Cystic fibrosis: gene therapy or preventive gene transfer?

In 1989, the association between Cftr (the gene) and cystic fibrosis or CF (the disease) was first reported. Since then, more than 500 mutations in Cftr have been identified. CFTR (the Cftr product) has been well characterised and shown to be involved in cAMP-dependent transmembrane Cl super(-) transport. Subsequently, several mouse Cftr knock-outs have been obtained and shown to lead to a deficiency in epithelial cell Cl super(-) transport. Transfer of Cftr into either CFTR-deficient or CFTR-mutant cells both in vitro and in vivo has been shown to restore a normal CFTR-dependent Cl super(-) transport. Moreover, a number of clinical studies have shown that gene transfer of wild-type human CFTR cDNA into the airways of CF patients leads to the transient restoration of the Cl super(-) transport function and/or the transmembrane potential difference across the airway epithelium.