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The ability to induce off-target effects on unintended genes is strongly correlated to the thermodynamic stability of the duplex formed between the seed region (positions 2-8 from the 5\' end of the siRNA guide strand) and target mRNA. siRNAs with seven deoxyribonucleotides exclusively in the seed region (sdRNA) may exhibit efficient target-specificity, but off-target effect-reduced RNAi activity.