Gene therapy speeds transgenic animal production
By Kwok Wan
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05/02/2008 - Researchers can now reduce the cost and time taken to breed goats that can produce therapeutic proteins using gene therapy. Experts say these transgenic animals could cut the cost of insulin and other cancer-fighting proteins.
Current methods of producing such animals involves microinjection and cloning, which is a more expensive and longer process.
"Having an easier way to harness nature's power to produce large quantities of specific proteins in milk could increase the availability of drugs for people who could otherwise not afford these treatments," said Ina Dobrinski, associate professor at the Center for Animal Transgenesis and Germ Cell Research at University of Pennsylvania, USA.
The scientist conducted their study by exploring whether exposure of mammalian germ line stem cells (the cell that produces sperm) to adeno-associated virus (AAV), a gene therapy vector, would lead to stable transduction and transgene transmission.
"To broaden the applicability of the results for different mammalian species, the approach was then applied to a large animal species in which germ cell transplantation-mediated transgenesis would provide an important alternate approach to the generation of transgenic animal models for biomedical research," said Prof Dobrinski.
To produce the larger transgenic animal, radiation was first used to kill a section of the male goat's germ cells. A modified AAV was then used to insert a gene into the remaining cells. When the gene took hold, then the male goats were mated with wild-type female goats. The researcher found that 10 per cent of the resulting offspring carried the transplanted germ cells, meaning the genetic modification had been passed on.
Not only is this is the first time that AAV-mediated transduction of mammalian germ cells leads to transmission of the transgene through the male germ line, but also the first report of transgenesis via germ cell transplantation in a non-rodent species. This means it might also be a possible approach to generate transgenic large animal models for biomedical research.
According to their paper in published the Federation of American Societies for Experimental Biology, other applications of the research could be used to boost food supply by reducing genetic disorders in animals over several generations. Some speculate that once the technique is refined, it could eliminate disease genes in humans over several generations, though this could bring up ethical concerns which would have to be resolved.
Currently, transgenic animals are generated with somatic cell nuclear transfer or pronuclear injection. These methods are inefficient and also carry a risk of producing offspring with developmental abnormalities. The use of retroviral or lentiviral vectors have been effective in rodents, but it requires them to be handled under strict biosafety precautions and therefore not practical for transgenesis in large animal.
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