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Gene therapy in cystic fibrosis

  • Michelle Prickett
    Affiliations
    Northwestern University Feinberg School of Medicine, Division of Pulmonary and Critical Care Medicine, Chicago, Ill
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  • Manu Jain
    Correspondence
    Reprint requests: Manu Jain, MD, MS, Northwestern University Feinberg School of Medicine, Division of Pulmonary and Critical Care Medicine, 240 E Huron Ave, McGaw Mezzanine, Chicago, IL 60611.
    Affiliations
    Northwestern University Feinberg School of Medicine, Division of Pulmonary and Critical Care Medicine, Chicago, Ill
    Search for articles by this author
Published:December 28, 2012DOI:https://doi.org/10.1016/j.trsl.2012.12.001
      Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane regulator (CFTR) gene and is the most common life-shortening genetic defect in Caucasians. Life expectancy in CF has improved substantially over the last 75 years because of treatments aimed at end-organ complications. Since the CFTR gene was discovered in 1989 more than 1900 mutations have been reported to cause CF and significant effort has been put forth into gene therapy to find a mutation independent “cure” for CF. Gene-based approaches have not yet led to a viable therapy but have provided insights into hurdles that limit the efficacy of gene therapy. This review will address the nomenclature of CFTR mutations, attempts at viral and nonviral gene therapy, and recent advances in mutation-specific molecules.

      Abbreviations:

      AAV (adeno-associated viruses), AAV2 (adeno-associated vector 2), CAR (coxsackie-adenovirus receptor), CF (cystic fibrosis), CFTR (cystic fibrosis transmembrane regulator), FEV1 (forced expiratory volume in 1 s), NPD (nasal potential differences), PTC (premature termination codon), RNA (mRNA messenger)
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