Enzyme-free nucleic acid dynamical systems

Abstract

Chemistries exhibiting complex dynamics-from inorganic oscillators to gene regulatory networks-have been long known but cannot be reprogrammed at will because of a lack of control over their evolved or serendipitously found molecular building blocks. Here we show that information-rich DNA strand displacement cascades could be systematically constructed to realize complex temporal trajectories specified by an abstract chemical reaction network model. We codify critical design principles in a compiler that automates the design process, and demonstrate our approach by building a novel DNA-only oscillator. Unlike biological networks that rely on the sophisticated chemistry underlying the central dogma, our test tube realization suggests that simple Watson-Crick base pairing interactions alone suffice for arbitrarily complex dynamics. Our result establishes a basis for autonomous and programmable molecular systems that interact with and control their chemical environment.

Dynamic Environments as a Tool to Preserve Desired Output in a Chemical Reaction Network

“…[1] Examples of networks giving temporal, or spatiotemporal, control over the concentrations of the molecules in the system include the generation of wave fronts, [2] pattern formation with as o-calledg o-fetch model, [3] oscillations, [4][5][6][7][8] supramolecular oscillators [9] synchronisation and pattern formation with multiple oscillators through diffusional spatiotemporal coupling, [10] adaptive response networks, [11] systemss howing homeostasis, [12] self-replicating systems that can diversify into differents pecies, [13] self-replicators that can transiently form micelles, [14,15] temporally controlled material properties [16][17][18] and transientv esicle, [19] droplet, [20] fibril and gel formation. [1] Examples of networks giving temporal, or spatiotemporal, control over the concentrations of the molecules in the system include the generation of wave fronts, [2] pattern formation with as o-calledg o-fetch model, [3] oscillations, [4][5][6][7][8] supramolecular oscillators [9] synchronisation and pattern formation with multiple oscillators through diffusional spatiotemporal coupling, [10] adaptive response networks, [11] systemss howing homeostasis, [12] self-replicating systems that can diversify into differents pecies, [13] self-replicators that can transiently form micelles, [14,15] temporally controlled material properties [16][17][18] and transi...…”

Cell-free transcriptional regulation via nucleic-acid-based transcription factors

“…Systems of synthetic oligonucleotides have been successfully designed as switches, amplifiers, logic gates, and oscillators. [24][25][26][27] By programming these circuits to produce specific TF sequences as outputs, they can function as embedded controllers for programming gene-expression dynamics under our framework. This use of nucleic-acid computing for the active, on-demand synthesis of functional RNAs could find applications in biological analysis, directed evolution, and molecular information processing.…”

Modular Design of Small Enzymatic Reaction Networks Based on Reversible and Cleavable Inhibitors

“…Recent examples include replicating systems, [4,5] transient self-assembly, [6][7][8] active colloids, [9] and many others. [15][16][17] However,the development of enzymatic reaction networks [18][19][20][21] has been slow.Incontrast to most DNA-based networks, [15,16] where interactions can be "programmed" based on base-pair interactions,t he reaction kinetics of enzymatic reactions cannot be predicted apriori. [15][16][17] However,the development of enzymatic reaction networks [18][19][20][21] has been slow.Incontrast to most DNA-based networks, [15,16] where interactions can be "programmed" based on base-pair interactions,t he reaction kinetics of enzymatic reactions cannot be predicted apriori.…”

“…[10] The past decade has seen the rapid development of synthetic nucleic-acid-based reaction networks based on genetic elements, [11][12][13][14] or toehold strand-displacement DNAn etworks. [15][16][17] However,the development of enzymatic reaction networks [18][19][20][21] has been slow.Incontrast to most DNA-based networks, [15,16] where interactions can be "programmed" based on base-pair interactions,t he reaction kinetics of enzymatic reactions cannot be predicted apriori. Still, the range of chemical transformations catalysed by enzymes is much more diverse than what can be expected in nucleic-acidbased networks,t hus potentially allowing abroader range of possible applications in, for example,m aterials science or sensing.…”