Expression and manufacturing of protein therapeutics in spirulina

Arthrospira platensis (commonly known as spirulina) is a photosynthetic cyanobacterium[1][1]. It is a highly nutritious food that has been consumed for decades in the US, and even longer by indigenous cultures[2][2]. Its widespread use as a safe food source and proven scalability have driven frequent attempts to convert it into a biomanufacturing platform. But these were repeatedly frustrated by spirulina’s genetic intractability. We report here efficient and versatile genetic engineering methodology for spirulina that allows stable expression of bioactive protein therapeutics at high levels. We further describe large-scale, indoor cultivation and downstream processing methods appropriate for the manufacturing of biopharmaceuticals in spirulina. The potential of the platform is illustrated by pre-clinical development and human testing of an orally delivered antibody therapeutic against campylobacter, a major cause of infant mortality in the developing world and a growing antibiotic resistance threat[3][3],[4][4]. This integrated development and manufacturing platform blends the safety of food-based biotechnology with the ease of genetic manipulation, rapid growth rates and high productivity characteristic of microbial platforms. These features combine for exceptionally low-cost production of biopharmaceuticals to address medical needs that are unfeasible with current biotechnology platforms. ### Competing Interest Statement J. R. and B. F. are the founders and current employees of Lumen Bioscience, Inc. (Lumen) and owns stock/stock options of Lumen. B. J., H. Z., M. G., T. A., J. A, N. K., R. K., C. G., K. C., J. F., R. L., T. P., C. B., S. E., M. Z., M. T., T. S., D. D., J. M., J. L., L. G., J. D., N. S., D. F., A. M., B. K., K. S., M. S., R. T., and C. B. are employees or paid advisors of Lumen; all current and former employees own stock/stock options of Lumen. D. C., E. A., T. N., A. R., A. T., A. K., and B. R. were employees of Lumen at the time of data generation. Lumen has issued patents (U.S. 10,131,870) and a pending patent application (International Application No. PCT/US2020/040794) relating to certain research described in this article. [1]: #ref-1 [2]: #ref-2 [3]: #ref-3 [4]: #ref-4