Evidence map›Paper›PMID 42801748›Full record

ArticleChembiochem : a European journal of chemical biology2026

A 4'-Thioribouridine Modification Mimics 2'-O-Methoxyethyl in ASO-Like 20-Mers Targeting PTEN Knockdown.

Joanna E Parkes, Caecilie M M Benckendorff, Anna L Malinowska, Jacob Roberts, Harley L Huynh, Sritama Bose, Loïc M Cochard, Aisling Ní Cheallaigh, Sarah L Lovelock, Peter L Oliver and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Chembiochem : a European journal of chemical biology, 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

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

11 authors.

Joanna E ParkesMRC Nucleic Acid Therapy Accelerator (NATA), Research Complex at Harwell (RCaH), Oxford, UK.ORCID https://orcid.org/0000-0002-4007-240X
Caecilie M M BenckendorffManchester Institute of Biotechnology & Department of Chemistry, University of Manchester, Manchester, UK.
Anna L MalinowskaMRC Nucleic Acid Therapy Accelerator (NATA), Research Complex at Harwell (RCaH), Oxford, UK.
Jacob RobertsManchester Institute of Biotechnology & Department of Chemistry, University of Manchester, Manchester, UK.
Harley L HuynhMRC Nucleic Acid Therapy Accelerator (NATA), Research Complex at Harwell (RCaH), Oxford, UK.
Sritama BoseMRC Nucleic Acid Therapy Accelerator (NATA), Research Complex at Harwell (RCaH), Oxford, UK.ORCID https://orcid.org/0000-0002-9007-4964
Loïc M CochardMRC Nucleic Acid Therapy Accelerator (NATA), Research Complex at Harwell (RCaH), Oxford, UK.
Aisling Ní CheallaighManchester Institute of Biotechnology & Department of Chemistry, University of Manchester, Manchester, UK.
Sarah L LovelockManchester Institute of Biotechnology & Department of Chemistry, University of Manchester, Manchester, UK.ORCID https://orcid.org/0000-0002-4584-3189
Peter L OliverMRC Nucleic Acid Therapy Accelerator (NATA), Research Complex at Harwell (RCaH), Oxford, UK.ORCID https://orcid.org/0000-0003-3347-2461
Gavin J MillerManchester Institute of Biotechnology & Department of Chemistry, University of Manchester, Manchester, UK.ORCID https://orcid.org/0000-0001-6533-3306

Funding

Medical Research Council MC/PC/20061Medical Research Council MR/W029324/1Medical Research Council MR/Z000025/1
6 · The paper itself

Abstract

Gapmer antisense oligonucleotides (ASOs) represent a clinically validated therapeutic platform, with a 2'-O-methoxyethyl modification commonplace within the flanking regions. An alternative sugar modification, incorporation of 4'-thioribose, has demonstrated enhanced nuclease resistance in siRNAs and aptamers, but incorporation of this motif into gapmer architectures remains underexplored. Herein, we report the synthesis of a 4'-thiouridine phosphoramidite building block and its incorporation into gapmer ASOs targeting PTEN. Evaluation of sequences containing 4'-thiouridine in the flanking regions (compared with 2'-O-methoxyethyl) and varying phosphorothioate linkage composition demonstrates that the modified gapmers maintain equivalent knockdown efficacy under transfection and gymnotic delivery. These findings indicate 4'-thioribose as an alternative sugar modification for wider exploration within gapmer ASOs.

Indexed as

Oligonucleotides, AntisensePTEN PhosphohydrolaseThiouridineGene Knockdown TechniquesHumansOrganophosphorus CompoundsOligonucleotides, AntisenseOrganophosphorus CompoundsphosphoramiditePTEN PhosphohydrolasePTEN protein, humanThiouridineaptamergene knockdownnucleaseoligonucleotidephosphoramiditePTENsmall interfering RNA

Identifiers

PMID42801748
PMCPMC13616438

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.