Controlling Circular RNA Encapsulation within Extracellular Vesicles for Gene Editing and Protein Replacement

IF 15.8 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

ACS Nano Pub Date : 2024-10-24 DOI:10.1021/acsnano.4c0753010.1021/acsnano.4c07530

Liang Fang, Wenchao Gu, Ruoxin Li, Chaoxin Chen, Simian Cai, Sijin Luozhong, Michelle Chen, Annie Hsu, Yi-Chih Tsai, Ketaki Londhe and Shaoyi Jiang*,

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Abstract

Extracellular vesicles (EVs) are a population of vesicular bodies originating from cells, and EVs have been proven to have the potential to deliver different cargos, such as RNAs. However, conventional methods are not able to encapsulate long RNAs into EVs efficiently or may compromise the integrity of EVs. In this study, we have devised a strategy to encapsulate long circRNAs (>1000 nt) into EVs by harnessing the sorting mechanisms of cells. This strategy utilizes the inherent richness of circular RNAs in EVs and a genetic engineering method to increase the cytoplasmic concentration of target circRNAs, facilitating highly efficient RNA back-splicing to drive the circularization of RNAs. This allows target circRNAs to load into EVs with high efficiency. Furthermore, we demonstrate the practical applications of this strategy, showing that these circRNAs can be delivered by EVs to recipient cells for protein expression and to mice for gene editing.

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控制细胞外囊泡中的环形 RNA 封装，实现基因编辑和蛋白质置换

细胞外囊泡（EVs）是一种源自细胞的囊泡体，EVs 已被证实具有传递 RNA 等不同载体的潜力。然而，传统的方法无法将长 RNA 有效地封装到 EVs 中，或者会损害 EVs 的完整性。在这项研究中，我们设计了一种策略，利用细胞的分拣机制将长 circRNA（1000 nt）封装到 EVs 中。这一策略利用了EVs中固有的丰富环状RNA，并通过基因工程方法提高了目标circRNA的细胞质浓度，促进了高效的RNA反向剪接，从而推动了RNA的环化。这使得目标 circRNA 能够高效地载入 EV。此外，我们还展示了这一策略的实际应用，表明这些 circRNA 可通过 EVs 运送到受体细胞进行蛋白质表达，也可运送到小鼠体内进行基因编辑。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ACS Nano 工程技术-材料科学：综合

CiteScore

26.00

自引率

4.10%

发文量

1627

审稿时长

1.7 months

期刊介绍： ACS Nano, published monthly, serves as an international forum for comprehensive articles on nanoscience and nanotechnology research at the intersections of chemistry, biology, materials science, physics, and engineering. The journal fosters communication among scientists in these communities, facilitating collaboration, new research opportunities, and advancements through discoveries. ACS Nano covers synthesis, assembly, characterization, theory, and simulation of nanostructures, nanobiotechnology, nanofabrication, methods and tools for nanoscience and nanotechnology, and self- and directed-assembly. Alongside original research articles, it offers thorough reviews, perspectives on cutting-edge research, and discussions envisioning the future of nanoscience and nanotechnology.