title: Design of 2'-O-Me RNA/ENA chimera oligonucleotides to induce exon skipping in dystrophin pre-mRNA.
abstract: 2'-O-Me RNA/ENA chimera oligonucleotides complementary to exon 45 and 46 of the dystrophin gene induced exon 45 and 46 skipping of the dystrophin pre-mRNA, respectively. The induction of exon skipping by the most effective 2'-O-Me RNA/ENA chimeras led to the expression of dystrophin in dystrophin-deficient myocytes by correcting the translational reading frames. Also, in the process of 2'-O-Me RNA/ENA chimera optimization to induce exon skipping in several exons, it was found that the optimized target sequences of the chimeras included guanosine- or adenosine-rich sequences that might function as spiking enhancer sequences (SES).
authors.affiliation: Lead Discovery Research Laboratories, Sankyo Co., Ltd., Tokyo 140-8710, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Takagi
authors.forename: Mariko
authors.initials: M
authors.lastname: Yagi
authors.forename: Kazuto
authors.initials: K
authors.lastname: Ishibashi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Takeshima
authors.forename: Agus
authors.initials: A
authors.lastname: Surono
authors.forename: Masafumi
authors.initials: M
authors.lastname: Matsuo
authors.forename: Makoto
authors.initials: M
authors.lastname: Koizumi
mesh_terms: D000241:Adenosine; D001483:Base Sequence; D015195:Drug Design; D016189:Dystrophin / Q000235:genetics* / Q000378:metabolism; D005091:Exons / Q000235:genetics*; D005786:Gene Expression Regulation; D006151:Guanosine; D006801:Humans; D009692:Nucleic Acid Heteroduplexes / Q000737:chemistry / Q000378:metabolism*; D009696:Nucleic Acids / Q000737:chemistry / Q000378:metabolism*; D009841:Oligonucleotides / Q000737:chemistry / Q000378:metabolism*; D012313:RNA / Q000737:chemistry / Q000378:metabolism*; D012322:RNA Precursors / Q000235:genetics*
chemical_list: D016189:Dystrophin; D009692:Nucleic Acid Heteroduplexes; D009696:Nucleic Acids; D009841:Oligonucleotides; D012322:RNA Precursors; D006151:Guanosine; D012313:RNA; D000241:Adenosine