Potential Use of Dendrimer/α-Cyclodextrin Conjugate as a Novel Carrier for Small Interfering RNA (siRNA)
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RNA interference (RNAi) is the mechanism of gene silencing-mediated messenger RNA degradation by small interference RNA (siRNA), which becomes a powerful tool for genetic analysis and novel gene therapy. However, one of the major obstacles for siRNA delivery is the difficulty to cross the biological membrane due to its hydrophilicity and high molecular weight. We evaluated the potential use of the starburst polyamidoamine dendrimer (generation 3) conjugate with α-cyclodextrin (α-CyD) having an average degree of substitution of 2.4 (α-CDE conjugate) as a siRNA carrier for RNAi. The ternary complex composed of pGL2 control vector (pDNA)/pGL2 siRNA/α-CDE conjugate showed higher pGL2 siRNA sequence-specific gene silencing effects without off-target effects than those of commercial transfection reagents such as Lipofectamine™2000 (LP), TransFast™ (TF) and Lipofectin™ (LF). These results suggest that α-CDE conjugate has the potential to be a novel carrier for siRNA.
Keywordsα-CDE conjugate gene silencing siRNA RNAi Lipofectamine
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This work was supported by a Grant-in-Aid from Tokyo Biochemical Research Foundation, a Grant-in-Aid from the Research Foundation for Pharmaceutical Sciences and a Grant-in-Aid for Scientists Research from Japan Society for the Promotion of Science.
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