Aerosol delivery of a beta-galactosidase adenoviral vector to the lungs of rodents.
Hum Gene Ther
; 6(8): 985-95, 1995 Aug.
Article
em En
| MEDLINE
| ID: mdl-7578420
ABSTRACT
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 microns and a geometric standard deviation of 1.7 microns. Cotton rats and mice exposed to viral aerosols demonstrated beta-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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Terapia Genética
/
Adenoviridae
/
Beta-Galactosidase
/
Técnicas de Transferência de Genes
/
Vetores Genéticos
/
Pulmão
Limite:
Animals
Idioma:
En
Revista:
Hum Gene Ther
Assunto da revista:
GENETICA MEDICA
/
TERAPEUTICA
Ano de publicação:
1995
Tipo de documento:
Article
País de afiliação:
Estados Unidos