Exon-skipping antisense oligonucleotides to correct missplicing in neurogenetic diseases

Nucleic Acid Ther. 2014 Feb;24(1):69-86. doi: 10.1089/nat.2013.0461.

Abstract

Alternative splicing is an important regulator of the transcriptome. However, mutations may cause alteration of splicing patterns, which in turn leads to disease. During the past 10 years, exon skipping has been looked upon as a powerful tool for correction of missplicing in disease and progress has been made towards clinical trials. In this review, we discuss the use of antisense oligonucleotides to correct splicing defects through exon skipping, with a special focus on diseases affecting the nervous system, and the latest stage achieved in its progress.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Ataxia Telangiectasia / genetics
  • Ataxia Telangiectasia / therapy
  • Blood-Brain Barrier
  • Congenital Disorders of Glycosylation / genetics
  • Congenital Disorders of Glycosylation / therapy
  • Cysts / genetics
  • Cysts / therapy
  • Drug Delivery Systems
  • Exons
  • Frontotemporal Dementia / genetics
  • Frontotemporal Dementia / therapy
  • Genetic Diseases, Inborn / genetics*
  • Genetic Diseases, Inborn / therapy*
  • Hereditary Central Nervous System Demyelinating Diseases / genetics
  • Hereditary Central Nervous System Demyelinating Diseases / therapy
  • Humans
  • Muscular Dystrophy, Duchenne / genetics
  • Muscular Dystrophy, Duchenne / therapy
  • Mutation
  • Nervous System Diseases / genetics*
  • Nervous System Diseases / therapy*
  • Neurofibromatoses / genetics
  • Neurofibromatoses / therapy
  • Niemann-Pick Disease, Type C / genetics
  • Niemann-Pick Disease, Type C / therapy
  • Oligonucleotides, Antisense / chemistry
  • Oligonucleotides, Antisense / genetics*
  • Oligonucleotides, Antisense / therapeutic use*
  • Pelizaeus-Merzbacher Disease / genetics
  • Pelizaeus-Merzbacher Disease / therapy
  • Phosphotransferases (Phosphomutases) / deficiency
  • Phosphotransferases (Phosphomutases) / genetics
  • RNA Splicing
  • Targeted Gene Repair / methods*

Substances

  • Oligonucleotides, Antisense
  • Phosphotransferases (Phosphomutases)

Supplementary concepts

  • Congenital disorder of glycosylation type 1A
  • Megalencephalic leukoencephalopathy with subcortical cysts