Gene-Edited Calf Shows Promise in Reducing Bovine Viral Diarrhea Virus (BVDV) Infections: A Breakthrough in Cattle Health

2023-08-07 20:09:00

Bovine Viral Diarrhea Virus (BVDV) is one of the most dangerous pathogens affecting the health and welfare of cattle worldwide, costing US industry billions of dollars each year. First identified in the 1940s, BVDV can be disastrous for pregnant cows as it can infect developing calves and often leads to miscarriages and low birth rates.

While some calves infected with BVDV manage to survive, they remain infected for life and transmit massive amounts of virus to other cattle. Moreover, although vaccines against the virus have been available for more than half a century, they are not always effective in stopping transmission.

Over the past two decades, scientists have succeeded in identifying the main cellular receptor (CD46) and the area where the virus binds to this receptor, causing infection in cattle. Now, a team of researchers led by the USDA’s Agricultural Research Services (ARS) have used gene-editing technology to slightly modify CD46 so that it doesn’t bind to the virus, while retaining all of its normal functions in cattle.

After successfully testing this idea in cell cultures in the lab, the scientists collaborated with Acceligen – a company specializing in precision breeding technology aimed at improving animal welfare and disease resistance – to genetically edit bovine skin cells in order to develop embryos carrying the modified gene. The team then transplanted the embryos into surrogate cows to assess whether this approach could reduce viral infection in live animals.

The technique proved to be very effective and the first CD46-modified calf, named Ginger, was born healthy on July 19, 2021. After keeping the calf under observation for a few months, experts housed it for a week with a BVDV-infected dairy calf that was born shedding the virus.

Ginger cells showed significantly reduced susceptibility to the virus, which resulted in no observable adverse health effects. While these results are very promising, scientists will continue to closely monitor Ginger’s health and ability to produce and raise her own calves.

This proof-of-concept study demonstrates the revolutionary possibilities of gene editing technology to reduce the burden of BVDV in cattle.

At the same time, since BVDV infection exposes calves to secondary bacterial infections, the use of gene-editing technology to breed cattle resistant to this virus may also reduce the need for antibiotics. in agriculture.

The research is published in the journal Nexus PNAS.

Learn more about gene editing

Gene editing is a group of technologies that gives scientists the ability to alter an organism’s DNA. These technologies make it possible to add, delete or modify genetic material at specific locations in the genome. Several genome editing approaches have been developed.

One of the best known is CRISPR-Cas9, which stands for “Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-associated protein 9”. The CRISPR-Cas9 system has generated a lot of excitement in the scientific community because it is faster, cheaper, more accurate and more efficient than other existing genome editing methods.

CRISPR-Cas9 was adapted from a natural genome editing system in bacteria. Bacteria capture DNA snippets from invading viruses and use them to create DNA segments known as CRISPR chips.

CRISPR chips allow bacteria to “remember” viruses (or closely related viruses). If the viruses attack again, the bacteria produce RNA segments from the CRISPR chips to target the viruses’ DNA. The bacteria then use Cas9 or a similar enzyme to split the DNA, which disables the virus.

In the lab, scientists create a small piece of RNA with a short “guide” sequence that attaches (binds) to a specific target sequence of DNA in a genome. RNA also binds to the Cas9 enzyme. As in bacteria, the modified RNA is used to recognize the DNA sequence and the Cas9 enzyme cuts the DNA at the targeted location.

Although Cas9 is the most commonly used enzyme, other enzymes (like Cpf1) can also be used. Once the DNA is cut, researchers use the cell’s own DNA repair machinery to add or remove pieces of genetic material, or to make changes to the DNA by replacing an existing segment with a DNA sequence. personalized DNA.

Gene editing is considered a type of genetic engineering. Other methods of genetic modification include gene targeting, zinc finger nucleases (ZFNs), and transcription activator-like effector nucleases (TALENs).

The applications of gene editing technologies are vast and include correcting genetic defects, treating and preventing the spread of disease, and improving crops. However, it also raises ethical questions, especially when it comes to editing the human genome. For example, there are concerns about its potential use in creating so-called “designer babies” with specific traits, such as intelligence or athletic ability.

There are also potential risks, such as off-target effects (unintended DNA changes), and the long-term effects of gene editing are still largely unknown. It is a rapidly evolving field with enormous potential, but it also requires careful regulation and monitoring.

Par Andrei Ionescu, Terre.com Personal editor

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