Engineering of Human Commensal Bacterium for the Controlled in vivo Delivery of Human Keratinocyte Growth Factor to Trea

用于将人角质形成细胞生长因子体内受控递送至治疗的人类共生细菌工程

• 批准号: G0600431/1
• 负责人: Zaed Hamady
• 金额: $ 22.84万
• 依托单位: University of Leeds
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2006
• 资助国家: 英国
• 起止时间: 2006 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0600431%2F1
• 关键词: Engineering; Human; Commensal; Bacterium; Controlled

Inflammatory Bowel Disease (IBD) affects 0.2% of the population in developed countries. Current therapy is restricted to drugs that suppress the body‘s immune system. These are not curative, may cause severe side effects and are likely to be needed for long periods. There is therefore a need for more targeted controlled forms of therapy. Various protein molecules have been identified as potential therapeutic factors for IBD. Due to their inherent instability and potential toxicity these factors can not be given to patients by conventional means. Recently developed genetically modified (GM) bacteria to produce and secrete various factors locally, which when administered to mouse models of IBD was as effective as steroids in preventing and treating IBD. The limitation of current bacterial delivery systems, however is that the production and release of the heterologous protein by the bacteria cannot be controlled; this is an important safety concern. Therefore, a novel approach proposed to develop a second generation of GM bacteria. This involves engineering a non pathogenic commensal bacterium to produce growth factor under the control of a naturally occurring plant product which can be included in a normal diet. We propose that the delivery of these proteins inside the bowel by GM bacteria would be safe and effective in preventing and treating IBD

发达国家 0.2% 的人口患有炎症性肠病 (IBD)。目前的治疗仅限于抑制人体免疫系统的药物。这些药物没有治疗作用，可能会导致严重的副作用，并且可能需要长期使用。因此，需要更有针对性的受控治疗形式。多种蛋白质分子已被确定为 IBD 的潜在治疗因子。由于其固有的不稳定性和潜在的毒性，这些因子不能通过常规方式给予患者。最近开发的转基因（GM）细菌可以在局部产生和分泌各种因子，当将其给予IBD小鼠模型时，在预防和治疗IBD方面与类固醇一样有效。然而，当前细菌递送系统的局限性在于细菌异源蛋白的产生和释放无法控制；这是一个重要的安全问题。因此，提出了开发第二代转基因细菌的新方法。这涉及改造一种非致病性共生细菌，使其在天然存在的植物产品的控制下产生生长因子，该植物产品可以包含在正常饮食中。我们认为，通过转基因细菌将这些蛋白质输送到肠道内对于预防和治疗 IBD 是安全有效的