RRC ID |
43780
|
Author |
Kubo T, Yanagihara K, Takei Y, Mihara K, Sato Y, Seyama T.
|
Title |
Lipid-conjugated 27-nucleotide double-stranded RNAs with dicer-substrate potency enhance RNAi-mediated gene silencing.
|
Journal |
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.
|
Volume |
9(5)
|
Pages |
1374-83
|
Published |
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
|
Times Cited |
14
|
WOS Category
|
MEDICINE, RESEARCH & EXPERIMENTAL
PHARMACOLOGY & PHARMACY
|
Resource |
Human and Animal Cells |
SH-10-TC(RCB1940) |