CRISPR/Cas-based devices for mammalian synthetic biology

Since its first demonstration for mammalian gene editing, CRISPR/Cas technology has been widely adopted in research, industry, and medicine. Beyond indel mutations induced by Cas9 activity, recent advances in CRISPR/Cas have enabled DNA or RNA base editing. In addition, multiple orthogonal methods for the spatiotemporal regulation of CRISPR/Cas activity and repurposed Cas proteins for the visualization and relocation of specific genomic loci in living cells have been described. By harnessing the versatility of CRISPR/Cas-based devices and gene circuits, synthetic biologists are developing memory devices for lineage tracing and technologies for unbiased, high-throughput interrogation of combinatorial gene perturbations. We envision that such approaches will enable researchers to gain deeper insights into the translation of genotypes to phenotypes in healthy and diseased states.