Cargando…

Pilot Production of SARS-CoV-2 Related Proteins in Plants: A Proof of Concept for Rapid Repurposing of Indoor Farms Into Biomanufacturing Facilities

The current CoVid-19 crisis is revealing the strengths and the weaknesses of the world’s capacity to respond to a global health crisis. A critical weakness has resulted from the excessive centralization of the current biomanufacturing capacities, a matter of great concern, if not a source of nationa...

Descripción completa

Detalles Bibliográficos
Autores principales: Diego-Martin, Borja, González, Beatriz, Vazquez-Vilar, Marta, Selma, Sara, Mateos-Fernández, Rubén, Gianoglio, Silvia, Fernández-del-Carmen, Asun, Orzáez, Diego
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785703/
https://www.ncbi.nlm.nih.gov/pubmed/33424908
http://dx.doi.org/10.3389/fpls.2020.612781
_version_ 1783632477714120704
author Diego-Martin, Borja
González, Beatriz
Vazquez-Vilar, Marta
Selma, Sara
Mateos-Fernández, Rubén
Gianoglio, Silvia
Fernández-del-Carmen, Asun
Orzáez, Diego
author_facet Diego-Martin, Borja
González, Beatriz
Vazquez-Vilar, Marta
Selma, Sara
Mateos-Fernández, Rubén
Gianoglio, Silvia
Fernández-del-Carmen, Asun
Orzáez, Diego
author_sort Diego-Martin, Borja
collection PubMed
description The current CoVid-19 crisis is revealing the strengths and the weaknesses of the world’s capacity to respond to a global health crisis. A critical weakness has resulted from the excessive centralization of the current biomanufacturing capacities, a matter of great concern, if not a source of nationalistic tensions. On the positive side, scientific data and information have been shared at an unprecedented speed fuelled by the preprint phenomena, and this has considerably strengthened our ability to develop new technology-based solutions. In this work, we explore how, in a context of rapid exchange of scientific information, plant biofactories can serve as a rapid and easily adaptable solution for local manufacturing of bioreagents, more specifically recombinant antibodies. For this purpose, we tested our ability to produce, in the framework of an academic lab and in a matter of weeks, milligram amounts of six different recombinant monoclonal antibodies against SARS-CoV-2 in Nicotiana benthamiana. For the design of the antibodies, we took advantage, among other data sources, of the DNA sequence information made rapidly available by other groups in preprint publications. mAbs were engineered as single-chain fragments fused to a human gamma Fc and transiently expressed using a viral vector. In parallel, we also produced the recombinant SARS-CoV-2 N protein and the receptor binding domain (RBD) of the Spike protein in planta and used them to test the binding specificity of the recombinant mAbs. Finally, for two of the antibodies, we assayed a simple scale-up production protocol based on the extraction of apoplastic fluid. Our results indicate that gram amounts of anti-SARS-CoV-2 antibodies could be easily produced in little more than 6 weeks in repurposed greenhouses with little infrastructure requirements using N. benthamiana as production platform. Similar procedures could be easily deployed to produce diagnostic reagents and, eventually, could be adapted for rapid therapeutic responses.
format Online
Article
Text
id pubmed-7785703
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-77857032021-01-07 Pilot Production of SARS-CoV-2 Related Proteins in Plants: A Proof of Concept for Rapid Repurposing of Indoor Farms Into Biomanufacturing Facilities Diego-Martin, Borja González, Beatriz Vazquez-Vilar, Marta Selma, Sara Mateos-Fernández, Rubén Gianoglio, Silvia Fernández-del-Carmen, Asun Orzáez, Diego Front Plant Sci Plant Science The current CoVid-19 crisis is revealing the strengths and the weaknesses of the world’s capacity to respond to a global health crisis. A critical weakness has resulted from the excessive centralization of the current biomanufacturing capacities, a matter of great concern, if not a source of nationalistic tensions. On the positive side, scientific data and information have been shared at an unprecedented speed fuelled by the preprint phenomena, and this has considerably strengthened our ability to develop new technology-based solutions. In this work, we explore how, in a context of rapid exchange of scientific