title: [Development of an ultrasound-mediated nucleic acid delivery system for treating muscular dystrophies].
abstract: Muscular dystrophies are a group of heterogeneous diseases that are characterized by progressive muscle weakness, wasting and degeneration. These muscular deficiencies are often caused by the loss of the protein dystrophin, a crucial element of the dystrophin-glycoprotein complex of muscle fibers. Duchenne muscular dystrophy (DMD) is a fatal, X-linked muscular disease that occurs in 1 out of every 3500 males. Therefore, feasible strategies for replacing or repairing the defective gene are required; however, to date, no effective therapeutic strategies for muscular dystrophies have been established. In this review, we first introduce gene therapies mediated by adeno-associated viruses (AAVs) including a functional dystrophin cDNA or antisense oligonucleotide (AO)-induced exon-skipping therapies, which are designed to exclude the mutated or additional exon(s) in the defective gene and thereby correct the translational reading frame. Recently, we developed "Bubble liposomes" (BLs), which are polyethylene glycol (PEG)-modified liposomes entrapping echo-contrast gas that is known as ultrasound (US) imaging gas. BL application combined with US exposure can function as a novel gene delivery tool, and we demonstrate that the US-mediated eruption of BLs is a feasible and efficient technique to deliver plasmid DNA or AOs for the treatment of muscular dystrophies.
authors.affiliation: Department of Drug Delivery and Molecular Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan. negishi@toyaku.ac.jp
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Negishi
authors.forename: Nobuhito
authors.initials: N
authors.lastname: Hamano
authors.forename: Hitomi
authors.initials: H
authors.lastname: Shiono
authors.forename: Saki
authors.initials: S
authors.lastname: Akiyama
authors.forename: Yoko
authors.initials: Y
authors.lastname: Endo-Takahashi
authors.forename: Ryo
authors.initials: R
authors.lastname: Suzuki
authors.forename: Kazuo
authors.initials: K
authors.lastname: Maruyama
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Aramaki
mesh_terms: D018076:DNA, Complementary / Q000008:administration & dosage*; D000229:Dependovirus; D016189:Dystrophin / Q000235:genetics*; D005091:Exons / Q000235:genetics; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D008081:Liposomes; D058990:Molecular Targeted Therapy; D009136:Muscular Dystrophies / Q000235:genetics* / Q000628:therapy*; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage*; D011092:Polyethylene Glycols; D014176:Protein Biosynthesis; D016364:Reading Frames / Q000235:genetics; D014465:Ultrasonics
chemical_list: D018076:DNA, Complementary; D016189:Dystrophin; D008081:Liposomes; D016376:Oligonucleotides, Antisense; D011092:Polyethylene Glycols