First Gene-edited Calf Developed to be Less Susceptible to BVDV

The first gene-edited calf intended to be less susceptible to the bovine viral diarrhea virus (BVDV) was found to be normal and healthy at 16 months, with no obvious effects from the on-target edit.

The live gene-edited calf with six amino acid substitution in the BVDV binding domain of bovine CD46 gene was produced using CRISPR-mediated homology-directed repair and somatic cell nuclear transfer. An 18-nt replacement in the CD46 gene was used to make a homology-directed repair, while somatic cell nuclear transfer was used to produce the calf to avoid the introduction of off-target modifications and disruption of the predicted tertiary structure of the protein or its expression levels.

Susceptibility challenge studies conducted suggest that the edit could be useful for reducing BVDV susceptibility in cattle. The researchers from the United States who developed the calf measured the CD46-dependence of diverse cell types from the skin and internal organs and found significant reduction in BVDV susceptibility. They also found strong reduction in both the duration and peak viral RNA load in the blood of the calf, which was consistent with reduced viral replications in tissues in vivo, suggesting that the calf remained uninfected throughout the challenge.

The development of the gene-edited calf is very promising to address BVDV, but the researchers recommend future studies to determine whether CD46-edited bovine dams are able to protect developing fetus from transplacental BVDV infection through experimental replication in different bovine animals.

More details in bioRxiv.