Evidence map›Paper›PMID 42286010›Full record

ArticleNature communications2026

Recognition of non-standard base pairs by triplex-forming oligonucleotides containing an expanded genetic alphabet.

Michael Brazzill, Ruolin Ma, Kieron Munn, Léna Prestifilippo, Andrew R Pickford, Hyo-Joong Kim, Cen Chen, Shuichi Hoshika, Steven A Benner, David A Rusling

Abstract read
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Michael BrazzillSchool of Medicine, Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, UK.
Ruolin MaSchool of Medicine, Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, UK.
Kieron MunnSchool of Medicine, Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, UK.
Léna PrestifilippoSchool of Medicine, Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, UK.
Andrew R PickfordCentre for Enzyme Innovation, School of the Environment and Life Sciences, University of Portsmouth, Portsmouth, UK.ORCID http://orcid.org/0000-0002-7237-0030
Hyo-Joong KimFoundation for Applied Molecular Evolution, Alachua, FL, USA.
Cen ChenFoundation for Applied Molecular Evolution, Alachua, FL, USA.ORCID http://orcid.org/0000-0002-6883-9369
Shuichi HoshikaFoundation for Applied Molecular Evolution, Alachua, FL, USA. shoshika@ffame.org.ORCID http://orcid.org/0000-0001-9128-1183
Steven A BennerFoundation for Applied Molecular Evolution, Alachua, FL, USA.ORCID http://orcid.org/0000-0002-3318-9917
David A RuslingSchool of Medicine, Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, UK. david.rusling@port.ac.uk.ORCID http://orcid.org/0000-0002-7442-686X

Funding

Basic Research for Diagnostics and Surveillance in Lower Resource EnvironmentsR01AI135146 · NIAID · FOUNDATION FOR APPLIED MOLECULAR EVOLUTN · PI BENNER, STEVEN A · 2021 to 2024
$2.8M
Academy of Medical Sciences BB/L021730/1Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) R01AI135146National Science Foundation (NSF) MCB-1939086NIAID NIH HHS R01 AI135146
6 · The paper itself

Abstract

The sequence-specific recognition of double-stranded DNA by biocompatible molecules is fundamental to molecular medicine and synthetic biology. Triplex-forming oligonucleotides (TFOs) enable programmable major groove recognition via Hoogsteen base pairing; however, the limited repertoire of natural nucleobases imposes strict constraints on target sequences and parallel motif triplexes require acidic conditions for stability. Here, we have expanded the triplex recognition space using nucleobases from an artificially expanded genetic information system (AEGIS). Through a systematic evaluation of 120 base triad combinations, we identify at least 12 modular triads that can be combined interchangeably to target duplex DNA containing standard, damaged, or synthetic base pairs with nanomolar affinity at neutral pH. We further demonstrate the versatility of this expanded recognition code by detecting oxidative lesions or AEGIS base pairs in enzymatically assembled duplex constructs using both chemically and enzymatically synthesized TFOs. This generalized framework provides a robust platform for precision gene-targeting, molecular sensing, and nucleic acid nanotechnology.

Indexed as

Base PairingDNAOligonucleotidesBase SequenceHydrogen-Ion ConcentrationNucleic Acid ConformationDNAOligonucleotidestriplex DNA

Identifiers

PMID42286010
PMCPMC13407867

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Registered trials

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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.