A genome-wide RNAi screen to identify genes involved in the incorporation of antisense oligonucleotides into the cells

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K06811
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: National Institute of Health Sciences
• Principal Investigator: Inoue Takao 国立医薬品食品衛生研究所, 遺伝子医薬部, 部長 (50361605)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 核酸医薬品

Outline of Final Research Achievements

In recent years, development of nucleic acid drugs such as antisense and siRNA has been progressing, attracting attention as next-generation drugs for hereditary and intractable diseases for which there is no cure. However, the pathways and molecular mechanisms by which nucleic acid drugs are taken up from outside the cell and reach their sites of action inside the cell have not been clarified. In this study, we constructed a screening system to comprehensively search for candidate molecules involved in these pathways using Gapmer-type antisense and splice-switching oligonucleotides, and succeeded in identifying a group of candidate genes.

Free Research Field

核酸・遺伝子医薬

Academic Significance and Societal Importance of the Research Achievements

アンチセンスの細胞内取り込みに関与する分子群の特定は、アンチセンスの細胞内送達を向上される技術の抄出に繋がるもので、医療分野の進展に資するものである。また、原料供給・製造/分析・品質担保に関する課題解決案の提示についても、対応するプロジェクト等が発動すれば、核酸医薬開発を進展に大きく寄与する。核酸医薬品はアンメットメディカルニーズに対応する新規モダリティとして期待が高まっていることから、本研究で得られた成果は社会的ニーズに直結すると判断される。