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

• Published in: Journal of visualized experiments no. 138
• Main Authors: Pourshafie, Naemeh, Lee, Philip R, Chen, Ke-Lian, Harmison, George G, Bott, Laura C, Fischbeck, Kenneth H, Rinaldi, Carlo
• Format: Journal Article
• Language: English
• Published: United States MyJove Corporation 10-08-2018
• Subjects: Genetics
• DOI: 10.3791/55724
• EISSN: 1940-087X

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.