Delivery of siRNA for synthetic lethality-based cancer therapy
| Project/Area Number |
25460041
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Physical pharmacy
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| Research Institution | University of Shizuoka |
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Principal Investigator |
Tomohiro Asai 静岡県立大学, 薬学部, 准教授 (00381731)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 合成致死性 / siRNA送達 / がん / PARP1 / PTEN / siRNA / RNA干渉 / DDS / 合成致死 |
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| Outline of Final Research Achievements |
Synthetic lethality has attracted considerable attention as a novel strategy for the treatment of cancer. To explore RNA interference (RNAi) cancer therapy based on synthetic lethality, poly [ADP-ribose] polymerase 1 (PARP1) gene in human breast cancer cells lacking phosphatase and tensin homolog deleted from chromosome 10 (PTEN) was silenced by small interfering RNA targeting PARP1 (siPARP1). For the efficient delivery of siPARP1 to cancer cells, dicetylphosphate-tetraethylenepentamine-based polycation liposomes (TEPA-PCL) were prepared. Treatment with siPARP1 formulated in TEPA-PCL (siPARP1/TEPA-PCL) selectively induced DNA damage and cytocidal effects in PTEN-null cells, but not in PTEN-positive cells. These results indicate that PARP1 knockdown using siPARP1/TEPA-PCL is likely to be an effective strategy to achieve synthetic lethality against PTEN-null cancer.
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Report
(4 results)
Research Products
(67 results)
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[Journal Article] Real-time trafficking of PEGylated liposomes in the rodent focal brain ischemia analyzed by positron emission tomography2014
Author(s)
Fukuta T, Ishii T, Asai T, Nakamura G, Takeuchi Y, Sato A, Agato Y, Shimizu K, Asai S, Fukumoto D, Harada N, Tsukada H, Kawaguchi AT, Oku N
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Journal Title
Artificial organs
Volume: 38
Issue: 8
Pages: 662-6
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Neuroprotective effect of nobiletin on cerebral ischemia-reperfusion injury in transient middle cerebral artery-occluded rats.2014
Author(s)
Yasuda N, Ishii T, Oyama D, Fukuta T, Agato Y, Sato A, Shimizu K, Asai T, Asakawa T, Kan T, Yamada S, Ohizumi Y, Oku N.
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Journal Title
Brain Res.
Volume: 1559
Pages: 46-54
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Systemic delivery of small interfering RNA by use of targeted polycation liposomes for cancer therapy.2013
Author(s)
Kenjo E, Asai T, Yonenaga N, Ando H, Ishii T, Hatanaka K, Shimizu K, Urita U, Dewa T, Nango M, Tsukada H, Oku N
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Journal Title
Biol. Pharm. Bull.
Volume: 36
Pages: 287-291
NAID
Related Report
Peer Reviewed
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[Journal Article] Liposomal amiodarone augments anti-arrhythmic effects and reduces hemodynamic adverse effects in an ischemia/reperfusion rat model.2013
Author(s)
Takahama H, Shigematsu H, Asai T, Matsuzaki T, Sanada S, Fu HY, Okuda K, Yamato M, Asanuma H, Asano Y, Asakura M, Oku N, Komuro I, Kitakaze M, Minamino T.
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Journal Title
Cardiovasc Drugs Ther.
Volume: 27
Issue: 2
Pages: 125-132
DOI
Related Report
Peer Reviewed
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