ArticleMolecular therapy : the journal of the American Society of Gene Therapy2025
Efficient and safe in vivo treatment of primary hyperoxaluria type 1 via LNP-CRISPR-Cas9-mediated glycolate oxidase disruption.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Overview of Delivery Methods for Gene Editing.Methods in molecular biology (Clifton, N.J.) · 2027Review
- Engineered Transformer Base Editor with Enhanced Editing Efficiency.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Animal Models of Hyperoxaluria and Their Relevance for Fundamental Research and Clinical Practice.International journal of molecular sciences · 2026Review
- Review
- Gene therapy for liver diseases: methods, challenges and opportunities.Journal of nanobiotechnology · 2026Review
- Clinical Approaches and Emerging Therapeutic Horizons in Primary Hyperoxaluria.Journal of clinical medicine · 2026Review
- Review
- Genetic Correction of the Most Common Mutation Causing Primary Hyperoxaluria Restores Enzyme Localization and Oxalate Metabolism.Journal of inherited metabolic disease · 2026Article
- High-Throughput Strategies for Streamlining Lipid Nanoparticle Development Pipeline.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Controlled access to lumasiran in primary hyperoxaluria type 1: evaluation of a new access route for orphan drugs in the Netherlands.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025Article
- Advancing gene editing therapeutics: Clinical trials and innovative delivery systems across diverse diseases.Molecular therapy. Nucleic acids · 2025Review
- Spleen-targeted NeoPol-mL242 mRNA vaccine induces robust T-cell responses in a hepatocellular carcinoma model.Journal of nanobiotechnology · 2025Article
- Hyperoxaluria: Diagnosis and Treatment.The Urologic clinics of North America · 2025Review
- 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
- Gene Editing: An Effective Tool for the Future Treatment of Kidney Disease.Journal of inflammation research · 2025Review
Corrections and comments
- Erratum issued
Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Primary hyperoxaluria type 1 (PH1) is a severe genetic metabolic disorder caused by mutations in the AGXT gene, leading to defects in enzymes crucial for glyoxylate metabolism. PH1 is characterized by severe, potentially life-threatening manifestations due to excessive oxalate accumulation, which leads to calcium oxalate crystal deposits in the kidneys and, ultimately, renal failure and systemic oxalosis. Existing substrate reduction therapies, such as inhibition of liver-specific glycolate oxidase (GO) encoded by HAO1 using siRNA or CRISPR-Cas9 delivered by adeno-associated virus, either require repeated dosing or have raised safety concerns. To address these limitations, our study employed lipid nanoparticles (LNPs) for CRISPR-Cas9 delivery to rapidly generate a PH1 mouse model and validate the therapeutic efficacy of LNP-CRISPR-Cas9 targeting the Hao1 gene. The LNP-CRISPR-Cas9 system exhibited efficient editing of the Hao1 gene, significantly reducing GO expression and lowering urinary oxalate levels in treated PH1 mice. Notably, these effects persisted for 12 months with no significant off-target effects, liver-induced toxicity, or substantial immune responses, highlighting the approach's safety and specificity. Furthermore, the developed humanized mouse model validated the efficacy of our therapeutic strategy. These findings support LNP-CRISPR-Cas9 targeting HAO1 as a promising and safer alternative for PH1 treatment with a single administration.
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