ArticleEMBO molecular medicine2024
Efficient and safe therapeutic use of paired Cas9-nickases for primary hyperoxaluria type 1.
Article in EMBO molecular medicine, 2024. 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
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
25 citing papers in PubMed, 21 citations in OpenAlex.
- Adeno-Associated Viral Vector (AAV)-Mediated In Vivo CRISPR-Cas9 Delivery.Methods in molecular biology (Clifton, N.J.) · 2027Article
- NHSL3 knockout modulates sorafenib response, growth, and motility in hepatocellular carcinoma cell models.Molecular biology reports · 2026Article
- The future of pediatric gene therapy: CRISPR-Cas9, AI, and personalized medicine.Pediatric research · 2026Review
- Orthogonal characterization of rAAV reveals vector attributes that drive ITR repair, self-complementary genome formation, and transgene expression.Molecular therapy. Nucleic acids · 2026Article
- Nickase NmCas9 unsilences paternal Ube3a in a mouse model of Angelman syndrome without causing AAV vector integration.Scientific reports · 2026Article
- Gene therapy for liver diseases: methods, challenges and opportunities.Journal of nanobiotechnology · 2026Review
- From Bench to Bedside: Ethical and Clinical Best Practices for Genome Editing Applications.International journal of molecular sciences · 2026Review
- Multi-targeting zinc finger nuclease vector unsilences paternal UBE3A in a mouse model of Angelman syndrome.Gene therapy · 2026Article
- Genetic Correction of the Most Common Mutation Causing Primary Hyperoxaluria Restores Enzyme Localization and Oxalate Metabolism.Journal of inherited metabolic disease · 2026Article
- Exploring CRISPR-Cas: The transformative impact of gene editing in molecular biology.Molecular therapy. Nucleic acids · 2025Review
- The Genetic Blueprint of Obesity: From Pathogenesis to Novel Therapies.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2025Review
- Tapping the microalgal potential: genetic precision and stress-induction for enhanced astaxanthin and biofuel production.Biotechnology for biofuels and bioproducts · 2025Review
- Hyperoxaluria: Diagnosis and Treatment.The Urologic clinics of North America · 2025Review
- Preclinical evaluation of AGT mRNA replacement therapy for primary hyperoxaluria type I disease.Science advances · 2025Article
- Advanced delivery systems for gene editing: A comprehensive review from the GenE-HumDi COST Action Working Group.Molecular therapy. Nucleic acids · 2025Review
- The Interface of Gene Editing with Regenerative Medicine.Engineering (Beijing, China) · 2025Article
- Cutting through the stones: Unlocking therapeutic potential with gene editing tools for primary hyperoxaluria type 1.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Lipid nanoparticle-mediated base-editing of the Hao1 gene achieves sustainable primary hyperoxaluria type 1 therapy in rats.Science China. Life sciences · 2024Article
- Gene Therapy for Inherited Liver Disease: To Add or to Edit.International journal of molecular sciences · 2024Review
- Opportunities in Primary and Enteric Hyperoxaluria at the Cross-Roads Between the Clinic and Laboratory.Kidney international reports · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 5 institutions in 3 countries.
Funding
Abstract
The therapeutic use of adeno-associated viral vector (AAV)-mediated gene disruption using CRISPR-Cas9 is limited by potential off-target modifications and the risk of uncontrolled integration of vector genomes into CRISPR-mediated double-strand breaks. To address these concerns, we explored the use of AAV-delivered paired Staphylococcus aureus nickases (D10ASaCas9) to target the Hao1 gene for the treatment of primary hyperoxaluria type 1 (PH1). Our study demonstrated effective Hao1 gene disruption, a significant decrease in glycolate oxidase expression, and a therapeutic effect in PH1 mice. The assessment of undesired genetic modifications through CIRCLE-seq and CAST-Seq analyses revealed neither off-target activity nor chromosomal translocations. Importantly, the use of paired-D10ASaCas9 resulted in a significant reduction in AAV integration at the target site compared to SaCas9 nuclease. In addition, our study highlights the limitations of current analytical tools in characterizing modifications introduced by paired D10ASaCas9, necessitating the development of a custom pipeline for more accurate characterization. These results describe a positive advance towards a safe and effective potential long-term treatment for PH1 patients.
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.