Aminoglycoside antibiotics restore CFTR function by overcoming premature stop mutations

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 (F508), 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 CF patients with this class of mutation.

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