CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, 11 BeiYiTiao, ZhongGuanCun, Beijing, 100190, China.
University of Chinese Academy of Sciences, Beijing, 100049, China.
Angew Chem Int Ed Engl. 2021 Jan 25;60(4):1853-1860. doi: 10.1002/anie.202011174. Epub 2020 Nov 24.
Chemically modified DNA has been widely developed to fabricate various nucleic acid nanostructures for biomedical applications. Herein, we report a facile strategy for construction of branched antisense DNA and small interfering RNA (siRNA) co-assembled nanoplatform for combined gene silencing in vitro and in vivo. In our design, the branched antisense can efficiently capture siRNA with 3' overhangs through DNA-RNA hybridization. After being equipped with an active targeting group and an endosomal escape peptide by host-guest interaction, the tailored nucleic acid nanostructure functions efficiently as both delivery carrier and therapeutic cargo, which is released by endogenous RNase H digestion. The multifunctional nucleic acid nanosystem elicits an efficient inhibition of tumor growth based on the combined gene silencing of the tumor-associated gene polo-like kinase 1 (PLK1). This biocompatible nucleic acid nanoplatform presents a new strategy for the development of gene therapy.
化学修饰的 DNA 被广泛开发用于构建各种核酸纳米结构，以应用于生物医学领域。在此，我们报告了一种简便的策略，用于构建分支反义 DNA 和小干扰 RNA（siRNA）共组装纳米平台，以实现体外和体内的联合基因沉默。在我们的设计中，分支反义 DNA 可以通过 DNA-RNA 杂交有效地捕获具有 3'突出端的 siRNA。通过主客体相互作用，将靶向基团和内涵体逃逸肽修饰到靶向载体上后，定制的核酸纳米结构可以有效地作为递送载体和治疗性载药，通过内源性 RNase H 酶切释放药物。基于对肿瘤相关基因 Polo 样激酶 1（PLK1）的联合基因沉默，多功能核酸纳米系统引发了有效的肿瘤生长抑制。这种生物相容性的核酸纳米平台为基因治疗的发展提供了一种新策略。
