Introducing sense into nonsense in treatments of human genetic diseases

Trends Genet. 2008 Nov;24(11):552-63. doi: 10.1016/j.tig.2008.08.010. Epub 2008 Oct 18.


Approximately one-third of alleles causing genetic diseases carry premature termination codons (PTCs), which lead to the production of truncated proteins. The past decade has seen considerable interest in therapeutic approaches aimed at readthrough of in-frame PTCs to enable synthesis of full-length proteins. However, attempts to readthrough PTCs in many diseases resulted in variable effects. Here, we focus on the efforts of such therapeutic approaches in cystic fibrosis and Duchenne muscular dystrophy and discuss the factors contributing to successful readthrough and how the nonsense-mediated mRNA decay (NMD) pathway regulates this response. A deeper understanding of the molecular basis for variable response to readthrough of PTCs is necessary so that appropriate therapies can be developed to treat many human genetic diseases caused by PTCs.

Publication types

  • Review

MeSH terms

  • Alleles
  • Codon, Nonsense / genetics*
  • Cystic Fibrosis / genetics
  • Cystic Fibrosis / therapy
  • Genetic Diseases, Inborn / genetics*
  • Genetic Diseases, Inborn / therapy*
  • Humans
  • Models, Biological
  • Muscular Dystrophy, Duchenne / genetics
  • Muscular Dystrophy, Duchenne / therapy
  • Oxadiazoles / therapeutic use
  • RNA Stability
  • RNA, Messenger / metabolism


  • Codon, Nonsense
  • Oxadiazoles
  • RNA, Messenger
  • ataluren