ArticleMolecular therapy : the journal of the American Society of Gene Therapy2020
A Highly Efficacious PS Gene Editing System Corrects Metabolic and Neurological Complications of Mucopolysaccharidosis Type I.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02702115 (A Phase I / 2, Multicenter, Open-label, Single-dose, Dose-ranging Study to Assess the Safety and Tolerability of SB-318, a rAAV2/6-based Gene Transfer in Subjects With Mucopolysaccharidosis I), which is not on this map. Cited by 38 papers.
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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.
A Phase I / 2, Multicenter, Open-label, Single-dose, Dose-ranging Study to Assess the Safety and Tolerability of SB-318, a rAAV2/6-based Gene Transfer in Subjects With Mucopolysaccharidosis I (MPS I)
Who cites it
38 citing papers in PubMed, 57 citations in OpenAlex.
- Non-viral delivery of genome-editing tools for treatment of genetic disorders.Acta pharmaceutica Sinica. B · 2026Review
- Genomic medicine in hepatology: mechanisms and liver treatment strategies.Molecular medicine (Cambridge, Mass.) · 2025Review
- Repair Drive improves gene editing in the liver.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Engineering memory T cells as a platform for long-term enzyme replacement therapy in lysosomal storage disorders.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- CRISPR/Cas9 technology in the modeling of and treatment of mucopolysaccharidosis.Biochemistry and biophysics reports · 2024Review
- Safe and effective liver-directed AAV-mediated homology-independent targeted integration in mouse models of inherited diseases.Cell reports. Medicine · 2024Article
- Comparative dose effectiveness of intravenous and intrathecal AAV9.CB7.hIDS, RGX-121, in mucopolysaccharidosis type II mice.Molecular therapy. Methods & clinical development · 2024Article
- A bibliometric analysis of gene editing and amyotrophic lateral sclerosis (from 2004 to 2024).Frontiers in neuroscience · 2024Article
- Utilizing noncatalytic ACE2 protein mutant as a competitive inhibitor to treat SARS-CoV-2 infection.Frontiers in immunology · 2024Article
- Mapping brain networks in MPS I mice and their restoration following gene therapy.Scientific reports · 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
- Gene therapy for lysosomal storage diseases: Current clinical trial prospects.Frontiers in genetics · 2023Review
- 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
- Genome Editing Tools for Lysosomal Storage Disorders.Advances in experimental medicine and biology · 2023Article
- Hot topics in cellular neuropathology III: using CRISPR/Cas9 technology for deciphering central nervous system disease targets.Frontiers in cellular neuroscience · 2023Article
- Identification of a novel fusion Iduronidase with improved activity in the cardiovascular system.Molecular genetics and metabolism reports · 2022Article
- Site-specific genome editing in treatment of inherited diseases: possibility, progress, and perspectives.Medical review (2021) · 2022Review
- Genome editing-mediated knock-in of therapeutic genes ameliorates the disease phenotype in a model of hemophilia.Molecular therapy. Nucleic acids · 2022Article
- Current landscape of gene-editing technology in biomedicine: Applications, advantages, challenges, and perspectives.MedComm · 2022Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Our previous study delivered zinc finger nucleases to treat mice with mucopolysaccharidosis type I (MPS I), resulting in a phase I/II clinical trial (ClinicalTrials.gov: NCT02702115). However, in the clinical trial, the efficacy needs to be improved due to the low transgene expression level. To this end, we designed a proprietary system (PS) gene editing approach with CRISPR to insert a promoterless α-l-iduronidase (IDUA) cDNA sequence into the albumin locus of hepatocytes. In this study, adeno-associated virus 8 (AAV8) vectors delivering the PS gene editing system were injected into neonatal and adult MPS I mice. IDUA enzyme activity in the brain significantly increased, while storage levels were normalized. Neurobehavioral tests showed that treated mice had better memory and learning ability. Also, histological analysis showed efficacy reflected by the absence of foam cells in the liver and vacuolation in neuronal cells. No vector-associated toxicity or increased tumorigenesis risk was observed. Moreover, no off-target effects were detected through the unbiased genome-wide unbiased identification of double-stranded breaks enabled by sequencing (GUIDE-seq) analysis. In summary, these results showed the safety and efficacy of the PS in treating MPS I and paved the way for clinical studies. Additionally, as a therapeutic platform, the PS has the potential to treat 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.