Optimising symbiont-mediated RNA interference as a control measure for Western Flower Thrips and Tomato Spotted Wilt Virus

Current control strategies for agricultural insect pests are heavily reliant on chemical pesticides. However, there is no safe targeted chemical pesticide; these chemicals can also affect non-target beneficial insect species such as pollinating bees. The applicants have recently developed a new technology, symbiont-mediated RNA interference (SMR), that can be applied in a wide range of insects. This proposal will extend their success in applying SMR to control populations of Western Flower Thrips (WFT). WFT are a major pest of both vegetables and ornamental crops, and they feed on leaves, flowers, and pollen, of many plant species. They are globally distributed as an invasive species that has spread from western USA in the last 50 years. As a pesticide, SMR offers two-tier specificity, meaning that only the target species, and not beneficial species such as bees, should be affected. This proposal explores how the technology can be optimised for population control of WFT and whether it can be extended to limit transmission of Tomato Spotted Wilt Virus. This plant virus is transmitted by WFT and can infect over 1,000 species of plants in 84 families, giving it one of the broadest host ranges of any plant pathogen; it causes annual losses to agriculture worldwide of over $1 billion value. Demonstrating that SMR can prevent virus transmission by an insect will be an important proof-of-concept, with implications for how the technology could be applied in other contexts such as limiting the spread of Dengue and Zika viruses by mosquitoes. In addition, the research programme will provide experimental data to demonstrate target species specificity, for instance whether there could be any detrimental effects on honey bees, and whether horizontal gene transfer and the evolution of resistance could be concerns with respect to future field applications of the SMR technology.

With support from a 15 month BBSRC Tools and Resources Development grant, Dyson and Whitten successfully established a new patented technology for gene silencing in insects, mediated by bacterial symbionts, and termed Symbiont-Mediated RNA interference (SMR). The group has successfully applied this technology as a population control measure in Western Flower Thrips (WFT) by targeting an essential insect gene expressed in larvae. WFT are a major worldwide pest of both vegetables and ornamental crops, and they feed on leaves, flowers, and pollen, of many plant species in different taxa. They are globally distributed as an invasive species that has spread from western North America in the last 50 years. In contrast to conventional pesticides, this new SMR biocide offers exquisite two-tier specificity in that it combines the sequence specificity of RNA interference together with the specificity of a symbiont-host association. This 'smart' technology has significant commercial potential, with the prospect of replacing conventional pesticides that are toxic to non-target fauna and to which resistance of target species is a very real problem. This proposal explores how the technology can be optimised for population control of WFT and whether it can be extended to limit transmission of Tomato Spotted Wilt Virus, establishing a proof of concept for applying SMR to limit insect spread of other RNA viruses. This plant virus is transmitted by WFT and can infect over 1,000 species of plants in 84 families, giving it one of the broadest host ranges of any plant pathogen; it causes annual losses to agriculture worldwide of over $1 billion value. In addition, the research programme will provide experimental data to demonstrate target species specificity, and whether horizontal gene transfer and the evolution of resistance could be concerns with respect to future field applications of the SMR technology.

The research in this proposal is designed to strengthen further the prospects for commercialization of a patented technology developed by the applicants, symbiont-mediated RNA interference (SMR), and to seek to replace harmful non-targeted chemical pesticides with a smart, environmentally-friendly alternative and so improve worldwide agricultural productivity.

At the end of a successful 15 month BBSRC-funded Tools and Resources Development grant to develop the SMR technology, the applicants, with help from Swansea University's Tech Transfer Office (Research, Enterprise and Innovation Services; REIS) sought protection of the intellectual property with a broad patent application (GB1415502.2). In addition, after completing further research to demonstrate application of the technology in Western Flower Thrips, a second, more specific patent application was filed (PCT/GB2016/051683). As a consequence of these patents, the applicants were contacted via REIS by the US agritech company TechAccel (www.techaccel.net/) and a collaborative research agreement between Swansea University and the company followed thereafter.

The proposal aims to optimize and satisfy certain safety criteria pertaining to the population control of an agricultural insect pest population using SMR. In addition, the proposal also seeks to demonstrate how the technology can be used to prevent transmission of a plant pathogenic virus by the insect. This virus has a huge worldwide impact on agricultural productivity. This study will provide a precedent for the control of other insect-vectored pathogens of agricultural importance and, in addition, viruses that cause human and animal disease. For example, the technology could be translated to limit transmission of arboviruses transmitted by Aedes mosquitoes, such as Dengue, Zika and Chikungunya. Consequently, the impact of this proposal is far-reaching and embraces agricultural productivity, and both human and animal health.