SBIR Phase II: Using a novel RNA therapy to immunize trees and vines against deadly bacteria

这个小企业创新研究（SBIR）第二阶段项目的更广泛的影响/商业潜力是开发第一种基于小RNA的免疫方法，用于几种致命的植物疾病，包括葡萄树中的Xylella fastidiosa（Xf）。Xf病害包括（1）橄榄快速衰退综合征，目前威胁整个南欧橄榄产业，杀死树龄超过1,000年的树木;（2）皮尔斯病，严重破坏南加州葡萄园;（3）柑橘杂色褪绿病，是威胁柑橘产业的几种病害之一。此外，该项目还寻求开发一种概念验证疫苗，以对抗影响美国葡萄树的其他几种最具影响力的病毒和真菌疾病。一次接种可以潜在地提供对多种病原体的终身保护，同时不伤害树木。如果不进行处理，几十年后，柑橘、橄榄和许多其他为数百万人生产食物的宝贵作物可能会在温室等昆虫保护结构之外不复存在。正在扩大规模的技术是基于一种新的感染性RNA，可用作抗病原体药物的运载工具。该项目的主要目标有4个：（1）优化针对Xf的siRNA，进一步改进葡萄藤作物的接种工艺;（2）在葡萄藤作物中靶向Xf;（3）靶向葡萄藤红斑病毒;（4）靶向由葡萄霜霉病菌引起的葡萄霜霉病。每种病原体的功效将在单独的试验中得到证明，最终为能够保护葡萄树免受多种致命病原体侵害的单一综合产品奠定基础。该技术寻求建立在模型工厂N中的验证的基础上。bethamiana通过扩大到葡萄藤中的功效的充分展示。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase II project is to develop the first small RNA-based immunization approach for several deadly plant diseases including Xylella fastidiosa (Xf) in grapevines. Xf diseases include (1) Olive Quick Decline Syndrome, which is currently threatening the entire Southern European olive industry and killing trees that are over 1,000 years old; (2) Pierce’s Disease, which has severely damaged Southern California vineyards; and (3) Citrus Variegated Chlorosis, which is one of several diseases threatening the citrus industry. In addition, the project seeks to develop a proof-of-concept inoculations against several other of the most impactful viral and fungal diseases affect grapevines in the United States. A single inoculation can potentially provide lifetime protection against multiple pathogens while not harming the tree. In the absence of treatment, in a few decades, citrus, olive, and many other valuable crops that produce food for millions of people may cease to exist outside of insect-protective structures like greenhouses. The technology being scaled-up is based on a novel infectious RNA that can be used as a delivery vehicle for anti-pathogenic agents. The proposed project has 4 key goals: (1) optimizing siRNAs against Xf and further improving the inoculation process for grapevine crops; (2) targeting Xf in grapevine crops; (3) targeting grapevine red blotch virus; (4) targeting downy mildew of grape caused by Plasmopara viticola fungus. Efficacy will be demonstrated in separate trials for each pathogen, ultimately laying the foundation for a single integrated product that would be able to protect grapevines against multiple deadly pathogens. This technology seeks to build on validations in the model plant N. bethamiana by scaling up to a full demonstration of efficacy in grapevines. Once efficacy is demonstrated, then field trials will be conducted.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.