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Reply to: On gene silencing by the X10-23 DNAzyme

Nature Chemistry volume 14, pages 859–861 (2022)Cite this article

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The Original Article was published on 18 July 2022

replying to: A. I. Taylor & P. Holliger Nature Chemistry https://doi.org/10.1038/s41557-022-00990-5 (2022).

In their recent communication, Taylor and Holliger argue that the gene silencing activity observed for the X10-23 DNAzyme is primarily the result of an antisense mechanism that is promoted by RNase H rather than the intrinsic catalytic activity of the enzyme1. The evidence they offer in support of their criticism derives from RNA cleavage assays performed under cell-free conditions that compare the 10-23 and X10-23 DNAzymes to unpublished FANAzymes (Fz12B and Fz166) from their laboratory. Despite several requests, the authors declined to share their unpublished work (cited as ref. 4 of their comment), which was needed to evaluate the biochemical properties of their reagents.

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Fig. 1: Evaluation of the secondary structure of KRAS RNA variant b (NCBI reference sequence NM_004985.5).

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No new data were included in the response.

References

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Acknowledgements

This work was supported by the W.M. Keck Foundation.

Author information

Authors and Affiliations

  1. Departments of Pharmaceutical Sciences, University of California, Irvine, CA, USA

    Robert C. Spitale & John C. Chaput

  2. Department of Chemistry, University of California, Irvine, CA, USA

    Robert C. Spitale & John C. Chaput

  3. Department of Molecular Biology and Biochemistry, University of California, Irvine, CA, USA

    Robert C. Spitale & John C. Chaput

  4. Department of Chemical and Biomolecular Engineering, University of California, Irvine, CA, USA

    John C. Chaput

Authors
  1. Robert C. Spitale
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Contributions

J.C.C. and R.C.S. wrote the response with input from K. Nguyen and Y. Wang. K.N. prepared the figure.

Corresponding author

Correspondence to John C. Chaput.

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Competing interests

J.C.C. is a consultant for 1E Therapeutics. The work reported here occurred prior to this relationship. R.C.S. declares no competing interests.

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Nature Chemistry thanks Yingfu Li and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Spitale, R.C., Chaput, J.C. Reply to: On gene silencing by the X10-23 DNAzyme. Nat. Chem. 14, 859–861 (2022). https://doi.org/10.1038/s41557-022-00983-4

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