles known as exosomes have the potential to act as oligonucleotide delivery vehicles, but robust and scalable methods for loading RNA therapeutic cargo into exosomes are lacking. Here, we show that hydrophobically modified small interfering RNAs (hsiRNAs) efficiently load into exosomes upon co-incubation, without altering vesicle size distribution or integrity. Exosomes loaded with hsiRNAs targeting Huntingtin mRNA were efficiently internalized by mouse primary cortical neurons and promoted dose-dependent silencing of Huntingtin mRNA and protein. Unilateral infusion of hsiRNA-loaded exosomes, but not hsiRNAs alone, into mouse striatum resulted in bilateral oligonucleotide distribution and statistically significant bilateral silencing of up to 35% of Huntingtin mRNA. The broad distribution and efficacy of hsiRNA-loaded exosomes delivered to brain is expected to advance the development of therapies for the treatment of Huntington's disease and other neurodegenerative disorders.


siRNA, Huntingtin, mRNA, messenger RNA, UMCCTS funding

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Copyright © 2016 American Society of Gene and Cell Therapy. Under a Creative Commons license.

DOI of Published Version



Mol Ther. 2016 Oct;24(10):1836-1847. doi: 10.1038/mt.2016.126. Epub 2016 Jun 27. Link to article on publisher's site

Journal/Book/Conference Title

Molecular therapy : the journal of the American Society of Gene Therapy


Full list of authors omitted for brevity. For full list see article.

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Link to Article in PubMed

PubMed ID


Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.