A chicken bioreactor for efficient production of functional cytokines

Herron, L. R. et al. (2018) A chicken bioreactor for efficient production of functional cytokines. BMC Biotechnology, 18, 82. (doi: 10.1186/s12896-018-0495-1) (PMID:30594166) (PMCID:PMC6311007)

Abstract

Background: The global market for protein drugs has the highest compound annual growth rate of any pharmaceutical class but their availability, especially outside of the US market, is compromised by the high cost of manufacture and validation compared to traditional chemical drugs. 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, but the production of therapeutic proteins in egg white of transgenic chickens would substantially lower costs across the entire production cycle compared to traditional cell culture-based production systems. This could lead to more affordable treatments and wider markets, including in developing countries and for animal health applications. Results: Here we report the efficient generation of new transgenic chicken lines to optimize protein production in eggs. As proof-of-concept, we describe the expression, purification and functional characterization of three pharmaceutical proteins, the human cytokine interferon α2a and two species-specific Fc fusions of the cytokine CSF1. Conclusion: Our work optimizes and validates a transgenic chicken system for the cost-effective production of pure, high quality, biologically active protein for therapeutics and other applications.

• Item Type: Articles
• Additional Information: This work was supported by BBSRC strategic funding to The Roslin Institute BBS/ E/D/20221658, BBSRC grants BB/I013113/1 (in collaboration with Zoetis, Inc.), BB/ M021920/1, and BBSRC-University of Edinburgh IAA award; the EPPF is supported by the Wellcome Trust Multi-User Equipment grants 081287/Z/06/Z, 101527/Z/13/ Z and the Wellcome-UoE ISSF award; M.L.T. and N.S. were supported by BBSRC grant BB/J01446X/1 and MRC grant MR/K000276/1 (respectively) to P.D.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Turnbull, Dr Matthew
• Authors: Herron, L. R., Pridans, C., Turnbull, M. L., Smith, N., Lillico, S., Sherman, A., Gilhooley, H. J., Wear, M., Kurian, D., Papadakos, G., Digard, P., Hume, D. A., Gill, A. C., and Sang, H. M.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: BMC Biotechnology
• Publisher: BioMed Central
• ISSN: 1472-6750
• ISSN (Online): 1472-6750
• Copyright Holders: Copyright © 2018 The Authors
• First Published: First published in BMC Biotechnology 18: 82
• Publisher Policy: Reproduced under a Creative Commons License