Ultrasound-enhanced delivery of Morpholino with Bubble liposomes ameliorates the myotonia of myotonic dystrophy model mice

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

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

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.

Original languageEnglish
Article number2242
JournalScientific reports
Volume3
DOIs
Publication statusPublished - 2013

Fingerprint

Dive into the research topics of 'Ultrasound-enhanced delivery of Morpholino with Bubble liposomes ameliorates the myotonia of myotonic dystrophy model mice'. Together they form a unique fingerprint.

Cite this