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Synthetic biology and microbioreactor platforms for programmable production of biologics at the point-of-care

Current biopharmaceutical manufacturing systems are not compatible with portable or distributed production of biologics, as they typically require the development of single biologic-producing cell lines followed by their cultivation at very large scales. Therefore, it remains challenging to treat pa...

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Autores principales: Perez-Pinera, Pablo, Han, Ningren, Cleto, Sara, Cao, Jicong, Purcell, Oliver, Shah, Kartik A., Lee, Kevin, Ram, Rajeev, Lu, Timothy K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4974573/
https://www.ncbi.nlm.nih.gov/pubmed/27470089
http://dx.doi.org/10.1038/ncomms12211
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author Perez-Pinera, Pablo
Han, Ningren
Cleto, Sara
Cao, Jicong
Purcell, Oliver
Shah, Kartik A.
Lee, Kevin
Ram, Rajeev
Lu, Timothy K.
author_facet Perez-Pinera, Pablo
Han, Ningren
Cleto, Sara
Cao, Jicong
Purcell, Oliver
Shah, Kartik A.
Lee, Kevin
Ram, Rajeev
Lu, Timothy K.
author_sort Perez-Pinera, Pablo
collection PubMed
description Current biopharmaceutical manufacturing systems are not compatible with portable or distributed production of biologics, as they typically require the development of single biologic-producing cell lines followed by their cultivation at very large scales. Therefore, it remains challenging to treat patients in short time frames, especially in remote locations with limited infrastructure. To overcome these barriers, we developed a platform using genetically engineered Pichia pastoris strains designed to secrete multiple proteins on programmable cues in an integrated, benchtop, millilitre-scale microfluidic device. We use this platform for rapid and switchable production of two biologics from a single yeast strain as specified by the operator. Our results demonstrate selectable and near-single-dose production of these biologics in <24 h with limited infrastructure requirements. We envision that combining this system with analytical, purification and polishing technologies could lead to a small-scale, portable and fully integrated personal biomanufacturing platform that could advance disease treatment at point-of-care.
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spelling pubmed-49745732016-08-18 Synthetic biology and microbioreactor platforms for programmable production of biologics at the point-of-care Perez-Pinera, Pablo Han, Ningren Cleto, Sara Cao, Jicong Purcell, Oliver Shah, Kartik A. Lee, Kevin Ram, Rajeev Lu, Timothy K. Nat Commun Article Current biopharmaceutical manufacturing systems are not compatible with portable or distributed production of biologics, as they typically require the development of single biologic-producing cell lines followed by their cultivation at very large scales. Therefore, it remains challenging to treat patients in short time frames, especially in remote locations with limited infrastructure. To overcome these barriers, we developed a platform using genetically engineered Pichia pastoris strains designed to secrete multiple proteins on programmable cues in an integrated, benchtop, millilitre-scale microfluidic device. We use this platform for rapid and switchable production of two biologics from a single yeast strain as specified by the operator. Our results demonstrate selectable and near-single-dose production of these biologics in <24 h with limited infrastructure requirements. We envision that combining this system with analytical, purification and polishing technologies could lead to a small-scale, portable and fully integrated personal biomanufacturing platform that could advance disease treatment at point-of-care. Nature Publishing Group 2016-07-29 /pmc/articles/PMC4974573/ /pubmed/27470089 http://dx.doi.org/10.1038/ncomms12211 Text en Copyright © 2016, The Author(s) 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
Perez-Pinera, Pablo
Han, Ningren
Cleto, Sara
Cao, Jicong
Purcell, Oliver
Shah, Kartik A.
Lee, Kevin
Ram, Rajeev
Lu, Timothy K.
Synthetic biology and microbioreactor platforms for programmable production of biologics at the point-of-care
title Synthetic biology and microbioreactor platforms for programmable production of biologics at the point-of-care
title_full Synthetic biology and microbioreactor platforms for programmable production of biologics at the point-of-care
title_fullStr Synthetic biology and microbioreactor platforms for programmable production of biologics at the point-of-care
title_full_unstemmed Synthetic biology and microbioreactor platforms for programmable production of biologics at the point-of-care
title_short Synthetic biology and microbioreactor platforms for programmable production of biologics at the point-of-care
title_sort synthetic biology and microbioreactor platforms for programmable production of biologics at the point-of-care
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4974573/
https://www.ncbi.nlm.nih.gov/pubmed/27470089
http://dx.doi.org/10.1038/ncomms12211
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