Publication Database

Abrogation of Marek's disease virus replication using CRISPR/Cas9 (2020)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Hagag, Ibrahim T. (WE 5)

Wight, Darren J. (WE 5)

Bartsch, Denise

Sid, Hicham

Jordan, Ingo

Bertzbach, Luca D. (WE 5)

Schusser, Benjamin

Kaufer, Benedikt B. (WE 5)

Quelle

Scientific reports

Bandzählung: 10

Heftzählung: 1

Seiten: Article number: 10919

ISSN: 2045-2322

Sprache

Englisch

Verweise

URL (Volltext): https://www.nature.com/articles/s41598-020-67951-1

DOI: 10.1038/s41598-020-67951-1

Pubmed: 32616820

Kontakt

Institut für Virologie

Robert-von-Ostertag-Str. 7-13
14163 Berlin
+49 30 838 51833
virologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

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.