ArticleJournal of virology2008
Frequency and spectrum of genomic integration of recombinant adeno-associated virus serotype 8 vector in neonatal mouse liver.
Article in Journal of virology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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
28 citing papers in PubMed, 56 citations in OpenAlex.
- Comprehensive analysis of off-target and on-target effects resulting from liver-directed CRISPR-Cas9-mediated gene targeting with AAV vectors.Molecular therapy. Methods & clinical development · 2024Article
- The longitudinal kinetics of AAV5 vector integration profiles and evaluation of clonal expansion in mice.Molecular therapy. Methods & clinical development · 2024Article
- Gene therapy for liver diseases - progress and challenges.Nature reviews. Gastroenterology & hepatology · 2023Review
- Choice of template delivery mitigates the genotoxic risk and adverse impact of editing in human hematopoietic stem cells.Cell stem cell · 2022Article
- Therapeutic homology-independent targeted integration in retina and liver.Nature communications · 2022Article
- AAV-mediated gene therapy for galactosialidosis: A long-term safety and efficacy study.Molecular therapy. Methods & clinical development · 2021Article
- AAV integration in human hepatocytes.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- The intersection of vector biology, gene therapy, and hemophilia.Research and practice in thrombosis and haemostasis · 2021Review
- Implementation of CRISPR/Cas9 Genome Editing to Generate Murine Lung Cancer Models That Depict the Mutational Landscape of Human Disease.Frontiers in cell and developmental biology · 2021Article
- Gene therapy for inherited metabolic diseases.Journal of mother and child · 2020Review
- Therapeutic expression of human clotting factors IX and X following adeno-associated viral vector-mediated intrauterine gene transfer in early-gestation fetal macaques.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Emerging Issues in AAV-MediatedMolecular therapy. Methods & clinical development · 2018Review
- Homologous recombination mediates stable Fah gene integration and phenotypic correction in tyrosinaemia mouse-model.World journal of hepatology · 2018Article
- In Utero Transfer of Adeno-Associated Viral Vectors Produces Long-Term Factor IX Levels in a Cynomolgus Macaque Model.Molecular therapy : the journal of the American Society of Gene Therapy · 2017Article
- Delivering efficient liver-directed AAV-mediated gene therapy.Gene therapy · 2017Article
- Engineering a gene silencing viral construct that targets the cat hypothalamus to induce permanent sterility: An update.Reproduction in domestic animals = Zuchthygiene · 2017Article
- Engineering Stem Cells for Biomedical Applications.Advanced healthcare materials · 2016Review
- Recombinant AAV as a platform for translating the therapeutic potential of RNA interference.Molecular therapy : the journal of the American Society of Gene Therapy · 2014Review
- Long-term correction of biochemical and neurological abnormalities in MLD mice model by neonatal systemic injection of an AAV serotype 9 vector.Gene therapy · 2014Article
- Biochemical and Physiological Improvement in a Mouse Model of Smith-Lemli-Opitz Syndrome (SLOS) Following Gene Transfer with AAV Vectors.Molecular genetics and metabolism reports · 2014Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Neonatal injection of recombinant adeno-associated virus serotype 8 (rAAV8) vectors results in widespread transduction in multiple organs and therefore holds promise in neonatal gene therapy. On the other hand, insertional mutagenesis causing liver cancer has been implicated in rAAV-mediated neonatal gene transfer. Here, to better understand rAAV integration in neonatal livers, we investigated the frequency and spectrum of genomic integration of rAAV8 vectors in the liver following intraperitoneal injection of 2.0 x 10(11) vector genomes at birth. This dose was sufficient to transduce a majority of hepatocytes in the neonatal period. In the first approach, we injected mice with a beta-galactosidase-expressing vector at birth and quantified rAAV integration events by taking advantage of liver regeneration in a chronic hepatitis animal model and following partial hepatectomy. In the second approach, we performed a new, quantitative rAAV vector genome rescue assay by which we identified rAAV integration sites and quantified integrations. As a result, we find that at least approximately 0.05% of hepatocytes contained rAAV integration, while the average copy number of integrated double-stranded vector genome per cell in the liver was approximately 0.2, suggesting concatemer integration. Twenty-three of 34 integrations (68%) occurred in genes, but none of them were near the mir-341 locus, the common rAAV integration site found in mouse hepatocellular carcinoma. Thus, rAAV8 vector integration occurs preferentially in genes at a frequency of 1 in approximately 10(3) hepatocytes when a majority of hepatocytes are once transduced in the neonatal period. Further studies are warranted to elucidate the relationship between vector dose and integration frequency or spectrum.
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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.