Recombinant human protein
Since the development of recombinant human insulin, protein-based therapeutics have been the fastest-growing segment of the pharmaceutical industry. Three of the five highest revenue drugs in oncology, Rituxan, Avastin and Herceptin, are monoclonal antibodies. The appearance of hundreds of non-antibody therapeutic proteins, including enzymes, cytokines and growth factors and blood proteins, validates predictions from 2004 that this would be an area of significant growth. Between 2011 and 2016, 62 new therapeutic protein drugs were approved by the US FDA.
Development of genetic modification systems for livestock offered the possibility of harnessing natural high-volume protein production systems (e.g. milk from farmed livestock and eggs from poultry) for the production of biologics. Transgenic sheep, goats and cows were generated that produced biopharmaceuticals in their milk, with the aim of establishing animal bioreactors for large scale production of high quality proteins, potentially at lower capital and production costs than cell culture systems. The first drug produced in a transgenic animal, antithrombin III in goat milk, was approved for use by the European Medicines Agency in 2006 and the FDA in 2009.
Hens that lay human proteins in eggs offer future therapy hope
Scientists at the University of Edinburgh’s Roslin Institute have produced GM chickens that make human proteins in their eggs, offering a more cost-effective method of producing certain types of drugs.
Interest in developing the laying hen as a bioreactor is based on the high protein synthetic capacity of the hen: an average 60 g egg contains nearly 3.5 g of protein in the egg white and each hen may lay over 300 eggs per year. Chickens are relatively inexpensive to keep and large flocks can be built quickly from small numbers of founder birds. In addition, chickens have closely-related glycosylation patterns to humans, which may result in reduced immunogenicity of biologics from egg white, as well as improving functionality of proteins where glycosylation is required for activity.
The study — which has initially focused on producing high quality proteins for use in scientific research — found the drugs work at least as well as the same proteins produced using existing methods. High quantities of the proteins can be recovered from each egg using a simple purification system and there are no adverse effects on the chickens themselves, which lay eggs as normal.
Researchers say the findings provide sound evidence for using chickens as a cheap method of producing high quality drugs for use in research studies and, potentially one day, in patients. Eggs are already used for growing viruses that are used as vaccines, such as the flu jab. This new approach is different because the therapeutic proteins are encoded in the chicken’s DNA and produced as part of the egg white.
The team have initially focused on two proteins that are essential to the immune system and have therapeutic potential — a human protein called IFNalpha2a, which has powerful antiviral and anti-cancer effects, and the human and pig versions of a protein called macrophage-CSF, which is being developed as a therapy that stimulates damaged tissues to repair themselves.
Just three eggs were enough to produce a clinically relevant dose of the drug. As chickens can lay up to 300 eggs per year, researchers say their approach could be more cost-effective than other production methods for some important drugs.
Researchers say they haven’t produced medicines for use in patients yet but the study offers proof-of-principle that the system is feasible and could easily be adapted to produce other therapeutic proteins. Protein-based drugs, which include antibody therapies such as Avastin and Herceptin, are widely used for treating cancer and other diseases. For some of these proteins, the only way to produce them with sufficient quality involves mammalian cell culture techniques, which are expensive and have low yields. Other methods require complex purification systems and additional processing techniques, which raise costs.
Scientists have previously shown that genetically modified goats, rabbits and chickens can be used to produce protein therapies in their milk or eggs. The researchers say their new approach is more efficient, produces better yields and is more cost-effective than these previous attempts.
The study was carried out at the University of Edinburgh’s Roslin Institute and Roslin Technologies, a company set up to commercialise research at The Roslin Institute.