Lumen Bioscience, Seattle, WA, USA.
Institute for Research in Biomedicine, Faculty of Biomedical Sciences, Università della Svizzera Italiana, Bellinzona, Switzerland.
Nat Biotechnol. 2022 Jun;40(6):956-964. doi: 10.1038/s41587-022-01249-7. Epub 2022 Mar 21.
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.
食用性光合蓝藻 Arthrospira platensis（螺旋藻）作为生物制造平台的应用受到缺乏遗传工具的限制。在这里，我们报告了用于螺旋藻中生物活性蛋白稳定、高水平表达的基因工程方法，包括大规模室内培养和下游处理方法。通过将外源基因靶向整合到螺旋藻染色体（chr）中，编码的蛋白类生物制药可占总生物量的 15%，在口服给药前无需纯化，在冷藏条件下稳定，并且在封装于干燥螺旋藻内时在胃转运过程中受到保护。口服给予针对弯曲杆菌（发展中国家婴儿死亡的主要原因）的螺旋藻表达抗体可预防小鼠疾病，并且 1 期临床试验证明了其对人体给药的安全性。螺旋藻通过将基于食品的生产宿主的安全性与微生物平台的可访问遗传操作和高生产力相结合，为制造口服递送的治疗性蛋白提供了有利的系统。
