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A DNA computing readout operation based on structure-specific cleavage

Abstract

We describe a structure-specific cleavage–based READOUT strategy for surface-based DNA computing. The strategy was demonstrated in the solution of a 4-variable/3-satisfiability (SAT) problem. The READOUT step identifies the DNA molecules present at the end of the computational process. The specificity of the sequence detection used here derives from the sequence specificity of DNA hybridization coupled with the structure specificity of the enzymatic cleavage. The process is linear, yielding a higher uniformity of detection of the DNA computing products compared to that obtained with PCR amplification. The structure-specific cleavage–based readout is simple, accurate, and compatible with multiple-word DNA computing.

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Figure 1: (A) Schematic representations of the invasive cleavage reaction and structure of the overlapping substrate17.
Figure 2: Overview of the invasive cleavage readout strategy.
Figure 3: DNA oligonucleotides in the READOUT operation.
Figure 4: Readout results for DNA computation.
Figure 5: Histogram of average background-to-signal ratio during the surface-based DNA computation.

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Acknowledgements

The authors would like to thank Professor Robert Corn, Dr. Victor I. Lyamichev, and Dr. Bruce P. Neri for useful discussions. This work was supported by the National Science Foundation, no. 98-SC-NSF-1003/subcontract through Duke University, GenTel, Inc., and Third Wave Technologies, Inc. L.M.S. has a financial interest in both GenTel, Inc. and Third Wave Technologies, Inc.

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Correspondence to Lloyd M. Smith.

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Wang, L., Hall, J., Lu, M. et al. A DNA computing readout operation based on structure-specific cleavage. Nat Biotechnol 19, 1053–1059 (2001). https://doi.org/10.1038/nbt1101-1053

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