SBIR Phase I: Enhancing the skin microbiome for mosquito repellency: Next generation mosquito repellent derived from big data analysis

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project is to develop a safe, natural, long-lasting and effective mosquito repellent product by exploiting the natural repellent compounds present in the skin microbiome. Mosquito-borne illnesses affect 700M people worldwide and cause several million deaths each year. Chikungunya, West Nile, Malaria, Zika, Dengue, are just some of the debilitating vectors spread by mosquitoes. Mosquito-derived diseases cost >$6.8B/year and the market for mosquito repellents is >$3.2B and growing. Many solutions are aimed at killing and disabling mosquitoes, but mosquitoes are a crucial part of the ecological food chain. Further, many repellents are extremely toxic, and mosquitoes are developing resistance. The proposed technology will be used to identify compounds that will drive the endogenous skin microbiome to a more mosquito repellent phenotype. Using these methods, it is possible to harness the biochemistry contained in the native skin microbiome to create an endogenous repellency that is a safe, natural, environmentally friendly, and effective barrier to mosquitoes. It is expected that this repellency approach may be used safely even with children and pregnant women. In addition, it may be possible to use this approach to develop repellents for multiple insects, repellent products for companion animals, and additional over-the-counter skin products. The intellectual merit of this SBIR Phase I project is to develop a new class of topical insect repellents by influencing repellency in the skin microbiome. This will be accomplished by developing and validating a platform technology to identify compounds produced by the microbiome that are associated with biochemical pathways of interest, and use the identified compounds to target those pathways whose end-products comprise natural mosquito-repellent compounds. The goal is to create a topical mosquito repellent product. For this project, the plan is to complete metagenome sequencing on skin samples collected from individuals that are either naturally repellent or attractive to Anopheles mosquitoes (the mosquito that carries Malaria). The next step is to predict metabolite compound turnover and use metabolomics to validate the results. In vitro assays and in silico models will be used to provide proof-of-concept for the use of those predicted compounds to induce the microbiota to produce mosquito repellent metabolites. 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.