Toward the therapeutic editing of mutated RNA sequences

Proc Natl Acad Sci U S A. 1995 Aug 29;92(18):8298-302. doi: 10.1073/pnas.92.18.8298.


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.

MeSH terms

  • Adenosine Deaminase / genetics
  • Animals
  • Base Sequence
  • Codon, Terminator
  • Dystrophin / genetics*
  • Genetic Therapy* / methods
  • Humans
  • Molecular Sequence Data
  • Mutation*
  • RNA / genetics*
  • RNA / therapeutic use
  • RNA Editing*
  • Xenopus


  • Codon, Terminator
  • Dystrophin
  • RNA
  • Adenosine Deaminase