The broader impact/commercial potential of this I-Corps project is in the use of precision genome editing, in conjunction with compute simulation techniques, to impact local eradication of invasive species, agricultural pests, or disease-transmitting organisms. These organisms pose serious challenges to human and environmental health and cause billions of dollars in economic damages to the US every year. Numerous approaches to control populations of pest organisms currently rely on physical (trapping, deterrence), chemical (pesticides, baited traps), or biological (viruses, predators) mechanisms. These currently available methods have been unable to "stem the tide" in invasive pests and their application has resulted in unintended environmental impacts. There is an urgent need for control technologies that are broadly applicable, highly scalable, and cost-effective. Recent advances in precision genome editing have enabled a next generation of engineered biocontrol agents that promise to be effective while minimizing unwanted impacts on the environment. The technology on which this project is based will provide a means to prevent the reproduction of pest organisms without the introduction of toxins or pesticides. This I-Corps project will focus on mosquito control since they transmit numerous serious diseases (Zika, Dengue, etc.) that are predicted to become increasingly prevalent in the US. <br/><br/>This I-Corps project is based on the concept of engineering barriers to sexual reproduction to control pest populations. Some of the most effective pest eradication campaigns in recent history have used radiation to sterilize male pests that are then released to compete with wild males. When the sterile males mate with females, no offspring are produced and the population numbers crash. However, many species cannot be sterilized using irradiation and remain competitive when released. The solution provided in this project is to hard-wire male-sterility into the genome of the target organism using modern tools in precision genome editing. The approach has been validated in laboratory organisms, and that the required components are functional in insects, fish, plants, and mammals. Additionally, computer simulation modeling has been encouraging and suggest this approach is more robust than other technologies that rely on genome editing.<br/><br/>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.