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Table 2 Technical challenges to gene-based therapies for ALI/ARDS models

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

Pulmonary defense mechanisms against inhaled particles

   Airway mucus and epithelial lining fluid

   Glycocalyceal barrier

   Tight intercellular epithelial junctions

   Limited endocytosis at luminal surface

Difficulties in transducing the acutely injured lung

   Loss of alveolar epithelium

   Pulmonary edema

   Collapsed and/or consolidated alveoli

   Bronchial plugging by mucus and debris

Limitations of vector systems

   Imunogenicity of viral vectors particularly in repeated doses

   Limitations regarding transgene size

   Limited transfection efficiency of nonviral vectors

Knowledge deficits regarding the optimal molecular targets

  1. ALI, acute lung injury; ARDS, acute respiratory distress syndrome.