LUNG GENE-THERAPY - IN-VIVO ADENOVIRUS-MEDIATED GENE-TRANSFER TO RHESUS-MONKEY AIRWAY EPITHELIUM

Somatic gene therapy of lung disorders such as cystic fibrosis (CF) ai ms at introducing the therapeutic gene into respiratory epithelium. We have tested the ability of recombinant human adenovirus to infect rhe sus monkey airway epithelium in vivo. Application of adenovirus harbor ing the lacZ marker gene to the airway surface resulted in large patch es of LacZ-positive cells in the trachea, bronchi, and bronchioles, 6 days after virus exposure, indicating a successful transfer of the lac Z gene to respiratory epithelium. Microscopic analysis showed that bas al, mucous goblet, and ciliated cells were lacZ positive. In addition, gene transfer to the submucosal glands was observed. Pathological exa mination of the organs revealed no virus-mediated toxic effects to the lungs and other organs. Using polymerase chain reaction (PCR) analysi s we found no spread of the virus to blood or any organ tested. These results indicate the potential use and safety of adenoviruses as a too l in human gene therapy procedures aimed at pulmonary diseases.