How a new technique to create transgenic chickens could have us cracking eggs for the next miracle cure.

origenchicken.jpg Can you guess which chick is transgenic?  Courtesy of Robert Kay, Origen Therapeutics

Move over lab mice, it’s time to make room for an invasion of “lab chickens.”

Origen Therapeutics, a California biotechnology company, has developed a new method to create transgenic chickens—fowl that express genes from other organisms. The new technique, which the company revealed in the June 8th issue of Nature, may make the squawking barnyard birds as easy to genetically manipulate as that workhorse of animal research, the mouse.

“This is the first time that we’ve had an open slate to make genetic modifications to the chicken,” said Robert Kay, Origen’s president and CEO.

Previous procedures for creating transgenic chickens put limitations on the size of a gene that could be inserted or gave scientists little control over where it would end up in the genome. Origen’s innovative process involves manipulating primordial germ cells—the precursors to sperm and egg cells—allowing scientists to create chickens that give birth to offspring with a wide range of potential new genes and traits.

The research team, a coalition of scientists from Origen and the University of California, Davis, extracted and cultured primordial germ cells from the blood of chicken embryos. By using a unique combination of growth factors, the researchers were able to coax chicken germ cells to proliferate on the lab bench, a process that, according to Kay, remains arduous.

The scientists then modified the germ cells by inserting a sequence of DNA that produces a protein that glows green under ultraviolet light. The germ cells were then re-inserted into the embryos, which were allowed to develop normally.

When the resulting chickens had offspring, they passed along the green gene via their sperm or eggs. Under UV light, the offspring glowed green, verifying that their bodies were making the new protein, and that a new line of permanently altered chickens had been produced.

When compared to other techniques, such as the use of viral vectors to embed foreign DNA, Origen’s method allows scientists to modify the chicken genome in a more targeted way and to insert considerably longer sequences of DNA, noted James Petitte, a poultry scientist at North Carolina State University

“It’s a step forward, there’s no question about it,” said Petitte, who has experimented with older methods for creating transgenic birds. Petitte also said that this new technique could eventually make chickens as useful to geneticists as mice.

Kay agreed with Petitte’s analysis, pointing out that green chickens are just a novelty and a test case. The real breakthrough is the ability to make a genetic modification to a chicken that will be transmitted through generations because it would have enormous practical potential for both agriculture and medicine. The method presents an opportunity to enhance chickens, genetically modifying them to be resistant to certain diseases—even avian flu.

origenembryo.jpg A transgenic embryo Courtesy of Robert Kay, Origen Therapeutics

Transgenic chickens could also be used to produce human proteins, such as antibodies or growth hormones, which would allow for a flock of transgenic chickens to lay eggs from which these substances could be extracted and, potentially, turned into pharmaceuticals.

“There are people who want to make proteins of very high medicinal importance,” said Perry Hackett, a geneticist at the University of Minnesota. “If you can get an animal to make it and secrete it, you should be able to get a quality protein for a whole lot less money. That’s one of the major drivers of making transgenic animals.”

Scientists can already create transgenic goats and cows that secrete human proteins in their mik, but producing such animals remains controversial. Hackett eventually quit studying transgenic fish because he faced so much opposition. Critics argue that genetic engineering is immoral, or that transgenic animals will escape from the laboratory and breed in the wild, allowing their modified genes to enter the natural environment.

Aside from ethical concerns, it will be a while before transgenic animals truly become usable pharmaceutical factories. Even if the relevant proteins can be produced and collected, many phases of testing will be required before they could be used in humans. So far, according to Kay, no human protein produced by any transgenic animal has been approved for medical use.

“Right now everything’s in the laboratory phase,” Petitte said. “It’s going to be a while before we see them commercially.”

But scientists remain optimistic—particularly about chickens. Eric Wong, a molecular biologist at Virginia Tech who participated in a project to create transgenic turkeys, points out that chickens reproduce quickly, can be bred for high egg production and are especially well suited to produce human proteins.

According to Kay, a 5,000-chicken flock could lay eggs containing a total of up to 100 kilograms of human proteins a year.

“The egg is a very nice vehicle for producing these proteins,” he said.

Originally published June 11, 2006

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