Gene therapy of cystic fibrosis by downregulation of ENaC using RNAi

The epithelial Na+ channel (ENaC) seems to play a key role in the pathogenesis of cystic fibrosis lung disease. Its hyperactivation leads to an increased absorption of Na+ by epithelial cells and consecutively to water hyperabsorption, causing an altered airway surface liquid composition (low volume hypothesis). Therefore inhibition of ENaC function in airway epithelia cells could be a promising therapeutic approach. Besides classical pharmacological application RNA interference for the inhibition of ENaC expression could have some advantage. Therefore we have designed specific synthetic siRNA sequences for the…