Advances in cystic fibrosis gene therapy

The first cystic fibrosis gene therapy trials were carried out in 1993, and although proof-of-principle for gene transfer to the lungs was established, efficiency was generally low. The authors review the most recent advances in preclinical airway gene transfer and summarize the results from the latest clinical trials.

Recent clinical trials report encouraging results. Repeat administration of adeno-associated virus to the lung was safe. Nonviral nanoparticles used, for the first time, in the nose of cystic fibrosis patients were also safe and led to partial correction of the chloride transport defect in nasal epithelium. Important advances have been made in preclinical research, including the development of new viral and nonviral gene transfer agents and improved plasmid DNA. In addition, physical delivery methods, such a magnetofection and electroporation, are being assessed to improve nonviral gene transfer.

Considerable progress has been made in understanding and overcoming the problems associated with gene transfer to airway epithelial cells, the target cells for cystic fibrosis gene therapy. It has also been recognized that novel preclinical and clinical assays are crucial for the success of cystic fibrosis gene therapy, and considerable effort is currently being put into assay development and trial designs.