Transduction efficiency of adenoviral vectors into human glioma cells increased by association with cationic liposomes.
Replication-deficient adenoviral vectors are promising agents for human gene therapy of the greater transduction efficiency than other vectors. However, there are distinct disadvantages, including high immunogenicity, which limits the administration to human organs, particularly the brain. Injection of adenoviral vectors into the human brain causes inflammatory responses and induces cerebral edema. The combined effect of adenoviral vectors and cationic liposomes in vitro was investigated in an effort to reduce the immune reaction against the antigens of adenoviral vectors. No toxicity of adenoviral vector-associated liposomes was observed within optimal lipid concentration. The transduction efficiency of the adenoviral vectors containing the beta-galactosidase gene increased almost 10-fold when associated with the cationic liposomes. Furthermore, greater cytotoxicity was induced when the adenoviral vector containing herpes simplex virus-thymidine kinase gene was combined with cationic liposomes than with only the adenoviral vector. These results suggest that the combination of adenoviral vectors and cationic liposomes allows the doses of adenoviral vectors to be reduced while maintaining transduction efficiency.
Ryuke
Y
Y
Department of Neurosurgery, Nagoya University School of Medicine, Nagoya.
Mizuno
M
M
Natsume
A
A
Yoshida
J
J
D000256:Adenoviridae / Q000235:genetics*; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics*; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008081:Liposomes; D013937:Thymidine Kinase / Q000235:genetics*; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured / Q000473:pathology; D001616:beta-Galactosidase / Q000235:genetics*
D008081:Liposomes; D013937:Thymidine Kinase; D001616:beta-Galactosidase