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Oligo-adenine (polyA) is primarily known for its critical role in mRNA stability, translational status, and gene regulation. Beyond its biological functions, extensive research has unveiled the diverse applications of polyA. In response to environmental stimuli, single polyA strands undergo distinctive structural transitions into diverse secondary configurations, which are reversible upon the introduction of appropriate counter-triggers. In this review, we systematically summarize recent advances of noncanonical structures derived from polyA, including A-motif duplex, A-cyanuric acid triplex, A-coralyne-A duplex, and T ⋅ A-T triplex. The structural characteristics and mechanisms underlying these conformations under specific external stimuli are addressed, followed by examples of their applications in stimuli-responsive DNA hydrogels, supramolecular fibre assembly, molecular electronics and switches, biosensing and bioengineering, payloads encapsulation and release, and others. A detailed comparison of these polyA-derived noncanonical structures is provided, highlighting their distinctive features. Furthermore, by integrating their stimuli-responsiveness and conformational characteristics, advanced material development, such as pH-cascaded DNA hydrogels and supramolecular fibres exhibiting dynamic structural transitions adapting environmental cues, are introduced. An outlook for future developments is also discussed. These polyA derived, stimuli-responsive, noncanonical structures enrich the arsenal of DNA "toolbox", offering dynamic DNA frameworks for diverse future applications., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

The assembly of pH-responsive DNA-based, phase-separated microdroplets (MDs) coacervates, consisting of frameworks composed of Y-shaped nucleic acid modules crosslinked by pH-responsive strands, is introduced. The phase-separated MDs reveal dynamic pH-stimulated switchable or oscillatory transient depletion and reformation. In one system, a photoisomerizable merocyanine/spiropyran photoacid is used for the light-induced pH switchable modulation of the reaction medium between the values pH=6.0-4.4. The dynamic transient photochemically-induced switchable depletion/reformation of phase-separated MDs, follows the rhythm of pH changes in solution. In a second system, the Landolt oscillatory reaction mixture pH 7.5→4.2→7.5 is applied to stimulate the oscillatory depletion/reformation of the MDs. The autonomous dynamic oscillation of the assembly/disassembly of the MDs follows the oscillating pH rhythm of the reaction medium., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Self-assembled supramolecular DNA tetrahedra composed of programmed sequence-engineered complementary base-paired strands represent elusive nanostructures having key contributions to the development and diverse applications of DNA nanotechnology. By appropriate engineering of the strands, DNA tetrahedra of tuneable sizes and chemical functionalities were designed. Programmed functionalities for diverse applications were integrated into tetrahedra structures including sequence-specific recognition strands (aptamers), catalytic DNAzymes, nanoparticles, proteins, or fluorophore. The article presents a comprehensive review addressing methods to assemble and characterize the DNA tetrahedra nanostructures, and diverse applications of DNA tetrahedra framework are discussed. Topics being addressed include the application of structurally functionalized DNA tetrahedra nanostructure for the assembly of diverse optical or electrochemical sensing platforms and functionalized intracellular sensing and imaging modules. In addition, the triggered reconfiguration of DNA tetrahedra nanostructures and dynamic networks and circuits emulating biological transformations are introduced. Moreover, the functionalization of DNA tetrahedra frameworks with nanoparticles provides building units for the assembly of optical devices and for the programmed crystallization of nanoparticle superlattices. Finally, diverse applications of DNA tetrahedra in the field of nanomedicine are addressed. These include the DNA tetrahedra-assisted permeation of nanocarriers into cells for imaging, controlled drug release, active chemodynamic/photodynamic treatment of target tissues, and regenerative medicine., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Since the discovery of the first peroxidase nanozyme (Fe 3 O 4 ), numerous nanomaterials have been reported to exhibit intrinsic enzyme-like activity toward inorganic oxygen species, such as H 2 O 2 , oxygen, and O 2 - . However, the exploration of nanozymes targeting organic compounds holds transformative potential in the realm of industrial synthesis. This review provides a comprehensive overview of the diverse types of nanozymes that catalyze reactions involving organic substrates and discusses their catalytic mechanisms, structure-activity relationships, and methodological paradigms for discovering new nanozymes. Additionally, we propose a forward-looking perspective on designing nanozyme formulations to mimic subcellular organelles, such as chloroplasts, termed "nano-organelles". Finally, we analyze the challenges encountered in nanozyme synthesis, characterization, nano-organelle construction and applications while suggesting directions to overcome these obstacles and enhance nanozyme research in the future. Through this review, our goal is to inspire further research efforts and catalyze advancements in the field of nanozymes, fostering new insights and opportunities in chemical synthesis., (© 2024 Wiley-VCH GmbH.)

The primer-guided entropy-driven high-throughput evolution of the DNA-based constitutional dynamic network, CDN, is introduced. The entropy gain associated with the process provides a catalytic principle for the amplified emergence of the CDN. The concept is applied to develop a programmable, spatially localized DNA circuit for effective in vitro and in vivo theranostic, gene-regulated treatment of cancer cells. The localized circuit consists of a DNA tetrahedron core modified at its corners with four tethers that include encoded base sequences exhibiting the capacity to emerge and assemble into a [2 × 2] CDN. Two of the tethers are caged by a pair of siRNA subunits, blocking the circuit into a mute, dynamically inactive configuration. In the presence of miRNA-21 as primer, the siRNA subunits are displaced, resulting in amplified release of the siRNAs silencing the HIF-1α mRNA and fast dynamic reconfiguration of the tethers into a CDN. The resulting CDN is, however, engineered to be dynamically reconfigured by miRNA-155 into an equilibrated mixture enriched with a DNAzyme component, catalyzing the cleavage of EGR-1 mRNA. The DNA tetrahedron nanostructure stimulates enhanced permeation into cancer cells. The miRNA-triggered entropy-driven reconfiguration of the spatially localized circuit leads to the programmable, cooperative bis-gene-silencing of HIF-1α and EGR-1 mRNAs, resulting in the effective and selective apoptosis of breast cancer cells and effective inhibition of tumors in tumor bearing mice.

An ortho-nitrobenzyl phosphate ester-caged nucleic acid hairpin structure coupled to the CRISPR-Cas12a complex is introduced as a functional reaction module for the light-induced activation of the CRISPR-Cas12a (LAC12a) machinery toward the amplified fluorescence detection of microRNA-21 (miRNA-21). The LAC12a machinery is applied for the selective, in vitro sensing of miRNA-21 and for the intracellular imaging of miRNA-21 in different cell lines. The LAC12a system is used to image miRNA-21 in different cell cycle phases of MCF-7 cells. Moreover, the LAC12a machinery integrated in cells enables the two-photon laser confocal microscopy-assisted, light-stimulated spatiotemporal, selective activation of the CRISPR-Cas12a miRNA-21 imaging machinery at the single-cell level and the evaluation of relative expression levels of miRNA-21 at distinct cell cycle phases. The method is implemented to map the distribution of cell cycle phases in an array of single cells.