Producing a transgenic chicken was no easy task. To ensure that the genetic modifications are passed on to offspring, they must be incorporated in the germline. A chicken’s embryonic stem cells do not contribute to the germ line, as they do with animals such as mice, and their primordial germ cells, which can differentiate into sperm and egg cells, were known to be notoriously difficult to grow in culture.

 

However, researchers at Origen developed new techniques and were able to grow the cells in the laboratory. The next step, funded by the NIST grant, will be to genetically engineer the primordial germ cells to create birds in which the chicken antibody genes will be replaced with human counterparts. These chickens, when exposed to antigens, will produce human polyclonal antibodies, in contrast to non-transgenic chickens, which would produce avian antibodies that would trigger an immune response in humans.

 

So why go to all the effort of developing transgenic chickens, rather than mammals? Because chickens have their own built-in production technology. As part of the normal process, chickens pass antibodies on to their chicks in the yolk to protect the young bird. Once the chicken’s immune system has been modified, the immunized chicken will produce eggs with yolks rich in human monoclonal antibodies, and will pass this ability on to its offspring.

 

Compared with the high-cost fermentation process required to produce monoclonal antibodies, the expense of housing the chickens and extracting the antibodies should be relatively low. Once the polyclonal antibody-laden eggs are produced by the chickens, the method of extraction is relatively quick and simple. The food industry has already developed high-speed machinery to separate the whites from the yolks. The yolks are then mixed with cold water and allowed to settle, and the polyclonal antibodies remain in the aqueous supernatant in a high concentration. The antibodies can be extracted using standard protein purification processes.

 

These high-tech chickens have come a long way since the time of the ancient Egyptians, who used chicken soup as a cure for the common cold, and Avicenna, a 10th century Persian physician, who wrote about its curative powers. In some ways, by using chickens as little mobile antibody factories, Origen Therapeutics is just carrying on the tradition.