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Adeno-associated-virus-mediated transduction of the mammary gland enables sustained production of recombinant proteins in milk
Biopharming for the production of recombinant pharmaceutical proteins in the mammary gland of transgenic animals is an attractive but laborious alternative compared to mammalian cell fermentation. The disadvantage of the lengthy process of genetically modifying an entire animal could be circumvented...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4604487/ https://www.ncbi.nlm.nih.gov/pubmed/26463440 http://dx.doi.org/10.1038/srep15115 |
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author | Wagner, Stefan Thresher, Rosemary Bland, Ross Laible, Götz |
author_facet | Wagner, Stefan Thresher, Rosemary Bland, Ross Laible, Götz |
author_sort | Wagner, Stefan |
collection | PubMed |
description | Biopharming for the production of recombinant pharmaceutical proteins in the mammary gland of transgenic animals is an attractive but laborious alternative compared to mammalian cell fermentation. The disadvantage of the lengthy process of genetically modifying an entire animal could be circumvented with somatic transduction of only the mammary epithelium with recombinant, replication-defective viruses. While other viral vectors offer very limited scope for this approach, vectors based on adeno-associated virus (AAV) appear to be ideal candidates because AAV is helper-dependent, does not induce a strong immune response and has no association with disease. Here, we sought to test the suitability of recombinant AAV (rAAV) for biopharming. Using reporter genes, we showed that injected rAAV efficiently transduced mouse mammary cells. When rAAV encoding human myelin basic protein (hMBP) was injected into the mammary glands of mice and rabbits, this resulted in the expression of readily detectable protein levels of up to 0.5 g/L in the milk. Furthermore we demonstrated that production of hMBP persisted over extended periods and that protein expression could be renewed in a subsequent lactation by re-injection of rAAV into a previously injected mouse gland. |
format | Online Article Text |
id | pubmed-4604487 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-46044872015-12-07 Adeno-associated-virus-mediated transduction of the mammary gland enables sustained production of recombinant proteins in milk Wagner, Stefan Thresher, Rosemary Bland, Ross Laible, Götz Sci Rep Article Biopharming for the production of recombinant pharmaceutical proteins in the mammary gland of transgenic animals is an attractive but laborious alternative compared to mammalian cell fermentation. The disadvantage of the lengthy process of genetically modifying an entire animal could be circumvented with somatic transduction of only the mammary epithelium with recombinant, replication-defective viruses. While other viral vectors offer very limited scope for this approach, vectors based on adeno-associated virus (AAV) appear to be ideal candidates because AAV is helper-dependent, does not induce a strong immune response and has no association with disease. Here, we sought to test the suitability of recombinant AAV (rAAV) for biopharming. Using reporter genes, we showed that injected rAAV efficiently transduced mouse mammary cells. When rAAV encoding human myelin basic protein (hMBP) was injected into the mammary glands of mice and rabbits, this resulted in the expression of readily detectable protein levels of up to 0.5 g/L in the milk. Furthermore we demonstrated that production of hMBP persisted over extended periods and that protein expression could be renewed in a subsequent lactation by re-injection of rAAV into a previously injected mouse gland. Nature Publishing Group 2015-10-14 /pmc/articles/PMC4604487/ /pubmed/26463440 http://dx.doi.org/10.1038/srep15115 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Wagner, Stefan Thresher, Rosemary Bland, Ross Laible, Götz Adeno-associated-virus-mediated transduction of the mammary gland enables sustained production of recombinant proteins in milk |
title | Adeno-associated-virus-mediated transduction of the mammary gland enables sustained production of recombinant proteins in milk |
title_full | Adeno-associated-virus-mediated transduction of the mammary gland enables sustained production of recombinant proteins in milk |
title_fullStr | Adeno-associated-virus-mediated transduction of the mammary gland enables sustained production of recombinant proteins in milk |
title_full_unstemmed | Adeno-associated-virus-mediated transduction of the mammary gland enables sustained production of recombinant proteins in milk |
title_short | Adeno-associated-virus-mediated transduction of the mammary gland enables sustained production of recombinant proteins in milk |
title_sort | adeno-associated-virus-mediated transduction of the mammary gland enables sustained production of recombinant proteins in milk |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4604487/ https://www.ncbi.nlm.nih.gov/pubmed/26463440 http://dx.doi.org/10.1038/srep15115 |
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