Protein production in chicken eggs cracked

By Anna Lewcock

- Last updated on GMT

Related tags: Interferon beta-1a

Researchers in Scotland have successfully bred five generations of
transgenic hens producing therapeutic proteins in the whites of
their eggs. This latest news takes the field a step closer to
establishing transgenic flocks that could conceivably serve as
natural biomanufacturing plants supplying the pharmaceutical
industry.

Research conducted by the Roslin Institute in Edinburgh, reports the successful production of two drug candidates in the eggs of the transgenic hens: a humanised monoclonal antibody (miR24) for the treatment of malignant melanoma, and interferon beta-1a for the treatment of multiple sclerosis.

The Institute has managed to maintain protein expression through several generations, leading to a flock of several hundred of the transgenic birds.

The organisation, renowned for its creation of Dolly the Sheep 10 years ago, is working in collaboration with gene therapy company Oxford BioMedica and biotech company Viragen to develop their avian transgenic system (OVA) as a large-scale biomanufacturing alternative for a variety of proteins.

It has previously been estimated that a small flock of a few hundred hens could satisfy the entire US market demand for interferon beta-1a.

The research group used viral vectors derived from the lentivirus equine infectious anaemia virus (EIAV) to insert genes for the desired pharmaceutical proteins into the chicken gene for ovalbumin, which makes up 54 per cent of egg white.

In the research published in today's Proceedings of the National Academy of Sciences (PNAS), the group reports that the hens successfully synthesised functional recombinant proteins, and that the protein continued to be expressed in later generations - a significant achievement that has proved a challenge in previous research.

"We are very pleased that the PNAS article chronicles our 'proof-of-principle' studies resulting in successful germline transmission of two therapeutic proteins,"​ said Viragen vice president Karen Jervis.

"We expect to report excellent new results with a third protein-drug candidate by the end of this month, assuming positive confirmations."

Chicken eggs make good candidates for the production of pharmaceutical proteins; for example, chicken proteins, unlike those in other transgenic animals, have a similar glycosylation profile (the pattern of sugar groups on the surface of the protein) to human proteins. This could be a distinct advantage for patients who develop antibodies to foreign sugar epitopes on traditionally manufactured treatments thus destroying the therapeutic benefit of the drug.

In addition, there is also the fact that the genetically altered chickens could produce 'virtually unlimited' numbers of eggs containing high volumes of drugs in the egg whites, according to Viragen. The proteins can then be harvested from the eggs and purified for therapeutic use.

Using chicken eggs as an alternative to cell cultures would also provide advantages in scale up, lower production costs and quality of the protein produced.

Viragen holds the worldwide exclusive licence to commercialise the Roslin Institute's avian transgenic technology, and sees it as a way to provide a faster, cheaper alternative to the construction of new biomanufacturing facilities.

"This technology could address a substantial need in the biopharmaceutical industry for efficient, high-volume production of biological products,"​ said Alan Kingsman, CEO of Oxford BioMedica.

With demand for therapeutic protein drugs on the increase, the use of transgenic hens to generate proteins could prove to be a cost-effective way of meeting these requirements. However, despite the fact that chicken eggs have been used in the manufacture of vaccines for over 30 years (which could ease the regulatory process), it is likely to be quite some time before patient trials are approved and medicines derived from the transgenic hen proteins hit the shelves.

Related topics: Ingredients

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