論文 - 詳細
| RRC ID | 43780 |
|---|---|
| 著者 | Kubo T, Yanagihara K, Takei Y, Mihara K, Sato Y, Seyama T. |
| タイトル | Lipid-conjugated 27-nucleotide double-stranded RNAs with dicer-substrate potency enhance RNAi-mediated gene silencing. |
| ジャーナル | Mol Pharm |
| Abstract |
Short interfering RNAs (siRNAs), used in RNA interference (RNAi) technology, are powerful tools for target-gene silencing in a sequence-specific manner. In this study, Dicer-substrate 27-nucleotide (nt) double-stranded RNAs (dsRNAs), which are known to have a highly potent RNAi effect, were conjugated with palmitic acid at the 5'-end of the sense strand to enhance intracellular delivery and RNAi efficacy. The palmitic acid-conjugated 27-nt dsRNAs (C16-ds27RNAs) were prepared by our simple synthesis strategy in good yield. The C16-ds27RNAs were cleaved by a Dicer enzyme, leading to the release of 21-nt siRNAs. The high level of stability in serum using C16-ds27RNAs was also confirmed. The C16-ds27RNAs showed enhanced RNAi potency targeted to both an exogenous luciferase and an endogenous vascular endothelial growth factor (VEGF) gene in the presence or absence of a transfection reagent, such as Lipofectamine 2000. In addition, the C16-ds27RNAs had a more potent gene-silencing activity than the other lipid-conjugated 21-nt siRNAs and 27-nt dsRNAs. The C16-ds27RNAs also exhibited significant membrane permeability. These results suggested that the C16-ds27RNAs will be useful for next-generation RNAi molecules that can address the problems of RNAi technology. |
| 巻・号 | 9(5) |
| ページ | 1374-83 |
| 公開日 | 2012-5-7 |
| DOI | 10.1021/mp2006278 |
| PMID | 22494497 |
| MeSH | Cell Line, Tumor Gene Silencing / physiology* HeLa Cells Humans Lipids / chemistry* Palmitic Acid / chemistry RNA Interference / physiology RNA, Double-Stranded / chemistry* RNA, Double-Stranded / genetics* Vascular Endothelial Growth Factor A / genetics* |
| IF | 4.321 |
| 引用数 | 14 |
| WOS 分野 | MEDICINE, RESEARCH & EXPERIMENTAL PHARMACOLOGY & PHARMACY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 22 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 3.0 |
| リソース情報 | |
| ヒト・動物細胞 | SH-10-TC(RCB1940) |