First gene-edited calf with reduced susceptibility to a major viral pathogen

Aspen M. Workman, Michael P. Heaton, Brian L. Vander Ley, Dennis A. Webster, Luke Sherry, Jonathan R. Bostrom, Sabreena Larson, Theodore S. Kalbfleisch, Gregory P. Harhay, Erin E. Jobman, Daniel F. Carlson, Tad S. Sonstegard

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Bovine viral diarrhea virus (BVDV) is one of the most important viruses affecting the health and well-being of bovine species throughout the world. Here, we used CRISPR-mediated homology-directed repair and somatic cell nuclear transfer to produce a live calf with a six amino acid substitution in the BVDV binding domain of bovine CD46. The result was a gene-edited calf with dramatically reduced susceptibility to infection as measured by reduced clinical signs and the lack of viral infection in white blood cells. The edited calf has no off-target edits and appears normal and healthy at 20 months of age without obvious adverse effects from the on-target edit. This precision bred, proof-of-concept animal provides the first evidence that intentional genome alterations in the CD46 gene may reduce the burden of BVDV-associated diseases in cattle and is consistent with our stepwise, in vitro and ex vivo experiments with cell lines and matched fetal clones.

Original languageEnglish
Article numberpgad125
JournalPNAS Nexus
Volume2
Issue number5
DOIs
StatePublished - May 1 2023

Bibliographical note

Publisher Copyright:
© 2023 The Author(s).

Keywords

  • BVDV
  • CD46
  • CRISPR
  • bovine viral diarrhea virus
  • gene editing

ASJC Scopus subject areas

  • General

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