Antisense oligonucleotide-directed inhibition of nonsense-mediated mRNA decay

Nat Biotechnol. 2016 Feb;34(2):164-6. doi: 10.1038/nbt.3427. Epub 2015 Dec 14.

Abstract

Nonsense-mediated mRNA decay (NMD) is a cellular quality-control mechanism that is thought to exacerbate the phenotype of certain pathogenic nonsense mutations by preventing the expression of semi-functional proteins. NMD also limits the efficacy of read-through compound (RTC)-based therapies. Here, we report a gene-specific method of NMD inhibition using antisense oligonucleotides (ASOs) and combine this approach with an RTC to effectively restore the expression of full-length protein from a nonsense-mutant allele.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Gene Expression Regulation / drug effects*
  • Gene Expression Regulation / genetics
  • Genetic Therapy / methods*
  • Humans
  • Nonsense Mediated mRNA Decay / drug effects*
  • Nonsense Mediated mRNA Decay / genetics*
  • Oligonucleotides, Antisense / genetics*
  • Oligonucleotides, Antisense / pharmacology*
  • Reproducibility of Results

Substances

  • Oligonucleotides, Antisense