ArticleJournal of virology2000
Recruitment of single-stranded recombinant adeno-associated virus vector genomes and intermolecular recombination are responsible for stable transduction of liver in vivo.
Article in Journal of virology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 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
90 citing papers in PubMed, 189 citations in OpenAlex.
- Efficient multi-kilobase knock-ins in mice and cell lines using CRISPR/Cas9 and rAAV donors with unbiased whole-genome characterization by LOCK-seq.Nucleic acids research · 2026Article
- New hope for older SMA patients with next-generation self-complementary AAV gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Residual DNA impurities in AAV vectors-nature and transcription.Molecular therapy. Methods & clinical development · 2025Article
- Evaluation of the loading capacity and patterns of packaged DNA in AAV genomes of different sizes using long-read sequencing.Molecular therapy. Methods & clinical development · 2025Article
- Gene therapy for the leukodystrophies: From preclinical animal studies to clinical trials.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- Assessment of Key Factors Impacting Variability in AAV Vector Genome Titration by Digital PCR.International journal of molecular sciences · 2024Article
- Lack of germline transmission in male mice following a single intravenous administration of AAV5-hFVIII-SQ gene therapy.Gene therapy · 2023Article
- The AAV capsid can influence the epigenetic marking of rAAV delivered episomal genomes in a species dependent manner.Nature communications · 2023Article
- Characteristics of BAY 2599023 in the Current Treatment Landscape of Hemophilia A Gene Therapy.Current gene therapy · 2023Review
- Evaluation of the SH-SY5Y cell line as anFrontiers in molecular neuroscience · 2023Article
- Direct ITR-to-ITR Nanopore Sequencing of AAV Vector Genomes.Human gene therapy · 2022Article
- Young mice administered adult doses of AAV5-hFVIII-SQ achieve therapeutic factor VIII expression into adulthood.Molecular therapy. Methods & clinical development · 2022Article
- Molecular analysis of AAV5-hFVIII-SQ vector-genome-processing kinetics in transduced mouse and nonhuman primate livers.Molecular therapy. Methods & clinical development · 2022Article
- Of rAAV and Men: From Genetic Neuromuscular Disorder Efficacy and Toxicity Preclinical Studies to Clinical Trials and Back.Journal of personalized medicine · 2020Review
- AAV-Genome Population Sequencing of Vectors Packaging CRISPR Components Reveals Design-Influenced Heterogeneity.Molecular therapy. Methods & clinical development · 2020Article
- Fetal Gene Therapy Using a Single Injection of Recombinant AAV9 Rescued SMA Phenotype in Mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Article
- Adeno-associated virus vector as a platform for gene therapy delivery.Nature reviews. Drug discovery · 2019Review
- Translational Aspects of Adeno-Associated Virus-Mediated Cardiac Gene Therapy.Human gene therapy · 2018Review
- Adeno-associated Virus (AAV) Dual Vector Strategies for Gene Therapy Encoding Large Transgenes.The Yale journal of biology and medicine · 2017Review
- Steerable Induction of the Thymosin β4/MRTF-A Pathway via AAV-Based Overexpression Induces Therapeutic Neovascularization.Human gene therapy · 2017Article
30 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
3 authors at 2 institutions in 1 country.
Funding
Abstract
Recombinant adeno-associated virus (rAAV) vectors stably transduce hepatocytes in experimental animals. Following portal-vein administration of rAAV vectors in vivo, single-stranded (ss) rAAV genomes become double stranded (ds), circularized, and/or concatemerized concomitant with a slow rise and, eventually, steady-state levels of transgene expression. Over time, at least some of the stabilized genomes become integrated into mouse chromosomal DNA. The mechanism(s) of formation of stable ds rAAV genomes from input ss DNA molecules has not been delineated, although second-strand synthesis and genome amplification by a rolling-circle model has been proposed. To begin to delineate a mechanism, we produced rAAV vectors in the presence of bacterial PaeR7 or Dam methyltransferase or constructed rAAV vectors labeled with different restriction enzyme recognition sites and introduced them into mouse hepatocytes in vivo. A series of molecular analyses demonstrated that second-strand synthesis and rolling-circle replication did not appear to be the major processes involved in the formation of stable ds rAAV genomes. Rather, recruitment of complementary plus and minus ss genomes and subsequent random head-to-head, head-to-tail, and tail-to-tail intermolecular joining were primarily responsible for the formation of ds vector genomes. These findings contrast with the previously described mechanism(s) of transduction based on in vitro studies. Understanding the mechanistic process responsible for vector transduction may allow the development of new strategies for improving rAAV-mediated gene transfer in vivo.
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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.