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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Main Authors: Cleto, Sara, Lee, Kevin, Perez-Pinera, Pablo, Han, Ningren, Cao, Jicong, Purcell, Oliver, Shah, Kartik A, Ram, Rajeev J, Lu, Timothy K
Other Authors: Massachusetts Institute of Technology. Department of Biological Engineering
Format: Article
Language:en_US
Published: Nature Publishing Group 2017
Online Access:http://hdl.handle.net/1721.1/109076
https://orcid.org/0000-0003-4513-8575
https://orcid.org/0000-0002-5253-3365
https://orcid.org/0000-0002-2031-8871
https://orcid.org/0000-0003-0420-2235
https://orcid.org/0000-0002-9999-6690
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author Cleto, Sara
Lee, Kevin
Perez-Pinera, Pablo
Han, Ningren
Cao, Jicong
Purcell, Oliver
Shah, Kartik A
Ram, Rajeev J
Lu, Timothy K
author2 Massachusetts Institute of Technology. Department of Biological Engineering
author_facet Massachusetts Institute of Technology. Department of Biological Engineering
Cleto, Sara
Lee, Kevin
Perez-Pinera, Pablo
Han, Ningren
Cao, Jicong
Purcell, Oliver
Shah, Kartik A
Ram, Rajeev J
Lu, Timothy K
author_sort Cleto, Sara
collection MIT
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 mit-1721.1/1090762022-09-29T21:14:45Z Synthetic biology and microbioreactor platforms for programmable production of biologics at the point-of-care Cleto, Sara Lee, Kevin Perez-Pinera, Pablo Han, Ningren Cao, Jicong Purcell, Oliver Shah, Kartik A Ram, Rajeev J Lu, Timothy K Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science Massachusetts Institute of Technology. Research Laboratory of Electronics Koch Institute for Integrative Cancer Research at MIT Perez-Pinera, Pablo Han, Ningren Cao, Jicong Purcell, Oliver Shah, Kartik A Ram, Rajeev J Lu, Timothy K Cleto, Sara 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. 2017-05-15T13:51:01Z 2017-05-15T13:51:01Z 2016-07 2015-11 Article http://purl.org/eprint/type/JournalArticle 2041-1723 http://hdl.handle.net/1721.1/109076 Perez-Pinera, Pablo; Han, Ningren; Cleto, Sara; Cao, Jicong; Purcell, Oliver; Shah, Kartik A.; Lee, Kevin; Ram, Rajeev and Lu, Timothy K. “Synthetic Biology and Microbioreactor Platforms for Programmable Production of Biologics at the Point-of-Care.” Nature Communications 7 (July 2016): 12211. © 2017 Macmillan Publishers Limited, part of Springer Nature https://orcid.org/0000-0003-4513-8575 https://orcid.org/0000-0002-5253-3365 https://orcid.org/0000-0002-2031-8871 https://orcid.org/0000-0003-0420-2235 https://orcid.org/0000-0002-9999-6690 en_US http://dx.doi.org/10.1038/ncomms12211 Nature Communications Creative Commons Attribution 4.0 International License http://creativecommons.org/licenses/by/4.0/ application/pdf Nature Publishing Group Nature
spellingShingle Cleto, Sara
Lee, Kevin
Perez-Pinera, Pablo
Han, Ningren
Cao, Jicong
Purcell, Oliver
Shah, Kartik A
Ram, Rajeev J
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
url http://hdl.handle.net/1721.1/109076
https://orcid.org/0000-0003-4513-8575
https://orcid.org/0000-0002-5253-3365
https://orcid.org/0000-0002-2031-8871
https://orcid.org/0000-0003-0420-2235
https://orcid.org/0000-0002-9999-6690
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