A new way to modify chicken genes

Scientists have found a new route to genetically modifying chickens, with implications not just for meatier drumsticks, but also new medicines and fowl resistant to avian flu.

Researchers at the University of California-Davis and Origen Therapeutics in Burlingame, Calif., showed that the earliest germ cells — which normally mature into sperm or eggs in chicken embryos — can be harvested, modified and reinserted in embryos, where they pass along the newly introduced traits to the next generation.

The key is assuring that the modified cells continue to fulfill their reproductive role, said Marie-Cecile van de Lavoir, a senior scientist at Origen and lead author of a report on the research, published Thursday in the journal Nature.

“As a result, we can now take transgene designs that work well in model systems and breed flocks of birds depositing therapeutic proteins in their eggs,” she added.

Humans, chickens and all other vertebrate animals are made up of two general types of cells: somatic, or body, cells, which form tissues and organs; and germ, or reproductive, cells that form sperm and eggs.

In the early embryo, only a few cells — known as primordial germ cells — become sperm or eggs in the adult animal. Previous attempts to culture such cells from mice and humans produced embryonic germ cells that looked and acted like embryonic stem cells.

The chicken was the first species from which the germ cells could be isolated and genetically modified while still retaining their reproductive programming.

The researchers believe their advances should make it as easy for scientists to produce genetically altered chickens as it has become to genetically manipulate mice.

“We anticipate it will have a tremendous impact on developmental biology research, enabling scientists to readily study various genes of interest,” said Mary Delany, a co-author and professor and chairman of UC-Davis’ animal-science department.

“The chicken has long been an important model organism for developmental biology, and this makes a great model even better.”

On the more practical side, “this system has promise for agricultural applications to introduce genes for beneficial traits such as disease resistance, and, in the pharmaceutical industry, to introduce genes for human proteins that have therapeutic value,” Delany explained.

Normally, breeding a new trait or gene mutation into a line of chickens would take years; the new method could produce modified chicks in a matter of weeks.

Origen scientists have already shown that therapeutic human proteins can be produced in chicken eggs, publishing research last year on the production of antibodies that greatly enhanced cancer-killing activity compared to antibodies produced by conventional means.

The new study, sponsored largely by the National Institutes of Health and the U.S. Department of Agriculture, began with 12 male cell lines derived from 114 embryos of Plymouth Rock chickens, a breed distinguished by black-and-white striped feathers.

After growing the cells in culture dishes, the researchers confirmed that they were still configured for reproduction. They also found that the cells retained the genetic mechanisms for unlimited cell replication.

Then, to demonstrate that the cells maintained their dedicated purpose to become sperm or eggs, the researchers injected cells from the cultured lines into the embryos of white-feathered leghorn chickens.

Twenty-four embryos, carrying cells from both the leghorns and the Plymouth Rocks, were raised to adulthood. Those birds were then mated to other leghorns, but produced offspring that carried the black-and-white striped feathers, confirming that the injected cells had remained viable and were able to pass along a physical characteristic to the next generation.