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Highly Accessed Open Badges Review

Clinical Review: Gene-based therapies for ALI/ARDS: where are we now?

James Devaney1, Maya Contreras12 and John G Laffey123*

Author Affiliations

1 Lung Biology Group, Regenerative Medicine Institute, National Centre for Biomedical Engineering Science, Orbsen Building, National University of Ireland, Newcastle Road, Galway, Ireland

2 Department of Anaesthesia and Intensive Care Medicine, Galway University Hospitals, Newcastle Road, Galway, Ireland

3 Anaesthesia, School of Medicine, Clinical Sciences Institute, National University of Ireland Galway, Newcastle Road, Galway, Ireland

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Critical Care 2011, 15:224  doi:10.1186/cc10216

Published: 20 June 2011


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.