Development of Host induced Gene Editing (Hi-GE): a novel platform for bacterial disease control

植物细菌性疾病和动物细菌性疾病分别对作物和牲畜造成毁灭性的破坏，造成重大的全球经济损失（每年价值数十亿英镑）。随着威胁人类健康的耐抗生素细菌的增加，农业综合企业面临着减少抗生素使用的压力。通过基因编辑（GE）开发抗菌耐药性显示出希望，但仍然受到缓慢/昂贵的基因发现的限制。细菌是引起植物新发感染性疾病的主要病原体之一。一个引人注目的例子是柑橘黄龙病，它被认为是世界上最具破坏性的柑橘疾病（Dala-Paula_et_al_2019）。柑橘绿化影响树木健康以及果实发育、成熟和品质。目前没有治疗方法或管理策略，受感染的树木在短短5年内就会死亡（Singerman_and_Rogers_2020）。在美国，在过去的十年里，柑橘绿化导致佛罗里达州的橙子产量下降了70%以上（USDA_2019），一盒橙子的价格上涨了3倍以上（Dala-Paula_et_al_2019）。热带生物科学公司正在开发高性能的热带作物商业品种（包括香蕉、咖啡、大米），以提高种植效率，增强消费者健康，并改进可持续的环境做法。我们的方法依赖于专有/专利的尖端GE技术，并克服了基因发现障碍。然而，我们目前的技术方法仅限于针对植物/病毒/真菌/害虫基因，而不能针对细菌。Tropic Biosciences成立于2016年，总部位于著名的Norwich Research Park，拥有世界领先的设施，由一群经验丰富的企业家和学者组成，包括：首席执行官Gilad Gershon，经验丰富的AgTech私募股权投资者/企业家；CSO Eyal Maori博士，Beelogics的科学联合创始人，被孟山都收购（2011年）；首席技术官Ofir Meir博士，Rosetta Green农业化学部门前负责人，被孟山都收购（2013年）。我们现在雇用了一个由80多名行业领先专家组成的团队，并筹集了2250万英镑的B轮融资（英国农业科技行业有史以来最大的一轮融资），通过对我们的新型香蕉品种的田间试验加速我们的增长轨迹，并进一步商业化我们专有的基因组编辑诱导基因沉默（GEiGS）技术平台。虽然GEiGS能够保护宿主免受病毒、真菌和害虫的侵害，但它不能针对细菌。这个研发项目首次扩展了我们对细菌的技术方法，与GEiGS具有很强的互补性。一个成功的项目，验证了概念的实验证明（技术就绪度3级），将开启内部开发高性能抗菌热带作物品种，抵抗新出现的细菌性植物疾病。通过向已建立的农业综合企业授权，Hi-GE平台还将促进非热带作物和动物抗菌特性的开发。

Bacterial diseases of plants and animals cause devastating damage to crops and livestock, respectively, resulting in significant global economic losses (worth multiple billions of pounds annually). With the rise of antibiotic-resistant bacteria threatening human health, agribusinesses are under pressure to reduce antibiotic use. Development of antibacterial resistance through gene editing(GE) shows promise, but remains limited by slow/costly gene discovery.Bacteria are one of the major pathogens causing emerging infectious plant diseases. One high-profile example is citrus greening or huanglongbing, which is recognised as the most devastating citrus disease worldwide(Dala-Paula_et_al_2019). Citrus greening affects tree health as well as fruit development, ripening, and quality. There is currently no cure or management strategy, with infected trees dying within as little as 5years(Singerman_and_Rogers_2020). In the US, over the last decade, citrus greening has caused Florida's orange production to decrease by over 70%(USDA_2019), and the price of a box of oranges to increase by over 3x(Dala-Paula_et_al_2019).Tropic Biosciences is developing high-performing commercial varieties of tropical crops (including banana, coffee, rice), which promote cultivation efficiencies, enhance consumer health, and improve sustainable environmental practices. Our approach relies on proprietary/patented cutting-edge GE technologies and has overcome the gene discovery barrier. However, our current technical approach is limited to targeting plant/viral/fungus/pest genes and cannot target bacteria.Headquartered at renowned Norwich Research Park, with access to world-leading facilities, Tropic Biosciences was founded in 2016 by a team of highly experienced entrepreneurs and academics, including: CEO Gilad Gershon, experienced AgTech private equity investor/entrepreneur; CSO Dr Eyal Maori, scientific co-founder of Beelogics, acquired by Monsanto(2011); and, CTO Dr Ofir Meir, former Head of the Agro Chemistry Division at Rosetta Green, acquired by Monsanto(2013).We now employ a team of 80+ industry-leading experts and have raised £22.5million Series B round (largest ever in the UK AgriTech sector) to accelerate our growth trajectory through field trials for our novel banana varieties and to further commercialise our proprietary Genome Editing induced Gene Silencing(GEiGS) technology platform.While GEiGS enables host protection against viruses, fungi, and pests, it cannot target bacteria. This R&D project extends our technical approach to bacteria for the first time and is highly complementary to GEiGS. A successful project, validating experimental proof of concept(technology readiness level 3) will unlock in-house development of high-performance antibacterial tropical crop varieties, resistant to emerging bacterial plant diseases. Through licensing to established agribusinesses, Hi-GE platform will also enable development of antibacterial traits in non-tropical crops and animals.