分泌物
肿瘤坏死因子α
生物
大肠杆菌
炎症
药物输送
免疫学
计算生物学
基因
纳米技术
材料科学
生物化学
作者
Jason P. Lynch,Coral Coral González-Prieto,Analise Reeves,Urmila Powale,Neha Godbole,Jacqueline M. Tremblay,Florian I. Schmidt,Hidde L. Ploegh,Jonathan N. Glickman,John M. Leong,Charles B. Shoemaker,Wendy S. Garrett,Cammie F. Lesser
出处
期刊:Research Square - Research Square
日期:2022-01-21
被引量:2
标识
DOI:10.21203/rs.3.rs-1233122/v1
摘要
Abstract New drug platforms are needed which enable the directed delivery of therapeutics to sites of disease to maximize efficacy and limit off-target effects. Here, we report the development of PROT3EcT, commensal Escherichia coli engineered for the direct secretion of proteins into their surroundings. PROT3EcT are composed of four modular components: an E. coli chassis, a modified bacterial protein secretion system, a regulatable transcriptional activator, and a secretable therapeutic payload. PROT3EcT that secrete functional single-domain antibodies, nanobodies (Nb), stably colonize and maintain a functional secretion system within the intestines of mice. A single prophylactic dose of PROT3EcT that secretes a tumor necrosis factor alpha (TNFα) neutralizing Nb is sufficient to ablate TNF levels and prevent the development of injury and inflammation in a chemically-induced model of inflammatory bowel disease. This work lays the foundation for the development of PROT3EcT as a therapeutic platform for the treatment of at least gastrointestinal-based diseases.
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