ArticleMolecular therapy. Methods & clinical development2016
Construction of a hybrid β-hexosaminidase subunit capable of forming stable homodimers that hydrolyze GM2 ganglioside in vivo.
Article in Molecular therapy. Methods & clinical development, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 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.
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Who cites it
39 citing papers in PubMed, 51 citations in OpenAlex.
- AAV-based gene therapy with modified HEXB confers lasting therapeutic benefits in GM2 gangliosidosis models.Cell reports. Medicine · 2026Article
- Intrathecal delivery of AAVrh10-mHexa combined with anti-inflammatory treatment reduces neuropathological markers and extends the lifespan of mice with early-onset Tay-Sachs disease.Metabolic brain disease · 2026Article
- Generation of mice with combined Hexa Gly269Ser KI or KO and Neu3 KO alleles to create new models of GM2 gangliosidoses.Biology open · 2025Article
- Characterization of Human Recombinant β1,4-GalNAc-Transferase B4GALNT1 and Inhibition by Selected Compounds.Molecules (Basel, Switzerland) · 2025Article
- Advances in Diagnosis, Pathological Mechanisms, Clinical Impact, and Future Therapeutic Perspectives in Tay-Sachs Disease.Neurology international · 2025Review
- Precise template-free correction restores gene function in Tay-Sachs disease while reframing is ineffective.Molecular therapy. Nucleic acids · 2025Article
- Intracerebroventricular administration of a modified hexosaminidase ameliorates late-stage neurodegeneration in a GM2 mouse model.PloS one · 2025Article
- Treating late-onset Tay Sachs disease: Brain delivery with a dual trojan horse protein.Molecular therapy. Methods & clinical development · 2024Article
- Intrathecal delivery of a bicistronic AAV9 vector expressing β-hexosaminidase A corrects Sandhoff disease in a murine model: A dosage study.Molecular therapy. Methods & clinical development · 2024Article
- Cinnamic acid, a natural plant compound, exhibits neuroprotection in a mouse model of Sandhoff disease via PPARα.NeuroImmune pharmacology and therapeutics · 2024Article
- Increasing β-hexosaminidase A activity using genetically modified mesenchymal stem cells.Neural regeneration research · 2024Article
- Article
- Life-Limiting Peripheral Organ Dysfunction in Feline Sandhoff Disease Emerges after Effective CNS Gene Therapy.Annals of neurology · 2023Article
- Zebra-Sphinx: Modeling Sphingolipidoses in Zebrafish.International journal of molecular sciences · 2023Review
- 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
- IgG Fusion Proteins for Brain Delivery of Biologics via Blood-Brain Barrier Receptor-Mediated Transport.Pharmaceutics · 2022Review
- Increased phosphorylation of HexM improves lysosomal uptake and potential for managing GM2 gangliosidoses.BBA advances · 2022Article
- Therapeutic Strategies For Tay-Sachs Disease.Frontiers in pharmacology · 2022Review
- Investigating Immune Responses to the scAAV9-International journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
9 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tay-Sachs or Sandhoff disease result from mutations in either the evolutionarily related HEXA or HEXB genes encoding respectively, the α- or β-subunits of β-hexosaminidase A (HexA). Of the three Hex isozymes, only HexA can interact with its cofactor, the GM2 activator protein (GM2AP), and hydrolyze GM2 ganglioside. A major impediment to establishing gene or enzyme replacement therapy based on HexA is the need to synthesize both subunits. Thus, we combined the critical features of both α- and β-subunits into a single hybrid µ-subunit that contains the α-subunit active site, the stable β-subunit interface and unique areas in each subunit needed to interact with GM2AP. To facilitate intracellular analysis and the purification of the µ-homodimer (HexM), CRISPR-based genome editing was used to disrupt the HEXA and HEXB genes in a Human Embryonic Kidney 293 cell line stably expressing the µ-subunit. In association with GM2AP, HexM was shown to hydrolyze a fluorescent GM2 ganglioside derivative both in cellulo and in vitro. Gene transfer studies in both Tay-Sachs and Sandhoff mouse models demonstrated that HexM expression reduced brain GM2 ganglioside levels.
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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.