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A chicken bioreactor for efficient production of functional cytokines

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 t...

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Autores principales: Herron, Lissa R., Pridans, Clare, Turnbull, Matthew L., Smith, Nikki, Lillico, Simon, Sherman, Adrian, Gilhooley, Hazel J., Wear, Martin, Kurian, Dominic, Papadakos, Grigorios, Digard, Paul, Hume, David A., Gill, Andrew C., Sang, Helen M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6311007/
https://www.ncbi.nlm.nih.gov/pubmed/30594166
http://dx.doi.org/10.1186/s12896-018-0495-1
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author Herron, Lissa R.
Pridans, Clare
Turnbull, Matthew L.
Smith, Nikki
Lillico, Simon
Sherman, Adrian
Gilhooley, Hazel J.
Wear, Martin
Kurian, Dominic
Papadakos, Grigorios
Digard, Paul
Hume, David A.
Gill, Andrew C.
Sang, Helen M.
author_facet Herron, Lissa R.
Pridans, Clare
Turnbull, Matthew L.
Smith, Nikki
Lillico, Simon
Sherman, Adrian
Gilhooley, Hazel J.
Wear, Martin
Kurian, Dominic
Papadakos, Grigorios
Digard, Paul
Hume, David A.
Gill, Andrew C.
Sang, Helen M.
author_sort Herron, Lissa R.
collection PubMed
description 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12896-018-0495-1) contains supplementary material, which is available to authorized users.
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spelling pubmed-63110072019-01-07 A chicken bioreactor for efficient production of functional cytokines Herron, Lissa R. Pridans, Clare Turnbull, Matthew L. Smith, Nikki Lillico, Simon Sherman, Adrian Gilhooley, Hazel J. Wear, Martin Kurian, Dominic Papadakos, Grigorios Digard, Paul Hume, David A. Gill, Andrew C. Sang, Helen M. BMC Biotechnol Research Article 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12896-018-0495-1) contains supplementary material, which is available to authorized users. BioMed Central 2018-12-29 /pmc/articles/PMC6311007/ /pubmed/30594166 http://dx.doi.org/10.1186/s12896-018-0495-1 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Herron, Lissa R.
Pridans, Clare
Turnbull, Matthew L.
Smith, Nikki
Lillico, Simon
Sherman, Adrian
Gilhooley, Hazel J.
Wear, Martin
Kurian, Dominic
Papadakos, Grigorios
Digard, Paul
Hume, David A.
Gill, Andrew C.
Sang, Helen M.
A chicken bioreactor for efficient production of functional cytokines
title A chicken bioreactor for efficient production of functional cytokines
title_full A chicken bioreactor for efficient production of functional cytokines
title_fullStr A chicken bioreactor for efficient production of functional cytokines
title_full_unstemmed A chicken bioreactor for efficient production of functional cytokines
title_short A chicken bioreactor for efficient production of functional cytokines
title_sort chicken bioreactor for efficient production of functional cytokines
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6311007/
https://www.ncbi.nlm.nih.gov/pubmed/30594166
http://dx.doi.org/10.1186/s12896-018-0495-1
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