GM chicken lays the “golden” egg

The new buzz word on the block is poultry “pharming,” the planned production of pharmaceutically useful proteins from genetically modified layer flocks.

Increasing concern over animal welfare means more people are pondering what they can do for poultry, but high-tech research is showing what poultry can do for people, over and above a tasty high-protein chicken egg breakfast.

Transgenic methods (moving genes between two totally unrelated living organisms), more commonly called Genetic Modification (GM), could light a high-tech fire under poultry production and utilisation. Overall aim is to insert specific genes into the poultry genome to template production of medically-useful proteins in the egg for subsequent harvest as feedstock for use in the manufacture of pharmaceutical products.  And because chickens are such prolific egg producers, just one gram of new protein per egg could be enough to make the whole thing practically feasible and commercially viable.

New buzz word on the block is poultry “pharming,” the planned production of pharmaceutically useful proteins from GM layer flocks.  Leading the way is Roslin Research Institute in Scotland (United Kingdom - UK), famous for its cloned sheep called Dolly. A less well known precedent at Roslin was Tracey, the blackface sheep in 1990, and genetically modified to produce milk rich in the protein AAT for the treatment of cystic fibrosis and emphysema.

Focus is now on chickens and the Isa Brown breed, a French-inspired cross involving two North American breeds (Rhode Island Red and Rhode Island White).  Net result is a veritable egg-laying machine (GM Isa Brown) dropping close to one egg every day of the year.

These are no ordinary Isa Browns. They have been genetically modified by inserting a human gene into the bird genome using a virus particle that normally causes disease in horses as the vector (vehicle).  By using these Gene Therapy techniques, the Equine Infectious Anaemia Lentivirus is used as a vector to carry and insert the human gene into the chicken embryos of newly laid eggs.  This produces a chimera, a blend of normal and GM cells.  Some of the resulting “Chimeric Cockerels” hatching from these eggs will carry the new gene for human protein production in their sperm cells.  From here on it is a question of breeding and multiplication, so that daughter hens possess the “new” human gene and therefore the capability and capacity to lay the “golden” eggs.

There is no criticism of hen welfare on this score because the inserted gene is tagged onto an intrinsic hen’s gene that codes and directs the production of ovalbumen, the major protein constituent of egg white or albumen.  Since the gene is only there to translate and template the production of the egg white in a self contained egg, the newly designed protein has no harmful effect on the hen itself.

Natural antimicrobial chemicals in egg white protect against any deterioration of the precious human protein.  In fact, egg white is perhaps the only animal product that can be left exposed without experiencing significant biological degradation.

The team at Roslin has already hatched a number of pharmaceuticals from these GM Isa Brown hens.  They include miR24, a monoclonal antibody with potential capacity to treat malignant melanoma (skin cancer), and the human interferon b-la with anti-viral activity and the beta interferon which is used to treat multiple sclerosis. Latest research by Roslin is on birds with capacity to make even higher concentrations of alpha interferon (1gm per 1000cc of egg white) which is used for treatment of hepatitis C.

These are not the first pharmaceuticals to be manufactured by metabolism of a GM animal.  The first pharmaceutical produced from a GM animal was a protein secreted into the milk of a GM goat for use as an anti-coagulant and anti-inflammatory drug.  It was developed by GTC Biotherapeutics (a U.S. company) by purifying the protein, which turned out to be a potentially safer alternative to equivalent proteins extracted from human blood products.

Goats and sheep were the “Pharming” pioneers, but many believe GM poultry and the eggs offer the best way forward both technically and commercially.  Eggs are essentially converted into bioreactors with many advantages.

Chickens start to lay eggs after just 26 weeks at the rate of around 1 per day and are more economic to raise and maintain than large farm animals. The Roslin team calculates that a 5,000 flock of hens could produce eggs containing up to l00kg of human protein in just one year.

Equally exciting is research at University of Cambridge (UK) to create a GM breed of chicken resistant to the avian influenza virus including the H5N1 subtype.  Aim is to produce a GM chicken with a metabolism that can halt multiplication of the H5N1 influenza “A” virus in chicken cells.  This can be achieved by inserting a gene into the chicken genome which directs the cell to produce strands of RNA to block viral genes or to synthesize anti-viral protein which destroy influenza “A” virus particles.

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