Evidence map›Paper›PMID 33767363›Full record

ArticleNature chemistry2021

A biologically stable DNAzyme that efficiently silences gene expression in cells.

Yajun Wang, Kim Nguyen, Robert C Spitale, John C Chaput

Abstract read
In one paragraph

Article in Nature chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.

0numbers the graph read from it
0cells of the map it votes in
87citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

87 citing papers in PubMed.

  1. Chemically Evolved XNAzyme Platforms for Effective In Vivo Gene Regulation.Small (Weinheim an der Bergstrasse, Germany) · 2026
    Article
  2. Article
  3. Review
  4. Programmable DNAzyme nanocatalysts for tumor immunometabolic modulation.Journal of Zhejiang University. Science. B · 2026
    Review
  5. Article
  6. Article
  7. Light-responsive DNA nanostructures.Nature reviews. Chemistry · 2026
    Review
  8. Review
  9. Article
  10. Review
  11. Review
  12. Designing nucleic acid-based therapeutics for cancer treatment: Updates on the state of the art.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Review
  13. Article
  14. Article
  15. Review
  16. Review
  17. Review
  18. Article
  19. Article
  20. Article

27 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors.

Yajun Wang *Department of Pharmaceutical Sciences, University of California, Irvine, CA, USA.
Kim Nguyen *Department of Pharmaceutical Sciences, University of California, Irvine, CA, USA.ORCID http://orcid.org/0000-0002-6599-2851
Robert C SpitaleDepartment of Pharmaceutical Sciences, University of California, Irvine, CA, USA.
John C ChaputDepartment of Pharmaceutical Sciences, University of California, Irvine, CA, USA. jchaput@uci.edu.ORCID http://orcid.org/0000-0003-1393-135X

Funding

Univ.of Calif., Irvine Cancer Center Support GrantP30CA062203 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI Christine Hui · 1994 to 2026
$57.9M
NCI NIH HHS P30 CA062203
6 · The paper itself

Abstract

Efforts to use RNA-cleaving DNA enzymes (DNAzymes) as gene-silencing agents in therapeutic applications have stalled due to their low efficacy in clinical trials. Here we report a xeno-nucleic-acid-modified version of the classic DNAzyme 10-23 that achieves multiple-turnover activity under cellular conditions and resists nuclease digestion. The new reagent, X10-23, overcomes the problem of product inhibition, which limited previous 10-23 designs, using molecular chemotypes with DNA, 2'-fluoroarabino nucleic acid and α-L-threofuranosyl nucleic acid backbone architectures that balance the effects of enhanced biological stability with RNA hybridization and divalent metal ion coordination. In cultured mammalian cells, X10-23 facilitates persistent gene silencing by efficiently degrading exogenous and endogenous messenger RNA transcripts. Together, these results demonstrate that new molecular chemotypes can improve the activity and stability of DNAzymes, and may provide a new route for nucleic acid enzymes to reach the clinic.

Indexed as

Gene SilencingCell Line, TumorDNA, CatalyticDNA, Single-StrandedGenetic EngineeringGreen Fluorescent ProteinsHumansProto-Oncogene Proteins p21(ras)DNA, CatalyticDNA, Single-StrandedGreen Fluorescent ProteinsKRAS protein, humanProto-Oncogene Proteins p21(ras)RNA-cleaving DNA 10-23

Identifiers

PMID33767363
PMCPMC12582164

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.