Development of spirulina for the manufacture and oral delivery of protein therapeutics.
Development of spirulina for the manufacture and oral delivery of protein therapeutics.
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DOI：
10.1038/s41587-022-01249-7
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发表时间：
2022-06
影响因子：
46.9
通讯作者：
Roberts, James
中科院分区：
文献类型：
--
作者：
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
由于缺乏遗传工具，可食用的光合作用蓝藻钝顶节旋藻(螺旋藻)作为生物制造平台的使用受到限制。本文报道了在螺旋藻中稳定、高效表达生物活性蛋白的基因工程方法，包括大规模、室内培养和下游加工方法。在将外源基因定向整合到螺旋藻染色体(ChR)后，编码的蛋白质生物药物可占总生物量的15%，口服前无需纯化，无需冷藏即可稳定，在干燥的螺旋藻中包装后可在胃转运过程中受到保护。口服针对弯曲杆菌的螺旋藻表达的抗体可以预防小鼠疾病， 1期临床试验证明人类给药是安全的。弯曲杆菌是发展中国家婴儿死亡的主要原因。螺旋藻结合了以食品为基础的生产宿主的安全性和可获得的遗传操作以及微生物平台的高生产率，为制造口服治疗蛋白提供了一个有利的系统。螺旋藻被用来制造针对弯曲杆菌的治疗性抗体。
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. Spirulina is used to manufacture a therapeutic antibody against campylobacter.
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影响因子：
14.9
作者：
Klindworth A;Pruesse E;Schweer T;Peplies J;Quast C;Horn M;Glöckner FO
通讯作者：
Glöckner FO
DOI：
10.1073/pnas.75.4.1929
发表时间：
1978-01-01
影响因子：
11.1
作者：
HINNEN, A;HICKS, JB;FINK, GR
通讯作者：
FINK, GR
影响因子：
6.7
作者：
Giallourou N;Medlock GL;Bolick DT;Medeiros PH;Ledwaba SE;Kolling GL;Tung K;Guerry P;Swann JR;Guerrant RL
通讯作者：
Guerrant RL
影响因子：
5.9
作者：
Masuda, Kazuya;Chitundu, Maureen
通讯作者：
Chitundu, Maureen
DOI：
10.1016/s0140-6736(16)31529-x
发表时间：
2016-09-24
期刊：
Lancet (London, England)
影响因子：
--
作者：
Liu J;Platts-Mills JA;Juma J;Kabir F;Nkeze J;Okoi C;Operario DJ;Uddin J;Ahmed S;Alonso PL;Antonio M;Becker SM;Blackwelder WC;Breiman RF;Faruque AS;Fields B;Gratz J;Haque R;Hossain A;Hossain MJ;Jarju S;Qamar F;Iqbal NT;Kwambana B;Mandomando I;McMurry TL;Ochieng C;Ochieng JB;Ochieng M;Onyango C;Panchalingam S;Kalam A;Aziz F;Qureshi S;Ramamurthy T;Roberts JH;Saha D;Sow SO;Stroup SE;Sur D;Tamboura B;Taniuchi M;Tennant SM;Toema D;Wu Y;Zaidi A;Nataro JP;Kotloff KL;Levine MM;Houpt ER
通讯作者：
Houpt ER