Gene therapy for cystic fibrosis

Abstract

Cystic fibrosis (CF) is associated with significant morbidity and mortality, despite significant advances in conventional treatment. The field of gene therapy has progressed rapidly since the cystic fibrosis transmembrane conductance regulator (CFTR) gene was cloned. In this review we discuss current knowledge on the underlying molecular defect in CF, and the progress in gene transfer studies from the early in vitro work through to clinical trials, including the development of endpoints to assess efficacy. We highlight the problems encountered, and likely future directions of the field.

Targeting a genetic defect: cystic fibrosis transmembrane conductance regulator modulators in cystic fibrosis

“…Non-viral vectors under investigation include cationic lipid GL67A, DNA nanoparticles (DNA complexed with peptides) and self-assembling polyethylenimine complexes [9,35,36]. DAVIES and ALTON [35] have reported that CFTR gene transfer can be reproducibly achieved with non-viral vectors.…”

Pegylated GL67 lipoplexes retain their gene transfection activity after exposure to components of CF mucus

“…1,2 The disease is characterized by the presence of thick secretions in the respiratory, gastrointestinal and reproductive tracts. 3 Much of the morbidity and mortality in CF patients result from pulmonary exacerbations.…”

“…Based on these considerations, we proposed (1) to examine whether gene transfer by lipoplexes was influenced by CF mucus components, (2) to explain the basis for the change in gene transfection activity, and (3) to determine whether lipoplexes that had been 'coated' with polyethylene glycol (pEG) were more resistant to CF mucus components than 'uncoated' lipoplexes.…”

Cell transfection in vitro and in vivo with nontoxic TAT peptide-liposome–DNA complexes

“…gene delivery ͉ green fluorescent protein ͉ intracellular trafficking G ene therapy is becoming an important strategy in the treatment of various diseases such as cancer (1)(2)(3), AIDS (3)(4)(5), and cystic fibrosis (6,7). Viral vectors, the current favorites for intracellular DNA delivery, suffer from immunogenicity, nonspecificity, and inherent risks of complications such as the interference with the activity of tissue-specific promoters (8)(9)(10).…”