An RNA/DNA hybrid origami-based nanoplatform for efficient gene therapy.
An RNA/DNA hybrid origami-based nanoplatform for efficient gene therapy.
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DOI：
10.1039/d1nr00517k
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发表时间：
2021-08
期刊：
影响因子：
6.7
通讯作者：
Xiaohui Wu;Qing Liu;Fengsong Liu;Tiantian Wu;Yingxu Shang;Jianbing Liu;Baoquan Ding
中科院分区：
文献类型：
--
作者：
Xiaohui Wu;Qing Liu;Fengsong Liu;Tiantian Wu;Yingxu Shang;Jianbing Liu;Baoquan Ding
核酸纳米结构是一种很有前途的生物材料，可用于同源基因治疗药物的递送。在此，我们报告了一种简单的策略，用于构建目标mRNA（支架）和反义（短链）共同组装的RNA/DNA杂交“折纸”，用于有效的基因治疗。在我们的设计中，mRNA通过高产量的RNA-DNA杂交被折叠成化学上定义明确的纳米结构。在加入活性细胞靶向适配体后，定制的RNA/DNA杂交折纸在细胞内RNase H消化反应中表现出有效的细胞摄取和反义的可控释放。生物相容性RNA/DNA折纸（RDO）通过沉默肿瘤相关基因polo样激酶1 (PLK1)，引起了明显的细胞增殖抑制。这种基于rdo的纳米平台为基因治疗的进一步发展提供了一种新的策略。
Nucleic acid nanostructures are promising biomaterials for the delivery of homologous gene therapy drugs. Herein, we report a facile strategy for the construction of target mRNA (scaffold) and antisense (staple strands) co-assembled RNA/DNA hybrid "origami" for efficient gene therapy. In our design, the mRNA was folded into a chemically well-defined nanostructure through RNA-DNA hybridization with high yield. After the incorporation of an active cell-targeting aptamer, the tailored RNA/DNA hybrid origami demonstrated efficient cellular uptake and controllable release of antisenses in response to intracellular RNase H digestion. The biocompatible RNA/DNA origami (RDO) elicited a noticeable inhibition of cell proliferation based on the silencing of the tumor-associated gene polo-like kinase 1 (PLK1). This RDO-based nanoplatform provides a novel strategy for the further development of gene therapy.