DNA Tetraplexes-Based Toehold Activation for Controllable DNA Strand Displacement Reactions

In order to maintain tissue homeostasis, cells communicate with the outside environment by receiving molecular signals, transmitting them, and responding accordingly with signaling pathways. Thus, one key challenge in engineering molecular signaling systems involves the design and construction of different modules into a rationally integrated system that mimics the cascade of molecular events. Herein, we rationally design a DNA-based artificial molecular signaling system that uses the confined microenvironment of a giant vesicle, derived from a living cell. This system consists of two main components. First, we build an adenosine triphosphate (ATP)-driven DNA nanogatekeeper. Second, we encapsulate a signaling network in the biomimetic vesicle, consisting of distinct modules, able to sequentially initiate a series of downstream reactions playing the roles of reception, transduction and response. Operationally, in the presence of ATP, nanogatekeeper switches from the closed to open state. The open state then triggers the sequential activation of confined downstream signaling modules.

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“…1b and Supplementary Figs. 30-33) 33 . The fluorescence kinetics verified this dynamic process (Fig.…”

Section: And 2 and Supplementarymentioning

confidence: 99%

DNA-based artificial molecular signaling system that mimics basic elements of reception and response

Peng

Wang

et al. 2020

Nat Commun

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“…In this design, the binding of aptamer and the target acts as the toehold of the following strand displacement reaction, termed aptamer-toehold, which is an extension of toehold-mediated strand displacement theory. [26][27][28] Fluorescence titration of GDMFs by increased concentrations of ATP is shown in Figure 6C, and the selectivity is shown in Figure S19B. Intracellular ATP imaging is shown in Figure 6D using HeLa cells, giving an obvious green signal from the cytoplasm in the fluorescein isothiocyanate (FITC) channel.…”

Section: Metal-crosslinked Dna Micelle Flaresmentioning

confidence: 99%

Spherically Directed Synthesis and Enhanced Cellular Internalization of Metal-Crosslinked DNA Micelles

Lyu

Guo

Cai

et al. 2019

Chem

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We describe a facile and universal method that uses spherically directed reduction of metal ions for in situ crosslinking of DNA micelles. By combining characterization results and simulation algorithms, we achieved accurate structural profiling of DNA micelles for the first time. The metal-crosslinked DNA micelle, or MDM, combines the facile preparation and dense ligand distribution of a DNA micelle with the physical properties of DNA-metal-particle conjugates. As a result of the metal crosslink, the internalization efficiency of MDM is much greater than that of DNA micelles. HIGHLIGHTS Spherically directed reduction is a universal method for DNA micelle crosslinkingThe detailed structural profile of DNA micelles was determinedThe internalization efficiency of MDM is greatly enhanced compared with DNA micelles Double-stranded DNA with two cholesterol modifications can also be used to form MDMs Lyu et al., Chem 5,[913][914][915][916][917][918][919][920][921][922][923][924][925][926][927][928] April 11, 2019 ª SUMMARY Using spherically directed reduction of metal ions, a facile and universal method for in situ crosslinking of DNA micelles is described. By incorporating a series of specific template domains into lipid-DNA monomers, copper-, silver-, and goldcrosslinked DNA micelles are formed. By combining characterization results and simulation algorithms, accurate structural profiling of DNA micelles is achieved for the first time. The prepared metal-crosslinked DNA micelles show obvious merits, including one-step formation of core structure and ligand corona, facile size tunability, monodispersity, stability against salt-induced aggregation, high utilization of DNA ligand, mild synthesis conditions, and less time consumption and better internalization. Based on our spherically directed synthesis, metalcrosslinked DNA micelle flares were further prepared for effective intracellular imaging by integrating an aptamer-toehold strategy. In addition, we extended the strategy to cholesterol-based double-stranded DNA micelles, giving strong evidence that our method is not only universal but also flexible.

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“…We demonstrated that the reaction rates can be tuned and controlled dynamically at room temperature through variation of the concentration of Hg 2+ ions [41]. Recently, displacement reaction triggered by functional toeholds formed such as ions [42] and micromolecule [43], has also been investigated. Herein we further utilize the concept of ‘‘metallo-toeholds’’ in which the toehold domains feature C:C mismatched bases.…”

Section: Introductionmentioning

confidence: 99%

DNA Logic Gate Based on Metallo-Toehold Strand Displacement

Deng

Ding

et al. 2014

PLoS ONE

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DNA is increasingly being used as an ideal material for the construction of nanoscale structures, circuits, and machines. Toehold-mediated DNA strand displacement reactions play a very important role in these enzyme-free constructions. In this study, the concept of metallo-toehold was utilized to further develop a mechanism for strand displacement driven by Ag+ ions, in which the intercalation of cytosine–cytosine mismatched base pairs on the toeholds provides additional control by varying of the concentration of Ag+ ions. The characteristics of displacement reaction in response to different concentration of Ag+ ions are investigated by fluorescence spectral and non-denaturing polyacrylamide gel electrophoresis. The reaction can successfully occur when the concentration of Ag+ ions is suitabe; excess Ag+ ions block the reaction. Furthermore, the displacement reaction can be tuned and controlled most efficiently under the condition of two C:C mismatched base pairs placed on the six-nt toehold. Based on our research, a mechanism was developed to construct Boolean logic gate AND and OR by employing strand displacement reaction as a tool, Ag+ and Hg2+ as input.

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DNA Tetraplexes-Based Toehold Activation for Controllable DNA Strand Displacement Reactions

Cited by 62 publications

References 54 publications

DNA-based artificial molecular signaling system that mimics basic elements of reception and response

DNA-based artificial molecular signaling system that mimics basic elements of reception and response

Spherically Directed Synthesis and Enhanced Cellular Internalization of Metal-Crosslinked DNA Micelles

DNA Logic Gate Based on Metallo-Toehold Strand Displacement

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