New Directions in Pulmonary Gene Therapy

Hum Gene Ther. 2020 Sep;31(17-18):921-939. doi: 10.1089/hum.2020.166.


The lung has long been a target for gene therapy, yet efficient delivery and phenotypic disease correction has remained challenging. Although there have been significant advancements in gene therapies of other organs, including the development of several ex vivo therapies, in vivo therapeutics of the lung have been slower to transition to the clinic. Within the past few years, the field has witnessed an explosion in the development of new gene addition and gene editing strategies for the treatment of monogenic disorders. In this review, we will summarize current developments in gene therapy for cystic fibrosis, alpha-1 antitrypsin deficiency, and surfactant protein deficiencies. We will explore the different gene addition and gene editing strategies under investigation and review the challenges of delivery to the lung.

Keywords: AAV; CRISPR/Cas; adenovirus; gene editing; lentivirus.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cystic Fibrosis / genetics
  • Cystic Fibrosis / therapy*
  • Cystic Fibrosis Transmembrane Conductance Regulator / deficiency
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
  • Dependovirus / genetics*
  • Gene Editing
  • Genetic Therapy / methods*
  • Genetic Vectors / administration & dosage*
  • Genetic Vectors / genetics
  • Humans
  • Pulmonary Surfactant-Associated Protein A / deficiency
  • Pulmonary Surfactant-Associated Protein A / genetics*
  • alpha 1-Antitrypsin / genetics*


  • CFTR protein, human
  • Pulmonary Surfactant-Associated Protein A
  • alpha 1-Antitrypsin
  • Cystic Fibrosis Transmembrane Conductance Regulator