E-RNAi tries to avoid sequence-regions of low complexity (regarding base composition) from the RNAi reagent. Those were associated with 'off-target' effects and cytotoxic effects. Two filters are applied in the design process:
regions of low complexity (such as sequences with simple base repeats) are filtered using mDust,
sequences with at least 6 contiguous CA[ACGT] (CAN) repeats are filtered.