Evidence map›Paper›PMID 19888330›Full record

ArticlePloS one2009

AAV recombineering with single strand oligonucleotides.

Matthew L Hirsch, Francesca Storici, Chengwen Li, Vivian W Choi, R Jude Samulski

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.3field-weighted citation impact, top 18% of its field
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

18 citing papers in PubMed, 25 citations in OpenAlex.

  1. AAV vector development, back to the future.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  2. Article
  3. DualHuman gene therapy · 2019
    Article
  4. Article
  5. Review
  6. Structure-Based Designed Nano-Dysferlin Significantly Improves Dysferlinopathy in BLA/J Mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2017
    Article
  7. Article
  8. Delivering Transgenic DNA Exceeding the Carrying Capacity of AAV Vectors.Methods in molecular biology (Clifton, N.J.) · 2016
    Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Oversized AAV transductifon is mediated via a DNA-PKcs-independent, Rad51C-dependent repair pathway.Molecular therapy : the journal of the American Society of Gene Therapy · 2013
    Article
  16. Review
  17. Article
  18. Little vector, big gene transduction: fragmented genome reassembly of adeno-associated virus.Molecular therapy : the journal of the American Society of Gene Therapy · 2010
    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

5 authors at 3 institutions in 1 country.

Matthew L HirschUNC Gene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
Francesca Storici
Chengwen Li
Vivian W Choi
R Jude Samulski
University of North Carolina at Chapel Hill · USGeorgia Institute of Technology · USHarvard University · US

Funding

Respiratory Syncytial Virus Based Vectors for CFTRP01HL051818 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SAMULSKI, RICHARD J · 1993 to 2008
$16.0M
Resolving rate limiting steps for AAV vectorsP01HL066973 · NHLBI · UNIVERSITY OF NORTH CAROLINA CHAPEL HILL · PI SAMULSKI, RICHARD J · 2001 to 2005
$9.3M
Rational and Combinatorial Engineering of AAV VectorsR01AI072176 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI HIRSCH, MATTHEW LOUIS, SAMULSKI, RICHARD J · 2008 to 2017
$3.7M
NHLBI NIH HHS HL051818NHLBI NIH HHS HL066973NHLBI NIH HHS P01 HL051818NHLBI NIH HHS P01 HL066973NIAID NIH HHS AI072176NIAID NIH HHS R01 AI072176NIGMS NIH HHS GM0529299
6 · The paper itself

Abstract

Adeno-associated virus (AAV) transduction initiates a signaling cascade that culminates in a transient DNA damage response. During this time, host DNA repair proteins convert the linear single-strand AAV genomes to double-strand circular monomers and concatemers in processes stimulated by the AAV inverted terminal repeats (ITRs). As the orientation of AAV genome concatemerization appears unbiased, the likelihood of concatemerization in a desired orientation is low (less than 1 in 6). Using a novel recombineering method, Oligo-Assisted AAV Genome Recombination (OAGR), this work demonstrates the ability to direct concatemerization specifically to a desired orientation in human cells. This was achieved by a single-strand DNA oligonucleotide (oligo) displaying homology to distinct AAV genomes capable of forming an intermolecular bridge for recombination. This DNA repair process results in concatemers with genomic junctions corresponding to the sequence of oligo homology. Furthermore, OAGR was restricted to single-strand, not duplexed, AAV genomes suggestive of replication-dependent recombination. Consistent with this process, OAGR demonstrated oligo polarity biases in all tested configurations except when a portion of the oligo targeted the ITR. This approach, in addition to being useful for the elucidation of intermolecular homologous recombination, may find eventual relevance for AAV mediated large gene therapy.

Indexed as

Recombination, GeneticCell LineDependovirusDNA DamageDNA ReplicationDNA, ViralGenetic TechniquesGenetic TherapyGenetic VectorsGenome, ViralGreen Fluorescent ProteinsHumansModels, GeneticOligonucleotidesSignal TransductionDNA, ViralGreen Fluorescent ProteinsOligonucleotides

Identifiers

PMID19888330
PMCPMC2765622
OpenAlexW1979743978

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.