Therapeutic potential of antisense oligonucleotides as modulators of alternative splicing

J Clin Invest. 2003 Aug;112(4):481-6. doi: 10.1172/JCI19547.

Abstract

An estimated 60% of all human genes undergo alternative splicing, a highly regulated process that produces splice variants with different functions. Such variants have been linked to a variety of cancers, and genetic diseases such as thalassemia and cystic fibrosis. This Perspective describes a promising approach to RNA repair based on the use of antisense oligonucleotides to modulate alternative splicing and engender the production of therapeutic gene products.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Alternative Splicing*
  • Antigens, Surface*
  • Carboxypeptidases / genetics
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Dystrophin / genetics
  • Globins / genetics
  • Glutamate Carboxypeptidase II
  • Humans
  • Ligands
  • Models, Biological
  • Models, Genetic
  • Oligonucleotides, Antisense / therapeutic use*
  • Polycystic Kidney Diseases / genetics
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-myc / genetics
  • RNA, Messenger / metabolism
  • Receptor, Insulin / genetics
  • Receptors, GABA-A / genetics
  • Receptors, Interleukin / genetics
  • Receptors, Interleukin-5
  • bcl-X Protein
  • tau Proteins / genetics

Substances

  • Antigens, Surface
  • BCL2L1 protein, human
  • CFTR protein, human
  • Dystrophin
  • GABRG2 protein, human
  • Ligands
  • Oligonucleotides, Antisense
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger
  • Receptors, GABA-A
  • Receptors, Interleukin
  • Receptors, Interleukin-5
  • bcl-X Protein
  • tau Proteins
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Globins
  • Receptor, Insulin
  • Carboxypeptidases
  • FOLH1 protein, human
  • Glutamate Carboxypeptidase II