ArticleMolecular therapy : the journal of the American Society of Gene Therapy2012
Patterns of scAAV vector insertion associated with oncogenic events in a mouse model for genotoxicity.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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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.
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Who cites it
66 citing papers in PubMed, 98 citations in OpenAlex.
- Article
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- Hearing loss: a global view for gene therapy approaches and challenges.European journal of pediatrics · 2025Review
- Gene Therapy: An Historical Overview for Familial Hearing Loss.International journal of molecular sciences · 2025Review
- Gene therapy in hemophilia: the dawn of a new era.Research and practice in thrombosis and haemostasis · 2025Review
- Integrated vector genomes may contribute to long-term expression in primate liver after AAV administration.Nature biotechnology · 2024Article
- Adeno-associated virus as a delivery vector for gene therapy of human diseases.Signal transduction and targeted therapy · 2024Review
- Thorough molecular configuration analysis of noncanonical AAV genomes in AAV vector preparations.Molecular therapy. Methods & clinical development · 2024Article
- Molecular Mechanisms in Pathophysiology of Mucopolysaccharidosis and Prospects for Innovative Therapy.International journal of molecular sciences · 2024Review
- Engineered lentivirus-derived nanoparticles (LVNPs) for delivery of CRISPR/Cas ribonucleoprotein complexes supporting base editing, prime editing and in vivo gene modification.Nucleic acids research · 2023Article
- Molecular evaluation and vector integration analysis of HCC complicating AAV gene therapy for hemophilia B.Blood advances · 2023Article
- Intrathecal AAV9/AP4M1 gene therapy for hereditary spastic paraplegia 50 shows safety and efficacy in preclinical studies.The Journal of clinical investigation · 2023Article
- Intrathymic AAV delivery results in therapeutic site-specific integration at TCR loci in mice.Blood · 2023Article
- Gene therapy for liver diseases - progress and challenges.Nature reviews. Gastroenterology & hepatology · 2023Review
- A Review of CRISPR Tools for Treating Usher Syndrome: Applicability, Safety, Efficiency, and In Vivo Delivery.International journal of molecular sciences · 2023Review
- A novel strategy for delivering Niemann-Pick type C2 proteins across the blood-brain barrier using the brain endothelial-specific AAV-BR1 virus.Journal of neurochemistry · 2023Article
- Choice of template delivery mitigates the genotoxic risk and adverse impact of editing in human hematopoietic stem cells.Cell stem cell · 2022Article
- The Arrival of Gene Therapy for Patients with Hemophilia A.International journal of molecular sciences · 2022Review
- Evaluating the state of the science for adeno-associated virus integration: An integrated perspective.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Review
- Strategies to improve safety profile of AAV vectors.Frontiers in molecular medicine · 2022Review
6 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Recombinant adeno-associated virus (rAAV) vectors have gained an extensive record of safety and efficacy in animal models of human disease. Infrequent reports of genotoxicity have been limited to specific vectors associated with excess hepatocellular carcinomas (HCC) in mice. In order to understand potential mechanisms of genotoxicity, and identify patterns of insertion that could promote tumor formation, we compared a self-complementary AAV (scAAV) vector designed to promote insertional activation (scAAV-CBA-null) to a conventional scAAV-CMV-GFP vector. HCC-prone C3H/HeJ mice and severe combined immunodeficiency (SCID) mice were infected with vector plus secondary treatments including partial hepatectomy (HPX) and camptothecin (CPT) to determine the effects of cell cycling and DNA damage on tumor incidence. Infection with either vector led to a significant increase in HCC incidence in male C3H/HeJ mice. Partial HPX after infection reduced HCC incidence in the cytomegalovirus-green fluorescent protein (CMV-GFP)-infected mice, but not in the cognate chicken β-actin (CBA)-null infected group. Tumors from CBA-null infected, hepatectomized mice were more likely to contain significant levels of vector DNA than tumors from the corresponding CMV-GFP-infected group. Most CBA-null vector insertions recovered from tumors were associated with known proto-oncogenes or tumor suppressors. Specific patterns of insertion suggested read-through transcription, enhancer effects, and disruption of tumor suppressors as likely mechanisms for genotoxicity.
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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.