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Frontiers Thermodynamic Control Of Small Rna Mediated Gene Silencing Genetics The seed region of siRNA guide strand and target mRNA (seedtarget duplex) (Figure 1a) 12 Furthermore, we have developed a DNARNA chimeric siRNA (chiRNA) with deoxyribonucleotides in the 5' proximal eight nucleotides of the guide strand and the complementary nucleotides The chiRNA showed virtually no offtarget effects,SiRNA screens is likely due to offtarget effects8 siRNA offtarget effects have been linked to the mechanism of action for miRNAs, 9 in which a short sequence on the 5′ end of the RNAi duplex (the "seed region," bases 2–8) is complementary to the 3′UTRs of multiple mRNAs, causing degradation of their associated transcripts7,10 Because Seed region sirna