Specific inhibition of epithelial Na+ channels by antisense oligonucleotides for the treatment of Na+ hyperabsorption in cystic fibrosis

摘要

Cystic fibrosis (CF) respiratory epithelia are characterized by a defect Cl(-) secretion and an increased Na(+) absorption through epithelial Na(+) channels (ENaC). The present study aimed to find an effective inhibitor of human ENaC with respect to replacing amiloride therapy for CF patients. Therefore, we developed specific antisense oligonucleotides (AON) that efficiently suppress Na(+) hyperabsorption by inhibiting the expression of the alpha-ENaC subunit.