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.

Mirror biology is the creation of synthetic organisms composed entirely of mirror-image biomolecules, such as D-amino acids and L-sugars, in contrast to the natural use of L-amino acids and D-sugars. Though this novel field promises significant advances in medicine, biomanufacturing, and environmental applications due to the enhanced stability and immune evasion of mirror organisms, its features raise unprecedented biosecurity risks, particularly when combined with cybersecurity vulnerabilities in the digital infrastructures used to design, synthesise, and control mirror life. We mapped the mirror biology development pipeline, from genetic circuit design and cloud-based bioinformatics to automated laboratory systems, to examine the unprecedented biosecurity risks associated with mirror biology. We highlighted key cyber biosecurity vulnerabilities, including data manipulation, unauthorised access, and firmware tampering. Case studies illustrate specific risks such as tampering with genetic design tools and introducing harmful DNA sequences into supply chains. The paper reviews existing technological safeguards, including encryption, zero-trust architectures, AI-enabled anomaly detection, and governance mechanisms such as biosafety oversight and redline enforcement. It emphasises the need for inclusive governance, capacity building, and international collaboration to ensure that mirror biology is not pursued as a field of organism- level research.