Referenced in: none

Automatically associated channels: ClC1 , ClC4

Title: Ultrasound-enhanced delivery of morpholino with Bubble liposomes ameliorates the myotonia of myotonic dystrophy model mice.

Authors: Michinori Koebis, Tamami Kiyatake, Hiroshi Yamaura, Kanako Nagano, Mana Higashihara, Masahiro Sonoo, Yukiko Hayashi, Yoichi Negishi, Yoko Endo-Takahashi, Dai Yanagihara, Ryoichi Matsuda, Masanori P Takahashi, Ichizo Nishino, Shoichi Ishiura

Journal, date & volume: Sci Rep, 2013 , 3, 2242

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23873129

Abstract
Phosphorodiamidate morpholino oligonucleotide (PMO)-mediated control of the alternative splicing of the chloride channel 1 (CLCN1) gene is a promising treatment for myotonic dystrophy type 1 (DM1) because the abnormal splicing of this gene causes myotonia in patients with DM1. In this study, we optimised a PMO sequence to correct Clcn1 alternative splicing and successfully remedied the myotonic phenotype of a DM1 mouse model, the HSALR mouse. To enhance the efficiency of delivery of PMO into HSALR mouse muscles, Bubble liposomes, which have been used as a gene delivery tool, were applied with ultrasound exposure. Effective delivery of PMO led to increased expression of Clcn1 protein in skeletal muscle and the amelioration of myotonia. Thus, PMO-mediated control of the alternative splicing of the Clcn1 gene must be important target of antisense therapy of DM1.