BEIJING - A transgenic goat capable of expressing active human Factor IX in her milk has entered lactation period in China.

The transgenic goat was created by scientists at the Shanghai Institute of Medical Genetics and the Genetics Institute of Fudan University, of Shanghai. The research is a key project of the State High Technology Research and Development Program, one of the most important state programs helping biotechnology development and commercialization in China.

“In October 1996, we, in collaboration with the Genetics Institute of Fudan University, successfully created five transgenic goats [three male and two female] with the target gene,“ said Huang Shuzhen, professor and vice director of the Shanghai Institute of Medical Genetics and leader of the research group.

“A female has given birth to a baby and she is expressing in her milk human Factor IX, a protein used for treatment of hemophilia,“ Huang said.

Chinese Develop More Efficient Process

The goats were created by adopting traditional transgenic technology. But “the method is wrought with inefficiencies. The probability of success through this method is low,“ Huang noted, for several reasons. One is the male pronucleus from livestock is not as clear as that of laboratory animals, making microinjection hard to target. Another problem is the integration rate of external genes is low. And a third challenge involves the transplanted embryo, which has trouble surviving.

“We have developed a more efficient process to create transgenic goats,“ said Huang. “In vitro fertilization and culturing procedures are adopted to find the best time for microinjection. This raises the survival rate of microinjected sperm to over 95 percent. Then gene determination is made on embryos to select the ones with integrated genes to transplant. Thirdly, an improved transplantation method is adopted to reduce the damage to eggs and to increase chances of pregnancy.“

Huang's group transplanted embryos with human Factor IX genes to the uteri of 32 goats. Sixty days after transplantation, 19 goats were pregnant, and 13 of them are expected to give birth to their babies in April or May.

In theory, the external gene integration rate is 100 percent in these baby goats, said Huang. “By using this technology, we achieve the result of an efficient process that created one transgenic goat from 2.5 attempts on average. The new procedure essentially allows us to use the transgenic goat as a biologic factory for production of biopharmaceuticals in batch.“

China began its research on transgenic animals in 1978. In 1990, an expression system of transgenic rabbits was developed. China's first transgenic goat was born in 1993. The goat was created by researchers at the Developmental Institute of the Chinese Academy of Sciences, in Beijing.

A total of 50 transgenic goats are now living at the Agricultural Institute of Yangzhou University, in Yangzhou, said Lao Weide, a professor at the university and a leader of the research team. “We have integrated two genes, a hepatitis B surface antigen [HBsAg] gene and erythropoietin [EPO] gene, into these transgenic goats. HBsAg was expressed in the milk of goats in 1993, and EPO was produced in larger amounts in 1997,“ Lao noted.

Lao is carrying out research on the bioactivity of the expressed proteins and working toward higher expression of target proteins. *

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