Single-Nucleotide-Resolution Computing and Memory in Living Cells
Single-Nucleotide-Resolution Computing and Memory in Living Cells
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DOI：
10.1016/j.molcel.2019.07.011
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发表时间：
2019-08-22
期刊：
影响因子：
16
通讯作者：
Lu, Timothy K.
中科院分区：
文献类型：
--
作者：
Farzadfard, Fahim;Gharaei, Nava;Lu, Timothy K.
在活细胞中处理和存储信息的能力对于开发下一代疗法和原位研究生物学至关重要。然而，现有战略的记录能力有限，难以推广。为了克服这些限制，我们开发了DOMINO，这是一个强大的可扩展平台，用于在细菌和真核细胞中编码逻辑和记忆。使用一个有效的单核苷酸分辨率的DNA操作读写头，DOMINO将活细胞的DNA转换成一个可寻址的，可读的，可写的计算和存储介质。DOMINO操作员能够进行模拟和数字分子记录，用于长期监测信号动力学和细胞事件。此外，多个操作符可以分层和互连，以编码独立于顺序的、顺序的和时间逻辑，从而允许记录和控制细胞中分子事件的组合、顺序和定时。我们设想，DOMINO将奠定基础，建立强大的和复杂的计算和记忆基因电路的许多生物技术和生物医学应用。
The ability to process and store information in living cells is essential for developing next-generation therapeutics and studying biology in situ. However, existing strategies have limited recording capacity and are challenging to scale. To overcome these limitations, we developed DOMINO, a robust and scalable platform for encoding logic and memory in bacterial and eukaryotic cells. Using an efficient single-nucleotide-resolution Read-Write head for DNA manipulation, DOMINO converts the living cells' DNA into an addressable, readable, and writable medium for computation and storage. DOMINO operators enable analog and digital molecular recording for long-term monitoring of signaling dynamics and cellular events. Furthermore, multiple operators can be layered and interconnected to encode order-independent, sequential, and temporal logic, allowing recording and control over the combination, order, and timing of molecular events in cells. We envision that DOMINO will lay the foundation for building robust and sophisticated computation-and-memory gene circuits for numerous biotechnological and biomedical applications.