The journal of gene medicine
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Cystic fibrosis (CF) is the most frequent lethal genetic disease in the Caucasian population. CF is caused by a defective gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP- and ATP-dependent Cl(-) channel and central regulatory protein in epithelia. CFTR influences the fluid composition of the mucus in the respiratory tract. The most common mutation inducing CF, ΔF508, impairs CFTR processing within the cell and thus prevents functional CFTR expression in the apical membrane. The present study aimed to investigate the functional restoration of CFTR in human CF airway epithelia after transfection with optimized wild-type (wt)CFTR-mRNA. ⋯ From these data, we conclude that CFTR-mRNA transfection could comprise a novel alternative for gene therapy to restore impaired CFTR function.
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Anti-tumor necrosis factor α therapeutics has the potential to alleviate pulmonary fibrosis. However, the systemic administration of anti-tumor necrosis factor α agents has brought about contradictory results and frequent adverse effects, such as infections, immunogenicity and malignancies, amongst others. In the present study, we attempted the local administration of tumor necrosis factor α antisense oligonucleotide and evaluated the treatment effects on pulmonary fibrosis in a bleomycin-induced pulmonary fibrosis mouse model. ⋯ These findings demonstrate that local administration of tumor necrosis factor α antisense oligonucleotide contributes to anti-fibrotic action via a sustained up-regulated level of regulatory T cells, which inhibits T(H)2-biased responses, pro-fibrotic mediator production and extracellular matrix deposition, with no systemic immunosupression associated with systemically induced regulatory T cells.