Cascaded dissipative DNAzyme-driven layered networks guide transient replication of coded-strands as gene models

Abstract

AbstractDynamic, transient, out-of-equilibrium networks guide cellular genetic, metabolic or signaling processes. Designing synthetic networks emulating natural processes imposes important challenges including the ordered connectivity of transient reaction modules, engineering of the appropriate balance between production and depletion of reaction constituents, and coupling of the reaction modules with emerging chemical functions dictated by the networks. Here we introduce the assembly of three coupled reaction modules executing a cascaded dynamic process leading to the transient formation and depletion of three different Mg2+-ion-dependent DNAzymes. The transient operation of the DNAzyme in one layer triggers the dynamic activation of the DNAzyme in the subsequent layer, leading to a three-layer transient catalytic cascade. The kinetics of the transient cascade is computationally simulated. The cascaded network is coupled to a polymerization/nicking DNA machinery guiding transient synthesis of three coded strands acting as “gene models”, and to the rolling circle polymerization machinery leading to the transient synthesis of fluorescent Zn(II)-PPIX/G-quadruplex chains or hemin/G-quadruplex catalytic wires.