Why implementation gaps could undermine synthetic nucleic acid oversight.

Area of Science:

• Biosecurity policy
• Synthetic biology
• Regulatory science

Background:

• Recent U.S. biosecurity policy shifts focus from organism-level to sequence-level governance of synthetic nucleic acids.
• This shift is driven by risks associated with de novo genome synthesis, AI-assisted design, and globalized DNA/RNA manufacturing.
• Current policy risks overburdening institutions and creating an "implementation gap" between policy ambition and operational capacity.

Purpose of the Study:

• Examine the implementation gap in sequence-level oversight of synthetic nucleic acids.
• Identify structural challenges and their interaction with institutional practices and resources.
• Propose reforms to align biosecurity policy with operational realities.

Main Methods:

• Analysis of policy frameworks, institutional practices, and case examples.
• Drawing on practitioner experience and current literature.
• Mixed-methods approach to capture both high-level design and practical implementation.

Main Results:

• Three core obstacles identified: ambiguous definitions, fragmented regulatory triggers, and underdeveloped institutional capacities.
• These weaknesses lead to overinclusive surveillance, inconsistent screening, and unmanaged inventories.
• Current systems strain resources without proportional security benefits.

Conclusions:

• Aligning biosecurity oversight with real-world capacity is crucial for effective and resilient systems.
• Seven reforms are proposed, including risk tiering, federal investment, policy pilots, and adaptive governance.
• Embedding implementer perspectives and calibrating oversight to realistic capacities will enhance biosecurity in the synthetic nucleic acid era.