Gene-editing technology produces calf with reduced susceptibility to a viral pathogen

A proof-of-concept study by U.S. researchers provides the first example of gene editing in cattle to reduce the impact of a major viral disease.

Researchers from USDA’s Agricultural Research Service (ARS), the University of Nebraska–Lincoln (UNL) and the University of Kentucky, collaborated with industry partners, Acceligen and Recombinetics, Inc., to produce a calf with resistance to bovine viral diarrhea virus (BVDV). The findings are published in PNAS Nexus.

BVDV is associated with gastrointestinal and respiratory diseases and reproductive failure in cattle worldwide. Despite more than 50 years of vaccine availability, controlling BVDV disease remains a problem since vaccines are not always effective in stopping transmission.

The main host cellular receptor mediating BVDV infection is CD46. The researchers aimed to use gene-editing technology to slightly alter CD46 so it wouldn’t bind the virus yet would retain all its normal bovine functions.

A healthy Gir calf was produced with a six amino acid substitution in the BVDV binding domain of CD46. This gene-edited calf showed reduced BVDV susceptibility, and no obvious adverse effects in the first 20 months of life. The health of the animal will continue to be observed, as will her ability to produce and raise calves.

The researchers say their results provide proof-of-concept for using intentional genome alterations in CD46 to reduce the burden of BVDV-associated diseases in cattle. However, determining the ability of CD46-edited animals to withstand BVDV viral challenges will require experimental replication in other breeds and with more animals.

Article: Workman, A. M., Heaton, M. P., Vander Ley, B. L., Webster, D. A., Sherry, L., Bostrom, J. R., Larson, S., Kalbfleisch, T. S., Harhay, G. P., Jobman, E. E., Carlson, D. F., Sonstegard, T. S., 2023. First gene-edited calf with reduced susceptibility to a major viral pathogen, PNAS Nexus, 2(5), pgad125, doi: 10.1093/pnasnexus/pgad125