A platform of genetically engineered bacteria as vehicles for localized delivery of therapeutics: Toward applications for Crohn's disease.
A platform of genetically engineered bacteria as vehicles for localized delivery of therapeutics: Toward applications for Crohn's disease.
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DOI：
10.1002/btm2.10113
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发表时间：
2018-09
影响因子：
7.4
通讯作者：
Bentley WE
中科院分区：
文献类型：
--
作者：
McKay R;Ghodasra M;Schardt J;Quan D;Pottash AE;Shang W;Jay SM;Payne GF;Chang MW;March JC;Bentley WE
对于针对胃肠道疾病的治疗，我们和其他人设想在疾病部位合成和分泌生物治疗药物的益生菌。为了实现这一目标，我们设计了一种新的生物技术。大肠杆菌，在一氧化氮（NO）存在下选择性合成和分泌模型生物标志物，一氧化氮是克罗恩病（CD）的肠道生物标志物。这是通过共表达成孔蛋白TolAIII与生物学粒细胞巨噬细胞集落刺激因子（GM-CSF）来实现的。我们还通过设计它们的运动回路和控制假趋性来设计这些细菌，使其在NO升高的部位积累。重要的是，因为我们专注于体外试验床，运动和生物治疗药物的生产是时空特征。靶向识别、合成和生物分子递送一起构成了可用于治疗CD的“智能”益生菌平台。此外，可以通过交换启动子和治疗基因来修改该平台以适应其他追求，以分别反映其他疾病生物标志物和治疗。
For therapies targeting diseases of the gastrointestinal tract, we and others envision probiotic bacteria that synthesize and excrete biotherapeutics at disease sites. Toward this goal, we have engineered commensal E. coli that selectively synthesize and secrete a model biotherapeutic in the presence of nitric oxide (NO), an intestinal biomarker for Crohn's disease (CD). This is accomplished by co‐expressing the pore forming protein TolAIII with the biologic, granulocyte macrophage‐colony stimulating factor (GM‐CSF). We have additionally engineered these bacteria to accumulate at sites of elevated NO by engineering their motility circuits and controlling pseudotaxis. Importantly, because we have focused on in vitro test beds, motility and biotherapeutics production are spatiotemporally characterized. Together, the targeted recognition, synthesis, and biomolecule delivery comprises a “smart” probiotics platform that may have utility in the treatment of CD. Further, this platform could be modified to accommodate other pursuits by swapping the promoter and therapeutic gene to reflect other disease biomarkers and treatments, respectively.
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