Cas13d knockdown of lung protease Ctsl prevents and treats SARS-CoV-2 infection.
Nat Chem Biol
; 18(10): 1056-1064, 2022 10.
Article
in English
| MEDLINE | ID: covidwho-1960395
ABSTRACT
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:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
COVID-19 Drug Treatment
Type of study:
Prognostic study
Limits:
Animals
Language:
English
Journal:
Nat Chem Biol
Journal subject:
Biology
/
Chemistry
Year:
2022
Document Type:
Article
Affiliation country:
S41589-022-01094-4
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