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Adenoviral vector-associated liposomes: efficient gene transfer to human glioma cells

Yasushi RYUKE, Masaaki MIZUNO, Atsushi NATSUME, Jun YOSHIDA

Dept. of Neurosurg., Nagoya Univ. School of Med., Nagoya 466-8560, Japan

Human malignant glioma is one of the most formidable neoplasms arising in the brain, and patients with the disease have an average survival time of less than 2 years. In an attempt to improve this grim prognosis of patients with malignant glioma, there is the application of recombinant DNA technology such as human gene therapy.Replication-deficient adenoviral vectors have been considered to be promising ones for human gene therapies, because they have higher transduction efficiency than other vectors. In contrast, they have disadvantages, such as high immnogenicity. In considering strategies for effective and safe gene transfer into human, replication-deficient adenoviral vectors became to be noticed because of higher transduction efficiency. However, it has been reported that adenoviral vectors have high immunogenicity and that their dose is limited in liver, lung, muscle, and brain. Especially in the brain, the volume of adenoviral vector is also another important parameter. When more than 10⁹ pfu of adenoviral vectors were injected into human brain, it was reported that the vectors caused inflammatory responses in the brain and induced severe brain edema. To make less immune reaction against antigens, we investigated the combined effect of adenoviral vectors and cationic liposomes. As a result, transduction efficiency of adenoviral vectors increased about 10-fold by associating with cationic liposomes. These results suggest that the combination of adenoviral vectors and cationic liposomes make possible to decrease the immunogenicity of adenoviral vectors.