The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project is the development of safe and effective, toxin-free biocontrol of insects and other invasive organisms. Mosquitoes and other insects cost upwards of $10 B/year to the world economy due to their impact on human health and revenue losses to agriculture. Current control measures available are neither effective, environmentally friendly, scalable for widespread application, nor cost effective to implement. This project aims to address the above deficiencies. The goal is to develop insect control methods that are effective, have minimal environmental impact and are cost effective to implement and hence attractive to commercialization. This SBIR Phase I project proposes to develop a genetically modified sterile male accelerated release technique (SMART) for Aedes aegypti mosquito control. The innovative development of SMART mosquitoes solves several issues in mosquito control, including: sorting of males and females, transportation of adult males, laborious release processes, and non-scalable operation. The SMART approach requires eggs that can be produced at a centralized facility, stored at room temperature until needed, and inexpensively shipped at room temperature in a small container. Customers need only add water with supplied nutrients to hatch the eggs, from which only males emerge that amplify male sterility by producing sterile males with each reproduction cycle. The scope of the research proposal is limited to creating synthetic genetic incompatibility in mosquitoes by targeting germline male sterility. The key technical objectives are to: 1) optimize components of programmable transcriptional activators in mosquitoes and 2) engineer synthetic genetic incompatibility into germline of Ae. aegypti. The anticipated outcome of this project will be state-of-the-art SMART mosquitos that are effective at biocontrol that is scalable and economical to implement. 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.