ArticleJournal of virology2010
Differential effects of DNA double-strand break repair pathways on single-strand and self-complementary adeno-associated virus vector genomes.
Article in Journal of virology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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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.
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.
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Who cites it
26 citing papers in PubMed, 35 citations in OpenAlex.
- Effective knockdown-replace gene therapy in a novel mouse model of DNM1 developmental and epileptic encephalopathy.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Temporal restriction of Cas9 expression improves CRISPR-mediated deletion efficacy and fidelity.Molecular therapy. Nucleic acids · 2024Article
- Casein kinase 2 activity is a host restriction factor for AAV transduction.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Inhibition of DNA-dependent protein kinase catalytic subunit boosts rAAV transduction of polarized human airway epithelium.Molecular therapy. Methods & clinical development · 2023Article
- AAV genome modification for efficient AAV production.Heliyon · 2023Review
- Evaluating the state of the science for adeno-associated virus integration: An integrated perspective.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Review
- Strategies to improve safety profile of AAV vectors.Frontiers in molecular medicine · 2022Review
- Herpes Simplex Virus 1 Coinfection Modifies Adeno-associated Virus Genome End Recombination.Journal of virology · 2021Article
- rAAV9-UPII-TK-EGFP can precisely transduce a suicide gene and inhibit the growth of bladder tumors.Cancer biology & therapy · 2020Article
- Ring finger protein 121 is a potent regulator of adeno-associated viral genome transcription.PLoS pathogens · 2019Article
- Stem cell-derived clade F AAVs mediate high-efficiency homologous recombination-based genome editing.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- RFX1 and RFX3 Transcription Factors Interact with the D Sequence of Adeno-Associated Virus Inverted Terminal Repeat and Regulate AAV Transduction.Scientific reports · 2018Article
- Deletion of the B-B' and C-C' regions of inverted terminal repeats reduces rAAV productivity but increases transgene expression.Scientific reports · 2017Article
- Identification and Validation of Small Molecules That Enhance Recombinant Adeno-associated Virus Transduction following High-Throughput Screens.Journal of virology · 2016Article
- The SUMOylation Pathway Restricts Gene Transduction by Adeno-Associated Viruses.PLoS pathogens · 2015Article
- Insight into the mechanism of inhibition of adeno-associated virus by the Mre11/Rad50/Nbs1 complex.Journal of virology · 2015Article
- Short-lived recombinant adeno-associated virus transgene expression in dystrophic muscle is associated with oxidative damage to transgene mRNA.Molecular therapy. Methods & clinical development · 2015Article
- Inverted terminal repeats of adeno-associated virus decrease random integration of a gene targeting fragment in Saccharomyces cerevisiae.BMC molecular biology · 2014Article
- 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 · 2013Article
- Hairpin-end conformation of adeno-associated virus genome determines interactions with DNA-repair pathways.Gene therapy · 2013Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
The linear DNA genomes of recombinant adeno-associated virus (rAAV) gene delivery vectors are acted upon by multiple DNA repair and recombination pathways upon release into the host nucleus, resulting in circularization, concatemer formation, or chromosomal integration. We have compared the fates of single-strand rAAV (ssAAV) and self-complementary AAV (scAAV) genomes in cell lines deficient in each of three signaling factors, ATM, ATR, and DNA-PK(CS), orchestrating major DNA double-strand break (DSB) repair pathways. In cells deficient in ATM, transduction as scored by green fluorescent protein (GFP) expression is increased relative to that in wild-type (wt) cells by 2.6-fold for ssAAV and 6.6-fold for scAAV vectors, arguing against a mechanism related to second-strand synthesis. The augmented transduction is not reflected in Southern blots of nuclear vector DNA, suggesting that interactions with ATM lead to silencing in normal cells. The additional functional genomes in ATM(-/-) cells remain linear, and the number of circularized genomes is not affected by the mutation, consistent with compartmentalization of genomes into different DNA repair pathways. A similar effect is observed in ATR-deficient cells but is specific for ssAAV vector. Conversely, a large decrease in transduction is observed in cells deficient in DNA-PK(CS), which is involved in DSB repair by nonhomologous end joining rather than homologous recombination. The mutations also have differential effects on chromosomal integration of ssAAV versus scAAV vector genomes. Integration of ssAAV was specifically reduced in ATM(-/-) cells, while scAAV integration was more profoundly inhibited in DNA-PK(CS)(-/-) cells. Taken together, the results suggest that productive rAAV genome circularization is mediated primarily by nonhomologous end joining.
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Registered trials
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.