Securing the Language of Life: Inheritable Watermarks from DNA Language Models to Proteins

DNA language models have revolutionized our ability to understand and design DNA sequences—the fundamental language of life—with unprecedented precision, enabling transformative applications in therapeutics, synthetic biology, and gene-editing. However, this capability also poses substantial dual-use risks, including the potential for creating pathogens, viruses, even bioweapons. To address these biosecurity challenges, we introduce two innovative watermarking techniques to reliably track the designed DNA: DNAMark and CentralMark. DNAMark employs synonymous codon substitutions to embed watermarks in DNA sequences while preserving the original function. CentralMark further advances this by creating inheritable watermarks that transfer from DNA to translated proteins, leveraging protein embeddings to ensure detection across the central dogma. Both methods utilize semantic embeddings to generate watermark logits, enhancing robustness against natural mutations, synthesis errors, and adversarial attacks. Evaluated on our therapeutic DNA benchmark, DNAMark and CentralMark achieve F1 detection scores above 0.85 under various conditions, while maintaining over 60\% sequence similarity to ground truth and degeneracy scores below 15\%. A case study on the CRISPR-Cas9 system underscores CentralMark’s utility in real-world settings. This work establishes a vital framework for securing DNA language models, balancing innovation with accountability to mitigate biosecurity risks.