Rapid advances in benchtop DNA synthesis technologies and emerging pathogens in recent years have elevated the importance of rapid nucleic acid screening for sequences of concern. The White House Office of Science and Technology Policy (OSTP) recently issued an updated framework outlining a unified process for screening synthetic nucleic acids, with an April 2025 deadline for implementation by federally funded researchers and institutions in the U.S. However, accurate, sensitive, and scalable characterization of synthetic nucleic acids remains an open challenge for current bioinformatic approaches and tools. To address this gap, my group at Rice University has developed a software platform (SeqScreen), specifically built from the ground up to provide a modular foundation for nucleic acid screening with relevance to biosurveillance and biosecurity. In this talk, I will cover: (i) the history of synthetic DNA screening approaches, (ii) the SeqScreen software platform, and (iii) conclude by discussing the utility of SeqScreen for detection of known and previously unseen DNA sequences of concern.