ACS Synthetic Biology
·
2022
·
IF 5.249
Dongying Wei,Yueyao Wang,Dongfan Song,Ze Zhang,Juan Wang,Jia-Yu Chen,Zhe Li,Hanyang Yu
Threose nucleic acid (TNA) is considered a potential RNA progenitor due to its chemical simplicity, base pairing property, and capability of folding into a functional tertiary structure. However, it is unknown whether the functional property can be maintained during transition from TNA to RNA. Here, we use a toggle in vitro selection to identify nucleic acid catalyst sequences that are active in both TNA and RNA backbones. One such nucleic acid enzyme with exchangeable backbone (CAMELEON) catalyzes an RNA cleavage reaction when prepared as TNA (T) and RNA (R). Further biochemical characterization reveals that CAMELEON R and T exhibit different catalytic behaviors such as rate enhancement and magnesium dependence. Structural probing and mutagenesis experiments suggest that they likely fold into distinct tertiary structures. This work demonstrates that the catalytic activity can be preserved during backbone transition from TNA to RNA and provides further experimental support for TNA as an RNA precursor in evolution.
研究领域:
生物化学
·
分子进化
·
核酸化学
✓ 已验证
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2022
·
IF 16.744
Jialing Hu,Zhiqiao Zou,Fengye Mo,Xue Lin,Yun Zhao,Tianhui Shi,Fuan Wang,Xiaoqing Liu
RNA-cleaving DNAzymes hold great promise for gene regulation, yet the low in vivo catalytic efficacy and the unavoidable nonspecific response in normal tissues hinder their practical applications. Herein, we develop a DNA prodrug-laden metallo-nanoassembly for sensitive orthogonal activation of DNAzymes to regulate disease gene with high precision and efficacy. With rich positive charges, metallo-nanoassemblies efficiently load DNA prodrugs (functional DNAzyme subunits), and thus improve drug stability and cellular uptake efficacy. Under tumor microenvironment, the cancer-specific biomarker triggers the amplified assembly of DNA prodrugs into active DNAzymes to efficiently cleave tumor-involved mRNA. Meanwhile, these glutathione-responsive metallo-nanoassemblies decompose and release metal ions as self-sufficient DNAzyme cofactors, which are accommodated into the afore-assembled DNAzymes to enhance the gene cleavage activity. Moreover, upon laser stimulus, these photothermal metallo-nanoassemblies can also remarkably promote the catalytic reaction of DNAzymes via the elevated local temperature. Such a smart delivery approach allows disease diagnosis via sensitive fluorescence and photothermal imaging, and achieves the precise and robust gene regulation with photothermal ablation as an auxiliary therapy. These results provide a new route to design programmable and activatable prodrugs for precision nanomedicine.
研究领域:
纳米医学
·
基因治疗
·
癌症研究
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
Science China-Chemistry
·
2019
·Vol. 63
·期 3
·404-410
·
IF 6.085
Lu Shasha,Wang Shuang,Zhao Jiahui,Sun Jian,Yang Xiurong
RNA-cleaving DNAzymes possess important roles in DNAzymes and have been widely used in the biosensors, DNA nanomachines owing to their ion-specific dependence. However, there are still challenges in constructing universal but versatile stimuli-responsive strategies of RNA-cleaving DNAzymes. Herein, a stimuli-responsive strategy for RNA-cleaving DNAzyme is proposed by the artful design of hairpin nanostructure, in which the activities of DNAzyme (Pb 2+ -dependent DNAzyme as a model) in the hairpin’s loop are pH-regulated by using the triplex stem as the “lock”. Upon introducing the “key”, pH values, the DNAzyme will be activated and fragment the substrate of it in the presence of Pb 2+ , accompanied by the turn-on of the fluorescence quenched by fluorescence resonance energy transfer (FRET). The regulation ability of pH can be controlled by the length and sequence of the triplex stem, and the wide pH regulation range may be helpful for the application of DNAzymes in biological medicine delivery systems.
研究领域:
生物化学
·
纳米技术
·
生物传感器
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2020
·
IF 8.758
Peng Liu,Xuanjun Liu,Yan Cheng,Shenghui Zhong,Xinyi Shi,Shengfeng Wang,Miao Liu,Jinsong Ding,Wenhu Zhou
The combination of gene therapy with chemotherapeutics provides an efficacious strategy for enhanced tumor therapy. RNA-cleaving DNAzyme has been recognized as a promising gene-silencing tool, while its combination with chemotherapeutic drugs has been limited by the lack of an effective codelivery system to allow sufficient intracellular DNAzyme activation, which requires specific metal ions as a cofactor. Here, a self-activatable DNAzyme/drug core–shell codelivery system is fabricated to combat triple-negative breast cancer (TNBC). The hydrophobic chemotherapeutic, rapamycin (RAP), is self-assembled into the pure drug nanocore, and the metal–organic framework (MOF) shell based on coordination between Mn2+ and tannic acid (TA) is coated on the surface to coload an autophagy-inhibiting DNAzyme. The nanosystem efficiently delivers the payloads into tumor cells, and upon endocytosis, the MOF shell is disintegrated to release the therapeutics in response to an acidic endo/lysosome environment and intracellular glutathione (GSH). Notably, the coreleased Mn2+ serves as the cofactor of DNAzyme for effective self-activation, which suppresses the expression of Beclin 1 protein, the key initiator of autophagy, resulting in a significantly strengthened antitumor effect of RAP. Using tumor-bearing mouse models, the nanosystem could passively accumulate into the tumor tissue, impose potent gene-silencing efficacy, and thus sensitize chemotherapy to inhibit tumor growth upon intravenous administration, providing opportunities for combined gene-drug TNBC therapy.
研究领域:
纳米技术
·
癌症治疗
·
基因治疗
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2021
·
IF 4.821
Xiaojie Song,Man-Man Lv,Qi-Yan Lv,Hui-Fang Cui,Jing Fu,Yu-Yang Huo
A novel and sensitive Helicobacter pylori assay strategy based on linear isothermal amplification reaction (LIAR) and DNAzymes catalyzed DNA sensor was developed. A 17 nt target DNA (tDNA) specific in the H. pylori genome was selected and used as primer in the LIAR. A template DNA was designed to produce an amplicon with Mg 2+ -dependent and RNA-cleaving DNAzyme (Md-Dz) activity. The amplicon (i.e. Md-Dz) was then detected with the DNA sensor. The DNA sensor was fabricated simply through immobilization of a hairpin DNA that contains both Md-Dz substrate and G-quadruplex DNAzyme (Gq-Dz), on gold electrodes. The Gq-Dz possesses peroxidase activity, catalyzing the electro-redox of the electrochemical signal probe hydroquinon. The LIAR, Md-Dz catalytic reaction, and DNA sensor fabrication and detection processes were characterized and optimized. The LIAR amplification efficiency is as high as ~5 × 10 5 fold, and the assay strategy is very sensitive, selective and repetitive. The differential pulse voltammetry (DPV) detection signals linearly correlate to the logarithmic tDNA concentration in the range of 0.1–10,000 fM, with a limit of detection (LOD) of 34 aM. The detection linear range for H. pylori genomic DNA is 2.1–67.2 pg, with an LOD of 1.3 pg . Muted DNA sequences and other pathogenic bacteria did not result in interferences. In addition, the DNA sensor is very stable in storage. More importantly, the DNA sensor and the assay strategy could be universally applicable to detect any biological sample and short DNA sequence of interests.
研究领域:
生物化学
·
分析化学
·
分子生物学
·
生物技术
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）