RNA-interference has been recognized as a powerful tool to control gene function and has been used for gene silencing by knocking down mRNA. Chemically modified RNAs, especially 2'-O-modification, successfully improved their physicochemical and pharmaceutical properties such as stability, nuclease resistance and delivery. Here, we report the synthesis of adenosine building blocks with different 2'-tethered modifications like aminoethyl and guanidinoethyl and show that they are compatible with RNAi function. They enhance the half life of the siRNA in serum suggesting that these modifications can enhance the pharmacokinetic properties and knock down activity of siRNAs in vivo.