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Anbei der Artikel aus dem Science Magazin für interessierte Leser.

Der Artikel ist insgesamt äußerst positiv. Es wird dann schon deutlich, warum der Kurs angezogen hat und die Handelsvolumen so gross geworden sind (ich rede nur von den US Kursen und Umsätzen, nicht von den künstlich gepushten Vorgängen der Ahnunglosen hier in Deutschland). Außerdem wird klar, warum sich offensichtlich ohne grosse Probleme weitere Investoren finden, die Viragen Liquidität zur Verfügung stellen und dabei sogar Aktien zu einem deutlich über dem aktuellen Kurs liegenden Preis als Gegenleistung akzeptieren. Natürlich muß man auch berücksichtigen, dass insgesamt das Klima und die Bereitschaft für Risikokapital in USA besser ist als in Deutschland. Nach der Pleite mit dem Neuen Markt herrscht hier nur noch Katzenjammer und Panikmache, so dass neue Technoligien auf absehbare Zeit wieder nur in den USA eine Chance haben werden.

Hier mal als Zusammenfassung die Highlights aus dem Artikel:
- seit mehreren Jahrzehnten wird versucht, Gen manipulierte Hühner zu erzeugen, die in den Eiern menschliche Proteine produzieren
- viele Firmen haben ihre vergeblichen Bemühungen, das zu erreichen, eingestellt, ca. ein halbes Dutzend ist übriggeblieben, die weiterhin daran arbeiten
- nach vielen vergeblichen Versuchen ist jetzt nach 20 Jahren der Durchbruch gelungen: 3 verschiedenen Forscher Teams ist es gelungen, in sogenannten `proof-of-priciple` Experimenten nachzuweisen, dass sie genmanipulierte Hühner erzeugt haben, die gewisse Enzyme in ihren Eiern produzieren
- am weitesten sind die Firmen BioAgri und Viragen (zusammen mit dem Roslin Institute)
- Viragen arbeitet an der Genmanipulation der befruchteten Eier, BioAgri an Genmanipulation des Samens der Hähne, um Genveränderte Nachkommen zu erzeugen
- beide Firmen sind aufgrund ihrer Erfolge in Verhandlungen mit Pharmafirmen um Genmanipulierte Hühner zur Erzeugung von menschlichen Proteinen zu entwickeln. Man geht davon aus, dass es bald zu einem Abschluß kommen wird
- sollte man hierbei erfolgreich sein, könnten die Produktionskosten für menschliche Proteine, die zur Herstellung von Medikamenten z.B. gegen Krebs und Virusinfektionen, benötigt werden, um einen Faktor 100 reduziert werden. Für die Firma, die erfolgreich ist, werden die Hühnereier dann tatsächlich zu `goldenen Eiern`, da damit völlig neue Möglichkeiten in der Medikamentenherstellung zur Verfügung stünden.

Fazit des Artikels: Glücklicherweise haben einige Firmen bei der Entwicklung dieser Technologie durchgehalten. Die Früchte können jetzt geerntet werden. Man kann jetzt sehr optimistisch sein.


Falls Viragen auch noch die letzten Hürden nimmt, würde sich die Tür für ein Milliardengeschäft öffnen. Dagegen dürfte die in den letzten Tagen dikutierte Entwicklung eines Impfstoffes gegen SARS wirklich bestenfalls lächerlich sein. Auch der Aktienkurs von Viragen dürfte dann wohl in ganz anderen Regionen stehen.

Wer sich über BioAgri informieren möchte, hier ist der Link: http://www.bioagricorp.com/ Aus der Homepage kann man entnehmen, dass die in 2003 den Gang an die Börse planen.


www.sciencemag.org SCIENCE VOL 300 2 MAY 2003 729

Hatching the Golden Egg:
A New Way to Make Drugs

After 2 decades of work, researchers have succeeded in creating gene-altered chickens that can lay eggs containing human proteins

Chicken farms are among the most pungent places on Earth, but if a few hardy entrepreneurs have their way, it may soon be the sweet smell of success that wafts from buildings housing thousands of transgenic hens. As many as a half-dozen small companies are hoping to turn the common chicken into a pharmaceutical bioreactor, one that can meet the growing demand for protein-based human therapeutics.

The idea is deceptively simple: Insert human genes into chickens and get them to make human proteins in egg whites. "Transgenic chickens should be near-perfect bioreactors for making large amounts of pure recombinant proteins," says Ann Gibbins, an avian biologist at the University of Guelph in Ontario, who did the pioneering studies in the field and trained many of those scientists now achieving success. But, as she found out the hard way, putting the scheme into practice has been tough. Now, after 2 decades of struggles, researchers are reporting numerous successes in making transgenic chickens. The next-generation bioreactor should follow close behind.

As far as the drug industry is concerned, such transgenic chickens will most certainly be laying golden eggs. It`s just a matter of time, drug companies say, before they will be riding a wave of new health products based on manufactured human proteins. Already, they have concocted more than 300 human antibodies in the lab and begun testing them against a variety of human ailments - from cancer to viral infections to immune system disorders. But the companies need a better way to make these products. Current methods can be inefficient: The biotech firm Amgen, for example, has been having trouble meeting demand for its arthritis medication Enbrel, which contains a human protein made by Chinese hamster ovary cells.

