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Glowing prospects for gene therapy or just a lot of monkey business?

American scientists from the Oregon Health Sciences University (OHSU) have perfected a new technique, that can create genetically modified nonhuman primate (NHP) models that will ultimately lead to a better understanding of genetic diseases in humans such as breast cancer, HIV and Alzheimers. The study is reported in this month's journal Molecular Human Reproduction.

 

Hydromedusan - Aequoria

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Researchers have successfully placed jellyfish genes into rhesus monkey macaque embryos. The jellyfish gene, derived from a type of bioluminescent hydromedusan (Aequoria) see pictures, was chosen because it instructs cells to produce a green flourescent protein (GFP) that acts as a kind of biological marker. When studied under ultra violet lighting the gene displays a green glow, making it relatively easy to track whether it has been transfered into a target embryo. The experiment was also designed to study the safety of a technique that is widely used in fertility clinics to help infertile men father biological children. The innovative proceedure (Intracytoplasmic Sperm Injection - ICSI) inolves using a fine needle to inject the man's sperm cells one at a time into the mother's egg cells.

In this experiment the OHSU researchers, under the direction of Gerald Schatten (lab coordinator and developmental biologist), first mixed the sperm of a rhesus monkey in a dish with strands of DNA containing the jellyfish gene. The DNA stuck to the outside of the rhesus sperm and was then transfered, via injection, into the egg cells. This successful transfer poses a potential area of risk in infertility treatments, because normally the membrane surrounding an egg excludes such alien DNA from viruses and other contaminants. "ICSI gets around a barrier to infections that we hadn't previously known existed," said Schatten, also adding that fertility clinics may need to develop ways to decontaminate sperm before attempting to inject them into eggs.

Within two days, more than one third of the monkey embryos produced by using the technique had begun to produce the flourescent green protein. In total, twenty genetically modified embryos were then transfered into the wombs of recipient rhesus monkey females. This experiment resulted in five pregnancies and three healthy male offspring. One of which is called ANDi (inserted DNA spelled backwards)

The presence of the foreign gene in ANDi has been verified by DNA analysis and his birth proves that transgenICSI is a viable method to ultimately produce genetically modified models for human disease. Such transgenic monkeys could be used to investigate the molecular basis of diseases such as cystic fibrosis, Alzheimer's, diabetes and muscular dystrophy which are currently being investigated using transgenic mice.

 

Bioluminescent bell of Aequoria

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This experiment fuels the debate of genetic engineering in humans. However, researchers at OHSU's primate centre said that they doubted that the same technique they used could be used to put new genes - for instance ones believed to correct or prevent diseases - into human embryos. Gerald Schatten claimed that "we do not support extending any of this in humans", also empasising the fact that "our goal is in making fertility treatments safer and creating better disease models for studying devastating human disorders."

Hydromedusan with streaming tentacles - Aequoria

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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 were published in the Jan. 12 2001 issue of Science.

 

   Learn more about the applications of GFP  Molecular Human Reproduction Online

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