ArticleMolecular therapy : the journal of the American Society of Gene Therapy2018
Dose-Dependent Prevention of Metabolic and Neurologic Disease in Murine MPS II by ZFN-Mediated In Vivo Genome Editing.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 125 citations in OpenAlex.
- The future of pediatric gene therapy: CRISPR-Cas9, AI, and personalized medicine.Pediatric research · 2026Review
- Non-viral delivery of genome-editing tools for treatment of genetic disorders.Acta pharmaceutica Sinica. B · 2026Review
- Review
- Advanced delivery systems for gene editing: A comprehensive review from the GenE-HumDi COST Action Working Group.Molecular therapy. Nucleic acids · 2025Review
- Intrathecal or intravenous AAV9-IDUA/RGX-111 at minimal effective dose prevents cardiac, skeletal and neurologic manifestations of murine MPS I.Molecular therapy. Methods & clinical development · 2024Article
- Gene Therapy for Inherited Liver Disease: To Add or to Edit.International journal of molecular sciences · 2024Review
- Targeting Neurological Aspects of Mucopolysaccharidosis Type II: Enzyme Replacement Therapy and Beyond.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024Review
- Comparative dose effectiveness of intravenous and intrathecal AAV9.CB7.hIDS, RGX-121, in mucopolysaccharidosis type II mice.Molecular therapy. Methods & clinical development · 2024Article
- Recent Advances in In Vivo Somatic Cell Gene Modification in Newborn Pups.International journal of molecular sciences · 2023Review
- A novel mucopolysaccharidosis type II mouse model with an iduronate-2-sulfatase-P88L mutation.Scientific reports · 2023Article
- Generation and characterization of an immunodeficient mouse model of mucopolysaccharidosis type II.Molecular genetics and metabolism · 2023Article
- Non-invasive intravenous administration of AAV9 transducing iduronate sulfatase leads to global metabolic correction and prevention of neurologic deficits in a mouse model of Hunter syndrome.Molecular genetics and metabolism reports · 2023Article
- In vivo adenine base editing corrects newborn murine model of Hurler syndrome.Molecular biomedicine · 2023Article
- Genome Editing Tools for Lysosomal Storage Disorders.Advances in experimental medicine and biology · 2023Article
- Neurologic Recovery in MPS I and MPS II Mice by AAV9-Mediated Gene Transfer to the CNS After the Development of Cognitive Dysfunction.Human gene therapy · 2023Article
- First-in-human in vivo genome editing via AAV-zinc-finger nucleases for mucopolysaccharidosis I/II and hemophilia B.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Phenotypic Correction of Murine Mucopolysaccharidosis Type II by Engraftment ofHuman gene therapy · 2022Article
- mRNA and gene editing: Late breaking therapies in liver diseases.Hepatology (Baltimore, Md.) · 2022Review
- Engineering the next generation of cell-based therapeutics.Nature reviews. Drug discovery · 2022Review
- Mammalian Sulfatases: Biochemistry, Disease Manifestation, and Therapy.International journal of molecular sciences · 2022Review
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mucopolysaccharidosis type II (MPS II) is an X-linked recessive lysosomal disorder caused by deficiency of iduronate 2-sulfatase (IDS), leading to accumulation of glycosaminoglycans (GAGs) in tissues of affected individuals, progressive disease, and shortened lifespan. Currently available enzyme replacement therapy (ERT) requires lifelong infusions and does not provide neurologic benefit. We utilized a zinc finger nuclease (ZFN)-targeting system to mediate genome editing for insertion of the human IDS (hIDS) coding sequence into a "safe harbor" site, intron 1 of the albumin locus in hepatocytes of an MPS II mouse model. Three dose levels of recombinant AAV2/8 vectors encoding a pair of ZFNs and a hIDS cDNA donor were administered systemically in MPS II mice. Supraphysiological, vector dose-dependent levels of IDS enzyme were observed in the circulation and peripheral organs of ZFN+donor-treated mice. GAG contents were markedly reduced in tissues from all ZFN+donor-treated groups. Surprisingly, we also demonstrate that ZFN-mediated genome editing prevented the development of neurocognitive deficit in young MPS II mice (6-9 weeks old) treated at high vector dose levels. We conclude that this ZFN-based platform for expression of therapeutic proteins from the albumin locus is a promising approach for treatment of MPS II and other lysosomal diseases.
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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.