ArticleBlood2023
Intrathymic AAV delivery results in therapeutic site-specific integration at TCR loci in mice.
Article in Blood, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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
18 citing papers in PubMed, 8 citations in OpenAlex.
- In-depth characterization of stem cell potency and genotoxicity for clinical-scaleMolecular therapy. Advances · 2026Article
- Intrasplenic Thymus Organogenesis from Injectable Tissue Fragments Restores Functional T-Cell Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Selection of human hematopoietic stem cells bearing the intended functional edit by transient AND-gate reporters.Nature biotechnology · 2026Article
- Nickase NmCas9 unsilences paternal Ube3a in a mouse model of Angelman syndrome without causing AAV vector integration.Scientific reports · 2026Article
- GDPD5-CD55-EGFR competitive binding axis regulates radioresistance and lipid accumulation in rectal cancer.Cell death & disease · 2026Article
- RAAVioli: A comprehensive approach to characterizing AAV vector integrations and rearrangements.Molecular therapy. Advances · 2026Article
- Chimeric enzymes enhance treatment potential for globoid cell leukodystrophy through hematopoietic stem cell gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- In vivo CAR cell therapy: from bench to bedside.Journal of hematology & oncology · 2025Review
- AAV-dCas9 vector unsilences paternal Ube3a in neurons by impeding Ube3a-ATS transcription.Communications biology · 2025Article
- AAV-Based Gene Therapy: Opportunities, Risks, and Scale-Up Strategies.International journal of molecular sciences · 2025Review
- 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
- Modulation of AAV transduction and integration targeting by topoisomerase poisons.Molecular therapy. Methods & clinical development · 2024Article
- 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
- AAV-mediated genome editing is influenced by the formation of R-loops.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- AAV vector-derived elements integrate into Cas9-generated double-strand breaks and disrupt gene transcription.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- T-cell specific in vivo gene delivery with DART-AAVs targeted to CD8.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Non-viral DNA delivery and TALEN editing correct the sickle cell mutation in hematopoietic stem cells.Nature communications · 2024Article
- AAV-mediated genome editing is influenced by the formation of R-loops.bioRxiv : the preprint server for biology · 2024Article
Corrections and comments
- Commented on by
Authors and funding
17 authors at 7 institutions in 3 countries.
Funding
Abstract
Adeno-associated virus (AAV) vectors have been successfully exploited in gene therapy applications for the treatment of several genetic disorders. AAV is considered an episomal vector, but it has been shown to integrate within the host cell genome after the generation of double-strand DNA breaks or nicks. Although AAV integration raises some safety concerns, it can also provide therapeutic benefit; the direct intrathymic injection of an AAV harboring a therapeutic transgene results in integration in T-cell progenitors and long-term T-cell immunity. To assess the mechanisms of AAV integration, we retrieved and analyzed hundreds of AAV integration sites from lymph node-derived mature T cells and compared these with liver and brain tissue from treated mice. Notably, we found that although AAV integrations in the liver and brain were distributed across the entire mouse genome, >90% of the integrations in T cells were clustered within the T-cell receptor α, β, and γ genes. More precisely, the insertion mapped to DNA breaks created by the enzymatic activity of recombination activating genes (RAGs) during variable, diversity, and joining recombination. Our data indicate that RAG activity during T-cell receptor maturation induces a site-specific integration of AAV genomes and opens new therapeutic avenues for achieving long-term AAV-mediated gene transfer in dividing cells.
Indexed as
Identifiers
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.