OHSU Researchers Produce First Genetically Modified Monkey
01/11/01 Portland, Ore.
Researchers at Oregon Health Sciences University report the production of the world's first genetically modified nonhuman primate as an important step toward designing and perfecting new treatments for human genetic disorders. This research was conducted by Anthony Chan, Ph.D., a staff scientist at Oregon Regional Primate Research Center and colleagues. Scientists were directed by Gerald Schatten, Ph.D., a senior scientist at the ORPRC; research director of the Center for Women's Health; and professor of obstetrics and gynecology, and cell and developmental biology, in OHSU's School of Medicine. These results will be published in the Jan. 12 issue of Science.
Currently mouse models are utilized for investigating many genetic disorders ranging from muscular dystrophy to cancer. However, many of these mouse models do not accurately mimic symptoms found in patients affected by these diseases. This need has prompted development of improved disease models in monkeys.
gfp insertion process (quicktime)
ANDi, (inserted DNA, spelled backward), is the first genetically modified rhesus monkey produced using techniques commonly utilized for genetic modification in other animals as well as in human gene therapy. DNA was introduced to monkey eggs through a neutralized retroviral vector, which carried a foreign gene, GFP (green fluorescent protein). After the foreign DNA was introduced, eggs were fertilized by intracytoplasmic sperm injection (ICSI). A total of 20 embryo transfers resulted in five pregnancies and three healthy male offspring, including ANDi. The presence of the foreign gene in ANDi has been verified by DNA analysis.
Scientists chose GFP due to its common use and documented safety in animals. While genetic testing has revealed the presence of this foreign DNA in accessible cells throughout the monkey, ANDi is healthy and is being reared in dedicated group housing with other rhesus monkeys at OHSU's Oregon Regional Primate Research Center.
"ANDi's birth along with last year's birth of Tetra, the first rhesus cloned by embryo splitting, is another incremental step in accelerating the discovery of innovative cures for devastating diseases. These diseases range from diabetes and Alzheimer's to breast cancer and HIV," said Schatten. "By developing cloned, genetically modified and stem-cell-derived primate models, scientists will be able to carefully and rigorously test the most innovative therapies, using the fewest animals, so that these treatments are perfected and optimized before being used to treat humans."
Judith Vaitukaitis, M.D., director of the National Center for Research Resources at the National Institutes of Health, notes the significance of this research toward developing and using animal models that are similar to humans. "While the mouse model can be credited with countless breakthroughs, scientists are increasingly turning to higher research animal models in order to develop new human gene transfer therapies. The modified monkey model helps bridge this gap. It provides a much needed animal model of a human disorder that allows scientists to test whether or not the level of expression of the transferred gene can correct for the patient's missing or malfunctioning gene and can assess whether the gene transfer vectors have any significant side effects." The NCRR and the National Institute of Child Health and Human Development, two institutes of the National Institutes of Health, funded this research.