Page 109 - Read Online

Zhong et al. Chem Synth 2023;3:27 https://dx.doi.org/10.20517/cs.2023.15 Page 3 of 25

[46]
[47]
macromolecules , and even cells (aptamers) . Additionally, nucleic acids possess catalytic properties such
[48]
[49]
as ribozymes and DNAzymes . The programmability of nucleic acid sequences and their functionality
provides a rich module toolbox for precisely designing and manipulating defined structures and reaction
pathways [50,51] . These are essential for the de novo construction of complex and diverse sets of artificial
signaling dynamic networks. The review aims to present recent advances in nucleic acid-based dynamic
networks for signal dynamics. First, we discuss nucleic acid-based dynamic networks capable of
fundamental signaling dynamics, such as network adaptivity, feedback, feedforward, communication, and
more. Then, we introduce nucleic acid-based far-from-equilibrium networks that can convert
environmental cues into spatiotemporal variations of output signals, such as pulsed and periodic signals.
Potential applications of nucleic acid-based dynamic networks in designing soft materials, pattern
dynamics, catalysis, and protocols are addressed. These have expedited different research in various fields,
such as systems chemistry, DNA nanotechnology, and materials science.

THE FUNDAMENTAL SIGNALING DYNAMIC PROCESSES
Biological transformations in living systems are often controlled by physically and chemically triggered
signaling dynamic networks [52-55] . These networks receive, process, encode, and integrate ever-changing
signals for conducting specific biological activities [9,56-57] . Recently, nucleic acids with programmable
properties and functionalities have been used as building blocks to construct artificial dynamic networks for
mimicking essential signaling dynamic processes [35,58] .

Adaptive feature
The adaptive feature is fundamental to these signaling dynamic networks, enabling them to respond nimbly
to changes in the environment [18,59] . Substantial research efforts have been directed toward assembling
adaptive nucleic acid-based dynamic networks [60-63] . For example, Wang et al. proposed a design to construct
an adaptive constitutional dynamic network (CDN) with four interconvertible nucleic acid constituents,
AA′, BB′, AB′, and BA′, as presented in Figure 1 . In the CDN, each of the constituents is modified by an
[63]
Mg -ion-dependent DNAzyme subunit, exhibiting different substrate recognition arms. These DNAzyme
2+
subunits act as catalytic reporter units to conduct the composition of the CDN by the cleavage of
corresponding fluorophore−quencher modified substrates. The constituents in four pairs - AA′/AB′, AA′/
BA′, BB′/AB′, and BB′/BA′- are antagonists since they share the component, and the constituents in two
pairs - AA′/BB′ and AB′/BA′ - do not share the component and thus act as agonists. The stabilization and
destabilization of one of the constituents can trigger the adaptive reconfiguration of the whole network,
resulting in the dictated transition of a composition of the CDN to energetically stabilized constituent
mixtures. For example, the triggered stabilization of AA' leads to the adaptive reconfiguration of CDN from
state I into state II, where AA′ is upregulated at the expense of constituents that share components with AA′,
such as AB′ and BA′, which are downregulated. The dissociation of AB′ and BA′ results in the concomitant
upregulation of the constituent BB′, which does not share components with AA′.

Under this antagonist-agonist model, the adaptive reconfiguration of CDN is achieved by different triggers,
such as fuels/anti-fuels-triggered strand displacement processes , fuel strand-induced formation of T-A·T
[61]
triplexes and their dissociation by anti-fuel strands , the light-induced stabilization/destabilization of
[64]
+
nucleic acid duplexes by photoisomerizable trans-/cis-azobenzene intercalators , and the K -ion formation
[65]
of G-quadruplexes and their dissociation by crown ethers . In addition, the programmable building block
[63]
of the network allows the construction of complex multi-constituent CDNs [62,66] . Constituents with duplex
[64]
structures can be extended to the constituents of the nucleic acid nanomachines, such as DNA tweezers ,
and 3D nucleic acid nanostructures , such as DNA tetrahedra, for the adaptive regulation of DNA
[66]
nanostructure and nanomachine networks. Scaling a two-dimensional [2 × 2] CDN by increasing the