PROT3EcT, engineered Escherichia coli for the targeted delivery of therapeutics.
PROT3EcT, engineered Escherichia coli for the targeted delivery of therapeutics.
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PROT3EcT，工程大肠杆菌，用于靶向治疗。
DOI：
10.1016/j.molmed.2023.07.007
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发表时间：
2023
影响因子：
13.6
通讯作者：
Lesser,CammieF
中科院分区：
文献类型：
--
作者：
González-Prieto,Coral;Lynch,JasonP;Lesser,CammieF
PROT3EcT（益生菌III型分泌大肠杆菌治疗）配备了III型分泌系统，可以将蛋白质传递到周围环境。PROT3EcT的设计是模块化的。编码蛋白质分泌系统的操纵子包含在一个可移动的元件中。它们的表达是通过一个主转录因子来控制的，这个主转录因子的表达可以是构成性的，也可以是受调控的。外源蛋白可以通过在其氨基末端附加III型分泌序列来设计其分泌。在炎症性肠病（IBD）的临床前小鼠模型中，TNF-PROT3EcT（一种分泌抗tnf - α中和纳米体的变体）抑制结肠炎的发展。鉴于大肠杆菌可以在胃肠道和实体肿瘤中定植，PROT3EcT可以被设计为靶向递送治疗有效载荷，用于治疗肠道炎症和感染以及癌症，潜在地限制脱靶副作用。
PROT3EcT (PRObiotic Type III secretion E coli Therapeutic) is outfitted with a type III secretion system modified to deliver proteins into its surroundings. The design of PROT3EcT is modular. The operons that encode the protein secretion system are contained within a moveable element. Their expression is controlled via a master transcription factor whose expression can be constitutive or regulated. Heterologous proteins can be engineered to be secreted by appending their amino termini with a type III secretion sequence.In a preclinical mouse model of inflammatory bowel disease (IBD), TNF-PROT3EcT, a variant that secretes an anti-TNFα neutralizing nanobody, inhibited the development of colitis. Given that E. coli can colonize both the gastrointestinal (GI) tract and solid tumors, PROT3EcT can be engineered for the targeted delivery of therapeutic payloads for the treatment of intestinal inflammation and infections as well as cancer, potentially limiting off-target side effects.