Rethinking governance of synthetic cells

Synthetic cells represent a class of engineered biological systems that span a continuum from non-replicating biochemical assemblies to genome-containing entities, exposing limitations in conventional approaches to biotechnology governance. These systems are enabled by advances in synthetic nucleic acid technologies, which provide the basis for their design, function, and programmability and expand the accessible design space of engineered biological systems. Building on a recent National Academies report, this perspective argues that continued advances in nucleic acid synthesis and design are a key driver of emerging biosafety and biosecurity challenges, particularly by challenging assumptions embedded in sequence- and organism-based approaches to oversight. We treat synthetic cells as a boundary case that highlights limitations in nucleic-acid-enabled biotechnology governance. Drawing on the report's property-based framework, we examine how governance misalignment arises in practice through the interaction of categorical triggers, institutional boundaries, and the timing of oversight across the research and development lifecycle. We further highlight limitations in how current risk assessment approaches are applied and provide structured questions that more explicitly support the evaluation of benefits alongside risks to improve consistency in function- and context-based assessment across institutional and policy settings. Together, these observations underscore the need to align governance approaches with system properties, intended use, and deployment context as engineering biology continues to expand beyond conventional biological categories.