Journal of Movement Disorders  2017;10(1):45-52

doi:10.14802/jmd.16054

Exosome-Based Delivery of miR-124 in a Huntington's Disease Model.

Soon Tae LEE 1 ; Wooseok IM ; Jae Jun BAN ; Mijung LEE ; Keun Hwa JUNG ; Sang Kun LEE ; Kon CHU ; Manho KIM

Affiliations

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Keywords

Huntington's disease; microRNA; R6/2; miR-124; exosome

Country

Republic of Korea

Language

English

Abstract

OBJECTIVE: 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. METHODS: We 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. RESULTS: 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. CONCLUSION: This study serves as a proof of concept for exosome-based delivery of miRNA in neurodegenerative diseases.