Pharmacologic- and gene-based therapies have historically been developed as two independent therapeutic platforms for cystic fibrosis (CF) lung disease. Inhibition of the dysregulated epithelial Na channel (ENaC) is one pharmacologic approach to enhance airway clearance in CF. We investigated pharmacologic approaches to enhance CFTR gene delivery with recombinant adeno-associated virus (rAAV) a...

Cystic fibrosis (CF), the most common genetic disease among Caucasian population, is caused by mutations in gene encoding for CF transmembrane conductance regulator (CFTR), a chloride epithelial channel whose dysfunction results severe airway obstruction and inflammation, eventually leading to respiratory failure. The discovery of CFTR 1989 provided new insights into basic defect allowed study ...

C ystic fibrosis (CF) (MIM 219700) is one of the most common autosomal recessive diseases in Caucasians. It affects about 1 in 2500 births and approximately 1 in 25 individuals are heterozygotes, with marked regional variations (www.genet.sickkids.on.ca/cftr). It is caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR or ABCC7) gene (MIM 602421), which is also in...

Cystic fibrosis (CF) is a frequent and lethal autosomal recessive disease. It results from different possible mutations in the CFTR gene, which encodes the CFTR chloride channel. We have previously studied the differential expression of genes in CF and CF corrected cell lines, and found a reduced expression of MTND4 in CF cells. MTND4 is a mitochondrial gene encoding the MTND4 subunit of the mi...

C ystic fibrosis (CF) (MIM 219700) is one of the most common autosomal recessive diseases in Caucasians. It affects about 1 in 2500 births and approximately 1 in 25 individuals are heterozygotes, with marked regional variations (www.genet.sickkids.on.ca/cftr). It is caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR or ABCC7) gene (MIM 602421), which is also in...

The use of genomic DNA rather than cDNA or mini-gene constructs in gene therapy might be advantageous as these contain intronic and long-range control elements vital for accurate expression. For gene therapy of cystic fibrosis though, no bacterial artificial chromosome (BAC), containing the whole CFTR gene is available. We have used Red homologous recombination to add a to a previously describe...

The gene product affected in cystic fibrosis, the cystic fibrosis transmembrane conductance regulator (CFTR), is a chlorideselective ion channel that is regulated by cAMP-dependent protein kinase-mediated phosphorylation, ATP binding and ATP hydrolysis. Mutations in the CFTR gene may result in cystic fibrosis characterized by severe pathology (e.g. recurrent pulmonary infection, male infertilit...

Cystic fibrosis (CF) is a lethal recessive genetic disease caused by mutations in the CFTR gene. The gene product is a PKA-regulated anion channel that is important for fluid and electrolyte transport in the epithelia of lung, gut, and ducts of the pancreas and sweat glands. The most common CFTR mutation, ΔF508, causes a severe, but correctable, folding defect and gating abnormality, resulting ...

microRNAs (miRNAs) are a class of regulatory small non-coding molecules that control gene expression at post-transcriptional level. Deregulation of miRNA functions affects a variety of biological processes also involved in the etiology of several human mendelian and complex diseases. Recently, aberrant miRNA expression has been observed in Cystic Fibrosis (CF), an autosomal-recessive genetic di...

We previously reported that Pseudomonas aeruginosa PA14 secretes a protein that can reduce the apical membrane expression of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Here we report that we have used a proteomic approach to identify this secreted protein as PA2934 [corrected], and we have named the gene cif, for CFTR inhibitory factor. We demonstrate that Cif is a ...