Emerging gene therapies for cystic fibrosis

Expert Rev Respir Med. 2019 Aug;13(8):709-725. doi: 10.1080/17476348.2019.1634547. Epub 2019 Jun 27.


Introduction: Cystic fibrosis (CF) remains a life-threatening genetic disease, with few clinically effective treatment options. Gene therapy and gene editing strategies offer the potential for a one-time CF cure, irrespective of the CFTR mutation class. Areas covered: We review emerging gene therapies and gene delivery strategies for the treatment of CF particularly viral and non-viral approaches with potential to treat CF. Expert opinion: It was initially anticipated that the challenge of developing a gene therapy for CF lung disease would be met relatively easily. Following early proof-of-concept clinical studies, CF gene therapy has entered a new era with innovative vector designs, approaches to subvert the humoral immune system and increase gene delivery and gene correction efficiencies. Developments include integrating adenoviral vectors, rapamycin-loaded nanoparticles, and lung-tropic lentiviral vectors. The characterization of novel cell types in the lung epithelium, including pulmonary ionocytes, may also encourage cell type-specific targeting for CF correction. We anticipate preclinical studies to further validate these strategies, which should pave the way for clinical trials. We also expect gene editing efficiencies to improve to clinically translatable levels, given advancements in viral and non-viral vectors. Overall, gene delivery technologies look more convincing in producing an effective CF gene therapy.

Trial registration: ClinicalTrials.gov NCT01621867 NCT02564354 NCT02532764 NCT03375047 NCT03288493 NCT03140969 NCT03605069 NCT03780257 NCT02939820 NCT03399448.

Keywords: CFTR; Cystic Fibrosis; gene delivery gene therapy; genome editing; non-viral vectors; viral vectors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cystic Fibrosis / genetics
  • Cystic Fibrosis / therapy*
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Gene Editing
  • Genetic Therapy*
  • Genetic Vectors
  • Humans
  • Mutation


  • Cystic Fibrosis Transmembrane Conductance Regulator

Associated data

  • ClinicalTrials.gov/NCT01621867
  • ClinicalTrials.gov/NCT02564354
  • ClinicalTrials.gov/NCT02532764
  • ClinicalTrials.gov/NCT03375047
  • ClinicalTrials.gov/NCT03288493
  • ClinicalTrials.gov/NCT03140969
  • ClinicalTrials.gov/NCT03605069
  • ClinicalTrials.gov/NCT03780257
  • ClinicalTrials.gov/NCT02939820
  • ClinicalTrials.gov/NCT03399448