2017 Fiscal Year Final Research Report
Development of new oncolytic adenovirus utilizing RNA stabilization system
| Project/Area Number |
15K15728
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Surgical dentistry
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| Research Institution | Hokkaido University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
北村 哲也 北海道大学, 歯学研究院, 助教 (00451451)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | アデノウイルス / 腫瘍溶解 / AU-rich element / E1A |
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| Outline of Final Research Achievements |
AU-rich elements (ARE) are RNA elements that enhance the rapid decay of mRNAs including those of the genes required for cell growth and proliferation. The stabilization of ARE-mRNA has been correlated with the malignancy of cancer cells. We herein developed an adenovirus designated Ad+AU including ARE in the 3’-untranslated region (3’-UTR) of the E1A gene. The expression level of E1A was high when the virus infected cancer cells, but was very low in normal cells. The productive rate of the virus correlated with the expression of E1A. Ad+AU exerted markedly stronger cytolytic effects in multiple cancer cell lines than in normal cells. The growth of human tumors that formed in nude mice was inhibited by an intratumoral injection of Ad+AU. These results indicate that Ad+AU has potential as an oncolytic adenovirus for a vast majority of cancers in which ARE-mRNA is stabilized.
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| Free Research Field |
分子腫瘍学
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