MIT biological engineers have devised a way to record complex histories in the DNA of human cells, allowing them to retrieve “memories” of past events, such as inflammation, by sequencing the DNA. This analog memory storage system — the first that can record the duration and/or intensity of events in human cells — could also help scientists study how cells differentiate into various tissues during embryonic development, how cells experience environmental conditions, and how they undergo genetic changes that lead to disease.
Ref: Continuous genetic recording with self-targeting CRISPR-Cas in human cells. Science (18 August 2016) | DOI: 10.1126/science.aag0511
The ability to record molecular events in vivo would enable monitoring of signaling dynamics within cellular niches and critical factors that orchestrate cellular behavior. We present a self-contained analog memory device for longitudinal recording of molecular stimuli into DNA mutations in human cells. This device consists of a self-targeting guide RNA (stgRNA) that repeatedly directs Streptococcus pyogenes Cas9 nuclease activity toward the DNA that encodes the stgRNA, thereby enabling localized, continuous DNA mutagenesis as a function of stgRNA expression. We demonstrate programmable and multiplexed memory storage in human cells triggered by exogenous inducers or inflammation, both in vitro and in vivo. This tool, Mammalian Synthetic Cellular Recorder Integrating Biological Events (mSCRIBE), provides a unique strategy for investigating cell biology in vivo and enables continuous evolution of targeted DNA sequences.