Strengthening global biosecurity for synthetic nucleic acid technology: from sequence screening to risk-based...

Synthetic nucleic acid technology has expanded rapidly, reducing the cost, time, and technical barriers associated with DNA and RNA synthesis. Existing governance frameworks have focused mainly on sequence-based screening of synthesis orders and customer verification. Although these measures remain essential, they are no longer sufficient as standalone safeguards in a landscape shaped by AI-assisted biological design, globally distributed synthesis capacity, uneven regulatory implementation, and unclear liability across the design-synthesis-use pathway. Protein language models, generative design tools, and other AI-assisted approaches may expand the sequence design space in ways that are harder to assess through homology-based screening alone. This review examines the current biosecurity architecture for synthetic nucleic acid technology and identifies structural limitations in sequence-centered governance. We propose a systems-based, risk-informed framework organized around four interacting dimensions: design capability, access, governance strength, and liability and attribution clarity. The framework is diagnostic and semi-structured rather than quantitative, and is intended to complement existing screening standards and national regulatory approaches. Building on it, we present a four-tier governance escalation model that links dimension profiles to proportionate policy responses and assigns responsibilities to synthesis providers, research institutions, governments, funders, and international bodies. A worked case study illustrates how the framework can be applied to a plausible governance scenario with growing synthetic biology capacity and uneven oversight. The approach integrates equity and proportionality as governance constraints, supporting biosecurity strengthening without undermining responsible innovation.