A. Birmingham et al., "3' UTR seed matches, but not overall identity, are associated with RNAi off-targets," Nat Methods, 3:199—204, 2006. (Cited in 94 papers)
In 2006, Devin Leake and colleagues at Dharmacon Research wanted to determine the accuracy of current algorithms for predicting siRNA mismatch events used in silencing. To do this they generated a database of mismatched siRNA events by experimental gene array for three genes and compared them to those predicted by the Smith-Waterman algorithm. They found that only a small region of the siRNA was important for silencing, and that the algorithm could not predict hundreds of mismatch events.
Only a small nucleotide "seed" portion of the siRNA (5—6 nucleotides) was important for binding to the gene targeted for silencing, which increased the potential for nonspecific binding. In addition, only the seed region "defines the specificity" of silencing events, says Volker Patzel at the Max Planck ...
