Physiological Barriers To Gene Delivery In The Lung

Efficient gene delivery is significantly limited by the multitude of barriers that serve to protect the lung against particle and bacterial insult. The upper airways are protected by the mucociliary escalator, a thick mucus layer (8-10 mm) that works in concert with ciliated epithelial cells to efficiently sweep particles out of the lungs into the mouth [132]. The liquid layer is extremely thin (average thickness <0.2 mm) in the alveolar regions of the lung [133]; however, an army of alveolar macrophages rapidly phagocytose most particles following deposition in this region [134]. Diseases such as cystic fibrosis and alpha-l-antitrypsin disease induce changes in lung physiology that include thickening of mucus secretions, inflammation, and bacterial colonization, which may further reduce the efficiency of gene delivery to the lungs.

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