Genetically Encoded and Biologically Produced All-DNA Nanomedicine Based on One-Pot Assembly of DNA Dendrimers for Targeted Gene Regulation

Genetically Encoded and Biologically Produced All-DNA Nanomedicine Based on One-Pot Assembly of DNA Dendrimers for Targeted Gene Regulation
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基于 DNA 树枝状聚合物一锅组装的基因编码和生物生产的全 DNA 纳米药物,用于靶向基因调控

DOI:
10.1002/anie.202012916
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发表时间:
2020
影响因子:
16.6
通讯作者:
Leilei Tian
Leilei Tian
中科院分区:
化学1区
文献类型:
--
作者:
Jingxiong Lu;Pengchao Hu;Lingyan Cao;Zixiang Wei;Fan Xiao;Zhe Chen;Yan Li;Leilei Tian

文献摘要

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全DNA纳米药物已成为潜在的抗肿瘤药物。DNA纳米技术为全DNA纳米医学提供了无限的可能性,可以控制治疗基序的大小,形状和负载的多样化。由于DNA是一种生物聚合物,因此可以在活细菌中遗传编码和生产全DNA纳米药物。在此,基于DNA树枝状聚合物的纳米药物被设计为适应生物生产,其由柔性3臂构建块构建,以实现高效的一锅法DNA组装。DNA纳米药物D4 - 3-As-DzSur首次成功地进行了基因编码、生物技术生产和直接自组装。生物学生产的D4 - 3-As-DzSur在靶向基因调控中的性能已通过体外和体内研究得到证实。  生物生产能力将实现全DNA纳米药物的低成本、大规模生产,并推动临床应用。
All‐DNA nanomedicines have emerged as potential anti‐tumor drugs. DNA nanotechnology provides all‐DNA nanomedicines with unlimited possibilities in controlling the diversification of size, shape, and loads of the therapeutic motifs. As DNA is a biological polymer, it is possible to genetically encode and produce the all‐DNA nanomedicines in living bacteria. Herein, DNA‐dendrimer‐based nanomedicines are designed to adapt to the biological production, which is constructed by the flexible 3‐arm building blocks to enable a highly efficient one‐pot DNA assembly. For the first time, a DNA nanomedicine, D4‐3‐As‐DzSur, is successfully genetically encoded, biotechnologically produced, and directly self‐assembled. The performance of the biologically produced D4‐3‐As‐DzSur in targeted gene regulation has been confirmed by in vitro and in vivo studies. The biological production capability will fulfill the low‐cost and large‐scale production of all‐DNA nanomedicines and promote clinical applications.