Potent programmable antiviral against dengue virus in primary human cells by Cas13b RNP with short spacer and delivery by VLP.
Mol Ther Methods Clin Dev
; 21: 729-740, 2021 Jun 11.
Article
in English
| MEDLINE | ID: covidwho-1253442
ABSTRACT
With sequencing as a standard frontline protocol to identify emerging viruses such Zika virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), direct utilization of sequence data to program antivirals against the viruses could accelerate drug development to treat their infections. CRISPR-Cas effectors are promising candidates that could be programmed to inactivate viral genetic material based on sequence data, but several challenges such as delivery and design of effective CRISPR RNA (crRNA) need to be addressed to realize practical use. Here, we showed that virus-like particle (VLP) could deliver PspCas13b-crRNA ribonucleoprotein (RNP) in nanomolar range to efficiently suppress dengue virus infection in primary human target cells. Shortening spacer length could significantly enhance RNA-targeting efficiency of PspCas13b in mammalian cells compared to the natural length of 30 nucleotides without compromising multiplex targeting by a crRNA array. Our results demonstrate the potentials of applying PspCas13b RNP to suppress RNA virus infection, with implications in targeting host RNA as well.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Language:
English
Journal:
Mol Ther Methods Clin Dev
Year:
2021
Document Type:
Article
Affiliation country:
J.omtm.2021.04.014
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