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    Acquiring resistance against a retroviral infection via CRISPR/Cas9 targeted genome editing in a commercial chicken line (2020)

    Art
    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Autoren
    Hellmich, Romina
    Sid, Hicham
    Lengyel, Kamila
    Flisikowski, Krzysztof
    Schlickenrieder, Antonina
    Bartsch, Denise
    Thoma, Theresa
    Bertzbach, Luca D. (WE 5)
    Kaufer, Benedikt B. (WE 5)
    Nair, Venugopal
    Preisinger, Rudolf
    Schusser, Benjamin
    Quelle
    Frontiers in genome editing
    Bandzählung: 2
    Seiten: Article 3
    ISSN: 2673-3439
    Sprache
    Englisch
    Verweise
    URL (Volltext): https://www.frontiersin.org/articles/10.3389/fgeed.2020.00003/full
    DOI: 10.3389/fgeed.2020.00003
    Kontakt
    Institut für Virologie

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

    Abstract / Zusammenfassung

    Genome editing technology provides new possibilities for animal breeding and aid in understanding host-pathogen interactions. In poultry, retroviruses display one of the most difficult pathogens to control by conventional strategies such as vaccinations. Avian leukosis virus subgroup J (ALV-J) is an oncogenic, immunosuppressive retrovirus that causes myeloid leukosis and other tumors in chickens. Severe economic losses caused by ALV-J remain an unsolved problem in many parts of the world due to inefficient eradication strategies and lack of effective vaccines. ALV-J attachment and entry are mediated through the specific receptor, chicken Na+/H+ exchanger type 1 (chNHE1). The non-conserved amino acid tryptophan 38 (W38) in chNHE1 is crucial for virus entry, making it a favorable target for the introduction of disease resistance. In this study, we obtained ALV-J-resistance in a commercial chicken line by precise deletion of chNHE1 W38, utilizing the CRISPR/Cas9-system in combination with homology directed repair. The genetic modification completely protected cells from infection with a subgroup J retrovirus. W38 deletion did neither have a negative effect on the development nor on the general health condition of the gene edited chickens. Overall, the generation of ALV-J-resistant birds by precise gene editing demonstrates the immense potential of this approach as an alternative disease control strategy in poultry.