ALVEOLAR STEM-CELL TRANSDUCTION BY AN ADENOASSOCIATED VIRAL VECTOR

In inherited disorders such as surfactant protein deficiencies or cyst ic fibrosis (CF), where lung damage develops progressively after birth , gene replacement is best accomplished in the neonatal period. We use the adeno-associated virus (AAV) as a vector for gene transfer in the newborn rabbit lung where stem cells are activated for lung growth an d differentiation. AAV-mediated gene transfer as assayed by lacZ gene expression occurred preferentially in alveoli in the alveolar epitheli al progenitor cell, the type II cell, and in the large airway tracheob ronchial basal and ciliated cells. Cell proliferation was confirmed by 5-bromodeoxyuridine (BRDU) labeling in regions of cell proliferation coincided with areas of significant lacZ expression. Thus, dividing an d differentiating cells can be targeted by AAVlacZ delivery to newborn lung.