The first gene-edited calf with resistance to bovine viral diarrhea virus was the subject of a recent study by scientists at the U.S. Department of Agriculture- Agricultural Research Service, the University of Nebraska–Lincoln, the University of Kentucky, and industry partners, Acceligen and Recombinetics Inc.
Bovine viral diarrhea virus is one of the most significant viruses affecting the health and wellbeing of cattle worldwide. Researchers have been studying it since the 1940s. The virus is contagious among cattle and can cause severe respiratory and intestinal diseases.
Despite more than 50 years of vaccine availability, controlling the virus remains a problem because vaccines aren’t always effective in stopping transmission. But in the past 20 years scientists discovered the main cellular receptor – CD46 – and the area where the virus binds to that receptor, causing infection in cows. Scientists modified the virus-binding site in the recent study to block infection.
Their objective was to use gene-editing technology to slightly alter CD46 so it wouldn't bind the virus yet would retain all of its normal bovine functions, said Aspen Workman, lead author and researcher at the Agricultural Research Service’s U.S. Meat Animal Research Center in Clay Center, Nebraska.
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The scientists first tested the idea in cell culture. After seeing promising outcomes in the laboratory, Acceligen edited cattle skin cells to develop embryos carrying the altered gene. The embryos were transplanted into surrogate cows to test whether the approach might also reduce virus infection in live animals.
It worked and the first CD46 gene-edited calf, named Ginger, was born healthy on July 19, 2021. The calf was observed for several months and later challenged with the virus to determine if she could become infected. She was housed for a week with a bovine viral diarrhea virus-infected dairy calf that was born shedding virus. Ginger's cells displayed significantly reduced susceptibility to the virus, which resulted in no observable adverse health effects.
The scientists will continue to observe Ginger's health and ability to produce and raise her own calves.
The proof-of-concept study demonstrates the possibility of reducing the burden of bovine viral diarrhea virus-associated diseases in cattle by gene editing. The edited calf also represents another potential opportunity to reduce the need for antibiotics in agriculture. The virus infection also puts calves at risk for secondary bacterial diseases. The promising trait is still in the research phase.
The study was published in PNAS Nexus. Visit academic.oup.com– search for “gene-edited calf” – for more information.
