ArticleMolecular therapy : the journal of the American Society of Gene Therapy2021
Correction of metabolic abnormalities in a mouse model of glycogen storage disease type Ia by CRISPR/Cas9-based gene editing.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 26 citations in OpenAlex.
- CRISPR-Cas9 Therapeutics in Early Clinical Development: Delivery and Molecular Diagnostics.Cells · 2026Review
- Generation of a glycogen storage disease mouse model with fatty liver and its treatment by PPAR-α agonist bezafibrate.Frontiers in pharmacology · 2026Article
- Article
- CRISPR/Cas System: A Powerful Strategy to Improve Monogenic Human Diseases as Therapeutic Delivery; Current Applications and Challenges.Current gene therapy · 2025Review
- Base-editing corrects metabolic abnormalities in a humanized mouse model for glycogen storage disease type-Ia.Nature communications · 2024Article
- Endocrine involvement in hepatic glycogen storage diseases: pathophysiology and implications for care.Reviews in endocrine & metabolic disorders · 2024Review
- Review
- Endogenous Glucose Production in Patients With Glycogen Storage Disease Type Ia Estimated by Oral D-[6,6-2H2]-glucose.The Journal of clinical endocrinology and metabolism · 2024Article
- Gene therapy for glycogen storage diseases.Journal of inherited metabolic disease · 2024Review
- Clinical applications of the CRISPR/Cas9 genome-editing system: Delivery options and challenges in precision medicine.Genes & diseases · 2024Review
- Advances in CRISPR-Cas technology and its applications: revolutionising precision medicine.Frontiers in genome editing · 2024Review
- CRISPR-Cas9-mediated somatic correction of a one-base deletion in the Ugt1a gene ameliorates hyperbilirubinemia in Crigler-Najjar syndrome mice.Molecular therapy. Methods & clinical development · 2023Article
- A splice-switching oligonucleotide treatment ameliorates glycogen storage disease type 1a in mice with G6PC c.648G>T.The Journal of clinical investigation · 2023Article
- CRISPR/Cas9-based double-strand oligonucleotide insertion strategy corrects metabolic abnormalities in murine glycogen storage disease type-Ia.Journal of inherited metabolic disease · 2023Article
- Genome editing usingMolecular therapy. Methods & clinical development · 2023Article
- CRISPR-Cas9 base editors and their current role in human therapeutics.Cytotherapy · 2023Review
- The landscape of CRISPR/Cas9 for inborn errors of metabolism.Molecular genetics and metabolism · 2023Review
- Gene therapy and genome editing for type I glycogen storage diseases.Frontiers in molecular medicine · 2023Review
- Lafora disease: Current biology and therapeutic approaches.Revue neurologique · 2022Review
- Basic Principles and Clinical Applications of CRISPR-Based Genome Editing.Yonsei medical journal · 2022Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Glycogen storage disease type Ia (GSD-Ia), deficient in glucose-6-phosphatase-α (G6PC), is characterized by impaired glucose homeostasis and a hallmark of fasting hypoglycemia. We have developed a recombinant adeno-associated virus (rAAV) vector-mediated gene therapy for GSD-Ia that is currently in a phase I/II clinical trial. While therapeutic expression of the episomal rAAV-G6PC clinical vector is stable in mice, the long-term durability of expression in humans is currently being established. Here we evaluated CRISPR/Cas9-based in vivo genome editing technology to correct a prevalent pathogenic human variant, G6PC-p.R83C. We have generated a homozygous G6pc-R83C mouse strain and shown that the G6pc-R83C mice manifest impaired glucose homeostasis and frequent hypoglycemic seizures, mimicking the pathophysiology of GSD-Ia patients. We then used a CRISPR/Cas9-based gene editing system to treat newborn G6pc-R83C mice and showed that the treated mice grew normally to age 16 weeks without hypoglycemia seizures. The treated G6pc-R83C mice, expressing ≥ 3% of normal hepatic G6Pase-α activity, maintained glucose homeostasis, displayed normalized blood metabolites, and could sustain 24 h of fasting. Taken together, we have developed a second-generation therapy in which in vivo correction of a pathogenic G6PC-p.R83C variant in its native genetic locus could lead to potentially permanent, durable, long-term correction of the GSD-Ia phenotype.
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Registered trials
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