Genetically modified chickens have been developed at the University of Edinburgh’s Roslin Institute to produce human proteins in their eggs, which is hoped can offer a cost-effective method of producing drugs. These human proteins can be recovered in high quantities using a simple purification system and have been shown to be as effective as proteins produced using the existing more expensive methods.
Here we report the efficient generation of new transgenic chicken lines to optimize protein production in eggs. As proof-of-concept, the expression, purification and functional characterisation has been described of three pharmaceutical proteins, the human cytokine interferon α2a and two species-specific Fc fusions of the cytokine CSF1.
Why Do We Need New Methods of Drug Production?
Currently, protein-based drugs are mainly produced utilising mammalian cell culture techniques. These methods of production are expensive and are generally produced only in low yields, as such the production of protein-based drugs is compromised by the high cost of manufacture and validation compared to traditional chemical drugs. In addition, current methods of drug production require complex purification systems and additional processing techniques, which in turn increases production costs.
It is thus imperative that novel, cheaper, cost-effective methods are needed for the production of drugs in high yields. Improvements in transgenic technologies will allow valuable proteins to be produced by genetically-modified animals and the production of therapeutic proteins in egg white of transgenic chickens would considerably lower costs across the whole production cycle in comparison to traditional cell culture-based production systems. This could lead to more affordable treatments and broader markets, such as in developing countries and animal health applications.
Towards Developing Eggs for the Production of Drugs
Scientists have previously produced genetically modified animals, such as goats, chickens and rabbits. They have shown that the milk or eggs of these animals can be utilised in the production of protein therapies/drugs. Scientists at the Roslin Institute propose that their novel method utilising chicken eggs is more efficient, produces better yields and is more cost-effective than these previous attempts. In fact, only three eggs were enough to produce a clinically relevant dose of the drug. Chickens are able to lay up to 300 eggs per year, and as such this novel approach should be more cost-effective that current production methods in the production of important drugs to treat cancer and other diseases.
Currently, scientists at the Roslin Institute are focusing on producing high quality proteins for use in scientific research and have observed no adverse effects on the chickens themselves, which lay eggs as normal. The scientists have initially focused on two proteins that are essential to the immune system and have therapeutic potential. (1). A human cytokine interferon alpha 2a, which has powerful antiviral and anti-cancer effects, and (2). The human and pig versions of the cytokine macrophage-CSF1, which is being developed as a therapy that stimulates damaged tissues to repair themselves. Initial studies have shown a proof-of-principle for the system, which is deemed feasible and as such could easily be adapted to produce other therapeutic proteins.
Egg-Based Flu Vaccines
Eggs are already used for growing viruses that are used as vaccines. For more than 70 years, the flu vaccine has been most commonly produced using an egg-based manufacturing process. Egg-based vaccine manufacturing is used to make both inactivated vaccines, the flu injection, and live attenuated vaccines, the flu nasal spray. Candidate vaccine viruses (CVVs) are injected into fertilised chicken’s eggs and incubated for several days to allow the viruses to replicate and then the virus-containing fluid is harvested from the eggs. The production of egg-based flu vaccines is different to the new approach being developed at the Roslin Institute as the therapeutic proteins are encoded in the chicken’s DNA and produced as part of the egg white.
What does the Future Hold?
This method is currently not being utilised for the production of drugs or medicines for use in humans, as it is still undergoing development. However, studies are showing that chickens are commercially viable for the production of high quality drugs cost effectively. The proteins produced via this novel method have applications in drug discovery studies, biotechnology applications, research studies and hopefully, one day, in patients. In essence, this work validates a transgenic chicken system for the cost-effective production of pure, high quality, biologically active protein for therapeutics and other applications.
References:
Herron LR et al (2018) A chicken bioreactor for efficient production of functional cytokines. BMC Biotechnology. Dec 29; 18(1):82.
https://www.ed.ac.uk/roslin/news-events/latest-news/hen-eggs-human-proteins-drug-hope
https://www.cdc.gov/flu/protect/vaccine/how-fluvaccine-made.htm#egg
