Volf, V.; Zhang, S.; Song, K. M.; Qian, S.; Chen, F.; Church, G.

Although DNA is increasingly being adopted as a generalizable medium for information storage and transfer, reliable methods for ensuring information security remain to be addressed. In this study, we developed and validated a cryptographic encoding scheme, Genomic Sequence Encryption (GSE), to address the challenge of information confidentiality and integrity in biological substrates. GSE enables genomic information encoding that is readable only with a cryptographic key. We show that GSE can be used for cell signatures that enable the recipient of a cell line to authenticate its origin and validate if the cell line has been modified in the interim. We implement GSE through multi-site base editing and encode information through editing across >100 genomic sites in mammalian cells. We further present an enrichment step to obtain individual stem cells with more than two dozen edits across a single genome with minimal screening. This capability can be used to introduce encrypted signatures in living animals. As an encryption scheme, GSE is falsification-proof and enables secure information transfer in biological substrates.