Synthetic biology. Genomically encoded analog memory with precise in vivo DNA writing in living cell populations.
Cellular memory is crucial to many natural biological processes and sophisticated synthetic biology applications. Existing cellular memories rely on epigenetic switches or recombinases, which are limited in scalability and recording capacity. In this work, we use the DNA of living cell populations as genomic "tape recorders" for the analog and distributed recording of long-term event histories. We describe a platform for generating single-stranded DNA (ssDNA) in vivo in response to arbitrary transcriptional signals. When coexpressed with a recombinase, these intracellularly expressed ssDNAs target specific genomic DNA addresses, resulting in precise mutations that accumulate in cell populations as a function of the magnitude and duration of the inputs. This platform could enable long-term cellular recorders for environmental and biomedical applications, biological state machines, and enhanced genome engineering strategies.
Synthetic Biology Group, Research Laboratory of Electronics, Department of Electrical Engineering and Computer Science and Department of Biological Engineering, Massachusetts Institute of Technology (MIT), 77 Massachusetts Avenue, Cambridge, MA 02139, USA. MIT Synthetic Biology Center, 500 Technology Square, Cambridge, MA 02139, USA. MIT Microbiology Program, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Fahim
F
Farzadfard
Synthetic Biology Group, Research Laboratory of Electronics, Department of Electrical Engineering and Computer Science and Department of Biological Engineering, Massachusetts Institute of Technology (MIT), 77 Massachusetts Avenue, Cambridge, MA 02139, USA. MIT Synthetic Biology Center, 500 Technology Square, Cambridge, MA 02139, USA. MIT Microbiology Program, 77 Massachusetts Avenue, Cambridge, MA 02139, USA. timlu@mit.edu.
Timothy K
TK
Lu
D001483:Base Sequence; D057005:Bioengineering; D002477:Cells; D004277:DNA, Single-Stranded / Q000235:genetics*; D004926:Escherichia coli / Q000235:genetics; D005815:Genetic Code; D023281:Genomics / Q000379:methods; D016247:Information Storage and Retrieval / Q000379:methods*; D008568:Memory; D008969:Molecular Sequence Data; D058615:Synthetic Biology; D013637:Tape Recording; D014158:Transcription, Genetic; D014956:Writing
D004277:DNA, Single-Stranded