Selection of Chemical Modifications in the siRNA Seed Region That Repress Off-Target Effect

RNA interference mediated by small interfering RNA (siRNA) has been widely used as a procedure to knock down the expression of an intended target gene with perfect sequence complementarity. However, siRNA often exhibits off-target effects on genes with partial sequence complementarities. Such off-target effect is an undesirable adverse effect for knocking down a target gene specifically. Here we describe the powerful strategy to avoid off-target effects without affecting the RNAi activity by the introduction of DNA or 2′-O-methyl modifications in the siRNA seed region. These two types of chemical modifications repress off-target effects through different molecular mechanisms.