Evidence map›Paper›PMID 40546945›Full record

ArticleiScience2025

Real-time genome imaging of host interactions in adeno-associated virus genome release.

Luisa F Bustamante-Jaramillo, Lei Yue, Joshua Fingal, Gustaf Rydell, Maria Johansson, Tomas Edreira, Oliver J Müller, Susanne Hille, Martin Müller, Franck Gallardo and 3 more

Abstract read
In one paragraph

Article in iScience, 2025. 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. 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

13 authors.

Luisa F Bustamante-JaramilloDepartment of Infectious Diseases, Institute of Biomedicine, Gothenburg University, Gothenburg, Sweden.
Lei YueDepartment of Infectious Diseases, Institute of Biomedicine, Gothenburg University, Gothenburg, Sweden.
Joshua FingalDepartment of Infectious Diseases, Institute of Biomedicine, Gothenburg University, Gothenburg, Sweden.
Gustaf RydellDepartment of Infectious Diseases, Institute of Biomedicine, Gothenburg University, Gothenburg, Sweden.
Maria JohanssonDepartment of Infectious Diseases, Institute of Biomedicine, Gothenburg University, Gothenburg, Sweden.
Tomas EdreiraDepartment of Chemistry and Molecular Biology, Gothenburg University, Gothenburg, Sweden.
Oliver J MüllerDepartment of Internal Medicine V, University of Kiel, and German Centre for Cardiovascular Research, Partner Site Hamburg/Kiel/Lübeck, Germany, Kiel, Germany.
Susanne HilleDepartment of Internal Medicine V, University of Kiel, and German Centre for Cardiovascular Research, Partner Site Hamburg/Kiel/Lübeck, Germany, Kiel, Germany.
Martin MüllerInfection, Inflammation and Cancer Program, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Franck GallardoNeo Vir Tech SAS, Centre Pierre Potier, Toulouse, France.
Qingxin ChenInfection, Inflammation and Cancer Program, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Marie-Lise BlondotCNRS UMR 5234, Université de Bordeaux, Bordeaux, France.
Michael KannDepartment of Infectious Diseases, Institute of Biomedicine, Gothenburg University, Gothenburg, Sweden.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Adeno-associated virus (AAVs) with a self-complementary genome (sc) comprising a gene of interest are used in gene therapy. Their efficiency is limited but the molecular factors contributing to this restriction are poorly understood. We utilized scAAV2 containing a fluorescent protein-binding anchor sequence on its genome allowing visualization of released genomes by time-lapse microscopy. Pairing this technique with capsid staining, we showed that scAAV2 genome release was initiated by a partial genome exposure, triggered by elevated calcium levels while the capsids interacted with proteins of the nuclear pore. Genome release occurred subsequently requiring Rad52 decamerization in the vicinity of the host chromatin. A fraction of the released genomes was degraded by Mre11, an essential factor for chromatin stability, and cellular DNA double-strand breaks. These steps were key-factors limiting transduction, suggesting that temporary modulation of DNA damage-response-proteins is a promising way to increase scAAV efficiency in therapy.

Indexed as

Cellular therapyGenomic analysisGenomicsVirology

Identifiers

PMID40546945
PMCPMC12178803

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.