Scientists in the US have created a gene-edited calf with what they have called “dramatically reduced” susceptibility to infection of bovine viral diarrhoea virus (BVDV).
At 20-months-old, the calf was observed without any “adverse effects” after exposure to BVDV during housing, scientists from the United States Department of Agriculture (USDA) noted.
The result of their work has been published in the scientific journal Proceedings of the National Academy of Sciences (PNAS) Nexus.
It was published by scientists from USDA’s Agricultural Research Service (ARS); the University of Nebraska–Lincoln (UNL); the University of Kentucky; industry partners, Acceligen and Recombinetics, Inc.
Gene-edited experiment
Previous research suggests that the CD46 gene is the main receptor for BVDV.
This experiment is the first evidence that changes in the gene may reduce the burden of the BVD virus and associated diseases in cattle, scientists said.
For the experiment, all protocols for reproductive cloning, fetal tissue collection and birthing were reviewed and approved by the Institutional Animal Care and Use Committee (IACUC) of Trans Ova Genetics.
All the protocols were also reviewed and approved by the IACUC of the University of Nebraska–Lincoln.
CD46 couldn’t be deleted entirely as it has other essential roles in biological processes, the scientists said.
For the study, scientists substituted six amino acids in CD46, to prevent the process of it binding with the BVD virus.
The scientists collaborated with Acceligen, a company specialising in precision breeding technology. From there they genetically edited the cells.
“This approach could significantly improve animal welfare, increase the long-term sustainability of cattle production, and provide an opportunity to reduce antibiotic use in agriculture, given that BVDV infection puts calves at risk for secondary bacterial diseases,” the study stated.
Birth
The scientists transplanted the embryos to surrogate cows and the technique was successful.
The first gene-edited calf, named Ginger, was delivered by caesarean section at the calculated time of full gestation for Gir cattle, which is 285 days, on July 19, 2021.
It was removed without nursing and fed a commercial bovine colostrum replacement solution by bottle. After this, it was fed a commercial calf milk-replacer.
A Holstein dairy calf the same age and sex was purchased at the same time and fed the same solutions for comparison purposes.
At 10 months-of-age they were housed for seven days, with a week-old Holstein calf born with BVDV.
Both calves developed a fever and had a reduction in circulating white blood cells. The un-edited calf had many signs of infection and BVDV was detected for 28 days.
The genetically edited calf displayed significantly reduced susceptibility to BVDV, which resulted in no observable adverse health effects.
BVDV RNA was only detected in the whole blood of the edited calf. It was only detected for three days.
The scientists will continue to closely observe Ginger’s health and ability to produce and raise her own calves.
The USDA scientists described the experiment as a “proof-of-concept study”.
Results
Determining the ability of CD46-edited animals to withstand BVDV challenges will require experimental replication in other breeds and with more animals.
Limitations to the study include not having a “breed-match control” to use, as Gir cattle are uncommon in the US, the scientists said.
The study also didn’t allow for direct determination of viral entry and experimentation in different tissues of the calf, as the scientists didn’t want to sacrafice their only CD46-edited animal.
Samples for BVD were only positive for the gene-edited calf when they were housed with the BVD-positive calf.
The scientists said it could therefore be that the infection was only being detected due to environmental exposure.
