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.
Subject(s)
COVID-19 , Carcinoma, Non-Small-Cell Lung , Cystic Fibrosis , Lung Neoplasms , COVID-19/genetics , COVID-19/therapy , Cystic Fibrosis/metabolism , Humans , Lung/metabolismSubject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/therapy , Critical Care/methods , Lung/virology , Pneumonia, Viral/therapy , Antiviral Agents/therapeutic use , COVID-19 , Coronavirus Infections/diagnosis , Coronavirus Infections/drug therapy , Coronavirus Infections/transmission , Coronavirus Infections/virology , Host Microbial Interactions , Humans , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Lung/pathology , Lung/physiopathology , Occupational Exposure/adverse effects , Occupational Exposure/prevention & control , Occupational Health , Pandemics , Patient Isolation , Patient Safety , Pneumonia, Viral/diagnosis , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , Respiratory Therapy , Risk Assessment , Risk Factors , SARS-CoV-2 , Treatment Outcome , Virulence , COVID-19 Drug TreatmentABSTRACT
In the last few months, the number of cases of a new coronavirus-related disease (COVID-19) rose exponentially, reaching the status of a pandemic. Interestingly, early imaging studies documented that pulmonary vascular thickening was specifically associated with COVID-19 pneumonia, implying a potential tropism of the virus for the pulmonary vasculature. Moreover, SARS-CoV-2 infection is associated with inflammation, hypoxia, oxidative stress, mitochondrial dysfunction, DNA damage, and lung coagulopathy promoting endothelial dysfunction and microthrombosis. These features are strikingly similar to what is seen in pulmonary vascular diseases. Although the consequences of COVID-19 on the pulmonary circulation remain to be explored, several viruses have been previously thought to be involved in the development of pulmonary vascular diseases. Patients with preexisting pulmonary vascular diseases also appear at increased risk of morbidity and mortality. The present article reviews the molecular factors shared by coronavirus infection and pulmonary vasculature defects, and the clinical relevance of pulmonary vascular alterations in the context of COVID-19.