title: DNA sense-and-respond protein modules for mammalian cells.
abstract: We generated synthetic protein components that can detect specific DNA sequences and subsequently trigger a desired intracellular response. These modular sensors exploit the programmability of zinc-finger DNA recognition to drive the intein-mediated splicing of an artificial trans-activator that signals to a genetic circuit containing a given reporter or response gene. We used the sensors to mediate sequence recognition-induced apoptosis as well as to detect and report a viral infection. This work establishes a synthetic biology framework for endowing mammalian cells with sentinel capabilities, which provides a programmable means to cull infected cells. It may also be used to identify positively transduced or transfected cells, isolate recipients of intentional genomic edits and increase the repertoire of inducible parts in synthetic biology.
authors.affiliation: Institute for Medical Engineering &Science, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA.|Department of Biological Engineering, MIT, Cambridge, Massachusetts, USA.|Synthetic Biology Center, MIT, Cambridge, Massachusetts, USA.
authors.forename: Shimyn
authors.initials: S
authors.lastname: Slomovic
authors.affiliation: Institute for Medical Engineering &Science, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA.|Department of Biological Engineering, MIT, Cambridge, Massachusetts, USA.|Synthetic Biology Center, MIT, Cambridge, Massachusetts, USA.|Harvard-MIT Program in Health Sciences and Technology, Cambridge, Massachusetts, USA.|Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.|Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, USA.
authors.forename: James J
authors.initials: JJ
authors.lastname: Collins
mesh_terms: D000818:Animals; D017209:Apoptosis; D015374:Biosensing Techniques; D004247:DNA / Q000737:chemistry*; D053263:Gene Regulatory Networks; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000737:chemistry; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008856:Microscopy, Fluorescence; D010957:Plasmids; D011401:Promoter Regions, Genetic; D015202:Protein Engineering; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry*; D051381:Rats; D015534:Trans-Activators / Q000235:genetics; D015533:Transcriptional Activation; D016335:Zinc Fingers
chemical_list: D011506:Proteins; D015534:Trans-Activators; D049452:Green Fluorescent Proteins; D004247:DNA