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        Chemical Synthesis of 2-O-Alkylated siRNAs

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        Chemical synthesis has been a major endeavor to create active siRNAs. The downregulation of mRNA by 21-mer double-stranded siRNAs can be improved by using modified nucleotides, especially 2′-O-alkylated ones. Besides the commercially available 2�-O-methyl ribosides, 2′-alkyl groups bearing positive charges are especially promising candidates. We have shown that in a proper formulation they are superior to unmodified siRNAs. This may be due to enhanced stability and most probably to a better uptake into the cells.
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