A proof of concept for exosome-based delivery of miRNA in neurodegenerative diseases

Huntington’s disease (HD) is a genetic neurodegenerative disease that is caused by abnormal CAG expansion. Altered microRNA (miRNA) expression also causes abnormal gene regulation in this neurodegenerative disease. The delivery of abnormally downregulated miRNAs might restore normal gene regulation and have a therapeutic effect.

Researchers at Seoul National University Hospital have developed an exosome-based delivery method to treat this neurodegenerative disease. miR-124, one of the key miRNAs that is repressed in HD, was stably overexpressed in a stable cell line. Exosomes were then harvested from these cells using an optimized protocol. The exosomes (Exo-124) exhibited a high level of miR-124 expression and were taken up by recipient cells. When Exo-124 was injected into the striatum of R6/2 transgenic HD mice, expression of the target gene, RE1-Silencing Transcription Factor, was reduced. However, Exo-124 treatment did not produce significant behavioral improvement.

Generation of Exo-124


A: Diagram showing the procedure used to generate Exo-124. We repeatedly harvested Exo-124 from HEK 293 cells overexpressing miR-124. B: The harvested Exo-124 pellets. C: Expression of CD9 and CD63 in Exo-124. Exosomes harvested from the conditioned medium expressed CD9 and CD63, whereas exosomes from the normal control medium did not express these markers. D: Compared to the control exosomes (Exo-ctr), Exo-124 expressed a high level of miR-124, as measured by real-time PCR (n = 3 per group). *p < 0.05.

Lee ST, Im W, Ban JJ, Lee M, Jung KH, Lee SK, Chu K, Kim M. (2017) Exosome-Based Delivery of miR-124 in a Huntington’s Disease Model. J Mov Disord 10(1):45-52. [article]

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