@article{Cui2025, 
author = {Zhifen Cui and Tianxiang Liu and Rebecca Bacon and Yue Zhao and Jeffrey I. Everitt and Jingyue Yan and Lingye Chen and Jiaoti Huang and Hongyan Wang and Yizhou Dong and Victor X. Jin and Shan-Lu Liu and Qianben Wang},
title = {Single-dose cathepsin L CRISPR nanotherapy mitigates PASC-like lung damage in hamsters},
year = {2025},
journal = {Nano Research},
volume = {18},
number = {9},
pages = {94907695},
keywords = {post-acute sequelae of COVID-19 (PASC), single-dose clustered regularly interspaced short palindromic repeats (CRISPR)–CasRx nanotherapy targeting cathepsin L (SCNC), host-directed antiviral strategy, alveolar epithelial regeneration, inflammation resolution},
url = {https://www.sciopen.com/article/10.26599/NR.2025.94907695},
doi = {10.26599/NR.2025.94907695},
abstract = {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 clustered regularly interspaced short palindromic repeats (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.}
}