2015 Fiscal Year Final Research Report
A unique anti-leukemic therapy using efficiently tRNA precursor cleavage enzyme in leukemia cells
Project/Area Number |
24591385
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Hematology
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Research Institution | Niigata University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
鳥羽 健 新潟大学, 医歯学総合病院, 講師 (60313540)
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Project Period (FY) |
2012-04-01 – 2016-03-31
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Keywords | TRUE gene silencing / tRNase ZL / Bcl-2 / small guide RNA / 白血病 / アポトーシス誘導 / 細胞増殖抑制 / マウス移植実験 |
Outline of Final Research Achievements |
TRUE gene silencing is a technology to eliminate specific cellular RNAs by using tRNase ZL and small guide RNA (sgRNA). Here we investigated how WT1-mRNA-targeting sgRNAs affect leukemic cells. We showed that sgRNA can be easily taken up by cells without any transfection reagents, and that the naked sgRNAs targeting the WT1 mRNA can reduce its mRNA levels and WT1 protein amounts in the WT1-expressing leukemic cells. Concomitantly, these sgRNAs efficiently induced apoptosis in these cells but not in WT1-nonexpressing cells. We also demonstrated that the reduction in the WT1 mRNA level is caused by its cleavage by tRNase ZL. Besides, we demonstrated that a heptamer, mh1(Bcl-2), which targets the human Bcl-2 mRNA, can be taken up by cells without any transfection reagents and that it can induce apoptosis of the leukemia cells. Mouse xenograft experiments showed that a median survival of the mh1(Bcl-2)-treated mice was longer than that of the control mice.
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Free Research Field |
血液内科学
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