Delivery systems of therapeutic nucleic acids for the treatment of acute lung injury/acute respiratory distress syndrome

Acute lung injury (ALI)/ acute respiratory distress syndrome (ARDS) is a devastating inflammatory lung disease with a high mortality rate. ALI/ARDS is induced by various causes, including sepsis, infections, thoracic trauma, and inhalation of toxic reagents. Corona virus infection disease-19 (COVID-19) is also a major cause of ALI/ ARDS. ALI/ARDS is characterized by inflammatory injury and increased vascular permeability, resulting in lung edema and hypoxemia. Currently available treatments for ALI/ARDS are limited, but do include mechanical ventilation for gas exchange and treatments supportive of reduction of severe symptoms. Anti-inflammatory drugs such as corticosteroids have been suggested, but their clinical effects are controversial with possible side-effects. Therefore, novel treatment modalities have been developed for ALI/ARDS, including therapeutic nucleic acids. Two classes of therapeutic nucleic acids are in use. The first constitutes knock-in genes for encoding therapeutic proteins such as heme oxygenase-1 (HO-1) and adiponectin (APN) at the site of disease. The other is oligonucleotides such as small interfering RNAs and antisense oligonucleotides for knock-down expression of target genes. Carriers have been developed for efficient delivery for therapeutic nucleic acids into the lungs based on the characteristics of the nucleic acids, administration routes, and targeting cells. In this review, ALI/ARDS gene therapy is discussed mainly in terms of delivery systems. The pathophysiology of ALI/ ARDS, therapeutic genes, and their delivery strategies are presented for development of ALI/ARDS gene therapy. The current progress suggests that selected and appropriate delivery systems of therapeutic nucleic acids into the lungs may be useful for the treatment of ALI/ARDS.

Automated summary

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a life-threatening inflammatory lung disease, mainly caused by sepsis, infections, trauma, toxic reagents, and COVID-19. Current treatment options for ALI/ARDS are limited, but gene therapy using therapeutic nucleic acids has shown potential. Two classes of therapeutic nucleic acids, knock-in genes and oligonucleotides, have been developed for the treatment of ALI/ARDS. Delivery systems for efficient delivery of therapeutic nucleic acids into the lungs have also been explored. This review discusses ALI/ARDS gene therapy mainly in terms of delivery systems and provides insights for the development of new treatment strategies.