Figure 1.

HCR mechanism.¹² Metastable scRNAs (h1 and h2) self-assemble into polymers upon detection of a cognate RNA target (X). (a) X nucleates with h1 by base-pairing to single-stranded toehold “a”, mediating a branch migration that opens h1 to form complex X·h1 with single-stranded domain “c*-b*”. (b) Complex X·h1 nucleates with h2 by base-pairing to toehold “c”, mediating a branch migration that opens h2 to form complex X·h1·h2 with single-stranded domain “b*-a*”, identical in sequence to X. (c) This provides the basis for a chain reaction of alternating h1 and h2 polymerization steps.