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Review
. 2022 Mar 12;11(6):984.
doi: 10.3390/cells11060984.

Novel Insights into the Therapeutic Potential of Lung-Targeted Gene Transfer in the Most Common Respiratory Diseases

Malik Bisserier  1 , Xiao-Qing Sun  2 , Shahood Fazal  1 , Irene C Turnbull  1 , Sébastien Bonnet  3   4 , Lahouaria Hadri  1
Affiliations
Review

Novel Insights into the Therapeutic Potential of Lung-Targeted Gene Transfer in the Most Common Respiratory Diseases

Malik Bisserier et al. Cells. .

Abstract

Over the past decades, a better understanding of the genetic and molecular alterations underlying several respiratory diseases has encouraged the development of new therapeutic strategies. Gene therapy offers new therapeutic alternatives for inherited and acquired diseases by delivering exogenous genetic materials into cells or tissues to restore physiological protein expression and/or activity. In this review, we review (1) different types of viral and non-viral vectors as well as gene-editing techniques; and (2) the application of gene therapy for the treatment of respiratory diseases and disorders, including pulmonary arterial hypertension, idiopathic pulmonary fibrosis, cystic fibrosis, asthma, alpha-1 antitrypsin deficiency, chronic obstructive pulmonary disease, non-small-cell lung cancer, and COVID-19. Further, we also provide specific examples of lung-targeted therapies and discuss the major limitations of gene therapy.

Keywords: AAV; COPD; COVID-19; gene editing; gene therapy; lung fibrosis; nanoparticles; pulmonary hypertension; respiratory disease; treatment.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Common respiratory diseases associated with genetic disorders or molecular alterations. Over the past decades, progress in molecular profiling has provided critical insights into the genetic profile of patients with respiratory diseases, such as pulmonary arterial hypertension, pulmonary fibrosis, asthma, cystic fibrosis, chronic obstructive pulmonary disease, alpha-1 antitrypsin deficiency, non-small-cell lung cancer, and COVID-19. Here, we display schematic representations of the main pathological features of the diseases mentioned above, including vascular remodeling, mucus gland hyperplasia, inflammatory cell infiltrates, bronchial smooth muscle hypertrophy, fibrosis, emphysema, and tumor formation. Created with BioRender.com (accessed on 3 March 2022).
Figure 2
Figure 2
Vector platforms and their characteristics available for gene transfer. The table lists the different types of vectors (adenovirus, adeno-associated virus, lentivirus, retrovirus, and nanoparticles) used in clinical and preclinical studies for treating respiratory diseases and refers to specific information related to expression levels, genome integration, transduction, packaging capacity, immunogenicity, and their use in clinical trials. Created with BioRender.com (accessed on 3 March 2022).
Figure 3
Figure 3
Main therapeutic candidates currently under investigation as lung-targeted gene therapies. Here, we provide examples of therapeutic candidates for gene therapy with substantial advances for the treatment of respiratory diseases, such as pulmonary hypertension, idiopathic pulmonary fibrosis, cystic fibrosis, asthma, chronic obstructive pulmonary disease, alpha-1 antitrypsin deficiency, non-small-cell lung cancer, and COVID-19. Created with BioRender.com (accessed on 3 March 2022).
See this image and copyright information in PMC

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