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

植物和动物的细菌性疾病分别对农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)。随着抗生素抗药性细菌的增加，威胁人类健康，农业综合企业面临减少抗生素使用的压力。通过基因编辑(GE)来开发抗菌素抗性是有希望的，但仍然受到基因发现缓慢/昂贵的限制。细菌是导致新出现的侵染性植物疾病的主要病原体之一。一个引人注目的例子是柑橘绿化或黄龙病，它被认为是世界上最具破坏性的柑橘病害(Dala-Paula_et_al_2019)。柑橘的绿色化不仅影响果实的发育、成熟和品质，而且影响树木的健康。目前没有治愈或管理策略，受感染的树木在短短5年内死亡(Singerman和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、水稻)，以提高种植效率，增强消费者健康，并改善可持续的环境实践。我们的方法依赖于专利/专利的尖端GE技术，并克服了基因发现的障碍。然而，我们目前的技术方法仅限于针对植物/病毒/真菌/虫害基因，不能针对细菌。热带生物科学公司总部位于著名的诺维奇研究园区，拥有世界领先的设施，于2016年由一支经验丰富的企业家和学者团队创立，其中包括：AgTech经验丰富的私募股权投资者/企业家首席执行官Gilad Gershon；被孟山都收购的BeeLogics科学联合创始人CSO EYAL Maori博士(2011年)；此外，首席技术官Ofir Meir博士，罗塞塔绿色公司(Rosetta Green)农业化学部前主管，被孟山都(Monsanto)收购(2013)。我们现在雇佣了一支80多名行业领先的专家团队，并已筹集了2,250万GB B系列资金(英国农业技术部门有史以来规模最大的一轮)，以通过我们新型香蕉品种的田间试验加快我们的增长轨迹，并进一步将我们专有的基因组编辑诱导基因沉默(GEiGS)技术平台商业化。虽然GEiGS能够保护宿主免受病毒、真菌和害虫的攻击，但它不能针对细菌。这个研发项目首次将我们的技术方法扩展到细菌，并对GEiGS具有很强的互补性。一个成功的项目，验证概念的实验验证(技术准备级别3)将开启高性能抗菌热带作物品种的内部开发，抵抗新出现的细菌性植物疾病。通过向现有的农业综合企业发放许可证，Hi-GE平台还将使非热带作物和动物的抗菌特性得以开发。

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.