Toward the therapeutic editing of mutated RNA sequences.
Year: 1995
Type: article
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: T M Woolf, J M Chase, D T Stinchcomb
Institution: University of Colorado Boulder
Language: English
Topic: RNA regulation and disease
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2055152936