“First Gene-Edited Calf With Reduced Susceptibility to a Major Viral Pathogen”, 2023-05-09 ():
Bovine viral diarrhea virus (BVDV) is one of the most burdensome viruses affecting the health and well-being of cattle throughout the world. The main host receptor mediating BVDV infection is CD46.
This proof-of-concept study showed that substituting 6 acids in CD46 caused a dramatic reduction in BVDV susceptibility in a gene-edited calf without causing any obvious adverse effects in the first 20 months of life. This provides the first example of CRISPR gene editing in cattle to reduce the impact of a major viral disease.
This approach could substantially improve animal welfare, increase the long-term sustainability of cattle production, and provide an opportunity to reduce antibiotic use in agriculture, given that BVDV infection puts calves at risk for secondary bacterial diseases.
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 6 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 [and in a natural exposure challenge study with the same edited calf]. 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.
[Keywords: CD46, gene editing, CRISPR, BVDV, bovine viral diarrhea virus]