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

The broader impact of this Small Business Innovation Research (SBIR) Phase I project is to develop the first small RNA-based vaccination approach for mature trees, vines, and bushes against Xylella fastidiosa (XF), one of agriculture’s most devastating bacterial diseases. XF diseases include (1) Olive Quick Decline Syndrome, which is currently threatening the entire Southern Europe 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. This project is based on a novel infectious RNA discovered by the Company’s team that can be used as a delivery vehicle for anti-pathogenic agents to target XF. A single inoculation can potentially provide lifetime protection while not harming the tree. As of today, there is no vaccination or cure for XF. If successful, this would represent a new platform potentially capable of vaccinating most trees against most fungal, bacterial, and viral diseases. In the absence of treatment, in a few decades, citrus, olives, and many other valuable crops that produce food for millions of people may cease to exist outside of insect-protective structures like greenhouses. The proposed project has four key milestones required to defeat XF: (1) identify small interfering RNAs (siRNAs) capable of targeting gene expression in a Gram-negative bacterium like XF, which has never been accomplished commercially, and integrate these siRNAs into a novel delivery vector, which can systemically infect plants with no apparent host range; (2) demonstrate that sufficient siRNAs are generated in phloem companion cells in a laboratory host to reduce titers of XF in the xylem where it exclusively resides; (3) show that the Company’s novel RNA vector, which can systemically infect all commercial varieties of citrus, can also systemically infect olive trees and/or grapevines; (4) amplify the RNA vector in trees susceptible to XF and demonstrate efficacy against XF in greenhouse trials. The proposed work will address the first two objectives in the model plant N. bethamiana and the third objective in olive and grapevines. 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.