Cell‐Penetrating and Neurotargeting Dendritic siRNA Nanostructures
2015
Abstract: We report the development of dendritic siRNAnanostructures that are able to penetrate even difficult totransfect cells such as neurons with the help of a specialreceptor ligand. The nanoparticles elicit strong siRNAresponses,despitethedendriticstructure.AnsiRNAdendrimerdirected against the crucial rabies virus (RABV) nucleoprotein(N protein) and phosphoprotein (P protein) allowed thesuppression of the virus titer in neurons below the detectionlimit. The cell-penetrating siRNA dendrimers, which wereassembled using click chemistry, open up new avenues towardfinding novel molecules able to cure this deadly disease. R NA interference is a powerful tool that allows thesequence-specific suppression of gene expression by smallinterfering RNAs (siRNAs). [1] The major obstacle preventingthewidespreaduseofsiRNA-basedtherapeuticsisthelackofefficient, specific, and nontoxic delivery systems to transportsiRNA duplexes into cells and tissue. [2] Commonly usedsiRNA-delivery vehicles, such as liposomes or cationicpolymeric systems, are heterogeneous in size and composi-tion,andseverecytotoxiceffectsareobservedin sensitivecelltypes such as neurons.
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