Scientists have successfully achieved the production of a functional humanised antibody in the whites of eggs laid by a transgenic hen, opening the door to using transgenic flocks as an alternative to mammalian cell culture for the production of many protein drugs, reports Phil Taylor.
US company Viragen, which is developing the avian transgenic production technology in collaboration with the Roslin Institute in Scotland (best known for cloning Dolly the sheep) and UK biotech firm Oxford BioMedica, said the achievement brought the use of chickens as bioreactors for protein production a step closer.
The companies previously published results demonstrating expression of a protein throughout the entire bird, which would be unsuitable for production purposes as the protein made in this way could affect the health of the hen. This latest result indicates that the collaborators have now been able to target the expression so that the functional protein is synthesised only as a component of the egg white.
"With this major milestone achievement, I am even more convinced that we are developing an elite manufacturing platform that should emerge as a method of choice for many products," said the project's scientific leader, Roslin senior scientist Dr Helen Sang.
Once running at scale, the companies believe that the eggs will form a reliable, efficient manufacturing vehicle for the antibody. According to the companies, eggs used as an alternative to standard biomanufacturing techniques such as mammalian cell culture would have advantages in ease of scale- up, lower costs of production and quality of the product produced.
A report published recently by TIFAC , which suggests that use of transgenic animals to make recombinant proteins is five to 10 times more economical in operational costs, as well as two to three times cheaper in startup costs, compared to cell culture production methods.
Moreover, the companies also believe their egg-produced antibodies will have superior quality to products made by conventional bioproduction techniques, because they should be more 'human' in their structure.
Human proteins have a pattern of sugar groups attached to them that play a significant role in the way they behave. This so-called glycosylation pattern is critical to the functionality, safety and tolerability of antibodies, and biopharmaceuticals based on this type of protein tend to work better if they have a sugar group pattern that make them look more human. For example, their clearance from the body is reduced and their half life is extended.
Many existing protein drug products are not glycosylated by virtue of their manufacturing process, which can lead to adverse immune responses and a significantly shorter half-life in the body, according to Viragen.
"So we aim to take such proteins and create new and improved versions, which should be better tolerated, possibly be dosed in lower quantities, and hopefully would be beneficial to the safety of the patients. The market opportunity is enormous," said Viragen president and CEO Charles Rice.
The biopharmaceutical drug market is projected to generate in excess of $50 billion in sales by 2010, and antibodies alone are expected to make up approximately $17 billion of that market, he added. "Our goal is clear - to develop a manufacturing platform for many of these products that offers compelling advantages over existing systems."
Oxford Biomedica contributed its LentiVector technology to the alliance, which is claimed to boost the efficiency of making transgenic birds 10-100 fold compared to vector systems based on retroviruses. The firm gets annual maintenance payments in the project, as well as milestone payments on the achievement of technical goals by Viragen and royalties on commercialisation of the technology.