Thursday, January 25, 2007

How would you like your meds? Scrambled or over easy?

By Karla Gale
NEW YORK (Reuters Health) - British scientists have succeeded in producing multiple generations of genetically altered, or transgenic, hens that produce functional pharmaceutical proteins in the whites of their eggs.

To transfer drug-making genes into chickens, Dr. Helen M. Sang, from the Roslin Institute in Midlothian, UK, and her associates used a lentivirus carrier from which all viral coding sequences were deleted. The genetic material was replaced with the gene regulating ovalbumin production combined with genes for making human interferon or an antibody targeting malignant melanoma.

"This construct is used to incorporate new protein genes into the chicken chromosome," Dr. Sang told Reuters Health. This was accomplished by injecting the lentiviral vector containing the coding sequences for the desired pharmaceutical protein into the fertilized embryo of a new laid egg.

When the resulting chick is old enough, it is then bred it and the offspring examined. "If the offspring are transgenic, we will see the new genes in every cell of their body, but only expressed in the oviduct," Sang continued.

In their paper in the early edition of the Proceedings of the National Academy of Sciences, the researchers explain how a single transgenic cockerel was crossed to normal hens. Of 463 chicks they examined, 19 (4 percent) were transgenic.

When transgenic hens lay eggs, the foreign protein is expressed in the oviduct where the egg white is made. In the case of interferon produced in egg white, the researchers were able to confirm that the compound was functional by showing that it was active against a test virus.

Sang hopes that using transgenic chickens to produce therapeutic proteins will "bring down the costs of drugs that currently are prohibitively expensive."

The Roslin Institute, renowned for its creation of Dolly the cloned sheep 10 years ago, is working in collaboration with gene therapy company Oxford BioMedica and biotech company Viragen to develop their transgenic chicken system as a large-scale biomanufacturing alternative for a variety of proteins.

"But it is still early days yet," said Sang. "We've made significant steps in developing a process that we hope will be an alternative production platform for protein drugs."

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