2013 Fiscal Year Final Research Report
The Development of Highly Effective BNA-based Antisense Oligonucleotides
| Project/Area Number |
24890102
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Chemical pharmacy
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| Research Institution | Osaka University |
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Principal Investigator |
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| Project Period (FY) |
2012-08-31 – 2014-03-31
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| Keywords | 核酸医薬 / 糖部架橋型人工核酸 / ターンオーバー / ホスホロチオアート / アンチセンス医薬 |
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| Research Abstract |
Despite recent great progress in antisense drugs coming from the development of high-affinity modified nucleic acids such as Bridged Nucleic Acids (BNAs), there still remain efficacy and safety issues. First, to test the hypothesis that increase of turnover ability of antisense molecules is associated with the increase of efficacy, cell-free turnover detection system was devised and turnover rates were estimated. As expected, antisense oligonucleotides with slow turnover rates showed no significant silencing in vivo. On the other hand, to increase the availability of dosed antisense molecules, small molecules that activate cellular uptake of antisense molecules or increase silencing effect via unknown mechanisms were screened from a drug library and very attractive molecules were found. Correctively, high-turnover antisense oligonucleotide in combination with a small molecule would sophisticate a current antisense therapy.
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Research Products
(11 results)
