Target induced reconstruction of DNAzymatic amplifier nanomachines in living cells for concurrent imaging and gene silencing

Li, Junjie; Li, Wan‐Ning; Du, Wenwen; Lv, Meng-Mei; Wu, Zhenkun; Jiang, Jian‐Hui

doi:10.1039/c8cc05832f

Cited by 23 publications

(18 citation statements)

References 49 publications

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“…Unlike conventional signal amplification methods using protein enzymes, these approaches allow programmed assembly of the nucleic acid reactants in response to the target molecules, providing an efficient strategy for nucleic acid-templated nonenzymatic amplification. Taken this unique property, others − and our group − have developed nucleic acid cascade circuits for sensitive imaging of RNAs in live cells. Despite the significant progress made, current methods are mainly dependent on free diffusion or random collision of the reactants, which rationally results in slow reaction kinetics and low amplification efficiency.…”

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confidence: 99%

Cascade Circuits on Self-Assembled DNA Polymers for Targeted RNA Imaging In Vivo

Zhu

Zhao

et al. 2020

Anal. Chem.

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DNA molecular probes have emerged as a powerful tool for RNA imaging. Hurdles in cell-specific delivery and other issues such as insufficient stability, limited sensitivity, or slow reaction kinetics, however, hinder the further application of DNA molecular probes in vivo. Herein, we report an aptamer-tethered DNA polymer for cell-specific transportation and amplified imaging of RNA in vivo via a DNA cascade reaction. DNA polymers are constructed through an initiator-triggered hybridization chain reaction using two functional DNA monomers. The prepared DNA polymers show low cytotoxicity and good stability against nuclease degradation and enable cell-specific transportation of DNA circuits via aptamer−receptor binding. Moreover, assembling the reactants of hairpins C1 and C2 on the DNA polymers accelerates the response kinetics and improves the sensitivity of the cascade reaction. We also show that the DNA polymers enable efficient imaging of microRNA-21 in live cells and in vivo via intravenous injection. The DNA polymers provide a valuable platform for targeted and amplified RNA imaging in vivo, which holds great implications for early clinical diagnosis and therapy.

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confidence: 99%

Cascade Circuits on Self-Assembled DNA Polymers for Targeted RNA Imaging In Vivo

Zhu

Zhao

et al. 2020

Anal. Chem.

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“…The cells would be damaged and even killed by the prerequisite fixation and pretreatment. In recent years, many enzyme-free amplification strategies such as catalytic hairpin assembly (CHA) reaction 18 and hybridization chain reaction 19 (HCR) have been developed for imaging of miRNA in living cells. However, the development of methods based on enzymatic amplification reactions in living cells remains a challenge in that there is no an effective platform to efficiently deliver the amplification reagents to cytoplasm.…”

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confidence: 99%

Biomineralized Metal–Organic Framework Nanoparticles Enable Enzymatic Rolling Circle Amplification in Living Cells for Ultrasensitive MicroRNA Imaging

Zhang

Nie

et al. 2019

Anal. Chem.

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The enzymatic amplification strategy in living cells faces challenges of highly efficient intracellular codelivery of amplification reagents including DNA polymerase. In this work, we develop biomineralized metal−organic framework nanoparticles (MOF NPs) as a carrier system for intracellular codelivery of ϕ29 DNA polymerase (ϕ29DP) and nucleic acid probes and realize a polymerization amplification reaction in living cells. A pH-sensitive biodegradable MOF NP of zeolitic imidazolate framework-8 (ZIF-8) is utilized to encapsulate ϕ29DP and adsorb nucleic acid probes. After uptake into cells, the encapsulated ϕ29DP and surface-adsorbed DNA probes are released and escaped from endolysosomes. In the presence of ϕ29DP and deoxyribonucleotide triphosphates (dNTPs), the intracellular miRNA-21 triggers a rolling circle amplification (RCA) reaction and the autonomous synthesized Mg 2+ -dependent DNAzyme cleaves the fluorogenic substrate, providing a readout fluorescence signal for the monitoring of miRNA-21. This is the first example of the intracellular RCA reaction in living cells. Therefore, the proposed method provides new opportunities for achieving enzymatic amplification reaction in living cells.

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“…Compared to other reactions such as enzyme or DNAzyme-mediated hydrolysis reactions which need enzymes or cofactors (metal ions, etc.) that are either difficult to deliver or requiring strict conditions to functionalize in cells to provide energies for dynamic systems, 15,[24][25][26] DNA displacement reactions present some unique advantages. For instance, they are completely enzyme-free reactions, which means that these DNA strand displacement-based dynamic systems can be initiated and driven solely by the DNA molecules in cells.…”

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confidence: 99%

Dynamic colloidal nanoparticle assembly triggered by aptamer–receptor interactions on live cell membranes

et al. 2019

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Target induced reconstruction of DNAzymatic amplifier nanomachines in living cells for concurrent imaging and gene silencing

Abstract: A novel DNAzymatic amplifier nanomachine that is reconstructed in response to an mRNA input has been developed to enable the functions of concurrent sensitive mRNA imaging and activatable gene therapy in living cells.

Cited by 23 publications

References 49 publications

Cascade Circuits on Self-Assembled DNA Polymers for Targeted RNA Imaging In Vivo

Cascade Circuits on Self-Assembled DNA Polymers for Targeted RNA Imaging In Vivo

Biomineralized Metal–Organic Framework Nanoparticles Enable Enzymatic Rolling Circle Amplification in Living Cells for Ultrasensitive MicroRNA Imaging

Dynamic colloidal nanoparticle assembly triggered by aptamer–receptor interactions on live cell membranes

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