Clinical applications of recombinant CSF1-Fc produced in the eggs of transgenic hens in veterinary and human medicine
Lead Research Organisation:
University of Edinburgh
Department Name: The Roslin Institute
Abstract
Biologics are pharmaceutical proteins very effective at treating a number of previously intractable medical conditions. They are an increasing proportion of the human drugs market, but widespread use in veterinary settings has been prevented by high production cost. Replacing the expensive mammalian cell culture systems with transgenic chickens has significant potential to reduce this cost. With our system, hens can produce protein of consistent quantity and activity over their entire laying lives, and purification is performed using standard techniques. Here we propose to take forward our recent success producing active pig CSF1-Fc in transgenic hens' eggs by purifying large quantities and testing in potential applications. We will scale up purification, perform full quality control, test in pig models of human disease, and provide material to other experts for evaluation. We will also produce a new transgenic line expressing dog CSF1-Fc for future studies in veterinary medicine.
Publications
Herron LR
(2018)
A chicken bioreactor for efficient production of functional cytokines.
in BMC biotechnology
Herron LR
(2018)
A chicken bioreactor for efficient production of functional cytokines.
in BMC biotechnology
| Description | Biologics are used to treat an ever-expanding range of diseases, but high capital investment and production costs can make them inaccessibly expensive. Improvements in transgenic technologies allow valuable proteins to be produced by genetically-modified animals; several therapeutic proteins from such animal bioreactors are already on the market after successful clinical trials and regulatory approval. Chickens have lagged behind mammals in bioreactor development, despite a number of potential advantages, due to the historic difficulty in producing transgenic birds. We achieved efficient generation of new transgenic chicken lines to optimise protein production in eggs. We measured the expression of these proteins and developed methods for purification followed by functional characterization of two pharmaceutical proteins, the human cytokine interferon a2a and an Fc fusion of the cytokine CSF1. The optimised system provides a platform for high yield production of valuable proteins. We have shown that recombinant protein synthesised by GM hens as a component of egg white can be purified using technology that is scalable for commercial production. Purified protein is of high quality and purity and of predicted biological activity. |
| Exploitation Route | The technologies developed may be used as a platform technology for producing biologics for the reagents and animal health markets. We have a partner to take this forward and several different academic and business collaborators. |
| Sectors | Agriculture, Food and Drink,Pharmaceuticals and Medical Biotechnology |
| Description | The PDRA funded on this grant was awarded a BBSRC-Royal Society of Edinburgh Enterprse Fellowship to develop the outputs of this project as a business. This has lead to support to take this project to commercialisation by Roslin Technologies Limited. Publication of the paper describing this project outcomes received a lot of interest from the press, with a positive reflection on this application of GM technology, and some contacts from interested companies. |
| First Year Of Impact | 2017 |
| Sector | Agriculture, Food and Drink |
| Impact Types | Economic |
| Description | MRC Confidence in Concept Increasing the efficiency and competitiveness of the chicken bioreactor biologics production platform |
| Amount | £81,423 (GBP) |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 09/2017 |
| End | 05/2018 |
| Description | Purification technologies |
| Organisation | Centre for Process Innovation (CPI) |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | We developed lab scale purification of recombinant proteins from the eggs of transgenic hens. |
| Collaborator Contribution | Working with the CPI we have developed a scalable purification process, yielding high quality, pure and biologically active recombinant protein. |
| Impact | Outcomes will be described in publications in 2018. |
| Start Year | 2015 |
| Description | Roslin Technologies Ltd. |
| Organisation | Roslin Technologies |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | Transfer of know-how and intellectual property to Roslin Technologies is in progress. RT is a company joint owned by University of Edinburgh and investors to translate inventions in agribiotech. |
| Collaborator Contribution | Currently the partners are developing the protein purification and marketing strategies. |
| Impact | none yet |
| Start Year | 2018 |
| Description | Cabaret of Dangerous Ideas: Dolly the Sheep: major discovery or minor distraction? Presenter, Edinburgh Festival Fringe. |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | Presentation with two colleagues, one a stem cell biologist and one a histrian of science in society, discussing the impact on research and society of the birth of Dolly the Sheep 20 years ago. Potential of GM technologies to confer resistance to diseases in farmed animals was discussed. Plenty of opportunity for audience contributions to debate. |
| Year(s) Of Engagement Activity | 2016 |
| URL | http://www.youtube.com/watch?v=LClmL5C9YJE&feature=youtu.be |
| Description | Glasgow Skeptics: open meeting in Glasgow |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | "Would you eat a GM chicken?" A presentation about GM farm animals with a focus on flu resistance via GM, plenty of discussion after the talk. |
| Year(s) Of Engagement Activity | 2014 |
| Description | News artcile on BBC news website |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | A press release was developed relating to our publication in BMC Biotechnology describing production and purification of bioactive proteins in the eggs of transgenic hens. This article was written by Pallab Ghosh of BBC and attracted a lot of attention and other news articles across the world. Contacts have been received from interested businesses. |
| Year(s) Of Engagement Activity | 2019 |
| URL | https://www.bbc.co.uk/news/uk-scotland-47022070 |