Evidence map›Paper›PMID 39934106›Full record

ArticleNature communications2025

Double-strand break repair pathways differentially affect processing and transduction by dual AAV vectors.

Anna C Maurer, Brian Benyamini, Oscar N Whitney, Vinson B Fan, Claudia Cattoglio, Djem U Kissiov, Gina M Dailey, Xavier Darzacq, Matthew D Weitzman, Robert Tjian

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Anna C MaurerDepartment of Molecular and Cell Biology, University of California, Berkeley, CA, USA. acmaurer@umich.edu.ORCID http://orcid.org/0000-0003-2768-7757
Brian BenyaminiDepartment of Molecular and Cell Biology, University of California, Berkeley, CA, USA.ORCID http://orcid.org/0009-0002-0926-5665
Oscar N WhitneyDepartment of Molecular and Cell Biology, University of California, Berkeley, CA, USA.
Vinson B FanDepartment of Molecular and Cell Biology, University of California, Berkeley, CA, USA.ORCID http://orcid.org/0000-0002-1688-7780
Claudia CattoglioDepartment of Molecular and Cell Biology, University of California, Berkeley, CA, USA.
Djem U KissiovDepartment of Molecular and Cell Biology, University of California, Berkeley, CA, USA.ORCID http://orcid.org/0000-0001-6279-342X
Gina M DaileyDepartment of Molecular and Cell Biology, University of California, Berkeley, CA, USA.ORCID http://orcid.org/0000-0002-8988-963X
Xavier DarzacqDepartment of Molecular and Cell Biology, University of California, Berkeley, CA, USA.
Matthew D WeitzmanDepartment of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine and the Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Robert TjianDepartment of Molecular and Cell Biology, University of California, Berkeley, CA, USA.ORCID http://orcid.org/0000-0003-0539-8217

Funding

Project 2: Evaluating the dynamic protein-protein interactions mediated by LCDs within EWS/FLI and its partners in living cells via single molecule imagingU54CA231641 · NCI · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI LESSNICK, STEPHEN L. · 2018 to 2018
$6.2M
Identifying cellular proteins associated with AAV genomesR21AI185720 · NIAID · CHILDREN'S HOSP OF PHILADELPHIA · PI WEITZMAN, MATTHEW D. · 2024 to 2025
$475k
California Institute for Regenerative Medicine (CIRM) EDUC4-12790Howard Hughes Medical Institute (HHMI) 34430NCI NIH HHS U54 CA231641NIAID NIH HHS R21 AI185720
6 · The paper itself

Abstract

Recombinant adeno-associated viral vectors (rAAV) are a powerful tool for gene delivery but have a limited DNA carrying capacity. Efforts to expand this genetic payload have focused on engineering the vector components, such as dual trans-splicing vectors which double the delivery size by exploiting the natural concatenation of rAAV genomes in host nuclei. We hypothesized that inefficient dual vector transduction could be improved by modulating host factors which affect concatenation. Since factors mediating concatenation are not well defined, we performed a genome-wide screen to identify host cell regulators. We discover that Homologous Recombination (HR) is inhibitory to dual vector transduction. We demonstrate that depletion or inhibition of HR factors BRCA1 and Rad51 significantly increase reconstitution of a large split transgene by increasing both concatenation and expression from rAAVs. Our results define roles for DNA damage repair in rAAV transduction and highlight the potential for pharmacological intervention to increase genetic payload of rAAV vectors.

Indexed as

DependovirusDNA End-Joining RepairGenetic VectorsRecombinational DNA RepairTransduction, GeneticDNA Breaks, Double-StrandedGene ExpressionRad51 RecombinaseTransgenesRad51 Recombinase

Identifiers

PMID39934106
PMCPMC11814140

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.