Abstract
Deoxyribonucleic acid provides unmatched information density and longevity for data storage, yet its easy amplification by polymerase chain reaction enables unauthorized replication at negligible cost. We introduce ZAT-DNA, which encodes information in patterns of canonical adenine and noncanonical 2-aminoadenine. As DNA polymerases cannot distinguish adenine from 2-aminoadenine, polymerase-based amplification erases these patterns, enforcing molecular-layer non-replicability intrinsic to the base-pairing ambiguity. We validate ZAT-DNA for secure key storage, demonstrating error-free encoding, storage, and high-fidelity nanopore retrieval of 32-bit and 64-bit cryptographic keys. ZAT-DNA blocks polymerase-based copying and protects non-fungible tokens by preventing functional duplication. For larger datasets, we present a hybrid “Babel-DNA” architecture: multiple encrypted images are co-encoded in a single regular DNA pool, with each selectively decryptable only via its cognate, non-replicable ZAT-DNA key. This provides a practical framework for molecular access control, secure DNA-encoded databases, and scarce molecular tokens.
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Acknowledgements
We would like to express our gratitude to Dr. Zhifeng Xu and Yin Liu from He-Chain Inc. for their helpful discussions. This work was supported by Shanghai Pilot Program for Basic Research, the National Science Fund for Distinguished Young Scholars of China 32125002 (YZ), and the New Cornerstone Science Foundation NCI202321 (YZ). This work was supported by the National Key Research and Development Program of China (No. 2023YFF1206102), the Natural Science Foundation of Tianjin (No. 25JCJQJC00340), the National Natural Science Foundation of China (Grant No. 32471492), the Emerging Frontiers Cultivation Program of Tianjin University Interdisciplinary Center (No. 202507000014), the Open Funding Project of State Key Laboratory of Microbial Metabolism (No. MMLKF25-11), the Beijing-Tianjin-Hebei Natural Science Foundation Cooperation Project (No. 25JJJJC0035) for financial support.
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YZ, LFS, and YZL have submitted two patent applications to the China National Intellectual Property Administration (CNIPA) pertaining to the ZAT-DNA aspect(s) of this work (Application No. 202211067651.3, Application No. 202311054830.8). The remaining authors declare no competing interests.
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Song, L., Wang, G., Wei, Y. et al. ZAT-DNA enables DNA data storage with molecular-layer non-replicability. Nat Commun (2026). https://doi.org/10.1038/s41467-026-72869-9
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DOI: https://doi.org/10.1038/s41467-026-72869-9