information, plant biofactories can serve as a rapid and easily adaptable solution for local manufacturing of bioreagents, more specifically recombinant antibodies. For this purpose, we tested our ability to produce, in the framework of an academic lab and in a matter of weeks, milligram amounts of six different recombinant monoclonal antibodies against SARS-CoV-2 in Nicotiana benthamiana. For the design of the antibodies, we took advantage, among other data sources, of the DNA sequence information made rapidly available by other groups in preprint publications. mAbs were engineered as single-chain fragments fused to a human gamma Fc and transiently expressed using a viral vector. In parallel, we also produced the recombinant SARS-CoV-2 N protein and the receptor binding domain (RBD) of the Spike protein in planta and used them to test the binding specificity of the recombinant mAbs. Finally, for two of the antibodies, we assayed a simple scale-up production protocol based on the extraction of apoplastic fluid. Our results indicate that gram amounts of anti-SARS-CoV-2 antibodies could be easily produced in little more than 6 weeks in repurposed greenhouses with little infrastructure requirements using N. benthamiana as production platform. Similar procedures could be easily deployed to produce diagnostic reagents and, eventually, could be adapted for rapid therapeutic responses. Frontiers Media S.A. 2020-12-23 /pmc/articles/PMC7785703/ /pubmed/33424908 http://dx.doi.org/10.3389/fpls.2020.612781 Text en Copyright © 2020 Diego-Martin, González, Vazquez-Vilar, Selma, Mateos-Fernández, Gianoglio, Fernández-del-Carmen and Orzáez. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Plant Science
Diego-Martin, Borja
González, Beatriz
Vazquez-Vilar, Marta
Selma, Sara
Mateos-Fernández, Rubén
Gianoglio, Silvia
Fernández-del-Carmen, Asun
Orzáez, Diego
Pilot Production of SARS-CoV-2 Related Proteins in Plants: A Proof of Concept for Rapid Repurposing of Indoor Farms Into Biomanufacturing Facilities
title Pilot Production of SARS-CoV-2 Related Proteins in Plants: A Proof of Concept for Rapid Repurposing of Indoor Farms Into Biomanufacturing Facilities
title_full Pilot Production of SARS-CoV-2 Related Proteins in Plants: A Proof of Concept for Rapid Repurposing of Indoor Farms Into Biomanufacturing Facilities
title_fullStr Pilot Production of SARS-CoV-2 Related Proteins in Plants: A Proof of Concept for Rapid Repurposing of Indoor Farms Into Biomanufacturing Facilities
title_full_unstemmed Pilot Production of SARS-CoV-2 Related Proteins in Plants: A Proof of Concept for Rapid Repurposing of Indoor Farms Into Biomanufacturing Facilities
title_short Pilot Production of SARS-CoV-2 Related Proteins in Plants: A Proof of Concept for Rapid Repurposing of Indoor Farms Into Biomanufacturing Facilities
title_sort pilot production of sars-cov-2 related proteins in plants: a proof of concept for rapid repurposing of indoor farms into biomanufacturing facilities
topic Plant Science
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785703/
https://www.ncbi.nlm.nih.gov/pubmed/33424908
http://dx.doi.org/10.3389/fpls.2020.612781
work_keys_str_mv AT diegomartinborja pilotproductionofsarscov2relatedproteinsinplantsaproofofconceptforrapidrepurposingofindoorfarmsintobiomanufacturingfacilities
AT gonzalezbeatriz pilotproductionofsarscov2relatedproteinsinplantsaproofofconceptforrapidrepurposingofindoorfarmsintobiomanufacturingfacilities
AT vazquezvilarmarta pilotproductionofsarscov2relatedproteinsinplantsaproofofconceptforrapidrepurposingofindoorfarmsintobiomanufacturingfacilities
AT selmasara pilotproductionofsarscov2relatedproteinsinplantsaproofofconceptforrapidrepurposingofindoorfarmsintobiomanufacturingfacilities
AT mateosfernandezruben pilotproductionofsarscov2relatedproteinsinplantsaproofofconceptforrapidrepurposingofindoorfarmsintobiomanufacturingfacilities
AT gianogliosilvia pilotproductionofsarscov2relatedproteinsinplantsaproofofconceptforrapidrepurposingofindoorfarmsintobiomanufacturingfacilities
AT fernandezdelcarmenasun pilotproductionofsarscov2relatedproteinsinplantsaproofofconceptforrapidrepurposingofindoorfarmsintobiomanufacturingfacilities
AT orzaezdiego pilotproductionofsarscov2relatedproteinsinplantsaproofofconceptforrapidrepurposingofindoorfarmsintobiomanufacturingfacilities