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) aims at introducing the therapeutic gene into respiratory epithelium. We have tested the ability of recombinant human adenovirus to infect rhesus monkey airway epithelium in vivo. Application of adenovirus harboring the lacZ marker gene to the airway surface resulted in large patches of lacZ-positive cells in the trachea, bronchi, and bronchioles, 6 days after virus exposure, indicating a successful transfer of the lacZ gene to respiratory epithelium. Microscopic analysis showed that basal, mucous goblet, and ciliated cells were lacZ positive. In addition, gene transfer to the submucosal glands was observed. Pathological examination of the organs revealed no virus-mediated toxic effects to the lungs and other organs. Using polymerase chain reaction (PCR) analysis 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 tool in human gene therapy procedures aimed at pulmonary diseases.
Bout
A
A
Department of Gene Therapy, Medical Biological Laboratory, TNO, Rijswijk, The Netherlands.
Perricaudet
M
M
Baskin
G
G
Imler
J L
JL
Scholte
B J
BJ
Pavirani
A
A
Valerio
D
D
D000260:Adenoviruses, Human / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D003550:Cystic Fibrosis / Q000628:therapy*; D004848:Epithelium / Q000382:microbiology / Q000473:pathology; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D007763:Lac Operon; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D014132:Trachea / Q000382:microbiology* / Q000473:pathology
D009838:Oligodeoxyribonucleotides