ArticleNature communications2022
Therapeutic homology-independent targeted integration in retina and liver.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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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.
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.
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Who cites it
25 citing papers in PubMed, 42 citations in OpenAlex.
- 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
- Loss of ABCA4 from photoreceptor discs is associated with glial transcriptomic changes in retinal organoids.Stem cells (Dayton, Ohio) · 2026Article
- Precise, predictable genome integrations by deep-learning-assisted design of microhomology-based templates.Nature biotechnology · 2026Article
- Gene therapy for liver diseases: methods, challenges and opportunities.Journal of nanobiotechnology · 2026Review
- Advancements in CRISPR-based therapies for ocular pathologies: from disease mechanisms to intervention strategies.Theranostics · 2026Review
- Spatiotemporal liver dynamics shape hepatocellular heterogeneity and impact in vivo gene engineering.Journal of hepatology · 2025Article
- Targeted in vivo gene integration of a secretion-enabled GLP-1 receptor agonist reverses diet-induced non-genetic obesity and pre-diabetes.Communications medicine · 2025Article
- Low Efficiency of Homology-Independent Targeted Integration for CRISPR/Cas9 Correction in the Vicinity of theInternational journal of molecular sciences · 2025Article
- CRISPR-Cas9-mediated homology-directed repair for precise gene editing.Molecular therapy. Nucleic acids · 2024Review
- Lipid Nanoparticles Enable Efficient In Vivo DNA Knock-In via HITI-Mediated Genome Editing.Biomolecules · 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
- Inherited Retinal Degenerations and Non-Neovascular Age-Related Macular Degeneration: Progress and Unmet Needs.Translational vision science & technology · 2024Review
- Optimization of HITI-Mediated Gene Insertion for Rhodopsin and Peripherin-2 in Mouse Rod Photoreceptors: Targeting Dominant Retinitis Pigmentosa.Investigative ophthalmology & visual science · 2024Article
- Optogenetics and Targeted Gene Therapy for Retinal Diseases: Unravelling the Fundamentals, Applications, and Future Perspectives.Journal of clinical medicine · 2024Review
- Safe and effective liver-directed AAV-mediated homology-independent targeted integration in mouse models of inherited diseases.Cell reports. Medicine · 2024Article
- AAV-mediated genome editing is influenced by the formation of R-loops.bioRxiv : the preprint server for biology · 2024Article
- In vivo genome editing via CRISPR/Cas9-mediated homology-independent targeted integration for Bietti crystalline corneoretinal dystrophy treatment.Nature communications · 2024Article
- Recent advances in CRISPR-Cas9-based genome insertion technologies.Molecular therapy. Nucleic acids · 2024Review
- Retinal Ciliopathies and Potential Gene Therapies: A Focus on Human iPSC-Derived Organoid Models.International journal of molecular sciences · 2024Review
- Precise genome-editing in human diseases: mechanisms, strategies and applications.Signal transduction and targeted therapy · 2024Review
Corrections and comments
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Authors and funding
23 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Challenges to the widespread application of gene therapy with adeno-associated viral (AAV) vectors include dominant conditions due to gain-of-function mutations which require allele-specific knockout, as well as long-term transgene expression from proliferating tissues, which is hampered by AAV DNA episomal status. To overcome these challenges, we used CRISPR/Cas9-mediated homology-independent targeted integration (HITI) in retina and liver as paradigmatic target tissues. We show that AAV-HITI targets photoreceptors of both mouse and pig retina, and this results in significant improvements to retinal morphology and function in mice with autosomal dominant retinitis pigmentosa. In addition, we show that neonatal systemic AAV-HITI delivery achieves stable liver transgene expression and phenotypic improvement in a mouse model of a severe lysosomal storage disease. We also show that HITI applications predominantly result in on-target editing. These results lay the groundwork for the application of AAV-HITI for the treatment of diseases affecting various organs.
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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.