Portland Ore. -- Researchers at Oregon Health Sciences University report dramatic progress toward establishing genetically modified, non-human primate models for the study of causes and cures for human disease. Scientists were able to do this by perfecting a technique called TransgenICSI, which has allowed them to introduce new genetic information into the eggs of monkeys. The research was conducted by Anthony Chan, Ph.D., a staff scientist at OHSU's Oregon Regional Primate Research Center, and colleagues in a lab coordinated by Gerald Schatten, Ph.D., professor of obstetrics and gynecology, and cell and developmental biology in the OHSU School of Medicine. Their findings are printed in the latest issue of Molecular Human Reproduction.
Currently, genetically modified or transgenic mice are used by researchers for investigations into the molecular basis of diseases such as Alzheimer's, cystic fibrosis, diabetes and muscular dystrophy. However, many researchers agree mice are not perfect model systems to investigate human disorders. This need has prompted research into developing a more suitable model for studying human disease in monkeys.
Researchers at OHSU were able to insert DNA material into the monkey eggs by attaching foreign genes to the outside of monkey sperm. The scientists inserted DNA from jellyfish that encodes a gene for a glowing green protein. The DNA was then inserted into the egg using an innovative procedure adapted from infertility clinics called intracytoplasmic sperm injection or ICSI. Within two days, almost half of the monkey embryos displayed a green glow.
Seven of these genetically modified embryos were then transferred to recipient rhesus monkey females. This resulted in George, a normal male monkey. Although integration of the foreign gene into George's genetic material has not been detected yet, his birth proves that TransgenICSI is a viable method to ultimately produce genetically modified models for human disease.
A study earlier this year by a group at the University of Hawaii, led by Ryuzo Yanagimachi, Ph.D., involves the production of transgenic mice. Using the same procedure, researchers in Hawaii showed only a small percentage of animals displayed characteristics of introduced DNA later in life. This information suggests that the odds of producing transgenic monkeys as disease models will improve as protocols are refined.
Another finding of this research is that foreign DNA bound to the surface of a sperm can be transmitted during ICSI. Although this has not yet been proved to be a clinical risk, this indicates that further steps may be necessary to improve the safety of this infertility therapy.
Recently, experimental gene therapy trials in humans resulted in the tragic death of an Arizona man at the University of Pennsylvania. Schatten points to this tragedy in explaining the importance of this work. "This tragedy underscores the urgency of obtaining non-human primate models before testing begins on some desperately ill patients," said Schatten. "While gene therapy promises cures for devastating diseases, the protocols for using it and even its safety are not yet perfected. Non-human primate models are the best way to learn the benefits and risks of gene therapy."
Journal
Molecular Human Reproduction