Evidence map›Paper›PMID 40931073›Full record

ArticleNature2025

Programmable antisense oligomers for phage functional genomics.

Milan Gerovac, Leandro Buhlmann, Yan Zhu, Svetlana Ðurica-Mitić, Valentin Rech, Samuel Carien, Tom Gräfenhan, Linda Popella, Jörg Vogel

Abstract read
In one paragraph

Article in Nature, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing 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

14 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. The biology of jumbo phages.Nature communications · 2026
    Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Mechanistic Studies of Antibacterial PNAs by RNA-Seq Analysis.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
  13. Bacteriophage genome-wide transposon mutagenesis.bioRxiv : the preprint server for biology · 2025
    Article
  14. Licence to knockdown - the phage gene silencer.Nature reviews. Microbiology · 2025
    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

9 authors.

Milan GerovacHelmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz Centre for Infection Research (HZI), Würzburg, Germany.ORCID 0000-0002-6929-7178
Leandro BuhlmannInstitute for Molecular Infection Biology (IMIB), Faculty of Medicine, University of Würzburg, Würzburg, Germany.ORCID 0009-0000-1943-2813
Yan ZhuHelmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz Centre for Infection Research (HZI), Würzburg, Germany.
Svetlana Ðurica-MitićInstitute for Molecular Infection Biology (IMIB), Faculty of Medicine, University of Würzburg, Würzburg, Germany.
Valentin RechInstitute for Molecular Infection Biology (IMIB), Faculty of Medicine, University of Würzburg, Würzburg, Germany.ORCID 0009-0002-8417-291X
Samuel CarienInstitute for Molecular Infection Biology (IMIB), Faculty of Medicine, University of Würzburg, Würzburg, Germany.ORCID 0009-0001-4135-090X
Tom GräfenhanCore Unit Systems Medicine, University of Würzburg, Würzburg, Germany.
Linda PopellaInstitute for Molecular Infection Biology (IMIB), Faculty of Medicine, University of Würzburg, Würzburg, Germany.ORCID 0000-0002-5309-5838
Jörg VogelHelmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz Centre for Infection Research (HZI), Würzburg, Germany. joerg.vogel@uni-wuerzburg.de.ORCID 0000-0003-2220-1404

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Bacteriophages are the most abundant entities on earth and exhibit vast genetic and phenotypic diversity. Exploitation of this largely unexplored molecular space requires identification and functional characterization of genes that act at the phage-host interface. So far, this has been restricted to few model phage-host systems that are amenable to genetic manipulation. Here, to overcome this limitation, we introduce a non-genetic mRNA targeting approach using exogenous delivery of programmable antisense oligomers to silence genes of DNA and RNA phages. A systematic knockdown screen of core and accessory genes of the nucleus-forming jumbo phage ΦKZ, coupled to RNA-sequencing and microscopy analyses, reveals previously unrecognized proteins that are essential for phage propagation and that, upon silencing, elicit distinct phenotypes at the level of the phage and host response. One of these factors is the RNase H-like protein ΦKZ155 (also known as Nlp2), which acts at a major decision point during infection, linking the formation of the protective phage nucleus to phage genome amplification. This non-genetic antisense oligomer-based gene silencing method promises to be a versatile tool for molecular discovery in phage biology, will help to elucidate defence and anti-defence mechanisms in non-model phage-host pairs, and offers potential for optimizing phage therapy and biotechnological procedures.

Indexed as

BacteriophagesGenomicsOligonucleotides, AntisenseGene Knockdown TechniquesGene SilencingGenome, ViralRibonuclease HViral ProteinsOligonucleotides, AntisenseRibonuclease HViral Proteins

Identifiers

PMID40931073
PMCPMC12571901

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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.