ArticleGene therapy2020
A novel gene editing system to treat both Tay-Sachs and Sandhoff diseases.
Article in Gene therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 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
36 citing papers in PubMed, 54 citations in OpenAlex.
- Review
- Microglial replacement in a Sandhoff disease mouse model reveals myeloid-derived β-hexosaminidase is necessary for neuronal health.Nature communications · 2025Article
- Advances in Diagnosis, Pathological Mechanisms, Clinical Impact, and Future Therapeutic Perspectives in Tay-Sachs Disease.Neurology international · 2025Review
- Evaluation of the PP6D5 Polymer as a Novel Non-Viral Vector in the Development of a CRISPR/nCas9-Based Gene Therapy for Tay-Sachs Disease.Pharmaceutics · 2025Article
- CRISPR/Cas System: A Powerful Strategy to Improve Monogenic Human Diseases as Therapeutic Delivery; Current Applications and Challenges.Current gene therapy · 2025Review
- Myeloid-derived β-hexosaminidase is essential for neuronal health and lysosome function: implications for Sandhoff disease.bioRxiv : the preprint server for biology · 2024Article
- Cuboids Prevail When Unraveling the Influence of Microchip Geometry on Macrophage Interactions and Metabolic Responses.ACS biomaterials science & engineering · 2024Article
- Nonviral delivery of nCas9 for "safe harbor" integration to treat MPS IVA.Molecular therapy. Methods & clinical development · 2024Article
- Systematic comparison of rAAV vectors manufactured using large-scale suspension cultures of Sf9 and HEK293 cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Increasing β-hexosaminidase A activity using genetically modified mesenchymal stem cells.Neural regeneration research · 2024Article
- Iron oxide-coupled CRISPR-nCas9-based genome editing assessment in mucopolysaccharidosis IVA mice.Molecular therapy. Methods & clinical development · 2023Article
- A promoterless AAV6.2FF-based lung gene editing platform for the correction of surfactant protein B deficiency.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Mapping brain networks in MPS I mice and their restoration following gene therapy.Scientific reports · 2023Article
- Gene expression changes in Tay-Sachs disease begin early in fetal brain development.Journal of inherited metabolic disease · 2023Article
- Advancement in CRISPR/Cas9 Technology to Better Understand and Treat Neurological Disorders.Cellular and molecular neurobiology · 2023Review
- Zebra-Sphinx: Modeling Sphingolipidoses in Zebrafish.International journal of molecular sciences · 2023Review
- Efficient CRISPR/Cas9 nickase-mediated genome editing in an in vitro model of mucopolysaccharidosis IVA.Gene therapy · 2023Article
- The landscape of CRISPR/Cas9 for inborn errors of metabolism.Molecular genetics and metabolism · 2023Review
- CRISPR/nCas9-Based Genome Editing on GM2 Gangliosidoses Fibroblasts via Non-Viral Vectors.International journal of molecular sciences · 2022Article
- Delivery and assessment of a CRISPR/nCas9-based genome editing system on in vitro models of mucopolysaccharidoses IVA assisted by magnetite-based nanoparticles.Scientific reports · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
The GM2-gangliosidoses are neurological diseases causing premature death, thus developing effective treatment protocols is urgent. GM2-gangliosidoses result from deficiency of a lysosomal enzyme β-hexosaminidase (Hex) and subsequent accumulation of GM2 gangliosides. Genetic changes in HEXA, encoding the Hex α subunit, or HEXB, encoding the Hex β subunit, causes Tay-Sachs disease and Sandhoff disease, respectively. Previous studies have showed that a modified human Hex µ subunit (HEXM) can treat both Tay-Sachs and Sandhoff diseases by forming a homodimer to degrade GM2 gangliosides. To this end, we applied this HEXM subunit in our PS813 gene editing system to treat neonatal Sandhoff mice. Through AAV delivery of the CRISPR system, a promoterless HEXM cDNA will be integrated into the albumin safe harbor locus, and lysosomal enzyme will be expressed and secreted from edited hepatocytes. 4 months after the i.v. of AAV vectors, plasma MUGS and MUG activities reached up to 144- and 17-fold of wild-type levels (n = 10, p < 0.0001), respectively. More importantly, MUGS and MUG activities in the brain also increased significantly compared with untreated Sandhoff mice (p < 0.001). Further, HPLC-MS/MS analysis showed that GM2 gangliosides in multiple tissues, except the brain, of treated mice were reduced to normal levels. Rotarod analysis showed that coordination and motor memory of treated mice were improved (p < 0.05). Histological analysis of H&E stained tissues showed reduced cellular vacuolation in the brain and liver of treated Sandhoff mice. These results demonstrate the potential of developing a treatment of in vivo genome editing for Tay-Sachs and Sandhoff 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.