Evidence map›Paper›PMID 41495895›Full record

ArticleNucleic acids research2026

Allele-specific knockdown by an engineered DNAzyme capable of RNase H1 evasion.

Erica M Lee, Kim Nguyen, Noah A Setterholm, Turnee N Malik, John C Chaput

Abstract read
In one paragraph

Article in Nucleic acids research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Erica M LeeDepartment of Pharmaceutical Sciences, University of California, Irvine, CA 92697, United States.
Kim NguyenDepartment of Pharmaceutical Sciences, University of California, Irvine, CA 92697, United States.
Noah A SetterholmDepartment of Pharmaceutical Sciences, University of California, Irvine, CA 92697, United States.
Turnee N MalikDepartment of Pharmaceutical Sciences, University of California, Irvine, CA 92697, United States.
John C ChaputDepartment of Pharmaceutical Sciences, University of California, Irvine, CA 92697, United States.ORCID 0000-0003-1393-135X

Funding

1E Therapeutics
6 · The paper itself

Abstract

DNA enzymes (DNAzymes) offer an attractive therapeutic approach for targeting disease-associated mutations in mRNA transcripts, but face limitations in development due to unintended engagement by RNase H1. Although chemical optimization has led to designs with improved catalytic activity, strategies to mitigate RNase H1 recognition remain underexplored. Here, we report the incorporation of threose nucleic acid (TNA) into the backbone architecture of the 10-23 DNAzyme variant known as Dz46. Substitution of the dC3 position in the catalytic loop with TNA increases activity, whereas installation of two TNA residues in the binding arm abrogates competition by RNase H1. The resulting enzyme enables allele-specific knockdown of an oncogenic KRAS mutation in mammalian cells and facilitates general knockdown of PCSK9 and GATA3 targets. Together, these results demonstrate the utility of TNA as a chemical tool for enhancing DNAzyme performance and evading RNase H1 activity in cells.

Indexed as

DNA, CatalyticRibonuclease HAllelesDNA, Single-StrandedGATA3 Transcription FactorGene Knockdown TechniquesHumansMutationProprotein Convertase 9Protein EngineeringProto-Oncogene Proteins p21(ras)DNA, CatalyticDNA, Single-StrandedGATA3 Transcription FactorProprotein Convertase 9Proto-Oncogene Proteins p21(ras)Ribonuclease Hribonuclease HIRNA-cleaving DNA 10-23

Identifiers

PMID41495895
PMCPMC12774632

What Socratic holds

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LicenceCC BY
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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 Socratic graph.