Physical Unclonable Functions in Human Cells

We introduce the genetic Physical Unclonable Functions (PUFs). A PUF is a physical entity which provides a measurable output that can be used as a unique and irreproducible identifier for the artifact wherein it is embedded. Popularized by the electronics industry, silicon PUFs leverage the inherent physical variations of semiconductor manufacturing to establish intrinsic security primitives for attesting integrated circuits. Owing to the stochastic nature of these variations and the multitude of steps involved, photo-lithographically manufactured silicon PUFs are impossible to reproduce (thus unclonable). Inspired by the success of silicon PUFs, we sought to exploit a combination of sequence-restricted barcodes and the inherent stochasticity of CRISPR-induced non-homologous end joining DNA error repair to create the first generation of genetic physical unclonable functions in three distinct human cells (HEK293, HCT116, and HeLa). Genetic PUFs can serve as a foundational principle for establishing provenance attestation protocols for protecting intellectual property and confirming authenticity of engineered cell lines.