Challenges and strategies for cystic fibrosis lung gene therapy.
Gene replacement therapy represents an interesting new approach for the treatment of cystic fibrosis (CF) lung disease. Basic research suggests that CF gene therapy is feasible, but major technological challenges must be addressed before clinical applications are likely to succeed. Therapeutic genes can be delivered to and expressed in human airways, but the number of cells expressing the transgene is relatively low. The inefficiency of gene delivery is largely attributable to the remarkable defenses of human airways. Maintaining long-term transgene expression in airway cells is also a significant obstacle. Recent advances have been made in the development of vectors, expression cassettes, and delivery techniques for enhancing airway gene transfer and expression. These advances have the potential to improve the efficiency of lung gene therapy and to achieve clinical benefits for CF patients in the future.
Koehler
D R
DR
Programme in Lung Biology Research and the Canadian Institutes of Health Research Group in Lung Development, The Hospital for Sick Children, Toronto, Ontario, M5G 1X8, Canada.
Hitt
M M
MM
Hu
J
J
D003550:Cystic Fibrosis / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D008168:Lung / Q000166:cytology / Q000502:physiology*
C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator