ArticleHuman gene therapy2016
Recombinant Adeno-Associated Virus Vector Genomes Take the Form of Long-Lived, Transcriptionally Competent Episomes in Human Muscle.
Article in Human gene therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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.
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
17 citing papers in PubMed, 31 citations in OpenAlex.
- Adeno-associated virus vectored immunoprophylaxis to prevent HIV in healthy adults: a phase 1 randomised controlled trial.The lancet. HIV · 2019Trial
- Spatial genomics of AAV vectors reveals mechanism of transcriptional crosstalk that enables targeted delivery of large genetic cargo.Nature biotechnology · 2026Article
- Biodistribution of AAV1, AAV5, AAV9, and AAVDJ serotypes after intra-cisterna magna delivery in non-human primates.Molecular therapy. Methods & clinical development · 2025Article
- Dynamic activation of rAAV transgene expression by a small molecule that recruits endogenous transcriptional machinery.Nucleic acids research · 2025Article
- Gene therapy in hemophilia: the dawn of a new era.Research and practice in thrombosis and haemostasis · 2025Review
- 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
- Interindividual variability in transgene mRNA and protein production following adeno-associated virus gene therapy for hemophilia A.Nature medicine · 2022Article
- Molecular analysis of AAV5-hFVIII-SQ vector-genome-processing kinetics in transduced mouse and nonhuman primate livers.Molecular therapy. Methods & clinical development · 2022Article
- AAV-mediated gene transfer of a checkpoint inhibitor in combination with HER2-targeted CAR-NK cells as experimental therapy for glioblastoma.Oncoimmunology · 2022Article
- Variability in Genome Editing Outcomes: Challenges for Research Reproducibility and Clinical Safety.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Review
- Adeno-Associated Virus Genome Interactions Important for Vector Production and Transduction.Human gene therapy · 2020Review
- Gene Therapy for Hemophilia: Facts and Quandaries in the 21st Century.Mediterranean journal of hematology and infectious diseases · 2020Review
- Design of non-viral vector with improved regulatory features towards therapeutic application.Bioinformation · 2020Article
- Adeno-Associated Virus Delivery of Anti-HIV Monoclonal Antibodies Can Drive Long-Term Virologic Suppression.Immunity · 2019Article
- Adeno-associated virus gene delivery of broadly neutralizing antibodies as prevention and therapy against HIV-1.Retrovirology · 2018Review
- Modern biotechnology-based therapeutic approaches against HIV infection.Biomedical reports · 2017Article
- Promise and problems associated with the use of recombinant AAV for the delivery of anti-HIV antibodies.Molecular therapy. Methods & clinical development · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
Gene augmentation therapy as a strategy to treat alpha-1 antitrypsin (AAT) deficiency has reached phase 2 clinical testing in humans. Sustained serum levels of AAT have been observed beyond one year after intramuscular administration of a recombinant adeno-associated virus (rAAV) vector expressing the AAT gene. In this study, sequential muscle biopsies obtained at 3 and 12 months after vector injection were examined for the presence of rAAV vector genomes. Each biopsy sample contained readily detectable vector DNA, the majority of which existed as double-stranded supercoiled and open circular episomes. Episomes persisted through 12 months, although at slightly lower levels than observed at 3 months. There was a clear dose response when comparing the low- and mid-vector-dose groups to the high-dose group. The highest absolute copy numbers were found in a high-dose subject, and serum AAT levels at 12 months confirmed that the high-dose group also had the highest sustained serum AAT levels. Sequence analysis revealed that the vast majority of episomes contained double-D inverted terminal repeats ranging from fully intact to severely deleted. Molecular clones of vector genomes derived directly from the biopsies were transcriptionally active, potentially identifying them as the source of serum AAT in the trial subjects.
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What OpenQuestion holds
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.