The traditional view of drugs is of small chemicals synthesised in a lab and packed in a small tablet. However, many of the world's biggest selling therapeutic agents are proteins, one of the most well known being insulin. Producing these proteins in bulk, in a cost-effective manner, is not always trivial, but new avian technology may be about to change things.
The term 'biologics' is applied to pharmaceutical drug products that are extracted, or semi-synthesised, from biological sources. Common biologics include many live and attenuated vaccines, gene therapies, allergenics, blood components or proteins including antibodies. Indeed antibodies are now some of the world-leading drugs, in terms of sales.
Recombinant proteins can be produced in bacterial expression systems, but sometimes specific modifications are required for activity and these generally are added with fidelity only in eukaryotic cells. Bacterial cells also do not always fold foreign proteins correctly. As a result, antibody therapeutics can be produced in tissue culture cells, but the amount that is produced is usually quite low.
Dr Andy Gill, the Commercial Manager of JBL Science, has recently co-led a study aimed at introducing new technology to the biologics area. The research, undertaken at the University of Edinburgh and published at the end of 2018, involved the creation of transgenic chickens that lay eggs containing large quantities of therapeutic proteins as a proof of principle.
The scientific team chose the human cytokine interferon alpha2a, as well as two species-specific fusions of the cytokine CSF-1. We managed to demonstrate good expression of these proteins in chicken egg white, and developed commercially-relevant purification strategies to remove the protein from the (rather gloopy) egg white. The best yields were up to 100 milligram protein per 100 ml egg white, which is within the region needed for cost-effective production processes.
Crucially, the proteins are fully functional, with activities measured that are at least as good, and sometimes better, than activities of commercial products. The upstream costs of a transgenic chicken production system are predicated to be substantially lower than those for mammalian cell culture. Initial analysis indicates that downstream processing costs should be equivalent to current methods, leading to an overall lower manufacturing cost.
Lead author of the study, Lissa Herron, said "our studies validate the transgenic chicken system for the cost-effective production of pure, high quality, biologically active proteins for therapeutics and other applications.The chicken bioreactor clearly has the potential to address the cost and availability of therapeutic proteins for both human and veterinary medicine.
"Relative to mammalian transgenic animal bioreactors, a flock of bioreactor chickens is faster and cheaper to produce, and egg white is a simpler mixture of proteins with a significantly lower lipid content than milk. In addition, the favourable glycosylation patterns and oxidative environment of the chicken system make it appealing for production of proteins with specific requirements for these characteristics that are currently difficult to recapitulate in cell culture."
The study has been published in BMC Biotechnology and a copy of the paper is available for free from the publishers here.