Cascaded, Feedback-Driven, and Spatially Localized Emergence of Constitutional Dynamic Networks Driven by Enzyme-Free Catalytic DNA Circuits

Zhixin Zhou*, Nina Lin, Yu Ouyang, Songqin Liu, Yuanjian Zhang*, Itamar Willner*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

The enzyme-free catalytic hairpin assembly (CHA) process is introduced as a functional reaction module for guided, high-throughput, emergence, and evolution of constitutional dynamic networks, CDNs, from a set of nucleic acids. The process is applied to assemble networks of variable complexities, functionalities, and spatial confinement, and the systems provide possible mechanistic pathways for the evolution of dynamic networks under prebiotic conditions. Subjecting a set of four or six structurally engineered hairpins to a promoter P1 leads to the CHA-guided emergence of a [2 × 2] CDN or the evolution of a [3 × 3] CDN, respectively. Reacting of a set of branched three-arm DNA-hairpin-functionalized junctions to the promoter strand activates the CHA-induced emergence of a three-dimensional (3D) CDN framework emulating native gene regulatory networks. In addition, activation of a two-layer CHA cascade circuit or a cross-catalytic CHA circuit and cascaded driving feedback-driven evolution of CDNs are demonstrated. Also, subjecting a four-hairpin-modified DNA tetrahedron nanostructure to an auxiliary promoter strand simulates the evolution of a dynamically equilibrated DNA tetrahedron-based CDN that undergoes secondary fueled dynamic reconfiguration. Finally, the effective permeation of DNA tetrahedron structures into cells is utilized to integrate the four-hairpin-functionalized tetrahedron reaction module into cells. The spatially localized miRNA-triggered CHA evolution and reconfiguration of CDNs allowed the logic-gated imaging of intracellular RNAs. Beyond the bioanalytical applications of the systems, the study introduces possible mechanistic pathways for the evolution of functional networks under prebiotic conditions.

Original languageEnglish
Pages (from-to)12617-12629
Number of pages13
JournalJournal of the American Chemical Society
Volume145
Issue number23
DOIs
StatePublished - 14 Jun 2023

Bibliographical note

Publisher Copyright:
© 2023 The Authors. Published by American Chemical Society.

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