ArticleCell reports. Medicine2024
Safe and effective liver-directed AAV-mediated homology-independent targeted integration in mouse models of inherited diseases.
Article in Cell reports. Medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Long-read target enrichment sequencing for rAAV integration site analysis in engineered clones with targeted viral insertion.Molecular therapy. Nucleic acids · 2026Article
- Functional editing of the OTC locus by targeted integration with phenotype correction and restoration of endogenous expression patterns.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Nucleases and Their Inhibitors: Exploring Biological Roles, Industrial Applications, and Challenges in Heterologous Expression.Biotechnology journal · 2026Review
- Promoting Research Excellence in Down Syndrome: Proceedings of the 5th International Conference of the Trisomy 21 Research Society.Neuromolecular medicine · 2026Article
- Gene therapy for liver diseases: methods, challenges and opportunities.Journal of nanobiotechnology · 2026Review
- Article
- GH-resistant (Laron) mice: gene therapy with a liver-specific GH receptor causes unbalanced upregulation of female-biased and growth-related genes.Frontiers in endocrinology · 2026Article
- Advancements in CRISPR-basedFrontiers in genome editing · 2026Review
- Current Status of Clinical Gene Therapy for Hemophilia and Globin Disorders.Journal of blood medicine · 2026Review
- Knowledge mapping and bibliometric insights into gene therapy for rare inherited hematologic pathologies: focus on sickle cell disease, hemophilia, and thalassemia.Orphanet journal of rare diseases · 2025Article
- Mucopolysaccharidoses-What Clinicians Need to Know: A Clinical, Biochemical, and Molecular Overview.Biomolecules · 2025Review
- Engineering adeno-associated viral vectors for CRISPR/Cas based in vivo therapeutic genome editing.Biomaterials · 2025Review
- Development of circular AAV cargos for targeted seamless insertion with large serine integrases.Molecular therapy. Methods & clinical development · 2025Article
- Generation and Treatment of a Novel Severe Model of Visceral Gaucher Disease by Genetic Therapy.Pharmaceutics · 2025Article
- Rescue of lysosomal acid lipase deficiency in mice by rAAV8 liver gene transfer.Communications medicine · 2025Article
- CRISPR and gene editing technologies for bleeding disorders.Therapeutic advances in hematology · 2025Review
- Review
Corrections and comments
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Authors and funding
23 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Liver-directed adeno-associated viral (AAV) vector-mediated homology-independent targeted integration (AAV-HITI) by CRISPR-Cas9 at the highly transcribed albumin locus is under investigation to provide sustained transgene expression following neonatal treatment. We show that targeting the 3' end of the albumin locus results in productive integration in about 15% of mouse hepatocytes achieving therapeutic levels of systemic proteins in two mouse models of inherited diseases. We demonstrate that full-length HITI donor DNA is preferentially integrated upon nuclease cleavage and that, despite partial AAV genome integrations in the target locus, no gross chromosomal rearrangements or insertions/deletions at off-target sites are found. In line with this, no evidence of hepatocellular carcinoma is observed within the 1-year follow-up. Finally, AAV-HITI is effective at vector doses considered safe if directly translated to humans providing therapeutic efficacy in the adult liver in addition to newborn. Overall, our data support the development of this liver-directed AAV-based knockin strategy.
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