Elucidation and Control of a Triggered Self-Assembling Nucleic Acid Polymer

We previously introduced hybridization chain reactions (HCR), in which metastable DNA hairpins undergo conditional self-assembly to form long nicked double-stranded ‘polymers' in the presence of a DNA initiator molecule (RM Dirks and NA Pierce, PNAS 2004, 10, 15275). HCR systems have been engineered to function as orthogonal in situ amplifiers for multiplexed bioimaging (HMT Choi et al., Nat Biotech, in press) and as programmable mechanical transducers for selectively killing cultured human cancer cells (S Venkataraman et al., PNAS 2010, 107, 16777). Here, we model the equilibrium and kinetic properties of HCR, revealing sources of non-ideal behavior and methods for controlling system performance. Our results demonstrate that HCR is accurately modeled as a living alternating copolymerization.