| RRC ID |
18126
|
| 著者 |
Abe N, Abe H, Nagai C, Harada M, Hatakeyama H, Harashima H, Ohshiro T, Nishihara M, Furukawa K, Maeda M, Tsuneda S, Ito Y.
|
| タイトル |
Synthesis, structure, and biological activity of dumbbell-shaped nanocircular RNAs for RNA interference.
|
| ジャーナル |
Bioconjug Chem
|
| Abstract |
RNA interference (RNAi) is one of the most promising new approaches for disease therapy. The design of a dumbbell-shaped nanocircular RNA allows it to act as a short interfering RNA (siRNA) precursor. To optimize the design, we studied the relationship between the nanostructure and RNAi activity by synthesizing various RNA dumbbells. An RNA dumbbell with a 23-bp stem and 9-nt loops was the most potent. Sequence analysis by mass spectrometry showed that Dicer could edit RNA dumbbells to siRNA species. The reaction offered the slow release of siRNA species, which conferred prolonged RNAi activity. Introduction of DNA into the loop position significantly stabilized the dumbbell in biological fluid without any loss of RNAi activity. In-depth pharmacological evaluation was performed by introducing dumbbells into HeLa cells that stably express the target luciferase gene. The dumbbells provided a rapid silencing effect and retained this effect for a longer time even at a lower concentration than that at which standard siRNA completely lost RNAi activity. We conclude that an RNA dumbbell with DNA loops is the most promising design for in vivo applications for RNA medicine.
|
| 巻・号 |
22(10)
|
| ページ |
2082-92
|
| 公開日 |
2011-10-19
|
| DOI |
10.1021/bc2003154
|
| PMID |
21899349
|
| MeSH |
Animals
Base Sequence
Cell Line
HeLa Cells
Humans
Mice
Molecular Sequence Data
NIH 3T3 Cells
Nanostructures / chemistry
Nucleic Acid Conformation
RNA / chemistry
RNA / genetics
RNA / metabolism*
RNA Interference*
RNA Stability
RNA, Small Interfering / genetics
RNA, Small Interfering / metabolism*
Ribonuclease III / metabolism
|
| IF |
4.031
|
| 引用数 |
25
|
|
WOS 分野
|
BIOCHEMICAL RESEARCH METHODS
CHEMISTRY, ORGANIC
BIOCHEMISTRY & MOLECULAR BIOLOGY
CHEMISTRY, MULTIDISCIPLINARY
|
| リソース情報 |
| ヒト・動物細胞 |
HL60(RCB0041) |
