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Single-Nucleotide-Resolution Computing and Memory in Living Cells.

Fahim Farzadfard1, Nava Gharaei2, Yasutomi Higashikuni3

  • 1Synthetic Biology Group, Research Laboratory of Electronics, Department of Electrical Engineering & Computer Science and Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; MIT Synthetic Biology Center, 500 Technology Square, Cambridge MA 02139, USA; MIT Microbiology Graduate Program, 77 Massachusetts Avenue, Cambridge MA 02139, USA.

Molecular Cell
|August 24, 2019
PubMed
Summary

We developed DOMINO, a new platform for cellular computation and memory. This DNA-based system offers scalable information processing in living cells for advanced therapeutics and biological studies.

Keywords:
DNA memoryDNA writinganalog and digital recording and computationbase editingcellular computationdynamic genome engineeringlogic circuitsmolecular recordingsynthetic gene circuits

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Area of Science:

  • Synthetic Biology
  • Molecular Engineering
  • Biotechnology

Background:

  • Cellular information processing is crucial for therapeutics and in situ biology.
  • Existing methods for cellular recording have limited capacity and scalability.

Purpose of the Study:

  • To develop a robust and scalable platform, DOMINO, for encoding logic and memory in living cells.
  • To enable advanced computation and storage using cellular DNA.

Main Methods:

  • Developed DOMINO, a platform utilizing a single-nucleotide-resolution Read-Write head for DNA manipulation.
  • Engineered DOMINO operators for analog and digital molecular recording.
  • Implemented layered and interconnected operators for complex logic encoding (order-independent, sequential, temporal).

Main Results:

  • DOMINO converts cellular DNA into an addressable, readable, and writable medium for computation and storage.
  • DOMINO enables long-term monitoring of cellular signaling dynamics and events.
  • Achieved encoding of complex logic, controlling the combination, order, and timing of molecular events.

Conclusions:

  • DOMINO provides a scalable solution for cellular computation and memory.
  • This platform facilitates sophisticated gene circuit development for biotechnological and biomedical applications.
  • DOMINO lays the foundation for future advancements in cellular engineering.