Exosome-Based Delivery of miR-124 in a Huntington's Disease Model.
- Author:
Soon Tae LEE
1
;
Wooseok IM
;
Jae Jun BAN
;
Mijung LEE
;
Keun Hwa JUNG
;
Sang Kun LEE
;
Kon CHU
;
Manho KIM
Author Information
- Publication Type:Original Article
- Keywords: Huntington's disease; microRNA; R6/2; miR-124; exosome
- MeSH: Animals; Cell Line; Exosomes; Huntington Disease*; Methods; Mice; MicroRNAs; Neurodegenerative Diseases; Transcription Factors
- From:Journal of Movement Disorders 2017;10(1):45-52
- CountryRepublic 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.
