Delivery of siRNA for synthetic lethality-based cancer therapy

2015 Fiscal Year Final Research Report

• Project/Area Number: 25460041
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Physical pharmacy
• Research Institution: University of Shizuoka
• Principal Investigator: Tomohiro Asai 静岡県立大学, 薬学部, 准教授 (00381731)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 合成致死性 / siRNA送達 / がん / PARP1 / PTEN

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.

Free Research Field

薬物送達学