title: Ultrasound-enhanced delivery of morpholino with Bubble liposomes ameliorates the myotonia of myotonic dystrophy model mice.
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.
authors.affiliation: Graduate School of Arts and Sciences, the University of Tokyo, Tokyo, Japan.
authors.forename: Michinori
authors.initials: M
authors.lastname: Koebis
authors.forename: Tamami
authors.initials: T
authors.lastname: Kiyatake
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamaura
authors.forename: Kanako
authors.initials: K
authors.lastname: Nagano
authors.forename: Mana
authors.initials: M
authors.lastname: Higashihara
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sonoo
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Negishi
authors.forename: Yoko
authors.initials: Y
authors.lastname: Endo-Takahashi
authors.forename: Dai
authors.initials: D
authors.lastname: Yanagihara
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Matsuda
authors.forename: Masanori P
authors.initials: MP
authors.lastname: Takahashi
authors.forename: Ichizo
authors.initials: I
authors.lastname: Nishino
authors.forename: Shoichi
authors.initials: S
authors.lastname: Ishiura
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D002460:Cell Line; D018118:Chloride Channels / Q000235:genetics; D004195:Disease Models, Animal; D004576:Electromyography; D023061:Gene Order; D018390:Gene Targeting; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics; D008081:Liposomes; D051379:Mice; D045423:Microbubbles; D060172:Morpholinos / Q000008:administration & dosage / Q000235:genetics*; D009223:Myotonic Dystrophy / Q000188:drug therapy / Q000235:genetics*; D014465:Ultrasonics
chemical_list: C086321:CLC-1 channel; D018118:Chloride Channels; D008081:Liposomes; D060172:Morpholinos