RRC ID 70487
Author Jester BW, Zhao H, Gewe M, Adame T, Perruzza L, Bolick DT, Agosti J, Khuong N, Kuestner R, Gamble C, Cruickshank K, Ferrara J, Lim R, Paddock T, Brady C, Ertel S, Zhang M, Pollock A, Lee J, Xiong J, Tasch M, Saveria T, Doughty D, Marshall J, Carrieri D, Goetsch L, Dang J, Sanjaya N, Fletcher D, Martinez A, Kadis B, Sigmar K, Afreen E, Nguyen T, Randolph A, Taber A, Krzeszowski A, Robinett B, Volkin DB, Grassi F, Guerrant R, Takeuchi R, Finrow B, Behnke C, Roberts J.
Title Development of spirulina for the manufacture and oral delivery of protein therapeutics.
Journal Nat Biotechnol
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.
Volume 40(6)
Pages 956-964
Published 2022-6-1
DOI 10.1038/s41587-022-01249-7
PII 10.1038/s41587-022-01249-7
PMID 35314813
PMC PMC9200632
MeSH Animals Biomass Humans Mice Photosynthesis Proteins / metabolism Spirulina* / genetics Spirulina* / metabolism
IF 36.553
Algae NIES-39