DNA CODEC: compressed obfuscated DNA encoding in cells for secure in vivo data storage

DNA represents a compelling medium for data storage due to its density, durability, and compatibility with biological systems. Current in vivo DNA data storage strategies are largely restricted to single-population systems, limiting scalability and access control. Here, we present DNA CODEC, a multi-population in vivo DNA data storage platform that combines high-density encoding with molecular obfuscation across engineered human cell populations. CODEC uses 10-ary Huffman coding with degenerate bases to optimize compressibility while maintaining decoding accuracy despite biological and technical noise. Data payloads are stably integrated into the human genome using CRISPR-based targeted insertion. Obfuscation is introduced through heterogeneous populations containing decoy clones with structurally similar, non-informative masking sequences to conceal the true payload. CODEC stably maintains genomic payloads across extended cell culture, demonstrating robustness to replication errors and population drift. Together, these features establish a scalable framework for high-fidelity and secure DNA data storage in biological systems. DNA is a dense and durable storage medium for digital information but its use in living cells remains difficult to scale and protect. Here, authors present DNA CODEC, a CRISPR-based system that distributes compressed data across engineered cell populations for stable storage and controlled access.