Evaluation of hepatotoxicity of oligonucleotide therapeutics
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
|
Project Status |
Completed (Fiscal Year 2017)
|
Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
|
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 / 相補配列依存的オフターゲット効果 |
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.
|
Report
(4 results)
Research Products
(22 results)
-
[Journal Article] 核酸医薬品の安全性評価に関する考え方 -仮想核酸医薬品をモデルにして- 第2回:局所投与剤の毒性評価2018
Author(s)
木下潔, 真木一茂, 荒戸照世, 太田哲也, 小野寺博志, 佐藤秀昭, 中澤隆弘, 平林容子, 笛木修, 三井田宏明, 吉田徳幸, 渡部一人, 小比賀聡, 井上貴雄
-
Journal Title
医薬品医療機器レギュラトリーサイエンス
Volume: 3
Pages: 157-163
Related Report
-
[Journal Article] 核酸医薬品の安全性評価に関する考え方 -仮想核酸医薬品をモデルにして- 第1回:オンターゲット毒性の評価2018
Author(s)
木下潔, 真木一茂, 荒戸照世, 太田哲也, 小野寺博志, 佐藤秀昭, 中澤隆弘, 平林容子, 笛木修, 三井田宏明, 吉田徳幸, 渡部一人, 小比賀聡, 井上貴雄
-
Journal Title
医薬品医療機器レギュラトリーサイエンス
Volume: 2
Pages: 105-111
Related Report
-
-
[Journal Article] Mediator cyclin-dependent kinases upregulate transcription of inflammatory genes in cooperation with NF-κB and C/EBPβ on stimulation of Toll-like receptor 9.2017
Author(s)
Yamamoto, S., Hagihara, T., Horiuchi, Y., Okui, A., Wani, S., Yoshida, T., Inoue, T., Tanaka, A., Ito, T., Hirose, Y., and Ohkuma, Y.
-
Journal Title
GENES TO CELLS
Volume: 22
Issue: 3
Pages: 265-276
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
-
-
-
[Presentation] 修飾型人工核酸の肝毒性評価2017
Author(s)
吉田 徳幸
Organizer
革新的バイオ研究開発シンポジウム
Place of Presentation
千里ライフサイエンスセンター(大阪)
Year and Date
2017-01-20
Related Report
Invited
-
[Presentation] Evaluation of Off-target Effects of Splice-switching Oligonucleotides2017
Author(s)
Tokuyuki Yoshida, Kiyomi Sasaki, Yuki Naito, Makoto Koizumi, Masakazu Tamura, Hiroaki Miida, Mitsuhiro Tagaya, Kazuchika Takagaki,Satoshi Obika, Mikihiko Naito, Takao Inoue
Organizer
13th Annual Meeting of the Oligonucleotide Therapeutics Society
Related Report
Int'l Joint Research
-
-
-
-
-
-
-
-
-
-
-
-
-
-