Control of Campylobacter by CRISPR/CAS systems

通过 CRISPR/CAS 系统控制弯曲杆菌

• 批准号: 77876
• 金额: $ 26.4万
• 依托单位: FOLIUM FOOD SCIENCE LIMITED
• 依托单位国家: 英国
• 项目类别: Collaborative R&D
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=77876
• 关键词: Control; Campylobacter; CRISPR; CAS; systems

Agriculture faces many major and diverse challenges including the need to meet the demand for increased productivity in the face of a growing world population whilst being effective custodians of environmental resources by being highly sustainable. For animal production, achieving these global goals whilst ensuring the highest standards of health and welfare, which incidentally in the contemporary context of growing antibiotic resistance impacting on human health, must rely upon prudent use if not "no use antibiotics ever" in maintaining animal health. This is a stretching aim that requires innovative, disruptive new pathogen control measures.Growing poultry for meat is one of the fastest growing sectors for protein production globally. Whilst biosecurity measures and some feed additive interventions impact on health and welfare of the birds, the human zoonotic _Campylobacter jejuni_ remains a significant human health issue with poultry still the primary source of human infections. The latest available government figures show reported number of cases increased from 52,381 in 2016 to 56,729 in 2017, an increase of 4,348 cases ([https://www.gov.uk/government/publications/campylobacter-infection-annual-data/campylobacter-data-2008-to-2017][0]) and this rise is despite improving biosecurity management practices on farm and through the food chain.The purpose of this proposal is to complete the development of a novel, disruptive technology to contribute to the reduction of Campylobacter illness in humans by interventions at production level, in poultry. To date, Folium Science has demonstrated the ability to selectively kill Salmonella by redirecting the bacterial immune system, the CRISPR-CAS system, to 'self-destruct'. This proof of concept is now being developed for commercial release as part of control measures on farm to reduce the burden of this pathogen. The first product is a well established probiotic that carries CRISPR-CAS programmed to target with exquisite specificity all Salmonella serotypes. The probiotic delivers the system to Salmonella inducing inhibition of growth.The challenge that remains is to take this technology and demonstrate that it can be reprogrammed to target _Campylobacter jejuni_ that, whilst having little effect in poultry as they grow, are major pathogens in humans. A programme of work to develop a pre-commercial prototype "Guided Biotic" specific for the control of _C. jejuni_ was interrupted at the design stage by laboratory closure and furlough of staff due to COVID19\. This application seeks to restore the programme. Having designs already made the steps to a pre-commercial prototype include (i) validation of restriction of the target without any off target effects, (ii) delivery using current probiotic delivery systems.[0]: https://www.gov.uk/government/publications/campylobacter-infection-annual-data/campylobacter-data-2008-to-2017

农业面临着许多重大和多样化的挑战，包括面对不断增长的世界人口，需要满足提高生产力的需求，同时通过高度可持续的方式有效地管理环境资源。就动物生产而言，在实现这些全球目标的同时，确保最高标准的健康和福利，顺便说一句，在影响人类健康的抗生素耐药性日益增加的当代背景下，必须依靠谨慎使用抗生素（如果不是“永远不使用抗生素”）来维持动物健康。这是一个艰巨的目标，需要创新的、具有破坏性的新病原体控制措施。饲养禽肉是全球蛋白质生产增长最快的部门之一。虽然生物安全措施和一些饲料添加剂干预措施对禽类的健康和福利有影响，但人类人畜共患病——空肠弯曲杆菌——仍然是一个重大的人类健康问题，家禽仍然是人类感染的主要来源。最新的政府数据显示，报告的病例数从2016年的52381例增加到2017年的56729例，增加了4348例（[https://www.gov.uk/government/publications/campylobacter-infection-annual-data/campylobacter-data-2008-to-2017][0]]），尽管农场和整个食物链的生物安全管理措施有所改善，但这一数字仍在上升。本提案的目的是完成一项新的破坏性技术的开发，通过在家禽生产水平上的干预措施，有助于减少人类弯曲杆菌疾病。迄今为止，Folium Science已经证明了通过重定向细菌免疫系统CRISPR-CAS系统“自我毁灭”来选择性杀死沙门氏菌的能力。目前正在开发这一概念验证，以供商业发布，作为农场控制措施的一部分，以减轻这种病原体的负担。第一个产品是一种成熟的益生菌，它携带CRISPR-CAS程序，以精确的特异性靶向所有沙门氏菌血清型。益生菌将系统传递给沙门氏菌，诱导生长抑制。仍然存在的挑战是利用这项技术并证明它可以被重新编程，以瞄准“空肠弯曲杆菌”，这种细菌虽然在家禽生长过程中对它们几乎没有影响，但却是人类的主要病原体。一项工作方案，开发一种专门用于控制c的商业前原型“引导生物”。由于2019冠状病毒病，实验室关闭和工作人员休假在设计阶段中断。此应用程序寻求恢复程序。设计已经向预商业原型迈出了步骤，包括(i)验证目标的限制，没有任何脱靶效应，（ii）使用当前的益生菌输送系统进行输送。[0]: https://www.gov.uk/government/publications/campylobacter感染-年度data/campylobacter -数据- 2008 - 2017