Cas13d knockdown of lung protease Ctsl prevents and treats SARS-CoV-2 infection.

Journal Article (Journal Article)

SARS-CoV-2 entry into cells requires specific host proteases; however, no successful in vivo applications of host protease inhibitors have yet been reported for treatment of SARS-CoV-2 pathogenesis. Here we describe a chemically engineered nanosystem encapsulating CRISPR-Cas13d, developed to specifically target lung protease cathepsin L (Ctsl) messenger RNA to block SARS-CoV-2 infection in mice. We show that this nanosystem decreases lung Ctsl expression in normal mice efficiently, specifically and safely. We further show that this approach extends survival of mice lethally infected with SARS-CoV-2, correlating with decreased lung virus burden, reduced expression of proinflammatory cytokines/chemokines and diminished severity of pulmonary interstitial inflammation. Postinfection treatment by this nanosystem dramatically lowers the lung virus burden and alleviates virus-induced pathological changes. Our results indicate that targeting lung protease mRNA by Cas13d nanosystem represents a unique strategy for controlling SARS-CoV-2 infection and demonstrate that CRISPR can be used as a potential treatment for SARS-CoV-2 infection.

Full Text

Duke Authors

Cited Authors

  • Cui, Z; Zeng, C; Huang, F; Yuan, F; Yan, J; Zhao, Y; Zhou, Y; Hankey, W; Jin, VX; Huang, J; Staats, HF; Everitt, JI; Sempowski, GD; Wang, H; Dong, Y; Liu, S-L; Wang, Q

Published Date

  • October 2022

Published In

Volume / Issue

  • 18 / 10

Start / End Page

  • 1056 - 1064

PubMed ID

  • 35879545

Electronic International Standard Serial Number (EISSN)

  • 1552-4469

Digital Object Identifier (DOI)

  • 10.1038/s41589-022-01094-4


  • eng

Conference Location

  • United States