ArticleJournal of virology2004
Intracellular viral processing, not single-stranded DNA accumulation, is crucial for recombinant adeno-associated virus transduction.
Article in Journal of virology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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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.
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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
46 citing papers in PubMed, 98 citations in OpenAlex.
- Targeting the peripheral nervous system in adipose tissue with engineered AAV vectors.Cell reports methods · 2026Article
- Optimizing single molecule, real-time sequencing for enhanced characterization of adeno-associated viral vector genomes.Molecular therapy. Advances · 2026Article
- Comparison of AAV9-driven motor neuron transduction following different CNS-directed delivery methods in mice.Scientific reports · 2026Article
- Review
- Residual DNA impurities in AAV vectors-nature and transcription.Molecular therapy. Methods & clinical development · 2025Article
- AAV capsids target muscle-resident cells with different efficiencies-A comparative study between AAV8, AAVMYO, and AAVMYO2.Molecular therapy. Methods & clinical development · 2025Article
- In Vivo Selection of S/MAR Sequences to Favour AAV Episomal Maintenance in Dividing Cells.International journal of molecular sciences · 2024Article
- Prospective approaches to gene therapy computational modeling - spotlight on viral gene therapy.Journal of pharmacokinetics and pharmacodynamics · 2024Review
- MiR133b-mediated inhibition of EGFR-PTK pathway promotes rAAV2 transduction by facilitating intracellular trafficking and augmenting second-strand synthesis.Journal of cellular and molecular medicine · 2023Article
- Base editing rescue of spinal muscular atrophy in cells and in mice.Science (New York, N.Y.) · 2023Article
- Vector genome loss and epigenetic modifications mediate decline in transgene expression of AAV5 vectors produced in mammalian and insect cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Limited potential of AAV-mediated gene therapy in transducing human mesenchymal stem cells for bone repair applications.Gene therapy · 2021Article
- Characterization of AAV vector particle stability at the single-capsid level.Journal of biological physics · 2018Article
- Development of a Click-Chemistry Reagent Compatible with Mass Cytometry.Scientific reports · 2018Article
- Biological Therapies for Atrial Fibrillation: Ready for Prime Time?Journal of cardiovascular pharmacology · 2016Review
- Self-Complementary Adeno-Associated Virus Vectors Improve Transduction Efficiency of Corneal Endothelial Cells.PloS one · 2016Article
- Adeno-associated Virus as a Mammalian DNA Vector.Microbiology spectrum · 2015Review
- Unique glycan signatures regulate adeno-associated virus tropism in the developing brain.Journal of virology · 2015Article
- Syntaxin 5-dependent retrograde transport to the trans-Golgi network is required for adeno-associated virus transduction.Journal of virology · 2015Article
- Functional analysis of the putative integrin recognition motif on adeno-associated virus 9.The Journal of biological chemistry · 2015Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Adeno-associated virus (AAV) is a unique gene transfer vector which takes approximately 4 to 6 weeks to reach its expression plateau. The mechanism for this slow-rise expression profile was proposed to be inefficient second-strand DNA synthesis from the input single-stranded (ss) DNA viral genome. In order to clarify the status of ss AAV genomes, we generated AAV vectors labeled with bromodeoxyuridine (BrdU), a nucleotide analog that can be incorporated into the AAV genome and packaged into infectious virions. Since BrdU-DNA can be detected only by an anti-BrdU antibody when DNA is in an ss form, not in a double-stranded (ds) form, ss AAV genomes with BrdU can be readily tracked in situ. Although ss AAV DNA was abundant by Southern blot analysis, free ss AAV genomes were not detectable after AAV transduction by this new detection method. Further Southern blot analysis of viral DNA and virions revealed that ss AAV DNA was protected within virions. Extracted cellular fractions demonstrated that viral particles in host cells remained infectious. In addition, a significant amount of AAV genomes was degraded after AAV transduction. Therefore, we conclude that the amount of free ss DNA is not abundant during AAV transduction. AAV transduction is limited by the steps that affect AAV ss DNA release (i.e., uncoating) before second-strand DNA synthesis can occur. AAV ss DNA released from viral uncoating is either converted into ds DNA efficiently or degraded by cellular DNA repair mechanisms as damaged DNA. This study elucidates a mechanism that can be exploited to develop new strategies to improve AAV vector transduction efficiency.
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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.