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

Nat Biotechnol. 2022 Jun;40(6):956-964. doi: 10.1038/s41587-022-01249-7. Epub 2022 Mar 21.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomass
  • Humans
  • Mice
  • Photosynthesis
  • Proteins / metabolism
  • Spirulina* / genetics
  • Spirulina* / metabolism

Substances

  • Proteins