Mannosylated neutrophil vesicles targeting macrophages alleviate liver inflammation by delivering CRISPR/Cas9 RNPs.

IF 12.4 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Theranostics Pub Date : 2025-05-08 eCollection Date: 2025-01-01 DOI:10.7150/thno.107791

Dongqing Wu, Hang Shu, Mengmeng Zhang, Xiaoli Wei, Jingjing Ji, Haiyuan Shen, Hejiao Zhang, Linxi Xie, Liangliang Zhou, Lei Yang, Jiali Jiang, Chen Chen, Shanfei Tian, Xinru Zhang, Xu Long, Xiaoyan He, Hua Wang

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引用次数: 0

Abstract

Background: Inflammation is a key driver of various liver diseases. NLRP3 inflammasome in hepatic macrophages is a key mediator of inflammation and has emerged as a promising target. Genome editing presents a powerful approach to modulate inflammation by directly disrupting genes such as NLRP3 directly. However, efficient and cell-specific delivery of CRISPR/Cas9 ribonucleoproteins (RNPs) remains challenging. Methods: We developed a novel delivery system by encapsulating CRISPR/Cas9 RNPs within mannosylated neutrophil membranes vesicles (Cas9/gNLRP3@M-N) to enhance targeting hepatic macrophages. Results: Cas9/gNLRP3@M-N selectively accumulated in hepatic macrophages, effectively disrupted the NLRP3 gene, attenuated inflammation in acute fulminant hepatitis, and improved disease outcomes in chronic steatohepatitis model. Conclusions: Cas9/gNLRP3@M-N represents a promising targeted gene-editing approach for the treatment of inflammatory liver diseases.

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靶向巨噬细胞的甘露糖基化中性粒细胞囊泡通过传递CRISPR/Cas9 RNPs缓解肝脏炎症。

背景：炎症是各种肝脏疾病的关键驱动因素。肝巨噬细胞中的NLRP3炎性体是炎症的关键介质，并已成为一个有希望的靶点。基因组编辑提供了一种通过直接破坏NLRP3等基因来调节炎症的有效方法。然而，CRISPR/Cas9核糖核蛋白（RNPs）的高效和细胞特异性递送仍然具有挑战性。方法：我们开发了一种新的递送系统，通过将CRISPR/Cas9 RNPs封装在甘露糖基化中性粒细胞膜囊泡（Cas9/gNLRP3@M-N）中来增强对肝巨噬细胞的靶向性。结果：Cas9/gNLRP3@M-N选择性地在肝巨噬细胞中积累，有效地破坏NLRP3基因，减轻急性暴发性肝炎的炎症，改善慢性脂肪性肝炎模型的疾病结局。结论：Cas9/gNLRP3@M-N代表了一种治疗炎症性肝病的有前景的靶向基因编辑方法。

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

Theranostics MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

25.40

自引率

1.60%

发文量

433

审稿时长

1 months

期刊介绍： Theranostics serves as a pivotal platform for the exchange of clinical and scientific insights within the diagnostic and therapeutic molecular and nanomedicine community, along with allied professions engaged in integrating molecular imaging and therapy. As a multidisciplinary journal, Theranostics showcases innovative research articles spanning fields such as in vitro diagnostics and prognostics, in vivo molecular imaging, molecular therapeutics, image-guided therapy, biosensor technology, nanobiosensors, bioelectronics, system biology, translational medicine, point-of-care applications, and personalized medicine. Encouraging a broad spectrum of biomedical research with potential theranostic applications, the journal rigorously peer-reviews primary research, alongside publishing reviews, news, and commentary that aim to bridge the gap between the laboratory, clinic, and biotechnology industries.