Customizable virus-like particles deliver CRISPR–Cas9 ribonucleoprotein for effective ocular neovascular and Huntington’s disease gene therapy

IF 38.1 1区材料科学 Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY

Nature nanotechnology Pub Date : 2025-02-10 DOI:10.1038/s41565-024-01851-7

Sikai Ling, Xue Zhang, Yao Dai, Zhuofan Jiang, Xujiao Zhou, Sicong Lu, Xiaoqing Qian, Jianping Liu, Niklas Selfjord, Tugce Munise Satir, Anders Lundin, Julia Liz Touza, Mike Firth, Natalie Van Zuydam, Bilada Bilican, Pinar Akcakaya, Jiaxu Hong, Yujia Cai

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引用次数: 0

Abstract

In vivo CRISPR gene editing holds enormous potential for various diseases. Ideally, CRISPR delivery should be cell type-specific and time-restricted for optimal efficacy and safety, but customizable methods are lacking. Here we develop a cell-tropism programmable CRISPR–Cas9 ribonucleoprotein delivery system (RIDE) based on virus-like particles. The efficiency of RIDE was comparable to that of adeno-associated virus and lentiviral vectors and higher than lipid nanoparticles. RIDE could be readily reprogrammed to target dendritic cells, T cells and neurons, and significantly ameliorated the disease symptoms in both ocular neovascular and Huntington’s disease models via cell-specific gene editing. In addition, RIDE could efficiently edit the huntingtin gene in patients’ induced pluripotent stem cell-derived neurons and was tolerated in non-human primates. This study is expected to facilitate the development of in vivo CRISPR therapeutics.

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可定制的病毒样颗粒递送CRISPR-Cas9核糖核蛋白，用于有效的眼部新生血管和亨廷顿病基因治疗

体内CRISPR基因编辑对多种疾病具有巨大的潜力。理想情况下，CRISPR传递应该是细胞类型特异性和时间限制的，以获得最佳的疗效和安全性，但缺乏可定制的方法。在这里，我们开发了一种基于病毒样颗粒的细胞亲和性可编程CRISPR-Cas9核糖核蛋白递送系统（RIDE）。RIDE的效率与腺相关病毒和慢病毒载体相当，高于脂质纳米颗粒。RIDE可以很容易地重新编程以靶向树突状细胞、T细胞和神经元，并通过细胞特异性基因编辑显着改善眼部新生血管和亨廷顿病模型的疾病症状。此外，RIDE可以在患者诱导的多能干细胞来源的神经元中有效编辑亨廷顿蛋白基因，并且在非人灵长类动物中耐受。这项研究有望促进体内CRISPR治疗方法的发展。

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

Nature nanotechnology 工程技术-材料科学：综合

CiteScore

59.70

自引率

0.80%

发文量

196

审稿时长

4-8 weeks

期刊介绍： Nature Nanotechnology is a prestigious journal that publishes high-quality papers in various areas of nanoscience and nanotechnology. The journal focuses on the design, characterization, and production of structures, devices, and systems that manipulate and control materials at atomic, molecular, and macromolecular scales. It encompasses both bottom-up and top-down approaches, as well as their combinations. Furthermore, Nature Nanotechnology fosters the exchange of ideas among researchers from diverse disciplines such as chemistry, physics, material science, biomedical research, engineering, and more. It promotes collaboration at the forefront of this multidisciplinary field. The journal covers a wide range of topics, from fundamental research in physics, chemistry, and biology, including computational work and simulations, to the development of innovative devices and technologies for various industrial sectors such as information technology, medicine, manufacturing, high-performance materials, energy, and environmental technologies. It includes coverage of organic, inorganic, and hybrid materials.