Evaluation of hepatotoxicity of oligonucleotide therapeutics

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K01352
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical engineering assessment
• Research Institution: National Institute of Health Sciences
• Principal Investigator: Yoshida Tokuyuki 国立医薬品食品衛生研究所, 遺伝子医薬部, 研究員 (00649387)
• Research Collaborator: INOUE Taskao ; SASAKI Kiyomi ; OBIKA Satoshi
• Project Period (FY): 2015-10-21 – 2018-03-31
• Keywords: 核酸医薬品 / 肝毒性 / ハイブリダイゼーション依存的オフターゲット効果 / 自然免疫

Outline of Final Research Achievements

We obtained experimental data for development of the methods for the evaluation of antisense oligonucleotides-induced hepatotoxicity. We identified antisense oligonucleotides that avoid hybridization-dependent off-target effects and activation of innate immunity as much as possible, and can induce hepatotoxicity in mice. We also performed microarray analysis using these antisense oligonucleotides to reveal the mechanism of antisense oligonucleotides-induced hepatotoxicity. We started to develop the methods for the evaluation of antisense oligonucleotides-induced hepatotoxicity.

Free Research Field

核酸医薬