ArticleJournal of virology2001
Extrachromosomal recombinant adeno-associated virus vector genomes are primarily responsible for stable liver transduction in vivo.
Article in Journal of virology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 226 papers, 1 of them a synthesis that pooled it.
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
226 citing papers in PubMed, 1 synthesis or guideline pooled it, 475 citations in OpenAlex.
- Recombinant Adeno-Associated Viral Vectors (rAAV)-Vector Elements in Ocular Gene Therapy Clinical Trials and Transgene Expression and Bioactivity Assays.International journal of molecular sciences · 2020Pooled it
- Gene Therapy Strategies for Uveal Melanoma: Adeno-associated Virus Delivery Challenges and Translational Opportunities.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- AAV Vectors in Regenerative Medicine and Cellular Reprogramming: Potential, Pitfalls, and Specificity Constraints.International journal of molecular sciences · 2026Review
- AAV immuno-gene therapy platform delivering vectorized cytokines defines a new modality for high-grade glioma treatment.Molecular therapy. Oncology · 2026Article
- Enhancement of therapeutic transgene insertion for treatment of murine phenylketonuria.Molecular therapy. Nucleic acids · 2026Article
- RAAVioli: A comprehensive approach to characterizing AAV vector integrations and rearrangements.Molecular therapy. Advances · 2026Article
- Human FGF1Cells · 2026Article
- AAV Capsid Modification and Its Influence on Viral Protein Stoichiometry and Packaging Fitness: Current Understandings and Future Direction.Molecular biotechnology · 2026Review
- Spatial genomics of AAV vectors reveals mechanism of transcriptional crosstalk that enables targeted delivery of large genetic cargo.Nature biotechnology · 2026Article
- Modified AAV5 capsid for improved brain biodistribution following direct injection in preclinical models.Molecular therapy. Methods & clinical development · 2025Article
- Liver-directed AAV gene therapy in mice corrects glycogen storage disease type IX γ2.Science advances · 2025Article
- Small molecule inhibition of SUMOylation increases expression from AAV vectors both during and after initial transduction in mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- The deLIVERed promises of gene therapy: Past, present, and future of liver-directed gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Impact of liver fibrosis on AAV-mediated gene transfer to mouse hepatocytes.Nature communications · 2025Article
- Liver fibrosis negatively impacts in vivo gene transfer to murine hepatocytes.Nature communications · 2025Article
- Distinct infectivity and neutralization antibody responses in the highly homologous AAV Go.1 and AAV5.Frontiers in medicine · 2025Article
- Cancer vaccines: an update on recent achievements and prospects for cancer therapy.Clinical and experimental medicine · 2024Review
- Review
- Advances in Pompe Disease Treatment: From Enzyme Replacement to Gene Therapy.Molecular diagnosis & therapy · 2024Review
- Optimizing liver health before and after gene therapy for hemophilia A.Blood advances · 2024Review
166 more citing papers are in PubMed but not listed here.
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 2 institutions in 1 country.
Funding
Abstract
Recombinant adeno-associated virus (rAAV) vectors stably transduce hepatocytes in experimental animals. Although the vector genomes are found both as extrachromosomes and as chromosomally integrated forms in hepatocytes, the relative proportion of each has not yet been clearly established. Using an in vivo assay based on the induction of hepatocellular regeneration via a surgical two-thirds partial hepatectomy, we have determined the proportion of integrated and extrachromosomal rAAV genomes in mouse livers and their relative contribution to stable gene expression in vivo. Plasma human coagulation factor IX (hF.IX) levels in mice originating from a chromosomally integrated hF.IX-expressing transposon vector remained unchanged with hepatectomy. This was in sharp contrast to what was observed when a surgical partial hepatectomy was performed in mice 6 weeks to 12 months after portal vein injection of a series of hF.IX-expressing rAAV vectors. At doses of 2.4 x 10(11) to 3.0 x 10(11) vector genomes per mouse (n = 12), hF.IX levels and the average number of stably transduced vector genomes per cell decreased by 92 and 86%, respectively, after hepatectomy. In a separate study, one of three mice injected with a higher dose of rAAV had a higher proportion (67%) of integrated genomes, the significance of which is not known. Nevertheless, in general, these results indicate that, in most cases, no more than approximately 10% of stably transduced genomes integrated into host chromosomes in vivo. Additionally, the results demonstrate that extrachromosomal, not integrated, genomes are the major form of rAAV in the liver and are the primary source of rAAV-mediated gene expression. This small fraction of integrated genomes greatly decreases the potential risk of vector-related insertional mutagenesis associated with all integrating vectors but also raises uncertainties as to whether rAAV-mediated hepatic gene expression can persist lifelong after a single vector administration.
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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.