Molecular access control for random-access DNA data storage

Abstract

DNA data storage offers exceptional density and millennial-scale stability, with advances in encoding schemes and reduced synthesis costs making large-scale archiving increasingly viable. However, while efforts have focused on reliable data retrieval, securing DNA-encoded information against unauthorized access remains largely unexplored. Here, we introduce DNA-GUARD (DNA Gated Unlocking and Access Restriction of Data), a molecular access-control system that restricts PCR-based retrieval and complements data encryption. Chemically modified "locker strands" outcompete PCR primers and, through 3' inverted dT modifications, block polymerase extension and amplification of sequences required for decoding. Complementary "key strands" tethered to magnetic particles sequester and remove locker strands, restoring access. We demonstrate scalability from 555-byte to 1-MB files, orthogonal control of multiple files in mixed libraries, and reliable repeated locking-unlocking cycles. DNA-GUARD is compatible with established DNA storage workflows and provides reversible physical access control that increases the sequencing effort required for unauthorized retrieval.