title: Novel cationic carotenoid lipids as delivery vectors of antisense oligonucleotides for exon skipping in Duchenne muscular dystrophy.
abstract: Duchenne Muscular Dystrophy (DMD) is a common, inherited, incurable, fatal muscle wasting disease caused by deletions that disrupt the reading frame of the DMD gene such that no functional dystrophin protein is produced. Antisense oligonucleotide (AO)-directed exon skipping restores the reading frame of the DMD gene, and truncated, yet functional dystrophin protein is expressed. The aim of this study was to assess the efficiency of two novel rigid, cationic carotenoid lipids, C30-20 and C20-20, in the delivery of a phosphorodiamidate morpholino (PMO) AO, specifically designed for the targeted skipping of exon 45 of DMD mRNA in normal human skeletal muscle primary cells (hSkMCs). The cationic carotenoid lipid/PMO-AO lipoplexes yielded significant exon 45 skipping relative to a known commercial lipid, 1,2-dimyristoyl-sn-glycero-3-ethylphosphocholine (EPC).
authors.affiliation: School of Biological Sciences, Royal Holloway-University of London, Egham, Surrey TW20 0EX, UK.
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Popplewell
authors.forename: Aseel
authors.initials: A
authors.lastname: Abu-Dayya
authors.forename: Tushar
authors.initials: T
authors.lastname: Khanna
authors.forename: Marcella
authors.initials: M
authors.lastname: Flinterman
authors.forename: Nada
authors.initials: N
authors.lastname: Abdul Khalique
authors.forename: Liji
authors.initials: L
authors.lastname: Raju
authors.forename: Christer L
authors.initials: CL
authors.lastname: Øpstad
authors.forename: Hans-Richard
authors.initials: HR
authors.lastname: Sliwka
authors.forename: Vassilia
authors.initials: V
authors.lastname: Partali
authors.forename: George
authors.initials: G
authors.lastname: Dickson
authors.forename: Michael D
authors.initials: MD
authors.lastname: Pungente
mesh_terms: D002338:Carotenoids / Q000008:administration & dosage*; D002412:Cations; D004337:Drug Carriers; D004587:Electrophoresis, Agar Gel; D005091:Exons; D006801:Humans; D008055:Lipids / Q000008:administration & dosage*; D018482:Muscle, Skeletal / Q000378:metabolism; D020388:Muscular Dystrophy, Duchenne / Q000188:drug therapy* / Q000235:genetics; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D002412:Cations; D004337:Drug Carriers; D008055:Lipids; D016376:Oligonucleotides, Antisense; D002338:Carotenoids