Why Implementation Gaps Could Undermine Synthetic Nucleic Acid Oversight

David R. Gillum^1*Rebecca Moritz²

• ¹University of Nevada, Reno, Reno, United States
• ²Tutela Strategies, LLC, Reno, United States

Introduction U.S. biosecurity policy has shifted from organism-level controls to sequence-level governance of synthetic nucleic acids in response to genome synthesis risks, AI-assisted design, and globalized DNA/RNA manufacturing. While intended to strengthen safety, this shift risks overburdening under-resourced institutions and creating oversight that looks thorough but adds little protection. This study examines the widening "implementation gap" between policy ambition and operational capacity. Methods Drawing on practitioner experience and current literature, we analyzed policy frameworks, institutional practices, and case examples to identify structural challenges in sequence-level oversight. Particular attention was given to how definitions, regulatory triggers, and institutional resources interact in practice, creating gaps between intent and capacity. This mixed approach captured oversight design and implementation realities across diverse settings. Results We found three core obstacles: ambiguous definitions of sequences of concern, fragmented and overlapping regulatory triggers, and underdeveloped screening and review capacity. Ambiguity generates uncertainty about what to flag, while fragmented rules add redundancies without clarifying responsibility. Limited resources further constrain oversight. These weaknesses produce overinclusive surveillance, inconsistent screening, unmanaged legacy inventories, and a lack of shared reference tools—straining resources without proportional security benefits. Discussion Aligning oversight with capacity is essential to avoid brittle systems with limited benefit. We propose seven reforms: functional risk tiering, federal investment in biosafety infrastructure, pilots and real-world testing, institutional certification, adaptive governance, pragmatic global harmonization, and coupling screening with operational safeguards. Embedding implementer perspectives and calibrating oversight to realistic capacities will help ensure credible, resilient, and effective biosecurity in the synthetic nucleic acid era.