2013 Fiscal Year Final Research Report

Development of mRNA ablation using completely new functional nucleic acid constructs

Research Project

Project/Area Number	23501304
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Clinical oncology
Research Institution	Niigata University
Principal Investigator	NARITA Miwako 新潟大学, 医歯学系, 准教授 (30281009)
Co-Investigator(Kenkyū-buntansha)	NASHIMOTO Masayuki 新潟薬科大学, 応用生物科学部, 教授 (30228069)
Project Period (FY)	2011 – 2013
Keywords	sgRNA / mRNA / apoptosis / tRNaseZL / WT1
Research Abstract	TRUE gene silencing is a new method to delete specific cellular RNAs by using tRNase ZL and small guide RNA (sgRNA) that cleaves a pre-tRNA-like or micro-pre-tRNA-like complex consisting of cellular target RNA. We investigated the possibility that heptamer-type sgRNA can be used as nucleic acid medicine to treat hematological malignancies. We investigated the effect of artificial sgRNAs on mRNAs which -targeting sgRNAs affect leukemic cells. We confirmed that sgRNA can be taken up by cells without any transfection reagents, and that the naked sgRNAs targeting several tumor-associated mRNA can reduce specific mRNA levels and the amounts of tumor-associated protein in several leukemic cell lines. These sgRNAs efficiently induced apoptosis in these cells. These encouraging findings lead us to follow the possibility that heptamer-type sgRNAs targeting anti-apoptotic mRNAs can be used as RNA medicine against hematological malignancies.