Location: Animal Health Genomics
Project Number: 3040-32000-036-005-S
Project Type: Non-Assistance Cooperative Agreement
Start Date: Jul 15, 2024
End Date: Jul 14, 2026
Objective:
The objective of this research is to use a combination CRISPR/Cas9 gene-editing and advanced reproductive technologies to produce cattle with genetic resistance to bovine viral diarrhea virus (BVDV).
We recently published a proof-of-concept study where we modified the host receptor for BVDV (CD46) via a precise 18-nucleotide edit that effectively blocked BVDV infection (Workman et al., 2023; https://doi.org/10.1093/pnasnexus/pgad125). This work led to the first CD46 gene-edited calf, Ginger, born in July of 2021. Upon viral challenge, Ginger did not get sick and her white blood cells remained uninfected throughout the challenge. This study demonstrated the possibility of reducing the burden of BVDV-associated diseases in cattle with gene-editing. Because Ginger’s breed (Gir) was developed from indicine cattle and this breed is uncommon in the U.S., our next research goal is to determine whether the viral resistance phenotype can be replicated in black Angus cattle, a popular U.S. beef breed.
Approach:
We will develop embryonic stem cell (ESC) lines from elite purebred black Angus animals. Two ESCs (one male and one female) will be selected and used as the starting material for CRISPR-mediated editing of the CD46 gene. Reproductive cloning via somatic cell nuclear transfer will then be used to produce cattle containing this intentional genomic alteration.
