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Aerosol Delivery of a β -Galactosidase Adenoviral Vector to the Lungs of Rodents

1995; Mary Ann Liebert, Inc.; Volume: 6; Issue: 8 Linguagem: Inglês

10.1089/hum.1995.6.8-985

1557-7422

Julie P. Katkin, Brian E. Gilbert, Claire Langston, K. French, Arthur L. Beaudet,

Respiratory viral infections research

Aerosol delivery of adenoviral vectors is of particular interest in regard to gene therapy for cystic fibrosis (CF), with potential advantages of more uniform respiratory delivery, a less invasive approach, and ease of repetition. The AdHCMVsp1LacZ (AdLacZ) adenoviral vector was used to evaluate the feasibility of aerosol delivery to the respiratory epithelium in rodents. The adenoviral vector tolerated aerosol generation as measured by recovery in an all-glass impinger. Using an Andersen sampler to mimic the human respiratory tract, aerosol particles were found to have an average mass mean aerodynamic diameter of 1.6 μm and a geometric standard deviation of 1.7 μm. Cotton rats and mice exposed to viral aerosols demonstrated β-galactosidase expression in up to 10–30% of the epithelial surface of the small and large airways, whereas expression in Sprague Dawley rats was largely limited to the alveolar epithelium. Transgene expression was distributed uniformly through both lungs in animals treated by aerosol. The variables for aerosol delivery are complex and include viral titer, aerosol device, duration of exposure, species of recipient, and respiratory behavior among other factors. Species differences in expression in airways as compared to alveolar epithelium have important implications for clinical application. Aerosol delivery of adenoviral vectors to the airway epithelium is a feasible strategy. The variables involved in aerosol delivery are very complex, and very meticulous protocols and large numbers of observations will be required to draw valid conclusions. Because of species differences and because of the unique pathology in cystic fibrosis (CF), some important questions can only be addressed adequately by studies in CF patients.