Study on the gene therapy using a new generation adenovirus vector (gutless adenovirus)

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We constructed a helper virus dependent adenoviral vector (HDAV), which deleted all genomes coding viral proteins. It carries only the therapeutic gene instead. We constructed two kinds of HDAV. One carries full-length dystrophin and lacZ gene as a marker, the other carries full-length dystrophin and CAR, an attachment receptor for adenovirus. These HDAVs are called HDAVLacZ-dys and HDAVCAR-dys, respectively. When the neonatal mdx mouse skeletal muscles are inoculated with the HDAVLacZ-dys vector under the non-immunosuppressive condition, 8-week after the inoculation dystrophin expression could be detected efficiently. We could confirm not only the dystrophin expression but also the normalization of the pathological abnormality in the transfected muscle cells. When HDAVCAR-dys vector was inoculated repetitively in to the maturated mdx mouse skeletal muscles, the number of dystrophin positive muscle cells increased by this repetitive infection. And the expression of the dystrophin could prolong for long time. We propose that the gene therapy by these strategies will be applied for many kinds of the muscular dystrophy.