Figure 3.

Natural circular RNA sponges inspire next-generation miRNA inhibitors. (a) Current vector-encoded miRNA inhibition technologies rely on linear RNA decoys, such as the Bulged Sponge or Tough Decoy designs. (b) Naturally occurring circular RNA sponges contain numerous miRNA seed matches thereby avoiding endonucleolytic cleavage upon miRNA recognition. Furthermore, high stability is conferred by the circular structure which evades miRNA-promoted decay by exonucleolytic degradation. (c) Circular RNA sponges may be optimized with high-affinity hairpins (such as those in the Tough Decoy) to further increase suppression of miRNA activity.