Potent programmable antiviral against dengue virus in primary human cells by Cas13b RNP with short spacer and delivery by VLP.
CRISPR-Cas13
RNA virus
VLP
and virus-like particle
delivery
dengue
flavivirus
zika
Journal
Molecular therapy. Methods & clinical development
ISSN: 2329-0501
Titre abrégé: Mol Ther Methods Clin Dev
Pays: United States
ID NLM: 101624857
Informations de publication
Date de publication:
11 Jun 2021
11 Jun 2021
Historique:
received:
25
03
2021
accepted:
22
04
2021
pubmed:
11
5
2021
medline:
11
5
2021
entrez:
10
5
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33969146
doi: 10.1016/j.omtm.2021.04.014
pii: S2329-0501(21)00080-2
pmc: PMC8087611
doi:
Types de publication
Journal Article
Langues
eng
Pagination
729-740Informations de copyright
© 2021 The Author(s).
Déclaration de conflit d'intérêts
S.O., E.S., P.P., A.S., and B.S. are co-inventors on a patent application based on this work.
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