Aminoglycoside antibiotics restore CFTR function by overcoming premature stop mutations

Nat Med. 1996 Apr;2(4):467-9. doi: 10.1038/nm0496-467.


Cystic fibrosis (CF) is caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR). A single recessive mutation, the deletion of phenylalanine 508 (deltaF508), causes severe CF and resides on 70% of mutant chromosomes. Severe CF is also caused by premature stop mutations, which are found on 5% of CF chromosomes. Here we report that two common, disease-associated stop mutations can be suppressed by treating cells with low doses of the aminoglycoside antibiotic G-418. Aminoglycoside treatment resulted in the expression of full-length CFTR and restored its cyclic AMP-activated chloride channel activity. Another aminoglycoside, gentamicin, also promoted the expression of full-length CFTR. These results suggest that treatment with aminoglycosides may provide a means of restoring CFTR function in patients with this class of mutation.

Publication types

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

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Cystic Fibrosis / genetics*
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
  • Gentamicins / pharmacology*
  • HeLa Cells
  • Humans
  • Mutation
  • Suppression, Genetic / drug effects*


  • Anti-Bacterial Agents
  • CFTR protein, human
  • Gentamicins
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • antibiotic G 418