小柯机器人

美国Lumen生物科学公司James Roberts研究团队近日取得一项新成果。他们研究开发出了用于生产和口服蛋白质治疗剂的工程化螺旋藻。相关论文2022年3月21日在线发表于《自然—生物技术》杂志上。

在这里，研究人员报告了在螺旋藻中稳定、高水平表达生物活性蛋白的基因工程方法，包括大规模的室内培养和下游加工方法。将外源基因靶向整合到螺旋藻染色体 (chr) 中后，编码的蛋白质生物药物可占总生物量的15%，在口服给药前无需纯化，无需冷藏即可稳定，并且当封装在干螺旋藻中时在胃转运过程中受到保护。口服螺旋藻表达的针对弯曲杆菌的抗体可预防小鼠疾病，一项1期临床试验证明了对人类给药的安全性。螺旋藻通过将基于食品的生产宿主的安全性与可获得的基因操作和微生物平台的高生产力相结合，为生产口服治疗性蛋白质提供了一个有利的系统。

据了解，由于缺乏遗传工具，可食用光合蓝藻(螺旋藻) 作为生物制造平台的使用而受到限制。

附：英文原文

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

Author: Jester, Benjamin W., Zhao, Hui, Gewe, Mesfin, Adame, Thomas, Perruzza, Lisa, Bolick, David T., Agosti, Jan, Khuong, Nhi, Kuestner, Rolf, Gamble, Caitlin, Cruickshank, Kendra, Ferrara, Jeremy, Lim, Rachelle, Paddock, Troy, Brady, Colin, Ertel, Stacey, Zhang, Miaohua, Pollock, Alex, Lee, Jamie, Xiong, Jian, Tasch, Michael, Saveria, Tracy, Doughty, David, Marshall, Jacob, Carrieri, Damian, Goetsch, Lauren, Dang, Jason, Sanjaya, Nathaniel, Fletcher, David, Martinez, Anissa, Kaldis, Bryce, Sigmar, Kristjan, Afreen, Esha, Nguyen, Tammy, Randolph, Amanda, Taber, Alexandria, Krzeszowski, Ashley, Robinett, Brittney, Volkin, David B., Grassi, Fabio, Guerrant, Richard, Takeuchi, Ryo, Finrow, Brian, Behnke, Craig, Roberts, James

Issue&Volume: 2022-03-21

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 phase1 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.

DOI: 10.1038/s41587-022-01249-7

Source: https://www.nature.com/articles/s41587-022-01249-7

Nature Biotechnology：《自然—生物技术》，创刊于1996年。隶属于施普林格·自然出版集团，最新IF：68.164
官方网址：https://www.nature.com/nbt/
投稿链接：https://mts-nbt.nature.com/cgi-bin/main.plex