Therapeutic approaches to repair defects in deltaF508 CFTR folding and cellular targeting

Adv Drug Deliv Rev. 2002 Dec 5;54(11):1395-408. doi: 10.1016/s0169-409x(02)00148-5.


The deltaF508 mutation in the cystic fibrosis transmembrane regulator (CFTR) gene is the most common mutation in CF. The mutant CFTR protein is defective with respect to multiple functions including cAMP-regulated chloride conductance, nucleotide transport, and regulatory actions on other ion channels. Since the deltaF508 protein is also temperature-sensitive and unstable during translation and folding in the endoplasmic reticulum (ER), most of the nascent chains are targeted for premature proteolysis from the ER. This paper focuses on the events that occur in the ER during folding and reviews potential targets for therapeutic intervention.

Publication types

  • Review

MeSH terms

  • Animals
  • Cystic Fibrosis / genetics
  • Cystic Fibrosis / metabolism*
  • Cystic Fibrosis / therapy
  • Cystic Fibrosis Transmembrane Conductance Regulator / biosynthesis*
  • Cystic Fibrosis Transmembrane Conductance Regulator / chemistry*
  • Endoplasmic Reticulum / metabolism
  • Humans
  • Isoflavones / pharmacology
  • Molecular Chaperones / pharmacology
  • Mutation
  • Phenylbutyrates / pharmacology
  • Phosphodiesterase Inhibitors / pharmacology
  • Protein Folding*
  • Xanthines / pharmacology


  • CFTR protein, human
  • Isoflavones
  • Molecular Chaperones
  • Phenylbutyrates
  • Phosphodiesterase Inhibitors
  • Xanthines
  • cystic fibrosis transmembrane conductance regulator delta F508
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • 4-phenylbutyric acid