| 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 |
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| Research Field |
Medical pharmacy
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| Research Institution | Osaka University |
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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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