Development of spirulina for the manufacture and oral delivery of protein therapeutics

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Issue Date
2022-03-21Author
Jester, Benjamin W.
Zhao, Hui
Gewe, Mesfin
Adame, Thomas
Perruzza, Lisa
Bolick, David T.
Agosti, Jan
Khuong, Nhi
Kuestner, Rolf
Gamble, Caitlin
Cruickshank, Kendra
Ferrara, Jeremy
Lim, Rachelle
Paddock, Troy
Brady, Colin
Ertel, Stacey
Zhang, Miaohua
Pollock, Alex
Lee, Jamie
Xiong, Jian
Tasch, Michael
Saveria, Tracy
Doughty, David
Marshall, Jacob
Carrieri, Damian
Goetsch, Lauren
Dang, Jason
Sanjaya, Nathaniel
Fletcher, David
Martinez, Anissa
Kadis, Bryce
Sigmar, Kristjan
Afreen, Esha
Nguyen, Tammy
Randolph, Amanda
Taber, Alexandria
Krzeszowski, Ashley
Robinett, Brittney
Volkin, David B.
Grassi, Fabio
Guerrant, Richard
Takeuchi, Ryo
Finrow, Brian
Behnke, Craig
Roberts, James
Publisher
Nature Research
Type
Article
Article Version
Scholarly/refereed, publisher version
Rights
This article is licensed under a Creative Commons Attribution 4.0 International License.
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Show full item recordAbstract
The use of the edible photosynthetic cyanobacterium Arthrospira platensis (spirulina) as a biomanufacturing platform has been limited by a lack of genetic tools. Here we report genetic engineering methods for stable, high-level expression of bioactive proteins in spirulina, including large-scale, indoor cultivation and downstream processing methods. Following targeted integration of exogenous genes into the spirulina chromosome (chr), encoded protein biopharmaceuticals can represent as much as 15% of total biomass, require no purification before oral delivery and are stable without refrigeration and protected during gastric transit when encapsulated within dry spirulina. Oral delivery of a spirulina-expressed antibody targeting campylobacter—a major cause of infant mortality in the developing world—prevents disease in mice, and a phase 1 clinical trial demonstrated safety for human administration. Spirulina provides an advantageous system for the manufacture of orally delivered therapeutic proteins by combining the safety of a food-based production host with the accessible genetic manipulation and high productivity of microbial platforms.
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Citation
Jester, B.W., Zhao, H., Gewe, M. et al. Development of spirulina for the manufacture and oral delivery of protein therapeutics. Nat Biotechnol 40, 956–964 (2022). https://doi.org/10.1038/s41587-022-01249-7
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