Synthetic biology. Genomically encoded analog memory with precise in vivo DNA writing in living cell populations.
Synthetic biology. Genomically encoded analog memory with precise in vivo DNA writing in living cell populations.
复制标题
DOI：
10.1126/science.1256272
复制
发表时间：
2014-11-14
期刊：
影响因子：
--
通讯作者：
Lu TK
中科院分区：
文献类型：
--
作者：
Farzadfard F;Lu TK
细胞记忆对于许多自然生物过程和复杂的合成生物学应用至关重要。现有的细胞记忆依赖于表观遗传开关或重组酶，其可扩展性和记录能力有限。在这里，我们使用活细胞群体的DNA作为基因组“磁带录音机”，用于模拟和分布式记录长期事件历史。我们描述了一个在体内响应任意转录信号产生单链DNA （ssDNA）的平台。当与重组酶共表达时，这些细胞内表达的ssdna靶向特定的基因组DNA地址，导致在细胞群体中积累的精确突变，作为输入的大小和持续时间的函数。该平台可以实现环境和生物医学应用、生物状态机和增强基因组工程策略的长期细胞记录仪。
Cellular memory is crucial to many natural biological processes and for sophisticated synthetic-biology applications. Existing cellular memories rely on epigenetic switches or recombinases, which are limited in scalability and recording capacity. Here, 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 co-expressed 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.
登录
查看更多内容
DOI：
10.1073/pnas.121164898
发表时间：
2001-06-05
影响因子：
11.1
作者：
Ellis, HM;Yu, DG;Court, DL
通讯作者：
Court, DL
影响因子：
46.9
作者：
Kramer, BP;Viretta, AU;Fussenegger, M
通讯作者：
Fussenegger, M
影响因子：
56.9
作者：
Church, George M.;Gao, Yuan;Kosuri, Sriram
通讯作者：
Kosuri, Sriram
影响因子：
64.8
作者：
Douglas, Shawn M.;Dietz, Hendrik;Liedl, Tim;Hoegberg, Bjoern;Graf, Franziska;Shih, William M.
通讯作者：
Shih, William M.
影响因子：
64.8
作者：
Goldman, Nick;Bertone, Paul;Chen, Siyuan;Dessimoz, Christophe;LeProust, Emily M.;Sipos, Botond;Birney, Ewan
通讯作者：
Birney, Ewan