論文 - 詳細
| RRC ID | 44769 |
|---|---|
| 著者 | Kubo T, Yanagihara K, Sato Y, Nishimura Y, Kondo S, Seyama T. |
| タイトル | Gene-silencing potency of symmetric and asymmetric lipid-conjugated siRNAs and its correlation with dicer recognition. |
| ジャーナル | Bioconjug Chem |
| Abstract |
Three types of siRNAs and three types of left-overhang siRNAs (LoRNAs) were synthesized along with their conjugations with palmitic acid (C16) to investigate the correlation between Dicer recognition and gene-silencing potency. The siRNA types were composed of 21-nucleotide (nt), 23-nt, and 25-nt lengths of sense and antisense strands with a 2-nt overhang at each 3'-end. The three LoRNA types were composed of a 21-nt, a 23-nt, and a 25-nt length of sense strand with a 2-nt DNA at the 3'-blunt-end and a 23-nt, a 25-nt, and a 27-nt length of antisense strand with a 2-nt overhang at the 3'-end. Additionally, each of these siRNAs and LoRNAs was modified with a C16 at the 5'- or 3'-end of the sense strand; these were named C16-siRNAs and C16-LoRNAs, respectively. The siRNAs and C16-siRNAs were barely cleaved by Dicer, and their gene-silencing efficacies were not excellent, contrary to our expectations. In contrast, most of the LoRNAs and C16-LoRNAs became substrates of Dicer, and they showed both strong gene-silencing efficacies and high nuclease resistance. Among the LoRNAs, the 25D-C16/27-nt LoRNA, which is composed of a 25-nt sense strand with a 2-nt DNA conjugated with C16 at the 3'-end and a 27-nt antisense strand with a 2-nt overhang at the 3'-end, showed an excellent gene-silencing effect with high cell membrane permeability and strong resistance against nuclease degradation. Additionally, the Lo25D-C16/27RNA excelled in all three aspects, nuclease resistance, cell membrane permeability, and RNAi efficacy, compared with the cholesterol conjugation. We are certain that Lo25D-C16/27RNA can be useful as a new generation of RNAi molecules with which to overcome some of the limitations of RNAi technology. |
| 巻・号 | 24(12) |
| ページ | 2045-57 |
| 公開日 | 2013-12-18 |
| DOI | 10.1021/bc400391n |
| PMID | 24274056 |
| MeSH | Animals Base Sequence Cholesterol / metabolism* DNA / genetics HeLa Cells Humans Intracellular Space / metabolism Palmitic Acid / metabolism* RNA Interference* RNA, Antisense / genetics RNA, Small Interfering / genetics* RNA, Small Interfering / metabolism* Ribonuclease III / metabolism* |
| IF | 4.031 |
| 引用数 | 10 |
| WOS 分野 | CHEMISTRY, MULTIDISCIPLINARY CHEMISTRY, ORGANIC BIOCHEMICAL RESEARCH METHODS BIOCHEMISTRY & MOLECULAR BIOLOGY |
| 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 | 4 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | HeLa |