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First gene-edited calf with reduced susceptibility to a major viral pathogen
Open accessPreprint — published as 10.1093/pnasnexus/pgad125
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 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 16 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.
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Highly accurate protein structure prediction with AlphaFold
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Metadata
- Authors
- Workman, A. M., Heaton, M. P., Vander Ley, B. L., Webster, D. A., Sherry, L., Larson, S., Kalbfleisch, T. S., Harhay, G. P., Jobman, E. E., Carlson, D. F., & Sonstegard, T. S.
- Affiliations
- Agricultural Research Service (US)
- Recombinetics (United States) (US)
- University of Nebraska–Lincoln (US)
- Corresponding author
- Workman, Aspen M
- ORCID
- Venue
- PNAS Nexus
- Publisher
- openRxiv
- Published
- 2022-12-08
- Volume
- 2
- Issue
- 5
- Pages
- pgad125-pgad125
- ISSN
- 2752-6542 (ISSN-L)
- PMC
- PMC10167990
- OpenAlex
- W4376104839
- Cited by
- 55
- References
- 1
- Citations by year
- 2026: 12 · 2025: 21 · 2024: 18 · 2023: 4
- FWCI
- 9.13
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- public-domain
- Locations
- PNAS Nexus (publishedVersion, public-domain)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, public-domain)
- PubMed (publishedVersion)
- Lincoln (University of Nebraska) (submittedVersion)
- Funders
- U.S. Department of Agriculture (3040-32000-034-00D)
- University of Nebraska-Lincoln
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Animal Genetics and Reproduction
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Keywords
- bovine viral diarrhea virus, CD46, CRISPR gene editing, somatic cell nuclear transfer, precision breeding, cattle, viral susceptibility, homology-directed repair, off-target editing
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