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By Sean Henahan, Access Excellence

LONDON, England- (24 July 1997)- Move over Dolly, and make room for Polly, the first sheep cloned by nuclear transfer technology bearing a human gene. Investors hope the lamb will make them a mint, but more importantly, the arrival of Polly could be good news for hemophiliacs and others who rely on expensive protein therapy of their diseases.

Polly was created by the same team at the Roslin Institute that gained fame earlier this year with the birth of Dolly, the first sheep cloned using adult animal cells. In Polly's case, the researchers did not use adult cells. Rather, they used fibroblast cells obtained from a sheep fetus. This is considered a somewhat less tricky procedure. However, Polly is the first sheep to receive genetically altered fetal cells, in this case modified with a human gene. The human gene was introduced into the nucleus of the lamb fibroblast which was then inserted in an enucleated donor ovum.

The current technique represents a significant advance over techniques currently used to produce transgenic animals. The current technology involves placing target genes from one species into the fertilized egg of another, and then waiting to see if the gene is expressed. This laborious process produces results about ten percent of the time at best. Since fertilized eggs are in short supply, the ability to use the more common fibroblast cells could increase the success and efficiency of cloning transgenic animals.

Graphic: Cloning Dolly. Polly also contains a human gene.

Five lambs were produced by the new technique. The scientists have so far found marker-genes in two of five lambs. These marker genes confirm that that the human gene was expressed in the sheep. While the researchers report that the gene inserted in the sheep is of "therapeutic value" they have yet to reveal what gene it is. The researchers took the controversial step of announcing their findings in a press release rather than in a peer-reviewed journal.

The Edinburgh company that sponsors the research, PPL, already produces transgenic sheep that produce alpha-1-antitrypsin, a protein used to treat the symptoms of cystic fibrosis.  Transgenic sheep have also been genetically engineered to produce proteins used by patients with clotting disorders such as hemophilia, including fibrinogen, factor VII and factor IX.

The new cloning technology will allow scientists to create large numbers of identical, milk-producing ewes. Using genetic engineering, the sheep can be modified to produce therapeutic proteins in their milk. These expensive proteins can then be removed from the milk and used therapeutically.

"This is a realization of our vision to produce instant flocks or herds which express high concentrations of valuable therapeutic proteins very quickly," Alan Colman, PPL's research director, told the media. He estimated the company could be selling therapeutic proteins from cloned sheep in about two years.

It is more than likely that rather than produce expensive herds of cloned sheep, the researchers would create a small number and then let nature takes its course, allowing the animals to breed naturally. Finding out how well the target genes carry from generation to generation is of great interest to the investigators.

They won't be selling anything produced by the first batch of transgenic sheep. This is because of concerns about scrapie infection, a sheep disease believed to be related to BSE, or mad-cow disease. The five experimental lambs did not come from a a scrapie-free herd. This problem highlights the downside of transgenic animal cloning, since there is some concern that humans could become infected with viruses or prions from the animals.

On a more positive note, the new research may open the way for scientists not only to add desired genes, but to remove undesired genes. This would be essential for removing antigens pig organs that might some day be used as replacement parts in humans.

Related information on the Internet
AE: Dolly Cloning Article
AE: Monkey Clone
AE: Tissue Generation and In Utero Surgery
AE: Chicken-Brain Exchange
Roslin Institute
Dolly Article in NATURE
Previous Wilmut Nature Article on Nuclear Cloning
AE Activity: Cracking the Code, Cloning Paper Plasmid

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