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Author Notes:

To whom correspondence should be addressed: Email: philip.j.santangelo@emory.edu or Email: gseelig@uw.edu

P.J.S. and G.S. conceived the project, B.G., Y-J.C., C.Z., S.P., P.J.S. and G.S. designed experiments, B.G., Y-J.C., C.Z., and S.P. performed the experiments, J.L.K. and P.S. developed the monovalent MTRIPs, B.G., Y-J.C., C.Z., analyzed the data, B.G. Y-J. C., C.Z., P.J.S, and G.S. wrote the paper.

We thank David Soloveichik, Erik Winfree, and David Yu Zhang for their help in designing the logic AND gate.

Competing financial interest statement No competing financial interest

Subjects:

Research Funding:

This material is based upon work supported by the Defense Advanced Research Projects Agency (DARPA) under Contract No. W911NF-11-2-0068 to GS and PJS.

Additional support for was provided by NSF CAREER Award No. 1253691 (PJS), regarding RNA imaging, and NIH GM094198 (PJS), for the use of hRSV cell models during development.

Keywords:

  • Science & Technology
  • Technology
  • Nanoscience & Nanotechnology
  • Materials Science, Multidisciplinary
  • Science & Technology - Other Topics
  • Materials Science
  • DNA ORIGAMI
  • ANTISENSE OLIGONUCLEOTIDES
  • DISPLACEMENT-REACTIONS
  • COMPUTATION
  • CASCADES
  • NANOTECHNOLOGY
  • AMPLIFICATION
  • HYBRIDIZATION
  • EXPRESSION
  • TRANSPORT

Computing in mammalian cells with nucleic acid strand exchange

Tools:

Journal Title:

Nature Nanotechnology

Volume:

Volume 11, Number 3

Publisher:

, Pages 287-294

Type of Work:

Article | Post-print: After Peer Review

Abstract:

DNA strand displacement has been widely used for the design of molecular circuits, motors, and sensors in cell-free settings. Recently, it has been shown that this technology can also operate in biological environments, but capabilities remain limited. Here, we look to adapt strand displacement and exchange reactions to mammalian cells and report DNA circuitry that can directly interact with a native mRNA. We began by optimizing the cellular performance of fluorescent reporters based on four-way strand exchange reactions and identified robust design principles by systematically varying the molecular structure, chemistry and delivery method. Next, we developed and tested AND and OR logic gates based on four-way strand exchange, demonstrating the feasibility of multi-input logic. Finally, we established that functional siRNA could be activated through strand exchange, and used native mRNA as programmable scaffolds for co-localizing gates and visualizing their operation with subcellular resolution.

Copyright information:

© 2016 Macmillan Publishers Limited.

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