5'-Morpholino modification of the sense strand of an siRNA makes it a more effective passenger.

The 5-monophosphate group plays an important role in strand selection during gene silencing mediated by small-interfering RNA. We show that blocking of 5 phosphorylation of the sense strand by introducing a 5-morpholino modification improves antisense strand selection and RNAi activity. The 5-morpholino modification of the antisense strand triggers complete loss of activity.