Contact: Lynn Odell
NYU Medical Center
(212) 263-5488
Tara Weaver
USDA
(301) 344-2824
A New Source of Medicines-Animal Urine
New York, NY -December 22, 1997-Scientists at NYU School of Medicine and the United States Department of Agriculture have, for the first time, coaxed animals to produce a human protein in their urine, a discovery that could lead to a new and vastly less expensive method to obtain rare therapeutic proteins for a range of human diseases.
The research team, led by NYU's Tung-Tien Sun, Ph.D., and the USDA Agricultural Research Service's Robert Wall, Ph.D., bred mice carrying a human gene that could only be turned on in the animals' bladder tissues. The animals then produced the gene's product, a human protein, in their urine, creating, in effect, a pharmaceutical factory. Genes contain the instructions for making proteins.
The team's findings are reported in the January issue of the journal Nature Biotechnology.
"We are very excited," said Dr. Sun, the Rudolf L. Baer Professor of Dermatology at NYU School of Medicine. "Using the bladder to manufacture pharmaceuticals could potentially reduce the huge costs of drugs, and save many lives. "Although it is still early, the bladder could become as important as the mammary gland as a source of therapeutic proteins."
Herds of "transgenic" goats and other animals, which carry foreign genes in their cells, are already being used to produce medicinal human proteins like Factor VIII -a treatment for hemophilia--in their milk. Conventional bioreactors require huge vats of genetically engineered bacteria or yeast to generate rare human proteins and are enormously complex and expensive. By comparison, transgenic animals provide a far cheaper and more manageable source of pharmaceuticals.
Until now, there has never been a report of a transgenic animal secreting a foreign protein into its urine. There already is a precedent for using urine as a source of pharmaceuticals. Premarin, a hormone-replacement drug for menopausal women and the most widely prescribed drug in the United States, is derived from the urine of pregnant mares.
Urine offers three major advantages over milk as a source of pharmaceuticals, according to Dr. Sun. First, milk can only be obtained from female animals, while all animals, regardless of gender, produce urine. Second, only female animals that have reached sexual maturity produce milk, while urine can be obtained throughout the entire lifespan of an animal, offering a steadier supply of therapeutic proteins. Third, the pharmaceutical product in milk has to be extensively purified because milk is filled with fat and protein, while urine contains little fat and protein, simplifying the purification of the product.
In their new study, the NYU-USDA team used a short piece of mouse DNA called a promoter, a sort of zip code, attached to a human gene for human growth hormone. The promoter itself was derived from a gene for a protein, called uroplakin II, found only in the uppermost tissue layers of the mouse bladder. The promoter ensures that the human gene will only be turned on in mouse bladder epithelial tissue. The genetically engineered construct was then injected into mice embryos and implanted in donor mice primed for pregnancy.
Nine transgenic mice were produced, and from some of these animals the team established three separate lines of transgenic mice. The mice successfully produced a steady amount of human growth hormone for more than eight months.
The research team also included David E. Kerr and Kenneth R. Bondioli formerly of the USDA, and Haiping Zhao, Fengxia Liang, and Gert Kreibich from NYU School of Medicine.
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