Gene therapy for asthma.

The accessibility of the airway epithelium and the limitations of current treatments for asthma make the disease a logical target for gene therapy. Study of the immunopathology of chronic airway inflammation has recently identified several pathways that lead to the maladaptive, antigen-induced polarization of CD4+ T cells to a type-2 phenotype. This polarization is thought to lead to IgE production and eosinophil recruitment and activation that is associated with epithelial cell injury and airway hyper-reactivity. Gene transfer to the bronchial epithelium has been used in experimental models to redirect these pathways toward a less injurious, type-1 phenotype. This mini-review highlights recent mechanism-based immunomodulatory and supportive gene transfer approaches to treat animal models of asthma. Although substantial hurdles to airway gene transfer remain, gene transfer offers the possibility of interrupting the pathophysiology of airway inflammation. Doing so can be expected to yield long-lasting protection from bronchospastic challenge and reduced dependence on inhaled and oral medications.