Genetic physical unclonable functions in human cells

A physical unclonable function (PUF) is a physical entity that 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, photolithographically manufactured silicon PUFs are impossible to reproduce (thus unclonable). Inspired by the success of silicon PUFs, we sought to create the first generation of genetic PUFs in human cells. We demonstrate that these PUFs are robust (i.e., they repeatedly produce the same output), unique (i.e., they do not coincide with any other identically produced PUF), and unclonable (i.e., they are virtually impossible to replicate). Furthermore, we demonstrate that CRISPR-engineered PUFs (CRISPR-PUFs) can serve as a foundational principle for establishing provenance attestation protocols.