单剂量组织蛋白酶L CRISPR纳米疗法减轻仓鼠pasc样肺损伤。

IF 9 2区 材料科学 Q1 CHEMISTRY, PHYSICAL
Nano Research Pub Date : 2025-09-01 Epub Date: 2025-08-19 DOI:10.26599/NR.2025.94907695
Zhifen Cui, Tianxiang Liu, Rebecca Bacon, Yue Zhao, Jeffrey I Everitt, Jingyue Yan, Lingye Chen, Jiaoti Huang, Hongyan Wang, Yizhou Dong, Victor X Jin, Shan-Lu Liu, Qianben Wang
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引用次数: 0

摘要

COVID-19急性后呼吸道后遗症(PASC)在许多SARS-CoV-2幸存者中持续存在,但没有专门针对其长期肺损伤的治疗方法。我们证明,单剂量靶向宿主酶组织蛋白酶L (SCNC)的CRISPR-CasRx纳米疗法可有效降低叙利亚仓鼠的急性SARS-CoV-2感染,其抗病毒功效与Paxlovid相当。重要的是,在感染后31天(公认的PASC时间点),SCNC在缓解肺泡上皮增生和肺部炎症方面优于Paxlovid。单细胞RNA测序显示,SCNC通过多种信号通路促进肺泡2型细胞向肺泡1型细胞分化,减少炎症浸润,从而增强肺泡修复。因此,SCNC发挥双重机制:宿主定向的病毒抑制和促进上皮修复,减少炎症。这将其与仅专注于病毒抑制或症状缓解的疗法区别开来。这些发现支持SCNC作为一种有希望的治疗急性感染的候选药物,特别是pasc相关的肺损伤,其中选择仍然有限。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Single-dose cathepsin L CRISPR nanotherapy mitigates PASC-like lung damage in hamsters.

Respiratory post-acute sequelae of COVID-19 (PASC) persists in many SARS-CoV-2 survivors, yet no therapies specifically address its long-term pulmonary damage. We demonstrate that a single-dose CRISPR-CasRx nanotherapy targeting the host enzyme cathepsin L (SCNC) effectively reduces acute SARS-CoV-2 infection in Syrian hamsters, with antiviral efficacy comparable to Paxlovid. Importantly, SCNC outperforms Paxlovid in alleviating alveolar epithelial hyperplasia and lung inflammation at 31 days post-infection, a recognized PASC time point. Single-cell RNA sequencing reveals that SCNC enhances alveolar repair by promoting the differentiation of alveolar type 2 cells into alveolar type 1 cells and by reducing inflammatory infiltration through multiple signaling pathways. Thus, SCNC exerts a dual mechanism: host-directed viral inhibition and promotion of epithelial repair with reduced inflammation. This distinguishes it from therapies focused solely on viral suppression or symptom relief. These findings support SCNC as a promising therapeutic candidate for acute infection and, particularly, for PASC-related lung injury, where options remain limited.

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来源期刊
Nano Research
Nano Research 化学-材料科学:综合
CiteScore
14.30
自引率
11.10%
发文量
2574
审稿时长
1.7 months
期刊介绍: Nano Research is a peer-reviewed, international and interdisciplinary research journal that focuses on all aspects of nanoscience and nanotechnology. It solicits submissions in various topical areas, from basic aspects of nanoscale materials to practical applications. The journal publishes articles on synthesis, characterization, and manipulation of nanomaterials; nanoscale physics, electrical transport, and quantum physics; scanning probe microscopy and spectroscopy; nanofluidics; nanosensors; nanoelectronics and molecular electronics; nano-optics, nano-optoelectronics, and nano-photonics; nanomagnetics; nanobiotechnology and nanomedicine; and nanoscale modeling and simulations. Nano Research offers readers a combination of authoritative and comprehensive Reviews, original cutting-edge research in Communication and Full Paper formats. The journal also prioritizes rapid review to ensure prompt publication.
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