RNA-DNA fibers and polygons with controlled immunorecognition activate RNAi, FRET and transcriptional regulation of NF-B in human cells
RNA-DNA fibers and polygons with controlled immunorecognition activate RNAi, FRET and transcriptional regulation of NF-B in human cells
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DOI：
10.1093/nar/gky1215
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发表时间：
2019-02-20
影响因子：
14.9
通讯作者：
Afonin, Kirill A.
中科院分区：
文献类型：
--
作者：
Ke, Weina;Hong, Enping;Afonin, Kirill A.
基于核酸的组装体彼此相互作用并以受控方式进一步与细胞机器通信，代表了一类新型可重构材料，可以克服传统生化方法的局限性并提高核酸的潜在治疗效用。这一概念使得能够开发具有精确控制的物理化学和生物特性的新型生物相容性智能设备和生物传感器。我们通过设计 RNA-DNA 纤维和多边形来扩展这一新概念，这些纤维和多边形能够在不同的人类细胞系中协作，并且具有经离体实验证实的明确的免疫刺激特性。构建体的细胞内相互作用导致大量不同 siRNA 的释放，同时产生荧光响应并激活 NF-B 诱饵 DNA 寡核苷酸。这项工作通过（i）引入非常简单的设计原理和组装方案扩展了核酸技术的可能性； (ii) 可能允许同时释放各种 siRNA 和功能性 DNA 序列，以及 (iii) 提供受控的重结合速率、人血清中的稳定性和免疫识别。
Nucleic acid-based assemblies that interact with each other and further communicate with the cellular machinery in a controlled manner represent a new class of reconfigurable materials that can overcome limitations of traditional biochemical approaches and improve the potential therapeutic utility of nucleic acids. This notion enables the development of novel biocompatible smart' devices and biosensors with precisely controlled physicochemical and biological properties. We extend this novel concept by designing RNA-DNA fibers and polygons that are able to cooperate in different human cell lines and that have defined immunostimulatory properties confirmed by ex vivo experiments. The mutual intracellular interaction of constructs results in the release of a large number of different siRNAs while giving a fluorescent response and activating NF-B decoy DNA oligonucleotides. This work expands the possibilities of nucleic acid technologies by (i) introducing very simple design principles and assembly protocols; (ii) potentially allowing for a simultaneous release of various siRNAs together with functional DNA sequences and (iii) providing controlled rates of reassociation, stabilities in human blood serum, and immunorecognition.