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What overhang composition should I select for my siRNAs?

Sequence composition of the overhang is a matter of customer preference. As the field of RNAi has progressed, Dharmacon and others have found that the composition of the overhang does not appear to play a critical role in target mRNA recognition and cleavage. The overhangs may play a structural role for presenting a symmetrical duplex to the RISC. Many investigators select dTdT because early evidence suggested that deoxyribonucleotides might confer nuclease resistance. Nevertheless, some investigators prefer overhangs that are complementary to the authentic mRNA target. What is most important is the identity of the 19-base core of the duplex towards a unique mRNA target. On the siRNA ordering pages, UU overhangs are the default option for siRNA duplexes. dTdT overhangs may be chosen rather than UU for no additional charge. All other 3'-overhang compositions are available, though an additional charge may apply.