A major advance towards producing prion-free cows that would be immune to mad cow disease has been made by researchers at companies in the US and Japan.
Their principal aim is to make genetically modified cattle that produce pharmaceuticals in their milk. But the companies hope that also making the animals resistant to BSE (bovine spongiform encephalopathy) will reassure consumers.
The researchers have now achieved the considerable feat of creating cell lines which have both copies of the cow’s PrP gene switched off. The PrP protein can be switched to an infectious state by contact with a mutated prion. This switch causes prion diseases such as BSE in cows and variant Creutzfeldt Jakob Disease (vCJD) in humans.
Making live animals from these cell lines should be relatively straightforward using cloning techniques similar to those that created Dolly the sheep.
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The companies say they have no intention of producing prion-free animals destined for human consumption. Instead they want to assuage public fears about pharmaceuticals derived from cow’s milk, even though the process used to extract proteins from milk has already been shown to remove prion contamination.
Consumer choice
“Because of public perception, we feel an added benefit would be to knock out the gene and remove the possibility that the animals could be infected,” says James Robl, chief scientific officer at US biotech company, which carried out the research jointly with the Kirin Brewery in Tokyo, Japan. “Japanese consumers have a high degree of concern about BSE.”
Some experts have suggested creating prion-free cattle to eliminate BSE from the beef herd. But it is not clear that consumers would prefer genetically modified beef over meat that has a very small chance of infection with prions. To date there have only been around 140 cases of vCJD in total worldwide, although the ultimate extent of the human epidemic remains uncertain.
Furthermore, replacing beef herds with prion-free cattle would take decades. “Getting a herd of any size would be quite difficult,” says Harry Griffin at the Roslin Institute in Scotland, where Dolly was cloned.
Another question mark hangs over what effect knocking out both copies of PrP will have on cows. Mice lacking both copies appear to be normal, although some disputed research suggests they may have disrupted sleep patterns.
Low yield
Hematech and Kirin’s aim is to produce cows that produce human antibodies that can be harvested from the animals’ milk. These could be used to treat people with specific infections for which there are no vaccines.
In 2002, they engineered a mini chromosome carrying the human antibody gene into cows. But, because the cattle still had their own version of the gene, the yield of human antibodies was low.
They have now managed to create around 150 cow embryos which have both copies of the bovine antibody gene knocked out. These will be born in 2005, and some have also been engineered to include the human version. The companies hope they will produce a better yield of human antibodies.
The prion-free cell lines also lack both copies of the bovine antibody gene, but Hematech has yet to clone these to produce embryos.
Although sheep with one copy of the PrP gene switched off have already been created at the Roslin Institute, it has proved difficult until now to knock both genes out in livestock animals.
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