The math of making drugs in chicken eggs is appealing. Each commercial hen lays about 250-plus eggs a year, at a nickel apiece. Each egg contains nearly 4 grams of egg white, comprising a mere eight proteins. Get a transgenic chicken to add 100 milligrams of a recombinant protein to that mix, Gibbins says, and the final cost for purified protein should be about $10 per gram, 100-fold less than the cost of current systems using cultured mammalian cells. Compared with other proposed animal production systems - cows or goats, for example - chicken flocks are easy to ramp up in months. There are other benefits as well: Commercial egg farms are already secure enough that a transgenic chicken, for instance, is unlikely to escape into the wild and breed. And there`s a bureaucratic comfort factor: The U.S. Department of Agriculture and the Food and Drug Administration are familiar with eggs as bioreactors because many vaccines, including those against influenza, are already produced in chicken eggs, although not transgenic ones.

Human biology also suggests why eggreactors should work better than alternatives such as bacteria or nonhuman mammalian cells. "Chickens add sugars to finished proteins in much the same way that humans do, something that can`t be said for most other protein production systems, current or envisioned," explains virologist Bill MacArthur, president of GeneWorks, a chicken research firm in Ann Arbor, Michigan. Proteins finished with the human glycosylation pattern are more active biologically.

But for all the potential benefits, "creating a transgenic chicken has proven to be a far greater challenge than we ever expected," says Gibbins. Although reports of success
have appeared in the literature every couple of years, none has panned out. Either the introduced genes failed to carry over into later generations or the chickens failed to produce the desired protein in their eggs. "It left us all thinking that it was going to take some kind of magic to ever make a transgenic chicken egg."

The magicians have arrived. At least three research teams using different methods have now shown that they can make transgenic chickens in proof-of-principle experiments. "Nobody has a transgenic chicken ready to produce a pharmaceutical today, but the field has now gotten to a place where this will happen," says developmental biologist Jim Petitte, whose group at North Carolina State University, Raleigh, developed a transgenic chicken that produces the bacterial enzyme ß-galactosidase in its eggs.

Needle in a haystack

Much of the trouble in creating a transgenic bird arises from some unusual features of avian reproductive biology: the sheer size of the egg and the difficulty of harvesting one before it has begun growing into a chick. The most common way to make a transgenic animal is to harvest a newly fertilized egg and inject foreign DNA directly into this single cell`s nucleus using a microscope and an ultrathin syringe needle. Eggs are easy to harvest when laid, but by that stage the zygote has already grown into a 60,000-cell mass. Harvesting the zygote from the chicken`s oviduct, difficult and expensive in itself, does yield a single cell, but one almost impossible to find within the viscous, yellow yolk.

Helen Sang, an avian molecular biologist at the Roslin Institute in Midlothian, U.K., is
one of the few researchers in the world to have figured out how to harvest a newly fertilized zygote and inject it with DNA or manipulate the 60,000-cell zygote of a freshly laid chicken egg and still get it to hatch into a transgenic chicken. Working with researchers from Viragen in Plantation, Florida, Sang has successfully created transgenic chickens that express a green fluorescent protein and are able to pass the introduced genes on to subsequent generations.

In this proof-of-principle study, Sang`s team used a lentivirus-based gene delivery system engineered at Oxford BioMedica in London to transfer the gene for green fluorescent protein or for ß-galactosidase into the DNA of chick embryos from freshly laid eggs. The injected embryos were then transferred to a host shell whose top had been carefully removed. Plastic wrap sealed the breech in the eggshell, allowing about 30% of the reconstructed eggs to develop and hatch normally. Of the eggs that hatched, 10 were transgenic roosters, evidence that the introduced gene had incorporated itself into the chicken`s DNA. Upon mating, each rooster successfully produced up to 29% transgenic offspring expressing the green fluorescent protein or ß-galactosidase, which Sang characterizes as "remarkably successful … far better than anything we`ve seen before." Using Oxford BioMedica`s lentivirus system, she is now developing a transgenic chicken designed to express a "clinically relevant human monoclonal antibody." By linking the gene for this antibody with the promoter for one of the egg-white proteins, Sang hopes to have it expressed in commercial quantities within the egg white.

Rather than try to manipulate a chicken egg, researchers at BioAgri in City of Industry, California, are working with rooster sperm. The key to this strategy is a monoclonal antibody, developed by BioAgri scientists, that binds specifically to the surface of sperm and allows DNA linked to the antibody to enter the sperm cell and incorporate itself into the sperm`s genome.

Using this sperm gene-transfer technique, developmental biologist Jin Qian and his colleagues have created two different transgenic chickens that produce human interferon a(alpha) and interferon ß(beta). The BioAgri researchers have shown that the interferon genes are stably transmitted across two generations of offspring so far. In addition, their subsequent study using green fluorescent protein linked to the lysozyme gene promoter demonstrated successful gene expression in egg white. The chicks from that experiment are nearing maturity and will be bred to see if this gene is passed to the offspring.

Based on their successes so far, both Viragen, which supports Sang`s work, and BioAgri are now negotiating with pharmaceutical companies to develop transgenic chickens that will make human proteins for clinical development. Petitte, who is not associated with either firm, wouldn`t be surprised if these deals were inked soon, a sign that this field is finally realizing its promise. "In the late `80s, lots of pharmaceutical and biotech companies had transgenic chicken programs because everyone saw the potential for lowering production costs, but they all got off the field when their programs went nowhere," says Petitte. "Fortunately, some of us were stubborn, and now the payoff is here. It`s time to be optimistic."

–JOE ALPER
Joe Alper is a writer in Louisville, Colorado.

Gruß Fraktal
 
aus der Diskussion: Viragen - aktueller Artikel im Science Magazin
Autor (Datum des Eintrages): Frakt@l  (12.05.03 17:52:13)
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