| Co-Investigator(Kenkyū-buntansha) |
HAYASHI Yasuyuki The Cancer Institute (JFCR), Department of Gene Research, Associate, 癌研究所・遺伝子研究施設部, 研究員 (90198862)
HASHIMOTO Shuichi MEIJI Health Science Institute, Senior Researcher, ヘルスサイエンス研究所, 課長研究員
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| Research Abstract |
Nearly 30% of hepatocellular carcinoma in Japan harbor mutation in the p53 tumor suppressor gene. In the present study we tried to construct an effective vector for gene therapy targeting the hepatoma carrying p53 mutation. As we have so far demonstrated that expression of M4 promoter of Hepatitis B virus (HBV) X gene is regulated specifically in the hepatic cells and that its high expression is dependent on the p53 mutation, this particular feature of M4 promoter works useful to develop a vector that contains any cell death-related gene downstream the M4 promoter.
In addition to the knowledge that HBY X is a transactivator, we recently found that central part of the X protein is related to cell death activity. Therefore a unique vector for p53 mutated hepatoma cell can be made by introducing the X gene as a cell death related gene into the El region of Ad5 vector. On the other hand, KB cell derived IL-6(KB) was found to be potent to induce cell death activity in p53 mutated cell. Thus, a transcription cassette can be developed by connecting the IL-6(KB) gene under the M4 promoter of X gene to induce cell death activity in the p53 mutated hepatic cells.
In September 1999, however, accidental death of OTC patients under the treatment of gene ' therapy using Ad5 vector was reported and US FDA suggested tentative disruption of using Ad5 vector for gene therapy. Under the situation, we also tentatively interrupted the ongoing experiments. In March 2000, intermediate survey report summarized that the accident was caused by clinical prescription and not by Ad5 vector itself. Accordingly we resumed the study with about a half a year of loss and the experiments are still underway.
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