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    张开翔等Y-Shaped Circular Aptamer–DNAzyme Conjugates for Highly Efficient in Vivo Gene Silencing

    2020-11-03   点击:[]

    Y-Shaped Circular Aptamer–DNAzyme Conjugates for Highly Efficient in Vivo Gene Silencing

    【作者】Kaixiang Zhang†, Yanan Li†, Junjie Liu, Xue Yang, Yuanhong Xu, Jinjin Shi*, Wei Liu*, and Jinghong Li*

    【期刊名】 CCC chemistry

    【影响因子】

    【作者单位】 School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, PR China

    【年,卷():页码】. 2020, 2, 631–641

    【关键词】in vivo gene silencing, circular DNA structure, aptamer, DNAzyme

    【摘要】Oligonucleotide drugs have been used widely as therapeutic agents for gene therapy, while their instability in biological media and inefficiency for intracellular delivery remain major hurdles for practical in vivo applications. Herein, we report a circular Y-shaped aptamer–DNAzyme conjugate (cYAD) for highly efficient in vivo gene silencing via RNA cleavage, which can been employed in various disease treatments, including cancer, inflammation, as well as viral infections. Systematic studies revealed that cyclization of the DNA structure could improve the stability of oligonucleotide drugs in vivo. Besides, the bivalent aptamer motifs provided a specific and enhanced tumor cell targeting ability for accumulation and retention of the oligonucleotide drugs at the tumor site. As a proof of concept, a widely applicable Na+-dependent fluorescent sensor, NaA43 DNAzyme, was used to inhibit MET gene expression in mice tumor model tissues, which exhibited highly efficient gene silencing performance in vivo, which confirmed our findings with cYAD. This strategy provides a novel approach for the construction of oligonucleotide drugs for practical therapeutic applications.


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