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Delivery of RNAi mediators

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Abstract Delivering polynucleotides into animals has been a major challenge facing their success as therapeutic agents. Given the matured understanding of antibody‐mediated delivery techniques, it is possible to rationally design delivery vehicles that circulate in the blood stream and are specifically delivered into target organs. If the targeting moiety is designed to contain the cargo of an RNAi mediator without impacting its paratope, directed delivery can be achieved. In this article, we review the state of art in delivery technology for RNA mediators and address how this technique could soon be used to enhance the efficacy of the numerous small RNA therapeutic programs currently under evaluation. Copyright © 2010 John Wiley & Sons, Ltd. This article is categorized under: Regulatory RNAs/RNAi/Riboswitches > RNAi: Mechanisms of Action RNA Methods > RNA Analyses in Cells RNA in Disease and Development > RNA in Disease

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The analysis of knockdown of GAPDH in SKBR3 or MCF7 xenograft tumor cells using receptor‐mediated siRNA delivery. We added 50‐ng GAPDH siRNA or a scrambled negative‐control siRNA with 100 ng of HER2 antibody conjugate. This complex was incubated for 30 min at room temperature and then injected directly into xenograft tumors made using either SKBR3 or MCF7 cell lines. Seventy‐two hours postinjection, the animals were sacrificed, and tumors were removed and analyzed using an in‐house GAPDH ELISA assay. The relative gene reduction compared with scrambled negative controls was determined. The circular panel illustrates a xenograft tumor that was generated in NOD/SCID mice before delivery of the T3 conjugate.

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RNA in Disease and Development > RNA in Disease
RNA Methods > RNA Analyses in Cells
Regulatory RNAs/RNAi/Riboswitches > RNAi: Mechanisms of Action

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