Publication: Potent programmable antiviral against dengue virus in primary human cells by Cas13b RNP with short spacer and delivery by VLP
Issued Date
2021-06-11
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ISSN
23290501
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2-s2.0-85107812455
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Mahidol University
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SCOPUS
Bibliographic Citation
Molecular Therapy - Methods and Clinical Development. Vol.21, (2021), 729-740
Suggested Citation
Ekapot Singsuksawat, Suppachoke Onnome, Pratsaneeyaporn Posiri, Amporn Suphatrakul, Nittaya Srisuk, Rapirat Nantachokchawapan, Hansa Praneechit, Chutimon Sae-kow, Pala Chidpratum, Khanit Sa-ngiamsuntorn, Suradej Hongeng, Panisadee Avirutnan, Thaneeya Duangchinda, Bunpote Siridechadilok Potent programmable antiviral against dengue virus in primary human cells by Cas13b RNP with short spacer and delivery by VLP. Molecular Therapy - Methods and Clinical Development. Vol.21, (2021), 729-740. doi:10.1016/j.omtm.2021.04.014 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/76141
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Title
Potent programmable antiviral against dengue virus in primary human cells by Cas13b RNP with short spacer and delivery by VLP
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.