Control of Gene Expression by Functional and Artificial Nucleic Acids
| Project/Area Number |
18550151
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Chemistry related to living body
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| Research Institution | Osaka University |
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Principal Investigator |
OBIKA Satoshi Osaka University, Graduate School of Pharmaceutical Sciences, Professor (80243252)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥4,240,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥540,000)
Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2006: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | Nucleic Acids / Oligonucleoides / Antigene / Control of Gene Expression / Bridged Nucleic Acids / DNA / Triplex DNA / 三重鎖核酸 |
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| Research Abstract |
In order to develop a novel strategy to control a gene expression, an olignnucleotidc-functional molecule conjugate has been synthesized and its biological properties were also studied. The results are summarized below.
1) Some heterocyclic compounds were designed, synthesized and incorporated into a bridged nucleic acid skeleton. The obtained bridged nucleic acids bearing unnatural nucleobases were also introduced into oligonucleotides, and their triplex-forming ability was investigated. Very interestingly, it was found that the recognition of pyrimicline-purine interruption site was successfully achieved by the bridged nucleic acid derivatives /
2) As a convenient method to introduce a functional group into oligonucleotides, a post-elongation modification method based on Click chemistry was developed. Furthermore, some oligonucleotides conjugated with a transcription factor-binding site (double stranded DNA) were also successfully prepared.
3) The oligonucleotides bearing unnatrural nucleobases prepared above were transfected into living cells, and their ability to control gene expression was evaluated. The oligonucleotides bearing unnatural nucleobases, by themselves or together with the antigene-block strategy developed by our group, showed effective regulation of gene expression. Furthermore, the oligonucleotides conjugated with a transcription factor-binding site promoted the target gene expression. These results are of great interest and would be useful for further biological application.
4) A relationship between chemical structures of oligonucleotide analogues and their triplex-forming ability was evaluated in detail, and the novel bridged nucleic acid, of which triplex-forming ability was higher than that of the pinto-type BNA, was successfully developed.
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Report
(3 results)
Research Products
(219 results)
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[Journal Article] A Bridged Nucleic Acid, 2',4'-BNA^<coc> : Synthesis of Fully Modified Oligonucleotides Bearing Thymine, 5-Methylcytosine, Adenine and Guanine 2',4'-BNA^<coc> Monomers, and RNA-selective Nucleic Acid Recognition2009
Author(s)
Y. Mitsuoka, T. Kodama, R. Ohnishi, Y. Hari, T. Imanishi, S. Obika
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Journal Title
Nucleic Acids Res. 37
Pages: 1225-1238
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Antisense Activity of 2',4'-BNA Targeted to PPAR Gamma in THP-1 and HCT116 Cells2007
Author(s)
K. Tachibana, T. Katayama, C. Ueda, M. Sumitomo, M. Tagami, K. Ishimoto, D. Yamasaki, T. Tanaka, T. Hamakubo, J. Sakai, T. Kodama, S. Obika, T. Imanishi, T. Doi
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Journal Title
Nucleic Acids Symp. Ser. 51
Pages: 441-442
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Modification of siRNA with bridged nucleic acids BNAs2008
Author(s)
H. Satoh, N. Tsuda, K. Narukawa, T. Imanishi, S. Obika
Organizer
31^<st> Annual Meeting of the Molecular Biology Society of Japan and 81^<st> Annual Meeting of the Japan Biochemical Society
Place of Presentation
Yokohama
Year and Date
2008-12-10
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Regulation of gene expression by BNA modified siRNA2008
Author(s)
H. Satoh, N. Tsuda, S. Haitani, A. Matsumoto, T. Imanishi, S. Obika
Organizer
Symposium on Biofunctional Chemistry of the Chemical Society of Japan, Forum for Young Scientist
Place of Presentation
Yokohama
Year and Date
2008-09-17
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Antigene Block Strategy2006
Author(s)
A. Itoh, N. Tsuda, S. Haitani, A. Matsumoto, T. Uneda, A. Tanabe, S. Obika, T. Imanishi
Organizer
1^<st> Annual Meeting of the Japanese Society for Chemical Biology
Place of Presentation
Tokyo
Year and Date
2006-05-08
Description
「研究成果報告書概要(欧文)」より
Related Report
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