There is great potential for siRNA in treatment of diseases through the reduction of damaging protein translation by RNA interference. However, delivery and cell uptake of siRNA poses a serious problem in its therapeutic applications. Methods to overcome this issue include chemical modification of the siRNA duplex to improve pharmacokinetics, stability and efficacy and conjugation to small ligand molecules to enable membrane penetration, targetability and potency. In this review, the most common modifications of siRNA will be discussed, along with ligand conjugates that are believed to be the most promising in advancing the field of targeted siRNA delivery.
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