Efficient Delivery of mRNA Using Crosslinked Nucleic Acid Nanogel as a Carrier
Efficient Delivery of mRNA Using Crosslinked Nucleic Acid Nanogel as a Carrier
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DOI：
10.1021/acsmaterialslett.0c00375
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发表时间：
2020-11-02
影响因子：
11.4
通讯作者：
Zhang, Chuan
中科院分区：
文献类型：
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作者：
Huang, Xiangang;Zheng, Ru;Zhang, Chuan
在体外转录的信使RNA（mRNA）可以在靶细胞中有效表达治疗性蛋白质而不需要担心诱变，这为治疗广泛的疾病带来了巨大的希望。然而，mRNA的安全和有效递送仍然是一个挑战，并且非常需要开发新的递送载体。本文设计并制备了一种基于核酸纳米凝胶的mRNA递送系统，用于稳定的mRNA编码基因表达，该系统可以有效地产生感兴趣的蛋白质并原位实现蛋白质的功能。通过简单的核酸杂交，我们证明了增强型绿色荧光蛋白编码的mRNA（EGFP-mRNA）或Cas9蛋白编码的mRNA（Cas9-mRNA）在核酸纳米凝胶中的有效负载，其可以有效地进入细胞并导致稳健的EGFP表达或CRISPR/Cas9介导的基因组编辑。这项研究提供了一种新的和通用的mRNA递送平台，具有递送用于生物医学目的的各种mRNA编码治疗蛋白的潜力。
In vitro-transcribed messenger RNA (mRNA) can efficiently express the therapeutic proteins in target cells without the concern of mutagenesis, which holds great promise for the treatment of a broad range of diseases. However, the safe and effective delivery of mRNA remains a challenge and the development of novel delivery vehicles is highly desirable. Herein, a nucleic acid nanogel-based mRNA delivery system is designed and prepared for robust mRNA-encoding gene expression, which can efficiently produce the interested proteins and realize the proteins' functions in situ. Via simple nucleic acid hybridization, we demonstrate the efficient loading of either the enhanced green fluorescence protein-encoded mRNA (EGFP-mRNA) or Cas9 protein-encoded mRNA (Cas9-mRNA) in a nucleic acid nanogel, which can effectively enter the cells and results in robust EGFP expression or CRISPR/Cas9-mediated genome editing. This study provides a novel and general mRNA delivery platform that has the potential to deliver various mRNA-encoding therapeutic proteins for biomedical purposes.