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Friday, January 26, 2007

How Scientists Inserted Genes Into Chickens to Make Drugged Eggs

To make new pharmaceutical drugs, you have to break a few eggs.

In this case, you have to break a few genes that produce proteins that are in eggs.

Scientists at the Roslin Institute in Midlothian, UK, inserted genes for interferon alpha 2a (an anti-viral protein often used to treat hepatitis, the active compound in Roferon-A,) interferon beta-1a (used to treat multiple sclerosis, the active compound in Avonex and Rebif,) or an antibody against melanoma (the really bad skin cancer) into chickens. The eggs that the chickens laid then had lots of the protein in them. You can purify the protein from the eggs to make drugs.

The rationale for doing this is that chicken farming is a lot cheaper than bacterial or mammalian tissue culture production in bioreactors, which is the current method of producing most large-molecule protein drugs.

So how do you make a Frankenchicken?

First, Dr. Helen M. Sang and her associates used a retrovirus. The particular retrovirus used was an Equine Infectious Anemia Virus (EIAV), a commonly used, commercial vector. The genes that cause disease and virus production have been removed from this virus so that other genes may be inserted.

Retroviruses break open the DNA of the host they infect and insert themselves into the host’s chromosomes. From within the hosts’ chromosomes, they use the hosts’ own protein-making and cell-making machinery to produce a few new viruses that then go infect other cells. That’s how they ride along for years, causing minimal or no disease. For example, HIV, a human retrovirus, infect human white blood cells and inserts itself into the white blood cells’ DNA.

All the disease-causing genes were removed from the EIAV vector. Then, the scientists added the genes of the drug proteins to the vector. Now, when the retroviral vector inserts into the host’s DNA, it will make the protein drug instead of making viral proteins and new viruses.

So why does the drug only appear in the eggs? Why isn’t the drug in the whole chicken?

The virus figures out where to insert itself into the host’s DNA by comparing its DNA sequence to the host’s. In a place where the virus’s DNA matches the host’s DNA closely enough, the DNA entwines around each other and the virus’s DNA splices into the host’s DNA.

Then, the scientists made some changes to the DNA around the drug genes so that it matched a particular chicken gene: ovalbumin. Ovalbumin is the predominant protein in egg whites.

The virus integrated into the ovalbumin gene’s place because that’s where the DNA sequences matched. Now, in the mature chicken, in cells that are supposed to make ovalbumin, the drug proteins are made instead. The only places in a chicken that make ovalbumin are the organs that make the eggs. Thus, the eggs are filled with the drug protein instead of ovalbumin.

The EIAV vector with the drug gene was used to infect chicken one-cell embryos. The gene in the viral vector replaced the ovalbumin gene in the chicken embryos’ DNA. The embryos were then put back into an egg (like a breakfast egg, like you buy a dozen of in the grocery store.) The one-cell embryo divided and grew normally inside the egg until it hatched, as a transgenic chick.

And that’s how you make a transgenic chicken and drug-filled eggs.

TK Kenyon
Author of Rabid: A Novel, coming in April, 2007 from Kunati Books
"-- shady clergy, top-secret scientific research, marital infidelity, lust, love, honor, faith-- "

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