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Quick and Easy, Transgenic Rodents Designed to Order

SANTA CRUZ, California, March 28, 2002 (ENS) - A California company has just launched a service to make and market transgenic animals, and several scientists have started placing orders. If making bioengineered mammals becomes cheap and easy, companies could soon be modifying farm animals or pets as well as lab animals.

A new technique of engineering animals with specified characteristics by injecting DNA directly into an animal's bloodstream has streamlined bioengineering, making creation of designer animals easier and cheaper than ever before.

Biotech company Tosk of San Francisco says it can add genes to mammalian cells with unprecedented efficiency with the help of fruit fly DNA that can jump in and out of chromosomes.

rat

Laboratory rat, not genetically modified (Photo courtesy Megan Mahoney)
Tosk advertises to laboratory researchers who want results faster than competing scientists. "Combining your favorite gene with our patented StealthGene vector lets us rapidly create the transgenic mice and rats you need," Tosk offers on its website.

Until Tosk patented its DNA injection process, genetically engineered mammals have usually been created by injecting DNA directly into an egg. The success rate is low. To get one genetically modified animal, a technician has to carry out dozens of injections and then implant the resulting embryos.

An alternative is to start with ordinary cells and then try to clone the few that integrate the extra DNA, another inefficient process.

Tosk's secret is jumping genes, or transposons, which are found in many organisms, Tosk's chief executive Patrick Fogarty told New Scientist magazine, http://www.newscientist.com .

Transposons are bits of DNA with no function, except for the ability to spread themselves around by moving in and out of DNA with the help of an enzyme called a transposase.

A typical transposon consists of a gene that codes for a transposase flanked by unique marker sequences. When the enzyme is produced, it homes in on the markers, snips out the entire transposon and pastes it elsewhere in the cell's genome, Fogarty explained.

One of the most active transposons is the P-element, found in fruit flies. For decades, scientists have used it to make transgenic flies by replacing the transposase gene with the genes they want to transfer. But nobody could get it to work well in mammals.

Now Fogarty, who left Stanford University to start Tosk, says that by manipulating the structure of the P-element, his team can get it to integrate into up to 80 percent of mouse and human cells in culture.

Tosk terms the genetically engineered animals that result from its procedure "constructs." The company publishes its prices online - mice: US$8,000 per construct; and rats: US$15,000 per construct. A 50 percent academic discount is available.

For extra convenience, Tosk now offers an on-site injection service. "We inject your rodents at your site," the company says. "A minimum of five constructs must be ordered, to be injected at the same facility at one time, to qualify for this service. Payment is due on-site at completion of injections."

Transgenic rodents are used to model human disease processes, and for the biological production of valuable human protein enzymes, hormones and growth factors.

The most controversial aspect of transgenic animal usage involves the "selective improvement" of species by the modification of the genome. The goals of this type of experiment may include decreased body fat, increased speed, novel disease resistance or higher yields of meat or milk.

With this technology, Fogarty aims to streamline drug identification and development to produce drugs that can address the problems of adult onset neurodegenerative diseases such as Alzheimer's, stroke, Parkinson's disease, and dementias. "Tosk is targeting this area," the company says, "because of the large market size, projected market growth, and desperate need for effective treatment."

Other biologists warn that Tosk results have yet to be independently confirmed. "But if it works the way they claim, it's revolutionary," Tom Rosenquist of Stony Brook University in New York told the New Scientist.

Supporters of transgenic mammal production say, as did Carole Lewis writing in "FDA Consumer," January-February 2001, that these animals are "just another class of products" developed through biotechnology."

Some critics feel deeply outraged. "I never imagined people would patent plants and animals," said a Guaymi indigenous man of Panama. "It's fundamentally immoral."

Some are sorting out the implications. Considering the cloning of the first sheep in 1997, R. Albert Mohler, Jr., president of the Southern Baptist Theological Seminary, wrote, "The troubling tangle of ethical issues involved in genetic technologies represents an urgent challenge to the Christian Church as the people of the truth. The new technologies cannot be naively dismissed nor blissfully embraced. This generation of Christians must regain the disciplines of moral discernment and cultural engagement."



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