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Development of spirulina for the manufacture and oral delivery of protein therapeutics
Jester, Benjamin W. Zhao, Hui Gewe, Mesfin Adame, Thomas Perruzza, Lisa Bolick, David T. Agosti, Jan Khuong, Nhi Kuestner, Rolf Gamble, Caitlin
Jester, Benjamin W.
Zhao, Hui
Gewe, Mesfin
Adame, Thomas
Perruzza, Lisa
Bolick, David T.
Agosti, Jan
Khuong, Nhi
Kuestner, Rolf
Gamble, Caitlin
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Abstract
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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Date
2022-03-21
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Publisher
Nature Research
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Keywords
Genetic engineering, Recombinant protein therapy, Expression systems, Protein delivery
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