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Small interfering RNA (siRNA) is a powerful tool for modulating gene expression by RNA interference (RNAi). Duplex RNA oligonucleotides induce cleavage of homologous target transcripts, thereby enabling posttranscriptional silencing of potentially any gene. As such, siRNAs may have utility as novel pharmaceuticals for a wide range of diseases. However, a lack of "drug-likeness," physiological barriers, and potential toxicities have meant that systemic delivery of SiRNAs in vivo remains a major challenge. Here we discuss various strategies that have been employed to solve the problem of SiRNA delivery. These include chemical modification of the SiRNA, direct conjugation to bioactive moieties, and nanoparticle formulations.

Original publication




Journal article


Methods Mol Biol

Publication Date





291 - 310


Cell-penetrating peptides, Lipid nanoparticles, Lipidoids, SiRNA conjugates, SiRNA delivery, Animals, Drug Carriers, Hydrophobic and Hydrophilic Interactions, RNA, Small Interfering