1998 Fiscal Year Final Research Report Summary
Development of inducible vectors for human gene therapy
| Project/Area Number |
09671420
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Nagoya University |
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Principal Investigator |
MIZUNO Masaaki School of Medicine, Nagoya University Research Assistant, 医学部, 助手 (70283439)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIDA Jun School of Medicine, Professor, 医学部, 教授 (40158449)
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| Project Period (FY) |
1997 – 1998
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| Keywords | BRAIN TUMOR / INTERFERON / GENE REGULATION / Tet SYSTEM / HSP / AAV VECTOR |
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| Research Abstract |
We have promoted the development of inducible vectors for human gene therapy for 2 years. We investigated the antitumor efficacy on human glioma cells when human interferon-beta (IFN-beta) gene therapy using heat-inducible adeno-associated virus (AAV) vectors was combined with low-temperature hyperthermia. We constructed AAV vectors that contain human IFN-beta gene and were driven by heat shock protein 70B (HSP70B) promoter (AAV-hsp-IFN-beta). The AAV-hsp-IFN-beta produced a small amount of human IFN-beta at 37ﾟC, but the amount increased >2-fold by heating medium at 39ﾟC for 8 h. At that time, the antitumor efficacy also increased remarkably and further was much stronger than that of AAV-hsp-IFN-beta alone. We observed cell death of human glioma cells induced by AAV-hsp-IFN-beta or low-temperature hyperthermia or both of them by using video-enhanced contrast differential interference contrast (VBC-DIC) microscopy. Infection of AAV-hsp-IFN-beta induced apoptosis and combination of AAV-hsp-IFN-beta and low-temperature hyperthermia induced both necrosis and apoptosis on human glioma cells. The same results were shown in the case of liposomes containing heat-inducible plasmids Also, Tet system was useful.
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