siRNA off-target effects can be reduced at concentrations that match their individual potency

This study demonstrates that siRNA off-targets (e.g. 3'UTR off-targets), can be significantly reduced when cells are treated with a relatively low dose of siRNA (e.g. 1nM) that is sufficient to effectively silence the intended target.

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Caffrey DR, Zhao J, Song Z, Schaffer ME, Haney SA, Subramanian RR, Seymour AB, Hughes JD