Abstract
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) confer substantial morbidity and mortality, and have no specific therapy. The accessibility of the distal lung epithelium via the airway route, and the relatively transient nature of ALI/ARDS, suggest that the disease may be amenable to gene-based therapies. Ongoing advances in our understanding of the pathophysiology of ALI/ARDS have revealed multiple therapeutic targets for gene-based approaches. Strategies to enhance or restore lung epithelial and/or endothelial cell function, to strengthen lung defense mechanisms against injury, to speed clearance of infection and to enhance the repair process following ALI/ARDS have all demonstrated promise in preclinical models. Despite three decades of gene therapy research, however, the clinical potential for gene-based approaches to lung diseases including ALI/ARDS remains to be realized. Multiple barriers to effective pulmonary gene therapy exist, including the pulmonary architecture, pulmonary defense mechanisms against inhaled particles, the immunogenicity of viral vectors and the poor transfection efficiency of nonviral delivery methods. Deficits remain in our knowledge regarding the optimal molecular targets for gene-based approaches. Encouragingly, recent progress in overcoming these barriers offers hope for the successful translation of gene-based approaches for ALI/ARDS to the clinical setting.
Highlights
Background and contextAcute lung injury (ALI) and acute respiratory distress syndrome (ARDS) constitute the leading cause of death in pediatric and adult critical care [1]
There are no specific therapies for ALI/ARDS, and management remains supportive, focusing on protective mechanical ventilation strategies [4], restrictive intravenous fluid management approaches [5], and rescue strategies such as prone positioning [6] or extracorporeal membrane oxygenation [7] for severely hypoxemic patients
Gene therapy: opportunities in ALI/ARDS Gene-based therapy involves the insertion of genes or smaller nucleic acid sequences into cells and tissues to replace the function of a defective gene, or to alter the production of a specific gene product, in order to treat a disease
Summary
Background and contextAcute lung injury (ALI) and acute respiratory distress syndrome (ARDS) constitute the leading cause of death in pediatric and adult critical care [1]. Nonviral gene-based strategies Nonviral delivery systems, while generally less efficient than viral vectors in transfecting the lung epithelium, are increasingly used to deliver smaller DNA/RNA molecules (Table 1).
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
