Abstract：
:Marek's disease virus (MDV) is a highly cell-associated alphaherpesvirus that causes deadly lymphomas in chickens. While vaccination protects against clinical symptoms, MDV field strains can still circulate in vaccinated flocks and continuously evolve towards greater virulence. MDV vaccines do not provide sterilizing immunity, allowing the virus to overcome vaccine protection, and has increased the need for more potent vaccines or alternative interventions. In this study, we addressed if the CRISPR/Cas9 system can protect cells from MDV replication. We first screened a number of guide RNAs (gRNAs) targeting essential MDV genes for their ability to prevent virus replication. Single gRNAs significantly inhibited virus replication, but could result in the emergence of escape mutants. Strikingly, combining two or more gRNAs completely abrogated virus replication and no escape mutants were observed upon serial passaging. Our study provides the first proof-of-concept, demonstrating that the CRISPR/Cas9 system can be efficiently used to block MDV replication. The presented findings lay the foundation for future research to completely protect chickens from this deadly pathogen.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Hagag IT,Wight DJ,Bartsch D,Sid H,Jordan I,Bertzbach LD,Schusser B,Kaufer BBdoi
10.1038/s41598-020-67951-1subject
Has Abstractpub_date
2020-07-02 00:00:00pages
10919issue
1issn
2045-2322pii
10.1038/s41598-020-67951-1journal_volume
10pub_type
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