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  • target RNA molecule and/or proteins or other factors that are essential for RNAi in a manner that would decrease the efficacy of RNAi mediated by such siRNA constructs. [0109] In another embodiment, the invention features a method for generating siRNA molecules with improved RNAi activity against PTP-1B, comprising (a) introducing nucleotides having any of Formula I-VI into a siRNA molecule, and
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