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ARS Home » Plains Area » Clay Center, Nebraska » U.S. Meat Animal Research Center » Animal Health Genomics » Research » Publications at this Location » Publication #402214

Research Project: Strategies to Control Respiratory Diseases of Cattle

Location: Animal Health Genomics

Title: A CD46-edited calf with reduced susceptibility to bovine viral diarrhea virus

item Workman, Aspen
item Heaton, Michael - Mike
item VANDER LEY, BRIAN - University Of Nebraska
item WEBSTER, DENNIS - Recombinetics, Inc
item SHERRY, LUKE - Recombinetics, Inc
item LARSON, SABREENA - Acceligen Inc
item KALBFLEISCH, THEODORE - University Of Kentucky
item Harhay, Gregory
item JOBMAN, ERIN - University Of Nebraska
item CARLSON, DANIEL - Recombinetics, Inc
item SONSTEGARD, TAD - Acceligen Inc

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 2/10/2023
Publication Date: N/A
Citation: N/A

Interpretive Summary:

Technical Abstract: Bovine viral diarrhea virus (BVDV) is one of the most important viruses causing respiratory and gastrointestinal diseases and reproductive failure in cattle throughout the world. The main BVDV cellular receptor in cattle is CD46 and residues G82QVLAL87 are among those essential for binding and entry. Substituting residues A82LPTFS87 in CD46 was previously shown to reduce BVDV susceptibility in vitro. Here we used CRISPR-mediated homology-directed repair and somatic cell nuclear transfer to produce a live calf with homozygous CD46 A82LPTFS87 substitutions. The result was a gene-edited calf with dramatically reduced susceptibility to infection as measured by 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 18 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 CD46 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.