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
リソース情報
ヒト・動物細胞 SH-10-TC(RCB1940)