Thursday, January 18, 2007

Drugs Sunny-Side Up

Transgenic hens lay eggs rich in therapeutic proteins.

By Katherine Bourzac

Scottish researchers have bred transgenic hens whose egg whites are rich in therapeutic proteins. Credit: Proceedings of the National Academy of Sciences

Researchers in the United Kingdom have made transgenic chickens that produce concentrated amounts of protein drugs in their egg whites. The finding suggests that genetically engineered chickens may prove to be a cheap alternative to the large-scale manufacture of protein-based drugs, including multiple sclerosis therapies and antibodies that rally the body against cancer.

The transgenic-chicken work, led by Helen Sang, a researcher at the Roslin Institute in Scotland, is the first viable demonstration that chickens can be genetically engineered to make significant amounts of therapeutic proteins in the whites of their eggs.

Therapeutic proteins are primarily manufactured in bioreactors, using vats of bacteria engineered to express a human gene. Bioreactor facilities, however, are expensive to build and maintain. And bacteria can't do everything the human body does. Human cells fold proteins and attach sugars to them. Without this extra care, many human proteins, including important components of the immune system, are inactive. Bacteria do a poor job of folding proteins and can't equip them with sugars.

"It's very expensive to do [these steps] after the proteins are made," says Karen Jervis, vice president of Viragen Ltd. Scotland, whose scientists were involved in the transgenic-chicken research. "So companies have chosen to make proteins that don't need sugars, and this restricts what's on the market."

Transgenic hens could provide a solution. The Roslin and Viragen scientists engineered chickens to make either of two human proteins: an antibody to melanoma or a type of interferon that is currently used to treat multiple sclerosis. First, they created versions of each human gene containing regulatory elements that ensured that the proteins would only be made in the subset of chicken cells that secrete egg-white proteins. Then they put this gene into a weakened virus and injected male chicken embryos with the virus. When the chicks became roosters, the scientists bred them with hens. The hens from this generation laid eggs with high concentrations of the proteins. Importantly, the ability to make the drugs in the egg whites is heritable.

Yashwant Deo, CEO of Athens, GA-based AviGenics, a private company also developing transgenic protein-producing hens, notes that the pharmaceutical industry has safely produced vaccines, including those for the flu, in eggs for years--not through transgenic manipulation but because viruses grow well in eggs. At five cents an egg, the system is cheap. "Making the transgenic bird is complex," Deo says. "Beyond that is chicken breeding."

Researchers are also developing transgenic mammals, such as goats that produce therapeutic proteins in their milk, as potential alternatives to bacterial bioreactors. Indeed, one company, GTC Biotherapeutics, based in Framingham, MA, has a drug for treating a hereditary blood-clot disorder on the market in Europe that's produced in the milk of transgenic goats.

However, Sang says, drug-laying hens will likely have advantages over transgenic mammals "in terms of cost and speed of production. They breed faster because they have a shorter reproductive cycle." There is also some evidence, says Jervis, that proteins made in chicken eggs may be more effective than those made in goats' milk because the way chickens add sugars to them may more closely resemble the way humans do. "There are so many protein drugs coming along," says Sang. "The pharmaceutical industry needs choices."