ArticleMolecular therapy : the journal of the American Society of Gene Therapy2012
AAV vectors containing rDNA homology display increased chromosomal integration and transgene persistence.
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 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 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-sized DNA insertion at genomic safe harbors in human cells using a site-directed transposase.Nucleic acids research · 2025Article
- Progress in Gene Therapy for Hereditary Tyrosinemia Type 1.Pharmaceutics · 2025Review
- Delivery of genetic medicines for muscular dystrophies.Cell reports. Medicine · 2025Review
- Harnessing eukaryotic retroelement proteins for transgene insertion into human safe-harbor loci.Nature biotechnology · 2025Article
- Unveiling the Future of Cardiac Care: A Review of Gene Therapy in Cardiomyopathies.International journal of molecular sciences · 2024Review
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- Genetic Therapy Approaches for Ornithine Transcarbamylase Deficiency.Biomedicines · 2023Review
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- Strategies to improve safety profile of AAV vectors.Frontiers in molecular medicine · 2022Review
- 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
- Evaluating the Genomic Parameters Governing rAAV-Mediated Homologous Recombination.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Efficient Nuclease-Directed Integration of Lentivirus Vectors into the Human Ribosomal DNA Locus.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- Targeted gene knockin in zebrafish using the 28S rDNA-specific non-LTR-retrotransposon R2Ol.Mobile DNA · 2019Article
- Cas9-nickase-mediated genome editing corrects hereditary tyrosinemia in rats.The Journal of biological chemistry · 2018Article
- Emerging Issues in AAV-MediatedMolecular therapy. Methods & clinical development · 2018Review
- Nuclease-Mediated Gene Therapies for Inherited Metabolic Diseases of the Liver.The Yale journal of biology and medicine · 2017Review
- GJA1-20k Arranges Actin to Guide Cx43 Delivery to Cardiac Intercalated Discs.Circulation research · 2017Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Although recombinant adeno-associated viral (rAAV) vectors are promising tools for gene therapy of genetic disorders, they remain mostly episomal and hence are lost during cell replication. For this reason, rAAV vectors capable of chromosomal integration would be desirable. Ribosomal DNA (rDNA) repeat sequences are overrepresented during random integration of rAAV. We therefore sought to enhance AAV integration frequency by including 28S rDNA homology arms into our vector design. A vector containing ~1 kb of homology on each side of a cDNA expression cassette for human fumarylacetoacetate hydrolase (FAH) was constructed. rAAV of serotypes 2 and 8 were injected into Fah-deficient mice, a model for human tyrosinemia type 1. Integrated FAH transgenes are positively selected in this model and rDNA-containing AAV vectors had a ~30× higher integration frequency than controls. Integration by homologous recombination (HR) into the 28S rDNA locus was seen in multiple tissues. Furthermore, rDNA-containing AAV vectors for human factor IX (hFIX) demonstrated increased transgene persistence after liver regeneration. We conclude that rDNA containing AAV vectors may be superior to conventional vector design for the treatment of genetic diseases, especially those associated with increased hepatocyte replication.
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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.