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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Bibliographic Details
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
Description
Summary: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.