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

这项小企业创新研究（SBIR）二期项目的更广泛影响/商业潜力是开发首个基于rna的小分子免疫方法，用于治疗几种致命的植物疾病，包括葡萄藤上的苛刻木杆菌（Xf）。Xf疾病包括：(1)橄榄树快速衰退综合征，目前威胁着整个南欧的橄榄产业，并杀死了超过1000年的树；(2)皮尔斯病，严重破坏了南加州的葡萄园；(3)柑橘黄萎病，柑橘黄萎病是危害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，以预防影响美国葡萄藤的其他几种最严重的病毒和真菌疾病。单次接种可以潜在地提供对多种病原体的终身保护，同时不会伤害树木。如果不进行治疗，在几十年内，柑橘、橄榄和许多其他为数百万人提供食物的有价值的作物可能会在温室等防虫结构之外不复存在。这项正在扩大规模的技术是基于一种新的传染性RNA，这种RNA可以用作抗致病性药物的递送载体。本项目主要有4个主要目标：(1)优化抗Xf sirna，进一步改进葡萄作物接种工艺；(2)在葡萄作物中靶向Xf；(3)靶向葡萄红斑病毒；(4)针对葡萄浆原菌引起的葡萄霜霉病。将在针对每种病原体的单独试验中证明其功效，最终为能够保护葡萄藤免受多种致命病原体侵害的单一综合产品奠定基础。这项技术寻求建立在模型植物N. bethamiana的验证基础上，通过扩大到葡萄藤的有效性的全面演示。一旦证明有效，就会进行实地试验。该奖项反映了美国国家科学基金会的法定使命，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.