Evaluation of Off-target Effects of Antisense Oligonucleotides
Project/Area Number |
25860116
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Medical pharmacy
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Research Institution | Osaka University |
Principal Investigator |
YOSHIDA Tokuyuki 大阪大学, 薬学研究科(研究院), 研究員 (00649387)
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Research Collaborator |
INOUE Taskao
SASAKI Kiyomi
NAITO Yuki
OBUKA Satoshi
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Project Period (FY) |
2013-04-01 – 2015-03-31
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Project Status |
Completed (Fiscal Year 2014)
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Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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Keywords | 核酸医薬品 / Gapmer型アンチセンス / オフターゲット効果 / ヒト肝細胞キメラマウス / アンチセンス |
Outline of Final Research Achievements |
RNA targeting oligonucleotide therapeutics, such as antisense oligonucleotides (ASO), carry the risk of causing unintended toxicities or side effects. One of the potential toxicities is hybridization-dependent off-target effects which are caused by Watson and Crick base-pairing to unintended RNAs. It is assumed that improvements in potency and cellular delivery arising from chemically modified nucleic acids could increase the risk of hybridization-dependent toxicities. However, it is unclear how ASO affect the expression of unintended RNAs, for example, mRNAs which are partially complementary to the ASO. To reveal this point, we performed microarray analysis using a human cell line and several ASO with gapmer design having 2′,4′-BNA. In this study, we reveal that the criteria for judgment of “off-target candidate genes” in in silico analysis, and the possible design of the methods for the evaluation of off-target effects of ASO.
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Report
(3 results)
Research Products
(12 results)
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[Journal Article] Design and evaluation of locked nucleic acid-based splice-switching oligonucleotides in vitro.2014
Author(s)
Shimo, T., Tachibana, K., Saito, K., Yoshida, T., Tomita, E., Waki, R., Yamamoto, T., Doi, T., Inoue, T., Kawakami, J., Obika, S.
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Journal Title
Nucleic Acids Res.
Volume: 42
Issue: 12
Pages: 8174-8187
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Evaluation of Off-target Effects of Antisense Oligonucleotides2014
Author(s)
Yoshida, T., Sasaki, K., Obika, S., Sato, Y., Inoue, T.
Organizer
10th Annual Meeting of the Oligonucleotide Therapeutics Society
Place of Presentation
Hilton San Diego Resort & Spa (San Diego,California)
Year and Date
2014-10-12 – 2014-10-15
Related Report
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[Presentation] オリゴ核酸による自然免疫活性化の評価法に関する研究2014
Author(s)
萩原衆子, 山本誠司, 吉田徳幸, 佐々木澄美, 飯村信, 小泉誠, 佐藤陽治, 植村英俊, 井上貴雄
Organizer
アンチセンス・遺伝子・デリバリーシンポジウム2014
Place of Presentation
東京医科歯科大学(東京)
Year and Date
2014-09-08 – 2014-09-09
Related Report
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[Presentation] siRNAの細胞内取り込み機構の解析2014
Author(s)
佐々木澄美, 吉田徳幸, 内田恵理子, 佐藤陽治, 井上貴雄
Organizer
第6回日本RNAi研究会
Place of Presentation
グランドプリンスホテル広島(広島)
Year and Date
2014-08-28 – 2014-08-30
Related Report
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