期刊
SCIENCE
卷 346, 期 6211, 页码 825-+出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1256272
关键词
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资金
- NIH New Innovator Award [1DP2OD008435]
- NIH National Centers for Systems Biology [1P50GM098792]
- U.S. Office of Naval Research [N000141310424]
- Defense Advanced Research Projects Agency
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.
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