Systemic Delivery of MicroRNA Using Recombinant Adeno-associated Virus Serotype 9 to Treat Neuromuscular Diseases in Rodents

Journal of Visualized Experiments : JoVE
Naemeh PourshafieCarlo Rinaldi

Abstract

RNA interference via the endogenous miRNA pathway regulates gene expression by controlling protein synthesis through post-transcriptional gene silencing. In recent years, miRNA-mediated gene regulation has shown potential for treatment of neurological disorders caused by a toxic gain of function mechanism. However, efficient delivery to target tissues has limited its application. Here we used a transgenic mouse model for spinal and bulbar muscular atrophy (SBMA), a neuromuscular disease caused by polyglutamine expansion in the androgen receptor (AR), to test gene silencing by a newly identified AR-targeting miRNA, miR-298. We overexpressed miR-298 using a recombinant adeno-associated virus (rAAV) serotype 9 vector to facilitate transduction of non-dividing cells. A single tail-vein injection in SBMA mice induced sustained and widespread overexpression of miR-298 in skeletal muscle and motor neurons and resulted in amelioration of the neuromuscular phenotype in the mice.

Citations

Jul 6, 2019·Frontiers in Molecular Neuroscience·Xiaoyu Dong, Shuyan Cong
Jan 28, 2021·Methods and Protocols·Ishani Dasgupta, Anushila Chatterjee

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Datasets Mentioned

BETA
MIMAT0004901
12

Methods Mentioned

BETA
transgenic
dissection
chemical modification

Software Mentioned

miRWalk
miRanda
Targetscan
miRDB

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