title: Toward the therapeutic editing of mutated RNA sequences.
abstract: If RNA editing could be rationally directed to mutated RNA sequences, genetic diseases caused by certain base substitutions could be treated. Here we use a synthetic complementary RNA oligonucleotide to direct the correction of a premature stop codon mutation in dystrophin RNA. The complementary RNA oligonucleotide was hybridized to a premature stop codon and the hybrid was treated with nuclear extracts containing the cellular enzyme double-stranded RNA adenosine deaminase. When the treated RNAs were translated in vitro, a dramatic increase in expression of a downstream luciferase coding region was observed. The cDNA sequence data are consistent with deamination of the adenosine in the UAG stop codon to inosine by double-stranded RNA adenosine deaminase. Injection of oligonucleotide-mRNA hybrids into Xenopus embryos also resulted in an increase in luciferase expression. These experiments demonstrate the principle of therapeutic RNA editing.
authors.affiliation: Ribozyme Pharmaceuticals, Inc., Boulder, CO 80301, USA.
authors.forename: T M
authors.initials: TM
authors.lastname: Woolf
authors.forename: J M
authors.initials: JM
authors.lastname: Chase
authors.forename: D T
authors.initials: DT
authors.lastname: Stinchcomb
mesh_terms: D000243:Adenosine Deaminase / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D018388:Codon, Terminator; D016189:Dystrophin / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D012313:RNA / Q000235:genetics* / Q000627:therapeutic use; D017393:RNA Editing; D014981:Xenopus
chemical_list: D018388:Codon, Terminator; D016189:Dystrophin; D012313:RNA; D000243:Adenosine Deaminase