Cationic lipids show promise as vectors for transfer of CFTR cDNA to airway epithelia of patients with cystic fibrosis (CF). However, previous studies have not compared the effect of DNA–lipid to DNA alone. Recently, we developed a formulation of plasmid encoding CFTR (pCF1CFTR) and cationic lipid (GL-67:DOPE) that generated greater gene transfer in mouse lung than previously described DNA–lipi...

The endogenous signaling molecule S-nitrosoglutathione (GSNO) and other S-nitrosylating agents can cause full maturation of the abnormal gene product DeltaF508 cystic fibrosis (CF) transmembrane conductance regulator (CFTR). However, the molecular mechanism of action is not known. Here we show that Hsp70/Hsp90 organizing protein (Hop) is a critical target of GSNO, and its S-nitrosylation result...

The positional cloning of the gene responsible for cystic fibrosis (CF) was the important first step in understanding the basic defect and pathophysiology of the disease. This study aims to provide a historical account of key developments as well as factors that contributed to the cystic fibrosis transmembrane conductance regulator (CFTR) gene identification work. A redefined gene structure bas...

The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-regulated chloride channel in the plasma membrane of several epithelial cells. Maturation of CFTR is inefficient in most cells, with only a fraction of nascent chains being properly folded and transported to the cell surface. The most common mutation in CFTR, CFTR-deltaF508, leads to the genetic disease cystic fibrosis. CF...

Cystic fibrosis (CF) is caused by mutations in the cystic transmembrane conductance regulator (CFTR) gene. It has been postulated that reduced HCO 3 ? transport through CFTR may lead to a decreased airway surface liquid pH. In contrast, others have reported no changes extracellular pH (pHe). We recently carcinoma Caco-2/pRS26 cells (transfected with short hairpin RNA for CFTR) or CF lung epithe...

The present study demonstrates that the human adenovirus (Ad) can augment transfer and expression of a gene within plasmid DNA unmodified by nonspecific linkers or by linker-ligand complexes. Following the transfection of COS-7 cells with pRSVL, a luciferase expression plasmid vector directed by the Rous sarcoma virus-long terminal repeat promoter, luciferase activity in the target cells was 10...

years ago the cystic fibrosis (CF) gene was cloned. The discovery of the gene encoding the CF transmembrane conductance regulator (CFTR) Cl – channel marked the opening of Chapter 1 in the development of gene transfer as a treatment for this common autosomal recessive disease. One year later, Chapter 1 ended when expression of CFTR in CF epithelial cells corrected the CF Cl – transport defect. ...

Cystic fibrosis (CF) is caused by CFTR (cystic fibrosis transmembrane conductance regulator) gene mutations. We ascertained five patients with a novel complex CFTR allele, with two mutations, H939R and H949L, inherited in cis in the same exon of CFTR gene, and one different mutation per patient inherited in trans in a wide population of 289 Caucasian CF subjects from South Italy. The genotype-p...

Cystic Fibrosis (CF) is the most common lethal rare genetic disease in the Caucasian populations. It is caused by a variety of sequence alterations in the Cystic Fibrosis Transmembrane Regulator (CFTR) gene. In Caucasian, one over 3,500 new born children suffers from the disease and one over 30 of them is at least carrier of a severe mutation in the CFTR gene. CF and CFTR-related disorders (CFT...