ArticleMolecular therapy : the journal of the American Society of Gene Therapy2018
Downregulation of SNCA Expression by Targeted Editing of DNA Methylation: A Potential Strategy for Precision Therapy in PD.
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 127 papers, 3 of them syntheses that pooled it.
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Who cites it
127 citing papers in PubMed, 3 syntheses or guidelines pooled it, 195 citations in OpenAlex.
- Next-generation pharmacological strategies for Parkinson's disease: a systematic literature review of symptom management and disease modification.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Pooled it
- Interrogating DNA methylation associated with Lewy body pathology in a cross brain-region and multi-cohort study.Nature communications · 2026Pooled it
- A Systematic Review of Parkinson's Disease Pharmacogenomics: Is There Time for Translation into the Clinics?International journal of molecular sciences · 2021Pooled it
- Recent Advances in CRISPR/Cas Technologies for Biological Discovery, Therapeutics, and Diagnostics.Biomolecules · 2026Review
- Rodent models and accompanying in vitro strategies for studying the etiology and therapy of Parkinson's disease.Journal of Parkinson's disease · 2026Review
- Silencing of humanJournal of Huntington's disease · 2026Article
- Alzheimer's Disease and MERC Dysfunction: Integrating Mechanisms, Biomarkers, and Therapeutic Strategies.Molecular neurobiology · 2026Review
- Human pluripotent stem cell engineering with CRISPR-Cas9 for Parkinson's disease.Experimental & molecular medicine · 2026Review
- CRISPR-Cas editing technologies for viral-mediated gene therapies of human diseases: Mechanisms, progress, and challenges.Molecular therapy. Nucleic acids · 2026Review
- Investigating the molecular mechanisms of glutamine metabolism and mitochondria-related biomarkers in Alzheimer's disease through transcriptomics and experimental validation.European journal of medical research · 2026Article
- Genetic therapies for neurological diseases.Pharmacological reviews · 2026Review
- Multifunctional Hybrid Nanomedicines for Neurodegenerative Diseases: A Paradigm Shift from Rational Design to Clinical Translation.International journal of nanomedicine · 2026Review
- Epigenetic Editing in Neurological and Neuropsychiatric Disorders: Pioneering Next-Gen Therapeutics for Precision Gene Control.Molecular neurobiology · 2025Review
- CRISPR-based Transcriptional Regulation: Technologies, Applications, and Future Directions.DNA · 2025Article
- Phospholipase C epsilon 1 as a therapeutic target in cardiovascular diseases.Journal of advanced research · 2025Review
- CRISPR Technology in Disease Management: An Updated Review of Clinical Translation and Therapeutic Potential.Cell proliferation · 2025Article
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- Nanotechnology and CRISPR/Cas-Mediated Gene Therapy Strategies: Potential Role for Treating Genetic Disorders.Molecular biotechnology · 2025Review
- Trends and challenges of AAV-delivered gene editing therapeutics for CNS disorders: Implications for neurodegenerative disease.Molecular therapy. Nucleic acids · 2025Review
- R406 and its structural analogs reduce SNCA/α-synuclein levels via autophagic degradation.Autophagy · 2025Article
67 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Elevated levels of SNCA have been implicated in the pathogenesis of Parkinson's disease (PD), while normal physiological levels of SNCA are needed to maintain neuronal function. We ought to develop new therapeutic strategies targeting the regulation of SNCA expression. DNA methylation at SNCA intron 1 regulates SNCA transcription, and PD brains showed differential methylation levels compared to controls. Thus, DNA methylation at SNCA intron 1 is an attractive target for fine-tuned downregulation of SNCA levels. Here we developed a system, comprising an all-in-one lentiviral vector, for targeted DNA methylation editing within intron 1. The system is based on CRISPR-deactivated Cas9 (dCas9) fused with the catalytic domain of DNA-methyltransferase 3A (DNMT3A). Applying the system to human induced pluripotent stem cell (hiPSC)-derived dopaminergic neurons from a PD patient with the SNCA triplication resulted in fine downregulation of SNCA mRNA and protein mediated by targeted DNA methylation at intron 1. Furthermore, the reduction in SNCA levels by the guide RNA (gRNA)-dCas9-DMNT3A system rescued disease-related cellular phenotype characteristics of the SNCA triplication hiPSC-derived dopaminergic neurons, e.g., mitochondrial ROS production and cellular viability. We established that DNA hypermethylation at SNCA intron 1 allows an effective and sufficient tight downregulation of SNCA expression levels, suggesting the potential of this target sequence combined with the CRISPR-dCas9 technology as a novel epigenetic-based therapeutic approach for PD.
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