ArticleJournal of virology2009
Reducing the risk of adeno-associated virus (AAV) vector mobilization with AAV type 5 vectors.
Article in Journal of virology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed.
- Sequence-based artificial intelligence-guided inhibitory peptides to counteract AAV neutralizing antibodies in gene therapy.Molecular therapy. Advances · 2026Article
- AAV vectors: The Rubik's cube of human gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Review
- Coupled myovascular expansion directs cardiac growth and regeneration.Development (Cambridge, England) · 2022Article
- Improved transduction of canine X-linked muscular dystrophy with rAAV9-microdystrophin via multipotent MSC pretreatment.Molecular therapy. Methods & clinical development · 2021Article
- Adeno-Associated Virus Vector Mobilization, Risk Versus Reality.Human gene therapy · 2020Article
- Adeno-Associated Virus Mediated Gene Therapy for Corneal Diseases.Pharmaceutics · 2020Review
- Relationship Between Neutralizing Antibodies Against Adeno-Associated Virus in the Vitreous and Serum: Effects on Retinal Gene Therapy.Translational vision science & technology · 2019Article
- Superior lentiviral vectors designed for BSL-0 environment abolish vector mobilization.Gene therapy · 2018Article
- Serotype survey of AAV gene delivery via subconjunctival injection in mice.Gene therapy · 2018Article
- Adeno-Associated Virus Vectors and Stem Cells: Friends or Foes?Human gene therapy · 2017Review
- Ret is essential to mediate GDNF's neuroprotective and neuroregenerative effect in a Parkinson disease mouse model.Cell death & disease · 2016Article
- Article
- Structural Studies of AAV2 Rep68 Reveal a Partially Structured Linker and Compact Domain Conformation.Biochemistry · 2015Article
- Insight into the mechanism of inhibition of adeno-associated virus by the Mre11/Rad50/Nbs1 complex.Journal of virology · 2015Article
- Preclinical toxicity evaluation of AAV for pain: evidence from human AAV studies and from the pharmacology of analgesic drugs.Molecular pain · 2014Review
- Highly divergent integration profile of adeno-associated virus serotype 5 revealed by high-throughput sequencing.Journal of virology · 2014Article
- Viral vectors for gene delivery to the central nervous system.Neurobiology of disease · 2012Review
- AAV's anatomy: roadmap for optimizing vectors for translational success.Current gene therapy · 2010Article
- Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Current adeno-associated virus (AAV) gene therapy vectors package a transgene flanked by the terminal repeats (TRs) of AAV type 2 (AAV2). Although these vectors are replication deficient, wild-type (wt) AAV2 prevalent in the human population could lead to replication and packaging of a type 2 TR (TR2)-flanked transgene in trans during superinfection by a helper virus, leading to "mobilization" of the vector genome from treated cells. More importantly, it appears likely that the majority of currently characterized AAV serotypes as well as the majority of new novel isolates are capable of rescuing and replicating AAV2 vector templates. To investigate this possibility, we flanked a green fluorescent protein transgene with type 2 and, the most divergent AAV serotype, type 5 TRs (TR2 or TR5). Consistent with AAV clades, AAV5 specifically replicated TR5 vectors, while AAV2 and AAV6 replicated TR2-flanked vectors. To exploit this specificity, we created a TR5 vector production system for Cap1 to Cap5. Next, we showed that persisting recombinant AAV genomes flanked by TR2s or TR5s were mobilized in vitro after addition of the cognate AAV Rep (as well as Rep6 for TR2) and adenoviral helper. Finally, we showed that a cell line containing a stably integrated wt AAV2 genome resulted in mobilization of a TR2-flanked vector but not a TR5-flanked vector upon adenoviral superinfection. Based on these data and the relative prevalence of wt AAV serotypes in the population, we propose that TR5 vectors have a significantly lower risk of mobilization and should be considered for clinical use.
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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.